The Effect of a Modified Tenodesis Wrist-hand Orthosis on Hand Function in Patients With Tetraplegia.

Background: An individual experiencing tetraplegia faces functional limitations due to impaired hand function. The use of an affordable tenodesis wrist-hand orthosis (WHO) can enable finger flexion with active wrist extension, thereby enhancing the three-jaw chuck grasp and overall hand functionality.

Objectives: To assess hand function and satisfaction in patients with tetraplegia using a modified tenodesis wrist-hand orthosis (WHO), utilizing the Duruöz Hand Index (DHI) and the Orthotics and Prosthetics User Survey (OPUS) satisfaction with device and services subscales.

Demographic profile and clinical characteristics of Fuchs' endothelial corneal dystrophy in a tertiary eye care center.

Purpose: This study was performed to determine the demographic profile and clinical characteristics in patients with Fuchs' endothelial corneal dystrophy (FECD) reporting to a tertiary eye care center in India. It is a retrospective, single-center, observational study.

Methods: The study included 280 patients (559 eyes) diagnosed with FECD presenting between January 2013 and December 2020.

Effect of Sec62 on the conformation of the Sec61 channel in yeast.

Most eukaryotic secretory and membrane proteins are funneled by the Sec61 complex into the secretory pathway. Furthermore, some substrate peptides rely on two essential accessory proteins, Sec62 and Sec63, being present to assist with their translocation via the Sec61 channel in post-translational translocation. Cryo-electron microscopy (cryo-EM) recently succeeded in determining atomistic structures of unbound and signal sequence-engaged Sec complexes from Saccharomyces cerevisiae, involving the Sec61 channel and the proteins Sec62, Sec63, Sec71 and Sec72.

Signal Peptide Features Determining the Substrate Specificities of Targeting and Translocation Components in Human ER Protein Import.

In human cells, approximately 30% of all polypeptides enter the secretory pathway at the level of the endoplasmic reticulum (ER). This process involves cleavable amino-terminal signal peptides (SPs) or more or less amino-terminal transmembrane helices (TMHs), which serve as targeting determinants, at the level of the precursor polypeptides and a multitude of cytosolic and ER proteins, which facilitate their ER import. Alone or in combination SPs and TMHs guarantee the initial ER targeting as well as the subsequent membrane integration or translocation.

Synthesis, Biological Evaluation and Docking Studies of Ring-Opened Analogues of Ipomoeassin F.

The plant-derived macrocyclic resin glycoside ipomoeassin F (Ipom-F) binds to Sec61α and significantly disrupts multiple aspects of Sec61-mediated protein biogenesis at the endoplasmic reticulum, ultimately leading to cell death. However, extensive assessment of Ipom-F as a molecular tool and a therapeutic lead is hampered by its limited production scale, largely caused by intramolecular assembly of the macrocyclic ring. Here, using in vitro and/or in cellula biological assays to explore the first series of ring-opened analogues for the ipomoeassins, and indeed all resin glycosides, we provide clear evidence that macrocyclic integrity is not required for the cytotoxic inhibition of Sec61-dependent protein translocation by Ipom-F.

Phenylbutyrate rescues the transport defect of the Sec61α mutations V67G and T185A for renin.

The human Sec61 complex is a widely distributed and abundant molecular machine. It resides in the membrane of the endoplasmic reticulum to channel two types of cargo: protein substrates and calcium ions. The gene encodes for the pore-forming Sec61α subunit of the Sec61 complex.

Bioinoculants-Natural Biological Resources for Sustainable Plant Production.

Agricultural sustainability is of foremost importance for maintaining high food production. Irresponsible resource use not only negatively affects agroecology, but also reduces the economic profitability of the production system. Among different resources, soil is one of the most vital resources of agriculture.

Selected Derivatives of Erythromycin B- and Anti-Malarial Studies.

Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their molecular docking into segments of the exit tunnel of the apicoplast ribosome from .

Mycolactone enhances the Ca2+ leak from endoplasmic reticulum by trapping Sec61 translocons in a Ca2+ permeable state.

The Mycobacterium ulcerans exotoxin, mycolactone, is an inhibitor of co-translational translocation via the Sec61 complex. Mycolactone has previously been shown to bind to, and alter the structure of the major translocon subunit Sec61α, and change its interaction with ribosome nascent chain complexes. In addition to its function in protein translocation into the ER, Sec61 also plays a key role in cellular Ca2+ homeostasis, acting as a leak channel between the endoplasmic reticulum (ER) and cytosol.

Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes.

Here, we review recent molecular modelling and simulation studies of the Sec translocon, the primary component/channel of protein translocation into the endoplasmic reticulum (ER) and bacterial periplasm, respectively. Our focus is placed on the eukaryotic Sec61, but we also mention modelling studies on prokaryotic SecY since both systems operate in related ways. Cryo-EM structures are now available for different conformational states of the Sec61 complex, ranging from the idle or closed state over an inhibited state with the inhibitor mycolactone bound near the lateral gate, up to a translocating state with bound substrate peptide in the translocation pore.

Quantitative Proteomics and Differential Protein Abundance Analysis after Depletion of Putative mRNA Receptors in the ER Membrane of Human Cells Identifies Novel Aspects of mRNA Targeting to the ER.

In human cells, one-third of all polypeptides enter the secretory pathway at the endoplasmic reticulum (ER). The specificity and efficiency of this process are guaranteed by targeting of mRNAs and/or polypeptides to the ER membrane. Cytosolic SRP and its receptor in the ER membrane facilitate the cotranslational targeting of most ribosome-nascent precursor polypeptide chain (RNC) complexes together with the respective mRNAs to the Sec61 complex in the ER membrane.

Zinc Biofortification in Food Crops Could Alleviate the Zinc Malnutrition in Human Health.

Micronutrient malnutrition is a global health issue and needs immediate attention. Over two billion people across the globe suffer from micronutrient malnutrition. The widespread zinc (Zn) deficiency in soils, poor zinc intake by humans in their diet, low bioavailability, and health consequences has led the research community to think of an economic as well as sustainable strategy for the alleviation of zinc deficiency.

Targeting Brain Cancer Cells by Nanorobot, a Promising Nanovehicle: New Challenges and Future Perspectives.

Advances in the field of nanotechnology and nanomedicine have resulted in the development of novel diagnosis and potential treatment for different types of diseases, including brain cancer. Nanomaterials are smaller in size, having a higher area to volume ratio, and can be conjugated with other molecules. Nanomaterials are excellent transport vehicles that can easily cross the extracellular matrix, cell membrane, and by crossing the blood-brain barrier, they can deliver the drugs to the remote and inaccessible internal parts of the brain.

How does Sec63 affect the conformation of Sec61 in yeast?

The Sec complex catalyzes the translocation of proteins of the secretory pathway into the endoplasmic reticulum and the integration of membrane proteins into the endoplasmic reticulum membrane. Some substrate peptides require the presence and involvement of accessory proteins such as Sec63. Recently, a structure of the Sec complex from Saccharomyces cerevisiae, consisting of the Sec61 channel and the Sec62, Sec63, Sec71 and Sec72 proteins was determined by cryo-electron microscopy (cryo-EM).

Effect of Concentration, Chain Length, Hydrophobicity, and an External Electric Field on the Growth of Mixed Alkanethiol Self-Assembled Monolayers: A Molecular Dynamics Study.

Growing functionalized self-assembled monolayers (SAMs) with fewer defects and lower cost is the focus of ongoing investigations. In the present study, molecular dynamics simulations were performed to investigate the process of SAM formation on a gold substrate from mixed alkanethiolates in ethanol solution. Using the mixed-SAM system of 11-mercaptoundecanoic acid (MUA) with either 1-decanethiol (C9CH3) or 6-mercaptohexanol (C6OH) in a 3:7 ratio as the standard SAM model, we systematically investigated the effects of the concentration, chain length, functional group, and an external electric field on SAM growth.

Current advancements and future perspectives of immunotherapy in colorectal cancer research.

5-Fluorouracil (5-FU) is the first-line chemotherapy drug for colorectal cancer but most of the patients get resistant to the drug on a longer course of treatment. After the successful use of immunotherapy in melanoma treatment, it was explored with enthusiasm in different types of solid cancers including colorectal cancer. Nivolumab and pembrolizumab (Programmed cell death-1 blocking antibodies) have shown efficacy in the mismatch repair deficient high microsatellite instability (dMMR-MSI-H) subtype of metastatic colorectal cancer (CRC) patients.

Deep-AmPEP30: Improve Short Antimicrobial Peptides Prediction with Deep Learning.

Antimicrobial peptides (AMPs) are a valuable source of antimicrobial agents and a potential solution to the multi-drug resistance problem. In particular, short-length AMPs have been shown to have enhanced antimicrobial activities, higher stability, and lower toxicity to human cells. We present a short-length (≤30 aa) AMP prediction method, Deep-AmPEP30, developed based on an optimal feature set of PseKRAAC reduced amino acids composition and convolutional neural network.

Refined Empirical Force Field to Model Protein-Self-Assembled Monolayer Interactions Based on AMBER14 and GAFF.

Understanding protein interaction with material surfaces is important for the development of nanotechnological devices. The structures and dynamics of proteins can be studied via molecular dynamics (MD) if the protein-surface interactions can be accurately modeled. To answer this question, we computed the adsorption free energies of peptides (representing eleven different amino acids) on a hydrophobic self-assembled monolayer (CH-SAM) and compared them to the benchmark experimental data set.

TNF Receptor Type II as an Emerging Drug Target for the Treatment of Cancer, Autoimmune Diseases, and Graft-Versus-Host Disease: Current Perspectives and Search for Small Molecule Binders.

There is now compelling evidence that TNF receptor type II (TNFR2) is predominantly expressed on CD4Foxp3 regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), and plays a major role in the expansion and function of Tregs and MDSCs. Consequently, targeting of TNFR2 by either antagonists or agonists may represent a novel strategy in the treatment of cancer and autoimmune diseases, by downregulating or upregulating suppressor cell activity. The advance in the understanding of complex structure of TNFR2 and its binding with TNF at molecular levels offers opportunity for structure-guided drug discovery.

AmPEP: Sequence-based prediction of antimicrobial peptides using distribution patterns of amino acid properties and random forest.

Antimicrobial peptides (AMPs) are promising candidates in the fight against multidrug-resistant pathogens owing to AMPs' broad range of activities and low toxicity. Nonetheless, identification of AMPs through wet-lab experiments is still expensive and time consuming. Here, we propose an accurate computational method for AMP prediction by the random forest algorithm.

Molecular Dynamics Information Improves cis-Peptide-Based Function Annotation of Proteins.

cis-Peptide bonds, whose occurrence in proteins is rare but evolutionarily conserved, are implicated to play an important role in protein function. This has led to their previous use in a homology-independent, fragment-match-based protein function annotation method. However, proteins are not static molecules; dynamics is integral to their activity.

Pipeline for inferring protein function from dynamics using coarse-grained molecular mechanics forcefield.

Dynamics is integral to the function of proteins, yet the use of molecular dynamics (MD) simulation as a technique remains under-explored for molecular function inference. This is more important in the context of genomics projects where novel proteins are determined with limited evolutionary information. Recently we developed a method to match the query protein's flexible segments to infer function using a novel approach combining analysis of residue fluctuation-graphs and auto-correlation vectors derived from coarse-grained (CG) MD trajectory.

Enhancement of the properties of a drug by mono-deuteriation: reduction of acid-catalysed formation of a gut-motilide enol ether from 8-deuterio-erythromycin B.

Erythromycin B is structurally very similar to erythromycin A, and also shares its clinically important antibacterial activity. Its potential advantage is that it is much more stable to acid. Both compounds are susceptible to 6-9-enol ether formation, involving loss of a proton from C-8.

De novo inference of protein function from coarse-grained dynamics.

Inference of molecular function of proteins is the fundamental task in the quest for understanding cellular processes. The task is getting increasingly difficult with thousands of new proteins discovered each day. The difficulty arises primarily due to lack of high-throughput experimental technique for assessing protein molecular function, a lacunae that computational approaches are trying hard to fill.

Factors affecting accessibility to blowflies of bodies disposed in suitcases.

Criminals have been known to dispose of bodies in zipped suitcases in an attempt to conceal murder. In order to investigate the forensic implications of this mode of disposal on calculating time of death, it is necessary to study the accessibility of bodies in suitcases to blowflies (Diptera: Calliphoridae) and the possibility of oviposition and infestation under these circumstances. An experimental apparatus was designed that incorporated different zips (toothed and coil) of various gauges (4-6 mm) above a chicken liver bait.