Sorghum bicolor) is an important grain and forage crop grown across the US. In some areas, sorghum can become feral along roadsides and other ruderal areas, as a result of seed spill during harvest or transport. In some of these situations, feral sorghum grows in or near established johnsongrass  populations. Johnsongrass, a wild relative of sorghum and an incredibly noxious weed, is capable of hybridizing with cultivated sorghum. Because commercial hybrid sorghum cultivars are produced with cytoplasmic male sterility, progeny of the hybrid crop which compose the founder feral populations also segregate for male sterility. Consequently, male sterility in feral sorghum may increase the risk of outcrossing with johnsongrass. Using field surveys and spatial modelling, the present study aimed at documenting the occurrence of feral sorghum and understanding the anthropogenic and environmental factors that influence its distribution. Further, this research documented the sympatry of feral sorghum and johnsongrass in the roadside habitat. A total of 2077 sites were visited during a systematic field survey conducted in fall 2014 in South Texas. Feral sorghum and johnsongrass were found in 360 and 939 sites, while the species co-existed at 48 sites . The binary logistic analysis showed a significant association between the presence of feral sorghum and road type, road body-type, micro-topography of the sampling site, nearby land use, and the presence of johnsongrass, but no association with the distance to the nearest grain sorting facility. The probability of finding feral sorghum away from johnsongrass patches was generally higher than finding them co-occur in the same location. A probability map for spatial distribution of feral sorghum was developed using the nearby land use type and the regional habitat suitability for johnsongrass as two key predictors. Overall, results show that feral sorghum and johnsongrass co-occur at low frequencies in the roadside habitats of South Texas, but these low levels still present a significant opportunity for hybridization between the two species outside of cultivated fields.Sorghum ( A ferndscapes –5. Animandscapes .The persistence of feral populations, similar to any plant population, can be influenced by the spatial and temporal heterogeneity of the habitat . In a heS. bicolor include shattercane (S. bicolor ssp. drummondii) and johnsongrass  [Sorghum is a major crop in terms of production, ranking fifth worldwide and in the US . As a drlepense) . Of thes1 hybrids are actually in a heterozygous condition for alleles conditioning fertility restoration. Consequently, segregation for male sterility would be expected in progeny  from the hybrid. In fact, approximately 25% of the feral sorghum plants established through seed dispersal (F2 seed harvested in hybrid sorghum fields) will be male sterile. In these circumstances, the co-occurrence of feral sorghum and johnsongrass presents an increased chance for outcrossing.Johnsongrass is one of the most troublesome weeds in the world, capable of spreading by both underground rhizomes and seeds . JohnsonTexas is the second largest sorghum producer in the US, closely following Kansas . In SoutA field survey was conducted along the roadsides of South Texas, from the Rio Grande Valley to the Upper Gulf Coast where grain sorghum cultivation is prevalent. The climate of the survey region is humid subtropical with mild winters and warm summers . Sorghum® map layer. The ITN files were loaded to a GPS device to facilitate navigation to the pre-determined survey sites. In each site, the presence/absence of feral sorghum and johnsongrass was recorded. If feral sorghum was present, observations were carried out on the feral population size and site characteristics within a 25 m strip along the roadside site  Upper Gulf Coast, from west of Houston, TX  to Victoria, TX , 2) Coastal Bend, from Victoria, TX to Kingsville, TX , and 3) Rio Grande Valley, from Kingsville, TX to Brownsville, TX . Survey sites within each region were chosen using a semi-stratified survey methodology, as described by Bagavathiannan and Norsworthy [ide site . If feraAt each site where feral sorghum was present, observations were also carried out on the road body-type , micro-topography of the site , vegetation cover of the habitat , and nearby land use type . The michttps://tnris.org/data-catalog/entry/txdot-roadways). The road type classifications were county roads, highways, local streets, federal roads, functional classification (FC) streets and third-party toll roads. However, the recorded feral sorghum populations were predominantly found in county roads, highways and FC streets and not the other road type categories. As shown in For each sampled site, the nearest road type was identified using Texas road maps (TxDOT Roadways) obtained from Texas Natural Resources Information System (TNRIS) online database  CropScape database . We drewUsing a binary logistic model, we modelled the probability of the presence of feral sorghum as a function of the road type , road body-type , micro-topography of the surveyed site , the nearby land use , presence/absence of johnsongrass and distance to grain sorting facilities. The above model was fitted using the PROC LOGISTIC procedure of SAS (version 9.4). The ‘odds ratio’ feature of PROC LOGISTIC was used to calculate the odds ratio and test for significance of the differences between the levels of predictors. Prior to analysis, all data were reordered to reduce the number of categories and avoid the effect of ‘quasi-complete separation of data points’. For example, 40 categories were initially recorded for nearby land use but were then reclassified to 16 groups. At 360 sites , the density of the feral sorghum population was recorded on scale of 1 to 5 see . The effL is the predicted value in logit and P is its respective back-transformation value in probability unit.A spatial model was developed to map the potential distribution of feral sorghum in the south Texas. Our initial analysis showed that the probability of finding feral sorghum at a given site is strongly associated with the nearby land use type and the occurrence of johnsongrass. For this purpose, we used a johnsongrass habitat suitability map produced based on broader climate variables . For each sample site, we extracted the suitability values from this map and the nearby land use from CropScape  as descrA total of 2,077 sites were visited for the presence of feral sorghum and johnsongrass in our survey. Feral sorghum was found in 17% (360) of the sites, whereas johnsongrass was more abundant and found in 45% (939) of the sites visited. To our knowledge, this is the first documented account of the occurrence of sorghum as feral populations outside of cultivated fields. Results from the logistic model showed a significant association between the presence of feral sorghum with the road type and its body-type, micro-topography of the site, nearby land use and the presence/absence of johnsongrass, but showed no relationship with distance to the nearest grain sorting facility .The odds ratio analysis showed that the likelihood of occurrence of feral sorghum along a gravel or dirt road is 1.5 or 2.4 times greater than that of a paved road, respectively . Dirt anFeral sorghum was more likely to be present at the road shoulders (53% of the sites) as shown by the odds ratio values , but theThe nearby land use had large effects on the presence of feral sorghum . ResultsThe population size of the feral sorghum at each site was scored  based onThe co-occurrence of feral sorghum and johnsongrass was rare and both species were found together only in 48 of the 2,077 survey sites visited (i.e. 2% of the sampled sites). Brassica napus) and alfalfa (Medicago sativa) [Given that feral sorghum and johnsongrass can hybridize, the co-occurrence of these two species may facilitate the persistence of feral sorghum through gene flow and introgression of adaptive traits from johnsongrass. In addition, cultivation of diverse sorghum lines, including sudangrass and sorghum-sudangrass hybrids, in the vicinity may enrich the diversity within the feral sorghum populations and thereby increase the adaptive ability of feral sorghum. Such an outcome has been reported for feral populations of oilseed rape ( sativa) –36. SincAlthough most of the feral sorghum populations were observed along the roadsides, they may have the potential for spread to their contagious natural and unmanaged areas. To investigate the potential for broader distribution of feral sorghum in South Texas, we calibrated a model using nearby land use type and regional habitat suitability for johnsongrass as reliable predictors. These two variables were chosen because they were statistically significant and the georeferenced data for the entire region was available. The combination of these two variables effectively predicted the distribution of feral sorghum, with an increasing trend in abundance from the Upper Gulf Coast towards the Rio Grande Valley, which corresponded to an increasing intensity of sorghum cultivation  and seedRoadsides are known to be the main corridors for the escape of crops away from the agricultural fields. The current survey showed that roadsides and field margins are the initial niches for feral sorghum to establish outside of cultivated fields. We found that the occurrence of feral sorghum in South Texas is highly associated with sorghum cultivation in the nearby area, providing propagules for the establishment of feral populations in field edges and roadsides during planting and grain transport operations. We did not find any relationship between the frequency of feral sorghum and road characteristics (i.e. road type and body type). Although johnsongrass can be found commonly along the roadsides in South Texas, the co-occurrence of feral sorghum and johnsongrass was infrequent. Yet, there are significant opportunities for outcrossing to occur between the two species outside of cultivated fields. More research is necessary to understand the frequency of outcrossing between the two species and fitness of the progenies. Experiments are on the way to characterize, using phenotypic and molecular markers, the progeny of seed harvested from feral sorghum plants during this survey in sites where both species co-existed. Further, field surveys and monitoring are being carried out to confirm and characterize potential hybrid progenies in nature in these feral sorghum-johnsongrass complex sites.


Kidney-Oriented UNderstanding of correcting CILiopathies) consortium, several groups and specialties united to perform scientific groundwork with the aim to develop genetic and therapeutic personalized care for NPH patients. At the start of this consortium, a genetic diagnosis for NPH was available for only 30–40% of patients, which improved to 50–60% during the course of the 4-year KOUNCIL project. Other major accomplishments of the consortium were (1) the establishment of a Dutch renal ciliopathy patient database with genotype and phenotype data; (2) composition of a proteomics-based integrated network of protein modules disrupted in NPH; (3) the development of non-invasive, urine-based assays that allow functional assessment of genomic variants in NPH and of therapeutic efficiency of drugs; and (4) chemical screening toward the identification of compounds that delay or prevent disease progression in NPH, which resulted in four potential medical interventions for NPH. In conclusion, the KOUNCIL consortium effectively channeled complementary approaches to broaden our understanding of NPH pathogenesis, resulted in 54 publications, improvement of genome diagnostics for NPH patients, awareness in the nephrology and clinical genetics communities for NPH, and new avenues for patient management.Nephronophthisis (NPH) is the most common monogenic cause of renal failure in children. Treatment options are limited to dialysis and transplantation. Therapeutics to significantly delay or prevent end-stage renal disease (ESRD) in children are currently not available. In the Dutch-Anglo KOUNCIL ( PS256100) is an autosomal recessive, genetically heterogeneous disorder that results in chronic renal disease in children and young adults  consortium was founded to perform scientific groundwork for the improvement of personalized care for NPH patients. Our consortium augmented the individual expertise of the collaborating workgroups toward reaching the challenging goals. The consortium included research groups with established expertise in renal ciliopathy research and diagnostics, including clinical geneticists, pediatric nephrologists, molecular biologists, cell biologists, and bioinformaticians  identify novel genes associated with NPH and related disorders by using next generation sequencing (NGS) approaches, (2) gain insights in genotype-phenotype relations through the setup and analysis of a renal ciliopathy database, (3) increase our understanding of the composition and function NPH-related protein modules in the ciliary proteome and explore mutational effects by state-of-the-art proteomics, and (4) initiate the development of targeted therapies to delay or prevent renal failure in NPH patients by drug screening in zebrafish and 3D culturing of cells derived from patients' urine samples.By bringing together the three university medical centers in our project we maximized patient inclusion. This was an important aspect of our study as NPH and -related disorders are individually rare. Combining our efforts has led to significant conclusions and high impact findings. The interactions within and between the different groups and work packages have been very open and effective, and by connecting different disciplines in the KOUNCIL project, a robust workflow could be implemented in the clinic that results from this synergy. We believe that without the close and successful collaboration within the consortium, the results would have been less optimal.http://www.agoraproject.nl) (http://www.kouncil.nl). Clinical data including renal and extrarenal phenotypic information was obtained and manually curated for inclusion in the renal ciliopathy database , and we hope to follow up on that initiative.The success of research consortia relies heavily on patient numbers, diagnostic accuracy, and deep-phenotyping of patients. In KOUNCIL, we used the AGORA data- and biobank protocols to systematically recruit and include patients (ject.nl) . Furthere Figure . So far,WDR60 , as a candidate-selected approach. From the second approach, four individual drugs and one drug combination significantly rescued the NPH phenotype in zebrafish embryos with acceptable toxicity profiles. These drugs warrant further To further advance therapy development, a major effort in KOUNCIL was the standardization of the use of URECs in molecular and cellular diagnostics . The 3D Our project advanced medical care for kidney patients and their families. First, NGS-based methods that were implemented in DNA diagnostics at the start of our project almost doubled the diagnostic yield for NPH-RC. Secondly, NGS-based DNA diagnostics for renal ciliopathies allow clinicians to make the NPH diagnosis at a much earlier stage, which resolves the need for invasive renal biopsies for diagnostic purposes. Third, a solidified work flow has been implemented for renal ciliopathy patients in our dedicated multidisciplinary outpatient clinics for kidney diseases in the Radboud university medical center, Nijmegen, The Netherlands and the University Medical Center Utrecht, Utrecht, The Netherlands. In London, UK, multi-disciplinary clinics for Bardet-Biedl Syndrome (BBS) patients are provided. NPH-RC patients are seen by a nephrologist, ophthalmologist, geneticist, dietician, general pediatricians, endocrinologist (diabetes type II), and a clinical psychologist. The aim is to provide a “one stop” visit to ensure that patients receive specialized and expert attention and management. This should result in a major change in how NPH and BBS is managed, with a focus on diagnosis, early intervention and appropriate health management. These multidisciplinary clinics form a role model for other hospitals worldwide and will hopefully be more widely implemented in the near future.The fourth improvement in patient care results from the setup of a renal ciliopathy database, which increased our insight into the relation between genotypes and phenotypes of NPH-RC patients. In the future, the database can be connected to other databases and converted to an interactive, international online registry. This will in turn allow for more refined insights in genotype-phenotype correlations and prognosis . FinallyKOUNCIL and KOUNCIL collaborations revealed several new renal ciliopathy genes and molecular mechanisms of disease, which significantly improved the diagnostic yield for NPH and related disorders as well as advanced knowledge of ciliopathy pathophysiology. In combination with the phenotypic characteristics sampled in our coded renal ciliopathy database, the power of genotype-phenotype correlations for NPH is just emerging and will require further prospective validation. Continued genetic screening and ongoing deep phenotyping of NPH-RC patients will further dissect these correlations, ultimately improving patient counseling. Understanding the impact of allelic variants from patients on disease manifestations demands understanding of the extensive molecular connectivity of cilium-directed pathways; to this end, we have developed a proteomics-based approach to evaluate the assembly defects of the ciliary transport particles (IFT) in a subset of ciliopathy patients. Although ciliopathies represent a class of rare pediatric diseases, through the work of KOUNCIL, we have found novel insights into the molecular mechanisms of chronic renal disease progression widespread in the general population. Preliminary work suggesting that cilia are key repressors of cellular fibrosis in the kidney, will direct and further streamline future efforts to develop therapeutic intervention with a focus on fibrosis treatment.It should be noted that development of methodologies independent of animal experimentation are a priority for most scientific bodies today. We have generated a robust protocol growing renal cells from urine that is non-invasive to patients, yet is patient-specific, and is amenable to screening . We showThe KOUNCIL consortium, consisting of pediatric nephrologists, clinical geneticists, molecular biologists and bioinformaticians, provided a unique, coherent inter- and transdisciplinary team to combat juvenile kidney failure. The resulting five PhD theses from three centers in two countries implicated the relevance of our consortium for the next generation of renal clinicians and scientists, and will continue to have a high impact on the renal field.This consortium aimed to improve the understanding of genetics and biology of renal ciliopathies with innovative NGS and biochemical techniques, and set the first important steps toward therapeutic approaches to delay the progressive degenerative defects in the kidney. The results of this consortium project have already significantly impacted the clinical management of NPH-RC by improvements in diagnosis, prognosis, and accuracy of genetic risk assessment. Our project has provided us with optimal preparations for the development and refinement of future personalized therapies, and is a message of hope for NPH patients for whom there is currently no satisfactory treatment.KR, RG, and HA performed the writing of the manuscript; ML, MO, and RR provided figures; RG, PB, RR, HA, and NK were work package leaders in the KOUNCIL consortium. All authors provided feedback on the revised manuscript.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 handling Editor declared a shared affiliation, though no other collaboration, with two of the authors: RR and MO.


DNA polymerase _ (pol _) holds a special position among the growing family of eukaryotic DNA polymerases. In fact, pol _ is associated with DNA primase to form a four subunit complex and, as a consequence, is the only enzyme able to start DNA synthesis de novo. Because of this peculiarity the major role of the DNA polymerase _-primase complex (pol-prim) is in the initiation of DNA replication at chromosomal origins and in the discontinuous synthesis of Okazaki fragments on the lagging strand of the replication fork. However, pol-prim seems to play additional roles in other complex cellular processes, such as the response to DNA damage, telomere maintenance, and the epigenetic control of higher order chromatin assembly.


Acoustic neuroma (AN), also called vestibular schwannoma, is a tumor composed of Schwann cells that most frequently involve the vestibular division of the VII cranial nerve. The most common symptoms include orofacial pain, facial paralysis, trigeminal neuralgia, tinnitus, hearing loss, and imbalance that result from compression of cranial nerves V–IX. Symptoms of acoustic neuromas can mimic and present as temporomandibular disorder. Therefore, a thorough medical and dental history, radiographic evaluation, and properly conducted diagnostic testing are essential in differentiating odontogenic pain from pain that is nonodontogenic in nature. This article reports a rare case of a young pregnant female patient diagnosed with an acoustic neuroma located in the cerebellopontine angle that was originally treated for musculoskeletal temporomandibular joint disorder. Orofacial pain is the most common problem encountered by the patient that leads to frequent visits to the dental office, as it mimics vast array of disorders arising from orofacial structures, diseases due to generalized musculoskeletal, peripheral, or central nervous system, and psychological abnormality . In someSeveral reports showed that otologic  and ophtTumors of the VIII cranial nerve or acoustic neuroma (AN) is a relatively uncommon, benign, usually slow-growing tumor that develops from the vestibulocochlear nerve supplying the inner ear –12.The Schwann cell sheath from which these tumors develop lies distal to the Glial-Schwann cell junction, which is usually located close to the point where the eighth nerve enters the internal auditory meatus. Consequently, AN arise almost invariably within the meatus itself but expand in a medial direction through the orifice of the meatus and into the potential space formed by the cerebellopontine angle. Here, their close proximity to the roots or proximal portions of various cranial nerves ultimately leads to the development of signs and symptoms due to the pressure on these nerves .Compression of these structures may result in a series of complications with the most common symptoms being tinnitus, hearing loss, and postural imbalance . DespiteTo date, there are very few case reports in the dental literature of AN mimicking orofacial pain of nonodontogenic origin; hence, the purpose of this article was to report one such rare case of AN impersonating nonodontogenic orofacial pain.A 30-year-old female patient in her third trimester visited a dentist with a chief complaint of pain in the right side of maxilla and preauricular region in the month of April 2014. Pain was gradual in onset, moderate in intensity, and continuous in nature. The pain radiated to the temporal and auricular region of the same side. Examination of the patient revealed tenderness of the TMJ and muscles of mastication on the right side and bilateral attrition of maxillary and mandibular first molars. The intensity of pain was measured using visual analogue scale which was at 8. Correlating the history and clinical findings, a diagnosis of temporomandibular joint disorder secondary to bruxism was considered. Patient was recalled after 15 days with instructions to use night guard, restricted mouth opening, soft diet, and physiotherapy.Patient reported reduced pain with VAS score of 4 after 20 days; hence, she was was advised to continue with the same instructions and constant follow-up.Patient reported back to the clinic with aggravated symptoms in December 2015. The pain presented as shock-like that aggravated on brushing and washing face with added symptoms of tinnitus, hearing impairment in right ear, and intermittent loss of balance. Radiographic examination revealed no abnormality with TMJ and surrounding structures. Hence, patient was referred to ENT specialist and audiometry was performed and 48 dB of hearing loss was noted in audiometry test. A more serious pathology was suspected and computed tomography (CT) and magnetic resonance imaging (MRI) were requested. Since the patient was in pain at the time of the examination and the pain had a neuropathic quality and presentation, carbamazepine was initially prescribed for her, which decreased her intensity of pain.Contrast CT  report sHistological analysis of the lesion revealed two microscopic patterns in varying amounts. Few areas showed streaming fascicles of spindle shaped Schwann cells (Antoni-A areas). These spindle shaped cells were arranged in a palisaded manner around acellular, eosinophilic areas (Verocay bodies). In other areas, the spindle shaped cells revealed relatively less cellular and less organized areas within a myxomatous stroma (Antoni-B areas). Few blood vessels showed hemorrhage and fibrin within the lumen. Immunohistochemical analysis revealed that the lesion was positive for S-100 protein Figures  and 8.A complete history, clinical examination, and through diagnostic work-up ruled out an odontogenic cause for the patient's pain. The absence of work, family, and personal conflicts excluded psychological pain. Initially, the clinical signs of bruxism that is attrition of posterior molars in maxilla and mandible along with the tenderness of the right TMJ tilted the diagnosis towards musculoskeletal-TMD. Bite guard, physiotherapy, and other instructions reduced the pain but the patient did not return for follow-up and further treatment because of pregnancy. After one and half years, the patient reported advanced clinical features and AN, and diagnosis was made based on MRI imaging.The AN originates from the Schwann cell, in the peripheral portion of superior and inferior vestibular nerves, and also from cochlear nerve . The AN In the present case, initial clinical features suggested orofacial pain but late stages exhibit neurological abnormalities like trigeminal neuralgia. Although the patient exhibited the classic symptoms of acoustic neuroma, namely, tinnitus and loss of hearing, the patient's primary concern was neuralgic pain that became unbearable. These symptoms had only been diagnosed as part of the patient's dental follow-up. Upon limited success of treatment of orofacial pain and considering her young age, the patient was referred for MRI suspecting an intracranial tumor, which led to the diagnosis of trigeminal neuralgia secondary to acoustic neuroma.Few case reports , 9, 20 wMRI images of AN in the literature  show “trEarly diagnosis of a vestibular schwannoma is key to preventing its serious consequences. There are three options for managing a vestibular schwannoma: observation, radiation, and surgical removal . In the Hence, the dentist should give more emphasis through history and clinical and radiological examination and also include AN in the differential diagnosis when considering orofacial pain, TMD, and trigeminal neuralgia in young age.


Without robust mechanisms to efficiently form new synaptic vesicles (SVs), the tens to hundreds of SVs typically present at the neuronal synapse would be rapidly used up, even at modest levels of neuronal activity. SV recycling is thus critical for synaptic physiology and proper function of sensory and nervous systems. Yet, more than four decades after it was originally proposed that the SVs are formed and recycled locally at the presynaptic terminals, the mechanisms of endocytic processes at the synapse are heavily debated. Clathrin-mediated endocytosis, a type of endocytosis that capitalizes on the clathrin coat, a number of adaptor and accessory proteins, and the GTPase dynamin, is well understood, while the contributions of clathrin-independent fast endocytosis, kiss-and-run, bulk endocytosis and ultrafast endocytosis are still being evaluated. This review article revisits and summarizes the current knowledge on the SV reformation with a focus on clathrin-mediated endocytosis, and it discusses the modes of SV formation from endosome-like structures at the synapse. Given the importance of this topic, future advances in this active field are expected to contribute to better comprehension of neurotransmission, and to have general implications for neuroscience and medicine. The core of intracellular communication in sensory and nervous systems is achieved through neurotransmission, a process that transmits signals from one nerve cell to another. It is initiated by a short-lived raise and fall of electrical membrane potential  of a neuron, which allows calcium entry in a presynaptic terminal and consequent fusion of synaptic vesicles (SVs) with the plasma membrane, resulting in neurotransmitter release. SVs are can store and secrete various neurotransmitters, and are involved in the fast, point-to-point signaling across synapses. Notably, the existence of SVs is fundamental for maintaining key neuronal properties, including quantal release, modulation and directionality of synaptic signals. Due to a small size of presynaptic terminals in the brain, the number of SVs is limited, and SVs would be rapidly used up without efficient SV re-formation mechanisms. Moreover, synapses rely on the controlled recycling of SV membrane and proteins after every fusion event to maintain the net surface area and ensure for the repeated rounds of vesicle fusion, irrespectively of any demand enforced by neuronal activity . Adaptor binding initiates recruitment of clathrin light and heavy chains in a form of triskelia that polymerize in the distinctive lattice, resulting in the formation of a deeply invaginated coated pit. The fission of such pit is mediated by dynamin, the GTPase that assembles in a collar-like structure at the pit neck. After the fission action of dynamin, a free coated vesicle can rapidly lose its coat through the action of synaptojanin-1, a phosphatase that hydrolyzes PIP2 to promote the dissociation of clathrin adaptors, and the ATPase Hsc70 and its cofactor auxilin (to disassemble clathrin). Further, numerous studies have revealed that this core machinery is controlled by a variety of accessory factors, whose function, in most cases, is still poorly understood  were described to co-exist and operate concurrently in the same cell. For example, clathrin-dependent endocytosis at the synapse represents a highly specialized endocytic form that occurs at the surface of all cells. The recognition of novel endocytic pathway as a distinct, discrete process is primarily based on the presence of defined lipids, cargo proteins and their regulators. The internalization route and cargo specificity seem to be determined by accessory factors that mediate cargo enrichment, the choice of the coat and coat-associated protein assembly and even a scission mechanism  mice) revealed a strong accumulation of clathrin-coated pits with long tubular necks, indicating a substantial delay of the fission reaction  swiftly shed their coat after fission through a synchronized action of synaptojanin-1 fast endocytosis, opens the question whether these structures are related to classical  endosomes. Traditionally, endosomes are viewed as relatively stable organelles that serve as the first molecular sorting stations for endocytic traffic  for a brief time frame and take part in SV reformation, or selectively in housekeeping recycling and/or signaling pathways. Several reports indicate that endososomal compartments may play a role as sorting stations for SV proteins  clathrin-mediated mechanism directly from endosome-like structures; (ii) clathrin-mediated mechanism after endosome-like structure back-fuses with the plasma membrane; (iii) a novel lipid- or protein-mediated means that are independent of classical coats; and (iv) tubulation followed by tubule fragmentation. For a schematic representation of these four scenarios, see Figure First, new SVs may be formed from endosome-like structures generated by (ultra)fast endocytosis through clathrin-mediated budding process that occurs at them : using acute photoinactivation of dynamin in z et al.  have shoz et al.  reveals z et al. . Furtherz et al. . Given tz et al. , the mosz et al. .Coats that assist vesicle formation share several common features, including the recruitment via small GTPases and acting as scaffolds in order to couple cargo selection to vesicle formation  for a brief time after internalization which allows them to utilize clathrin coat machinery to get broken into new functional SVs.Endocytic processes and the mechanisms of SV recycling at the presynaptic sites are well investigated during the past decades, yet a lot remains unknown. Molecular mechanisms of (ultra)fast endocytic pathways that mediate the recapture of SV membrane after exocytosis are presently under intense investigation, and new breakthroughs along these lines are expected soon. The essential features of clathrin-mediated endocytic process at the synapse have been well understood, however, the question of its relevance at the physiological temperatures has recently been raised. I consider that clathrin-mediated endocytosis will persist in being considered a key step in the (re)formation of new SVs at the synapse. Specifically, in my opinion, the endosome-like structures formed by ultrafast endocytosis may maintain key features of plasma membrane PThe dynamics and fate of endosome-like structures and newly endocytosed vesicles is also not well understood. It is enigmatic how the pace and flexibility of the SV recycling are controlled and maintained. The high speed of SV recycling and the small size of transient intermediate recycling forms hamper the progress here. The recent emergence of mouse models with defective endocytosis provides new tools: these models accumulate recycling intermediates at the synapse that are stable for longer periods (minutes to hours), in opposition to their lifetime of few milliseconds to seconds at the wild-type functional synapse (Ferguson et al., The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Asymmetrical polymersomes are nano- to micro-sized polymeric capsules with asymmetrical membranes, which means, they have different outer and inner coronas so that they can exhibit better endocytosis rate and endosomal escape ability than other polymeric systems with symmetrical membranes. Hence, asymmetrical polymersomes are highly promising as self-assembled nano-delivery systems in the future for in vivo therapeutics delivery and diagnostic imaging applications. In this review, we prepared a summary about recent research progresses of asymmetrical polymersomes in the following aspects: synthesis, preparation, applications in drug delivery and others.Scientists have been attracted by polymersomes as versatile drug delivery systems since the last two decades. Polymersomes have the potential to be versatile drug delivery systems because of their tunable membrane formulations, stabilities  Polymersomes, which also can be called polymeric vesicles, have attracted scientists' interests in recent years. Compared to other nanometer scale self-assembling delivery systems, such as polymer micelles, nanoparticles and nanogels, polymersomes provide a more stable condition for the storage of drugs, especially for nanoscopic emulsions  polymerization is the most commonly used technique to synthesis triblock copolymers  and direct hydration method  (PNIPAm)  and the cancer cells' endosomes and lysosomes are acidic (pH 4.0−6.5) -based oxygen carriers with oxygen affinity and high Hb loading content and meanwhile no interference with blood cells. Further studies have shown that these vesicles have great stability and efficacy, which have the potential to be alternative blood substitutes  is a widespread diagnosis apparatus that is clinically used for taking pictures of organs and structures inside the body to find blood vessels, bleeding, tumors or infection. Using asymmetric polymersomes to deliver contrast agents has better sensitivity and lower toxicity. Liu et al.  reportedin vivo behavior of polymersomes. Actually, there are not comprehensive studies that investigated the influence of shape and topology on the in vivo behavior of polymersomes.Polymersomes with non-spherical shapes play important roles in applications such as vaccine development. Non-spherical shape can cause different interaction to immune cells because the shapes determine the Researchers have found that tubular structures are one of the most promising morphologies rather than spheres. Owing to the resembling with bacterial topologies, tubular structures offer larger contact areas between particles and cells. Van Hest's group has developed a series of methods that reshaped spherical vesicles to tubular structures. The ability of tunable membrane gives these spherical structures a chance to apply to the immunology field  polymersomes with anisamide (Anis) to target the cancer cell receptor sigma  increasing the loading capacity and encapsulation rate of drugs into asymmetrical polymersomes; (2) enhancing the efficiency of controlled release with the goal of achieving zero-order release and stimuli-responsive release; (3) improving the delivery efficiency of macromolecular therapeutics such as protein and nucleic acid drugs; (4) improving the in vivo circulation half-life and the efficiency for specifically targeted drug delivery.In this review, we summed up the recent progresses of asymmetrical polymersomes from the aspects of preparation, delivery, applications and targeting of asymmetrical polymersomes. Asymmetrical polymersomes with asymmetrical membranes and large watery cores can encapsulate various therapeutic molecules including both hydrophilic and hydrophobic molecules. Their tunable membrane formulations, stability YZ, XL, XZ, YY, HL, XZ, and WY: conceived and participated in its design, searched databases, extracted and assessed studies and helped to draft the manuscript. WY: conceived the initial idea and the conceptualization, participated in the data extraction and analysis, and revised the manuscript. XZ and HL: participated in the conceptualization and design of the study and analysis, and YZ: wrote the manuscript. All authors read and approved the final manuscript.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.


Portosystemic shunts are enlarged vessels that form collateral pathologicalpathways between the splanchnic circulation and the systemic circulation.Although their causes are multifactorial, portosystemic shunts all have onemechanism in common-increased portal venous pressure, which diverts the bloodflow from the gastrointestinal tract to the systemic circulation. Congenital andacquired collateral pathways have both been described in the literature. The aimof this pictorial essay was to discuss the distinct anatomic and imagingfeatures of portosystemic shunts, as well as to provide a robust method ofdifferentiating between acquired portosystemic shunts and similar pathologies,through the use of illustrations and schematic drawings. Imaging ofportosystemic shunts provides subclinical markers of increased portal venouspressure. Therefore, radiologists play a crucial role in the identification ofportosystemic shunts. Early detection of portosystemic shunts can allow ampletime to perform endovascular shunt operations, which can relieve portalhypertension and prevent acute or chronic complications in at-risk patientpopulations. Improvements in imaging methods have increased the importanceof recognizing anomalous portosystemic shunts, especially in situations in which thesigns of portal hypertension and its complications are detected by the radiologistfirst, even before the manifestation of clinical signs.Recent studies in the radiology literature of Brazil have stressed the importance ofimaging in facilitating the diagnosis of hepatobiliary disorders,8. Congenital shuntscan be intrahepatic or extrahepatic, and their classification is complex. The studyof such shunts is beyond the scope of this essay. Rather, we have concentrated ondescribing and illustrating the anatomical and imaging aspects of the main drainagepathways of acquired portosystemic shunts.Portosystemic shunts, also known as portosystemic collaterals, are abnormalcommunications between the portal system and the systemic circulation, and suchshunts can be congenital or acquired.Portal hypertension secondary to chronic liver disease (cirrhosis) is the factor mostoften associated with portosystemic shunt. Portal obstruction can occur atpostsinusoidal, sinusoidal, or presinusoidal sites, portal vein thrombosis being themajor cause of prehepatic portal hypertension, as well as potentially being relatedto inflammation, bleeding disorders, trauma, and neoplasiaFor a complete understanding of the pathophysiology of hepatofugal redistribution ofportal blood flow, it is necessary to examine clinical and chronological data, aswell as to recognize its aspects on the various imaging modalities., as depicted in The portal venous system consists of vasculature that drains the digestive tract,spleen, pancreas, and biliary system. The portal vein lies in a transverse fissure,between the quadrate and caudate lobes, on the visceral surface of the liver.Typically, the portal vein arises from the junction of the superior mesenteric veinand the splenic vein, at the level of the neck of the pancreas.The falciform ligament on the diaphragmatic surface of the liver and the roundligament on its visceral surface are the fibrous remnants of the umbilical vein,which carried blood from the placenta to the porta hepatis during the fetal period.The venous ligament corresponds to the drainage pathway for flow diverted from theumbilical vein to the inferior vena cava via the ductus venosus. In adults, theseligaments are major anatomical landmarks. The falciform ligament separates themedial segment of the left hepatic lobe (segment IV) from its lateral segments(segments II and III) on its superior surface. On the visceral surface of the liver,the round ligament marks the boundary between the quadrate lobe and the left hepaticlobe, the venous ligament, because of its posterior location, demarcating thedivision between the caudate lobe and the left hepatic lobe, as shown in .The splenic vein has several tributaries, including vascular branches that drain thepancreas, the short gastric veins, and the left gastroepiploic vein. The superiormesenteric vein drains the right colon, the small bowel, and the pancreas, whereasthe inferior mesenteric vein drains the left colon and the rectum . Suchvaricosities are usually identified after thrombosis of the portal vein withcavernous transformation  and the vessels of the abdominal wall (systemiccirculation)ormation .Anastomoses between the superior mesenteric vein and renal capsular veins are rareshunts, of uncertain pathophysiology, which drain into the right renal vein,inferior vena cava, and systemic circulation. In the various imaging modalities,anastomoses can be identified by the presence of dilated, tortuous vessels alongsidethe renal capsule . that create communication between the intestinaltract or the superior/inferior retroperitoneal tributaries and the systemiccirculation , as depicted in The mesenteric varices are also uncommon collaterals. In a rightdiaphragmatic shunt, the vessel originates from a medial peripheral branch of theportal vein and crosses to the diaphragmatic surface of the liver, creating ananastomosis with the internal thoracic vein or intercostal veins.In a left diaphragmatic shunt, the vessel originates from a left peripheral branch ofthe portal vein and communicates with the inferior phrenic vein at the level of thetriangular ligament, subsequently draining into the left renal vein or inferior venacavaPortal hypertension has a variety of presentations, as do portosystemic shunts inimaging studies. Radiologists should be prepared for the various presentations ofsuch shunts, reporting their characteristics objectively, which will facilitate thediagnostic investigation and treatment of these anomalies.


Vascular illness of the brain constitutes the third cause of death and the first cause of disability in Cuba and many other countries. Presently, no medication has been registered as a neuroprotector. Neuroprotection with intranasal Neuro-EPO  has emerged as a multifunctional therapy that plays a significant role in neural survival and functional recovery in an animal model of stroke. On the other hand, there is limited access to the brain through the blood brain barrier (BBB) for intravenously applied EPO, and the high EPO dosages needed to obtain a protective effect increase the danger of elevated hematocrit levels and practically exclude chronic or subchronic treatment with EPO. A promising approach has been recently developed with a nonerythropoietic variant of EPO, Neuro-EPO, with low sialic acid content, a very short plasma half-life, and without erythropoietic activity, probably similar to endogenous brain EPO. The objective of this work was to determine the neuroprotective effect of intranasal Neuro-EPO in comparison with the human recombinant EPO injected intraperitoneally in the acute phase of cerebral ischemia, employing the common carotid artery occlusion model in gerbils. Neuro-EPO has demonstrated a better neuroprotective effect, evidenced through increased viability, improvements of the neurological state and cognitive functions, as well as protection of the CA3 region of the hippocampus, temporal cortex, and the thalamus. In conclusion, the intranasal application of Neuro-EPO has a better neuroprotective effect than intraperitoneal EPO, evidenced by the significant improvement of neurological, cognitive, and histological status in the animal model of stroke employed.


To analyze the local distribution of pelvic recurrence after total mesorectal excision, with a view to simplifying the formulation of optimal individualized radiotherapy plans.We retrospectively investigated the data of 168 patients diagnosed with recurrent pelvic cancer treated at Fudan University Shanghai Cancer Center between January 2008 and December 2012. The following were collected depending on availability: operative report, histological report, specimen photographs, initial preoperative images, images confirming local recurrence, and clinical history.A total of 203 lesions of local recurrence were identified. The most common sites of pelvic recurrence were the mesorectum, including the anastomotic stoma in 53.0% of cases; presacral space in 27.4%, and pelvic floor and perineum in 21.4% the cases. Recurrence was most common in the lower pelvic region , accounting for approximately 76.2% (128 cases) of cases. In patients with mid-rectal and distal rectal carcinoma,Patients with pelvic cancer may benefit by individualized treatment plans aimed at achieving a balance between tumor control and minimal risk of irradiation-induced toxicity. Multi-disciplinary treatment (MDT) is currently considered the gold standard in the management of locally advanced rectal cancer. Radiotherapy (RT), as a part of MDT, plays an important role in reducing locoregional failure rate and improving, at least to some extent, the survival of patients –3. The bGenerally, the choice of the RT protocol in cases of rectal cancer is based on the incidence and predominant site of local recurrence and on the local distribution of the lymphatic system. Some guidelines , 18 haveThe superior margin of the pelvic irradiation field is usually marked at the point of the bifurcation of the common iliac vessels into the external and internal iliac vessels, with the approximate boney landmark being the sacral promontory . HoweverTherefore, RT fields should target only those areas of the pelvis and perineum that are at a high risk of local recurrence. Reducing the size of the RT portals to cover only these at-risk sites should minimize normal tissue toxicity. This study was aimed at analyzing the local distribution of pelvic recurrence after TME.After a thorough search for all the medical records and imaging study reports from the database maintained at our center, 962 patients were identified as having pelvic failure after definitive TME surgery. Among these patients, 762 and 32 were excluded due to the lack of useful imaging dataor previous radiotherapy history, respectively. Finally, 168 cases with postoperative pelvic recurrence were included in our study.The clinical and pathological features of the enrolled patients are listed in Table A total of 203 recurrent lesions were observed in the 168 patients , the distances of the primary tumors from the anal verge were less than 4 cm. All 3 patients with external iliac failure had an initial pathologic stage of T3N+. No obvious trend was observed in the case of recurrence in the external iliac region and initial pathologic TN stage.A significant correlation was observed between the primary tumor location and the level of pelvic recurrence. Local failure tended to occur in close proximity to the site of the primary tumor Table . For exaTable This was a retrospective study to evaluate the pattern of pelvic failure after TME in locally advanced rectal cancer. With an understanding of the patterns of pelvic recurrence, we aimed to determine whether the CTV could be optimized and, if so, in what category of patients could the optimization be achieved. Our data showed that mesorectum/anastomotic stoma, presacral area, and pelvic floor/perineum were the most common sites for recurrence of locally advanced rectal cancer after definitive surgery, and different patterns of recurrence were associated with different primary tumor locations. Therefore, we believe that the radiation target volume should be determined on a case by case basis to achieve optimal treatment outcomes.Although the upper border of the CTV is usually marked by the sacral promontory in many radiotherapy centers worldwide, our data demonstrate that the percentage of recurrence in the upper pelvic region was only 8.3% among all cases of pelvic failure. In particular, for cases of mid- and lower rectal carcinoma, the percentage of recurrence was less than 5%. Similar recommendations favoring the downward shift of the upper margin of the CTV also been put forth previously. Syk et al. reported that 29 of 33 local recurrences were located in the lower two-thirds of the pelvis and that lowering the cranial border of the CTV to 3.5 cm below the sacral promontory would still cover all the cases of pelvic failure . A SwediIn the light of the abovementioned considerations, a recent update of Roel's guidelines discusses the possibility of modifying the cranial level of the CTV . Before Further, in the recent update of the consensus guidelines published for rectal cancer , one of With respect to the inguinal and external iliac regions, the consensus  was thatAs per the recommendations, inguinal regions are not commonly involved in rectal cancer, except in case of positive inguinal nodes, massive tumor extension into the internal or external anal sphincter, or infiltration of the lower third of the vagina , 20–21. This study does have a few limitations, including some of the inherent inadequacies of retrospective investigations. First, the study population included cases of pelvic recurrence of rectal cancer, rather than a prospective cohort of patients who received definitive TME surgery. Therefore, in our study, only the characteristics of local recurrence could be assessed, and not the exact rate of pelvic failure. Although the percentage of recurrence at a given site could be partly inferred in terms of the overall recurrence rate, the values were not always consistent. Secondly, about 80% of the patients in our study population received initial definitive surgery at other hospitals, and half did not receive adjuvant chemotherapy, despite locally advanced rectal cancer. Thus, the quality of initial treatment administered to the patients may be questionable in some cases because of the lack of availability of sufficient data from the patient's medical records.Thirdly, the location and size of the primary tumor are important determinants of the site of pelvic recurrence. For instance, as shown in Figure This study was a retrospective investigation of data collected for all patients who were diagnosed with pelvic recurrence of rectal cancer at Fudan University Shanghai Cancer Center between January 2008 and December 2012. The criteria for inclusion were as follows: history of primary rectal cancer, with distance from anal verge <12 cm; histologically confirmed adenocarcinoma; history of definitive TME surgery; initial pathological stage T3 or T4 and/or N+; no history of initial distant metastases; no history of previous RT, before or after TME; and availability of images indicating the precise site of recurrence. Patients with a history of any of the following were excluded: ischemic heart disease; inflammatory bowel disease; malabsorption syndrome; peripheral neuropathy; or psychological disorders.Local recurrence was diagnosed by radiologic evidence of any infiltrative, expansive, or asymmetric pelvic mass with some degree of contrast enhancement that could not be explained by normal or postoperative changes. All patients with local recurrence were reviewed individually. Data were collected from the following patient records, if they were available: operative report, histological report, specimen photographs, initial preoperative imaging, imaging evidence of local recurrences, and clinical history. The data were reviewed on a case-by-case basis by 2 radiation oncologists (J Zhu and YJ Zhu), one radiologist (T Tong), and one surgeon (Y Xu).The collected data comprised demographic and clinical-pathological features , as well as characteristics of recurrence . The identified precise locations of pelvic recurrence included the mesorectum and anastomotic stoma, presacral space, pelvic floor and perineum, internal iliac area, external iliac area, and inguinal area. For patients with recurrence at multiple pelvic sites, all sites were recorded individually.The level of pelvic relapse was classified as follows . The uppThe patient characteristics were described by frequency and percentage of classified variables, by mean and standard deviations for normally distributed continuous data, and by the median, minimum, and maximum for non-normally distributed continuous data. Pearson's chi-squared test and Fisher's exact test were used to evaluate associations between categorical variables. A P-value of < 0.05 was considered statistically significant.Most pelvic recurrences occurred in the lower pelvis. Less than 5% of the cases of relapse in the upper pelvis were observed in cases of mid- and distal-rectal carcinoma. Recurrence in the external iliac and inguinal area was rare in patients with distal rectal cancer. These findings suggest that individualized treatment plans need to be drawn for patients to achieve a balance between tumor control and reduced risk of irradiation-induced toxicity and thereby achieve improved treatment outcomes.


Bamboo mosaic virus (BaMV), is a member of the Potexvirus genus of Flexiviridae. BaMV can infect at least 12 species in 3 genera of bamboo. Symptoms include chlorotic mosaic on infected leaves and necrotic streaking on shoots and culms. With a high incidence of more than 90% infection in many bamboo plantations, the virus causes great economic loss, particularly in Taiwan, in terms of the quality and quantity of bamboo shoot production, a popular food.Bamboo mosaic was first reported in Brazil in 1975, then in Taiwan, Australia, USA, India, China, etc. The causal agent, However, study of BaMV did not start extensively until BaMV was identified as a member of the Potexvirus genus at the molecular level, in the early 1990s. Furthermore, the satellite RNA (satRNA) associated with BaMV (satBaMV) was found to be the only satRNA in Potexvirus. After completion of the full-length sequencing of genomic RNA of BaMV and generation of the BaMV infectious cDNA clone, study of BaMV stepped into a new dimension. Since then, BaMV has been extensively studied at the molecular level, covering different both basic and applied research, by a group of researchers in Taiwan. To date, more than 100 BaMV papers have been published in SCI international journals.Like all potexviruses, BaMV has a flexuous morphology with a single-stranded positive-sense RNA genome. By investigating BaMV, the filamentous structure of flexible viruses was first determined at the near-atomic level by cryo-electron microscopy. This finding solved the mystery of how flexible virus particles maintain structural integrity as mechanical forces deform their structure. In addition, two types of subviral agents, defective RNA and satellite RNA, were found associated with BaMV in the field. Besides studying the viral RNA genomic structure and function, BaMV research has also focused on the virus-host interaction.Meng and Lee). The authors also detail the interactions between replicase and the host proteins identified in Nicotiana benthamiana. Chen et al. cover the location of cis-acting elements in the viral RNA and their specific functions, including the recognition of the replicase complex for minus-strand, plus-strand and subgenomic RNA syntheses, viral RNA packaging, and viral movement. Moreover, the authors reveal the host factors that might be involved in delivering BaMV cargoes during intracellular movement, including the delivery of viral RNA to the chloroplast for replication and viral RNA complex to move cell to cell (Cheng). Huang et al. describe the strategies used to identify the host proteins positively and negatively regulating the BaMV RNA replication and viral movements. One of the host proteins reported to be downregulated after BaMV infection is now revealed as carbonic anhydrase . Nuclear-encoded chloroplast carbonic anhydrase may be involved in the re-initiation step of BaMV RNA replication.In this Research Topic, we summarize the BaMV research with 6 reviews and 4 research articles. To uncover the functional activity of replicase encoded by a positive-sense RNA virus, Meng and Lee describe the enzymatic activities associated with each of the functional domains of the BaMV-encoded replicase, including its unique capping mechanism, which may be conserved across the alphavirus superfamily (Alazem and Lin). BaMV is unique in some isolates carrying satBaMVs, particularly the interfering satBaMV, with crucial roles in modulating BaMV replication and viral symptom development. Lin and Lin summarize the molecular mechanisms underlying the interaction of interfering satBaMV and BaMV (Lin and Lin).In addition to host factors revealed in replication and movement, the study of BaMV-plant interactions explores a role for abscisic acid (ABA), a plant hormone, in the antiviral silencing pathway that could lead to interference in virus accumulation. Alazem and Lin describe how ABA affects the accumulation of BaMV and other viruses via the gene silencing pathway  could stimulate effective neutralizing antibodies against JEV infection in mice. This study demonstrates an alternative way to produce an effective vaccine candidate against JEV in plants by the BaMV-based vector system.Finally, We thank our colleagues and friends, in total 27 authors, for their valuable contributions to this eBook and cohesive collaboration in the study of BaMV biology in the past 2 decades. We are also grateful to Dr. Anne Simon (University of Maryland), who encouraged us to initiate this Research Topic. We hope the knowledge we have gained from BaMV can serve as the groundwork and biotechnological application for Potexvirus research and RNA research as well.All authors listed have made substantial, direct and intellectual contribution to the work, and approved it for publication.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.


During the last years, compelling evidence has pointed out that organic acids also display unexpected roles in controlling whole plant cell physiology. These novel roles have become evident by the contribution of a broad spectrum of research laboratories, which have analyzed plants with modified levels of these compounds and found surprising effects  application on early growth, net photosynthetic rate, gas exchange, osmoregulation, and enzymatic activities in three different maize cultivars. They found that application of GABA improves maize seedling growth, in association with improved net photosynthetic rate and antioxidant enzyme activities.Lehmann et al. analyzed the enhanced CO2 release of illuminated leaves transferred into darkness , using species that exhibit different values of LEDR. For this, the authors fed [13C]-malate and [13C]-pyruvate labeled at specific positions via the xylem stream to the leaves in order to assess the contribution of these organic acids to LEDR. By this approach, they obtained direct experimental evidence about the respiration of both carboxyl groups of malate during LEDR. The results obtained indicate that the two carboxyl groups of malate undergo isotopic randomization by fumarase in the leaves, introducing an additional level of complexity to the interpretation of respiratory substrates.Igamberdiev and Eprintsev discuss the rate limiting enzymes involved in the metabolism and accumulation of particular organic acids, such as citrate, malate, aconitate, hydroxycitrate, 2-oxoglutarate, malonate, oxalate, and oxamalonate, emphasizing that the function of these molecules can drastically change depending on the pH of the regarded cellular compartment. Moreover, organic acids are able to extensively modify the cellular, subcellular, or extracellular compartment in which they are found, due to their particular chemical properties.4 plants in using different types of organic acids and C4 decarboxylases is discussed in Ludwig, along with the advantages of this plasticity in changing environments. The complexity of the biochemistry and overall biology of C4 plants is revised, pointing out different aspects of C4 photosynthesis, which remain to be analyzed. This insight will be valuable for the transfer of C4traits into C3 crops in order to increase yield or mitigating the effects of climate change.The flexibility of CEngqvist clearly illustrates the limited availability of experimental data for the functional annotation of enzymes involved in organic acid metabolism, especially in crops and forestry trees. In this sense, the over-reliance on bioinformatic predictions for enzyme annotations may lead to mistakes in enzyme annotations across genomes, and may represent missed opportunities to discover enzymes with unique properties. In this scenario, the development of novel high-throughput platforms for functional characterization of enzymes is a key future challenge.Finally, This collection of papers highlights recent advances on different aspects of organic acid research. Together, they contribute to the identification of new and diverse roles of organic acids in plant biochemistry and physiology, pinpointing important areas for future research, such as the role of organic acids as signaling molecules, the emerging more complex biochemistry of C4 plants regarding the use of mixed types of organic acids, and the development of novel high-throughput platforms for the molecular analysis of enzymes involved in organic acid metabolism to improve their functional annotation.All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.This work was supported by the Deutsche Forschungsgemeinschaft through grant EXC 1028 and the EU 7th Framework Programme Cooperation FP7-289582.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 fingerprint is a commonly used biometric modality that is widely employed for authentication by law enforcement agencies and commercial applications. The designs of existing fingerprint matching methods are based on the hypothesis that the same sensor is used to capture fingerprints during enrollment and verification. Advances in fingerprint sensor technology have raised the question about the usability of current methods when different sensors are employed for enrollment and verification; this is a fingerprint sensor interoperability problem. To provide insight into this problem and assess the status of state-of-the-art matching methods to tackle this problem, we first analyze the characteristics of fingerprints captured with different sensors, which makes cross-sensor matching a challenging problem. We demonstrate the importance of fingerprint enhancement methods for cross-sensor matching. Finally, we conduct a comparative study of state-of-the-art fingerprint recognition methods and provide insight into their abilities to address this problem. We performed experiments using a public database (FingerPass) that contains nine datasets captured with different sensors. We analyzed the effects of different sensors and found that cross-sensor matching performance deteriorates when different sensors are used for enrollment and verification. In view of our analysis, we propose future research directions for this problem. The use of fingerprints is the oldest and most prevalent method for person identification and authentication. Fingerprint matching problems have been widely explored, and there is significant discussion of fingerprint matching methods in the literature. However, most existing algorithms are designed to work with a specific type of sensor, i.e., the sensor used for enrollment and verification. The rapid growth of new applications and advances in fingerprint sensor technology have given rise to fingerprint sensor interoperability or cross-sensor matching problems, i.e., problems matching an individual’s fingerprints obtained from different sensors.Fingerprint sensing technologies are based on diverse operational principles such as ultrasound, optical, and capacitive technologies. In ultrasound sensors, the image is based on the response of the acoustic wave bounced off the fingertip. In optical sensors, the finger is placed on the transparent prism surface, and light is reflected from the valleys and absorbed at the ridges. The ridges look dark and the valleys appear bright. The capacitive sensor is composed of small capacitive plates located under the sensor, and air works as the dielectric medium. The strength of the electric field is a function of the distance of the valleys and ridges from the plates . The undSome research has been conducted to show the importance of exploring the impact of changing fingerprint sensors on fingerprint matching systems ,3,4. ShiAn analysis of the structure of fingerprints, which revealed that fingerprints captured with different sensors vary in small-scale structural inconsistencies such as micro-texture patterns and fine ridge details such as width and pores. Ridge patterns, ridge orientations, and minutiae form the main structural component, which is invariant to the technology types and interaction types of sensors.An analysis of inter-ridge spacing, which shows that the spacing between successive ridges varies among the impressions of the same finger captured with different sensors and has a significant impact on cross-sensor matching. This issue must be addressed when designing a cross-sensor matching method.An analysis of two state-of-the-art enhancement algorithms, which shows that there is a need to develop new enhancement algorithms for cross-sensor matching that are able to preserve ridge patterns and suppress small-scale structural inconsistencies, extraneous ridges, and minutiae.An analysis of the three state-of-the-art matching methods, which reveals that there is a need to develop new algorithms for cross-sensor matching. In general, there is a better level of interoperability between optical sensors than capacitive sensors. New feature extraction techniques must be developed for cross-sensor matching, keeping in view the structural components of fingerprints that are variant or invariant to the technology types and interaction types of sensors.This study was conducted to analyze the characteristics of fingerprints and the impact of cross-sensor matching on state-of-the-art fingerprint enhancement and matching methods. The matching methods include Minutiae Cylinder-Code (MCC), Bozoroth3 (NBIS software), and VeriFinger, a commercial SDK. The experiments were performed using the public database FingerPass. Specifically, our contributions are as follows:The remainder of this paper is organized as follows: Fingerprint sensor interoperability addresses the ability of a fingerprint-matching system to compensate for the variability in the fingerprints of an individual acquired using different sensors. Variations in the fingerprints are introduced because of differences in capturing the technology of sensors, interaction type, sensor resolution, and scanning area. Based on technology type, sensors can be categorized as capacitive, optical, temperature differential, touchless, ultrasound, piezoelectric, or multispectral . Each tyTexture features, such as local binary patterns (LBPs), histograms of oriented gradients (HoGs), and Gabor responses ,7,8,9,10It can be observed in The impact of sensor interoperability on fingerprint recognition has not been widely investigated. Exploring this problem will aid in understanding the effects of changing the sensors. There is a need to examine fingerprints captured via different sensors and their characteristics for the development of cross-sensor feature extraction and matching algorithms.Databases play a key role in evaluating the performance of a fingerprint matching system; however, few benchmark databases exist for the fingerprint interoperability problem. Such databases include the MCYT , GUC100 Among available public domain databases, FingerPass is the only large database that contains the maximum variety of cross-device fingerprints with different variations, which makes it a challenging database for a fingerprint recognition system. Most existing methods in the literature are designed for use with a specific technology type; consequently, their performance deteriorates when both gallery and probe fingerprints originate from different sensors. Recent work has shown the impact of diverse fingerprint sensor devices on the match error rate (EER) of fingerprint systems. Jain and Ross  investigFew studies have focused on minimizing the effects of sensor interoperability. To address the effects of low interoperability between optical sensors, Marasco et al.  proposedSome works have investigated the effect of scale on cross-sensor matching and have made some improvements. Ren et al.  proposedAs obvious from the above discussion that few studies have investigated the fingerprint sensor interoperability problem, their contributions toward solving this problem are marginal. Consequently, it remains a challenge. The main problems, such as fingerprint texture variation and the distortions in fingerprints that arise when using different sensors, have not yet been addressed properly.Fingerprint enhancement methods play an important role in improving image quality by enhancing ridge structures prior to feature extraction . The rolAs a proof of concept, we performed three experiments using the VeriFinger and MCC algorithms  is the basic metric for assessing performance. The EER is the operating point at which the FMR  and the FNMR are equal. The FMR is the rate at which the matching method falsely considers two different fingerprints to be from the same person. The FNMR is the rate at which the matching method considers the fingerprints of the same person to come from different persons.Regular Matching, a comparison of two fingerprints acquired with the same sensor , in which case EER is referred to as native EER, and (ii) Cross Matching, a comparison of two fingerprints captured with different sensors , in which case EER is termed as interoperable (cross) EER.For evaluating the methods to assess the fingerprint sensor interoperability problem, we consider two matching scenarios: (i) The MCC system results are shown in The EER results for the Bozoroth3 method are presented in From the above results and discussion, we can see that, although the VeriFinger outperforms the MCC and Bozoroth3 methods, it also produces poor results for cross-sensor matching. For further comparison, For MCC, the lowest median cross EER and the mean cross EER are 6.72% and 16.63%, respectively, which are much higher than those for VeriFinger; the highest cross EERs are on FPC, AEC, and ATC datasets, which were collected with capacitive sensors. In contrast, the lowest mean interoperable EER is obtained by V3O and FXO, which were captured using optical press sensors.For Bozoroth3, the lowest median cross EER and the mean cross EER, were 42.52% on V3O and 37.91% on TCC, respectively, and these values are much higher than those for both VeriFinger and MCC. The highest cross EERs are on FXO, ATC, and FPC datasets; the ATC and FPC datasets were collected from capacitive sensors, whereas the FXO dataset was collected from an optical press sensor. Overall, the cross EERs of this method are much higher than those of VeriFinger and MCC. The three methods result in higher cross EERs on ATC and FPC, which is likely because of the resolution of the fingerprints.For further insight into the performance of the three methods for cross-sensor matching, we selected one optical sensor (V3O) and one capacitive sensor (ATC) and plotted detection error tradeoff (DET) curves. Further, we examine the cross-sensor matching performance of the three methods based on the technology types of the sensors. In this case, the datasets can be categorized into two groups: optical and capacitive. There are four cross-sensor matching scenarios: (i) optical vs. optical, where both the probe and the gallery are captured with optical sensors but of different types, (ii) capacitive vs. capacitive, where both the probe and the gallery are captured with capacitive sensors but of different types, (iii) optical vs. capacitive, where the the probe is captured with an optical sensor and the gallery is captured with a capacitive sensor, and (iv) the reverse of Scenario (iii). The optical group contains FXO through AEO, whereas the capacitive group includes ATC through TCC. To examine the impact of sensor interaction type on cross-sensor matching, the datasets are grouped into two categories: press and sweep. There are four cross-sensor matching scenarios: (i) sweep vs. sweep, where both probe and gallery sets are captured with different sensors of the sweep interaction type, (ii) press vs. press, where both probe and gallery sets are captured with different sensors of the press interaction type, (iii) sweep vs. press, where the probe set is captured with a sensor of the sweep interaction type and the gallery set is captured with a sensor of the press interaction type, and (iv) the reverse of Scenario (iii). The sweep group contains AEO, ATC, and SWC, whereas the press group includes all other datasets. To examine the impact of technology types together with interaction types of sensors on cross-sensor matching performance, the mean cross EERs of the three methods are shown in The performance of the three state-of-the-art methods was examined for regular matching, cross-sensor matching, and cross-sensor matching, keeping in view technology types, interaction types, and technology types combined with interaction types. This analysis shows that, although VeriFinger provides improved cross-sensor matching results in comparison with MCC and Bozoroth3, its performance is also not optimal for cross-sensor matching. This leads to the conclusion that there is a need to develop new algorithms for cross-sensor matching problems.We performed a large-scale analysis of the fingerprint sensor interoperability problem. We provide insight into the real issues involved in the fingerprint sensor interoperability problem. Low-level structural inconsistencies and distortions occur in fingerprints that are captured with different sensors. It is shown here that enhancement algorithms have a significant impact on cross-sensor matching. We also analyzed the cross-matching performance of three state-of-the-art methods on a public multi-sensor database.Several variations are introduced in fingerprints captured with different sensors due to differences among sensors in terms of capturing technology, interaction type, sensor resolution, and scanning area. These variations appear as inconsistencies in fingerprint texture and fine ridge details such as width, pores, and inter-ridge spacing, making it difficult to extract discriminative descriptions of fingerprints, which are captured with different sensors. However, ridge patterns and minutiae points are invariant across different sensors and form the discriminative description of fingerprints for cross-sensor matching. The challenge is to enhance the ridge patterns and minutiae while suppressing small-scale inconsistencies such as micro-texture patterns and fine ridge details such as width and pores. To evaluate the potential of existing enhancement methods to meet this challenge, we analyzed the performance of two state-of-the-art enhancement algorithms. We found that, although an enhancement method can overcome this issue and improve cross-matching performance, existing methods designed for regular matching are not robust enough for cross-sensor matching. Therefore, there is a need to design interoperable enhancement algorithms that preserve ridge patterns and suppress inconsistent small details.The performance analysis of three state-of-the-art methods shows that, when the same sensor is used for enrollment and verification, the native EER is generally very low, particularly for VeriFinger. Performance is significantly reduced, even for the best performing method VeriFinger, when different sensors are used for enrollment and verification. This highlights the research challenge of cross-device matching. VeriFinger was shown to be the best of the three matching methods; it yielded lower EER values than MCC and Bozoroth3. VeriFinger also uses minutiae along with several other properties such as ridge count, which highlights that fusing other features with minutiae can have a positive impact on reducing the interoperability problem.An analysis of cross-sensor matching based on the technology types of sensors shows that optical sensors result in relatively low mean cross EERs. By contrast, the capacitive sensors yielded the worst mean cross EERs for all three matching methods. Therefore, the best choice for cross-sensor matching is to use optical sensors for enrollment and verification.An analysis of cross-sensor matching based on the technology types and interaction types of sensors revealed that optical sensors with the press interaction type resulted in the lowest mean cross EERs for all three methods; by contrast, capacitive sensors with the press interaction type yielded the worst mean cross EERs. Furthermore, capacitive sweep vs. capacitive press (and vice versa) resulted in high mean cross EERs. Therefore, the level of interoperability between optical-press sensors is better than that between capacitive sensors, be they press or sweep.In addition to the technology type and interaction type of sensors, the size and resolution of fingerprints generate an important effect on error rates. The impact of different transformation models, such as scaling and resolution compensation models, must be investigated on cross-sensor matching. The effect of technology type and interaction type of sensors on image quality should also be examined.Most systems use only a single impression of the fingerprint to extract features. However, the effect of using multiple impressions of fingerprints to capture more features should be investigated for better results.Our study of the fingerprint sensor interoperability problem shows that fingerprints captured with sensors of different technology types and interaction types involve different types of distortions and small-scale inconsistencies such as micro-texture patterns and pores. Moreover, the fingerprints differ in scale and resolution. The main structure that is invariant among fingerprints captured with different sensors consists of ridge patterns, ridge orientations, and minutiae. In view of this, future studies should develop fingerprint enhancement algorithms for cross-sensor matching that can enhance ridge patterns and minutiae and suppress inconsistencies such as micro-texture patterns. Fingerprints captured with different sensors vary in scale and resolution; cross-sensor matching requires the development of new extraction techniques that are robust against variations of orientations, scale, and resolution.