Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiological and behavioral responses, and their variability, in squid, Doryteuthis pealeii, embryos and paralarvae reared under chronic ocean acidification

Ocean acidification (OA) and related stressors, like warming, are occurring rapidly in coastal systems. There is concern about the impacts these stressors may have on the early development of species that use the nearshore as nursery habitat. The inshore longfin squid, Doryteuthis pealeii, plays an important role in the northwest Atlantic food web, and annually lays its eggs in the nearshore benthos during summer. This thesis sought to characterize morphological, physiological, and behavioral responses of D. pealeii embryos and paralarvae to OA. Experiments began in 2013, where I exposed squid eggs to a range of acidification levels (40
A Pediatric Case of Glioblastoma Multiforme Associated With a Novel Germline p.His112CysfsTer9 Mutation in the MLH1 Gene Accompanied by a p.Arg283Cys Mutation in the TP53 Gene: A Case Report

Targeted gene panel testing has the power to interrogate hundreds of genes and evaluate the genetic risk for many types of hereditary cancers simultaneously. We screened a 13-year-old male patient diagnosed with glioblastoma multiforme with the aim to get further insights into the biology of his condition. Herein, we applied gene panel sequencing and identified a heterozygous frameshift mutation c. 333_334delTC; p.His112CysfsTer9 in the MLH1 gene in blood and tumor tissue accompanied by a known heterozygous missense variant of unknown significance c.847C > T; p.Arg283Cys in the TP53 gene. Parental screening revealed the presence of the same TP53 variant in the father and the same MLH1 variant in the mother, who was in fact undergoing treatment for early-stage breast cancer at the time of her son’s unfortunate diagnosis. This case reports for the first time the co-occurrence of a genetic mutation in the MLH1 gene of the mismatch repair pathway, commonly associated with the Lynch syndrome, accompanied by a rare variant in the TP53 gene. This report underlines the need for broad panel gene testing in lieu of single-gene or syndrome-focused gene screening and evaluation of the effects of multiple pathogenic or modifier variants on the phenotypic spectrum of the disease.
Clathrin’s adaptor interaction sites are repurposed to stabilize microtubules during mitosis

Clathrin plays an important role to ensure mitotic spindle stability and efficient chromosome alignment, independently of its well-characterized functions in vesicle trafficking. While clathrin clearly localizes to the mitotic spindle and kinetochore-fiber microtubule bundles, the mechanisms by which clathrin stabilizes microtubules have remained elusive. Here we show that clathrin adaptor interaction sites on clathrin heavy chain (CHC) are repurposed during mitosis to directly recruit the microtubule-stabilizing protein GTSE1 to the mitotic spindle. Structural analyses reveal that multiple clathrin-box motifs on GTSE1 interact directly with different clathrin adaptor interaction sites on CHC, in a manner structurally analogous to that which occurs between adaptor proteins and CHC near membranes. Specific disruption of this interaction in cells releases GTSE1 from spindles and causes defects in chromosome alignment. Surprisingly, this disruption causes destabilization of astral microtubules, but not kinetochore-microtubule attachments, and the resulting chromosome alignment defect is due to a failure of chromosome congression independent of kinetochore-microtubule attachment stability. Finally, we show that GTSE1 recruited to the spindle by clathrin stabilizes microtubules and promotes chromosome congression by inhibiting the activity of the microtubule depolymerase MCAK. This work thus uncovers a novel role of clathrin to stabilize non-kinetochore-fiber microtubules to support chromosome congression. This role is carried out via clathrin adaptor-type interactions of CHC with GTSE1, defining for the first time an important repurposing of this endocytic interaction mechanism during mitosis.
Regulation of CSF and Brain Tissue Sodium Levels by the Blood-CSF and Blood-Brain Barriers During Migraine

Background Cerebrospinal fluid (CSF) and brain tissue sodium levels increase during migraine. However, little is known regarding the underlying mechanisms of sodium homeostasis disturbance in the brain during the onset and propagation of migraine. Exploring the cause of sodium dysregulation in the brain is important, since correction of the altered sodium homeostasis could potentially treat migraine. Under the hypothesis that disturbances in sodium transport mechanisms at the blood-CSF barrier (BCSFB) and/or the blood-brain barrier (BBB) are the underlying cause of the elevated CSF and brain tissue sodium levels during migraines, we developed a mechanistic, differential equation model of a rat’s brain to compare the significance of the BCSFB and the BBB in controlling CSF and brain tissue sodium levels. The model includes the ventricular system, subarachnoid space, brain tissue and blood. Sodium transport from blood to CSF across the BCSFB, and from blood to brain tissue across the BBB were modeled by influx permeability coefficients Pcp and Pbc, respectively, while sodium movement from CSF into blood across the BCSFB, and from brain tissue to blood across the BBB were modeled by efflux permeability coefficients and , respectively. We then performed a global sensitivity analysis to investigate the sensitivity of the ventricular CSF, subarachnoid CSF and brain tissue sodium concentrations to pathophysiological variations in and . Our results show that the ventricular CSF sodium concentration is highly influenced by perturbations of Pcp, and to a much lesser extent by perturbations of . Brain tissue and subarachnoid CSF sodium concentrations are more sensitive to pathophysiological variations of Pbc and than variations of Pcp and within 30 minutes of the onset of the perturbations. However, Pcp is the most sensitive model parameter, followed by Pbc and , in controlling brain tissue and subarachnoid CSF sodium levels within 2 hours of the perturbation onset.
A comparison of macroecological and stacked species distribution models to predict future global terrestrial vertebrate richness

Predicting future changes in species richness in response to climate change is one of the key challenges in biogeography and conservation ecology. Stacked species distribution models (S‐SDMs) are a commonly used tool to predict current and future species richness. Macroecological models (MEMs), regression models with species richness as response variable, are a less computationally intensive alternative to S‐SDMs. Here, we aim to compare the results of two model types (S‐SDMS and MEMs), for the first time for more than 14,000 species across multiple taxa globally, and to trace the uncertainty in future predictions back to the input data and modelling approach used.
Dirofilaria immitis infestation in imported police (K-9) dogs in Iraq:

Dirofilaria immitis, the cause of heartworm infestation (HWI) or dirofilariasis, affects members of the Canidae and remains a worldwide clinical problem. In Iraq, dirofilariasis was believed absent until 2009, when the Karbala Governorate was reported as an endemic area for canine dirofilariasis. Consequently, this study intended to investigate the occurrence of Dirofilaria immitis in police dogs in one police academy in Iraq and to study the gross and histopathological changes in 5 dead dogs, as well as to identify the species of the causative parasite using PCR technique. Thirty-nine police dogs, aged between 6 months and 12 years were included in this study. For the microfilariae investigation, 5 ml blood samples were collected from all dogs in EDTA tubes and examined by Knott’s method. The systemic necropsy performed in five dead dogs showed severe clinical signs of dirofilariasis and tissue specimens were sent for routine histopathological processing. For the molecular analysis, adult worms of the detected Dirofilaria spp. were used for DNA extraction andamplification of the cox1 gene. Fifteen of 39 (38.46%) dogs were diagnosed with moderate to severe microfilariasis. The dead dogs revealed typical severe clinical signs of dirofilariasis. Moreover, typical gross and histopathological changes were also seen, accompanied by generalized thromboembolic lesions, suggesting the occurrence of the caval syndrome. The PCR investigation confirmed that D. immitis was the species present in Iraq. In conclusion, this study establishes that Iraq is a newly reported endemic area for dirofilariasis. Moreover, the infestation occurring in these cases most probably happened inside Iraq. The authors recommend doing further epidemiological studies concerning the occurrence of D. immitis in local dogs as well as in the imported dogs in all Iraqi governorates to better understand the epidemiological map of this disease and to introduce an active treatment and preventive program. Awareness and education regarding this disease should be provided to the veterinarians, dog guiders and people in direct contact with dogs, as this disease is one of the important zoonotic diseases.
An evaluation of the Kangaroo Creek Gang drug education package

The purposes of this study were (a) t0 analyse the impl~mcntntion of the Kangaroo Creek Gang Drug Education Package (KCGDEP) (Kangaroo Creek Gang, 1988b), and (b) to evaluate teachers' perceptions of the KCGDEP in terms of its goals, format, processes and outcomes. The KCGDEP ' was found to have been implemented in 24% of the primary schools surveyed (~ ~ 100), with a mean of 5.1% of teachers in these schools using the package. Teachers' perceptions of the KCGDEP were analysed through the administration of a curriculum evaluation questionnaire, adapted from Piper (1976, p. 83-89), and teacher interviews. This process was carried out in six w.A. primary schools. Data collected in this way showed that teachers who had implemented the KCGDEP had favourable perceptions of it. A chi-square test showed that implementation of the KCGDEP was contingent on inservicing. Teachers' use of the KCGDEP, however, was idiosyncratic and did not correspond with the intentions of itr, developers. Moreover, teachers were not convinced of the efficacy of the KCGDEP as an effective means of drug education. This was highlighted by the fact that teachers were not familiar with the packAge's rationale or its approach to drug education. As a result of data
Direct microRNA sequencing using Nanopore Induced Phase-Shift Sequencing (NIPSS)

MicroRNAs (miRNAs) are a class of short non-coding RNAs that function in RNA silencing and post-transcriptional gene regulation. Besides their participation in regulating normal physiological activities, specific miRNA types could act as oncogenes, tumor suppressors or metastasis regulators, which are critical biomarkers for cancer. However, direct characterization of miRNA is challenging due to its unique properties such as its low abundance, sequence similarities and short length. Nanopore Induced Phase Shift Sequencing (NIPSS), which is a variant form of nanopore sequencing, could directly sequence any short analytes including miRNA. In practice, NIPSS clearly discriminates between different identities, isoforms and epigenetic variants of model miRNA sequences. This work demonstrates the first report of direct miRNA sequencing, which serves as a complement to existing miRNA sensing routines by the introduction of single molecule resolution. Future engineering of this technique may assist miRNA based early stage diagnosis or inspire novel cancer therapeutics.
Protein network structure enables switching between liquid and gel states

Biomolecular condensates are emerging as an important organizational principle within living cells. These condensed states are formed by phase separation, yet little is known about how material properties are encoded within the constituent molecules and how the specificity for being in different phases is established. Here we use analytic theory to explain the phase behavior of the cancer-related protein SPOP and its substrate DAXX. Binary mixtures of these molecules have a phase diagram that contains dilute liquid, dense liquid, and gel states. We show that these discrete phases appear due to a competition between SPOP-DAXX and DAXX-DAXX interactions. The stronger SPOP-DAXX interactions dominate at sub-stoichiometric DAXX concentrations leading to the formation of crosslinked gels. The theory shows that the driving force for gel formation is not the binding energy, but rather the entropy of distributing DAXX molecules on the binding sites. At high DAXX concentrations the SPOP-DAXX interactions saturate, which leads to the dissolution of the gel and the appearance of a liquid phase driven by weaker DAXX-DAXX interactions. This competition between interactions allows multiple dense phases to form in a narrow region of parameter space. We propose that the molecular architecture of phase-separating proteins governs the internal structure of dense phases, their material properties and their functions. Analytical theory can reveal these properties on the long length and time scales relevant to biomolecular condensates.
Variational Autoencoder Modular Bayesian Networks for Simulation of Heterogeneous Clinical Study Data

In the area of Big Data, one of the major obstacles for the progress of biomedical research is the existence of data “silos” because legal and ethical constraints often do not allow for sharing sensitive patient data from clinical studies across institutions. While federated machine learning now allows for building models from scattered data of the same format, there is still the need to investigate, mine, and understand data of separate and very differently designed clinical studies that can only be accessed within each of the data-hosting organizations. Simulation of sufficiently realistic virtual patients based on the data within each individual organization could be a way to fill this gap. In this work, we propose a new machine learning approach [Variational Autoencoder Modular Bayesian Network (VAMBN)] to learn a generative model of longitudinal clinical study data. VAMBN considers typical key aspects of such data, namely limited sample size coupled with comparable many variables of different numerical scales and statistical properties, and many missing values. We show that with VAMBN, we can simulate virtual patients in a sufficiently realistic manner while making theoretical guarantees on data privacy. In addition, VAMBN allows for simulating counterfactual scenarios. Hence, VAMBN could facilitate data sharing as well as design of clinical trials.
Platelet-Derived Exosomal MicroRNA-25-3p Inhibits Coronary Vascular Endothelial Cell Inflammation Through Adam10 via the NF-κB Signaling Pathway in ApoE−/− Mice

Introduction: Coronary artery disease originates from the blockage of the inner walls of the coronary arteries due to a plaque buildup. Accumulating studies have highlighted the role of microRNAs (miRs) delivered by exosomes in the progression of coronary artery disease. Thus, the current study was to elucidate the role and mechanism by which miR-25-3p influences oxidized low density lipoprotein (ox-LDL)-induced coronary vascular endothelial cell (CVEC) inflammation. Methods: Primarily isolated CVECs were treated with ox-LDL to induce inflammation. Atherosclerosis models were induced in ApoE−/− mice and the peripheral blood platelet exosomes (PLT-Exo) were extracted and induced by thrombin, followed by co-culture with CVECs. The relationship between miR-25-3p and A disintegrin and metalloprotease 10 (Adam10) as well as the involvement of the NF-κB signaling pathway was evaluated. In order to evaluate the effect of PLT-Exo containing miR-25-3p on ox-LDL-induced CVEC inflammation, lipid accumulation and fibrosis, miR-25-3p mimic/inhibitor (in vitro), miR-25-3p agomir (in vivo), and si-Adam10 were delivered. Results: MiR-25-3p was expressed poorly in ox-LDL-induced CVECs and vascular tissues but exhibited high levels of expression in thrombin-induced PLT-Exo of atherosclerosis models of ApoE−/− mice. CVECs endocytosed PLT-Exo upregulated the miR-25-3p expression. Adam10 was identified as a target gene of miR-25-3p. The thrombin-induced activated PLT-Exo carrying miR-25-3p reduced Adam10 expression to inhibit ox-LDL-induced CVEC inflammation and lipid deposition through downregulating levels of α-smooth muscle actin, Collagen I a1, Collagen III a1, triglycerides, total cholesterol, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Furthermore, the NF-κB signaling pathway participated in the inhibitory effect of PLT-Exo carrying miR-25-3p. Conclusion: Collectively, PLT-Exo overexpressing miR-25-3p attenuates ox-LDL-induced CVEC inflammation in ApoE−/− mouse models of atherosclerosis.
Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

Supplemental oxygen therapy (hyperoxia) is a widely used treatment for alveolar hypoxia in preterm infants. Despite being closely monitored, hyperoxia exposure is believed to undermine neonatal nephrogenesis and renal function caused by elevated oxidative stress. Previous studies have mostly focused on the hyperoxia-induced impairment of glomerular development, while the long-term impact of neonatal hyperoxia on tubular development and the regulatory component involved in this process remain to be clarified. Here, we examined tubular histology and apoptosis, along with the expression profile of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling, hypoxia-inducible factor 1α (HIF-1α), and catalase, following hyperoxia exposure in neonatal rats. Hematoxylin and eosin (H&E) staining revealed the early disappearance of the nephrogenic zone, as well as dilated lumens and reduced epithelial cells, of mature proximal tubules following neonatal hyperoxia. A robust increase in tubular cell apoptosis caused by neonatal hyperoxia was found using a TUNEL assay. Moreover, neonatal hyperoxia altered renal MAPK/ERK signaling activity and downregulated the expression of HIF-1α and catalase in the proximal tubules throughout nephrogenesis from S-shaped bodies to mature proximal tubules. Cell apoptosis in the proximal tubules was positively correlated with HIF-1α expression on the 14th postnatal day. Our data indicates that proximal tubular development is impaired by neonatal hyperoxia, which is accompanied by altered MAPK/ERK signaling as well as downregulated HIF-1α and catalase. Therapeutic management that targets MAPK/ERK signaling, HIF-1α, or catalase may serve as a protective agent against hyperoxia-induced oxidative damage to neonatal proximal tubules.
Characterization of cxorf21 Provides Molecular Insight Into Female-Bias Immune Response in SLE Pathogenesis

Background: Ninety percent of systemic lupus erythematosus (SLE) patients are women. X chromosome-dosage increases susceptibility to SLE and primary Sjögren's syndrome (pSS). Chromosome X open reading frame 21 (CXorf21) escapes X-inactivation and is an SLE risk gene of previously unknown function. We undertook the present study to delineate the function of CXorf21 in the immune system as well as investigate a potential role in the sex bias of SLE and pSS. Methods: Western blot protein analysis, qPCR, BioPlex cytokine immunoassay, pHrodo™ assays, as well as in vitro CRISPR-Cas9 knockdown experiments were employed to delineate the role of CXorf21 in relevant immunocytes. Results: Expressed in monocytes and B cells, CXorf21 basal Mrna, and protein expression levels are elevated in female primary monocytes, B cells, and EBV-transformed B cells compared to male cells. We also found CXorf21 mRNA and protein expression is higher in both male and female cells from SLE patients compared to control subjects. TLR7 ligation increased CXorf21 protein expression and CXorf21 knockdown abrogated TLR7-driven increased IFNA1 mRNA expression, and reduced secretion of both TNF-alpha and IL-6 in healthy female monocytes. Similarly, we found increased pH in the lysosomes of CXorf21-deficient female monocytes. Conclusion: CXorf21 is more highly expressed in female compared to male cells and is involved in a sexually dimorphic response to TLR7 activation. In addition, CXorf21 expression regulates lysosomal pH in a sexually dimorphic manner. Thus, sexually dimorphic expression of CXorf21 skews cellular immune responses in manner consistent with expected properties of a mediator of the X chromosome dose risk in SLE and pSS.
Quantifying topography-guided actin dynamics across scales using optical flow

Periodic surface topographies with feature sizes comparable to those of in vivo collagen fibers are used to measure and compare actin dynamics for two representative cell types that have markedly different migratory modes and physiological purposes: slowly migrating epithelial MCF10A cells and polarizing, fast migrating, neutrophil-like HL60 cells. Both cell types exhibit reproducible guidance of actin waves (esotaxis) on these topographies, enabling quantitative comparisons of actin dynamics. We adapt a computer-vision algorithm, optical flow, to measure the directions of actin waves at the submicron scale. Clustering the optical flow into regions that move in similar directions enables micron-scale measurements of actin-wave speed and direction. Although the speed and morphology of actin waves differ between MCF10A and HL60 cells, the underlying actin guidance by nanotopography is similar in both cell types at the micron and sub-micron scales.
Detection error influences both temporal seroprevalence predictions and risk factors associations in wildlife disease models

Abstract Understanding the prevalence of pathogens in invasive species is essential to guide efforts to prevent transmission to agricultural animals, wildlife, and humans. Pathogen prevalence can be difficult to estimate for wild species due to imperfect sampling and testing (pathogens may not be detected in infected individuals and erroneously detected in individuals that are not infected). The invasive wild pig (Sus scrofa, also referred to as wild boar and feral swine) is one of the most widespread hosts of domestic animal and human pathogens in North America. We developed hierarchical Bayesian models that account for imperfect detection to estimate the seroprevalence of five pathogens (porcine reproductive and respiratory syndrome virus, pseudorabies virus, Influenza A virus in swine, Hepatitis E virus, and Brucella spp.) in wild pigs in the United States using a dataset of over 50,000 samples across nine years. To assess the effect of incorporating detection error in models, we also evaluated models that ignored detection error. Both sets of models included effects of demographic parameters on seroprevalence. We compared our predictions of seroprevalence to 40 published studies, only one of which accounted for imperfect detection. We found a range of seroprevalence among the pathogens with a high seroprevalence of pseudorabies virus, indicating significant risk to livestock and wildlife. Demographics had mostly weak effects, indicating that other variables may have greater effects in predicting seroprevalence. Models that ignored detection error led to different predictions of seroprevalence as well as different inferences on the effects of demographic parameters. Our results highlight the importance of incorporating detection error in models of seroprevalence and demonstrate that ignoring such error may lead to erroneous conclusions about the risk associated with pathogen transmission. When using opportunistic sampling data to model seroprevalence and evaluate risk factors, detection error should be included.