Bacterial Resistance to Nanosilver: Molecular Mechanisms and Possible Ways to Overcome them

This review contains the results of experimental studies of recent years dedicated to the resistance of bacteria to the action of nanosized silver and describes the putative molecular mechanisms of its development. Emphasis is placed on the study of works devoted to the investigation of the mechanisms of the resistance of bacteria to silver ions, which are the main factor of the bactericidal action of nanoparticles. The review also contains suggestions for further research aimed at developing of ways to overcome the problem of resistance of individual bacterial strains to the action of nanosilver and methods preventing its further spread.

     

The Crisis of "the Activity Approach" in Psychology and Possible Ways to Overcome It

Soviet reflex theorists, like their American S-R counterparts, face a major theoretical hurdle: it is one thing to assert that in principle complex human behavior may be accounted for by the appropriate combination of elementary conditioned reflex patterns; it is quite another to demonstrate the adequacy of such an explanation for any particular bit of complex behavior.     

Bacterial Mechanisms to Overcome Inhibitory Effects of Dietary Tannins

High concentrations of tannins in fodder plants inhibit gastrointestinal bacteria and reduce ruminant performance. Increasing the proportion of tannin-resistant bacteria in the rumen protects ruminants from antinutritional effects. The reason for the protective effect is unclear, but could be elucidated if the mechanism(s) by which tannins inhibit bacteria and the mechanisms of tannin resistance were understood. A review of the literature indicates that the ability of tannins to complex with polymers and minerals is the basis of the inhibitory effect on gastrointestinal bacteria. Mechanisms by which bacteria can overcome inhibition include tannin modification/degradation, dissociation of tannin–substrate complexes, tannin inactivation by high-affinity binders, and membrane modification/repair and metal ion sequestration. Understanding the mechanism of action of tannins and the mechanism(s) bacteria use to overcome the inhibitory effects will allow better management of the rumen ecosystem to reduce the antinutritional effects of tannin-rich fodder plants and thereby improve ruminant production.     

P-糖蛋白在乳腺癌多药耐药中的作用及其调控机制

P-糖蛋白（P-glycoprotein, P-gp）是ABC转运蛋白超家族的一员,能将其药物底物单向转运出细胞. P-gp的过表达被认为是乳腺癌多药耐药（multi-drug resistance, MDR）的主要原因之一. 在乳腺癌MDR的发生和发展中,P-gp受到多种信号通路和转录因子的调控,调控网路非常复杂. 揭示P-gp在乳腺癌中的调控机制,对于克服乳腺癌MDR极其重要. 本文综述了其在乳腺癌MDR中的作用及其调控机制的最新研究进展.     

Sphingolipids in Neuroblastoma: Their Role in Drug Resistance Mechanisms

Disseminated neuroblastoma usually calls for chemotherapy as the primary approach for treatment. Treatment failure is often attributable to drug resistance. This involves a variety of cellular mechanisms, including increased drug efflux through expression of ATP-binding cassette transporters (e.g., P-glycoprotein) and the inability of tumor cells to activate or propagate the apoptotic response. In recent years it has become apparent that sphingolipid metabolism and the generation of sphingolipid species, such as ceramide, also play a role in drug resistance. This may involve an autonomous mechanism, related to direct effects of sphingolipids on the apoptotic response, but also a subtle interplay between sphingolipids and ATP-binding cassette transporters. Here, we present an overview of the current understanding of the multiple levels at which sphingolipids function in drug resistance, with an emphasis on sphingolipid function in neuroblastoma and how modulation of sphingolipid metabolism may be used as a novel treatment paradigm.     

Thinking and Ways of Investigating It

The thought process, of course, breaks down into different elements. Thus, in problem solving, analysis articulates what is given (known) and what unknown; and analysis of information in accordance with the requirements of the particular problem leads to identification of the conditions constituting what is known and what is unknown. Each element of the thought process, viewed from the perspective of the result achieved, is a unitary act (a mental action, an operation). However, in studying thought we must not forget that what makes each element a unitary act is the objectively determined and explicit end result of the thought process. What is initial and primary are not these operations, but the integral thought process of which they are discrete constituents.     

DDC- and 3TC-bis(SATE) Monophosphate Prodrugs Overcome Cellular Resistance Mechanisms to HIV-1 Associated with Cytidine Kinase Deficiency

Abstract

A 2,3′-dideoxycytidine (ddC)-resistant T-lymphoid cell line (MOLT-4/8^rddC²⁵⁰), in which deoxycytidine kinase (dCK) gene-expression was decreased when compared with parental cells, has been selected. Cytotoxic and antiretroviral activity of ddC and 3TC was significantly lower in MOLT-4/8^rddC²⁵⁰ than in parental MOLT-4/8 cells. ddC- and 3TC-bis(SATE)phosphotriesters completely overcame cellular resistance mechanisms and showed comparable both cytotoxic and antiretroviral activity in parental and ddC-resistant cells.     

Probiotics and Psychobiotics: the Role of Microbial Neurochemicals

Probiotics and Antimicrobial Proteins - In light of recent data, microorganisms should be construed as organisms that are capable of communication and collective behaviors. Microbial communication...     

Targeting the Cell Stress Response of Plasmodium falciparum to Overcome Artemisinin Resistance

Successful control of falciparum malaria depends greatly on treatment with artemisinin combination therapies. Thus, reports that resistance to artemisinins (ARTs) has emerged, and that the prevalence of this resistance is increasing, are alarming. ART resistance has recently been linked to mutations in the K13 propeller protein. We undertook a detailed kinetic analysis of the drug responses of K13 wild-type and mutant isolates of Plasmodium falciparum sourced from a region in Cambodia (Pailin). We demonstrate that ART treatment induces growth retardation and an accumulation of ubiquitinated proteins, indicative of a cellular stress response that engages the ubiquitin/proteasome system. We show that resistant parasites exhibit lower levels of ubiquitinated proteins and delayed onset of cell death, indicating an enhanced cell stress response. We found that the stress response can be targeted by inhibiting the proteasome. Accordingly, clinically used proteasome inhibitors strongly synergize ART activity against both sensitive and resistant parasites, including isogenic lines expressing mutant or wild-type K13. Synergy is also observed against Plasmodium berghei in vivo. We developed a detailed model of parasite responses that enables us to infer, for the first time, in vivo parasite clearance profiles from in vitro assessments of ART sensitivity. We provide evidence that the clinical marker of resistance (delayed parasite clearance) is an indirect measure of drug efficacy because of the persistence of unviable parasites with unchanged morphology in the circulation, and we suggest alternative approaches for the direct measurement of viability. Our model predicts that extending current three-day ART treatment courses to four days, or splitting the doses, will efficiently clear resistant parasite infections. This work provides a rationale for improving the detection of ART resistance in the field and for treatment strategies that can be employed in areas with ART resistance.     

Focus: Antimicrobial Resistance: Know your Microbe Foes: The Role of Surveillance in Combatting Antimicrobial Resistance

Antibiotic-resistant organisms (AROs) are difficult and costly to treat, associated with high mortality rates, and are on the rise. In the United States, there is limited tracking of AROs, which can contribute to transmission and inhibit infection prevention interventions. Surveillance is limited by a lack of standardized methods for colonization screening and limited communication regarding patient ARO-status between healthcare settings. Some regional surveillance and reporting efforts are in place for extensively-resistant AROs such as carbapenem-resistant Enterobacterales (CRE), but need to be further expanded nationwide and to include other AROs such as extended-spectrum β-lactamase (ESBL) producing organisms. Increased surveillance of ARO infections and colonization will inform future targeted intervention and infection prevention strategies.     

益生菌及其细胞组分的免疫调节作用

益生菌对肠道黏膜系统的调节作用是应用益生菌提高宿主抵抗某些病源菌感染及预防肿瘤发生的基础。但是,益生菌的作用机理目前还不完全清楚。益生菌细胞壁组分可能是引发免疫反应的功能性物质,而构成各种益生菌细胞壁组分的差异可能是益生菌免疫调节作用存在菌种特异性的主要原因。肠道派伊尔斑外层的M细胞是介导益生菌或其细胞组分进入上皮下层的主要通道,进入上皮下层的益生菌或其细胞残片可以被黏膜免疫系统的树突状细胞(DC)或巨噬细胞吞噬,并呈递给淋巴细胞。益生菌及其细胞组分在黏膜局部刺激黏膜免疫系统,也可以引起系统免疫反应,但其通过局部免疫刺激引起系统免疫反应的机理目前还不清楚。研究益生菌细胞组分构成和益生菌免疫激活作用之间的关系,及由局部免疫刺激引发系统免疫反应的机理是益生菌免疫刺激作用机理研究需要解决的两大问题。     

When It Hurts (and Helps) to Try: The Role of Effort in Language Learning

Compared to children, adults are bad at learning language. This is counterintuitive; adults outperform children on most measures of cognition, especially those that involve effort (which continue to mature into early adulthood). The present study asks whether these mature effortful abilities interfere with language learning in adults and further, whether interference occurs equally for aspects of language that adults are good (word-segmentation) versus bad (grammar) at learning. Learners were exposed to an artificial language comprised of statistically defined words that belong to phonologically defined categories (grammar). Exposure occurred under passive or effortful conditions. Passive learners were told to listen while effortful learners were instructed to try to 1) learn the words, 2) learn the categories, or 3) learn the category-order. Effortful learners showed an advantage for learning words while passive learners showed an advantage for learning the categories. Effort can therefore hurt the learning of categories.     

生物碱抗心律失常的作用及其分子机制

生物碱是广泛存在于生物体内尤其是天然植物中的碱性含氮有机化合物，部分生物碱具有抗心律失常、抗高血压、抗炎以及抗肿瘤等多种生理功能。心律失常是由心脏电生理活动紊乱引起的疾病，是心血管疾病高发病率和死亡率的主要原因，在世界范围内严重威胁人类生命健康。文中综述生物碱在抗心律失常中的作用和分子机制研究进展，并展望其开发应用前景。