Miracle-dz/UniFAR-FTUs huggingface dataset:
Isolation and characterization of a novel copper‐inducible metallothionein gene of a ciliate, Tetrahymena tropicalis lahorensis

The two isoforms of copper metallothionein (CuMT) gene of a copper resistant ciliate, Tetrahymena tropicalis lahorensis (Ttl), have been isolated and characterized. The molecular cloning and nucleotide sequencing of cDNAs coding for the two CuMT isoforms revealed that TtlCuMT1 gene has 300, while TtlCuMT2 has 327 nucleotides, both with ATG as the initiation codon and TGA as the translational termination codon. TAG codes for glutamine in TtlCuMT2 gene which is peculiar to Tetrahymena. The deduced or translated TtlCuMT1 and TtlCuMT2 peptide sequences contain 100 and 108 amino acid residues including 28 and 32 cysteine residues, respectively. The amino acid sequences of TtlCuMT1 and TtlCuMT2 have special features of two and three CXCXXCXCXXCXC intragenic tandem repeats with a conserved structural pattern of cysteine, respectively. The predicted tertiary structures of these two isoforms indicate two domains. Domain I and the initial part of domain II showed >98% homology with other Tetrahymena CuMT. On the basis of the differences in the domain II, the metallothionein subfamily 7b can be divided into two groups, one (TtlCuMT1) comprising >100 amino acids and the other (TtlCuMT2) comprising <100 amino acids. This is a novel finding of the present study as no such report on this type of classification exists at the moment. TtlCuMT1 has 95%, while TtlCuMT2 has 97% resemblance with the previously reported CuMT genes of Tetrahymena spp. SDS‐PAGE analysis using fluorescent probe as well as coomassie brilliant blue staining also confirmed the presence of metallothionein. J. Cell. Biochem. 110: 630–644, 2010. © 2010 Wiley‐Liss, Inc.
Maternal Identity Change as a Consequence of Antenatal Hospitalization

Despite low fertility rates in Western countries, maternity remains one of the major goals of women from various socioeconomic backgrounds. While most women will have low-risk pregnancies, common serious disorders of pregnancy, such as preeclampsia, premature rupture of the membranes, placenta previa, or fetal growth restriction, may compromise maternal and infant outcomes. The experiences of urban and rural women in Australia who have had difficulties in maintaining their pregnancies are analyzed in this article. We study the impact of individual and social factors that facilitate or impede women's adjustment to the risks associated with these disorders. The analysis of in-depth interviews with 27 women hospitalized antenatally indicates that most women were unfamiliar with the diagnoses and acted as passive “decision takers,” complying with medical advice to remain in the hospital. Admission to a tertiary hospital ward that provided care to women with pregnancy disorders promoted the formation of a new identity, that of a woman whose pregnancy did not follow the expected path. Further, hospitalization offered women the opportunity to interact with others in similar difficult situations and, hence, feel less isolated.
Acute adaptation to low volume eccentric exercise.

PURPOSE Many symptoms of eccentric muscle damage can be substantially reduced if a similar eccentric bout is repeated within several weeks of the initial bout. The purpose of this study was to determine whether a nondamaging, low repetition, low volume eccentric exercise bout could also provide a protective/adaptive effect. METHODS Subjects were assigned to a control (CON), eccentric exercise (ECC), or low volume familiarized eccentric exercise group (LV+ECC). Before the study, the LV+ECC group performed six maximal eccentric contractions during two familiarization sessions. The main eccentric bout targeted the elbow flexor muscle group and consisted of 36 maximal eccentric contractions. Muscle soreness, upper arm girth, elbow angle, creatine kinase activity, isometric torque, and concentric and eccentric torque at 0.52 and 3.14 rad.s-1 were assessed 0, 1, 2, 3, 4, 7, and 10 d postexercise. RESULTS No evidence of muscle damage was observed as a result of the low volume eccentric bouts. Nevertheless, with the exception of muscle soreness and concentric torque, all variables recovered more rapidly in the LV+ECC group (P < 0.05). CONCLUSION Adaptation to eccentric exercise can occur in the absence of significant muscle damage. Exposure to a small number of nondamaging eccentric contractions can significantly improve recovery after a subsequent damaging eccentric bout. Furthermore, this adaptation appears to be mode-specific and not applicable to concentric contractions.
Dose-Dependent Changes in Influenza Virus-Infected Dendritic Cells Result in Increased Allogeneic T-Cell Proliferation at Low, but Not High, Doses of Virus

ABSTRACT During the acute phase of infection with influenza A virus, the degree of lymphopenia correlates with severity of disease. Factors that contribute to T-cell activation during influenza virus infection may contribute to this observation. Since the immune response is initiated when dendritic cells (DC) interact with T cells, we have established an in vitro system to examine the effects of influenza virus infection on DC function. Our results show that allogeneic T-cell proliferation was dependent on the dose of A/PR/8/34 used to infect DC, with enhanced responses at low, but not high, multiplicities of infection. The lack of enhancement at high virus doses was not primarily due to the increased rate of DC apoptosis, but required viral replication and neuraminidase (NA) activity. Clusters that formed between DC or between DC and T cells were also dependent on the viral dose. This change in cellular interaction may oppose T-cell proliferation in response to DC infected with high doses of PR8, since the increased contact between DC resulted in the exclusion of T cells. The enhanced alloreactive T-cell response was restored by neutralization of transforming growth factor β1 (TGF-β1). It is likely that NA present on viral particles released from DC infected with high doses of PR8 activates TGF-β1. Future studies will determine the mechanism by which TGF-β1 modifies the in vitro T-cell response and address the contribution of this cytokine to the lymphopenia observed in severe disease.
Percutaneous CT-guided multisampling core needle biopsy of thoracic lesions.

OBJECTIVE The purpose of our study was to evaluate the diagnostic yield and the complication rate of percutaneous CT-guided coaxial 18-gauge (1.25-mm diameter) multisampling (five samples) core needle biopsy (CNB) of suspected thoracic lesions. MATERIALS AND METHODS The records of 75 consecutive patients (29 women, 46 men; age range, 33-92 years) who underwent percutaneous CT-guided adjustable coaxial 18-gauge multisampling (five samples) CNB of a suspected thoracic lesion (eight mediastinal lesions, two chest wall lesions, two pleural lesions, and 63 intrapulmonary lesions) were reviewed. RESULTS Ninety-seven percent (73/75) of CNB specimens were considered adequate for a specific diagnosis by the histopathology staff. Diagnostic yield was 97% (95% confidence interval, 91-99%) (72/74) (number of correct diagnoses obtained at CNB / number of definitive diagnoses). There were 61 malignant lesions and 11 benign lesions. There was no false-negative result when CNB was considered adequate for a specific diagnosis by the histopathology staff. Pneumothorax occurred in 19% (12/63 intrapulmonary lesions). One patient required placement of a chest tube. Minor postbiopsy hemoptysis occurred and resolved spontaneously in 11% (7/63) of patients. CONCLUSION Percutaneous CT-guided coaxial multisampling large CNB of suspected thoracic lesions, in a mainly cancer-based population, is an accurate procedure for a specific histologic diagnosis and has a low rate of complications.
The pat1 protein kinase controls transcription of the mating‐type genes in fission yeast.

The developmental programme of fission yeast brings about a transition from mitotic cell division to the dormant state of ascospores. In response to nitrogen starvation, two cells of opposite mating type conjugate to form a diploid zygote, which then undergoes meiosis and sporulation. This differentiation process is characterized by a transcriptional induction of the mating‐type genes. Conjugation can also be induced in pat1‐ts mutants by a shift to a semi‐permissive temperature. The pat1 gene encodes a protein kinase, which also functions further downstream in the developmental pathway controlling entry into meiosis. We have analysed transcriptional induction of mating‐type genes in various strains‐‐with and without a pat1‐ts allele. In wild‐type cells of P‐mating type derepression occurs in two rounds. First, the mat1‐Pc gene is induced in response to nitrogen starvation. Mutants in the map1 gene are defective in this process. In the following step the mat1‐Pm gene is expressed in response to a pheromone signal generated by cells of M mating type. Both these controls are derepressed in the pat1‐ts mutant at semipermissive temperature. Previous work has established that expression of the mating‐type genes in the zygote leads to complete loss of pat1 protein kinase activity causing entry into meiosis. Thus, pat1 can promote its own inactivation. We suggest a model according to which a stepwise inactivation of pat1 leads to sequential derepression of the processes of conjugation and meiosis.
The Transcription Factor Repertoire of Flt3+ Hematopoietic Stem Cells

Hematopoietic stem cells maintain the development of all mature blood cells throughout life due to their sustained self-renewal capacity and multilineage differentiation potential. During development into specific cell lineages, the options of stem cells and multipotent progenitor cells become increasingly restricted concomitant with a successive decline in self-renewal potential. Here we describe an Flt3+CD11b+ multipotent progenitor that can be amplified in vitro with a specific combination of cytokines to yield homogeneous populations in high cell numbers. By employing gene expression profiling with DNA microarrays, we studied the transcription factor repertoire of Flt3+CD11b+ progenitors and related it to the transcription factor repertoire of hematopoietic stem cells and embryonic stem cells. We report here on overlapping and nonoverlapping expression patterns of transcription factors in these cells and thus provide novel insights into the dynamic networks of transcriptional regulators in embryonic and adult stem cells. Additionally, the results obtained open the perspective for elucidating lineage and ‘stemness’ determinants in hematopoiesis.
Molecular Epidemiology of Clostridium difficile Infection in a Major Chinese Hospital: an Underrecognized Problem in Asia?

ABSTRACT Clostridium difficile infection is almost unrecognized in mainland China. We have undertaken a study in a large Chinese teaching hospital in Changsha, Hunan, China, to identify cases of C. difficile, record patient characteristics, and define the molecular epidemiology with respect to ribotype distribution and cross-infection. Between April 2009 and February 2010, we examined fecal samples from 70 hospitalized patients with diarrhea who were receiving or had received antibiotics within the previous 6 weeks. Clinical information was collected and the samples were cultured for C. difficile retrospectively. Isolates were ribotyped, and multiple-locus variable-number tandem-repeat assay (MLVA) subtyping was performed on clusters of the same ribotype. The mean age of patients from whom C. difficile was cultured was 58 years, with only 4/21 patients aged >65 years. All patients, with a single exception, had received a third-generation cephalosporin and/or a quinolone antibiotic. Twenty-one isolates of C. difficile were recovered, and seven different ribotypes were identified, the dominant types being 017 (48%), 046 (14%), and 012 (14%). We identified two clusters of cross-infection with indistinguishable isolates of ribotype 017, with evidence of spread both within and between wards. We have identified C. difficile as a possibly significant problem, with cross-infection and a distinct ribotype distribution, in a large Chinese hospital. C. difficile may be underrecognized in China, and further epidemiological studies across the country together with the introduction of routine diagnostic testing are needed to ascertain the size of this potentially significant problem.
Reference and cut-off values for serum ferritin, mean cell volume, and hemoglobin to diagnose iron deficiency in infants aged 9 to 12 months.

BACKGROUND The number of different laboratory tests and reference values are used to diagnose iron deficiency, but there is no agreement regarding the diagnostic criteria for infants. Aim of study. To establish reference values for serum ferritin, mean cell volume, and hemoglobin in infants aged from 9 to 12 months in Estonia and to evaluate the diagnostic characteristics of serum ferritin, mean cell volume, and hemoglobin in the diagnosis of iron deficiency. METHODS Altogether 195 healthy infants aged 9-12 months participated in the study. They were randomly selected out of 300 families from seven different counties from all over Estonia. Serum ferritin, hemoglobin, soluble transferrin receptor (sTfR) levels and mean cell volume were measured. The best cut-off values for serum ferritin, mean cell volume, and hemoglobin to diagnose iron deficiency, defined by sTfR>2.45 mg/L (n=25), were determined by receiver operating characteristic curves. RESULTS The mean and reference values (5th and 95th centiles) for ferritin was 24 microg/L (4-55), 73 fl (68-80) for mean cell volume, and 112 g/L (101-128) for hemoglobin. The best cut-off values to diagnose iron deficiency were <10.9 microg/L for serum ferritin (sensitivity of 83% and specificity of 80%), <71 fl for mean cell volume (86% and 83%, respectively), and <107 g/L for hemoglobin (67% and 87%, respectively). The sensitivity and specificity of serum ferritin and mean cell volume in the diagnosis of iron deficiency were better than those of hemoglobin. CONCLUSION For the diagnosis of iron deficiency in infants aged 9-12 months, the cut-off values of <10.9 microg/L and <71 fl should be used for serum ferritin and mean cell volume, respectively.
Sodium-glucose cotransporter 2 inhibitors and cardiovascular outcomes

ABSTRACT Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of cardiovascular (CV) morbidity and mortality. Furthermore, many patients with T2DM have comorbidities that are risk factors for CV disease. While intensive glucose control reduces the risk of diabetic microvascular complications, its relationship to CV outcomes remains unclear. Consequently, the management of CV risk factors in patients with T2DM is complex, and factors other than blood glucose must be considered. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a class of oral glucose-lowering agents, are associated with reductions in blood pressure and body weight, in addition to decreasing hyperglycemia, and therefore have the potential to reduce CV risk in patients with T2DM. The clinical trial results of SGLT2 inhibitors regarding CV safety and outcomes are discussed, including data from the recently published EMPA-REG OUTCOME study. This trial was the first dedicated CV outcomes study to demonstrate that a glucose-lowering agent lowered CV mortality and all-cause mortality, and reduced hospitalization for heart failure in patients with T2DM at high risk of CV events.
Transplanted LDL and mannose‐6‐phosphate receptor internalization signals promote high‐efficiency endocytosis of the transferrin receptor.

The internalization signals of several constitutively recycling receptors have recently been identified as regions of four or six amino acids that include an aromatic residue, usually tyrosine. Here, we show that transplanted signals from the low density lipoprotein receptor (LDLR) and cation‐independent mannose‐6‐phosphate receptor (Man‐6‐PR) promote rapid internalization of the transferrin receptor (TR), directly establishing that recognition signals are interchangeable, self‐determined structural motifs and that signals from type I membrane proteins are active in a type II receptor. We also show that the chemical and spatial patterns of critical residues in both four‐ and six‐residue internalization motifs are consistent with a tight turn structure. A six‐residue LDLR signal is needed for activity in TR, suggesting that an amino‐terminal aromatic side chain is obligatory. In contrast, the carboxy‐terminal aromatic side chain in the TR signal can be replaced by a large hydrophobic residue. Thus, internalization signals apparently require an aromatic amino‐terminal residue and either an aromatic or large hydrophobic carboxy‐terminal residue rather than a conserved tyrosine per se. Consistent with this conclusion, predicted internalization signals from the poly‐Ig receptor, YSAF, and asialoglycoprotein receptor (ASGPR) subunit H1, YQDL, also promote internalization of TR.
Evaluating spatial and temporal effects of accidents likelihood using random effects panel count model

The application of Poisson and Negative Binomial models has been widely used in modeling road accident count. However, several restrictions on the data have been highlighted in the use of such model. Among which are the assumption of variance and mean to be equal, no serial correlation exist and the effect of unmeasured variables that may affect the dependent variable or so called the unobserved heterogeneity. Hence, an appropriate solution to this issue is to treat the data in a form time series and cross section data panel using panel model approach. This study analyzes the number of road accidents occurrences using time series cross sectional data for 14 states in Malaysia. The random effects negative binomial (RENB) model and the cross-sectional negative binomial (NB) models are examined. The models were developed to identify the contributing factors that affect the number of road accidents in Malaysia. We examine various factors associated with road accidents occurrence that includes the registered vehicle in the state, the amount of rainfall, the number of rainy day, time trend and the monthly effect of seasonality. Various model specifications were estimated. The specification comparisons indicate benefit from using the NB model when spatial and temporal effects are unobserved. While the RENB model appears to be more superior in the present case of accident count when incorporating temporal and cross sectional variations in which offers advantages in model flexibility.
Neurotoxicity of Pneumolysin, a Major Pneumococcal Virulence Factor, Involves Calcium Influx and Depends on Activation of p38 Mitogen-Activated Protein Kinase

Neuronal injury in bacterial meningitis is caused by the interplay of host inflammatory responses and direct bacterial toxicity. We investigated the mechanisms by which pneumolysin, a cytosolic pneumococcal protein, induces damage to neurons. The toxicity after exposure of human SH-SY5Y neuroblastoma cells and hippocampal organotypic cultures to pneumolysin was time- and dose-dependent. Pneumolysin led to a strong calcium influx apparently mediated by pores on the cell membrane formed by the toxin itself and not by voltage-gated calcium channels. Buffering of intracellular calcium with BAPTA-AM [1, 2-bis (o-aminophenoxy) ethane N, N, N', N'-tetraacetic acid tetra(acetomethoxyl) ester] improved survival of neuronal cells following challenge with pneumolysin. Western blotting revealed increased phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) as early as 30 min after challenge with pneumolysin. SB 203580, a potent and selective inhibitor of p38 MAPK, rescued human neuronal cells from pneumolysin-induced death. Inhibition of the mitochondrial permeability transition pore using bongkrekate and caspase inhibition also improved survival following challenge with the toxin. Modulation of cell death pathways activated by pneumolysin may influence the outcome of pneumococcal meningitis.
The predictive value of ultrasound findings in the management of thyroid nodules.

BACKGROUND Thyroid nodules are a common medical problem, but whether fine-needle aspiration cytology (FNAC) is mandated for smaller non-palpable nodules, is controversial. AIM To evaluate whether ultrasonographic features of thyroid nodules are associated with histological malignancy, and to identify useful criteria for clinical decision-making. DESIGN Prospective observational study. METHODS From January 1991 to September 2004, 5198 patients were referred to our hospital for ultrasound evaluation of thyroid nodules. Overall, 7455 nodules (diameters from 6 to 100 mm) were examined; 2865 (38.4%) were <10 mm in diameter. All patients with suspicious or malignant cytology underwent surgery. RESULTS Of the 349 nodules undergoing surgery, 284 were malignant. The prevalence of cancer was slightly higher in nodules>or=10 mm in diameter vs. those<10 mm (5.5% vs. 3.0%, p<0.01). However, histological type and local aggressiveness were largely independent of nodule size. Microcalcifications (72.2% vs. 28.7%; p<0.001; OR 6.4, 95%CI 4.9-8.4), blurred margins (52.8% vs. 18.8%; p<0.001; OR 4.8, 95%CI 3.8-6.1), solid hypoechoic appearance (80.6% vs. 52.4%; p<0.001; OR 3.8, 95%CI 2.8-5.1), size>or=10 mm (77.4% vs. 64.9%; p<0.001; OR 1.9, 95%CI 1.4-2.5) and intranodular vascular pattern type 2 (61.6% vs. 49.7%; p<0.001; OR 1.6, 95%CI 1.2-2.0) were all significantly more frequent in malignant than in benign nodules. These associations were similar when large and small nodules were analysed separately. DISCUSSION No single parameter, including nodule size, satisfactorily identifies a subset of patients to be electively investigated by FNAC, although several may be useful in this regard.
Characterization of genes involved in molybdenum transport in Azotobacter vinelandii

Expression of alternative nitrogenases in Azotobacter vinelandii is repressed by molybdenum. Two strains with Tn5 insertion mutations showed alternative nitrogenase‐dependent diazotrophic growth in the presence of Mo. The mutations were in a region which contained four open reading frames (ORFs 1–4). The genetic structure and predicted products of ORFs 2, 3 and 4 are typical of the membrane‐associated elements of the ATP‐binding cassette (ABC) superfamily of transport systems. The products of 0RF3 and 0RF4 are homologous with the products of the Escherichia coli genes chlD and the partially sequenced chlJ, respectively, both of which are implicated in molybdenum transport. ORF1, which is in the relative position of bacterial permease genes commonly specifying periplasmic binding proteins, encodes a 29 kDa protein with a novel primary structure. It lacks a potential signal sequence, and its C‐terminal half consists of a tandem repeat of a segment which is homologous with the Mr 7 kDa molybdenum‐pterin binding protein Mop from Clostridium pasteurianum. This suggests that a substituted pterin may be involved in the initial capture or early metabolism of molybdenum.