Adult mammalian brains continuously generate new neurons, a phenomenon called adult neurogenesis. Both environmental stimuli and endogenous factors are important regulators of adult neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and adult neurogenesis in brain function, such as learning, memory, and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on adult neurogenesis. Thousands of new neurons are daily added to the adult brain of different species, including humans , and thiNeurogenesis includes the generation, proliferation, fate specification and integration of new functional neurons in the existing neural circuits from undifferentiated progenitor cells. Traditionally, it was believed that neurogenesis mainly occurred during the embryonic stages of the central nervous system (CNS), ending permanently at puberty .3H]-thymidine autoradiography , lining the wall of the lateral ventricles, and in the subgranular zone (SGZ) of the hippocampal dentate gyrus . The neuSimilarly, a cohort of glucogenic and neurogenic signals  regulateTable 1), being possible that several modulating factors remain unknown  of the anterior hypothalamus . The neuDespite the existence of a SCN biological clock , KruegerCortical columns, also called neuronal assemblies, are examples of anatomically well-defined neural networks. It is believed that neuronal assemblies are the basic units of the brain processing during wakefulness, oscillating between functional states such as wake-like and sleep-like states . During in silico suggest that neuronal over-stimulated assemblies will quickly enter in the sleep-like state, inducing surrounding neuronal assemblies to enter in the same state and leading to the whole-animal sleep. Thus, this model considers both the evolution of a global state of sleep and the emerging features of individual networks.This model postulates that states vary throughout time due to the individual behavior of each network, the interaction with other assemblies and threshold-based transitions . NeuronaSleep is currently seen as being imposed by the brain and regulated by an endogenous biological clock. However, this paradigm does not address many well-known phenomena of sleep, such as sleep inertia, restoring peak performance during sleep, homeostatic mechanisms of sleep, insomnia, somnolence or fatigue. The model of neuronal assemblies is more flexible, being easier to propose explanations for some sleep phenomena. For instance, sleep inertia may be a manifestation of some neuronal assemblies that remain in sleep-like state, after a sufficient number of neuronal assemblies are in wake-like state. In insomnia, some neuronal assemblies can be asleep, while others remain awake. The degree of sleepiness or the speed and accuracy of performance may be dependent on the fraction of neuronal assemblies that remain in wake-like state or sleep-like state. Brain imaging techniques evidenced that patients with insomnia display specific activation of wakefulness in some brain areas, while other areas have characteristics of sleep activity .To date, the model of neuronal assemblies does not provide answers on how many assemblies are needed to enter in a sleep-like state. However, similar limitations exist in the current paradigm of sleep regulation, which proposes a top–down imposition of sleep on the brain by regulatory circuits, not specifying which and how many areas need to be activated to induce sleep. Despite the insufficient understanding of the mechanisms of sleep, this model provides an evolutionary conceptual framework for further researches .There is a correlation between sleep and neurogenesis across lifespan, since cell proliferation is maximal during early development stages, when daily amounts of sleep are higher. In addition, seasonal variability in neurogenesis and in sleep expression are associated in some species that migrate or hibernate . In adulM. bonariensis and M. rufoaxillaris), reporting a decrease in the hippocampal volume during the non-breeding season in both species. They justified this decrease with seasonal changes in spatial memory demands. During the breeding season, an enlarged hippocampus is important for hosts’ nests location. In contrast, during the non-breeding season, the lack of this demand is associated with a decrease in the relative hippocampal volume.3]-thymidine and released and recaptured birds after 6 or more weeks. Newly formed neurons appeared in the hippocampus throughout the year, however, with a marked peak during the fall (October). This peak was halved in captive chickadees. Despite the addition of new neurons, they found no differences in the number of neurons along seasons. This evidence suggests that new neurons were born in different periods of the year, lived for few months, occurring, subsequently, neuronal loss. The authors hypothesized that new neurons added during the fall are part of an important process of new spatial memories acquisition, which is particularly important at this time of the year due to the food hoarding. They proposed that storing memories turned these neurons unviable for future processing, requiring them to be replaced.Studies with different species of birds found similar results: an increase in hippocampal volume during the fall, correlated with an increase of cell proliferation. This structural change appears to be associated with seasonal demands of spatial memory  and songThese set of studies suggest that sleep and neurogenesis are both essential to promote memory and learning, namely song learning and production. However, in birds, neurogenesis is higher when they sleep less. This negative correlation may be explained by the fact that short sleep deprivation (such as that seen in birds in the migratory season) can modulate the increase of neurogenesis, an effect verified in some experiments with rodents , as willSeasonal changes in hippocampal neurogenesis of rodents have been documented, however, no direct correlation with seasonal sleep patterns was established. Structural and functional seasonal plasticity are essential properties of nervous system in several species inhabiting seasonal environments . DespiteSleep is a circadian rhythm . If sleeThere is substantial literature on the influence of daily rhythms in cell proliferation. In two studies, for instance, using male mice, it was observed that the number of proliferating cells in the SGZ is independent of the period of day. In the first study, BrdU was administered at six equally spaced periods, during 24 h of light-dark cycle. The number of BrdU-labeled cells, analyzed 2 h after the BrdU injections, showed no significant changes throughout light-dark cycle . A seconIn order to analyze the association between circadian phase and exercise in neurogenesis, In a study with adult rats , two groMost experiments with rodents reject the hypothesis that cell proliferation in the SGZ has a significant daily rhythm. Studies with mice show that proliferating cell rate more dependent on daily exercise than on circadian rhythms . One stuMoreover, although the SGZ is the most significant region of cell proliferation, a small amount of proliferating cells was found in the hilus . StudiesIt has been proposed that the influence of daily rhythms on cell proliferation rate is modulated by adrenal steroid levels, which are regulated by the activation of the HPA axis .The HPA axis is the greatest part of the neuroendocrine system and controls several body processes. Its complex set of direct influences and feedback interactions includes the paraventricular nucleus (PVN) of the hypothalamus. The PVN has neuroendocrine neurons responsible for synthesizing and releasing vasopressin and corticotropin-releasing hormone (CRH). These two hormones regulate the anterior lobe of the pituitary gland, stimulating the secretion of adrenocorticotropic hormone (ACTH). The ACTH stimulates the adrenal cortex to synthesize and release glucocorticoid hormones (mainly cortisol in humans), which act in a negative feedback cycle on the hypothalamus and pituitary gland. The CRH secretion can be influenced by stress, physical activity, illness, sleep/wake cycle and circadian rhythm .The activity of the HPA axis has marked circadian effects . CircadiTable 2).Sleep disruption induces psychological and neurobiological changes , and affSleep has been hypothesized as a facilitator of adult hippocampal neurogenesis, since prolonged sleep deprivation of adult rodents has a negative impact on cell proliferation, survival, maturation and differentiation of new neurons in the SGZ . HoweverSprague-Dawley rats for 48 h, using a disk-over-water paradigm. After, one group was allowed to sleep for 8 h, while the other group had an additional sleep deprivation period for 8 h. A control group was not sleep-deprived. After, animals were BrdU-injected and brain samples were collected 2 h later. The dentate gyrus of rats sleep-deprived for 56 h showed a reduction on cell proliferation of 36%, comparatively to animals of the control group. A similar reduction (of 39%) was observed in rats allowed to a sleep recovery for 8 h, demonstrating that the suppressive effects of prolonged sleep deprivation on cell proliferation are maintained after a sleep recovery for 8 h.The effects of prolonged sleep deprivation on cell proliferation rate vary between studies and can be persistent. Sprague-Dawley rats. They examined the effects of acute (24 h) and prolonged (72 h) sleep deprivation on cell proliferation on the granule cell layer, marking proliferating cells with BrdU. Two hours after the injections, the number of BrdU-labeled cells of animals acute sleep-deprived did not differ from undisturbed animals. However, BrdU-labeled cells were significantly reduced in animals submitted to a prolonged sleep deprivation. This reduction remained 1 week after the injections as well as 3 weeks after, when BrdU-labeled cells should express mature neuronal nuclei.Mice with 6–8 weeks old were sleep-deprived for 10–12 h, starting at the beginning of their sleep period. Mice of the control group were undisturbed. After sleep deprivation, corticosterone levels in plasma were similar to control mice, suggesting that the animals of the experimental group were not stressed. Mice were BrdU-injected and, 2 h later, they were euthanized. As result, the number of BrdU-labeled cells was no altered, confirming the hypothesis that the basal rate of cell proliferation in the SGZ is not affected by short sleep restriction .In an experiment by Sprague-Dawley rats were sleep-fragmented for 12 days by a treadmill and compared with sleep-fragmented control group. A treadmill control group was used to evaluate whether the physical activity, alone, would affect neurogenesis. Animals of these group were placed in an identical treadmill for 12 days, which was activated during equal periods of time but only in the waking phase. A cage control group was undisturbed. Animals were injected with BrdU on day 4 and 5 after the beginning of the experimental procedure, and returned to their cages for 14 days. Thereafter, to assess cognitive performance, animals were stimulated for 5 days with a Barnes maze with a constante escape tunnel position and 2 days with a rotated escape tunnel. Then, animals were sacrificed and their samples of dentate gyrus were collected and immunolabeled for BrdU and NeuN. Sleep fragmentation reduced BrdU-labeled cells by 32% in the sleep fragmentation group, comparatively to the sleep fragmentation and the treadmill control groups. In the cognitive assessment, animals of the sleep fragmentation group demonstrated a gradual reduced in escape time, but slower than animals of the other groups. Their most used search strategy was non-spatial and random, which persisted 2 weeks after the end of the experimental procedure -1 is one of several growth factors known as neurogenesis promoters . ProlongGrowth hormone (GH) could also be related with neurogenesis regulation. A recent study showed that GH administration strongly promotes adult cell proliferation in the dentate gyrus of rats, and protects the hippocampal neuronal precursors of the negative effects of chronic sleep deprivation . The proIn vitro, exposure to IL-6 and TNF-a diminishes cell proliferation and, in vivo, they can modulate the damaging effects of neuroinflammation in hippocampal neurogenesis -6 and tumor necrosis factor (TNF-a). There are evidences that both IL-6 and TNF-a are increased after chronic sleep deprivation , and IL-ogenesis .Figure 1), which may, in fact, affect selectively different stages of neurogenesis process  or in a non-hippocampal-dependent spatial task (a visible platform). After each training day, on group of animals were kept awake for the first 6 h of its normal rest time. Animals were BrdU-injected 1 week before the beginning of the training. During the experience, the generated cells a week before the training should be mature and incorporated in the hippocampal network. Rats trained on hippocampal-dependent spatial task had a pronounced increase of newborn cells survival. However, this effect was suppressed in animals submitted to the same task but sleep-deprived. In the sleep-deprived group spatial learning was impaired but, surprisingly, non-spatial learning was improved. In both groups, fully rested animals applied a spatial strategy in both tasks, which interfered with the performance in the non-spatial task. In sleep-restricted group, this spatial strategy was eliminated, and animals used only non-spatial information, improving non-spatial performance. These findings suggest that sleep loss altered behavioral strategies and reversed neurogenic effects of hippocampus-dependent learning In humans, imaging studies have confirmed the role of sleep in the hippocampal functions, particularly in learning and memory . In addiAccording to some models, new memories are formed due to a structural remodeling of existing synapses and due to an adaptation of the synaptic strength in the existing circuits. Sleep, after the initial learning, appears to contribute to this process through the neural repetition and reactivation of neural plasticity process . This syRecent evidences showed that hippocampal neurogenesis is reduced in animal models of depression. Furthermore, antidepressant treatment promotes neurogenesis . This raSleep disruption has been associated with mood regulation deficits, however, by an unknown mechanisms. In has been hypothesized that chronic sleep deprivation contributes to the etiology of depression by inhibits cell proliferation and hippocampal neurogenesis. Studies with rodents have shown that prolonged sleep deprivation progressively leads to physiological and neurobiological modifications similar to those experienced in patients with major depressive disorder MDD; .Sprague-Dawley rats (Table 3). Zolpidem was ingested twice daily, at the onset and at the middle of the rest phase, for 2 days (acute administration) or 21 days (chronic administration). Acute ingestion significantly suppressed cell proliferation in the aged animals. In both groups, cell proliferation supression was higher in the hilus than in the SGZ. The lower dose of Zolpidem reduced neurogenesis by 25% in the dentate gyrus of young animals and the higher dose had no significative effects. The authors argued that the chronic administration of hypnotic drugs in young animals may cause a disruption of normal sleep, which may be related to a reduction in cell survival. In aged animals, the low dose increased cell survival in the SGZ by 11% and decrease cell survival in the hilus by 6%. In aged animals, hypnotic drugs may improve the speel quality , causing a benefical effects on neurogenesis. However, even in aged group, chronic ingestion of Zolpidem had little or no effect on cell proliferation in both groups of rats, suggesting little benefic effects of hypnotic drugs on neurogenesis . Thus, stimulating adult hippocampal neurogenesis may be a new drug target or mechanism of antidepressants, to reach its therapeutic effects  of chemical antidepressants – a monoamine oxidase inhibitor (MAOI); a selective serotonin reuptake inhibitors (SSRIs) and a tricyclic antidepressants (TCAs) – increased the BrdU-positive cells by 20–40% (In a study of y 20–40% . Acute ay 20–40% .To examine the specificity of the neurogenic effects of antidepressants on neurogenesis, the influence of Haloperidol, a non-antidepressant psychotropic drug, on neurogenesis was evaluated. As a result, chronic administration of Haloperidol did not significantly alter the number of BrdU-positive cells .Sprague-Dawley rats were and treated with electroconvulsive seizures. Animals of the control group were handled identically, but received no shock. A SSRI, a TCA, or saline was injected once or twice daily. As result, VEGF was identified as a key mediator of the actions of two classes of antidepressants and it was induced by the SSRI, the TCA and by the electroconvulsive seizure, in a time window consistent with the time window of cell proliferation and maturation and the time window of the therapeutic action of antidepressants (The neural mechanisms underlying the therapeutic effects of antidepressants still unknown, but the upregulation of growth factors and neurogenesis may be involved. ressants .The current knowledge on adult neurogenesis comes from laboratory studies with animal models. However, adult neurogenesis has been demonstrated in humans , despiteRecent developments of magnetic resonance imaging techniques are promising and opens the possibility to study neurogenesis in humans under several experimental conditions and to study of the association between different pathologies and neurogenesis . FurtherConsidering all studies with animal models discussed throughout this review, there are several controversial and contradictory results. Results obtained with some species and under certain experimental conditions can not be replicated in other species, since neurogenesis and sleep regulation may be conditioned by the individual and genetic features of each specie. Thus, studies of neurogenesis with animal models need to be extended to produce more robust results on the underlying mechanisms of the modulatory effects of sleep on neurogenesis.versus NREM deprivation also need to be replicated to reach more robust conclusions.More studies are needed to determine the antineurogenic effects of sleep deprivation on different hippocampal areas, given the evidence of a functional differentiation of different hippocampal subfields. It is also necessary to explore the effects of sleep deprivation on neurogenesis of other brain areas, which could be useful to understanding the functional outcome of neurogenesis. The effects found in the basal rate of cell proliferation in the REMS The neurogenic link between sleep, learning, hippocampus-dependent memory and mood disorders need to be clarified, and the functional relevance of increased neurogenesis caused by antidepressant treatments need to be explored with clinical studies in humans. It is necessary to understand if neurogenesis is related with a behavioral and molecular response to antidepressant treatments in MDD patients. Finally, the negative hypnotic effects of neurogenesis need to be clarified and tested in humans, since they can have unknown side effects in human adult neurogenesis, with repercussions to other cognitive and emotional functions.The knowledge of neurogenesis in adult mammals has significantly progressed over the last decade . The decin vivo imaging techniques, data from animal models suggests that newly generated neurons in adulthood may be involved in hippocampal plasticity.While studies on adult human neurogenesis await the development of Chronic sleep disruption decreases adult neurogenesis in rodents. However, short sleep deprivation seems to enhance cell proliferation and survival. The chronic effects of sleep deprivation may impair the hippocampal integrity and may ultimately lead to cognitive dysfunction, contributing to the development of mood disorders and other pathologies. Whether adult neurogenesis plays a role in such modulation is yet to be determined. Targeting adult neurogenesis during sleep disorders might therefore to provide one interesting approach to reverse the potential disruption of chronic sleep disorders on cognitive and emotional function.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The three main processes shaping the evolutionary ecology of antibiotic resistance (AbR) involve the emergence, invasion and occupation by antibiotic-resistant genes of significant environments for human health. The process of emergence in complex bacterial populations is a high-frequency, continuous swarming of ephemeral combinatory genetic and epigenetic explorations inside cells and among cells, populations and communities, expanding in different environments (migration), creating the stochastic variation required for evolutionary progress. Invasion refers to the process by which AbR significantly increases in frequency in a given (invaded) environment, led by external invaders local multiplication and spread, or by endogenous conversion. Conversion occurs because of the spread of AbR genes from an exogenous resistant clone into an established (endogenous) bacterial clone(s) colonizing the environment; and/or because of dissemination of particular resistant genetic variants that emerged within an endogenous clonal population. Occupation of a given environment by a resistant variant means a permanent establishment of this organism in this environment, even in the absence of antibiotic selection. Specific interventions on emergence influence invasion, those acting on invasion also influence occupation and interventions on occupation determine emergence. Such interventions should be simultaneously applied, as they are not simple solutions to the complex problem of AbR. In evolutionary theory, processes are the generators of patterns , and responsible for the emergence, variation and maintenance of novel patterns  submitted to predator-prey evolution Endler . However19 bacteria containing class 1 integrons (a sophisticated genetic platform able to recruit AbR genes) are released in sewage in the United Kingdom every year, high integron concentration also being detected in different environmental settings and hosts  , and globalization of planet biology – including human population growth; livestock and production methods; international travel or long distant trade of humans, animals and vegetables, breakdown in public health infrastructure, and eventually geo-anthropological changes , might have also contributed to the Earth invasion by AbR bacteria  and high-risk bacterial clones .For instance, we should consider different definitions of AbR  from relatively simple interactions among pieces Baquero . In AbR,blaCTX-M-15, or blaTEM, among other AbR genes  creating the dense stochastic variation required for evolutionary progresses. As in the case of mutational events, bacteria continuously play a risky game, exposing themselves to decreased fitness, to feed a ‘capital of diversity’ and consequently the possibility to adapt to unexpected deleterious events. This is an example of Gradients are the consequence of the diffusion of chemical and physical conditions in a continuous space. Gradients are generated by the asymmetrical presence of such conditions, which are concentrated at certain points of the space. When antibiotics are given to a patient , there is a wide set of gradients of antibiotic concentrations in the organic spaces, so that bacteria are confronted with a diversity of concentrations  interactions involving processes of mutation, conjugation, recombination (modularization), migration, growth and death. The possibility of these interactions will certainly depend on a number of parameters, including the frequency of each one of the biological elements and the ecological connectivity between them  will definitely require excellent adhesive properties to compensate the natural cellular turnover of the intestinal tract, or, eventually, be very efficient in local multiplication, taking advantage of the available local nutrients (nutrient-niche hypothesis)  by which particular invasive alien resistant clones are able to successfully invade a given compartment  depends on the clones themselves and the recipient environment. Bacterial clones differ in their invasion ability, particularly if the initial invading population is of low bacterial density. Organisms with small The recipient environment might be variable in the acceptation of foreign invaders, determined by various favouring conditions of the host, for instance, the nutritional and immunological landscape of the intestine  because of the spread of AbR genes from an exogenous resistant clone into well-established, high-density bacterial clone(s) colonizing the environment (endogenous); and/or (ii) because of dissemination of particular resistant genetic variants that has emerged within an endogenous colonizing clonal population. In endogenous conversion, clonal shifts might be weak, and the invasive process depends on the local spread of invasive genes and genetic variants, following selection, horizontal gene transfer or recombination.rrl chromosomal genes, which are progressively ‘converted to linezolid resistance, the resistance of Mycobacterium smegmatis to aminoglycosides and the resistance of Streptococcus pneumoniae to evernimicin  or/and involving contaminated equipment, water and food; indeed, antibiotic exposure facilitates occupancy , diagnostics and therapy, with emphasis on personalized medicine and genomic medicine  the use of this drug. On the other hand, an entirely new way of treating infections, for instance based on the modulation of pathogenic immune-inflammatory host's responses, being microbes only the occasion for such effect has recently been suggested  of AbR. In this work, we are particularly focusing the interventions that might have a Public Health dimension, exerting a societal impact by acting on the eco-epidemiology of AbR rather than on the prevention of AbR in the individual patient.As can easily be deduced from the former sections, interventions on emergence should influence invasion, those acting on invasion influences also occupation, and interventions on occupation are determinant for emergence. Because of that, we listed below general interventions that might reduce the entire loop of processes shaping AbR. Some of them are already implemented in our days, and some others should be considered for future application.selection of resistant organisms include the following: (i) Overall reduction of antibiotic use in humans, animals and agriculture; early diagnosis of bacterial and viral diseases and infection severity will benefit the identification of situations deserving antibiotic therapy . (ii) Substitution of antibiotics by other drugs (such as anti-inflammatory compounds) in mild infectious diseases  Vaccination-based interventions to decontaminate  colonized hosts; indeed, antipneumococcal and anti-Haemophilus vaccination have significantly decreased AbR rates in these organisms, and there is active vaccination research focused on Staphylococcus aureus and Escherichia coli . (ii) Probiotic–prebiotics, cation-feed supplements in farms, clonal and microbiota-transplantation procedures in the aim of ecological displacement of resistant populations can have disparate effects  Decontamination of human and animal wastewater and sewage in hospitals, farms, but also urban sewage, treatment plant discharge, sewage overflow, run-off manure-fertilized agricultural fields and livestock farms; particular interest of decontamination in developing countries where the resistant organisms released in the environment have larger chances to be reacquired by humans and animals. (ii) Surface microbial decontamination of floors and equipment in hospitals and farms. (iii) Prevention of environmental releases and decontamination of antimicrobial substances, including biocides, metals and industrial pollutants, as influencing the environmental selection of resistant organisms. (iv) Bioremediation of contaminated compartments with the substitution of resistant bacteria with susceptible ones, eventually with/or specific bacteriophages. This has also been suggested at patient level with faecal transplant with susceptible bacteria in colonized patients with highly resistant bacteria  Health workers hand washing in hospitals and long-term care facilities, with particular attention of the possible ‘best transmitters’  Drinking, washing and bathing water decontamination, particularly in nondeveloped areas; methods range from conventional chlorination to the use of phages in contaminated surface water streams, (ii) prevention of meat contamination by intestinal bacteria in slaughterhouses, (iii) hygienic procedures in food handlers, (iv) safe food storage to prevent growth of antibiotic-resistant bacteria, (v) use of phages to eliminate dangerous high-risk clones from food and eventually inhibiting emerging outbreaks  Enhancers of the biological cost of resistance, so that the growth rate of resistant organisms decreases over that of susceptible ones. (ii) Clonal or population replacement of resistant organisms by homogenic susceptible ones, eventually using specific selection with nontherapeutic antimicrobials. (iii) Antagonistic pleiotropy strategies, so that resistance to a given antibiotic provokes susceptibility to another whose susceptibility should be preserved  Application of ‘drugs’ preventing plasmid (and ICE) stability and conjugation, particularly from the recipient cells, as unsaturated fatty acid derivatives and tanzawaic acids, or antipheromone compounds. (ii) Application of wide host range cocktails of plasmid-dependent phages directed to plasmid-encoded sex apparatus  Use of antisense oligomers, and external guide sequence antisense oligoribonucleotides  success and most probably are insufficient to deal with the multidimensionality of the problem  and should encompass the infected patients, but also the patients’ group and their environment in an integrated way. It is also worth noting that many of our proposed interventions to control AbR are identical to those required to control infectious diseases, or even to decrease general health risks in the population. Consistently with the classic concepts of McKeown , the adv


Presbyornis pervetus from the western United States, and the Gastornis phalanx is within the known size range of mid-latitude individuals. The occurrence of Presbyornis above the Arctic Circle in the Eocene could be the result of annual migration like that of its living duck and geese relatives, or it may have been a year-round resident similar to some Eocene mammals on Ellesmere and some extant species of sea ducks. Gastornis, along with some of the mammalian and reptilian members of the Eocene Arctic fauna, likely over-wintered in the Arctic. Despite the milder (above freezing) Eocene climate on Ellesmere Island, prolonged periods of darkness occurred during the winter. Presence of these extinct birds at both mid and high latitudes on the northern continents provides evidence that future increases in climatic warming (closer to Eocene levels) could lead to the establishment of new migratory or resident populations within the Arctic Circle.Fossils attributable to the extinct waterfowl clade Presbyornithidae and the large flightless Gastornithidae from the early Eocene (~52–53 Ma) of Ellesmere Island, in northernmost Canada are the oldest Cenozoic avian fossils from the Arctic. Except for its slightly larger size, the Arctic presbyornithid humerus is not distinguishable from fossils of  Gastornis  and potentially Presbyornis (Anseriformes) from the early Eocene  of Ellesmere Island, Canadian High Arctic57Presbyornis and Gastornis material from Ellesmere Island9Fossil birds from within the Arctic Circle are rare. The Cretaceous record is restricted to the flightless diving hesperornithiform birds from Devon IslandGastornis (Diatryma) and a Presbyornis-like birdGastornis material reported from Ellesmere Island is the northernmost record of that taxon in North AmericaBeginning in the 1970s, paleontologists Mary Dawson, Robert (Mac) West, Malcolm McKenna, and J. Howard Hutchison collected fossil vertebrates from the Paleogene sequence of the Eureka Sound Group exposed on Ellesmere Island, and more recent expeditions have added to the accumulated diverse vertebrate fauna, including fish, turtles, crocodilians, many clades of mammals ranging from primates to brontotheres, and birdset al.et al.Eocene terrestrial vertebrates are known from multiple sites on Ellesmere Island, but the best documented and most diverse faunal assemblage, including the bird fossils described here, is from strata of the Eureka Sound Group exposed near Bay Fiord on central Ellesmere Island . Althoug15Today’s general consensus is that the Eureka Sound is a group divisible into numerous formations, and generally Miall’sThe Margaret Formation comprises coarsening-upward sequences of interbedded cross-bedded sandstone, siltstone, mudstone, and coal that are interpreted as proximal delta-front to delta-plain paleoenvironments characterized by abundant shoreline sands, alluvial to estuarine channels, coal swamps, lagoons and bays, and well-forested, low-gradient interfluves151820PalaeosyopsAt Bay Fiord, Eocene vertebrate fossils occur in two fossil assemblages in the Margaret Formation that are separated by a 478 m thick stratigraphic gap in the fossil recordThe gastornithid, presbyornithid and indeterminate avian phalanx specimens described below were collected by J. Howard Hutchison from localities ELS76-85, ELS76-42 and ELS76-43, respectively. Fieldwork at Bay Fiord in 2010 concluded that ELS76-42 and ELS76-43 are on the same stratigraphic horizon within the lower fossil assemblage at approximately the 1420–1425 m level on the composite stratigraphic section of Eberle and EberthFamily Gastornithidae Fürbringer 1888Gastornis sp.Material. Canadian Museum of Nature  CMN 32412. The specimen is a nearly complete pedal phalanx from locality ELS76-85, Margaret Formation, Eureka Sound Group, central Ellesmere Island, Nunavut, Canada .Gastornis24Description. CMN 32412 lacks the stouter and more trapezoidal outline of more distal phalanges of Order Anseriformes Wagler 1831Family Presbyornithidae Wetmore 1926Presbyornis cf. P. pervetus Wetmore 1926Material. CMNFV 53369. The specimen is the distal approximately one-third of a left humerus , from loDescription. The bone is dark brown in color, and it exhibits some sand-induced surface pitting. That pitting is more pronounced on the distal end of the bone. Despite that overprint, the surface of the bone appears to have been smooth, indicating that the specimen likely is from an osteologically adult individualm. flexor carpi ulnaris of LivezeyFrom the proximal end towards the distal end of the cranial surface, the shaft flattens from a distinctly convex surface proximally. There is a distinct brachial (muscle) fossa that is deepest ventrodistally and shallows dorsally. The fossa’s distal end has a distinct border. Overall, the fossa is ovoid in outline with its long axis oriented dorsoproximal to ventrodistal. The distal edge of the brachial fossa is at the same proximodistal level as the proximal end of the ventral collateral ligament attachment at the apex of the ventral supracondylar tubercle. Just ventral to the proximal end of the apex of the supracondylar tubercle is a poorly preserved muscle scar pit , but they are poorly preserved because the division between the two pits cannot be discerned. The dorsal epicondyle extends further proximal than the supracondylar tubercle/collateral ligament scar. The ventral side of the specimen is poorly preserved and no muscle scars are visible.Aves indet.Material. CMNFV 53368, a phalanx  from locDescription. The specimen appears to be the proximal phalanx likely from digit III of the left side. The bone is off-white to gray in color and is deeply pitted all over its surface. The pitting is caused by sand grains that were embedded in the bone surface, and does not indicate an early ontogenetic age . The proComparisons.Gastornis specimen (62.2 mm) is less than the largest specimens of Gastornis from North America (68.6–80.1 mm) and that from Louvois, France (75.9 mm)Gastornis from LouvoisGastornis specimens appear to be absent in this specimen. The proximal widening of the articular region  is similar across specimens. The Ellesmere specimen lacks the medially expanded plantar rim of the trochlea  that is visible in dorsal view in the Paleocene Louvois specimenGastornis specimens24Gastornis from WyomingGastornisThe length of the Ellesmere Presbyornis pervetus , but it also easily could belong to another taxon of bird (given its somewhat more robust morphology), though its size and morphology is certainly inconsistent with that of the much larger Gastornis, which has stouter and more robust pedal phalanges  and flightless, it likely also was a year-round resident of the Arctic. In contrast, the volant Presbyornis might have been a seasonal migrant to the Arctic. The previously reported geographic distribution of Presbyornis pervetus was restricted to Utah, Wyoming, and ColoradoGastornis in the early Eocene of North America).Despite the mild Eocene Arctic climate, the vertebrate fauna would have experienced months of total darkness and cooler temperatures during the winter. Recent isotopic work suggests that some mammals, including the hippo-like Presbyornis, which is phylogenetically within the crown group of galloanserines3132Presbyornis would be the discovery of juvenile specimens in the Arctic. However, both of the Ellesmere specimens reported above are from osteologically adult individuals. Furthermore, migratory behavior is not a requirement for a large geographic range because many extant non-migratory species have large geographic ranges . However, as a filter-feeding bird, Presbyornis likely would have had a difficult time obtaining food during the winter decrease in (primary) productivity that occurred during the extended dark and low light periods of the Paleogene Arctic winters.Extant galloanserines include migratory species, and migration in birds is (at least in part) genetically controlled40Presbyornis in the Arctic Eocene may have been as a resident, as closely related galloanserine birds are able to survive the much harsher Arctic winters today.In contrast to migration, some galloanserine birds today  are Arctic residents44Presbyornis in the Arctic Circle could be either the result of a migratory population or alternatively a northern geographic expansion paralleling the pattern observed for many extant birds over the last century of warming. If anything, species of Presbyornis likely were affected by warming events in the early Eocene parallel to the response of extant birds to current warming. In contrast, the large flightless Gastornis definitely was an Arctic resident. The diet of gastornithids is debated and varies between carnivory and some type of durophagous herbivory505Gastornis would have had the same access to dietary materials through the winter that kept the resident mammals alive. That the jaw anatomy (and inferred adductor musculature) of Gastornis suggests that it fed on tough plant materialThe current geographic ranges of migratory birds are shifting towards higher latitudes, and climatic warming has been implicated in phenological changes among birds47Presbyornis (P. pervetus and P. mongoliensis) is known from North America and Asia during the Early Eocene333556Coryphodon, the rodent Paramys, the mesonychid Pachyaena, and the carnivoran Miacis, which inhabited mid- and high latitude North America, as well as Asia and Europe in the early Eocene, and the North American/Asian distribution of Presbyornis parallels that of several Arctic genera, including the hyaenodontid creodont Prolimnocyon, the brontotheres Eotitanops and Palaeosyops, and the tapiroids Heptodon and Homogalax that occur only in North America and Asia (not Europe)5859Gastornithidae is Holarctic in distribution and Occurrence of a diversity of terrestrial and aquatic vertebrate taxa in early Eocene-aged strata on Ellesmere Island indicates that a complex Arctic ecosystem was present during that time, and that productivity must have been high enough to sustain those higher trophic levels of vertebrates, even during the darkness that occurred through part of the Eocene winter. Given the geological and paleontological background (on Ellesmere Island and elsewhere), it is plausible that the current trend of climatic warming in the 20th and 21st centuries could lead to the establishment of Arctic resident populations of tetrapod species that currently occur much further south, as well as facilitate the intercontinental dispersal of avian clades among the continents of the Northern Hemisphere.How to cite this article: Stidham, T. A. and Eberle, J. J. The palaeobiology of high latitude birds from the early Eocene greenhouse of Ellesmere Island, Arctic Canada. Sci. Rep.6, 20912; doi: 10.1038/srep20912 (2016).


Food-borne diseases are a widespread and growing public health and economic problem. Recent modifications in food production and processing practices and ever-changing food habits of the consumer are important factors for the incidence of food-borne infections. Many recognized pathogens are of great concern today and new challenges have appeared in the recent years as the role of the interaction between pathogens during infection. Salmonella, Campylobacter, bacterial toxins, and viruses. In particular, the scientific report of EFSA and ECDS 2012 [ Salmonella continues, whereas for other etiological agents of FBD a slight or no decrease  or an increase (verotoxigenic Escherichia coli) in human cases has been observed. Another common cause of FBD worldwide is Staphylococcus aureus, responsible of an estimated 241,000 illnesses per year only in the United States [Despite chill chains, chemical preservatives, and a better understanding of microorganisms, food-borne diseases (FBD) represent an important health problem for developed and developing countries. It has been estimated that about 30% of people in industrialized countries suffer from a food-borne disease each year  and 25% S. aureus including MRSA in raw retail meat impose a potential hazard to consumers, both as classic FBD and as a potential source of colonization of food handlers. An emerging problem that involves this field is therefore the increase of multidrug resistance in pathogenic, opportunistic, and spoilage bacteria, which can reach humans through the food chain. In recent years, for example, a new strain of S. aureus, livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), has been recognized as a novel pathogen that has become a rapidly emerging cause of human infections [In this special issue you will find an in-depth analysis on the importance of Staphylococcal food-borne disease. Recent findings of high prevalence offections . As demofections –7, genes Giardia duodenalis is often seen as an opportunistic pathogen and one of the major food and waterborne parasites. For example, the Giardia coinfection with pathogens like Vibrio cholerae and Rotavirus seems to play a significant role in the occurrence of this parasite. Some important factors are responsible for the regulation of the diarrheal disease spectrum of a population, as the age distribution of the diarrheal cases that was very much dependent on the coinfection rate of Giardia infection.This special issue also shows that, in some cases, the same pathogenic microorganisms, as well as representing a direct risk to health, can make the host more receptive to infection by other types of microorganisms, such as food-borne infections by protozoa.Outbreak investigations have suggested that a lot of risk factors linked to the raw ingredients, improper handling of cooked or processed food, an inadequate cleaning, and disinfection of equipment used in food processing, are the main source of contamination. For this reason, it is important to have new technologies that make it possible to determine such problem in real time. Here you can find a new method to detect food contamination by sensory analysis of foods. A novel electronic nose (EN) represents the tool that provides this capability. The characteristic flavour of volatile organic compounds (VOCs), the so-called fingerprint, may offer information about safety and quality of food, performing sometimes as an indicator of process mistakes as well . Indeed  Bacillus cereus, in different types of food is also reported. Several B. cereus strains possess the genetic fittings to produce two different types of toxins, the heat-stable cereulide or different heat-labile proteins with enterotoxigenic potential. Unlike the diarrheal toxins, cereulide is (pre-) formed in food and can cause food-borne intoxication shortly after ingestion of contaminated food. It is possible to use a lux-based real-time monitoring system to assess the significance of the detection of emetic strains and to determine the actual risk of cereulide toxin production in different types of food. Luciferase signals were quantified with software and foods were categorized into three main classes regarding their toxin formation capability: high-risk, risk, and low risk foods. This generalized scheme allows a basic preevaluation of foods and their ingredients concerning their capability to support cereulide formation and should facilitate hazard identification.In this special issue a method to determine the actual risk of cereulide toxin production, by E. coli, Listeria, and Salmonella [Even if the use of refrigeration temperature is the most employed preservative method, spoilage and psychrotrophic pathogens can grow at low temperatures, representing a threatening public health concern and shortening the shelf life of raw foods. Many outbreaks associated with fresh ready to-eat produce have been previously reported due tolmonella . If bactlmonella . Exposurlmonella . Thus, t Leuconostoc spp. isolated from Algerian raw camel milk because of its beneficial effects on human health. Leuconostoc spp. plays a crucial role in food biopreservation through the production of bacteriocins with different inhibition spectra and exerts beneficial effects on the microbiological stability and production of aroma compounds in various food products. This study also represents the first report on the application of MALDI TOF MS analysis for the faster and more reliable identification of L. mesenteroides based on their low molecular-weight protein profile. The application of MALDI TOF peptide mass fingerprinting has been successfully applied to this bacterial group and has proven to be a simple, quick, and inexpensive complementary method for bacterial identification at the species level.The other alternative to chemical food preservatives is the use of lactic acid bacteria (LAB). LAB strains are food-grade organisms that may be used in biopreservation strategies due to their ability to produce several antimicrobial compounds, including organic acids, hydrogen peroxide, and bacteriocins . These m Emerging Microbial Concerns in Food Safety and New Control Measures. We hope that readers of this special issue will find some information of interest in order to expand their knowledge in this field and to increase their level of attention on matters here reported.This editorial collects a brief summary of the topics discussed in the articles that are published inMoreno BondiPatrizia MessiPrakash M. HalamiChrissanthy PapadopoulouSimona de Niederhausern


Therefore, rice area mapping and forecasting its production is important for food security, where demands often exceed production due to an ever increasing population. Timely and accurate estimation of rice areas and forecasting its production can provide invaluable information for governments, planners, and decision makers in formulating policies in regard to import/export in the event of shortfall and/or surplus. The aim of this paper was to review the applicability of the remote sensing-based imagery for rice area mapping and forecasting its production. Recent advances on the resolutions  and availability of remote sensing imagery have allowed us timely collection of information on the growth and development stages of the rice crop. For elaborative understanding of the application of remote sensing sensors, following issues were described: the rice area mapping and forecasting its production using optical and microwave imagery, synergy between remote sensing-based methods and other developments, and their implications as an operational one. The overview of the studies to date indicated that remote sensing-based methods using optical and microwave imagery found to be encouraging. However, there were having some limitations, such as: (i) optical remote sensing imagery had relatively low spatial resolution led to inaccurate estimation of rice areas; and (ii) radar imagery would suffer from speckles, which potentially would degrade the quality of the images; and also the brightness of the backscatters were sensitive to the interacting surface. In addition, most of the methods used in forecasting rice yield were empirical in nature, so thus it would require further calibration and validation prior to implement over other geographical locations.Rice is one of the staple foods for more than three billion people worldwide. Rice paddies accounted for approximately 11.5% of the World's arable land area during 2012. Rice provided ∼19% of the global dietary energy in recent times and its annual average consumption  This ap4.3.i.e., meteorological parameters, and crop growth models) provided promising results in both mapping and forecasting of rice crop. However, they have several limitations, such as:(i)i.e., located sparsely in a large geographic landscape), incomplete and unavailable in a timely manner, and do not adequately represent the diversity over large areas [Utilization of meteorological data has several implications that include: spatial distribution of meteorological stations Forecasting of rice production in the vicinity of the meteorological stations might be more accurate compared to other parts of the landscape, if the meteorological parameter-based models would be properly calibrated and validated. However, it would not be possible to install more and more meteorological stations across the landscape due to the expenses related to the installation, maintenance, data collection, and its processing ;(iii)Long-term meteorological data are hard to find in most of the rice crop growing countries in the world , which a(iv)In generating the spatial dynamics for a meteorological variable of interest, GIS-based interpolation techniques are usually used, which can produce different map outputs using the same input datasets . Therefo(v)etc.); which are usually expensive, labour-intensive, time consuming in acquisition [Crop growth models are found to be more complex and require many input parameters. These include: several biophysical parameters  and plant parameters , which make it unfit for forecasting rice crop production prior to harvesting. Furthermore, the use of optical imagery in forecasting rice production was found to be encouraging, but mostly empirical-based. It is to be noted that most of the methods suffer from various aspects in particular how to implement them in other geographical locations i.e., not transferable/extendable due to climatic variability ; soil characteristics ; management practices ; and selection of rice varieties . Climate change is also evident in many regions of the World  and/or human-driven land use changes. Also, factors such as plant diseases and insect infestation could be responsible for production losses, which could be monitored using remote sensing platforms [Here, we have provided an overview of using remote sensing sensors and their limitations in mapping the rice crop area and forecasting its production. In terms of the mapping the rice areas, the optical remote sensing imagery has relatively low spatial resolution, which results in over- and underestimation of the area under cultivation. The SAR imagery has several limitations in mapping rice areas, such as the fact speckles degrade the quality of the images, brightness of the backscatters is highly sensitive to the interacting surface, geometric distortions (particularly in irregular topography), low classification accuracy due to use of single polarization, and costly mapping of large geographic areas. In addition, the temporal resolution of microwave imagery was relatively low (960–2000 ) which w960–2000 . In addilatforms ; howeveri.e., humidity, cloud, and rainy conditions), which sometimes limit the availability and make acquisition problematic. Also, the availability of the satellite data must be assured. The development of image classification methods must be effective, efficient, and easy to implement. Based on the literature, upcoming satellites such as future MODIS and the RADARSAT constellation will enhance the temporal, spectral, and spatial resolutions that could be a good fit in mapping rice areas and forecasting its production.Despite the reasonable accuracies of rice area mapping and forecasting its production using remote sensing-based methods, such developments have many challenges as an operational one, which can be viewed as: (i) data acquisition; and (ii) development of appropriate methods. It is quite difficult to obtain cloud-free chronology of remote sensing data over the entire growing season of rice crop due to weather conditions (


Cryptosporidium parvum, Giardia duodenalis , Trypanosoma cruzi, Schistosoma species and others alter gastrointestinal motility, absorption, or secretion at least in part via effects on the ENS. Recent findings also implicate enteric parasites such as C. parvum and G. duodenalis in the development of post-infectious complications such as irritable bowel syndrome, which further underscores their effects on the gut-brain axis. This article critically reviews recent advances and the current state of knowledge on the impact of enteric parasitism on the neural control of gut functions, and provides insights into mechanisms underlying these abnormalities.Gastrointestinal motility and transport of water and electrolytes play key roles in the pathophysiology of diarrhea upon exposure to enteric parasites. These processes are actively modulated by the enteric nervous system (ENS), which includes efferent, and afferent neurons, as well as interneurons. ENS integrity is essential to the maintenance of homeostatic gut responses. A number of gastrointestinal parasites are known to cause disease by altering the ENS. The mechanisms remain incompletely understood.  Functional aspects including peristalsis, electrolyte and nutrient transport, and local blood flow are regulated by the intrinsic network of GI ganglia, the enteric nervous system , vimentin, glutamine synthetase and S100  acts through muscarinic receptors to directly affect intestinal smooth muscle contractility  hypersecretion, glucose malabsorption and a reduced barrier function , had no effect on the PGE2-stimulated tissue  and TTX eliminated the differences in ion transport and conductance  is an intestinal flagellated protozoan parasite of the upper small intestine. Very common worldwide, Giardia was recently included in the World Health Organization’s (WHO) Neglected Disease Initiative  that produces nitric oxide (NO) is involved in the elimination of Giardia infection ; depletion of mast cell granule contents with compound 48/80 prior to CCK treatment also completely blocked the CCK-induced muscle contraction suggesting a role for mast cells in CCK modified levels during giardiasis may not be responsible for this effect , and a parasitic intestinal phase. This nematode causes villus atrophy, crypt hyperplasia, mucosal mast cell hyperplasia  initial degeneration of a proportion of the mucosal nerves during the acute phase of inflammation and (2) a subsequent reinnervation phase after parasite expulsion. Observations of the nerves profiles revealed a large increase in the proportion of small nerve fibers and a reduction in the frequency of large nerve between D18 and D28 PI. This shift to smaller fibers is consistent with nerve regeneration. The degeneration during the acute inflammatory phase and regeneration thereafter is coordinated with the phases of mast cell degranulation and subsequent hyperplasia suggesting an important role of mast cell products in nerve remodeling. These data show an important communication process between the immune and nervous systems during Nippostrongylus infection that offer a favorable ground for further evaluation.N. brasiliensis infection, fluid transport is impaired in infected animals, while after worm expulsion fluid transport becomes significantly greater than in uninfected animals , the neurotensin receptor 1, the somatostatin receptor 2, GABAA receptors Beta 3 subunit, and the serotonin receptor 5-HT3A, are also altered by infection. While 5-HT3 antagonists are known to inhibit chemical but not mechanical pain in rats  and develop quickly to produce the infective larvae that migrate to muscle tissues. Gastrointestinal symptoms are the first to appear and include nausea, vomiting, epigastric pains, diarrhea and/or constipation. Trichinella-infection, similar to Nippostrongylus-infection, induces an inflammatory response, mastocytosis, and alteration of nutrients absorption, alteration of muscle cell structure and contractility, and intestinal hypersensitivity. The infection also affects remote segments free of parasites and of inflammation like the ileum , immunological (mastocytosis) and neuronal components .During T. spiralis-induced inflammation SP and VIP are significantly reduced in the jejunum and in the ileum of infected ferrets , and can also accidentally infect humans where it usually remains asymptomatic. However abdominal pain, irritability, itching and eosinophilia have also been reported in infected humans. This tapeworm has no hooks to damage host tissue and is non-invasive but metabolites produced by H. diminuta have been shown to disrupt the action of the GI tract, and may increase salivary secretion, inhibit gastric secretion, and activate trypsin in the chyme of the duodenum -containing macrophages  play a critical role in preserving tissue integrity and repair  is significantly enhanced in infected animals, and is further increased at 12 weeks and 40 weeks of infection, supporting long lasting effects of schistosomiasis , and it affects the neuro-regulation of internal organs including the heart, esophagus, peripheral nervous system and colon. The final stage of the impaired gut motility in Chagas’ disease results in dilatation of the digestive tract, and often leads to megacolon and megaesophagus, accompanied by severe weight loss due to secondary achalasia. The trypanosome induces an inflammatory response, cellular tissue lesions, and fibrosis. In addition, the amastigote stage destroys intramural neurons of the ANS that are the cause of megaintestine and cardiac aneurysms. Indeed, the digestive form of Chagas’ disease denervates the myenteric plexus. The neurological involvement is different between the acute, intermediate and chronic stages of T. cruzi infection and will determine the severity of the sequelae in patients  promote impulses of the ENS and neural inhibitory stimulation in different regions of the intestinal tract  neurons was not altered by infection, the number of neurons per ganglion increased , different times (acute vs. chronic), and in response to different infective forms . However little is known of the mechanisms by which T. gondii induces myenteric neurons alterations. An effect of the host immune system, via IFN-γ or IL-12 production has been proposed in the control of multiplication and virulence of the parasite , and the Natural Sciences and Engineering Research Council of Canada Collaborative Research and Training Experience Program (NSERC CREATE), #413888-2012, www.nserc-crsng.gc.ca.The authors are grateful for the funding support provided by the Natural Sciences and Engineering Research Council of Canada (NSERC), Discovery Grant #183681-2011, (The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Quinoa seeds are highly nutritious due to the quality of their proteins and lipids and the wide range of minerals and vitamins they store. Three compartments can be distinguished within the mature seed: embryo, endosperm, and perisperm. The distribution of main storage reserves is clearly different in those areas: the embryo and endosperm store proteins, lipids, and minerals, and the perisperm stores starch. Tissues equivalent (but not homologous) to those found in grasses can be identified in quinoa, suggesting the effectiveness of this seed reserve distribution strategy; as in cells of grass starchy endosperm, the cells of the quinoa perisperm endoreduplicate, increase in size, synthesize starch, and die during development. In addition, both systems present an extra-embryonic tissue that stores proteins, lipids and minerals: in gramineae, the aleurone layer(s) of the endosperm; in quinoa, the micropylar endosperm; in both cases, the tissues are living. Moreover, the quinoa micropylar endosperm and the coleorhiza in grasses play similar roles, protecting the root in the quiescent seed and controlling dormancy during germination. This investigation is just the beginning of a broader and comparative study of the development of quinoa and grass seeds. Several questions arise from this study, such as: how are synthesis and activation of seed proteins and enzymes regulated during development and germination, what are the genes involved in these processes, and lastly, what is the genetic foundation justifying the analogy to grasses. Oryza sativa L.), wheat (Triticum aestivum L.), maize (Zea mays L.), barley (Hordeum vulgare L.), oat (Avena sativa L.), rye  are members of the monocot family Poaceae, which are cultivated for the edible components of their grains or cariopses and consist of a single seed enclosed by dry and indehiscent pericarp, firmly adhered to the rest of the integuments.Cereals, e.g., rice  and Polygonaceae  families, also cultivated for the edible components of their grains. The dispersal unit in pseudocereals is the grain botanically called achene, which consists of a single seed enclosed in a dry and indehiscent pericarp . According to Pseudocereals are dicots  and include species of the Amaranthaceae , thus suggesting the effectiveness of this seed reserve compounds distribution strategy and justifying the advantages that led evolutionary distant plants to develop seeds with analogous nutrients distribution.Quinoa seeds are highly nutritious due to the quality of their proteins and lipids and the wide range of minerals and vitamins they store. The ability of quinoa to produce high-quality proteins under extreme environmental conditions makes it an important crop not only for Andean communities but also for the diversification of future agricultural systems. Cereals and quinoa are grain crops and thus essentially full of starch, but they also contain significant quantities of proteins, oil, and minerals. In quinoa and grasses, the distribution of main storage reserves is clearly divided and three main storage compartments can be distinguished in the mature seed: (i) a tissue that stores mainly starch, which is the perisperm in quinoa and the starchy endosperm in grasses, with (ii) an embryo that stores principally proteins and lipids, and (iii) a non-embryonic tissue that stores proteins, lipids, and minerals, which is the aleurone layer in gramineae and the micropylar cone in quinoa. In this study we demonstrate that tissues equivalent (but not homologous) to those found in grasses can be identified in quinoa . The seed coat derives from ovule integuments, each one constituted by two to three layers. The seed coat consists of a testa and a tegmen, each one two layers thick. During seed development, the endotesta layer and both layers of the tegmen are almost completely consumed ; on the contrary, cells of the exotesta enlarge and develop thick tangential cell walls; these cells remain intact and are dismantled just after germination .According to In grasses, the pericarp is adhered to the remains derived from the ovule integuments, which are, at maturity, usually reduced to a thin layer . The anaFigure 1). A micropylar endosperm forming a cone surrounds the root apical meristem of the embryo . The embryo consists of a hypocotyl–radicle axis and two cotyledons . In the axis, both the root apical meristem, with the root cap, and the shoot apical meristem are differentiated. The shoot apical meristem forms a conical structure between the two cotyledons lacking leaf primordia , bitegmic (with two integuments), and crassinucellate . The knob is formed by transfer cells on the outside, with ingrowths in their outer cell walls , dense cytoplasm, and numerous small vacuoles . During germination, this remnant of the suspensor presumably offers less mechanical resistance and might help facilitate radicle protrusion during germination.The suspensor connects the embryo to the nucellus during early seed development, holding the growing embryo in a fixed position within the seed and allowing nutrients to be transported to the embryo . It is avacuoles . When thFigure 5A). During quinoa perisperm development, three major developmental phases can be distinguished: (1) early development of the nucellus, including mitotic activity, the last stage of which takes place before anthesis, establishing the final cell number and tissue configuration; (2) cellular differentiation, which can be broken down into the partly overlapping processes of cellular expansion, endoreduplication, accumulation of starch reserves, and programmed cell death (PCD); and (3) maturation, which comprises the shutdown of biosynthetic processes, desiccation induction, and quiescence . Cells destined to be consumed during embryo development do not accumulate storage reserves. In mature seeds, the remaining endosperm forms a micropylar cone, crossed in the center by the suspensor . According to Figure 4). During seed development, cells of the ephemeral endosperm are crushed and finally disintegrated. In contrast, cells of the micropylar cone , which is one or two cell layers thick, store lipids and proteins that are used by the embryo during germination.Endosperm development in quinoa, as in cereals, is of the nuclear type. According to Figure 5B).The ovule is hemianatropous (the hemianatropous condition results from the curvature of the ovule such that the micropyle comes to lie at right angles to the funiculus), bitegmic (with two integuments), and tenuinucellate . Similar to quinoa endosperm, after fertilization, the initial endosperm nucleus divides repeatedly without cell wall formation in the parietal cytoplasm surrounding the central vacuole , facilitating solute transfer from the vascular bundle of the pedicel toward the endosperm  and are characterized by their dense cytoplasm contents, abundance of small vacuoles, and a complex membrane system but they do not accumulate storage reserves and their death generates a space filled with crushed endosperm cells surrounding the embryo . The coleorhiza originates together with the root cap and the suspensor .The coleorhiza is a non-vascularized, multicellular embryonic tissue that covers the cereal root apical meristem. It is an embryonic tissue located between the root apical meristem and the suspensor, characteristic of the grass embryo and absent in quinoa embryo . In other species , the micropylar endosperm is just the micropylar portion of a larger tissue covering the root apical meristem. The micropylar endosperm has been studied in the species Arabidopsis thaliana  and the radicle can overcome its resistance . In quinOn the other hand, endosperm weakening, as well as radicle growth potential, are known to be regulated by plant hormones : abscisiIn grasses, there is no micropylar endosperm, and the coleorhiza plays a role in protecting emerging roots during germination . AccordiIn quinoa perisperm, starch accumulates forming compound and simple grains . In cereFigure 7A). At the end of development, single grains are deposited in the extraplastidial space . TEM images suggest that they are cytosolic in origin, but further studies are needed, considering that, to our knowledge, the formation of starch grains in the cytosol has not been previously reported. In rice endosperm, compound grains are generated by divisions of amyloplasts, which occur simultaneously at multiples constriction sites, and small amyloplasts bud from their surface , starch synthase (SS), starch-branching (BE), and starch-debranching (DBE) enzymes . The comFigure 7B).In quinoa, it has yet to be determined if the synthesis of ADP-glucose by the enzyme ADP-glucose AGPase occurs entirely in plastids, as in the rest of dicotyledons studied to date. However, in advanced stages of quinoa seed development, once compound starch grain formation is complete, simple starch grains do form filling the space between amyloplasts  and lipid bodies , respectA 2S cysteine-rich globulin (8–9 kDa) is also described for quinoa seeds by Figure 8). For each PSV, several electron-dense globoid crystals are formed . Before globoid formation, vesicles of phytic acid can be observed as bubbles concentrated on the outside of the PSV ; there, phytic acid associates with ions to form electron-dense globoids of phytin. To our knowledge, the formation of globoid crystals in the PSV had not been previously photo-documented in angiosperm seeds. Energy dispersive X-ray (EDX) analysis of globoid crystals reveals the presence of P, K, and Mg  to the vacuole through the Golgi apparatus and PSVs are formed when vacuoles fragment .Lipid bodies are found in the quinoa embryo and micropylar endosperm, as well as in grass aleurone and embryo tissues. Lipid bodies originate in the ER . Lipids Quinoa perisperm consists of uniform, non-living, thin-walled cells full of starch grains. In grass starchy endosperm cells are full of starch grains, but also contain prolamin protein bodies. Thus, the two storage tissues are similar in terms of general characteristics and function, although genetically different.During perisperm and endosperm development, two important aspects of both quinoa perisperm and cereal starchy endosperm are endoreduplication (for a review see In spite of their different origins, quinoa perisperm and grass starchy endosperm exhibit similar developmental programs and functional fates, i.e., endoreduplication, starch accumulation, and programmed cell death. Given the conservation of this seed developmental trajectory in quinoa and cereals, we infer the existence of convergent evolution in these two phylogenetically distant taxa.The micropylar endosperm of quinoa and the coleorhiza of cereals serve the same role during germination: both tissues store reserves, protecting the root apical meristem in the quiescent seed and control dormancy during germination.Because of the supposedly independent origin of monocotyledons and dicotyledons, efforts to solve questions related to seed evolution and particularly that of what determines the fate of storage tissues should be furthered for both grasses and quinoa. Hence, the present study may constitute a contribution toward a more complete understanding of seed biology and thus may provide support for broader phylogenetic studies.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Solid malignancies at the foot and ankle region are rare and include mainly soft-tissue sarcomas, bone sarcomas, and skin malignancies. Complete surgical resection with clear margins still remains the mainstay of therapy in these malignancies. However, attainment of negative surgical margins in patients with locally advanced tumors of the foot and ankle region may require extensive surgery and could result in loss of extremity function. In these circumstances, plastic surgical techniques can frequently reduce functional impairment and cover soft-tissue defects, particularly in cases of large tumor size or localization adjacent to critical anatomic structures, thereby improving the quality of life for these patients. The aim of this article is to illustrate the various treatment options of plastic surgery in the multimodal therapy of patients with malignant tumors of the foot and ankle region.This article is based on the review of the current literature and the evaluation of the author’s own patient database.The local treatment of malignant extremity tumors has undergone major changes over the last few decades. Primary amputations have been increasingly replaced by limb-sparing techniques, preserving extremity function as much as possible. Although defect coverage at the foot and ankle region is demanding due to complex anatomical features and functional requirements, several plastic surgical treatment options can be implemented in the curative treatment of patients with malignant solid tumors in this area. Soft-tissue defects after tumor resection can be covered by a variety of local flaps. If local flaps are not applicable, free flap transfers, such as the anterolateral thigh flap, parascapular flap, or latissimus dorsi flap, can be utilized to cover nearly all kinds of defects in the foot and ankle region.Soft-tissue reconstruction in the foot and ankle region is a vital component of limb-sparing surgery. It enables complete resection of locally advanced tumors and subsequent adjuvant radiotherapy. Modern plastic surgical techniques should, therefore, be integrated in the multimodal treatment concept of malignancies in the foot and ankle region. Malignant neoplasms on the foot and ankle make up about 4% of all bone and soft-tissue tumors of the body –3. Soft-Contemporary treatment strategies should include concepts of complete resection with negative surgical margins in combination with plastic reconstructive surgery, especially considering the postoperative functional aspects. The factors that determine the resectability of sarcomas are mainly the tumor size and localization. Regarding surgical resectability, the localization of the tumor is of great relevance. Deep or subfascial localization is associated with a higher risk of local recurrence or distant metastasis when compared with superficial or epifascial localization –9. RegarIn cases with extensive infiltration of functional structures, amputation still has to be considered as a treatment option in order to obtain clear margins , 11, 12.The implementation of a radical surgical procedure in the distal region of the limb is often difficult due to a limited soft-tissue situation. Attainment of clear margins becomes much more difficult in distal tumors and can result in soft-tissue defects. Plastic surgical techniques remain particularly indispensable in the treatment of such distal tumors. The extent of resection after histological confirmation depends on the size, grading, and local relationship to functional structures. Decisions regarding further leading reconstructive procedures also depend on it. Negative margins should be the goal of surgical therapy. Performance of the appropriate margins in soft-tissue sarcomas is often complicated by the extended growth of the tumor. Margins to adjacent functional structures should be taken into account in the oncosurgical considerations. These functional structures are fascia, synovia, periosteum, and perivascular and perineural tissue. When there is tumor infiltration of such structures, en-block resection should be performed. The course of vascular structures should be taken into account during the resection to allow planning of reconstructive procedures by using pedicled or free tissue transplantation.2 with local flaps in weight-bearing areas and with skin grafts in non-weight-bearing areas (Type I). Local flaps are more durable than skin grafts and allow normal weight-bearing on the reconstructed surface. Plain local flaps, such as V-Y flaps and transposition flaps, should be preferred to avoid a soft-tissue surplus, which could enhance strains on the scar at walking and, thus, increasing the risk of ulceration. Skin grafting represents a simple and safe procedure to cover small defects with a well-vascularized wound bed. However, skin grafts are usually suitable for smaller defects at the dorsum and non-weight-bearing areas at the instep but are fragile and can generate painful scars and ulcerations when transplanted on tenuous soft tissue. Therefore, Hidalgo and Shaw do not recommend skin grafting alone for larger defects. Such Type II defects, which are defined to be larger than 3 cm2 without bone involvement were preferred to be covered by free fasciocutaneous, free musculocutaneous flaps, or local flaps to ensure a durable soft-tissue coverage preventing recurrent ulcerations, improving the scar qualities, and reducing strains on the scars. Large tissue losses with bone involvement (Type III) were recommended to be reconstructed with free flaps or free osteocutaneous transfers if necessary. Here, adequate soft-tissue coverage also provides an essential base for following necessary surgical bone procedures. Bulky soft-tissue surpluses can be thinned out easily in future procedures after healing.Whereas limb salvage has become the standard of care in the treatment of tumor in an extremity, the unique anatomy of the foot presents challenges in reconstructing a viable and functional limb. The defect coverage in the area of the foot and ankle region is demanding due to complex anatomical features and functional requirements. The skeletal stability of the foot and ankle region, the resilience of the soft tissues, and the preservation of sensation are at the forefront of reconstructive considerations. Here, profound knowledge of the anatomy of the foot and ankle area is essential for the development of a rational treatment algorithm for covering soft-tissue defects. Hidalgo and Shaw studied the arterial anatomy and the cutaneous nerve supply of the plantar skin extensively in the 1980s, providing guidelines of safe plantar incisions and flap design , 26. PriThe reconstruction of the highly specific, thick, load-capable, and stress-resistant skin of the weight-bearing proximal and distal plantar area is more difficult, because the patient’s own tissue from other donor regions of the body does not often meet the requirements with regard to tissue quality and functional needs. By contrast, soft-tissue coverage of the dorsum of the foot and the ankle region is of thin and pliable skin with a delicate subcutaneous adipose tissue layer. This feature is often severe in surgical interventions, for example, in osteosynthetic care of ankle fractures. In this case, due to the peculiarity of the soft-tissue cover, wound complications with exposure of structures, such as tendons, joint capsule, bone, and hardware, can occur. Furthermore, the mobility of the soft tissue covering the foot and ankle is due to quite limited multiple zones of adherence. Consequently, defects in serving areas can rarely be treated by local tissue displacement. In such cases, tissue from other parts of the body must be free transplanted. However, the tissue units used for microvascularized transfer are often bulky and have to be thinned out and adapted in the course of correction operations for subsequent shoe care and esthetic perception. Furthermore, the fact that the free transplanted tissue is not innervated must be considered. This fact may stimulate the formation of pressure ulcers. The reconstruction of complex defects of the foot has experienced a steady improvement in recent decades. Achievements in the therapy have been kept particularly for innovative surgical techniques and a better understanding of the specific tissue situation and functional requirements of the foot and ankle area.Tumor removal is often accompanied by major tissue defects. Furthermore, there might be an exposure of functional structures, such as bones, tendons, nerves, and blood vessels. Therefore, plastic surgical reconstruction methods must be an integral part of oncosurgical treatment concepts. Moreover, transfer of healthy tissue with adequate blood supply enables adjuvant radiation and chemotherapy, and might improve the effectiveness by improving oxygen nourishment in the tumor bed. A simple reconstructive procedure, such as skin grafting, is, therefore, not usual, since the resulting soft-tissue coverage is often insufficient for adjuvant radiotherapy. However, the reconstructive ladder should still be addressed when considering soft-tissue coverage at the foot and ankle area. Some local flaps have proven to be very efficacious in the treatment of foot and ankle defects. Small defects at the non-weight-bearing sole can be covered by simple cutaneous or myocutaneous V-Y flaps. Due to its reliable vascular supply, its proportions and the moderate donor site defect, the distally based sural flap has proven itself in the coverage of smaller defects at the hind foot and malleolar region –33. The If local flaps are not applicable for soft-tissue coverage, free tissue transfers can be utilized. Following the resection of a malignant tumor in the foot, the use of microvascularized tissue has been proven to be a successful surgical technique, offering an alternative to ablative surgery with functional restoration of the salvaged limb. Large defects of the foot can be treated by free microvascular myocutaneous or fasciocutaneous tissue transfer. If small defects, exposing bones or tendons, are not eligible for local flaps, small free microvascular flaps can be applied. These flaps cause a very low donor site morbidity. Myocutaneous and fasciocutaneous flaps have the advantage of replacing the missing tissue volume. Osseous surfaces can also be adequately covered and padded. If local flaps are not available, the implementation of a free tissue transfer should be taken into consideration. Such flaps provide adequate soft-tissue coverage for adjuvant radiation. A new group of propeller perforator flaps based on perforators from the anterior and posterior tibial artery and from the peroneal artery has been established in recent years, which also allows good defect management. In the Tokyo consensus, a propeller flap is defined as an island flap that reaches the recipient site through an axial rotation. The classification is based on the nourishing pedicle , the degrees of skin island rotation (from 90 to 180°), and, when possible, the artery of origin of the perforator , 44. DonAs a reconstructive option after tumor resection, local flaps represent a reliable tool and can cover a wide range of smaller defects. Nevertheless, concerns over distant iatrogenic implantation of tumor cells at the donor site of local flaps exist when tumor resection and flap coverage were performed in the same surgical procedure. Reviewing the literature, there has, unfortunately, been no systematic analysis on this issue. However, iatrogenic tumor metastases at donor tissue sites after local flap reconstruction are a rare occurrence and should not preclude the use of local flap reconstruction . They haUnfortunately, not all postoperative wound complications can be anticipated. For defects that extend to the tendons or joints, flap reconstruction is always required for adequate closure. A forced wound closure and “unexpected” wound complications can be slow to heal, devastating for the patient, and delay adjuvant radiotherapy. In this instance, early referral to a plastic surgeon is necessary in these cases to prevent devitalized superficial tissue from becoming infected and generating a deep infection that involves tendon, bone, or hardware. The use of free tissue transfer remains at the highest level on the reconstructive ladder. Although it is more complex, free tissue transfer may be necessary as a first choice. Our experience indicates that microvascularized tissue transfer is often the most suitable first option in accordance with established reconstructive principles. Furthermore, wound complications can occur more often after adjuvant radiation. Although defects, at first appearance, may be closed primarily or by using simple methods, such as split-thickness skin grafts, one must take the possibility of postoperative and postradiogenic wound complication into consideration. In those cases where there is an increased risk of exposure of tendons, bones or osteosynthetic material, a prophylactic use of an effective free flap for reconstruction should be considered. In the presence of avascular scar tissue, it should be removed before reconstruction. The use of prophylactic flaps in foot and ankle reconstruction is of great interest in patients with a high risk of wound healing disorders.In addition to transplantation of tissue to cover the defects, the replacement of functional structures, such as tendons, vessels, and nerves, are at the forefront. Common peroneal nerve lesions or extensive loss of the anterior tibialis muscle might be an inevitable part of oncological resection and lead to a drop foot deformity. Primary transfer of the posterior tibialis tendon to the anterior tibialis tendon can restore the active extension of the foot , 53. TheSurgical therapy provides the basis for local tumor control in soft-tissue sarcoma. The goal defined is the resection of the tumor with clear surgical margins, followed by adjuvant radiotherapy in highly malignant tumors. In many cases, more complex plastic surgical reconstructions, such as the replacement of nerves, blood vessels, and bone, or transfer of muscles or tendons, are required due to the close proximity to functionally relevant anatomical structures. Defects can be covered by means of plastic surgery techniques so that the foremost unresectable tumors become curable. In our institution, we use the treatment algorithm depicted in Figure At the present time, due to efforts in reconstructive plastic surgery, complex tumor resection with clear margins can be performed while still preserving the function that once may have been considered unsalvageable, particularly in the case of advanced tumors.Patients are frequently presented with incompletely resected tumors. In such situations, the resection required is usually far more complex and extensive than the primary intervention. Due to this fact and the rarity and wide heterogeneity of soft-tissue sarcomas, they should be treated in specialized centers with plastic surgery as part of an interdisciplinary and multimodal treatment concept.Our experience shows that reconstructive plastic surgery can play an integral role in the multimodal treatment concept including radiation and chemotherapy. The current plastic surgery techniques allow for the preservation and reconstruction of function after the resection of malignant tumors. The quality of life of the oncologic patient can be significantly improved by knowing and applying the opportunities of plastic reconstructive surgery.AR and KH have written and prepared the manuscript. AD and ML reviewed and edited the manuscript. OG, PK, and BB helped to prepare the manuscript and the figures.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


For this, three piles were elaborated by the turning composting system, using as raw materials winery-distillery wastes (grape marc and exhausted grape marc) and animal manures (cattle manure and poultry manure). The classical analytical methods showed a suitable development of the process in all the piles, but these techniques were ineffective to study the humification process during the composting of this type of materials. However, their combination with the advanced instrumental techniques clearly provided more information regarding the turnover of the organic matter pools during the composting process of these materials. Thermal analysis allowed to estimate the degradability of the remaining material and to assess qualitatively the rate of OM stabilization and recalcitrant C in the compost samples, based on the energy required to achieve the same mass losses. FT-IR spectra mainly showed variations between piles and time of sampling in the bands associated to complex organic compounds (mainly at 1420 and 1540 cm-1) and to nitrate and inorganic components , indicating composted material stability and maturity; while CPMAS 13C NMR provided semi-quantitatively partition of C compounds and structures during the process, being especially interesting their variation to evaluate the biotransformation of each C pool, especially in the comparison of recalcitrant C vs labile C pools, such as Alkyl /O-Alkyl ratio.The objective of this work was to study the co-composting process of wastes from the winery and distillery industry with animal manures, using the classical chemical methods traditionally used in composting studies together with advanced instrumental methods (thermal analysis, FT-IR and CPMAS  Currently, the European Union EU-27) is the world’s leader in the wine sector, with 55% of the global vineyard and around 60% of wine production, France, Italy and Spain being the largest world wine producing countries , which i7 is the Several alternatives have been proposed to recycle these wastes and thus, minimize the potential environmental risk associated to their disposal, which include simple options, such as the use for feedstuff production, and advanced treatments to obtain added-value products  or energy ,3. HowevComposting is a widely used technology to transform residual organic matter, with a significant reduction of volume and weight during the process, in a sanitized, stabilized and mature product, easy to store and marketable as organic amendment or fertilizer . TherefoCurrently, there is a clear consensus about the absence of one specific parameter to ascertain stability, maturity and /or quality in compost using an only technique, due to the high variability observed in the composts, since their characteristics strongly depend on the raw material and the composting system used . This fa13C NMR techniques) were selected due to their efficiency for the characterization of the organic matter pools in different organic materials, especially composts. Thermal decomposition analyses, including thermogravimetry (TG), derivative thermogravimetry (DTG) and differential thermal analysis (DTA) have been reported as useful tools for structural and chemical assessment of natural organic matter . Th. Th13C-N–45 ppm) . The scaThe main physico-chemical, chemical and biological properties of the final composts obtained are shown in Organic matter (OM) concentrations were similar in all the composts and higher than the minimum values established by the Spanish and the European legislation  , 49. TN Regarding other parameters related to the compost maturity and/or stability, the contents in water-soluble polyphenols, compounds that in high levels inhibit the germination , were qu13C-NMR has provided semi-quantitatively partition of C compounds and structures during the process, being especially interesting their variation to evaluate the biotransformation of each C pool, especially in the comparison of recalcitrant C vs labile C pools, e.g. Alkyl /O-Alkyl ratio. Therefore, the combination of instrumental techniques clearly complemented the existing classical analytical tools, especially those based on non-specific chemical determinations. Also, the knowledge of the structural and functional nature of mature compost will help to predict the behavior of compost in agronomic uses.In conclusion, the classical analytical methods have shown a suitable development of the composting process in all the piles, with a more significant effect of the winery-distillery waste used than of the type of manure, but obtaining in all the scenarios end-products with suitable properties and a good degree of maturity for their agricultural use. However, the classical analytical approach has also been shown to be ineffective to study the humification process during composting of this type of materials. Therefore, thermal analysis techniques has been useful to elucidate the degradability of the remaining material and additionally, to assess qualitatively the rate of OM stabilization and recalcitrant C in the compost samples; FT-IR has allowed to identify functional groups in composting, which indicates composted material stability and maturity; while CPMAS S1 Fig(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.


Eukaryotic cells may divide via the critical cellular process of cell division/mitosis, resulting in two daughter cells with the same genetic information. A large number of dedicated proteins are involved in this process and spatiotemporally assembled into three distinct super-complex structures/organelles, including the centrosome/spindle pole body, kinetochore/centromere and cleavage furrow/midbody/bud neck, so as to precisely modulate the cell division/mitosis events of chromosome alignment, chromosome segregation and cytokinesis in an orderly fashion. In recent years, many efforts have been made to identify the protein components and architecture of these subcellular organelles, aiming to uncover the organelle assembly pathways, determine the molecular mechanisms underlying the organelle functions, and thereby provide new therapeutic strategies for a variety of diseases. However, the organelles are highly dynamic structures, making it difficult to identify the entire components. Here, we review the current knowledge of the identified protein components governing the organization and functioning of organelles, especially in human and yeast cells, and discuss the multi-localized protein components mediating the communication between organelles during cell division. Cell division/mitosis is a precisely modulated process of chromosome segregation and nuclear division in which one eukaryotic cell divides into two daughter cells with identical chromosomes in order to produce more cells for growth and replace any damaged, dying or senescent cells , a six-subunit complex comprised of ORC1-6, binds to chromosomes at the replication origin sites and acts as a central component for eukaryotic chromosome replication initiation  in budding yeast and related/homologous structures in other organisms have been characterized as the microtubule organizing centers (MTOCs) , an integrated database of the midbody, centrosome and kinetochore most recently updated in June 27, 2014, a large number of proteins that are predicted to be located on the MTOC are still not well validated   studies has led to the proposal of several structural models of the kinetochore with only weak supporting evidence. However, in recent studies, the first three-dimensional images of the kinetochore core structure have been obtained from budding yeast. These images show that the size of the kinetochore is approximately 126 nm, with a large central hub surrounded by multiple outer globular domains that form a ring-like structure around the microtubules (Gonen et al., During cytokinesis, many proteins promote furrow ingression, dividing one cell into two daughter cells still connected by midbody, a cellular substructure contains many transient protein complexes formed at the narrow intracellular bridge (Steigemann and Gerlich, Previous studies have shown that the midbody proteins are organized in three parts, the bulge, the dark zone and the flanking zone (Mullins and Biesele, Actually, many components of each substructure of the midbody and bud neck subregions listed in Tables Homo sapiens, and 278 in Saccharomyces cerevisiae (Figure Homo sapiens, while there are 41 proteins in S. cerevisiae.A large number of proteins have been shown to participate in the process of cell division and spatiotemporally assemble as super-complexes at defined subcellular localizations, such as kinetochores at the centromeric chromatin, the centrosome near the nucleus, and the midbody between two daughter cells. According to the MiCroKiTS database search, during cell division, there are a total of approximately 754 identified proteins localized at the organelles of the centrosome, kinetochore and midbody in e Figure . DespiteProteins with multiple localizations are the key factors for mediating the communication between the organelles. In human cells, Ndc80 complex dynamically localizes at centrosome, and then concentrates at centromere and becomes a stable component of kinetochore until completion of the mitosis (Hori et al., Yueyuan zheng, Junjie Guo, and Xu Li contribute to the literature collection and help to draft the manuscript. Mingming Hou, Yubin Xie, Xuyang Fu, Shengkun Dai, and Rucheng Diao participate in drafting the manuscript and revising it critically for important intellectual content. Yanyan Miao writes the manscript and interprets the data. Jian Ren contributes to the conception and design of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.