Real-time bio-layer interferometry ubiquitination assays as alternatives to western blotting.

Ubiquitination is a crucial cellular pathway enabling normal cellular functions. Abnormalities in the ubiquitination process can lead to cellular dysfunction and cause a range of diseases. Efforts to screen and develop small molecule inhibitors targeting portions of the ubiquitination cascade require rapid and robust methods for detecting ubiquitination.

Differential consumption of alcohol, caffeine, and caffeinated alcohol by adolescent rats, and effects on post-adolescent gene expression signatures in the nucleus accumbens and orbitofrontal cortex.

Caffeinated alcoholic beverages (CABs) are widely consumed despite little known about their behavioral and biological effects. Furthermore, CABs are also popular among adolescents, a particularly vulnerable and maturing demographic. In this preliminary study, we compared levels of daily adolescent voluntary consumption of caffeine (0.

Ensemble-based virtual screening of African natural products to target human thymidylate synthase.

Human thymidylate synthase (hTS) is a validated drug target for chemotherapy. A virtual screening experiment was used to prioritize a list of compounds from African Natural Products Databases docked against the orthosteric binding pocket of hTS. Consensus scores of binding affinities from ensemble-based virtual screening, hydrated docking and MM-PBSA calculations ranked compounds NEA4433 and NEA4434 as the best candidates owing to binding affinity scores in the picomolar order, their excellent ADMET profiles and the good stability of the protein-ligand complexes formed.

Electronic health records and clinical documentation in medical residency programs: preparing residents to become master clinicians.

Objective: The ubiquity of electronic health records (EHRs) has made incorporating EHRs into medical practice an essential component of resident's training. Patient encounters, an important element of practice, are impacted by EHRs through factors that include increasing documentation requirements. This research sheds light on the role of EHRs on resident clinical skills development with emphasis on their role in patient encounters.

KOMPUTE: imputing summary statistics of missing phenotypes in high-throughput model organism data.

Motivation: The International Mouse Phenotyping Consortium (IMPC) is striving to build a comprehensive functional catalog of mammalian protein-coding genes by systematically producing and phenotyping gene-knockout mice for almost every protein-coding gene in the mouse genome and by testing associations between gene loss-of-function and phenotype. To date, the IMPC has identified over 90 000 gene-phenotype associations, but many phenotypes have not yet been measured for each gene, resulting in largely incomplete data; ∼75.6% of association summary statistics are still missing in the latest IMPC summary statistics dataset (IMPC release version 16).

Synthesis of hydrazinylthiazole carboxylates: a mechanistic approach for treatment of diabetes and its complications.

The deaths of thousands of people and millions affected by diabetes mellitus triggered us to look for alternative possible solutions to cure diabetes and its complications. A series of hydrazinylthiazole carboxylates () was prepared by cyclocondensation reaction of thiosemicarbazones with ethyl 2-chloroacetoacetate. These compounds were screened for antidiabetic potential through α-amylase inhibition, antiglycation and antioxidant assays.

Electron paramagnetic resonance spectroscopic characterization of the human KCNE3 protein in lipodisq nanoparticles for structural dynamics of membrane proteins.

One of the major challenges in solubilization of membrane proteins is to find the optimal physiological environment for their biophysical studies. EPR spectroscopy is a powerful biophysical technique for studying the structural and dynamic properties of macromolecules. However, the challenges in the membrane protein sample preparation and flexible motion of the spin label limit the utilization of EPR spectroscopy to a majority of membrane protein systems in a physiological membrane-bound state.

A Review of the Residual Stress Generation in Metal Additive Manufacturing: Analysis of Cause, Measurement, Effects, and Prevention.

Metal additive manufacturing (AM) is capable of producing complex parts, using a wide range of functional metals that are otherwise very difficult to make and involve multiple manufacturing processes. However, because of the involvement of thermal energy in the fabrication of metallic AM parts, residual stress remains one of the major concerns in metal AM. This residual stress has negative effects on part quality, dimensional accuracy, and part performance.

Induced Heteroresistance in Carbapenem-Resistant (CRAB) via Exposure to Human Pleural Fluid (HPF) and Its Impact on Cefiderocol Susceptibility.

Infections caused by Carbapenem-resistant (CRAB) isolates, such as hospital-acquired pneumonia (HAP), bacteremia, and skin and soft tissue infections, among others, are particularly challenging to treat. Cefiderocol, a chlorocatechol-substituted siderophore antibiotic, was approved by the U.S.

The Eyewitness Community Survey: An Engaging Citizen Science Tool to Capture Reliable Data while Improving Community Participants' Environmental Health Knowledge and Attitudes.

Many youths and young adults have variable environmental health knowledge, limited understanding of their local environment's impact on their health, and poor environmentally friendly behaviors. We sought to develop and test a tool to reliably capture data, increase environmental health knowledge, and engage youths as citizen scientists to examine and take action on their community's challenges. The Eyewitness Community Survey (ECS) was developed through several iterations of co-design.

Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology.

Ocular lens development entails epithelial to fiber cell differentiation, defects in which cause congenital cataract. We report the first single-cell multiomic atlas of lens development, leveraging snRNA-seq, snATAC-seq, and CUT&RUN-seq to discover novel mechanisms of cell fate determination and cataract-linked regulatory networks. A comprehensive profile of - and -regulatory interactions, including for the cataract-linked transcription factor MAF, is established across a temporal trajectory of fiber cell differentiation.

How transposable elements are recognized and epigenetically silenced in plants?

Plant genomes are littered with transposable elements (TEs). Because TEs are potentially highly mutagenic, host organisms have evolved a set of defense mechanisms to recognize and epigenetically silence them. Although the maintenance of TE silencing is well studied, our understanding of the initiation of TE silencing is limited, but it clearly involves small RNAs and DNA methylation.

A Simple Mathematical Model Demonstrates the Potential for Cell-Based Hormone Therapy to Address Dysregulation of the Hypothalamus-Pituitary-Ovary Axis in Females with Loss of Ovarian Function.

Tissue-engineering and cell-based strategies provide an intriguing approach to treat complex conditions such as those of the endocrine system. We have previously developed a cell-based hormone therapy (cHT) to address hormonal insufficiency associated with the loss of ovarian function. To assess how the cHT strategy may achieve its efficacy, we developed a mathematical model to determine if known autocrine, paracrine, and endocrine effects of the native hypothalamus-pituitary-ovary (HPO) axis could explain our previously observed effects in ovariectomized rats following treatment with cHT.

Statistical considerations and database limitations in NMR-based metabolic profiling studies.

Introduction: Interpretation and analysis of NMR-based metabolic profiling studies is limited by substantially incomplete commercial and academic databases. Statistical significance tests, including p-values, VIP scores, AUC values and FC values, can be largely inconsistent. Data normalization prior to statistical analysis can cause erroneous outcomes.

J-domain Proteins form Binary Complexes with Hsp90 and Ternary Complexes with Hsp90 and Hsp70.

Hsp90 and Hsp70 are highly conserved molecular chaperones that help maintain proteostasis by participating in protein folding, unfolding, remodeling and activation of proteins. Both chaperones are also important for cellular recovery following environmental stresses. Hsp90 and Hsp70 function collaboratively for the remodeling and activation of some client proteins.

High salt-induced PSI-supercomplex is associated with high CEF and attenuation of state transitions.

While PSI-driven cyclic electron flow (CEF) and assembly of thylakoid supercomplexes have been described in model organisms like Chlamydomonas reinhardtii, open questions remain regarding their contributions to survival under long-term stress. The Antarctic halophyte, C. priscuii UWO241 (UWO241), possesses constitutive high CEF rates and a stable PSI-supercomplex as a consequence of adaptation to permanent low temperatures and high salinity.

3D printable adhesive elastomers with dynamic covalent bond rearrangement.

Repairable adhesive elastomers are emerging materials employed in compelling applications such as soft robotics, biosensing, tissue regeneration, and wearable electronics. Facilitating adhesion requires strong interactions, while self-healing requires bond dynamicity. This contrast in desired bond characteristics presents a challenge in the design of healable adhesive elastomers.

Evolution of lean meat tenderness stimulated by coordinated variation of water status, protein structure and tissue histology during cooking of braised pork.

Tenderness of lean meat in braised pork is of great importance to the consumer palatability and acceptance. The influence of water status, protein structure and histological changes on lean meat tenderness during cooking was investigated. Results indicated that lean meat began to tenderize mainly after 20 min-cooking.

Apolipoprotein A4 Elevates Sympathetic Activity and Thermogenesis in Male Mice.

Long-chain fatty acids induce apolipoprotein A4 (APOA4) production in the small intestine and activate brown adipose tissue (BAT) thermogenesis. The increase in BAT thermogenesis enhances triglyceride clearance and insulin sensitivity. Acute administration of recombinant APOA4 protein elevates BAT thermogenesis in chow-fed mice.

Comprehensive Research of FSW Joints of AZ91 Magnesium Alloy.

For the friction stir welding (FSW) of AZ91 magnesium alloy, low tool rotational speeds and increased tool linear speeds (ratio 3.2) along with a larger diameter shoulder and pin are utilized. The research focused on the influence of welding forces and the characterization of the welds by light microscopy, scanning electron microscopy with an electron backscatter diffraction system (SEM-EBSD), hardness distribution across the joint cross-section, joint tensile strength, and SEM examination of fractured specimens after tensile tests.

Nanoscale friction and wear behavior of a CVD-grown aged WS monolayer: the role of wrinkles and surface chemistry.

Friction reduction by transition metal dichalcogenide (TMD) monolayers is well documented; however, wrinkle formation on the surface of TMDs takes place due to strain relaxation over time and leads to the deterioration of the tribological properties at a small scale. Herein, we report the role of wrinkles on the wear behavior of a chemical vapor deposition (CVD) grown aged WS monolayer and the comparison with wrinkle-free regions. Atomic force microscopy (AFM) was utilized to perform load-dependent experiments, and we noticed that the wear initiated near wrinkles resulted in the disintegration of the monolayer.

Causal Effects of Modifiable Behaviors on Prostate Cancer in Europeans and East Asians: A Comprehensive Mendelian Randomization Study.

Objective: Early evidence is disputable for the effects of modifiable lifestyle behaviors on prostate cancer (PCa) risk. No research has yet appraised such causality in different ancestries using a Mendelian randomization (MR) approach.

Methods: A two-sample univariable and multivariable MR analysis was performed.

Contrasting Torpor Use by Reproductive Male Common Noctule Bats in the Laboratory and in the Field.

Metabolic processes of animals are often studied in controlled laboratory settings. However, these laboratory settings often do not reflect the animals' natural environment. Thus, results of metabolic measurements from laboratory studies must be cautiously applied to free-ranging animals.