Multiple Lines Of Evidence Research Articles

Functional genomics implicates natural killer cells in the pathogenesis of ankylosing spondylitis

Multiple lines of evidence indicate that ankylosing spondylitis (AS) is a lymphocyte-driven disease. However, which lymphocyte populations are critical in AS pathogenesis is not known. In this study, we aimed to identify the key cell types mediating the genetic risk in AS using an unbiased functional genomics approach. We integrated genome-wide association study (GWAS) data with epigenomic and transcriptomic datasets of human immune cells. To quantify enrichment of cell type-specific open chromatin or gene expression in AS risk loci, we used three published methods - LDSC-SEG, SNPsea, scDRS - that have successfully identified relevant cell types in other diseases. Natural killer (NK) cell-specific open chromatin regions are significantly enriched in heritability for AS, compared to other immune cell types such as T cells, B cells, and monocytes. This finding was consistent between two AS GWAS. Using RNA-seq data, we validated that genes in AS risk loci are enriched in NK cell-specific gene expression. Using the human Space-Time Gut Cell Atlas, we also found significant upregulation of AS-associated genes predominantly in NK cells. We performed co-localization analyses between GWAS risk loci and genetic variants associated with gene expression (eQTL) to find putative target genes. This revealed four AS risk loci affecting regulation of candidate target genes in NK cells: two known loci, ERAP1 and TNFRSF1A, and two under-studied loci, ENTR1 (aka SDCCAG3) and B3GNT2. Our findings suggest that NK cells may play a crucial role in AS development and highlight four putative target genes for functional follow-up in NK cells.

Multiple Machine Learning Models, Molecular Subtyping and Singlecell Analysis Identify PANoptosis-related Core Genes and their Association with Subtypes in Crohn's Disease.

PANoptosis plays an important role in many inflammatory diseases. However, there are no reports on the association between PANoptosis and CD. This study used five machine learning algorithms - least absolute shrinkage and selection operator, support vector machine, random forest, decision tree and Gaussian mixture models - to construct CD's PANoptosis signature. Unsupervised hierarchical clustering analysis was used to identify PANoptosis-associated subgroups of CD. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were conducted to compare the PANoptosis-associated subgroups of CD among the potential biological mechanisms. Single sample GSEA was used to assess immune microenvironmental differences among the subgroups. The potential role of PANoptosis in CD was further explored using single-cell RNA-Seq (scRNA-Seq) for PANoptosis scoring, differential analysis, pseudotime analysis, cellular communication analysis and weighted gene co-expression network analysis (WGCNA) analysis. CD's PANoptosis signature consisted of seven genes: CEACAM6, CHP2, PIK3R1, CASP10, PSMB1, PSMB8 and UBC. The PANoptosis signature in multiple cohorts had a strong ability to recognise CD. The levels of immune cell infiltration and the vigour of the immune responses significantly varied between the two subpopulations of CD associated with PANoptosis. Multiple lines of evidence from the GO, KEGG, GSEA, GSVA, scRNA-Seq and WGCNA analyses suggested that I-kappaB kinase/NF- kappaB signalling, mitogen-activated protein kinase (MAPK), leukocyte activation and leukocyte migration were mechanisms closely associated with PANoptosis in CD. This study is the first to construct a PANoptosis signature with excellent efficacy in recognising CD. PANoptosis may mediate the process of CD through inflammatory and immune mechanisms, such as NF- kappaB, MAPK and leukocyte migration.

A New Dawn for Protist Biogeography

ABSTRACTAimBiogeographers have believed for a long time that the geographical distributions of protists are only determined by environmental conditions, because dispersal is not limited. During the past two decades, the field has come a long way to show that historical and spatial factors also significantly contribute to shaping protist distributions, calling for a reappraisal of our understanding of protist biogeography.MethodsWe review the current state‐of‐the‐art on the field of protist biogeography, highlighting several outstanding questions and opportunities. Our review brings together insights from different disciplines, ranging from morphology‐based research to environmental, population and speciation genomics.ResultsProtist communities harbour cosmopolitan and geographically restricted species and are shaped by both local environmental conditions and historical processes, yet the relative contributions of these patterns and processes likely differs depending on the geographic scale, protist lineage and the habitat that is being investigated. The field is ready to move beyond the decades‐long ubiquity versus (moderate) endemicity discourse and to instead ask why and where specific protist species and clades are more prone to widespread or restricted distributions. With the advent of next‐generation sequencing technologies, from whole‐genome sequencing to environmental and ancient DNA surveys, it is now possible to integrate insights from multiple lines of evidence and investigate protist communities, species and populations at an unprecedented scale and detail.OutlookTo further advance the field, the protist community needs to focus on understudied habitats and protist lineages, study the impact of protist traits on biogeographical patterns, perform targeted field and experimental work to disentangle the processes that underlie protist biogeographies and expand and develop databases with sequence, trait, distributional and phylogenetic information of protists. Given that a good understanding of species boundaries is central to unravelling protist biogeography, it remains crucial to invest in polyphasic taxonomic research.

A continental-wide decline of occupancy and diversity in five Neotropical carnivores

The Neotropics are a global biodiversity hotspot that has undergone dramatic land use changes over the last decades. However, a temporal perspective on the continental-wide distributions of species in this region is still missing. To unveil it, we model the entire area of occupancy of five Neotropical carnivore species at two time periods (2000–2013 and 2014–2021) using integrated species distribution models (ISDMs) in a Bayesian framework. The carnivores are the jaguarundi (Herpailurus yagouaroundi), margay (Leopardus wiedii), maned wolf (Chrysocyon brachyurus), tayra (Eira barbara), and giant otter (Pteronura brasiliensis). We mapped the temporal change, the areas where gains and losses accumulated for all species (hotspots of change) and calculated the temporal species turnover and change in spatial turnover. We show that (1) most carnivore species have declined their area of occupancy (i.e., range size) in the last two decades, (2) their diversity has decreased over time, mostly in the Chaco region, and (3) that hotspots of fast species composition turnover are in Chaco, the Caatinga region, and northwest of Mexico. We discuss how these newly identified hotspots of change overlap with regions of well-known and pronounced land use transformation. These estimated patterns of overall decline are alarming, more so given that four out of the five species had been classified as not threatened by IUCN. The official global threat status of these species may need to be re-evaluated. All this would be invisible if standard forecasts, local expert knowledge, or static threat criteria, such as range size, were used. We thus provide a new approach to evaluate past species range dynamics based on multiple lines of evidence, which can be employed over more species in the future, particularly in under-sampled regions.

Analysis of bigmouth buffalo Ictiobus cyprinellus spawning phenology in Minnesota reveals 50-year recruitment failure and conservation concern

The bigmouth buffalo Ictiobus cyprinellus (Catostomidae) is a freshwater fish native to North America that is known for its longevity. During the 1970s, the bigmouth buffalo was recorded as declining in Canada, Minnesota, and North Dakota and became a protected species in Canada. In the USA, population declines are exacerbated by wasteful recreational bowfishing, lack of fisheries management, and overall lack of knowledge. However, recent studies have revealed the exceptional lifespan of bigmouth buffalo, their negligible senescence, slow growth, delayed maturity, and episodic recruitment. Yet little is known about the spawning phenology of bigmouth buffalo, nor their age demographics in east central Minnesota. In this 2021–2023 study of bigmouth buffalo from Rice Lake National Wildlife Refuge we found that 99.7% (389 of 390) of the extant population hatched prior to 1972 despite annual spawning in Rice Lake. Moreover, recruitment success declined significantly since water control measures were established (1953). We found males arrive to spawning grounds with females but depart later, that both the midpoint and duration of spawn significantly vary across years, and that more massive females of the same age range invest disproportionately more in ovaries. Extensive post-spawn seining revealed bigmouth buffalo young-of-the-year in low numbers, but by mid-to-late summer they were no longer evident having likely succumbed to predation. Overall, these findings thoroughly reveal one of the oldest populations of vertebrate currently known (median age of 79 years as of 2024) and expose the stark vulnerability of a bigmouth buffalo population for which substantial recruitment has not occurred for more than six decades. Multiple lines of evidence indicate that the long-lived bigmouth buffalo is vulnerable, that a precautionary approach is immediately needed, and that the unlimited and unregulated kill-fishery be closed.

Neutrophil extracellular traps activate Notch–γ-secretase signaling in hidradenitis suppurativa

BackgroundHidradenitis suppurativa (HS) is an inflammatory chronic skin disorder of unknown etiology characterized by inflamed abscess-like nodules and boils resulting in sinus tract formation, tissue scarring and massive infiltration of neutrophils. Multiple lines of evidence have highlighted the potential association between alterations in the Notch pathway and HS pathogenesis, but the mechanisms remain incompletely characterized. ObjectiveHerein, we aim to elucidate the role of neutrophil extracellular traps in Notch-γ-secretase, signaling. MethodsTwenty-six HS lesional tissues, primary HS macrophages and skin fibroblasts were interrogated by quantitative PCR, western blot, and Elisa analyses. γ-Secretase, and TACE activities were measured in HS skin lesions, macrophages and skin fibroblasts. Immunofluorescence and RNAscope analyzes were performed in HS and control skin. ResultsA prominent presence of Notch ligands, DLL4 and JAG2 were detected at the protein and mRNA levels in HS skin lesion when compared to control. Levels of DLL4, JAG1, cit-H3-DNA and γ-secretase activity correlated with HS disease severity. Additionally, significantly elevated levels of Notch ligands and γ-secretase activity were found in dissected sinus tracts when compared to the rest of HS tissue. Immunofluorescence microscopy in HS skin lesions showed activation of Notch 1 signaling in macrophages and skin fibroblasts. Neutrophil extracellular traps (NETs) purified from HS patients displayed elevated levels of DLL4. HS-NETs activated the Notch pathway in macrophages and dermal fibroblasts isolated from HS patients. HS skin fibroblasts displayed elevated levels of CD90 and DPP4 in association with increased migratory capacity and Notch activation. Inhibition of Notch decreased migratory capacity and pro-fibrotic markers in HS fibroblasts. ConclusionThese data support a pathogenic connection between NETs, Notch- γ-secretase activation and the release of pro-fibrotic molecules that promote dysregulation of macrophages and skin fibroblasts in HS. Unveiling the relevance of these molecular events not only expands our understanding of HS but also opens new venues for the development of targeted therapies to address the fibrotic complications of advanced stages of HS.

Association between Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on the susceptibility to psoriasis and oxidative stress (OS) in a cohort of pediatric psoriatic patients in Sri Lanka: A cross sectional study.

Pediatric psoriasis accounts for nearly one-third of the global psoriasis burden. Multiple lines of evidence have shown the relationship between Angiotensin-converting enzyme (ACE) Insertion (I)/deletion(D) polymorphism with psoriasis susceptibility, and oxidative stress (OS) in psoriatic patients. However, such studies, particularly on pediatric psoriasis, are scarce in the local setting. Our study investigated the prevalence of ACE I/D polymorphism and its associations with oxidative stress in pediatric psoriasis patients in Sri Lanka. Thirty patients were recruited for this study after obtaining ethical clearance. The polymerase chain reaction was used to explore the ACE I/D polymorphism. Serum Nitric Oxide (NO) levels and the Total Antioxidant Capacity (TAC) were measured using the Griess assay and the FRAP assay. Clinical details were obtained from the clinic reports. Female predominance (76.67%) in pediatric psoriasis was reported, while Plaque psoriasis (66.67%) was found to be the most prevalent form. I/D was reported as the predominant genotype (66.67%) while I/I and D/D genotypes were recorded in 23.33% and 10% of patients, respectively. Significantly higher NO levels were observed in I/D patients than in I/I patients but not among other groups. No differences in TAC among ACE genotypes were reported. This pilot study revealed female gender and I/D genotype with increased NO levels as risk factors for pediatric psoriasis in Sri Lanka. However, it is prudent to increase the sample size to further validate the results.

Sexually divergent selection, allometric constraints, and the evolution of sexual dimorphism in cichlids from Lake Tanganyika.

The evolution of sexual dimorphism is widely acknowledged as manifestation of sex-specific genetic architecture. Although empirical studies suggested that sexual dimorphism evolves as a joint consequence of constraints arising from the genetic architecture and sexually divergent selection, it remains unclear whether and how these established microevolutionary processes scale up to the macroevolutionary patterns of sexual dimorphism among taxa. Here, we studied how sexual selection and parental care drive sexual dimorphism in cichlid fishes from Lake Tanganyika. We found that male-male competition, female choice, and maternal mouthbrooding are associated with sexual dimorphism in body length, body color, and head length, respectively, despite strong allometric relationships between body length and head length. Within-species (static) allometry of head length on body length evolved as sex-specific responses to mouthbrooding where females evolved higher intercepts while males evolved steeper slopes. Thus, selection to increase mouth size in mouthbrooders may have broken down and reorganized the pattern of allometric constraints that are inherently strong and concordant between sexes. Furthermore, sex-specific responses to mouthbrooding left a remarkably clear signature on the macroevolutionary pattern, resulting in a decoupling of co-evolution in parameters of static allometries observed exclusively within maternal mouthbrooders. Our study provides multiple lines of evidence that are consistent with the idea that macroevolutionary patterns of sexual dimorphism in Lake Tanganyika cichlids result from sexually divergent selection. Our approach illustrates that an examination of within-population phenotypic variance in the phylogenetic comparative framework may facilitate nuanced understandings of how macroevolutionary patterns are generated by underlying microevolutionary processes.

Scientific analysis of folk contract documents from Tianshui region: insights of fiber use and preservation state

Folk contract documents (FCD) are valuable materials for studying social history, and the paper they use reflects the social realities of different eras and social classes. Research and scientific analysis of numerous FCD samples after the fourteenth century are rare. We conducted a study on 96 Tianshui folk contract documents (TFCD, 107 paper samples) from the Tianshui area of Gansu Province, Northwest China, taking into account both the textual content and the materiality of paper carriers, and interpreted the results from multiple lines of evidence and discussion. Physical performance analysis revealed that the paper used by the northern folk exhibits a lower apparent density, which is not conducive to the long-term preservation of paper. The preservation status investigation, curtain pattern analysis, and fiber analysis show that the paper used in the TFCD differs from traditional cultural paper regarding disease types, production precision, and fiber materials, providing a basis for its protection and restoration. The analysis of chemical components indicated that the aging and yellowing of paper can be correlated with the content of sulfur and carbonyl groups. The feasibility of using pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) analysis to quickly identify papermaking fibers in a large number of paper samples was proposed. By utilizing various techniques to inspect the paper of documents, this study helps to enhance the academic understanding of FCD materials. In addition, it expands the knowledge base of Northwest handmade paper.

How can event attribution science underpin financial decisions on Loss and Damage?

With climate extremes hitting nations across the globe, disproportionately burdening vulnerable developing countries, the prompt operation of the Loss and Damage fund is of paramount importance. As decisions on resource disbursement at the international level, and investment strategies at the national level, loom, the climate science community's role in providing fair and effective evidence is crucial. Attribution science can provide useful information for decision makers, but both ethical implications and deep uncertainty cannot be ignored. Considering these aspects, we articulate a vision that integrates established attribution methods and multiple lines of evidence within a coherent logical framework.

Different species or altitudinal morphotypes? Testing the taxonomic value of Dianthus brachycalyx (Caryophyllaceae)

AbstractDefining species boundaries within plant groups distributed along wide elevational and geographic gradients may lead to unstable taxonomic delimitations using morphological data only. Within the taxonomically challenging genus Dianthus, through an integrative approach we tested the taxonomic value of D. brachycalyx, a putative species endemic to mountain peaks of the central‐southern Apennines, with respect to the widespread central‐Mediterranean D. virgineus. We measured 30 morphological characters in 452 individuals from 25 populations and obtained 3202 single nucleotide polymorphisms using ddRAD‐seq techniques in 394 individuals from 36 populations. For climatic niche comparison, we built a dataset of 348 occurrence points. By comparing morphometric, genetic, and climatic niche data, we showed that D. brachycalyx cannot be considered a distinct species. Morphometric separation between the two species is detectable, but high‐elevation populations of D. virgineus are similar to D. brachycalyx. Genetic analyses revealed that the genetic structure of populations of D. brachycalyx and D. virgineus is mainly shaped by isolation‐by‐distance, irrespective of their taxonomic attribution. The climatic niches of the two species are overlapping, and the niche differences are just due to different availability of climatic conditions in their ranges. Accordingly, multiple lines of evidence do not support a separation of D. brachycalyx from D. virgineus, and the former should be considered a heterotypic synonym of the latter.

Patterns of Immune Dysregulation in Bipolar Disorder.

Bipolar disorder is a debilitating mood disorder associated with a high risk of suicide and characterized by immune dysregulation. In this study, we used a multi-faceted approach to better distinguish the pattern of dysregulation of immune profiles in individuals with BD. We analyzed peripheral blood mononuclear cells (bipolar disorder N=39, control N=30), serum cytokines (bipolar disorder N=86, control N=58), whole blood RNA (bipolar disorder N=25, control N=25), and whole blood DNA (bipolar disorder N=104, control N=66) to identify immune-related differences in participants diagnosed with bipolar disorder compared to controls. Flow cytometry revealed a higher proportion of monocytes in participants with bipolar disorder together with a lower proportion of T helper cells. Additionally, the levels of 18 cytokines were significantly elevated, while two were reduced in participants with bipolar disorder. Most of the cytokines altered in individuals with bipolar disorder were proinflammatory. Forty-nine genes were differentially expressed in our bipolar disorder cohort and further analyses uncovered several immune-related pathways altered in these individuals. Genetic analysis indicated variants associated with inflammatory bowel disease also influences bipolar disorder risk. Our findings indicate a significant immune component to bipolar disorder pathophysiology and genetic overlap with inflammatory bowel disease. This comprehensive study supports existing literature, whilst also highlighting novel immune targets altered in individuals with bipolar disorder. Specifically, multiple lines of evidence indicate differences in the peripheral representation of monocytes and T cells are hallmarks of bipolar disorder.

Organic matter accumulation drives methylotrophic methanogenesis and microbial ecology in a hypersaline coastal lagoon

AbstractHypersalinity is common in coastal wetlands throughout warm, tropical, and arid regions. Climate‐induced changes in rainfall, sea level, and anthropogenic modification to basins and coastlines are likely to further increase salinization in these ecosystems. Yet, carbon cycling in hypersaline coastal wetlands is not well understood, and poorly constrained in climate models. In the Coorong, a eutrophic, hypersaline coastal lagoon, recognized as internationally important under the Ramsar convention, organic matter rapidly accumulates in deeper areas of the lagoon, through the settling of fine detrital particles, phytoplankton and suspended sediments. During initial surveys, elevated surface water methane (CH4) concentrations were observed above these fine depositional sediments. To identify the drivers of CH4 production, organic matter and sediment characteristics were assessed in surface sediments. Genetic markers (i.e., 16rDNA and the mcrA functional gene) were used to characterize microbial communities. With multiple lines of evidence, this study identifies organic matter, methanogen abundance, and salinity as important drivers of CH4 production, which is concentrated in depositional zones. Archaea were also more abundant in depositional zones, including methylotrophic methanogens: Methanofastidiosales, Methanomasiliicoccales, Methermicoccaceae, and Methanococcoides. These methanogens were highly correlated to CH4 in porewater, suggesting an influence of methylotrophic methanogenesis. To investigate further, metabolic genes were predicted from 16S rRNA with PICRUSt2. This represents the first effort to analyze CH4 dynamics in the Coorong, underscoring the need to integrate these unique ecosystems into global climate models to enhance our understanding of greenhouse gas dynamics and emissions in a changing climate.

A 47,000 year archaeological and palaeoenvironmental record from Juukan 2 rockshelter on the western Hamersley Plateau of the Pilbara region, Western Australia

Archaeological and palaeoenvironmental investigations at Juukan 2 rockshelter have yielded new information on the ancient Aboriginal occupation of the Pilbara uplands in northwest Australia. Using multiple lines of evidence, including lithic, faunal, pollen, ancient DNA, radiocarbon dating, optically stimulated luminescence, and Bayesian chronological modelling, we show that Aboriginal people occupied the western Hamersley Plateau as early as 47,000 years ago (47 ka). Late Pleistocene populations utilised a diverse range of tool technologies, including bone points, grindstones, and flaked stone artefacts. Palaeoclimatic conditions at Juukan 2 rockshelter varied greatly over the past 47 ka, with repeated site visits by people, including during the peak hyper-arid phase of the Last Glacial Maximum (LGM) c. 21 ± 2 ka. Ancient starch analyses of the ground stone artefacts show the processing of Ipomoea (Bush Potato) from around 42 ka to the present day. Pronounced increases in the discard of stone artefacts and bone in the last 3500 years are interpreted to be the result of increased frequency of site use. A braided hair fragment dated to this period has demonstrated genetic links between the earlier rockshelter occupants and contemporary Puutu Kunti Kurrama and Pinikura peoples, who have maintained strong cultural connections to the area.

Genomic data provides insights into the evolutionary history and adaptive differentiation of two tetraploid strawberries.

Over the decades, evolutionists and ecologists have shown intense interest in the role of polyploidization in plant evolution. Without clear knowledge of the diploid ancestor(s) of polyploids, we would not be able to answer fundamental ecological questions such as the evolution of niche differences between them or its underlying genetic basis. Here, we explored the evolutionary history of two Fragaria tetraploids, Fragaria corymbosa and Fragaria moupinensis. We de novo assembled five genomes including these two tetraploids and three diploid relatives. Based on multiple lines of evidence, we found no evidence of subgenomes in either of the two tetraploids, suggesting autopolyploid origins. We determined that Fragaria chinensis was the diploid ancestor of F. corymbosa while either an extinct species affinitive to F. chinensis or an unsampled population of F. chinensis could be the progenitor of F. moupinensis. Meanwhile, we found introgression signals between F. chinensis and Fragaria pentaphylla, leading to the genomic similarity between these two diploids. Compared to F. chinensis, gene families related to high ultraviolet (UV)-B and DNA repair were expanded, while those that responded towards abiotic and biotic stresses (such as salt stress, wounding, and various pathogens) were contracted in both tetraploids. Furthermore, the two tetraploids tended to down-regulate defense response genes but up-regulate UV-B response, DNA repairing, and cell division gene expression compared to F. chinensis. These findings may reflect adaptions toward high-altitude habitats. In summary, our work provides insights into the genome evolution of wild Fragaria tetraploids and opens up an avenue for future works to answer deeper evolutionary and ecological questions regarding the strawberry genus.

Natural Bioactive Compounds from Macroalgae and Microalgae for the Treatment of Alzheimer's Disease: A Review.

Neuroinflammation, toxic protein aggregation, oxidative stress, and mitochondrial dysfunction are key pathways in neurodegenerative diseases like Alzheimer's disease (AD). Targeting these mechanisms with antioxidants, anti-inflammatory compounds, and inhibitors of Aβ formation and aggregation is crucial for treatment. Marine algae are rich sources of bioactive compounds, including carbohydrates, phenolics, fatty acids, phycobiliproteins, carotenoids, fatty acids, and vitamins. In recent years, they have attracted interest from the pharmaceutical and nutraceutical industries due to their exceptional biological activities, which include anti-inflammation, antioxidant, anticancer, and anti-apoptosis properties. Multiple lines of evidence have unveiled the potential neuroprotective effects of these multifunctional algal compounds for application in treating and managing AD. This article will provide insight into the molecular mechanisms underlying the neuroprotective effects of bioactive compounds derived from algae based on in vitro and in vivo models of neuroinflammation and AD. We will also discuss their potential as disease-modifying and symptomatic treatment strategies for AD.

Integrative systematic revision of the Montseny brook newt (Calotriton arnoldi), with the description of a new subspecies.

The Montseny brook newt (Calotriton arnoldi), a glacial relict endemic to a small, isolated massif in northeast Spain, is considered the only Critically Endangered urodele in Europe. Its restricted range is divided by a deep valley that acts as an impassable barrier to dispersal, separating two isolated metapopulations (Western and Eastern) that correspond to independent lineages with different evolutionary trajectories, based on genetic and genomic data. Here, we address the ecological differentiation between lineages and discuss its potential effect on the phenotypic distinctness of each lineage. Based on multiple lines of evidence, we formally describe the Western Montseny brook newt as a new subspecies: Calotriton arnoldi laietanus ssp. nov. Finally, our study underscores the importance of considering taxonomic progress in the conservation policies of endangered species, ensuring appropriate management and protection of the newly described taxa.

Inhibition of astroglial hemichannels prevents synaptic transmission decline during spreading depression

BackgroundSpreading depression (SD) is an intriguing phenomenon characterized by massive slow brain depolarizations that affect neurons and glial cells. This phenomenon is repetitive and produces a metabolic overload that increases secondary damage. However, the mechanisms associated with the initiation and propagation of SD are unknown. Multiple lines of evidence indicate that persistent and uncontrolled opening of hemichannels could participate in the pathogenesis and progression of several neurological disorders including acute brain injuries. Here, we explored the contribution of astroglial hemichannels composed of connexin-43 (Cx43) or pannexin-1 (Panx1) to SD evoked by high-K+ stimulation in brain slices.ResultsFocal high-K+ stimulation rapidly evoked a wave of SD linked to increased activity of the Cx43 and Panx1 hemichannels in the brain cortex, as measured by light transmittance and dye uptake analysis, respectively. The activation of these channels occurs mainly in astrocytes but also in neurons. More importantly, the inhibition of both the Cx43 and Panx1 hemichannels completely prevented high K+-induced SD in the brain cortex. Electrophysiological recordings also revealed that Cx43 and Panx1 hemichannels critically contribute to the SD-induced decrease in synaptic transmission in the brain cortex and hippocampus.ConclusionsTargeting Cx43 and Panx1 hemichannels could serve as a new therapeutic strategy to prevent the initiation and propagation of SD in several acute brain injuries.

Caught in the Act: Incipient Speciation at the Southern Limit of Viburnum in the Central Andes.

A fundamental objective of evolutionary biology is to understand the origin of independently evolving species. Phylogenetic studies of species radiations rarely are able to document ongoing speciation; instead, modes of speciation, entailing geographic separation and/or ecological differentiation, are posited retrospectively. The Oreinotinus clade of Viburnum has radiated recently from north to south through the cloud forests of Mexico and Central America to the Central Andes. Our analyses support a hypothesis of incipient speciation in Oreinotinus at the southern edge of its geographic range, from central Peru to northern Argentina. Although several species and infraspecific taxa have been recognized in this area, multiple lines of evidence and analytical approaches (including analyses of phylogenetic relationships, genetic structure, leaf morphology, and climatic envelopes) favor the recognition of just a single species, V. seemenii. We show that what has previously been recognized as V. seemenii f. minor has recently occupied the drier Tucuman-Bolivian forest region from Samaipata in Bolivia to Salta in northern Argentina. Plants in these populations form a well-supported clade with a distinctive genetic signature and they have evolved smaller, narrower leaves. We interpret this as the beginning of a within-species divergence process that has elsewhere in the neotropics resulted repeatedly in Viburnum species with a particular set of leaf ecomorphs. Specifically, the southern populations are in the process of evolving the small, glabrous, and entire leaf ecomorph that has evolved in four other montane areas of endemism. As predicted based on our studies of leaf ecomorphs in Chiapas, Mexico, these southern populations experience generally drier conditions, with large diurnal temperature fluctuations. In a central portion of the range of V. seemenii, characterized by wetter climatic conditions, we also document what may be the initial differentiation of the leaf ecomorph with larger, pubescent, and toothy leaves. The emergence of these ecomorphs thus appears to be driven by adaptation to subtly different climatic conditions in separate geographic regions, as opposed to parapatric differentiation along elevational gradients as suggested by Viburnum species distributions in other parts of the neotropics.

Rare Earth Element Accumulation in Fiddler Crabs (Minuca rapax) from the Rio Doce Tropical Estuary Strongly Affected by Mine Tailings Following the Fundão Disaster.

A mining tailing dam rupture in Brazil in November 2015 released millions of tons of mining waste into the Rio Doce ecosystem, leading to long-term aquatic ecosystem impacts. Although multiple lines of evidence indicate tailings associations with potentially toxic elements in estuarine sediments and biological impact and bioaccumulation pathways in fishes, the extent of contamination in base benthic species is still largely unknown. Moreover, Rare Earth Elements (REE) have not received any attention in this regard. This study assessed REE in fiddler crabs (Minuca rapax) sampled from the Rio Doce estuary in 2017, nearly 2years after the disaster. The ΣREE in crab hepatopancreas and muscle were high (327.83mgkg-1 w.w. and 33.84mgkg-1 w.w., respectively, compared to other assessments in crabs, indicating a preference for REE bioaccumulation in the hepatopancreas compared to muscle. Neodimium, La, and Ce were detected at the highest concentrations. The REE from the Rio Doce Basin were, thus, transported and deposited in the estuary with the mine tailings slurry, leading to bioaccumulation in crabs. This may lead to trophic effects and other ecological impacts not readily measured by typical impact assessment studies, revealing an invisible and not typically acknowledged damage to the Rio Doce estuary.