Miracle-dz/UniFAR-FTUs huggingface dataset:
State-dependent Conformations of the Translocation Pathway in the Tyrosine Transporter Tyt1, a Novel Neurotransmitter:Sodium Symporter from Fusobacterium nucleatum*

The gene of a novel prokaryotic member (Tyt1) of the neurotransmitter:sodium symporter (NSS) family has been cloned from Fusobacterium nucleatum. In contrast to eukaryotic and some prokaryotic NSSs, which contain 12 transmembrane domains (TMs), Tyt1 contains only 11 TMs, a characteristic shared by ∼70% of prokaryotic NSS homologues. Nonetheless upon heterologous expression in an engineered Escherichia coli host, Tyt1 catalyzes robust Na+-dependent, highly selective l-tyrosine transport. Genetic engineering of Tyt1 variants devoid of cysteines or with individually retained endogenous cysteines at positions 18 or 238, at the cytoplasmic ends of TM1 and TM6, respectively, preserved normal transport activity. Whereas cysteine-less Tyt1 was resistant to the inhibitory effect of sulfhydryl-alkylating reagents, N-ethylmaleimide inhibited transport by Tyt1 variants containing either one or both of the endogenous cysteines, and this inhibition was altered by the substrates sodium and tyrosine, consistent with substrate-induced dynamics in the transport pathway. Our findings support a binding model of Tyt1 function in which an ordered sequence of substrate-induced structural changes reflects distinct conformational states of the transporter. This work identifies Tyt1 as the first functional bacterial NSS member putatively consisting of only 11 TMs and shows that Tyt1 is a suitable model for the study of NSS dynamics with relevance to structure/function relationships of human NSSs, including the dopamine, norepinephrine, serotonin, and γ-aminobutyric acid transporters.
Race-ethnicity differences in folic acid intake in women of childbearing age in the United States after folic acid fortification: findings from the National Health and Nutrition Examination Survey, 2001-2002.

BACKGROUND Neural tube defects are serious birth defects of the brain and spinal cord. Up to 70% of neural tube defects can be prevented by the consumption of folic acid by women before and early during pregnancy. OBJECTIVE The objective was to examine folic acid intake in women of childbearing age in the United States. DESIGN We analyzed nutrient intake data reported by 1685 nonpregnant women aged 15-49 y who participated in the National Health and Nutritional Examination Survey, 2001-2002. RESULTS The adjusted geometric mean consumption of folic acid from fortified foods was 128 microg/d (95% CI: 123, 134 microg/d) in nonpregnant women. Eight percent (95% CI: 5.8%, 11.0%) of nonpregnant women reported consuming >or=400 microg folic acid/d from fortified foods. This proportion was lower among non-Hispanic black women (5.0%) than among non-Hispanic white (8.9%) or Hispanic (6.8%) women. A smaller percentage of non-Hispanic black (19.1%) and Hispanic (21%) women than of non-Hispanic white women (40.5%) consumed >or=400 microg folic acid from supplements, fortified foods, or both, in addition to food folate, as recommended by the Institute of Medicine to reduce the frequency of neural tube defects. CONCLUSIONS Most nonpregnant women of childbearing age in the United States reported consuming less than the recommended amount of folic acid. The proportion with low daily folic acid intake was significantly higher in non-Hispanic black and Hispanic women than in non-Hispanic white women. At the present level of folic acid fortification, most women need to take a folic acid-containing dietary supplement to achieve the Institute of Medicine recommendation.
Insulin Resistance and &bgr;-Cell Dysfunction in Relation to Cardiometabolic Risk Patterns

Context Insulin resistance (IR) and β-cell dysfunction are two major defects synergistically inducing the development of diabetes and related cardiometabolic disorders. Objective To investigate the independent and joint associations of IR and β-cell dysfunction with the prevalence of multiple cardiometabolic disorders, including obesity, central obesity, diabetes, dyslipidemia, and hypertension. Design and Settings A nationally representative population of 93,690 Chinese adults. Main Outcome Measures IR and β-cell dysfunction were assessed by the homeostasis model assessment of IR (HOMA-IR) and of β-cell function (HOMA-B), respectively. Results High HOMA-IR was independently associated with high prevalence of all estimated cardiometabolic disorders, whereas low HOMA-B was independently associated with high prevalence of diabetes, dyslipidemia, and hypertension but low prevalence of obesity and central obesity. When examined jointly, the associations of HOMA-IR and HOMA-B with multiple cardiometabolic disorders showed different patterns with varying magnitudes. The strongest joint associations were observed for diabetes, with low HOMA-B associated with high prevalence of diabetes regardless of HOMA-IR; joint associations with dyslipidemia and hypertension prevalence appeared to be additive and had moderate changing trends; and low HOMA-B was not associated with high prevalence of obesity or central obesity unless combined with high HOMA-IR. Conclusion IR was associated with more prevalent cardiometabolic disorders than was β-cell dysfunction, and combinations of IR and β-cell dysfunction showed distinct relations with cardiometabolic risk patterns in Chinese adults.
Benchmarking Attribute Selection Techniques for Discrete Class Data Mining

Data engineering is generally considered to be a central issue in the development of data mining applications. The success of many learning schemes, in their attempts to construct models of data, hinges on the reliable identification of a small set of highly predictive attributes. The inclusion of irrelevant, redundant, and noisy attributes in the model building process phase can result in poor predictive performance and increased computation. Attribute selection generally involves a combination of search and attribute utility estimation plus evaluation with respect to specific learning schemes. This leads to a large number of possible permutations and has led to a situation where very few benchmark studies have been conducted. This paper presents a benchmark comparison of several attribute selection methods for supervised classification. All the methods produce an attribute ranking, a useful devise for isolating the individual merit of an attribute. Attribute selection is achieved by cross-validating the attribute rankings with respect to a classification learner to find the best attributes. Results are reported for a selection of standard data sets and two diverse learning schemes C4.5 and naive Bayes.
Association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk.

BACKGROUND Although the effects of individual foods or nutrients on the development of diseases and their risk factors have been investigated in many studies, little attention has been given to the effect of overall dietary patterns. OBJECTIVE Our objective was to examine the associations of 2 major dietary patterns, Western and prudent, with biomarkers of obesity and cardiovascular disease (CVD) risk. DESIGN We used factor analysis to define major dietary patterns for a subsample of men (n = 466) from the Health Professionals Follow-up Study by using dietary information collected from food-frequency questionnaires (FFQs) in 1994. We calculated partial correlation coefficients between pattern scores and biomarker values adjusted for age, smoking status, energy and alcohol intake, physical activity, hours of television watching, and body mass index. RESULTS We derived 2 major dietary patterns that were generally reproducible over time. The first pattern (prudent) was characterized by higher intakes of fruit, vegetables, whole grains, and poultry. The second pattern (Western) was characterized by higher intakes of red meats, high-fat dairy products, and refined grains. Using pattern scores from 1994 and adjusting for potential confounders, we found significant positive correlations between the Western pattern and insulin, C-peptide, leptin, and homocysteine concentrations, and an inverse correlation with plasma folate concentrations. The prudent pattern was positively correlated with plasma folate and inversely correlated with insulin and homocysteine concentrations. CONCLUSION Major dietary patterns are predictors of plasma biomarkers of CVD and obesity risk, suggesting that the effect of overall diet on CVD risk may be mediated through these biomarkers.
Microstructure of Titania‐Opacified Porcelain Enamels

The microstructure of TiO2−opacified porcelain enamels was examined by optical microscopy and by transmission electron microscopy. The mosaic pattern found appears to correspond to the positions of the frit particles from which the enamel was made. Significant differences were observed in the crystallization behavior of adjoining frit particles. There is evidence that rutile grows from frit particle surfaces, whereas anatase is body-nucleated. The anatase-to-rutile inversion is a ripening process rather than a phase transformation. Processes occurring during the firing of a TiO2 enamel include crystallization from single-phase glass, crystallization from multiphase glass, and a ripening process.
Studies in calcium metabolism. I. The calciuretic effect of dietary protein.

Data are presented from several studies concerning the effect of varying protein intake on urinary calcium excretion, A markedly positive correlation was found between protein ingestion and calciunia. Although the response was not linear, varying protein intake from 0 g to 90 g N per day results in approximately an 800% increase in calcium excretion, irrespective of calcium intake. This effect of protein occurred in all our studies of individuals, and was also observed with pure L-amino acid mixtures. Am. J. ('lin. Nutr. 27: 584 -589, 1974. As early as 1920, Sherman (I) observed that adding meat to the diet caused a urinary calcium increase in man; a similar effect was later noted by others (2-6). The increase in protein intake, due to the addition of meat to the diet was considered primarily responsible for this calciuretic effect. McCance et al. (7) further showed that the calciuretic effect could be induced by supplementing the diet with peptone, gluten. gelatin, or egg white. In most of these reports, only a few subjects were studied, and many components of the diet, other than calcium, were not balanced at varying levels of protein intake. A number of dietary factors besides protein have been shown to significantly affect the urinary calcium excretion (8- 11). The importance of these prior studies is, therefore, obscured because many dietary t'actors were not controlled. During the past few years. we have studied the metabolic responses to varying protein intake by using well-controlled formula diets. Because the effects of many dietary factors can be eliminated or minimized by these well- balanced formula diets, it is possible to make a critical evaluation of the effect of protein intake on urinary calcium excretion.
Immunolocalization of the Na+/H+exchanger isoform NHE2 in rat kidney.

Four Na+/H+exchangers (NHE1 to NHE4) have been detected in the kidney. Renal NHE2 expression sites have not been fully established. We have raised rabbit antisera against an oligopeptide related to the amino acids 652 to 661 of rat NHE2. Western blot analysis of plasma membrane fractions isolated from rat renal cortex showed that affinity-purified anti-NHE2 antibody detected an 85-kDa protein in apical but not in basolateral membranes. The labeling of this 85-kDa protein was specifically blocked by preincubation of the antibody with its monomeric peptide, indicating specific recognition. Indirect immunolabeling was performed on sections of paraformaldehyde-fixed rat kidney embedded in paraffin. Strong staining was seen in the apical membrane of cortical thick ascending limbs, distal convoluted tubules, and connecting tubules. Much weaker apical staining was found in medullary thick ascending limbs of Henle. In the inner medulla, some thin limbs were intensively labeled by the anti-NHE2 antibody. No staining could be detected in any segments of the proximal tubule and collecting duct.
Folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh.

BACKGROUND Indian Asian men residing in the United Kingdom have a higher prevalence of hyperhomocysteinemia than do their European counterparts. This has been largely attributed to dietary deficiencies in cobalamin associated with vegetarianism among these Indian Asians. OBJECTIVE We aimed to ascertain the prevalence of folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh. DESIGN Plasma concentrations of homocysteine, folate, and cobalamin and urinary concentrations of creatinine were assessed in 1650 adults in Bangladesh. RESULTS The prevalence of hyperhomocysteinemia (men: >11.4 micromol/L; women: >10.4 micromol/L) was markedly (P < 0.0001) greater among men (63%; x +/- SD: 15.3 +/- 9.5 micromol/L) than among women (26%; 9.5 +/- 4.7 micromol/L). Folate was lower (9.8 +/- 6.5 and 12.3 +/- 7.6 nmol/L, respectively), whereas cobalamin was higher (281 +/- 115 and 256 +/- 118 pmol/L, respectively) (P < 0.0001 for both) among men than among women. Folate explained 15% and cobalamin explained 5% of the variation in homocysteine concentrations. For men, folate (P = 0.005) and cobalamin (P = 0.03) were positively correlated with urinary creatinine. Smoking (P < 0.0003) and betelnut use (P < 0.0002) were independent negative predictors of folate. CONCLUSIONS Bangladeshi men have a high prevalence of hyperhomocysteinemia, which is more closely associated with folate than with cobalamin, although other factors, eg, smoking and betelnut use, may also contribute to its cause. The positive correlations between urinary creatinine and plasma folate and cobalamin were unanticipated and could suggest that, in marginal nutrition, these vitamins may be limiting for creatine biosynthesis.
Rapid reversal of the effects of the portal signal under hyperinsulinemic conditions in the conscious dog.

Experiments were performed on two groups of 42-h-fasted conscious dogs ( n = 6/group). Somatostatin was given peripherally with insulin (4-fold basal) and glucagon (basal) intraportally. In the first experimental period, glucose was infused peripherally to double the hepatic glucose load (HGL) in both groups. In the second experimental period, glucose (21.8 μmol ⋅ kg-1 ⋅ min-1) was infused intraportally and the peripheral glucose infusion rate (PeGIR) was reduced to maintain the precreating HGL in the portal signal (PO) group, whereas saline was given intraportally in the control (CON) group and PeGIR was not changed. In the third period, the portal glucose infusion was stopped in the PO group and PeGIR was increased to sustain HGL. PeGIR was continued in the CON group. The glucose loads to the liver did not differ in the CON and PO groups. Net hepatic glucose uptake was 9.6 ± 2.5, 11.6 ± 2.6, and 15.5 ± 3.2 vs. 10.8 ± 1.8, 23.7 ± 3.0, and 15.5 ± 1.1 μmol ⋅ kg-1 ⋅ min-1, and nonhepatic glucose uptake (non-HGU) was 29.8 ± 1.1, 40.1 ± 4.5, and 49.5 ± 4.0 vs. 26.6 ± 4.3, 23.2 ± 4.0, and 40.4 ± 3.1 μmol ⋅ kg-1 ⋅ min-1in the CON and PO groups during the three periods, respectively. Cessation of the portal signal shifted NHGU and non-HGU to rates similar to those evident in the CON group within 10 min. These results indicate that even under hyperinsulinemic conditions the effects of the portal signal on hepatic and peripheral glucose uptake are rapidly reversible.
Beyond MITF: Multiple transcription factors directly regulate the cellular phenotype in melanocytes and melanoma

MITF governs multiple steps in the development of melanocytes, including specification from neural crest, growth, survival, and terminal differentiation. In addition, the level of MITF activity determines the phenotype adopted by melanoma cells, whether invasive, proliferative, or differentiated. However, MITF does not act alone. Here, we review literature on the transcription factors that co‐regulate MITF‐dependent genes. ChIP‐seq studies have indicated that the transcription factors SOX10, YY1, and TFAP2A co‐occupy subsets of regulatory elements bound by MITF in melanocytes. Analyses at single loci also support roles for LEF1, RB1, IRF4, and PAX3 acting in combination with MITF, while sequence motif analyses suggest that additional transcription factors colocalize with MITF at many melanocyte‐specific regulatory elements. However, the precise biochemical functions of each of these MITF collaborators and their contributions to gene expression remain to be elucidated. Analogous to the transcriptional networks in morphogen‐patterned tissues during embryogenesis, we anticipate that the level of MITF activity is controlled not only by the concentration of activated MITF, but also by additional transcription factors that either quantitatively or qualitatively influence the expression of MITF‐target genes.
Translational Research in Alzheimer’s and Prion Diseases

Translational neuroscience integrates the knowledge derived by basic neuroscience with the development of new diagnostic and therapeutic tools that may be applied to clinical practice in neurological diseases. This information can be used to improve clinical trial designs and outcomes that will accelerate drug development, and to discover novel biomarkers which can be efficiently employed to early recognize neurological disorders and provide information regarding the effects of drugs on the underlying disease biology. Alzheimer’s disease (AD) and prion disease are two classes of neurodegenerative disorders characterized by incomplete knowledge of the molecular mechanisms underlying their occurrence and the lack of valid biomarkers and effective treatments. For these reasons, the design of therapies that prevent or delay the onset, slow the progression, or improve the symptoms associated to these disorders is urgently needed. During the last few decades, translational research provided a framework for advancing development of new diagnostic devices and promising disease-modifying therapies for patients with prion encephalopathies and AD. In this review, we provide present evidence of how supportive can be the translational approach to the study of dementias and show some results of our preclinical studies which have been translated to the clinical application following the ‘bed-to-bench-and-back’ research model.
Both hypothyroidism and hyperthyroidism increase plasma irisin levels in rats

Abstract Background A recently discovered hormone, irisin is accepted to be significantly involved in the regulation of body weight. Thyroid functions may be, directly or indirectly, associated with irisin. Aim The aim of the present study is to determine the effect of experimental thyroid dysfunction on irisin levels in rats. Methods The study registered 40 adult male Sprague-Dawley rats, which were allocated to groups as follows: 1. Control; 2. Hypothyroidism induced by injection of 10 mg/kg/day intraperitoneal propylthiouracil (PTU) for 3 weeks; 3. Hypothyroidism (PTU 2 weeks) + L-thyroxin (1.5 mg/kg/day for 1 week); 4. Hyperthyroidism induced in rats by 3-week thyroxin (0.3 mg/kg/day); 5. Hyperthyroidism + PTU. At the end of the study, blood samples were collected to quantify free triiodothyronine (FT3), free triiodothyronine (FT4) and irisin levels. Results FT3 and FT4 levels were reduced in hypothyroidism and were significantly elevated in hyperthyroidism (p < 0.001). Irisin values, on the other hand, were found to be elevated in both hypothyroidism and hyperthyroidism groups (p < 0.001). Conclusion The results of the study suggest that irisin values increase in thyroid dysfunction, hypo- and hyperthyroidism, and that when hypothyroidism is corrected by thyroxin administration and hyperthyroidism by PTU injection, plasma irisin values go back to normal.
Preconditioning reduces tissue complement gene expression in the rabbit isolated heart.

Both preconditioning and inhibition of complement activation have been shown to ameliorate myocardial ischemia-reperfusion injury. The recent demonstration that myocardial tissue expresses complement components led us to investigate whether preconditioning affects complement expression in the isolated heart. Hearts from New Zealand White rabbits were exposed to either two rounds of 5 min global ischemia followed by 10 min reperfusion (ischemic preconditioning) or 10 μM of the ATP-dependent K+(KATP) channel opener pinacidil for 30 min (chemical preconditioning) before induction of 30 min global ischemia followed by 60 min of reperfusion. Both ischemic and chemical preconditioning significantly ( P < 0.05) reduced myocardial C1q, C1r, C3, C8, and C9 mRNA levels. Western blot and immunohistochemistry demonstrated a similar reduction in C3 and membrane attack complex protein expression. The KATPchannel blocker glyburide (10 μM) reversed the depression of C1q, C1r, C3, C8, and C9 mRNA expression observed in the pinacidil-treated hearts. The results suggest that reduction of local tissue complement production may be one means by which preconditioning protects the ischemic myocardium.
Impact of Official Matches on Soccer Referees’ Power Performance

Abstract The evaluation of match officials’ neuromuscular performance is now an important consideration and the vertical jump test is considered suitable for assessing lower limb power, partly because it is directly related to refereeing. The aim of this study, therefore, was to determine the effect of soccer matches on match officials’ vertical jump performance by assessing various biomechanical variables. Eighteen field referees (FRs) and 36 assistant referees (ARs) who officiated in 18 official matches participated in this study. Before the match, at half time and immediately after the match, officials performed two countermovement jumps. Flight phase time (FT), maximum force production (MFpropulsion), time to production of maximum force (TMFpropulsion), production of maximum power (MP), maximum landing force (MFlanding) and time to stabilization (TTS) were calculated for all jumps. There was a tendency for match officials’ jumping performance to improve after matches than beforehand (FR: effect size (ES) = 0.19 ± 0.36, possibly trivial; AR: ES = 0.07 ± 0.17, likely trivial). There were also likely small and very likely moderate differences between FRs’ MP in pre-match and half-time jumps (ES = 0.46 ± 0.47) and in their pre- and post-match jumps (ES = 0.71 ± 0.48). These results indicate that refereeing soccer matches does not reduce vertical jump performance; the subsequent neuromuscular fatigue is not sufficient to affect landing technique.