Miracle-dz/UniFAR-FTUs huggingface dataset:
Object manifold geometry across the mouse cortical visual hierarchy

Despite variations in appearance we robustly recognize objects. Neuronal populations responding to objects presented under varying conditions form object manifolds and hierarchically organized visual areas untangle pixel intensities into linearly decodable object representations. However, the associated changes in the geometry of object manifolds along the cortex remain unknown. Using home cage training we showed that mice are capable of invariant object recognition. We simultaneously recorded the responses of thousands of neurons to measure the information about object identity across the visual cortex and found that lateral areas LM, LI and AL carry more linearly decodable object information compared to other visual areas. We applied the theory of linear separability of manifolds, and found that the increase in classification capacity is associated with a decrease in the dimension and radius of the object manifold, identifying the key features in the geometry of the population neural code that enable invariant object coding.
Vertebrate palaeodistributional patterns and continental drift

The patterns of distribution of vertebrates (primarily terrestrial forms) are analysed from the Silurian onwards, using palaeogeographical maps which show epicontinental seas as well as intercontinental oceans. Silurian vertebrates (fish) are known almost exclusively from Euramerica. Many Devonian fish which are normally found in fresh waters seem to have been able to cross intervening seas between one continent and another. It is suggested that this ability may be physiologically related to their capacity to use aerial respiration. There is some evidence for a separate Devonian osteostracan fish fauna in China. Amphibians are first known from the uppermost Devonian of the Euramerican continent, and land vertebrates are known almost exclusively from that continent until the Mid Permian. It is suggested that tetrapods may have evolved in Euramerica, and were only able to colonize Asia and Gondwanaland after continental drift had linked these areas with Euramerica, causing the Uralian and Alleghanian orogenies.
Neuronal death in pneumococcal meningitis is triggered by pneumolysin and pilus-1 interactions with β-actin

Neuronal damage is a major consequence of bacterial meningitis, but little is known about mechanisms that lead to neuronal death. Streptococcus pneumoniae (pneumococcus) is a leading cause of bacterial meningitis and many survivors develop neurological sequelae after the acute infection has resolved, possibly due to neuronal damage. Here, we studied mechanisms for pneumococcal interactions with neurons. Using human primary neurons and co-immunoprecipitation assays, we showed that pneumococci interact with the cytoskeleton protein β-actin through the pilus-1 adhesin RrgA and the cytotoxin pneumolysin (Ply), thereby promoting adhesion and uptake into neurons and neuronal death. Using our bacteremia-derived meningitis mouse model, we observed that RrgA- and Ply-expressing pneumococci co-localize with neuronal β-actin. We found that pneumococcal-infected neurons show increased intracellular Ca2+ levels depending on RrgA and mainly Ply which likely cause actin cytoskeleton disassembly leading to neuronal damage. Finally, neuronal death caused by pneumococcal infection could be inhibited using antibody against β-actin.
Sphagnum peat moss thermotolerance is modulated by the microbiome

Sphagnum peat mosses is a major genus that is common to peatland ecosystems, where the species contribute to key biogeochemical processes including the uptake and long-term storage of atmospheric carbon. Warming threatens Sphagnum mosses and the peatland ecosystems in which they reside, potentially affecting the fate of vast global carbon stores. The competitive success of Sphagnum species is attributed in part to their symbiotic interactions with microbial associates. These microbes have the potential to rapidly respond to environmental change, thereby helping their host plants survive under changing environmental conditions. To investigate the importance of microbiome thermal origin on host plant thermotolerance, we mechanically separated the microbiome from Sphagnum plants residing in a whole-ecosystem warming study, transferred the component microbes to germ-free plants, and exposed the new hosts to temperature stress. Although warming decreased plant photosynthesis and growth in germ-free plants, the addition of a microbiome from a thermal origin that matched the experimental temperature completely restored plants to their pre-warming growth rates. Metagenome and metatranscriptome analyses revealed that warming altered microbial community structure, including the composition of key cyanobacteria symbionts, in a manner that induced the plant heat shock response, especially the Hsp70 family and jasmonic acid production. The plant heat shock response could be induced even without warming, suggesting that the warming-origin microbiome provided the host plant with thermal preconditioning. Together, our findings show that the microbiome can transmit thermotolerant phenotypes to host plants, providing a valuable strategy for rapidly responding to environmental change.
Transcription factor-based gene therapy to treat glioblastoma through direct neuronal conversion

Glioblastoma (GBM) is the most prevalent and aggressive adult primary cancer in the central nervous system (CNS). Therapeutic approaches for glioblastoma are under intense investigation, such as the emerging immunotherapy, but so far only marginal progress has been made due to the heterogeneity and highly invasive nature of glioblastoma. Here, we propose an alternative approach to tackle GBM through reprogramming proliferative GBM cells into non-proliferative neurons. We report efficient neuronal conversion from human GBM cells by overexpressing single neural transcription factor Neurogenic differentiation 1 (NeuroD1), Neurogenin-2 (Neurog2) or Achaete-scute homolog 1 (Ascl1). Subtype characterization reveals that the majority of Neurog2- and NeuroD1-converted neurons are glutamatergic, while Ascl1 favors GABAergic neuron generation. The GBM cell-converted neurons not only express pan-neuronal markers, such as NeuN and MAP2, but also exhibit neuron-specific electrophysiological activities. We further conducted transcriptome analyses to investigate the underlying cell conversion mechanism. Our RNA-seq analyses discover that neuronal genes are activated among glioma cells after overexpression of neural transcription factors, and different signaling pathways are activated by different neural transcription factors. Importantly, the neuronal conversion of GBM cells is accompanied by significant inhibition of GBM cell proliferation in both in vitro and in vivo models. Therefore, these results suggest that GBM cells can be reprogrammed into different subtypes of neurons, leading to a potential alternative approach to treat brain tumor. Significance Converting dividing glioblastoma cells into non-dividing neurons may provide an innovative therapeutic approach to treat glioblastoma. Highlights Efficient neuronal conversion of human glioblastoma cells achieved by overexpression of neural transcription factors Neurog2- and NeuroD1-converted neurons are mostly glutamatergic, while Ascl1-converted neurons are mainly GABAergic Transcriptome analyses reveal the activation of neuronal genes after overexpression of neural transcription factors in glioblastoma cells Inhibition of cell proliferation during glioblastoma cell conversion both in vitro and in vivo
FACT is recruited to the +1 nucleosome of transcribed genes and spreads in a Chd1-dependent manner

The histone chaperone FACT occupies transcribed regions where it plays prominent roles in maintaining chromatin integrity and preserving epigenetic information. How it is targeted to transcribed regions, however, remains unclear. Proposed models for how FACT finds its way to transcriptionally active chromatin include docking on the RNA polymerase II (RNAPII) C-terminal domain (CTD), recruitment by elongation factors, recognition of modified histone tails and binding partially disassembled nucleosomes. Here, we systematically tested these and other scenarios in Saccharomyces cerevisiae and found that FACT binds transcribed chromatin, not RNAPII. Through a combination of experimental and mathematical modeling evidence, we propose that FACT recognizes the +1 nucleosome, as it is partially unwrapped by the engaging RNAPII, and spreads to downstream nucleosomes aided by the chromatin remodeler Chd1. Our work clarifies how FACT interacts with genes, suggests a processive mechanism for FACT function, and provides a framework to further dissect the molecular mechanisms of transcription-coupled histone chaperoning. Highlights High-resolution mapping of FACT localization in yeast FACT binds partially unwrapped nucleosomes in transcribed genes, not RNAPII FACT distribution along genes requires Chd1 Processive mechanism for FACT function
Of Blickets, Butterflies, and Baby Dinosaurs: Children’s Diagnostic Reasoning Across Domains

The three studies presented here examine children’s ability to make diagnostic inferences about an interactive causal structure across different domains. Previous work has shown that children’s abilities to make diagnostic inferences about a physical system develops between the ages of 5 and 8. Experiments 1 (N = 242) and 2 (N = 112) replicate this work with 4- to 10-year-olds and demonstrate that this developmental trajectory is preserved when children reason about a closely matched biological system. Unlike Experiments 1 and 2, Experiment 3 (N = 110) demonstrates that children struggle to make similar inferences when presented with a parallel task about category membership in biology. These results suggest that children might have the basic capacity for diagnostic inference at relatively early ages, but that the content of the inference task might interfere with their ability to demonstrate such capacities.
Multifractality in postural sway supports quiet eye training in aiming tasks: A study of golf putting

The ‘quiet eye’ (QE) approach to visually-guided aiming behavior invests fully in perceptual information’s potential to organize coordinated action. Sports psychologists refer to QE as the stillness of the eyes during aiming tasks and increasingly into self- and externally-paced tasks. Amidst the ‘noisy’ fluctuations of the athlete’s body, quiet eyes might leave fewer saccadic interruptions to the coupling between postural sway and optic flow. Postural sway exhibits fluctuations whose multifractal structure serves as a robust predictor of both visual and haptic perceptual responses. Postural sway generates optic flow centered on an individual’s eye height. We predicted that perturbing the eye height by attaching wooden blocks below the feet would perturb the putting more so in QE-trained participants than in those trained technically. We also predicted that the efficacy of QE and responses to this perturbation would depend on multifractality in postural sway. Specifically, we predicted that less multifractality would predict more adaptive responses to the perturbation and higher putting accuracy. Results showed that lower multifractality led to more frequent successful putts, and the perturbation of eye height led to less frequent successful putts, particularly for QE-trained participants. Models of radial error (i.e., the distance between the ball’s final position and the hole) indicated that lower estimates of multifractality due to nonlinearity coincided with a more adaptive response to the perturbation. These results suggest that reduced multifractality may act in a context-sensitive manner to restrain motoric degrees of freedom to achieve the task goal.
A computationally designed fluorescent biosensor for D-serine

Periplasmic solute-binding proteins (SBPs) have evolved to balance the demands of ligand affinity, thermostability and conformational change to carry out diverse functions in small molecule transport, sensing and chemotaxis. Although the ligand-induced conformational changes that occur in SBPs make them useful components in biosensors, their complexity can be difficult to emulate and they are challenging targets for protein engineering and design. Here we have engineered a fluorescent biosensor with specificity for the signalling molecule D-serine (D-SerFS) from a D-alanine-specific SBP. Through a combination of binding site and remote mutations, the affinity, specificity and thermostability were optimized to allow the detection of changes in D-serine levels using two-photon excitation fluorescence microscopy in situ and in vivo. This work illustrates the multidimensional constraints that are imposed by the trade-offs between structural dynamics, ligand affinity and thermostability, and how these must be balanced to achieve desirable activities in the engineering of complex, dynamic proteins.
Temporal landscape of mutation accumulation in SARS-CoV-2 genomes from Bangladesh: possible implications from the ongoing outbreak in Bangladesh

Along with intrinsic evolution, adaptation to selective pressure in new environments might have resulted in the circulatory SARS-CoV-2 strains in response to the geoenvironmental conditions of a country and the demographic profile of its population. Thus the analysis of genomic mutations of these circulatory strains may give an insight into the molecular basis of SARS-CoV-2 pathogenesis and evolution favoring the development of effective treatment and containment strategies. With this target, the current study traced the evolutionary route and mutational frequency of 198 Bangladesh originated SARS-CoV-2 genomic sequences available in the GISAID platform over a period of 13 weeks as of 14 July 2020. The analyses were performed using MEGA 7, Swiss Model Repository, Virus Pathogen Resource and Jalview visualization. Our analysis identified that majority of the circulating strains in the country belong to B and/or L type among cluster A to Z and strikingly differ from both the reference genome and the first sequenced genome from Bangladesh. Mutations in Nonspecific protein 2 (NSP2), NSP3, RNA dependent RNA polymerase (RdRp), Helicase, Spike, ORF3a, and Nucleocapsid (N) protein were common in the circulating strains with varying degrees and the most unique mutations(UM) were found in NSP3 (UM-18). But no or limited changes were observed in NSP9, NSP11, E (Envelope), NSP7a, ORF 6, and ORF 7b suggesting the possible conserved functions of those proteins in SARS-CoV-2 propagation. However, along with D614G mutation, more than 20 different mutations in the Spike protein were detected basically in the S2 domain. Besides, mutations in SR-rich region of N protein and P323L in RDRP were also present. However, the mutation accumulation showed an association with sex and age of the COVID-19 positive cases. So, identification of these mutational accumulation patterns may greatly facilitate drug/ vaccine development deciphering the age and the sex dependent differential susceptibility to COVID-19.
Stable isotope informed genome-resolved metagenomics uncovers potential trophic interactions in rhizosphere soil

The functioning, health, and productivity of soil is intimately tied to a complex network of interactions, particularly in plant root-associated rhizosphere soil. We conducted a stable isotope-informed, genome-resolved metagenomic study to trace carbon from Avena fatua grown in a 13CO2 atmosphere into soil. We collected paired rhizosphere and non-rhizosphere soil at six and nine weeks of plant growth and extracted DNA that was then separated by density using gradient centrifugation. Thirty-two fractions from each sample were grouped by density, sequenced, assembled, and binned to generate 55 unique microbial genomes that were >70% complete. The complete 18S rRNA sequences of several micro-eukaryotic bacterivores and fungi were enriched in 13C. We generated several circularized bacteriophage (phage) genomes, some of which were the most labelled entities in the rhizosphere. CRISPR locus targeting connected one of these phage to a Burkholderiales host predicted to be a plant pathogen. Another highly labeled phage is predicted to replicate in a Catenulispora sp. , a possible plant growth-promoting bacterium. We searched the genomes for traits known to be used in interactions involving bacteria, micro-eukaryotes and plant roots and found that heavily isotopically-labeled bacteria have the ability to modulate plant signaling hormones, possess numerous plant pathogenicity factors, and produce toxins targeting micro-eukaryotes. Overall, 13C stable isotope-informed genome-resolved metagenomics revealed that very active bacteria often have the potential for strong interactions with plants and directly established that phage can be important agents of turnover of plant-derived carbon in soil.
Gender (im)balance in citation practices in cognitive neuroscience

In the field of neuroscience, despite the fact that the proportion of peer-reviewed publications authored by women has increased in recent decades, the proportion of citations of women-led publications has not seen a commensurate increase: In five broad-scope journals, citations of papers first- and/or last-authored by women have been shown to be fewer than would be expected if gender was not a factor in citation decisions (Dworkin et al., 2020). Given the important implications that such underrepresentation may have on the careers of women researchers, it is important to determine whether this same trend is true in subdisciplines of the field, where interventions might be more effective. Here, we report the results of an extension of the analyses carried out by Dworkin et al. (2020) to citation patterns in the Journal of Cognitive Neuroscience (JoCN). The results indicate that the underrepresentation of women-led publications in reference sections is also characteristic of papers published in JoCN over the past decade. Furthermore, this pattern of citation imbalances is present for all gender classes of authors, implicating systemic factors. These results contribute to the growing body of evidence that intentional action is needed to address inequities in the way that we carry out and communicate our science.
Potentially zoonotic gastrointestinal nematodes co‐infecting free ranging non‐human primates in Kenyan urban centres

Background Natural infections with soil transmitted nematodes occur in non-human primates (NHPs) and have the potential to cross primate-species boundaries and cause diseases of significant public health concern. Despite their presence in most urban centres in Kenya, comprehensive studies on their gastrointestinal parasites are scant. Objective Conduct a cross-sectional survey to identify zoonotic nematodes in free-ranging NHPs found within four selected urban and peri-urban centres in Kenya. Methods A total of 86 NHPs: 41 African green monkeys [AGM] (Chlorocebus aethiops), 30 olive baboons (Papio anubis), 5 blue monkeys (Cercopithecus mitis stuhlmanni) and 10 red tailed monkeys (Cercopithecus ascanius) were sampled once in situ and released back to their habitat. Microscopy was used to identify nematodes egg and larvae stages in the samples. Subsequently, PCR coupled with high-resolution melting (PCR-HRM) analysis and sequencing were used to identify nodule worms. Results NHPs inhabiting densely populated urban environs in Kenya were found infected with a rich diversity of nematodes including three potentially zoonotic nematodes including Oesophagostomum stephanostomum, Oesophagostomum bifurcum and Trichostrongylus colubriformis and co-infections were common. Conclusion Phylogenetic analysis showed that O. stephanostomum from red tailed and blue monkeys have a close evolutionary relatedness to human isolates suggesting the zoonotic potential of this parasite. Moreover, we also report the first natural co-infection of O. bifurcum and O. stephanostomum in free-ranging AGMs.
SARS-CoV-2 infects brain choroid plexus and disrupts the blood-CSF-barrier

Coronavirus disease-19 (COVID-19), caused by the SARS-CoV-2 virus, leads primarily to respiratory symptoms that can be fatal, particularly in at risk individuals. However, neurological symptoms have also been observed in patients, including headache, seizures, stroke, and fatigue. The cause of these complications is not yet known, and whether they are due to a direct infection of neural cells, such as neurons and astrocytes, or through indirect effects on supportive brain cells, is unknown. Here, we use brain organoids to examine SARS-CoV-2 neurotropism. We examine expression of the key viral receptor ACE2 in single-cell RNA sequencing (scRNA-seq) revealing that only a subset of choroid plexus cells but not neurons or neural progenitors express this entry factor. We then challenge organoids with both SARS-CoV-2 spike protein pseudovirus and live virus to demonstrate high viral tropism for choroid plexus epithelial cells but not stromal cells, and little to no infection of neurons or glia. We find that infected cells of the choroid plexus are an apolipoprotein and ACE2 expressing subset of epithelial barrier cells. Finally, we show that infection with live SARS-CoV-2 leads to barrier breakdown of the choroid plexus. These findings suggest that neurological complications may result from effects on the choroid plexus, an important barrier that normally prevents entry of immune cells and cytokines into the cerebrospinal fluid (CSF) and brain.
eDNA metabarcoding as a biomonitoring tool for marine protected areas

Monitoring of marine protected areas (MPAs) is critical for marine ecosystem management, yet current protocols rely on SCUBA-based visual surveys that are costly and time consuming, limiting their scope and effectiveness. Environmental DNA (eDNA) metabarcoding is a promising alternative for marine ecosystem monitoring, but more direct comparisons to visual surveys are needed to understand the strengths and limitations of each approach. This study compares fish communities inside and outside the Scorpion State Marine Reserve off Santa Cruz Island, CA using eDNA metabarcoding and underwater visual census surveys. Results from eDNA captured 76% (19/25) of fish species and 95% (19/20) of fish genera observed during pairwise underwater visual census. Species missed by eDNA were due to the inability of MiFish 12S barcodes to differentiate species of rockfishes (Sebastes, n=4) or low site occupancy rates of crevice-dwelling Lythrypnus gobies. However, eDNA detected an additional 30 fish species not recorded in paired visual surveys, but previously reported from prior visual surveys, highlighting the sensitivity of eDNA. Significant variation in eDNA signatures by location (50m) and site (~1000m) demonstrates the sensitivity of eDNA to address key questions such as community composition inside and outside MPAs. Interestingly, eDNA results recorded higher species richness outside the MPA while visual surveys observed the opposite pattern. This result is likely caused by swamping effects of high fish abundance in MPAs that reduce detection probabilities of pelagic and intertidal taxa. Results demonstrate the utility of eDNA metabarcoding for monitoring marine ecosystems, providing an important complementary tool to visual methods.