Gilliamdencker5503
Heavy-ion beam (HIB) irradiation has been widely used in microbial mutation breeding. However, a global cellular response to such radiation remains mostly uncharacterised. In this study, we used transcriptomics to analyse the damage repair response in Saccharomyces cerevisiae following a semi-lethal HIB irradiation (80 Gy), which induced a significant number of DNA double-strand breaks. Our analysis of differentially expressed genes (DEGs) from 50 to 150 min post-irradiation revealed that upregulated genes were significantly enriched for gene ontology and Kyoto encyclopaedia of genes and genomes terms related to damage repair response. Based on the number of DEGs, their annotation, and their relative expression, we established that the peak of the damage repair response occurred 75 min post-irradiation. Moreover, we exploited the data from our recent study on X-ray irradiation-induced repair to compare the transcriptional patterns induced by semi-lethal HIB and X-ray irradiations. Although these two radiations have different properties, we found a significant overlap (> 50%) for the DEGs associated with five typical DNA repair pathways and, in both cases, identified homologous recombination repair (HRR) as the predominant repair pathway. Nevertheless, when we compared the relative enrichment of the five DNA repair pathways at the key time point of the repair process, we found that the relative enrichment of HRR was higher after HIB irradiation than after X-ray irradiation. Additionally, the peak stage of HRR following HIB irradiation was ahead of that following X-ray irradiation. Since mutations occur during the DNA repair process, uncovering detailed repair characteristics should further the understanding of the associated mutagenesis features.Wood in service is sequestering carbon, but it is principally prone to deterioration where different fungi metabolize wood, and carbon dioxide is released back to the atmosphere. A key prerequisite for fungal degradation of wood is the presence of moisture. Conversely, keeping wood dry is the most effective way to protect wood from wood degradation and for long-term binding of carbon. Wood is porous and hygroscopic; it can take up water in liquid and gaseous form, and water is released from wood through evaporation following a given water vapour pressure gradient. During the last decades, the perception of wood-water relationships changed significantly and so did the view on moisture-affected properties of wood. Among the latter is its susceptibility to fungal decay. This paper reviews findings related to wood-water relationships and their role for fungal wood decomposition. These are complex interrelationships not yet fully understood, and current knowledge gaps are therefore identified. Studies with chemicacted to provide new insights.L-Arginine (L-Arg) depletion has attracted great attention in cancer therapy. Although two types of arginine-depleting enzymes, arginine deiminase (ADI) and human arginase I, are undergoing clinical trials, random site of PEGylation, low efficacy of heavy metal as co-factor, and immunogenicity limit the performance of these drugs and cause difficulty in a homogeneous production. Here we screened ten catalytic metal ions and have successfully produced a site-specific mono-PEGylated human arginase I mutant by conjugating the Cys45 residue to PEG-maleimide to minimize the decrease in activity and produce a homogeneous product. The catalytic efficiency trend of metal ion-enriched human arginase I mutant (HAI) was Co2+ > Ni2+ ≫ Mn2+. The overall kcat/KM values of Co-HAI and Ni-HAI were higher than Mn-HAI by ~ 8.7- and ~ 5.2-folds, respectively. Moreover, the results of enzyme kinetics and circular dichroism spectrometry demonstrated that the 20 or 40 kDa linear and branched PEG attached on the HAI surface did not affect the enzyme activity and the protein secondary structures. In vitro studies showed that both Co-HAI-PEG20L and Ni-HAI-PEG20L inhibited the growth of eight types of cancer cell lines. The pharmacodynamic study in mice demonstrated that the i.p. administration of Co-HAI-PEG20L at 13 mg/kg and Ni-HAI-PEG20L at 15 mg/kg was able to maintain a L-Arg level below its detection limit for over 120 h after one injection. The body weights of mice could return to normal levels within 5 days after injection, showing that the doses were well-tolerated. Therefore, both the Ni-HAI-PEG20L and Co-HAI-PEG20L are promising candidates for cancer therapy. KEY POINTS • Mono-PEGylation applied on human arginase I mutant (HAI) successfully. • The catalytic efficiency of Co- and Ni-enriched HAI was higher than the wild type. • At least eight types of cancer cell lines were inhibited by Co- and Ni-HAI-PEG20L. • Co- and Ni-HAI-PEG20L were able to achieve weekly depletion of L-Arg. Graphical abstract.BACKGROUND Secondary peritonitis is associated with high rates of morbidity and mortality. Data on the effect of staged re-laparotomy or re-laparoscopy as a surgical option in the management of abdominal sepsis due to secondary peritonitis are limited and conflicting. Herein, we report the outcomes of patients undergoing staged peritoneal lavage (SPL) for secondary peritonitis in our department. METHODS This is a single-center retrospective analysis of the data of patients undergoing SPL for secondary peritonitis. SPL was performed via either re-laparotomy or re-laparoscopy. The simplified acute physiology score (SAPS II) was calculated at the time of the initial operation and for each SPL. The end points of interest included the evolution of sepsis characterized by the SAPS II score, the mortality rate and the rate of definitive abdominal wall closure. RESULTS The data of 74 patients with a median age of 73 years requiring at least one SPL between 2012 and 2019 were analyzed. The median number of SPL performed was three (range 1-12). A sequential drop of SAPS II score from 41 at the initial procedure to 32 at the third SPL was documented. The overall mortality rate was 16.2%, definitive abdominal closure was achieved in all surviving patients and the median length of stay was 17.5d CONCLUSION Staged re-laparotomy or re-laparoscopy with peritoneal lavage may reduce the severity of peritonitis and reduce the risk of mortality in patients with abdominal sepsis. Maintaining the abdominal wall under constant retraction using a rigid mesh while creating an open abdomen is a crucial step in achieving definite abdominal wall closure. Thus, staged peritoneal lavage may be a good surgical option for selected patients with peritonitis.BACKGROUND Central venous catheters should be positioned at the cavoatrial junction or the right atrium. If catheters are inserted to a depth derived by adding the length between the needle insertion point and the clavicular notch and the length between the clavicular notch and the carina, the catheter tip can be placed near the carina. Based on this, we aim to make a formula to place a catheter tip near the cavoatrial junction. SBI-0640756 METHODS This prospective nonrandomized interventional study included patients who needed a central venous catheter from June 2017 to July 2018. The location of the cavoatrial junction was identified using a fluoroscopic technique. The following variables were measured L1, the length between the needle insertion point and the clavicular notch; L2, the length between the clavicular notch and the carina; and α, the length between the carina and the cavoatrial junction. RESULTS A total of 70 patients were enrolled. The mean age was 65.5 ± 11.6 years, and 62.9% were male. The mean L1 and L2 were 7.6 ± 1.4 and 7.0 ± 1.4 cm, respectively. The mean α was 4.4 ± 1.5 cm (95% CI 4.1-4.8), and it was not affected by demographic factors, such as sex, age, height or weight. CONCLUSIONS Central venous catheters in adult patients can be placed near the cavoatrial junction using a simple formula the distance between the insertion point and the clavicular notch + the distance between the clavicular notch to the carina + 4.4 cm.BACKGROUND In limited-resource countries, the morbidity and mortality related to inguinal hernias is unacceptably high. This review addresses the issue by identifying capacity-building education of non-surgeons performing inguinal hernia repairs in developing countries and analyzing the outcomes. METHODS PubMed was searched and included are studies that reported on task sharing and surgical outcomes for inguinal hernia surgery. Educational methods with quantitative and qualitative effects of the capacity-building methods have been recorded. Excluded were papers without records of outcome data. RESULTS Seven studies from African countries reported 14,108 elective inguinal hernia repairs performed by 230 non-surgeons with a mortality rate of 0.36%. Complications were reported in 4 of the 7 studies with a morbidity rate of 14.2%. Two studies reported on follow-up one with no recurrences in 408 patients at 7.4 months and the other one with 0.9% recurrences in 119 patients at 12 months. Direct comparison of outcomes from trained non-surgeons to surgeons or surgically trained medical doctors is limited but suggests no difference in outcomes. Quantitative capacity-building effects include increase in surgical workforce, case volume, elective procedures, mesh utilization, and decreased referrals to higher level of care institutions. Qualitative capacity-building effects include feasibility of prospective research in limited-resource settings, improved access to surgical care, and change in practice pattern of local physicians after training for mesh repair. CONCLUSION Systematic training of non-surgeons in inguinal hernia repair is potentially a high-impact capacity-building strategy. High-risk patients should be referred to a fully trained surgeon whenever possible. Randomized study designs and long-term outcomes beyond 1 year are needed.BACKGROUND Mental disorders are overrepresented in prisoners, placing them at an increased risk of suicide. Advancing our understanding of how different mental disorders relate to distinct stages of the suicidal process-the transition from ideation to action-would provide valuable information for clinical risk assessment in this high-risk population. METHODS Data were drawn from a representative sample of 1212 adults (1093 men) incarcerated across 13 New Zealand prisons, accounting for 14% of the national prison population. Guided by an ideation-to-action framework, three mutually exclusive groups of participants were compared on the presence of mental disorders assessed by validated DSM-IV diagnostic criteria prisoners without any suicidal history (controls; n = 778), prisoners who thought about suicide but never made a suicide attempt (ideators; n = 187), and prisoners who experienced suicidal ideation and acted on such thoughts (attempters; n = 247). RESULTS One-third (34.6%) of participants reported a lif suicide.Two QTLs on ChrB09 significantly associated with both early and late leaf spots were identified by genome-wide association study in the US peanut mini-core collection. Early leaf spot (ELS) and late leaf spot (LLS) are two serious peanut diseases in the USA, causing tens of millions of dollars of annual economic losses. However, the genetic factors underlying resistance to those diseases in peanuts have not been well-studied. We conducted a genome-wide association study for the two peanut diseases using Affymetrix version 2.0 SNP array with 120 genotypes mainly coming from the US peanut mini-core collection. A total of 46 quantitative trait loci (QTLs) were identified with phenotypic variation explained (PVE) from 10.19 to 24.11%, in which eighteen QTLs are for resistance to ELS and 28 QTLs for LLS. Among the 46 QTLs, there were four and two major QTLs with PVE higher than 16.99% for resistance ELS and LLS, respectively. Of the six major QTLs, five were located on the B sub-genome and only one was on the A sub-genome, which suggested that the B sub-genome has more potential resistance genomic regions than the A sub-genome.