BioEssays最新文献

The precise regulation of the transcription of genes is essential for normal development and for the maintenance of life. Aberrant gene expression changes drive many human diseases. Despite this, we still do not completely understand how precise gene regulation is controlled in living systems. Enhancers are key regulatory elements that enable cells to specifically activate genes in response to environmental cues, or in a stage or tissue-specific manner. Any model of enhancer activity needs to answer two main questions: (1) how enhancers are able to identify and act on specific genes and (2) how enhancers influence transcription. To address these points, we first outline some of the basic principles that can be established from simpler prokaryotic systems, then discuss recent work on aberrant enhancer activity in leukemia. We argue that highly specific protein-protein interactions are a key driver of enhancer-promoter proximity, allowing enhancer-bound factors to directly act on RNA polymerase and activate transcription.

Recent studies show the importance of mesoscale changes to plasma membrane (PM) topography during cell shape change. Local folding and flattening of the cell surface is mechanosensitive, changing in response to both microenvironment structural elements and intracellular cytoskeletal activities. These topography changes elicit local mechanical signaling events that act in conjunction with molecular signal transduction pathways to remodel the cell cortex. Experimental manipulations of local PM curvature show its sufficiency for recruiting Arp2/3 actin network induction pathways. Additionally, studies of diverse cell shape changes-ranging from neutrophil migration to early Drosophila embryo cleavage to neural stem cell asymmetric division-show that local generation of PM folding is linked with local Arp2/3 actin network induction, which then remodels the PM topography during dynamic control of cell structure. These examples are reviewed in detail, together with known and potential causes of PM topography changes, downstream effects, and higher-order feedback.

The public health issue of bacterial multi-resistance to antibiotics has gained awareness among the public, researchers, and the pharmaceutical sector. Nevertheless, the spread of antimicrobial resistance has been considerably aggravated by human activities, climate change, and the subsequent increased release of antibiotics, drug-resistant bacteria, and antibiotic resistance genes in the environment. The extensive use of antibiotics for medical and veterinary purposes has not only induced increasing resistance but also other health problems, including negative effects on the patient's microbiome. Preventive strategies, new treatment modalities, and increased surveillance are progressively set up. A comprehensive approach is, however, lacking for urgently tackling this adverse situation. To address this challenge, we discussed here the main causes driving antimicrobial resistance and pollution of the environment by factors favorable to the emergence of drug resistance. We next propose some key priorities for research, prevention, surveillance, and education to supervise an effective clinical and sustainable response.

Spermatozoa reach the fallopian tube during ovulation by traveling through the female reproductive tract mucus. This non-Newtonian viscoelastic medium facilitates spermatozoon movement to accomplish fertilization or, in some cases, blocks spermatozoon movement, leading to infertility. While rheological properties are known to affect spermatozoon motility with in vitro models using synthetic polymers, their precise effects in vivo are understudied. This paper reviews the rheological measurements of reproductive tract mucus during ovulation in humans and model animals, focusing on viscosity and its potential effect on spermatozoa. Mucus viscosity in the female reproductive tract's different compartments is poorly understood. While information on this subject is incomplete, most mammals appear to have a viscosity decrease along their female reproductive tracts. Based on this sparse information, we hypothesize that viscosity changes in female reproductive tracts may guide spermatozoa to eggs, a novel concept that could improve our understanding of reproductive biology.

Bacterial pathogens deliver effector proteins into host cells by deploying sophisticated secretion systems. This effector translocation during host-pathogen interactions is a prerequisite for the manipulation of host cells and organisms and is important for pathogenesis. Analyses of dynamics and kinetics of translocation, subcellular localization, and cellular targets of effector proteins lead to understanding the mode of action and function of effector proteins in host-pathogen interplay. This review provides an overview of biochemical and genetic tools that have been developed to study protein effector translocation qualitatively or quantitatively. After introducing the challenges of analyses of effector translocation during host-pathogen interaction, we describe various methods ranging from static visualization in fixed cells to dynamic live-cell imaging of effector protein translocation. We show the main findings enabled by the approaches, emphasize the advantages and limitations of the methods, describe recent approaches that allow real-time tracking of effector proteins in living cells on a single molecule level, and highlight open questions in the field to be addressed by application of new methods.