Miracle-dz/UniFAR-FTUs huggingface dataset:
Carnitine‐dependent metabolic activities in Saccharomyces cerevisiae: three carnitine acetyltransferases are essential in a carnitine‐dependent strain

L‐Carnitine is required for the transfer of activated acyl‐groups across intracellular membranes in eukaryotic organisms. In Saccharomyces cerevisiae, peroxisomal membranes are impermeable to acetyl‐CoA, which is produced in the peroxisome when cells are grown on fatty acids as carbon source. In a reversible reaction catalysed by carnitine acetyltransferases (CATs), activated acetyl groups are transferred to carnitine to form acetylcarnitine which can be shuttled across membranes. Here we describe a mutant selection strategy that specifically selects for mutants affected in carnitine‐dependent metabolic activities. Complementation of three of these mutants resulted in the cloning of three CAT encoding genes: CAT2, coding for the carnitine acetyltransferase associated with the peroxisomes and the mitochondria; YAT1, coding for the carnitine acetyltransferase, which is presumably associated with the outer mitochondrial membrane, and YER024w (YAT2), which encodes a third, previously unidentified carnitine acetyltransferase. The data also show that (a) L‐carnitine and all three CATs are essential for growth on non‐fermentable carbon sources in a strain with a disrupted CIT2 gene; (b) Yat2p contributes significantly to total CAT activity when cells are grown on ethanol; and that (c) the carnitine‐dependent transfer of activated acetyl groups plays a more important role in cellular processes than previously realised. Copyright © 2001 John Wiley & Sons, Ltd.
Alcohol Drinking Patterns and Differences in Alcohol-Related Harm: A Population-Based Study of the United States

Alcohol use and associated alcohol-related harm (ARH) are a prevalent and important public health problem, with alcohol representing about 4% of the global burden of disease. A discussion of ARH secondary to alcohol consumption necessitates a consideration of the amount of alcohol consumed and the drinking pattern. This study examined the association between alcohol drinking patterns and self-reported ARH. Pearson chi-square test (χ 2) and logistic regression analyses were used on data from the National Comorbidity Survey Replication (NCS-R). The NCS-R is a cross-sectional nationally representative sample. Data was obtained by face-to-face interviews from 9282 adults aged ≥18 years in the full sample, and 5,692 respondents in a subsample of the full sample. Results presented as odds ratio (OR) and 95% confidence intervals (95% CI). Alcohol drinking patterns (frequency of drinking, and drinks per occasion) were associated with increased risks of self-reported ARH; binge or “risky” drinking was strongly predictive of ARH than other categories of drinks per occasion or frequency of drinking; and men had significantly higher likelihood of ARH in relation to frequency of drinking and drinks per occasion. Findings provide evidence for public health practitioners to target alcohol prevention strategies at the entire population of drinkers.
Coupon Tests of Fibre Reinforced Plastics at Elevated Temperatures in Offshore Processing Environments

A programme of tests has been conducted to characterise the strength reduction of three GRP composite materials as a function of temperature and testing environment. The GRP materials and testing environments were selected to be of maximum relevance to the offshore industry. The materials were E-glass fibre reinforcement in matrices of three resins: two epoxies and phenolic. The testing environments were sea water and crude oil condensate. The temperature range tested was ambient to 150°C. The tests were performed on coupon specimens laminated using fibres in the form of woven mat. The fibres were aligned so as to allow testing in both fibre dominated and resin dominated failure modes. A novel environmental tensile testing facility was developed for this work, and this is described briefly. Results are presented for the strength of the three materials as a function of temperature in each failure mode when tested dry. These are then compared with equivalent results for the specimens tested in the liquid environments. This is the first reported measurement of GRP strength in liquid environments at these very high temperatures. It is demonstrated from the results that strength reduction is exhibited predominantly in the matrix dominated failure mode, though a small but significant strength reduction is also seen in the fibre dominated mode. Causes for these strength reductions are identified as lowered glass transition temperature and degradation of the glass and glass/resin interfaces respectively. The strength reductions for each combination of material and environment are quantified. Finally, appropriate limits to operating temperature are suggested for each material when used in an offshore environment.
Prosocial Involvement as a Positive Youth Development Construct: A Conceptual Review

This paper discusses the concept of prosocial involvement as a positive youth development construct. How prosocial involvement is defined and how the different theories conceptualize prosocial involvement are reviewed. Antecedents of prosocial involvement such as biological traits, personality, cognitive and emotional processes, socialization experience, culture, and their social context are examined. The relationship between prosocial involvement and adolescent developmental outcomes, together with strategies to promote prosocial involvement in adolescents, are discussed. Finally, directions for future research and practice are proposed.
Detection of submucosal gastric fundal varices with multi-detector row CT angiography

Background and aim: The diagnosis of submucosal fundal varices is challenging. Currently, endoscopy and endoscopic ultrasound (EUS) are considered most useful for this purpose. The aim of this study was to evaluate if multi-detector row CT (MDCT) angiography contributes to the diagnosis of submucosal fundal varices. Patients and methods: Twenty two patients with endoscopically suspected fundal varices were prospectively included in the study. All patients underwent EUS and MDCT angiography. Levels of agreement between EUS and MDCT angiography for the detection of submucosal and perigastric fundal varices were evaluated by three blinded independent readers. In addition, variceal size and location, as well as afferent and efferent vessels of the submucosal varices, were determined. Results: Good or excellent image quality of MDCT angiography was obtained in 21/22 patients (95%). Based on EUS, submucosal varices were detected in 16 of 22 patients (73%) and perigastric varices in 22/22 patients (100%). Using MDCT angiography, the presence of submucosal varices was confirmed in all of these 16 patients by all three readers. Perigastric varices were also confirmed in all 22 patients by all three readers. In addition, all three readers noted the presence of a submucosal varix in an additional patient which was not detected on initial EUS. MDCT angiography showed an excellent interobserver reliability with regard to variceal diameter (κ=0.90) and variceal location (κ=0.94). Based on MDCT angiography, afferent and efferent vessels of submucosal varices included the left gastric vein in 11 (65%), the posterior/short gastric veins in 15 (88%), gastrorenal shunts in 10 (59%), the left inferior phrenic vein in six (35%), and the left pericardiophrenic vein in six (35%) of 17 patients. Conclusions: MDCT angiography is equivalent to EUS in terms of detection and characterisation of fundal varices, in particular with regard to the distinction between submucosal and perigastric fundal varices.
Modulation of different K+ currents in Drosophila: a hypothetical role for the Eag subunit in multimeric K+ channels

We examined the role of the ether a go-go (eag) gene in modulation of K+ currents and the possibility of its protein product Eag as a subunit in the heteromultimeric assembly of K+ channels by voltage-clamp analysis of larval muscle membrane currents. Previous DNA sequence studies indicate that the eag gene codes for a polypeptide homologous to, but distinct from, the Shaker (Sh) K+ channel subunits (Warmke et al., 1991), and electrophysiological recordings revealed allele- specific effects of eag on four identified K+ currents in Drosophila larval muscles (Zhong and Wu, 1991). Further studies of eag alleles indicated that none of the eag mutations, including alleles producing truncated mRNA messages, eliminate any of the four K+ currents, and that the mutational effects exhibit strong temperature dependence. We found that both W7, an antagonist of Ca2+/calmodulin, and cGMP analogs modulated K+ currents and that their actions were altered or even abolished by eag mutations. These results suggest a role of eag in modulation of K+ currents that may subserve integration of signals at a converging site of the two independent modulatory pathways. The Sh locus is known to encode certain subunits of the IA channel in larval muscle. The existence of multiple eag and Sh alleles enabled an independent test of the idea of Eag as a K+ channel subunit by studying IA in different double-mutant combinations. An array of allele-specific interaction between eag and Sh was observed, which reflects a close association between the Sh and eag subunits within the IA channel. Taken together, our data strengthen the possibility that the eag locus provides a subunit common to different K+ channels. The role of the eag subunit for modulating channels, as opposed to that of Sh subunits required for gating, selectivity, and conductance of the channel, suggest a combinatorial genetic framework for generating diversified K+ channels.
Beneficial effects of Brassica juncea on cognitive functions in rats

Abstract Context. Brassica juncea (BJ; Linnaeus) Czern & Coss (Brassicaceae), commonly known as Indian mustard, are enriched in redox-active polyphenols with antidiabetic activities. Diverse other health benefits of this edible plant have been described in classical Ayurvedic texts. Objective: The reported experiments were designed to assess therapeutic potential of a methanol extract of BJ leaves for treatment of cognitive disorders associated with diabetes or caused by central cholinergic dysfunctions. Materials and methods: Elevated plus-maze and active- and passive-avoidance tests were used to assess anti-amnesic potentials of BJ (100, 200 and 400 mg/kg/day, p.o., for 10 days) in alloxan diabetic or scopolamine-challenged rats. Treatment effects on brain acetylcholinesterase (AChE), superoxide dismutase (SOD) and catalase (CAT) activities were quantified in behavioral tested animals. Results: Anti-amnesic efficacy of all three tested BJ doses against scopolamine-induced amnesia was almost equal in all behavioral tests. Such efficacy of the extract in diabetic rats was increased always with its increasing doses. All treatments of BJ dose dependently decreased the elevated level of AChE, and significantly increased the SOD and CAT levels in brain homogenates of scopolamine-challenged and diabetic rats. Minimal effective oral daily doses of BJ in all tests were 100 mg/kg/day for 10 consecutive days. Discussion and conclusion: Our observation indicates that BJ could be a therapeutic option for treatment of cognitive disorders associated with diabetes, or caused by cholinergic deficit and brain oxidative status. They also indicate that the bioactive constituents or mode of actions involved in observed effects of the extract in scopolamine-challenged or diabetic rats are most probably not the same.
Endurance Exercise Training in Orthostatic Intolerance: A Randomized, Controlled Trial

Orthostatic intolerance is a syndrome characterized by chronic orthostatic symptoms of light-headedness, fatigue, nausea, orthostatic tachycardia, and aggravated norepinephrine levels while standing. The aim of this study was to assess the protective effect of exercise endurance training on orthostatic symptoms and to examine its usefulness in the treatment of orthostatic intolerance. 2768 military recruits were screened for orthostatic intolerance by questionnaire. Tilt-table testing identified 36 cases of orthostatic intolerance out of the 2768 soldiers. Subsequently, 31 of these subjects with orthostatic intolerance entered a randomized, controlled trial. The patients were allocated randomly to either a “training” (3 months jogging) or a “control” group. The influence of exercise training on orthostatic intolerance was assessed by determination of questionnaire scores and tilt-table testing before and after intervention. After training, only 6 individuals of 16 still had orthostatic intolerance compared with 10 of 11 in the control group. The Fisher exact test showed a highly significant difference in diagnosis between the 2 groups (P=0.008) at the end of the study. Analysis of the questionnaire-score showed significant interaction between time and group (P=0.001). The trained subjects showed an improvement in the average symptom score from 1.79±0.4 to 1.04±0.4, whereas the control subjects showed no significant change in average symptom score (2.09±0.6 and 2.14±0.5, respectively). Our data demonstrate that endurance exercise training leads to an improvement of symptoms in the majority of patients with orthostatic intolerance. Therefore, we suggest that endurance training should be considered in the treatment of orthostatic intolerance patients.
FtsZ regulates frequency of cell division in Escherichia coli

Cell division is regulated so that it occurs only once per cell cycle. In Escherichia coli, a rod-shaped bacterium, division normally takes place at the center of the long axis of the cell; however, in the minicell mutant, division can also take place at the cell pole. Such divisions take place at the expense of normal divisions, resulting in an overall increase in nucleated cell length. We report here that increasing the level of FtsZ can completely suppress the cell length of the minicell mutant by increasing the frequency at which cell division events take place. This result suggests that the level of FtsZ controls the frequency of cell division in E. coli.
Effect of patellar taping on knee kinetics of patients with patellofemoral pain syndrome.

STUDY DESIGN Single-group repeated measures examining patients with patellofemoral pain syndrome. OBJECTIVE To examine the effect of McConnell patellar taping on single-leg vertical jump height and knee extensor moment and power during a vertical jump and lateral step-up. BACKGROUND Patellar taping is used by clinicians in an attempt to maximize knee extensor function during sporting activities and rehabilitation of patients with patellofemoral pain syndrome. No studies have examined the effect of patellar taping on vertical jump height and knee extensor moment and power during a maximal vertical jump or lateral step-up. METHODS AND MEASURES Fourteen women (24.4 +/- 5.8 years) with unilateral patellofemoral pain performed a single-leg vertical jump and lateral step-up during 4 knee conditions: patellar tape, placebo tape, no tape, and the uninvolved knee. Maximal knee extensor moment, knee power, and vertical jump height were measured for each condition using a force platform and motion analysis system. RESULTS Analysis of variance and post hoc analyses revealed a main effect for knee condition. The patellar tape condition resulted in a greater knee extensor moment (1.57 +/- 0.32 N.m/kg) and power (3.47 +/- 0.67 W/kg) than did the no-tape (1.31 +/- 0.39 N.m/kg and 2.79 +/- 1.21 W/kg) and placebo tape (1.33 +/- 0.30 N.m/kg and 2.70 +/- 0.99 W/kg) conditions. Additional analyses showed that the vertical-jump height was significantly greater in the uninvolved lower extremity (25.69 +/- 2.66 cm) compared with the patellar tape (23.33 +/- 4.22 cm), placebo tape (23.08 +/- 4.20 cm), and no-tape (23.45 +/- 4.54 cm) conditions. The patellar tape condition did not show a different vertical jump height than the placebo or no-tape conditions. CONCLUSIONS These results suggest that patellar taping compared with no tape may improve the knee extensor moment and power during weight-bearing activities such as the lateral step-up exercise and the vertical jump.
SDF-1/CXCR4 Signaling Preserves Microvascular Integrity and Renal Function in Chronic Kidney Disease

The progressive decline of renal function in chronic kidney disease (CKD) is characterized by both disruption of the microvascular architecture and the accumulation of fibrotic matrix. One angiogenic pathway recently identified as playing an essential role in renal vascular development is the stromal cell-derived factor-1α (SDF-1)/CXCR4 pathway. Because similar developmental processes may be recapitulated in the disease setting, we hypothesized that the SDF-1/CXCR4 system would regulate microvascular health in CKD. Expression of CXCR4 was observed to be increased in the kidneys of subtotally nephrectomized (SNx) rats and in biopsies from patients with secondary focal segmental glomerulosclerosis (FSGS), a rodent model and human correlate both characterized by aberration of the renal microvessels. A reno-protective role for local SDF-1/CXCR4 signaling was indicated by i) CXCR4-dependent glomerular eNOS activation following acute SDF-1 administration; and ii) acceleration of renal function decline, capillary loss and fibrosis in SNx rats treated with chronic CXCR4 blockade. In contrast to the upregulation of CXCR4, SDF-1 transcript levels were decreased in SNx rat kidneys as well as in renal fibroblasts exposed to the pro-fibrotic cytokine transforming growth factor β (TGF-β), the latter effect being attenuated by histone deacetylase inhibition. Increased renal SDF-1 expression was, however, observed following the treatment of SNx rats with the ACE inhibitor, perindopril. Collectively, these observations indicate that local SDF-1/CXCR4 signaling functions to preserve microvascular integrity and prevent renal fibrosis. Augmentation of this pathway, either purposefully or serendipitously with either novel or existing therapies, may attenuate renal decline in CKD.
Treatment of Intractable Childhood Epilepsy with High‐Dose Valproate

Summary: Forty‐six children with refractory epilepsy (12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 20 with undetermined epilepsy) were treated by high‐dose (serum level above 100 μg/ml) valproate (VPA) therapy. Monotherapy was used with 34 patients and two drugs with 12. Serum VPA concentrations ranged from 105.1 to 198.4 μg/ml. Assessment of initial response to treatment, after the serum level had reached the appropriate level, showed seizures to be completely controlled in 15 (32.6%) of 46 patients and improved in 12 (26.1%) (50% or more). Follow‐up of more than 6 months after the time of initial response showed control of seizures in 14 (30.4%) and improvement in 11 (23.9%). The initial effect on EEG was the disappearance of epileptic discharges in 3 (6.5%) of 46 patients and marked improvement in 15 (32.6%). Follow‐up revealed the disappearance of epileptic discharges in 7 (15.2%) and marked improvement in 9 patients (19.6%). High‐dose VPA therapy was especially effective for West syndrome and for epilepsy with continuous spike‐waves during slow‐wave sleep. Control of atypical absences and myoclonic seizures was relatively good. Hypofibrinogenemia and thrombocytopenia were sometimes encountered but these side effects were reversible with reduction of dosage.
Preclinical efficacy of Sym004, novel anti-EGFR antibody mixture, in esophageal squamous cell carcinoma cell lines

Epidermal growth factor receptor (EGFR) is a well-validated oncological target molecule for monoclonal antibody therapies and Sym004 is a novel anti-EGFR antibody mixture comprising two recombinant chimeric IgG1 antibodies against non-overlapping epitopes of EGFR. Because EGFR is highly expressed in the majority of esophageal squamous cell carcinomas (ESCCs), we investigated the efficacy of Sym004 in human ESCC cell lines. Forty eight ESCC cell lines were treated with three kinds of anti-EGFR antibodies (Sym004, cetuximab, and panitumumab). Genetic background was investigated by next generation sequencing. The internalization of anti-EGFR antibodies into ESCC cells and inhibition of the EGFR signaling cascade by anti-EGFR antibodies were investigated in vitro. Furthermore, growth inhibition by anti-EGFR antibody treatment was investigated in vitro and in vivo. Sym004 treatments were more effective at inducing EGFR internalization and degradation than the two other anti-EGFR antibodies. Sym004 was more sensitive significantly to cell lines with EGFR gene amplification than those without amplification (P = 0.002). Growth inhibition of Sym004 was greater than in that of cetuximab or panitumumab in vitro and in vivo. These studies showed that Sym004 exhibited antitumor activity in some ESCC cell lines in preclinical settings and warrant a clinical evaluation in patients with ESCC. EGFR amplification is a potential biomarker of response to Sym004.
Endometrial Cancer: What Is New in Adjuvant and Molecularly Targeted Therapy?

Endometrial cancer is the most common gynaecological cancer in western countries. Radiotherapy remains the mainstay of postoperative management, but accumulating data show that adjuvant chemotherapy may display promising results after staging surgery. The prognosis of patients with metastatic disease remains disappointing with only one-year survival. Progestins represent an effective option, especially for those patients with low-grade estrogen and/or progesterone receptor positive disease. Chemotherapy using the combination of paclitaxel, doxorubicin, and cisplatin is beneficial for patients with advanced or metastatic disease after staging surgery and potentially for patients with early-stage disease and high-risk factors. Toxicity is a point in question; however, the combination of paclitaxel with carboplatin may diminish these concerns. In women with multiple medical comorbidities, single-agent chemotherapy may be better tolerated with acceptable results. Our increased knowledge of the molecular aspects of endometrial cancer biology has paved the way for clinical research to develop novel targeted antineoplastic agents (everolimus, temsirolimus, gefitinib, erlotinib, cetuximab, trastuzumab, bevacizumab, sorafenib) as more effective and less toxic options. Continued investigation into the molecular pathways of endometrial cancer development and progression will increase our knowledge of this disease leading to the discovery of novel, superior agents.