LevSeq: Rapid Generation of Sequence-Function Data for Directed Evolution and Machine Learning.

Sequence-function data provides valuable information about the protein functional landscape but is rarely obtained during directed evolution campaigns. Here, we present Long-read every variant Sequencing (LevSeq), a pipeline that combines a dual barcoding strategy with nanopore sequencing to rapidly generate sequence-function data for entire protein-coding genes. LevSeq integrates into existing protein engineering workflows and comes with open-source software for data analysis and visualization.

The Fifth Annual Symposium of the Midwest Aging Consortium.

As the healthcare burden caused by an increasingly aging population rapidly rises, a pressing need exists for innovative geroscience research that can elucidate aging mechanisms and precipitate the development of therapeutic interventions to support healthy aging. The Fifth Annual Midwest Aging Consortium Aging Research symposium, held from April 28-30, 2024, was hosted by The Ohio State University in Columbus, Ohio and featured presentations from investigators across the Midwestern United States. This report summarizes the research presented at the symposium, whose topics included cellular senescence and the aging brain, metabolism and metabolic interventions, nutrition, redox mechanisms and biomarkers, and stress mechanisms.

Selection of Honey Bee () Genotypes for Three Generations of Low and High Population Growth of the Mite .

Honey bee () population declines have been associated with the parasitic mite, , which is currently primarily controlled by the use of acaricides. An alternative is to breed for resistance to , which was conducted in this study by bidirectional selection for mite fall to obtain colonies with low (resistant) or high (susceptible) population growth (LVG and HVG, respectively). Selection for three generations resulted in approx.

Near-infrared diffuse optical characterization of human thyroid using ultrasound-guided hybrid time-domain and diffuse correlation spectroscopies.

Thyroid vascularization and hemodynamics become altered in thyroid pathologies and could thus inform diagnostics, therapy planning, and follow-up. However, the current non-invasive monitoring methods available in clinics lack the necessary sensitivity and/or are impractical for large-scale deployment. As a step towards proposing a new modality, we applied the first platform, to our knowledge, designed to do simultaneous measurements of neck anatomy and thyroid microvascular hemodynamics and metabolism in a single probe placement, integrating state-of-the-art near-infrared spectroscopy techniques and clinical ultrasound.

SiRCle (Signature Regulatory Clustering) model integration reveals mechanisms of phenotype regulation in renal cancer.

Background: Clear cell renal cell carcinoma (ccRCC) tumours develop and progress via complex remodelling of the kidney epigenome, transcriptome, proteome and metabolome. Given the subsequent tumour and inter-patient heterogeneity, drug-based treatments report limited success, calling for multi-omics studies to extract regulatory relationships, and ultimately, to develop targeted therapies. Yet, methods for multi-omics integration to reveal mechanisms of phenotype regulation are lacking.

The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk.

Bariatric surgery is effective for the treatment and remission of obesity and type 2 diabetes, but pharmacological approaches which exert similar metabolic adaptations are needed to avoid post-surgical complications. Here we show how G49, an oxyntomodulin (OXM) analog and dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas, and liver which is initiated by a rapid release of free fatty acids (FFAs) by white adipose tissue (WAT) in a GCGR-dependent manner. This interactome leads to elevations in adiponectin and fibroblast growth factor 21 (FGF21), causing WAT beiging, brown adipose tissue (BAT) activation, increased energy expenditure (EE) and weight loss.

A Call for Pediatric Clinicians to Address Environmental Health Concerns in Rural Settings.

Children in rural communities encounter unique environmental exposures, many of which can result in negative long-term health consequences. Children are particularly at risk from these exposures due to their close interaction with the environment and developing physiology. The authors describe 3 rural environmental hazards: wood stove smoke, well water contaminants, and agricultural pollutants.

High throughput compressive fluorescence lifetime imaging with a silicon photomultiplier detector.

Fluorescence lifetime imaging microscopy (FLIM) is a powerful technique for studying biological processes. There exists a growing interest in developing strategies to enhance throughput and reduce acquisition time of FLIM systems, which commonly employ laser scanning excitation and time-correlated single-photon counting (TCSPC) detection. In this work, we propose a wide-field FLIM microscope based on compressive sensing and high photon rate detection (beyond pile-up limit) based on a high-efficiency silicon photomultiplier detector as a single-pixel camera.

scDOT: optimal transport for mapping senescent cells in spatial transcriptomics.

The low resolution of spatial transcriptomics data necessitates additional information for optimal use. We developed scDOT, which combines spatial transcriptomics and single cell RNA sequencing to improve the ability to reconstruct single cell resolved spatial maps and identify senescent cells. scDOT integrates optimal transport and expression deconvolution to learn non-linear couplings between cells and spots and to infer cell placements.

generation and reaction of a sub-picosecond electron pulse: ultrafast broadband spectroscopy.

A sub-picosecond resolved broadband transient absorption spectrometer for generation and study of ultrafast reaction of short pulse electrons in water has been reported. A femtosecond near infrared (NIR) laser driven multiphoton ionization of water was used for the generation of an ultra-short electron pulse in aqueous media. The dynamics of such electrons have been investigated using a broadband pump-probe spectrometer with a temporal resolution of sub-picosecond.

The Fourth Annual Symposium of the Midwest Aging Consortium.

The Midwest Aging Consortium (MAC) has emerged as a critical collaborative initiative aimed at advancing our understanding of aging and developing strategies to combat the rising prevalence of age-related diseases. Founded in 2019, MAC brings together researchers from various disciplines and institutions across the Midwestern United States to foster interdisciplinary geroscience research. This report summarizes the highlights of the Fourth Annual Symposium of MAC, which was held at Iowa State University in May 2023.

Single Cell MALDI-MSI Analysis of Lipids and Proteins within a Replicative Senescence Fibroblast Model.

In this study, we evaluate lipids and select proteins in human lung fibroblasts (hLFs) to interrogate changes occurring due to aging and senescence. To study single cell populations, a comparison of cells adhered onto slides using poly-d-lysine versus centrifugal force deposition was first analyzed to determine whether specific alterations were observed between preparations. The poly-d-lysine approach was then utilized to interrogate the lipidome of the cell populations and further evaluate potential applications of the MALDI-immunohistochemistry (IHC) platform for single-cell-level analyses.

Federated Unlearning: A Survey on Methods, Design Guidelines, and Evaluation Metrics.

Federated learning (FL) enables collaborative training of a machine learning (ML) model across multiple parties, facilitating the preservation of users' and institutions' privacy by maintaining data stored locally. Instead of centralizing raw data, FL exchanges locally refined model parameters to build a global model incrementally. While FL is more compliant with emerging regulations such as the European General Data Protection Regulation (GDPR), ensuring the right to be forgotten in this context-allowing FL participants to remove their data contributions from the learned model-remains unclear.

Changes in Phenotypic and Molecular Features of Naïve and Central Memory T Helper Cell Subsets following SARS-CoV-2 Vaccination.

Molecular changes in lymphocytes following SARS-CoV-2 vaccination are incompletely understood. We hypothesized that studying the molecular (transcriptomic, epigenetic, and T cell receptor (TCR) repertoire) changes in CD4 T cells following SARS-CoV-2 vaccination could inform protective mechanisms and refinement of future vaccines. We tested this hypothesis by reporting alterations in CD4 T cell subsets and molecular features of CD4 naïve and CD4 central memory (CM) subsets between the unvaccinated and vaccinated groups.

Recovering single-cell expression profiles from spatial transcriptomics with scResolve.

Many popular spatial transcriptomics techniques lack single-cell resolution. Instead, these methods measure the collective gene expression for each location from a mixture of cells, potentially containing multiple cell types. Here, we developed scResolve, a method for recovering single-cell expression profiles from spatial transcriptomics measurements at multi-cellular resolution.

Hydraulic recharge and element dynamics during salinization in an overexploited coastal aquifer of the world's driest zone: Atacama Desert.

The management of water resources in hyper-arid coastal regions is a challenging task because proper information regarding groundwater recharge and water budget is needed for maintaining the hydraulic balance in optimal conditions, avoiding salinization and seawater intrusion. Thus, this article deals with the estimation of the hydraulic recharge and the study of the effects of salinization on the dynamics of major and trace elements in an alluvial aquifer located in the world's driest zone, the northern Atacama Desert. The result of stable water isotopes (δD and δO) and tritium (H) indicated that groundwater in the area is not recent, whereas C results estimated a groundwater residence time ranging between 11,628 and 16,067 yBP.

Trace elements and heavy metal(loid)s triggering ecological risks in a heavily polluted river-reservoir system of central Mexico: Probabilistic approaches.

The contamination of trace elements and heavy metal(loid)s in water bodies has emerged as a global environmental concern due to their high toxicity at low concentrations to both biota and humans. This study aimed to evaluate the ecological risk associated with the occurrence and spatial distribution of Mn, Fe, Co, Cd, Ni, Zn, Sb, As, Tl, Cu, Pb, U, and V in the heavily polluted waters of an important river-reservoir system (Atoyac River Basin) in central Mexico, using two-level tired probabilistic approaches: Risk Quotient based on Species Sensitivity Distribution (RQ) and Joint Probability Curves (JPCs). The concentrations of these elements varied widely, ranging from 0.

Transcriptional regulator MarT negatively regulates MarT-regulated motility gene I, a new gene involved in invasion and virulence of .

The speciation of occurred by acquisition of genomic islands from other bacterial species and continued to diverge into subspecies and serovars with diferent range of host. serovar Typhimurium (STM) is a generalist pathogen infecting hosts that include birds, mice, and humans, whilst serovar Typhi (STY) is a restricted-host pathogen, infecting only humans. Despite their ranges of hosts, STM and STY possess 97-98% identity.

p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia.

Ventricular fibrillation (VF) is a leading immediate cause of sudden cardiac death. There is a strong association between aging and VF, although the mechanisms are unclear, limiting the availability of targeted therapeutic interventions. Here we found that the stress kinases p38γ and p38δ are activated in the ventricles of old mice and mice with genetic or drug-induced arrhythmogenic conditions.

Potential ecological risk assessment of microplastics in environmental compartments in Mexico: A meta-analysis.

Microplastic (MP) environmental contamination has been widely studied in Mexico. However, the evaluation of the associated risk to MPs in environmental compartments is scarce. Therefore, this study addresses this issue using diverse indicators such as the Pollution Load Index (PLI), the Polymer Risk Index (PRI), and the Potential Ecological Risk Index (PERI).