Acute lipid droplet accumulation induced by the inhibition of the phospholipase DDHD2 does not affect the level, solubility, or phosphoserine-129 status of α-synuclein.

α-Synuclein (αS) is a 140 amino-acid neuronal protein highly enriched in presynaptic nerve terminals. Its progressive accumulation in Lewy bodies and neurites is the hallmark of Parkinson's disease (PD). A growing number of studies highlights a critical interplay between lipid metabolism and αS biology.

Deregulated ion channels contribute to RHOBTB2-associated developmental and epileptic encephalopathy.

While de novo missense variants in the BTB domains of atypical RhoGTPase RHOBTB2 cause a severe developmental and epileptic encephalopathy, de novo missense variants in the GTPase domain or bi-allelic truncating variants are associated with more variable neurodevelopmental and seizure phenotypes. Apart from the observation of RHOBTB2 abundance resulting from BTB-domain variants and increased seizure susceptibility in Drosophila overexpressing RhoBTB, our knowledge on RHOBTB2-related pathomechanisms is limited. We now found enrichment for ion channels among the differentially expressed genes from RNA-Seq on fly heads overexpressing RhoBTB.

Length-Dependent Conduction of Polyynes: Searching for the Limit of the Tunneling Regime.

Rigid, conjugated molecules are excellent candidates as molecular wires since they can achieve full extension between electrodes while maintaining conjugation. Molecular design can be used to minimize the accessible pi surface and interactions between the bridging wire and the electrode. Polyynes are archetypal molecular wires that feature a rigid molecular framework with a cross-section of a single carbon atom.

Nephronectin Is Required for Vascularization in Zebrafish and Sufficient to Promote Mammalian Vessel-Like Structures in Hydrogels for Tissue Engineering.

Background: Organs and tissues need to be vascularized during development. Similarly, vascularization is required to engineer thick tissues. How vessels are formed during organogenesis is not fully understood, and vascularization of engineered tissues remains a significant challenge.

Loading monocytes with magnetic nanoparticles enables their magnetic control without toxicity.

Background: With the help of superparamagnetic iron oxide nanoparticles (SPIONs), cells can be magnetically directed so that they can be accumulated at target sites. This principle can be used to make monocytes magnetically steerable in order to improve tumor accumulation, e.g.

The proof is in the pudding: patient engagement in studying cannabidiol in mild cognitive impairment.

Background: Patient engagement (PE) in clinical trials has gained importance yet remains uncommon, particularly in patients with mild cognitive impairment (MCI), a critical precursor to Alzheimer's disease (AD). Cannabidiol (CBD) shows potential in slowing MCI progression due to its neuroprotective and anti-inflammatory properties. In CBD research, PE is underutilized too.

Mechanism of sensor kinase CitA transmembrane signaling.

Membrane bound histidine kinases (HKs) are ubiquitous sensors of extracellular stimuli in bacteria. However, a uniform structural model is still missing for their transmembrane signaling mechanism. Here, we used solid-state NMR in conjunction with crystallography, solution NMR and distance measurements to investigate the transmembrane signaling mechanism of a paradigmatic citrate sensing membrane embedded HK, CitA.

Alternating electrical fields to stimulate osteogenic cells and biomimetic calcium phosphate-coated titanium substrates-A combinatorial approach to bone regeneration.

Biophysical stimuli such as alternating electrical fields can mimic endogenous electrical potentials and currents in natural bone. This can help to improve the healing and reconstruction of bone tissue. However, little is known about the combined influence of biomaterials and alternating electric fields on bone cells.

Perinatal dysfunction of innate immunity in cystic fibrosis.

In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate immune system in CF etiology, we investigated a CF pig model and compared these results with those for preschool children with CF.

Stepwise reduction of an asymmetric π-expanded pyracylene towards the crystalline radical trianion.

The chemical reduction of a pyracylene-hexa--hexabenzocoronene-(HBC)-fused nanographene TPP was investigated with K and Rb metals to reveal its multi-electron acceptor abilities. The reaction of TPP with the above alkali metals, monitored by UV-vis-NIR and H NMR spectroscopy, evidenced the stepwise reduction process. The use of different solvents and secondary ligands enabled isolation of single crystals of three different reduced states of TPP with 1, 2, and 3 electrons added to its π-system.

A framework for the simulation of individual glycan coordinates to analyze spatial relationships within the glycocalyx.

The glycocalyx is a dense and dynamic layer of glycosylated species that covers every cell in the human body. It plays crucial roles in various cellular processes in health and disease, such as cancer immune evasion, cancer immune therapy, blastocyst implantation, and functional attenuation of membrane protein diffusion. In addition, alterations in glycocalyx structure may play an important role in ocular surface diseases, e.

Paying attention to the SARS-CoV-2 dialect : a deep neural network approach to predicting novel protein mutations.

Predicting novel mutations has long-lasting impacts on life science research. Traditionally, this problem is addressed through wet-lab experiments, which are often expensive and time consuming. The recent advancement in neural language models has provided stunning results in modeling and deciphering sequences.

Only IF/TA in the Histological Evaluation of Post-Reperfusion Baseline Biopsies Correlates With Kidney Transplant Outcome.

Here, we retrospectively evaluated the informational yield of 338 post-reperfusion kidney transplant biopsies (including 95 living donations) assessed according to BANFF for the histological characteristics interstitial fibrosis and tubular atrophy (IF/TA), glomerulosclerosis, arteriosclerosis, and acute tubular injury (ATI). Associations with delayed graft function (DGF) and death-censored graft survival were explored through Cox-regression analyses. The maximum follow-up time was 11.

Increased serum NfL and GFAP levels indicate different subtypes of neurologic immune-related adverse events during treatment with immune checkpoint inhibitors.

Neurologic immune-related adverse events (nirAEs) represent rare, yet severe side effects associated with immune checkpoint inhibitor (ICI) therapy. Given the absence of established diagnostic biomarkers for nirAEs, we aimed to evaluate the diagnostic utility of serum Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP). Fifty-three patients were included at three comprehensive cancer centers, of these 20 patients with manifest nirAEs and 11 patients with irHypophysitis.

Semantic search helper: A tool based on the use of embeddings in multi-item questionnaires as a harmonization opportunity for merging large datasets - A feasibility study.

Background: Recent advances in natural language processing (NLP), particularly in language processing methods, have opened new avenues in semantic data analysis. A promising application of NLP is data harmonization in questionnaire-based cohort studies, where it can be used as an additional method, specifically when only different instruments are available for one construct as well as for the evaluation of potentially new construct-constellations. The present article therefore explores embedding models' potential to detect opportunities for semantic harmonization.

TOWARDS FAST HARD-CONSTRAINED PARALLEL TRANSMIT DESIGN IN ULTRAHIGH FIELD MRI WITH PHYSICS-DRIVEN NEURAL NETWORKS.

Parallel transmission (pTx) is an important technique for reducing transmit field inhomogeneities at ultrahigh-field (UHF) MRI. pTx typically involves solving an optimization problem for radiofrequency pulse design, with hard constraints on specific-absorption rate (SAR) and/or power, which may be time-consuming. In this work, we propose a novel approach towards incorporating hard constraints to physics-driven neural networks.

A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.

Coronaviruses (CoV) encode sixteen non-structural proteins (nsps), most of which form the replication-transcription complex (RTC). The RTC contains a core composed of one nsp12 RNA-dependent RNA polymerase (RdRp), two nsp8s and one nsp7. The core RTC recruits other nsps to synthesize all viral RNAs within the infected cell.

Flow cytometry-based monitoring of myeloid-derived suppressor cells in the peripheral blood of patients with solid tumors.

Myeloid-derived suppressor cells (MDSCs) ameliorate inflammation by inhibiting T cell responses. In pathological conditions, such as autoimmunity, chronic infections or cancer they accumulate in the periphery. In cancer, MDSCs can also be part of the tumor microenvironment and are associated with a worse prognosis and limited response to immunotherapy.

Unveiling the P-solubilizing potential of bacteria enriched from natural colonies of Red Sea Trichodesmium spp.

Phosphorus (P) is pivotal for all organisms, yet its availability is, particularly in the marine habitat, limited. Natural, puff-shaped colonies of Trichodesmium, a genus of diazotrophic cyanobacteria abundant in the Red Sea, have been demonstrated to capture and centre dust particles. While this particle mining strategy is considered to help evade nutrient limitation, details behind the mechanism remain elusive.

Impact of intravenous CT contrast agents on internal calibration techniques to determine trabecular BMD of the lumbar spine.

Objectives: Contrast agents are frequently administered in computed tomography (CT) scans used for opportunistic screening of osteoporosis. The objective of this study is to compare the impact of contrast-related bone mineral density (BMD) increase between phantom-based and internal CT calibration techniques.

Materials And Methods: Phantom-based and internal CT calibration techniques were used to determine trabecular BMD in 93 existing clinical CT scans of the lumbar spine of 34 subjects, scanned before and after administration of contrast agents.

Idecabtagene vicleucel or ciltacabtagene autoleucel for relapsed or refractory multiple myeloma: An international multicenter study.

Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM), but direct comparisons are lacking. Leveraging an international multicenter RRMM cohort, we compared the outcome of ide-cel ( = 162) versus cilta-cel ( = 42). Co-primary efficacy endpoints of the study were overall response rate (ORR) and progression-free survival (PFS).

[Histomorphologically defined renal cell carcinomas 2025 : Current WHO classification and emerging future subtypes].

Background: The latest edition of the WHO classification of urinary and male genital tumours was published in 2022. The revision was based on the newest scientific literature. This article summarizes the updated recommendations regarding the classification of histomorphologically defined tumours.

Empowering personalized oncology: evolution of digital support and visualization tools for molecular tumor boards.

Background: Molecular tumor boards (MTBs) play a pivotal role in personalized oncology, leveraging complex data sets to tailor therapy for cancer patients. The integration of digital support and visualization tools is essential in this rapidly evolving field facing fast-growing data and changing clinical processes. This study addresses the gap in understanding the evolution of software and visualization needs within MTBs and evaluates the current state of digital support.