Mn(III)-porphyrins in battle against neurodegenerative and cancer diseases.

Manganese(III)-porphyrins - Mn(III)P-exhibit remarkable redox activity, influencing oxidative and antioxidative processes in biological systems. In this study, we explore the dual roles of Mn(III)-2-TE-PyP and Mn(III)-4-TE-PyP in modulating hyaluronan degradation, a key factor in both neuroprotection and cancer therapy. While Mn(III)-2-TE-PyP enhances oxidative degradation of high-molecular weight hyaluronan, facilitating immune recognition of cancer cells, its structural isomer Mn(III)-4-TE-PyP acts as a potent antioxidant, safeguarding neuronal integrity against oxidative stress.

The fern Nephrolepis exaltata is largely unresponsive to climate change conditions at both physiological and metabolic levels.

Climate change is impacting the performance of plants worldwide. However, the impact on ferns, the second-most diverse lineage of vascular plants, has received little attention. Here, we investigated the effects of one of the most claimed scenarios of the climatic change: drought (D), high temperature (HT) and high CO concentration (CO) on a fern (Nephrolepis exaltata) and a commonly studied angiosperm (Brassica oleracea) at photosynthetic, anatomical, and metabolic levels.

Autism-like phenotype across the lifespan of Shank3B-mutant mice of both sexes.

Background: High heritability (80-90%) of the autism spectrum disorder (ASD) and sex-biased incidence (3-4 times more boys than girls) suggest the roles of genetic predisposition and sex in the etiopathogenesis of the disorder. As ASD is commonly diagnosed in early childhood, most of the research is focused on children, yet animal research predominantly uses adult-aged animals. The effect of aging on the core and secondary ASD symptomatology is understudied, both in patients and animal models of ASD.

PEX39 facilitates the peroxisomal import of PTS2-containing proteins.

Peroxisomes are metabolic organelles essential for human health. Defects in peroxisomal biogenesis proteins (also known as peroxins (PEXs)) cause devastating disease. PEX7 binds proteins containing a type 2 peroxisomal targeting signal (PTS2) to enable their import from the cytosol into peroxisomes, although many aspects of this process remain enigmatic.

Notch activity is modulated by the aGPCR Latrophilin binding the DSL ligand in C. elegans.

The Notch pathway is a highly conserved signaling cascade across metazoans that regulates numerous physiological processes, including cell proliferation, differentiation, and fate determination. Given its fundamental roles, the pathway is tightly regulated by diverse molecules through multiple mechanisms. Here, we identify the Adhesion GPCR latrophilin (LPHN/ADGRL) as a positive modulator of Notch signaling, which increases Notch receptor activation and the translocation of its intracellular domain into the nucleus.

The Effect of Parental Faecal Microbiome Transplantation from Children with Autism Spectrum Disorder on Behavior and Gastrointestinal Manifestations in the Male Offspring of Shank3 Mice.

The increasing incidence of autism spectrum disorder (ASD) increases the urgency of establishing the mechanism of its development for effective prevention and treatment. ASD's etiology includes genetic predisposition and environmental triggers, both of which can play a role in the changed microbiota. Recent research has proved the impact of maternal microbiota on the neurodevelopment of the child.

An NADH-controlled gatekeeper of ATP synthase.

ATP fuels crucial cellular processes and is obtained mostly by oxidative phosphorylation (OXPHOS) at the inner mitochondrial membrane. While significant progress has been made in mechanistic understanding of ATP production, critical aspects surrounding its substrate supply logistics are poorly understood. We identify an interaction between mitochondrial apoptosis-inducing factor 1 (AIFM1) and adenylate kinase 2 (AK2) as gatekeeper of ATP synthase.

Development of Magnetic Sponges Using Steel Melting on 3D Carbonized Spongin Scaffolds Under Extreme Biomimetics Conditions.

This study presents a novel approach to fabricating magnetic sponge-like composites by melting various types of steel onto three-dimensional (3D) carbonized spongin scaffolds under extreme biomimetic conditions. Spongin, a renewable marine biopolymer with high thermal stability, was carbonized at 1200 °C to form a turbostratic graphite matrix capable of withstanding the high-temperature steel melting process (1450-1600 °C). The interaction between molten steel vapors and the carbonized scaffolds resulted in the formation of nanostructured iron oxide (primarily hematite) coatings, which impart magnetic properties to the resulting composites.

Advancing research on regulatory autoantibodies targeting GPCRs: Insights from the 5th international symposium.

The 5th International Symposium on Regulatory Autoantibodies Targeting GPCR (RAB-GPCRs) advanced the understanding of the significant role played by autoantibodies targeting G-protein-coupled receptors (GPCRs) in various human diseases. Once considered passive markers, RAB-GPCRs are now recognized as active modulators of cellular signaling, immune regulation, and inflammation. The symposium highlighted their involvement in multiple prominent pathologies, including autoimmune diseases, cardio- and cerebrovascular diseases, and neuroimmunologic disorders such as myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 syndrome (ME/CFS/PCS), as well as solid organ and hematopoietic stem cell transplantation (SOT/HSCT).

Association of negative affect with resting heart rate variability in medical students.

Resting heart rate variability (HRV) reflects rhythmic changes in heart rate over time associated with autonomic nervous system (ANS) activity. It has served as a predictor of health and the development of various diseases. Therefore, it is important to determine factors that could potentially influence HRV.

RalGAP complexes control secretion and primary cilia in pancreatic disease.

κB-Ras/RalGAP complexes limit the activity of Ral GTPases, which function in EGFR/Ras signaling. RalGAP expression is down-regulated in pancreatic cancer; however, the role of RalGAP and Ral GTPases in tumor development in vivo remained unclear. Here, we show that pancreatic RalGAPβ deficiency alone is sufficient to induce inflammation and neoplasia in vivo.

Serial-femtosecond crystallography reveals how a phytochrome variant couples chromophore and protein structural changes.

The photoreaction and commensurate structural changes of a chromophore within biological photoreceptors elicit conformational transitions of the protein promoting the switch between deactivated and activated states. We investigated how this coupling is achieved in a bacterial phytochrome variant, Agp2-PAiRFP2. Contrary to classical protein crystallography, which only allows probing (cryo-trapped) stable states, we have used time-resolved serial femtosecond x-ray crystallography (tr-SFX) and pump-probe techniques with various illumination and delay times with respect to photoexcitation of the parent Pfr state.

Primary human neutrophils and monocytes migrate along endothelial cell boundaries to optimize search efficiency under static in vitro conditions.

Neutrophils and monocytes are sentinels of inflammatory signals. To reach the sites of action, both cell types attach to and then transmigrate the endothelial cell layer that lines the luminal side of blood vessels. While it has been reported that neutrophils and monocytes actively migrate along the surface of the vasculature, it remains elusive whether and how these motion patterns augment the efficiency of the immune system.

Characterization of lipid chain order and dynamics in asymmetric membranes by solid-state NMR spectroscopy.

We studied the structure and dynamics of asymmetric POPC/(POPE/POPG) and POPS/(POPE/POPG) lipid membranes. To this end, the outer layer of multilamellar POPE/POPG (molar ratio 9 : 1) vesicles was exchanged (using methyl-β-cyclodextrin) by either chain deuterated POPC- or POPS-, for which H NMR order parameters were measured. As controls, we prepared symmetric POPC-/POPE/POPG and POPS-/POPE/POPG membranes of the composition of just the outer membrane of the asymmetric multilamellar vesicles and pure POPC- or POPS- multilamellar vesicles.

Cholesterol allosteric modulation of the oxytocin receptor.

G-protein coupled receptors are critical components in cellular signaling, mediating various physiological responses to external stimuli. Here, we investigate the intricate relationship between cholesterol and the oxytocin receptor (OXTR), focusing on the binding mechanisms and the allosteric cross talk of bound cholesterol to the orthosteric ligand binding pocket. Utilizing molecular docking and molecular dynamics simulations, we identify cholesterol binding sites both on the agonist-bound and antagonist-bound state, which show differing distributions and residence times of the cholesterol molecules.

Oxidant-Based Cytotoxic Agents During Aging: From Disturbed Energy Metabolism to Chronic Inflammation and Disease Progression.

In humans, aging is an inevitable consequence of diminished growth processes after reaching maturity. The high order of biomolecules in cells and tissues is continuously disturbed by numerous physical and chemical destructive impacts. Host-derived oxidant-based cytotoxic agents (reactive species, transition free metal ions, and free heme) contribute considerably to this damage.

The Effect of Polyethylene Terephthalate Nanoplastics on Amyloid-β Peptide Fibrillation.

Exposure of organisms to nanoplastics (NPs) is inevitable given their global abundance and environmental persistence. Polyethylene terephthalate (PET) is a common plastic used in a wide range of products, including clothing and food and beverage packaging. Recent studies suggest that NPs can cross the blood-brain barrier and cause potential neurotoxicity.

mdciao: Accessible Analysis and Visualization of Molecular Dynamics Simulation Data.

We present mdciao, an open-source command line tool and Python Application-Programming-Interface (API) for easy, one-shot analysis and representation of molecular dynamics (MD) simulation data. Building upon the widely used concept of residue-residue contact-frequencies, mdciao offers a wide spectrum of further analysis and representations, enriched with available domain specific annotations. The user-friendly interface offers pre-packaged solutions for non-expert users, while keeping customizability for expert ones.

Intra-individual variability of the human seminal plasma metabolome.

In contrast to the conventional spermiogram, metabolomics approaches give insights into the molecular composition of semen and may provide more detailed information on the fertility status of the respective donor. Given the intra-individual variability of spermiogram parameters between two donations, this study sought to elucidate the biological variability of the seminal plasma metabolome over an average period of 8 weeks. Two time-shifted semen samples from 15 healthy donors were compared by a targeted metabolomics approach utilizing the Biocrates AbsoluteIDQ p180 kit.

Molecules in the Serotonin-Melatonin Synthesis Pathway Have Distinct Interactions with Lipid Membranes.

The neurotransmitter serotonin is involved in physiological processes such as appetite, sleep, and mood and diseases such as anxiety and depression. Traditionally, the effects of serotonin were thought to be initiated by binding to its target transmembrane receptors. It is also known that serotonin can bind directly to the membrane with high affinity and modulate lipid dynamics, lateral segregation of lipids, vesicular association, and membrane protein activity.

Large scale investigation of GPCR molecular dynamics data uncovers allosteric sites and lateral gateways.

G protein-coupled receptors (GPCRs) constitute a functionally diverse protein family and are targets for a broad spectrum of pharmaceuticals. Technological progress in X-ray crystallography and cryogenic electron microscopy has enabled extensive, high-resolution structural characterisation of GPCRs in different conformational states. However, as highly dynamic events underlie GPCR signalling, a complete understanding of GPCR functionality requires insights into their conformational dynamics.

Computational Engineering of siderocalin to modulate its binding affinity to the antihypertension drug candesartan.

Lipocalin family proteins have been shown to bind a vast array of small molecules and have subsequently been adapted to selectively bind specific ligands. In this study, candesartan, an antihypertension drug, was identified to bind mouse and human siderocalin in biomolecular NMR experiments, allowing for structural insights into the candesartan-siderocalin interaction. The ligand binding site was determined through an integrative structural biology approach using in silico ligand docking guided by NMR experiments.