TomoScore: A Neural Network Approach for Quality Assessment of Cellular cryo-ET.

Electron cryo-tomography (cryo-ET) is a powerful imaging tool that allows three-dimensional visualization of subcellular architecture. During morphological analysis, reliable tomogram segmentation can only be achieved through high-quality data. However, unlike single-particle analysis or subtomogram averaging, the field lacks a useful quantitative measurement of cellular tomogram quality.

Correction: Jiménez-Ortigosa et al. Cryo-Electron Tomography of Plasma Membrane Proteins. 2021, , 120.

The authors wish to update the article title to "Cryo-Electron Tomography of Plasma Membrane Proteins" [...

HIV-1 Vpu protein forms stable oligomers in aqueous solution via its transmembrane domain self-association.

We report our findings on the assembly of the HIV-1 protein Vpu into soluble oligomers. Vpu is a key HIV-1 protein. It has been considered exclusively a single-pass membrane protein.

Membrane translocation process revealed by in situ structures of type II secretion system secretins.

The GspD secretin is the outer membrane channel of the bacterial type II secretion system (T2SS) which secrets diverse toxins that cause severe diseases such as diarrhea and cholera. GspD needs to translocate from the inner to the outer membrane to exert its function, and this process is an essential step for T2SS to assemble. Here, we investigate two types of secretins discovered so far in Escherichia coli, GspD, and GspD.

HIV-1 Vpu protein forms stable oligomers in aqueous solution via its transmembrane domain self-association.

We report our findings on the assembly of the HIV-1 protein Vpu into soluble oligomers. Vpu is a key to HIV-1 protein. It has been considered exclusively a single-pass membrane protein.

Pancreatic K3.1 channels in health and disease.

Ion channels play an important role for regulation of the exocrine and the endocrine pancreas. This review focuses on the Ca-regulated K channel K3.1, encoded by the gene, which is present in both parts of the pancreas.

At Crossroads in a Virtual City: Effect of Spatial Disorientation on Gait Variability and Psychophysiological Response among Healthy Older Adults.

Introduction: Aging has been associated with a decline in cognitive and motor performance, often expressed in multitasking situations, which could include wayfinding. A major challenge to successful wayfinding is spatial disorientation, occurring mostly at crossings. Although gait changes have been observed in various dual-task conditions, little is known about the effect of disorientation on gait and psychophysiological response among older adults during wayfinding.

Conformational motions and ligand-binding underlying gating and regulation in IPR channel.

Inositol-1,4,5-trisphosphate receptors (IPRs) are activated by IP and Ca and their gating is regulated by various intracellular messengers that finely tune the channel activity. Here, using single particle cryo-EM analysis we determined 3D structures of the nanodisc-reconstituted IPR1 channel in two ligand-bound states. These structures provide unprecedented details governing binding of IP, Ca and ATP, revealing conformational changes that couple ligand-binding to channel opening.

Precision requirements and data compression in CryoEM/CryoET.

With larger, higher speed detectors and improved automation, individual CryoEM instruments are capable of producing a prodigious amount of data each day, which must then be stored, processed and archived. While it has become routine to use lossless compression on raw counting-mode movies, the averages which result after correcting these movies no longer compress well. These averages could be considered sufficient for long term archival, yet they are conventionally stored with 32 bits of precision, despite high noise levels.

Structural basis for tunable affinity and specificity of LxCxE-dependent protein interactions with the retinoblastoma protein family.

The retinoblastoma protein (Rb) and its homologs p107 and p130 are critical regulators of gene expression during the cell cycle and are commonly inactivated in cancer. Rb proteins use their "pocket domain" to bind an LxCxE sequence motif in other proteins, many of which function with Rb proteins to co-regulate transcription. Here, we present binding data and crystal structures of the p107 pocket domain in complex with LxCxE peptides from the transcriptional co-repressor proteins HDAC1, ARID4A, and EID1.

Prediction of Disorientation by Accelerometric and Gait Features in Young and Older Adults Navigating in a Virtually Enriched Environment.

Objective: To determine whether gait and accelerometric features can predict disorientation events in young and older adults.

Methods: Cognitively healthy younger (18-40 years, = 25) and older (60-85 years, = 28) participants navigated on a treadmill through a virtual representation of the city of Rostock featured within the Gait Real-Time Analysis Interactive Lab (GRAIL) system. We conducted Bayesian Poisson regression to determine the association of navigation performance with domain-specific cognitive functions.

Cryo-ET of parasites gives subnanometer insight into tubulin-based structures.

Tubulin is a conserved protein that polymerizes into different forms of filamentous structures in , an obligate intracellular parasite in the phylum Apicomplexa. Two key tubulin-containing cytoskeletal components are subpellicular microtubules (SPMTs) and conoid fibrils (CFs). The SPMTs help maintain shape and gliding motility, while the CFs are implicated in invasion.

Using Cryo-ET to distinguish platelets during pre-acute myeloid leukemia from steady state hematopoiesis.

Early diagnosis of acute myeloid leukemia (AML) in the pre-leukemic stage remains a clinical challenge, as pre-leukemic patients show no symptoms, lacking any known morphological or numerical abnormalities in blood cells. Here, we demonstrate that platelets with structurally abnormal mitochondria emerge at the pre-leukemic phase of AML, preceding detectable changes in blood cell counts or detection of leukemic blasts in blood. We visualized frozen-hydrated platelets from mice at different time points during AML development in situ using electron cryo-tomography (cryo-ET) and identified intracellular organelles through an unbiased semi-automatic process followed by quantitative measurement.

Context-Aware Human Activity Recognition in Industrial Processes.

The automatic, sensor-based assessment of human activities is highly relevant for production and logistics, to optimise the economics and ergonomics of these processes. One challenge for accurate activity recognition in these domains is the of activities: Similar movements can correspond to different activities, depending on, e.g.

Comprehensive structure and functional adaptations of the yeast nuclear pore complex.

Nuclear pore complexes (NPCs) mediate the nucleocytoplasmic transport of macromolecules. Here we provide a structure of the isolated yeast NPC in which the inner ring is resolved by cryo-EM at sub-nanometer resolution to show how flexible connectors tie together different structural and functional layers. These connectors may be targets for phosphorylation and regulated disassembly in cells with an open mitosis.

In situ structure of the AcrAB-TolC efflux pump at subnanometer resolution.

The tripartite AcrAB-TolC assembly, which spans both the inner and outer membranes in Gram-negative bacteria, is an efflux pump that contributes to multidrug resistance. Here, we present the in situ structure of full-length Escherichia coli AcrAB-TolC determined at 7 Å resolution by electron cryo-tomography. The TolC channel penetrates the outer membrane bilayer through to the outer leaflet and exhibits two different configurations that differ by a 60° rotation relative to the AcrB position in the pump assembly.

Deep learning-based mixed-dimensional Gaussian mixture model for characterizing variability in cryo-EM.

Structural flexibility and/or dynamic interactions with other molecules is a critical aspect of protein function. Cryogenic electron microscopy (cryo-EM) provides direct visualization of individual macromolecules sampling different conformational and compositional states. While numerous methods are available for computational classification of discrete states, characterization of continuous conformational changes or large numbers of discrete state without human supervision remains challenging.

Traceless parallel peptide purification by a first-in-class reductively cleavable linker system featuring a safety-release.

Hundreds of peptides can be synthesized by automated parallel synthesizers in a single run. In contrast, the most widely used peptide purification method - high-pressure liquid chromatography (HPLC) - only allows one-by-one processing of each sample. The chromatographic purification of many peptides, therefore, remains a time-consuming and costly effort.

Cryo-Electron Tomography of Candida glabrata Plasma Membrane Proteins.

Fungal plasma membrane proteins have long been recognized as targets for the development of antifungal agents. Despite recent progress in experimental approaches and computational structural predictions, our knowledge of the structural dynamics and spatial distribution of these membrane proteins in the context of their native lipid environment remains limited. By applying cryo-electron tomography (cryoET) and subtomogram analysis, we aim to characterize the structural characteristics and spatial distribution of membrane proteins present in plasma membranes.