Miracle-dz/UniFAR-FTUs huggingface dataset:
Sodium L-Glutamate-Induced Physiological Changes in Lactobacillus Brevis NCL912 During GABA Production Under Acidic Conditions

Previous studies showed that γ-Aminobutyric Acid (GABA) can protect some GABA-producing bacteria against acid stress through glutamate decarboxylation. However, the acid stress mechanism is a comprehensive network related to numerous genes and proteins. Other than the Glutamate Decarboxylase (GAD)/GABA antiporter system, limited information is available about the physiological modifications that occur in Lactobacillus brevis during GABA production under acidic conditions. Therefore, this study aims to investigate the physiological modifications that occur in a GABA-producing L. brevis NCL912 during GABA production under acidic conditions. The differential protein expression of L. brevis NCL912 under different culture conditions was determined by using proteome analysis. Eleven of the protein spots were identified by mass spectrometry. Among the 11 proteins, 10 were upregulated, whereas one was downregulated. The function of downregulated protein was unknown. The upregulated proteins were involved in stress response, protein synthesis, quorum sensing, glycolysis and membrane lipid synthesis. Stress response, protein synthesis, glycolysis-related proteins are general acid stress proteins, while LuxS-dependent quorum sensing system and membrane lipid synthesis-related proteins might be induced by sodium L-glutamate during GABA production under acid stress. In conclusion, sodium L-glutamate might trigger other acid-tolerance responses, except the GAD/GABA system in L. brevis NCL912 during GABA production under acidic conditions.
Subacute toxicity of urea herbicide, isoproturon, in male rats.

Isoproturon, a substituted phenylurea herbicide, was evaluated for its cumulative toxic effect on growth, organ weight and histomorphology of different organs in adult male rats. The compound (200, 400 and 800 mg/kg/day for 6 days/week), suspended in refined groundnut oil, was administered to rats p.o. for 7 and 10 weeks. There were no definite signs and symptoms of toxicity in treated rats but the herbicide significantly decreased the weekly body weight of rats at 800 mg/kg dose. Isoproturon, in all the three doses, increased the weight of liver in a dose-dependent manner. At 800 mg/kg dose, isoproturon increased the weight of kidney and heart, and decreased the weight of epididymis. Histopathological alterations in the organs were dose-dependent. Salient microscopic changes induced by isoproturon were hepatocellular degenerative changes and focal necrosis in liver, glomerular and tubular degeneration in kidney and haemosiderosis in spleen. Testis showed degeneration and desquamation of cells of germinal layers. Tubular lumens of testis and epididymis exhibited reduced number of spermatids and spermatozoa, respectively, indicating retardation of spermatogenesis.
Individualized analysis of differentially expressed miRNAs with application to the identification of miRNAs deregulated commonly in lung cancer tissues

&NA; Identifying differentially expressed microRNAs (DE miRNAs) between cancer samples and normal controls is a common way to investigate carcinogenesis mechanisms. However, for a DE miRNA detected at the population‐level, we do not know whether it is DE in a particular cancer sample. Here, based on the finding that the within‐sample relative expression orderings of miRNA pairs are highly stable in a particular type of normal tissues but widely disrupted in the corresponding cancer tissues, we proposed a method, called RankMiRNA, to identify DE miRNAs in each cancer tissue compared with its own normal state. Evaluated with pair‐matched miRNA expression profiles of cancer tissues and adjacent normal tissues for lung and liver cancers, RankMiRNA exhibited excellent performance. Finally, we exemplified an application of the individual‐level differential expression analysis by finding miRNAs DE in at least 90% lung cancer tissues, defined as common DE miRNAs of lung cancer. After identifying DE miRNAs for each of 991 lung cancer samples from The Cancer Genome Atlas with RankMiRNA, we found that hsa‐mir‐210 was upregulated, while hsa‐mir‐490 and hsa‐mir‐486 were downregulated in > 90% of the 991 lung cancer samples. These common DE miRNAs were validated in independent pair‐matched samples of cancer tissues and adjacent normal tissues measured with different platforms. In conclusion, RankMiRNA provides us a novel tool to find common and subtype‐specific miRNAs for a type of cancer, allowing us to study cancer mechanisms in a novel way.
Pregnancy Outcomes in Women With Diabetes—Lessons Learned From Clinical Research: The 2015 Norbert Freinkel Award Lecture

Among women with diabetes, the worst pregnancy outcome is seen in the subgroup of women with diabetic nephropathy. Development of severe preeclampsia that leads to early preterm delivery is frequent. Predictors and pathophysiological mechanisms for the development of preeclampsia among women with diabetes and observational studies that support antihypertension treatment for pregnant women with microalbuminuria or diabetic nephropathy preventing preeclampsia and early preterm delivery are presented here. Obtaining and maintaining strict glycemic control before and during pregnancy is paramount to prevent preterm delivery. The cornerstones of diabetes management are appropriate diet and insulin, although the risk of severe hypoglycemia always needs to be taken into account when tailoring a diabetes treatment plan. Pathophysiological mechanisms of the increased risk of hypoglycemia during pregnancy are explored, and studies evaluating the use of insulin analogs, insulin pumps, and continuous glucose monitoring to improve pregnancy outcomes and to reduce the risk of severe hypoglycemia in pregnant women with type 1 diabetes are reported. In addition to strict glycemic control, other factors involved in fetal overgrowth are explored, and restricting maternal gestational weight gain is a promising treatment area. The optimal carbohydrate content of the diet is discussed. In summary, the lessons learned from this clinical research are that glycemic control, gestational weight gain, and antihypertension treatment all are of importance for improving pregnancy outcomes in pregnant women with preexisting diabetes. An example of how to use app technology to share the recent evidence-based clinical recommendations for women with diabetes who are pregnant or planning pregnancy is given.
Single muscle fiber contractile properties in diabetic RAT muscle

Introduction: Diabetes is associated with accelerated loss of muscle mass and function. We compared the contractile properties of single muscle fibers in young rat soleus muscle of uncontrolled streptozotocin‐induced diabetic animals (n = 10) and nondiabetic controls (n = 10). Methods: Single fiber maximal force, shortening velocity, and power were assessed during maximal activation with calcium using the slack test 4 weeks after induction. Myosin heavy chain expression was determined using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Oxidized myosin levels were detected by analyzing protein carbonyls in muscle homogenates. All fibers expressed the type I myosin heavy chain isoform. Results: Diabetic rats had higher blood glucose (537 vs. 175 mg/dl; P < 0.001) and lower body weight (171 vs. 356 g; P < 0.001) than controls. Muscle fibers from diabetic rats showed smaller cross‐sectional area (1128 vs. 1812 μm2), lower maximal force (258 vs. 492 μN), and reduced absolute power (182 vs. 388 μN FL/s) (all P < 0.0001). No differences were seen in shortening velocity, specific force or specific power. Myosin carbonylation was higher (P < 0.01) in diabetic rats. Conclusions: After 4 weeks of untreated diabetes, there are significant alterations in muscle at the level of isolated single fibers and myosin protein, although some contractile properties seem to be protected. Muscle Nerve, 2015 Muscle Nerve 53: 958–964, 2016
All-elastomer in-plane MEMS capacitive tactile sensor for normal force detection

An all-elastomer microelectromechanical systems (MEMS) sensor to detect an applied normal force by measuring a change in capacitance was designed and fabricated; this is the first sensor of its kind to utilize in-plane conductive elastomer capacitors. Other works have demonstrated capacitive tactile sensors, but capacitors were oriented out-of-plane and often required more complex fabrication processes. This fabrication process uses silicon to mold and cure conductive and dielectric elastomers, which requires fewer steps and enables nonplanar electrode geometries. Experimental results for planar geometries matched a reduced order model for low strains (up to 15% strain) and a 10 μm dielectric gap resulted in a sensitivity of 85 fF/N. An “interdigitated” nonplanar electrode geometry was also fabricated and found to increase sensitivity by an order of magnitude (up to 1.1 pF/N) over basic “flat plate” electrodes.
Cost-effectiveness of free HIV voluntary counseling and testing through a community-based AIDS service organization in Northern Tanzania.

OBJECTIVES We evaluated the cost-effectiveness of fee-based and free testing strategies at an HIV voluntary counseling and testing (VCT) program integrated into a community-based AIDS service organization in Moshi, Tanzania. METHODS We waived the usual fee schedule during a 2-week free, advertised VCT campaign; analyzed the number of clients testing per day during prefree, free, and postfree testing periods; and estimated the cost-effectiveness of limited and sustained free testing strategies. RESULTS The number of clients testing per day increased from 4.1 during the prefree testing interval to 15.0 during the free testing campaign (P<.0001) and remained significantly increased at 7.1 (P<.0001) after resumption of the standard fees. HIV seroprevalence (16.7%) and risk behaviors were unchanged over these intervals. Modeled over 1 year, the costs per infection averted with the standard fee schedule, with a 2-week free VCT campaign, and with sustained free VCT year-round were $170, $105, and $92, respectively, and the costs per disability-adjusted life year gained were $8.72, $5.40, and $4.72, respectively. CONCLUSIONS The provision of free VCT enhances both the number of clients testing per day and its cost-effectiveness in resource-limited settings.
Low-Density Lipoprotein Receptor Gene Mutation Analysis and Structure–Function Correlation in an Omani Arab Family With Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal dominant disorder typified by elevated low-density lipoprotein cholesterol (LDL-C) levels caused by mutations in the LDL receptor (LDLR), apolipoprotein B (ApoB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Previously, we reported a novel mutation in the exon-3 of LDLR gene, observed in a 9-year-old Omani Arab female. Here, we investigated the mode of inheritance of this mutation and confirmed that FH in this family is due to mutation only in the LDLR and not PCSK9 and ApoB genes. Further, the effect of the mutation has been appraised in silico on the tertiary structure of LDLR. A model of the mutant LDLR has been constructed using the coordinates of the wild-type LDLR extracellular domain. Based on the model, we present a mechanistic justification behind the observed detrimental effect of the mutation on LDL-C levels.
The effect of pre‐operative methylprednisolone on early endothelial damage after total knee arthroplasty: a randomised, double‐blind, placebo‐controlled trial

We wished to evaluate whether inhibition of the systemic inflammatory response by a single pre‐operative dose of methylprednisolone reduced markers of early endothelial damage after fast‐track total knee arthroplasty. We randomly allocated 70 patients undergoing elective unilateral total knee arthroplasty (1:1) to receive either pre‐operative intravenous methylprednisolone 125 mg (methylprednisolone group) or isotonic saline (control group). All procedures were performed under spinal anaesthesia without a tourniquet, using a standardised multimodal analgesic regime. The outcomes included changes in Syndecan‐1 concentrations, a marker of glycocalyx degradation, markers of endothelial cell damage and activation (plasma soluble thrombomodulin and sE‐Selectin), and permeability by vascular endothelial growth factor, as well as C‐reactive protein concentrations. Blood samples were collected at baseline and 2 h, 6 h and 24 h after surgery, with complete sampling from 63 patients for analyses. Methylprednisolone significantly reduced markers of endothelial damage at 24 h following surgery compared with saline (methylprednisolone group vs. control group, adjusted means (SEM)) expressed by circulating Syndecan‐1: 11.6 (1.0) ng.ml−1 vs. 13.4 (1.1) ng.ml−1 p = 0.046; soluble thrombomodulin: 5.1 (0.1) ng.ml−1 vs. 5.7 (0.2) ng.ml−1, p = 0.009; sE‐Selectin: 64.8 (1.8) ng.ml−1 vs. 75.7 (1.9) ng.ml−1, p = 0.001, and vascular endothelial growth factor: 35.3 (2.7) ng.ml−1 vs. 58.5 (2.8) ng.ml−1, p < 0.001. The effect of the intervention increased with time for soluble thrombomodulin, sE‐Selectin and vascular endothelial growth factor, and was more pronounced in patients with high baseline values. Finally, methylprednisolone reduced the C‐reactive protein response 24 h postoperatively; 31.1 (1.1) mg.l−1 vs. 68.4 (1.1) mg.l−1, p < 0.001. Pre‐operative administration of methylprednisolone 125 mg reduced circulating markers of endothelial activation and damage, as well as the systemic inflammatory response (C‐reactive protein) early after fast‐track total knee arthroplasty. These findings may have a positive effect on surgical outcome, but require studies in major surgery.
Access to dental care among adults with physical and intellectual disabilities: residence factors.

BACKGROUND There is limited information about access and barriers to dental care among adults with disabilities. METHODS A mailed questionnaire survey of carers of 18-44-year-old South Australians with physical and intellectual disabilities (care recipients; n = 485) in family homes, community housing and institutions. Bivariate associations were tested using chi-square tests. Odds ratios (ORs) and 95 per cent confidence intervals (CI) were estimated for irregular dental visits (IDV). RESULTS Carers from family homes and community housing were more likely to report problems in obtaining dental care than those at institutions (p < 0.001). Lack of dentists with adequate skills in special needs dentistry (SND) was the most frequently reported problem for carers from family homes and community housing. IDV were less likely (p < 0.01) for care recipients in institutions and community housing than in family homes. After adjusting for care recipients' age, gender and disability, odds of IDV was lower in community housing (OR = 0.2, 95% CI = 0.1, 0.3) and in institutions (OR = 0.1, 95% CI = 0.04, 0.3) relative to family homes. CONCLUSIONS Care recipients in institutions and community housing had better access to dental care than those at family homes. The shortage of dentists in SND and treatment costs needs to be addressed.
Optimizing outcomes in patients with hepatitis C virus genotype 2 or 3

On-treatment predictors of response could be useful in optimizing treatment for patients with hepatitis C virus (HCV) genotype 2 or 3. Early virological response (EVR) has limited value as a predictor of response in genotype 2 or 3 patients, as it is achieved by 97% of this population. However, rapid virological response (RVR) measured at week 4 is a strong predictor of sustained virological response (SVR) in this group, and patients achieving an RVR may be suitable candidates for shorter treatment durations. Several small studies investigating the efficacy of shortened treatment durations in this population have been published; however, differences in study design have made their collective interpretation difficult. We discuss these studies, followed by a comparison of the data from ACCELERATE, the largest, randomized trial carried out to investigate abbreviated therapy in genotype 2 and 3 patients. The data confirm that RVR, and its use alongside significant baseline predictors, can assist in optimizing therapy. Patients achieving an RVR have high SVR rates and might be candidates for shorter treatment duration, particularly those displaying a low viral load at baseline; however, the need to consider the increased rate of relapse versus the benefits of abbreviated therapy must also be considered. Conversely, in patients who do not achieve an RVR there is evidence to suggest they may benefit from intensified therapy (longer therapy and/or increased doses). As in genotype 1 and 4 patients, response-guided therapy aims to optimize treatment outcomes for individuals, without compromising SVR rates.
Variable expression of activation‐linked surface antigens on human mast cells in health and disease

Summary: Mast cells (MC) are multipotent effector cells of the immune system. They contain an array of biologically active mediator substances in their granules. MC also express a number of functionally important cell surface antigens, including stem cell factor receptor (SCFR=kit=CD117), high affinity IgER (FcεRI), or C5aR (CD88). Respective ligands can induce or promote degranulation, migration, or cytokine production. Other integral surface molecules can mediate adhesion or cell aggregation. Recent data suggest that a number of critical molecules are variably expressed on the surface of human MC. In fact, depending on the environment (organ), stage of cell maturation, type of disease, and other factors, MC express variable amounts of activation‐linked antigens (CD25, CD63, CD69, CD88), cell recognition molecules (CD2, CD11, CD18, CD50, CD54), or cytokine receptors. At present, however, little is known about the mechanisms and regulation of expression of such antigens. The present article gives an overview of MC phenotypes in health and disease, and attempts to provide explanations for the phenotypic variability of MC.
Differential Gain of Closely Spaced Energy States in Quantum Dashes

Simple quasi-equilibrium model for quantum dash (QDash) active material is derived for closely spaced energy states. The model is used to study the differential gain of Qdash for different key parameters. Expressions for the electron and the hole occupation probabilities as a function of electron concentration are derived. The derived analytical model shows excellent agreement with numerical simulation. The differential gain of Qdash active layer is calculated for different doping concentration and different electron energy separation between adjacent states. We find that when the electron energy states are widely separated, the differential gain can be slightly enhanced at low-energy detuning by doping the dashes by p-type doing. On the other hand, our calculations reveal that when the electron energy states are close to each other, doping the dashes by either n-type or p-type concentration will not enhance the differential gain.
A potential role for Elf-1 in terminal transferase gene regulation

The terminal deoxynucleotidyltransferase (TdT) gene represents an attractive model for the analysis of gene regulation during an early phase of lymphocyte development. In previous studies, we identified a DNA element, termed D', which is essential for TdT promoter activity in immature lymphocytes, and two classes of D'-binding factors, Ikaros proteins and Ets proteins. Here, we report a detailed mutant analysis of the D' element which suggests that an Ets protein, rather than an Ikaros protein, activates TdT transcription. Since multiple Ets proteins are expressed in developing lymphocytes and are capable of binding to the D' element, DNA affinity chromatography was used to determine if one of the Ets proteins might bind to the D' element with a uniquely high affinity, thereby implicating that protein as a potential TdT activator. Indeed, one binding activity was greatly enriched in the high-salt eluates from a D' affinity column. Peptide microsequencing revealed that the enriched protein was Elf-1. Immunoblot analyses confirmed that in nuclear extracts, Elf-1 has a significantly higher affinity for the D' sequence than does another Ets protein, Ets-1. Transactivation and expression studies support the hypothesis that Elf-1 activates TdT transcription in immature T and B cells. Finally, a D' mutation which selectively reduces Elf-1 binding, but not the binding of other Ets proteins, was found to greatly reduce TdT promoter activity. Although Elf-1 previously had been implicated in the inducible activation of genes in mature T and B cells, our results suggest that it also plays an important role in regulating genes during an early phase of lymphocyte development.
The distribution of whole blood viscosity, its determinants and relationship with arterial blood pressure in the community: cross-sectional analysis from the Gutenberg Health Study

Background: Blood viscosity has a role in modulating cardiovascular homeostasis; changes in this parameter have been associated with cardiovascular mortality and morbidity. However, it remains unclear whether these changes are (1) involved in the pathophysiology of disease, (2) an epiphenomenon, or (3) the expression of counterregulatory mechanisms. We report data on the normal values of blood viscosity and its association with cardiovascular risk factors, prevalent cardiovascular disease, and blood pressure in a large population-based cohort study. Methods and results: Viscosity was calculated using validated formulae and its associations were explored in 15,010 participants (mean 55.0, min–max: 35–74 years old; 49.5% women) from the Gutenberg Health Study as well as in a subgroup of 3223 subjects (61.1% women, mean age 49.2, min–max 35–74 years old) without risk factors or self-reported cardiovascular disease. Age- and gender-adjusted mean values for viscosity were defined. Regression models showed a relationship between classical risk factors and blood viscosity measures; the overall R2 of the multiple linear regression model was however as low as 0.067 and 0.049 for high and low shear stress viscosity, respectively. After correction for cardiovascular risk factors, there was a very mild association between viscosity and prevalent coronary artery disease and heart failure. Systolic, mean and diastolic blood pressure increased with increasing blood viscosity after correction for age and gender. Conclusions: We provide reference values for viscosity in a population-based cohort. Blood viscosity decreases in older subjects and shows a very mild association with cardiovascular risk factors and prevalent disease in our cohort. There is a linear positive association between viscosity and blood pressure.