Miracle-dz/UniFAR-FTUs huggingface dataset:
Reducing Data Deficiencies: Preliminary Elasmobranch Fisheries Surveys in India, Identify Range Extensions and Large Proportions of Female and Juvenile Landings

Chondrichthyes, an ancient and diverse class of vertebrates, are crucial to the health of marine ecosystems. Excessive demand for chondrichthyan products has increased fishing pressure, threatening ∼30% of species with extinction in recent decades. India is the second-largest shark landing nation globally and the province of Gujarat, is the largest contributor to its shark exports. Despite their significant contribution to global fish supplies, chondrichthyan fisheries in Gujarat remain understudied and many species, data deficient, posing challenges to the conservation of remaining populations in the region. Here, we report results from taxonomic assessment of elasmobranchs at four key landing sites in Gujarat. We identified thirty-one species of sharks and rays with a significant bias toward capture of females and juveniles by fisheries. Our data indicate the presence of nursery areas for species such as Sphyrna lewini and Rhynchobatus laevis in the neritic areas off Gujarat. Further, we discovered extensions of the current distribution range for three species -Torpedo sinuspersici, Carcharhinus sorrah, and Rhinobatos punctifer. Taxonomic identities for a subset of species were confirmed using genomic analyses conducted with portable DNA sequencing tools. We present assessments for six data deficient species in the region – Rhinobatos annandalei, Rhinoptera jayakari, Maculabatis bineeshi, Pateobatis bleekeri, T. sinuspersici, and Carcharhinus amboinensis. Our investigation underscores species with urgent conservation needs and reduces data deficiencies. These data will inform and pivot future scientific and conservation efforts to protect remaining populations of some of the most vulnerable Chondrichthyes in the Arabian Seas Region.
The Role of Working Memory in the Processing of Scalar Implicatures of Patients With Schizophrenia Spectrum and Other Psychotic Disorders

A number of studies have demonstrated pragmatic language difficulties in people with Schizophrenia Spectrum and Other Psychotic Disorders. However, research about how people with schizophrenia spectrum and other psychotic disorders understand scalar implicatures (SIs) is surprisingly rare, since SIs have generated much of the most recent literature. Scalar implicatures are pragmatic inferences, based on linguistic expressions like some, must, or, which are part of a scale of informativeness (e.g., some/many/all). Logically, the less informative expressions imply the more informative ones, but pragmatically people usually infer that the presence of a less informative term implies that the more informative term was not applicable. In one of the few existing studies with people with schizophrenia spectrum and other psychotic disorders, Wampers et al. (2018) observed that in general, people with schizophrenia spectrum and other psychotic disorders were less likely to derive SIs than controls. The current study has three main aims. First, we want to replicate the original finding with the scalar terms some-all. Second, we want to investigate how these patients deal with different scalar terms, that is, we want to investigate if scalar diversity is also observed in this clinical group. Third, we investigate the role of working memory, often seen as another important mechanism to enable inferring SIs. Twenty-one individuals with a psychotic disorder and 21 matched controls answered 54 under-informative statements, in which seven different pairs of scalar terms were used. In addition, working memory capacity was measured. Patients with schizophrenia spectrum and other psychotic disorders did not make more logical interpretations when processing quantifiers, disconfirming Wampers et al. (2018). However, certain scalar scales elicited more pragmatic interpretations than others, which is in line with the scalar diversity hypothesis. Additionally, we observed only partial evidence for the role of working memory. Only for the scalar scale and-or, a significant effect of working memory was observed. The implications of these results for patients with schizophrenia spectrum and other psychotic disorders are discussed, but also the role of working memory for pragmatic inferences, as well as the place of SIs in experimental pragmatics.
Stable Meta-Networks, Noise, and Artifacts in the Human Connectome: Low- to High-Dimensional Independent Components Analysis as a Hierarchy of Intrinsic Connectivity Networks

Connectivity within the human connectome occurs between multiple neuronal systems—at small to very large spatial scales. Independent component analysis (ICA) is potentially a powerful tool to facilitate multi-scale analyses. However, ICA has yet to be fully evaluated at very low (10 or fewer) and ultra-high dimensionalities (200 or greater). The current investigation used data from the Human Connectome Project (HCP) to determine the following: (1) if larger networks, or meta-networks, are present at low dimensionality, (2) if nuisance sources increase with dimensionality, and (3) if ICA is prone to overfitting. Using bootstrap ICA, results suggested that, at very low dimensionality, ICA spatial maps consisted of Visual/Attention and Default/Control meta-networks. At fewer than 10 components, well-known networks such as the Somatomotor Network were absent from results. At high dimensionality, nuisance sources were present even in denoised high-quality data but were identifiable by correlation with tissue probability maps. Artifactual overfitting occurred to a minor degree at high dimensionalities. Basic summary statistics on spatial maps (maximum cluster size, maximum component weight, and average weight outside of maximum cluster) quickly and easily separated artifacts from gray matter sources. Lastly, by using weighted averages of bootstrap stability, even ultra-high dimensional ICA resulted in highly reproducible spatial maps. These results demonstrate how ICA can be applied in multi-scale analyses, reliably and accurately reproducing the hierarchy of meta-networks, large-scale networks, and subnetworks, thereby characterizing cortical connectivity across multiple spatial scales.
Effects of Virtual Reality Intervention on Cognition and Motor Function in Older Adults With Mild Cognitive Impairment or Dementia: A Systematic Review and Meta-Analysis

Background: Virtual reality (VR) intervention is an innovative and efficient rehabilitative tool for patients affected by stroke, Parkinson's disease, and other neurological disorders. This meta-analysis aims to evaluate the effects of VR intervention on cognition and motor function in older adults with mild cognitive impairment or dementia. Methods: Seven databases were systematically searched for relevant articles published from inception to April 2020. Randomized controlled trials examining VR intervention in adults with mild cognitive impairment or dementia aged >60 years were included. The primary outcome of the study was cognitive function, including overall cognition, global cognition, attention, executive function, memory, and visuospatial ability. The secondary outcome was motor function, consisting of overall motor function, balance, and gait. A subgroup analysis was also performed based on study characteristics to identify the potential factors for heterogeneity. Results: Eleven studies including 359 participants were included for final analysis. Primary analysis showed a significant moderate positive effect size (ES) of VR on overall cognition (g = 0.45; 95% confidence interval (CI) = 0.31–0.59; P < 0.001), attention/execution (g = 0.49; 95% CI = 0.26–0.72; P < 0.001), memory (g = 0.57; 95% CI = 0.29–0.85; P < 0.001), and global cognition (g = 0.32; 95% CI = 0.06–0.58; P = 0.02). Secondary analysis showed a significant small positive ES on overall motor function (g = 0.28; 95% CI = 0.05–0.51; P = 0.018). The ES on balance (g = 0.43; 95% CI = 0.06–0.80; P = 0.02) was significant and moderate. The ES on visuospatial ability and gait was not significant. In the subgroup analysis, heterogeneity was detected in type of immersion and population diagnosis. Conclusions: VR intervention is a beneficial non-pharmacological approach to improve cognitive and motor function in older adults with mild cognitive impairment or dementia, especially in attention/execution, memory, global cognition, and balance. VR intervention does not show superiority on visuospatial ability and gait performance.
Editorial: Genetics of Familial Hypercholesterolemia: New Insight

Mehiläinen Airport Health Centre, Vantaa, Finland, Department of Forensic Medicine, University of Helsinki, Helsinki, Finland, 3 Lysosomal Disorders Unit, Royal Free London National Health Service Foundation Trust, London, United Kingdom, Genetics and Genomics Department, University College London, London, United Kingdom, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway, Norwegian National Advisory Unit on Familial
Microglia: A Double-Edged Sword in Intracerebral Hemorrhage From Basic Mechanisms to Clinical Research

Microglia are the resident immune cells of the central nervous system (CNS). It is well established that microglia are activated and polarized to acquire different inflammatory phenotypes, either pro-inflammatory or anti-inflammatory phenotypes, which act as a critical component in the neuroinflammation following intracerebral hemorrhage (ICH). Microglia produce pro-inflammatory mediators at the early stages after ICH onset, anti-inflammatory microglia with neuroprotective effects appear to be suppressed. Previous research found that driving microglia towards an anti-inflammatory phenotype could restrict inflammation and engulf cellular debris. The principal objective of this review is to analyze the phenotypes and dynamic profiles of microglia as well as their shift in functional response following ICH. The results may further the understanding of the body’s self-regulatory functions involving microglia following ICH. On this basis, suggestions for future clinical development and research are provided.
GABA, Glutamate, and NAA Levels in the Deep Cerebellar Nuclei of Essential Tremor Patients

Background: Essential tremor is among the commonly observed movement disorders in clinical practice, however the exact pathophysiological mechanisms underlying tremor are unknown. It has been suggested that Purkinje cell alterations play a causal factor in tremorgenesis. Altered levels of inhibitory (GABA) and excitatory (glutamate+glutamine, Glx) neurotransmitters could be markers for Purkinje cell alterations. We hypothesize that GABA and Glx levels in the dentate nuclei could be differentially altered in patients responsive to either anticonvulsants or β-adrenergic blockers. Methods: In this explorative study in patients with essential tremor, we measured gamma-aminobutyric acid (GABA) and glutamate+glutamine (Glx) levels in the dentate nucleus region using 1H-magnetic resonance spectroscopy (MRS) in seven patients using propranolol, five patients using anticonvulsants, and eight healthy controls. Results: There were no group differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. There was no correlation with tremor severity. Discussion: Our results are in line with previously published studies; however, additional studies on a larger number of patients are warranted to confirm these findings. Furthermore medication-subgroups did not exhibit differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. A recent study, of similar size, found an inverse association between tremor severity and the GABA+/Glx ratio in the cerebellum of essential tremor patients. We were unable to replicate these findings. The field of tremor research is plagued by heterogeneous results, and we would caution against drawing firm conclusions based on pilot studies.
ANTIGENIC CHARACTERISTICS OF MORAXELLA NONLIQUEFACIENS FIMBRIAE IN DOUBLE IMMUNODIFFUSION

Rabbit antisera against purified fimbriae (pili) from Moraxella nonliquefaciens detected three fimbrial antigenic components, one or two of which appeared to be present in other fimbriated strains of M. nonliquefaciens and the closely related M. bovis. Maximal precipitation with the antisera required some denaturation of the antigen. Ultrasonication, repeated freeze‐thawing, heating, and agents like KBr, NaSCN and urea were effective in liberating the antigen in diffusible forms. The morphology of the fimbriae was altered by heat treatment in 1 M KBr.
Mitotic checkpoint gene expression is tuned by coding sequences

The mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Proper functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about SAC gene expression. Here, we show in fission yeast (S. pombe) that a combination of short mRNA half-lives and long protein half-lives supports stable SAC protein levels. For the SAC genes mad2+ and mad3+, their short mRNA half-lives are supported by a high frequency of non-optimal codons. In contrast, mad1+ mRNA has a short half-life despite a low frequency of non-optimal codons and despite the lack of known destabilizing motifs. Hence, different SAC genes employ different strategies of expression. We further show that Mad1 homodimers form co-translationally, which may necessitate a certain codon usage pattern. Taken together, we propose that the codon usage of SAC genes is fine-tuned for proper SAC function. Our work shines light on gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.
Foxd3 controls heterochromatin-mediated silencing of repeat elements in mouse embryonic stem cells and represses the 2-cell transcription program

Repeat element transcription plays a vital role in early embryonic development. Expression of repeats such as MERVL characterises mouse embryos at the 2-cell stage, and defines a 2-cell-like cell (2CLC) population in a mouse embryonic stem cell culture. Repeat element sequences contain binding sites for numerous transcription factors. We identify the forkhead domain transcription factor FOXD3 as a regulator of repeat element transcription in mouse embryonic stem cells. FOXD3 binds to and recruits the histone methyltransferase SUV39H1 to MERVL and major satellite repeats, consequentially repressing the transcription of these repeats by the establishment of the H3K9me3 heterochromatin modification. Notably, depletion of FOXD3 leads to the de-repression of MERVL and major satellite repeats as well as a subset of genes expressed in the 2-cell state, shifting the balance between the stem cell and 2-cell like population in culture. Thus, FOXD3 acts as a negative regulator of repeat transcription, ascribing a novel function to this transcription factor.
Neurodegenerative and functional signatures of the cerebellar cortex in m.3243A > G patients

Mutations of the mitochondrial DNA are an important cause of inherited diseases that can severely affect the tissue’s homeostasis and integrity. The m.3243A>G mutation is the most commonly observed across mitochondrial disorders and is linked to multisystemic complications, including cognitive deficits. In line with in vitro experiments demonstrating the m.3243A>G’s negative impact on neuronal energy production and integrity, m.3243A>G patients show cerebral gray matter tissue changes. However, its impact on the most neuron-dense, and therefore energy-consuming brain structure – the cerebellum – remains elusive. In this work, we used high resolution structural and functional data acquired using 7 Tesla MRI to characterize the neurodegenerative and functional signatures of the cerebellar cortex in m.3243A>G patients. Our results reveal altered tissue integrity within distinct clusters across the cerebellar cortex, apparent by their significantly reduced volume and longitudinal relaxation rate compared to healthy controls, indicating macroscopic atrophy and microstructural pathology. Spatial characterization reveals that these changes occur especially in regions related to the frontoparietal brain network that is involved in information processing and selective attention. In addition, based on resting-state fMRI data, these clusters exhibit reduced functional connectivity to frontal and parietal cortical regions, especially in patients characterized by (i) a severe disease phenotype and (ii) reduced information processing speed and attention control. Combined with our previous work, these results provide insight into the neuropathological changes and a solid base to guide longitudinal studies aimed to track disease progression.
Definitive hematopoietic stem cells minimally contribute to embryonic hematopoiesis

Hematopoietic stem cells (HSCs) are rare cells that arise in the embryo and sustain adult hematopoiesis. Although the functional potential of nascent HSCs is detectable by transplantation, their native contribution during development is unknown, in part due to the overlapping genesis and marker gene expression with other embryonic blood progenitors. Using single cell transcriptomics, we defined gene signatures that distinguish nascent HSCs from embryonic blood progenitors. Applying a new lineage tracing approach, we selectively tracked HSC output in situ and discovered significantly delayed lymphomyeloid contribution. Using a novel inducible HSC injury model, we demonstrated a negligible impact on larval lymphomyelopoiesis following HSC depletion. HSCs are not merely dormant at this developmental stage as they showed robust regeneration after injury. Combined, our findings illuminate that nascent HSCs self-renew but display differentiation latency, while HSC-independent embryonic progenitors sustain developmental hematopoiesis. Understanding the differences among embryonic HSC and progenitor populations will guide improved de novo generation and expansion of functional HSCs.
Diverse mechanisms for epigenetic imprinting in mammals

Genomic imprinting and X chromosome inactivation (XCI) require epigenetic mechanisms to direct allele-specific expression. Despite their critical roles in embryonic development, how universal epigenetic regulators coordinate these specific tasks from single locus to chromosome-scale remains understudied. Here, we systematically disrupted multiple essential epigenetic pathways within polymorphic F1 zygotes to examine postimplantation effects on canonical and non-canonical genomic imprinting as well as X chromosome inactivation. We find that DNA methylation and Polycomb group repressors are both indispensable for autosomal imprinting, albeit at distinct gene sets. Moreover, the extraembryonic ectoderm relies on a broader spectrum of unique imprinting mechanisms, including non-canonical targeting of maternal endogenous retrovirus (ERV) driven promoters by G9a. We further utilize our data to identify Polycomb dependent and independent gene clusters on the imprinted X chromosome, which appears to reflect distinct domains of Xist-mediated suppression. Our data has allowed us to assemble a comprehensive inventory of the epigenetic mechanisms utilized in eutherian mammals to maintain parent-specific imprinting, including an expanded view of the placental lineage that comprises multiple unique pathways.
GLUCOCORTICOIDS REGULATE MITOCHONDRIAL FATTY ACID OXIDATION IN FETAL CARDIOMYOCYTES

The late gestational rise in glucocorticoids contributes to the structural and functional maturation of the perinatal heart. Here, we hypothesised that glucocorticoid action contributes to the metabolic switch in perinatal cardiomyocytes from carbohydrate to fatty acid oxidation. In primary mouse fetal cardiomyocytes, dexamethasone treatment induced expression of genes involved in fatty acid oxidation and increased mitochondrial oxidation of palmitate, dependent upon glucocorticoid receptor (GR). Dexamethasone did not, however, induce mitophagy or alter the morphology of the mitochondrial network. In neonatal mice, dexamethasone treatment induced cardiac expression of fatty acid oxidation genes in vivo. However, dexamethasone treatment of pregnant C57Bl/6 mice at embryonic day (E)13.5 or E16.5 failed to induce fatty acid oxidation genes in fetal hearts assessed 24 hours later. Instead, at E17.5, fatty acid oxidation genes were down-regulated by dexamethasone, as was GR itself. PGC-1α, required for glucocorticoid-induced maturation of primary mouse fetal cardiomyocytes in vitro, was down-regulated in vivo in fetal hearts at E17.5, 24 hours after dexamethasone administration. Similarly, following a course of antenatal corticosteroids in a sheep model of preterm birth, both GR and PGC-1α were down-regulated in fetal heart. These data suggest endogenous glucocorticoids support the perinatal switch to fatty acid oxidation in cardiomyocytes through changes in gene expression rather than gross changes in mitochondrial volume or mitochondrial turnover. Moreover, our data suggest that treatment with exogenous glucocorticoids may interfere with normal fetal heart maturation, possibly by down-regulating GR. This has implications for clinical use of antenatal corticosteroids when preterm birth is considered a possibility.
Marker-assisted mapping enables effective forward genetic analysis in the arboviral vector Aedes aegypti, a species with vast recombination deserts

Aedes aegypti is a major vector of arboviruses that cause dengue, chikungunya, yellow fever and Zika. Although recent success in reverse genetics has facilitated rapid progress in basic and applied research, integration of forward genetics with modern technologies remains challenging in this important species, as up-to-47% of its chromosome is refractory to genetic mapping due to extremely low rate of recombination. Here we report the development of a marker-assisted-mapping (MAM) strategy to readily screen for and genotype only the rare but informative recombinants, drastically increasing both the resolution and signal-to-noise ratio. Using MAM, we mapped a transgene that was inserted in a >100 Mb recombination desert and a sex-linked spontaneous red-eye (re) mutation just outside the region. We subsequently determined, by CRISPR/Cas9-mediated knockout, that cardinal is the causal gene of re, which is the first forward genetic identification of a causal gene in Ae. aegypti. This study provides the molecular foundation for using gene-editing to develop versatile and stable genetic sexing methods by improving upon the current re-based genetic sexing strains. MAM does not require densely populated markers and can be readily applied throughout the genome to facilitate the mapping of genes responsible for insecticide- and viral-resistance. By enabling effective forward genetic analysis, MAM bridges a significant gap in establishing Ae. aegypti as a model system for research in vector biology. As large regions of suppressed recombination are also common in other plant and animal species including those of economic significance, MAM will have broad applications beyond vector biology.