-
Skipper Carroll opublikował 1 rok, 8 miesięcy temu
Protein expression evolves under greater evolutionary constraint than mRNA levels, and translation efficiency represents a primary determinant of protein levels during stimuli adaptation. This raises the question as to the translatome remodelers that titrate protein output from mRNA populations. Here, we uncover a network of RNA-binding proteins (RBPs) that enhances the translation efficiency of glycolytic proteins in cells responding to oxygen deprivation. Val-boroPro cell line A system-wide proteomic survey of translational engagement identifies a family of oxygen-regulated RBPs that functions as a switch of glycolytic intensity. Tandem mass tag-pulse SILAC (TMT-pSILAC) and RNA sequencing reveals that each RBP controls a unique but overlapping portfolio of hypoxic responsive proteins. These RBPs collaborate with the hypoxic protein synthesis apparatus, operating as a translation efficiency checkpoint that integrates upstream mRNA signals to activate anaerobic metabolism. This system allows anoxia-resistant animals and mammalian cells to initiate anaerobic glycolysis and survive hypoxia. We suggest that an oxygen-sensitive RBP cluster controls anaerobic metabolism to confer hypoxia tolerance.Bacteria of Lactobacillus sp. are very useful to humans. However, the biology and genomic diversity of their (bacterio)phage enemies remains understudied. Knowledge on Lactobacillus phage diversity should broaden to develop efficient phage control strategies. To this end, organic waste samples were screened for phages against two wine-related Lactobacillus plantarum strains. Isolates were shotgun sequenced and compared against the phage database and each other by phylogenetics and comparative genomics. The new isolates had only three distant relatives from the database, but displayed a high overall degree of genomic similarity amongst them. The latter allowed for the use of one isolate as a representative to conduct transmission electron microscopy and structural protein sequencing, and to study phage adsorption and growth kinetics. The microscopy and proteomics tests confirmed the observed diversity of the new isolates and supported their classification to the family Siphoviridae and the proposal of the new phage genus „Silenusvirus”.This prospective clinical study was to compare the effect of panretinal photocoagulation (PRP) associated with intravitreal conbercept injections versus PRP alone in the treatment of proliferative diabetic retinopathy (PDR). For each of 15 patients included, one eye was randomly assigned to receive treatment with PRP, and the other eye received conbercept combined PRP. Ophthalmic examinations, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) were performed at baseline and at each monthly visit until 6 months. Fluorescein angiography (FA) was acquired at baseline, 3 months and 6 months. Between group and within group analysis was done by using generalized estimating equations (GEE). The combination group had a significant decrease of neovascularization (NV) leakage area than the PRP group at month 3 and month 6 after treatment, and a better best-corrected visual acuity (BCVA) during the first three months. Within-group analysis indicated a significant decrease in NV leakage at month 3 and month 6 in both groups, and a significant increase in BCVA at 1 month in the combination group. link2 In summary, the combination of intravitreal injection of conbercept and PRP can significantly reduce the NV of PDR patients and achieve better BCVA during the drug’s lifespan compared with PRP alone.Purpose To evaluate the symptoms and signs of ocular surface disease (OSD) and tear-film matrix metalloproteinase-9 (MMP-9) overexpression using point-of-care testing (InflammaDry test) in patients with primary open-angle glaucoma (POAG). Methods This prospective, case-control study included 67 patients diagnosed with POAG and 47 healthy control subjects. The OSD assessment included Schirmer-I test, the Oxford corneal stain scale, tear breakup time (TBUT), and the five-item dry eye questionnaire (DEQ-5). Measurement of extracellular MMP-9 level was performed using the InflammaDry test. The OSD parameters and MMP-9 expression levels were compared between the POAG group and the control group. Additional subgroup analysis in POAG group was performed according to number of topical glaucoma medications (Bottle 1, 2, or 3 medications). Results There were significant differences between the control and POAG groups for all OSD parameters. MMP-9 overexpression was observed in 71.6% of POAG group, whereas only 31.9% of control group showed MMP-9 overexpression. The subgroup analysis revealed that DEQ-5, Oxford stain score, Schirmer-I, and MMP-9 overexpression demonstrated no significant difference among the three groups. Abnormal TBUT (≤5 s) was observed in 37.5%, 59.1%, and 76.2% for each subgroup according to number of bottles (1, 2, and 3), and strong MMP-9 overexpression were also detected in 25.0%, 40.9%, and 61.9%, respectively (P = 0.032, P = 0.043). Conclusions The use of preservative-containing medications may affect the ocular surface in patients with POAG. Graded measurement of tear-film MMP-9 could provide more information on OSD and might be a more useful marker for inflammation than then conventional results obtained by using an MMP-9 kit.High resolution X-ray nano-tomography experiments are often limited to a few tens of micrometer size volumes due to detector size. It is possible, through the use of multiple overlapping tomography scans, to produce a large area scan which can encompass a sample in its entirety. Mounting and positioning regions to be scanned is highly challenging and normally requires focused ion beam approaches. In this work we have imaged intact beetle scale cells mounted on the tip of a needle using a micromanipulator stage. Here we show X-ray holotomography data for single ultra-white scales from the beetles Lepidiota stigma (L. stigma) and Cyphochilus which exhibit the most effective scattering of white light in the literature. The final thresholded matrices represent a scan area of 25 × 70 × 362.5 µm and 25 × 67.5 × 235µm while maintaining a pixel resolution of 25 nm. This tomographic approach allowed the internal structure of the scales to be captured completely intact and undistorted by the sectioning required for traditional microscopy techniques.This project investigated whether structural changes are present in the subthalamic nucleus (STN) of people with mild-to-moderate severity of Parkinson’s disease (PD). Within-subject measures of STN volume and fractional anisotropy (FA) were derived from high-resolution 7Tesla magnetic resonance imaging (MRI) for 29 subjects with mild-to-moderate PD (median disease duration = 2.3±1.9 years) and 18 healthy matched controls. Manual segmentation of the STN was performed on 0.4 mm in-plane resolution images. link3 FA maps were generated and FA values were averaged over the left and right STN separately for each subject. Motor sign severity was assessed using the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Linear effects models showed that STN volume was significantly smaller in the PD subjects compared to controls (p = 0.01). Further, after controlling for differences in STN volumes within or between groups, the PD group had lower FA values in the STN compared to controls (corrected p ≤ 0.008). These findings demonstrate that morphological changes occur in the STN, which likely impact the function of the hyperdirect and indirect pathways of the basal ganglia and movement control.Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ2 test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1-4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.In this manuscript, a series of amine tagged short cyclic molecules (cyclopropylamine, cyclobutylamine, cyclopentylamine and cyclohexylamine) were thermally grafted onto p-type silicon (111) hydride surfaces via nucleophilic addition. The chemistries of these grafting were verified via XPS, AFM and sessile droplet measurements. Confocal microscopy and cell viability assay was performed on these surfaces incubated for 24 hours with triple negative breast cancer cells (MDA-MB 231), gastric adenocarcinoma cells (AGS) endometrial adenocarcinoma (Hec1A). All cell types had shown a significant reduction when incubated on these ring-strain cyclic monolayer surfaces than compared to standard controls. The expression level of focal adhesion proteins (vinculin, paxilin, talin and zyxin) were subsequently quantified for all three cell types via qPCR analysis. Cells incubate on these surface grafting were observed to have reduced levels of adhesion protein expression than compared to positive controls (collagen coating and APTES). A potential application of these anti-adhesive surfaces is the maintenance of the chondrocyte phenotype during in-vitro cell expansion. Articular chondrocytes cultured for 6 days on ring strained cyclopropane-modified surfaces was able to proliferate but had maintained a spheroid/aggregated phenotype with higher COL2A1 and ACAN gene expression. Herein, these findings had help promote grafting of cyclic monolayers as an viable alternative for producing antifouling surfaces.Mucus is responsible for controlling transport and barrier function in biological systems, and its properties can be significantly affected by compositional and environmental changes. In this study, the impacts of pH and CaCl2 were examined on the solution-to-gel transition of mucin, the primary structural component of mucus. Microscale structural changes were correlated with macroscale viscoelastic behavior as a function of pH and calcium addition using rheology, dynamic light scattering, zeta potential, surface tension, and FTIR spectroscopic characterization. Mucin solutions transitioned from solution to gel behavior between pH 4-5 and correspondingly displayed a more than ten-fold increase in viscoelastic moduli. Addition of CaCl2 increased the sol-gel transition pH value to ca. 6, with a twofold increase in loss moduli at low frequencies and ten-fold increase in storage modulus. Changing the ionic conditions-specifically [H+] and [Ca2+] -modulated the sol-gel transition pH, isoelectric point, and viscoelastic properties due to reversible conformational changes with mucin forming a network structure via non-covalent cross-links between mucin chains.


