The extensive mC epitranscriptome of Thermococcus kodakarensis is generated by a suite of RNA methyltransferases that support thermophily.

RNAs are often modified to invoke new activities. While many modifications are limited in frequency, restricted to non-coding RNAs, or present only in select organisms, 5-methylcytidine (mC) is abundant across diverse RNAs and fitness-relevant across Domains of life, but the synthesis and impacts of mC have yet to be fully investigated. Here, we map mC in the model hyperthermophile, Thermococcus kodakarensis.

Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells.

Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma.

Purpose: Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target antigen expression, antigen escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated by cancer-associated fibroblasts (CAF), which may contribute to the limited efficacy of mesothelin-directed CAR T cells in early-phase clinical trials. To provide a more favorable TME for CAR T cells to target pancreatic ductal adenocarcinoma (PDAC), we generated T cells with an antimesothelin CAR and a secreted T-cell-engaging molecule (TEAM) that targets CAF through fibroblast activation protein (FAP) and engages T cells through CD3 (termed mesoFAP CAR-TEAM cells).

PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.

Background: Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery.

US Department of Veterans Affairs Post-Baccalaureate Registered Nurse Residency: Developing Nurses Equipped with Knowledge and Skills to Care for Nation's Veterans.

Nurse residency programs were developed to improve novice nurse competencies, mitigate burnout, lower recruitment costs and nurse attrition, and the quality of patient care. The Office of Academic Affiliations (OAA), US Department of Veterans Affairs (VA), established a 12-month postbaccalaureate nurse residency (PB-RNR) program at 49 sites to develop competent, confident, practice-ready registered nurses equipped with the knowledge and skills to care for veterans. The OAA evaluation of the PB-RNR program demonstrated improved new nurse graduate competence, confidence, recruitment, and retention rates after completion of training at participating VA medical facilities.

Impact of Social and Relational Adversity on Access to Services among US Children with Autism Spectrum Disorder 2016-2019.

To explore the impact of social and relational adversity on access to key health services among US children with autism spectrum disorders (ASD), cross-sectional analyses of the 2016-2019 National Survey of Children's Health assessed use of key health services by children with ASD, accounting for differences in demographic characteristics, medical needs, and experience of social and relational adversities. sUS children with ASD were more than twice as likely as peers without ASD to report two or more social adversities and more than three times as likely to report two or more relational adversities. In multivariable models, relational adversities were significantly associated with greater odds of medication use for ASD (OR 1.

Reactivation of Myc transcription in the mouse heart unlocks its proliferative capacity.

It is unclear why some tissues are refractory to the mitogenic effects of the oncogene Myc. Here we show that Myc activation induces rapid transcriptional responses followed by proliferation in some, but not all, organs. Despite such disparities in proliferative response, Myc is bound to DNA at open elements in responsive (liver) and non-responsive (heart) tissues, but fails to induce a robust transcriptional and proliferative response in the heart.

Integration of polarized spatial frequency domain imaging (pSFDI) with a biaxial mechanical testing system for quantification of load-dependent collagen architecture in soft collagenous tissues.

Collagen fiber networks provide the structural strength of tissues, such as tendons, skin and arteries. Quantifying the fiber architecture in response to mechanical loads is essential towards a better understanding of the tissue-level mechanical behaviors, especially in assessing disease-driven functional changes. To enable novel investigations into these load-dependent fiber structures, a polarized spatial frequency domain imaging (pSFDI) device was developed and, for the first time, integrated with a biaxial mechanical testing system.

A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection.

The response to respiratory viruses varies substantially between individuals, and there are currently no known molecular predictors from the early stages of infection. Here we conduct a community-based analysis to determine whether pre- or early post-exposure molecular factors could predict physiologic responses to viral exposure. Using peripheral blood gene expression profiles collected from healthy subjects prior to exposure to one of four respiratory viruses (H1N1, H3N2, Rhinovirus, and RSV), as well as up to 24 h following exposure, we find that it is possible to construct models predictive of symptomatic response using profiles even prior to viral exposure.

Evolutionary transition from blood feeding to obligate nonbiting in a mosquito.

The spread of blood-borne pathogens by mosquitoes relies on their taking a blood meal; if there is no bite, there is no disease transmission. Although many species of mosquitoes never take a blood meal, identifying genes that distinguish blood feeding from obligate nonbiting is hampered by the fact that these different lifestyles occur in separate, genetically incompatible species. There is, however, one unique extant species with populations that share a common genetic background but blood feed in one region and are obligate nonbiters in the rest of their range: Contemporary blood-feeding and obligate nonbiting populations represent end points of divergence between fully interfertile southern and northern populations.

Robotic Mitral Valve Repair for Simple and Complex Degenerative Disease: Midterm Clinical and Echocardiographic Quality Outcomes.

Background: Severe primary (degenerative) mitral regurgitation (MR) is repaired with durable results when simple single-scallop disease is addressed. The midterm quality outcomes of minimally invasive repair for complex disease are unknown, however.

Methods And Results: From January 2008 to January 2015, 487 patients (56±11 years, 360 men, ejection fraction 65±6%, 98.

Evolutionary divergence of core and post-translational circadian clock genes in the pitcher-plant mosquito, Wyeomyia smithii.

Background: Internal circadian (circa, about; dies, day) clocks enable organisms to maintain adaptive timing of their daily behavioral activities and physiological functions. Eukaryotic clocks consist of core transcription-translation feedback loops that generate a cycle and post-translational modifiers that maintain that cycle at about 24 h. We use the pitcher-plant mosquito, Wyeomyia smithii (subfamily Culicini, tribe Sabethini), to test whether evolutionary divergence of the circadian clock genes in this species, relative to other insects, has involved primarily genes in the core feedback loops or the post-translational modifiers.

Ventricular arrhythmia risk stratification in patients with tetralogy of Fallot at the time of pulmonary valve replacement.

Background: Most patients with repaired tetralogy of Fallot require pulmonary valve replacement (PVR), but the evaluation for and management of ventricular arrhythmia remain unclear. This study is aimed at clarifying the optimal approach to this potentially life-threatening issue at the time of PVR.

Methods And Results: A retrospective analysis was performed on 205 patients with repaired tetralogy of Fallot undergoing PVR at our institution between 1988 and 2010.

What can proteomics tell us about platelets?

More than 130 years ago, it was recognized that platelets are key mediators of hemostasis. Nowadays, it is established that platelets participate in additional physiological processes and contribute to the genesis and progression of cardiovascular diseases. Recent data indicate that the platelet proteome, defined as the complete set of expressed proteins, comprises >5000 proteins and is highly similar between different healthy individuals.

One-year outcomes in eyes remaining phakic after Descemet membrane endothelial keratoplasty.

Purpose: To assess 1-year outcomes in patients remaining phakic after Descemet membrane endothelial keratoplasty (DMEK).

Setting: Private clinic, Indianapolis, Indiana, USA.

Design: Interventional case series.

Innominate vein-right atrial bypass for relief of superior vena cava syndrome due to pacemaker lead thrombosis.

We present a patient with superior vena cava (SVC) obstruction due to multiple intraluminal pacemaker leads. Previous attempts at balloon dilatation of the SVC and surgical angioplasty did not provide a long-term solution. A Gore-Tex (W.

Use of preoperative magnetic resonance imaging to predict rotator cuff tear pattern and method of repair.

Purpose: To determine the magnetic resonance imaging (MRI) criteria for predicting rotator cuff tear pattern and method of repair.

Type Of Study: Retrospective MRI/arthroscopy correlation.

Methods: Sixty-six preoperative MRI scans were evaluated.

A report card on diversity: lessons for business from higher education.

Institutions of higher learning in the United States have long played a disproportionate role in supplying leadership talent to the world's business and professional organizations. For 30 years, the most selective schools have been working to increase diversity in their student bodies. New research by the former presidents of Princeton and Harvard suggests that the experiences and initiatives of these academic institutions can provide business leaders with insight into how to create diverse organizations that succeed.

Purification and Characterization of a Soluble Phosphatidylinositol 4-Kinase from Carrot Suspension Culture Cells.

Previously we reported the presence of a soluble phosphatidylinositol 4-kinase (PI 4-Kinase) in carrot (Daucus carota L.) suspension culture cells (C.M.

Protein synthesis in perfused rat lungs: determinations based on incorporation of radioactive proline.

Functional compartmentation and metabolism of radioactive proline was evaluated to define conditions under which synthesis of lung proteins could be measured accurately based on proline incorporation. Rat lungs were perfused with Krebs-Henseleit bicarbonate buffer equilibrated with O2/N2/CO2 (20:75:5) and containing 4.5% (w/v) bovine serum albumin, 5.