Browse Articles

Chirality-driven spin dynamics and manipulation in all-inorganic chiral heterostructures

Investigation of vanadium oxide/activated carbon composites

MRAP2 modifies the signaling and oligomerization state of the melanocortin-4 receptor

Abstract The melanocortin-4 receptor is a G protein-coupled receptor and a key regulator of appetite and metabolism. It can interact with the melanocortin-receptor accessory protein 2, a single transmembrane helix protein known to interact with several different G protein-coupled receptors. However, the consequences of this interaction are not completely understood. Here we report that co-expression of melanocortin-receptor accessory protein 2 has multiple effects on the melanocortin-4 receptor: it enhances G protein-mediated signaling and simultaneously impairs β-arrestin2 recruitment and, consequently, internalization. In addition, co-expression of melanocortin-receptor accessory protein 2 leads to an increased number of monomers of melanocortin-4 receptor by disrupting receptor oligomers. A structural homology model of the active state melanocortin-4 receptor – melanocortin-receptor accessory protein 2 – Gαs complex suggests interaction sites that are relevant for receptor activation. Our data indicate that melanocortin-receptor accessory protein 2 is an accessory protein that interacts with and influences melanocortin-4 receptor structure, biasing its signaling towards G protein-mediated effects.

In silico investigation of the puzzling dopamine effects on excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons

Abstract It has been shown that in the CA1 region of the hippocampus, dopamine modulates memory functions by influencing spike-timing-dependent plasticity (STDP) and intrinsic neuronal properties. Although experimental findings have suggested potential mechanisms, their detailed interplay remains incompletely understood. Here, using a realistic CA1 pyramidal neuron model, we have investigated the possible effects of dopaminergic modulation on a neuron’s signal integration and synaptic plasticity processes. The results suggest a physiological plausible explanation for the puzzling experimental observation that long-term potentiation (LTP) increases in spite of a reduction in the neuron’s excitability, and explains why physiological dopamine levels are necessary for LTP induction. The model suggests experimentally testable predictions on which ion channel kinetic properties can modulate the interplay between synaptic plasticity and neuronal excitability, thereby identifying potential molecular targets for therapeutic intervention.

Observing differential spin currents by resonant inelastic X-ray scattering

Secondary grain boundary dislocations alter segregation energy spectra

Abstract Grain boundaries (GBs) trigger structure-specific chemical segregation of solute atoms. According to the three-dimensional (3D) topology of grains, GBs - although defined as two-dimensional defects - cannot practically be free of curvature. This leads to discrete variations in the GB plane orientations. Topologically required arrays of secondary GB dislocations accommodate these variations as well as deviations from ideal coincidence site lattice GBs. We report here that these pattern-forming secondary GB dislocations can have an additional and, in some cases, even a much stronger effect on GB segregation than defect-free GBs. Using nanoscale correlative tomography combining crystallography and chemical analysis, we quantified the relationship between secondary GB dislocations and their segregation energy spectra for a model Fe-W alloy. This discovery unlocks design opportunities for advanced materials, leveraging the additional degrees of freedom provided by topologically-necessary secondary GB dislocations to modulate segregation.

China’s environmental governance efficiency evaluation based on novel cross-efficiency network DEA model

Apoptotic bodies in phytoplankton suggest evolutionary conservation of cell death mechanisms

Abstract Programmed Cell Death (PCD) in eukaryotes is a regulated process occurring during development, cell differentiation and aging. Apoptosis is a particularly well studied morphotype of PCD, only observed in animal cells (metazoan). Its most definitive hallmark is the formation and release of membrane-enclosed extracellular vesicles called Apoptotic Bodies (ABs). Although apoptotic-like features have been described in plants, yeast, protozoa and phytoplankton, the production of ABs has been thought to be limited to multicellular animals. Here we report the production and release of extracellular ABs in a non-metazoan unicellular eukaryote, the cryptophyte alga Guillardia theta. Morphologies of G. theta cells during aging and pharmacologically-induced cell death confirm the presence of ABs and apoptosis in phytoplankton. G. theta ABs have similar composition to metazoan ABs, carrying DNA, proteins, lipids, carbohydrates, fragments of organelles and cytosol portions. Our results demonstrate that G. theta, a microalga that arose from secondary endosymbiosis, experiences apoptotic cell death in physiological conditions, similar to animal cells. Since secondary endosymbiosis occurred prior to the origin of multicellularity, our discovery questions the evolutionary origin of PCD.

Neighborhood level socioeconomic disparities are associated with reduced colorectal cancer survival

Abstract We evaluated the relationship between residing in persistent poverty (PP) and low socioeconomic census tracts on all-cause and colorectal cancer (CRC)-specific mortality, providing a current assessment of economic disadvantage and health outcomes. Using Surveillance, Epidemiology, and End Results Program Data (2006–2020), CRC cases were identified using ICD-10 codes and stage I-III were included in the analysis. Overlap propensity score weighting with marginal structural models estimated the risk of all-cause and CRC-specific mortality. Individuals living in PP had higher risk of all-cause mortality at 15-year follow-up, with an adjusted risk difference (ARD) and adjusted risk ratio (aRR) of 7.2 (95% CI 5.9–8.7) and 1.1 (95% CI 1.1–1.1), respectively, with similar results for CRC-specific mortality. Individuals living in low socioeconomic census tracts had higher risk of all-cause (ARD: 5.3, 95% CI 4.0–6.6; aRR: 1.1, 95% CI 1.6–1.1) and CRC-specific mortality (ARD: 2.7, 95% CI 1.7–3.7; aRR: 1.1, 95% CI 1.1–1.1) at 15-year follow-up. Thus, residing in PP or low socioeconomic census tract may impact health outcomes.

CurT/CURT1 proteins are involved in cell and chloroplast division coordination of cyanobacteria and green algae

Abstract Plant proteins of the CURVATURE THYLAKOID 1 (CURT1) family and their prokaryotic CurT homologues are key determinants of the three-dimensional structure of the thylakoid membrane systems in chloroplasts and cyanobacteria. As the evolutionary origin of the CURT1/CurT family appears to coincide with the evolution of thylakoids themselves, shaping the thylakoid system has widely been regarded as their primary role. In this study we present strong evidence that CurT, beyond regulation of thylakoid architecture, is involved in cell division and thylakoid fission/partitioning in both Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942, likely through physical interaction with the key cell division protein FtsZ. Similarly, triple mutants of Chlamydomonas reinhardtii CURT1A, B, and C display an asymmetric chloroplast division phenotype, thus suggesting an evolutionary conserved functionality of CurT/CURT1 in cell/chloroplast division in single-celled oxygenic photosynthesizers.

Comprehensive investigation of emission homogeneity of InGaAs multiple quantum wells using spatially resolved spectroscopy

Conformal integration of multifunctional nanomembranes on fibers towards intelligent optical platform

A scalable benchmark to evaluate the robustness of image stitching under simulated distortions

A hypothalamic circuit that modulates feeding and parenting behaviours

Structural basis for ligand promiscuity and high signaling activity of Kaposi’s Sarcoma-associated Herpesvirus-encoded GPCR

Abstract Kaposi’s Sarcoma-associated Herpesvirus encodes ORF74, a viral G protein-coupled receptor homologous to CXCR2, which plays a crucial role in Kaposi’s Sarcoma development through its high basal signaling activity. Our cryoEM analysis of ORF74 in ligand-free, BRIL-fused ligand-free, and CXCL1/Gitrimer-bound forms elucidates its ligand-independent signaling activity. A widely open, static extracellular cavity facilitates ligand promiscuity by enabling dynamic access and diverse binding modes. Structural alterations in CWxP, E/DRY, and NPxxY micro-switches stabilize the active conformation, leading to constitutive signaling. Metadynamics simulations reveal a dynamic ensemble between local switch structures corresponding to the inactive and active states, supporting spontaneous activation. CXCR2-ORF74 chimeras highlight intracellular loops 2 and 3 as key modulators of basal and agonist-induced activity. This study defines the structural basis of ORF74’s ligand promiscuity, spontaneous activation, and high basal signaling, providing insights into its role in viral oncogenesis.

Impact of AI-quantified fluid dynamics on visual outcomes over 5 years in patients with treatment-naïve nAMD from the FRB! registry

An ultrafast diamond nonlinear photonic sensor

Abstract The integration of light and materials technology is key to the creation of innovative sensing technologies. Sensing of electric and magnetic fields, and temperature with high spatio-temporal resolution is a critical task for the development of the next-generation of nanometer-scale quantum devices. Color centers in diamonds are attractive for potential applications owing to their characteristic quantum states, although they require metallic contacts for the introduction of external microwaves. Here, we build an ultrafast diamond nonlinear photonic sensor to assess the surface electric field; an electro-optic sensor based on nitrogen-vacancy centers in a diamond nanotip breaks the spatial-limit of conventional pump-probe techniques. The 10-fs near-infrared optical pulse modulates the surface electric field of a 2D transition metal dichalcogenide and we monitor the dynamics of the local electric field at nanometer-femtosecond spatio-temporal resolutions. Our nanoscopic technique will provide new horizons to the sensing of advanced nano materials.

Temporal neural operator for modeling time-dependent physical phenomena

Development of clinical immunity to Plasmodium vivax following repeat controlled human malaria infection

Abstract Clinical immunity to malaria can lead to asymptomatic infection, but the underlying mechanisms remain unclear. To examine the development of clinical immunity, we conducted a multi-cohort, repeat controlled human malaria infection (CHMI) study with Plasmodium vivax, and a heterologous rechallenge with P. falciparum (ClinicalTrials.gov NCT03797989). Malaria-naïve adults underwent CHMI up to three times, by administration of red blood cells infected with P. vivax PvW1 clone or P. falciparum 3D7 clone. Nineteen participants underwent primary CHMI with P. vivax, 12 returned for secondary homologous CHMI and 2 for tertiary homologous CHMI. Six participants who had completed P. vivax CHMI then underwent heterologous rechallenge with P. falciparum. We find that clinical immunity to P. vivax develops rapidly after a single CHMI, protecting participants against fever and laboratory abnormalities. This is underpinned by the attenuation of inflammatory cytokines and chemokines, as well as reduced coagulation and endothelium activation. In contrast, there is no evidence of anti-parasite immunity, suggesting that mechanisms of clinical immunity can operate independently of pathogen load to reduce the damage caused by malaria infection. In addition, we show that clinical immunity to P. vivax is parasite species-specific and provides no protection against CHMI with P. falciparum.

Dry resist lamination for wafer-scale fabrication of microfluidic superfusion devices

Abstract We present a cleanroom fabrication process of free-standing open space microfluidic devices with channel widths of ~ 30 µm on the wafer scale by means of photolithography in combination with lamination technology.