Effects of intranasal administration of hormonal steroids on serum testosterone and spermatogenesis in rhesus monkey (Macaca mulatta)

Spraying estradiol-17β, progesterone or norethisterone intranasally in adult male rhesus monkeys (7.5-11 kg BW) at a daily dose of 30 μg/day for a period of 60 days resulted in a decrease of testicular size, arrest of spermatogenesis and a significant reduction in serum levels of testosterone. No changes were observed in the solvent-treated controls

Co-cultivation of Curcuma longa with Piriformospora indica Enhances the Yield and Active Ingredients

The rhizome of Curcuma longa is used in the traditional medicinal system. Its secondary metabolites curcumin and the volatile oil possess wound-healing properties and inhibitory activities against certain pathogenic fungi and bacteria. Piriformospora indica is a root endophytic fungus that colonizes many plant roots and promotes the growth. P. indica was cultivated in the 5 litre capacity fermentor under standard conditions. The filtered biomass was then mixed with raw talcum powder. The propagative buds were treated with this formulation containing both sterile and inoculated fungus. We demonstrated that co- cultivation of C. longa and P. indica resulted in pronounced productivity and enhanced secondary metabolites- curcumin and volatile oil in farmers’ field. To the authors best of knowledge this is the first report where symbiotic fungus has added value to this medicinal plant in the agricultural field

Sodium hypochlorite concentration and post-endodontic pain - unveiling the optimal balance: a systematic review and meta-analysis

Introduction This study systematically reviewed literature regarding the effect of different concentrations of sodium hypochlorite (NaOCl) used during root canal treatment (RCT) on post-endodontic pain (PEP) and rescue analgesia. Methods Following registration with PROSPERO (CRD42023388916), a search was conducted using PubMed, Scopus, Web of Science, and Embase databases. Randomized controlled trials (RaCTs) of patients receiving RCT which assessed PEP at different time intervals were included. Following data extraction and Cochrane risk of bias assessment 2, meta-analyses were performed to evaluate PEP during the first 48h along with rescue analgesic intake. The certainty of the evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation approach. Results Five RaCTs with 674 patients were included. One study exhibited a low risk of bias, while four raised some concerns. Patients treated with low concentrations of NaOCl (≤3%) were significantly less likely to report PEP at 24h (OR=2.32; [95%CI, 1.63-3.31]; P<0.05) and 48h (OR=2.49; [95% CI,1.73-3.59]; P<0.05) as compared with high concentrations of NaOCl (≥5%). Furthermore, with low concentrations of NaOCl, significantly lesser moderate-severe PEP was reported at 24h (OR=2.32; [95%CI, 1.47-3.62]; P<0.05) and 48h (OR=2.35; [95%CI, 1.32-4.16]; P<0.05) and lesser analgesia was needed (OR=2.43; [95%CI, 1.48-4.00]; P<0.05). Conclusions While PEP can be influenced by several factors, low certainty evidence suggests that when NaOCl is used as an irrigant during RCT, PEP may be less likely with lower concentrations of NaOCl. Moderate certainty evidence indicates that lesser analgesia may be required with lower concentrations of NaOCl. These results should be cautiously interpreted

A chickpea genetic variation map based on the sequencing of 3,366 genomes

Zero hunger and good health could be realized by 2030 through effective conservation, characterization and utilization of germplasm resources1 . So far, few chickpea (Cicerarietinum) germplasm accessions have been characterized at the genome sequence level2 . Here we present a detailed map of variation in 3,171 cultivated and 195 wild accessions to provide publicly available resources for chickpea genomics research and breeding. We constructed a chickpea pan-genome to describe genomic diversity across cultivated chickpea and its wild progenitor accessions. A divergence tree using genes present in around 80% of individuals in one species allowed us to estimate the divergence of Cicer over the last 21 million years. Our analysis found chromosomal segments and genes that show signatures of selection during domestication, migration and improvement. The chromosomal locations of deleterious mutations responsible for limited genetic diversity and decreased fitness were identified in elite germplasm. We identified superior haplotypes for improvement-related traits in landraces that can be introgressed into elite breeding lines through haplotype-based breeding, and found targets for purging deleterious alleles through genomics-assisted breeding and/or gene editing. Finally, we propose three crop breeding strategies based on genomic prediction to enhance crop productivity for 16 traits while avoiding the erosion of genetic diversity through optimal contribution selection (OCS)-based pre-breeding. The predicted performance for 100-seed weight, an important yield-related trait, increased by up to 23% and 12% with OCS- and haplotype-based genomic approaches, respectively. On the basis of WGS of 3,366 chickpea germplasm accessions, we report here a rich map of the genetic variation in chickpea. We provide a chickpea pan-genome and offer insights into species divergence, the migration of the cultigen (C. arietinum), rare allele burden and fitness loss in chickpea. We propose three genomic breeding approaches— haplotype-based breeding, genomic prediction and OCS—for developing tailor-made high-yielding and climate-resilient chickpea varieties. We sequenced 3,366 chickpea germplasm lines, including 3,171 cultivated and 195 wild accessions at an average coverage of around 12× (Methods, Extended Data Fig. 1, Supplementary Data 1 Tables 1, 2). Alignment of WGS data to the CDC Frontier reference genome11 identified 3.94 million and 19.57 million single-nucleotide polymorphisms (SNPs) in 3,171 cultivated and 195 wild accessions, respectively (Extended Data Table 1, Supplementary Data 1 Tables 3–7, Supplementary Notes). This SNP dataset was used to assess linkage disequilibrium (LD) decay (Supplementary Data 2 Tables 1, 2, Extended Data Fig. 2, Supplementary Notes) and identify private and population-enriched SNPs (Supplementary Data 3 Tables 1–4, Supplementary Notes). These private and population-enriched SNPs suggest rapid adaptation and can enhance the genetic foundation in the elite gene pool

Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis

Background Non-absorbable disaccharides (lactulose and lactitol) are recommended as first-line treatment for hepatic encephalopathy. The previous (second) version of this review included 10 randomised clinical trials (RCTs) evaluating non-absorbable disaccharides versus placebo/no intervention and eight RCTs evaluating lactulose versus lactitol for people with cirrhosis and hepatic encephalopathy. The review found no evidence to either support or refute the use of the non-absorbable disaccharides and no differences between lactulose versus lactitol. Objectives To assess the beneficial and harmful effects of i) non-absorbable disaccharides versus placebo/no intervention and ii) lactulose versus lactitol in people with cirrhosis and hepatic encephalopathy. Search methods We carried out electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 10), MEDLINE, EMBASE, and Science Citation Index Expanded to 19 October 2015; manual searches of meetings and conference proceedings; checks of bibliographies; and correspondence with investigators and pharmaceutical companies. Selection criteria We included RCTs, irrespective of publication status, language, or blinding. Data collection and analysis Two review authors, working independently, retrieved data from published reports and correspondence with investigators. The primary outcomes were mortality, hepatic encephalopathy, and serious adverse events. We presented the results of meta-analyses as risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). We assessed the quality of the evidence using 'Grading of Recommendations Assessment Development and Evaluation' (GRADE) and bias control using the Cochrane Hepato-Biliary Group domains. Our analyses included regression analyses of publication bias and other small study effects, Trial Sequential Analyses to detect type 1 and type 2 errors, and subgroup and sensitivity analyses. Main results We included 38 RCTs with a total of 1828 participants. Eight RCTs had a low risk of bias in the assessment of mortality. All trials had a high risk of bias in the assessment of the remaining outcomes. Random-effects meta-analysis showed a beneficial effect of non-absorbable disaccharides versus placebo/no intervention on mortality when including all RCTs with extractable data (RR 0.59, 95% CI 0.40 to 0.87; 1487 participants; 24 RCTs; I2 = 0%; moderate quality evidence) and in the eight RCTs with a low risk of bias (RR 0.63, 95% CI 0.41 to 0.97; 705 participants). The Trial Sequential Analysis with the relative risk reduction (RRR) reduced to 30% confirmed the findings when including all RCTs, but not when including only RCTs with a low risk of bias or when we reduced the RRR to 22%. Compared with placebo/no intervention, the non-absorbable disaccharides were associated with beneficial effects on hepatic encephalopathy (RR 0.58, 95% CI 0.50 to 0.69; 1415 participants; 22 RCTs; I2 = 32%; moderate quality evidence). Additional analyses showed that non-absorbable disaccharides can help to reduce serious adverse events associated with the underlying liver disease including liver failure, hepatorenal syndrome, and variceal bleeding (RR 0.47, 95% CI 0.36 to 0.60; 1487 participants; 24 RCTs; I2 = 0%; moderate quality evidence). We confirmed the results in Trial Sequential Analysis. Tests for subgroup differences showed no statistical differences between RCTs evaluating prevention, overt, or minimal hepatic encephalopathy. The evaluation of secondary outcomes showed a potential beneficial effect of the non-absorbable disaccharides on quality of life, but we were not able to include the data in an overall meta-analysis (very low quality evidence). Non-absorbable disaccharides were associated with non-serious (mainly gastrointestinal) adverse events (very low quality evidence). None of the RCTs comparing lactulose versus lactitol evaluated quality of life. The review found no differences between lactulose and lactitol for the remaining outcomes (very low quality evidence). Authors' conclusions This review includes a large number of RCTs evaluating the prevention or treatment of hepatic encephalopathy. The analyses found evidence that non-absorbable disaccharides may be associated with a beneficial effect on clinically relevant outcomes compared with placebo/no intervention. Plain language summary Are non-absorbable disaccharides associated with beneficial or harmful effects in people with cirrhosis and hepatic encephalopathy? Background Cirrhosis is a chronic disorder of the liver. People with cirrhosis may develop hepatic encephalopathy, a condition that results in poor brain functioning. Hepatic encephalopathy may be clinically obvious (overt) with changes including poor concentration, tremor, and alterations in consciousness. Others have no obvious clinical changes (minimal) but, when tested, some aspects of brain function such as attention and the ability to perform complex tasks are impaired. The reason why people develop hepatic encephalopathy is complex. The accumulation of ammonia plays a key role. The non-absorbable disaccharides, lactulose and lactitol, are indigestible sugars that reduce the levels of ammonia in the blood. Review question We investigated the use of non-absorbable disaccharides for the prevention and treatment of hepatic encephalopathy in people with cirrhosis by reviewing randomised clinical trials (RCTs). Search date The search date was October 2015. Study funding sources Seven RCTs received financial support and 11 RCTs received lactitol or inactive placebo free of charge from a pharmaceutical company. Study characteristics We included 29 RCTs comparing non-absorbable disaccharides with inactive placebo or no intervention and nine RCTs comparing lactulose with lactitol. Seven of the included RCTs evaluated the prevention of hepatic encephalopathy and 31 evaluated the treatment of hepatic encephalopathy. Sixteen of the treatment RCTs included people with overt hepatic encephalopathy while 15 included people with minimal hepatic encephalopathy. The duration of treatment varied depending on the type of hepatic encephalopathy from five days to one year. Key results People who received non-absorbable disaccharides were less likely to die than people given a placebo or no treatment. They were also less likely to develop serious complications of their liver disease such as liver failure, bleeding, and infections. The non-absorbable disaccharides were also effective in preventing the development of hepatic encephalopathy and increased the number of participants who recovered from hepatic encephalopathy. There was some evidence from a small number of trials that lactulose has a beneficial effect on the quality of life, but we were unable to include the data in an overall analysis. The non-absorbable disaccharides were associated with adverse events including diarrhoea, nausea, bloating, and flatulence. None of the RCTs comparing lactulose versus lactitol reported quality of life. The analyses showed no differences between the two interventions for the remaining outcomes. Quality of the evidence In the comparison of non-absorbable disaccharides versus placebo/no intervention, we found moderate quality evidence of benefit for the outcomes of death, hepatic encephalopathy, and serious complications. The evidence for the remaining outcomes was of very low quality

Transcriptome analysis reveals key genes associated with root‑lesion nematode Pratylenchus thornei resistance in chickpea

The root-lesion nematode, Pratylenchus thornei, is one of the major plant-parasitic nematode species causing significant yield losses in chickpea (Cicer arietinum). In order to identify the underlying mechanisms of resistance to P. thornei, the transcriptomes of control and inoculated roots of three chickpea genotypes viz. D05253 > F3TMWR2AB001 (resistant advanced breeding line), PBA HatTrick (moderately resistant cultivar), and Kyabra (susceptible cultivar) were studied at 20 and 50 days post inoculation using the RNA-seq approach. On analyzing the 633.3 million reads generated, 962 differentially expressed genes (DEGs) were identified. Comparative analysis revealed that the majority of DEGs upregulated in the resistant genotype were downregulated in the moderately resistant and susceptible genotypes. Transcription factor families WRKY and bZIP were uniquely expressed in the resistant genotype. The genes Cysteine-rich receptor-like protein kinase 10, Protein lifeguard-like, Protein detoxification, Bidirectional sugar transporter Sugars Will Eventually be Exported Transporters1 (SWEET1), and Subtilisin-like protease were found to play cross-functional roles in the resistant chickpea genotype against P. thornei. The identified candidate genes for resistance to P. thornei in chickpea can be explored further to develop markers and accelerate the introgression of P. thornei resistance into elite chickpea cultivars

Whole genome resequencing and phenotyping of MAGIC population for high resolution mapping of drought tolerance in chickpea

Terminal drought is one of the major constraints to crop production in chickpea (Cicer arietinum L.). In order to map drought tolerance related traits at high resolution, we sequenced multi-parent advanced generation intercross (MAGIC) population using whole genome resequencing approach and phenotyped it under drought stress environments for two consecutive years (2013-14 and 2014-15). A total of 52.02 billion clean reads containing 4.67 TB clean data were generated on the 1136 MAGIC lines and eight parental lines. Alignment of clean data on to the reference genome enabled identification of a total, 932,172 of SNPs, 35,973 insertions, and 35,726 deletions among the parental lines. A high-density genetic map was constructed using 57,180 SNPs spanning a map distance of 1606.69 cM. Using compressed mixed linear model, genome-wide association study (GWAS) enabled us to identify 737 markers significantly associated with days to 50% flowering, days to maturity, plant height, 100 seed weight, biomass, and harvest index. In addition to the GWAS approach, an identity-by-descent (IBD)-based mixed model approach was used to map quantitative trait loci (QTLs). The IBD-based mixed model approach detected major QTLs that were comparable to those from the GWAS analysis as well as some exclusive QTLs with smaller effects. The candidate genes like FRIGIDA and CaTIFY4b can be used for enhancing drought tolerance in chickpea. The genomic resources, genetic map, marker-trait associations, and QTLs identified in the study are valuable resources for the chickpea community for developing climate resilient chickpeas

Aszites, Pfortaderthrombose und hepatische Enzephalopathie bei Leberzirrhose: Aktuelle Therapieempfehlungen

Treatment of Ascites, Portal Vein Thrombosis and Hepatic Encephalopathy in Patients with Cirrhosis of the Liver Background: Ascites, portal vein thrombosis and hepatic encephalopathy are important complications of cirrhosis of the liver. Guidelines for the treatment of ascites have recently been published. Method: This manuscript summarizes up-to-date recommendations on the basis of the DGVS S3 guideline and of other guidelines as well as of the authors' experience. Results and Conclusions: TIPS (transjugular intrahepatic porto-systemic shunt) is the preferred treatment for refractory or recidivant ascites unless there are contraindications. The therapy of hepatorenal syndrome type 1 with albumin and the vasoconstrictor Terlipressin has been proven effective. Treatment of portal vein thrombosis comprises a strategy of anticoagulation, TIPS and liver transplantation. The most important therapeutic strategy for hepatic encephalopathy is the search for as well as the treatment of trigger events. Rifaximin is being increasingly used for the treatment and prophylaxis of hepatic encephalopathy

Pearl millet genome sequence provides a resource to improve agronomic traits in arid environments

Pearl millet [Pennisetum glaucum (L.) R. Br., syn. Cenchrus americanus (L.) Morrone], is a staple food for over 90 million poor farmers in arid and semi-arid regions of sub-Saharan Africa and South Asia. We report the ~1.79 Gb genome sequence of reference genotype Tift 23D2B1-P1-P5, which contains an estimated 38,579 genes. Resequencing analysis of 994 (963 inbreds of the highly cross-pollinated cultigen, and 31 wild accessions) provides insights into population structure, genetic diversity, evolution and domestication history. In addition we demonstrated the use of re-sequence data for establishing marker trait associations, genomic selection and prediction of hybrid performance and defining heterotic pools. The genome wide variations and abiotic stress proteome data are useful resources for pearl millet improvement through deploying modern breeding tools for accelerating genetic gains in pearl millet.publishersversionPeer reviewe

E2F1 Mediated Apoptosis Induced by the DNA Damage Response Is Blocked by EBV Nuclear Antigen 3C in Lymphoblastoid Cells

EBV latent antigen EBNA3C is indispensible for in vitro B-cell immortalization resulting in continuously proliferating lymphoblastoid cell lines (LCLs). EBNA3C was previously shown to target pRb for ubiquitin-proteasome mediated degradation, which facilitates G1 to S transition controlled by the major transcriptional activator E2F1. E2F1 also plays a pivotal role in regulating DNA damage induced apoptosis through both p53-dependent and -independent pathways. In this study, we demonstrate that in response to DNA damage LCLs knocked down for EBNA3C undergo a drastic induction of apoptosis, as a possible consequence of both p53- and E2F1-mediated activities. Importantly, EBNA3C was previously shown to suppress p53-induced apoptosis. Now, we also show that EBNA3C efficiently blocks E2F1-mediated apoptosis, as well as its anti-proliferative effects in a p53-independent manner, in response to DNA damage. The N- and C-terminal domains of EBNA3C form a stable pRb independent complex with the N-terminal DNA-binding region of E2F1 responsible for inducing apoptosis. Mechanistically, we show that EBNA3C represses E2F1 transcriptional activity via blocking its DNA-binding activity at the responsive promoters of p73 and Apaf-1 apoptosis induced genes, and also facilitates E2F1 degradation in an ubiquitin-proteasome dependent fashion. Moreover, in response to DNA damage, E2F1 knockdown LCLs exhibited a significant reduction in apoptosis with higher cell-viability. In the presence of normal mitogenic stimuli the growth rate of LCLs knockdown for E2F1 was markedly impaired; indicating that E2F1 plays a dual role in EBV positive cells and that active engagement of the EBNA3C-E2F1 complex is crucial for inhibition of DNA damage induced E2F1-mediated apoptosis. This study offers novel insights into our current understanding of EBV biology and enhances the potential for development of effective therapies against EBV associated B-cell lymphomas