Defective kinase activity of IKKα leads to combined immunodeficiency and disruption of immune tolerance in humans.

IKKα is a multifunctional serine/threonine kinase that controls various biological processes, either dependent on or independent of its kinase activity. However, the importance of the kinase function of IKKα in human physiology remains unknown since no biallelic variants disrupting its kinase activity have been reported. In this study, we present a homozygous germline missense variant in the kinase domain of IKKα, which is present in three children from two Turkish families.

Tumor-derived RHOA mutants interact with effectors in the GDP-bound state.

RHOA mutations are found at diverse residues in various cancer types, implying mutation- and cell-specific mechanisms of tumorigenesis. Here, we focus on the underlying mechanisms of two gain-of-function RHOA mutations, A161P and A161V, identified in adult T-cell leukemia/lymphoma. We find that RHOA and RHOA are both fast-cycling mutants with increased guanine nucleotide dissociation/association rates compared with RHOA and show reduced GTP-hydrolysis activity.

MHC Class II Deficiency: Clinical, Immunological, and Genetic Insights in a Large Multicenter Cohort.

Background: Major histocompatibility complex class II deficiency, a combined immunodeficiency, results from loss of HLA class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation stands as the sole curative approach, although factors influencing patient outcomes remain insufficiently explored.

Objectives: To elucidate the clinical, immunologic, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates.

PPInterface: A Comprehensive Dataset of 3D Protein-Protein Interface Structures.

The PPInterface dataset contains 815,082 interface structures, providing the most comprehensive structural information on protein-protein interfaces. This resource is extracted from over 215,000 three-dimensional protein structures stored in the Protein Data Bank (PDB). The dataset contains a wide range of protein complexes, providing a wealth of information for researchers investigating the structural properties of protein-protein interactions.

DiPPI: A Curated Data Set for Drug-like Molecules in Protein-Protein Interfaces.

Proteins interact through their interfaces, and dysfunction of protein-protein interactions (PPIs) has been associated with various diseases. Therefore, investigating the properties of the drug-modulated PPIs and interface-targeting drugs is critical. Here, we present a curated large data set for drug-like molecules in protein interfaces.

Dysbiosis in pregnant mice induced by transfer of human vaginal microbiota followed by reversal of pathological changes in the uterus and placenta via progesterone treatment.

Objective: The vaginal microbiota dysbiosis induces inflammation in the uterus that triggers tissue damage and is associated with preterm birth. Progesterone is used to prevent labor in pregnant women at risk of preterm birth. However, the mechanism of action of progesterone still needs to be clarified.

The vaginal microbiome composition during pregnancy in a region compromising different ethnic origins.

Background: The vaginal microbiota plays a significant role in pregnancy outcomes and newborn health. Indeed, the composition and diversity of the vaginal microbiota can vary among different ethnic groups. Our study aimed to investigate the composition of the vaginal microbiome throughout the three trimesters of pregnancy and to identify any potential variations or patterns in the Turkish population compromising mixed ethnicities.

Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

Introduction: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs.

ProInterVal: Validation of Protein-Protein Interfaces through Learned Interface Representations.

Proteins are vital components of the biological world and serve a multitude of functions. They interact with other molecules through their interfaces and participate in crucial cellular processes. Disruption of these interactions can have negative effects on organisms, highlighting the importance of studying protein-protein interfaces for developing targeted therapies for diseases.

Association of childhood asthma with Gasdermin B (GSDMB) and Oromucoid-like 3 (ORMDL3) genes.

Objective: Genome-length association studies have shown that Gasdermin B (GSDMB) and Orosomucoid-like 3 (ORMDL3) genes located on the long arm of chromosome 17 are associated with asthma. In this study, it was aimed to determine the possible relationship between asthma control test (ACT), exercise provocation test (ECT), and fractional nitric oxide (FENO) levels and GSDMB and ORMDL3 gene expressions.

Methods: 59 asthmatic and 38 non-asthmatic children were included in the study.

Attenuation of Type IV pili activity by natural products.

The virulence factor Type IV pili (T4P) are surface appendages used by the opportunistic pathogen for twitching motility and adhesion in the environment and during infection. Additionally, the use of these appendages by for biofilm formation increases its virulence and drug resistance. Therefore, attenuation of the activity of T4P would be desirable to control infections.

Shared Proteins and Pathways of Cardiovascular and Cognitive Diseases: Relation to Vascular Cognitive Impairment.

One of the primary goals of systems medicine is the detection of putative proteins and pathways involved in disease progression and pathological phenotypes. Vascular cognitive impairment (VCI) is a heterogeneous condition manifesting as cognitive impairment resulting from vascular factors. The precise mechanisms underlying this relationship remain unclear, which poses challenges for experimental research.

Conformational diversity and protein-protein interfaces in drug repurposing in Ras signaling pathway.

We focus on drug repurposing in the Ras signaling pathway, considering structural similarities of protein-protein interfaces. The interfaces formed by physically interacting proteins are found from PDB if available and via PRISM (PRotein Interaction by Structural Matching) otherwise. The structural coverage of these interactions has been increased from 21 to 92% using PRISM.

Structural coverage of the human interactome.

Complex biological processes in cells are embedded in the interactome, representing the complete set of protein-protein interactions. Mapping and analyzing the protein structures are essential to fully comprehending these processes' molecular details. Therefore, knowing the structural coverage of the interactome is important to show the current limitations.

Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency.

Background: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown.

Objective: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up.

Defective Treg generation and increased type 3 immune response in leukocyte adhesion deficiency 1.

In 15 Turkish LAD-1 patients and controls, we assessed the impact of pathogenic ITGB2 mutations on Th17/Treg differentiation and functions, and innate lymphoid cell (ILC) subsets. The percentage of peripheral blood Treg cells, in vitro-generated induced Tregs differentiated from naive CD4 T cells were decreased despite the elevated absolute counts of CD4 cells in LAD-1 patients. Serum IL-23 levels were elevated in LAD-1 patients.

A Genome-Wide Functional Screen Identifies Enhancer and Protective Genes for Amyloid Beta-Peptide Toxicity.

Alzheimer's disease (AD) is known to be caused by amyloid β-peptide (Aβ) misfolded into β-sheets, but this knowledge has not yet led to treatments to prevent AD. To identify novel molecular players in Aβ toxicity, we carried out a genome-wide screen in , using a library of 5154 gene knock-out strains expressing Aβ. We identified 81 mammalian orthologue genes that enhance Aβ toxicity, while 157 were protective.

Piperidine-based natural products targeting Type IV pili antivirulence: A computational approach.

Type IV (T4) pilus is among the virulence factors with a key role in serious bacterial diseases. Specifically, in Neisseria meningitidis and Pseudomonas aeruginosa, it determines pathogenicity and causes infection. Here, a computational approach has been pursued to find piperidine-based inhibitor molecules against the elongation ATPase of T4 pili in these two selected pathogens.