Synthetic plasma pool cohort correction for affinity-based proteomics datasets allows multiple study comparison.

Proteomics stands as the crucial link between genomics and human diseases. Quantitative proteomics provides detailed insights into protein levels, enabling differentiation between distinct phenotypes. OLINK, a biotechnology company from Uppsala, Sweden, offers a targeted, affinity-based protein measurement method called Target 96, which has become prominent in the field of proteomics.

A 'through-DNA' mechanism for co-regulation of metal uptake and efflux.

Transition metals like Zn are essential for all organisms including bacteria, but fluctuations of their concentrations in the cell can be lethal. Organisms have thus evolved complex mechanisms for cellular metal homeostasis. One mechanistic paradigm involves pairs of transcription regulators sensing intracellular metal concentrations to regulate metal uptake and efflux.

A 'through-DNA' mechanism for metal uptake-vs.-efflux regulation.

Transition metals like Zn are essential for all organisms including bacteria, but fluctuations of their concentrations in the cell can be lethal. Organisms have thus evolved complex mechanisms for cellular metal homeostasis. One mechanistic paradigm involves pairs of transcription regulators sensing intracellular metal concentrations to regulate metal uptake and efflux.

Epigenomic profiling of the infrapatellar fat pad in osteoarthritis.

Osteoarthritis is a prevalent, complex disease of the joints, and affects multiple intra-articular tissues. Here, we have examined genome-wide DNA methylation profiles of primary infrapatellar fat pad and matched blood samples from 70 osteoarthritis patients undergoing total knee replacement surgery. Comparing the DNA methylation profiles between these tissues reveal widespread epigenetic differences.

Difference in functional connectivity between end-stage renal disease patients with and without restless legs syndrome: A prospective study.

Purpose: The purpose of this study was to examine differences in functional connectivity between patients with end-stage renal disease (ESRD) with and without restless legs syndrome (RLS). In addition, the study aimed to identify any potential associations between RLS severity and functional connectivity.

Methods: We enrolled patients with ESRD who had been undergoing hemodialysis.

Genome-wide meta-analysis of 92 cardiometabolic protein serum levels.

Objectives: Global cardiometabolic disease prevalence has grown rapidly over the years, making it the leading cause of death worldwide. Proteins are crucial components in biological pathways dysregulated in disease states. Identifying genetic components that influence circulating protein levels may lead to the discovery of biomarkers for early stages of disease or offer opportunities as therapeutic targets.

Single-cell multimodal imaging uncovers energy conversion pathways in biohybrids.

Microbe-semiconductor biohybrids, which integrate microbial enzymatic synthesis with the light-harvesting capabilities of inorganic semiconductors, have emerged as promising solar-to-chemical conversion systems. Improving the electron transport at the nano-bio interface and inside cells is important for boosting conversion efficiencies, yet the underlying mechanism is challenging to study by bulk measurements owing to the heterogeneities of both constituents. Here we develop a generalizable, quantitative multimodal microscopy platform that combines multi-channel optical imaging and photocurrent mapping to probe such biohybrids down to single- to sub-cell/particle levels.

Bridging the diversity gap: Analytical and study design considerations for improving the accuracy of trans-ancestry genetic prediction.

Genetic prediction of common complex disease risk is an essential component of precision medicine. Currently, genome-wide association studies (GWASs) are mostly composed of European-ancestry samples and resulting polygenic scores (PGSs) have been shown to poorly transfer to other ancestries partly due to heterogeneity of allelic effects between populations. Fixed-effects (FETA) and random-effects (RETA) trans-ancestry meta-analyses do not model such ancestry-related heterogeneity, while ancestry-specific (AS) scores may suffer from low power due to low sample sizes.

Lack of Efficacy and Safety of Eculizumab for Treatment of Antibody-Mediated Rejection Following Renal Transplantation.

Background: We evaluated the efficacy and safety of eculizumab in comparison with plasmapheresis and intravenous immunoglobulin therapy in renal transplant recipients diagnosed with antibody-mediated rejection (AMR).

Methods: This was a multicenter, open-label, prospective, randomized analysis. The patients were randomized by therapy type (eg, eculizumab infusions or standard of care [SOC]: plasmapheresis/intravenous immunoglobulin).

Two GPSes in a Ball: Deciphering the Endosomal Tug-of-War Using Plasmonic Dark-Field STORM.

Live video recording of intracellular material transport is a promising means of deciphering the fascinating underlying mechanisms driving life at the molecular level. Such technology holds the key to realizing real-time observation at appropriate resolutions in three-dimensional (3D) space within living cells. Here, we report an optical microscopic method for probing endosomal dynamics with proper spatiotemporal resolution within 3D space in live cells: plasmonic dark-field STORM (pdf-STORM).

Gene-based whole genome sequencing meta-analysis of 250 circulating proteins in three isolated European populations.

Objective: Deep sequencing offers unparalleled access to rare variants in human populations. Understanding their role in disease is a priority, yet prohibitive sequencing costs mean that many cohorts lack the sample size to discover these effects on their own. Meta-analysis of individual variant scores allows the combination of rare variants across cohorts and study of their aggregated effect at the gene level, boosting discovery power.

Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.

In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading. Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR). A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.

Artificial Control of Cell Signaling Using a Photocleavable Cobalt(III)-Nitrosyl Complex.

Cells use gaseous molecules such as nitric oxide (NO) to transmit both intracellular and intercellular signals. In principle, the endogenous small molecules regulate physiological changes, but it is unclear how randomly diffusive molecules trigger and discriminate signaling programs. Herein, it is shown that gasotransmitters use time-dependent dynamics to discriminate the endogenous and exogenous inputs.

Single-Molecule Rotation for EGFR Conformational Dynamics in Live Cells.

Monitoring the dynamics of proteins in live cells on appropriate spatiotemporal scales may provide key information regarding long-standing questions in molecular and cellular regulatory mechanisms. However, tools capable of imaging the conformational changes over time have been elusive. Here, we present a single-molecule stroboscopic imaging probes by developing gyroscopic plasmonic nanoparticles, allowing for replication of protein-protein interactions and the conformational dynamics based on rotational and lateral velocities.

Suppression of tumor growth in lung cancer xenograft model mice by poly(sorbitol-co-PEI)-mediated delivery of osteopontin siRNA.

Small interfering RNA (siRNA)-mediated gene silencing represents a promising strategy for treating diseases such as cancer; however, specific gene silencing requires an effective delivery system to overcome the instability and low transfection efficiency of siRNAs. To address this issue, a polysorbitol-based transporter (PSOT) was prepared by low molecular weight branched polyethylenimine (bPEI) crosslinked with sorbitol diacrylate (SDA). Osteopontin (OPN) gene, which is highly associated with non-small cell lung cancer (NSCLC) was targeted by siRNA therapy using siRNA targeting OPN (siOPN).

Confirmation of the coexistence of two tautomers of 2-mercaptothiazoline on the Ge(100) surface.

We confirmed the coverage dependent variation of tautomers of 2-mercaptothiazoline (the thiolate and thione forms) adsorbed on the Ge(100) surface under UHV conditions by using HRXPS measurements in conjunction with the DFT calculation method, which was studied before only in aqueous systems. The C 1s, S 2p, and N 1s core-level spectra obtained using HRXPS revealed the simultaneous presence of two distinct adsorption structures in different proportions at both low (0.15 ML) and high (0.

Adsorption sequence of multifunctional groups: a study on the reaction pathway and the adsorption structure of homocysteine on the Ge(100) surface.

We investigated the adsorption mechanism of homocysteine (HS-CH2-CH2-CH(NH2)-COOH) on the Ge(100) surface along with its electronic structures and adsorption geometries to determine the sequence of adsorption of this amino acid's functional groups using core-level photoemission spectroscopy (CLPES) in conjunction with density functional theory (DFT) calculations. We found that the "SH-dissociated OH-dissociated N-dative-bonded structure" and the "SH-dissociated OH-dissociation-bonded structure" were preferred at a monolayer (ML) coverage of 0.30 (lower coverage) and 0.

Aerosol delivery of kinase-deficient Akt1 attenuates Clara cell injury induced by naphthalene in the lungs of dual luciferase mice.

Conventional lung cancer therapies are associated with poor survival rates; therefore, new approaches such as gene therapy are required for treating cancer. Gene therapies for treating lung cancer patients can involve several approaches. Among these, aerosol gene delivery is a potentially more effective approach.