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Maternal nutrition is critical in mammalian development, influencing the epigenetic reprogramming of gametes, embryos, and fetal programming. We evaluated the effects of different levels of sulfur (S) and cobalt (Co) in the maternal diet throughout the pre- and periconceptional periods on the biochemical and reproductive parameters of the donors and the DNA methylome of the progeny in Bos indicus cattle. The low-S/Co group differed from the control with respect to homocysteine, folic acid, B12, insulin growth factor 1, and glucose. The oocyte yield was lower in heifers from the low S/Co group than that in the control heifers. Embryos from the low-S/Co group exhibited 2320 differentially methylated regions (DMRs) across the genome compared with the control embryos. We also characterized candidate DMRs linked to the DNMT1 and DNMT3B genes in the blood and sperm cells of the adult progeny. A DMR located in DNMT1 that was identified in embryos remained differentially methylated in the sperm of the progeny from the low-S/Co group. Therefore, we associated changes in specific compounds in the maternal diet with DNA methylation modifications in the progeny. Our results help to elucidate the impact of maternal nutrition on epigenetic reprogramming in livestock, opening new avenues of research to study the effect of disturbed epigenetic patterns in early life on health and fertility in adulthood. Considering that cattle are physiologically similar to humans with respect to gestational length, our study may serve as a model for studies related to the developmental origin of health and disease in humans.
The World Health Organization Disability Assessment Schedule II (WHODAS II) was developed for assessing disability. This study provides data on the validity and utility of the Spanish version of the WHODAS II in a large sample of patients with schizophrenia.
The sample included 352 patients with a schizophrenia spectrum disorder. They completed a comprehensive assessment battery including measures of psychopathology, functionality and quality-of-life. A sub-sample of 36 patients was retested after six months to assess its temporal stability.
Participation in society (6.3%) and Life activities (4.0%) were the domains with the highest percentage of missing data. The internal consistency (Cronbach's alpha) of the total scale was 0.94, and the test-retest stability reached an intraclass correlation coefficient of 0.92. It became apparent that the six primary factor model represents a better fit with reality than other competing models. Relationships between the WHODAS and measures of symptomatology, social and work-related functionality, and quality-of-life were in the expected direction and the scale was ultimately found to be able to differentiate among patients with different degrees of disease severity and different work status.
Assessment of disability using appropriate tools is a crucial aspect in the context of mental health and, in this regard, the Spanish version of the WHODAS II shows ample evidence of validity in patients with schizophrenia. The most important contribution of this study is that it is the first analysing the Spanish version of the WHODAS II (36-item version) in a large sample of patients with schizophrenia.
The stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) and total mercury concentrations (THg) of the three marine catfish species Aspistor luniscutis, Bagre bagre and Genidens genidens were evaluated to understand their trophic relationship in northern Rio de Janeiro state, south-eastern Brazil. The δ13C was similar among the three marine catfishes, whereas δ15N was similar in A. luniscutis and B. bagre and lower in G. genidens. THg was higher in G. genidens and lower in B. bagre. The greater assimilation of Sciaenidae fishes and squids by A. luniscutis and B. bagre resulted in smaller isotopic niche areas and trophic diversity but higher isotopic niche overlap, trophic redundancy and evenness. For G. genidens, the similar assimilation of all prey items resulted in the broadest isotopic niche among the marine catfishes. The higher mercury content in G. genidens is consistent with an increased important contribution of prey with a higher Hg burden. The bioaccumulation process was indicated by significant correlations of δ15N and THg with total length and total mass. Additionally, a significant correlation between THg and δ15N reflected the biomagnification process through the food web.
This paper presents a theoretical and experimental study of the long-standing fluid mechanics problem involving the temporal resolution of a large localised initial disturbance into a sequence of solitary waves. This problem is of fundamental importance in a range of applications, including tsunami and internal ocean wave modelling. This study is performed in the context of the viscous fluid conduit system – the driven, cylindrical, free interface between two miscible Stokes fluids with high viscosity contrast. Owing to buoyancy-induced nonlinear self-steepening balanced by stress-induced interfacial dispersion, the disturbance evolves into a slowly modulated wavetrain and further into a sequence of solitary waves. An extension of Whitham modulation theory, termed the solitary wave resolution method, is used to resolve the fission of an initial disturbance into solitary waves. The developed theory predicts the relationship between the initial disturbance’s profile, the number of emergent solitary waves and their amplitude distribution, quantifying an extension of the well-known soliton resolution conjecture from integrable systems to non-integrable systems that often provide a more accurate modelling of physical systems. The theoretical predictions for the fluid conduit system are confirmed both numerically and experimentally. The number of observed solitary waves is consistently within one to two waves of the prediction, and the amplitude distribution shows remarkable agreement. Universal properties of solitary wave fission in other fluid dynamics problems are identified.
OBJECTIVES/SPECIFIC AIMS: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs) recurrence ranges from 16% to 43% and presents significant challenges to clinicians, patients, and families. This comparative effectiveness research study aims to disseminate, implement and evaluate whether an existing intervention, consisting of decolonization and decontamination procedures, which has been determined to be effective in hospital intensive care unit settings, can be implemented by Community Health Workers (CHWs) or “promotoras” conducting home visits prevent recurrence of CA-MRSA and transmission within their households for patients presenting to primary care with SSTIs. METHODS/STUDY POPULATION: In partnership with 3 Community Health Centers and 4 community hospitals in NYC, this study will recruit patients (n=278) with confirmed MRSA SSTIs and their household members. Participants are randomized to receive either a CHW/Promotora-delivered decolonization-decontamination intervention or usual care, which includes hygiene education. The highly engaged stakeholder team meets monthly to review interim results, identify areas for refinement and new research questions, and develop and implement strategies to improve participant engagement and retention. RESULTS/ANTICIPATED RESULTS: MRSA and MSSA were found in 19% and 21.1% of wound cultures, respectively. 59.5% with MRSA+ wound culture had one or more MRSA+ surveillance culture; 67.8% with MSSA+ wound culture had one or more MSSA+ surveillance culture. The “warm handoff” approach, developed and implemented by the stakeholder team to engage patients from their initial consent to return of lab results and scheduling of the home visits, helped improve completion of baseline home visits by 14%, from 45% to 59% of eligible participants. Home visits have demonstrated that 60% of households had at least one surface contaminated with S. aureus. Of the surfaces that tested positive in the households, nearly 20% were MRSA and 81% were MSSA; 32.5% of household members had at least one surveillance culture positive for S. aureus (MRSA: 7.7%, MSSA: 92.3%). DISCUSSION/SIGNIFICANCE OF IMPACT: This study aims to understand the systems-level, patient-level, and environmental-level factors associated with SSTI recurrence and household transmission, and to examine the interactions between bacterial genotypic and clinical/phenotypic factors on decontamination, decolonization, SSTI recurrence and household transmission. This study will evaluate the barriers and facilitators of implementation of home visits by CHWs in underserved populations, and aims to strengthen the weak evidence base for implementation of strategies to reduce SSTI recurrence and household transmission.
This study aimed to evaluate the effects of an intervention including nutritional telemonitoring, nutrition education, and follow-up by a nurse on nutritional status, diet quality, appetite, physical functioning and quality of life of Dutch community-dwelling elderly. We used a parallel arm pre-test post-test design with 214 older adults (average age 80 years) who were allocated to the intervention group (n 97) or control group (n 107), based on the municipality. The intervention group received a 6-month intervention including telemonitoring measurements, nutrition education and follow-up by a nurse. Effect measurements took place at baseline, after 4·5 months, and at the end of the study. The intervention improved nutritional status of participants at risk of undernutrition (β (T1)=2·55; 95 % CI 1·41, 3·68; β (T2)=1·77; 95 % CI 0·60, 2·94) and scores for compliance with Dutch guidelines for the intake of vegetables (β=1·27; 95 % CI 0·49, 2·05), fruit (β=1·24; 95 % CI 0·60, 1·88), dietary fibre (β=1·13; 95 % CI 0·70, 1·57), protein (β=1·20; 95 % CI 0·15, 2·24) and physical activity (β=2·13; 95 % CI 0·98, 3·29). The intervention did not have an effect on body weight, appetite, physical functioning and quality of life. In conclusion, this intervention leads to improved nutritional status in older adults at risk of undernutrition, and to improved diet quality and physical activity levels of community-dwelling elderly. Future studies with a longer duration should focus on older adults at higher risk of undernutrition than this study population to investigate whether the impact of the intervention on nutritional and functional outcomes can be improved.
Lutein, a fat-soluble carotenoid with antioxidant properties, may have an effect on respiratory health. However, the evidence is inconsistent. We aimed to cross-sectionally investigate the association between lutein intake and lung function by measuring forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC% in adults (aged 45–79 years). We included 4402 participants from the Rotterdam Study, a prospective cohort study in The Netherlands. Lutein intake was assessed using a validated FFQ. Lung function was assessed using spirometry around the same time point as the dietary assessment. No independent association was found between lutein intake and FEV1 (−12·17 (95 % CI −34·21, 9·87) ml per sd increase in lutein) after adjustment for age, sex, height, cohort effect, ethnicity, education, weight, total daily energy intake, smoking status, physical activity, and intakes of fatty acids, dietary fibre, alcohol, β-carotene, β-crypotoxanthin, lycopene and zeaxanthin. There was also no association between lutein and FVC or FEV1/FVC%. However, after stratification by smoking status, lutein intake was significantly associated with lower FEV1/FVC% in current smokers (−1·69 (95 % CI −2·93, −0·45) % per sd increase of lutein) independent of other carotenoids. The present study does not support an independent association between lutein intake and lung function in adults. However, future studies should focus on the potential inverse association between high lutein intake and lung function in specific risk groups such as smokers.
Gas detecting and sensing is a largely studied field of knowledge, but total understanding is not yet achieved and the ideal device is still far in the future. Many experimental efforts have been devoted to find the minimum optimal temperature and operational conditions for SnO2 to sense hydrocarbons; different methods to build gas-detecting devices keep being developed all around the world, from paste-based bulk devices to nanostructured thick and thin films, but little effort has been aim to characterize the reactions by calculating their related enthalpies. Computational methods have been widely used to characterize, understand and model many physicochemical interactions. In this regard, three main courses can be followed: Ab initio (first principles of quantum mechanics), DFT (Density Functional Theory) and MD (Molecular Dynamics) simulation. In this research, DFT modelling tool is employed to understand and characterize the gas-sensing reactions of Tin Oxide when exposed to an atmosphere with Methane. In CASTEP, a robust DFT module of the Materials Studio suite, one SnO2 (110) crystal plane is exposed to CH4 and the structure is optimized many times for each possible step of the reaction, recording the energies related with each optimization stage, in sum giving us the Transition State (TS) of the reaction. Based on the data, a promising reaction-path is proposed and analyzed for the (110) surface.
The association between myocardial infarction (MI) and depression is well described. Yet, the underlying mechanisms are unclear and the contribution of psychological factors is uncertain. We aimed to determine the risk of recognized (RMI) and unrecognized (UMI) myocardial infections on depression, as both have a similar impact on cardiovascular health but differ in psychological epiphenomena.
Participants of the Rotterdam Study, 1823 men aged ⩾55 years, were followed for the occurrence of depression. RMI and UMI were ascertained using electrocardiography and medical history at baseline. We determined the strength of the association of RMI and UMI with mortality, and we studied the relationship of RMI and UMI with depressive symptoms and the occurrence of major depression.
The risk of mortality was similar in men with RMI [adjusted hazard ratio (aHR) 1.71, 95% confidence interval (CI) 1.45–2.03] and UMI (aHR 1.58, 95% CI 1.27–1.97). Men with RMI had on average [unstandardized regression coefficient (B) 1.14, 95% CI 0.07–2.21] higher scores for depressive symptoms. By contrast, we found no clear association between UMI and depressive symptoms (B 0.55, 95% CI −0.51 to 1.62) in men. Analysis including occurrence of major depression as the outcome were consistent with the pattern of association.
The discrepant association of RMI and UMI with mortality compared to depression suggests that the psychological burden of having experienced an MI contributes to the long-term risk of depression.
We present a review of our recent studies of Bias Temperature Instability (BTI) in Metal-Oxide-Semiconductor Field-Effect-Transistors (MOSFETs) fabricated with different material systems, highlighting the reliability opportunities and challenges of each novel device family. We discuss first the intrinsic reliability improvement offered by SiGe and Ge p-channel technologies, if a Si cap is used to passivate the channel, in order to fabricate a standard SiO2/HfO2 gate stack. We focus on SiGe gate stack optimizations for maximum BTI reliability, and on a simple physics-based model able to reproduce the experimental trends. This model framework is then used to understand the suboptimal BTI reliability and excessive time-dependent variability induced by oxide defect charging in different high-mobility channel gate stacks, such as Ge/GeOx/high-k and InGaAs/high-k. Finally we discuss how to pursue a reduction of charge trapping in alternative material systems in order to boost the device reliability and minimize time-dependent variability.
Familial aggregation of isolated abdominal aortic and isolated intracranial aneurysms have been described. Therefore, districtual aneurysm without a systemic genetic disease (e.g. Marfan, Ehlers Danlos etc.) can have a genetic basis. The authors are reporting on the development, in the sixth decade of life, of popliteal aneurysm in two identical twins E.U. and E.C. Zygosity was established on the basis of blood-group determinations, HLA haplotypes and cytogenetic variants. Mild clinical symptoms (intermittent claudication, calf cramps) had begun in E.C. at 21 years of age. Later, at 52 years of age, a thrombosis of the aneurysmatic sac on one side required surgical treatment. E.U. showed no clinical symptoms until the age of 60, when, within the interval of a few months, bilateral thrombosis had developed. The weight difference in the two subjects (E.C. 72 Kg, E.U. 64 Kg) may explain the difference between them as regards the age of onset of symptoms and body sides (one or both) affected. Angiographic, macroscopic and histologic aspects are documented. On surgical intervention, the aneursym was found at the biforcation of the popliteal artery, but no anomalous insertion of gas-trocnemii appeared to cause pressure on the artery leading to aneurysmatic dilatation. The aneurysmatic sac measured 2.5 cm in diameter and on histological examination, using haematoxylin-eosin and Van Gieson stain, showed fragmented elastic, collagen fibres.
Intestinal mucositis is an important toxic side effect of 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii is known to protect from intestinal injury via an effect on the gastrointestinal microbiota. The objective of the present study was to evaluate the effect of S. boulardii on intestinal mucositis induced by 5-FU in a murine model. Mice were divided into saline, saline (control)+5-FU or 5-FU+S. boulardii (16 × 109 colony-forming units/kg) treatment groups, and the jejunum and ileum were removed after killing of mice for the evaluation of histopathology, myeloperoxidase (MPO) activity, and non-protein sulfhydryl group (mainly reduced glutathione; GSH), nitrite and cytokine concentrations. To determine gastric emptying, phenol red was administered orally, mice were killed 20 min after administration, and the absorbance of samples collected from the mice was measured by spectrophotometry. Intestinal permeability was measured by the urinary excretion rate of lactulose and mannitol following oral administration. S. boulardii significantly reversed the histopathological changes in intestinal mucositis induced by 5-FU and reduced the inflammatory parameters: neutrophil infiltration (control 1·73 (sem 0·37) ultrastructural MPO (UMPO)/mg, 5-FU 7·37 (sem 1·77) UMPO/mg and 5-FU+S. boulardii 4·15 (sem 0·73) UMPO/mg); nitrite concentration (control 37·00 (sem 2·39) μm, 5-FU 59·04 (sem 11·41) μm and 5-FU+S. boulardii 37·90 (sem 5·78) μm); GSH concentration (control 477·60 (sem 25·25) μg/mg, 5-FU 270·90 (sem 38·50) μg/mg and 5-FU+S. boulardii 514·00 (sem 38·64) μg/mg). Treatment with S. Boulardii significantly reduced the concentrations of TNF-α and IL-1β by 48·92 and 32·21 % in the jejunum and 38·92 and 61·79 % in the ileum. In addition, S. boulardii decreased the concentrations of chemokine (C–X–C motif) ligand 1 by 5-fold in the jejunum and 3-fold in the ileum. Interestingly, S. boulardii reduced the delay in gastric emptying (control 25·21 (sem 2·55) %, 5-FU 54·91 (sem 3·43) % and 5-FU+S. boulardii 31·38 (sem 2·80) %) and induced the recovery of intestinal permeability (lactulose:mannitol ratio: control 0·52 (sem 0·03), 5-FU 1·38 (sem 0·24) and 5-FU+S. boulardii 0·62 (sem 0·03)). In conclusion, S. boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in intestinal mucositis induced by 5-FU.
SMYB1 is a Schistosoma mansoni protein highly similar to members of the Y-box binding protein family. Similar to other homologues, SMYB1 is able to bind double- and single-stranded DNA, as well as RNA molecules. The characterization of proteins involved in the regulation of gene expression in S. mansoni is of great importance for the understanding of molecular events that control morphological and physiological changes in this parasite. Here we demonstrate that SMYB1 is located in the cytoplasm of cells from different life-cycle stages of S. mansoni, suggesting that this protein is probably acting in mRNA metabolism in the cytoplasm and corroborating previous findings from our group that showed its ability to bind RNA. Protein–protein interactions are important events in all biological processes, since most proteins execute their functions through large supramolecular structures. Yeast two-hybrid screenings using SMYB1 as bait identified a partner in S. mansoni similar to the SmD3 protein of Drosophila melanogaster (SmRNP), which is important in the assembly of small nuclear ribonucleoprotein complexes. Also, pull-down assays were conducted using immobilized GST-SMYB1 proteins and confirmed the SMYB1-SmRNP interaction. The interaction of SMYB1 with a protein involved in mRNA processing suggests that it may act in processes such as turnover, transport and stabilization of RNA molecules.
In the housefly, mosaics appear spontaneously but rarely. Sexual mosaics or gynandromorphs also appear in strains in which sex determination is based on autosomal sex factors. Rare cases of recombination in the male have been reported by some authors. In field and laboratory populations, mitotic plates with figures indicating exchange of chromatid segments are regularly observed in tissues of individuals of both sexes and at all stages of development. All these anomalies are interpreted as outward manifestation of the same phenomenon: mitotic recombination. The cytological basis of mitotic recombination, its relative frequency, its influence on linkage and genetic variability are discussed.
The distribution of sex-determinants in field populations of Musca domestica domestica L. was studied in 62 samples of flies collected at 53 sites (animal farms) between 1975 and 1981 in an area stretching North–South from Denmark (+ Iceland) to Sicily.
Karyological observations and genetic analyses demonstrated the existence of three types of population along a latitudinal cline. Populations of Northern Europe were of the standard type (XX females and XY males) with the Y chromosome determining sex. Those of Central and Southern Italy from sites below 100 m.a.s.l. (metres above sea level) were autosomal (XX females and males), sex in them being determined by autosomal sex-determinants for both femaleness and maleness. In the large intermediate zone the populations were mixed and had several karyotypes in both sexes. In this zone an altitudinal gradient was also observed, with autosomal determinants less common at higher altitudes. Genetic tests showed, in the autosomal and in the mixed populations, the presence of two autosomal male factors: M III, the most common, on autosome III and M II, on autosome II.
The gradient in sex determinants found in flies of Western Europe appears to be a dynamic phenomenon of relatively recent origin. Both climatic influence and selective pressure with insecticides have probably contributed towards the micro-evolution of populations with different sex-determinants in the houseflies of the area studied.
Houseflies collected from eight pig-breeding farms were used to investigate the nature of sex determinants in fly populations of South-East England. Earlier observations had shown that their sex determination mechanism was not of the standard (XX females, XY males) type.
Most flies of both sexes were XX; the male determining Y chromosome of standard populations was rare. Test-crosses to females of standard multimarked strains and crosses using aneuploid (OX) flies identified two dominant male determinants, one on autosome 3 (M III) and another on the X chromosome (Xm), and provided the first demonstration in this species of an active involvement of the X chromosome in sex determination. A small secondary constriction on X appeared to indicate reliably the presence of Xm. Most individuals in field populations were Xm homozygotes, implying the presence of an unlocated female determinant F,† epistatic to Xm and M III.
M III was less common and differed in frequency between samples. Its increased frequency in a strain selected in the laboratory with the pyrethroid insecticide permethrin might be due either to genetic drift, or to linkage between M III and a gene on autosome 3 that confers resistance to pyrethroids in houseflies.
Genetic and cytological analyses of house-flies collected from 12 pig-breeding farms throughout the British Isles demonstrated that the non-standard sex determination mechanism prevailing in South-East England, involving a dominant female determinant (F) and virtual homozygosity for a male determinant on the X chromosome (Xm, both males and females morphologically XX), was not typical of the country as a whole. Instead there was a gradual decrease in the frequency of F, Xm and a rarer male determinant M III, and a concomitant increase in the standard male determining Y chromosome, on moving north, east and west of this region. Only the Scottish and probably the Irish populations were fully standard (XX females XY males), although one from the East Anglian coast in which non-standard determinants were rare was predominantly of this type. Populations from intermediate areas possessed complex multifactorial mechanisms in which Y, F Xm and M III coexisted. It is hypothesized that this radial cline in sex determinants, like the latitudinal cline known from mainland Europe, represents a transient polymorphism caused by the recent and continuing invasion of non-standard determinants into originally standard populations. The cause(s) of this apparently rapid evolutionary change, however, remain unclear.
Evolutionary and closer structural relationships are demonstrated by phylogenetic analysis, peptide prediction and molecular modelling between Solanum tuberosum apyrase, Schistosoma mansoni SmATPase 2 and Leishmania braziliensis NDPase. Specific protein domains are suggested to be potentially involved in the immune response, and also seem to be conserved during host and parasite co-evolution. Significant IgG antibody reactivity was observed in sera from patients with American cutaneous leishmaniasis (ACL) and schistosomiasis using potato apyrase as antigen in ELISA. S. mansoni adult worm or egg, L. braziliensis promastigote (Lb) and Trypanosoma cruzi epimastigote (EPI) have ATP diphosphohydrolases, and antigenic preparations of them were evaluated. In ACL patients, IgG seropositivity was about 43% and 90% for Lb and potato apyrase, respectively, while IgM was lower (<19%) for both. In schistosomiasis patients IgM (>40%) or IgG (100%) seropositivity for both soluble egg (SEA) and adult worm (SWAP) antigens was higher than that found for potato apyrase (IgM=10%; IgG=39%). In Chagas disease, IgG seropositivity for EPI and potato apyrase was 97% and 17%, respectively, while the IgM was low (3%) for both antigens. The study of the conserved domains from both parasite proteins and potato apyrase could lead to the development of new drug targets or molecular markers.
Water maser emission has been detected only toward three planetary nebulae (PNe). In particular, in K3-35, the first PN where water vapor maser emission was detected, the components are located in a torus-like structure with a radius of 85 AU and also at the surprisingly large distance of 5000 AU from the star, in the tips of the bipolar lobes. The existence of these water molecules in PNe is puzzling, probably related to some unknown mechanism shielding them against the ionizing radiation. We report the detection of HCO+ (J = 1 − 0) emission toward K 3-35, that not only suggests that dense molecular gas (~105 cm−3) is present in this PN, but also that this kind of PN can enrich their surroundings with organic molecules.