Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for Clonal Evolution among Highly Polymorphic Genes in Methicillin-Resistant Staphylococcus aureus

ABSTRACT The evolution of Staphylococcus aureus has been described as predominantly clonal, based on evidence from seven housekeeping genes. We aimed to test if this was also true for more polymorphic genes. In a collection of 60 isolates including major European epidemic methicillin-resistant S. aureus (MRSA) and sporadic MRSA strains, we compared the partial gene sequences of seven housekeeping genes (arcC, aroE, glpF, gmk, pta, tpi, and yqiL), six core adhesion genes (present in all strains) (clfA, clfB, fnbA, map, sdrC, and spa), and four accessory adhesion genes (not present in all strains) (ebpS, fnbB, sdrD, and sdrE). Nucleotide diversity of adhesion genes was 2- to 10-fold higher than genes used for multilocus sequence typing. All genes showed evidence for purifying selection with a weakly reduced level among accessory adhesion genes. Among these highly variable genes, there was no evidence for a difference in molecular evolution between epidemic and sporadic strains. Gene trees constructed from concatenated sequences of housekeeping, core adhesion, and accessory adhesion genes were highly congruent, indicating clonality, despite some evidence for homologous exchange. Further evidence for clonality was found with an overall positive correlation of allelic and nucleotidic divergence for both seven housekeeping genes and six core adhesion genes. However, for small allelic differences that fit the demarcations of clonal complexes (CCs) there was no such correlation, suggesting that recombination occurred. Therefore, despite an overall clonal population structure, recombination between related isolates within CCs might have contributed to S. aureus evolution.
Standardising HbA1c-based diabetes diagnosis: opportunities and challenges

ABSTRACT Globally, the incidence of diabetes mellitus is rising at an alarming rate and has become a health crisis that threatens the economies of all nations. Therefore, diagnosing diabetes has become an important issue in the management of diabetes. Glycated hemoglobin (HbA1c) is now recommended as a means to diagnose diabetes, but its use still has limitations. In this article, the biology, measurement, standardization, and opportunities and challenges of the use of HbA1c to diagnose diabetes are reviewed. More specifically, its use in China and the Asian region is discussed in detail.
Morphometric and Morphological Study of the Dental Roots of the Upper First Premolars

El conocimiento de la anatomia dental, principalmente la porcion radicular, es de gran importancia para algunas especialidades, como la endodoncia y periodoncia. El objetivo de este estudio fue analizar la morfometria radicular de los primeros premolares superiores, el control de la longitud media de las raices, y tambien, sus inclinaciones y la ubicacion del area de furca en bi y tri-radiculares. En este estudio se utilizaron 659 primeros premolares superiores humanos pertenecientes al Departamento de Morfologia de la Facultad de Odontologia de Araraquara, UNESP, Brasil. Los dientes fueron previamente seleccionados, de modo que solo los que tienen raices perfectas fueron utilizados. Los dientes se dividieron en tres grupos: mono radiculares, bi radiculares y tri radiculares. Despues de haber sido separado, algunas medidas especificas con un caliper digital, Brown & Sharp se realizaron en cada grupo. En nuestro estudio podemos concluir que: 1 -Los primeros premolares superiores mono radiculares presentan una longitud radicular promedio mas alto que los bi radiculares y estos, por sobre los tri radiculares, 2 - los primeros premolares superiores bi radiculares presentaron una longitud radicular promedio mas alto para la raiz vestibular en relacion a la raiz palatina, ademas las raices presentan un mayor porcentaje de inclinacion hacia distal. La bifurcacion puede ser localizada en el tercio medio, asi como en el tercio apical, 3 - los primeros premolares superiores tri radiculares presentan una longitud radicular promedio mas alta en la raiz palatina en relacion con las raices vestibulares. La inclinacion radicular es variable, y la raiz distovestibular presenta mayor porcentaje de inclinacion mesial, mientras que las demas raices hacia distal. La trifurcacion se encuentra, en todos los casos, en el tercio medio.
Spiralin, a mycoplasmal membrane lipoprotein, induces T-cell-independent B-cell blastogenesis and secretion of proinflammatory cytokines

Mycoplasmas are bacteria which can cause respiratory, arthritic, and urogenital diseases. During the early phase of infection, mycoplasmas usually induce an inflammatory response and a humoral response preferentially directed against their membrane-bound, surface-exposed lipoproteins. In this report, we describe the effects on immune cells of spiralin, a well-characterized mycoplasmal lipoprotein. Purified spiralin stimulated the in vitro proliferation of human peripheral blood mononuclear cells and murine splenocytes. The stimulation pathway was probably different from that followed by Escherichia coli lipopolysaccharide because the effect of spiralin was not abolished by polymyxin B. Comparison of the effects of whole, native spiralin with those induced by proteinase K-digested spiralin or by the C-terminal half of spiralin (peptide p[13.5]T) revealed that the first half of the protein, which contains the lipoylated N terminus, is responsible for the mitogenic activity. In contrast to whole spiralin, proteinase K-digested spiralin did not trigger murine B-cell differentiation and immunoglobulin G and M secretion. Stimulation of human or murine immune cells led to early secretion of proinflammatory cytokines (human tumor necrosis factor alpha and murine interleukin 1 or 6). Spiralin induced the T-cell-independent blastogenesis of murine B cells but did not stimulate T cells. Altogether, our data demonstrate that spiralin possesses potent immunostimulating activity, similar to that reported for lipoproteins of pathogenic gracilicutes (gram-negative eubacteria; e.g., Borrelia burgdorferi OspA and E. coli Braun lipoprotein), and are consistent with the fact that lipoproteins are major antigens during mycoplasma infections.
Investment in the public good through conditional phenotypes   of large effect

We investigate the evolution of an individual's willingness to invest in a public good (what we call, helping) in a patch‐structured population with limited natal dispersal. We assume that an individual's decision to invest is informed by its dispersal status: an individual makes one decision given it is native to the patch on which it breeds, and is free to make a different decision given that it is not native to the patch on which it breeds. Unlike previous work, we assume that investment in the public good, and the public good, itself, both have a large effect on individual fecundity. Kin selection analysis reveals that only extreme investment decisions (i.e. ‘always invest’ or ‘never invest’) can be evolutionarily stable. Numerical results suggest that the evolutionary instability of the ‘never invest’ phenotype (what we call, complete nonhelping) implies the evolutionary stability of ‘always invest’ (what we call, complete helping). In addition, numerical results show that bistability of extreme phenotypes is possible, indicating that the adaptive significance of altruism, in this context, is greater than has been previously recognized. Numerical results are supported by computer simulation, and results, themselves, are briefly discussed in a concluding section.
The phoBR operon in Escherichia coli K-12

The phoB and phoR genes encode a transcription activator and a sensory protein of the phosphate regulon, respectively. It is shown here that they were transcribed as an operon in which the phoB gene was promoter proximal. Although an operon structure was suggested previously (K. Makino, H. Shinagawa, M. Amemura, and A. Nakata, J. Mol. Biol. 190:37-44 and 192:549-556, 1986), previous results showed only that phoR gene expression during phosphate limitation is dependent on the upstream phoB promoter. The phoR gene could still have had its own promoter for expression in the presence of phosphate. Two polar transposon-induced mutations are described which simultaneously abolished phoB and phoR gene function in cis; one mutation mapped in the phoB gene, and the other mapped upstream of the phoB gene. These results demonstrate an operon structure, in which phoR gene function required expression from the phoB promoter. Unexpectedly, an antisense pho omega Mu d1(lacZ) insertion within the promoter-proximal end of the phoB gene expressed the lacZ reporter gene, thus allowing for the possibility that the phoBR operon is regulated by an antisense RNA.
The association between physical activity and overweight and obesity in a population of children at high and low altitudes in Southwestern Saudi Arabia

Objective: To assess the relationship between overweight and obesity and physical activity in Saudi children born and permanently domiciled at high and low altitudes in Southwestern Saudi Arabia. Subjects and Methods: A cross-sectional study of 145 healthy Saudi children aged 10–15 years who were born and lived permanently at high altitude (3000–3100 m) and 154 healthy Saudi children of comparable age who were born and lived permanently at a relatively low altitude (500 m) was conducted. For each subject selected, body weight and body height were measured using an Avery beam weighing scale and a stadiometer, respectively. Body mass index (BMI) was calculated using the equation BMI = (weight [kg]/height [m2]). Physical activity scores were determined using International Physical Activity Questionnaire-Short Form-A. Resting radial pulse rate (beat/minutes) was determined clinically. Results: Physical activity was significantly and inversely associated with overweight and obesity in boys at both high (χ2 = 15.8, P< 0.001) and low (χ2 = 14.7, P< 0.001) altitudes, but there was no clear trend for girls at either altitude. The lack of association between physical activity and overweight and obesity in girls was attributed to the low and homogeneous level of physical activity. Conclusion: Physical activity should be encouraged as a strategy for weight reduction in the overweight and the obese and the prevention of overweight and obesity in Saudi children at high and low altitudes.
The Effect of Different Repeated-High-Intensity-Effort Bouts on Subsequent Running, Skill Performance, and Neuromuscular Function.

PURPOSE To assess the impact of different repeated-high-intensity-effort (RHIE) bouts on player activity profiles, skill involvements, and neuromuscular fatigue during small-sided games. PARTICIPANTS 22 semiprofessional rugby league players (age 24.0 ± 1.8 y, body mass 95.6 ± 7.4 kg). METHODS During 4 testing sessions, they performed RHIE bouts that each differed in the combination of contact and running efforts, followed by a 5-min off-side small-sided game before performing a second bout of RHIE activity and another 5-min small-sided game. Global positioning system microtechnology and video recordings provided information on activity profiles and skill involvements. A countermovement jump and a plyometric push-up assessed changes in lower- and upper-body neuromuscular function after each session. RESULTS After running-dominant RHIE bouts, players maintained running intensities during both games. In the contact-dominant RHIE bouts, reductions in moderate-speed activity were observed from game 1 to game 2 (ES = -0.71 to -1.06). There was also moderately lower disposal efficiency across both games after contact-dominant RHIE activity compared with running-dominant activity (ES = 0.62-1.02). Greater reductions in lower-body fatigue occurred as RHIE bouts became more running dominant (ES = -0.01 to -1.36), whereas upper-body fatigue increased as RHIE bouts became more contact dominant (ES = -0.07 to -1.55). CONCLUSIONS Physical contact causes reductions in running intensity and the quality of skill involvements during game-based activities. In addition, the neuromuscular fatigue experienced by players is specific to the activities performed.
Incidence and Risk Factors in Secondary Glaucomas After Blunt and Penetrating Ocular Trauma

PurposeThis retrospective study was designed to evaluate the risk factors for the development of posttraumatic glaucoma after ocular trauma. MethodsData were obtained from the records of 102 patients (105 eyes) that experienced blunt or penetrating ocular trauma and presented to our center between January 1987 and April 2006. Logistic regression was used to evaluate the association between the baseline structural and functional ocular characteristics and posttraumatic glaucoma. Odds ratios with 95% confidence intervals (CI) were obtained. ResultsNeed for glaucoma surgery was independently associated with hyphema (odds ratio: 0.279; 95% CI: 0.085-0.916), corneal injury (odds ratio: 12.143; 95% CI: 2.029-72.66), presence of optic atrophy (odds ratio: 8.000; 95% CI: 1.615-39.636), visual acuity <20/200 (odds ratio: 50.00; 95% CI: 10.183-245.501), and a history of penetrating ocular trauma (odds ratio: 10.00; 95% CI: 2.819-38.635). Corneal (odds ratio: 1.113; 95% CI: 1.022-1.213) and vitreal injuries (odds ratio: 10.410; 95% CI: 1.232-87.97) were found to be statistically significant factors for the development of early glaucoma. ConclusionsThis study found several independent predictive factors that were significantly associated with the need for glaucoma surgery in cases of posttraumatic glaucoma, including hyphema, corneal injury, presence of optic atrophy, visual acuity <20/200, and a history of penetrating ocular trauma. Additionally, some factors were found to affect the development of early glaucoma after ocular trauma, such as corneal and vitreal injury.
ConoSurf: Open‐source 3D scanning system based on a conoscopic holography device for acquiring surgical surfaces

A difficulty in computer‐assisted interventions is acquiring the patient's anatomy intraoperatively. Standard modalities have several limitations: low image quality (ultrasound), radiation exposure (computed tomography) or high costs (magnetic resonance imaging). An alternative approach uses a tracked pointer; however, the pointer causes tissue deformation and requires sterilizing. Recent proposals, utilizing a tracked conoscopic holography device, have shown promising results without the previously mentioned drawbacks.
Rhou maintains the epithelial architecture and facilitates differentiation of the foregut endoderm

Rhou encodes a Cdc42-related atypical Rho GTPase that influences actin organization in cultured cells. In mouse embryos at early-somite to early-organogenesis stages, Rhou is expressed in the columnar endoderm epithelium lining the lateral and ventral wall of the anterior intestinal portal. During foregut development, Rhou is downregulated in regions where the epithelium acquires a multilayered morphology heralding the budding of organ primordia. In embryos generated from Rhou knockdown embryonic stem (ES) cells, the embryonic foregut displays an abnormally flattened shape. The epithelial architecture of the endoderm is disrupted, the cells are depleted of microvilli and the phalloidin-stained F-actin content of their sub-apical cortical domain is reduced. Rhou-deficient cells in ES cell-derived embryos and embryoid bodies are less efficient in endoderm differentiation. Impaired endoderm differentiation of Rhou-deficient ES cells is accompanied by reduced expression of c-Jun/AP-1 target genes, consistent with a role for Rhou in regulating JNK activity. Downregulation of Rhou in individual endoderm cells results in a reduced ability of these cells to occupy the apical territory of the epithelium. Our findings highlight epithelial morphogenesis as a required intermediate step in the differentiation of endoderm progenitors. In vivo, Rhou activity maintains the epithelial architecture of the endoderm progenitors, and its downregulation accompanies the transition of the columnar epithelium in the embryonic foregut to a multilayered cell sheet during organ formation.
Diurnal variation in cycling performance: Influence of warm-up

We examined the effects of time of day on a cycling time trial with and without a prolonged warm-up, among cyclists who tended towards being high in “morningness”. Eight male cyclists (mean ± s: age = 24.9 ± 3.5 years, peak power output = 319 ± 34 W, chronotype = 39 ± 6 units) completed a 16.1-km time trial without a substantial warm-up at both 07:30 and 17:30 h. The time trial was also completed at both times of day after a 25-min warm-up at 60% of peak power. Power output, heart rate, intra-aural temperature and category ratings of perceived exertion (CR-10) were measured throughout the time trial. Post-test blood lactate concentration was also recorded. Warm-up generally improved time trial performance at both times of day (95% CI for improvement = 0 to 30 s), but mean cycling time was still significantly slower at 07:30 h than at 17:30 h after the warm-up (95% CI for difference = 33 to 66 s). Intra-aural temperature increased as the time trial progressed (P < 0.0005) and was significantly higher throughout the time trials at 17:30 h (P = 0.001), irrespective of whether the cyclists performed a warm-up or not. Blood lactate concentration after the time trial was lowest at 07:30 h without a warm-up (P = 0.02). No effects of time of day or warm-up were found for CR-10 or heart rate responses during the time trial. These results suggest that 16.1-km cycling performance is worse in the morning than in the afternoon, even with athletes who tend towards ‘morningness’, and who perform a vigorous 25-min warm-up. Diurnal variation in cycling performance is, therefore, relatively robust to some external and behavioural factors.
Molecular cloning and characterization of the pseudorabies virus US 1 gene

Using polymerase chain reaction, a 1050-bp sequence of the US1 gene was amplified from the pseudorabies virus (PRV) Becker strain genome; identification of the US1 gene was confirmed by further cloning and sequencing. Bioinformatics analysis indicated that the PRV US1 gene encodes a putative polypeptide with 349 amino acids. The encoded protein, designated PICP22, had a conserved Herpes_IE68 domain, which was found to be closely related with the herpes virus immediate early regulatory protein family and is highly conserved among the counterparts encoded by Herpes_IE68 genes. Multiple nucleic acid sequence and amino acid sequence alignments suggested that the product of PRV US1 has a relatively higher homology with ICP22like proteins of genus Varicellovirus than with those of other genera of Alphaherpesvirinae. In addition, phylogenetic analysis showed that PRV US1 has a close evolutionary relationship with members of the genus Varicellovirus, especially Equid herpes virus 1 (EHV-1), EHV-4 and EHV-9. Antigen prediction indicated that several potential B-cell epitopes are located in PICP22. Also, subcellular localization analysis demonstrated that PICP22 is predominantly located in the cytoplasm,
Methadone and metabolite urine concentrations in patients maintained on methadone.

As regulatory control over methadone maintenance relaxes, the need for methods of monitoring compliance will increase. In community clinics, monitoring would most likely involve immunoassays of outpatients' trough urine specimens. There are no published norms for such data. Therefore, we determined concentrations of methadone in 1093 urine specimens collected thrice weekly in 27 outpatients during up to 17 weeks of observed methadone ingestion (35 to 80 mg/day) using a semiquantitative homogeneous enzyme immunoassay (CEDIA). We used a separate CEDIA assay to measure methadone's main metabolite, 2-ethylidene-3,3-diphenylpyrrolidine (EDDP), which may help detect compliance in fast metabolizers or patients who adulterate samples to simulate compliance. Methadone concentrations were more variable than those of EDDP. Concentrations of methadone were < 100 ng/mL in one specimen, between 100 and 300 ng/mL in 27, and >or= 300 ng/mL in all others. EDPP concentrations were >or= 100 ng/mL in all specimens, suggesting that EDDP should be detectable in urine from compliant patients. Methadone and EDDP concentrations significantly increased with methadone dose and (in one participant with poor clinic attendance) significantly decreased following missed methadone doses. Nevertheless, variability was too great to permit estimation of methadone dose (or detect a single missed administration) from any single specimen.
Man-Made Mineral Fiber Hazardous Properties Assessment Using Transgenic Rodents: Example of Glass Fiber Testing

Transgenic BigBlue rats were exposed to CM 44 glass fibers (6.3 mg/m 3) by nose only, 6 h/day for 5 days. Two endpoints were examined 1, 3, 14, 28, and 90 days following exposure: fiber biopersistence and mutations in lung DNA. The half-time of the fibers >20 µm was 12.8 days, and mutant frequencies of control and exposed rats were similar across all time points. The mutation spectra of both series were similar after 28 days of fixation time. These results showed that a glass fiber with a high clearance in the lung seems to not present any significant effect on mutagenesis on lung DNA and are in marked contrast to results for asbestos, which caused a twofold mutant frequency increase as described in a previous study (Rihn et al., 2000b).
Histone Deacetylase Inhibitors Reduce Steroidogenesis through SCF-Mediated Ubiquitination and Degradation of Steroidogenic Factor 1 (NR5A1)

ABSTRACT Histone deacetylase (HDAC) inhibitors such as trichostatin A and valproic acid modulate transcription of many genes by inhibiting the activities of HDACs, resulting in the remodeling of chromatin. Yet this effect is not universal for all genes. Here we show that HDAC inhibitors suppressed the expression of steroidogenic gene CYP11A1 and decreased steroid secretion by increasing the ubiquitination and degradation of SF-1, a factor important for the transcription of all steroidogenic genes. This was accompanied by increased expression of Ube2D1 and SKP1A, an E2 ubiquitin conjugase and a subunit of the E3 ubiquitin ligase in the Skp1/Cul1/F-box protein (SCF) family, respectively. Reducing SKP1A expression with small interfering RNA resulted in recovery of SF-1 levels, demonstrating that the activity of SCF E3 ubiquitin ligase is required for the SF-1 degradation induced by HDAC inhibitors. Overexpression of exogenous SF-1 restored steroidogenic activities even in the presence of HDAC inhibitors. Thus, increased SF-1 degradation is the cause of the reduction in steroidogenesis caused by HDAC inhibitors. The increased SKP1A expression and SCF-mediated protein degradation could be the mechanism underlying the mode of action of HDAC inhibitors.
Targeting the Endocannabinoid System in Psychiatric Illness

Abstract Prevalence of psychiatric disorders continues to rise globally, yet remission rates and patient outcome remain less than ideal. As a result, novel treatment approaches for these disorders are necessary to decrease societal economic burden, as well as increase individual functioning. The recent discovery of the endocannabinoid system has provided an outlet for further research into its role in psychiatric disorders, because efficacy of targeted treatments have been demonstrated in medical illnesses, including cancers, neuropathic pain, and multiple sclerosis. The present review will investigate the role of the endocannabinoid system in psychiatric disorders, specifically schizophrenia, depressive, anxiety, and posttraumatic stress disorders, as well as attention-deficit hyperactivity disorder. Controversy remains in prescribing medicinal cannabinoid treatments due to the fear of adverse effects. However, one must consider all potential limitations when determining the safety and tolerability of cannabinoid products, specifically cannabinoid content (ie, &Dgr;9-tetrahydrocannabinol vs cannabidiol) as well as study design. The potential efficacy of cannabinoid treatments in the psychiatric population is an emerging topic of interest that provides potential value going forward in medicine.