Miracle-dz/UniFAR-FTUs huggingface dataset:
Endosomal recycling to the surface mediated by Gpa1 and PI3-Kinase is inhibited by glucose starvation

Cell surface protein trafficking is regulated in response to nutrient availability, with multiple pathways directing surface membrane proteins to the lysosome for degradation in response to suboptimal extracellular nutrients. Internalised protein and lipid cargoes recycle back to the surface efficiently in glucose replete conditions, but this trafficking is attenuated following glucose starvation. We find cells with either reduced or hyperactive phosphatidylinositol 3-kinase activity are defective for recycling. Furthermore, we find the yeast Gα subunit Gpa1, which localises to endosomes and functionally couples with phosphatidylinositol 3-kinase, is required for surface recycling of cargoes. Following glucose starvation, nuclear translocation of Mig1 increases GPA2 levels and inhibits recycling, potentially by diverting Gpa1 to the surface and interfering with its endosomal role in recycling. Glucose privation therefore triggers a survival mechanism to increase retention of surface cargoes in endosomes and promote their lysosomal degradation.
Integrative physiological, biochemical and transcriptomic analysis of hexaploid wheat roots and shoots provides new insights into the molecular regulatory network during Fe & Zn starvation

In plants, iron (Fe) & zinc (Zn) uptake and transportation from the rhizosphere to the grain is a critical process regulated by complex transcriptional regulatory networks. However, understanding the combined effect of Fe & Zn starvation on their uptake and transportation and the molecular regulatory networks that control them lack in wheat. Here, we performed a comprehensive physiological, biochemical and transcriptome analysis in two bread wheat genotypes, i.e. Narmada 195 and PBW 502, differing in inherent Fe & Zn content to understand the mechanism of Fe & Zn homeostasis. Compared to PBW 502, Narmada 195 exhibited increased tolerance to Fe & Zn withdrawal by an increased level of antioxidant enzymes and DPPH radical scavenging activity along with less malondialdehyde (MDA), H2O2 level, increased PS accumulation and lower reduction of root and shoot Fe & Zn content and length, leaf chlorosis, and leaf area. By integrating physiological and biochemical data along with co-expression & functional genome annotation and gene expression analysis, we identified 25 core genes associated with four key pathways, i.e. Met cycle (10), PS biosynthesis (4), antioxidant (3) and transport system (8) that were significantly modulated by Fe & Zn withdrawal in both the genotypes. Genes of these four pathways were more considerably up-regulated in Narmada 195, allowing better tolerance to Fe & Zn withdrawal and efficient uptake and transportation of Fe & Zn. Chromosomal distribution and sub-genome wise mapping of these genes showed a contribution from all the chromosomes except group 5 chromosomes with the highest number of genes mapped to chromosome 4 (24%) and sub-genome D (40%). Besides, we also identified 26 miRNAs targeting 14 core genes across the four pathways. Together, our work provides a crucial angle for an in-depth understanding of regulatory cross-talk among physiological, biochemical and transcriptional reprogramming underlying Fe & Zn withdrawal in wheat. Core genes identified can serve as valuable resources for further functional research for genetic improvement of Fe & Zn content in wheat grain. Highlight Our work provides a crucial angle for a comprehensive understanding of the regulatory mechanism underlying Fe & Zn withdrawal associated with physiological, biochemical and transcriptional reprogramming in wheat.
Naturalistic audio-movies reveal common spatial organization across “visual” cortices of different blind individuals

Occipital cortices of different sighted people contain analogous maps of visual information (e.g., foveal vs. peripheral space). In congenital blindness, “visual” cortices enhance responses to nonvisual stimuli. Do deafferented visual cortices of different blind people represent common informational maps? We leverage a naturalistic stimulus paradigm and inter-subject pattern similarity analysis to address this question. Blindfolded sighted (S, n=22) and congenitally blind (CB, n=22) participants listened to three auditory excerpts from movies; a naturalistic spoken narrative; and matched degraded auditory stimuli (i.e., shuffled sentences and backwards speech) while undergoing fMRI scanning. In a parcel-based whole brain analysis, we measured the spatial activity patterns evoked by each unique, ten-second segment of each auditory clip. We then compared each subject’s spatial pattern to that of all other subjects in the same group (CB or S) within and across segments. In both blind and sighted groups, segments of meaningful auditory stimuli produced distinctive patterns of activity that were shared across individuals. Crucially, only in the CB group, this segment-specific, cross-subject pattern similarity effect emerged in visual cortex, but only for meaningful naturalistic stimuli and not backwards speech. These results suggest that spatial activity patterns within deafferented visual cortices encode meaningful, segment-level information contained in naturalistic auditory stimuli, and that these representations are spatially organized in a similar fashion across blind individuals. Significance Statement Recent neuroimaging studies show that the so-called “visual” cortices activate during non-visual tasks in people who are born blind. Do the visual cortices of people who are born blind develop similar representational maps? While congenitally blind individuals listened to naturalistic auditory stimuli (i.e., sound clips from movies), distinct timepoints within each stimulus elicited unique spatial activity patterns in visual cortex, and these patterns were shared across different people. These findings suggest that in blindness, the visual cortices encode meaningful information embedded in naturalistic auditory signals in a spatially distributed manner, and that a common representational map can emerge in visual cortex independent of visual experience.
Mechanistic basis for understanding the dual activities of the bifunctional Azotobacter vinelandii mannuronan C-5 epimerase and alginate lyase AlgE7

The functional properties of alginates are dictated by the monomer composition and molecular weight distribution. Mannuronan C-5 epimerases determine the former by epimerizing β-D-mannuronic acid residues (M) into α-L-guluronic acid residues (G). The molecular weight is affected by alginate lyases, which cleave alginate chains through β-elimination. The reaction mechanisms for the epimerization and cleavage are similar and some enzymes can perform both. These dualistic enzymes share high sequence identity with mannuronan C-5 epimerases without lyase activity, and the mechanism behind their activity as well as the amino acids responsible for it are still unknown. In this study, we investigate mechanistic determinants of the bifunctional epimerase and lyase activity of AlgE7 from Azotobacter vinelandii. Based on sequence analyses, a range of AlgE7 variants were constructed and subjected to activity assays and product characterization by NMR. Our results show that the lyase activity of AlgE7 is regulated by the type of ion present: Calcium promotes it, whereas NaCl reduces it. By using defined poly-M and poly-MG substrates, the preferred cleavage sites of AlgE7 were found to be M↓XM and G↓XM, where X can be either M or G. By studying AlgE7 mutants, R148 was identified as an important residue for the lyase activity, and the point mutant R148G resulted in an enzyme with only epimerase activity. Based on the results obtained in the present study we suggest a unified catalytic reaction mechanism for both epimerase and lyase activities where H154 functions as the catalytic base and Y149 as the catalytic acid. Importance Post-harvest valorisation and upgrading of algal constituents is a promising strategy in the development of a sustainable bioeconomy based on algal biomass. In this respect, alginate epimerases and lyases are valuable enzymes for tailoring of the functional properties of alginate, a polysaccharide extracted from brown seaweed with numerous applications in food, medicine and material industries. By providing a better understanding of the reaction mechanism and of how the two enzyme reactions can be altered by changes in reaction conditions, this study opens for further applications of bacterial epimerases and lyases in enzymatic tailoring of alginate polymers.
Transport Motility of Phagosomes on Actin and Microtubules Regulates Timing and Kinetics of Their Maturation

Phagosome maturation, in which ingested pathogens are degraded through a complex sequence of biochemical changes, is an essential process in infection control and tissue homeostasis. The maturation of phagosomes requires their intracellular transport. However, mechanisms underlying this dynamical-biochemical interdependence is poorly understood due to the lack of methods to independently manipulate either process. Here we present a study to magnetically manipulate the transport of single phagosomes and simultaneously measure their maturation and degradative functions. We reveal that the transport velocity of phagosomes acts as a maturation clock to regulate the timing of biochemical signaling activities in phagosomes. We show that velocity of phagosomes on microtubules determines their rate of fusion with lysosomes and consequently the rate of lumen acidification, following a linear relationship. Meanwhile, the timing of phagosome transport from actin cortex to microtubules controls the kinetics of early phagosome assembly and rate of transition to late phagosomes.
Sex- and context-dependent effects of acute isolation on vocal and non-vocal social behaviors in mice

Humans are extraordinarily social, and social isolation has profound effects on our behavior, ranging from increased social motivation following short periods of social isolation to increased anti-social behaviors following long-term social isolation. Mice are frequently used as a model to understand how social isolation impacts the brain and behavior. While the effects of chronic social isolation on mouse social behavior have been well studied, much less is known about how acute isolation impacts mouse social behavior and whether these effects vary according to the sex of the mouse and the behavioral context of the social encounter. To address these questions, we characterized the effects of acute (3-day) social isolation on the vocal and non-vocal social behaviors of male and female mice during same-sex and opposite-sex social interactions. Our experiments uncovered pronounced effects of acute isolation on social interactions between female mice, while revealing more subtle effects on the social behaviors of male mice during same-sex and opposite-sex interactions. Our findings advance the study of same-sex interactions between female mice as an attractive paradigm to investigate neural mechanisms through which acute isolation enhances social motivation and promotes social behavior.
Bipartite functional fractionation within the neural system for social cognition supports the psychological continuity of self vs. other

Research of social neuroscience establishes that regions in the brain’s default network (DN) and semantic network (SN) are engaged by socio-cognitive tasks. Research of the human connectome shows that DN and SN regions are both situated at the high-order end of cortical gradient but differ in their positions on this gradient. In the present study, we integrated these two bodies of research, used the psychological continuity of self vs. other as a ‘test-case’, and used fMRI to investigate whether these networks would encode social concepts differently. We found a robust dissociation between the DN and SN – while both networks contained sufficient information for decoding broad-stroke distinction of social categories, the DN carried more generalisable information for cross-classifying across social distance and emotive valence than did the SN. We also found that the overarching distinction of self vs. other was a principal divider of the representational space while social distance was an auxiliary factor (subdivision, nested within the principal dimension), and this representational landscape was more manifest in the DN than in the SN. Taken together, our findings demonstrate how insights from connectome research can benefit social neuroscience, and have implications for clarifying the two networks’ differential contributions to social cognition.
The response of desert biocrust bacterial communities to hydration-desiccation cycles

Rain events in arid environments are highly unpredictable, interspersing extended periods of drought. Therefore, following changes in desert soil bacterial communities during hydration-desiccation cycles in the field, was seldom attempted. Here, we assessed rain-mediated dynamics of active community in the Negev Desert biological soil crust (biocrust), and evaluated the changes in bacterial composition, potential function, and photosynthetic activity. We predicted that increased biocrust moisture would resuscitate the phototrophs, while desiccation would inhibit their activity. Our results show that hydration increased chlorophyll content, resuscitated the biocrust Cyanobacteria, and induced potential phototrophic functions. However, decrease in the soil water content did not immediately decrease the phototrophs activity, though chlorophyll levels decreased. Moreover, while the Cyanobacteria relative abundance significantly increased, Actinobacteria, the former dominant taxa, significantly decreased in abundance. We propose that, following a rain event biocrust moisture significantly decreased, almost to drought levels, yet the response of the active bacterial community lagged, in contrast to topsoil. Possible explanations to the described rain-mediated bacteria dynamics are discussed.
Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction

During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule is a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology.
Cytoplasmic pressure maintains epithelial integrity and inhibits cell motility

Cytoplasmic pressure, a function of actomyosin contractility and water flow, can regulate cellular morphology and dynamics. In mesenchymal cells, cytoplasmic pressure powers cell protrusion through physiological three-dimensional extracellular matrices. However, the role of intracellular pressure in epithelial cells is relatively unclear. Here we find that high cytoplasmic pressure is necessary to maintain barrier function, one of the hallmarks of epithelial homeostasis. Further, our data show that decreased cytoplasmic pressure facilitates lamellipodia formation during the epithelial to mesenchymal transition (EMT). Critically, activation of the actin nucleating protein Arp2/3 is required for the reduction in cytoplasmic pressure and lamellipodia formation in response to treatment with hepatocyte growth factor (HGF) to induce EMT. Thus, elevated cytoplasmic pressure functions to maintain epithelial tissue integrity, while reduced cytoplasmic pressure triggers lamellipodia formation and motility during HGF-dependent EMT.
Dorsomedial striatal activity tracks completion of behavioral sequences

For proper execution of goal-directed behaviors, individuals require both a general representation of the goal and an ability to monitor their own progress toward that goal. Here, we examine how dorsomedial striatum (DMS), a region pivotal for forming associations among stimuli, actions, and outcomes, encodes the execution of goal-directed action sequences that require self-monitoring of behavior. We trained rats to complete a sequence of at least 5 consecutive lever presses (without visiting the reward port) to obtain a reward and recorded the activity of individual cells in DMS while rats performed the task. We found that the pattern of DMS activity gradually changed during the execution of the sequence, permitting accurate decoding of sequence progress from neural activity at a population level. Moreover, this sequence-related activity was blunted on trials where rats did not complete a sufficient number of presses. Overall, these data suggest a link between DMS activity and the execution of behavioral sequences that require monitoring of ongoing behavior.
The evolution of germ-soma specialization under different genetic and environmental effects

Division of labor exists at different levels of biological organization - from cell colonies to human societies. One of the simplest examples of the division of labor in multicellular organisms is germ-soma specialization, which plays a key role in the evolution of organismal complexity. Here we formulate and study a general mathematical model exploring the emergence of germ-soma specialization in colonies of cells. We consider a finite population of colonies competing for resources. Colonies are of the same size and are composed by asexually reproducing haploid cells. Each cell can contribute to activity and fecundity of the colony, these contributions are traded-off. We assume that all cells within a colony are genetically identical but gene expression is affected by variation in the microenvironment experienced by individual cells. Through analytical theory and evolutionary agent-based modeling we show that the shape of the trade-off relation between somatic and reproductive functions, the type and extent of variation in within-colony microenvironment, and, in some cases, the number of genes involved, are important predictors of the extent of germ-soma specialization. Specifically, increasing convexity of the trade-off relation, the number of different environmental gradients acting within a colony, and the number of genes (in the case of random microenvironmental effects) promote the emergence of germ-soma specialization. Overall our results contribute towards a better understanding of the role of genetic, environmental, and microenvironmental factors in the evolution of germ-soma specialization.
Robust phylogenetic position of the enigmatic hydrozoan Margelopsis haeckelii revealed within the family Corymorphidae

The life-cycle and polyp morphology of representatives of Margelopsidae are very different from all other species in the hydrozoan clade Aplanulata. Their evolutionary origin and phylogenetic position has been the subject of significant speculation. A recent molecular study based only on COI data placed Margelopsidae as a sister group to all Aplanulata, an unexpected result because margelopsid morphology suggests affiliation with Tubulariidae or Corymorphidae. Here we used multigene analyses, including nuclear (18S rRNA and 28S rRNA) and mitochondrial (16S rRNA and COI) markers of the hydroid stage of the margelopsid species Margelopsis haeckelii Hartlaub, 1897 and the medusa stage of Margelopsis hartlaubii Browne, 1903 to resolve their phylogenetic position with respect to other hydrozoans. Our data provide strong evidence that M. haeckelii, the type species of Margelopsis, is a member of the family Corymorphydae. In contrast, M. hartlaubii Browne, 1903 is sister to Plotocnide borealis Wagner, 1885, a member of Boreohydridae. These results invalidate the family Margelopsidae. The phylogenetic signal of polyp and medusa stages is discussed in light of concept of inconsistent evolution and molecular phylogenetic analysis.
Sex Differences in Behavioral and Brainstem Transcriptomic Neuroadaptations following Neonatal Opioid Exposure in Outbred Mice

Abstract The opioid epidemic led to an increase in the number of neonatal opioid withdrawal syndrome (NOWS) cases in infants born to opioid-dependent mothers. Hallmark features of NOWS include weight loss, severe irritability, respiratory problems, and sleep fragmentation. Mouse models provide an opportunity to identify brain mechanisms that contribute to NOWS. Neonatal outbred Swiss Webster Cartworth Farms White (CFW) mice were administered morphine (15 mg/kg, s.c.) twice daily from postnatal day 1 (P1) to P14, an approximation of the third trimester of human gestation. Female and male mice underwent behavioral testing on P7 and P14 to determine the impact of opioid exposure on anxiety and pain sensitivity. Ultrasonic vocalizations (USVs) and daily body weights were also recorded. Brainstems containing pons and medulla were collected during morphine withdrawal on P14 for RNA sequencing. Morphine induced weight loss from P2 to P14, which persisted during adolescence (P21) and adulthood (P50). USVs markedly increased at P7 in females, emerging earlier than males. On P7 and P14, both morphine-exposed female and male mice displayed hyperalgesia on the hot plate and tail-flick assays, with females showing greater hyperalgesia than males. Morphine-exposed mice exhibited increased anxiety-like behavior in the open-field arena on P21. Transcriptome analysis of the brainstem, an area implicated in opioid withdrawal and NOWS, identified pathways enriched for noradrenergic signaling in females and males. We also found sex-specific pathways related to mitochondrial function and neurodevelopment in females and circadian entrainment in males. Sex-specific transcriptomic neuroadaptations implicate unique neurobiological mechanisms underlying NOWS-like behaviors.
Substitutions and codon usage in SARS-CoV-2 in mammals indicate natural selection and host adaptation

The outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, rapidly spread to create a global pandemic and has continued to spread across hosts from humans to animals, transmitting particularly effectively in mink. How SARS-CoV-2 evolves in animals and humans and the differences in the separate evolutionary processes remain unclear. We analyzed the composition and codon usage bias of SARS-CoV-2 in infected humans and animals. Compared with other animals, SARS-CoV-2 in mink had the most substitutions. The substitutions of cytidine in SARS-CoV-2 in mink account for nearly 50% of the substitutions, while those in other animals represent only 30% of the substitutions. The incidence of adenine transversion in SARS-CoV-2 in other animals is threefold higher than that in mink-CoV (the SARS-CoV-2 virus in mink). A synonymous codon usage analysis showed that SARS-CoV-2 is optimized to adapt in the animals in which it is currently reported, and all the animals showed decreased adaptability relative to that of humans, except for mink. A binding affinity analysis indicated that the spike protein of the SARS-CoV-2 variant in mink showed a greater preference for binding with the mink receptor ACE2 than with the human receptor, especially as the mutation Y453F and F486L in mink-CoV lead to improvement of binding affinity for mink receptor. Our study focuses on the divergence of SARS-CoV-2 genome composition and codon usage in humans and animals, indicating possible natural selection and current host adaptation.