Nonclassical action of Ku70 promotes Treg-suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma.

Ku70, a DNA repair protein, binds to the damaged DNA ends and orchestrates the recruitment of other proteins to facilitate repair of DNA double-strand breaks. Besides its essential role in DNA repair, several studies have highlighted nonclassical functions of Ku70 in cellular processes. However, its function in immune homeostasis and antitumor immunity remains unknown.

Early steps of protein disaggregation by Hsp70 chaperone and class B J-domain proteins are shaped by Hsp110.

Hsp70 is a key cellular system counteracting protein misfolding and aggregation, associated with stress, ageing, and disease. Hsp70 solubilises aggregates and aids protein refolding through substrate binding and release cycles regulated by co-chaperones: J-domain proteins (JDPs) and nucleotide exchange factors (NEFs). Here, we elucidate the collaborative impact of Hsp110 NEFs and different JDP classes throughout Hsp70-dependent aggregate processing.

Co-Infection in COVID-19 Patients: Virulence Genes and Their Influence on Respiratory Epithelial Cells in Light of Risk of Severe Secondary Infection.

Pandemics from viral respiratory tract infections in the 20th and early 21st centuries were associated with high mortality, which was not always caused by a primary viral infection. It has been observed that severe course of infection, complications and mortality were often the result of co-infection with other pathogens, especially . During the COVID-19 pandemic, it was also noticed that patients infected with had a significantly higher mortality rate (61.

Networking the desert plant microbiome, bacterial and fungal symbionts structure and assortativity in co-occurrence networks.

In nature, microbes do not thrive in seclusion but are involved in complex interactions within- and between-microbial kingdoms. Among these, symbiotic associations with mycorrhizal fungi and nitrogen-fixing bacteria are namely known to improve plant health, while providing resources to benefit other microbial members. Yet, it is not clear how these microbial symbionts interact with each other or how they impact the microbiota network architecture.

Carbon Source and Substrate Surface Affect Biofilm Formation by the Plant-Associated Bacterium P482.

The ability of bacteria to colonize diverse environmental niches is often linked to their competence in biofilm formation. It depends on the individual characteristics of a strain, the nature of the colonized surface (abiotic or biotic), or the availability of certain nutrients. P482 efficiently colonizes the rhizosphere of various plant hosts, but a connection between plant tissue colonization and the biofilm formation ability of this strain has not yet been established.

Vitamin B Metabolism: A Network of Multi-Protein Mediated Processes.

The water-soluble vitamin, vitamin B, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its deficiency can lead to hematological and neurological disorders; however, the manifestation of these clinical outcomes is relatively late. It leads to difficulties in the early diagnosis of vitamin B deficiency.

USP28 protects development of inflammation in mouse intestine by regulating STAT5 phosphorylation and IL22 production in T lymphocytes.

Introduction: Ubiquitin-specific proteases (USPs), a large subset of more than 50 deubiquitinase proteins, have recently emerged as promising targets in cancer. However, their role in immune cell regulation, particularly in T cell activation, differentiation, and effector functions, remains largely unexplored.

Methods: We utilized a USP28 knockout mouse line to study the effect of USP28 on T cell activation and function, and its role in intestinal inflammation using the dextran sulfate sodium (DSS)-induced colitis model and a series of in vitro assays.

Mass Spectrometry Proteomics Characterization of Plasma Biomarkers for Colorectal Cancer Associated With Inflammation.

Background: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed.

Novel benzimidazole angiotensin receptor blockers with anti-SARS-CoV-2 activity equipotent to that of nirmatrelvir: computational and enzymatic studies.

Background: Hypertension worsens outcomes in SARS-CoV-2 patients. Sartans, a type of antihypertensive angiotensin receptor blocker-(ARB), reduce COVID-19 morbidity and mortality by targeting angiotensin-converting enzyme-2 (ACE2). This study aimed to evaluate the antiviral and antihypertensive effects of nirmatrelvir, commercial sartans (candesartan, losartan, and losartan carboxylic (Exp3174)), and newly synthesized sartans (benzimidazole-N-biphenyl carboxyl (ACC519C) and benzimidazole-N-biphenyl tetrazole (ACC519T)), compared to nirmatrelvir, the antiviral component of Paxlovid.

Plasma Proteomics Elucidated a Protein Signature in COVID-19 Patients with Comorbidities and Early-Diagnosis Biomarkers.

Despite great scientific efforts, deep understanding of coronavirus-19 disease (COVID-19) immunopathology and clinical biomarkers remains a challenge. Pre-existing comorbidities increase the mortality rate and aggravate the exacerbated immune response against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which can result in more severe symptoms as well as long-COVID and post-COVID complications. In this study, we applied proteomics analysis of plasma samples from 28 patients with SARS-CoV-2, with and without pre-existing comorbidities, as well as their corresponding controls to determine the systemic protein changes caused by the SARS-CoV-2 infection.

Keratinocyte-derived small extracellular vesicles supply antigens for CD1a-resticted T cells and promote their type 2 bias in the context of filaggrin insufficiency.

Introduction: Exosome-enriched small extracellular vesicles (sEVs) are nanosized organelles known to participate in long distance communication between cells, including in the skin. Atopic dermatitis (AD) is a chronic inflammatory skin disease for which filaggrin () gene mutations are the strongest genetic risk factor. Filaggrin insufficiency affects multiple cellular function, but it is unclear if sEV-mediated cellular communication originating from the affected keratinocytes is also altered, and if this influences peptide and lipid antigen presentation to T cells in the skin.

Biochemical evidence for conformational variants in the anti-viral and pro-metastatic protein IFITM1.

Interferon induced transmembrane proteins (IFITMs) play a dual role in the restriction of RNA viruses and in cancer progression, yet the mechanism of their action remains unknown. Currently, there is no data about the basic biochemical features or biophysical properties of the IFITM1 protein. In this work, we report on description and biochemical characterization of three conformational variants/oligomeric species of recombinant IFITM1 protein derived from an expression system.

Toward an understanding of the DNA replication initiation in bacteria.

Although the mechanism of DNA replication initiation has been investigated for over 50 years, many important discoveries have been made related to this process in recent years. In this mini-review, we discuss the current state of knowledge concerning the structure of the origin region in bacterial chromosomes and plasmids, recently discovered motifs recognized by replication initiator proteins, and proposed in the literature models describing initial origin opening. We review structures of nucleoprotein complexes formed by replication initiators at chromosomal and plasmid replication origins and discuss their functional implications.

Biotechnological strategies for controlled accumulation of flavones in hairy root culture of Scutellaria lateriflora L.

Accumulation of medicinally important flavones and acteoside was evaluated in Scutellaria lateriflora hairy root cultures subjected to different experimental strategies - feeding with precursors of phenolics biosynthesis (phenylalanine, cinnamic acid, and sodium cinnamate), addition of elicitors (chitosan, jasmonic acid) and Amberlite XAD-4 and XAD-7 resins and permeabilization with dimethyl sulfoxide (DMSO) and methanol. The production profile of S. lateriflora cultures changed under the influence of the applied strategies.

Dual-Activity Fluoroquinolone-Transportan 10 Conjugates Offer Alternative Leukemia Therapy during Hematopoietic Cell Transplantation.

Hematopoietic cell transplantation (HCT) is often considered a last resort leukemia treatment, fraught with limited success due to microbial infections, a leading cause of mortality in leukemia patients. To address this critical issue, we explored a novel approach by synthesizing antileukemic agents containing antibacterial substances. This innovative strategy involves conjugating fluoroquinolone antibiotics, such as ciprofloxacin (CIP) or levofloxacin (LVX), with the cell-penetrating peptide transportan 10 (TP10).

An engineered A549 cell line expressing CD13 and TMPRSS2 is permissive to clinical isolate of human coronavirus 229E.

The lack of suitable in vitro culture model has hampered research on wild-type (WT) human coronaviruses. While 3D tissue or organ cultures have been instrumental for this purpose, such models are challenging, time-consuming, expensive and require extensive cell culture adaptation and directed evolution. Consequently, high-throughput applications are beyond reach in most cases.

Rep protein accommodates together dsDNA and ssDNA which enables a loop-back mechanism to plasmid DNA replication initiation.

For DNA replication initiation in Bacteria, replication initiation proteins bind to double-stranded DNA (dsDNA) and interact with single-stranded DNA (ssDNA) at the replication origin. The structural-functional relationship of the nucleoprotein complex involving initiator proteins is still elusive and different models are proposed. In this work, based on crosslinking combined with mass spectrometry (MS), the analysis of mutant proteins and crystal structures, we defined amino acid residues essential for the interaction between plasmid Rep proteins, TrfA and RepE, and ssDNA.

Conformation-specific Synthetic Antibodies Discriminate Multiple Functional States of the Ion Channel CorA.

CorA, the primary magnesium ion channel in prokaryotes and archaea, is a prototypical homopentameric ion channel that undergoes ion-dependent conformational transitions. CorA adopts five-fold symmetric non-conductive states in the presence of high concentrations of Mg, and highly asymmetric flexible states in its complete absence. However, the latter were of insufficient resolution to be thoroughly characterized.

Sex-dependent differences in behavioral and immunological responses to antibiotic and bacteriophage administration in mice.

Introduction: The problem of antibiotic resistance is a global one, involving many industries and entailing huge financial outlays. Therefore, the search for alternative methods to combat drug-resistant bacteria has a priority status. Great potential is seen in bacteriophages which have the natural ability to kill bacterial cells.