Rearranging the centromere of the human Y chromosome with φC31 integrase

We have investigated the ability of the integrase from the Streptomyces φC31 ‘phage to either delete or invert 1 Mb of DNA around the centromere of the human Y chromosome in chicken DT40 hybrid somatic cells. Reciprocal and conservative site-specific recombination was observed in 54% of cells expressing the integrase. The sites failed to recombine in the remaining cells because the sites had been damaged. The sequences of the damaged sites indicated that the damage arose as a result of repair of recombination intermediates by host cell pathways. The liability of recombination intermediates to damage is consistent with what is known about the mechanism of serine recombinase reactions. The structures of the products of the chromosome rearrangements were consistent with the published sequence of the Y chromosome indicating that the assembly of the highly repeated region between the sites is accurate to a resolution of about 50 kb. Mini-chromosomes lacking a centromere were not recovered which also suggested that neo-centromere formation occurs infrequently in vertebrate somatic cells. No ectopic recombination was observed between a φC31 integrase attB site and the chicken genome

Mild and Highly Efficient Stereoselective Synthesis of 2,3-Unsaturated Glycopyranosides using La(NO3)3 · 6H2O as a Catalyst: Ferrier Rearrangement

A mild and highly efficient stereoselective reaction of 3,4,6-tri-O-acetyl-D-glucal with a variety of nucleophiles, viz. alcohols, phenols, thiols, thiophenols, and allyl trimethyl silane (TMS), in the presence of 5 mol% of lanthanum(III) nitrate hexahydrate under solvent-free conditions yielded the corresponding 2,3-unsaturated glycopyranosides (pseudoglycals) in excellent yields

Gfi1aa and Gfi1b set the pace for primitive erythroblast differentiation from hemangioblasts in the zebrafish embryo

The transcriptional repressors G fi 1(a) and G fi 1b are epigenetic regulators with unique and overlapping roles in hematopoiesis. In different contexts, G fi 1 and G fi 1b restrict or promote cell proliferation, prevent apoptosis, in fl uence cell fate decisions, and are essential for terminal differentiation. Here, we show in primitive red blood cells (prRBCs) that they can also set the pace for cellular differentiation. In zebra fi sh, prRBCs express 2 of 3 zebra fi sh G fi 1/ 1bparalogs,G fi 1aaandG fi 1b.Therecentlyidenti fi edzebra fi sh gfi1aa gene trap allele qmc551 drives erythroid green fl uorescent protein (GFP) instead of G fi 1aa expression, yet homozygous carriers have normal prRBCs. prRBCs display a maturation defect only after splice morpholino-mediated knockdown of G fi 1b in gfi1aa qmc551 homozygous embryos. To study the transcriptome of the G fi 1aa/1b double-depleted cells, we performed an RNA-Seq experi- ment on GFP-positive prRBCs sorted from 20-h our-old embryos that were heterozygous or homozygous for gfi1aa qmc551 ,aswellas wt or morphant for gfi1b .Wesubsequentlycon fi rmed and extended these data in whole-mount in situ hybridization experiments on newly generated single- and double-mutant embryos. Combi ned, the data showed that in the absence of G fi 1aa, the synchronously developing prRBCs were delayed in activating late erythr oid differentiation, as they struggled to suppress early erythroid and endothelial transcripti on programs. The latter highlighted the bipotent natu re of the progenitors from which prRBCs arise. In the absence of G fi 1aa, G fi 1b promoted erythroid differentiation as stepwise loss of wt gfi1b copies progressively delayed G fi 1aa-depleted prRBCs even further, showing that G fi 1aa and G fi 1b together set the pace for prRBC diffe rentiation from hemangioblasts

Bio-inoculated Nutrient Management Influence on Soil Nutrient Availability Pattern and Growth of Hybrid Pigeonpea (ICPH 2740) under Establishment Methods and Crop Geometry

Background A two-year field study was conducted at the ICRISAT research farm during the rainy seasons of 2021 and 2022 to investigate the impact of crop geometry, crop establishment method and sustainable nutrient management practices on nutrient availability pattern and growth of hybrid pigeon pea. Methods The experiment followed a split-split plot design. The collected data was analysed using radar graph and heat maps for nutrient availability and dry matter respectively. Result Data revealing that transplanted plots registered higher nutrient availability and proportionate root and total dry matter production at various growth stages. Among plant geometry the root and total dry matter production was higher with 100×100 cm. when considering planting methods, transplanting with a square system of 100×100 cm, combined with an integrated nutrient management approach consisting of 150% (or) 100% soil test based NPK, vermicompost at a rate of 5 t ha-1, phosphate-solubilizing bacteria (PSB) and seed treatment with Rhizobium, resulted in average of 31.5% higher dry matter production over alone inorganic nutrient management practices. Thus, a square geometry of 100×100 cm, along with sustainable integrated nutrient management (100% soil test based NPK, vermicompost at a rate of 5 t ha-1, PSB and seed treatment with Rhizobium), resulted in higher nutrient availability and dry matter production. These findings highlight the importance of careful selection of planting methods, crop geometry and nutrient management practices for maximizing the nutrient mining for production of high dry matter production of hybrid pigeonpea

First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal

BACKGROUND: Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. METHODS AND FINDINGS: We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42-4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43-5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. CONCLUSIONS: We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian reg

Trajectories of self-rated health in people with diabetes: Associations with functioning in a prospective community sample

© 2013 Schmitz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Self-rated health (SRH) is a single-item measure that is one of the most widely used measures of general health in population health research. Relatively little is known about changes and the trajectories of SRH in people with chronic medical conditions. The aims of the present study were to identify and describe longitudinal trajectories of self-rated health (SRH) status in people with diabetes. Methods: A prospective community study was carried out between 2008 and 2011. SRH was assessed at baseline and yearly at follow-ups (n=1288). Analysis was carried out through trajectory modeling. The trajectory groups were subsequently compared at 4 years follow-up with respect to functioning. Results: Four distinct trajectories of SRH were identified: 1) 72.2% of the participants were assigned to a persistently good SRH trajectory; 2) 10.1% were assigned to a persistently poor SRH trajectory; 3) mean SRH scores changed from good to poor for one group (7.3%); while 4) mean SRH scores changed from poor to medium/good for another group (10.4%). Those with a persistently poor perception of health status were at higher risk for poor functioning at 4 years follow-up than those whose SRH scores decreased from good to poor. Conclusions: SRH is an important predictor for poor functioning in diabetes, but the trajectory of SRH seems to be even more important. Health professionals should pay attention to not only SRH per se, but also changes in SRH over time.This work was supported by Operating Grant MOP-84574 from the Canadian Institutes of Health Research (CIHR). GG was supported by a doctoral fellowship from the CIHR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A Possible Contribution of Altered Cathepsin B Expression to the Development of Skin Sclerosis and Vasculopathy in Systemic Sclerosis

Cathepsin B (CTSB) is a proteolytic enzyme potentially modulating angiogenic processes and extracellular matrix remodeling. While matrix metalloproteinases are shown to be implicated in tissue fibrosis and vasculopathy associated with systemic sclerosis (SSc), the role of cathepsins in this disease has not been well studied. The aim of this study is to evaluate the roles of CTSB in SSc. Serum pro-CTSB levels were determined by enzyme-linked immunosorbent assay in 55 SSc patients and 19 normal controls. Since the deficiency of transcription factor Fli1 in endothelial cells is potentially associated with the development of SSc vasculopathy, cutaneous CTSB expression was evaluated by immunostaining in Fli1+/− and wild type mice as well as in SSc and control subjects. The effects of Fli1 gene silencing and transforming growth factor-β (TGF-β) on CTSB expression were determined by real-time PCR in human dermal microvascular endothelial cells (HDMECs) and dermal fibroblasts, respectively. Serum pro-CTSB levels were significantly higher in limited cutaneous SSc (lcSSc) and late-stage diffuse cutaneous SSc (dcSSc) patients than in healthy controls. In dcSSc, patients with increased serum pro-CTSB levels showed a significantly higher frequency of digital ulcers than those with normal levels. CTSB expression in dermal blood vessels was increased in Fli1+/− mice compared with wild type mice and in SSc patients compared with healthy controls. Consistently, Fli1 gene silencing increased CTSB expression in HDMECs. In cultured dermal fibroblasts from early dcSSc, CTSB expression was decreased compared with normal fibroblasts and significantly reversed by TGF-β1 antisense oligonucleotide. In conclusion, up-regulation of endothelial CTSB due to Fli1 deficiency may contribute to the development of SSc vasculopathy, especially digital ulcers, while reduced expression of CTSB in lesional dermal fibroblasts is likely to be associated with skin sclerosis in early dcSSc

Factors associated with infant mortality in Nepal: a comparative analysis of Nepal demographic and health surveys (NDHS) 2006 and 2011

Background: Infant mortality is one of the priority public health issues in developing countries like Nepal. The infant mortality rate (IMR) was 48 and 46 per 1000 live births for the year 2006 and 2011, respectively, a slight reduction during the 5 years’ period. A comprehensive analysis that has identified and compared key factors associated with infant mortality is limited in Nepal, and, therefore, this study aims to fill the gap. Methods: Datasets from Nepal Demographic and Health Surveys (NDHS) 2006 and 2011 were used to identify and compare the major factors associated with infant mortality. Both surveys used multistage stratified cluster sampling techniques. A total of 8707 and 10,826 households were interviewed in 2006 and 2011, with more than 99% response rate in both studies. The survival information of singleton live-born infants born 5 years preceding the two surveys were extracted from the ‘childbirth’ dataset. Multiple logistic regression analysis using a hierarchical modelling approach with the backward elimination method was conducted. Complex Samples Analysis was used to adjust for unequal selection probability due to the multistage stratified cluster-sampling procedure used in both NDHS.Results: Based on NDHS 2006, ecological region, succeeding birth interval, breastfeeding status and type of delivery assistance were found to be significant predictors of infant mortality. Infants born in hilly region (AOR = 0.43, p = 0.013) and with professional assistance (AOR = 0.27, p = 0.039) had a lower risk of mortality. On the other hand, infants with succeeding birth interval less than 24 months (AOR = 6.66, p = 0.001) and those who were never breastfed (AOR = 1.62, p = 0.044) had a higher risk of mortality. Based on NDHS 2011, birth interval (preceding and succeeding) and baby’s size at birth were identified to be significantly associated with infant mortality. Infants born with preceding birth interval (AOR = 1.94, p = 0.022) or succeeding birth interval (AOR = 3.22, p = 0.002) shorter than 24 months had higher odds of mortality while those born with a very large or larger than average size had significantly lowered odds (AOR = 0.17, p = 0.008) of mortality. Conclusion: IMR and associated risk factors differ between NDHS 2006 and 2011 except ‘succeeding birth interval’ which attained significant status in the both study periods. This study identified the ecological region, birth interval, delivery assistant type, baby’s birth size and breastfeeding status as significant predictors of infant mortality

Registration of ‘LCS Compass’ Wheat

‘LCS Compass’ (Reg. No. CV-1149, PI 675458), a hard red winter (HRW) wheat (Triticum aestivum L.), was developed and tested as VA10HRW-13 and co-released by the Virginia Agricultural Experiment Station and Limagrain Cereal Seeds, LLC, in 2015. LCS Compass was derived from the cross ‘Vision 20’ /‘Stanof’ using a modified bulk breeding method. LCS Compass is a widely adapted, high-yielding, awned, semidwarf (Rht1) HRW wheat with early to medium maturity and resistance or moderate resistance to diseases prevalent in the mid-Atlantic and Great Plains regions of the United States. In the 2013 Uniform Bread Wheat Trial conducted over 18 locations in eastern states, LCS Compass produced an average grain yield of 4609 kg ha−1 that was similar to ‘Vision 30’ (4697 kg ha−1). In the northern Great Plains, the average grain yield of LCS Compass (4015 kg ha−1) over 44 locations in 2013 was similar to ‘Jerry’ (4013 kg ha−1). In the South Dakota crop zone 3 variety test, LCS Compass had a 3-yr (2015–2017) yield average of 5575 kg ha−1 and was one of highest-yielding cultivars among the 19 cultivars tested over the 3-yr period. LCS Compass has good end-use quality in both the eastern and Great Plains regions of the United States