An anomalous abundance of tryptophan residues in ceramide synthases based on analysis of all membrane proteins in the Swiss-Prot database.

The relationship between membrane proteins and the lipid constituents of the membrane bilayer depends on finely-tuned atomic interactions, which itself depends on the precise distribution of amino acids within the 3D structure of the protein. In this regard, tryptophan (Trp), one of the least abundant amino acids, is found at higher levels in transmembrane proteins where it likely plays a role in helping anchor them to the membrane. We now re-evaluate Trp distribution in membrane proteins using all known proteins in the Swiss-Prot database and confirm that it is somewhat higher (∼1.

A framework for neural organoids, assembloids and transplantation studies.

As the field of neural organoids and assembloids rapidly expands, there is an emergent need for guidance and advice on designing, conducting and reporting experiments to increase the reproducibility and utility of these models. Here, our consortium- representing specialized laboratories from around the world- presents a framework for the experimental process that ranges from ensuring the quality and integrity of human pluripotent stem cells to characterizing and manipulating neural cells in vitro, and from transplantation techniques to considerations for modeling human development, evolution, and disease. As with all scientific endeavors, we advocate for rigorous experimental designs tailored to explicit scientific questions, and transparent methodologies and data sharing, to provide useful knowledge for both current research practices and for developing regulatory standards.

Everyone is using biological structures, but how does one find the structure(s) one wants?

A comment on how easy (or difficult) it is to find a stucture of interest and some suggestions on what could be done to start to address the problem.

International consensus statement on microbiome testing in clinical practice.

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value.

Wavelet-based time-frequency intermuscular beta-band coherence decreases with age but increases after mental fatigue in ankle muscles during gait independent of age.

Mental fatigue can affect cognitive function and interfere with motor performance. We examined if mental fatigue affected gait through age-specific modulation of wavelet-based time-frequency intermuscular beta-band coherence in muscles while walking on a treadmill at 1.2 m·s-1.

Enhanced spectral reconstruction of ultrafast spatiotemporal encoded 2D NMR spectroscopy.

Background: Nuclear Magnetic Resonance (NMR) is extensively utilized in research as a non-invasive technique for investigating molecular structures and composite components. The spatiotemporal encoding (SPEN) technique effectively accelerates multi-dimensional NMR experiments. In ultrafast SPEN NMR, the acquired data are divided into odd and even segments corresponding to the positive and negative gradients during the decoding stage, respectively.

EZH2 inhibition enhances T cell immunotherapies by inducing lymphoma immunogenicity and improving T cell function.

T cell-based immunotherapies have demonstrated effectiveness in treating diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) but predicting response and understanding resistance remains a challenge. To address this, we developed syngeneic models reflecting the genetics, epigenetics, and immunology of human FL and DLBCL. We show that EZH2 inhibitors reprogram these models to re-express T cell engagement genes and render them highly immunogenic.

Automated Approach to Accurate, Precise, and Fast Detector Simulation and Reconstruction.

Detector simulation and reconstruction are a significant computational bottleneck in particle physics. We develop particle-flow neural-assisted simulations (parnassus) to address this challenge. Our deep learning model takes as input a point cloud (particles impinging on a detector) and produces a point cloud (reconstructed particles).

Reversing protonation of weakly basic drugs greatly enhances intracellular diffusion and decreases lysosomal sequestration.

For drugs to be active they have to reach their targets. Within cells this requires crossing the cell membrane, and then free diffusion, distribution, and availability. Here, we explored the in-cell diffusion rates and distribution of a series of small molecular fluorescent drugs, in comparison to proteins, by microscopy and fluorescence recovery after photobleaching (FRAP).

Guanidinium Substitution Improves Self-Healing and Photodamage Resilience of MAPbI.

Self-healing materials can become game changers for developing sustainable (opto)electronics. APbX halide (=X) perovskites, HaPs, have shown a remarkable ability to self-heal damage. While we demonstrated self-healing in pure HaP compounds, in single crystals, and in polycrystalline thin films (as used in most devices), HaP compositions with multiple A (and X) constituents are preferred for solar cells.

A Redox-Active Ionic Liquid Surface Treatment for Healing CsPbBr Nanocrystals.

Additive engineering of lead halide perovskites has been a successful strategy for reducing a variety of deleterious defect types. Ionic liquids (ILs) are a unique group of such additives that have been used to passivate halide vacancies in both bulk lead halide perovskites and their colloidal nanocrystal analogues. Herein, we expand the types of defects that can be addressed through IL treatments in CsPbBr nanocrystals with a novel phosphonium tribromide IL that heals metallic lead surface defects through redox chemistry.

Design and synthesis of piperine-based photoaffinity probes for revealing potential targets of piperine in neurological disease.

Piperine (PIP) has attracted extensive attention due to its diverse biological activities. In this study, we developed two photoaffinity probes PIP-1 and PIP-2, which are biologically safe and retain PIP's bioactivity, to investigate its protein targets . Using labeling and cell imaging, we were able to effectively detect and visualize the drug targets of PIP with our probes.

Gingival spatial analysis reveals geographic immunological variation in a microbiota-dependent and -independent manner.

In mucosal barriers, tissue cells and leukocytes collaborate to form specialized niches that support host-microbiome symbiosis. Understanding the spatial organization of these barriers is crucial for elucidating the mechanisms underlying health and disease. The gingiva, a unique mucosal barrier with significant health implications, exhibits intricate tissue architecture and likely contains specialized immunological regions.

The Society for Immunotherapy of Cancer Perspective on Tissue-Based Technologies for Immuno-Oncology Biomarker Discovery and Application.

With immuno-oncology becoming the standard of care for a variety of cancers, identifying biomarkers that reliably classify patient response, resistance, or toxicity becomes the next critical barrier towards improving care. Multi-parametric, multi-omics, and computational platforms generating an unprecedented depth of data are poised to usher in the discovery of increasingly robust biomarkers for enhanced patient selection and personalized treatment approaches. Deciding which developing technologies to implement in clinical settings ultimately, applied either alone or in combination, relies on weighing pros and cons, from minimizing patient sampling to maximizing data outputs, and assessing reproducibility and representativeness of findings, while lessening data fragmentation towards harmonization.

Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane.

The nuclear envelope is a specialized subdomain of the endoplasmic reticulum and comprises the inner and outer nuclear membranes. Despite the crucial role of the inner nuclear membrane in genome regulation, its lipid metabolism remains poorly understood. Phosphatidic acid (PA) is essential for membrane growth as well as lipid storage.

Intracellular polarization of RNAs and proteins in the human small intestinal epithelium.

The intestinal epithelium is a polarized monolayer of cells, with an apical side facing the lumen and a basal side facing the blood stream. In mice, both proteins and mRNAs have been shown to exhibit global basal-apical polarization; however, polarization in the human intestine has not been systematically explored. Here, we employed laser-capture microdissection to isolate apical and basal epithelial segments from intestinal tissues of 8 individuals and performed RNA sequencing and mass-spectrometry proteomics.

Group Social Dynamics in a Seminatural Setup Reflect the Adaptive Value of Aggression in Male Mice.

Background: Maladaptive aggression in humans is associated with several psychiatric conditions and lacks effective treatment. Nevertheless, tightly regulated aggression is essential for survival throughout the animal kingdom. Studying how social dominance hierarchies regulate aggression and access to resources in an enriched environment (EE) can narrow the translational gap between aggression in animal models and normal and pathological human behavior.

N Dissociation vs Reversible 1,2-Methyl Migration in PCP Cobalt(I) Complexes in the Stereoselective Isomerization () of Allyl Ethers.

With growing efforts pushing toward sustainable catalysis, using earth-abundant metals has become increasingly important. Here, we present the first examples of cobalt PCP pincer complexes that demonstrate dual stereoselectivity for allyl ether isomerization. While the cationic cobalt complex [((PCP)Co)-μ-N][BAr ] () mainly favors the -isomer of the enol ether, the corresponding methyl complex [(PCP)CoMe] () mostly gives the -isomer.

Schizophrenia Biomarkers: Blood Transcriptome Suggests Two Molecular Subtypes.

Schizophrenia is a chronic illness that imposes a significant burden on patients, their families, and the health care system. While it has a substantial genetic component, its heterogeneous nature-both genetic and clinical-limits the ability to identify causal genes and mechanisms. In this study, we analyzed the blood transcriptomes of 398 samples (212 patients with schizophrenia and 186 controls) obtained from five public datasets.

Utilizing insights of DNA repair machinery to discover MMEJ deletions and novel mechanisms.

We developed Del-read, an algorithm targeting medium-sized deletions (6-100 bp) in short-reads, which are challenging for current variant callers relying on alignment. Our focus was on Micro-Homolog mediated End Joining deletions (MMEJ-dels), prevalent in myeloid malignancies. MMEJ-dels follow a distinct pattern, occurring between two homologies, allowing us to generate a comprehensive list of MMEJ-dels in the exome.

Generalized cell phenotyping for spatial proteomics with language-informed vision models.

We present a novel approach to cell phenotyping for spatial proteomics that addresses the challenge of generalization across diverse datasets with varying marker panels. Our approach utilizes a transformer with channel-wise attention to create a language-informed vision model; this model's semantic understanding of the underlying marker panel enables it to learn from and adapt to heterogeneous datasets. Leveraging a curated, diverse dataset with cell type labels spanning the literature and the NIH Human BioMolecular Atlas Program (HuBMAP) consortium, our model demonstrates robust performance across various cell types, tissues, and imaging modalities.