Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytoplasmic feminizing elements in a two‐population model: infection dynamics, gene flow modification, and the spread of autosomal suppressors

We investigate the dynamics of a cytoplasmic parasitic element with feminizing effect in a two‐population model. We assume that the host species has a ZZ/ZW sex determination system. Our analysis reveals that the feminizer and the W chromosome can stably coexist by dominating different populations if the transmission rate differs significantly between the populations and migration is sufficiently weak. In the equilibrium of coexistence, genetic influx at any host autosomal locus is strongly enhanced in the population where infection is prevalent but not modified in the other population. We further explore conditions for the spread of autosomal suppressor genes that reduce transmission of feminizing elements to the cost of host viability, and compute their equilibrium frequencies. Our results confirm the hypothesis that selfish genetic elements convert infected host populations into genetic sinks, thereby restricting the spread of transmission suppressors.
Expression Levels of Histone Deacetylases Determine the Cell Fate of Hematopoietic Progenitors*

Histone deacetylases (HDACs) are globally implicated in the growth and differentiation of mammalian cells; however, relatively little is known about their specific roles in hematopoiesis. In this study, we investigated the expression of HDACs in human hematopoietic cells and their functions during hematopoiesis. The expression of HDACs was very low in hematopoietic progenitor cells, which was accompanied by histone hyperacetylation. HDACs were detectable in more differentiated progenitors and erythroid precursors but down-regulated in mature myeloid cells especially granulocytes. In contrast, acute myeloid leukemias showed HDAC overexpression and histone hypoacetylation. Transcription of the HDAC1 gene was repressed by CCAAT/enhancer binding proteins during myeloid differentiation, and activated by GATA-1 during erythro-megakaryocytic differentiation. Small interfering RNA-mediated knockdown of HDAC1 enhanced myeloid differentiation in immature hematopoietic cell lines and perturbed erythroid differentiation in progenitor cells. Myeloid but not erythro-megakaryocytic differentiation was blocked in mice transplanted with HDAC1-overexpressing hematopoietic progenitor cells. These findings suggest that HDAC is not merely an auxiliary factor of genetic elements but plays a direct role in the cell fate decision of hematopoietic progenitors.
EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer.

PURPOSE To prospectively identify markers of response to therapy and outcome in an organ-sparing trial for advanced oropharyngeal cancer. PATIENTS AND METHODS Pretreatment biopsies were examined for expression of epidermal growth factor receptor (EGFR), p16, Bcl-xL, and p53 as well as for p53 mutation. These markers were assessed for association with high-risk human papillomavirus (HPV), response to therapy, and survival. Patient variables included smoking history, sex, age, primary site, tumor stage, and nodal status. RESULTS EGFR expression was inversely associated with response to induction chemotherapy (IC) (P = .01), chemotherapy/radiotherapy (CRT; P = .055), overall survival (OS; P = .001), and disease-specific survival (DSS; P = .002) and was directly associated with current smoking (P = .04), female sex (P = .053), and lower HPV titer (P = .03). HPV titer was significantly associated with p16 expression (P < .0001); p16 was significantly associated with response to IC (P = .008), CRT (P = .009), OS (P = .001), and DSS (P = .003). As combined markers, lower HPV titer and high EGFR expression were associated with worse OS (rho(EGFR) = 0.008; rho(HPV) = 0.03) and DSS (rho(EGFR) = 0.01; rho(HPV) = 0.016). In 36 of 42 biopsies, p53 was wild-type, and only one HPV-positive tumor had mutant p53. The combination of low p53 and high Bcl-xL expression was associated with poor OS (P = .005) and DSS (P = .002). CONCLUSION Low EGFR and high p16 (or higher HPV titer) expression are markers of good response to organ-sparing therapy and outcome, whereas high EGFR expression, combined low p53/high Bcl-xL expression, female sex, and smoking are associated with a poor outcome. Smoking cessation and strategies to target EGFR and Bcl-xL are important adjuncts to the treatment of oropharyngeal cancer.
Ethnic differences in SCORE cardiovascular risk in Oslo, Norway

Aim To compare the estimated 10-year risk of cardiovascular death between ethnic Norwegians and five immigrant groups in Norway, according to the European Systematic Coronary Risk Evaluation (SCORE) system. Methods Data were obtained from the Oslo Health Study and the Oslo Immigrant Health Study (2000-2002). Fourteen thousand eight hundred and fifty-six individuals born between 1940 and 1971 in Norway, Turkey, Iran, Pakistan, Sri Lanka and Vietnam were included in the study. The European SCORE high-risk models, one including total cholesterol and the other including total cholesterol/HDL cholesterol ratio, were used to estimate 10-year cardiovascular mortality risk. A model assuming no smoking was also applied. Age was projected to 60 years and estimates were adjusted for age at screening. Results Norwegians had higher total cholesterol and systolic blood pressure, but lower triglycerides and higher HDL cholesterol compared with immigrants. The mean SCORE (total cholesterol model) varied between 6.6% (Turkey) and 5.4% (Sri Lanka) in men, and 2.1% (Norway) and 1.5% (Pakistan, Sri Lanka and Vietnam) in women. Application of the ratio model gave higher estimated risk in all immigrant groups except for Vietnamese, with 10-year risk varying between 7.7% (Turkey/Pakistan) and 5.7% (Vietnam) in men, and 2.0% (Norway) and 1.5% (Vietnam) in women. When the ratio model was applied assuming no smoking in all ethnic groups, the mean SCORE risk was reduced by 30% in Turkish men and 25% in Norwegian women, with less significant reductions observed in the other groups. Conclusion Norwegians ranked high with the SCORE total cholesterol model and Norwegian men low with the SCORE ratio model. Although the predictive accuracy of the SCORE models for immigrants in Norway remains to be evaluated, our findings suggest that the ratio model could be more applicable to the entire population in Norway. Eur J Cardiovasc Prev Rehabil 16:229-234 © 2009 The European Society of Cardiology
Projections from the lateral and interposed cerebellar nuclei to the thalamus of the rat: A light and electron microscopic study using single and double anterograde labelling

The lateral and interposed cerebellar nuclei may have different functions in the control of movement. Efferent fibres from both nuclei project predominantly to areas of the thalamus, which in turn project to the motor cortex. In this study, single and double anterograde‐tracing techniques have been used to examine and compare the pathways from the lateral and interposed nuclei to the thalamus in the rat by using both light and electron microscopy to look for evidence of organisational or structural features that may underlie the proposed functional differences between these nuclei.
Evolving Picture of Invasive Pneumococcal Disease in Massachusetts Children: A Comparison of Disease in 2007–2009 With Earlier Periods

Background: As expected, the heptavalent pneumococcal conjugate vaccine (PCV7) had a significant impact on invasive pneumococcal disease (IPD) in children. In addition to the substantial decline in IPD, increased disease due to nonvaccine serotypes and a changing clinical presentation emerged. The objective of this study is to describe these trends in IPD in the late PCV7-era. Methods: We report on continued, prospective, population-based surveillance of childhood IPD in Massachusetts children during the period 2007 to 2009 and make comparisons with the earlier 2001 to 2006 PCV7-era. Demographic and clinical data were collected for all cases. Streptococcus pneumoniae isolates from normally sterile sites were serotyped and further evaluated using antimicrobial susceptibility testing, multilocus sequence typing and eBURST analysis. IPD incidence rates are calculated by age, year and serotype. Results: There were 326 cases of IPD between 2007 and 2009 in children < 18 years of age. Overall IPD incidence rate was 7.5 cases per 100,000 population and was not statistically different from the observed incidence in 2001 to 2006 (P > 0.05). As compared with the earlier period, the proportion of bacteremic pneumonia among all IPD cases was almost 3-fold greater in 2009 to 2010 (P < 0.01). PCV7 serotypes accounted for 7%, whereas the 13-valent pneumococcal conjugate vaccine serotypes accounted for 77% of all cases between 2007 and 2009. IPD due to serotypes 19A and 7F increased, and 19A and 7F were isolated in 41% and 20% of all IPD cases in the same period, respectively. Serotype 19A also comprised a majority of the penicillin- and ceftriaxone-resistant isolates. Analysis of multilocus sequence typing data showed a significant increase in ST191, ST695 and ST320 and a significant decrease in ST199 and ST180. Conclusions: The reduction in IPD after introduction of PCV7 persists in Massachusetts children; however, serotypes causing IPD have changed significantly in the last decade. Continued surveillance is necessary to determine the impact of 13-valent pneumococcal conjugate vaccine, as well as track potential changes in disease incidence and character due to non–13-valent pneumococcal conjugate vaccine serotypes.
Two Novel Vaginal Microbicides (Polystyrene Sulfonate and Cellulose Sulfate) Inhibit Gardnerella vaginalis and Anaerobes Commonly Associated with Bacterial Vaginosis

ABSTRACT This is the first report demonstrating the in vitro inhibitory activity of two novel microbicides (cellulose sulfate and polystyrene sulfonate) against bacterial vaginosis (BV)-associated bacteria. Vaginal application of these microbicides not only may reduce the risk of acquisition of human immunodeficiency virus and other sexually transmitted infection-causing organisms but may also decrease the incidence of BV.
BIOTECHNOLOGICALLY RELEVANT ENZYMES AND PROTEINS Molecular cloning and characterization of a new cold-active esterase from a deep-sea metagenomic library

A clone which conferred lipolytic activity at low temperature was identified from a fosmid library constructed from a South China Sea marine sediment sample. The gene responsible, estF, consisted of 1,080 bp that encoded 359 amino acid residues, with a typical N-terminal signal peptide of 28 amino acid residues. A phylogenetic analysis of amino acid sequence with other lipolytic enzymes revealed that EstF and seven closely related putative lipolytic enzymes comprised a unique clade in the phylogenetic tree. Moreover, these hypothetic esterases showed unique conservative sites in the amino acid sequence. The recombinant EstF was overexpressed and purified, and its biochemical properties were partially characterized. The optimal substrate for EstF to hydrolyze among a panel of p-nitrophenyl esters (C2 to C16) was pnitrophenyl butyrate (C4), with a Km of 0.46 mM. Activity quickly decreased with substrates containing an acyl chain length longer than 10 carbons. We found that EstF was active in the temperature range of 0–60°C, showed the best activity at 50°C, but was unstable at 60°C. It exhibited a high level of activity in the pH range of 7.0–10.0 showing the highest activity at pH 9.0.
An Investigation of Poultry Litter as a Nitrogen Source for Wheat

Many farmers have been reluctant to use poultry litter as a nutrient source for wheat due to fears of excessive lodging and uncertainty regarding yield response. This three-year research project investigated yield response and lodging caused by applying raw broiler litter, granulated poultry litter, pelleted poultry litter, and commercial fertilizer nitrogen (N) to wheat (Triticum aestivum) at Zadoks growth stage (G.S.) 25 and 30. Results from this research project indicate that in two out of three years both raw broiler litter and commercial fertilizer N resulted in a significant yield response to N additions, and the raw broiler litter additions resulted in yields equivalent to what was obtained using commercial fertilizer N. There were no differences in yield or lodging between poultry litter applications made at G.S. 25 or 30. Granulated poultry litter resulted in equivalent yields to what was obtained using commercial N fertilizer in one out of two years. The raw broiler litter, granulated poultry litter, and pelleted poultry litter caused no more lodging than the commercial fertilizer N.
Safety and efficacy of intravesical bacillus Calmette-Guerin instillations in steroid treated and immunocompromised patients.

PURPOSE We assessed the safety and efficacy of intravesical bacillus Calmette-Guerin instillations in steroid treated and immunocompromised patients. MATERIALS AND METHODS We retrospectively reviewed the charts of 697 patients treated with bacillus Calmette-Guerin instillations at our institution from 1991 to 2004. In 24 patients (3.5%) an underlying comorbidity directly affecting the immune system was diagnosed before bacillus Calmette-Guerin administration or steroids were administered at least 6 weeks before and at the time of bacillus Calmette-Guerin instillations. The immunosuppressive effect of steroids was assessed by the percent of lymphocytes. End points were the bacillus Calmette-Guerin response at 6 months, defined as normal cystoscopy, cytology and biopsy when available, and treatment related toxicity. RESULTS Four patients (17%) had active lymphoma or chronic lymphocytic leukemia during bacillus Calmette-Guerin administration and 21 (88%) had a concurrent condition for which oral steroids (11), inhaled steroids (14) or oral and inhaled steroids (4) were administered. Patients treated with oral steroids had a lower percent of lymphocytes than patients treated with inhaled steroids and 15 age matched patients with high risk superficial bladder cancer and no steroid treatment (12.3% vs 17.5% and 18.6%, respectively). The overall bacillus Calmette-Guerin response rate at 6 months was 58%. Ten of the 24 patients had disease recurrence and 3 had disease progression at a median followup of 63.5 months (IQR 19.5, 89). One patient treated with oral steroids had self-limited febrile disease and worsening of myalgia 48 hours after his third bacillus Calmette-Guerin cycle. No other systemic adverse event following bacillus Calmette-Guerin therapy was recorded and all patients completed scheduled treatments. CONCLUSIONS Intravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids. The bacillus Calmette-Guerin response rate at 6 months and the side effects profile associated with bacillus Calmette-Guerin therapy in these patients were comparable to those in patients with no evidence of immunosuppression. Further studies are warranted to assess the safety and efficacy of bacillus Calmette-Guerin instillations in critically immunocompromised patients.
The effects of commonly prescribed drugs in patients with Alzheimer’s disease on the rate of deterioration

Background: Prescribed drugs in patients with Alzheimer’s disease may affect the symptomatic progression of their disease, both positively and negatively. Aim: To examine the effects of drugs on the progression of disease in a representative group of patients with Alzheimer’s disease. Methods: Patients with the diagnosis of probable Alzheimer’s disease were recruited from the community. The prescribed drugs taken by 224 patients (mean age 82.3 years) were recorded at initial assessment and then correlated in logistic regression analysis with progression of the disease, defined as an increase of one point or more in the Global Deterioration Scale over the next 12-month period. Results: Patients who were taking antipsychotic drugs and sedatives had a significantly higher risk of deterioration than those who were taking none (odds ratios (ORs) 2.74 (95% confidence interval (CI) 1.17 to 6.41) and 2.77 (95% CI 1.14 to 6.73), respectively). Higher risk of deterioration was observed in those who were taking both antipsychotic and sedative drugs together (OR 3.86 (95% CI 1.28 to 11.7). Patients taking drugs licensed for dementia, drugs affecting the renin–angiotensin system and statins had a significantly lower risk of deterioration than those who were not taking any of these drugs (ORs 0.49 (95% CI 0.25 to 0.97), 0.31 (95% CI 0.11 to 0.85) and 0.12 (95% CI 0.03 to 0.52), respectively). Conclusion: Our findings have implications for both clinicians and trialists. Most importantly, clinicians should carefully weigh any potential benefits of antipsychotics and benzodiazepines, especially in combination, against the risk of increased decline. Researchers need to be aware of the potential of not only licensed drugs for dementia but also drugs affecting the renin–angiotensin system and statins in reducing progression in clinical trials.
Left ventricular diastolic dysfunction in newly diagnosed untreated hypertensive patients

Abstract Essential hypertension is characterized by a left ventricular dysfunction. However, the majority of the studies performed so far investigated patients under drug treatment and/or with concomitant diseases, such as obesity, diabetes, metabolic syndrome or coronary heart disease, which per se may affect diastolic function independently on the blood pressure elevation. The present study aimed at investigating left ventricular diastolic function in untreated, uncomplicated and newly diagnosed hypertensive patients by employing both routine echo-Doppler and pulse tissue-Doppler technique. Data were collected in 86 middle-aged essential hypertensive patients and in 18 sex-matched normotensive controls. At the echo-Doppler approach, about half of the hypertensive patients displayed a diastolic dysfunction (n = 44, E/A: 0.79 ± 0.02). They showed body mass index values slightly greater than hypertensive patients without diastolic dysfunction but superimposable blood pressure values and metabolic variables. When assessed via the pulse tissue-Doppler approach, patients with a reduced E/A displayed an Em/Am ratio significantly lower than patients without diastolic dysfunction and control subjects. This was the case when the data were related to the lateral and septal mitral annulus or averaged together. Furthermore, whereas myocardial systolic peak velocity (Sm) was lower in hypertensive patients than in control subjects, no significant between-groups difference in E/Em ratio was observed. Differently from the data obtained via the echo-Doppler approach, the tissue-Doppler method in patients without diastolic dysfunction showed a significant higher deceleration and isovolumetric relaxation times, with a lower Em velocity compared with the normotensive subjects. At the stepwise multiple regression analysis E/A ratio and E’/A’ values were related with left ventricular mass index and body mass index after correction for age. These data provide evidence that diastolic dysfunction is of frequent detection in the earlier uncomplicated phases of the disease and that tissue Doppler detects an initial impairment of left ventricular relaxation in the patients in which at echo Doppler is still normal.
V3-independent determinants of macrophage tropism in a primary human immunodeficiency virus type 1 isolate

Human immunodeficiency virus type 1 isolates differ in their ability to productively infect macrophages, and several groups have mapped the genetic basis for macrophage tropism to regions of env that include the third hypervariable region (V3 loop). We recently described a primary isolate (89.6) which is highly macrophage tropic and yet differs from other macrophage-tropic strains studied in that it is cytopathic in T cells. Genetic mapping of macrophage tropism determinants in this virus was done by using chimeras generated with the prototypic non-macrophage-tropic strain HXB2. Replacement of a 2.7-kb env-containing region of HXB with corresponding sequences from 89.6 conferred the macrophage-tropic phenotype, but insertion of the 89.6 V3 loop along with V4/V5 sequences did not. Conversely, placement of HXB sequences that included V3 into 89.6 did not impair this strain's ability to replicate in macrophages. Sequence analysis of V3 shows that 89.6 differs markedly from previously described macrophage-tropic consensus sequences and that it is more similar to highly charged non-macrophage-tropic strains. This suggests either that macrophage tropism is defined by structural determinants resulting from complex interactions among multiple env regions rather than V3 sequence-specific requirements or that there are multiple mechanisms by which different strains may establish productive macrophage infection. In addition, because the HXB V3 loop supports productive macrophage infection in the background of 89.6, phenotypic characterization of V3 sequences should be considered specific to the viral context in which they are placed.
Change in Cognitive Function Over 12 Months Among Patients With an Implantable Cardioverter-Defibrillator

Background:Patients with implantable cardioverter-defibrillators (ICDs) have decreased cognitive function associated with arrhythmic and/or cardiac disorders, such as ischemic cardiomyopathy. Little is known about changes in cognitive function over time among ICD patients. Aims:The aim of this study was to evaluate baseline-to-12-month changes in cognitive function in memory (total recall and delayed recall), psychomotor speed, and executive function among ICD patients. Methods:In this prospective study, 115 (mean [SD] age, 64.83 [9.06] years, 75% mean) and 77 ICD patients completed baseline and 12-month face-to-face interviews, respectively, which included neuropsychological tests to evaluate cognitive function. Results:Patients who completed baseline and 12-month testing had decreased total and delayed recall memory (all P < .05). No significant changes from baseline to 12 months were observed in psychomotor speed (t = 0.33; P = .74) and executive function (t = −1.12; P = .27). Using 1.0 standard deviation or below the mean as a cutoff criterion, 12% to 22% of ICD patients had poor cognitive function over time. Particularly, at baseline, 17 (15%) and 15 (13%) of the 115 patients had poor memory in total and delayed recall, respectively. At 12 months, 12 (16%) and 9 (12%) of the 77 patients had poor memory in total and delayed recall, respectively. Conclusions:In this sample of patients with ICDs, memory was poor at baseline and decreased over 12 months. Future studies are indicated to determine how this change in memory influences outcomes such as medication adherence.
Eating disorders risk groups in the Czech Republic--cross-sectional epidemiologic pilot study.

OBJECTIVE determination of risk groups for eating disorders in the population of young girls, primarily affiliated to certain sports or professional categories. METHOD standardized Eating Attitude Test (EAT) questionnaire (40 questions) and general attitude questionnaire (43 other questions specific to eating disorders) were used. RESULTS out of the total 403 persons questioned 11.7% had a score from EAT questionnaire > 29 points. These persons represent a potential risk population for the eventual development of eating disorder. Out of the total 403 persons 10.9% had the Body Mass Index (BMI) lower or equal to 17.5. Out of these, only 5 individuals had the score > 29 because, especially at potential or initial stages, these two parameters do not have to necessarily correspond. Top gymnasts and figure skaters, followed by the models, dancers, ballet dancers and the cosmetic school students can be classified as having the highest degree of risk. DISCUSSION assessment of the frequency of the condition which already shows signs of the beginning of a food intake disorder is important prerequisite for primary and secondary prevention of this disorder.