Miracle-dz/UniFAR-FTUs huggingface dataset:
Monoclonal Antibodies against the Adeno-Associated Virus Type 2 (AAV-2) Capsid: Epitope Mapping and Identification of Capsid Domains Involved in AAV-2–Cell Interaction and Neutralization of AAV-2 Infection

ABSTRACT The previously characterized monoclonal antibodies (MAbs) A1, A69, B1, and A20 are directed against assembled or nonassembled adeno-associated virus type 2 (AAV-2) capsid proteins (A. Wistuba, A. Kern, S. Weger, D. Grimm, and J. A. Kleinschmidt, J. Virol. 71:1341–1352, 1997). Here we describe the linear epitopes of A1, A69, and B1 which reside in VP1, VP2, and VP3, respectively, using gene fragment phage display library, peptide scan, and peptide competition experiments. In addition, MAbs A20, C24-B, C37-B, and D3 directed against conformational epitopes on AAV-2 capsids were characterized. Epitope sequences on the capsid surface were identified by enzyme-linked immunoabsorbent assay using AAV-2 mutants and AAV serotypes, peptide scan, and peptide competition experiments. A20 neutralizes infection following receptor attachment by binding an epitope formed during AAV-2 capsid assembly. The newly isolated antibodies C24-B and C37-B inhibit AAV-2 binding to cells, probably by recognizing a loop region involved in binding of AAV-2 to the cellular receptor. In contrast, binding of D3 to a loop near the predicted threefold spike does not neutralize AAV-2 infection. The identified antigenic regions on the AAV-2 capsid surface are discussed with respect to their possible roles in different steps of the viral life cycle.
Improvement of Short- and Long-Term Outcomes for Very Low Birth Weight Infants: Edmonton NIDCAP Trial

OBJECTIVE: Our objective was to determine the impact of Newborn Individualized Developmental Care and Assessment Program (NIDCAP)-based care on length of stay of very low birth weight (VLBW) infants. Secondary outcome measures were days of ventilation, incidence of chronic lung disease, and 18-month neurodevelopmental outcomes. METHODS: This cluster-randomized, controlled trial took place in a large NICU in Canada, with follow-up evaluation at 18 months of age, from September 1999 to September 2004. One hundred VLBW singleton infants and 10 VLBW twin sets were assigned randomly to NIDCAP-based or control care, and 90% participated in follow-up assessments. The intervention was NIDCAP-based care (N = 56), that is, care by NIDCAP-educated staff members and behavioral observations. The control group (N = 55) received standard NICU care. Statistical analyses were adjusted for cluster randomization. Although the intervention was not blinded, the pediatricians making the decisions to discharge the infants were not involved in the study, and the follow-up staff members were blinded with respect to group. RESULTS: NIDCAP group infants had reduced length of stay (median: NIDCAP: 74 days; control: 84 days; P = .003) and incidence of chronic lung disease (NIDCAP: 29%; control: 49%; odds ratio: 0.42 [95% confidence interval: 0.18–0.95]; P = .035). At 18 months of adjusted age, NIDCAP group infants had less disability, specifically mental delay (NIDCAP: 10%; control: 30%; odds ratio: 0.25 [95% confidence interval: 0.08–0.82]; P = .017). CONCLUSION: NIDCAP-based care for VLBW infants improved short- and long-term outcomes significantly.
Gastric emptying after sleeve gastrectomy: statistical evidence of a controlled prospective study with gastric scintigraphy.

AIM Laparoscopic sleeve gastrectomy (LSG) is a stand-alone bariatric procedure, its feasibility and efficacy being confirmed by long-term data. The effect of the procedure is believed to be based on the gastric restriction and reduction of ghrelin. Nevertheless it remains still controversial the role of LSG on gastric emptying and the impact that this may have on weight loss outcomes. Our aim is to assess gastric emptying after LSG using gastric scintigraphy. METHODS For this prospective randomized study, 45 patients undergoing LSG at our Centre for the Multidisciplinary Treatment of Severe Obesity from April 2009 to April 2011 were enrolled and observed prospectively (Group A). The inclusion criteria followed the guidelines for bariatric surgery. All patients performed gastric emptying scintigraphy through a standard semisolid meal (250 kcal), marked with 0.5 mCiTc 99. Group A performed the exam before (A1) and after the operation (A2). A control group (Group B) included 20 patients undergoing scintigraphic assessment for other reasons. RESULTS LSG was performed following a standardized technique. No complications were observed. The scintigraphic study showed a reduced half-life tracer (A1 vs. A2: 80.4±16.5 min vs. 64.3±22 min P=0.06), without a significant difference. Comparing the two groups no differences occurred before operation (B vs. A1). Gastric emptying time resulted significatively reduced in group A2 rather than in group A1 and B. CONCLUSION Gastric motility plays a role in the pathogenesis of obesity. Our experience suggests that LSG reduces gastric emptying time, but further studies are necessary to reach statystical significativity.
Altered Distribution of Peripheral Blood Maturation-Associated B-Cell Subsets in Chronic Alcoholism.

BACKGROUND Although decreased counts of peripheral blood (PB) B cells-associated with an apparently contradictory polyclonal hypergammaglobulinemia-have been reported in chronic alcoholism, no information exists about the specific subsets of circulating B cells altered and their relationship with antibody production. Here, we analyzed for the first time the distribution of multiple maturation-associated subpopulations of PB B cells in alcoholism and its potential relationship with the onset of liver disease. METHODS PB samples from 35 male patients-20 had alcoholic hepatitis (AH) and 15 chronic alcoholism without liver disease (AWLD)-were studied, in parallel to 19 male healthy donors (controls). The distribution of PB B-cell subsets (immature/regulatory, naïve, CD27(-) and CD27(+) memory B lymphocytes, and circulating plasmablasts of distinct immunoglobulin-Ig-isotypes) was analyzed by flow cytometry. RESULTS Patients with AH showed significantly decreased numbers of total PB B lymphocytes (vs. controls and AWLD), at the expense of immature, memory, and, to a lesser extent, also naïve B cells. AWLD showed reduced numbers of immature and naïve B cells (vs. controls), but higher PB counts of plasmablasts (vs. the other 2 groups). Although PB memory B cells were reduced among the patients, the percentage of surface (s)IgA(+) cells (particularly CD27(-) /sIgA(+) cells) was increased in AH, whereas both sIgG(+) and sIgA(+) memory B cells were significantly overrepresented in AWLD versus healthy donors. Regarding circulating plasmablasts, patients with AH only showed significantly reduced counts of sIgG(+) cells versus controls. In contrast, the proportion of both sIgA(+) and sIgG(+) plasmablasts-from all plasmablasts-was reduced in AH and increased in AWLD (vs. the other 2 groups). CONCLUSIONS AH and AWLD patients display a significantly reduced PB B-cell count, at the expense of decreased numbers of recently produced immature/regulatory B cells and naïve B cells, together with an increase in Ig-switched memory B lymphocytes and plasmablasts, particularly of IgA(+) cells.
Current management of complete and partial molar pregnancy.

Molar pregnancy is composed of two separate entities, partial (PHM) and complete (CHM), which are distinct in terms of epidemiology, genetics, histopathology, clinical presentation and risk of persistent gestational trophoblastic tumor (GTT). The most common presenting symptom in patients with CHM is vaginal bleeding. Approximately half the patients with CHM show signs of exuberant trophoblastic growth, with uterine enlargement and high levels of human chorionic gonadotropin (hCG). In contrast, patients with PHM usually present as though they have an incomplete or missed abortion, with bleeding, small uteri and low hCG levels. Cytogenetically, all chromosomal material in CHM is derived from the male. Hence, no fetal parts are identified. In PHM, dispermy results in a triploid conceptus, in which an abnormal fetus is present and ultimately dies. The diagnosis of CHM is usually confirmed by sonography when a vesicular pattern is noted. The ultrasound pattern in PHM is less consistent and depends on careful measurement of the gestational sac. Patients with CHM with marked trophoblastic hyperplasia, elevated hCG levels and enlarged uteri can develop significant medical complications, which should be recognized early and treated aggressively. These include acute respiratory distress syndrome, hyperthyroidism, preeclampsia and theca lutein cysts. All molar pregnancies should be evacuated promptly following a definitive diagnosis. If the patient no longer wishes to preserve her fertility, a hysterectomy will reduce the risk of developing nonmetastatic GTT. Following evacuation, careful hCG monitoring is mandatory since it is the most reliable and sensitive method for the early detection of GTT. (ABSTRACT TRUNCATED AT 250 WORDS)
A New Tool to Measure Training Load in Soccer Training and Match Play

Abstract An accurate evaluation of training load is paramount for the planning and periodization of training. The aim of the present study was to evaluate the relationship between a new method to monitor training load in soccer (Visual Analogic Scale training load; VAS-TL), and two established heart rate-based methods (TRIMP and Edwards’ method). 51 soccer players (age 15.6±0.3 years) answered 2 questions to assess perceived exertion and fatigue (VAS1-TL, and VAS2-TL) after training sessions and official matches. Performance in the Yo-Yo tests, VAS scores and heart rate of training sessions and matches, and match activity were analysed. We found significant correlations (r=0.60–0.72; p<0.05) between VAS-TL, TRIMP, and the Edwards’ training load method, with the highest correlations achieved in the matches. Although the different methods to monitor training load were correlated with the distance covered during the match (r=0.53–0.78; p<0.05), only VAS1-TL was associated with high-intensity activities (r=0.43–0.54; p<0.05). The new VAS-based perceived exertion method to monitor training load is easy to apply and is sensitive to differences in positional role and physical capacity. Thus, the applied method may be used in addition to the usual training load methods, allowing for daily quantification of individual training load in soccer.
Dipeptidyl Peptidase (DPP) IV Inhibitor Attenuates Kidney Injury in Streptozotocin Induced Diabetic Rats

Dipeptidyl peptidase (DPP) IV inhibitors are likely beneficial for preventing diabetic complication and modulating glucagon-like peptide-1 receptor (GLP-1R) expression. The aim of this study was to determine if the DPP IV inhibitor, LAF237, has renoprotective qualities in streptozotocin-induced diabetic rats. Diabetic and non-diabetic rats were treated with an oral dose of 4 or 8mg/kg/day LAF237 or placebo for 24 weeks, and renal injury was observed by light and electron microscopy. We also assessed DPP IV activity, active GLP-1 level, cAMP and 8-OhdG excretion, and GLP-1R, cleaved caspase 3 and transforming growth factor (TGF)-β 1 expression. LAF237 significantly decreased proteinuria, albuminuria and urinary albumin/creatinine ratio, improved creatinine clearance, and dose-dependently inhibited interstitial expansion, glomerulosclerosis and the thickening of the glomerular basement membrane in diabetic rats. Notably, LAF237 markedly down-regulated DPP IV activity and increased active GLP-1 levels, which likely prevented oxidative DNA damage and renal cell apoptosis by activating the GLP-1R and modulating cAMP. Renoprotection was also associated with a reduction in TGF-β 1 overexpression. Our study suggests that DPP IV inhibitors may ameliorate diabetic nephropathy as well as reduce the overproduction of TGF-β 1. The observed renoprotection is probably attributable to inhibition of DPP IV activity, mimicking incretin action and activating the GLP-1R. primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism.
In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency.

BACKGROUND A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. OBJECTIVE In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. METHODS We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography-tandem mass spectrometry. RESULTS Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased by >8-fold. CONCLUSIONS Our findings provide strong evidence that coexisting carnitine deficiency masks some indicators of biotin deficiency and support the potential importance of the ratios of acylcarnitines arising from the acyl-CoA substrates and products for biotin-dependent carboxylases in detecting the biotin deficiency that is masked by coexisting carnitine deficiency.
Reduction of fertility and alteration of uterine pH in heifers fed excess ruminally degradable protein.

The objective of these studies was to elucidate the causes underlying the reduction of fertility associated with feeding of excess ruminally degradable protein to cattle. Holstein heifers were fed total mixed rations that either met (Normal) or exceeded (High) ruminally degradable protein requirements. In Exp. 1 heifers (n = 80) were inseminated at estrus after being fed the experimental diets for 4 wk. First-service conception rates were 82 and 61% for the Normal and High groups, respectively (P < .05). Plasma urea nitrogen (PUN) levels were elevated (10.2 +/- .17 vs 14.8 +/- .19 mg/dL) in the High group throughout the experiment (P < .05). In Exp. 2, heifers (n = 32) receiving the same diets as in Exp. 1 were fitted with catheters in a jugular vein, in the bladder, and in the uterus on either the day before expected estrus or d 6 after estrus. On estrus or d 7, plasma and urinary NH4 and urea nitrogen and uterine pH were determined at 4-h intervals for 24 h beginning just before feeding. Plasma NH4 was variable and did not differ between treatments or days of the estrous cycle. During the 24-h period, urinary urea nitrogen and PUN were elevated (P < .05) in the High groups and did not differ between days of the cycle. Urinary NH4 excretion was elevated (P < .05) during the 24-h period only in the High group on d 7. Uterine pH did not change over time after feeding. (ABSTRACT TRUNCATED AT 250 WORDS)
Rapamycin downregulates thymidylate synthase and potentiates the activity of pemetrexed in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) accounts for 80–85% of lung cancer cases, and almost half of newly diagnosed patients have metastatic disease. Pemetrexed is a widely used drug for NSCLC and inhibits several folate-dependent enzymes including thymidylate synthase (TS). Increased expression of TS confers resistance to pemetrexed in vitro and predicts poor response to pemetrexed. Rapamycin is an mTOR inhibitor and suppresses cap-dependent synthesis of specific mRNA species. Here, we show that the combination of rapamycin and pemetrexed synergistically inhibits proliferation of NSCLC cells. Although pemetrexed as a single agent induced TS, pretreatment with rapamycin suppressed pemetrexed-induced TS expression. In vivo, the combination of rapamycin and pemetrexed inhibited growth of NSCLC xenografts, which correlated with decreased mTOR activity and suppression of pemetrexed-induced TS expression. The ability of rapamycin to enhance the efficacy of pemetrexed and prevent TS expression has implications for the design of Phase I and/or Phase II NSCLC clinical trials with mTOR inhibitors in combination with pemetrexed.
A Modular Enhancer Is Differentially Regulated by GATA and NFAT Elements That Direct Different Tissue-Specific Patterns of Nucleosome Positioning and Inducible Chromatin Remodeling

ABSTRACT We investigated alternate mechanisms employed by enhancers to position and remodel nucleosomes and activate tissue-specific genes in divergent cell types. We demonstrated that the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene enhancer is modular and recruits different sets of transcription factors in T cells and myeloid cells. The enhancer recruited distinct inducible tissue-specific enhanceosome-like complexes and directed nucleosomes to different positions in these cell types. In undifferentiated T cells, the enhancer was activated by inducible binding of two NFAT/AP-1 complexes which disrupted two specifically positioned nucleosomes (N1 and N2). In myeloid cells, the enhancer was remodeled by GATA factors which constitutively displaced an upstream nucleosome (N0) and cooperated with inducible AP-1 elements to activate transcription. In mast cells, which express both GATA-2 and NFAT, these two pathways combined to activate the enhancer and generate high-level gene expression. At least 5 kb of the GM-CSF locus was organized as an array of nucleosomes with fixed positions, but the enhancer adopted different nucleosome positions in T cells and mast cells. Furthermore, nucleosomes located between the enhancer and promoter were mobilized upon activation in an enhancer-dependent manner. These studies reveal that distinct tissue-specific mechanisms can be used either alternately or in combination to activate the same enhancer.
Arenibacter antarcticus sp. nov., isolated from marine sediment.

A strictly aerobic, Gram-stain-negative, pale-golden, rod-shaped bacterium, designated as R18H21T, was isolated from marine sediment collected from the Ross Sea, Antarctica. Strain R18H21T grew at 4-40 °C (optimum 25 °C), at pH 6.3-9.2 (optimum 7.5-8.5) and in 0.5-6 % (w/v) NaCl (optimum 2 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain R18H21T belonged to the genus Arenibacter, with the highest similarity to two type strains, Arenibacter latericius KMM 426T (96.6 %) and Arenibacter certesii KMM 3941T (96.6 %), and lower similarities (95.2-95.9 %) to five other members of the genus Arenibacter. The major fatty acids were iso-C17 : 0 3-OH, Summed Feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), iso-C15 : 0, iso-C15 : 1 G. The major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and an unidentified phospholipid. The respiratory quinone of strain R18H21T was menaquinone-6. The DNA G+C content was 40.0 mol%. Based on phylogenetic, physiological and chemotaxonomic features, strain R18H21T has been classified as a novel species in the genus Arenibacter, for which the name Arenibacterantarcticus sp. nov. is proposed. The type strain of the novel species is R18H21T (=GDMCC 1.1159T=KCTC 52924T).
Effects of Valsalva Maneuver on Anterior Chamber Parameters and Choroidal Thickness in Healthy Chinese: An AS-OCT and SS-OCT Study.

PURPOSE This study concurrently evaluated the effects of the Valsalva maneuver (VM) on the anterior and posterior ocular biometric parameters in a healthy Chinese cohort. METHODS This prospective, cross-sectional study used anterior segment optical coherence tomography (AS-OCT) and swept-source optical coherence tomography (SS-OCT) to measure the anterior and posterior ocular biometric parameters before and during the VM. Sixty-three volunteers (126 eyes; 17 males and 46 females) were enrolled. The IOP, blood pressure (BP), and refractive error were recorded before and during a VM. RESULTS The mean IOP showed a statistically significant increase (from 13.86-14.25 mm Hg, P = 0.005), but the different layers of the retina and the choroidal thickness (CT) showed no significant changes. The anterior chamber parameters decreased sharply from the baseline, with a smaller angle opening distance (AOD500; from 0.35-0.31 mm, P < 0.001), AOD750 (from 0.44-0.39 mm, P = 0.007), trabecular-iris space area (TISA500; from 0.14-0.13 mm, P = 0.027), TISA750 (from 0.25-0.23 mm, P = 0.007), and anterior chamber volume (ACV; from 143.09-139.84 mm3P = 0.036). Regression analyses revealed an association between ΔIOP and the baseline IOP (β = 0.26 [0.15, 0.37], P < 0.001) and ΔACW (β = -3.24 [-5.65, -0.83], P = 0.008). CONCLUSIONS This study is the first to provide simultaneous evaluation of the effects of the VM on anterior and posterior ocular biometric parameters. The VM caused a significant IOP increase and narrowing of the angles in healthy subjects. However, it did not change the CT in the macular region. The relationship between IOP elevation and choroidal expansion during the VM needs further investigation.
Bronchial measurement with three-dimensional quantitative thin-section CT in patients with cystic fibrosis.

PURPOSE To prospectively compare bronchial measurements obtained with three-dimensional quantitative thin-section computed tomography (CT) with those obtained with thin-section CT scores in the assessment of the severity of pulmonary cystic fibrosis (CF). MATERIALS AND METHODS Ethics committee approval was obtained. Sixteen patients with CF (mean age, 26.6 years; range, 18-42 years) and five healthy volunteers (mean age, 27.4 years; range, 21-44 years) gave written informed consent, underwent multi-detector row CT and a pulmonary function test (PFT), and were divided into three groups: group A, healthy volunteers; group B, patients with mild CF (forced expiratory volume in 1 second [FEV(1)] > 80%); and group C, patients with severe CF (FEV(1) < 80%). Two observers obtained thin-section CT scores with eight scoring systems. Bronchial cross-sectional wall area (WA), lumen area (LA), airway area, and wall thickness (WT) were measured with customized software and were normalized on the basis of subject body surface. Morphologic characteristics, PFT results, thin-section CT scores, and quantitative measurements were compared among the three groups with analysis of variance. Correlations among bronchial measurements, PFT results, and CT scores were calculated with the Spearman correlation coefficient. RESULTS Thin-section CT scores were different between group C and either group A or group B (P < .05). WA and WT were significantly different among all groups (P < .05). Interscore correlations and correlations between bronchial parameters and scores were high (r > 0.89, P < .0001). Scores, WA, and WT were significantly correlated with PFT obstructive indexes (P < .047). CONCLUSION WA and WT assessed with dedicated software on multi-detector row CT images allow evaluation of the severity of pulmonary CF.