Miracle-dz/UniFAR-FTUs huggingface dataset:
Independent Recruitment of Mediator and SAGA by the Activator Met4

ABSTRACT Mediator is a key RNA polymerase II (Pol II) cofactor in the regulation of eukaryotic gene expression. It is believed to function as a coactivator linking gene-specific activators to the basal Pol II initiation machinery. In support of this model, we provide evidence that Mediator serves in vivo as a coactivator for the yeast activator Met4, which controls the gene network responsible for the biosynthesis of sulfur-containing amino acids and S-adenosylmethionine. In addition, we show that SAGA (Spt-Ada-Gcn5-acetyltransferase) is also recruited to Met4 target promoters, where it participates in the recruitment of Pol II by a mechanism involving histone acetylation. Interestingly, we find that SAGA is not required for Mediator recruitment by Met4 and vice versa. Our results provide a novel example of functional interplay between Mediator and coactivators involved in histone modification.
Acute myocardial infarction in a young woman with ulcerative colitis

Rationale: Myocardial infarction due to nonatherosclerotic coronary thrombosis in young woman with ulcerative colitis is rare. Patient concerns: A 23-year-old Chinese woman with a 3-year history of ulcerative colitis was admitted to the coronary care unit due to prolonged chest pain. Diagnoses: Myocardial infarction due to nonatherosclerotic coronary thrombosis was diagnosed in this young woman. Lessons: Coronary artery thrombosis in ulcerative colitis is a serious condition and can occur in the young population.
The relationship between metronidazole concentration and clinicopathological parameters in patients with colon cancer: A pilot study

__________________________________________________________________________________________ Purpose: To evaluate the concentration of metronidazole (MTZ) and its hydroxy metabolite (MTZOH) in cancer tissue and adjacent normal tissue in colorectal cancer patients in correlation with clinicopathologic parameters. Material and methods: MTZ and MTZOH concentration were measured in tumor tissue and surrounding healthy tissue by LC-ESI-MS-MS method. Results: We found different concentration of MTZ and MTZOH in colorectal cancer and healthy tissue, however the results were not statistically significant. MTZ concentration was elevated in tumors located in rectum, in patients over 60 years old, in patients without metastases to regional lymph nodes (N0) while decreasing with increasing tumor size. Women accumulated greater amounts of MTZ in comparison to men. Conclusion: Comparison of the concentration of the drug and its metabolite in tumor and normal colon tissue shows its different reaction to MTZ. MTZ concentration in the tumor and normal colon tissue is sex-dependent.
Modulating emotional responses: effects of a neocortical network on the limbic system

Humans share with animals a primitive neural system for processing emotions such as fear and anger. Unlike other animals, humans have the unique ability to control and modulate instinctive emotional reactions through intellectual processes such as reasoning, rationalizing, and labeling our experiences. This study used functional MRI to identify the neural networks underlying this ability. Subjects either matched the affect of one of two faces to that of a simultaneously presented target face (a perceptual task) or identified the affect of a target face by choosing one of two simultaneously presented linguistic labels (an intellectual task). Matching angry or frightened expressions was associated with increased regional cerebral blood flow (rCBF) in the left and right amygdala, the brain's primary fear centers. Labeling these same expressions was associated with a diminished rCBF response in the amygdalae. This decrease correlated with a simultaneous increase in rCBF in the right prefrontal cortex, a neocortical region implicated in regulating emotional responses. These results provide evidence for a network in which higher regions attenuate emotional responses at the most fundamental levels in the brain and suggest a neural basis for modulating emotional experience through interpretation and labeling.
Clinical significance of peripheral blood Epstein–Barr viral load monitoring using polymerase chain reaction in renal transplant recipients

Abstract: PTLD is a complication of EBV infection. We examined the efficacy of EBV‐PCR monitoring to detect early replication in an attempt to prevent EBV‐associated PTLD. Blood EBV levels in 156 renal transplant recipients (58 children) from three institutions over nine yr were retrospectively analyzed. Patients who were asymptomatic and at high risk for PTLD were monitored for EBV infection by PCR or serology followed by PCR at the time of EBV seropositivity. More children than adults had positive EBV‐PCR (12/58 vs. 2/98, p < 0.001). Adults remained asymptomatic and viremia resolved post‐therapy. 3/12 EBV‐PCR positive children developed PTLD (3/12 children vs. 0/2 adults, p = NS). Two out of three with PTLD were initially monitored by serology, and later by PCR. PTLD resolved post‐therapy in all three patients. The remaining 9/12 EBV‐PCR positive children stayed asymptomatic. None of the children and adults with negative EBV‐PCR developed PTLD. EBV‐PCR monitoring in high‐risk renal transplant recipients, especially in children, may allow early diagnosis and intervention, and therefore may help in preventing EBV‐associated PTLD.
Psychiatric comorbidity, continuing care and mutual help as predictors of five-year remission from substance use disorders.

OBJECTIVE In a cohort of 2,595 male patients in VA intensive treatment programs for substance use disorders (SUD), we tested whether psychiatric comorbidity, outpatient care and mutual help group attendance during the first two follow-up years predicted remission status at Year 5, controlling for covariates. METHOD Logistic regression modeling of longitudinal data was used to test the hypotheses. RESULTS Dual diagnosis patients were less likely to be in remission at Year 5 than SUD-only patients. Outpatient care was at best only weakly related to Year 5 remission status. By contrast, mutual help involvement substantially improved the chances of substance use remission at Year 5 for both SUD-only and dual diagnosis patients. Mutual help involvement did not, however, offset the poorer prognosis for dual diagnosis patients. CONCLUSIONS Because mutual help groups specifically targeted to individuals with comorbid substance use and psychiatric disorders are currently rare, further research is recommended to investigate whether they are more effective than standard SUD mutual help groups in facilitating the recovery of persons with dual diagnoses.
EFFECT OF SEMINAL PLASMA CALCITONIN LEVELS ON SPERM MOTILITY

This study investigated the effect of the seminal and blood plasma calcitonin levels on the sperm motility in idiopathic infertile patients. The number of sperm cells and their motility were evaluated in the spermiograms of 52 idiopathic infertile patients. The levels of seminal plasma calcitonin were studied with double antibody technique using a DPC kit. Fifty-two patients were divided into 2 groups according to the motility rates of sperm and 20 healthy volunteers were assigned to a control group. The difference between the groups was evaluated by using Kruskall-Wallis and Mann-Whitney U tests, and the correlation of seminal and blood calcitonin levels with sperm motility were determined. The difference in motility rates between the 3 groups was statistically significant ( p =. 000, p <. 05). Blood plasma calcitonin levels were in normal ranges in all cases and no significant difference was found among the 3 groups ( h 2 = 2.7219, p =. 2589, p >. 05). While sperm motility was correlated with seminal calcitonin levels ( r =. 8581), blood calcitonin levels did not show a correlation with sperm motility rate ( r = -.0265). Moreover, there was no correlation between seminal and blood plasma levels of calcitonin ( r = -.0010). Motility rates decreased in the patients with low seminal calcitonin levels and seminal calcitonin levels had a significant effect on sperm motility.
Comparison of Genotypes of Salmonella enterica Serovar Enteritidis Phage Type 30 and 9c Strains Isolated during Three Outbreaks Associated with Raw Almonds

ABSTRACT In 2000 to 2001, 2003 to 2004, and 2005 to 2006, three outbreaks of Salmonella enterica serovar Enteritidis were linked with the consumption of raw almonds. The S. Enteritidis strains from these outbreaks had rare phage types (PT), PT30 and PT9c. Clinical and environmental S. Enteritidis strains were subjected to pulsed-field gel electrophoresis (PFGE), multilocus variable-number tandem repeat analysis (MLVA), and DNA microarray-based comparative genomic indexing (CGI) to evaluate their genetic relatedness. All three methods differentiated these S. Enteritidis strains in a manner that correlated with PT. The CGI analysis confirmed that the majority of the differences between the S. Enteritidis PT9c and PT30 strains corresponded to bacteriophage-related genes present in the sequenced genomes of S. Enteritidis PT4 and S. enterica serovar Typhimurium LT2. However, PFGE, MLVA, and CGI failed to discriminate between S. Enteritidis PT30 strains related to outbreaks from unrelated clinical strains or between strains separated by up to 5 years. However, metabolic fingerprinting demonstrated that S. Enteritidis PT4, PT8, PT13a, and clinical PT30 strains metabolized l-aspartic acid, l-glutamic acid, l-proline, l-alanine, and d-alanine amino acids more efficiently than S. Enteritidis PT30 strains isolated from orchards. These data indicate that S. Enteritidis PT9c and 30 strains are highly related genetically and that PT30 orchard strains differ from clinical PT30 strains metabolically, possibly due to fitness adaptations.
Autophagy Induction in T Cell-Independent Acute Hepatitis Induced by Concanavalin a in SCID/NOD Mice

Concanavalin A (Con A) is known to induce acute hepatitis that is mediated by activation of NKT- and T-cell and cytokine production in immunocompetent mice. The observation of Con A-induced autophagic cell death of hepatoma cells via a Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 mediated autophagic pathway made us re-evaluate the effect of Con A-induced hepatitis in mice. Con A was administrated intravenously to BABL/c, SCID, or SCID/NOD mice at doses of 20, 30 or 40 mg/kg, respectively, to induce acute hepatitis. The levels of hepatitis and autophagy induction were both analyzed. We found that Con A can induce acute hepatitis in SCID or SCID/NOD mice with a kinetics similar to that of BALB/c, but requiring a higher dose of Con A. No lymphocyte infiltrations were found in SCID or SCID/NOD mice, and the cytokine productions were different. An autophagy with microtubule-associated protein light chain 3-II conversion was demonstrated in the liver post-Con A injection in SCID/NOD mice. Due to the mannose/glucose-specific binding on cell membrane, Con A can induce a T-cell-independent acute hepatitis with autophagy in SCID/NOD mice.
Interpersonal Coping Among Boys With ADHD

Objective: The authors investigate self-reported coping with interpersonal stressors among boys with and without ADHD in two studies and provide initial evidence for effects of different subgroups of ADHD on coping in Study 2. Method: In Study 1, 20 Austrian adolescents with ADHD were compared to 20 healthy controls. In Study 2, 44 German children and adolescents with ADHD (35 without and 9 with conduct disorders) were compared to 44 healthy controls matched by age and grade level, respectively. Results: Increased maladaptive coping was found in both studies. Study 2 revealed heightened maladaptive coping among both subgroups of ADHD, but the subgroup of ADHD with conduct disorders was more affected compared to healthy controls than the subgroup with ADHD alone. Conclusion: Results suggest an impaired interpersonal coping style in ADHD and point to the potential benefit of stress management and social skills trainings for boys with ADHD. (J. of Att. Dis. 2008; 11(4) 427—436)
Subsets of Glioblastoma Multiforme Defined by Molecular Genetic Analysis

Glioblastoma multiforme is a clinically and histologically heterogeneous lesion; however, to date, it has not been possible to subdivide glioblastomas on a clinical, histopathological or biological basis. Previous studies have demonstrated that loss of portions of chromosomes 10 and 17 and amplification of the epidermal growth factor receptor (EGFR) gene are the most frequent genetic alterations in glioblastoma. We therefore examined 74 glioblastomas from 67 patients for loss of heterozygosity on chromosomes 10 and 17, and for amplification of the epidermal growth factor receptor gene, to determine whether glioblastomas can be subtyped on a genetic basis. Using Southern blot analysis we were able to detect different patterns of genomic alterations. Eighteen of 67 informative patients were characterized by a loss of heterozygosity on the short arm of chromosome 17 in the tumor tissue. Forty‐five of 64 informative patients showed a loss of heterozygosity on chromosome 10. Amplification of the epidermal growth factor receptor gene was noted in 25 of 67 patients and was restricted to those glioblastomas that had lost portions of chromosome 10. Epidermal growth factor receptor gene amplification occurred significantly more often in patients without chromosome 17p loss than in patients with chromosome 17p loss (p = 0.01). In addition, those glioblastomas with a loss of chromosome 17p occurred in patients significantly younger than those with glioblastomas characterized by EGFR gene amplification (p = 0.001). These data emphasize the genetic heterogeneity of glioblastoma and suggest the division of glioblastoma into genetic subsets.
Massively parallel neural computation

Reverse-engineering the brain is one of the US National Academy of Engineering’s “Grand Challenges. ” The structure of the brain can be examined at many different levels, spanning many disciplines from low-level biology through psychology and computer science. This thesis focusses on real-time computation of large neural networks using the Izhikevich spiking neuron model. Neural computation has been described as “embarrassingly parallel” as each neuron can be thought of as an independent system, with behaviour described by a mathematical model. However, the real challenge lies in modelling neural communication. While the connectivity of neurons has some parallels with that of electrical systems, its high fan-out results in massive data processing and communication requirements when modelling neural communication, particularly for real-time computations. It is shown that memory bandwidth is the most significant constraint to the scale of real-time neural computation, followed by communication bandwidth, which leads to a decision to implement a neural computation system on a platform based on a network of Field Programmable Gate Arrays (FPGAs), using commercial off-the-shelf components with some custom supporting infrastructure. This brings implementation challenges, particularly lack of on-chip memory, but also many advantages, particularly high-speed transceivers. An algorithm to model neural communication that makes efficient use of memory and communication resources is developed and then used to implement a neural computation system on the multi-FPGA platform. Finding suitable benchmark neural networks for a massively parallel neural computation system proves to be a challenge. A synthetic benchmark that has biologically-plausible fan-out, spike frequency and spike volume is proposed and used to evaluate the system. It is shown to be capable of computing the activity of a network of 256k Izhikevich spiking neurons with a fan-out of 1k in real-time using a network of 4 FPGA boards. This compares favourably with previous work, with the added advantage of scalability to larger neural networks using more FPGAs. It is concluded that communication must be considered as a first-class design constraint when implementing massively parallel neural computation systems.
The Final pH of Bacteria Comprising the Predominant Flora on Sound and Carious Human Root and Enamel Surfaces

Acidogenesis at low pH appears to be an important bacterial cariogenic trait. However, most information in this regard pertains to only a few of the acidogenic dental plaque bacteria. Therefore, the 'final' pH in sugar broth was determined for a wide variety of oral bacteria. Their source was: (1) carious material from advanced root lesions (ARL), (2) plaque from sound root surfaces of root-caries-free subjects (SRS), (3) plaque from "white spot" coronal lesions and sound coronal surfaces of caries-active subjects, and (4) plaque from sound coronal surfaces of caries-free subjects. Strains from groups 1 and 2 (ARL, 389 strains; SRS, 358 strains) were previously identified (van Houte et al., 1994) to the genus/species level and belonged to the predominant cultivable flora (PCF). Strains from groups 3 and 4 also belonged to the PCF but were not identified. All strains were placed in one of 4 final pH categories: < 4.2, 4.2 - 4.4, 4.4 - 4.6, and ≥ 4.6. The main findings were: (1) ARL samples contained many strains with a final pH < 4.2 (mean percentage of 25.7). They included all strains of Lactobacillus and mutans streptococci (MS), most Bifidobacterium strains and non-mutans streptococci (non-MS), and about 20% of the Actinomyces strains. By contrast, SRS samples contained far fewer strains with a final pH < 4.2 (mean percentage of 8.4) which were nearly all non-MS. (2) Organisms with a final pH < 4.4 constituted mean percentages of 41.5 and 32.1 for the ARL and SRS samples, respectively. (3) The final pH distribution of strains in samples from coronal surfaces showed a tendency relative to caries activity (group 3 vs. group 4) similar to that for groups 1 and 2. Our findings further support the concept that increased cariogenic conditions are associated with increased proportions of organisms capable of acidogenesis at a low pH and that this shift involves organisms other than the MS and lactobacilli.
The Urban Poor's Economic Profile of Tobacco Use

Objectives: Low-income minority tobacco users are price sensitive and are more likely to quit when tobacco prices go up. No prior research documents economic characteristics of low-income tobacco users. The study investigates economic profile of tobacco use among urban low-income African Americans. Methods: In this baseline study (n = 338), tobacco users and nonusers were compared, and their economic conditions of tobacco use including (current and past) employment barriers were examined. Results: The study results demonstrate that tobacco use status appeared to be associated with employment barriers among low income populations. Controlling for other independent variables in the multivariate logistic regression model, previous criminal activity, planning to move out, and female gender were found to be linked to labor force status. Conclusions: More research efforts on how indigent tobacco-using individuals develop their employment skills and become economically independent are needed.
Assessing Human Health Response in Life Cycle Assessment Using ED10s and DALYs: Part 1—Cancer Effects

Life cycle assessment (LCA) is a framework for comparing products according to their total estimated environmental impact, summed over all chemical emissions and activities associated with a product at all stages in its life cycle (from raw material acquisition, manufacturing, use, to final disposal). For each chemical involved, the exposure associated with the mass released into the environment, integrated over time and space, is multiplied by a toxicological measure to estimate the likelihood of effects and their potential consequences. In this article, we explore the use of quantitative methods drawn from conventional single‐chemical regulatory risk assessments to create a procedure for the estimation of the cancer effect measure in the impact phase of LCA. The approach is based on the maximum likelihood estimate of the effect dose inducing a 10% response over background, ED10, and default linear low‐dose extrapolation using the slope βED10 (0.1/ED10). The calculated effects may correspond to residual risks below current regulatory compliance requirements that occur over multiple generations and at multiple locations; but at the very least they represent a “using up” of some portion of the human population's ability to accommodate emissions. Preliminary comparisons are performed with existing measures, such as the U.S. Environmental Protection Agency's (U.S. EPA's) slope factor measure q1*. By analyzing bioassay data for 44 chemicals drawn from the EPA's Integrated Risk Information System (IRIS) database, we explore estimating ED10 from more readily available information such as the median tumor dose rate TD50 and the median single lethal dose LD50. Based on the TD50, we then estimate the ED10 for more than 600 chemicals. Differences in potential consequences, or severity, are addressed by combining βED10 with the measure disability adjusted life years per affected person, DALYp. Most of the variation among chemicals for cancer effects is found to be due to differences in the slope factors (βED10) ranging from 10−4 up to 104 (risk of cancer/mg/kg‐day).
Neurodegenerative diseases with cytoskeletal pathology: A biochemical classification

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