Miracle-dz/UniFAR-FTUs huggingface dataset:
Neural Selectivity for Visual Motion in Macaque Area V3A

Abstract The processing of visual motion is conducted by dedicated pathways in the primate brain. These pathways originate with populations of direction-selective neurons in the primary visual cortex, which projects to dorsal structures like the middle temporal (MT) and medial superior temporal (MST) areas. Anatomical and imaging studies have suggested that area V3A might also be specialized for motion processing, but there have been very few studies of single-neuron direction selectivity in this area. We have therefore performed electrophysiological recordings from V3A neurons in two macaque monkeys (one male and one female) and measured responses to a large battery of motion stimuli that includes translation motion, as well as more complex optic flow patterns. For comparison, we simultaneously recorded the responses of MT neurons to the same stimuli. Surprisingly, we find that overall levels of direction selectivity are similar in V3A and MT and moreover that the population of V3A neurons exhibits somewhat greater selectivity for optic flow patterns. These results suggest that V3A should be considered as part of the motion processing machinery of the visual cortex, in both human and non-human primates.
Reproductive Cycle and Life-History Traits of the Viviparous Skink Mabuya frenata in Southeastern Brazil

The reproductive and fat body cycles and some life-history traits of the viviparous skink Mabuya frenata were studied in a seasonal habitat in the state of Sao Paulo, southeastern Brazil. Reproductive activity is markedly cyclical in both sexes. Females reach sexual maturity at juvenile body sizes, have an extended gestation period lasting 9-12 months, and give birth to 2-8 young (mean 4.9 ? 1.1), mainly during August through October. Fat stored in fat bodies during the wet season is used up during gestation in females and during increased spermatogenic activity in males. Females reach a larger adult body size than males, but males have relatively larger heads. The reproductive and life-history traits observed for M. frenata are similar to those of other South American Mabuya.
The zinc finger antiviral protein ZAP destabilises viral transcripts and restricts human cytomegalovirus

Interferon-stimulated gene products (ISGs) play a crucial role in early infection control. The ISG zinc finger CCCH-type antiviral protein 1 (ZAP/ZC3HAV1) antagonises several RNA viruses by binding to CG-rich RNA sequences, whereas its effect on DNA viruses is largely unknown. Here, we decipher the role of ZAP in the context of human cytomegalovirus (HCMV) infection, a β-herpesvirus that is associated with high morbidity in immunosuppressed individuals and newborns. We show that expression of the two major isoforms of ZAP, the long (ZAP-L) and short (ZAP-S), is induced during HCMV infection and that both negatively affect HCMV replication. Transcriptome and proteome analyses demonstrated that the expression of ZAP decelerates the progression of HCMV infection. SLAM-sequencing revealed that ZAP restricts HCMV at early stages of infection by destabilising a distinct subset of viral transcripts with low CG content. In summary, this report provides evidence of an important antiviral role for ZAP in host defense against HCMV infection and highlights its differentiated function during DNA virus infection.
Generation of glucocorticoid resistant SARS-CoV-2 T-cells for adoptive cell therapy

Adoptive cell therapy with viral-specific T cells has been successfully used to treat life-threatening viral infections, supporting the application of this approach against COVID-19. We expanded SARS-CoV-2 T-cells from the peripheral blood of COVID-19-recovered donors and non-exposed controls using different culture conditions. We observed that the choice of cytokines modulates the expansion, phenotype and hierarchy of antigenic recognition by SARS-CoV-2 T-cells. Culture with IL-2/4/7 but not other cytokine-driven conditions resulted in >1000 fold expansion in SARS-CoV-2 T-cells with a retained phenotype, function and hierarchy of antigenic recognition when compared to baseline (pre-expansion) samples. Expanded CTLs were directed against structural SARS-CoV-2 proteins, including the receptor-binding domain of Spike. SARS-CoV-2 T-cells could not be efficiently expanded from the peripheral blood of non-exposed controls. Since corticosteroids are used for the management of severe COVID-19, we developed an efficient strategy to inactivate the glucocorticoid receptor gene (NR3C1) in SARS-CoV-2 CTLs using CRISPR-Cas9 gene editing.
Prey-Driven Behavioral Habitat Use in a Low-Energy Ambush Predator

Food acquisition is an important modulator of animal behavior and habitat selection that can affect fitness. Optimal foraging theory predicts that predators should select habitat patches to maximize their foraging success and net energy gain, which predators can achieve by targeting spaces with high prey availability. However, it is debated whether prey availability drives fine-scale habitat selection for predators. We assessed whether an ambush predator, the timber rattlesnake (Crotalus horridus), exhibits optimal foraging site selection based on the spatial distribution and availability of prey. We evaluated the spatial concordance of radio-telemetered timber rattlesnake foraging locations and passive infrared game camera trap detections of potential small mammal prey (Peromyscus spp., Tamias striatus, and Sciurus spp.) in a mixed-use forest in southeastern Ohio from 2016–2019. We replicated a characteristic timber rattlesnake ambush position by focusing cameras over logs and modeled small mammal encounters across the landscape in relation to remotely-sensed forest and landscape structural features. To determine whether snakes selectively forage in areas with higher prey availability, we projected the estimated prey spatial relationships across the landscape and modeled their overlap of occurrence with observed timber rattlesnake foraging locations. We broadly predicted that prey availability was greatest in mature deciduous forests, but T. striatus and Sciurus spp. exhibited greater spatial heterogeneity compared to Peromyscus spp. We also combined predicted species encounter rates to encompass a body size gradient in potential prey. The spatial distribution of cumulative small mammal encounters (i.e. overall prey availability), rather than the distribution of any one species, was highly predictive of snake foraging. Timber rattlesnakes appear to select foraging locations where the probability of encountering prey is greatest. Our study provides evidence for fine-scale optimal foraging in a low-energy, ambush predator and offers new insights into drivers of snake foraging and habitat selection.
Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication

Mosquito-borne flaviviruses (MBFVs) including dengue, West Nile, yellow fever, and Zika viruses have an RNA genome encoding one open reading frame flanked by 5′ and 3′ untranslated regions (UTRs). The 3′ UTRs of MBFVs contain regions of high sequence conservation in structured RNA elements known as dumbbells (DBs) that regulate translation and replication of the viral RNA genome, functions proposed to depend on the formation of an RNA pseudoknot. To understand how DB structure provides this function, we used x-ray crystallography and structural modeling to reveal the details of its three-dimensional fold. The structure confirmed the predicted pseudoknot and molecular modeling revealed how conserved sequences form a four-way junction that appears to stabilize the pseudoknot. Single-molecule FRET suggests that the DB pseudoknot is a stable element that can regulate the switch between translation and replication during the viral lifecycle by modulating long-range RNA conformational changes.
A homologue of the mammalian tumour suppressor protein PTEN is a functional lipid phosphatase and required for chemotaxis in filamentous fungi

Phosphoinositides (PI) are essential components of eukaryotic membranes and function in a large number of signalling processes. While lipid second messengers are well studied in mammals and yeast, their role in filamentous fungi is poorly understood. We used fluorescent PI-binding molecular probes to localise the phosphorylated phosphatidylinositol species PI[3]P, PI[3,5]P2, PI[4]P and PI[4,5]P2 in hyphae of the endophyte Epichloë festucae in axenic culture and during interaction with its grass host Lolium perenne. We also analysed the roles of the phosphatidylinositol-4-phosphate 5-kinase MssD and the predicted phosphatidylinositol-3,4,5-triphosphate 3-phosphatase TepA, a homologue of the mammalian tumour suppressor protein PTEN. Deletion of tepA in E. festucae and in the root-infecting tomato pathogen Fusarium oxysporum had no impact on growth in culture or the host interaction phenotype. However, this mutation did uncover the presence of PI[3,4,5]P3 in septa of E. festucae and showed that TepA is required for chemotropism in F. oxysporum. The identification of PI[3,4,5]P3 in septa of ΔtepA strains suggests that filamentous fungi are able to generate PI[3,4,5]P3 using an alternative biosynthetic pathway and that fungal PTEN homologues are functional lipid phosphatases. The F. oxysporum chemotropism defect demonstrates a conserved role of PTEN homologues in chemotaxis across protists, fungi and mammals.
Attention network modulation via tRNS correlates with attention gain

Transcranial Random Noise Stimulation (tRNS) can enhance vision in the healthy and diseased brain. Yet, the impact of tRNS on large-scale cortical networks is still unknown. We investigated the impact of tRNS coupled with behavioral training on resting-state functional connectivity and attention. We trained human subjects for four consecutive days on two attention tasks, while receiving tRNS over the intraparietal sulci, the middle temporal areas, or sham stimulation. We measured resting state functional connectivity of nodes of the dorsal and ventral attention network (DVAN) before and after training. We found a strong behavioral improvement and increased connectivity within the DVAN after parietal stimulation only. Crucially, behavioral improvement positively correlated with connectivity measures. We conclude changes in connectivity is a marker for the enduring effect of tRNS upon behavior. Our results suggest that tRNS has strong potential to augment cognitive capacity in healthy individuals and promote recovery in the neurological population.
Antibody potency, effector function and combinations in protection from SARS-CoV-2 infection in vivo

SARS-CoV-2, the causative agent of COVID-19, is responsible for over 24 million infections and 800,000 deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a mouse adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). In vitro antibody neutralization potency did not uniformly correlate with in vivo activity, and some hu-mAbs were more potent in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors is essential for optimal protection against SARS-CoV-2 MA. The data indicate that hu-mAb protective activity is dependent on intact effector function and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.
GP96 Drives Exacerbation of Secondary Bacterial Pneumonia following Influenza A Virus Infection

Secondary bacterial pneumonia following an influenza A virus (IAV) infection is a major cause of morbidity and mortality. Although it is generally accepted that preceding IAV infection leads to increased susceptibility to secondary bacterial infection, details regarding the pathogenic mechanism during the early stage of superinfection remain elusive. ABSTRACT Influenza A virus (IAV) infection predisposes the host to secondary bacterial pneumonia, known as a major cause of morbidity and mortality during influenza virus epidemics. Analysis of interactions between IAV-infected human epithelial cells and Streptococcus pneumoniae revealed that infected cells ectopically exhibited the endoplasmic reticulum chaperone glycoprotein 96 (GP96) on the surface. Importantly, efficient pneumococcal adherence to epithelial cells was imparted by interactions with extracellular GP96 and integrin αV, with the surface expression mediated by GP96 chaperone activity. Furthermore, abrogation of adherence was gained by chemical inhibition or genetic knockout of GP96 as well as addition of RGD peptide, an inhibitor of integrin-ligand interactions. Direct binding of extracellular GP96 and pneumococci was shown to be mediated by pneumococcal oligopeptide permease components. Additionally, IAV infection induced activation of calpains and Snail1, which are responsible for degradation and transcriptional repression of junctional proteins in the host, respectively, indicating increased bacterial translocation across the epithelial barrier. Notably, treatment of IAV-infected mice with the GP96 inhibitor enhanced pneumococcal clearance from lung tissues and ameliorated lung pathology. Taken together, the present findings indicate a viral-bacterial synergy in relation to disease progression and suggest a paradigm for developing novel therapeutic strategies tailored to inhibit pneumococcal colonization in an IAV-infected respiratory tract. IMPORTANCE Secondary bacterial pneumonia following an influenza A virus (IAV) infection is a major cause of morbidity and mortality. Although it is generally accepted that preceding IAV infection leads to increased susceptibility to secondary bacterial infection, details regarding the pathogenic mechanism during the early stage of superinfection remain elusive. Here, we focused on the interaction of IAV-infected cells and Streptococcus pneumoniae, which revealed that human epithelial cells infected with IAV exhibit a cell surface display of GP96, an endoplasmic reticulum chaperon. Notably, extracellular GP96 was shown to impart efficient adherence for secondary infection by S. pneumoniae, and GP96 inhibition ameliorated lung pathology of superinfected mice, indicating it to be a useful target for development of therapeutic strategies for patients with superinfection.
A Checklist of the Herpetofauna of the Palau Islands (Republic of Belau), Oceania

The Palau islands of western Micronesia comprise one of the most physiographically varied archipelagos in the Pacific. There are some 350 islands of volcanic and coralline origin that range from Babeldaob at 333 km2 (about 80% of Palau's total land area) to others, unnamed, that are less than one hectare. A barrier reef encircles most of the archipelago creating a lagoon up to 20 km wide. The majority of the islands are uninhabited, accessible with difficulty only by boat at high tide, and are densely vegetated over steep, rocky terrain. Because of their proximity to the Philippines, New Guinea, the Moluccas, and Borneo, the Palau islands host a significantly richer herpetofauna with more unique taxa than is found on other Pacific islands to the east. As with most other Pacific island groups, however, the herpetofauna has been poorly documented. Since the earliest investigations that began in the nineteen century, Palau's herpetofauna has been uncovered piecemeal. No sustained field effort had been conducted until we began a systematic survey of the islands in 1992. Since then we have collected in Palau every month of the year at least once. This checklist of 46 species of reptiles and amphibians includes almost twice as many taxa as were known from Palau (Owen, 1977) at the beginning of our study. Among these are new species or Palauan records of Gehyra, Hemiphyllodactylus, Lepidodactylus, Nactus, Perochirus, Emoia and Sphenomorphus. Because of the difficulties in surveying so many islands we believe that additional taxa and distributional records await discovery; even the smallest island in Palau can turn up surprises. Nonetheless, it is appropriate to consolidate what is now known about this intriguing fauna and environment. We provide an historical summary of previous collecting efforts, an overview of the islands' geology and habitats, and for each species account we include distributional information, taxonomic and systematic discussion, natural history observations, and a comprehensive bibliography.
Thalamus and claustrum control parallel layer 1 circuits in retrosplenial cortex

The granular retrosplenial cortex (RSG) is critical for both spatial navigation and fear conditioning, but the neural codes enabling these seemingly disparate functions remain unknown. Here, using optogenetic circuit mapping, we reveal a double dissociation that allows parallel circuits in superficial RSG to process navigation- versus fear-related inputs. The anterior thalamus, a source of head direction information, strongly recruits small, low rheobase (LR) pyramidal cells in RSG layer 3. Neighboring regular-spiking (RS) cells are instead preferentially controlled by claustral and anterior cingulate inputs, sources of higher-order and fear-related information. Precise sublaminar axonal and dendritic arborization within RSG layer 1 enable this parallel processing. Synaptic dynamics and computational modeling suggest LR neurons are optimally-tuned conjunctive encoders of direction and distance inputs from the thalamus and dorsal subiculum, respectively. RS cells are better positioned to support contextual fear memories. Thus, parallel input streams to computationally-distinct principal neurons help facilitate diverse RSG functions.
Data-driven multiplexed microtomography of endogenous subcellular dynamics

Simultaneous imaging of various facets of intact biological systems across multiple spatiotemporal scales would be an invaluable tool in biomedicine. However, conventional imaging modalities have stark tradeoffs precluding the fulfilment of all functional requirements. Here we propose the refractive index (RI), an intrinsic quantity governing light-matter interaction, as a means for such measurement. We show that major endogenous subcellular structures, which are conventionally accessed via exogenous fluorescence labeling, are encoded in 3D RI tomograms. We decode this information in a data-driven manner, thereby achieving multiplexed microtomography. This approach inherits the advantages of both high-specificity fluorescence imaging and label-free RI imaging. The performance, reliability, and scalability of this technology have been extensively characterized, and its application within single-cell profiling at unprecedented scales has been demonstrated.
The maternal foam plug constitutes a reservoir for the desert locust’s bacterial symbionts

A hallmark of the desert locust’s ancient and deserved reputation as a devastating agricultural pest is that of the long-distance, multi-generational migration of locust swarms to new habitats. The bacterial symbionts that reside within the locust gut comprise a key aspect of its biology, augmenting its immunity and having also been reported to be involved in the swarming phenomenon through the emission of attractant volatiles. However, it is still unclear whether and how these beneficial symbionts are transmitted vertically from parent to offspring. Using comparative 16S rRNA amplicon sequencing and direct experiments with engineered bacteria, we provide here evidence of the vertical transmission of locust gut bacteria. The females perform this activity by way of inoculation of the egg-pod’s foam plug, through which the larvae pass upon hatching. Furthermore, analysis of the biochemical structure of the foam revealed chitin to be its major component, along with immunity-related proteins such as lysozyme, which could be responsible for the inhibition of some bacteria in the foam while allowing other, more beneficial, strains to proliferate. Our findings reveal a potential vector for the transgenerational transmission of symbionts in locusts, which contributes to the locust swarm’s ability to invade and survive in new territories.
Neural Interactions in Developing Rhythmogenic Spinal Networks: Insights From Computational Modeling

The mechanisms involved in generation of rhythmic locomotor activity in the mammalian spinal cord remain poorly understood. These mechanisms supposedly rely on both intrinsic properties of constituting neurons and interactions between them. A subset of Shox2 neurons was found to contribute to generation of spinal locomotor activity. The preceding study (Ha and Dougherty, 2018) revealed the presence of bidirectional electrical coupling between these neurons in neonatal spinal cords, which can be critically involved in neuronal synchronization and generation of populational bursting. Gap junctional connections found between functionally-related Shox2 interneurons decrease with age, possibly being replaced by increasing interactions through chemical synapses. Here, we developed a computational model of a population of these neurons sparsely connected by electrical or/and chemical synapses and investigated the dependence of frequency of populational bursting on the type and strength of neuronal interconnections. The model provides important insights into the mechanisms of the locomotor rhythm generation.
Optimizing automated detection of high frequency oscillations using visual markings does not improve SOZ localization

Objective High frequency oscillations (HFOs) are a biomarker of the seizure onset zone (SOZ) and can be visually or automatically detected. In theory, one can optimize an automated algorithm’s parameters to maximize SOZ localization accuracy; however, there is no consensus on whether or how this should be done. Therefore, we optimized an automated detector using visually identified HFOs and evaluated the impact on SOZ localization accuracy. Methods We detected HFOs in intracranial EEG from 20 patients with refractory epilepsy from two centers using (1) unoptimized automated detection, (2) visual identification, and (3) automated detection optimized to match visually detected HFOs. Results SOZ localization accuracy based on HFO rate was not significantly different between the three methods. Across patients, visually optimized detector settings varied, and no single set of settings produced universally accurate SOZ localization. Exploratory analysis suggests that, for many patients, detection settings exist that would improve SOZ localization. Conclusions SOZ localization accuracy was similar for all three methods, was not improved by visually optimizing detector settings, and may benefit from patient-specific parameter optimization. Significance Visual HFO marking is laborious, and optimizing automated detection using visual markings does not improve localization accuracy. New patient-specific detector optimization methods are needed.