Miracle-dz/UniFAR-FTUs huggingface dataset:
Enriched environment and stress exposure influence splenic B lymphocyte composition

Prolonged chronic stress has deleterious effects on immune function and is associated with numerous negative health outcomes. The spleen harbors one-fourth of the body’s lymphocytes and mediates both innate and adaptive immune responses. However, the subset of splenic lymphocytes that respond, either adaptively or maladaptively, to various stressors remains largely unknown. Here we investigated the effects of unpredictable chronic mild stress (CMS) exposure on spleen composition in male mice housed in two different caging conditions: standard caging (Cntl) and enriched environment (EE). EE-caged mice exhibited the greatest absolute number of splenocytes and CMS exposure significantly lowered splenocyte numbers in both caging conditions. Glucocorticoid production, measured by mean fecal corticosterone metabolites (FCM), was significantly lower in EE-caged mice vs. Cntl-caged mice. Surprisingly, CMS exposure resulted in an increase in mean FCM in EE-caged mice, but no significant change in Cntl-caged mice. CMS altered the splenic B:T lymphocyte ratio; it reduced the frequency of B cells, but increased the frequency of T cells in EE-caged mice. Splenocyte number and B:T lymphocyte ratio showed a negative relationship with mean FCM. EE-caged mice had a lower frequency of immature and germinal B cells than Cntl-caged mice. CMS markedly increased the frequency of immature and marginal zone B cells, but decreased the frequency of follicular B cells in both caging conditions. Mean FCM correlated positively with frequency of immature, marginal zone and germinal center B cells, but negatively with frequency of follicular B cells. To conclude, splenic immune cells, particularly B lymphocyte composition, are modulated by caging environment and stress and may prime mice differently to respond to immune challenges.
Reciprocal regulation of chromatin state and architecture by HOTAIRM1 contributes to temporal collinear HOXA gene activation

Abstract Thousands of long non-coding RNAs (lncRNAs) have been identified in mammals, many of which represent important regulators of gene expression. However, the mechanisms used by lncRNAs to control transcription remain largely uncharacterized. Here, we report on HOTAIRM1, a promising lncRNA biomarker in leukemia and solid tumors. We find that HOTAIRM1 contributes to three-dimensional chromatin organization changes required for the temporal collinear activation of HOXA genes. We show that distinct HOTAIRM1 variants preferentially associate with either UTX/MLL or PRC2 complexes to modulate the levels of activating and silencing marks at the bivalent domain. HOTAIRM1 contributes to physical dissociation of chromatin loops at the cluster proximal end, which delays recruitment of the histone demethylase UTX and transcription of central HOXA genes. Interestingly, we find overall proximal HOXA gene activation without chromatin conformation changes by HOTAIRM1 in a different cell type. Our results reveal a previously unappreciated relationship between chromatin structure, architecture and lncRNA function.
Portability of Tag SNPs Across Isolated Population Groups: An Example from India

Isolated population groups are useful in conducting association studies of complex diseases to avoid various pitfalls, including those arising from population stratification. Since DNA resequencing is expensive, it is recommended that genotyping be carried out at tagSNP (tSNP) loci. For this, tSNPs identified in one isolated population need to be used in another. Unless tSNPs are highly portable across populations this strategy may result in loss of information in association studies. We examined the issue of tSNP portability by sampling individuals from 10 isolated ethnic groups from India. We generated DNA resequencing data pertaining to 3 genomic regions and identified tSNPs in each population. We defined an index of tSNP portability and showed that portability is low across isolated Indian ethnic groups. The extent of portability did not significantly correlate with genetic similarity among the populations studied here. We also analyzed our data with sequence data from individuals of African and European descent. Our results indicated that it may be necessary to carry out resequencing in a small number of individuals to discover SNPs and identify tSNPs in the specific isolated population in which a disease association study is to be conducted.
Prevalence and Associated Factors of Erectile Dysfunction among Married Men in Vietnam

Background Sexuality is an essential part of life; however, erectile dysfunction (ED) has been one of the most common complaints among men with sexual health issues all over the world. ED includes dysfunction in erection and penile erectile pain. In Vietnam, ED is a subject a not readily discussed. Thus, relatively little is known about ED among Vietnamese men. Aims To identify the prevalence of ED and its associated variables and the need for treatment of ED among married men in Vietnam. Methods This was a cross-sectional study. A total sample size included 746 married men, aged 20–60 years, living in four representative wards of the Hue City and randomly selected by systematic sampling methods. Respondents completed a self-reported questionnaire. The International Index of Erectile Function (IIEF-5) scale was used to determine ED severity, and the Depression Anxiety Stress Scales (DASS-21) was used to measure depression, anxiety, and stress. Quality of life was assessed using the WHO Quality of Life score (WHOQoL). A multivariate logistic regression model was used to determine the relationships between independent variables and ED. Results Mean age of married men was 44.3 ± 8.7. Two-thirds (66.9%) of respondents experienced ED symptoms. In terms of severity, 40.8% reported mild ED; 20.3% mild–moderate ED; 5.0% moderate ED; and 0.8% severe ED. Depression, anxiety, and stress problems were 5.0, 3.6, and 2.8%, respectively. One-third (33.1%) of the respondents reported having low quality of life, and 32.6% reported having medium quality of life. The vast majority (86.9%) had consensual sex with their wives/partners. Variables associated with increased IIEF-5 score were increased WHOQoL score, increased body mass index (BMI), religion, and no consumption of alcohol. Increasing age, disease history, increased anxiety, and no consensual sex with their wife/partner were associated with a lower IIEF-5 score. If experiencing ED, 55.5% would seek help from medical doctors, 55.1% discussed it with their wives/partners, and 23.1% turned to their friends for help. Conclusion The prevalence of ED was high, although only 5.8% experienced moderate to severe ED. The key factors associated with ED were age, religion, disease history, BMI, alcohol consumption, anxiety, quality of life, and consensual sex with their wives/partners. Sexual health education should be more specifically targeted for men, including the provision of local sexual health-care services for men.
Rhythm Transcription of Polyphonic Piano Music Based on Merged-Output HMM for Multiple Voices

In a recent conference paper, we have reported a rhythm transcription method based on a merged-output hidden Markov model (HMM) that explicitly describes the multiple-voice structure of polyphonic music. This model solves a major problem of conventional methods that could not properly describe the nature of multiple voices as in polyrhythmic scores or in the phenomenon of loose synchrony between voices. In this paper, we present a complete description of the proposed model and develop an inference technique, which is valid for any merged-output HMMs, for which output probabilities depend on past events. We also examine the influence of the architecture and parameters of the method in terms of accuracies of rhythm transcription and voice separation and perform comparative evaluations with six other algorithms. Using MIDI recordings of classical piano pieces, we found that the proposed model outperformed other methods by more than 12 points in the accuracy for polyrhythmic performances and performed almost as good as the best one for non-polyrhythmic performances. This reveals the state-of-the-art methods of rhythm transcription for the first time in the literature. Publicly available source codes are also provided for future comparisons.
Understanding Broadscale Wildfire Risks in a Human-Dominated Landscape

ABSTRACT. Broadscale statistical evaluations of wildfire incidence can answer policy-relevantquestions about the effectiveness of microlevel vegetation management and can identify subjectsneeding further study. A dynamic time series cross-sectional model was used to evaluate the statisticallinks between forest wildfire and vegetation management, human land use, and climatic factors inFlorida counties. Four forest wildfire risk functions were estimated: one for fires regardless of ignitionsource, and three others for fires of specific ignition sources: arson, lightning, and accident(unintentional anthropogenic). Results suggest that current wildfire risk is negatively related to severalyears of past wildfire and very recent site prep burning, and risk is positively related to pulpwoodremovals. The effect of traditional prescribed burning on wildfire risk varies by ignition source. El Nirio-Southern Oscillation (ENSO) sea surface temperature (SST) anomalies were also significantly linkedto forest wildfire risk, but a measure of the wildland-urban interface was not significant. Although thesecounty-level results hold promise for aggregate risk assessment, modeling at finer spatial andtemporal scales might further enhance our understanding of how land managers can best reduce thelonger term risk of catastrophic wildfire damages. For. Sci. 48(4):685-693.Key Words: Vegetation management, wildfire production, wildland-urban interface, El Niiio-SouthernOscillation.
The Impact of Gut Microbiota on Gender-Specific Differences in Immunity

Males and females are known to have gender-specific differences in their immune system and gut microbiota composition. Whether these differences in gut microbiota composition are a cause or consequence of differences in the immune system is not known. To investigate this issue, gut microbiota from conventional males or females was transferred to germ-free (GF) animals of the same or opposing gender. We demonstrate that microbiota-independent gender differences in immunity are already present in GF mice. In particular, type I interferon signaling was enhanced in the intestine of GF females. Presumably, due to these immune differences bacterial groups, such as Alistipes, Rikenella, and Porphyromonadaceae, known to expand in the absence of innate immune defense mechanism were overrepresented in the male microbiota. The presence of these bacterial groups was associated with induction of weight loss, inflammation, and DNA damage upon transfer of the male microbiota to female GF recipients. In summary, our data suggest that microbiota-independent gender differences in the immune system select a gender-specific gut microbiota composition, which in turn further contributes to gender differences in the immune system.
Evaluation of Late Results in Breast Reconstruction by Latissimus Dorsi Flap and Prosthesis Implantation

Background: Breast reconstruction by latissimus dorsi myocutaneous flap in combination with a prosthesis is a widely used, well-established procedure. Short- and medium-term evaluation after this procedure is well described in the literature, but there have been no evaluations of the late course (over 10 years) published until now. Methods: In a retrospective study, 68 patients operated on by means of this technique at the authors’ institution from 1981 to 1993 resulting in a minimal follow-up of 10 years were included. Patients were invited to an interrogation, clinical examination, and photographic documentation (n = 51). Incidence of late flap or prosthesis-related complications, number of and indications for corrective procedures, and the correlation of the patients’ subjective judgment and objective results in the late course have been the main interest of the authors’ survey. Results: The authors found that 50 percent of the patients needed a late reoperation for change or removal of the prosthesis. Seven (10 percent) of 68 patients needed a definitive removal of the implant in the late course. Assessment of the photographic documentation of the late result by four nonprofessionals showed that the objective aesthetic results of a considerable number of the authors’ reconstructions were not sufficient. Conclusion: The procedure combines two basic techniques of reconstructive surgery, the soft-tissue restoration by a pedicled flap as the autologous reconstructive component and the volume reconstruction by prosthesis. Therefore, these patients are subject to a cumulation of the basic morbidity of the two techniques. The authors conclude that the indication for this procedure should be restricted to patients not qualifying for “pure” reconstructive techniques.
Symptom severity and lifetime and prospective health service use among military veterans evaluated for PTSD

We used structural equation modeling with 174 treatment‐seeking military trauma survivors evaluated for posttraumatic stress disorder (PTSD) at a VA Medical Center PTSD clinic to examine relationships among lifetime mental health service use, PTSD symptom severity and medical problems (from self‐report), as well as prospective (1‐year) mental health and medical care use visit counts extracted from medical records. We discovered an adequate statistical fit to a hypothesized model of previous and prospective health service use, and current PTSD severity and health‐related problems. Previous inpatient mental health treatment was significantly related to PTSD severity and prospective outpatient mental health use. However, PTSD severity was unrelated to prospective use of mental health or medical services. Health problems were related to prospective medical service use. Clinical and administrative implications in predicting health care use among trauma survivors are discussed. Depression and Anxiety 24:178–184, 2007. © 2006 Wiley‐Liss, Inc.
Drug Use and Receipt of Highly Active Antiretroviral Therapy among HIV-Infected Persons in Two U.S. Clinic Cohorts

Objective Drug use and receipt of highly active antiretroviral therapy (HAART) were assessed in HIV-infected persons from the Comprehensive Care Center (CCC; Nashville, TN) and Johns Hopkins University HIV Clinic (JHU; Baltimore, MD) between 1999 and 2005. Methods Participants with and without injection drug use (IDU) history in the CCC and JHU cohorts were evaluated. Additional analysis of persons with history of IDU, non-injection drug use (NIDU), and no drug use from CCC were performed. Activity of IDU and NIDU also was assessed for the CCC cohort. HAART use and time on HAART were analyzed according to drug use category and site of care. Results 1745 persons were included from CCC: 268 (15%) with IDU history and 796 (46%) with NIDU history. 1977 persons were included from JHU: 731 (35%) with IDU history. Overall, the cohorts differed in IDU risk factor rates, age, race, sex, and time in follow-up. In multivariate analyses, IDU was associated with decreased HAART receipt overall (OR = 0.61, 95% CI: [0.45–0.84] and OR = 0.58, 95% CI: [0.46–0.73], respectively for CCC and JHU) and less time on HAART at JHU (0.70, [0.55–0.88]), but not statistically associated with time on HAART at CCC (0.78, [0.56–1.09]). NIDU was independently associated with decreased HAART receipt (0.62, [0.47–0.81]) and less time on HAART (0.66, [0.52–0.85]) at CCC. These associations were not altered significantly whether patients at CCC were categorized according to historical drug use or drug use during the study period. Conclusions Persons with IDU history from both clinic populations were less likely to receive HAART and tended to have less cumulative time on HAART. Effects of NIDU were similar to IDU at CCC. NIDU without IDU is an important contributor to HAART utilization.
Antidepressant-like effect of Hoodia gordonii in a forced swimming test in mice: evidence for involvement of the monoaminergic system

Hoodia gordonii is a plant species used traditionally in southern Africa to suppress appetite. Recently, it has been associated with a significant increase in blood pressure and pulse rate in women, suggesting sympathomimetic activity. The present study investigated the possible antidepressant-like effects of acute and repeated (15 days) administration of H. gordonii extract (25 and 50 mg/kg, po) to mice exposed to a forced swimming test (FST). Neurochemical analysis of brain monoamines was also carried out to determine the involvement of the monoaminergic system on these effects. Acute administration of H. gordonii decreased the immobility of mice in the FST without accompanying changes in general activity in the open-field test during acute treatment, suggesting an antidepressant-like effect. The anti-immobility effect of H. gordonii was prevented by pretreatment of mice with PCPA [an inhibitor of serotonin (5-HT) synthesis], NAN-190 (a 5-HT1A antagonist), ritanserin (a 5-HT2A/2C antagonist), ondansetron (a 5-HT3A antagonist), prazosin (an α1-adrenoceptor antagonist), SCH23390 (a D1 receptor antagonist), yohimbine (an α2-adrenoceptor antagonist), and sulpiride (a D2 receptor antagonist). A significant increase in 5-HT levels in the striatum was detected after acute administration, while 5-HT, norepinephrine and dopamine were significantly elevated after chronic treatment. Results indicated that H. gordonii possesses antidepressant-like activity in the FST by altering the dopaminergic, serotonergic, and noradrenergic systems.
istribution , metabolism and excretion of a synthetic ndrogen 7-methyl-19-nortestosterone , a potential ale-contraceptive ramod

A synthetic androgen 7 -Methyl-19-nortestosterone (MENT) has a potential for therapeutic use in ‘androgen replacement therapy’ for hypogonadal men or as a hormonal malecontraceptive in normal men. Its tissue distribution, excretion and metabolic enzyme(s) have not been reported. Therefore, the present study tested the distribution and excretion of MENT in Sprague-Dawley rats castrated 24 h prior to the injection of tritium-labeled MENT (3H-MENT). Rats were euthanized at different time intervals after dosing, and the amount of radioactivity in various tissues/organs was measured following combustion in a Packard oxidizer. The radioactivity (% injected dose) was highest in the duodenal contents in the first 30 min of injection. Specific uptake of the steroid was observed in target tissues such as ventral prostate and seminal vesicles at 6 h, while in other tissues radioactivity equilibrated with blood. Liver and duodenum maintained high radioactivity throughout, as these organs were actively involved in the metabolism and excretion of most drugs. The excretion of 3H-MENT was investigated after subcutaneous injection of 3H-MENT into male rats housed in metabolic cages. Urine and feces were collected at different time intervals (up to 72 h) following injection. Results showed that the radioactivity was excreted via feces and urine in equal amounts by 30 h. Aiming to identify enzyme(s) involved in the MENT metabolism, we performed in vitro metabolism of 3H-MENT using rat and human liver microsomes, cytosol and recombinant cytochrome P450 (CYP) isozymes. The metabolites were separated by thin-layer chromatography (TLC). Three putative metabolites (in accordance with the report of Agarwal and Monder [Agarwal AK, Monder C. In vitro metabolism of 7 -methyl-19-nortestosterone by rat liver, prostate, and epididymis. Endocrinology 1988;123:2187–93]), [i] 3-hydroxylated MENT by both rat and human liver cytosol; [ii] 16 -hydroxylated MENT (a polar metabolite) by both rat and human hepatic microsomes; and [iii] 7 -methyl-19-norandrostenedione (a nonpolar metabolite) by human hepatic microsomes, were obtained. By employing chemical inhibitors and specific anti-CYP antibodies, 3H-MENT was found to be metabolized specifically by rat CYP 2C11 and 3-hydroxysteroid dehydrogenase (3-HSD) enzymes whereas in humans it was accompli
Transcriptome landscape of Lactococcus lactis reveals many novel RNAs including a small regulatory RNA involved in carbon uptake and metabolism

ABSTRACT RNA sequencing has revolutionized genome-wide transcriptome analyses, and the identification of non-coding regulatory RNAs in bacteria has thus increased concurrently. Here we reveal the transcriptome map of the lactic acid bacterial paradigm Lactococcus lactis MG1363 by employing differential RNA sequencing (dRNA-seq) and a combination of manual and automated transcriptome mining. This resulted in a high-resolution genome annotation of L. lactis and the identification of 60 cis-encoded antisense RNAs (asRNAs), 186 trans-encoded putative regulatory RNAs (sRNAs) and 134 novel small ORFs. Based on the putative targets of asRNAs, a novel classification is proposed. Several transcription factor DNA binding motifs were identified in the promoter sequences of (a)sRNAs, providing insight in the interplay between lactococcal regulatory RNAs and transcription factors. The presence and lengths of 14 putative sRNAs were experimentally confirmed by differential Northern hybridization, including the abundant RNA 6S that is differentially expressed depending on the available carbon source. For another sRNA, LLMGnc_147, functional analysis revealed that it is involved in carbon uptake and metabolism. L. lactis contains 13% leaderless mRNAs (lmRNAs) that, from an analysis of overrepresentation in GO classes, seem predominantly involved in nucleotide metabolism and DNA/RNA binding. Moreover, an A-rich sequence motif immediately following the start codon was uncovered, which could provide novel insight in the translation of lmRNAs. Altogether, this first experimental genome-wide assessment of the transcriptome landscape of L. lactis and subsequent sRNA studies provide an extensive basis for the investigation of regulatory RNAs in L. lactis and related lactococcal species.
Effect of 6-thioguanine on the stability of duplex DNA

The incorporation of 6-thioguanine (S6G) into DNA is a prerequisite for its cytotoxic action, but duplex structure is not significantly perturbed by the presence of the lesion [J. Bohon and C. R. de los Santos (2003) Nucleic Acids Res., 31, 1331–1338]. It is therefore possible that the mechanism of cytotoxicity relies on a loss of stability rather than a pathway involving direct structural recognition. The research described here focuses on the changes in thermodynamic properties of duplex DNA owing to the introduction of S6G as well as the kinetic properties of base pairs involving S6G. Replacement of a guanine in a G•C pair by S6G results in ∼1 kcal/mol less favorable Gibbs free energy of duplex formation at 37°C. S6G•T and G•T mismatch-containing duplexes have almost identical Gibbs free energy at 37°C, with values ∼3 kcal/mol less favorable than that of the control. Base pair stability is affected by S6G. The lifetime of the normal G•C base pair is ∼125 ms, whereas that of the G•T mismatch is below the detection limit. The lifetimes of S6G•C and S6G•T pairs are ∼7 and 2 ms, respectively, demonstrating that, although S6G significantly decreases the stability of the pairing with cytosine, it slightly increases that of a mismatch.