Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibiotic-induced microbiome depletion protects against MPTP-induced dopaminergic neurotoxicity in the brain

Although the brain–gut axis appears to play a role in the pathogenesis of Parkinson’s disease, the precise mechanisms underlying the actions of gut microbiota in this disease are unknown. This study was undertaken to investigate whether antibiotic-induced microbiome depletion affects dopaminergic neurotoxicity in the mouse brain after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP significantly decreased dopamine transporter (DAT) immunoreactivity in the striatum and tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra of water-treated mice. However, MPTP did not decrease DAT or TH immunoreactivity in the brains of mice treated with an antibiotic cocktail. Furthermore, antibiotic treatment significantly decreased the diversity and altered the composition of the host gut microbiota at the genus and species levels. Interestingly, MPTP also altered microbiome composition in antibiotic-treated mice. These findings suggest that antibiotic-induced microbiome depletion might protect against MPTP-induced dopaminergic neurotoxicity in the brain via the brain–gut axis.
Tri-trophic interactions mediate the spread of a vector-borne plant pathogen.

Many insect herbivores are vectors that transmit plant pathogens as they forage. Within food webs, vectors interact with a range of host plants, other herbivores, and predators. Yet, few studies have examined how tri-trophic interactions involving vectors affect the spread of pathogens. Here we assessed effects of food web structure on aphid vectors and the prevalence of an aphid-borne persistent pathogen (Pea enation mosaic virus, PEMV) in pea plants. We experimentally manipulated ladybird predators, alternative host-plants, and non-vector herbivores and assessed responses of pea aphids and PEMV using structural equation models. We show that variation in bottom-up, top-down, and horizontal interactions mediated PEMV prevalence. Predators reduced PEMV prevalence by consuming aphids, but an alternative host plant (vetch) had the opposite effect by promoting aphid movement and abundance. Non-vector herbivores (pea leaf weevil) increased PEMV susceptibility in peas. In turn, weevils offset the positive effects of predators on PEMV, but increased the negative effects of vetch. Our results show that tri-trophic interactions within insect and plant food webs can mediate vector biology with synergistic and opposing effects on pathogens. Continuing to assess how community-wide interactions affect vectors will aid in our understanding of vector-borne pathosystems. This article is protected by copyright. All rights reserved.
Self-Reported Sleep Duration and Pattern in Old Order Amish and Non-Amish Adults.

STUDY OBJECTIVES We hypothesized that sleep duration in the Amish would be longer than in non-Amish. METHODS Sleep duration was obtained by questionnaire administered to Amish individuals (n = 3,418) and from the 2015-2016 National Health and Nutrition Examination Survey (NHANES; n = 1,912). Self-reported sleep duration was calculated as the difference in usual times that the participants went to bed at night and woke up in the morning. RESULTS In Amish (43.7 ± 16.7 years) and NHANES (50.0 ± 20.6 years), women had a longer sleep duration than men (P < .0001 in both groups) and sleep was significantly longer in those aged 18-29 years and ≥ 70 years, compared to those aged 30-69 years. Seasonal-adjusted sleep duration was shorter in Amish than that in NHANES (7.8 minutes shorter, age- and sex-adjusted P < .0001). However, Amish were less likely to report sleeping fewer than 7 hours per night (15.4% in Amish versus 20.5% in NHANES, P < .0001). Amish went to bed 80.4 minutes earlier than NHANES and arose 87.6 minutes earlier (age-, sex-, and season-adjusted P < .0001 for both). In the Amish, sleep duration was longer in clerks than in farmers (P < .0001) and was significantly correlated among household members (.15 < r < .62, P < .001), although there was no evidence that this trait was heritable (h² approximately 0) after adjustment for household. CONCLUSIONS The lower frequency of short sleepers in the Amish may contribute to the relatively lower risks of cardiometabolic diseases observed in this population.
Verruculosins A–B, New Oligophenalenone Dimers from the Soft Coral-Derived Fungus Talaromyces verruculosus

In an effort to discover new bioactive anti-tumor lead compounds, a specific tyrosine phosphatase CDC25B and an Erb family receptor EGFR were selected as drug screening targets. This work led to the investigation of the soft coral-derived fungus Talaromyces verruculosus and identification of two new oligophenalenone dimers, verruculosins A–B (1–2), along with three known analogues, bacillisporin F (3), duclauxin (4), and xenoclauxin (5). Compound 1 was the first structure of the oligophenalenone dimer possessing a unique octacyclic skeleton. The detailed structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic data, X-ray crystallography, optical rotation, Electronic Circular Dichroism (ECD) analysis, and nuclear magnetic resonance (NMR) calculations. Among which, compounds 1, 3, and 5 exhibited modest inhibitory activity against CDC25B with IC50 values of 0.38 ± 0.03, 0.40 ± 0.02, and 0.26 ± 0.06 µM, respectively.
β-Carotene: A Natural Compound Improves Cognitive Impairment and Oxidative Stress in a Mouse Model of Streptozotocin-Induced Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a cascade of changes in cognitive, behavioral, and social activities. Several areas of the brain are involved in the regulation of memory. Of most importance are the amygdala and hippocampus. Antioxidant therapy is used for the palliative treatment of different degenerative diseases like diabetes, cirrhosis, and Parkinson’s, etc. The objective of this study was to assess the effectiveness of exogenous antioxidants, in particular, β carotene (1.02 and 2.05 mg/kg) against intracerebroventricular injected streptozotocin-induced memory impairment in mice. Streptozotocin (3 mg/kg, i.c.v) was administered in two separate doses (on 1st and 3rd days of treatment) for neurodegeneration. Fifty Albino mice (male) were selected in the protocol, and they were classified into five groups (Group I—control, Group II—disease, Group III—standard, Group IV–V—β-carotene-treated) to investigate the cognitive enhancement effect of selected antioxidants. The cognitive performance was observed following the elevated plus-maze, passive avoidance, and open field paradigms. Acetylcholine esterase, β-amyloid protein, and biochemical markers of oxidative stress such as glutathione peroxidase, superoxide dismutase, and catalase were analyzed in brain homogenates. In silico activity against acetylcholinesterase (AChE) was determined by the molecular modeling of β-carotene. β-carotene at a dose of 2.05 mg/kg was found to attenuate the deleterious effects of streptozotocin-induced behavioral and biochemical impairments, including the inhibition of acetylcholinesterase activity. The in silico studies confirmed the binding capacity of β-carotene with the acetylcholinesterase enzyme. The administration of β-carotene attenuated streptozotocin-induced cognitive deficit via its anti-oxidative effects, inhibition of acetylcholinesterase, and the reduction of amyloid β-protein fragments. These results suggest that β-carotene could be useful for the treatment of neurodegenerative diseases such as Alzheimer’s disease.
“Some of us, we don’t know where we’re going to be tomorrow.” Contextual factors affecting PrEP use and adherence among a diverse sample of transgender women in San Francisco

ABSTRACT Transgender women (TW) are disproportionately affected by HIV. Antiretroviral pre-exposure prophylaxis (PrEP) can reduce TW’s vulnerability to HIV, but PrEP uptake has been limited among TW. To explore barriers to PrEP uptake, the study team conducted two semi-structured focus groups with TW in San Francisco at risk for HIV acquisition. A within-case, across-case approach was used to code and analyze emerging themes. Focus group participants were racially and ethnically diverse. A few participants in both groups had heard of PrEP, but some had not. Several said that their health care providers had not told them about PrEP. Participants in both groups had questions about side effects. They expressed medical mistrust and said poverty is an important context for their lives. They described a need for gender affirming health care services and raised concerns about interactions of PrEP with feminizing hormones. Information about side effects and interactions between gender affirming hormones and PrEP need to be explicitly addressed in PrEP education campaigns focusing on TW. Health care institutions and health departments should train clinical staff how to provide affirming care. Gender identity nondiscrimination laws and policies could improve transgender people’s ability to earn a living and access health care.
Long‐term evolution of the natural isolate of Escherichia coli 536 in the mouse gut colonized after maternal transmission reveals convergence in the constitutive expression of the lactose operon

In vitro experimental evolution has taught us many lessons on the molecular bases of adaptation. To move towards more natural settings, evolution in the mice gut has been successfully performed. Yet, these experiments suffered from the use of laboratory strains as well as the use of axenic or streptomycin‐treated mice to maintain the inoculated strains. To circumvent these limitations, we conducted a one‐year experimental evolution in vivo using a natural isolate of E. coli, strain 536, in conditions mimicking as much as possible natural environment with mother‐to‐offspring microbiota transmission. Mice were then distributed in 24 independent cages and separated into two different diets: a regular one (chow diet, CD) and high‐fat and high‐sugar one (Western Diet, WD). Genome sequences revealed an early and rapid selection during the breastfeeding period that selected the constitutive expression of the well‐characterized lactose operon. E. coli was lost significantly more in CD than WD; however, we could not detect any genomic signature of selection, nor any diet specificities during the later part of the experiments. The apparently neutral evolution presumably due to low population size maintained nevertheless at high frequency the early selected mutations affecting lactose regulation. The rapid loss of lactose operon regulation challenges the idea that plastic gene expression is both optimal and stable in the wild.
Depression, anxiety and acute pain: links and management challenges

ABSTRACT Pain is a subjective experience that is influenced by genetics, gender, social, cultural and personal parameters. Opposed to chronic pain, which by definition has to last for at least 3 months, acute pain is mostly because of trauma, acute medical conditions or treatment. The link between mood disorders and acute pain has proven to be increasingly significant since the link is bi-directional, and both act as risk factors for each other. Depression and anxiety are associated with increased perception of pain severity, whereas prolonged duration of acute pain leads to increased mood dysregulation. Although both depression and anxiety have a proven association with acute pain, the link between depression and acute pain is more thoroughly studied. Pain can be the presenting or sole complaint in depressed patients who present to primary care practices and is often overlooked by clinicians. However, reports on the perception of experimentally-induced pain in depressed patients are mixed, showing both an increased and decreased pain threshold and pain tolerance across various studies. Although less data is published about anxiety and pain, the relationship is consistent across studies as increased anxiety leads to increased severity of pain perceived and decreased pain tolerance. Anxiety as well as fear, stress, and catastrophizing are also shown to be mediators in the causal pathway between pain and disability.
Intracerebroventricular enzyme replacement therapy with β-galactosidase reverses brain pathologies due to GM1 gangliosidosis in mice

Autosomal recessive mutations in the galactosidase β1 (GLB1) gene cause lysosomal β-gal deficiency, resulting in accumulation of galactose-containing substrates and onset of the progressive and fatal neurodegenerative lysosomal storage disease, GM1 gangliosidosis. Here, an enzyme replacement therapy (ERT) approach in fibroblasts from GM1 gangliosidosis patients with recombinant human β-gal (rhβ-gal) produced in Chinese hamster ovary cells enabled direct and precise rhβ-gal delivery to acidified lysosomes. A single, low dose (3 nm) of rhβ-gal was sufficient for normalizing β-gal activity and mediating substrate clearance for several weeks. We found that rhβ-gal uptake by the fibroblasts is dose-dependent and saturable and can be competitively inhibited by mannose 6-phosphate, suggesting cation-independent, mannose 6-phosphate receptor–mediated endocytosis from the cell surface. A single intracerebroventricularly (ICV) administered dose of rhβ-gal (100 μg) resulted in broad bilateral biodistribution of rhβ-gal to critical regions of pathology in a mouse model of GM1 gangliosidosis. Weekly ICV dosing of rhβ-gal for 8 weeks substantially reduced brain levels of ganglioside and oligosaccharide substrates and reversed well-established secondary neuropathology. Of note, unlike with the ERT approach, chronic lentivirus-mediated GLB1 overexpression in the GM1 gangliosidosis patient fibroblasts caused accumulation of a prelysosomal pool of β-gal, resulting in activation of the unfolded protein response and endoplasmic reticulum stress. This outcome was unsurprising in light of our in vitro biophysical findings for rhβ-gal, which include pH-dependent and concentration-dependent stability and dynamic self-association. Collectively, our results highlight that ICV-ERT is an effective therapeutic intervention for managing GM1 gangliosidosis potentially more safely than with gene therapy approaches.
Metschnikowia pulcherrima Selected Strain for Ethanol Reduction in Wine: Influence of Cell Immobilization and Aeration Condition

One of the most important problems in the winemaking field is the increase of ethanol content in wine. Wines with high ethanol level negatively affect wine flavor and human health. In this study, we evaluated the use of a selected strain of Metschnikowia pulcherrima in immobilized form and under different aeration conditions, to reduce the ethanol content evaluating the volatile profile of the resulting wines. In a preliminary screening the best conditions regarding free/immobilized cells, static/aerated fermentation and inoculation level were identified. Bench-Top fermentation trials with different aeration conditions showed that the use of M. pulcherrima selected strain with aeration flow of 20 mL/L/min during the first 72 h of fermentation, led an ethanol reduction of 1.38% (v/v) in comparison with Saccharomyces cerevisiae control strain. The analytical profile of the resulting wines did not show any negative feature. Indeed, the concentration of ethyl acetate, that above its sensory threshold impacts negatively the wine sensory profile, was found at an acceptable level. On the other hand, an increase in the concentration of significant fruity and flower compounds was found.
Effectiveness of a Pharmacogenetic Tool at Improving Treatment Efficacy in Major Depressive Disorder: A Meta-Analysis of Three Clinical Studies

Several pharmacogenetic tests to support drug selection in psychiatric patients have recently become available. The current meta-analysis aimed to assess the clinical utility of a commercial pharmacogenetic-based tool for psychiatry (Neuropharmagen®) in the treatment management of depressive patients. Random-effects meta-analysis of clinical studies that had examined the effect of this tool on the improvement of depressive patients was performed. Effects were summarized as standardized differences between treatment groups. A total of 450 eligible subjects from three clinical studies were examined. The random effects model estimated a statistically significant effect size for the pharmacogenetic-guided prescription (d = 0.34, 95% CI = 0.11–0.56, p-value = 0.004), which corresponded to approximately a 1.8-fold increase in the odds of clinical response for pharmacogenetic-guided vs. unguided drug selection. After exclusion of patients with mild depression, the pooled estimated effect size increased to 0.42 (95% CI = 0.19–0.65, p-value = 0.004, n = 287), corresponding to an OR = 2.14 (95% CI = 1.40–3.27). These results support the clinical utility of this pharmacogenetic-based tool in the improvement of health outcomes in patients with depression, especially those with moderate–severe depression. Additional pragmatic RCTs are warranted to consolidate these findings in other patient populations.
The upper disparity limit increases gradually with eccentricity

Stereopsis is important for tasks of daily living such as eye-hand coordination. It is best in central vision but is also mediated by the periphery. Previously we have shown that individuals with central-field loss who have residual stereopsis in the periphery perform better at an eye-hand-coordination task when they perform the task binocularly rather than monocularly. Here we seek to determine what sets the limit of stereopsis, defined as the largest disparity that supports the sustained appearance of depth, in the near periphery in healthy individuals. While stereoacuity thresholds increase sharply with eccentricity, Panum's area increases much more slowly. We used a rigorous method to determine the uppermost limit of disparity. At long durations, the two half-images that define a large disparity appear as two isolated targets in the same flat plane; small incremental changes in disparity produce changes in the separation between the half-images, and disparity magnitude can be judged on the basis of separation, like a monocular width judgment. The disparity limit is the point at which the threshold for judging dichoptic separation between the half-images is equal to the monocular width-discrimination threshold. The disparity limit at 10° was a factor of 2–4 times larger than the fovea, regardless of the meridian tested. The increase in the disparity limit with eccentricity was shallow, similar to that of Panum's area. Within this disparity limit, disparity increment thresholds were comparable for foveal and peripheral targets, illustrating the significance and utility of peripheral stereopsis, especially in the absence of foveal stereopsis.
Risk of Dementia in Patients with Leptospirosis: A Nationwide Cohort Analysis

Background: Studies have linked some bacterial infections with an increased likelihood for development of dementia. However, there is a paucity of data on the relationship between dementia and leptospirosis. In view of this, we conducted a retrospective cohort study to determine whether leptospirosis is a risk factor for dementia. Methods: Data were collected from the Taiwan National Health Insurance Research Databases (2000–2010) to investigate the incidence of and risk factors for dementia in patients with leptospirosis. Patients with leptospirosis who did not have a history of dementia were enrolled in the study. For each leptospirosis patient, four controls were randomly selected after frequency matching of age, sex, and index date. Cox proportional hazard regression models were used for the analyses of dementia risk. Results: A greater risk of dementia was observed in the leptospirosis cohort than in the non-leptospirosis cohort both in patients without any comorbidity (adjusted HR (aHR) = 1.23, 95% CI = 1.06–1.43) and with a comorbidity (aHR = 2.06, 95% CI = 1.7–2.5). Compared with the non-leptospirosis cohort without these comorbidities, the leptospirosis cohort with ≥2 comorbidities exhibited a significantly increased risk of dementia (aHR = 6.11, 95% CI = 3.15–11.9), followed by those with any one comorbidity (adjusted HR = 3.62, 95% CI = 1.76–7.46). Conclusions: Patients with leptospirosis were at a 1.89-fold greater risk of subsequent dementia, but potential genetic susceptibility bias in the study group is a major confound.
Proximate Composition and Nutritional Profile of Rainbow Trout (Oncorhynchus mykiss) Heads and Skipjack tuna (Katsuwonus Pelamis) Heads

In order to evaluate the application potential of rainbow trout (Oncorhynchus mykiss) heads and skipjack tuna (Katsuwonus pelamis) heads; proximate composition, amino acids, fatty acids, carnosine, and anserine contents were analyzed in this study. Rainbow trout heads showed significantly higher protein (29.31 g/100 g FW, FW is abbreviation of fresh weight) and lipid (6.03 g/100 g FW) contents than skipjack tuna heads (18.47 g/100 g FW protein and 4.83 g/100 g FW lipid) (p < 0.05). Rainbow trout heads and skipjack tuna heads exhibited similar amino acid composition. Essential amino acids constituted more than 40% of total amino acids in both rainbow trout head and skipjack tuna head. The fatty acid profile was different between rainbow trout heads and skipjack tuna heads. Rainbow trout heads mainly contained 38.64% polyunsaturated fatty acids (PUFAs) and 38.57% monounsaturated fatty acids (MUFAs), whereas skipjack tuna heads mainly contained 54.46% saturated fatty acids (SFAs). Skipjack tuna heads contained 4563 mg/kg FW anserine and 1761 mg/kg FW carnosine, which were both significantly higher than those of rainbow trout heads (p < 0.05). These results demonstrate that both rainbow trout heads and skipjack tuna heads may be used as materials for recycling high-quality protein. Meanwhile, rainbow trout heads can be used to extract oil with high contents of unsaturated fatty acids, while skipjack tuna heads may be a source for obtaining carnosine and anserine.
A Radiogenomic Approach for Decoding Molecular Mechanisms Underlying Tumor Progression in Prostate Cancer

Prostate cancer (PCa) is a genetically heterogeneous cancer entity that causes challenges in pre-treatment clinical evaluation, such as the correct identification of the tumor stage. Conventional clinical tests based on digital rectal examination, Prostate-Specific Antigen (PSA) levels, and Gleason score still lack accuracy for stage prediction. We hypothesize that unraveling the molecular mechanisms underlying PCa staging via integrative analysis of multi-OMICs data could significantly improve the prediction accuracy for PCa pathological stages. We present a radiogenomic approach comprising clinical, imaging, and two genomic (gene and miRNA expression) datasets for 298 PCa patients. Comprehensive analysis of gene and miRNA expression profiles for two frequent PCa stages (T2c and T3b) unraveled the molecular characteristics for each stage and the corresponding gene regulatory interaction network that may drive tumor upstaging from T2c to T3b. Furthermore, four biomarkers (ANPEP, mir-217, mir-592, mir-6715b) were found to distinguish between the two PCa stages and were highly correlated (average r = ± 0.75) with corresponding aggressiveness-related imaging features in both tumor stages. When combined with related clinical features, these biomarkers markedly improved the prediction accuracy for the pathological stage. Our prediction model exhibits high potential to yield clinically relevant results for characterizing PCa aggressiveness.