Epinephrine inhibits PI3Kα via the Hippo kinases.

The phosphoinositide 3-kinase p110α is an essential mediator of insulin signaling and glucose homeostasis. We interrogated the human serine, threonine, and tyrosine kinome to search for novel regulators of p110α and found that the Hippo kinases phosphorylate p110α at T1061, which inhibits its activity. This inhibitory state corresponds to a conformational change of a membrane-binding domain on p110α, which impairs its ability to engage membranes.

Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication.

Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets.

Insulin signaling and osmotic stress response regulate arousal and developmental progression of C. elegans at hatching.

The progression of animal development from embryonic to juvenile life depends on the coordination of organism-wide responses with environmental conditions. We found that two transcription factors that function in interneuron differentiation in Caenorhabditis elegans, fax-1, and unc-42, are required for arousal and progression from embryogenesis to larval life by potentiating insulin signaling. The combination of mutations in either transcription factor and a mutation in daf-2 insulin receptor results in a novel perihatching arrest phenotype; embryos are fully developed but inactive, often remaining trapped within the eggshell, and fail to initiate pharyngeal pumping.

The FDA-approved drug Alectinib compromises SARS-CoV-2 nucleocapsid phosphorylation and inhibits viral infection in vitro.

While vaccines are vital for preventing COVID-19 infections, it is critical to develop new therapies to treat patients who become infected. Pharmacological targeting of a host factor required for viral replication can suppress viral spread with a low probability of viral mutation leading to resistance. In particular, host kinases are highly druggable targets and a number of conserved coronavirus proteins, notably the nucleoprotein (N), require phosphorylation for full functionality.

Effect of Osteopathic Manipulative Therapy on Generalized Anxiety Disorder.

Context: Traditional management options for generalized anxiety disorder (GAD) have produced low remission rates. As a result, the medical community has turned to complementary and alternative medicine for adjunctive treatment.

Objective: To investigate the efficacy of adjunctive osteopathic manipulative therapy (OMTh; manipulative care provided by foreign-trained osteopaths) in individuals with GAD.

Preventing Self-Harm in the Nonpsychiatric Health Care Setting.

The Pennsylvania Patient Safety Reporting System is a confidential, statewide Internet reporting system to which all Pennsylvania hospitals, outpatient-surgery facilities, birthing centers, and abortion facilities must file information on incidents and serious events.Safety Monitor is a column from Pennsylvania's Patient Safety Authority, the authority that informs nurses on issues that can affect patient safety and presents strategies they can easily integrate into practice. For more information on the authority, visit www.

Protecting Patients with Latex Allergies.

: The Pennsylvania Patient Safety Reporting System is a confidential, statewide Internet reporting system to which all Pennsylvania hospitals, outpatient-surgery facilities, birthing centers, and abortion facilities must file information on incidents and serious events.Safety Monitor is a column from Pennsylvania's Patient Safety Authority, the authority that informs nurses on issues that can affect patient safety and presents strategies they can easily integrate into practice. For more information on the authority, visit www.

A tissue-specific enhancer of the C. elegans nhr-67/tailless gene drives coordinated expression in uterine stem cells and the differentiated anchor cell.

The nhr-67 nuclear receptor gene of Caenorhabditis elegans encodes the ortholog of the Drosophila tailless and vertebrate Tlx genes. In C. elegans, nhr-67 plays multiple roles in the development of the uterus during L2 and L3 larval stages.

Latex Allergy Risks Live On.

Reduction in the prevalence of IgE-mediated allergy to latex proteins from gloves in patients may lead to lax attention by health care personnel to avoid use of latex products in latex-allergic subjects. Recent evidence from the Pennsylvania Patient Safety Reporting System shows an alarming continuation of adverse events mostly from latex urinary catheters. We are strongly advocating that health care personnel must continue to pay close attention to avoidance of latex in patients with a history of latex allergy.

Optimization and Comparative Analysis of Plant Organellar DNA Enrichment Methods Suitable for Next-generation Sequencing.

Plant organellar genomes contain large, repetitive elements that may undergo pairing or recombination to form complex structures and/or sub-genomic fragments. Organellar genomes also exist in admixtures within a given cell or tissue type (heteroplasmy), and an abundance of subtypes may change throughout development or when under stress (sub-stoichiometric shifting). Next-generation sequencing (NGS) technologies are required to obtain deeper understanding of organellar genome structure and function.

Bypassing Negative Epistasis on Yield in Tomato Imposed by a Domestication Gene.

Selection for inflorescence architecture with improved flower production and yield is common to many domesticated crops. However, tomato inflorescences resemble wild ancestors, and breeders avoided excessive branching because of low fertility. We found branched variants carry mutations in two related transcription factors that were selected independently.

Dissecting Plant Chromosomes by the Use of Ionizing Radiation.

Radiation treatment of genomes is used to generate chromosome breaks for numerous applications. This protocol describes the preparation of seeds and the determination of the optimal level of irradiation dosage for the creation of a radiation hybrid (RH) population. These RH lines can be used to generate high-resolution physical maps for the assembly of sequenced genomes as well as the fine mapping of genes.

The role of mitochondria in plant development and stress tolerance.

Eukaryotic cells require orchestrated communication between nuclear and organellar genomes, perturbations in which are linked to stress response and disease in both animals and plants. In addition to mitochondria, which are found across eukaryotes, plant cells contain a second organelle, the plastid. Signaling both among the organelles (cytoplasmic) and between the cytoplasm and the nucleus (i.

A cascade of arabinosyltransferases controls shoot meristem size in tomato.

Shoot meristems of plants are composed of stem cells that are continuously replenished through a classical feedback circuit involving the homeobox WUSCHEL (WUS) gene and the CLAVATA (CLV) gene signaling pathway. In CLV signaling, the CLV1 receptor complex is bound by CLV3, a secreted peptide modified with sugars. However, the pathway responsible for modifying CLV3 and its relevance for CLV signaling are unknown.

Tomato yield heterosis is triggered by a dosage sensitivity of the florigen pathway that fine-tunes shoot architecture.

The superiority of hybrids has long been exploited in agriculture, and although many models explaining "heterosis" have been put forth, direct empirical support is limited. Particularly elusive have been cases of heterozygosity for single gene mutations causing heterosis under a genetic model known as overdominance. In tomato (Solanum lycopersicum), plants carrying mutations in SINGLE FLOWER TRUSS (SFT) encoding the flowering hormone florigen are severely delayed in flowering, become extremely large, and produce few flowers and fruits, but when heterozygous, yields are dramatically increased.

Prevalence of Internet addiction in Latino adolescents with psychiatric diagnosis.

Internet addiction (IA) is particularly relevant in the adolescent population. The aim of this study was to describe the prevalence of IA in a clinical sample of Latino adolescents receiving ambulatory psychiatric treatment. The correlation between their pattern of Internet use and their respective psychiatric diagnosis was also studied.

The WTM genes in budding yeast amplify expression of the stress-inducible gene RNR3.

Cellular responses to DNA damage and inhibited replication are evolutionarily conserved sets of pathways that are critical to preserving genome stability. To identify new participants in these responses, we undertook a screen for regulators that, when present on a high-copy vector, alter expression of a DNA damage-inducible RNR3-lacZ reporter construct in Saccharomyces cerevisiae. From this screen we isolated a plasmid encoding two closely related paralogs, WTM1 and WTM2, that greatly increases constitutive expression of RNR3-lacZ.

Clinicians' perceptions of the problem of antimicrobial resistance in health care facilities.

Background: Many clinicians do not comply with guidelines regarding antimicrobial resistance (AR). In response, the Centers for Disease Control and Prevention developed a national Campaign to Prevent Antimicrobial Resistance in Healthcare Settings that presents 4 strategies and 12 evidence-based steps.

Methods: To assess clinicians' perceptions of AR, barriers and facilitators to preventing AR, and how best to reach clinicians, a questionnaire and 4 focus groups were conducted after presentation of the Campaign at 4 Pittsburgh Regional Healthcare Initiative hospitals.

Greater adherence to highly active antiretroviral therapy (HAART) between pregnant versus non-pregnant women living with HIV.

One of the most remarkable advances in the control of the HIV/AIDS pandemic has been the introduction of highly active antiretroviral therapy (HAART). The use of HAART has been associated to reductions in AIDS-related mortality in most countries where HAART is available. Unfortunately, the adherence required to keep good control of viral replication is higher than what is required in other medical conditions.

Suppressor mutations derived from the most severe protein folding mutation known.

This brief report describes the isolation and initial characterization of revertants to the most severe temperature sensitive folding mutant known. The revertants or suppressors may describe amino acid interactions that occur during the folding of the P22 tailspike polypeptide chain. Results indicate that several different types of suppressors may have been obtained.

Automated external defibrillators: an update of additions to the ACLS algorithms.

Instruction in the use of the automated external defibrillator is now a mandatory component of ACLS certification. Here's a review of changes to the ACLS algorithm.