Spectroscopic evidence of the interaction of titanium(IV) coordination complexes with a phosphate head group in phospholipids.

Biological membranes are potentially involved in the transport of metal ions, such as Ti(IV), and, sometimes, their associated ligands. Understanding the interactions of Ti(IV) ions and complexes with biological membranes provides a basis for elucidating the action mechanism of titanium anticancer drugs. Herein, we investigated the interactions of two neutral titanium(IV) complexes, [HTi(Cat)] (1) and [HTi(Napht)] (2), incorporated into DOPC multi-bilayers using ATR-FTIR spectroscopy.

Albumin orchestrates a natural host defense mechanism against mucormycosis.

Mucormycosis is an emerging, life-threatening human infection caused by fungi of the order Mucorales. Metabolic disorders uniquely predispose an ever-expanding group of patients to mucormycosis via poorly understood mechanisms. Therefore, it is highly likely that uncharacterized host metabolic effectors confer protective immunity against mucormycosis.

Epidermal growth factor receptor signaling governs the host inflammatory response to invasive aspergillosis.

The epidermal growth factor receptor (EGFR) has been identified as an epithelial cell receptor for Mucorales fungi and . Blocking EGFR with small molecule inhibitors reduces disease severity in mouse models of mucormycosis and oropharyngeal candidiasis. In contrast, cases of invasive aspergillosis have been reported in cancer patients who were treated with EGFR inhibitors, suggesting that EGFR signaling may play a protective role in the host defense against this infection.

Biomechanical and clinical outcomes after distal biceps tendon reattachment using an endo button technique and an interference screw.

Background: Rupture of the long head of the distal bifid biceps tendon is a rare injury, for which surgical anatomical repair should be considered in active patients. The aim of this study was to review our patients who benefited from the EndoButton technique via a single anterior approach, comparing the clinical outcomes with the contralateral uninjured side and assessing their quality of life. Our hypothesis was that an "anatomical" insertion, through an anterior approach, by reinserting the 2 distinct tendons on the radial tuberosity, would restore the supination ability of the forearm more effectively than flexion strength.

Functional redundancy in Candida auris cell surface adhesins crucial for cell-cell interaction and aggregation.

Candida auris is an emerging nosocomial fungal pathogen associated with life-threatening invasive disease due to its persistent colonization, high level of transmissibility and multi-drug resistance. Aggregative and non-aggregative growth phenotypes for C. auris strains with different biofilm forming abilities, drug susceptibilities and virulence characteristics have been described.

A secondary mechanism of action for triazole antifungals in Aspergillus fumigatus mediated by hmg1.

Triazole antifungals function as ergosterol biosynthesis inhibitors and are frontline therapy for invasive fungal infections, such as invasive aspergillosis. The primary mechanism of action of triazoles is through the specific inhibition of a cytochrome P450 14-α-sterol demethylase enzyme, Cyp51A/B, resulting in depletion of cellular ergosterol. Here, we uncover a clinically relevant secondary mechanism of action for triazoles within the ergosterol biosynthesis pathway.

Combining Desferriferrioxamine B and 1-Hydroxy-2-Piperidone ((PIPO)H) to Chelate Zirconium. Solution Structure of a Model Complex of the [Zr]Zr-DFOcyclo*-mAb Radioimmunoconjugate.

Zr-immunoPET is a hot topic as Zr cumulates the advantages of Cu and I without their drawbacks. We report the synthesis of a model ligand of a chiral bioconjugable tetrahydroxamic chelator combining the desferriferrioxamine B siderophore and 1-hydroxy-2-piperidone ((PIPO)H), a chiral cyclic hydroxamic acid derivative, and the study by NMR spectroscopy of its zirconium complex. Nuclear Overhauser effect measurements (ROESY) indicated that the complex exists in the form of two diastereomers, in 77 : 23 ratio, resulting from the combination of the central chiralities at the 3-C of the (PIPO)H component and at the Zr cation.

Functional Redundancy in Cell Surface Adhesins Crucial for Cell-Cell Interaction and Aggregation.

is an emerging nosocomial fungal pathogen associated with life-threatening invasive disease due to its persistent colonization, high level of transmissibility and multi-drug resistance. Aggregative and non-aggregative growth phenotypes for strains with different biofilm forming abilities, drug susceptibilities and virulence characteristics have been described. Using comprehensive transcriptional analysis we identified key cell surface adhesins that were highly upregulated in the aggregative phenotype during and grown biofilms using a mouse model of catheter infection.

Functional Redundancy in Cell Surface Adhesins Crucial for Cell-Cell Interaction and Aggregation.

is an emerging nosocomial fungal pathogen associated with life-threatening invasive disease due to its persistent colonization, high level of transmissibility and multi-drug resistance. Aggregative and non-aggregative growth phenotypes for strains with different biofilm forming abilities, drug susceptibilities and virulence characteristics have been described. Using comprehensive transcriptional analysis we identified key cell surface adhesins that were highly upregulated in the aggregative phenotype during and grown biofilms using a mouse model of catheter infection.

Cyclotribenzylene alkynylgold(I) phosphine complexes: synthesis, chirality, and exchange of phosphine.

Two different alkynyl-substituted -symmetric cyclotribenzylenes (CTB) were synthesized in racemic and enantiomerically pure forms, and six gold(I) phosphine complexes differing by the nature of the CTB and the phosphine were prepared and characterized, in particular by NMR spectroscopy, DOSY, electronic circular dichroism (ECD), and electrospray ionization mass spectrometry (ESI-MS). Their ECD patterns depended on the substitution of the starting CTBs and were shifted bathochromically by comparison with the latter. ESI-MS in the presence of HCOH allowed us to detect the complexes as proton adducts.

fungi suppress nitric oxide production by macrophages.

In October 2022, fungi were listed in the "High Priority Group" on the first-ever list of fungal priority pathogens by the World Health Organization. As the causative agent of mucormycosis, have become of great clinical and public health importance with growing mucormycosis numbers, notably with the exponential rise of COVID-19-associated mucormycosis cases. Despite the dire need, there are limited therapeutic options to treat mucormycosis.

Common analysis of direct RNA sequencinG CUrrently leads to misidentification of mC at GCU motifs.

RNA modifications, such as methylation, can be detected with Oxford Nanopore Technologies direct RNA sequencing. One commonly used tool for detecting 5-methylcytosine (mC) modifications is Tombo, which uses an "Alternative Model" to detect putative modifications from a single sample. We examined direct RNA sequencing data from diverse taxa including viruses, bacteria, fungi, and animals.

The Common Denominators of Parkinson's Disease Pathogenesis and Methamphetamine Abuse.

The pervasiveness and mortality associated with methamphetamine abuse have doubled during the past decade, suggesting a possible worldwide substance use crisis. Epitomizing the pathophysiology and toxicology of methamphetamine abuse proclaims severe signs and symptoms of neurotoxic and neurobehavioral manifestations in both humans and animals. Most importantly, chronic use of this drug enhances the probability of developing neurodegenerative diseases manifolds.

BACE1-dependent metabolism of neuregulin 1: Bridging the gap in explaining the occurrence of schizophrenia-like symptoms in Alzheimer's disease with psychosis?

Alzheimer's disease is a neurodegenerative disease mainly characterized by cortico-neuronal atrophy, impaired memory and other cognitive declines. On the other hand, schizophrenia is a neuro-developmental disorder with an overtly active central nervous system pruning system resulting into abrupt connections with common symptoms including disorganised thoughts, hallucination and delusion. Nevertheless, the fronto-temporal anomaly presents itself as a common denominator for the two pathologies.

Novel Host Pathways Govern Epithelial Cell Invasion of Aspergillus fumigatus.

Invasive aspergillosis is initiated when Aspergillus fumigatus adheres to and invades the pulmonary epithelial cells that line the airways and alveoli. To gain deeper insight into how pulmonary epithelial cells respond to A. fumigatus invasion, we used transcriptome sequencing (RNA-seq) to determine the transcriptional response of the A549 type II alveolar epithelial cell line to infection with strains CEA10 and Af293, two clinical isolates of A.

Common Analysis of Direct RNA SequencinG CUrrently Leads to Misidentification of 5-Methylcytosine Modifications at GCU Motifs.

RNA modifications, such as méthylation, can be detected with Oxford Nanopore Technologies direct RNA sequencing. One commonly used tool for detecting 5-methylcytosine (mC) modifications is Tombo, which uses an "Alternative Model" to detect putative modifications from a single sample. We examined direct RNA sequencing data from diverse taxa including virus, bacteria, fungi, and animals.

Depletion of Extracellular Chemokines by Aspergillus Melanin.

Aspergillus fumigatus is an environmental fungus that can cause life-threatening pulmonary disease. Infections initiate when conidia are inhaled and land deep inside the small airways and alveoli of the lungs, where they interact with epithelial cells. These cells provide a physical barrier and secrete chemokines to attract innate immune cells to the site of infection.

Melatonin as a Harmonizing Factor of Circadian Rhythms, Neuronal Cell Cycle and Neurogenesis: Additional Arguments for Its Therapeutic Use in Alzheimer's Disease.

The synthesis and release of melatonin in the brain harmonize various physiological functions. The apparent decline in melatonin levels with advanced aging is an aperture to the neurodegenerative processes. It has been indicated that down regulation of melatonin leads to alterations of circadian rhythm components, which further causes a desynchronization of several genes and results in an increased susceptibility to develop neurodegenerative diseases.

Inhibition of Ribosome Assembly and Ribosome Translation Has Distinctly Different Effects on Abundance and Paralogue Composition of Ribosomal Protein mRNAs in Saccharomyces cerevisiae.

Many mutations in genes for ribosomal proteins (r-proteins) and assembly factors cause cell stress and altered cell fate, resulting in congenital diseases collectively called ribosomopathies. Even though all such mutations depress the cell's protein synthesis capacity, they generate many different phenotypes, suggesting that the diseases are not due simply to insufficient protein synthesis capacity. To learn more, we investigated how the global transcriptome in Saccharomyces cerevisiae responds to reduced protein synthesis generated in two different ways: abolishing the assembly of new ribosomes and inhibiting ribosomal function.

Cdk5-p25 as a key element linking amyloid and tau pathologies in Alzheimer's disease: Mechanisms and possible therapeutic interventions.

Despite the fact that the small atypical serine/threonine cyclin-dependent kinase 5 (Cdk5) is expressed in a number of tissues, its activity is restricted to the central nervous system due to the neuron-only localization of its activators p35 and p39. Although its importance for the proper development and function of the brain and its role as a switch between neuronal survival and death are unmistakable and unquestionable, Cdk5 is nevertheless increasingly emerging, as supported by a large number of publications on the subject, as a therapeutic target of choice in the fight against Alzheimer's disease. Thus, its aberrant over activation via the calpain-dependent conversion of p35 into p25 is observed during the pathogenesis of the disease where it leads to the hyperphosphorylation of the β-amyloid precursor protein and tau.

A gut-oral microbiome-driven axis controls oropharyngeal candidiasis through retinoic acid.

A side effect of antibiotics is outgrowth of the opportunistic fungus Candida albicans in the oropharynx (oropharyngeal candidiasis, OPC). IL-17 signaling is vital for immunity to OPC, but how the microbiome impacts antifungal immunity is not well understood. Mice in standard specific pathogen-free (SPF) conditions are resistant to OPC, whereas we show that germ-free (GF) or antibiotic-treated mice are susceptible.

A Single Bioinspired Hexameric Nickel Catechol-Alloxazine Catalyst Combines Metal and Radical Mechanisms for Alkene Hydrosilylation.

Mechanisms combining organic radicals and metallic intermediates hold strong potential in homogeneous catalysis. Such activation modes require careful optimization of two interconnected processes: one for the generation of radicals and one for their productive integration towards the final product. We report that a bioinspired polymetallic nickel complex can combine ligand- and metal-centered reactivities to perform fast hydrosilylation of alkenes under mild conditions through an unusual dual radical- and metal-based mechanism.