Biogeography, systematics and taxonomy are complementary scientific disciplines. To understand a species' origin, migration routes, distribution and evolutionary history, it is first necessary to establish its taxonomic boundaries. Here, we use an integrative approach that takes advantage of complementary disciplines to resolve an intriguing scientific question. Populations of an unknown moss found in the Canary Islands (Tenerife Island) resembled two different Californian endemic species: Orthotrichum shevockii and O. kellmanii. To determine whether this moss belongs to either of these species and, if so, to explain its presence on this distant oceanic island, we combined the evaluation of morphological qualitative characters, statistical morphometric analyses of quantitative traits, and molecular phylogenetic inferences. Our results suggest that the two Californian mosses are conspecific, and that the Canarian populations belong to this putative species, with only one taxon thus involved. Orthotrichum shevockii (the priority name) is therefore recognized as a morphologically variable species that exhibits a transcontinental disjunction between western North America and the Canary Islands. Within its distribution range, the area of occupancy is limited, a notable feature among bryophytes at the intraspecific level. To explain this disjunction, divergence time and ancestral area estimation analyses are carried out and further support the hypothesis of a long-distance dispersal event from California to Tenerife Island.

Natural hazards are becoming increasingly expensive as climate change and development are exposing communities to greater risks. Preparation and recovery are critical for climate change resilience, and social media are being used more and more to communicate before, during, and after disasters. While there is a growing body of research aimed at understanding how people use social media surrounding disaster events, most existing work has focused on a single disaster case study. In the present study, we analyze five of the costliest disasters in the last decade in the United States (Hurricanes Irene and Sandy, two sets of tornado outbreaks, and flooding in Louisiana) through the lens of Twitter. In particular, we explore the frequency of both generic and specific food-security related terms, and quantify the relationship between network size and Twitter activity during disasters. We find differences in tweet volume for keywords depending on disaster type, with people using Twitter more frequently in preparation for Hurricanes, and for real-time or recovery information for tornado and flooding events. Further, we find that people share a host of general disaster and specific preparation and recovery terms during these events. Finally, we find that among all account types, individuals with "average" sized networks are most likely to share information during these disasters, and in most cases, do so more frequently than normal. This suggests that around disasters, an ideal form of social contagion is being engaged in which average people rather than outsized influentials are key to communication. These results provide important context for the type of disaster information and target audiences that may be most useful for disaster communication during varying extreme events.

Demographic estimates are presented for the Aurignacian techno-complex (~42,000 to 33,000 y calBP) and discussed in the context of socio-spatial organization of hunter-gatherer populations. Results of the analytical approach applied estimate a mean of 1,500 persons (upper limit: 3,300; lower limit: 800) for western and central Europe. The temporal and spatial analysis indicates an increase of the population during the Aurignacian as well as marked regional differences in population size and density. Demographic increase and patterns of socio-spatial organization continue during the subsequent early Gravettian period. We introduce the concept of Core Areas and Extended Areas as informed analytical spatial scales, which are evaluated against additional chronological and archaeological data. Lithic raw material transport and personal ornaments serve as correlates for human mobility and connectedness in the interpretative framework of this study. Observed regional differences are set in relation with the new demographic data. Our large-scale approach on Aurignacian population dynamics in Europe suggests that past socio-spatial organization followed socially inherent rules to establish and maintain a functioning social network of extremely low population densities. The data suggest that the network was fully established across Europe during the early phase of the Gravettian, when demographic as well as cultural developments peaked.

To investigate the role of thoracic spine manipulation (TSM) on pain and disability in the management of mechanical neck pain (MNP).

Recent studies have indicated that several critical illnesses are associated with an increased risk of cardiovascular diseases (CVDs). Nonetheless, studies of the association between heat-related illnesses (HRIs) and subsequent CVDs are still limited. We sought to evaluate whether heat stroke (HS) was associated with an increased CVD incidence.

Social insects provide promising new avenues for aging research. Within a colony, individuals that share the same genetic background can differ in lifespan by up to two orders of magnitude. Reproducing queens (and in termites also kings) can live for more than 20 years, extraordinary lifespans for insects. We studied aging in a termite species, Cryptotermes secundus, which lives in less socially complex societies with a few hundred colony members. Reproductives develop from workers which are totipotent immatures. Comparing transcriptomes of young and old individuals, we found evidence for aging in reproductives that was especially associated with DNA and protein damage and the activity of transposable elements. By contrast, workers seemed to be better protected against aging. Thus our results differed from those obtained for social insects that live in more complex societies. Yet, they are in agreement with lifespan estimates for the study species. Our data are also in line with expectations from evolutionary theory. For individuals that are able to reproduce, it predicts that aging should only start after reaching maturity. As C. secundus workers are immatures with full reproductive options we expect them to invest into anti-aging processes. Our study illustrates that the degree of aging can differ between social insects and that it may be associated with caste-specific opportunities for reproduction.

Understanding how people modify their stepping to maintain gait stability may provide information on fall risk and help to understand strategies used to reduce loss of balance. The purpose of this study was to identify the stepping strategies healthy young individuals select to maintain balance while walking on a destabilizing surface in various directions. A treadmill mounted on top of a 6 degree-of-freedom motion base was used to generate support surface oscillations in different degrees of freedom and amplitudes. Fifteen healthy young adults (21.3 ± 1.4 years) walked at self-selected speeds while continuous sinusoidal oscillations were imposed to the support surface in a one degree of freedom: rotation or translation in the mediolateral (ML) direction and rotation or translation in the anteroposterior (AP) direction, with each condition repeated at three different amplitudes. We compared step width, length, and frequency and the mean and variability of margin of stability (MoS) during each experimental walking condition with a control condition, in which the support surface was stationary. Subjects chose a common strategy of increasing step width (p < 0.001) and decreasing step length (p = 0.008) while increasing mediolateral MoS (p < 0.001), particularly during oscillations that challenged frontal plane control, with rotations of the walking surface producing the greatest changes to stepping.

Tamoxifen, a selective estrogen-receptor modulator, is widely used in mouse models to temporally control gene expression but is also known to affect body composition. We report that tamoxifen has significant and sustained effects on glucose tolerance, independent of effects on insulin sensitivity, in mice. IP, but not oral, tamoxifen delivery improved glucose tolerance in three inbred mouse strains. The extent and persistence of tamoxifen-induced effects were sex and strain dependent. These findings highlight the need to revise commonly used tamoxifen-based protocols for gene manipulation in mice by including longer chase periods after injection, oral delivery, and the use of tamoxifen-treated littermate controls.

The cysteine-rich secretory proteins (CRISPs) are a group of proteins that show a pronounced expression biased to the male reproductive tract. Although sperm encounter CRISPs at virtually all phases of sperm development and maturation, CRISP2 is the sole CRISP produced during spermatogenesis, wherein it is incorporated into the developing sperm head and tail. In this study we tested the necessity for CRISP2 in male fertility using Crisp2 loss-of-function mouse models. In doing so, we revealed a role for CRISP2 in establishing the ability of sperm to undergo the acrosome reaction and in establishing a normal flagellum waveform. Crisp2-deficient sperm possess a stiff midpiece and are thus unable to manifest the rapid form of progressive motility seen in wild type sperm. As a consequence, Crisp2-deficient males are subfertile. Furthermore, a yeast two-hybrid screen and immunoprecipitation studies reveal that CRISP2 can bind to the CATSPER1 subunit of the Catsper ion channel, which is necessary for normal sperm motility. Collectively, these data define CRISP2 as a determinant of male fertility and explain previous clinical associations between human CRISP2 expression and fertility.

Next generation sequencing multi-gene panels have greatly improved the diagnostic yield and cost effectiveness of genetic testing and are rapidly being integrated into the clinic for hereditary cancer risk. With this technology comes a dramatic increase in the volume, type and complexity of data. This invaluable data though is too often buried or inaccessible to researchers, especially to those without strong analytical or programming skills. To effectively share comprehensive, integrated genotypic-phenotypic data, we built Color Data, a publicly available, cloud-based database that supports broad access and data literacy. The database is composed of 50 000 individuals who were sequenced for 30 genes associated with hereditary cancer risk and provides useful information on allele frequency and variant classification, as well as associated phenotypic information such as demographics and personal and family history. Our user-friendly interface allows researchers to easily execute their own queries with filtering, and the results of queries can be shared and/or downloaded. The rapid and broad dissemination of these research results will help increase the value of, and reduce the waste in, scientific resources and data. Furthermore, the database is able to quickly scale and support integration of additional genes and human hereditary conditions. We hope that this database will help researchers and scientists explore genotype-phenotype correlations in hereditary cancer, identify novel variants for functional analysis and enable data-driven drug discovery and development.

Aging is the main risk factor for many prevalent diseases. However, the molecular mechanisms regulating aging at the cellular level are largely unknown. Using single cell yeast as a model organism, we found that reducing yeast histone proteins accelerates chronological aging and increasing histone supply extends chronological life span. We sought to identify pathways that regulate chronological life span by controlling intracellular histone levels. Thus, we screened the histone H3/H4 mutant library to uncover histone residues and posttranslational modifications that regulate histone gene expression. We discovered 15 substitution mutations with reduced histone proteins and 5 mutations with increased histone proteins. Among these mutations, we found Set1 complex-catalyzed H3K4me3 promotes histone gene transcription and maintains normal chronological life span. Unlike the canonical functions of H3K4me3 in gene expression, H3K4me3 facilitates histone gene transcription by acting as a boundary to restrict the spread of the repressive HIR/Asf1/Rtt106 complex from histone gene promoters. Collectively, our study identified a novel mechanism by which H3K4me3 antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and extend chronological life span.

Natural products that target the eukaryotic ribosome are promising therapeutics to treat a variety of cancers. It is therefore essential to determine their molecular mechanism of action to fully understand their mode of interaction with the target and to inform the development of new synthetic compounds with improved potency and reduced cytotoxicity. Toward this goal, we have previously established a short synthesis pathway that grants access to multiple congeners of the lissoclimide family. Here we present the X-ray co-crystal structure at 3.1 Å resolution of C45, a potent congener with two A-ring chlorine-bearing stereogenic centers with 'unnatural' configurations, with the yeast 80S ribosome, intermolecular interaction energies of the C45/ribosome complex, and single-molecule FRET data quantifying the impact of C45 on both human and yeast ribosomes. Together, these data provide new insights into the role of unusual non-covalent halogen bonding interactions involved in the binding of this synthetic compound to the 80S ribosome.

TDP-43 regulates cellular levels of Cajal bodies (CBs) that provide platforms for the assembly and RNA modifications of small nuclear ribonucleoproteins (snRNPs) involved in pre-mRNA splicing. Alterations in these snRNPs may be linked to pathogenesis of amyotrophic lateral sclerosis. However, specific roles for TDP-43 in CBs remain unknown. Here, we demonstrate that TDP-43 regulates the CB localization of four UG-rich motif-bearing C/D-box-containing small Cajal body-specific RNAs (C/D scaRNAs; i.e. scaRNA2, 7, 9 and 28) through the direct binding to these scaRNAs. TDP-43 enhances binding of a CB-localizing protein, WD40-repeat protein 79 (WDR79), to a subpopulation of scaRNA2 and scaRNA28; the remaining population of the four C/D scaRNAs was localized to CB-like structures even with WDR79 depletion. Depletion of TDP-43, in contrast, shifted the localization of these C/D scaRNAs, mainly into the nucleolus, as well as destabilizing scaRNA2, and reduced the site-specific 2'-O-methylation of U1 and U2 snRNAs, including at 70A in U1 snRNA and, 19G, 25G, 47U and 61C in U2 snRNA. Collectively, we suggest that TDP-43 and WDR79 have separate roles in determining CB localization of subsets of C/D and H/ACA scaRNAs.

Postprandial lipemia is a risk factor for cardiovascular disease. Dairy products differ in nutrient content and food matrix, and little is known about how different dairy products affect postprandial triglyceride (TG) concentrations.

Pancreatic digestive enzymes present in meconium might be responsible for meconium-induced lung injury. The local Renin Angiotensin System plays an important role in lung injury and inflammation. Particularly, angiotensin converting enzyme-2 (ACE-2) has been identified as a protective lung enzyme against the insult. ACE-2 converts pro-apoptotic Angiotensin II to anti-apoptotic Angiotensin 1-7. However, the effect of meconium on ACE-2 has never been studied before.

Histone H3 lysine 79 (H3K79) methylation is enriched on actively transcribed genes, and its misregulation is a hallmark of leukemia. Methylation of H3K79, which resides on the structured disk face of the nucleosome, is mediated by the Dot1L methyltransferase. Dot1L activity is part of a trans-histone crosstalk pathway, requiring prior histone H2B ubiquitylation of lysine 120 (H2BK120ub) for optimal activity. However, the molecular details describing both how Dot1L binds to the nucleosome and why Dot1L is activated by H2BK120 ubiquitylation are unknown. Here, we present the cryoelectron microscopy (cryo-EM) structure of Dot1L bound to a nucleosome reconstituted with site-specifically ubiquitylated H2BK120. The structure reveals that Dot1L engages the nucleosome acidic patch using a variant arginine anchor and occupies a conformation poised for methylation. In this conformation, Dot1L and ubiquitin interact directly through complementary hydrophobic surfaces. This study establishes a path to better understand Dot1L function in normal and leukemia cells.

The proximodistal axis is considered a major organizational principle of the hippocampus. At the interface between the hippocampus and other brain structures, CA2 apparently breaks this rule. The region is involved in social, temporal, and contextual memory function, but mechanisms remain elusive. Here, we reveal cell-type heterogeneity and a characteristic expression gradient of the transcription factor Sox5 within CA2 in the rat. Using intracellular and extracellular recordings followed by neurochemical identification of single cells, we find marked proximodistal trends of synaptic activity, subthreshold membrane potentials, and phase-locked firing coupled to theta and gamma oscillations. Phase-shifting membrane potentials and opposite proximodistal correlations with theta sinks and sources at different layers support influences from different current generators. CA2 oscillatory activity and place coding of rats running in a linear maze reflect proximodistal state-dependent trends. We suggest that the structure and function of CA2 are distributed along the proximodistal hippocampal axis.

Active defense against a conspecific aggressor is essential for survival. Previous studies revealed strong c-Fos expression in the ventrolateral part of the ventromedial hypothalamus (VMHvl) in defeated animals. Here, we examined the functional relevance and in vivo responses of the VMHvl during conspecific defense. We found that VMHvl cells expressing estrogen receptor α (Esr1) are acutely excited during active conspecific defense. Optogenetic inhibition of the cells compromised an animal's ability to actively defend against an aggressor, whereas activating the cells elicited defense-like behaviors. Furthermore, the VMHvl is known for its role in aggression. In vivo recording and c-Fos mapping revealed differential organization of the defense and aggression-responsive cells in the VMHvl. Specifically, defense-activated cells are concentrated in the anterior part of the VMHvl, which preferentially targets the periaqueductal gray (PAG). Thus, our study identified an essential neural substrate for active conspecific defense and expanded the function of the VMHvl.

Infection by rapidly growing Mycobacterium abscessus is increasingly prevalent in cystic fibrosis (CF), a genetic disease caused by a defective CF transmembrane conductance regulator (CFTR). However, the potential link between a dysfunctional CFTR and vulnerability to M. abscessus infection remains unknown. Herein, we exploit a CFTR-depleted zebrafish model, recapitulating CF immuno-pathogenesis, to study the contribution of CFTR in innate immunity against M. abscessus infection. Loss of CFTR increases susceptibility to infection through impaired NADPH oxidase-dependent restriction of intracellular growth and reduced neutrophil chemotaxis, which together compromise granuloma formation and integrity. As a consequence, extracellular multiplication of M. abscessus expands rapidly, inducing abscess formation and causing lethal infections. Because these phenotypes are not observed with other mycobacteria, our findings highlight the crucial and specific role of CFTR in the immune control of M. abscessus by mounting effective oxidative responses.

High-salt diets inhibit the suppressive function of thymus-derived natural regulatory T cells (tTreg). Transforming growth factor β (TGF-β)-induced ex vivo regulatory T cells (iTreg) comprise another Treg subset that exhibits similarities and differences with tTreg. Here, we demonstrate that iTregs are completely stable and fully functional under high salt conditions. High salt does not influence the development, differentiation, and functional activities of iTreg but affects Foxp3 stability and function of tTreg in vitro and in vivo. In addition, high salt does not significantly change the transcription profiles of the iTreg signature or pro-inflammatory genes. Therefore, we conclude that iTreg, unlike tTreg, are stable and functional in the presence of high salt. Our findings provide additional evidence that iTreg may have different biological features from tTreg and suggest a greater potential for clinical utility in patients with autoimmune diseases, in which the complicated role of environmental factors, including diet, must be considered.