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.

Integrated Ising Model with global inhibition for decision making.

Humans and other organisms make decisions choosing between different options, with the aim to maximize the reward and minimize the cost. The main theoretical framework for modeling the decision-making process has been based on the highly successful drift-diffusion model, which is a simple tool for explaining many aspects of this process. However, new observations challenge this model.

An Information-Theoretic Proof of a Hypercontractive Inequality.

The famous hypercontractive estimate discovered independently by Gross, Bonami and Beckner has had a great impact on combinatorics and theoretical computer science since it was first used in this setting in a seminal paper by Kahn, Kalai and Linial. The usual proofs of this inequality begin with two-point space, where some elementary calculus is used and then generalised immediately by introducing another dimension using submultiplicativity (Minkowski's integral inequality). In this paper, we prove this inequality using information theory.

Synergy as the Failure of Distributivity.

The concept of emergence, or synergy in its simplest form, is widely used but lacks a rigorous definition. Our work connects information and set theory to uncover the mathematical nature of synergy as the failure of distributivity. For the trivial case of discrete random variables, we explore whether and how it is possible to get more information out of lesser parts.

Computational elucidation of nonverbal behavior and body language in music therapy.

Music therapy has shown efficacy in serious and chronic conditions, mental disorders, and disabilities. However, there is still much to explore regarding the mechanisms through which music interventions exert their effects. A typical session involves interactions between the therapist, the client, and the musical work itself, and to help address the challenges of capturing and comprehending its dynamics, we extend our general computational paradigm (CP) for analyzing the expressive and social behavioral processes in arts therapies.

Features of membrane protein sequence direct post-translational insertion.

The proper folding of multispanning membrane proteins (MPs) hinges on the accurate insertion of their transmembrane helices (TMs) into the membrane. Predominantly, TMs are inserted during protein translation, via a conserved mechanism centered around the Sec translocon. Our study reveals that the C-terminal TMs (cTMs) of numerous MPs across various organisms bypass this cotranslational route, necessitating an alternative posttranslational insertion strategy.