Notes

Ways to engage stakeholders in analysis to improve intense attention supply.
Predictive biology is the next great chapter in synthetic and systems biology, particularly for microorganisms. Tasks that once seemed infeasible are increasingly being realized such as designing and implementing intricate synthetic gene circuits that perform complex sensing and actuation functions, and assembling multi-species bacterial communities with specific, predefined compositions. These achievements have been made possible by the integration of diverse expertise across biology, physics and engineering, resulting in an emerging, quantitative understanding of biological design. As ever-expanding multi-omic data sets become available, their potential utility in transforming theory into practice remains firmly rooted in the underlying quantitative principles that govern biological systems. In this Review, we discuss key areas of predictive biology that are of growing interest to microbiology, the challenges associated with the innate complexity of microorganisms and the value of quantitative methods in making microbiology more predictable.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. 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. 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. PD-1/PD-L1 Inhibitor 3 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.
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