Mechanosensitive channel YnaI has lipid-bound extended sensor paddles

The general mechanism of bacterial mechanosensitive channels (MS) has been characterized by extensive studies on a small conductance channel MscS from Escherichia coli (E. coli). However, recent structural studies on the same channel have revealed controversial roles of various channel-bound lipids in channel gating. To better understand bacterial MscS-like channels, it is necessary to characterize homologs other than MscS. Here, we describe the structure of YnaI, one of the closest MscS homologs in E. coli, in its non-conducting state at 3.3 Å resolution determined by cryo electron microscopy. Our structure revealed the intact membrane sensor paddle domain in YnaI, which was stabilized by functionally important residues H43, Q46, Y50 and K93. In the pockets between sensor paddles, there were clear lipid densities that interact strongly with residues Q100 and R120. These lipids were a mixture of natural lipids but may be enriched in cardiolipin and phosphatidylserine. In addition, residues along the ion-conducting pathway and responsible for the heptameric assembly were discussed. Together with biochemical experiments and mutagenesis studies, our results provide strong support for the idea that the pocket lipids are functionally important for mechanosensitive channels.

Evaluation of Water Retention Capacity of Bulkheads in Underground Coal Mines

The mechanism of water flow in and around the bulkheads and the surrounding rock is studied for Panel No. 21102 in the Sanhejian coal mine in Xuzhou, China. Based on an analysis of the properties of the bulkheads and the surrounding rock, three types of water conducting pathways are identified: (1) a water conducting pathway at the interface between the bulkhead and the surrounding rock; (2) a water conducting pathway in the faults of the rock; and (3) a water conducting pathway in the fractures of the rock. The possibility of these three pathways for water flow at Panel No. 21102 is analyzed, and the connectivity coefficient of the water conducting pathway is determined. The expression for calculating the critical hydraulic gradient of the rock by using the connectivity coefficient in the water conducting pathways is presented which is based on the permeability and integrity of the rock. The ratios of the critical hydraulic gradient to the steady state hydraulic gradient are calculated for 13 mines in China. An acceptable safety factor in controlling the water flow for the bulkhead is found to be 1.68. When the safety factor is less than 1.68, water leakage has occurred in a number of cases. Finally, changes in the water pressure in the bulkheads with time and changes in the seepage flow with time in the surrounding rock are analyzed. It is found that there is a good correlation between the rate of water flow and water pressure which confirms that water pressure plays a decisive role in controlling seepage from the rock in and around the bulkheads.

The Impact of Childhood and Adult Educational Attainment and Economic Status on Later Depressive Symptoms and Its Intergenerational Effect

This study aimed to investigate a process accounting for the socioeconomic inequality in depressive symptoms from generation to generation. To examine the process, this study utilized data from three generations of grandparents, mothers, and daughters. This study employed data from the Korean Longitudinal Survey of Women and Families, collected from a large-scale national representative sample in South Korea. Conducting pathway analysis, the study tested direct and indirect pathways between mother’s socioeconomic status (SES) experienced in childhood and their offspring’s depressive symptoms through maternal SES and depressive symptoms in adulthood. This study found that early economic hardship increased the risk of depressive symptoms in daughters through maternal low education and depressive symptoms (β = 0.03, p < 0.05), which was consistent with the theoretical framework, which relied on a life-course model highlighting that early life experiences affect later adult health and can potentially have effects across generations. This finding suggests that interventions that work with maternal education and depression may benefit from efforts to break the likelihood of continuity of depressive symptoms into the next generation, especially for their own daughters.

Viral rhodopsins 1 are an unique family of light-gated cation channels

Phytoplankton is the base of the marine food chain as well as oxygen and carbon cycles and thus plays a global role in climate and ecology. Nucleocytoplasmic Large DNA Viruses that infect phytoplankton organisms and regulate the phytoplankton dynamics encompass genes of rhodopsins of two distinct families. Here, we present a functional and structural characterization of two proteins of viral rhodopsin group 1, OLPVR1 and VirChR1. Functional analysis of VirChR1 shows that it is a highly selective, Na+/K+-conducting channel and, in contrast to known cation channelrhodopsins, it is impermeable to Ca2+ ions. We show that, upon illumination, VirChR1 is able to drive neural firing. The 1.4 Å resolution structure of OLPVR1 reveals remarkable differences from the known channelrhodopsins and a unique ion-conducting pathway. Thus, viral rhodopsins 1 represent a unique, large group of light-gated channels (viral channelrhodopsins, VirChR1s). In nature, VirChR1s likely mediate phototaxis of algae enhancing the host anabolic processes to support virus reproduction, and therefore, might play a major role in global phytoplankton dynamics. Moreover, VirChR1s have unique potential for optogenetics as they lack possibly noxious Ca2+ permeability.

Lysenin Channels as Sensors for Ions and Molecules

Lysenin is a pore-forming protein extracted from the earthworm Eisenia fetida, which inserts large conductance pores in artificial and natural lipid membranes containing sphingomyelin. Its cytolytic and hemolytic activity is rather indicative of a pore-forming toxin; however, lysenin channels present intricate regulatory features manifested as a reduction in conductance upon exposure to multivalent ions. Lysenin pores also present a large unobstructed channel, which enables the translocation of analytes, such as short DNA and peptide molecules, driven by electrochemical gradients. These important features of lysenin channels provide opportunities for using them as sensors for a large variety of applications. In this respect, this literature review is focused on investigations aimed at the potential use of lysenin channels as analytical tools. The described explorations include interactions with multivalent inorganic and organic cations, analyses on the reversibility of such interactions, insights into the regulation mechanisms of lysenin channels, interactions with purines, stochastic sensing of peptides and DNA molecules, and evidence of molecular translocation. Lysenin channels present themselves as versatile sensing platforms that exploit either intrinsic regulatory features or the changes in ionic currents elicited when molecules thread the conducting pathway, which may be further developed into analytical tools of high specificity and sensitivity or exploited for other scientific biotechnological applications.

Viral channelrhodopsins: calcium-dependent Na+/K+ selective light-gated channels

Phytoplankton is the base of the marine food chain, oxygen, carbon cycle playing a global role in climate and ecology. Nucleocytoplasmic Large DNA Viruses regulating the dynamics of phytoplankton comprise genes of rhodopsins of two distinct families. We present a function-structure characterization of two homologous proteins representatives of family 1 of viral rhodopsins, OLPVR1 and VirChR1. VirChR1 is a highly selective, Ca2+-dependent, Na+/K+- conducting channel and, in contrast to known cation channelrhodopsins (ChRs), is impermeable to Ca2+ ions. In human neuroblastoma cells, upon illumination, VirChR1 depolarizes the cell membrane to a level sufficient to fire neurons. It suggests its unique optogenetic potential. 1.4 Å resolution structure of OLPVR1 reveals their remarkable difference from the known channelrhodopsins and a unique ion-conducting pathway. The data suggest that viral channelrhodopsins mediate phototaxis of algae enhancing the host anabolic processes to support virus reproduction, and therefore, their key role in global phytoplankton dynamics.

Non-neoplastic pathology at the crossroads between neck imaging and cardiothoracic imaging

The thoracic inlet is located at the crossroads between imaging of the neck and chest. It represents an important anatomic landmark, serving as the central conducting pathway for many vital structures extending from the neck into the chest and vice versa. Many important body systems are located within this region, including the enteric, respiratory, vascular, lymphatic, neurologic, and endocrine systems. A detailed examination of this region is essential when reviewing neck and thoracic imaging. This article will discuss the normal anatomic boundaries of the thoracic inlet and present an image-rich systematic discussion of the non-neoplastic pathology that can occur in this region. The neoplastic pathology of the thoracic inlet will be covered in a companion article.

Active site rearrangement and structural divergence in prokaryotic respiratory oxidases

Cytochrome bd–type quinol oxidases catalyze the reduction of molecular oxygen to water in the respiratory chain of many human-pathogenic bacteria. They are structurally unrelated to mitochondrial cytochrome c oxidases and are therefore a prime target for the development of antimicrobial drugs. We determined the structure of the Escherichia coli cytochrome bd-I oxidase by single-particle cryo–electron microscopy to a resolution of 2.7 angstroms. Our structure contains a previously unknown accessory subunit CydH, the L-subfamily–specific Q-loop domain, a structural ubiquinone-8 cofactor, an active-site density interpreted as dioxygen, distinct water-filled proton channels, and an oxygen-conducting pathway. Comparison with another cytochrome bd oxidase reveals structural divergence in the family, including rearrangement of high-spin hemes and conformational adaption of a transmembrane helix to generate a distinct oxygen-binding site.