A comprehensive review of the biodiversity of freshwater fish species in Valleys worldwide and in the Kingdom of Saudi Arabia.

An overview of freshwater fish variety worldwide and the variables influencing trends in variation between and within river basins are given in this review. Continental freshwater ecosystems are highly diverse and species-rich, housing nearly 18,000 species of fish (=50% of all fish species) in <0.5% of the total land area and providing a negligible (<0.01%) share of the planet's water supply. Large lowland tropical river basins such as the Amazon, Congo, and Mekong basins are home to the greatest freshwater fish diversity. Freshwater species of fish depth variation at the global magnitude is correlated with the total amount and variation of aquatic habitats and the environment's equilibrium overtime during the evolution of scales. The river continuum concept states that there is a predictable shift in fish species depth, diversity of species, and functional characteristics along gradients of environment from headwater to estuary. The ongoing trade of minerals and organic matter related to nearby floodplains is a strong factor in the number and variety of riverine fishes in most parts of the world (the flood pulse concept). Without coordinated conservation efforts, freshwater fishes will suffer significant losses in abundance and diversity due to the numerous threats they currently face worldwide. However, further development, adaptation, training, and guidance are needed. New technologies based on water conservation, suitable species, and local traditions are needed. Waste materials and local feed additives can also be used. Farmers should be provided with the necessary training and information.

Soils of two Antarctic Dry Valleys exhibit unique microbial community structures in response to similar environmental disturbances.

BACKGROUND: Isolating the effects of deterministic variables (e.g., physicochemical conditions) on soil microbial communities from those of neutral processes (e.g., dispersal) remains a major challenge in microbial ecology. In this study, we disturbed soil microbial communities of two McMurdo Dry Valleys of Antarctica exhibiting distinct microbial biogeographic patterns, both devoid of aboveground biota and different in macro- and micro-physicochemical conditions. We modified the availability of water, nitrogen, carbon, copper ions, and sodium chloride salts in a laboratory-based experiment and monitored the microbial communities for up to two months. Our aim was to mimic a likely scenario in the near future, in which similar selective pressures will be applied to both valleys. We hypothesized that, given their unique microbial communities, the two valleys would select for different microbial populations when subjected to the same disturbances. RESULTS: The two soil microbial communities, subjected to the same disturbances, did not respond similarly as reflected in both 16S rRNA genes and transcripts. Turnover of the two microbial communities showed a contrasting response to the same environmental disturbances and revealed different potentials for adaptation to change. These results suggest that the heterogeneity between these microbial communities, reflected in their strong biogeographic patterns, was maintained even when subjected to the same selective pressure and that the 'rare biosphere', at least in these samples, were deeply divergent and did not act as a reservoir for microbiota that enabled convergent responses to change in environmental conditions. CONCLUSIONS: Our findings strongly support the occurrence of endemic microbial communities that show a structural resilience to environmental disturbances, spanning a wide range of physicochemical conditions. In the highly arid and nutrient-limited environment of the Dry Valleys, these results provide direct evidence of microbial biogeographic patterns that can shape the communities' response in the face of future environmental changes.

A Strategic Guide to Improve and De-Risk Vaccine Development: CEPI's CMC Framework.

The Coalition for Epidemic Preparedness Innovations (CEPI) has developed a robust CMC (Chemistry, Manufacturing, and Controls) Framework to enhance the likelihood of successful vaccine development. This Framework serves as a comprehensive guide, aiding developers in building effective strategies to overcome the challenges posed by the different phases of vaccine development, including the ones often referred to as the "valleys of death". The Framework lists stage-appropriate deliverables, categorized and refined, spanning five key areas: manufacturing process, formulation and stability, analytics, supply chain, and compliance. By emphasizing the critical aspects of CMC development, CEPI's objective is to expedite the progression of vaccine candidates from research to deployment, reducing delays, mitigating risks, and optimizing the overall development process, all while upholding uncompromising quality standards, ultimately increasing the probability of success.

Effect of montmorillonite modified straw biochar on transfer behavior of lead and copper in the historical mining areas of dry-hot valleys.

Due to the rapid development of human beings, heavy metals are occurred in the Yunnan-Guizhou Plateau and Panxi Plateau, the special dry and hot climate areas. Pb and Cu can be quickly transferred through water-plant-animal, further harm to human health by food chain. Therefore, the study of heavy metal treatment is imminent. In this study, Biochar-montmorillonite composites were prepared by co-pyrolysis and characterized, and their ability to remove lead and copper from water-soil process were tracked. And their effectiveness in remediating soil contaminated by lead and copper was documented. The composite material has the rich pore structure, large specific surface area (81.5 m2/g) and a variety of surface functional groups such as C-C, CO, ester-metal and metal-oxygen bonds. Pb and Cu can be effectively adsorbed and fixed to the level of no harm to human health. The adsorption reaction of lead and copper on the Biochar-montmorillonite composites is more suitable to be described by Langmuir adsorption and pseudo-second-order kinetics models. The saturation adsorption capacity of the composite for Pb was measured as 212.5 mg/g. For Cu, it was 136.5 mg/g. The data were fitted by a two-compartment first-order kinetic model. ffast for Pb and Cu is estimated to be 0.81 and 0.78, respective. Fast adsorption is dominant and belongs to typical chemical adsorption, which is consistent with the second-order kinetic results. With 5 % of the composite, approximately 80 % of exchangeable heavy metals in those soils collected from the Yunnan-Guizhou Plateau and Panxi Plateau were reduced. The biochar-montmorillonite composites made Pb and Cu change to stable residual state, up to 35 %. Besides, it effectively restored the activity of urease and sucrase in soils. Results indicated that biochar-montmorillonite composites can be effectively used as an environment-friendly adsorbent or passivator to purify heavy metals in soils.

Microbial diversity in Antarctic Dry Valley soils across an altitudinal gradient.

Introduction: The Antarctic McMurdo Dry Valleys are geologically diverse, encompassing a wide variety of soil habitats. These environments are largely dominated by microorganisms, which drive the ecosystem services of the region. While altitude is a well-established driver of eukaryotic biodiversity in these Antarctic ice-free areas (and many non-Antarctic environments), little is known of the relationship between altitude and microbial community structure and functionality in continental Antarctica. Methods: We analysed prokaryotic and lower eukaryotic diversity from soil samples across a 684 m altitudinal transect in the lower Taylor Valley, Antarctica and performed a phylogenic characterization of soil microbial communities using short-read sequencing of the 16S rRNA and ITS marker gene amplicons. Results and Discussion: Phylogenetic analysis showed clear altitudinal trends in soil microbial composition and structure. Cyanobacteria were more prevalent in higher altitude samples, while the highly stress resistant Chloroflexota and Deinococcota were more prevalent in lower altitude samples. We also detected a shift from Basidiomycota to Chytridiomycota with increasing altitude. Several genera associated with trace gas chemotrophy, including Rubrobacter and Ornithinicoccus, were widely distributed across the entire transect, suggesting that trace-gas chemotrophy may be an important trophic strategy for microbial survival in oligotrophic environments. The ratio of trace-gas chemotrophs to photoautotrophs was significantly higher in lower altitude samples. Co-occurrence network analysis of prokaryotic communities showed some significant differences in connectivity within the communities from different altitudinal zones, with cyanobacterial and trace-gas chemotrophy-associated taxa being identified as potential keystone taxa for soil communities at higher altitudes. By contrast, the prokaryotic network at low altitudes was dominated by heterotrophic keystone taxa, thus suggesting a clear trophic distinction between soil prokaryotic communities at different altitudes. Based on these results, we conclude that altitude is an important driver of microbial ecology in Antarctic ice-free soil habitats.

DNA repair enzymes of the Antarctic Dry Valley metagenome.

Microbiota inhabiting the Dry Valleys of Antarctica are subjected to multiple stressors that can damage deoxyribonucleic acid (DNA) such as desiccation, high ultraviolet light (UV) and multiple freeze-thaw cycles. To identify novel or highly-divergent DNA-processing enzymes that may enable effective DNA repair, we have sequenced metagenomes from 30 sample-sites which are part of the most extensive Antarctic biodiversity survey undertaken to date. We then used these to construct wide-ranging sequence similarity networks from protein-coding sequences and identified candidate genes involved in specialized repair processes including unique nucleases as well as a diverse range of adenosine triphosphate (ATP) -dependent DNA ligases implicated in stationary-phase DNA repair processes. In one of the first direct investigations of enzyme function from these unique samples, we have heterologously expressed and assayed a number of these enzymes, providing insight into the mechanisms that may enable resident microbes to survive these threats to their genomic integrity.

Magnetoelectric tuning of spin, valley, and layer-resolved anomalous Nernst effect in transition-metal dichalcogenides bilayers.

The anomalous Nernst coefficient (ANC) for transition-metal dichalcogenide (TMD) bilayers is studied with a focus on the interplay between layer pseudospin, spin, and valley degrees of freedom when electric and exchange fields are present. Breaking the inversion and time reversal symmetries via respectively electric and exchange fields results for bilayer TMDs in a spin-valley-layer polarized total ANC. Conditions are determined for controlling the spin, valley, and layer-resolved contributions via electric field tuning. Our results demonstrate the control of layer degree of freedom in bilayer TMDs magnetoelectrically which is of relevance for possible applications in spin/valley caloritronics.

Semiconductor Characterization by Terahertz Excitation Spectroscopy.

Surfaces of semiconducting materials excited by femtosecond laser pulses emit electromagnetic waves in the terahertz (THz) frequency range, which by definition is the 0.1-10 THz region. The nature of terahertz radiation pulses is, in the majority of cases, explained by the appearance of ultrafast photocurrents. THz pulse duration is comparable with the photocarrier momentum relaxation time, thus such hot-carrier effects as the velocity overshoot, ballistic carrier motion, and optical carrier alignment must be taken into consideration when explaining experimental observations of terahertz emission. Novel commercially available tools such as optical parametric amplifiers that are capable of generating femtosecond optical pulses within a wide spectral range allow performing new unique experiments. By exciting semiconductor surfaces with various photon energies, it is possible to look into the ultrafast processes taking place at different electron energy levels of the investigated materials. The experimental technique known as the THz excitation spectroscopy (TES) can be used as a contactless method to study the band structure and investigate the ultrafast processes of various technologically important materials. A recent decade of investigations with the THz excitation spectroscopy method is reviewed in this article. TES experiments performed on the common bulk A3B5 compounds such as the wide-gap GaAs, and narrow-gap InAs and InSb, as well as Ge, Te, GaSe and other bulk semiconductors are reviewed. Finally, the results obtained by this non-contact technique on low-dimensional materials such as ultrathin mono-elemental Bi films, InAs, InGaAs, and GaAs nanowires are also presented.

Antarctic permafrost degassing in Taylor Valley by extensive soil gas investigation.

Ongoing studies conducted in northern polar regions reveal that permafrost stability plays a key role in the modern carbon cycle as it potentially stores considerable quantities of greenhouse gases. Rapid and recent warming of the Arctic permafrost is resulting in significant greenhouse gas emissions, both from physical and microbial processes. The potential impact of greenhouse gas release from the Antarctic region has not, to date, been investigated. In Antarctica, the McMurdo Dry Valleys comprise 10 % of the ice-free soil surface areas in Antarctica and like the northern polar regions are also warming albeit at a slower rate. The work presented herein examines a comprehensive sample suite of soil gas (e.g., CO2, CH4 and He) concentrations and CO2 flux measurements conducted in Taylor Valley during austral summer 2019/2020. Analytical results reveal the presence of significant concentrations of CO2, CH4 and He (up to 3.44 vol%, 18,447 ppmv and 6.49 ppmv, respectively) at the base of the active layer. When compared with the few previously obtained measurements, we observe increased CO2 flux rates (estimated CO2 emissions in the study area of 21.6 km2 ≈ 15 tons day-1). We suggest that the gas source is connected with the deep brines migrating from inland (potentially from beneath the Antarctic Ice Sheet) towards the coast beneath the permafrost layer. These data provide a baseline for future investigations aimed at monitoring the changing rate of greenhouse gas emissions from Antarctic permafrost, and the potential origin of gases, as the southern polar region warms.

The spatial distribution and biogeochemical drivers of nitrogen cycle genes in an Antarctic desert.

Antarctic deserts, such as the McMurdo Dry Valleys (MDV), represent extremely cold and dry environments. Consequently, MDV are suitable for studying the environment limits on the cycling of key elements that are necessary for life, like nitrogen. The spatial distribution and biogeochemical drivers of nitrogen-cycling pathways remain elusive in the Antarctic deserts because most studies focus on specific nitrogen-cycling genes and/or organisms. In this study, we analyzed metagenome and relevant environmental data of 32 MDV soils to generate a complete picture of the nitrogen-cycling potential in MDV microbial communities and advance our knowledge of the complexity and distribution of nitrogen biogeochemistry in these harsh environments. We found evidence of nitrogen-cycling genes potentially capable of fully oxidizing and reducing molecular nitrogen, despite the inhospitable conditions of MDV. Strong positive correlations were identified between genes involved in nitrogen cycling. Clear relationships between nitrogen-cycling pathways and environmental parameters also indicate abiotic and biotic variables, like pH, water availability, and biological complexity that collectively impose limits on the distribution of nitrogen-cycling genes. Accordingly, the spatial distribution of nitrogen-cycling genes was more concentrated near the lakes and glaciers. Association rules revealed non-linear correlations between complex combinations of environmental variables and nitrogen-cycling genes. Association rules for the presence of denitrification genes presented a distinct combination of environmental variables from the remaining nitrogen-cycling genes. This study contributes to an integrative picture of the nitrogen-cycling potential in MDV.

Glacial Legacies: Microbial Communities of Antarctic Refugia.

In the cold deserts of the McMurdo Dry Valleys (MDV) the suitability of soil for microbial life is determined by both contemporary processes and legacy effects. Climatic changes and accompanying glacial activity have caused local extinctions and lasting geochemical changes to parts of these soil ecosystems over several million years, while areas of refugia may have escaped these disturbances and existed under relatively stable conditions. This study describes the impact of historical glacial and lacustrine disturbance events on microbial communities across the MDV to investigate how this divergent disturbance history influenced the structuring of microbial communities across this otherwise very stable ecosystem. Soil bacterial communities from 17 sites representing either putative refugia or sites disturbed during the Last Glacial Maximum (LGM) (22-17 kya) were characterized using 16 S metabarcoding. Regardless of geographic distance, several putative refugia sites at elevations above 600 m displayed highly similar microbial communities. At a regional scale, community composition was found to be influenced by elevation and geographic proximity more so than soil geochemical properties. These results suggest that despite the extreme conditions, diverse microbial communities exist in these putative refugia that have presumably remained undisturbed at least through the LGM. We suggest that similarities in microbial communities can be interpreted as evidence for historical climate legacies on an ecosystem-wide scale.

Dynamic DNA methylation changes reveal tissue-specific gene expression in sugarcane.

DNA methylation is an important mechanism for the dynamic regulation of gene expression and silencing of transposons during plant developmental processes. Here, we analyzed genome-wide methylation patterns in sugarcane (Saccharum officinarum) leaves, roots, rinds, and piths at single-base resolution. DNA methylation patterns were similar among the different sugarcane tissues, whereas DNA methylation levels differed. We also found that DNA methylation in different genic regions or sequence contexts plays different roles in gene expression. Differences in methylation among tissues resulted in many differentially methylated regions (DMRs) between tissues, particularly CHH DMRs. Genes overlapping with DMRs tended to be differentially expressed (DEGs) between tissues, and these DMR-associated DEGs were enriched in biological pathways related to tissue function, such as photosynthesis, sucrose synthesis, stress response, transport, and metabolism. Moreover, we observed many DNA methylation valleys (DMVs), which always overlapped with transcription factors (TFs) and sucrose-related genes, such as WRKY, bZIP, WOX, SPS, and FBPase. Collectively, these findings provide significant insights into the complicated interplay between DNA methylation and gene expression and shed light on the epigenetic regulation of sucrose-related genes in sugarcane.

The influence of sedimentation regime on natural radionuclide activity concentration in marine sediments of the East Siberian Arctic Shelf.

Transport and accumulation of radionuclides in the Arctic depends on many biogeochemical processes, which are changing at accelerated rates due to climate change and human economic activity. We present the results of a study on the features distribution of some natural radionuclides in the marine sediments on the East Siberian Arctic Shelf collected during several expeditions from 2008 to 2019. Average activity concentration of 232Th, 40K and 226Ra under the influence of different sedimentation regime increases from 40.7, 418 and 30.8 Bq/kg to 41.6, 423 and 34.9 Bq/kg respectively from coastal shelf marine sediments (<50% clay) to outer shelf marine sediments (>50% clay). Sediment particle size has a greater impact on radionuclides in the coastal shelf. An increase in the activity concentrations of 232Th and 226Ra with the increasing clay particles were found. On the outer shelf with a change in the sedimentation regime, the influence of the size composition decreased, at the same time, there is a correlation between the organic carbon concentration and the radionuclide activity concentration. Absolute maximums of natural radionuclide activity concentration (232Th = 70.9, 226Ra = 70.4, 40K = 591 Bq/kg) were detected in the Chaun Bay. The highest activity concentration of 226Ra was found in paleo-river valleys marine sediments. A low 232Th/226Ra activity concentration ratio indicates the enrichment of paleo-river valleys marine sediments with 226Ra. In the deep-sea sediments of the shelf slope on the contrary paleo-river valleys, this ratio is greatly increased.

Survey for Major Grapevine Viruses in Commercial Vineyards of Northwestern Argentina.

This study aimed to survey the occurrence of eight grapevine viruses in commercial vineyards located in the Calchaquíes Valleys in the northwest region of Argentina. A total of 103 samples of mature canes of vines showing either none or some viral-like symptoms were randomly collected. The samples were tested by RT-PCR/PCR-based assays for the screening of the following viruses: Grapevine fanleaf virus (GFLV), Grapevine leafroll-associated viruses (GLRaV-1, -2, -3, -4), Grapevine virus A (GVA), Grapevine rupestris stem pitting-associated viruses (GRSPaV), and Grapevine red blotch virus (GRBV). Sixty percent of the analyzed samples showed infection with some of the analyzed viruses, except GRBV. GLRaV-3 and GFLV were the most frequent viruses, present in 34% and 21% of the positive samples, respectively. This study represents the first survey report of the presence of grapevine viruses in the region of the Calchaquíes Valleys and contributes to the knowledge to maintain the sanitary status of commercial vineyards in Argentina.

Phosphorus Shapes Soil Microbial Community Composition and Network Properties During Grassland Expansion Into Shrubs in Tibetan Dry Valleys.

Alpine ecosystem stability and biodiversity of the Tibetan plateau are facing threat from dry valley vegetation uplift expansion, a process which is highly connected to variations in the soil microbial community and soil nutrients. However, the variation of microbial community properties and their relationship to soil nutrients have scarcely been explored in Tibetan dry valleys, which is a gap that hampers understanding the dry valley ecosystem's response to vegetation change. In this study, we sampled grasslands (G), a grass-shrub transition area (T), and shrublands (S) along an uplift expansion gradient and investigated the link between microbial community properties and soil nutrients. The results showed that shrub degradation by grass expansion in Tibetan dry valley was accompanied by increasing relative phosphorus (P) limitation, which was the main driver for bacterial and fungal composition variation as it offered highest total effect on PC1 (0.38 and 0.63, respectively). Total phosphorus (TP) was in the center module of bacterial and fungal network under shrub soil and even acted as key nodes in fungal networks. During the replacement by grass, TP was gradually marginalized from both bacterial and fungal center network module and finally disappeared in networks, with ammonia and nitrate gradually appearing in the bacterial network. However, TC and total nitrogen (TN) were always present in the center modules of both fungal and bacterial network. These support that a TP variation-induced compositional and network functional shift in the microbial community was a potential reason for vegetation uplift expansion in Tibetan dry valley. This study highlighted the effect of TP on microbial community properties during dry valley vegetation uplift expansion and offered basic information on Tibetan alpine dry valley ecosystem's response to climate change.

Observation of Remote Electroconvection and Inert-Cation Concentration Valley within Supporting Electrolytes in a Microfluidic-Based Electrochemical Device.

The electrochemical system is playing an increasingly important role in the advanced technology development for drinkable water and energy storage. While the binary electrolyte has been widely studied, such as the associated intriguing interfacial instabilities, multi-component electrolyte is by far less known. Here, based on the classic Cu|CuSO4 |Cu electrochemical system, the effect of supporting electrolyte is systematically investigated by highlighting the inert cations. In an annulus microfluidic device, the suppression of a previously known electro-osmotic instability and the emergence of an array of the remote electroconvection along the azimuthal direction is found. A distinctive inert-cation concentration valley propagates radially outward at a speed limited by the electromigration velocity. Remarkably, the simultaneous visualization of spatiotemporal evolution demonstrates the correlation of the concentration valley and electroconvection at a microscopic level. The underlying physical mechanism of their correlation is discussed, and the scaling analysis agrees with experiments. This work might inspire more future work on the multi-component electrolyte, such as for the suppression of interfacial hydrodynamic instability and mitigation of dendrite growth, with the technological implications for water treatment and energy storage in batteries.

Epigenetic regulation of seed-specific gene expression by DNA methylation valleys in castor bean.

BACKGROUND: Understanding the processes governing angiosperm seed growth and development is essential both for fundamental plant biology and for agronomic purposes. Master regulators of angiosperm seed development are expressed in a seed-specific manner. However, it is unclear how this seed specificity of transcription is established. In some vertebrates, DNA methylation valleys (DMVs) are highly conserved and strongly associated with key developmental genes, but comparable studies in plants are limited to Arabidopsis and soybean. Castor bean (Ricinus communis) is a valuable model system for the study of seed biology in dicots and source of economically important castor oil. Unlike other dicots such as Arabidopsis and soybean, castor bean seeds have a relatively large and persistent endosperm throughout seed development, representing substantial structural differences in mature seeds. Here, we performed an integrated analysis of RNA-seq, whole-genome bisulfite sequencing, and ChIP-seq for various histone marks in the castor bean. RESULTS: We present a gene expression atlas covering 16 representative tissues and identified 1162 seed-specific genes in castor bean (Ricinus communis), a valuable model for the study of seed biology in dicots. Upon whole-genome DNA methylation analyses, we detected 32,567 DMVs across five tissues, covering ~33% of the castor bean genome. These DMVs are highly hypomethylated during development and conserved across plant species. We found that DMVs have the potential to activate transcription, especially that of tissue-specific genes. Focusing on seed development, we found that many key developmental regulators of seed/endosperm development, including AGL61, AGL62, LEC1, LEC2, ABI3, and WRI1, were located within DMVs. ChIP-seq for five histone modifications in leaves and seeds clearly showed that the vast majority of histone modification peaks were enriched within DMVs, and their remodeling within DMVs has a critical role in the regulation of seed-specific gene expression. Importantly, further experiment analysis revealed that distal DMVs may act as cis-regulatory elements, like enhancers, to activate downstream gene expression. CONCLUSIONS: Our results point to the importance of DMVs and special distal DMVs behaving like enhancers, in the regulation of seed-specific genes, via the reprogramming of histone modifications within DMVs. Furthermore, these results provide a comprehensive understanding of the epigenetic regulator roles in seed development in castor bean and other important crops.

Limits to the three domains of life: lessons from community assembly along an Antarctic salinity gradient.

Extremophiles exist among all three domains of life; however, physiological mechanisms for surviving harsh environmental conditions differ among Bacteria, Archaea and Eukarya. Consequently, we expect that domain-specific variation of diversity and community assembly patterns exist along environmental gradients in extreme environments. We investigated inter-domain community compositional differences along a high-elevation salinity gradient in the McMurdo Dry Valleys, Antarctica. Conductivity for 24 soil samples collected along the gradient ranged widely from 50 to 8355 µS cm-1. Taxonomic richness varied among domains, with a total of 359 bacterial, 2 archaeal, 56 fungal, and 69 non-fungal eukaryotic operational taxonomic units (OTUs). Richness for bacteria, archaea, fungi, and non-fungal eukaryotes declined with increasing conductivity (all P < 0.05). Principal coordinate ordination analysis (PCoA) revealed significant (ANOSIM R = 0.97) groupings of low/high salinity bacterial OTUs, while OTUs from other domains were not significantly clustered. Bacterial beta diversity was unimodally distributed along the gradient and had a nested structure driven by species losses, whereas in fungi and non-fungal eukaryotes beta diversity declined monotonically without strong evidence of nestedness. Thus, while increased salinity acts as a stressor in all domains, the mechanisms driving community assembly along the gradient differ substantially between the domains.

Improving Translational Paradigms in Drug Discovery and Development.

Despite improved knowledge regarding disease causality, new drug targets, and enabling technologies, the attrition rate for compounds entering clinical trials has remained consistently high for several decades, with an average 90% failure rate. These failures are manifested in an inability to reproduce efficacy findings from animal models in humans and/or the occurrence of unexpected safety issues, and reflect failures in T1 translation. Similarly, an inability to sequentially demonstrate compound efficacy and safety in Phase IIa, IIb, and III clinical trials represents failures in T2 translation. Accordingly, T1 and T2 translation are colloquially termed 'valleys of death'. Since T2 translation dealt almost exclusively with clinical trials, T3 and T4 translational steps were added, with the former focused on facilitating interactions between laboratory- and population-based research and the latter on 'real world' health outcomes. Factors that potentially lead to T1/T2 compound attrition include: the absence of biomarkers to allow compound effects to be consistently tracked through development; a lack of integration/'de-siloing' of the diverse discipline-based and technical skill sets involved in drug discovery; the industrialization of drug discovery, which via volume-based goals often results in quantity being prioritized over quality; inadequate project governance and strategic oversight; and flawed decision making based on unreliable/irreproducible or incomplete data. A variety of initiatives have addressed this problem, including the NIH National Center for Advancing Translational Sciences (NCATS), which has focused on bringing an unbiased academic perspective to translation, to potentially revitalize the process. This commentary provides an overview of the basic concepts involved in translation, along with suggested changes in the conduct of biomedical research to avoid valleys of death, including the use of Translational Scoring as a tool to avoid translational attrition and the impact of the FDA Accelerated Approval Pathway in lowering the hurdle for drug approval. © 2021 Wiley Periodicals LLC.

Ephemeroptera (Mayflies) Assemblages and Environmental Variation along Three Streams Located in the Dry-Hot Valleys of Baima Snow Mountain, Yunnan, Southwest China.

Mountain freshwater ecosystems are threatened all over the world by a range of human-induced stresses, ensuing in a rapid loss of habitats and species diversity. Many macroinvertebrates are reactive to habitat disturbance, and mayflies (Ephemeroptera) are amongst the most sensitive groups. Despite they are susceptible to environmental deviation, knowledge concerning their species richness and diversity is still unknown in remote areas. The objectives of this study were to (1) investigate the mayfly species assemblage and community composition along different mountain streams and assess potential differences, and (2) identify the environmental variation and its influence on the structure of mayfly communities within such freshwater systems. We collected biological and environmental data from 35 sites situated along elevation gradients in the Baima Snow Mountain, northwest Yunnan, China. Multivariate analyses were performed on the environmental variables and the mayfly species composition, as well as on richness and diversity indices. We found that the community composition of mayflies was different across all three watercourses. Among the 18 Ephemeroptera taxa identified, Baetis sp. and Baetiella marginata were highly dominant, accounting for over 50% of the dissimilarity of each stream. In terms of species assemblages, almost all sites in the Yeri stream hosted good-quality habitats for several mayfly species, as reflected by the highest species richness. The Benzilan stream followed, whereas the Sharong stream showed relatively low mayfly assemblage. This variation was explained by the high environmental heterogeneity between the three watercourses. In particular, the RDA model revealed that among the different environmental factors analyzed, altitude, conductivity, total dissolved solids, water temperature, dissolved silicon, and pH explained most of the variation in species composition. Moreover, the altitude alone explained 17.74% of the variation, and in-depth analysis confirmed its significant effect on diversity indices. Further research should focus on evaluating the scale of threats to this important group of insects in the mountain freshwater ecosystem, particularly the impact of human-induced disturbances such as land use/landcover alterations.