Energetics of substrate transport in proton-dependent oligopeptide transporters.

The PepT transporter mediates the transport of peptides across biological membranes. Despite advancements in structural biology, including cryogenic electron microscopy structures resolving PepT in different states, the molecular basis of peptide recognition and transport by PepT is not fully elucidated. In this study, we used molecular dynamics simulations, Markov State Models (MSMs), and Transition Path Theory (TPT) to investigate the transport mechanism of an alanine-alanine peptide (Ala-Ala) through the PepT transporter.

Enhanced sensitivity via non-Hermitian topology.

Sensors are indispensable tools of modern life that are ubiquitously used in diverse settings ranging from smartphones and autonomous vehicles to the healthcare industry and space technology. By interfacing multiple sensors that collectively interact with the signal to be measured, one can go beyond the signal-to-noise ratios (SNR) attainable by the individual constituting elements. Such techniques have also been implemented in the quantum regime, where a linear increase in the SNR has been achieved via using entangled states.

Don't mind the gap: reframing the Perren strain rule for fracture healing using insights from virtual mechanical testing.

Aims: The "2 to 10% strain rule" for fracture healing has been widely interpreted to mean that interfragmentary strain greater than 10% predisposes a fracture to nonunion. This interpretation focuses on the gap-closing strain (axial micromotion divided by gap size), ignoring the region around the gap where osteogenesis typically initiates. The aim of this study was to measure gap-closing and 3D interfragmentary strains in plated ovine osteotomies and associate local strain conditions with callus mineralization.

Synaptic alterations in pyramidal cells following genetic manipulation of neuronal excitability in monkey prefrontal cortex.

The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in primate cognition, integrating multimodal information to generate top-down signals for cognitive control. During cognitive tasks, the DLPFC displays activity patterns of exceptional complexity and duration not observed in other cortical areas or species. These activity patterns are likely associated with the unique physiological and morphological properties of primate DLPFC pyramidal neurons (PNs).

Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.

Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance.

Evolution takes multiple paths to evolvability when facing environmental change.

Life at all scales is surprisingly effective at exploiting new opportunities, as demonstrated by the rapid emergence of antimicrobial resistance and novel pathogens. How populations acquire this level of evolvability and the various ways it aids survival are major open questions with direct implications for human health. Here, we use digital evolution to show that changing environments facilitate the simultaneous evolution of high mutation rates and a distribution of mutational effects skewed toward beneficial phenotypes.

Getting better with age: Lessons from the Kenya Long-term Exclosure Experiment (KLEE).

The Kenya long-term exclosure experiment (KLEE) was established in 1995 in semi-arid savanna rangeland to examine the separate and combined effects of livestock, wildlife and megaherbivores on their shared environment. The long-term nature of this experiment has allowed us to measure these effects and address questions of stability and resilience in the context of multiple drought-rainy cycles. Here we outline lessons learned over the last 29 years, and how these inform a fundamental tension in long-term studies: how to balance the need for question-driven research with the intangible conviction that long-term data will yield valuable findings.

Abnormal cytoskeletal remodeling but normal neuronal excitability in a mouse model of the recurrent developmental and epileptic encephalopathy-susceptibility KCNB1-p.R312H variant.

Integrin_K Channel_Complexes (IKCs), are implicated in neurodevelopment and cause developmental and epileptic encephalopathy (DEE) through mechanisms that were poorly understood. Here, we investigate the function of neocortical IKCs formed by voltage-gated potassium (Kv) channels Kcnb1 and α5β5 integrin dimers in wild-type (WT) and homozygous knock-in (KI) Kcnb1 mouse model of DEE. Kcnb1 mice suffer from severe cognitive deficit and compulsive behavior.

Surface electromyography evaluation for decoding hand motor intent in children with congenital upper limb deficiency.

Children born with congenital upper limb absence exhibit consistent and distinguishable levels of biological control over their affected muscles, assessed through surface electromyography (sEMG). This represents a significant advancement in determining how these children might utilize sEMG-controlled dexterous prostheses. Despite this potential, the efficacy of employing conventional sEMG classification techniques for children born with upper limb absence is uncertain, as these techniques have been optimized for adults with acquired amputations.

Rectification effects of regional air-sea interactions over western boundary current on large-scale sea surface temperature and extra-tropical storm tracks.

The warm Western Boundary Currents (WBCs) and their zonal extensions are persistent, deep, strong and narrow oceanic currents. They are known to anchor and energize the Extra-Tropical storm tracks by frontal thermal air-sea interactions. However, even in the latest generation of climate models, WBCs are characterized by large biases, and both the present storm-track activity and its recent intensification are poorly estimated.

Elucidating governing factors of PFAS removal by polyamide membranes using machine learning and molecular simulations.

Per- and polyfluoroalkyl substances (PFASs) have recently garnered considerable concerns regarding their impacts on human and ecological health. Despite the important roles of polyamide membranes in remediating PFASs-contaminated water, the governing factors influencing PFAS transport across these membranes remain elusive. In this study, we investigate PFAS rejection by polyamide membranes using two machine learning (ML) models, namely XGBoost and multimodal transformer models.

Heat stable and intrinsically sterile liquid protein formulations.

Over 80% of biologic drugs, and 90% of vaccines, require temperature-controlled conditions throughout the supply chain to minimize thermal inactivation and contamination. This cold chain is costly, requires stringent oversight, and is impractical in remote environments. Here, we report chemical dispersants that non-covalently solvate proteins within fluorous liquids to alter their thermodynamic equilibrium and reduce conformational flexibility.

Sleep drive is coupled to tissue damage via shedding of Caenorhabditis elegans EGFR ligand SISS-1.

The benefits of sleep extend beyond the nervous system. Peripheral tissues impact sleep regulation, and increased sleep is observed in response to damaging conditions, even those that selectively affect non-neuronal cells. However, the 'sleep need' signal released by stressed tissues is not known.

Dynamic control of 2D non-Hermitian photonic corner skin modes in synthetic dimensions.

Non-Hermitian models describe the physics of ubiquitous open systems with gain and loss. One intriguing aspect of non-Hermitian models is their inherent topology that can produce intriguing boundary phenomena like resilient higher-order topological insulators (HOTIs) and non-Hermitian skin effects (NHSE). Recently, time-multiplexed lattices in synthetic dimensions have emerged as a versatile platform for the investigation of these effects free of geometric restrictions.

Operando real-space imaging of a structural phase transformation in the high-voltage electrode LiNiMnO.

Discontinuous solid-solid phase transformations play a pivotal role in determining the properties of rechargeable battery electrodes. By leveraging operando Bragg Coherent Diffractive Imaging (BCDI), we investigate the discontinuous phase transformation in LiNiMnO within an operational Li metal coin cell. Throughout Li-intercalation, we directly observe the nucleation and growth of the Li-rich phase within the initially charged Li-poor phase in a 500 nm particle.

MaizeCODE reveals bi-directionally expressed enhancers that harbor molecular signatures of maize domestication.

Modern maize (Zea mays ssp. mays) was domesticated from Teosinte parviglumis (Zea mays ssp. parviglumis), with subsequent introgressions from Teosinte mexicana (Zea mays ssp.

Strained two-dimensional tungsten diselenide for mechanically tunable exciton transport.

Tightly bound electron-hole pairs (excitons) hosted in atomically-thin semiconductors have emerged as prospective elements in optoelectronic devices for ultrafast and secured information transfer. The controlled exciton transport in such excitonic devices requires manipulating potential energy gradient of charge-neutral excitons, while electrical gating or nanoscale straining have shown limited efficiency of exciton transport at room temperature. Here, we report strain gradient induced exciton transport in monolayer tungsten diselenide (WSe) across microns at room temperature via steady-state pump-probe measurement.

Orthogonal and multiplexable genetic perturbations with an engineered prime editor and a diverse RNA array.

Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation.

Recycling e-waste into gold-loaded covalent organic framework catalysts for terminal alkyne carboxylation.

The rising demand for gold requires innovative methods for its recovery from e-waste. Here we present the synthesis of two tetrazine-based vinyl-linked covalent organic frameworks: TTF-COF and TPE-COF that adsorb gold ions and nanoparticles and catalyze the carboxylation of terminal alkynes. These covalent organic frameworks have low band gaps and high photocurrent responses.

Quantum quench dynamics of geometrically frustrated Ising models.

Geometric frustration in two-dimensional Ising models allows for a wealth of exotic universal behavior, both Ising and non-Ising, in the presence of quantum fluctuations. In particular, the triangular antiferromagnet and Villain model in a transverse field can be understood through distinct XY pseudospins, but have qualitatively similar phase diagrams including a quantum phase transition in the (2+1)-dimensional XY universality class. While the quantum dynamics of modestly-sized systems can be simulated classically using tensor-based methods, these methods become infeasible for larger lattices.

Understanding water reaction pathways to control the hydrolytic reactivity of a Zn metal-organic framework.

Metal-organic frameworks (MOFs) are a class of porous materials that are of topical interest for their utility in water-related applications. Nevertheless, molecular-level insight into water-MOF interactions and MOF hydrolytic reactivity remains understudied. Herein, we report two hydrolytic pathways leading to either structural stability or framework decomposition of a MOF (ZnMOF-1).

Global mean sea level likely higher than present during the holocene.

Global mean sea-level (GMSL) change can shed light on how the Earth system responds to warming. Glaciological evidence indicates that Earth's ice sheets retreated inland of early industrial (1850 CE) extents during the Holocene (11.7-0 ka), yet previous work suggests that Holocene GMSL never surpassed early industrial levels.

High-performance 2D electronic devices enabled by strong and tough two-dimensional polymer with ultra-low dielectric constant.

As the feature size of microelectronic circuits is scaling down to nanometer order, the increasing interconnect crosstalk, resistance-capacitance (RC) delay and power consumption can limit the chip performance and reliability. To address these challenges, new low-k dielectric (k < 2) materials need to be developed to replace current silicon dioxide (k = 3.9) or SiCOH, etc.

Deep-learning enabled generalized inverse design of multi-port radio-frequency and sub-terahertz passives and integrated circuits.

Millimeter-wave and terahertz integrated circuits and chips are expected to serve as the backbone for future wireless networks and high resolution sensing. However, design of these integrated circuits and chips can be quite complex, requiring years of human expertise, careful tailoring of hand crafted circuit topologies and co-design with parameterized and pre-selected templates of electromagnetic structures. These structures (radiative and non-radiative, single-port and multi-ports) are subsequently optimized through ad-hoc methods and parameter sweeps.