Efficient Biosynthesis of Polyhydroxybutyrate from Xylose via an In Vitro Synthetic Enzymatic Biosystem with Self-Sustained Cofactor Regeneration.

In vitro biotransformation mediated by in vitro synthetic enzymatic biosystems (ivSEBs) represents a highly promising platform for sustainable biomanufacturing, offering enhanced reaction efficiency by circumventing cellular constraints. This study develops an ivSEB comprising 17 enzymes for the cell-free biosynthesis of polyhydroxybutyrate (PHB) from D-xylose via acetyl-coenzyme A (CoA). This ivSEB integrates partial glycolysis and the pentose phosphate pathway, enabling self-sustained balance of several cofactors including CoA, NADP/NADPH, and ATP/ADP.

Dissection of the MeCP2 repressor protein enables CRISPR platform optimization via localization engineering.

Clustered regularly interspaced short palindromic repeat interference (CRISPRi), the fusion of nuclease-inactive Cas9 with transcriptional repressor domains, is a powerful platform enabling site-specific gene knockdown across diverse biological contexts. Previously described CRISPRi systems typically utilize two distinct domain classes: (1) Krüppel-associated box domains and (2) truncations of the multifunctional protein, MeCP2. Despite widespread adoption of MeCP2 truncations for developing CRISPRi platforms, individual contributions of subdomains within MeCP2's transcriptional repression domain (TRD) toward enhancing gene knockdown remain unclear.

Regional specialization of movement encoding across the primate sensorimotor cortex.

The process by which the cerebral cortex generates movements to achieve different tasks remains poorly understood. Here, we leveraged the rich repertoire of well-controlled primate locomotor behaviors to study how task-specific movements are encoded across the dorsal premotor cortex (PMd), primary motor cortex (M1), and primary somatosensory cortex (S1) under naturalistic conditions. Neural population activity was confined within low-dimensional manifolds and partitioned into task-dependent and task-independent subspaces.

Generating combinatorial diversity via engineered V(D)J-like recombination in Saccharomyces cerevisiae.

V(D)J recombination is integral to the development of antibody diversity and proceeds through a complex DNA cleavage and repair process mediated by several proteins, including recombination-activating genes 1 and 2, RAG1 and RAG2. V(D)J recombination occurs in all jawed vertebrates but is absent from evolutionarily distant relatives, including the yeast Saccharomyces cerevisiae. As yeast grow quickly and are a platform for antibody display, engineering yeast to undergo V(D)J recombination could expand their applicability for studying antibody development.

Novel lineages of bacteria with reduced genomes from the gut of farm animals.

Genome reduction and associated metabolic deficiencies have been described in various lineages of parasitic and symbiotic microorganisms that obtain essential nutrients from their partners, and in some free-living microorganisms that inhabit stable environments. The animal gut is a relatively stable ecosystem, characterized by an abundance of organic substances and a high concentration of microorganisms, which provides favorable conditions for the survival of microorganisms with reduced genomes. Metagenomic analysis of 49 samples of feces of farm animals (cows, sheep, yaks, and horses) revealed uncultured lineages of bacteria with reduced genomes (<1 Mbp): family UBA1242 (, ), order Rs-D84 (), and family UBA9783 (, ), defined in genome-taxonomy database.

Genetic Mapping of QTL Associated with 100-Kernel Weight Using a DH Population in Maize.

Grain yield establishment is a complex progress and the genetic basis of one of the most important yield components, 100-kernel weight, remains largely unknown. Here, we employed a double haploid (DH) population containing 477 lines which was developed from a cross of two maize elite inbred lines, PHBA6 and Chang7-2, to identify quantitative trait loci (QTL) that related to 100-kernel weight. The phenotypes of the DH population were acquired over three years in two different locations, while the DH lines were genotyped by next-generation sequencing technology of massively parallel 3' end RNA sequencing (MP3RNA-seq).

Feasibility Study of Using Alternating Current Excitation to Obtain Electrodermal Activity with a Wearable System.

This study investigates the feasibility of using a wearable system with full-wave alternating current (AC) excitation to measure electrodermal activity (EDA). Typically measured using direct current (DC) excitation, EDA is often affected by signal drift due to electrode-skin polarisation. To address this, a portable device was developed that applies fixed-amplitude, full-wave AC signals and records EDA under controlled conditions.

A lysosomal surveillance response to stress extends healthspan.

Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homoeostasis and health. However, how lysosomal activity can be boosted to counteract ageing and ageing-related diseases remains elusive. Here we reveal that silencing specific vacuolar H-ATPase subunits (for example, vha-6), which are essential for intestinal lumen acidification in Caenorhabditis elegans, extends lifespan by ~60%.

Single-Nucleotide Polymorphisms (SNPs) in Vitamin D Physiology Genes May Modulate Serum 25(OH)D Levels in Well-Trained CrossFit Athletes, Which May Be Associated with Performance Outcomes.

Vitamin D is a key micronutrient in the function of the skeletomuscular system. Athletes are at increased risk of developing vitamin D deficiency during the execution of very demanding disciplines such as CrossFit. Single-nucleotide polymorphisms (SNPs) may influence circulating 25-hydroxy-vitamin D (25(OH)D) levels.

Research on the Influence of Orthogonal Design Optimized Elicitor Combinations on Fucoxanthin Accumulation in and Its Expression Regulation.

Fucoxanthin, a carotenoid with notable pharmaceutical potential, has attracted significant attention due to its efficient accumulation in marine microalgae and the importance of optimizing its induction conditions. In this study, was employed as a model organism to screen optimal conditions for fucoxanthin accumulation using a three-factor, four-level orthogonal design. Furthermore, the underlying mechanisms related to photosynthetic physiology and gene regulation were explored.

Finite Volume Effects in Water Nanodroplets: A Molecular Level Investigation.

Aqueous interfaces are responsible for a plethora of processes. At the nanoscale, interfaces are overwhelmingly influenced by finite volume effects that are thought to impact both molecular level and macroscopic properties. Here, finite volume effects are investigated using electrophoretic mobility and vibrational sum frequency scattering of water nanodroplets in oil and oil nanodroplets in water, made from the same chemicals.

Human Bone-Derived Endothelial Cells Mediate Bone Regeneration via Distinct Expression of KIT Ligand.

Effective bone regeneration remains a significant challenge in surgical practice, particularly due to the limitations associated with autologous bone grafting, such as donor site morbidity and limited bone availability. This study investigated the potential of human bone-derived endothelial cells (b-ECs) in mediating bone regeneration, especially in conjunction with bone marrow-derived mesenchymal stem cells (bm-MSCs). It is demonstrated that b-ECs retain unique osteoinductive properties post-isolation, crucial for promoting bone formation in vivo.

Specific Stimulation and Multiplex Secretion Analysis of T Cells Using a Suspendable Hydrogel Platform Enables Immunophenotyping at the Single-Cell Scale.

The ability to characterize and separate cells based on their surface marker expression profiles using flow cytometry revolutionized our understanding of the immune system at the level of single cells. However, the use of surface protein quantification to functionally evaluate T cells following stimulation fails to capture important outcomes of T cell activation, most prominently, cytokine secretion. This key limitation hinders elucidation of the mechanistic correlates of T cell function, which in turn limits our ability to design effective cell therapies for diseases such as cancer and autoimmune disorders.

Morphodynamics of human early brain organoid development.

Brain organoids enable the mechanistic study of human brain development and provide opportunities to explore self-organization in unconstrained developmental systems. Here we establish long-term, live light-sheet microscopy on unguided brain organoids generated from fluorescently labelled human induced pluripotent stem cells, which enables tracking of tissue morphology, cell behaviours and subcellular features over weeks of organoid development. We provide a novel dual-channel, multi-mosaic and multi-protein labelling strategy combined with a computational demultiplexing approach to enable simultaneous quantification of distinct subcellular features during organoid development.

Advancing nanopore technology toward protein identification and sequencing.

Proteins drive most cellular functions and are key players in diseases, yet proteomics still lags behind genomics due to the complexity, diversity, and dynamic nature of proteoforms. Nanopore technology - known for real-time, single-molecule DNA sequencing - is a promising contender to revolutionize protein analysis. The method has recently been adapted to proteins, showing strong potential for protein identification.

PRRX1 is a key regulator in the phenotypic transition between human normal dermal and keloid fibroblasts.

Background: Scarring after skin trauma is a major clinical challenge, as it affects patients' appearance and function.

Objective: Given that human foetal skin possesses scarless wound healing ability, we aimed to understand the differences among human foetal skin, postnatal skin, and keloid tissue to find out the key factors affecting wound healing outcome.

Methods: We used spatial transcriptomics (ST), histological imaging, and other methods to investigate the cellular and molecular characteristics underlying scarless healing by comparing these skin types.

Qatar national cancer care and research: pioneering strategies for global health excellence.

Qatar's cancer care strategy is shaped by the National Cancer Strategy (2011) and subsequent frameworks 2017-22, leading to the Qatar Cancer Plan 2023-2026. These initiatives emphasise prevention, early detection, and evidence-based management to reduce the effects of cancer on patients and the health-care system. Investments in advanced medical infrastructure, cutting-edge technology, and specialised professionals have considerably strengthened cancer care.

ProtMamba: a homology-aware but alignment-free protein state space model.

Motivation: Protein language models are enabling advances in elucidating the sequence-to-function mapping, and have important applications in protein design. Models based on multiple sequence alignments efficiently capture the evolutionary information in homologous protein sequences, but multiple sequence alignment construction is imperfect.

Results: We present ProtMamba, a homology-aware but alignment-free protein language model based on the Mamba architecture.

Development of a Biodegradable Green Emitter Chitosan-Based OLED for Implantable Biomedical Devices.

Light is a crucial tool in medicine for diagnosis and treatment. New light sources called organic light-emitting devices (OLEDs) have been integrated with various extracorporeal and implantable devices to sense or stimulate specific cellular responses. However, one of the current challenges remaining is to design a transient OLED that functions effectively and completely dissolves inside the human body when it is no longer needed, without affecting homeostasis.

Porphyran from discolored nori prevents metabolic syndrome through microbiota-bile acid-ceramide pathway.

Nori is a component of the traditional Japanese diet. The Japanese have a low prevalence of obesity and cardiovascular disease worldwide, and components of nori may have disease-preventive effects. Here, we focused on porphyran, which is abundant in nori that is discarded due to discoloration, and investigated the effects of nori-derived porphyran on gut microbiota, bile acid composition, and ceramide synthesis.

Membrane potential fluctuations and water asymmetry on plasma cell and model lipid membranes: origins, implications and properties.

Membrane potential fluctuations have previously been detected using second harmonic (SH) water imaging on neuronal cells and model lipid bilayer membranes. We report that such fluctuations are also visible when membrane potential-sensitive fluorophores are used as contrast agents, and fluctuations are imaged on both free-standing lipid membranes (FLMs) and on the plasma membranes of neuroblastoma cells. We show that upon K depolarization, non-uniform recovery responses occur across cells and within single cells.

Spotiflow: accurate and efficient spot detection for fluorescence microscopy with deep stereographic flow regression.

Identification of spot-like structures in large, noisy microscopy images is a crucial step for many life-science applications. Imaging-based spatial transcriptomics (iST), in particular, relies on the precise detection of millions of transcripts in low signal-to-noise images. Despite recent advances in computer vision, most of the currently used spot detection techniques are still based on classical signal processing and require tedious manual tuning per dataset.

A causal Bayesian model to evaluate shoulder pathology effect on glenoid bone mineral density.

Background: The effect of shoulder pathologies on glenoid bone mineral density (BMD) remains unclear and can be critical in surgical treatments. It is thus useful to predict this effect and understand how it is influenced by sex, age, and body mass index (BMI), in various glenoid locations.

Methods: We developed a causal model and used do-calculus to identify the minimal adjustment set of covariate variables and developed a varying-intercept varying-slope Bayesian model.

Predictive Screening for Inflammatory Disorders of Pregnancy Using Targeted Maternal Cell-Free RNA Assays: Proof-of-Principle Data from Large Animal and Human Cohorts.

The management and prevention of key inflammatory-associated pregnancy complications such as chorioamnionitis and pre-eclampsia is hampered by a lack of early gestation risk screening tools. In a proof-of-principle study we used targeted cell-free RNA analyses of maternal plasma samples from large animal (sheep) and human pregnancy cohorts to develop a minimally invasive screening test for inflammatory markers. This study utilised a preterm sheep model of sterile and bacterial chorioamnionitis.

Engineering next-generation microfluidic technologies for single-cell phenomics.

The completion of the Human Genome Project catalyzed the development of 'omics' technologies, enabling the detailed exploration of biological systems at an unprecedented molecular scale. Microfluidics has transformed the omics toolbox by facilitating large-scale, high-throughput and highly accurate measurements of DNA and RNA, driving the transition from bulk to single-cell analyses. This transition has ushered in a new era, moving beyond a gene- and protein-centric perspective toward a holistic understanding of cellular phenotypes.