Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilises angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147 and GRP78 may also function as receptors for SARS-CoV-2. To determine the expression and in situ localisation of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analysed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, proteomic datasets, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples. We demonstrate absent to low ACE2 promoter activity in a variety of lung epithelial cell samples and low ACE2 gene expression in both microarray and scRNAseq datasets of epithelial cell populations. Consistent with gene expression, rare ACE2 protein expression was observed in the airway epithelium and alveoli of human lung, confirmed with proteomics. We present confirmatory evidence for the presence of TMPRSS2, CD147 and GRP78 protein in vitro in airway epithelial cells and confirm broad in situ protein expression of CD147 and GRP78 in the respiratory mucosa. Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 expression in human lung, perhaps in periods of SARS-CoV-2 infection, and also suggest that alternative receptors for SARS-CoV-2 exist to facilitate initial host cell infection. ACE2 gene and protein expression is low to absent in airway and alveolar epithelial cells in human lungs. This study suggests the presence of a mechanism dynamically regulating ACE2 expression in human lung or other receptors for SARS-CoV-2. https://bit.ly/3f85R1I
Prevalence and management of child sexual abuse cases presented at Nigerian hospitals: A systematic review

Introduction: Aim of this study was to review all suspected sexual abuse (SA) cases presenting at Nigerian hospitals, in order to examine both the prevalence of child sexual abuses (CSA) cases and the availability of hospital protocols and medical and forensic services for their evaluation, management and follow-up. Methods: A systematic review of literature including only studies published in English from 2006 to 2016 and cited in the Medline, Scopus and Web of Science databases was carried out. Results: A total of 16 hospital-based studies were included. Out of the total of 166,985 suspected SA cases presented at hospitals, only 1,553 (0.93%) of them were confirmed. Most of them (n = 1,164, 74.95%) occurred in children (< 18 years) and majority of the CSA victims were female (n = 1,155, 99.23%). HIV screening (n = 13, 81.25%) and vaginal swab (n = 8, 50%) were the most common investigations carried out by clinicians, whereas the most common medical treatments offered by the health facilities were emergency contraceptives (n = 8, 50%) and HIV post exposure prophylaxis (n = 7, 43.75%), with only a quarter of the cases (n = 4, 25%) offering any form of psychological counseling to victims and/or their parents. Written protocol for CSA evaluation and management was absent in nearly all of the health facilities. Conclusions: In Nigeria, healthcare and forensic management of CSA are poor, probably due to late presentation of victims at the hospital and to negligence on the part of health and security personnel. CSA is also possibly under-reported, with serious implications for the child and society. Prevention, proper medical treatment, management and follow-up for victims and their families, as well as making the perpetrators answerable for their crimes are highly recommended measures to tackle this issue. Affiliations:
Humans sacrifice decision-making for action execution when a demanding control of movement is required

A growing body of evidence suggests that decision-making and action execution are governed by partly overlapping operating principles. Especially, previous work proposed that a shared decision urgency/movement vigor signal, possibly computed in the basal ganglia, coordinates both deliberation and movement durations in a way that maximizes the reward rate. Recent data support one aspect of this hypothesis, indicating that the urgency level at which a decision is made influences the vigor of the movement produced to express this choice. Here we investigated whether conversely, the motor context in which a movement is executed determines decision speed and accuracy. Twenty human subjects performed a probabilistic decision task in which perceptual choices were expressed by reaching movements toward targets whose size and distance from a starting position varied in distinct blocks of trials. We found strong evidence for an influence of the motor context on most of the subjects’ decision policy but contrary to the predictions of the “shared regulation” hypothesis, we observed that slow movements executed in the most demanding motor blocks in terms of accuracy were often preceded by faster and less accurate decisions compared to blocks of trials in which big targets allowed expression of choices with fast and inaccurate movements. These results suggest that decision-making and motor control are not regulated by one unique “invigoration” signal determining both decision urgency and action vigor, but more likely by independent, yet interacting, decision urgency and movement vigor signals. NEW & NOTEWORTHY Recent hypotheses propose that choices and movements share optimization principles derived from economy, possibly implemented by one unique context-dependent regulation signal determining both processes speed. In the present behavioral study conducted on human subjects, we demonstrate that action properties indeed influence perceptual decision-making, but that decision duration and action vigor are actually independently set depending on the difficulty of the movement executed to report a choice.
Activity dependent translation in astrocytes dynamically alters the proteome of the perisynaptic astrocyte process

Gene expression requires two steps – transcription and translation – which can be regulated independently to allow nuanced, localized, and rapid responses to cellular stimuli. Neurons are known to respond transcriptionally and translationally to bursts of brain activity, and a transcriptional response to this activation has also been recently characterized in astrocytes. However, the extent to which astrocytes respond translationally is unknown. We tested the hypothesis that astrocytes also have a programmed translational response by characterizing the change in transcript ribosome occupancy in astrocytes using Translating Ribosome Affinity Purification(TRAP) subsequent to a robust induction of neuronal activity in vivo via acute seizure. We identified a change in transcripts on astrocyte ribosomes, highlighted by a rapid decrease in transcripts coding for ribosomal and mitochondrial components, and a rapid increase in transcripts related to cytoskeletal dynamics, motor activity, ion transport, and cell communication. This indicates a set of dynamic responses, some of which might be secondary to activation of Receptor Tyrosine Kinase(TRK) signaling. Using acute slices, we quantified the extent to which individual cues and sequela of neuronal activity can activate translation acutely in astrocytes. We identified both BDNF and ion concentration changes as contributors to translation induction, with potassium using both action-potential sensitive and insensitive components. We showed this translational response requires the presence of neurons, indicating the response is non-cell autonomous. We also show that this induction of new translation extends into peripheral astrocyte processes (PAPs). Accordingly, proteomics following fear conditioning in mice, showed that new translation influences peri-synaptic astrocyte protein composition in vivo under physiological conditions. Regulation of translation in astrocytes by neuronal activity suggests an additional mechanism by which astrocytes may dynamically modulate nervous system functioning. Main Points Astrocytes have a programmed, transcript-specific translational response to neuronal activity. Both BDNF and K+, cues of neuronal activity, trigger this response. This response requires the presence of neurons. This response alters the astrocytic protein composition at the synapse.
Toll‐Like Receptor 9 Plays a Pivotal Role in Angiotensin II–Induced Atherosclerosis

Background Toll‐like receptor (TLR) 9 recognizes bacterial DNA, activating innate immunity, whereas it also provokes inflammation in response to fragmented DNA released from mammalian cells. We investigated whether TLR9 contributes to the development of vascular inflammation and atherogenesis using apolipoprotein E–deficient (Apoe −/−) mice. Methods and Results Tlr9‐deficient Apoe −/− (Tlr9 −/− Apoe −/−) mice and Apoe −/− mice on a Western‐type diet received subcutaneous angiotensin II infusion (1000 ng/kg per minute) for 28 days. Angiotensin II increased the plasma level of double‐stranded DNA, an endogenous ligand of TLR9, in these mice. Genetic deletion or pharmacologic blockade of TLR9 in angiotensin II–infused Apoe −/− mice attenuated atherogenesis in the aortic arch (P<0.05), reduced the accumulation of lipid and macrophages in atherosclerotic plaques, and decreased RNA expression of inflammatory molecules in the aorta with no alteration of metabolic parameters. On the other hand, restoration of TLR9 in bone marrow in Tlr9 −/− Apoe −/− mice promoted atherogenesis in the aortic arch (P<0.05). A TLR9 agonist markedly promoted proinflammatory activation of Apoe −/− macrophages, partially through p38 mitogen‐activated protein kinase signaling. In addition, genomic DNA extracted from macrophages promoted inflammatory molecule expression more effectively in Apoe −/− macrophages than in Tlr9 −/− Apoe −/− macrophages. Furthermore, in humans, circulating double‐stranded DNA in the coronary artery positively correlated with inflammatory features of coronary plaques determined by optical coherence tomography in patients with acute myocardial infarction (P<0.05). Conclusions TLR9 plays a pivotal role in the development of vascular inflammation and atherogenesis through proinflammatory activation of macrophages. TLR9 may serve as a potential therapeutic target for atherosclerosis.
Stable Zn isotopes reveal the uptake and toxicity of zinc oxide engineered nanomaterials in Phragmites australis

The uptake, transport, and toxicity mechanisms of zinc oxide (ZnO) engineered nanomaterials (ZnO-ENMs) in aquatic plants remain obscure. We investigated ZnO-ENM uptake and phytotoxicity in Phragmites australis by combining Zn stable isotopes and microanalysis. Plants were exposed to four ZnO materials: micron-size ZnO, nanoparticles (NPs) of <100 nm or <50 nm, and nanowires of 50 nm diameter at concentrations of 0-1000 mg l−1. All ZnO materials reduced growth, chlorophyll content, photosynthetic efficiency, and transpiration and led to Zn precipitation outside the plasma membranes of root cells. Nanoparticles <50 nm released more Zn2+ and were more toxic, thus causing greater Zn precipitation and accumulation in the roots and reducing Zn isotopic fractionation during Zn uptake. However, fractionation by the shoots was similar for all treatments and was consistent with Zn2+ being the main form transported to the shoots. Stable Zn isotopes are useful to trace ZnO-ENM uptake and toxicity in plants. Environmental Significance Statement Our understanding of zinc oxide nanomaterials interaction with wetland plants is hampered by the lack of scientific consensus about their uptake and toxicity mechanisms in these species. This is a serious concern given the alarming global increase in the discharge of these nanomaterials into the environment and the key ecological roles of wetland plants. The Zn isotopic signature of plant tissue integrates all the Zn metabolic pathway throughout the plant’s life, giving insight about the form of Zn taken up, even if this later transforms into another Zn species. Thus, our findings clarify the exposure routes and the mechanisms of action of zinc oxide engineered nanomaterials in wetland plants while advancing the toolbox for plant physiology and environmental studies. Table of contents The Zn stable isotope composition of plants demonstrates that ZnO engineered nanomaterials dissolve before their uptake and accumulation by the roots (brightest inclusions in root cortex above).
An emerging target paradigm evokes fast visuomotor responses on human upper limb muscles

To reach towards a seen object, visual information has to be transformed into motor commands. Visual information such as the object’s colour, shape, and size is processed and integrated within numerous brain areas, then ultimately relayed to the motor periphery. In some instances we must react as fast as possible. These fast visuomotor transformations, and their underlying neurological substrates, are poorly understood in humans as they have lacked a reliable biomarker. Stimulus-locked responses (SLRs) are short latency (<100 ms) bursts of electromyographic (EMG) activity representing the first wave of muscle recruitment influenced by visual stimulus presentation. SLRs provide a quantifiable output of rapid visuomotor transformations, but SLRs have not been consistently observed in all subjects in past studies. Here we describe a new, behavioural paradigm featuring the sudden emergence of a moving target below an obstacle that consistently evokes robust SLRs. Human participants generated visually-guided reaches toward or away from the emerging target using a robotic manipulandum while surface electrodes recorded EMG activity from the pectoralis major muscle. In comparison to previous studies that investigated SLRs using static stimuli, the SLRs evoked with this emerging target paradigm were larger, evolved earlier, and were present in all participants. Reach reaction times (RTs) were also expedited in the emerging target paradigm. This paradigm affords numerous opportunities for modification that could permit systematic study of the impact of various sensory, cognitive, and motor manipulations on fast visuomotor responses. Overall, our results demonstrate that an emerging target paradigm is capable of consistently and robustly evoking activity within a fast visuomotor system. SUMMARY We present a new behavioual paradigm that elicits robust fast visuomotor responses on human upper limb muscles during visually guided reaches.
Positive selection of ORF3a and ORF8 genes drives the evolution of SARS-CoV-2 during the 2020 COVID-19 pandemic

In this study, we analyzed full-length SARS-CoV-2 genomes from multiple countries to determine early trends in the evolutionary dynamics of the novel COVID-19 pandemic. Results indicated SARS-CoV-2 evolved early into at least three phylogenetic groups, characterized by positive selection at specific residues of the accessory proteins OFR3a and ORF8a. We also report evidence of epistatic interactions among sites in the genome that may be important in the generation of variants adapted to humans. These observations might impact not only public health, but also suggest more studies are needed to understand the genetic mechanisms that may affect the development of therapeutic and preventive tools, like antivirals and vaccines.
Zebrafish IL-4-like cytokines and IL-10 suppress inflammation but only IL-10 is essential for gill homeostasis

Healthy fish stocks are central to global food security. Key to fish health is robust immunity at mucosal surfaces, and especially at the gills. However, a balance must be struck between tolerating commensal microorganisms and reacting appropriately toward pathogens. In mammals, IL-4 and IL-13 in concert with IL-10 are essential for balancing immune response to pathogens and suppressing inflammation. Whether their fish counterparts perform similar roles is an open question. Here, we have generated IL-4/13A and IL-4/13B mutant zebrafish and, together with existing IL-10 mutants, characterized the consequences of loss-of-function of these cytokines. We demonstrate that these cytokines are required to suppress inflammation. Further, IL-4/13A and IL-4/13B are required for the maintenance of a Th2-like phenotype in the gills. As in mammals, IL-10 appears to have a more striking anti-inflammatory function than IL-4-like cytokines. Thus, both IL-10 and IL-4/13 paralogues in zebrafish exhibit aspects of conserved function with their mammalian counterparts.
Phylogenomic Analyses of Non-Dikarya Fungi Supports Horizontal Gene Transfer Driving Diversification of Secondary Metabolism in the Amphibian Gastrointestinal Symbiont, Basidiobolus

Research into secondary metabolism (SM) production by fungi has resulted in the discovery of diverse, biologically active compounds with significant medicinal applications. However, the fungi rich in SM production are taxonomically restricted to Dikarya, two phyla of Kingdom Fungi, Ascomycota and Basidiomycota. Here, we explore the potential for SM production in Mucoromycota and Zoopagomycota, two phyla of nonflagellated fungi that are not members of Dikarya, by predicting and identifying core genes and gene clusters involved in SM. The majority of non-Dikarya have few genes and gene clusters involved in SM production except for the amphibian gut symbionts in the genus Basidiobolus. Basidiobolus genomes exhibit an enrichment of SM genes involved in siderophore, surfactin-like, and terpene cyclase production, all these with evidence of constitutive gene expression. Gene expression and chemical assays confirm that Basidiobolus has significant siderophore activity. The expansion of SMs in Basidiobolus are partially due to horizontal gene transfer from bacteria, likely as a consequence of its ecology as an amphibian gut endosymbiont.
Development of a simple and accurate molecular tool for Spodoptera frugiperda species identification using LAMP

The fall armyworm, Spodoptera frugiperda is a native species in the Americas. However, nowadays it is one of the most serious invasive lepidopteran pests in African and Asian countries. S. frugiperda has been spread very quickly after the first outbreak was reported in many countries. Based on mt genome sequence alignment, S. frugiperda specific sequence region was identified in tRNAs coding region between NADH dehydrogenase, ND3 and ND5. By using this unique region, species diagnostic primers were designed and applied in LAMP (lamp loop mediated isothermal amplification) assay as well as conventional PCR to identify the field-collected samples of S. frugiperda. Optimal incubation condition of LAMP assay was 61°C for 90 minutes with 4 LAMP primers, and additional loop primer increased the amplification efficiency. Also, wide range of DNA concentration responded in LAMP assay and minimum detectable DNA concentration was 10 pg. This LAMP assay was also applied in DNA releasing technique from larval and adult sample, without DNA extraction, 95°C incubation for five minutes of the tissue sample. This new molecular diagnostic method is easy to use and accurate. It possibly applied in intensive field monitoring of S. frugiperda and its ecological studies.
A smartphone microscope method for simultaneous detection of (oo)cyst of Cryptosporodium and Giardia

Gastrointestinal disorders caused by ingestion of (oo)cysts of Cryptosporodium and Giardia is one of the major health problems in developing countries. We developed a smartphone based microscopic assay method to screen (oo)cysts of Cryptosporodium and Giardia contamination in vegetable and water samples. We used sapphire ball lens as the major imaging element to modify a smartphone as a microscope. Imaging parameters such as field of view and magnification, and image contrast under different staining and illumination conditions were measured. The smartphone microscope method consisting of ball lens of 1 mm diameter, white LED as illumination source and Lugols’s iodine staining provided magnification and contrast capable of distinguishing (oo)cysts of Crypstopsporodium and Giardia in the same sample. The analytical performance of the method was tested by spike recovery experiments. The spiking recovery experiments performed on cabbage, carrot, cucumber, radish, tomatoes, and water resulted 26.8±10.3, 40.1±8.5, 44.4±7.3, 47.6±11.3, 49.2 ±10.9, and 30.2±7.9% recovery for Cryptosporodium, respectively and 10.2±4.0, 14.1±7.3, 24.2±12.1, 23.2±13.7, 17.1±13.9, and 37.6±2.4 % recovery for Giardia, respectively. These recovery results were found to be similar when compared with the commercial brightfield and fluorescence microscopes. We tested the smartphone microscope system for detecting (oo)cysts on 7 types of vegetable (n=196) and river water (n=18) samples. Forty two percent vegetable and thirty-nine percent water samples were found to be contaminated with Cryptosporodium oocyst. Similarly, thirty one percent vegetable and thirty three percent water samples were contaminated with Giardia cyst. This study showed that the developed method can be a cheaper alternative for simultaneous detection of (oo)cysts in vegetable and water samples.
Sequence, infectivity and replication kinetics of SARS-CoV-2 isolated from COVID-19 patients in Canada

SARS-CoV-2 emerged in December 2019 in Wuhan, China and has since infected over 1.5 million people, of which over 107,000 have died. As SARS-CoV-2 spreads across the planet, speculations remain about the range of human cells that can be infected by SARS-CoV-2. In this study, we report the isolation of SARS-CoV-2 from two COVID-19 patients in Toronto, Canada. We determined the genomic sequences of the two isolates and identified single nucleotide changes in representative populations of our virus stocks. More importantly, we tested a wide range of human immune cells for productive infection with SARS-CoV-2. Here we confirm that human primary peripheral blood mononuclear cells (PBMCs) are not permissive to SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor small nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine cell susceptibility and pathogenicity using in vitro and in vivo infection models.
Phage and bacteria diversification through a prophage acquisition ratchet

Lysogeny is prevalent in the microbial-dense mammalian gut. This contrasts the classical view of lysogeny as a refuge used by phages under poor host growth conditions. Here we hypothesize that as carrying capacity increases, lysogens escape phage top-down control through superinfection exclusion, overcoming the canonical trade-off between competition and resistance. This hypothesis was tested by developing an ecological model that combined lytic and lysogenic communities and a diversification model that estimated the accumulation of prophages in bacterial genomes. The ecological model sampled phage-bacteria traits stochastically for communities ranging from 1 to 1000 phage-bacteria pairs, and it included a fraction of escaping lysogens proportional to the increase in carrying capacity. The diversification model introduced new prophages at each diversification step and estimated the distribution of prophages per bacteria using combinatorics. The ecological model recovered the range of abundances and sublinear relationship between phage and bacteria observed across eleven ecosystems. The diversification model predicted an increase in the number of prophages per genome as bacterial abundances increased, in agreement with the distribution of prophages on 833 genomes from marine and human-associated bacteria. The study of lysogeny presented here offers a framework to interpret viral and microbial abundances and reconciles the Kill-the-Winner and Piggyback-the-Winner paradigms in viral ecology.