Punctuated virus-driven succession generates dynamical alternations in CRISPR-mediated microbe-virus coevolution.

The coevolutionary dynamics of lytic viruses and microbes with CRISPR-Cas immunity exhibit alternations between sustained host control of viral proliferation and major viral epidemics in previous computational models. These dynamics have yet to be observed in other host-pathogen systems. Here, we address the breakdown of control and transition to large outbreaks with a stochastic eco-evolutionary model.

Raptinal: a powerful tool for rapid induction of apoptotic cell death.

Chemical inducers of apoptosis have been utilized for decades as tools to uncover steps of the apoptotic cascade and to treat various diseases, most notably cancer. While there are several useful compounds available, limitations in potency, universality, or speed of cell death of these pro-apoptotic agents have meant that no single compound is suitable for all (or most) purposes. Raptinal is a recently described small molecule that induces intrinsic pathway apoptosis rapidly and reliably, and consequently, has been utilized in cell culture and whole organisms for a wide range of biological studies.

An explainable language model for antibody specificity prediction using curated influenza hemagglutinin antibodies.

Despite decades of antibody research, it remains challenging to predict the specificity of an antibody solely based on its sequence. Two major obstacles are the lack of appropriate models and the inaccessibility of datasets for model training. In this study, we curated >5,000 influenza hemagglutinin (HA) antibodies by mining research publications and patents, which revealed many distinct sequence features between antibodies to HA head and stem domains.

High-quality genome assemblies for nine non-model North American insect species representing six orders (Insecta: Coleoptera, Diptera, Hemiptera, Hymenoptera, Lepidoptera, Neuroptera).

Field-collected specimens were used to obtain nine high-quality genome assemblies from a total of 10 insect species native to prairies and savannas of central Illinois (USA): Mellilla xanthometata (Lepidoptera: Geometridae), Stenolophus ochropezus (Coleoptera: Carabidae), Forcipata loca (Hemiptera: Cicadellidae), Coelinius sp. (Hymenoptera: Braconidae), Thaumatomyia glabra (Diptera: Chloropidae), Brachynemurus abdominalus (Neuroptera: Myrmeleontidae), Catonia carolina (Hemiptera: Achilidae), Oncometopia orbona (Hemiptera: Cicadellidae), Flexamia atlantica (Hemiptera: Cicadellidae) and Stictocephala bisonia (Hemiptera: Membracidae). Sequencing library preparation from single specimens was successful despite extremely small DNA yields (<0.

Paracrine signals influence patterns of fibrocartilage differentiation in a lyophilized gelatin hydrogel for applications in rotator cuff repair.

Rotator cuff injuries present a clinical challenge for repair due to current limitations in functional regeneration of the native tendon-to-bone enthesis. A biomaterial that can regionally instruct unique tissue-specific phenotypes offers potential to promote enthesis repair. We have recently demonstrated the mechanical benefits of a stratified triphasic biomaterial made up of tendon- and bone-mimetic collagen scaffold compartments connected a continuous hydrogel, and we now explore the potential of a biologically favorable enthesis hydrogel for this application.

MANCR lncRNA Modulates Cell-Cycle Progression and Metastasis by Cis-Regulation of Nuclear .

A significant number of the genetic alterations observed in cancer patients lie within nonprotein-coding segments of the genome, including regions coding for long noncoding RNAs (lncRNAs). LncRNAs display aberrant expression in breast cancer (BrCa), but the functional implications of this altered expression remain to be elucidated. By performing transcriptome screen in a triple negative BrCa (TNBC) isogenic 2D and 3D spheroid model, we observed aberrant expression of >1000 lncRNAs during BrCa progression.

Neutrophils exposed to a cholesterol metabolite secrete extracellular vesicles that promote epithelial-mesenchymal transition and stemness in breast cancer cells.

Small extracellular vesicles (sEVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment (TME). Here, we investigate the mechanisms by which sEVs derived from neutrophils treated with the cholesterol metabolite, 27-hydroxycholesterol (27HC), influence breast cancer progression. sEVs released from 27HC treated neutrophils enhance epithelial-mesenchymal transition (EMT) and stem-like properties in breast cancer cells, resulting in loss of adherence, increased migratory capacity and resistance to cytotoxic chemotherapy.

How Does Allocate Proteome?

Microorganisms are shown to actively partition their intracellular resources, such as proteins, for growth optimization. Recent experiments have begun to reveal molecular components unpinning the partition; however, quantitatively, it remains unclear how individual parts orchestrate to yield precise resource allocation that is both robust and dynamic. Here, we developed a coarse-grained mathematical framework that centers on guanosine pentaphosphate (ppGpp)-mediated regulation and used it to systematically uncover the design principles of proteome allocation in .

Respiratory infection with influenza A virus delays remyelination and alters oligodendrocyte metabolism.

Peripheral viral infection disrupts oligodendrocyte (OL) homeostasis such that endogenous remyelination may be affected. Here, we demonstrate that influenza A virus infection perpetuated a demyelination- and disease-associated OL phenotype following cuprizone-induced demyelination that resulted in delayed OL maturation and remyelination in the prefrontal cortex. Furthermore, we assessed cellular metabolism , and found that infection altered brain OL and microglia metabolism in a manner that opposed the metabolic profile induced by remyelination.

Drop-by-Drop Addition of Reagents to a Double Emulsion.

Developments in droplet microfluidics have facilitated an era of high-throughput, sensitive single-cell, or single-molecule measurements capable of tackling the heterogeneity present in biological systems. Relying on single emulsion (SE) compartments, droplet assays achieve absolute quantification of nucleic acids, massively parallel single-cell profiling, and more. Double emulsions (DEs) have seen recent interest for their potential to build upon SE techniques.

Point-of-Care Multiplex Detection of Respiratory Viruses.

The COVID-19 pandemic, in addition to the co-occurrence of influenza virus and respiratory syncytial virus (RSV), has emphasized the requirement for efficient and reliable multiplex diagnostic methods for respiratory infections. While existing multiplex detection techniques are based on reverse transcription quantitative polymerase chain reaction (RT-qPCR) and extraction and purification kits, the need for complex instrumentation and elevated cost limit their scalability and availability. In this study, we have developed a point-of-care (POC) device based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) that can simultaneously detect four respiratory viruses (SARS-CoV-2, Influenza A, Influenza B, and RSV) and perform two controls in less than 30 min, while avoiding the use of the RNA extraction kit.

Lipid droplet-associated hydrolase mobilizes stores of liver X receptor sterol ligands and protects against atherosclerosis.

Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures.

Dried Blood Matrix as a New Material for the Detection of DNA Viruses.

The gold standard for diagnosing viruses such as the Hepatitis B Virus has remained largely unchanged, relying on conventional methods involving extraction, purification, and polymerase chain reaction (PCR). This approach is hindered by limited availability, as it is time-consuming and requires highly trained personnel. Moreover, it suffers from low recovery rates of the nucleic acid molecules for samples with low copy numbers.

Targeted whole-genome recovery of single viral species in a complex environmental sample.

Characterizing unknown viruses is essential for understanding viral ecology and preparing against viral outbreaks. Recovering complete genome sequences from environmental samples remains computationally challenging using metagenomics, especially for low-abundance species with uneven coverage. We present an experimental method for reliably recovering complete viral genomes from complex environmental samples.

Assessing Illinois companion animal veterinarians' antimicrobial prescription practices and the factors that influence their decisions when treating bacterial infections in dogs and cats.

Aims: Judicious antimicrobial use in companion animal practice is critical for maintaining the effectiveness of antimicrobial agents against bacterial infections and reducing the selection of antimicrobial-resistant bacteria. This study aimed to provide insights into companion animal veterinarians' antimicrobial treatment recommendations for common bacterial infections in dogs and cats and describe the factors influencing their prescription choices.

Methods And Results: An online survey using QualtricsXM® software was administered between September and November 2022 to companion animal veterinarians who were Illinois State Veterinary Medical Association members.

Donor Sex and Passage Conditions Influence MSC Osteogenic Response in Mineralized Collagen Scaffolds.

Contemporary tissue engineering efforts often seek to use mesenchymal stem cells (MSCs) due to their multi-potent potential and ability to generate a pro-regenerative secretome. While many have reported the influence of matrix environment on MSC osteogenic response, few have investigated the effects of donor and sex. Here, a well-defined mineralized collagen scaffold is used to study the influence of passage number and donor-reported sex on MSC proliferation and osteogenic potential.

Endometrial decidualization status modulates endometrial microvascular complexity and trophoblast outgrowth in gelatin methacryloyl hydrogels.

The endometrium undergoes rapid cycles of vascular growth, remodeling, and breakdown during the menstrual cycle and pregnancy. Decidualization is an endometrial differentiation process driven by steroidal sex hormones that is critical for blastocyst-uterine interfacing and blastocyst implantation. Certain pregnancy disorders may be linked to decidualization processes.

Acquired Temozolomide Resistance Instructs Patterns of Glioblastoma Behavior in Gelatin Hydrogels.

Acquired drug resistance in glioblastoma (GBM) presents a major clinical challenge and is a key factor contributing to abysmal prognosis, with less than 15 months median overall survival. Aggressive chemotherapy with the frontline therapeutic, temozolomide (TMZ), ultimately fails to kill residual highly invasive tumor cells after surgical resection and radiotherapy. Here, a 3D engineered model of acquired TMZ resistance is reported using two isogenically matched sets of GBM cell lines encapsulated in gelatin methacrylol hydrogels.

How Do Environmental Toxicants Affect Oocyte Maturation Via Oxidative Stress?

In mammals, oogenesis initiates before birth and pauses at the dictyate stage of meiotic prophase I until luteinizing hormone (LH) surges to resume meiosis. Oocyte maturation refers to the resumption of meiosis that directs oocytes to advance from prophase I to metaphase II of meiosis. This process is carefully modulated to ensure a normal ovulation and successful fertilization.

Capturing cell morphology dynamics with high temporal resolution using single-shot quantitative phase gradient imaging.

Significance: Label-free quantitative phase imaging can potentially measure cellular dynamics with minimal perturbation, motivating efforts to develop faster and more sensitive instrumentation. We characterize fast, single-shot quantitative phase gradient microscopy (ss-QPGM) that simultaneously acquires multiple polarization components required to reconstruct phase images. We integrate a computationally efficient least squares algorithm to provide real-time, video-rate imaging (up to ).

Introducing carbon assimilation in yeasts using photosynthetic directed endosymbiosis.

Conversion of heterotrophic organisms into partially or completely autotrophic organisms is primarily accomplished by extensive metabolic engineering and laboratory evolution efforts that channel CO into central carbon metabolism. Here, we develop a directed endosymbiosis approach to introduce carbon assimilation in budding yeasts. Particularly, we engineer carbon assimilating and sugar-secreting photosynthetic cyanobacterial endosymbionts within the yeast cells, which results in the generation of yeast/cyanobacteria chimeras that propagate under photosynthetic conditions in the presence of CO and in the absence of feedstock carbon sources like glucose or glycerol.

Cancer-associated snaR-A noncoding RNA interacts with core splicing machinery and disrupts processing of mRNA subpopulations.

RNA polymerase III (Pol III) activity in cancer is linked to the production of small noncoding (nc)RNAs that are otherwise silent in most tissues. snaR-A (small NF90-associated RNA isoform A) - a hominid-specific ncRNA shown to enhance cell proliferation, migration, and invasion - is a cancer-emergent Pol III product that remains largely uncharacterized despite promoting growth phenotypes. Here, we applied a combination of genomic and biochemical approaches to study the biogenesis and subsequent protein interactions of snaR-A and to better understand its role as a putative driver of cancer progression.

Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample.

Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds.