Miracle-dz/UniFAR-FTUs huggingface dataset:
Chewing Stimulates Secretion of Human Salivary Secretory Immunoglobulin A

Immunoglobulin A (IgA) is the most abundant immunoglobulin in saliva and other mucosal secretions and plays an important role in mucosal immunity. The present study examined whether secretion of IgA, like other salivary proteins, is increased by reflex stimulation. Parotid saliva was collected from subjects into separate vials under resting conditions and during chewing-stimulated secretion over 45 min. Enzyme-linked immunosorbent assay (ELISA) indicated that chewing increased IgA secretion. The extent and pattern of the increase were similar to those of total protein and acinar cell amylase. SDS gel electrophoresis and Western blotting showed that high-molecular-weight forms of IgA-containing secretory component predominated in all saliva samples. Secretory component, the cleaved epithelial receptor for polymeric IgA, was secreted in a pattern very similar to that of IgA. It is concluded that chewing stimulates epithelial cell transcytosis of IgA and increases secretion of secretory IgA into saliva.
Epistatic interactions with a common hypomorphic RET allele in syndromic Hirschsprung disease

Hirschsprung disease (HSCR) stands as a model for genetic dissection of complex diseases. In this model, a major gene, RET, is involved in most if not all cases of isolated (i.e., nonsyndromic) HSCR, in conjunction with other autosomal susceptibility loci under a multiplicative model. HSCR susceptibility alleles can harbor either heterozygous coding sequence mutations or, more frequently, a polymorphism within intron 1, leading to a hypomorphic RET allele. On the other hand, about 30% of HSCR are syndromic. Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat‐Wilson (MWS), Bardet‐Biedl (BBS), Shah‐Waardenburg (WS4), cartilage‐hair‐hypoplasia (CHH), Smith‐Lemli‐Opitz (SLO), Goldberg‐Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS). According to the HSCR syndrome, the penetrance of HSCR trait varies from 5 to 70%. Trisomy 21 (T21) also predisposes to HSCR. We were able to collect a series of 393 patients affected by CCHS (n = 173), WS4 (n = 24), BBS (n = 51), MWS (n = 71), T21 (n = 46), and mental retardation (MR) with HSCR (n = 28). For each syndrome, we studied the RET locus in two subgroups of patients; i.e., with or without HSCR. We genotyped the RET locus in 393 patients among whom 195 had HSCR, and compared the distribution of alleles and genotypes within the two groups for each syndrome. RET acts as a modifier gene for the HSCR phenotype in patients with CCHS, BBS, and Down syndrome, but not in patients with MWS and WS4. The frequent, low penetrant, predisposing allele of the RET gene can be regarded as a risk factor for the HSCR phenotype in CCHS, BBS, and Down syndrome, while its role is not significant in MWS and WS4. These data highlight the pivotal role of the RET gene in both isolated and syndromic HSCR. Hum Mutat 28(8), 790–796, 2007. © 2007 Wiley‐Liss, Inc.
Single-Ended Schmitt-Trigger-Based Robust Low-Power SRAM Cell

This paper presents a Schmitt-trigger-based single-ended 11T SRAM cell, which significantly improves read and write static noise margin (SNM) and consumes low power. Simulation results show that the cell also achieves the lowest leakage power dissipation among the cells considered for comparison. We also investigate the impact of process, voltage, and temperature variations on various performance parameters, such as hold SNM, read SNM, write margin, immunity to half-select issue, ION/IOFF ratio of read path, and leakage power of the cell; Monte Carlo simulation results confirm the robustness of the proposed cell toward these issues. Layout drawn in a 45-nm technology rule shows that the proposed cell occupies 2.02× greater area as compared with 6T SRAM cells. However, 6.9× higher ION/IOFF ratio of the read path of the proposed cell as compared with 6T cell holds potential to significantly subside the area overhead. A new figure of merit that comprehensively captures stability, delay, power dissipation, and area of an SRAM cell is also proposed. Based on the proposed metric, we observe that the proposed cell outperforms all, but one of the SRAM cells considered in this paper.
Prevalence of myopia and its association with body stature and educational level in 19-year-old male conscripts in seoul, South Korea.

PURPOSE To examine prevalence of refractive errors and its associated factors, such as body stature and educational level, among 19-year-old males in Seoul, Korea. METHODS A population-based cross-sectional study was performed in male subjects (n = 23,616; age = 19 years) who were normally resident in Seoul for male compulsory conscripts during the study period (2010). Refractive examination was performed with cycloplegia. Height, weight, and educational level were examined. Myopia was defined as a spherical equivalent less than -0.5 diopters (D) and high myopia less than -6.0 D. The association of myopia with body stature and educational level was analyzed using logistic regression analysis. RESULTS The prevalence of myopia in 19-year-old males in Seoul was 96.5%. The prevalence of high myopia was 21.61%. Body stature was not significantly associated with myopia. Four- to 6-year university students (odds ratio [OR] 1.69; P < 0.001) and 2 to 3-year college students (OR 1.68; P < 0.001) showed significantly higher risk for myopia than those with lower academic achievement (< high school graduation). CONCLUSIONS The 19-year-old male population in Seoul, Korea, demonstrated a very high myopic prevalence. Myopic refractive error was associated with academic achievement, not with body stature.
Tobacco industry manipulation of data on and press coverage of the illicit tobacco trade in the UK

Background In the UK, transnational tobacco companies (TTCs) have been arguing that levels of illicit trade are high and increasing and will rise further if standardised packaging is implemented. This paper examines trends in and accuracy of media reporting of, and industry data on, illicit tobacco in the UK. Methods Quantification of the volume, nature and quality of press articles citing industry data on illicit tobacco in UK newspapers from March 2008 to March 2013. Examination of published TTC data on illicit, including a comparison with independent data and of TTC reporting of Her Majesty's Revenue and Customs data on illicit. Results Media stories citing industry data on illicit tobacco began in June 2011, 2 months after the Tobacco Control Plan for England, which heralded standardised packaging, was published. The majority of data cited are based on industry Empty Pack Surveys for which no methodology is available. For almost all parts of the country where repeat data were cited in press stories, they indicated an increase, often substantial, in non-domestic/illicit cigarettes that is not supported by independent data. Similarly, national data from two published industry sources show a sudden large increase in non-domestic product between 2011 and 2012. Yet the methodology of one report changes over this period and the other provides no published methodology. In contrast, independent data show steady declines in non-domestic and illicit cigarette penetration from 2006 to 2012 and either a continued decline or small increase to 2013. Conclusions Industry claims that use of Non-UK Duty Paid/illicit cigarettes in the UK is sharply increasing are inconsistent with historical trends and recent independent data. TTCs are exaggerating the threat of illicit tobacco by commissioning surveys whose methodology and validity remain uncertain, planting misleading stories and misquoting government data. Industry data on levels of illicit should be treated with extreme caution.
Extensive intraspecific chloroplast DNA (cpDNA) variation in the alpine Draba aizoides L. (Brassicaceae): haplotype relationships and population structure

Chloroplast DNA (cpDNA) sequence variation is currently the most widely used tool for the inference of phylogenetic relationships among plants at all taxonomic levels. Generally, noncoding regions tend to evolve faster than coding sequences and have recently been applied to the study of phylogenetic relationships among closely related taxa. An implicit assumption of many of these studies is that intraspecific cpDNA variation is either absent or low and therefore will not interfere with the reconstruction of interspecific relationships. A survey of cpDNA sequence variation in the common alpine plant species Draba aizoides L. was undertaken to assess levels of intraspecific cpDNA sequence variation. These levels were compared to levels of interspecific sequence divergence between D. aizoides and related alpine Draba species. Intraspecific cpDNA sequence divergence was extensive in D. aizoides, and intraspecific differences were often larger than interspecific differences. cpDNA haplotype relationships were explored using a maximum parsimony approach and minimum‐spanning networks. Results from both methods were largely congruent but comparisons provided interesting insights into the presumed evolutionary history of cpDNA haplotypes. A combined effect of cpDNA introgression and complex lineage sorting was inferred to explain the pattern of cpDNA variation found in D. aizoides. Our results suggest that intraspecific cpDNA variation can be extensive and that intraspecific variation needs to be taken into account when inferring phylogenetic relationships among closely related taxa.
Impact of acyclovir on genital and plasma HIV-1 RNA, genital herpes simplex virus type 2 DNA, and ulcer healing among HIV-1-infected African women with herpes ulcers: a randomized placebo-controlled trial.

BACKGROUND Little is known about the impact of episodic treatment of herpes on human immunodeficiency virus type 1 (HIV-1). METHODS Women from Ghana and the Central African Republic who had genital ulcers were enrolled in a randomized, double-blind, placebo-controlled trial of acyclovir plus antibacterials and were monitored for 28 days. Ulcer etiologies and detection of lesional HIV-1 RNA were determined by polymerase chain reaction (PCR). Cervicovaginal HIV-1 RNA and herpes simplex virus type 2 (HSV-2) DNA and plasma HIV-1 RNA were quantitated by real-time PCR. Primary analyses included 118 HIV-1-infected women with HSV-2 ulcers (54 of whom were given acyclovir and 64 of whom were given placebo). RESULTS Acyclovir had little impact on (1) detection of cervicovaginal HIV-1 RNA (risk ratio [RR], 0.96; 95% confidence interval [CI], 0.8-1.2) at day 7 of treatment, (2) the mean cervicovaginal HIV-1 RNA load (-0.06 log(10) copies/mL; 95% CI, -0.4 to 0.3 log(10) copies/mL) at day 7 of treatment, or (3) the plasma HIV-1 RNA load (+0.09 log(10) copies/mL; 95% CI, -0.1 to 0.3 log(10) copies/mL) at day 14 of treatment. At day 7, women receiving acyclovir were less likely to have detectable lesional HIV-1 RNA (RR, 0.70; 95% CI, 0.4-1.2) or cervicovaginal HSV-2 DNA (RR, 0.69; 95% CI, 0.4-1.3), had a lower quantity of HSV-2 DNA (-0.99 log(10) copies/mL; 95% CI, -1.8 to -0.2 log(10) copies/mL), and were more likely to have a healed ulcer (RR, 1.26; 95% CI, 0.9-1.9). CONCLUSION Episodic therapy for herpes reduced the quantity of cervicovaginal HSV-2 DNA and slightly improved ulcer healing, but it did not decrease genital and plasma HIV-1 RNA loads. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT00158483 .
Immediate treatment effects of high-dose methotrexate and cranial irradiation on neuropsychological functions of children treated for acute lymphoblastic leukemia at a regional cancer center

Abstract Context: Overall cure rates for pediatric acute lymphoblastic leukemia (ALL) have improved; however, the neuropsychological sequelae of ALL treatment have not been adequately documented in India. Aims: The present study assesses the immediate effects of ALL treatment on neuropsychological functioning, at the Regional Cancer Center in Chennai, South India. Materials and Methods: Newly diagnosed with ALL patients (n = 24) (aged 6-15 years; 13M:11F) registered between March 2008 and February 2009 were included. Patients who had received high-dose methotrexate (HD-MTX) and cranial radiotherapy (CRT) as part of their treatment were enrolled for the study. Neurocognitive assessments were done to assess various functions such as performance intelligence, visuo-perception, visuo-spatial, perceptual organization, processing speed, planning, working memory, and immediate verbal memory (IVM) (Malin′s intelligence scale); verbal fluency (ideation fluency test) and verbal attention (vigilance test). Three assessments were done during induction (baseline), after re-induction phase (second) and during the maintenance phase (third). Results: The patients performed significantly worse in the third assessment (mean duration from diagnosis 17.48 months) on performance intelligence quotient (PIQ), visuo-perception, visuo-spatial, processing speed, planning, IVM, verbal attention, and verbal fluency (P < 0.05), there were no significant changes observed in visuo-perceptual organization and working memory (P > 0.05). Significant difference was observed between age groups 6 and 10 (41.7%) and 11-15 years (58.3%) in perceptual organization, verbal fluency, and verbal attention (P < 0.05) and no gender difference was observed across the three assessments (P > 0.05). Conclusions: Combining HD MTX and CRT had an immediate effect on neuropsychological sequelae among the children with ALL, however, long-term evaluation is recommended to study the long-term effects.
Two MER2‐negative individuals with the same novel CD151 mutation and evidence for clinical significance of anti‐MER2

BACKGROUND: MER2 (RAPH1), the only antigen of the RAPH blood group system, is located on the tetraspanin CD151. Only four examples of alloanti‐MER2 are known. We report here two new examples of alloanti‐MER2, in women of Pakistani and Turkish origin, one of whom showed signs of a hemolytic transfusion reaction (HTR) after transfusion of 3 units of red cells (RBCs).
Influence of Prior Coronary Stenting on the Immediate and Mid-term Outcome of Isolated Coronary Artery Bypass Surgery

Background There has been little emphasis on the possible consequences of prior stent placement on the outcome of coronary bypass surgery (CABG). We compared the results of isolated CABG patients who had prior stents with those who had not with respect to preoperative status, operative procedure, and postoperative immediate and long-term outcome. Methods Records of 1471 patients undergoing isolated CABG at our institution between January 1, 2000, and March 31, 2005, were reviewed. Patients were divided into three groups. Group I had no stents (n = 1317). Group II had one to three stents (n = 137). Group III had more than three stents (n = 17). Groups were compared with respect to preoperative risk factors, operative procedures, and postoperative results. Long-term survival data were obtained on 97.6% of patients with a mean follow-up, 4.1 ± 2.3 years. Results Stented patients were younger (66.1 ± 10.8 vs. 69.1 ± 10.8 years, P = 0.006), had more unstable angina (68.2% vs. 58.9%, P = 0.02), hypercholesterolemia (83.8% vs. 61.2%, P = 0.00), chronic obstructive pulmonary disease (13.6% vs. 8.4%, P = 0.03), peripheral vascular disease (15.2% vs. 8.4%, P = 0.00), and previous CABG (10.1% vs. 4.2%, P = 0.00), fewer low ejection fractions (1.3% vs. 5.2%, P = 0.02), left main disease (25.3% vs. 32.6%, P = 0.04), diabetes (31.2% vs. 40.8%, P = 0.01), or diffuse disease (19.5 ± 10.5 vs. 22.5 ± 10.9, P = 0.00), had more off pump procedures (53.2% vs. 45.3%, P = 0.03), fewer internal thoracic artery grafts (80.5% vs. 86.6%, P = 0.03), fewer grafts placed (>3: 52.6% vs. 61.8%, P = 0.02), more complications (76.5% vs. 42.6%, P = 0.005), atrial fibrillation (47.1% vs. 19.7%, P = 0.011), longer hospital stays (12.2 vs. 8.3 days, P = 0.019). Percentage survival for groups I, II, and III at 60 months was 82.1%, 84.7%, and 72.6%, respectively. Conclusions Stents placed before surgery in isolated CABG patients may be associated with higher preoperative risk, altered operative procedures, more postoperative complications, longer hospitalizations, and more readmissions. Overall, stented patients experienced more preoperative hospitalizations, catheterizations, and percutaneous coronary interventions (PCIs) than nonstented patients. Survival for those with more than three stents may be diminished.
Recombinant production of the human aquaporins in the yeast Pichia pastoris (Invited Review)

Abstract Aquaporins are water facilitating proteins embedded in the cellular membranes. Such channels have been identified in almost every living organism – including humans. These proteins are vital molecules and their malfunction can lead to several severe disorders and diseases. Hence, an increased understanding of their structure, function and regulation is of the utmost importance for developing current and future drugs. Heading towards this goal, the first problem to overcome is to acquire the proteins in sufficient amounts to enable functional and structural characterization. Using a suitable host organism, large amounts of target molecules can possibly be produced, but for membrane proteins limitations are frequently encountered. In the work described here, we have produced the 13 human aquaporins (hAQPs) in one of the most successful hosts for recombinant overproduction of eukaryotic proteins; the yeast Pichia pastoris, in order to explore the underlying bottleneck to a successful membrane protein production experiment. Here we present exceptional yield of hAQP1, whereas some other hAQPs were below the threshold needed for scaled up production. In the overproduction process, we have established methods for efficient production screening as well as for accurate determination of the initial production yield. Furthermore, we have optimized the yield of low producing targets, enabling studies of proteins previously out of reach, exemplified with hAQP4 as well as the homologue PfAQP. Taken together, our results. present insight into factors directing high production of eukaryotic membrane proteins together with suggestions on ways to optimize the recombinant production in the yeast P. pastoris.
The Bcl-2 Homolog Nrz Inhibits Binding of IP3 to Its Receptor to Control Calcium Signaling During Zebrafish Epiboly

Phosphorylation of a Bcl-2–like protein allows calcium signals needed for the early stages of development. Nrz-IP3 Tug-of-War During early development of zebrafish, cells migrate over the yolk in a process known as epiboly. Epiboly requires Ca2+-dependent myosin contraction along actin filaments at the leading edge of the migratory epithelium. Growth factors stimulate production of inositol trisphosphate (IP3), which binds to and activates the IP3 receptor, a Ca2+ channel on the endoplasmic reticulum (ER). Bonneau et al. found that the Bcl-2–like protein Nrz was phosphorylated in zebrafish during early epiboly and that replacing endogenous Nrz with a mutant that could not be phosphorylated disrupted normal Ca2+ oscillations, actin assembly at the leading edge, and epiboly progression. In human cultured cells, wild-type Nrz, but not Nrz with phosphomimetic mutations, bound to the IP3 receptor, prevented its interaction with IP3, and blocked Ca2+ release from the ER. Thus, these data suggest that phosphorylation of Nrz during early epiboly enables IP3 to bind to its receptor and promote Ca2+ waves that are important for assembly of the actin-myosin ring required for cell migration. Members of the Bcl-2 protein family regulate mitochondrial membrane permeability and also localize to the endoplasmic reticulum where they control Ca2+ homeostasis by interacting with inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs). In zebrafish, Bcl-2–like 10 (Nrz) is required for Ca2+ signaling during epiboly and gastrulation. We characterized the mechanism by which Nrz controls IP3-mediated Ca2+ release during this process. We showed that Nrz was phosphorylated during early epiboly, and that in embryos in which Nrz was knocked down, reconstitution with Nrz bearing mutations designed to prevent its phosphorylation disrupted cyclic Ca2+ transients and the assembly of the actin-myosin ring and led to epiboly arrest. In cultured cells, wild-type Nrz, but not Nrz with phosphomimetic mutations, interacted with the IP3 binding domain of IP3R1, inhibited binding of IP3 to IP3R1, and prevented histamine-induced increases in cytosolic Ca2+. Collectively, these data suggest that Nrz phosphorylation is necessary for the generation of IP3-mediated Ca2+ transients and the formation of circumferential actin-myosin cables required for epiboly. Thus, in addition to their role in apoptosis, by tightly regulating Ca2+ signaling, Bcl-2 family members participate in the cellular events associated with early vertebrate development, including cytoskeletal dynamics and cell movement.
Astrocyte–neuron vulnerability to prenatal stress in the adult rat brain

Chronic activation of the stress response during pregnancy has been shown to be injurious to the development of the offspring. We have previously demonstrated that restraint prenatal stress inflicted during the last week of pregnancy in rats increased dopamine and glutamate receptors in forebrain areas of the adult offsprings. In this study, the same prenatal insult was employed to assess morphological changes in astrocytes and in the dendritic arborization in frontal cortex, striatum, and hippocampus of the adult rat brain. On postnatal day 90, brains were processed for immunocytochemistry using primary antibodies to glial fibrillary acidic protein (GFAP; the main cytoskeletal astroglial protein), S100B protein (an astroglial‐derived neurotrophic factor), MAP‐2 (a microtubule‐associated protein present almost exclusively in dendrites), and synaptophysin (Syn; one major integral protein of the synaptic vesicles membrane). The results show a significant increase in the cell area of GFAP‐immunoreactive (‐IR) astrocytes, with high levels of S100B protein and a significant decrease in the relative area of MAP‐2‐IR neuronal processes in prenatally stressed adult rats. The expression of synaptophysin decreased in all areas studied. These results demonstrate that prenatal stress induces a long‐lasting astroglial reaction and a reduced dendritic arborization, with synaptic loss in the brain of adult offspring. In addition to the neurochemical alterations previously reported, these morphological changes might be underlying the behavioral and learning impairment previously observed in prenatally stressed rats. © 2006 Wiley‐Liss, Inc.