A deep learning pipeline for three-dimensional brain-wide mapping of local neuronal ensembles in teravoxel light-sheet microscopy.

Teravoxel-scale, cellular-resolution images of cleared rodent brains acquired with light-sheet fluorescence microscopy have transformed the way we study the brain. Realizing the potential of this technology requires computational pipelines that generalize across experimental protocols and map neuronal activity at the laminar and subpopulation-specific levels, beyond atlas-defined regions. Here, we present artficial intelligence-based cartography of ensembles (ACE), an end-to-end pipeline that employs three-dimensional deep learning segmentation models and advanced cluster-wise statistical algorithms, to enable unbiased mapping of local neuronal activity and connectivity.

Multiplexed spatial mapping of chromatin features, transcriptome and proteins in tissues.

The phenotypic and functional states of cells are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome and metabolome. Spatial omics approaches have enabled the study of these layers in tissue context but are often limited to one or two modalities, offering an incomplete view of cellular identity. Here we present spatial-Mux-seq, a multimodal spatial technology that allows simultaneous profiling of five different modalities: two histone modifications, chromatin accessibility, whole transcriptome and a panel of proteins at tissue scale and cellular level in a spatially resolved manner.

Early childhood growth and nutritional status in India: trends in five National Family Health Surveys spanning 1992 and 2021.

Background/objective: To evaluate the weight and height status of under-five children between 1992 and 2021 in relation to nutritional context.

Subjects/methods: The study is based on the lengths/heights and weights of children <5 years in five national surveys (n = 505,026). After evaluating normality of the distributions, heights, and weights were expressed as z-scores relative to the WHO reference.

Pulsed laser deposition assisted epitaxial growth of cesium telluride photocathodes for high brightness electron sources.

The development of high-brightness electron sources is critical to state-of-the-art electron accelerator applications like X-ray free electron laser (XFEL) and ultra-fast electron microscopy. Cesium telluride is chosen as the electron source material for multiple cutting-edge XFEL facilities worldwide. This manuscript presents the first demonstration of the growth of highly crystalized and epitaxial cesium telluride thin films on 4H-SiC and graphene/4H-SiC substrates with ultrasmooth film surfaces.

Electrophysiological characterization of human KCNT1 channel modulators and the therapeutic potential of hydroquinine and tipepidine in KCNT1 mutation-associated epilepsy mouse model.

Patients suffering epilepsy caused by the gain-of-function mutants of the hKCNT1 potassium channels are drug refractory. In this study, we cloned a novel human KCNT1B channel isoform using the brain cDNA library and conducted patch-clamp and molecular docking analyses to characterize the pharmacological properties of the hKCNT1B channel using thirteen drugs. Among cinchona alkaloids, we found that hydroquinine exerted the strongest blocking effect on the hKCNT1B channel, especially the F313L mutant.

Evaluating AI performance in nephrology triage and subspecialty referrals.

Artificial intelligence (AI) has shown promise in revolutionizing medical triage, particularly in the context of the rising prevalence of kidney-related conditions with the aging global population. This study evaluates the utility of ChatGPT, a large language model, in triaging nephrology cases through simulated real-world scenarios. Two nephrologists created 100 patient cases that encompassed various aspects of nephrology.

Implications of frequent hitter E3 ligases in targeted protein degradation screens.

Targeted protein degradation (TPD) offers a promising approach for chemical probe and drug discovery that uses small molecules or biologics to direct proteins to the cellular machinery for destruction. Among the >600 human E3 ligases, CRBN and VHL have served as workhorses for ubiquitin-proteasome system-dependent TPD. Identification of additional E3 ligases capable of supporting TPD would unlock the full potential of this mechanism for both research and pharmaceutical applications.

The interplay of uncertainty, relevance and learning influences auditory categorization.

Auditory perception requires categorizing sound sequences, such as speech or music, into classes, such as syllables or notes. Auditory categorization depends not only on the acoustic waveform, but also on variability and uncertainty in how the listener perceives the sound - including sensory and stimulus uncertainty, the listener's estimated relevance of the particular sound to the task, and their ability to learn the past statistics of the acoustic environment. Whereas these factors have been studied in isolation, whether and how these factors interact to shape categorization remains unknown.

Cytoplasmic mRNA decay and quality control machineries in eukaryotes.

mRNA degradation pathways have key regulatory roles in gene expression. The intrinsic stability of mRNAs in the cytoplasm of eukaryotic cells varies widely in a gene- and isoform-dependent manner and can be regulated by cellular cues, such as kinase signalling, to control mRNA levels and spatiotemporal dynamics of gene expression. Moreover, specialized quality control pathways exist to rid cells of non-functional mRNAs produced by errors in mRNA processing or mRNA damage that negatively impact translation.

American alligators (Alligator mississippiensis) as wetland ecosystem carbon stock regulators.

Blue carbon refers to organic carbon sequestered by oceanic and coastal ecosystems. This stock has gained global attention as a high organic carbon repository relative to other ecosystems. Within blue carbon ecosystems, tidally influenced wetlands alone store a disproportionately higher amount of organic carbon than other blue carbon systems.

Relationship between functional structures and horizontal connections in macaque inferior temporal cortex.

Horizontal connections in anterior inferior temporal cortex (ITC) are thought to play an important role in object recognition by integrating information across spatially separated functional columns, but their functional organization remains unclear. Using a combination of optical imaging, electrophysiological recording, and anatomical tracing, we investigated the relationship between stimulus-response maps and patterns of horizontal axon terminals in the macaque ITC. In contrast to the "like-to-like" connectivity observed in the early visual cortex, we found that horizontal axons in ITC do not preferentially connect sites with similar object selectivity.

A novel label-free method to determine equilibrium dissociation constants of antibodies binding to cell surface proteins.

Solution-based affinity assays are used for the selection and characterization of proteins that could be developed into therapeutic molecules. However, these assays have limitations for cell-surface proteins as in most cases their purification requires detergent solubilization and are unlikely to assume conformations in solution that resemble their native states in cell membranes. This report describes a novel electrochemiluminescence-based method, called MSD-CAT, for the affinity analysis of antibodies binding to cell-surface receptors.

NIRS-BIDS: Brain Imaging Data Structure Extended to Near-Infrared Spectroscopy.

Functional near-infrared spectroscopy (fNIRS) is an increasingly popular neuroimaging technique that measures cortical hemodynamic activity in a non-invasive and portable fashion. Although the fNIRS community has been successful in disseminating open-source processing tools and a standard file format (SNIRF), reproducible research and sharing of fNIRS data amongst researchers has been hindered by a lack of standards and clarity over how study data should be organized and stored. This problem is not new in neuroimaging, and it became evident years ago with the proliferation of publicly available neuroimaging datasets.

NAD World 3.0: the importance of the NMN transporter and eNAMPT in mammalian aging and longevity control.

Over the past five years, systemic NAD (nicotinamide adenine dinucleotide) decline has been accepted to be a key driving force of aging in the field of aging research. The original version of the NAD World concept was proposed in 2009, providing an integrated view of the NAD-centric, systemic regulatory network for mammalian aging and longevity control. The reformulated version of the concept, the NAD World 2.

Waste marble sludge and calcined clay brick powders in conventional cement farina production for cleaner built environment.

In the manufacturing of some sectors, such as marble and brick, certain byproducts, such as sludge, powder, and pieces containing valuable chemical compounds, emerge. Some concrete plants utilize these byproducts as mineralogical additives in Turkey. The objective of the experimental study is to ascertain whether the incorporation of waste from the marble and brick industries, in powder form, into cement manufacturing as a mineralogical additive or substitute is a viable option.

Strengthening biopolymer adhesives through ureolysis-induced calcium carbonate precipitation.

Common adhesives for nonstructural applications are manufactured using petrochemicals and synthetic solvents. These adhesives are associated with environmental and health concerns because of their release of volatile organic compounds (VOCs). Biopolymer adhesives are an attractive alternative because of lower VOC emissions, but their strength is often insufficient.

A global dataset of freshwater fish trophic interactions.

Freshwater management and research frequently rely on trophic data to manage freshwater fishes, yet it is difficult to perform a simple search of dietary information for any one species. FishBase represents the largest effort to organize freshwater dietary data into a singular, navigable dataset. Nonetheless, FishBase excludes a large portion of the ecological literature because it was developed before the creation of most modern scientific search engines.

Automatic speech recognition predicts contemporaneous earthquake fault displacement.

Significant progress has been made in probing the state of an earthquake fault by applying machine learning to continuous seismic waveforms. The breakthroughs were originally obtained from laboratory shear experiments and numerical simulations of fault shear, then successfully extended to slow-slipping faults. Here we apply the Wav2Vec-2.

msiFlow: automated workflows for reproducible and scalable multimodal mass spectrometry imaging and microscopy data analysis.

Multimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI MSI) and microscopy holds potential for understanding pathological mechanisms by mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing software solutions for MALDI MSI data analysis are incomplete, require programming skills and contain laborious manual steps, hindering broadly applicable, reproducible, and high-throughput analysis to generate impactful biological discoveries. Here, we present msiFlow, an accessible open-source, platform-independent and vendor-neutral software for end-to-end, high-throughput, transparent and reproducible analysis of multimodal imaging data.