Ensuring that protected areas (PAs) maintain the biodiversity within their boundaries is fundamental in achieving global conservation goals. Despite this objective, wildlife abundance changes in PAs are patchily documented and poorly understood. Here, we use linear mixed effect models to explore correlates of population change in 1,902 populations of birds and mammals from 447 PAs globally. On an average, we find PAs are maintaining populations of monitored birds and mammals within their boundaries. Wildlife population trends are more positive in PAs located in countries with higher development scores, and for larger-bodied species. These results suggest that active management can consistently overcome disadvantages of lower reproductive rates and more severe threats experienced by larger species of birds and mammals. The link between wildlife trends and national development shows that the social and economic conditions supporting PAs are critical for the successful maintenance of their wildlife populations. Protected areas are intended to safeguard wildlife, but their effectiveness has at times been questioned. Barnes, Craigie, and colleagues show that protected areas do offer refuge—maintaining their bird and mammal abundances—but with greater success for larger-bodied species and in more developed nations. Biodiversity is in crisis1Despite a central objective of PAs being to conserve wildlife populations within their boundaries, many PAs are experiencing undesirable wildlife population declines8It is thus vital to quantify how well PAs are conserving wildlifeWildlife population change is an important and useful metric for evaluating wildlife conservation outcomes in PAs. It is sensitive to long-term environmental changeWe find that on average PAs are maintaining the abundance of populations of monitored birds and mammals within their boundaries, and that wildlife population trends are more positive in countries with higher development scores, as well as for larger bodied species. This body mass finding suggests active management can overcome disadvantages of more severe threats experienced by larger species18(Loxodonta africana) and also affected rhinoceros species (Diceros bicornis and Cerotherium simium)The full data set contains 1,902 population time series for 556 species in 447 PAs  across 7Overall, the mean percentage annual change in population size within PAs was near zero . The differences between birds and mammals (birds more positive), and between Europe and Africa (Europe more positive) are likely an effect of differing regional histories, as well as current pressures. Large-scale land conversion outside the tropics has led to broad-scale historical extirpationsStrikingly, larger-bodied species had more positive population trends in all models except Europe, indicating that PAs are more likely to maintain populations of larger-bodied wildlife than smaller bodied species. This finding is consistent across geographic realms, and taxonomic class, so it was not driven by the difference in body mass between birds and mammals. In the mammal and Africa models the relationship of body mass to trend was u-shaped , suggestOne explanation for these findings is that threat processes of high severity  are impacting intermediate bodied species particularly badly—a pattern previously detected among threat processes for mammals and birds2728Indicators of greater human wealth (gross domestic product) and development (Human Development Index) were associated with more positive population trends. Wealth and development have been shown to have a complex relationship with conservation. Poor outcomes have been associated with both historical and accelerating threatening processes, while increasing wildlife trends can be associated with greater awareness and management capacity, that is, wealthier countries may have more resources available for PA management, and spend more on conservation3233This finding of an association with development is promising, as it shows that additional capacity or decreased dependence on natural resources, can help ameliorate wildlife declines in PAs. Thus, economic development and the associated improvement in food security and governance may lead to effective conservation. In reality, outcomes are likely related to a balance of multiple socio-economic factors. Regardless of which of these explanations is dominant, extra effort will be required to retain species in developing regions. However, to avoid the extinction filter in developing regions resulting in wildlife loss catching up with historic losses in developed countries, extra effort will be required to retain species in these countries. The marginal finding that higher national Gini indices predict more positive population trends is unexpected. The result can be explained by a small number of countries  that have both very high Gini indices and relatively positive wildlife trends.et al.37Counter-intuitively, more positive trends in PAs were correlated with increased anthropogenic landscape changes, indicated by locally denser road networks in the mammals and Africa models, and land-use change in the Europe model. Development of new roads may open up areas and cause wildlife and habitat declinesSeveral well-studied ecological factors that conservation theory predicts should be important determinants of wildlife trends, including PA sizeThe ability of PAs to maintain species populations is critical to global conservation. Our finding that abundances of monitored birds and mammals are maintained within PA boundaries is encouraging. However, our results show that PAs do not work equally well for all species or in all circumstances. Moreover the recent poaching crisis in Africa shows that population gains can be rapidly reversed, if the threatening processes grow too large to mitigate41Further, it is clear that PAs do not exist in a vacuum. Our results show that the social and economic conditions that support PA management are critical for the maintenance of wildlife populations within PA boundaries. Anthropogenic drivers of wildlife abundance change appear to have more influence than those drivers affecting ecological processes such as PA size, at least over the period of a few decades. Much of the research effort into PAs targets ecological processes but it seems greater return would come from focusing efforts more on anthropogenic drivers of PA performance.Managing PAs' socio-political, rather than simply ecological, dimensions is pivotal to wildlife conservation in PAs. Human dependence on PA resources in poorer countries must be addressed if existing PAs are to retain their contents as these nations continue to develop. Finally, to understand the return on our investment in PAs in the long-term, best practice adaptive management and systematic monitoring of biological outcomes, including appropriate counterfactual monitoring, is essentialet al.44A global database of population abundance time series of all available time series for native birds and mammals in terrestrial PAs worldwide was compiled from sources including the Living Planet DatabasePopulation trends were estimated by fitting a generalized linear regression model on time with a log-link function to each population time series464849, a priori hypotheses, and references underpinning the selection of each factor are provided in Variables were selected to represent characteristics of PAs considered most likely to be important determinants in maintaining wildlife populations in PAs for vertebrate species, based on both theoretical supposition and empirical observation as identified via a comprehensive literature reviewa priori over what distance potential correlates would be most likely to be acting. PAs represented only by point information in the WDPA were included in the analysis by creating appropriately sized circular buffers using the ArcGIS buffer tool under an equal-area (Mollewide) projection2) recorded for the individual PAs in the WDPA. In cases where the projection of the PA data set differed from the explanatory data layer, the PAs were reprojected using ArcGIS. Details of the preparation of the individual explanatory variables are provided in http://shoreline.noaa.gov/data/datasheets/wvs.html).Spatial data were analysed using ArcGIS 10.0 and R 2.15.0 ref.  using thExplanatory variables were transformed to normalize distributions, where necessary, and standardised using the R function ‘scale' so all variables in the data set had equal means and standard deviations but different ranges. Normalized and standardised variables were evaluated to determine collinearity by visual inspection of the data and by calculating Pearson's correlation coefficient see .The slope of the generalized linear regressions for all populations was used as the response variable to address the question: what factors predict trend in abundance for bird and mammal species in terrestrial PAs? We applied a linear mixed-effects modelling approach to explore the key correlates of wildlife population of birds and mammals through time in PAs. Explanatory variables were hierarchically spatially structured; at the species, PA and national levels. We used linear mixed-effects modelling to account for the data structure and investigate the relationship between population trends and the suite of potential explanatory variables. Mixed-effects models allow partitioning of the variance in population trends in a nested hierarchy60Model selection was made following an information-theoretic approach, using the corrected Akaike Information Criterion AICc46L. africana) and rhinoceroses (D. bicornis and C. simium). The elephant and rhino outliers were highly positive; if data including the recent years' poaching-related population declines of these species had been available these species may not have been outliers. Fitting genus and order as random effects, to test for phylogenetic influence as reflected by taxonomy, did not improve model fit significantly for any models. When they were fitted, body mass parameter estimates remained stable and significant.For each model with a ΔAICc of less than four the fitted residuals were examined using qq-plots, Cook's distance leverage plots and histograms. Models selection was tested for sensitivity to outliers through systematic removal and replacement of outlying data. Outliers were identified using qqplots and Cooks distance leverage plots of the model residuals. When outliers were removed the preferred models and their parameter estimates were remarkably consistent, and additionally exhibited low sensitivity the removal of extremely large species such as Africa Elephant .Supplementary Figures 1-6, Supplementary Tables 1-6, Supplementary Note 1, Supplementary ReferencesTable listing all species included in the analysisTable listing all protected areas included in the analysis


Alcohol consumption may not increase the rate of sperm residual histones and protamine deficiency; however, it causes an increase in the percentage of spermatozoa with DNA fragmentation and apoptosis. In a medical problem as spinal cord injury, poor semen parameters and sperm DNA damage were reported. Infection induces reactive oxygen species production, decreases the total antioxidant capacity and sperm DNA fragmentation or antigen production that lead to sperm dysfunctions and DNA fragmentation. While reactive oxygen species generation increases with age, oxidative stress may be responsible for the age-dependent sperm DNA damage. The exposing of reproductive organs in older men to oxidative stress for a long time may produce more DNA-damaged spermatozoa than youngers. Examining the sperm chromatin quality in testicular cancer and Hodgkin’s lymphoma patients prior to chemotherapy demonstrated the high incidence of DNA damage and low compaction in spermatozoa at the time of the diagnosis. In chemotherapy cycle with genotoxic agents in cancer patients, an increase in sperm DNA damage was shown after treatment. In overall, those factors occurring during the prenatal or the adult life alter the distribution of proteins associated with sperm chromatin induce changes in germ cells which can be detected in infertile patients.The sperm DNA damage may occur in testis, genital ducts, and also after ejaculation. Mechanisms altering chromatin remodeling are abortive apoptosis and oxidative stress resulting from reactive oxygen species. Three classifications of intratesticular, post-testicular, and external factors have been correlated with increased levels of human sperm DNA damage which can affect the potential of fertility. Lifestyle, environment, medical, and iatrogenic factors might be considered to cause dysmetabolism to make distracting interactions and endocrine disrupting compounds. As a result, these may induce chromatin/DNA alteration in germ cells, which may be transmitted across generations with phenotypic consequences Spermatogenesis includes proliferation, meiotic DNA, and differentiation of spermatids into spermatozoa. Due to the complexity and relatively long period of spermatogenesis, the sperm DNA and chromatin may alter at any stage of this process. During spermiogenesis phase, the nuclear histones are replaced at first by transition proteins and then by protamines. The chromatin stability is achieved by disulfide bonds formation during epididymal transit of spermatozoa , 2.It is shown that protamine-induced sperm chromatin condensation is very essential for normal sperm fertility potential and subsequently for normal fertilization and embryonic development , 4. TherSeveral etiological factors including intratesticular, post-testicular, and external factors have been correlated with increased levels of human sperm DNA damage which can affect the potential of male fertility. Medical dysfunctions like diabetes mellitus (DM) may have detrimental effects on sperm fertility potential and DNA integrity, also varicocele samples contain a higher proportion of spermatozoa with abnormal DNA and immature chromatin than those from fertile men as well as infertile men without varicocele . Therefore, varicocele leads to production of spermatozoa with less condensed chromatin and this is one of the potential causes of infertility. In this study, further topics being discussed as well , Table IDiabetes mellitus (DM)DM is one of the most common diseases that threats human health in the modern world  production in diabetic patients and beneficial effects of antioxidants -30. Agbahese men . Also, these men   test showed that in infertile men with varicocele there is a high relative proportion of sperm cells with extreme levels of nuclear damage  is a medical problem with arising 1000 new cases per year . ApproxiAs it is shown, spermatozoa with poor DNA integrity may lead to fertilization failure, delayed embryo development, and early pregnancy loss , 55. Evehigh levels of ROS and abortive apoptosis are two main causes of sperm chromatin/DNA damage in SCI men  test and found a remarkable percentage of CMA3 positive sperm cells in the SCI group and concluded that SCI has a negative effect on the sperm protamination. Furthermore, they used the Toluidine Blue (TB) and Aniline Blue staining and reported increased sperm DNA fragmentation and abnormal chromatin condensation as well as high DNA denaturation respectively  showed that obese patients have a lot of spermatozoa with DNA fragmentation in their ejaculates . There is a significant association between active smoking and reduced seminal quality, sperm DNA integrity and nuclear maturation, increased sperm DNA fragmentation and induced alterations of the sperm plasma membrane (166-170). High levels of DNA strand breaks in smoker men may be due to the presences of carcinogens and mutagens in cigarette smoke (171). In a study performed on 655 smokers and 1131 non-smokers, a significant decrease was shown in sperm density (15.3%) as well as other parameters including total sperm count (17.5%), and total number of motile spermatozoa (16.6%) (172). Therefore, smoking may have detrimental effects on the quality and quantity of sperm in male and decreases the antioxidant activity in seminal plasma (173).et al demonstrated increasing (approximately 48%) in seminal leukocyte concentrations and ROS levels in infertile smoker men when compared with non-smokers. They concluded that there may be a positive association between leukocytospermia and ROS levels (166). Potts et al also investigated sperm DNA damages of 35 fertile smokers and 35 fertile nonsmokers with SCSA and reported the higher sperm DNA damage in smokers compared to nonsmokers (174). Several investigators have shown a correlation between cigarette smoking, OS and sperm DNA damage . Recent studies have shown that Radio-frequency electromagnetic radiation, of mobile phones, may cause to increase of mitochondrial ROS production and DNA fragmentation (185-187). So, it is believed that extensive mobile phone use by men may affect male fertility potential and even the health of their offspring .Air pollution2 or SO2 and sperm chromatin and/or DNA damage. Serum levels of LH, FSH, and T did not differ significantly, whereas the sperm parameters were significantly different in motorway tollgate workers (190). Over the past decades, many studies have shown that environmental pollution is implicated in poor sperm quality . There is some evidence of increased percentage of spermatozoa with chromatin abnormality with fragmented DNA in selected population like motorway workers because of prolonged exposure. However, there was no significant relationship between blood concentrations of Pb, NOIn another selected examined sample study, likely, much higher levels of sperm DNA damage were seen in men following periods of high air pollution from burning of coal, with no obvious change in other semen parameters (191). Ultimately, it could be hypothesized that a combination of pollutants would be responsible for sperm abnormalities, rather than a single heavy metal (190). Some findings provided evidence that polymorphisms of some genes may be useful biomarkers to identify individuals susceptible to DNA damage. XRCC1 Polymorphisms may alter sperm polycyclic aromatic hydrocarbon-DNA (PAH DNA) levels and could be considered as the useful biomarkers to detect individual susceptibility to DNA damage resulting from exposure to PAHs (192). Polymorphisms of the DNA repair genes XPD6 and XPD23 and a polymorphism CYP1A1MspI as a metabolic gene were associated with high levels of sperm DNA fragmentation in men with a high exposure level of air pollution (193). Evidencesuggest that men will respond in a different manner to the same level of exposure and that individual responses may be modified by different level of gene expression (194).High temperatureThe High temperature is a physical factor which is concerned about for decades. It can affect the male reproductive system either directly, causing decreased or altered sperm production, or indirectly through the endocrine system causing a hormonal imbalance (195). Data from experimental studies showed scrotal heating due to the posture of sleeping and sitting, driving and clothing may affect testicular function and is related to male infertility (196-198). However, making the selection of an appropriate control group is difficult or impossible and current data is not available from human sperm DNA quality in response to heat. However, in an experimental study, when mice were exposed to increased temperature, a stress-induced apoptosis in epididymis and testis which are very functional was seen. Germ cells in the testis were either lost by apoptosis or went on to complete their developmental process and were recovered as motile spermatozoa with fragmented DNA (199).In highly compacted toroidal nucleo-protamine complexes, there is a nonrandom distribution of genes have potential to be involved in the genomic activation in the early embryo. In addition, protamines and other sperm chromatin associated proteins may provide epigenetic information to serve the reorganization of paternal chromatin after fertilization. Meanwhile, DNA strand breaks delay the replication until either the damage can be repaired or until embryo development with damaged DNA is no longer probable. An overall consideration of the current record on human sperm chromatin/DNA shows that environmental, clinical and iatrogenic relevant factors might reflect dysmetabolism. The consequence of dysmetabolism is endocrine disrupting compounds which alter remodeling of sperm chromatin which can be detected in infertile patients. Although SCSA is considered as the gold standard and other detecting methods of individual sperm such as SCD, CMA3, TB, and AB are preferred for their simplicity, this should be noted that post meiotic damage may regularly occur in the sperm DNA and a prognostic test to help as a true screening test to appraise DNA integrity of motile and non-apoptotic fraction of the sperm population have not been achieved.All investigators disclose no conflict of interest in this study.


Researchers have designed increasingly sophisticated bioreactors with dynamic mechanical regimes, but the response of chondrocytes to dynamic compression and shear loading remains poorly characterized due to wide variation in study design, system variables, and outcome measurements. We assessed the literature pertaining to the use of dynamic compressive bioreactors for in vitro generation of cartilaginous tissue from primary and expanded chondrocytes. We used specific search terms to identify relevant publications from the PubMed database and manually sorted the data. It was very challenging to find consensus between studies because of species, age, cell source, and culture differences, coupled with the many loading regimes and the types of analyses used. Early studies that evaluated the response of primary bovine chondrocytes within hydrogels, and that employed dynamic single-axis compression with physiologic loading parameters, reported consistently favorable responses at the tissue level, with upregulation of biochemical synthesis and biomechanical properties. However, they rarely assessed the cellular response with gene expression or mechanotransduction pathway analyses. Later studies that employed increasingly sophisticated biomaterial-based systems, cells derived from different species, and complex loading regimes, did not necessarily corroborate prior positive results. These studies report positive results with respect to very specific conditions for cellular responses to dynamic load but fail to consistently achieve significant positive changes in relevant tissue engineering parameters, particularly collagen content and stiffness. There is a need for standardized methods and analyses of dynamic mechanical loading systems to guide the field of tissue engineering toward building cartilaginous implants that meet the goal of regenerating articular cartilage.Articular cartilage functions to transmit and translate loads. In a classical structure–function relationship, the tissue resides in a dynamic mechanical environment that drives the formation of a highly organized tissue architecture suited to its biomechanical role. The dynamic mechanical environment includes multiaxial compressive and shear strains as well as hydrostatic and osmotic pressures. As the mechanical environment is known to modulate cell fate and influence tissue development toward a defined architecture  These searches yielded a total of 1,799 results; however, many individual publications were repetitive with alternative search terms. We then manually assessed the manuscripts to find those in which articular chondrocytes or articular cartilage-derived progenitor cells were used in experiments and dynamic compression was included as at least one element of the loading regime. This resulted in a final list of 63 manuscripts, which we then critically evaluated for their major findings and compared them to each other, noting the many differences in input and output variables used. The results are comprehensively detailed in the tables that accompany this review.Dynamic loading parameters including frequency, amplitude, duration, and timing clearly influence biochemical and biomechanical outcomes in these studies; however, comparisons between studies should be performed cautiously as each study employs a unique cell source and culture conditions. It is also worth noting that less than half of the compiled studies report sample sizes. In compiling the review, we specifically noted the lack of discussion of species differences by authors when comparing their results with the work of others. Thus, we used this parameter as part of the structural separation of the types of studies we found to emphasize its importance as a variable in the results obtained.The earliest studies to define the role of dynamic mechanical stimulation of chondrocytes within a tissue engineering system, as opposed to explant culture, used primary bovine chondrocytes seeded into hydrogel-based substrates and investigated the cellular biochemical response, using assays to quantify changes in proteoglycan, collagen, and total protein content. These studies showed that chondrocytes significantly increased proteoglycan synthesis but variably regulated collagen synthesis in response to short-duration dynamic loading at various frequencies, with a majority of positive results at 1 Hz  and catabolic  genes with increased loading duration relative to both preload gene expression and to continuously loaded hydrogels. For the same intermittent regime, investigation of delayed versus immediate loading was performed in a cross-over study with 7 days in free-swelling or dynamic loading with a subsequent switch, and both anabolic and catabolic genes increased under dynamic loading regardless of timing without significant differences in the total GAG content  significantly upregulated COL2A1 mRNA when subjected to dynamic load compared with static load, that gene expression is directly correlated to loading duration, and that the proximal region of the COL2A1 gene promotor mediates transcriptional activity under dynamic compression. When the same group investigated extracellular matrix production under dynamic load in the same system, they found that dynamic compression increased both GAG and collagen production when normalized to cell count; however, they did not compare the groups statistically , and poly-caprolactone can be manufactured to meet specifications including porosity, bioresorption rate, and mechanical stiffness. These properties, in turn, highly influence cell phenotype and modulate the cellular responses to the mechanical environment, specifically through load distribution and mechanotransduction. Unlike the prototypical agarose hydrogel system described earlier, the large variety of scaffold-based substrates make it harder to gain an understanding of the response to chondrocytes to a dynamic loading regime when using them. Nonetheless, it is worth reviewing the results from these studies in isolation. When neonatal primary bovine chondrocytes were seeded into PGA scaffolds, precultured for 21 days, and continuously loaded at either 0.001 or 0.1 Hz and 10 or 50% compression for 24 h, they significantly increased both total protein and GAG production in comparison with free-swelling and 10% statically loaded controls, with greatest effect seen at 0.1 Hz and 50% compression  and matrix accumulation  when compared with unloaded controls , and stiffness when compared with unloaded controls after 28 days in culture , gene expression  is necessary to fully appreciate the response of cells to a complex loading regime. Primary cells retain their chondrocytic phenotype. However, if expansion of cells is needed, techniques that effectively limit the dedifferentiation seen in monolayer will need to be further developed. Expansion at physioxia, or with certain growth factors have been shown to influence phenotypic drift, but no such techniques were used in the studies we analyzed (Jakob et al., in vitro loading systems: care must be taken when drawing conclusions from the results obtained in such simplified conditions in the laboratory.Those conclusions notwithstanding, it is clear from our analysis that it is time for standardized protocols and analyses to be introduced. At the gene level, Jeon et al. , 2013 shin vitro methods to generate articular cartilage utilizing chondrocytes cultured in a dynamic mechanical environment. These various methods have been developed with the goal to generate articular cartilage for the repair of focal tissue defects following traumatic injury. For successful translation of these methods to clinical application consideration must also be given to scalability, reproducibility, and cost. Presently, there are no FDA approved biologic implants grown in a dynamic compressive bioreactor; the first therapeutic would require substantial investment for comparison with either microfracture or autologous chondrocyte implantation for repair of focal articular cartilage defects. Furthermore, the few studies utilizing human-derived cells in dynamic compressive bioreactors did not reach significance for most outcome parameters measured, highlighting wide variation between donors. It must also be noted that these studies primarily utilized chondrocytes derived from osteoarthritic tissue, which is not representative of either the target tissue or the intended population for focal cartilage repair. Moving forward, we must learn from these studies not only to work toward standardization of bioreactors but also to pay attention to translation for clinical application with use of human cells from non-diseased tissue.This review focused exclusively on No human or animal subjects were used in this study.DA and BJ conceived of the review topic and participated in manuscript writing, editing, and preparation for publication. DA reviewed the primary literature and cataloged the results.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.


Understanding species-habitat relationships is vital to successful conservation, but the tools used to communicate species-habitat relationships are often poorly suited to the information needs of conservation practitioners. Here we present a novel method for translating a statistical species-habitat model, a regression analysis relating ring-necked pheasant abundance to landcover, into an interactive online tool. The Pheasant Habitat Simulator combines the analytical power of the R programming environment with the user-friendly Shiny web interface to create an online platform in which wildlife professionals can explore the effects of variation in local landcover on relative pheasant habitat suitability within spatial scales relevant to individual wildlife managers. Our tool allows users to virtually manipulate the landcover composition of a simulated space to explore how changes in landcover may affect pheasant relative habitat suitability, and guides users through the economic tradeoffs of landscape changes. We offer suggestions for development of similar interactive applications and demonstrate their potential as innovative science delivery tools for diverse professional and public audiences. Conservation requires understanding relationships between species and their environments, but research concerning species-habitat relationships is often communicated through science outlets poorly suited to the information needs of conservation practitioners who implement management actions ,2]. Con. Con2]. Statistical species-habitat models relate the spatial distribution of a species of interest to environmental variables such as geology and human infrastructure, providing spatially explicit descriptions of species-habitat relationships for ecological inference and conservation planning . SpeciesAlthough species-habitat models are clearly applicable to conservation, information is often presented as regression equations or static thematic maps of a large geographical area. It would be difficult for anyone to directly visualize the application of a regression equation to a landscape of interest. Likewise, static graphics too often provide little practical insight because they do not offer enough fine-scale detail that may influence local  management decisions ,15]. Fu. Fu15]. Phasianus colchicus) at a spatial scale relevant to on-the-ground management ,,. Here wenagement . We preshttps://pheasant.shinyapps.io/pheasanthabitatsimulator/), here presented, translates a statistical model of pheasant-habitat relationships in Nebraska into dynamic visualizations of the predicted effectiveness and financial tradeoffs of management actions via an interactive application built on an open-source web platform.Ring-necked pheasants are a culturally and economically important gamebird, naturalized and widespread across the United States. Despite the considerable scientific and management effort dedicated to North American pheasant conservation, pheasant populations continue to decline, largely due to changes in land use and agricultural practices ,22]. Ph. Ph22]. The Pheasant Habitat Simulator combines the analytical capacities of the R environment  and the The Pheasant Habitat Simulator display is a web page organized by a navigation bar with four tabs: “Welcome”, “Custom Management”, “Economic Module,” and “About” (see following sections for detail). When a user opens the application, they are directed to the “Welcome” tab, which contains a static, thematic depiction of the most recent estimated pheasant relative abundance for the state of Nebraska, and instructions on how to use the application . The “Cuhttps://github.com/lsw5077/Pheasant-Habitat-Simulator). Two distribution methods provide multiple levels of engagement to suit the interests and needs of diverse users. The web-page version of the application is intended for users primarily interested in understanding pheasant-habitat relationships. For users seeking to understand the code or build their own species-habitat application, the annotated code and data are available via github. Also available at the github repository is a portable version of the app, which can be downloaded and transferred to a portable memory device or used offline on a PC . The portable app contains the app and the corresponding data, a copy of R portable, and a deployment skeleton that enables users to run the app simply by clicking an icon [The Pheasant Habitat Simulator is accessible online as a webpage and a github repository  can be reduced to a Poisson regression equation, it is intuitive and relatively straightforward to render a pheasant habitat suitability surface according to user-specified landcover composition. Based on Jorgensen et al.’s (2014) corrected model, the Pheasant Habitat Simulator takes the proportions (un-centered and un-standardized) of rangeland (R), CRP (C), trees (T), wetland (W), and the linear, quadratic, and cubic effects of row crop (RC), and small grain (G), surrounding each pixel (p) to predict relative pheasant habitat suitability at each pixel in the fine-scale background raster:This equation differs slightly from the one reported in Jorgensen et al. (2014) in that it does not include elevation, which was not determined to predict pheasant abundance. Regression coefficients were estimated accounting for imperfect detection; here, we assume constant detection probability. We use the regression equation, which was estimated from pheasant count data across the state of Nebraska, to predict the distribution of pheasant relative habitat suitability categories according to user-specified landcover composition. Predictions were based on mean parameter estimates. We do not depict statistical uncertainty because we wanted to keep the tool accessible to a broad audience, including those with limited statistical expertise. However, we have made provisions for users to investigate the role of uncertainty in model predictions to the extent that they are interested. The reactive plots are stored after each iteration, allowing users the opportunity to download individual plots to assess for themselves how similar landcover compositions may create slightly different pheasant habitat suitability surfaces. Landcover values set by the user enter the regression as variables that then predict the distribution of relative pheasant habitat suitability categories using given values for CRP, rangeland, row crops, small grains, trees and wetlands in the average township of counties throughout the state. Calculating the predictions for all pixels in the generated grid results in a predictive raster plot displayed below the landcover grid showing the distribution of relative habitat suitability categories as a probability surface that corresponds not to the landcover plot directly above it, but rather to the hidden random fine-scale raster used to predict it . The useWildlife managers often use financial incentives to facilitate the establishment of wildlife habitat on private lands. For example, a wildlife manager may work with a private landowner to convert cultivated land to grassland by enrolling land in CRP. Because such financial incentive programs are an important tool for wildlife management, it is essential for managers to understand the financial costs and potential trade-offs of specific land use changes designed to improve wildlife habitat suitability. The “Economic Module” tab  guides tBecause CRP is one of the most important tools available to wildlife managers seeking to foster pheasant populations, the Economic Module estimates costs in 10-year increments to reflect the length of a typical CRP contract. Assuming all agricultural landcover changes result from partnerships between wildlife managers and private landowners, we estimate the incentive cost of constructing the user-defined agricultural composition as the difference between the original collective gross income to private landowners of the landscape and the collective gross income of the new, user-defined landscape, multiplied by 10 years, plus the 10-year cost of the CRP contracts. We used county-specific values for the production potential of bushels/acre and the value of crops in dollars/bushel, pasture rental rates, and enrollment rates in CRP for each county per the National Agricultural Statistics Service .In addition to incentivizing desired agricultural practices, wildlife managers also implement long-term habitat improvement actions intended to be effective for at least the duration of a CRP contract . Jorgensen et al. (2014) demonstrate that the proportion of the landscape covered in trees negatively correlates with pheasant abundance, while wetlands are positively correlated. Using expert opinion elicited from wildlife managers in Nebraska, we estimated a statewide average per-acre cost of tree removal ($650/acre) and wetland restoration ($6250/acre). The total 10-year management cost is calculated as:We assume no economic cost for increasing the proportion of trees, as planting trees for agricultural benefit is increasingly uncommon in Nebraska. We also assume no direct economic benefit to removing trees, as Nebraska does not have a largescale forestry industry. Thus, a management cost is incurred if the user decreases the proportion of trees on the simulated landscape. In contrast, we assume no cost to managers of removing wetlands, so a wetland management cost is only incurred if the user increases the proportion of wetlands within the landscape. The overall cost of creating user-defined landscape conditions is calculated by summing the total agricultural cost and the total 10-year management cost.Progress in the field of conservation is hindered by a tradition of unidirectional information flow: scientific knowledge often moves, inefficiently, from scientists to conservation administrators to conservation practitioners without the opportunity for practitioners to contribute their needs and insights . Web-basWhile the case study we have presented here was created to meet a very specific need, our framework may be readily modified and improved upon to meet the needs of many professionals and researchers seeking to quickly develop management-applicable decision support tools based on statistical models. Although the model and economic calculations in our example are specific to ring-necked pheasants in Nebraska, species-habitat models are increasingly ubiquitous in the primary literature, and many rely on a data structure very similar to that used to develop the Pheasant Habitat Simulator . Researchers or managers with some basic R coding skills, and an interest in developing a similar application can easily adjust our workflow  to create a personalized Species Habitat Simulator specific to their region and/or species of interest. Furthermore, the dynamic user interface could be expanded to facilitate other models , for wildlife management and conservation.Interactive decision support tools such as the Pheasant Habitat Simulator can be created and distributed through existing conservation partnerships and information channels. In many cases, administrators at conservation agencies establish objectives and conduct research, whether in house or in collaboration with an academic institution. The research team delivers findings as a research product and the administration translates findings into policies that are then implemented by conservation practitioners. We propose that interactive decision support tools such as the Pheasant Habitat Simulator represent the natural evolution of conservation research deliverables. They may be requested and produced in a similar manner to a report or presentation, with the important distinction that they may be beta tested by and customized to the needs of conservation practitioners. Furthermore, an enterprising programmer based at an agency or NGO may extract a species-habitat equation from a published manuscript and create a decision support tool for their system of interest, thus making efficient use of time and resources.https://github.com/lsw5077/Pheasant-Habitat-Simulator).In the specific case of the Pheasant Habitat Simulator, the Nebraska Game and Parks Commission requested a decision support tool through their research partnership with the Nebraska Cooperative Fish and Wildlife Research Unit and the Rainwater Basin Joint Venture. The Pheasant Habitat Simulator was collaboratively built by graduate students and early career researchers, and then delivered to administrators at the agency, who now have the ability to widely distribute it among wildlife managers. Distribution to wildlife managers will ideally be paired with an in-person workshop or training, which can be scheduled to coincide with regional or divisional meetings when conservation practitioners convene in one location. Conservation partnerships such as the one that produced the Pheasant Habitat Simulator are widespread, with partnerships often leading to decades-long research and conservation efforts in which decision support tools are invaluable. Any organization wishing to collaborate with other conservation entities could ostensibly modify our framework to other species of conservation or management concern and host updated versions on their own website. Furthermore, because the Pheasant Habitat Simulator is an open-source tool housed on a collaborative programing website (github), we have provided the space for users to share their own improvements, large or small. The tool will thus be collaboratively improved and maintained for as long a time as it is interesting and useful. Indeed, we invite readers to provide feedback and make changes to the application on github (Given the constraints of time and funding for development of effective science communication tools, it is essential that we streamline the process by which research results are applied to real-world problems. Researchers benefit by communicating models to practitioners effectively, as they can avoid problems caused by misinterpretation or oversimplification of ecological concepts . Our exa


Animal and human studies revealed that patterned neuronal activity is an inherent feature of developing nervous systems. This review summarizes our current knowledge about the mechanisms generating early electrical activity patterns and their impact on structural and functional development of the cerebral cortex. All neocortical areas display distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, intermittent spontaneous activity is synchronized within small neuronal networks, becoming more complex with further development. This transition is accompanied by a gradual shift from electrical to chemical synaptic transmission, with a particular role of non-synaptic tonic currents before the onset of phasic synaptic activity. In this review article we first describe functional impacts of classical neurotransmitters  and modulatory systems  on early neuronal activities in the neocortex with special emphasis on electrical synapses, nonsynaptic and synaptic currents. Early neuronal activity influences probably all developmental processes and is crucial for the proper formation of neuronal circuits. In the second part of our review, we illustrate how specific activity patterns might interfere with distinct neurodevelopmental processes like proliferation, migration, axonal and dendritic sprouting, synapse formation and neurotransmitter specification. Finally, we present evidence that transient alterations in neuronal activity during restricted perinatal periods can lead to persistent changes in functional connectivity and therefore might underlie the manifestation of neurological and neuropsychiatric diseases. Animal and human studies have demonstrated that patterned neuronal activity is an inherent feature of developing neuronal networks. Spontaneous activity patterns demonstrate specific properties during distinct developmental stages, in accordance with the establishment of neuronal connectivity  or preplate  from astrocytes . Vesicular glutamate transporters, which are essential elements for synaptic glutamate release, are expressed in the neocortical anlage of rodents already at E14 , and rely on voltage-gated Ca2+ channels  and show substantially faster kinetics  and activation of phosphatidylinositol 3-kinase are key downstream elements in the activity-dependent apoptosis pathway, which promotes survival via the AKT pathway  on studies demonstrating that conditions leading to disturb neuronal activity cause neurodevelopmental diseases; and (ii) on diseases in which putative alterations in immature neuronal activity have been associated with their clinical manifestation.One intriguing observation supporting the role of neuronal activity in the structural and functional development of the neocortex is that substances interfering with early neuronal activity often cause disturbances in neocortical development. Recently, a pilot study performed in preterm babies  revealed that several drugs  that are routinely used in neonatal intensive care units alter the properties of spontaneous brain activity  does not induce obvious neurodegeneration in rats  and isoflurane (0.75 vol. % for 6 h) results in a significant increase in the number of apoptotic neurons in rats  anesthesia in the first postnatal weeks  leads to a widespread neurodegeneration in the cortex of immature rats  must be carefully evaluated.The clinically most relevant case for pharmacologically induced neurodevelopmental disorder is still the fetal alcohol spectrum disorder (FASD), caused by ethanol consumption during pregnancy (for review Olney, A receptor-mediated responses (Lovinger et al., in vitro results obtained in acute hippocampal slices of P3–7 rats demonstrated that ethanol significantly increases the frequency of giant depolarizing potentials (GDPs; Galindo et al., A receptors mediate excitatory actions (Ben-Ari et al., in vivo GABAA receptors provide a dominant inhibitory action already in early postnatal rodent cortex (Kirmse et al., in vivo recordings in neonatal rats demonstrated that at P4–7 alcohol almost completely suppresses gamma oscillations and spindle bursts as well as sensory-evoked responses, whereas its action at P14–17 was much weaker (Lebedeva et al., in vivo an alcohol-induced reduction of neuronal activity appears to contribute to its neurodegenerative effect (for review Lotfullina and Khazipov, 2+ transients in migrating mouse neurons and the rate of neuronal migration (Kumada et al., Ethanol inhibits NMDA receptor-mediated signals and enhances GABAin vitro and in vivo (Brockmann et al., The most common cause of neonatal encephalopathy is perinatal asphyxia, a relevant complication occurring in about 2% of human births. Consequences are several brain dysfunctions like cerebral palsy, sensory and cognitive impairments, epilepsy or autism spectrum disorders (ASD; Vannucci, In vitro experiments revealed that immature rodent cortical neurons are more resistant against hypoxic-ischemic conditions (Luhmann and Kral, in vitro and in vivo (Nimmervoll et al., Epilepsy is one of the most common neurological disorders. An imbalance between excitation and inhibition, e.g., by disturbances in neuronal excitability or neurotransmitter systems and aberrant connectivity, underlies the generation of seizures (Goldberg and Coulter, The massively enhanced neuronal activity during a seizure causes a functional remodeling of neuronal circuits, which may increase the risk to develop further seizures, a concept termed “seizures beget seizures”. While this concept is still under discussion in the adult brain, experimental data demonstrate that neonatal seizures indeed increase the risk to manifest epilepsy (for review Ben-Ari and Holmes, in vitro experiments with in-toto hippocampal preparations, which demonstrated that seizure-like activity in one hemisphere induces functional alterations in the contralateral hemisphere thereby inducing an epileptogenic mirror focus in rats (Khalilov et al., A receptor α1 subunit (Zhang et al., The most striking evidence comes from One intriguing consequence of these observations is that it might be possible to prevent epileptogenesis after neonatal seizures or other early peri-/postnatal insults. A study in a genetic mouse model for neonatal epilepsies demonstrated that epileptiform-like activity and behavioral deficits in adult animals can be prevented by continuous application of the loop diuretics bumetanide, which reduces the depolarizing GABAergic responses and attenuates pathophysiological electrical activity (Ben-Ari et al., Schizophrenia is a relatively frequent and complex brain disorder. The risk of manifesting schizophrenia is inheritable in more than 50% of clinical cases (Schwab and Wildenauer, Recent experiments using mice that express a genetic background found in schizophrenic patients in combination with an intra-uterine insult, in this case a mimeticum for a viral infection, demonstrate that properties of spontaneous activity in the mouse prefrontal cortex changes already at early postnatal stages (Hartung et al., ASD describe a heterogeneous class of disorders associated with social disability, communication impairment, repetitive behaviors and restricted interests (for review in Ecker et al., It has been recently demonstrated that the frequency of GDPs is reduced in the immature hippocampus of BTBR-mice, which represents an animal model of idiopathic autism (Cellot et al., 2-subunit of glycine receptors have also been found in patients affected by ASD (Piton et al., One unequivocally identified cause for ASD is prenatal exposure of the anticonvulsant valproate (for review Roullet et al., In this review we provide a body of evidence indicating that spontaneous neuronal activity during early developmental stages is critically involved in a variety of neurodevelopmental processes. Altered neuronal activity seems to be involved in the etiology of neurological and neuropsychiatric diseases. Since the impact of genetic models on spontaneous neuronal activity has only occasionally been monitored, it is possible that several genetic models of neurodevelopmental diseases underestimate the contribution of electrical activity to the etiology of these disorders. In addition, we like to emphasize that our knowledge is rather limited, whether the specific spontaneous activity patterns occurring in a defined spatiotemporal sequence mediate distinct developmental processes. Further experiments, using a combination of electrophysiological, optogenetic and molecular techniques, will be required to address this intriguing question. However, even our limited knowledge on the impact of neuronal activity on early brain development already initiated new therapeutic options for the treatment of neurological and neuropsychiatric diseases and instructed that neurodevelopmental consequences of early pharmacological interventions must be considered.SK, AS, OB, J-WY, HJL and WK wrote and corrected the 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.


Facing stressful conditions imposed by their environment that could affect their growth and their development throughout their life cycle, plants must be able to perceive, to process, and to translate different stimuli into adaptive responses. Understanding the organism-coordinated responses involves fine description of the mechanisms occurring at the cellular and molecular level. These mechanisms involve numerous components that are organized into complex transduction pathways and networks, from signal perception to physiological responses. The major challenge of plant signaling is to understand how the large diversity of molecules identified as signals, sensors, or effectors could drive a cell to the appropriate plant response, to cope with various environmental challenges. The objective of this Research Topic is to give an overview of various signaling mechanisms or to present new molecular signals involved in stress response and to demonstrate how basic/fundamental research on cell signaling will help to understand stress responses at the whole plant level.Vilela et al. present an extensive review of the role of Casein Kinase 2 (CK2), an evolutionary conserved Ser/Thr protein kinase found in all eukaryotes, during abscisic acid (ABA) signaling and drought stress tolerance. For instance CK2 has a pivotal role in the regulation of ABA signaling through its action on Zea mays OST1/SnRK2.6 (Open Stomata 1/Sucrose Non Fermenting Kinase 2.6) a well-known Ser/Thr protein kinase involved in ABA signaling  retards ethylene-promoted senescence (as previously reported for the ABA-promoted senescence) through an elusive mechanism resulting in the modification of plastidic lipid metabolism and maintenance of plasma membrane integrity. Lovieno et al. using a RNA sequencing approach, report on global transcriptomic changes associated with drought and rehydration in tomato. Transcriptomic analyses together with physiological measurements, quantification of metabolites and biometric parameters, yielded promising candidate genes and that could be used as specific physiological markers of plant drought response. Using a transgenic approach, two studies have functionally validated the role of two transcription factors during drought stress in rice and in soybean . Jiang et al. improved rice drought tolerance by overexpressing the Arabidopsis thaliana transcription factor WRKY57 (AtWRKY57) which was previously shown to enhanced drought resistance in Arabidopsis  negatively regulates drought responses when overexpressed in Arabidopsis. GIGANTEA (GI), a plant specific nuclear protein, is a key component of flowering time regulation but is also known to be involved in a multitude of physiological responses. Finally, Li et al. report that mutation of Oryza sativa GI confers tolerance to osmotic stress and regulates transcript abundance of some gene encoding ABA-induced proteins. Tolerance to salinity and high temperature is also reviewed by HanumanthaRao et al. who presented an integrative view of mungbean responses from physiological, biochemical, and molecular aspects to agronomical perspectives and field management practices. Lastly, although Boron is considered as an essential micronutrients for plants, abnormal concentrations can be toxic and limit crop productivity. Fang et al. report that boron could alter calcium signaling and actin filament organization thus impacting on plant development . In addition to their essential function in plant primary metabolism, several molecules have now been considered as signal molecules. For instance, the signaling function of sugars has become the focus of numerous research efforts. Nguyen et al. using transgenic plants overexpressing sucrose synthase, reveal a novel sugar signaling pathway controlling pronounced phenotypic changes in tobacco. We can expect that future research will confirm the role of sugars throughout all stages of the plant's life cycle since sugar-signaling pathways could interact with other stimuli such as phytohormones or light , widely considered as detrimental, also emerges as signaling molecule in plants. The review of Wang and Liao provides brief update on its role in growth, development and abiotic stress tolerance. CO has a positive effects on salt or heavy metal stresses in relation with other signaling molecules, such as phytohormones or NO and ROS. Last but not least, research conducted by Kim et al. reveals links between N metabolism and epigenetics (gene methylation). They report that ammonium treatment inhibits chromomethylase 3-mediated methylation of the gene encoding one of the two nitrate reductase isoform (Nia2) in Arabidopsis. These results bring new insights concerning the regulation of nitrate assimilation and its signaling properties and open interesting perspectives for the role of epigenetics in plant responses to stress.Under a changing climate, drought becomes one of the most critical abiotic stresses that severely reduces crop production. Molecular mechanisms involved in plant drought adaptation are addressed in several articles/contributions. Reversible protein phosphorylation, catalyzed by antagonistic activities of protein kinases and phosphatases, is a predominant molecular switch controlling the outcome of cell signaling after stress perception. Durian et al. provide an overview of the Protein Phosphatase 2A (PP2A) functions, a crucial component that controls pathogenic responses in various plant species. The authors describe, in an exhaustive manner, the connections of these multifunctional enzymes with the signaling pathway that controls plant immunity, cell death and more globally primary and secondary metabolism. Using an elegant biochemical and targeted approach, Sheikh et al. reveal a post-translational regulation of AtWKRY46 transcription factor by a MAPK3-dependent phosphorylation that mediates the stability of this transcription factor after PAMP elicitation in Arabidopsis. It is noteworthy that knowledge about plant molecular responses to biotic stress is obtained from model plants as well as from cultivated species. Thus, this topic reports the identification of regulators of plant immunity in different economically important crops. In soybean, Cheng et al. report the characterization of a novel member of the isoflavone reductase gene family, GmIFR, regulated by phytohormones  and involved in the resistance to the oomycete Phytophthora sojae. Using a quite similar functionally transgenic approach, Dai et al. have identified and characterized a new defense protein PR4-1 from a wild chinese grape Vitis pseudoreticula. When overexpressed in Vitis vinifera, it improved tolerance to powdery mildew. RNAseq methodology is now widely used to investigate gene expression in response to microbes in non-model species. Based on the analysis of the differentially expressed genes, Gao et al. propose a model illustrating the main molecular responses and gum polysaccharide formation in peach tree (Prunus persica) infected by Lasiodiplodia theobromae, the fungal agent of peach tree gummosis.Biotic stresses also cause major losses in crop productivity. Deciphering mechanisms involved in plant defense to pathogens will help to develop breeding and biotechnological strategies for crop protection. Yuan et al. compare by a RNAseq approach two symbiotic systems with notable different nodulation phenotypes in soybean roots. Many of the differentially expressed genes identified are related to plant immunity and could explain the different nodulation phenotypes. Their work highlights the delicate balance between beneficial and detrimental effects of microbes and, as written by the authors, it “sheds new light on the host legume control of nodulation specificity.”Ranty et al. provide a broad perspective on the role of Ca 2+ in plant responses to abiotic and biotic stress. The specific effects of this ubiquitous second messenger and the role of calcium sensor proteins are discussed. The authors put forward hypotheses to explain one crucial question of cell signaling: how are signals perceived and how do cells respond spatially and temporally to these signals to program a specific response at the organism level? More specifically, Sinha et al. have examined the transcriptome dynamics in chickpea plants exposed to a combination of water deficit stress and Ralstonia solanacearum infection and have identified a set of genes uniquely expressed in response to combined stress. Also comparing pathogenic and drought stress but focusing on the analysis of redox homeostasis and the role phytohormones, Cui et al. show that co-stress by virus and drought had much severer effects than single stress in V. vinifera. Finally, Singh and Jha have studied crosstalk between salt stress and the bacteria Bacillus licheniformis HSW-16. They report biochemical and physiological characterization associated with bacteria-induced systemic tolerance to salt stress.Crosstalk between abiotic and biotic stress responses are the last aspect developed in this topic. Comparative approaches can be interesting to test the hypotheses of common signaling pathways and of physiological responses that are subject to pleiotropic gene action. In a mini-review article, In conclusion, this Research Topic provides new results and reviews on the signaling pathways induced by abiotic and biotic environmental changes such as drought, high salinity, nutrient, pollutants, or microbial attacks. We think that the diversity of methodology, biological models, and physiological context used to decipher and understand these complex molecular mechanisms at the whole plant level will allow the development of sustainable practices and re-orientation of agricultural managements to improve stress tolerance in crops.All authors listed have made a 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.