Miracle-dz/UniFAR-FTUs huggingface dataset:
Identifying priority areas for research and conservation of the largetooth sawfish Pristis pristis in Colombia and Panama

Sawfishes are considered one of the most endangered families of fishes in the world. Their diadromous ecology and vulnerability to fishing nets have brought most populations to the brink of collapse. Conservation of the surviving populations is hindered by the paucity of historic and contemporary catch and observational records, and assessments of suitable coastal and riverine habitats. Colombia and Panama are two of 14 countries considered as a high priority for the development of species-specific national legal protection of the critically endangered largetooth sawfish (Pristis pristis). To construct a baseline for the temporal and spatial distribution of the largetooth sawfish in Colombia and Panama, we collected historical records from museum databases and from literature over the past century, analysed available small-scale fisheries landings databases, and conducted interviews with fish workers in 38 locations across both countries. We found 257 records of sawfish occurrences across both countries between 1896 and 2015, with 69% of the records before the year 2000. The declining trend in the frequency of observations was corroborated by fishers, who reported fewer sawfish catches over the last 20 years. Using kernel density estimation of recent encounter locations, we identify potential hotspots that may represent extant populations of sawfish. These locations are broadly characterized by their remoteness and high mangrove forest cover. Given the length and cultural diversity of the Pacific coastlines of Colombia and Panama, and the inaccessibility of many of the communities, our findings provide important guidance to target rapid conservation and fisheries interventions to priority areas. We suggest that the relative success of community-managed fishing areas in the region makes this a valuable platform on which to build local stewardship of marine resources, while raising awareness of the need to safeguard critically endangered largetooth sawfish.
PECAM-1 preserves cardiac function in pressure overload-induced biomechanical stress

Background Haemodynamic forces play a critical role in proper development of the heart, however much less is known about the mechanisms that regulate cardiac remodelling and function in response to haemodynamic stress in the adult. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell adhesion and signalling molecule that has important roles in regulation of junctional integrity, transendothelial migration and mechanotransduction in response to fluid shear stress. Our previous work identified a role for PECAM-1 in regulating baseline cardiac function via regulation of endothelial-cardiomyocyte communication. Methods This study investigates the role of PECAM-1 in cardiac remodelling in response to biomechanical stress due to pressure overload induced by transaortic constriction (TAC). Results Our data reveal that loss of PECAM-1 is associated with systolic dysfunction that is further accentuated following TAC. Adaptive increases in cardiomyocyte cross-sectional area, capillary density and hypertrophic gene expression were all affected with loss of PECAM-1. In control mice, maintained cardiac function was associated with activation of the c-Jun NH(2)-terminal kinase (JNK) pathway, whereas PECAM-1 deletion significantly decreased JNK activation after pressure overload. Our data suggest that in the absence of PECAM-1 signalling, inadequate remodelling of the heart under increased mechanical strain leads to further deterioration of cardiac function, characterized by reduced cardiomyocyte hypertrophy, capillary density and defects in the JNK signalling pathway. Conclusions Our study reveals a role for PECAM-1 in preservation of cardiac function in response to biomechanical stress induced by pressure overload.
Tonic activity in lateral habenula neurons promotes disengagement from reward-seeking behavior

Survival requires both the ability to persistently pursue goals and the ability to determine when it is time to stop, an adaptive balance of perseverance and disengagement. Neural activity in the lateral habenula (LHb) has been linked to aversion and negative valence, but its role in regulating the balance between reward-seeking and disengaged behavioral states remains unclear. Here, we show that LHb neural activity is tonically elevated during minutes-long disengagements from reward-seeking behavior, whether due to repeated reward omission or following sufficient consumption of reward. Further, we show that LHb inhibition extends ongoing reward-seeking behavioral states but does not prompt re-engagement. We find no evidence for similar tonic activity fluctuations in ventral tegmental area (VTA) dopamine neurons. Our findings implicate the LHb as a key mediator of disengagement from reward-seeking behavior in multiple contexts and argue against the idea that the LHb contributes to decisions solely by signaling aversion.
Effects of forced cohesin eviction and retention on X-inactivation and autosomes

Depletion of architectural factors globally alters chromatin structure, but only modestly affects gene expression. We revisit the structure-function relationship using the inactive X chromosome (Xi) as a model. We investigate cohesin imbalances by forcing its depletion or retention using degron-tagged RAD21 (cohesin subunit) or WAPL (cohesin release factor). Interestingly, cohesin loss disrupts Xi superstructure, unveiling superloops between escapee genes, with minimal effect on gene repression. By contrast, forced cohesin retention markedly affects Xi superstructure and compromises spreading of Xist RNA-Polycomb complexes, attenuating Xi silencing. Effects are greatest at distal chromosomal ends, where looping contacts with the Xist locus are weakened. Surprisingly, cohesin loss created an “Xi superloop” and cohesin retention created “Xi megadomains” on the active X. Across the genome, a proper cohesin balance protects against aberrant inter-chromosomal interactions and tempers Polycomb-mediated repression. We conclude that a balance of cohesin eviction and retention regulates X-inactivation and inter-chromosomal interactions across the genome.
Human Urine Alters Methicillin-Resistant Staphylococcus aureus Virulence and Transcriptome

Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples often precedes potentially life-threatening MRSA bacteremia. ABSTRACT Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of hospital-associated urinary tract infections (UTI), especially in catheterized individuals. Despite being rare, MRSA UTI are prone to potentially life-threatening exacerbations such as bacteremia that can be refractory to routine antibiotic therapy. To delineate the molecular mechanisms governing MRSA urinary pathogenesis, we exposed three S. aureus clinical isolates, including two MRSA strains, to human urine for 2 h and analyzed virulence characteristics and changes in gene expression. The in vitro virulence assays showed that human urine rapidly alters adherence to human bladder epithelial cells and fibronectin, hemolysis of sheep red blood cells (RBCs), and surface hydrophobicity in a staphylococcal strain-specific manner. In addition, transcriptome sequencing (RNA-Seq) analysis of uropathogenic strain MRSA-1369 revealed that 2-h-long exposure to human urine alters MRSA transcriptome by modifying expression of genes encoding enzymes catalyzing metabolic pathways, virulence factors, and transcriptional regulators. In summary, our results provide important insights into how human urine specifically and rapidly alters MRSA physiology and facilitates MRSA survival in the nutrient-limiting and hostile urinary microenvironment. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples often precedes potentially life-threatening MRSA bacteremia. In this report, we describe how exposure to human urine alters MRSA global gene expression and virulence. We hypothesize that these alterations may aid MRSA in acclimating to the nutrient-limiting, immunologically hostile conditions within the urinary tract leading to MRSA UTI.
Modulation of the IKS channel by PIP2 requires two binding sites per monomer

The phosphatidyl-inositol-4,5-bisphosphate (PIP2) lipid has been shown to be crucial for the coupling between the voltage sensor and the pore of the potassium voltage-gated KV7 channel family, especially the KV7.1 channel. The latter, expressed in the myocardium membrane is complexed with its auxiliary subunits, KCNE1 to generate the so-called IKS current. We present here molecular models of transmembrane domain of this complex in its three known states, namely the Resting/Closed (RC), the Intermediate/Closed (IC), and the Activated/Open (AO), robustness of which is assessed by agreement with a range of biophysical data. Molecular Dynamics (MD) simulations of these models embedded in a lipid bilayer including phosphatidyl-inositol-4,5-bisphosphate (PIP2) lipids show that in presence of KCNE1, two PIP2 lipids are necessary to stabilize each state. The simulations also show that KCNE1 interacts with both PIP2 binding sites, forming a tourniquet around the pore and preventing its opening. The present investigation provides therefore key molecular elements that govern the role of PIP2 in KCNE1 modulation of IKS channels, possibly a common mechanism by which auxiliary KCNE subunits might modulate a variety of other ion channels.
FOXO1 and FOXO3 Cooperatively Regulate Innate Lymphoid Cell Development

The natural killer (NK) and non-cytotoxic innate lymphoid cells (ILC) lineages play vital role in the regulation of the immune system. Yet understanding of mechanisms controlling NK/ILC development remains incomplete. The evolutionary conserved FOXO family of forkhead transcription factors are critical regulators of cellular processes. We found that the loss of FOXO1 and FOXO3 together caused impaired activation of the NK gene expression program and reduced ETS binding already at the common lymphoid progenitor (CLP) level and a block at the ILC progenitor (ILCP) to NK progenitor transition. FOXO controlled NK cell maturation in organ specific manner and their ability to respond to IL-15. At the ILCP level, disruption of the ILC lineage specific gene programs was associated with broad perturbation of the generation of the non-cytotoxic ILC subsets. We concluded that FOXO1 and FOXO3 cooperatively regulate ILC lineage specification at the progenitor level as well as the generation of mature ILCs.
The New Frontier of Host-Directed Therapies for Mycobacterium avium Complex

Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In order to address similar challenges facing the management of patients with tuberculosis, recent attention has focused on the development of novel adjunctive, host-directed therapies (HDTs), with the goal of accelerating the clearance of mycobacteria by immune defenses and reducing or reversing mycobacterial-induced lung damage. In this review, we will summarize the evidence supporting specific adjunctive, HDTs for MAC, with a focus on the repurposing of existing immune-modulatory agents targeting a variety of different cellular pathways. We also highlight areas meriting further investigation.
Protein Phosphatase PP1 Negatively Regulates IRF3 in Response to GCRV Infection in Grass Carp (Ctenopharyngodon idella)

Protein phosphatase-1 (PP1) has an important role in many cell functions, such as cell differentiation, development, immune response and tumorigenesis. However, the specific role of PP1 in the antiviral response in fish remains to be elucidated. In this study, the PPP1R3G homolog was identified in the grass carp (Ctenopharyngodon idella) and its role in defence against the GCRV infection was investigated. Phylogenetic analysis demonstrated that CiPPP1R3G clustered with homologues from other teleosts. Temporal expression analysis in vivo revealed that the expression level of CiPPP1R3G was significantly up-regulated in response to GCRV infection in grass carps, especially in the intestine and head-kidney. Cellular distribution analysis revealed that CiPPP1R3G was located in the nucleus and cytoplasm. Overexpression of CiPPP1R3G significantly negatively regulated the expression of CiIRF3, thus inhibiting its activation. In summary, we systematically analyzed the PPP1R3G gene in grass carp and illustrated its function as a negative regulator in the anti-GCRV immune responses.
Equity at the Ballot Box: Health as a Resource for Political Participation Among Low-Income Workers in Two United States Cities

Objective: The purpose of this study is to identify health resources associated with propensity to vote at the local-level among low-wage workers in two United States. cities. Literature confirms individuals of lower income have a lower propensity of turning out to vote, yet few studies have focused on low-income populations to identify the variation in factors associated with voting within this group. Furthermore, few studies have investigated health and voter turnout at the local-level. In this study, we examine factors related to political participation at the local-level within a low-wage sample, examine mental, physical, behavioral, and social health and their association with voter turnout, and assess if these relationships differ by city. Methods: We use cross-sectional survey data from a sample of 974 low-wage workers in Minneapolis, MN and Raleigh, NC. We computed descriptive statistics and employed a logistic regression to predict their likelihood of local voter turnout, with the key independent variables being health resources, such as self-rated health, body mass index (BMI), mental disability, smoking status, and health insurance status. We employed a logistic regression fully interacted with a city indicator variable to assess if these associations differed by city. Results: In both cities, less than 50 percent of respondents reported voting in the last election for mayor or city council. About three-quarters of the sample reported food or housing insecurity and the majority of respondents reported utilizing some government assistance, such as supplemental nutrition programs. BMI greater than 30 was significantly associated with lower likelihood of voter turnout compared to those of lower BMI status (marginal effect = −0.10, p = 0.026). Never smoking or quitting was significantly associated with higher likelihood of voter turnout compared to those who reported being a current smoker (marginal effect = 0.10, p = 0.002). Those with health insurance were significantly more likely to report voting compared to those without any insurance (marginal effect = 0.10, p = 0.022). These results did not significantly differ by city. Conclusions: Our research suggests low-wage workers face significant health burdens which may impact their propensity to vote at the local-level, and these associations do not significantly vary by city despite demographic and political differences between two jurisdictions.
A Novel Scale for Assessment of Stroke Severity at Symptom Onset: Correlation With Neurological Deterioration and Outcome

Objective: To propose a novel scale for the assessment of stroke severity at symptom onset and to investigate whether it is associated with ultra-early neurological deterioration (UND) and functional outcomes. Methods: The Chongqing Stroke Scale (CQSS) was constructed based on key aspects of history, emphasizing language, motor function, and level of consciousness to yield a total 0–11 scale. The diagnostic performance of the CQSS was assessed in 215 ischemic stroke patients between June 2017 and October 2017 in a tertiary hospital. Patients were included if they presented within 24 h after onset of symptoms and they or their witness can recall the scenario at symptom onset. UND was defined as an increase ≥2 points on the CQSS between symptom onset and admission. Functional outcomes were assessed using the 3-month modified Rankin scale. The correlation between the CQSS score and baseline National Institutes of Health Stroke Scale (NIHSS) score was assessed. The sensitivity, specificity, and positive and negative predictive values of CQSS for the outcomes were calculated. Logistic regression was used to test the association between the CQSS score and functional outcomes. Results: A total of 215 patients with available CQSS scores were included. Baseline CQSS scores at symptom onset were correlated with the admission NIHSS score (r = 0.56, p < 0.001) and functional outcome at 3 months (r = 0.47, p < 0.001). Baseline CQSS ≥ 6 was an independent predictor of functional outcome at 3 months (odds ratio, 12.61; 95% confidence interval 5.68–27.97, p < 0.001). UND was observed in 20 (9.30%) patients. The 90-day mortality was significantly higher in patients with UND than those without UND (25.0 vs. 8.2%, p < 0.001). After adjusting for age, admission systolic blood pressure, hypertension, and diabetes, UND independently predicted poor functional outcome in the multivariate logistic regression model (odds ratio, 9.69; 95% confidence interval 3.19–29.45, p < 0.001). Conclusions: The newly developed CQSS is a simple and easy-to-perform scale that allows a quantitative evaluation of the stroke severity at symptom onset and an assessment of UND before hospital admission. It is associated with NIHSS and predicts functional outcome in patients with acute ischemic stroke.
Effect of Item Order on Certain Psychometric Properties: A Demonstration on a Cyberloafing Scale

Many studies have been conducted on the effect of item order in self-report questionnaires on mean scores. This research aims to study the effect of item order on measurement invariance in addition to mean scores. To this end, two groups randomly obtained from the same sample were presented a fixed order form in which all items belonging to the same dimension were adjacent to each other, and a random order form in which the items were randomly sequenced respectively. The results obtained revealed a statistically significant difference between the mean scores of the two forms. In the next stage of the study, the fit indices obtained from the confirmatory factor analysis (CFA) applied to the two separate forms and the modification indices (MI) suggested by the software were compared. Both forms returned high modification suggestions for adjacent items or items presented near each other. Additionally, it was found that high χ2 reductions suggested by the MIs in one form resulted in low χ2 reductions in the other. Lastly, multiple group CFA (mg-CFA) was conducted to determine whether or not measurement invariance was achieved through different item order presentations of the scale. The findings indicate that measurement invariance could not be achieved even at the first stage of analysis. It may specifically be stated that presenting respondents items under the same dimension together ensures empirical findings congruent with theoretical structure.
Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice

Protecting white matter is one of the key treatment strategies for spinal cord injury (SCI), including alleviation of myelin loss and promotion of remyelination. Rapamycin has been shown neuroprotective effects against SCI and cardiotoxic effects while enhancing autophagy. However, specific neuroprotection of rapamycin for the white matter after cervical SCI has not been reported. Therefore, we aim to evaluate the role of rapamycin in neuroprotection after hemi-contusion SCI in mice. Forty-six 8-week-old mice were randomly assigned into the rapamycin group (n = 16), vehicle group (n = 16), and sham group (n = 10). All mice of the rapamycin and vehicle groups received a unilateral contusion with 1.2-mm displacement at C5 followed by daily intraperitoneal injection of rapamycin or dimethyl sulfoxide solution (1.5 mg⋅kg–1⋅day–1). The behavioral assessment was conducted before the injury, 3 days and every 2 weeks post-injury (WPI). The autophagy-related proteins, the area of spared white matter, the number of oligodendrocytes (OLs) and axons were evaluated at 12 WPI, as well as the glial scar and the myelin sheaths formed by Schwann cells at the epicenter. The 1.2 mm contusion led to a consistent moderate–severe SCI in terms of motor function and tissue damage. Rapamycin administration promoted autophagy in spinal cord tissue after injury and reduced the glial scar at the epicenter. Additionally, rapamycin increased the number of OLs and improved motor function significantly than in the vehicle group. Furthermore, the rapamycin injection resulted in an increase of Schwann cell-mediated remyelination and weight loss. Our results suggest that rapamycin can enhance autophagy, promote Schwann cell myelination and motor function recovery by preserved neural tissue, and reduce glial scar after hemi-contusive cervical SCI, indicating a potential strategy for SCI treatment.
Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy

Multiple lines of evidence are indicating that cancer development and malignant progression are not exclusively epithelial cancer cell-autonomous processes but may also depend on crosstalk with the surrounding tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are abundantly represented in the TME and are continuously interacting with cancer cells. CAFs are regulating key mechanisms during progression to metastasis and response to treatment by enhancing cancer cells survival and aggressiveness. The latest advances in CAFs biology are pointing to CAFs-secreted factors as druggable targets and companion tools for cancer diagnosis and prognosis. Especially, extensive research conducted in the recent years has underscored the potential of several cytokines as actionable biomarkers that are currently evaluated in the clinical setting. In this review, we explore the current understanding of CAFs secretome determinants and functions to discuss their clinical implication in oncology.