Synthesis and electronic structure elucidation of bioinspired heterobimetallic nickel complexes.

Despite relevance to metalloenzyme active-sites, the selective synthesis of heterobimetallic compounds featuring unbiased, biologically relevant coordination environments remains a challenge. Herein, we disclose a stepwise synthetic strategy, leveraging kinetic stabilization by an alkali metal cation, as a means of accessing spectroscopically pure M(II)/Ni(II) (M = Co & Cu) bimetallics. Electron paramagnetic resonance spectroscopy, variable temperature magnetometry, and DFT calculations support perturbation of the electronic structure as a function of the heterometal within these closely related complexes.

CryoEM-enabled visual proteomics reveals de novo structures of oligomeric protein complexes.

Single particle cryoelectron microscopy (cryoEM) and cryoelectron tomography (cryoET) are powerful methods for unveiling unique and functionally relevant structural states. Aided by mass spectrometry and machine learning, they promise to facilitate the visual exploration of proteomes. Leveraging visual proteomics, we interrogate structures isolated from a complex cellular milieu by cryoEM to identify and classify molecular structures and complexes de novo.

Biological Processes as Exploratory Dynamics.

Many biological processes can be thought of as the result of an underlying dynamics in which the system repeatedly undergoes distinct and abortive trajectories with the dynamical process only ending when some specific process, purpose, structure or function is achieved. A classic example is the way in which microtubules attach to kinetochores as a prerequisite for chromosome segregation and cell division. In this example, the dynamics is characterized by apparently futile time histories in which microtubules repeatedly grow and shrink without chromosomal attachment.

Spatial Proofreading Amplification of Transcript and Protein Signals.

Spatial transcriptomics experiments greatly benefit from brighter signals that improve detection efficiency and shorten imaging times. Here, we introduce a new enzyme-free signal amplification method inspired by the kinetic proofreading principle, in which short oligonucleotide probes are iteratively deposited at their target site and covalently photo-crosslinked to the cell, forming highly stable DNA assemblies. The method results in more than 500-fold signal amplification and supports multiplex readout capabilities.

Rational Design of Immunogenic Nanoparticles as a Platform for Enhanced Ovarian Cancer Immunotherapy in Mice.

Ovarian cancer immunotherapy remains a challenge based on the "cold" tumor microenvironment. Herein we present a rational design to create immunogenic nanoparticles as a multi-agent platform that promotes immune response in a mouse model of ovarian cancer. The hybrid lipid-silica nanosystem is capable of co-loading four types of cargo molecules including a model antigen, nucleic acid-based adjuvant Cytosine-p-linked to Guanine (CpG, TLR3/9 agonist), lipid-based adjuvant (MPLA, TLR4 agonist) integrated into the lipid coat, and optionally a small molecule drug, such as the chemotherapeutic agent oxaliplatin, a well-established treatment for ovarian cancer.

Atlas of amnion development during the first trimester of human pregnancy.

The amnion is a critical extra-embryonic structure that supports foetal development, yet its ontogeny remains poorly defined. Here, using single-cell transcriptomics, we identified major cell types and subtypes in the human amnion across the first trimester of pregnancy, broadly categorized into epithelial, mesenchymal and macrophage lineages. We uncovered epithelial-mesenchymal and epithelial-immune transitions, highlighting dynamic remodelling during early pregnancy.

Fe-phosphates in Jezero Crater as evidence for an ancient habitable environment on Mars.

Phosphorus is an essential component for life, and in-situ identification of phosphate minerals that formed in aqueous conditions directly contributes toward one of the main goals of the Mars 2020 Perseverance rover: to seek signs of ancient habitable environments. In Jezero crater, proximity science analyses within a conglomerate outcrop, "Onahu" demonstrate the presence of rare Fe-bearing phosphate minerals (likely metavivianite, ferrolaueite, (ferro)beraunite, and/or santabarbaraite) embedded in a carbonate-rich matrix. While Fe-phosphates have been inferred previously on Mars, this work presents the most definitive in-situ identification of martian Fe-phosphate minerals to date, using textural, chemical, spectral, and diffraction analyses of discrete green-blue grains.

Stacking-Selective Epitaxy of Rare-Earth Diantimonides.

Deterministic control of the layering configuration of two-dimensional quantum materials plays a central role in studying their emergent electronic properties. Here we demonstrate control over competing stacking configurations in thin film crystals of the rare-earth diantimonides by synthesizing in proximity to competing structural orders. A crossover between the epitaxially stabilized monoclinic structure and the orthorhombic structure commonly observed in bulk crystals is navigated through three axes─the relative cation/anion ratio, growth temperature, and choice of lanthanide ion─culminating with a comparative magnetotransport study of single-yet-distinct phase CeSb films.

Is the whole the sum of its parts? Neural computation of consumer bundle valuation in humans.

Humans are often tasked with making decisions about bundles of multiple items and very little is known about how the human brain aggregates, computes and represents value in such cases. We investigated how the human brain evaluates consumer items, both individually and in bundles, and how this activity relates to choice behavior. Participants underwent a deep-fMRI scanning protocol while we elicited behavioral valuations for single and bundled items.

A SUMO-interacting motif in the guanine nucleotide exchange factor EPAC1 is required for subcellular targeting and function.

Exchange protein directly activated by cAMP (EPAC1), a multifunctional intracellular cAMP receptor, dynamically localizes to various cellular loci, engaging with diverse molecular partners to maintain cellular homeostasis. The study investigates the role of the SUMO interacting motif (SIM) in the subcellular targeting and cellular functions of EPAC1. It reveals that the SIM is a critical structural element for EPAC1's association with RanBP2/Nup358, a nucleoporin of the cytoplasmic filament component of the nuclear pore complex (NPC).

Refractive Index-Corrected Light-Sheet Microscopy for Macro-View Cardiovascular Imaging.

Light-sheet fluorescence microscopy (LSFM) enables rapid data acquisition with minimal phototoxicity, while optical clearing reduces light scattering by matching sample and imaging medium refractive indices (RIs). Emerging clearing methods extend from cells and organoids to entire organs and organisms, prompting macro-view LSFM microscopes with macro-objectives for low-magnification imaging of larger specimens at adequate resolution. In cardiovascular studies, multiple organs often require imaging, yet clearing protocols optimized for different organs alter the sample RIs inconsistently.

Targeting ribosomes reprograms the tumour microenvironment and augments cancer immunotherapy.

Background: Hyperactive ribosome biogenesis is a hallmark of tumours. Current ribosome-related studies are concentrated on cancer cells. Ribosomes can regulate both tumour and non-cancer cells within the tumour microenvironment, yet the immunomodulatory effects of cellular ribosome biogenesis blockade remain inadequately understood.

Elucidating the Roles of Intrinsically Disordered Proteins in Eukaryotic Transcriptional Regulation with Single-Molecule Imaging.

Over 30% of the eukaryotic proteome is comprised of intrinsically disordered protein regions (IDRs) that cannot fold into stable three-dimensional structures. Despite lacking well-defined structures, many IDRs play functional roles in critical cellular processes. One such process is transcription, where many regulatory proteins are intrinsically disordered proteins (IDPs) containing substantial IDRs.

Mechanism of cotranslational protein N-myristoylation in human cells.

N-myristoyltransferases (NMTs) cotranslationally transfer the fatty acid myristic acid to the N terminus of newly synthesized proteins, regulating their function and cellular localization. These enzymes are important drug targets for the treatment of cancer and viral infections. N-myristoylation of nascent proteins occurs specifically on N-terminal glycine residues after the excision of the initiator methionine by methionine aminopeptidases (METAPs).

Using Electrooculography and Electrodermal Activity During a Cold Pressor Test to Identify Physiological Biomarkers of State Anxiety: Feature-Based Algorithm Development and Validation Study.

Background: Anxiety has become a significant health concern affecting mental and physical well-being, with state anxiety (s-anxiety)-a transient emotional response-linked to adverse cardiovascular and long-term health outcomes. Traditional physiological monitoring lacks the contextual sensitivity needed to assess anxiety in real time. Electrooculography (EOG) and electrodermal activity (EDA), 2 biosignals measurable by wearables, offer promising avenues for identifying biomarkers of s-anxiety in naturalistic environments.

Life Detection Knowledge Base: Taxonomy of Potential Biosignatures.

The Life Detection Knowledge Base (LDKB) is a community webtool developed to test and evaluate strategies to search for evidence of life beyond Earth, with an emphasis on recognizing potential false-positive and false-negative results. As part of the LDKB framework, we developed a taxonomy of potential biosignatures. The taxonomy brings together a broad array of life-detection strategies into a common and systematic structure that allows for equitable evaluations based on a specific set of criteria, chosen to assess the likelihood of false-positive and false-negative interpretations.

Rare earth element nucleosynthetic anomalies and dust transport in the protoplanetary disk.

The size, density, and chemical characteristics of solar system bodies have been shaped by material transport during the protoplanetary disk stage. This includes transport from the inner to outer solar system of refractory dust grains that carry nucleosynthetic anomalies. Here, we show that rare earth element (REE) isotopes in fine-grained calcium-aluminum-rich inclusions (CAIs) display anomalies stemming from incomplete mixing of -, -, and -process nucleosynthesis.

Forecast error growth: A dynamic-stochastic model.

There is a history of simple forecast error growth models designed to capture the key properties of error growth in operational numerical weather prediction (NWP) models. We propose here such a scalar model that relies on the previous ones and incorporates multiplicative noise in a nonlinear stochastic differential equation (SDE). We analyze the properties of this SDE, including the shape of the error growth curve for small times and its stationary distribution, and prove well-posedness and positivity of solutions.

Two parallel lineage-committed progenitors contribute to the developing brain.

The hindbrain is a life-sustaining brain region. In one model, a common neural progenitor generates all brain regions. Here our studies of mouse embryos and human pluripotent stem cells (hPSCs) support a different model: two parallel brain progenitors emerge simultaneously during gastrulation, anterior neural ectoderm (forebrain/midbrain progenitor) and posterior neural ectoderm (hindbrain progenitor).

Modifications of microbiome-derived cell-free RNA in plasma discriminates colorectal cancer samples.

Circulating cell-free RNA (cfRNA) in plasma represents a promising avenue for cancer detection. We report low-input multiple methylation sequencing, a method for profiling modification patterns in cfRNA, enabling the detection of diverse transfer RNAs and small noncoding RNAs derived from both the human genome and the microbiome. RNA modification patterns in microbiome-derived cfRNA accurately reflect host microbiota activity and hold potential for the early detection of colorectal cancer.

Qutrit toric code and parafermions in trapped ions.

The development of programmable quantum devices can be measured by the complexity of many-body states that they are able to prepare. Among the most significant are topologically ordered states of matter, which enable robust quantum information storage and processing. While topological orders are more readily accessible with qudits, experimental realizations have thus far been limited to lattice models of qubits.

Unveiling the charge transport blockade in the D2 branch of the photosystem II reaction center.

Photosynthesis, the fundamental process sustaining life on Earth, depends on the photosystem II (PSII) reaction center's ability to initiate the charge transport process. In this study, we have investigated this charge transport process with a focus on the dissimilarity between the two branches of the PSII reaction center, D1 and D2. Utilizing Marcus theory, we have calculated the reorganization energies and activation barriers for all the key steps involved in the charge transport process.

Polyfunctional T follicular helper cells drive checkpoint-inhibitor diabetes and are targeted by JAK inhibitor therapy.

Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, but their use is limited by the development of autoimmunity in healthy tissues as a side effect of treatment. Such immune-related adverse events (IrAE) contribute to hospitalizations, cancer treatment interruption, and even premature death. ICI-induced autoimmune diabetes mellitus (ICI-T1DM) is a life-threatening IrAE that presents with rapid pancreatic β-islet cell destruction leading to hyperglycemia and life-long insulin dependence.

An Analysis of Child Abuse Detected by Skeletal Surveys Before and During the COVID-19 Pandemic.

Unlabelled: The COVID-19 pandemic and the stay-at-home order may have impacted the risk of child physical abuse (CPA). Analyzing injury types in suspected CPA cases before and during the pandemic can provide valuable insights. The objective of this study is to compare the incidences and types of injuries detected by skeletal surveys in suspected CPA cases at a large academic children's hospital before and during the COVID-19 pandemic.

When and where soil dryness matters to ecosystem photosynthesis.

Projected increases in the intensity and frequency of droughts in the twenty-first century are expected to cause a substantial negative impact on terrestrial gross primary productivity (GPP). Yet, the relative role of soil water supply (indicated by soil moisture) and atmospheric water demand (indicated by vapour pressure deficit, VPD) on GPP remains debated, primarily due to their strong covariations, the presence of confounding factors and unresolved causal relationships among the interconnected hydrometeorological drivers of GPP. Here using a causality-guided explainable artificial intelligence framework, we show that soil moisture is the dominant regulator of water stress, surpassing the role of VPD, when and where soil water supply limits ecosystem functions.