Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of Viral Glycoprotein Targeting by Membrane-associated-RING-CH Proteins

An emerging class of cellular inhibitory proteins has been identified that targets viral glycoproteins. These include the membrane-associated RING-CH (MARCH) family of E3 ubiquitin ligases that, among other functions, downregulate cell-surface proteins involved in adaptive immunity. The RING-CH domain of MARCH proteins is thought to function by catalyzing the ubiquitination of the cytoplasmic tails (CTs) of target proteins, leading to their degradation. MARCH proteins have recently been reported to target retroviral envelope glycoproteins (Env) and vesicular stomatitis virus G glycoprotein (VSV-G). However, the mechanism of antiviral activity remains poorly defined. Here we show that MARCH8 antagonizes the full-length forms of HIV-1 Env, VSV-G, Ebola virus glycoprotein (EboV-GP), and the spike (S) protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) thereby impairing the infectivity of virions pseudotyped with these viral glycoproteins. This MARCH8-mediated targeting of viral glycoproteins requires the E3 ubiquitin ligase activity of the RING-CH domain. We observe that MARCH8 protein antagonism of VSV-G is CT-dependent. In contrast, MARCH8-mediated targeting of HIV-1 Env, EboV-GP and SARS-CoV-2 S protein by MARCH8 does not require the CT, suggesting a novel mechanism of MARCH-mediated antagonism of these viral glycoproteins. Confocal microscopy data demonstrate that MARCH8 traps the viral glycoproteins in an intracellular compartment. We observe that the endogenous expression of MARCH8 in several relevant human cell types is rapidly inducible by type I interferon. These results help to inform the mechanism by which MARCH proteins exert their antiviral activity and provide insights into the role of cellular inhibitory factors in antagonizing the biogenesis, trafficking, and virion incorporation of viral glycoproteins. Importance Viral envelope glycoproteins are an important structural component on the surface of enveloped viruses that direct virus binding and entry and also serve as targets for the host adaptive immune response. In this study, we investigate the mechanism of action of the MARCH family of cellular proteins that disrupt the trafficking and virion incorporation of viral glycoproteins across several virus families. This research provides novel insights into how host cell factors antagonize viral replication, perhaps opening new avenues for therapeutic intervention in the replication of a diverse group of highly pathogenic enveloped viruses.
Baseline Lateral Habenula Firing Rate Negatively Correlates with Increase in Ethanol Intake over Days in Adult Long Evans Rats

While many adults consume alcohol, yet only some individuals are at a risk to develop alcohol use disorder (AUD). Variability in the risk for alcohol abuse is multifactorial and includes differences in behavioral and neuronal traits. The lateral habenula (LHb) has been shown to mediate aversive state-related behavioral responses. Interestingly, in both humans and rodents, depression-like symptoms are associated with high LHb activity. Additionally, there is a high co-morbidity between major depressive disorder and AUD. However, LHb lesions in rodents increase ethanol intake over time. Thus, we wanted to determine how baseline LHb activity correlates with ethanol intake over days. Specifically, we wanted to test whether individual variation in baseline LHb activity in ethanol-naive rats is related to home-cage ethanol drinking patterns. Hence, in this study, we determined the correlation between individual variability in baseline LHb neural activity, the negative-affective state-related ultrasonic vocalizations (USVs; 22-28 kHz), and the extent of ethanol intake over days. We first surgically implanted a unilateral 16-wire electrode array in the LHb of adult male Long Evans rats (n=11). Following recovery from surgery, rats were placed in sound-insulated chambers for two hours, where they were free to explore while we simultaneously recorded neuronal signals from their LHb and the USVs emitted by them. Next, these rats underwent an intermittent access to ethanol (IAE) paradigm, where they received 20% ethanol for 24 hours on alternate days (Monday-Wednesday-Friday) and ad-libitum water in their home cages for four weeks. The change in ethanol intake over days differed between rats, with some rats escalating their ethanol intake in the four weeks, while other rats showing no meaningful change in ethanol intake over days as compared to the first session. We found a significant negative correlation between average baseline LHb firing rates in rats and the changes in ethanol intake in the first week of IAE. Specifically, rats with higher baseline LHb firing rats, unlike rats with lower baseline firing rates, did not escalate their ethanol intake from the first session to the second and fourth ethanol sessions of the IAE paradigm. We also found a moderate positive correlation between the number of 22-28 kHz USVs and the average LHb firing rates of these rats. These results indicate that higher baseline LHb neuronal activity in normal adult ethanol naive rats is associated with decreased motivation to seek and consume ethanol during the early stages of ethanol consumption.
Phenotypic plasticity is aligned with phenological adaptation on both micro- and macroevolutionary timescales

In seasonally-variable environments, phenotypic plasticity in phenology may be critical for adaptation to fluctuating environmental (temperature) conditions. Using an 18-generation longitudinal dataset from natural insect (damselfly) populations, we show that phenology has strongly advanced. Individual fitness data suggest this is likely an adaptive response towards a thermally-dependent fitness optimum. A laboratory experiment revealed that developmental plasticity qualitatively matches environmental-dependence of selection, partially explaining observed phenological advance. Expanding our analysis to the macroevolutionary level, we use a database of over 1-million occurrence records and spatiotemporally-matched temperature data from 49 Swedish Odonate species to infer macroevolutionary dynamics of phenology. Phenological plasticity was more closely aligned with adaptation for species that have recently colonized northern latitudes, with more phenological mismatch at lower latitudes. Our results show that phenological plasticity plays a key role in microevolutionary dynamics within a single species, and such plasticity may have facilitated post-Pleistocene range expansion in this insect clade.
Self-organization in natural swarms of Photinus carolinus synchronous fireflies

Flash bursts relay around vegetation across the swarm, illuminating the role of the environment in shaping self-organization. Fireflies flashing in unison is a mesmerizing manifestation of animal collective behavior and an archetype of biological synchrony. To elucidate synchronization mechanisms and inform theoretical models, we recorded the collective display of thousands of Photinus carolinus fireflies in natural swarms, and provide the first spatiotemporal description of the onset of synchronization. At low firefly density, flashes appear uncorrelated. At high density, the swarm produces synchronous flashes within periodic bursts. Using three-dimensional reconstruction, we demonstrate that flash bursts nucleate and propagate across the swarm in a relay-like process. Our results suggest that fireflies interact locally through a dynamic network of visual connections defined by visual occlusion from terrain and vegetation. This model illuminates the importance of the environment in shaping self-organization and collective behavior.
Opposing effects of competitive exclusion determine invasion outcomes and structure ant assemblages

Insight into how species’ phenotypic differences shape coexistence is key to understanding the processes structuring, maintaining and threatening biodiversity. In line with modern coexistence theory, increasing studies on plants show that traits may not only confer niche differences fostering the coexistence of dissimilar species, but also competitive advantages promoting the exclusion of weaker competitors. These variable relationships between traits and the outcomes of interspecific competition, and particularly their effects on assemblage structure, are relatively unexplored for animals in natural settings. Here we show that the abundance of an invasive ant as well as the composition and structure of native ground-foraging ant assemblages in a tropical grassland are largely attributable to differences in the morphological, dietary, physiological and behavioural traits between invasive and native species. Crucially, we find that individual traits vary in association with niche differences and competitive advantages, which have opposing effects on competitive exclusion. Competition along these separate trait axes consequently generates contrasting patterns of overdispersion and clustering in the functional structure of invaded assemblages. Our results highlight that different traits across the phenotypic spectrum may distinctly influence stabilizing and equalizing mechanisms of coexistence, ultimately modulating the role and effect of competition in structuring biodiversity.
Does insect herbivory suppress ecosystem productivity? Evidence from a temperate woodland

Our current understanding of the relationship between insect herbivory and ecosystem productivity is limited. Previous studies have typically quantified only leaf area loss, or have been conducted during outbreak years. These set-ups often ignore the physiological changes taking place in the remaining plant tissue after insect attack, or may not represent typical, non-outbreak herbivore densities. Here, we estimate the amount of carbon lost to insect herbivory in a temperate deciduous woodland both through leaf area loss and, notably, through changes in leaf gas exchange in non-consumed leaves under non-outbreak densities of insects. We calculate how net primary productivity changes with decreasing and increasing levels of herbivory, and estimate what proportion of the carbon involved in the leaf area loss is transferred further in the food web. We estimate that the net primary productivity of an oak stand under ambient levels of herbivory is 54 - 69% lower than that of a completely intact stand. The effect of herbivory quantified only as leaf area loss (0.1 Mg C ha−1 yr−1) is considerably smaller than when the effects of herbivory on leaf physiology are included (8.5 Mg C ha−1 yr−1). We propose that the effect of herbivory on primary productivity is non-linear and mainly determined by changes in leaf gas exchange. We call for replicated studies in other systems to validate the relationship between insect herbivory and ecosystem productivity described here.
Intrinsic reinstatement of induced oscillatory context

Declarative memory retrieval is thought to rely on the reinstatement, at retrieval, of contextual cues present during encoding, as evidenced in the context and state-dependent literature. Specifically, previous work has shown that reinstating the oscillatory activity present during encoding, at retrieval, is particularly supportive of memory recall. Our study builds on previous findings suggesting that the oscillatory activity present at encoding may be automatically reinstated during retrieval. To explore the roles of consolidation, prefrontal involvement, and frequency specific activity in this process of oscillatory reinstatement, 115 healthy young adults were randomly assigned to one of five conditions. In each condition, transcranial alternating current stimulation (tACS) was administered at either one of two frequencies (60Hz or 6Hz), over the left dorsolateral prefrontal cortex (left-DLPFC, Experimental) or the right primary motor cortex (right-PMC, Control), during learning of written words. This was followed by a retention interval of either 90 minutes or 1 week and a testing phase, during which EEG activity was recorded. Our results showed significant (and frequency specific) oscillatory reinstatement, after stimulation of the left-DLPFC, in the 1-week retention condition. Oscillatory reinstatement effects were non-significant after stimulation of the right-PMC, or in the 90 minutes retention interval condition. Our results highlight that the oscillatory activity induced during encoding is consolidated as context alongside the information and is reinstated intrinsically during retrieval. The implications of our findings for models of human memory, future avenues of research and clinical applications are discussed.
DYNAMIC VARIATION IN A SOCIALLY EXCHANGED FLUID INDICATES A ROLE IN THE REGULATION OF ANT COLONY DEVELOPMENT AND MATURATION

Socially exchanged fluids, like seminal fluid and milk, present a direct and effective means through which an individual can influence conspecifics. As organisms heavily adapted to social life, social insects have evolved a suite of behavioral, morphological and molecular mechanisms to ensure cooperation and inclusive fitness benefits for all group members, just as multicellular organisms have. As a part of their social physiology, some species have developed a social circulatory system, where exogenous food and endogenously produced material, such as hormones, proteins and small molecules, are transferred mouth-to-mouth from the foregut of one individual to another. This fluid transfer – stomodeal trophallaxis – ensures that both food and endogenously produced components are distributed throughout the social network. To understand how the endogenous materials in trophallactic fluid relate to colony life, we investigated trophallactic fluid of the carpenter ant Camponotus floridanus, monitoring this fluid within colonies under different biotic and abiotic conditions and in different individuals within colonies. Using quantitative proteomic analyses of over 100 colony and single-individual trophallactic fluid samples, we established a set of core trophallactic fluid proteins. By combining frequentist, empirical Bayesian and machine-learning classification tools, we identified sets of proteins that are significantly induced in trophallactic fluid under different conditions: proteins that differ between young and mature colonies in the field, proteins that differ between colonies in the field and in the lab, and proteins that differ between the trophallactic fluid of nurses and foragers. Results reveal that different stages of the colony life cycle utilize classic metabolic processes in different ways, with young colonies prioritizing direct carbohydrate processing, while mature colonies prioritizing transmission of stored resources over the trophallactic network. Further, proteins from pathways that govern the fecundity-longevity trade-off and that have been previously implicated in social insect caste determination are being transferred between individuals within colonies, potentially acting as superorganismal hormones. Nurses in particular show higher abundances in proteins and pathways involved in defense against aging. Thus, we show that the protein composition of ant trophallactic fluid varies with social and developmental conditions both at the colony and at the individual level, suggesting that the trophallactic fluid proteome plays a key role in the social physiology of colonies.
Microenvironment Impacts the Molecular Architecture and Interactivity of Resident Cells in Marmoset Brain

The microenvironments of the brain consist of specialized cell types that together influence physiological functions in health and pathological outcomes in disease. Despite apparent differences in the density of neurons and oligodendrocytes in various milieus, such as gray matter (GM) and white matter (WM), the extent of structural and functional heterogeneity of other resident cells remains unclear. We profiled RNA in ~500,000 nuclei from 19 tissue types across the central nervous system of the healthy adult common marmoset (Callithrix jacchus) and mapped 87 identified subclusters (including neurons, glia, and vasculature) spatially onto a 3D MRI atlas. We performed cross-species comparison, explored regulatory pathways, surveyed cellular determinants of neurological disorders, and modeled regional intercellular communication. We found spatially segregated microglia, oligodendrocyte lineage cells, and astrocytes in WM and GM. WM-glia are diverse, are enriched with genes involved in stimulus response and biomolecule modification, and interact with other resident cells more extensively than their GM counterparts. GM-glia preserve the expression of developmental morphogens into adulthood and share 6 differentially enriched transcription factors that restrict the transcriptome complexity. Our work in marmoset, an experimentally tractable animal model with >5 times more WM volume and complexity than mouse, identifies novel WM-glia subtypes and their contributions to different neurological disorders. A companion Callithrix jacchus Primate Cell Atlas (CjPCA) is available through an online portal https://cjpca.ninds. nih.gov to facilitate data exploration.
Infant gut strain persistence is associated with maternal origin, phylogeny, and functional potential including surface adhesion and iron acquisition

Gut microbiome succession impacts infant development. However, it remains unclear what factors promote persistence of initial bacterial colonists in the developing gut. Here, we performed strain-resolved metagenomic analyses to compare gut colonization of preterm and full-term infants throughout the first year of life and evaluated links between strain persistence and strain origin as well as genetic potential. Analysis of 206 fecal metagenomes collected from full-term and preterm infants and their mothers revealed that infants’ initially distinct microbial communities converged by age one. Approximately 11% of early colonists, primarily Bacteroides and Bifidobacterium, persisted during the first year of life, and these were more prevalent in full-term compared to preterm infants. Gut-associated strains from mothers were significantly more likely to persist in the infant gut than other strains. Enrichment in genes for surface adhesion, iron acquisition and carbohydrate degradation may explain persistence of some strains through the first year of life.
The CXCR6/CXCL16 axis links inflamm-aging to disease severity in COVID-19 patients

Advancing age and chronic health conditions, significant risk factors for severe COVID-19, are associated with a pro-inflammatory state, termed inflamm-aging. CXCR6+ T cells are known to traffic to the lung and have been reported to increase with age. The ligand of CXCR6, CXCL16, is constitutively expressed in the lung and upregulated during inflammatory responses and the CXCR6/CXCL16 axis is associated with severe lung disease and pneumonia. Genome-wide association studies have also recently identified 3p21.31, encompassing the CXCR6 gene, as a susceptibility locus for severe COVID-19. We assessed numbers T cells expressing the chemokine receptor CXCR6 and plasma levels of CXCL16, in control and COVID-19 patients. Results demonstrated that circulating CD8+CXCR6+ T cells were significantly elevated with advancing age, yet virtually absent in patients with severe COVID-19. Peripheral levels of CXCL16 were significantly upregulated in severe COVID-19 patients compared to either mild COVID-19 patients or SARS-CoV-2 negative controls. This study supports a significant role of the CXCR6/CXCL16 axis in the immunopathogenesis of severe COVID-19.
Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes

Intestinal immunity is coordinated by specialized mononuclear phagocyte populations, constituted by a diversity of cell subsets. Although the cell subsets constituting the mononuclear phagocyte network are thought to be similar in both small and large intestine, these organs have distinct anatomy, microbial composition, and immunological demands. Whether these distinctions demand organ-specific mononuclear phagocyte populations with dedicated organ-specific roles in immunity are unknown. Here we implement a new strategy to subset murine intestinal mononuclear phagocytes and identify two novel subsets which are colon-specific: a macrophage subset and a Th17-inducing dendritic cell (DC) subset. Colon-specific DCs and macrophages co-expressed CD24 and CD14, and surprisingly, both were dependent on the transcription factor IRF4. Novel IRF4-dependent CD14+CD24+ macrophages were markedly distinct from conventional macrophages and failed to express classical markers including CX3CR1, CD64 and CD88, and surprisingly expressed little IL-10, which was otherwise robustly expressed by all other intestinal macrophages. We further found that colon-specific CD14+CD24+ mononuclear phagocytes were essential for Th17 immunity in the colon, and provide definitive evidence that colon and small intestine have distinct antigen presenting cell requirements for Th17 immunity. Our findings reveal unappreciated organ-specific diversity of intestine-resident mononuclear phagocytes and organ-specific requirements for Th17 immunity.
Training Data: How can we best prepare instructors to teach data science in undergraduate biology and environmental science courses?

There is a clear and concrete need for greater quantitative literacy in the biological and environmental sciences. Data science training for students in higher education necessitates well-equipped and confident instructors across curricula. However, not all instructors are versed in data science skills or research-based teaching practices. Our study sought to survey the state of data science education across institutions of higher learning, identify instructor needs, and illuminate barriers to teaching data science in the classroom. We distributed a survey to instructors around the world, focused on the United States, and received 106 complete responses. Our results indicate that instructors across institutions use, teach, and view data management, analysis, and visualization as important for students to learn. Code, modeling, and reproducibility were less valued by instructors, although there were differences by institution type (doctoral, masters, or baccalaureate), and career stage (time since terminal degree). While there were a variety of barriers highlighted by respondents, instructor background, student background, and space in the curriculum were the greatest barriers of note. Interestingly, instructors were most interested in receiving training for how to teach code and data analysis in the undergraduate classroom. Our study provides an important window into how data science is taught in higher education as well as suggestions for how we can best move forward with empowering instructors across disciplines.