Miracle-dz/UniFAR-FTUs huggingface dataset:
Hydrophobic environment is a key factor for the stability of thermophilic proteins

The stability of thermophilic proteins has been viewed from different perspectives and there is yet no unified principle to understand this stability. It would be valuable to reveal the most important interactions for designing thermostable proteins for such applications as industrial protein engineering. In this work, we have systematically analyzed the importance of various interactions by computing different parameters such as surrounding hydrophobicity, inter‐residue interactions, ion‐pairs and hydrogen bonds. The importance of each interaction has been determined by its predicted relative contribution in thermophiles versus the same contribution in mesophilic homologues based on a dataset of 373 protein families. We predict that hydrophobic environment is the major factor for the stability of thermophilic proteins and found that 80% of thermophilic proteins analyzed showed higher hydrophobicity than their mesophilic counterparts. Ion pairs, hydrogen bonds, and interaction energy are also important and favored in 68%, 50%, and 62% of thermophilic proteins, respectively. Interestingly, thermophilic proteins with decreased hydrophobic environments display a greater number of hydrogen bonds and/or ion pairs. The systematic elimination of mesophilic proteins based on surrounding hydrophobicity, interaction energy, and ion pairs/hydrogen bonds, led to correctly identifying 95% of the thermophilic proteins in our analyses. Our analysis was also applied to another, more refined set of 102 thermophilic–mesophilic pairs, which again identified hydrophobicity as a dominant property in 71% of the thermophilic proteins. Further, the notion of surrounding hydrophobicity, which characterizes the hydrophobic behavior of residues in a protein environment, has been applied to the three‐dimensional structures of elongation factor‐Tu proteins and we found that the thermophilic proteins are enriched with a hydrophobic environment. The results obtained in this work highlight the importance of hydrophobicity as the dominating characteristic in the stability of thermophilic proteins, and we anticipate this will be useful in our attempts to engineering thermostable proteins. © Proteins 2013. © 2012 Wiley Periodicals, Inc.
Human T‐cell leukemia virus type I infection in hemodialysis patients

Human T‐cell leukemia virus Type I (HTLV‐I) has been detected in a high proportion of individuals in Kumamoto prefecture (Kyushu) and Okinawa, where adult T‐cell leukemia (ATL) is more likely to occur. The seroprevalence of antibody to HTLV‐I was evaluated in hemodialysis patients and healthy individuals in the ATL endemic area. The prevalence of antibody to HTLV‐I in 13,329 healthy controls was 3.6%, compared with 19.7% in 949 chronic hemodialysis patients. The prevalence of hemodialysis patients was significantly higher (P < 0.01) than that in healthy individuals. Of 681 blood transfused patients who had undergone hemodialysis, 153 (22.5%) were seropositive, compared with 34 (12.7%) of the 268 who had not received the blood transfusion. The incidence was higher in dialysis patients who had been transfused than in those who had never received blood transfusions. Immune defects associated with uremia may have predisposed the patients to HTLV‐I infection. Repeated antigenic stimulation from multiple infectious agents may have also played a role. The findings suggest an association between maintenance hemodialysis and HTLV‐I infection, which can not be explained solely by blood or blood products.
Transport Infrastructure and Poverty Reduction in Vietnam

Julia Banwatt is a 2014 Master of Public Policy Candidate at the School of Public Policy and Governance. Julia holds a Bachelor of Science with a specialization in Biology from Dalhousie University. Her academic interests include policy issues relating to literacy and education, health and science, and international development. The first part of this two-part paper is a case study of Vietnam that examines the contribution of rural transportation infrastructure improvements to the remarkable success of Vietnam’s Poverty Reduction Strategy. The second part of the paper examines transport infrastructure policy and situates the Vietnamese case in existing transport policy literature. It highlights areas in which lessons learned in Vietnam are generalizable to other parts of the world and concludes that well-designed transport policy has the potential to be a highly effective tool for addressing poverty.
The effect of acute dichlorodiphenyltrichloroethane exposure on hypermethylation status and down‐regulation of p53 and p16INK4a genes in rat liver

The aim of the study was to investigate the early effect of acute dichlorodiphenyltrichloroethane (DDT) exposure on the methylation status of the promoter region of two tumor suppressor genes: p53 and p16INK4a (p16) in rat liver. We analyzed their transcript and protein expression profiles concurrently with the examination of transcriptional and protein expression levels of DNA (cytosine‐5)‐methyltransferase 1 (Dnmt1). Male Wistar rats were treated with a single dose of DDT (57 mg kg−1 of body weight) and the methylation status of p53 and p16 genes was examined after 24 h using methylation‐sensitive restriction analysis—MSRA. The obtained results indicate that DDT induced alternations in methylation of the promoter region in both p53 and p16 genes. In all the tested samples, the promoter CpG islands of p53 (−261, −179, and −450) were methylated within 100% as compared to control samples (0%). The methylation status of the p16 promoter (−11 and +77) was also altered due to exposure to DDT. Methylated cytosines were detectable in 75% of the tested DNA samples. The Real‐time PCR and western blot analyses showed a decrease in mRNA and protein levels of p53, respectively, which was related to the increase in DNA synthesis. These relationships were also observed for mRNA and protein expressions of p16, although to a slighter extent. We also showed that hypermethylation in the promoter region of both tumor suppressor genes was consistent with an increased Dnmt1 mRNA level, and this relationship was further confirmed at the protein level of DNMT1. Concluding, our data suggests that epigenetically mediated changes in gene expression may play an important role in the mechanism of DDT toxicity, including carcinogenic action. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 584–592, 2016.
Melatonin maintains mitochondrial membrane potential and attenuates activation of initiator (casp‐9) and effector caspases (casp‐3/casp‐7) and PARP in UVR‐exposed HaCaT keratinocytes

Abstract: Melatonin is a recognized antioxidant with high potential as a protective agent in many conditions related to oxidative stress such as neurodegenerative diseases, ischemia/reperfusion syndromes, sepsis and aging. These processes may be favorably affected by melatonin through its radical scavenging properties and/or antiapoptotic activity. Also, there is increasing evidence that these effects of melatonin could be relevant in keratinocytes, the main cell population of the skin where it would contribute to protection against damage induced by ultraviolet radiation (UVR). We therefore investigated the kinetics of UVR‐induced apoptosis in cultured keratinocytes characterizing the morphological and mitochondrial changes, the caspases‐dependent apoptotic pathways and involvement of poly(ADP‐ribose) polymerase (PARP) activation as well as the protective effects of melatonin. When irradiated with UVB radiation (50 mJ/cm2), melatonin treated, cultured keratinocytes were more confluent, showed less cell blebbing, more uniform shape and less nuclear condensation as compared to irradiated, nonmelatonin‐treated controls. Preincubation with melatonin also led to normalization of the decreased UVR‐induced mitochondrial membrane potential. These melatonin effects were followed by suppression of the activation of mitochondrial pathway‐related initiator caspase 9 (casp‐9), but not of death receptor‐dependent casp‐8 between 24 and 48 hr after UVR exposure. Melatonin down‐regulated effector caspases (casp‐3/casp‐7) at 24–48 hr post‐UV irradiation and reduced PARP activation at 24 hr. Thus, melatonin is particularly active in UV‐irradiated keratinocytes maintaining the mitochondrial membrane potential, inhibiting the consecutive activation of the intrinsic apoptotic pathway and reducing PARP activation. In conclusion, these data provide detailed evidence for specific antiapoptotic mechanisms of melatonin in UVR‐induced damage of human keratinocytes.
Rheolytic thrombectomy with distal filter embolic protection as adjunctive therapies to high‐risk saphenous vein graft intervention

Percutaneous intervention of saphenous vein graft (SVG), especially those with heavy atherothrombotic load, presents high risk for distal embolization and no‐reflow. Using the distal filters alone may occasionally be disadvantageous because of the large debris burden and the inability to assess the underlying culprit lesions and vessel size accurately. We present a case of intervention of an occluded SVG using a combination of rheolytic thrombectomy and distal filter embolic protection as a pretreatment before stenting. This strategy has the potential to reduce further the risk of no‐reflow and to provide visualization for proper assessment of the underlying anatomy especially in clot‐laden vessels. Catheter Cardiovasc Interv 2004;61:202–205. © 2004 Wiley‐Liss, Inc.
Oxygen uptake in relation to body weight in a Hillstream fish Glyptothorax telchitta (Ham.)

Oxygen uptake (VO 2 ) through the gills of a hill-stream fish Glyptothorax telchitta from the Saptakoshi river (Nepal) has been studied in relation to different body weights. The oxygen uptake was determined at 24.0±1°C using a cylindrical glass respirometer with continuous water flow system. The aquatic oxygen uptake through the gills increased from 1.048 to 8.115 mlO 2 kg -1 . h -1 within the body weight range of 3.215 to 31.355 g. A fish of 17.052 g average body weight consumes 4.461 mlO 2 -1 . h -1 . The relation between oxygen uptake (VO 2 ) and body weight was determined by performing regression analysis using logarithmic transformation. It has been found that with a unit increase in body weight, the oxygen uptake per unit time (mlO 2 h -1 ) increases by a power of 0.930 showing significant positive correlation whereas, the weight specific oxygen uptake decreases by a power of 0.070 showing significant but negative correlation. DOI: http://dx.doi. org/10.3126/njbs.v1i0. 7464 Nepalese Journal of Biosciences 1: 11-18 (2011)
In Vitro Expression of Structural Defects in the Lecithin-Cholesterol Acyltransferase Gene (*)

Classic LCAT deficiency (CLD) and fish eye disease (FED) are two clinically distinct syndromes, associated with defects in the lecithin-cholesterol acyltransferase (LCAT) gene resulting in total (CLD) or partial (FED) enzyme deficiency. In order to investigate the underlying molecular mechanisms that lead to different phenotypic expression in CLD and FED, LCAT mutants associated with either CLD (LCAT, LCAT, and LCAT) or FED (LCAT, LCAT, LCAT, LCAT, LCAT, and LCAT) were expressed in vitro in human embryonic kidney 293 cells and characterized with respect to LCAT expression and enzyme activity. Evaluation of mutant LCAT gene transcription by Northern blot analysis demonstrated LCAT mRNA of normal size and concentration. Although all constructs gave rise to similar intracellular LCAT mass, the amount of enzyme present in the media for LCAT, LCAT, and LCAT was reduced to less than 10% of normal, suggesting that these mutations disrupted LCAT secretion. Western blot analysis of cell culture media containing wild type or mutant LCAT demonstrated the presence of a single normal-sized band of 67 kDa. The ability of the different enzymes to esterify free cholesterol in high density lipoprotein-like proteoliposomes (α-LCAT-specific activity) was reduced to less than 5% of normal for CLD mutants LCAT and LCAT and FED mutants LCAT, LCAT, LCAT, and LCAT, whereas that of LCAT, LCAT, and LCAT ranged from 45 to 110% of control. Although most FED mutant LCAT enzymes retained the ability to esterify free cholesterol present in α- and β-lipoproteins of heat-inactivated plasma, esterification was undetectable in all CLD mutants (LCAT, LCAT, and LCAT). In contrast, all mutant enzymes retained the ability to hydrolyze the water soluble, short-chained fatty acid substrate p-nitrophenolbutyrate. In summary, our studies establish the functional significance of nine LCAT gene defects associated with either FED or CLD. Characterization of the expressed LCAT mutants identified multiple, overlapping functional abnormalities that include defects in secretion and/or disruption of enzymic activity. All nine LCAT mutants retained the ability to hydrolyze the water-soluble PNPB substrate, indicating intact hydrolytic function. Based on these studies we propose that mutations in LCAT residues 147, 156, 228 (CLD) and 10, 123, 158, 293, 300, and 347 (FED) do not disrupt the functional domain mediating LCAT phospholipase activity, but alter structural domains involved in lipid binding or transesterification.
Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome.

The Smith-Lemli-Opitz syndrome (SLOS; also known as "RSH syndrome" [MIM 270400]) is an autosomal recessive multiple malformation syndrome due to a defect in cholesterol biosynthesis. Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and typically have low serum cholesterol levels. On the basis of this biochemical abnormality, it has been proposed that mutations in the human sterol Delta7-reductase (7-DHC reductase; E.C.1.3.1.21) gene cause SLOS. However, one could also propose a defect in a gene that encodes a protein necessary for either the expression or normal function of sterol Delta7-reductase. We cloned cDNA encoding a human sterol Delta7-reductase (DHCR7) on the basis of its homology with the sterol Delta7-reductase from Arabidopsis thaliana, and we confirmed the enzymatic function of the human gene product by expression in SLOS fibroblasts. SLOS fibroblasts transfected with human sterol Delta7-reductase cDNA showed a significant reduction in 7-DHC levels, compared with those in SLOS fibroblasts transfected with the vector alone. Using radiation-hybrid mapping, we show that the DHCR7 gene is encoded at chromosome 11q12-13. To establish that defects in this gene cause SLOS, we sequenced cDNA clones from SLOS patients. In three unrelated patients we have identified four different mutant alleles. Our results demonstrate both that the cDNA that we have identified encodes the human sterol Delta7-reductase and that mutations in DHCR7 are responsible for at least some cases of SLOS.
cDNA clones for the ecdysone‐inducible polypeptide (EIP) mRNAs of Drosophila Kc cells

The ecdysone‐inducible polypeptides (EIPs) 28, 29 and 40 were identified previously as polypeptides whose synthesis is stimulated early in the ecdysone response of Drosophila Kc cells. We have now shown, using two‐dimensional gels, that each of these EIPs consists of three species differing in pI, and all stimulated by ecdysone. Translations and hybrid‐arrested translations indicated that the poly(A)+ EIP mRNAs increase ˜10‐fold in abundance during the first 4 h of ecdysone treatment. By a differential screen of a cDNA library we have identified cDNA clones corresponding to all three EIPs. Two kinds of clones were isolated: one hybridizes to the EIP 40 mRNA(s); the second hybridizes to the mRNA(s) encoding all the EIPs 28 and 29. The EIP 28/29 and EIP 40 loci detected by these clones are each present at single sites on the polytene chromosomes and each is at or in the vicinity of an ecdysone‐regulated puff.
Structure and Function in Rhodopsin

An increase in fluorescence is observed upon light activation of bovine rhodopsin. The rate of increase is monoexponential (t1/2 = 15.5 min) at 20°C in 0.1% lauryl maltoside, pH 6.0, and parallels the rate of decay of metarhodopsin II. We show that the increase in fluorescence is due to the release of free retinal, which no longer quenches the tryptophan fluorescence. An extrinsic fluorescence reporter group, pyrene maleimide, attached to bovine rhodopsin also shows an increase in pyrene fluorescence on illumination. The rate of increase in pyrene fluorescence matches the rate of increase in tryptophan fluorescence. This result has been used to develop a micromethod, requiring on the order of 1 μg of rhodopsin, for measurement of metarhodopsin II decay. An Arrhenius plot derived from the fluorescence assay shows the energy of activation barrier for retinal release from rhodopsin to be 20.2 kcal/mol in 0.1% dodecyl maltoside at pH 6.0.
Surface Electrocardiogram Predictors of Sudden Cardiac Arrest.

BACKGROUND Heart disease is a major cause of death in industrialized nations, with approximately 50% of these deaths attributable to sudden cardiac arrest. If patients at high risk for sudden cardiac arrest can be identified, their odds of surviving fatal arrhythmias can be significantly improved through prophylactic implantable cardioverter defibrillator placement. This review summarizes the current knowledge pertaining to surface electrocardiogram (ECG) predictors of sudden cardiac arrest. METHODS We conducted a literature review focused on methods of predicting sudden cardiac arrest through noninvasive electrocardiographic testing. RESULTS Several electrocardiographic-based methods of risk stratification of sudden cardiac arrest have been studied, including QT prolongation, QRS duration, fragmented QRS complexes, early repolarization, Holter monitoring, heart rate variability, heart rate turbulence, signal-averaged ECG, T wave alternans, and T-peak to T-end. These ECG findings have shown variable effectiveness as screening tools. CONCLUSION At this time, no individual ECG finding has been found to be able to adequately stratify patients with regard to risk for sudden cardiac arrest. However, one or more of these candidate surface ECG parameters may become useful components of future multifactorial risk stratification calculators.
The Effect of Dietary and Exercise Interventions on Body Weight in Prostate Cancer Patients: A Systematic Review

Prostate cancer prognosis may therefore be improved by maintaining healthy weight through diet and physical activity. This systematic review looked at the effect of diet and exercise interventions on body weight among men treated for prostate cancer. MEDLINE, EMBASE, CINAHL, and Cochrane Library databases were searched from the earliest record to August 2013. Randomized controlled trials of diet and exercise interventions in prostate cancer patients that reported body weight or body composition changes were included. A total of 20 trials were included in the review. Because of the heterogeneity of intervention components, a narrative review was conducted. Interventions were categorized as diet (n = 6), exercise (n = 8), or a combination of both diet and exercise (n = 6). The sample size ranged from 8 to 155 and the duration from 3 wk to 4 yr. Four diet interventions and 1 combined diet and exercise intervention achieved significant weight loss with mean values ranging from 0.8 kg to 6.1 kg (median 4.5 kg). Exercise alone did not lead to weight loss, though most of these trials aimed to increase fitness and quality of life rather than decrease body weight. Diet intervention, alone or in combination with exercise, can lead to weight loss in men treated for prostate cancer.
Report on microbial aggregation (clustering) by 2QR-complex polysaccharides

Pathogenic microorganisms have developed tools to breach the natural host defense system to colonize and invade our tissues. The majority of microbial problems are initiated by adhesion of harmful microorganisms to human epithelial surfaces (skin and mucosa) (1, 2). To effectively bind to host tissue surfaces, many microorganisms possess multiple adhesin proteins on their outer surface. These adhesins bind to polysaccharide groups that are present on receptor molecules at the surface of our epithelial cells (3).
Allergic sensitisation to common antigens among Ethiopian asthmatic patients

This review was conducted with the aim of identifying the allergic sensitisation patterns to common antigens among asthmatic patients and to assess for possible sociodemographic correlates. Records were reviewed retrospectively for patients who had undergone skin prick testing as part of a routine care for asthma between June 2012 and June 2013 at the Pulmonology clinic of Ayder Referral Hospital, Mekelle, Ethiopia. The records of 47 patients were eligible for the study and were hence reviewed. The mean age of these patients was 41.3 years. Skin prick testing was positive for one or more antigens in 53.2% of patients. The three most common positive antigen tests were for Dermatophagoides farinae (27.7% patients), Dermatophagoides pteronyssinus (25.5%), and dog hair (12.8%). The conclusions from the study are that allergic sensitisation among Ethiopian asthmatic patients was common and that house dust mites were the most commonest sensitisers. Further studies are recommended to investigate sensitisation for additional allergens and to better assess correlations with risk factors.
Intra-Industry Trade and National Entry Policy

This paper analyses entry policy in an open economy using an intra-industry trade model. Entry policy is the policy by which a government regulates the number of firms in the country. Implementation of this policy is accompanied by subsidies. In this paper, only one country implements this policy and the other country does not enforce any regulations. We show that the national entry policy makes both countries better off than they would be at the market equilibrium if a certain condition is met. This means that national entry policy is not necessarily a beggar-thy-neighbour policy. Copyright 2006 Blackwell Publishing Ltd
Unstable and Thalassemic α Chain Hemoglobin Variants: A Cause of Hb H Disease and Thalassemia Intermedia

We report an update of the α-globin gene point mutations resulting in structural modification associated with an α-thalassemia (α-thal) phenotype. These variants, barely symptomatic in the heterozygous state, are either unstable due to folding defects and/or defects in binding to α-hemoglobin stabilizing protein (AHSP). This is predicted to result in precipitation of the unstable α chains or Hb variant, a concomitant decrease in the overall quantity of normal α-globin in the red cells and a potential degree of anemia and possibly, hemolysis. Genotype/phenotype correlation and potential genetic risk in combination with common or less common α-thal defects are discussed.