Miracle-dz/UniFAR-FTUs huggingface dataset:
SET-mediated Promoter Hypoacetylation Is a Prerequisite for Coactivation of the Estrogen-responsive pS2 Gene by PRMT1*

Induction of transcription requires an ordered recruitment of coregulators and specific combinations of histone modifications at the promoter. Occurrence of histone H4 arginine (Arg) 3 methylation by protein arginine methyltransferase 1 (PRMT1) represents an early promoter event in ER (estrogen receptor)-regulated gene activation. However, its in vivo significance in ER signaling and the prerequisites for PRMT1 recruitment to promoters have not been established yet. We show here that endogenous PRMT1 is a crucial and non-redundant coactivator of ER-mediated pS2 gene induction in MCF7 cells. By investigating promoter requirements for PRMT1 recruitment we find that the patient SE translocation (SET) protein, which was reported to protect histone tails from acetylation, associates with the uninduced pS2 gene promoter and dissociates early upon estrogen treatment. Knockdown of SET or trichostatin A (TSA) treatment causes premature acetylation of H4 and abrogation of H4 Arg3 methylation at the pS2 gene promoter resulting in diminished transcriptional induction. Thus, SET prevents promoter acetylation and is a prerequisite for the initial acetylation-sensitive steps of pS2 gene activation, namely PRMT1 function. Similar to pS2 we identify lactoferrin as a PRMT1-dependent and TSA-sensitive ER target gene. In contrast, we find that the C3 gene, another ER target, is activated in a PRMT1-independent manner and that SET is involved in C3 gene repression. These findings establish the existence of PRMT1-dependent and -independent ER target genes and show that proteins guarding promoter hypoacetylation, like SET, execute a key function in the coactivation process by PRMT1.
Activation of septal 5‐HT1A receptors alters spatial memory encoding, interferes with consolidation, but does not affect retrieval in rats subjected to a water‐maze task

Using Long‐Evans rats tested in a water maze, this study assessed the role of 5‐HT1A/5‐HT7 receptors of the medial septum in encoding, consolidation, and retrieval of spatial information. The testing protocol (acquisition: daily four‐trial sessions over three consecutive days; retention: probe trial on day 4) was first validated by showing that intraseptal infusions of lidocaine (LIDO; 40 μg/0.5 μL) disrupted acquisition and retrieval of the task. 8‐OH‐DPAT (4 μg/0.5 μL) infused before each acquisition session prevented learning/retention of the platform location, an effect attenuated by pretreatment with the 5‐HT1A receptor antagonist WAY 100635. With the 5‐HT7 antagonist SB 269970, the 8‐OH‐DPAT‐induced acquisition deficit seemed attenuated, but there was no subsequent retention. When infused immediately, 1, 4, or 6 h after each acquisition session, 8‐OH‐DPAT did not hinder consolidation. When the infusions were performed 2 h postacquisition, however, consolidation was disrupted. Finally, when infused before a probe trial after drug‐free acquisition, 8‐OH‐DPAT had no effect, suggesting no interference with retrieval processes. We also established that 8‐OH‐DPAT had no effects when the platform was visible, and altered neither home‐cage activity nor anxiety‐related behavior (elevated plus‐maze). Altogether, these results show that 5‐HT1A receptors in the septal region contribute both to declarative‐like information encoding and subsequently, within a given postacquisition time window, to its consolidation. They do not participate in the retrieval of recently learned declarative‐like information. These observations suggest that 5‐HT1A receptors of the medial septum contribute to a serotonin‐mediated mechanism involved in the encoding and consolidation, not the retrieval of spatial hippocampal‐ dependent knowledge. These results might have some relevance to approaches aimed at modifying serotonergic functions in the brain for the treatment of disorders such as depression, anxiety, post‐traumatic stress, and amnesia. © 2007 Wiley‐Liss, Inc.
Pathogenesis of Infection by Clinical and Environmental Strains of Vibrio vulnificus in Iron-Dextran-Treated Mice

ABSTRACT Vibrio vulnificus is an opportunistic pathogen that contaminates oysters harvested from the Gulf of Mexico. In humans with compromising conditions, especially excess levels of iron in plasma and tissues, consumption of contaminated seafood or exposure of wounds to contaminated water can lead to systemic infection and disfiguring skin infection with extremely high mortality. V. vulnificus-associated diseases are noted for the rapid replication of the bacteria in host tissues, with extensive tissue damage. In this study we examined the virulence attributes of three virulent clinical strains and three attenuated oyster or seawater isolates in mouse models of systemic disease. All six V. vulnificus strains caused identical skin lesions in subcutaneously (s.c.) inoculated iron dextran-treated mice in terms of numbers of recovered CFU and histopathology; however, the inocula required for identical frequency and magnitude of infection were at least 350-fold higher for the environmental strains. At lethal doses, all strains caused s.c. skin lesions with extensive edema, necrosis of proximate host cells, vasodilation, and as many as 108CFU/g, especially in perivascular regions. These data suggest that the differences between these clinical and environmental strains may be related to growth in the host or susceptibility to host defenses. In non-iron dextran-treated mice, strains required 105-fold-higher inocula to cause an identical disease process as with iron dextran treatment. These results demonstrate that s.c. inoculation of iron dextran-treated mice is a useful model for studying systemic disease caused by V. vulnificus.
Genetic Basis for the Structural Difference between Streptococcus pneumoniae Serotype 15B and 15C Capsular Polysaccharides

ABSTRACT In a search for the genetic basis for the structural difference between the related Streptococcus pneumoniae capsular serotypes 15B and 15C and for the reported reversible switching between these serotypes, the corresponding capsular polysaccharide synthesis (cps) loci were investigated by keeping in mind that at the structural level, the capsules differ only in O acetylation. The cps locus of a serotype 15B strain was identified, partially PCR amplified with primers based on the related serotype 14 sequence, and sequenced. Sequence analysis revealed, among other open reading frames, an intact open reading frame (designated cps15bM) whose product, at the protein level, exhibited characteristics of previously identified acetyltransferases. Genetic analysis of the corresponding region in a serotype15C strain indicated that the same gene was present but had a premature stop in translation. Closer analysis indicated that the serotype 15B gene contained a short tandem TA repeat consisting of eight TA units. In serotype 15C, this gene contained nine TA units that resulted in a frameshift and a truncated product. Genetic analysis of 17 serotype 15B and 15C clinical isolates revealed a perfect correlation between the serotype and the length of the short tandem repeat in the putative O-acetyltransferase gene. The number of TA repeating units varied between seven and nine in the various isolates. Together, the data strongly suggest that the structural difference between serotypes 15B and 15C is based on variation in the short tandem TA repeat in the O-acetyltransferase gene and that the transition between serotypes is due to slipped-strand mispairing with deletion or insertion of TA units in the cps15bM gene.
Outcomes after initial receipt of social security benefits among homeless veterans with mental illness.

OBJECTIVE This study examined the relationship between receiving disability payments and changes in health status, community adjustment, and subjective quality of life. METHODS The study evaluated outcomes among homeless mentally ill veterans who applied for Social Security Disability Insurance or Supplemental Security Income through a special outreach program. Veterans who were awarded benefits were compared with those who were denied benefits; their sociodemographic characteristics, clinical status, and social adjustment were evaluated just before receiving the initial award decision and again three months later. RESULTS Beneficiaries (N=50) did not differ from those were denied benefits (N=123) on any baseline sociodemographic or clinical characteristics. However, beneficiaries were more willing to delay gratification, as reflected in scores on a time preference measure. Three months after the initial decision, beneficiaries had significantly higher total incomes and reported a higher quality of life. They spent more on housing, food, clothing, transportation, and tobacco products but not on alcohol or illegal drugs. No differences were found between groups on standardized measures of psychiatric status or substance abuse. CONCLUSIONS Receipt of disability payments is associated with improved subjective quality of life and is not associated with increased alcohol or drug use.
‘I think my body has become addicted to those tablets’. Chronic heart failure patients’ understanding of and beliefs about their illness and its treatment: A qualitative longitudinal study from Uganda

Background Patients with heart failure in Uganda present for health care with advanced structural heart disease, have repeated hospitalizations and poorly controlled disease symptoms. The reasons for these are unclear. Literature from other settings shows that patients’ understanding of their illness and their beliefs influence their health related behaviour. The study aimed to explore the beliefs of patients with heart failure, their understanding of their illness and its treatment, and how this influenced their health related behaviour to inform future health education programs, information and palliative care services. Methods Serial qualitative in-depth interviews were conducted with Heart Failure patients who were purposively sampled and recruited in Mulago National Referral Hospital until thematic saturation was reached. In-depth interviews were conducted at three time points over the course of their illness with intervals of 3 months between interviews. A grounded theory approach was used in data analysis. The University of Edinburgh ethics committee, Mulago Hospital Research Ethics committee and the Uganda National Council of Science and Technology (Reference numbers D/GC/178; MREC 33, SS 3083 respectively) approved the research. Results A total of 40 face to face qualitative longitudinal interviews (36-patient alone, 4 paired-patient and family carer), were conducted with 21 patients. The findings revealed that heart failure patients were unaware of the symptoms of the illness and their definition of illness differed from that of health professionals. Patients understood their diagnosis, cause of illness, prognosis and the importance of the medicines differently from health professionals, and had insufficient information on self-care. Lay beliefs were used to explain many aspects of the illness and treatments. All these influenced where patients sought care and their adherence to treatment, self-care and follow up leading to uncontrolled disease. Conclusion There is a high level of health illiteracy among heart failure patients in Uganda. Patients rely on lay beliefs to make health decisions and medical information is often miscomprehended. There is an urgent need for health education using culturally appropriate information.
2-[18F]Fluoro-2-Deoxyglucose Positron Emission Tomography for the Detection of Disease in Patients with Prostate-Specific Antigen Relapse after Radical Prostatectomy

Experimental Design: Retrospective cohort study in 91 patients with prostate-specific antigen (PSA) relapse following prostatectomy, imaged with 2-[18F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET) in a tertiary care cancer center between February 1997 and March 2003. Comparison was made with magnetic resonance imaging (n = 64), bone scan (n = 56), and computed tomography (n = 37). The standard of reference included biopsy or clinical and imaging follow-up. We calculated sensitivity and specificity of PET and correlated PET findings with PSA values, other clinical parameters, and conventional imaging, when available. Results: PET was true positive in 28 of 91 (31%) patients, showing isolated disease in the prostate bed (n = 3) or metastatic disease with (n = 2) or without (n = 23) simultaneous disease in the prostate bed. In detail, PET identified lesions in the prostate bed (n = 5, all true positives), bones (n = 22; 20 true positives, 2 false positives), lymph nodes (n = 7; 6 true positives, 1 likely false positive), and one liver metastasis. Mean PSA was higher in PET-positive than in PET-negative patients (9.5 ± 2.2 versus 2.1 ± 3.3 ng/mL). PSA of 2.4 ng/mL and PSA velocity of 1.3 ng/mL/y provided the best tradeoff between sensitivity (80%; 71%) and specificity (73%; 77%) of PET in a receiver operating curve analysis. Combination with other clinical parameters in a multivariate analysis did not improve disease prediction. There were only two patients in whom other imaging studies showed isolated local recurrence or metastatic disease. Conclusions: FDG-PET detected local or systemic disease in 31% of patients with PSA relapse referred for this test. There is a link to tumor burden and tumor biology in that the probability for disease detection increased with PSA levels.
Prevalence of Enamel Hypoplasia in Deciduous Canines of Patients with Complete Cleft Lip and Palate

Objective To evaluate the prevalence and type of enamel hypoplasia in deciduous canines of patients with complete unilateral and bilateral cleft lip and palate, as well as its distribution according to gender, dental arch, and side of cleft. Design Cross sectional. Setting Hospital for Rehabilitation of Craniofacial Anomalies, Bauru, São Paulo, Brazil. Material and Methods Three-hundred twelve Caucasian children (193 boys, 119 girls), aged 3 to 10 years, presenting complete unilateral and bilateral cleft lip and palate were included in this study. A single examiner carried out clinical examination under natural light with a dental probe and dental mirror and, after drying of the tooth, by means of a simplified hypoplasia index. Results A prevalence of 43.8% was observed for unilateral and 39% for bilateral clefts. Both groups revealed similar distributions regarding the maxillary and mandibular dental arches and gender. Similar distribution was also observed on the cleft and noncleft sides for the unilateral cleft group. The most frequent type and severity was obvious hypoplasia, followed by minimal hypoplasia, both roughly round. Conclusion The results suggest that the cleft does not influence the occurrence of hypoplasia in deciduous canines.
Dialectical behavior therapy for adolescents with bipolar disorder: results from a pilot randomized trial.

OBJECTIVE The purpose of this study was to conduct a pilot randomized trial of dialectical behavior therapy (DBT) versus psychosocial treatment as usual (TAU) for adolescents diagnosed with bipolar disorder (BP). METHODS We recruited participants 12-18 years of age with a primary BP diagnosis (I, II, or operationalized not otherwise specified [NOS] criteria) from a pediatric specialty clinic. Eligible patients were assigned using a 2:1 randomization structure to either DBT (n=14) or psychosocial TAU (n=6). All patients received medication management from a study-affiliated psychiatrist. DBT included 36 sessions (18 individual, 18 family skills training) over 1 year. TAU was an eclectic psychotherapy approach consisting of psychoeducational, supportive, and cognitive behavioral techniques. An independent evaluator, blind to treatment condition, assessed outcomes including affective symptoms, suicidal ideation and behavior, nonsuicidal self-injurious behavior, and emotional dysregulation, quarterly over 1 year. RESULTS Adolescents receiving DBT attended significantly more therapy sessions over 1 year than did adolescents receiving TAU, possibly reflecting greater engagement and retention; both treatments were rated as highly acceptable by adolescents and parents. As compared with adolescents receiving TAU, adolescents receiving DBT demonstrated significantly less severe depressive symptoms over follow-up, and were nearly three times more likely to demonstrate improvement in suicidal ideation. Models indicate a large effect size, for more weeks being euthymic, over follow-up among adolescents receiving DBT. Although there were no between-group differences in manic symptoms or emotional dysregulation with treatment, adolescents receiving DBT, but not those receiving TAU, evidenced improvement from pre- to posttreatment in both manic symptoms and emotional dysregulation. CONCLUSIONS DBT may offer promise as an adjunct to pharmacotherapy in the treatment of depressive symptoms and suicidal ideation for adolescents with BP. The DBT focus on commitment to treatment may be important for the treatment of early-onset BP. Larger controlled trials are needed to establish the efficacy of this approach, examine impact on suicidal behavior, and demonstrate cost effectiveness.
Positive-hole correction of multiple-jet impactors for collecting viable microorganisms.

Multiple-jet impactors, typically with 200 or 400 holes, are used widely for collecting aerosols of living bacteria and fungi. In this type of impactor, the air jets impinge directly onto nutrient agar in a petri dish which is incubated after sampling until collected cells multiply into colonies. The observed number of colonies can be adjusted for the probability that more than one viable particle was collected through a sampling hole and merged with other microorganisms at an impaction site to produce a single colony. A "positive-hole" correction table has been published for a 400-hole impactor, but none has been produced previously for the 200-hole impactor. The expected number of sampled particles required to fill each of 1 through 200 and 1 through 400 impaction sites and the standard deviations of these values were calculated from probability theory. The results were compared with a Monte Carlo simulation. By using correction tables (which include the standard deviation of an expected value) an investigator can report the most probable viable particle count and a 95% confidence interval (mean +/- 2 standard deviations). The range of collected particles that could have produced an observed number of colonies increases as the number of collected particles increases, and investigators should acknowledge the uncertainty associated with adjusted counts. It is advisable to use an impactor with the greatest practical number of sampling holes because this decreases the likelihood that multiple particles are deposited at the impaction sites. (ABSTRACT TRUNCATED AT 250 WORDS)
Mutations in the hMLH1 gene in Slovenian patients with gastric carcinoma

Alterations of multiple oncogenes and tumor suppressor genes, together with genetic instability, are responsible for carcinogenesis in gastric cancer. The microsatellite mutator phenotype is the cause of many somatic frameshift and point mutations in non‐coding repetitive sequences and in coding regions associated with cell proliferation and apoptosis. Genetic mutations in hMLH1 and transcriptional silencing of its promoter by hypermethylation lead to the inactivation of the mismatch repair system. In our study, we screened for mutations the hMLH1 gene in patients expressing the microsatellite instability genotype by using single‐strand conformational polymorphism analysis and direct sequencing. Seven changes were identified; of these, three (A92P, E433Q, and K618A) were germline mutations and the other four (IVS5 453 + 79 A > G, I219V, 1039 − 7 del (T)n, and IVS15 1668 − 19 A > G) germline polymorphisms. A92P and E433Q are novel, previously unidentified mutations. In addition, we found a rather complex distribution of mutations and polymorphisms in individual patients and in two cases also a methylated hMLH1 promoter.
The Role of Protease Inhibitors in the Pathogenesis of HIV-Associated Lipodystrophy: Cellular Mechanisms and Clinical Implications

Metabolic complications associated with HIV infection and treatment frequently present as a relative lack of peripheral adipose tissue associated with dyslipidemia and insulin resistance. In this review we explain the connection between abnormalities of intermediary metabolism, observed either in vitro or in vivo, and this group of metabolic effects. We review molecular mechanisms by which the HIV protease inhibitor (PI) class of drugs may affect the normal stimulatory effect of insulin on glucose and fat storage. We then propose that both chronic inflammation from HIV infection and treatment with some drugs in this class trigger cellular homeostatic stress responses with adverse effects on intermediary metabolism. The physiologic outcome is such that total adipocyte storage capacity is decreased, and the remaining adipocytes resist further fat storage. The excess circulating and dietary lipid metabolites, normally “absorbed” by adipose tissue, are deposited ectopically in lean (muscle and liver) tissue, where they impair insulin action. This process leads to a pathologic cycle of lipotoxicity and lipoatrophy and a clinical phenotype of body fat distribution with elevated waist-to-hip ratio similar to the metabolic syndrome.
Hours Worked Across the World: Facts and Driving Forces

I summarise new facts on hours worked differences across countries and their driving forces. The facts are derived from a comprehensive analysis of micro data sets. First, hours worked are substantially higher in poor than in rich countries. Second, lower hours worked in Europe than in the US can partly be explained by differences in vacation weeks and partly by differences in the demographic structure. Moreover, employment rates tend to be higher and weekly hours worked lower in Western Europe and Scandinavia than in the US, with the opposite being true in Eastern and Southern Europe. Last, among core-aged individuals, married women form the group that exhibits the largest differences in hours worked across countries. International differences in taxation, and especially in the tax treatment of married couples, are an important driver of these differences.
Treatment of Talar Osteochondral Lesions Using Local Osteochondral Graft

Twelve patients with an osteochondral lesion of the talus were treated with excision of the lesions and local osteochondral autogenous grafting. The lesion was accessed through a replaceable bone block removed from the anterior tibial plafond. The graft was harvested from the medial or lateral talar articular facet on the same side of the lesion. The average age of the patients was 41 years and duration of symptoms was 90 months (ave.). There were six males and six females with the right talus involved in eight and the left in four patients. Graft sizes ranged from four to eight millimeters in diameter. There was a significant improvement in the AOFAS score from 64.4 (ave.) pre-operatively to 90.8 (ave.) postoperatively (p>0.0001), at a follow-up of 25.3 months (ave.). The AOFAS score was slightly higher in patients under 40 years of age and in those without pre-existing joint arthritis. All patients were very satisfied with the procedure. Arthroscopy performed in two patients at six and 12 months following surgery showed good graft incorporation. No complications occurred at the donor site or the site of bone block removal on the distal tibia. The results show that stage III and IV talar osteochondral lesions can be accessed successfully excising a tibial bone block and using local autogenous osteochondral graft harvested from the ipsilateral talar articular facet.