Inhibition mechanism of potential antituberculosis compound lansoprazole sulfide.

Tuberculosis is one of the most common causes of death worldwide, with a rapid emergence of multi-drug-resistant strains underscoring the need for new antituberculosis drugs. Recent studies indicate that lansoprazole-a known gastric proton pump inhibitor and its intracellular metabolite, lansoprazole sulfide (LPZS)-are potential antituberculosis compounds. Yet, their inhibitory mechanism and site of action still remain unknown.

Electron transfer in the respiratory chain at low salinity.

Recent studies have established that cellular electrostatic interactions are more influential than assumed previously. Here, we use cryo-EM and perform steady-state kinetic studies to investigate electrostatic interactions between cytochrome (cyt.) c and the complex (C) III-IV supercomplex from Saccharomyces cerevisiae at low salinity.

Stimulation of cytochrome c oxidase activity by detergents.

Cytochrome c oxidase (CytcO) is an integral membrane protein, which catalyzes four-electron reduction of oxygen linked to proton uptake and pumping. Amphipathic molecules bind in sites near the so-called K proton pathway of CytcO to reversibly modulate its activity. However, purification of CytcO for mechanistic studies typically involves the use of detergents, which may interfere with binding of these regulatory molecules.

Long-range charge transfer mechanism of the IIIIV mycobacterial supercomplex.

Aerobic life is powered by membrane-bound redox enzymes that shuttle electrons to oxygen and transfer protons across a biological membrane. Structural studies suggest that these energy-transducing enzymes operate as higher-order supercomplexes, but their functional role remains poorly understood and highly debated. Here we resolve the functional dynamics of the 0.

Structure-Activity Relationships and Therapeutic Applications of Retinoids in View of Potential Benefits from Drug Repurposing Process.

Vitamin A, an essential micronutrient, is integral to various biological processes crucial for organismal development and maintenance. Dietary sources of vitamin A encompass preformed retinol, retinyl esters, and provitamin A carotenoids. Retinoic acid (RA), a key component, plays pivotal roles in vision, cell proliferation, apoptosis, immune function, and gene regulation.

Structure and function of the III-IV-cyt supercomplex.

The respiratory chain in aerobic organisms is composed of a number of membrane-bound protein complexes that link electron transfer to proton translocation across the membrane. In mitochondria, the final electron acceptor, complex IV (CIV), receives electrons from dimeric complex III (CIII), via a mobile electron carrier, cytochrome . In the present study, we isolated the CIIICIV supercomplex from the fission yeast and determined its structure with bound cyt.

Structure of the - respiratory supercomplex from .

Energy conversion by electron transport chains occurs through the sequential transfer of electrons between protein complexes and intermediate electron carriers, creating the proton motive force that enables ATP synthesis and membrane transport. These protein complexes can also form higher order assemblies known as respiratory supercomplexes (SCs). The electron transport chain of the opportunistic pathogen is closely linked with its ability to invade host tissue, tolerate harsh conditions, and resist antibiotics but is poorly characterized.

Isotretinoin-associated acne fulminans: A multicentre, retrospective study of the European Academy of Dermatology and Venereology Task Force on Acne, Rosacea and Hidradenitis Suppurativa.

Background: Acne fulminans (AF) is a rare severe acne entity. Although occasionally reported, it is unclear whether AF development is associated with oral isotretinoin treatment.

Objectives: To investigate the occurrence of isotretinoin-associated AF, clinical characteristics and prognosis at follow-up.

Immunohistochemical analysis of the ligamentum mucosum is the key to understand its clinical usefulness.

Ligamentum Mucosum(LM) is a ligamentous structure within the synovial layer of the knee joint capsule. For a long time LM was perceived as the vestigial remnant from the embryological development of the knee. Being treated as an irrelevant structure LM was often the first victim of shaver during arthroscopy.

Structure of mycobacterial respiratory complex I.

Oxidative phosphorylation, the combined activity of the electron transport chain (ETC) and adenosine triphosphate synthase, has emerged as a valuable target for the treatment of infection by and other mycobacteria. The mycobacterial ETC is highly branched with multiple dehydrogenases transferring electrons to a membrane-bound pool of menaquinone and multiple oxidases transferring electrons from the pool. The proton-pumping type I nicotinamide adenine dinucleotide (NADH) dehydrogenase (Complex I) is found in low abundance in the plasma membranes of mycobacteria in typical in vitro culture conditions and is often considered dispensable.

Cryo-EM structure and function of S. pombe complex IV with bound respiratory supercomplex factor.

Fission yeast Schizosaccharomyces pombe serves as model organism for studying higher eukaryotes. We combined the use of cryo-EM and spectroscopy to investigate the structure and function of affinity purified respiratory complex IV (CIV) from S. pombe.

Microanatomical study of arachnoid granulations and meningeal architecture around Meckel's cave.

Although the microanatomy of Meckel's cave (MC) has been well studied, there are still controversies regarding the meningeal architecture of the space. Moreover, there are only general mentions of the arachnoid granulations near MC in just a few sources. This study is aimed at determining the frequency, location, and anatomical variability of the main clusters of arachnoid granulations around MC.

SYMPTOMATOLOGY AND TREATMENT OF COVID-19 AFFECTING SKIN APPENDAGES: A NARRATIVE REVIEW BEYOND COVID-TOES.

SARS-CoV-2 is the cause of COVID-19 disease and responsible for a pandemic since the 2020. Multiple organ involvement has been described including cutaneous symptoms. Affection of skin appendages, however, seems to be under-reported except for COVID-toes.

A Multicenter Cohort Study Evaluating the Teratogenic Effects of Isotretinoin on Neonates.

(1) Background: Isotretinoin (ISO) is a systemic retinoid known for its teratogenic effects on embryos and fetuses. The aim of this study was to compare the pregnancy outcomes of women who were exposed to isotretinoin with those of women without such exposure from a teratogenic point of view. (2) Methods: A total of 1459 female patients from three clinical hospitals in Poland and Romania, segregated into two groups depending on their ISO exposure, were evaluated between January and December 2019.

The use of isotretinoin in acne therapy in early childhood and its effect on the occurrence of acne symptoms later in life. Eight-year follow-up.

Introduction: Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous follicles that affects patients of all ages.

Aim: Use of isotretinoin in the early stages of the disease to prevent subsequent lesions of acne, including prolonged treatment and acne scars at a later age.

Material And Methods: A retrospective, comparative study was carried between January 2010 and November 2018.

Structural basis of mammalian complex IV inhibition by steroids.

The mitochondrial electron transport chain maintains the proton motive force that powers adenosine triphosphate (ATP) synthesis. The energy for this process comes from oxidation of reduced nicotinamide adenine dinucleotide (NADH) and succinate, with the electrons from this oxidation passed via intermediate carriers to oxygen. Complex IV (CIV), the terminal oxidase, transfers electrons from the intermediate electron carrier cytochrome to oxygen, contributing to the proton motive force in the process.

Electron and proton transfer in the M. smegmatis IIIIV supercomplex.

The M. smegmatis respiratory IIIIV supercomplex consists of a complex III (CIII) dimer flanked on each side by a complex IV (CIV) monomer, electronically connected by a di-heme cyt. cc subunit of CIII.

Children with psoriasis and COVID-19: factors associated with an unfavourable COVID-19 course, and the impact of infection on disease progression (Chi-PsoCov registry).

Background: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children.

Partial Ribosomal Nontranscribed Spacer Sequences Distinguish Rhagoletis zephyria (Diptera: Tephritidae) From the Apple Maggot, R. pomonella.

The apple maggot, Rhagoletis pomonella (Walsh), was introduced into the apple-growing regions of the Pacific Northwest in the U.S.A.

The respiratory supercomplex from C. glutamicum.

Corynebacterium glutamicum is a preferentially aerobic gram-positive bacterium belonging to the phylum Actinobacteria, which also includes the pathogen Mycobacterium tuberculosis. In these bacteria, respiratory complexes III and IV form a CIIICIV supercomplex that catalyzes oxidation of menaquinol and reduction of dioxygen to water. We isolated the C.

Structure of mycobacterial CIIICIV respiratory supercomplex bound to the tuberculosis drug candidate telacebec (Q203).

The imidazopyridine telacebec, also known as Q203, is one of only a few new classes of compounds in more than 50 years with demonstrated antituberculosis activity in humans. Telacebec inhibits the mycobacterial respiratory supercomplex composed of complexes III and IV (CIIICIV). In mycobacterial electron transport chains, CIIICIV replaces canonical CIII and CIV, transferring electrons from the intermediate carrier menaquinol to the final acceptor, molecular oxygen, while simultaneously transferring protons across the inner membrane to power ATP synthesis.

Rieske head domain dynamics and indazole-derivative inhibition of Candida albicans complex III.

Electron transfer between respiratory complexes drives transmembrane proton translocation, which powers ATP synthesis and membrane transport. The homodimeric respiratory complex III (CIII) oxidizes ubiquinol to ubiquinone, transferring electrons to cytochrome c and translocating protons through a mechanism known as the Q cycle. The Q cycle involves ubiquinol oxidation and ubiquinone reduction at two different sites within each CIII monomer, as well as movement of the head domain of the Rieske subunit.