Hotspots for Disease-Causing Mutations in the Mitochondrial TIM23 Import Complex.

The human mitochondrial proteome comprises approximately 1500 proteins, with only 13 being encoded by mitochondrial DNA. The remainder are encoded by the nuclear genome, translated by cytosolic ribosomes, and subsequently imported into and sorted within mitochondria. The process of mitochondria-destined protein import is mediated by several intricate protein complexes distributed among the four mitochondrial compartments.

An Update of Phenotypic-Genotypic IMNEPD Cases and a Bioinformatics Analysis of the New Gene Variants.

Background/objectives: Biallelic mutations in the gene are associated with a rare genetic disease known as infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). In this study, we describe a new case carrying a previously identified mutation, provide an updated analysis of the relative frequencies of the clinical features across all published cases (including the three latest studies), and perform a bioinformatics analysis of the newly identified PTRH2 protein variants from a structural perspective.

Methods: Clinical examination of the patients was carried out, and genetic testing was performed using a genome sequencing strategy.

Biochemical and neurophysiological effects of deficiency of the mitochondrial import protein TIMM50.

TIMM50, an essential TIM23 complex subunit, is suggested to facilitate the import of ~60% of the mitochondrial proteome. In this study, we characterized a disease-causing mutation in human fibroblasts and noted significant decreases in TIM23 core protein levels (TIMM50, TIMM17A/B, and TIMM23). Strikingly, TIMM50 deficiency had no impact on the steady-state levels of most of its putative substrates, suggesting that even low levels of a functional TIM23 complex are sufficient to maintain the majority of TIM23 complex-dependent mitochondrial proteome.

Could tolerance to DNA be broken in the gut in systemic lupus erythematosus?

The bacteria in the human colon outnumber the total number of nucleated cells in the human body by approximately 10:1. The DNA that the bacteria contain is enriched around 20-fold in immune stimulatory CpG motifs compared to the DNA of host cells. In addition, this DNA can have alternative more immunogeneic DNA structures and it may be presented to the immune system alongside other proinflammatory bacterial innate ligands such as LPS.

Optimization of W-band interaction structure developed using three different micro-fabrication techniques.

In this paper, an experimental investigation has been performed for the three different micro-fabrication techniques for optimization in the development process of the W-band planar beam-wave interaction structure. The W-band planar beam-wave interaction structure has been developed using three different micro-fabrication methods, namely micro-EDM (electric discharge milling), wire-EDM, and micro-milling. The effect of each fabrication method on the developed structure is analyzed using scanning electron microscopy and ZETA 3D optical microscopy for their optimization.

Biochemical and neurophysiological effects of deficiency of the mitochondrial import protein TIMM50.

TIMM50, an essential TIM23 complex subunit, is suggested to facilitate the import of ∼60% of the mitochondrial proteome. In this study, we characterized a disease causing mutation in human fibroblasts and noted significant decreases in TIM23 core protein levels (TIMM50, TIMM17A/B, and TIMM23). Strikingly, TIMM50 deficiency had no impact on the steady state levels of most of its putative substrates, suggesting that even low levels of a functional TIM23 complex are sufficient to maintain the majority of TIM23 complex-dependent mitochondrial proteome.

Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue.

Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across the follicle associated epithelium into the subepithelial dome. The initial response to antigens and how bacteria are handled is incompletely understood. By iterative application of spatial transcriptomics and multiplexed single-cell technologies, we identify that the double negative 2 subset of B cells, previously associated with autoimmune diseases, is present in the subepithelial dome in health.

Role of microRNAs and their putative mechanism in regulating potato (Solanum tuberosum L.) life cycle and response to various environmental stresses.

The exponentially increasing population and the demand for food is inextricably linked. This has shifted global attention to improving crop plant traits to meet global food demands. Potato (Solanum tuberosum L.

A double-blinded study for quantifiable assessment of the diagnostic accuracy of AI tool "ADVEN-i" in identifying diseased fundus images including diabetic retinopathy on a retrospective data.

Purpose: To quantifiably assess the diagnostic accuracy of Adven-I, a proprietary artificial intelligence (AI)-driven diagnostic system that automatically detects diseases from fundus images. The purpose is to quantify the performance of Adven-i in differentiating a nonreferable (within normal limits) image from a referable (diseased fundus) image and further segregating diabetic retinopathy (DR) from the rest of the abnormalities (non-DR) encompassing the wide spectrum of abnormal pathologies. The assessment is carried out in comparison to manual reading as the reference gold standard.

Time-varying risks of infection in patients as they proceed through the phases of 'pre-RA': results from the Scottish Early RA inception cohort.

Unlabelled: ObjectiveRheumatoid arthritis (RA) develops after progressing through sequential 'pre-RA' phases. The mechanisms driving progression from one phase to the next remain poorly understood. This study examined the longitudinal rates of community and hospital infections in patients during sequential stages of pre-RA and early arthritis.

Transverse myelitis associated with systemic lupus erythematosus (SLE-TM): A review article.

Systemic lupus erythematosus-related transverse myelitis (SLE-TM) is a rare but serious complication of SLE, which may result in significant morbidity. Its incidence is estimated between 0.5% and 1% of all SLE patients but may be the presenting feature in 30%-60% of these patients.

Gene Variants: Recent Review of the Phenotypic Features and Their Bioinformatics Analysis.

Peptidyl-tRNA hydrolase 2 (PTRH2) is an evolutionarily highly conserved mitochondrial protein. The biallelic mutations in the gene have been suggested to cause a rare autosomal recessive disorder characterized by an infantile-onset multisystem neurologic endocrine and pancreatic disease (IMNEPD). Patients with IMNEPD present varying clinical manifestations, including global developmental delay associated with microcephaly, growth retardation, progressive ataxia, distal muscle weakness with ankle contractures, demyelinating sensorimotor neuropathy, sensorineural hearing loss, and abnormalities of thyroid, pancreas, and liver.

Computational identification of a multi-peptide vaccine candidate in E2 glycoprotein against diverse Hepatitis C virus genotypes.

Hepatitis C Virus (HCV) is estimated to affect nearly 180 million people worldwide, culminating in ∼0.7 million yearly casualties. However, a safe vaccine against HCV is not yet available.

Epidemiology of Ebolaviruses from an Etiological Perspective.

Since the inception of the ebolavirus in 1976, 32 outbreaks have resulted in nearly 15,350 deaths in more than ten countries of the African continent. In the last decade, the largest (2013-2016) and second largest (2018-2020) ebolavirus outbreaks have occurred in West Africa (mainly Guinea, Liberia, and Sierra Leone) and the Democratic Republic of the Congo, respectively. The 2013-2016 outbreak indicated an alarming geographical spread of the virus and was the first to qualify as an epidemic.

Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by destruction of the myelin sheath structure. The loss of myelin leads to damage of a neuron's axon and cell body, which is identified as brain lesions on magnetic resonance image (MRI). The pathogenesis of MS remains largely unknown.

Underrepresentation of ethnic minorities in hypertension research-a survey of enablers and barriers among South Asian and African communities in Glasgow.

Background: Hypertension is the biggest contributor to the global cardiovascular burden with evidence for ethnic differences in treatment response and outcomes. Under-representation of ethnic minorities in clinical research is well known, and despite wide-ranging public engagement events by the Glasgow Blood Pressure Clinic team, there was a lack of participation of ethnic minorities in both engagement activities and clinical trials conducted by them. This study aims to explore the awareness and knowledge of hypertension and the facilitators and barriers to participation in hypertension clinical research among South Asian (SA) and African (AFR) communities in Glasgow.

Computational design of immunogenic peptide constructs comprising multiple human leukocyte antigen restricted dengue virus envelope epitopes.

Dengue virus (DENV) is endemic in 100 countries with the ability to impact nearly 50% of world population. DENV envelope (E) protein is responsible for viral attachment to host cells and has been target of various countermeasure development efforts. The current study focuses on a consensus computational approach to identify cross-reactive, immunogenic DENV-2 E peptides displaying promiscuity with a wide array of human leukocyte antigen (HLA) molecules.

Inhibitory activities of grape bioactive compounds against enzymes linked with human diseases.

A quest for identification of novel, safe and efficient natural compounds, as additives in the modern food and cosmetic industries, has been prompted by concerns about toxicity and side effects of synthetic products. Plant phenolic compounds are one of the most documented natural products due to their multifarious biological applications. Grape (Vitis vinifera) is an important source of phenolic compounds such as phenolic acids, tannins, quinones, coumarins and, most importantly, flavonoids/flavones.

Structural and Functional Aspects of Ebola Virus Proteins.

Ebola virus (EBOV), member of genus , family , have a non-segmented, single-stranded RNA that contains seven genes: (a) nucleoprotein (NP), (b) viral protein 35 (VP35), (c) VP40, (d) glycoprotein (GP), (e) VP30, (f) VP24, and (g) RNA polymerase (L). All genes encode for one protein each except GP, producing three pre-proteins due to the transcriptional editing. These pre-proteins are translated into four products, namely: (a) soluble secreted glycoprotein (sGP), (b) Δ-peptide, (c) full-length transmembrane spike glycoprotein (GP), and (d) soluble small secreted glycoprotein (ssGP).

Immunoinformatics aided design of peptide-based vaccines against ebolaviruses.

Ebolaviruses are at the forefront of emerging viruses and present a very perceptible threat to global peace and harmony. In the last decade, Ebola virus disease has claimed more than 90% of total lives since its inception in 1976. Owing to multiple host immune evasion methods employed by the virus and the limitations of traditional vaccine development approaches, finding a globally effective and reliable counter measure against Ebola virus remains a challenge.

Conserved immunogenic peptides of Ebola glycoprotein elicit immune response in human peripheral blood mononuclear cells.

In the past 45 years, ebolaviruses have periodically caused epidemics on the African continent. In December 2019, approval of a recombinant vector-based EBOV vaccine, named Ervebo, came as encouraging news; still, there is a long way to go in the development of an accessible, global, and pan-ebolavirus vaccine. The current study expanded our previous in silico work which was conducted on ebolavirus glycoprotein and this resulted in the identification of three potentially immunogenic peptides (P1 - FKRTSFFLWVIILFQRTFSIPL, P2 - LANETTQALQLF, and P3 - RATTELRTFSILNRKAIDF).

Enzymatic vitreolysis using reengineered derived collagenase.

Purpose: Collagen is a key player contributing to vitreoelasticity and vitreoretinal adhesions. Molecular reorganization causes spontaneous weakening of these adhesions with age, resulting in the separation of the posterior hyaloid membrane (PHM) from the retina in what is called complete posterior vitreous detachment (PVD). Incomplete separation of the posterior hyaloid or tight adherence or both can lead to retinal detachment, vitreomacular traction syndrome, or epiretinal membrane formation, which requires surgical intervention.