Mogensenbowman8217

A polyphasic approach was used to describe strain K13G38T, a novel actinomycete isolated from peat swamp forest soil collected from Surat Thani Province, Thailand. The 16S rRNA gene phylogenetic analysis indicated that the strain belonged to the genus Amycolatopsis and showed the highest sequence similarities to both Amycolatopsis acidiphila JCM 30562T and Amycolatopsis bartoniae DSM 45807T (96.8% sequence similarity). Furthermore, strain K13G38T, which formed extensively branched substrate and aerial mycelia, exhibited chemotaxonomical characteristics of the genus Amycolatopsis which included phospholipid pattern type II and cell-wall chemotype IV. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, two unidentified phospholipids, and an unidentified aminolipid. MK-9(H4) was a predominant menaquinone of the organism. The major cellular fatty acids were iso-C160, anteiso-C170, and C160. The genomic DNA size of strain K13G38T was 8.5 Mbp with 69.5 mol% G+C content. On the basis of phenotypic characteristics, overall genomic relatedness index and phylogenetic distinctiveness, strain K13G38T represents a novel species of the genus Amycolatopsis, for which the name A. acididurans sp. nov. is proposed. The type strain is K13G38T (=TBRC 12507T = NBRC 114553T).Targeting aberrant glycoforms has been validated for in vitro cancer diagnostic development, and several assays are currently in routine clinical use. Because N-glycans in Fc region of antibodies show cross-reactivity with various lectins, high-quality aglycosylated antibodies are exceptionally important for immunoassay platform-based quantitative measurements. Previously, aglycosylated antibody acquisition relied on incomplete, uneconomical and onerous enzymatic and chemical methods. Here, we edited four murine immunoglobulin G genes using adenine base-editing and homology-directed recombination (HDR)-mediated gene editing methods to generate aglycosylated antibody-producing mice. Resulting aglycosylated antibodies showed required analytical performances without compromised protein stability. Thus, this aglycosylated monoclonal antibody-lectin coupled immunoassay for the quantification of tumour markers (ALIQUAT) method can provide a robust, versatile and accessible immunoassay platform to quantify specific glycoforms in precision cancer diagnostics. Moreover, the engineered mice can be used as a host to produce various aglycosylated antibodies in a convenient and robust fashion, thereby expanding in vitro diagnostic development opportunities that utilize glycoforms as a disease-specific biomarkers.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Platinum (Pt) compounds entered the clinic as anticancer agents when cisplatin was approved in 1978. More than 40 years later, even in the era of precision medicine and immunotherapy, Pt drugs remain among the most widely used anticancer drugs. As Pt drugs mainly target DNA, it is not surprising that recent insights into alterations of DNA repair mechanisms provide a useful explanation for their success. check details Many cancers have defective DNA repair, a feature that also sheds new light on the mechanisms of secondary drug resistance, such as the restoration of DNA repair pathways. In addition, genome-wide functional screening approaches have revealed interesting insights into Pt drug uptake. About half of cisplatin and carboplatin but not oxaliplatin may enter cells through the widely expressed volume-regulated anion channel (VRAC). The analysis of this heteromeric channel in tumour biopsies may therefore be a useful biomarker to stratify patients for initial Pt treatments. Moreover, Pt-based approaches may be improved in the future by the optimization of combinations with immunotherapy, management of side effects and use of nanodelivery devices. Hence, Pt drugs may still be part of the standard of care for several cancers in the coming years.Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor essential for cancer cell survival. The reprogramming of lipid metabolism has emerged as a hallmark of cancer, yet the relevance of HIF-1α to this process remains elusive. In this study, we profile HIF-1α-interacting proteins using proteomics analysis and identify fatty acid-binding protein 5 (FABP5) as a critical HIF-1α-binding partner. In hepatocellular carcinoma (HCC) tissues, both FABP5 and HIF-1α are upregulated, and their expression levels are associated with poor prognosis. FABP5 enhances HIF-1α activity by promoting HIF-1α synthesis while disrupting FIH/HIF-1α interaction at the same time. Oleic-acid treatment activates the FABP5/HIF-1α axis, thereby promoting lipid accumulation and cell proliferation in HCC cells. Our results indicate that fatty-acid-induced FABP5 upregulation drives HCC progression through HIF-1-driven lipid metabolism reprogramming.We assessed the impact of donor type on long-term outcomes of allogeneic hematopoietic cell transplantation (HCT) in 440 consecutive adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1), particularly focusing on the donor type-specific difference in graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS). Donor sources were matched sibling donor (MSD; n = 199), matched unrelated donor (MUD; n = 110), 1-allele-mismatched unrelated donor (1-MMUD; n = 83), and cord blood (CB; n = 48). Cumulative incidence of severe chronic GVHD was 14.8% for MSD-HCT, 30.1% for MUD-HCT, 9.6% for 1-MMUD-HCT, and 4.2% for CBT, respectively (P  less then  0.001), while no difference was observed in grade III-IV acute GVHD. After a median follow-up of 58.1 months, cumulative incidence of relapse was 26.1% for MSD-HCT, 27.2% for MUD-HCT, 31.2% for 1-MMUD-HCT, and 7.2% for CBT, respectively (P = 0.042). Disease-free survival and overall survival were comparable among all donor sources. However, GRFS for MSD-HCT, MUD-HCT, 1-MMUD-HCT, and CBT was 33.1%, 14.5%, 42.1%, and 50.3%, respectively (P = 0.001). In multivariate analysis, CBT showed a comparable GRFS to MSD-HCT (HR, 0.78; P = 0.290), while MUD-HCT was associated with a poorer GRFS (HR, 1.53; P = 0.002). Given the encouraging GRFS of CBT, our data suggest that CBT remains a valid option for adult ALL in CR1.Nephrotic syndrome (NS) is a renal disorder that is characterized by massive proteinuria, hypoalbuminemia and edema. One of the main causes of NS is focal segmental glomerulosclerosis (FSGS), which has extremely poor prognosis. Although steroids and immunosuppressants are the first line of treatment, some FSGS cases are refractory, prompting the need to find new therapeutic strategies. We have previously demonstrated that an optimized combination treatment of mild electrical stimulation (MES) and heat shock (HS) has several biological benefits including the amelioration of the pathologies of the genetic renal disorder Alport syndrome. Here, we investigated the effect of MES + HS on adriamycin (ADR)-induced NS mouse model. MES + HS suppressed proteinuria and glomerulosclerosis induced by ADR. The expressions of pro-inflammatory cytokines and pro-fibrotic genes were also significantly downregulated by MES + HS. MES + HS decreased the expression level of cleaved caspase-3 and the number of TUNEL-positive cells, indicating that MES + HS exerted anti-apoptotic effect. Moreover, MES + HS activated the Akt signaling and induced the phosphorylation and inhibition of the apoptotic molecule BAD. In in vitro experiment, the Akt inhibitor abolished the MES + HS-induced Akt-BAD signaling and anti-apoptotic effect in ADR-treated cells. Collectively, our study suggested that MES + HS modulates ADR-induced pathologies and has renoprotective effect against ADR-induced NS via regulation of Akt-BAD axis.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

To evaluate the potential of an integrated virtual medical retina clinic in secondary care for diabetic patients screened and referred by the UK National Diabetic Eye Screening Program (DESP).

This retrospective cohort study included diabetic patients referred by the DESP to either a virtual or a traditional doctor's appointment (face-to-face, F2F) at the Moorfields Eye Hospital NHS Foundation Trust (London, UK) between January 2015 and December 2018. The primary outcome was the proportion of patients that qualified for a virtual-clinic appointment according to hospital guidance. Secondary outcomes included the rate of attendance, mean time from DESP referral to initial hospital appointment, mean time-to-discharge and -to-treatment of either panretinal photocoagulation or intravitreal injection of anti-vascular endothelial growth factor.

We included 12,563 patients in this study. While 8833 patients (70.7%) would have qualified for a virtual appointment according to local triage guidance, only 2306 (18.service demands without diminishing quality of clinical care. Collectively, our analyses suggest that virtual consultations are a faster and clinically appropriate alternative for a substantial proportion of diabetic patients.

A significant proportion of diabetic patients referred to a F2F clinic could initially be managed in a virtual clinic. Increasing the adoption of virtual clinics in the management of diabetic patients that do not need long-term management or monitoring in secondary services may help alleviate service demands without diminishing quality of clinical care. Collectively, our analyses suggest that virtual consultations are a faster and clinically appropriate alternative for a substantial proportion of diabetic patients.The cryptic 'lost years' of sea turtles challenge conservation efforts due to unknown movements and habitat utilisation of young life stages. Behavioural information strengthens dispersal and habitat utilisation models estimating unidentified movements. In this study, leatherback hatchlings were actively tracked with miniature acoustic tags off the east coast of Costa Rica for 83.15 min (± 9.12 SD) to determine their movements and swimming behaviour. Drifters were deployed throughout the tracking process to obtain surface current data. Hatchling (n = 42) over-ground and in-water swimming speed and bearing were calculated. Mean over-ground distance travelled was 2.03 km (± 0.71 km SD) with an over-ground average swim speed of 0.41 m/s (± 0.15 m/s SD). Mean bearing was 108.08° (± 20.19° SD) compared to the 137.56° (± 44.00° SD) bearing of nearshore ocean currents during tracking. Hatchling mean in-water swimming speed was 0.25 m/s (± 0.09 m/s SD). The lower in-water speed suggests hatchlings were advected by the currents, with overall movement strongly influenced by the current direction. This information can be assimilated into broader spatiotemporal distribution models to interpret the influence of directional swimming on ecosystem utilisation and help to achieve informed management decisions across all life stages of the population.Chronic liver injury leads to liver inflammation and fibrosis, through which activated myofibroblasts in the liver secrete extracellular matrix proteins that generate the fibrous scar. The primary source of these myofibroblasts are the resident hepatic stellate cells. Clinical and experimental liver fibrosis regresses when the causative agent is removed, which is associated with the elimination of these activated myofibroblasts and resorption of the fibrous scar. Understanding the mechanisms of liver fibrosis regression could identify new therapeutic targets to treat liver fibrosis. This Review summarizes studies of the molecular mechanisms underlying the reversibility of liver fibrosis, including apoptosis and the inactivation of hepatic stellate cells, the crosstalk between the liver and the systems that orchestrate the recruitment of bone marrow-derived macrophages (and other inflammatory cells) driving fibrosis resolution, and the interactions between various cell types that lead to the intracellular signalling that induces fibrosis or its regression.