Long-term normalization of calcineurin activity in model mice rescues Pin1 and attenuates Alzheimer's phenotypes without blocking peripheral T cell IL-2 response.

Background: Current treatments for Alzheimer's disease (AD) have largely failed to yield significant therapeutic benefits. Novel approaches are desperately needed to help address this immense public health issue. Data suggests that early intervention at the first stages of mild cognitive impairment may have a greater chance for success.

Evaluation of severe acute respiratory syndrome coronavirus 2 monoclonal antibodies in high-risk solid organ transplant recipients across three major coronavirus disease 2019 variant waves.

Background: Coronavirus disease 2019 (COVID-19) continues to impact immunocompromised populations including solid organ transplant recipients (SOTRs). Monoclonal antibodies (mAbs) have shown effectiveness in reducing COVID-19-related hospitalizations and emergency department (ED) visits in SOTRs at different time frames in the COVID-19 pandemic; however, less data exist on the impact of mAbs for SOTRs across variant waves and with the advent of available COVID-19 vaccines.

Methods: This retrospective study included SOTR outpatients who tested positive for SARS-CoV-2 and received mAbs from December 2020 to February 2022 (n = 233); using in-house sequencing of clinical samples, we monitored the emergence of Alpha, Delta, and Omicron variants.

Extensively Drug-Resistant in Critically Ill Patients: A Case Series and Literature Review.

The bacterial genus , like other members of the family, consists of aerobic, non-motile, Gram-negative bacilli. spp. is considered predominantly opportunistic pathogens as, historically, most documented infections have been in immunocompromised individuals.

Effects of Sensory Garments on Sleep of Children with Autism Spectrum Disorder.

Objective: The purpose of this study is to assess the effectiveness of the use of sensory garments for improving sleep in children with autism spectrum disorder.

Method: Using a single-subject ABAB reversal design, the researchers evaluated the effectiveness of a sensory garment on sleep duration, sleep latency, and parental stress related to a child's sleep. Four children aged 4-10 participated.

Successful Treatment of Invasive Mucormycosis in Orthotopic Liver Transplant Population.

Mucormycosis is caused by ubiquitous fungi and encompasses a variety of different opportunistic syndromes in humans that disproportionately affect immunocompromised patients. Mortality has been documented to range between 50 and 100%; however, location of infection greatly dictates likelihood of survival. Treatment of mucormycosis involves aggressive surgical intervention and combination therapy of antifungal agents.

Pin1 Regulates IL-5 Induced Eosinophil Polarization and Migration.

Eosinophils become polarized in response to cytokines such IL-5 or eotaxin prior to directional migration. Polarization is preceded by F-actin assembly, but the mechanisms that regulate these events and how the shape change influences cell migration from the peripheral blood into the lung remain unclear. In this study, we show that the prolyl isomerase, Pin1, is required for IL-5-induced Eos polarization and migration.

Evaluating appropriateness and diagnostic stewardship opportunities of multiplex polymerase chain reaction gastrointestinal testing within a hospital system.

Objective: This single-center, retrospective, observational cohort study evaluates the appropriateness of the BioFire® FilmArray® Gastrointestinal (GI) multiplex PCR panel testing at a community-teaching hospital.

Methods: All adult, hospitalized patients at Prisma Health Richland Hospital with a documented GI multiplex PCR panel from 1 April 2015 through 28 February 2018 were included in the analysis. Inappropriate use of the GI panel was defined as a test obtained without documented diarrhea, greater than 2 days of hospitalization, redundant use with other diagnostic tests (e.

Use of continuous-infusion ceftolozane/tazobactam for resistant Gram-negative bacterial infections: a retrospective analysis and brief review of the literature.

Ceftolozane/tazobactam (C/T), a novel antipseudomonal cephalosporin plus β-lactamase inhibitor, is used in multidrug-resistant Gram-negative infections. Continuous infusion (CI) of C/T is an attractive concept for aiding in transitions of care and maximising the pharmacodynamics of cephalosporins (T). This was a single-centre retrospective analysis of CI C/T use in adults from December 2016 to June 2019 in the inpatient or outpatient setting.

Alzheimer's Disease, Dendritic Spines, and Calcineurin Inhibitors: A New Approach?

Therapeutics to effectively treat Alzheimer's disease (AD) are lacking. In vitro, animal and human studies have implicated the excessive activation of the protein phosphatase calcineurin (CN) as an early step in the pathogenesis of AD. We discuss recent data showing that the prolyl isomerase Pin1 is suppressed by CN-mediated dephosphorylation induced by Aβ42 signaling.

Pin1 mediates Aβ-induced dendritic spine loss.

Early-stage Alzheimer's disease is characterized by the loss of dendritic spines in the neocortex of the brain. This phenomenon precedes tau pathology, plaque formation, and neurodegeneration and likely contributes to synaptic loss, memory impairment, and behavioral changes in patients. Studies suggest that dendritic spine loss is induced by soluble, multimeric amyloid-β (Aβ), which, through postsynaptic signaling, activates the protein phosphatase calcineurin.

A p53 enhancer region regulates target genes through chromatin conformations in cis and in trans.

We examined how a p53 enhancer transmits regulatory information in vivo. Using genetic ablation together with digital chromosome conformation capture and fluorescent in situ hybridization, we found that a Drosophila p53 enhancer region (referred to as the p53 response element [p53RE]) physically contacts targets in cis and across the centromere to control stress-responsive transcription at these sites. Furthermore, when placed at ectopic genomic positions, fragments spanning this element re-established chromatin contacts and partially restored target gene regulation to mutants lacking the native p53RE.

A cell-based screening platform identifies novel mosquitocidal toxins.

Pesticides currently in widespread use often lack species specificity and also become less effective as resistance emerges. Consequently, there is a pressing need to develop novel agents that are narrowly targeted and safe to humans. A cell-based screening platform was designed to discover compounds that are lethal to mosquito (Anopheles and Aedes) cells but show little or no activity against other insect (Drosophila) or human cell lines.

Host plant quality of Tamarix ramosissima and T. parviflora for three sibling species of the biocontrol insect Diorhabda elongata (Coleoptera: Chrysomelidae).

Several sibling species of the leaf beetle Diorhabda elongata (Brullé) have been introduced into North America for the biocontrol of saltcedars (Tamarix spp.), but only one, D. carinulata (Desbrochers), has been extensively used in the field.

Activation of tumor cell integrin alphavbeta3 controls angiogenesis and metastatic growth in the brain.

The incidence of brain metastasis is rising and poses a severe clinical problem, as we lack effective therapies and knowledge of mechanisms that control metastatic growth in the brain. Here we demonstrate a crucial role for high-affinity tumor cell integrin alpha(v)beta(3) in brain metastatic growth and recruitment of blood vessels. Although alpha(v)beta(3) is frequently up-regulated in primary brain tumors and metastatic lesions of brain homing cancers, we show that it is the alpha(v)beta(3) activation state that is critical for brain lesion growth.

Phosphorylation of the Gal4 DNA-binding domain is essential for activator mono-ubiquitylation and efficient promoter occupancy.

Recent analysis of a Gal4 mutant (Gap71) carrying three point mutations (S22D, K23Q and K25F) in its DNA-binding domain (DBD), has demonstrated that it cannot occupy GAL promoters efficiently in cells and that it is not mono-ubiquitylated, suggesting a functional link between this modification and stable DNA binding in cells. The mechanistic underpinning of this phenotype is that this protein is hypersensitive to a newly discovered activity of the proteasomal ATPases--their ability to actively dissociate transcription factor-DNA complexes after direct interaction with the activation domain. In this paper, we examine the roles of each of the three point mutations contained in Gap71 individually.