Miracle-dz/UniFAR-FTUs huggingface dataset:
Human cerebral cortex networks use expanding and contracting state dynamic to shape cortical functions

We lack viable explanations of how brain functions emerge from collective activities of neurons in networks. We recorded field potentials from many local networks in the human cerebral cortex during a wide variety of brain functions. The network dynamics showed that each local cortical network produced fluctuating attractor states. The state trajectories continuously stretched and contracted during all brain functions, leaving no stable patterns. Different local networks all produced this dynamic, despite different architectures. Single trial stimuli and tasks modified the stretching and contractions. These modified fluctuations cross-correlated among particular networks during specific brain functions. Spontaneous states, rest, sensory, motor and cognitive states all emerged from this dynamic. Its mathematical structure provides a general explanation of cortical dynamics that can be tested experimentally. This universal dynamic is a simple functional organizing principle for brain functions at the mm3 scale that is distinct from existing frameworks.
Sequential dynein effectors regulate axonal autophagosome motility in a maturation-dependent pathway

Autophagy is a degradative pathway required to maintain neuronal homeostasis. Neuronal autophagosomes form constitutively at the axon terminal and mature via lysosomal fusion during dynein-mediated transport to the soma. How the dynein-autophagosome interaction is regulated during maturation is unknown. Here, we identify a series of handoffs between dynein effectors as autophagosomes transit along the axons of primary neurons. In the distal axon, JIP1 initiates autophagosomal transport, while autophagosomes in the mid-axon require HAP1 and Huntingtin for motility. We demonstrate that HAP1 is a bonafide dynein activator, binding the dynein-dynactin complex via canonical and noncanonical interactions. JIP3 is found on most axonal autophagosomes but specifically regulates the transport of acidified autolysosomes. Inhibiting autophagosomal transport disrupts maturation, while inhibiting autophagosomal maturation perturbs the association and function of dynein effectors. Thus maturation and transport are tightly linked. These results describe a novel maturation-based dynein effector handoff on neuronal autophagosomes that is key to autophagosomal motility, cargo degradation, and the maintenance of axonal health. Summary Neuronal autophagosomes form in the distal axon and mature via fusion with lysosomes during their dynein-driven transport to the soma. Dynein is regulated on autophagosomes by distinct effector proteins—JIP1, HAP1, and JIP3—depending on location and autophagosomal maturity. In this sequential pathway, transport and maturation state are tightly linked to maintain neuronal health.
Alcohol dependence activates ventral tegmental area projections to central amygdala in male mice and rats

The neural adaptations that occur during the transition to alcohol dependence are not entirely understood, but may include a gradual recruitment of brain stress circuitry by mesolimbic reward circuitry that is activated during early stages of alcohol use. Here, we focused on dopaminergic and non-dopaminergic projections from the ventral tegmental area (VTA), important for mediating acute alcohol reinforcement, to the central nucleus of the amygdala (CeA), important for alcohol dependence-related negative affect and escalated alcohol drinking. The VTA projects directly to the CeA, but the functional relevance of this circuit is not fully established. Therefore, we combined retrograde and anterograde tracing, anatomical, and electrophysiological experiments in mice and rats to demonstrate that the CeA receives input from both dopaminergic and non-dopaminergic projection neurons primarily from the lateral VTA. We then used slice electrophysiology and fos immunohistochemistry to test the effects of alcohol dependence on activity and activation profiles of CeA-projecting neurons in the VTA. Our data indicate that alcohol dependence activates midbrain projections to the central amygdala, suggesting that VTA projections may trigger plasticity in the CeA during the transition to alcohol dependence and that this circuit may be involved in mediating behavioral dysregulation associated with alcohol dependence.
Genomic diversity and antimicrobial resistance among non-typhoidal Salmonella associated with human disease in The Gambia

Non-typhoidal Salmonella associated with multidrug resistance cause invasive disease in sub-Saharan African. Specific lineages of serovars S. Typhimurium and S. Enteritidis are implicated. We characterised the genomic diversity of 100 clinical Non-typhoidal Salmonella collected from 93 patients in 2001 from the eastern and 2006 to 2018 in the western regions of The Gambia respectively. Phenotypic susceptibility applied Kirby Baur disk diffusion and whole genome sequencing utilized Illumina platforms. The predominant serovars were S. Typhimurium ST19 (31/100) and S. Enteritidis ST11 (18/100) restricted to invasive disease with the notable absence of S. Typhimurium ST313. Phylogenetic analysis performed in the context of 495 African strains from the European Nucleotide Archive confirmed the presence of the S. Enteritidis virulent epidemic invasive multidrug resistant West African clade. Multidrug resistance including chloramphenicol and azithromycin has emerged among the West African S. Enteritidis clade 7/9 (78%) with potential for spread, thus having important implications for patient management warranting systematic surveillance and epidemiologic investigations to inform control. Data summary Sequences are deposited in the NCBI sequence reads archive (SRA) under BioProject ID:PRJEB38968. The genomic assemblies are available for download from the European Nucleotide Archive (ENA): http://www.ebi. ac.uk/ena/data/view/. Accession numbers SAMEA6991082 to SAME6991180
MondoA Drives Malignancy in cALL through Enhanced Adaptation to Metabolic Stress

Cancer cells are in most instances characterized by rapid proliferation and uncontrolled cell division. Hence, they must adapt to proliferation-induced metabolic stress through intrinsic or acquired anti-metabolic stress responses to maintain homeostasis and survival. One mechanism to achieve this is to reprogram gene expression in a metabolism-dependent manner. MondoA (also known as MLXIP), a member of the MYC interactome, has been described as an example of such a metabolic sensor. However, the role of MondoA in malignancy is not fully understood and the underlying mechanism in metabolic responses remains elusive. By assessing patient data sets we found that MondoA overexpression is associated with a worse survival in pediatric common acute lymphoblastic leukemia (cALL). Using CRISPR/Cas9 and RNA interference approaches, we observed that MondoA depletion reduces transformational capacity of cALL cells in vitro and dramatically inhibits malignant potential in an in vivo mouse model. Interestingly, reduced expression of MondoA in patient data sets correlated with enrichment in metabolic pathways. The loss of MondoA correlated with increased tricarboxylic acid (TCA) cycle activity. Mechanistically, MondoA senses metabolic stress in cALL cells by restricting oxidative phosphorylation through reduced PDH activity. Glutamine starvation conditions greatly enhance this effect and highlight the inability to mitigate metabolic stress upon loss of MondoA in cALL. Our findings give a novel insight into the function of MondoA in pediatric cALL and support the notion that MondoA inhibition in this entity offers a therapeutic opportunity and should be further explored. Key Points MondoA maintains aggressiveness and leukemic burden in common ALL, modulating metabolic stress response.
Machine learning-enabled phenotyping for GWAS and TWAS of WUE traits in 869 field-grown sorghum accessions

Sorghum is a model C4 crop made experimentally tractable by extensive genomic and genetic resources. Biomass sorghum is also studied as a feedstock for biofuel and forage. Mechanistic modelling suggests that reducing stomatal conductance (gs) could improve sorghum intrinsic water use efficiency (iWUE) and biomass production. Phenotyping for discovery of genotype to phenotype associations remain bottlenecks in efforts to understand the mechanistic basis for natural variation in gs and iWUE. This study addressed multiple methodological limitations. Optical tomography and a novel machine learning tool were combined to measure stomatal density (SD). This was combined with rapid measurements of leaf photosynthetic gas exchange and specific leaf area (SLA). These traits were then the subject of genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) across 869 field-grown biomass sorghum accessions. SD was correlated with plant height and biomass production. Plasticity in SD and SLA were interrelated with each other, and productivity, across wet versus dry growing seasons. Moderate-to-high heritability of traits studied across the large mapping population supported identification of associations between DNA sequence variation, or RNA transcript abundance, and trait variation. 394 unique genes underpinning variation in WUE-related traits are described with higher confidence because they were identified in multiple independent tests. This list was enriched in genes whose orthologs in Arabidopsis have functions related to stomatal or leaf development and leaf gas exchange. These advances in methodology and knowledge will aid efforts to improve the WUE of C4 crops.
Growth and transgenerational acclimatization of juvenile Pocillopora damicornis

Global carbon emissions and associated increase in ocean temperatures are understood to be the main driving force in the degradation of coral reefs. Elevated temperatures impact various life stages of scleractinian corals, from the free-floating planulae of brooding corals to older, sexually viable individuals. With global warming, questions have arisen over whether organismal adaptation will be enough to keep up with the pace of environmental change. Researchers have pursued investigations of whether or not rapid acclimatization, through transgenerational plasticity, can help protect populations until genetic adaptation occurs. Acclimatization in corals has been widely studied in all life stages of corals, with the important exception of recently settled juveniles. In this study, I built upon past research by exposing adult Pocillopora damicornis colonies to elevated (28.5°C) or ambient (25.5°C) temperatures and examining the settlement ability and growth of their planulae ex situ. Juveniles from preconditioned parents fared better in higher temperatures compared to their naïve counterparts. Lunar timing of planula release between treatments peaked at different times in the lunar cycle. Peak planula release occurred on lunar day 23 for prestressed corals and on lunar day 7 for corals from ambient temperature seawaters. While future projects should follow up on these preliminary trials with in situ experiments to assess this phenomenon in the field, this study represents an important step in understanding how corals may be able to acclimatize and eventually adapt to climate change.
Genome ARTIST_v2 software – a support for annotation of class II natural transposons in new sequenced genomes

Transposon annotation is a very dynamic field of genomics and various tools assigned to support this bioinformatics endeavor were reported. Genome ARTIST (GA) software was initially developed for mapping artificial transposons mobilized during insertional mutagenesis projects. Now, the new functions of GA_v2 qualify it as an effective companion for mapping and annotation of class II natural transposons in assembled genomes, contigs or sequencing reads. Tabular export of mapping and annotation data for subsequent high-throughput data analysis, the export of a list of flanking sequences around either the coordinates of insertion or around the target site duplications (TSDs) and generation of a consensus sequence for the respective flanking sequences are all key assets of GA_v2. Additionally, we developed two accompanying short scripts that enable the user to annotate transposons existent in assembled genomes and to use various annotation offered by FlyBase for Drosophila melanogaster genome. Herein, we present the applicability of GA_v2 for a preliminary annotation of the class II transposon P-element in the genome of D. melanogaster strain Horezu, Romania, which was sequenced with Nanopore technology in our laboratory. Our results point that GA_v2 is a reliable tool to be integrated in pipelines designed to perform transposon annotation in new sequenced genomes. GA_v2 is open source software compatible with Ubuntu, Mac OS and Windows and is available at https://github.com/genomeartist/genomeartist and at www.genomeartist. ro.
Randomness of Möbius coefficents and brownian motion: growth of the Mertens function and the Riemann Hypothesis

The validity of the Riemann Hypothesis (RH) on the location of the non-trivial zeros of the Riemann ζ-function is directly related to the growth of the Mertens function M(x) = ∑x k=1 μ(k), where μ(k) is the Möbius coefficient of the integer k: the RH is indeed true if the Mertens function goes asymptotically as M(x) ' x . We show that this behavior can be established on the basis of a new probabilistic approach based on the global properties of Mertens function. To this aim, we focus the attention on the square-free numbers and we derive a series of probabilistic results concerning the prime number distribution along the series of square-free numbers, the average number of prime divisors, the Erdős-Kac theorem for square-free numbers, etc. These results lead us to the conclusion that the Mertens function is subject to a normal distribution as much as any other random walk, therefore with an asymptotic behaviour given by x . This represents a theoretical advance in the field. We also argue how the Riemann Hypothesis implies the Generalised Riemann Hypothesis for the Dirichlet L-functions. Next we study the local properties of the Mertens function dictated by the Möbius coefficients restricted to the square-free numbers. Motivated by the natural curiosity to see how close to a purely random walk is any sub-sequence extracted by the sequence of the Möbius coefficients for the square-free numbers, we perform a massive statistical analysis on these coefficients, applying to them a series of randomness tests of increasing precision and complexity: together with several frequency tests within a block, the list of our tests include those for the longest run of ones in a block, the binary matrix rank test, the Discrete Fourier Transform test, the non-overlapping template matching test, the entropy test, the cumulative sum test, the random excursion tests, etc. The successful outputs of all these tests (with a level of confidence of 99% that all the sub-sequences analyzed are indeed random) can be seen as impressive “experimental” confirmations of the brownian nature of the restricted Möbius coefficients and the probabilistic normal law distribution of the Mertens function analytically established earlier. In view of the theoretical probabilistic argument and the large battery of statistical tests, we can conclude that while a violation of the RH is strictly speaking not impossible, it is however ridiculously improbable.
Short-beaked echidna (Tachyglossus aculeatus) home range at Fowlers Gap Arid Zone Research Station, NSW

Echidnas (Tachyglossus aculeatus) are found Australian-wide and appear to be remarkably well-adapted to arid zones, yet, nearly all echidna research has been conducted in temperate, tropical and alpine zones. This study investigated the home range and movement of echidnas in western New South Wales. Radio telemetry tracking was used to locate the echidnas daily during the study period (March-May 2019 and August 2019); the home range was 1.47± 1.21 km2. This is over twice the reported home range of temperate environments (>0.65 km2) suggesting that echidnas exhibit larger home ranges in arid zones. This study provides insight into the movement and home range of echidnas in arid zones, revealing that desert echidnas have large home ranges, dependent on the availability of resources.
Rhythmic Modulation of Visual Perception by Continuous Rhythmic Auditory Stimulation

At any given moment our sensory systems receive multiple, often rhythmic, inputs from the environment. Processing of temporally structured events in one sensory modality can guide both behavioral and neural processing of events in other sensory modalities, but whether this occurs remains unclear. Here, we used human electroencephalography (EEG) to test the cross-modal influences of a continuous auditory frequency-modulated (FM) sound on visual perception and visual cortical activity. We report systematic fluctuations in perceptual discrimination of brief visual stimuli in line with the phase of the FM-sound. We further show that this rhythmic modulation in visual perception is related to an accompanying rhythmic modulation of neural activity recorded over visual areas. Importantly, in our task, perceptual and neural visual modulations occurred without any abrupt and salient onsets in the energy of the auditory stimulation and without any rhythmic structure in the visual stimulus. As such, the results provide a critical validation for the existence and functional role of cross-modal entrainment and demonstrates its utility for organizing the perception of multisensory stimulation in the natural environment. SIGNIFICANCE STATEMENT Our sensory environment is filled with rhythmic structures that are often multi-sensory in nature. Here, we show that the alignment of neural activity to the phase of an auditory frequency-modulated (FM) sound has cross-modal consequences for vision: yielding systematic fluctuations in perceptual discrimination of brief visual stimuli that are mediated by accompanying rhythmic modulation of neural activity recorded over visual areas. These cross-modal effects on visual neural activity and perception occurred without any abrupt and salient onsets in the energy of the auditory stimulation and without any rhythmic structure in the visual stimulus. The current work shows that continuous auditory fluctuations in the natural environment can provide a pacing signal for neural activity and perception across the senses.
“High resolution discovery of regulatory DNA with synthetic wild-type and ablated genome constructs”

Genomic enhancer elements play a role in modulating gene expression by interacting with effector proteins known as transcription factors. We present a new computational method, “STARR-scan”, which identifies transcription factor motif appearances in synthetic DNA constructs that are correlated with enhancer activity. Using a tiled STARR-seq assay, we demonstrate that STARR-scan can suggest the biological function of transcription factors previously suspected to activate the APOBEC-3B gene. Using the same methodology, STARR-scan can suggest transcription factors with previously unknown biological activity which may regulate the APOBEC-3B gene. These novel factors may have biological significance in our understanding of cancer biology.
Pick Your Poison: Molecular Evolution of Venom Proteins in Asilidae (Insecta: Diptera)

Robber flies are an understudied family of venomous, predatory Diptera. With the recent characterization of venom from three asilid species, it is possible for the first time to study the molecular evolution of venom genes in this unique lineage. To accomplish this, a novel whole-body transcriptome of Eudioctria media was combined with 10 other publicly available asiloid thoracic or salivary gland transcriptomes to identify putative venom gene families and assess evidence of pervasive positive selection. A total of 348 gene families of sufficient size were analyzed, and 33 of these were predicted to contain venom genes. We recovered 151 families containing homologs to previously described venoms, and 40 of these were uniquely gained in Asilidae. Our gene family clustering suggests that many asilidin venom gene families are not natural groupings as originally delimited. Additionally, robber-fly venoms have relatively few sites under positive selection, consistent with the hypothesis that the venom of older lineages are dominated by negative selection acting to maintain toxic function.
Is degree of sociality associated with reproductive senescence? A comparative analysis across birds and mammals

Our understanding on how widespread reproductive senescence is in the wild and how the onset and rate of reproductive senescence vary among species in relation to life histories and lifestyles is currently limited. More specifically, whether the species-specific degree of sociality is linked to the occurrence, onset and rate of reproductive senescence remains unknown. Here, we investigate these questions using phylogenetic comparative analyses across 36 bird and 101 mammal species encompassing a wide array of life histories, lifestyles and social traits. We found that female reproductive senescence (1) is widespread and occurs with similar frequency (about two thirds) in birds and mammals; (2) occurs later in life and is slower in birds than in similar-sized mammals; (3) occurs later in life and is slower with an increasingly slower pace of life in both vertebrate classes; and (4) is only weakly associated, if any, with the degree of sociality in both classes after accounting for the effect of body size and pace of life. However, when allowing for species differences in pace of life, a higher degree of sociality was associated with later and weaker reproductive senescence in females, which suggests that degree of sociality is indirectly related to reproductive senescence via the pace of life. Subject Areas ecology, evolution