Browse Articles

Hippocampo-neocortical interaction as compressive retrieval-augmented generation

Abstract Many aspects of learning, memory, and problem solving involve interplay between episodic (hippocampal) and semantic (neocortical) systems, but the neural mechanisms supporting this are unclear. We present a computational model in which sequential experiences are encoded in hippocampus in compressed form and replayed to train a neocortical generative network. This network captures the gist of specific episodes and extracts statistical patterns that generalise to new situations, enabling efficient reconstruction of the past and prediction of the future. The two systems interact during encoding, recall and problem solving, with the hippocampus retrieving relevant episodic information into working memory as a basis for generation using the ‘general knowledge’ of the neocortical network. We simulate this interaction as ‘retrieval-augmented generation’, with the addition of mechanisms to compress episodic memories into hippocampus and to consolidate them into neocortex. The model explains changes to memories over time, including schema-based distortions, and shows how episodic and semantic memory contribute to problem solving.

Systematic assessment for potential endogenous normalizers for microRNA analysis in fecal samples

Abstract MicroRNAs (miRNA) are considered promising biomarkers for inflammatory and neoplastic diseases in fecal samples, but despite reproducible miRNA detection, there is no consensus on appropriate normalization in fecal samples. In this study, we aimed to explore an endogenous normalizer for miRNA analysis in fecal samples. For this purpose, we performed a multistep study with 3 independent cohorts. In the first step, we investigated miRNA profiling using serial dilutions of blood and fecal samples from healthy subjects. In the second part, we tested the analysis using a cohort of IBD patients ( n  = 30) with active disease and in remission and 59 patients with different liver pathologies or healthy subjects. Finally, the data were validated using an independent cohort of patients with liver disease ( n  = 360). After extraction, miRNAs were analyzed using Affymetrix GeneChip microarray technology in the screening and confirmation cohorts, and TaqMan qPCR was performed for validation. Analysis of the blood stool mixture cohort revealed 5 miRNAs that were stable in all three subgroups. Among them, miR-638 was found to have a Log 2 FC of 0.0004 and was selected for further analysis as one of the best studied miRNAs from previous reports. The stability of miR-638 in microarray analysis was demonstrated in two independent cohorts of patients with IBD and liver disease. We observed no effect of age or other factors on miR-638 levels in fecal samples. Furthermore, its relatively high concentration in feces and its stability against potential blood contamination may offer great advantages over the previously used miR-16, suggesting miR-638 as a potential endogenous fecal normalizer.

Amplified Arctic iceberg traffic reshapes benthic biodiversity

Abstract The Arctic is undergoing rapid warming, resulting in retreating sea ice and glaciers 1 , yet how cryospheric changes propagate into the deep ocean remains poorly understood 2 . Here we identify a climate-driven mechanism linking accelerating glacier disintegration to an increase in deep-sea hard-bottom habitats far beyond calving fronts. Seafloor observations in Fram Strait show a localized increase in the density and patchiness of dropstones delivered by debris-laden icebergs. At the same time, four decades of shipboard records show that the occurrence of icebergs increased abruptly in the early 2000s. Backtracking links these icebergs to the main outlet glaciers in northeast Greenland and the Russian High Arctic. In northeast Greenland, the timing of glacier destabilization coincides with this rise, whereas sparse satellite coverage in the Russian sector limits temporal attribution despite indications of enhanced glacier activity. A model sensitivity study shows that, apart from intensified calving, a more dynamic sea ice cover enhances downstream transport of glacial ice. Along these pathways, increased iceberg activity could reshape deep-sea habitats through enhanced melt and associated lithogenic input, and elevate navigational hazards as maritime traffic expands in the Arctic. Although modest compared with the iceberg discharges of Pleistocene Heinrich events, this mechanism provides a modern analogue of long-range cryospheric influence on the seafloor in a warming climate.

Hydrogen bond stabilized *CO intermediate enables CO2 electroreduction to multi-electron products on silver catalysts

Abstract Silver is an extensively investigated electrode material for electrochemical CO 2 reduction owing to its high electrical conductivity and structural stability. However, a key limitation of silver catalysts is their weak adsorption of the *CO intermediate. This intrinsic constraint restricts the reaction primarily to two-electron pathways, hindering the formation of multi-electron products. Here we demonstrate that surface molecular modification can address this limitation. By anchoring bromothymol blue molecules onto the silver surface, we engineer a localized hydrogen-bonding network that stabilizes *CO intermediates via O···H–O interactions, prolonging their surface residence time. In situ spectroscopy and theoretical simulations reveal that this local microenvironment thermodynamically stabilizes *CO against desorption while kinetically facilitating its subsequent hydrogenation and C-C coupling. Consequently, the retained *CO undergoes deeper reduction pathways, generating CH 4 , C 2 H 4 , C 2 H 5 OH, and CH 3 COOH. At a current density of 400 mA cm −2 , the Faradaic efficiency for multi-electron products reaches 24.2%. This work shifts the design paradigm from metal-centric electronic tuning to local microenvironment engineering, offering an alternative strategy for enabling multi-electron transfer on non-copper catalysts.

Evaluation of locally available materials as thermal insulators for PV modules

Author Correction: ATF7IP/SETDB1-mediated epigenetic programming regulates thymic homing and T lymphopoiesis of hematopoietic progenitors during embryogenesis

Diagnosis-to-treatment interval is associated with outcomes in follicular lymphoma treated with immunochemotherapy

Abstract A short diagnosis-to-treatment interval independently predicts inferior outcomes in follicular lymphoma. Using international discovery and validation cohorts, we demonstrate its prognostic value beyond established prognostic indices, with implications for risk stratification, clinical trial design, and interpretation.

Diethylenetriamine-functionalized magnetic graphene oxide as a powerful metal-free and recoverable nanocatalyst

Spinal neuromotor rehabilitation using a portable isokinetic training robot

Rare-Earth modified biodegradable Zn alloys with high strength and enhanced osteogenesis

Beijing, Baltimore, or both: a randomized draw

Deep transfer learning for detection of placenta-mediated diseases from ultrasound images

Dielectrophoretic and acoustophoretic dual-sensing electroluminescent display

CD49d: beyond a prognostic marker in CLL

Gut microbiome diversity across seasons and locations in thai captive Asian elephants (elephas maximus)

Balanced electrochemical reaction kinetics and mass transfer for stable zinc negative electrode

Albumin-derived pseudo-Dutcher bodies in nonsecretory myeloma

Experimental assessment and sequential flow–deformation analysis of dewatering strategies in sheet pile-supported excavations

Author Correction: De novo design of quasisymmetric two-component protein cages

Glioma-intrinsic MAPK/ERK signaling promotes immunotherapy efficacy through T cell infiltration and interferon responses

Abstract Glioblastoma (GBM) remains a formidable challenge in neuro-oncology, with immune checkpoint blockade (ICB) only showing efficacy in some patients, while the mechanisms governing therapeutic responsiveness are poorly defined. Although MAPK/ERK signaling correlates with survival following ICB, its causal role and mechanisms underlying tumor immunogenicity remain unclear. Here, we perform in vivo kinome-wide CRISPR/Cas9 screens in murine gliomas where we identify RAF-MEK-ERK axis as the strongest modulators of glioma susceptibility to anti-programmed cell death protein 1 (anti-PD-1) therapy and CD8 + T cell recognition. Experimentally-induced ERK phosphorylation (p-ERK) enhances survival after anti-PD-1 and anti-CTLA-4 therapy, leading to durable antitumor immunity upon rechallenge. Additionally, glioma cell p-ERK promotes increased interferon responses and T cell infiltration. Notably, BRAF/MEK inhibition disrupts interferon programs and tumor-microglia interactions in BRAF V600E ex vivo in human GBM/brain slice cultures. Our findings elucidate that tumor-intrinsic MAPK/ERK promotes immunotherapy response, interferon responses, T cell tumor infiltration, and GBM cell-microglia interactions.