THE PROBLEM OF THE RELATIONSHIP OF SCIENCE AND RELIGION IN THE SYSTEM OF SECULAR GENERAL EDUCATION

The relationship between science and religion throughout history ranged from opposition to their unity. The long-standing prevalence of theology over science has caused a counter-atheistic reaction, which has grown into the absolutization of science in all spheres of life. The introduction to the secular general education of the course “Fundamentals of Religious Cultures and Secular Ethics” was ambiguously accepted by society. The author substantiates the position that science and religion are not mutually exclusive, but rather can complement each other, forming a unified picture of the world among the younger generation.Взаимоотношения науки и религии на протяжении всей истории выстраивались от противопоставления до их единства. Многолетнее преобладание богословия над наукой вызвало встречную атеистическую реакцию, переросшую в абсолютизацию науки во всех сферах бытия. Введение в светское общее образование курса «Основы религиозных культур и светской этики» было неоднозначно воспринято обществом. Автор обосновывает позицию, что наука и религия не взаимно исключают друг друга, а напротив, могут дополнять друг друга, формируя у подрастающего поколения единую картину мира

Lipopolysaccharide is Inserted into the Outer Membrane through An Intramembrane Hole, A Lumen Gate, and the Lateral Opening of LptD

Lipopolysaccharide (LPS) is essential for the vitality of most Gram-negative bacteria and plays an important role in bacterial multidrug resistance. The LptD/E translocon inserts LPS into the outer leaflet, the mechanism of which is poorly understood. Here, we report mutagenesis, functional assays, and molecular dynamics simulations of the LptD/E complex, which suggest two distinct pathways for the insertion of LPS. The N-terminal domain of LptD comprises a hydrophobic slide that injects the acyl tails of LPS directly into the outer membrane through an intramembrane hole, while the core oligosaccharide and O-antigen pass a lumen gate that triggers the unzipping of the lateral opening between strands β1C and β26C of the barrel of LptD, to finalize LPS insertion. Mutation of the LPS transport related residues or block of the LPS transport pathways results in the deaths of Escherichia coli. These findings are important for the development of novel antibiotics

BamA β16C strand and periplasmic turns are critical for outer membrane protein insertion and assembly

Outer membrane β-barrel proteins play important roles in importing nutrients, exporting wastes and conducting signals in Gram-negative bacteria, mitochondria and chloroplasts. The outer membrane proteins are inserted and assembled into the outer membrane by OMP85 family proteins. In Escherichia coli , the b-barrel assembly machinery (BAM) contains four lipoproteins BamB, BamC, BamD and BamE, and one outer membrane protein BamA, forming a "top hat"-like structure. Structural and functional studies of the E. coli BAM machinery have revealed that the rotation of periplasmic ring may trigger the barrel b1C-b6C scissor-like movement that promote the unfolded outer membrane protein insertion without using ATP. Here we report the BamA C-terminal barrel structure of Salmonella enterica Typhimurium str. LT2 and functional assays, which reveal that the BamA's C-terminal residue Trp, the b16C strand of the barrel and the periplasmic turns are critical for the functionality of BamA. These findings indicate that the unique b16C and the periplasmic turns of BamA are important for the out membrane insertion and assembly. The periplasmic turns might mediate the rotation of the periplasmic ring to the scissor-like movement of BamA b1C-b6C, triggering the outer membrane protein insertion. These results are important for understanding the outer membrane protein insertion in Gram-negative bacteria, as well as in mitochondria and chloroplasts

Microbiome alteration Via Fecal Microbiota Transplantation Is Effective For Refractory Immune Checkpoint inhibitor-induced Colitis

Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line immunosuppression (infliximab or vedolizumab). Ten patients (83%) achieved symptom improvement after FMT, and three patients (25%) required repeat FMT, two of whom had no subsequent response. At the end of the study, 92% achieved IMC clinical remission. 1

Structural basis of outer membrane protein insertion by the BAM complex

All Gram-negative bacteria, mitochondria and chloroplasts have outer membrane proteins (OMPs) that perform many fundamental biological processes. The OMPs in Gram-negative bacteria are inserted and folded into the outer membrane by the β-barrel assembly machinery (BAM). The mechanism involved is poorly understood, owing to the absence of a structure of the entire BAM complex. Here we report two crystal structures of the Escherichia coli BAM complex in two distinct states: an inward-open state and a lateral-open state. Our structures reveal that the five polypeptide transport-associated domains of BamA form a ring architecture with four associated lipoproteins, BamB–BamE, in the periplasm. Our structural, functional studies and molecular dynamics simulations indicate that these subunits rotate with respect to the integral membrane β-barrel of BamA to induce movement of the β-strands of the barrel and promote insertion of the nascent OMP

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

A Data Clustering Algorithm for Detecting Selective Forwarding Attack in Cluster-Based Wireless Sensor Networks

In cluster-based wireless sensor networks, cluster heads (CHs) gather and fuse data packets from sensor nodes; then, they forward fused packets to the sink node (SN). This helps wireless sensor networks balance energy effectively and efficiently to prolong their lifetime. However, cluster-based WSNs are vulnerable to selective forwarding attacks. Compromised CHs would become malicious and launch selective forwarding attacks in which they drop part of or all the packets from other nodes. In this paper, a data clustering algorithm (DCA) for detecting a selective forwarding attack (DCA-SF) is proposed. It can capture and isolate malicious CHs that have launched selective forwarding attacks by clustering their cumulative forwarding rates (CFRs). The DCA-SF algorithm has been strengthened by changing the DCA parameters (Eps, Minpts) adaptively. The simulation results show that the DCA-SF has a low missed detection rate of 1.04% and a false detection rate of 0.42% respectively with low energy consumption