Associations between common genetic variants and income provide insights about the socio-economic health gradient.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects.

Renal denervation in the setting of heart failure.

Renal Denervation (RDN) has emerged over the last decade as a third pillar in the treatment of arterial hypertension, alongside pharmacotherapy and lifestyle modifications. Mechanistically, it reduces central sympathetic overactivation, a process also relevant to heart failure. In this mini-review, we summarize the development of RDN for heart failure, discuss the current evidence supporting its effects, and provide an outlook on future developments.

Biomarkers associated with anastomotic leakage after esophagectomy: a systematic review.

Purpose: Anastomotic leakage (AL) is one of the most important complications that occurs after upper gastrointestinal surgery, registering rates of 20-30% after esophagectomy. The role of systemic inflammatory biomarkers to predict anastomotic leaks is controversial and needs systematization.

Methods: A systematic review based on the PRISMA guidelines criteria was performed.

fMRI data acquisition and analysis for task-free, anesthetized rats.

Templates for the acquisition of large datasets such as the Human Connectome Project guide the neuroimaging community to reproducible data acquisition and scientific rigor. By contrast, small animal neuroimaging often relies on laboratory-specific protocols, which limit cross-study comparisons. The establishment of broadly validated protocols may facilitate the acquisition of large datasets, which are essential for uncovering potentially small effects often seen in functional MRI (fMRI) studies.

The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow.

The default mode network (DMN) is implicated in many aspects of complex thought and behavior. Here, we leverage postmortem histology and in vivo neuroimaging to characterize the anatomy of the DMN to better understand its role in information processing and cortical communication. Our results show that the DMN is cytoarchitecturally heterogenous, containing cytoarchitectural types that are variably specialized for unimodal, heteromodal and memory-related processing.

Semi-mechanistic efficacy model for PARP + ATR inhibitors-application to rucaparib and talazoparib in combination with gartisertib in breast cancer PDXs.

Background: Promising cancer treatments, such as DDR inhibitors, are often challenged by the heterogeneity of responses in clinical trials. The present work aimed to build a computational framework to address those challenges.

Methods: A semi-mechanistic pharmacokinetic-pharmacodynamic model of tumour growth inhibition was developed to investigate the efficacy of PARP and ATR inhibitors as monotherapies, and in combination.

Stalled disomes marked by Hel2-dependent ubiquitin chains undergo Ubp2/Ubp3-mediated deubiquitination upon translational run-off.

Stalled ribosomes cause collisions, impair protein synthesis, and generate potentially harmful truncated polypeptides. Eukaryotic cells utilize the ribosome-associated quality control (RQC) and no-go mRNA decay (NGD) pathways to resolve these problems. In yeast, the E3 ubiquitin ligase Hel2 recognizes and polyubiquitinates disomes and trisomes at the 40S ribosomal protein Rps20/uS10, thereby priming ribosomes for further steps in the RQC/NGD pathways.

Neural circuits underlying context-dependent competition between defensive actions in Drosophila larvae.

To ensure their survival, animals must be able to respond adaptively to threats within their environment. However, the precise neural circuit mechanisms that underlie flexible defensive behaviors remain poorly understood. Using neuronal manipulations, machine learning-based behavioral detection, electron microscopy (EM) connectomics and calcium imaging in Drosophila larvae, we map second-order interneurons that are differentially involved in the competition between defensive actions in response to competing aversive cues.

Bias-corrected serum creatinine from UK Biobank electronic medical records generates an important data resource for kidney function trajectories.

Loss of kidney function is a substantial personal and public health burden. Kidney function is typically assessed as estimated glomerular filtration rate (eGFR) based on serum creatinine. UK Biobank provides serum creatinine measurements from study center assessments (SC, n = 425,147 baseline, n = 15,314 with follow-up) and emerging electronic Medical Records (eMR, "GP-clinical") present a promising resource to augment this data longitudinally.

Enhanced phosphorus weathering contributed to Late Miocene cooling.

Late Miocene climate evolution provides an opportunity to assess Earth's climate sensitivity to carbon cycle perturbation under warmer-than-modern conditions. Despite its relevance for understanding the climate system, the driving mechanisms underlying profound climate and carbon cycle changes - including the enigmatic Late Miocene cooling from 7 to 5.4 million years ago - remain unclear.

A catalogue of land-based adaptation and mitigation solutions to tackle climate change.

Informing and engaging all actors in the land sector, including land-owners and managers, researchers, policy-makers and citizens, on the most effective sustainable land-based solutions and behavioural changes is a key strategy for achieving climate change adaptation and mitigation targets at the global as well as at EU and local level. One requisite to support actors in the land sector is to provide them publicly available, reliable and ready-to-use information related to the implementation of Land-based Adaptation and Mitigation Solutions (LAMS). Here we introduce a LAMS catalogue, a collection of meaningful quantitative and qualitative information on 60 solutions characterised according to a set of specifications (e.

PARP inhibition-associated heterochromatin confers increased DNA replication stress and vulnerability to ATR inhibition in SMARCA4-deficient cells.

DNA replication stress (RS), a prevalent feature of various malignancies, arises from both genetic mutations and genotoxic exposure. Elevated RS levels increase the vulnerability of cancer cells to ataxia telangiectasia and Rad3-related kinase inhibitors (ATRis). Here, we screened for DNA damage response inhibitors that enhance ATRi-induced cytotoxicity using SWI/SNF complex-deficient cells and identified a potent synergy between ATRi and poly(ADP-ribose) polymerase inhibitor (PARPi), particularly in SMARCA4-deficient cells.

Plant interactions associated with a directional shift in the richness range size relationship during the Glacial-Holocene transition in the Arctic.

A nearly ubiquitous negative relationship between taxonomic richness and mean range-size (average area of taxa) is observed across space. However, the complexity of the mechanism limits its applicability for conservation or range prediction. We explore whether the relationship holds over time, and whether plant speciation, environmental heterogeneity, or plant interactions are major factors of the relationship within northeast Siberia and Alaska.

Molecular Insights into α-Synuclein Fibrillation: A Raman Spectroscopy and Machine Learning Approach.

The aggregation of α-synuclein is crucial to the development of Lewy body diseases, including Parkinson's disease and dementia with Lewy bodies. The aggregation pathway of α-synuclein typically involves a defined sequence of nucleation, elongation, and secondary nucleation, exhibiting prion-like spreading. This study employed Raman spectroscopy and machine learning analysis, alongside complementary techniques, to characterize the biomolecular changes during the fibrillation of purified recombinant wild-type α-synuclein protein.

Low Temperature Atomic Layer Deposition of (00l)-Oriented Elemental Bismuth.

This study presents the first successful demonstration of growing elemental bismuth (Bi) thin films via thermal atomic layer deposition (ALD) using Bi(NMe2)3 as the precursor and Sb(SiMe3)3 as the co-reactant. The films were deposited at a relatively low temperature of 100 °C, with a growth per cycle (GPC) of 0.31-0.

Dysregulation of deubiquitinylases: a linchpin of gastrointestinal diseases.

Ubiquitinylation of proteins regulates manifold processes and is reversed by deubiquitinylating enzymes (DUBs), which are therefore implicated in a plethora of cellular processes. DUBs are frequently upregulated in many diseases, while in a few cases downregulation of DUBs is associated with disease progression. This review focuses on the involvement of DUBs in the development and progression of gastrointestinal diseases with a particular emphasis on hepatic steatosis and hepatocellular, cholangio-, esophageal, gastric, colorectal, and pancreatic ductal carcinomas.

Overcoming the technical challenge of venous resection with pancreatectomy: Which factors determine survival?

Background: Pancreatectomy with venous resection (PVR) is nowadays considered standard. However, there is still concern about increased postoperative morbidity and impaired long-term outcome depending on the type of venous resection and reconstruction. The aim was to investigate the predictors of morbidity and long-term survival in patients undergoing PVR in a high-volume center.

Impact of segment length on bony changes following microvascular jaw reconstruction using virtually planned fibula flaps - A retrospective study.

Postoperative bone resorption within the first year after a free fibular flap is a common problem and poses major challenges for subsequent therapies. Due to the concerns of increased bone resorption, short segments in particular, i.e.

Skeletal Editing through Cycloaddition and Subsequent Cycloreversion Reactions.

ConspectusSkeletal editing, which involves adding, deleting, or substituting single or multiple atoms within ring systems, has emerged as a transformative approach in modern synthetic chemistry. This innovative strategy addresses the ever-present demand for developing new drugs and advanced materials by enabling precise modifications of molecular frameworks without disrupting essential functional complexities. Ideally performed at late stages of synthesis, skeletal editing minimizes the need for the cost- and labor-intensive processes often associated with synthesis, thus accelerating the discovery and optimization of complex molecular architectures.