PDE8 controls CD4(+) T cell motility through the PDE8A-Raf-1 kinase signaling complex

The levels of cAMP are regulated by phosphodiesterase enzymes (PDEs), which are targets for the treatment of inflammatory disorders. We have previously shown that PDE8 regulates T cell motility. Here, for the first time, we report that PDE8A exerts part of its control of T cell function through the V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) kinase signaling pathway. To examine T cell motility under physiologic conditions, we analyzed T cell interactions with endothelial cells and ligands in flow assays. The highly PDE8-selective enzymatic inhibitor PF-04957325 suppresses adhesion of in vivo myelin oligodendrocyte glycoprotein (MOG) activated inflammatory CD4(+) T effector (Teff) cells to brain endothelial cells under shear stress. Recently, PDE8A was shown to associate with Raf-1 creating a compartment of low cAMP levels around Raf-1 thereby protecting it from protein kinase A (PKA) mediated inhibitory phosphorylation. To test the function of this complex in Teff cells, we used a cell permeable peptide that selectively disrupts the PDE8A-Raf-1 interaction. The disruptor peptide inhibits the Teff-endothelial cell interaction more potently than the enzymatic inhibitor. Furthermore, the LFA-1/ICAM-1 interaction was identified as a target of disruptor peptide mediated reduction of adhesion, spreading and locomotion of Teff cells under flow. Mechanistically, we observed that disruption of the PDE8A-Raf-1 complex profoundly alters Raf-1 signaling in Teff cells. Collectively, our studies demonstrate that PDE8A inhibition by enzymatic inhibitors or PDE8A-Raf-1 kinase complex disruptors decreases Teff cell adhesion and migration under flow, and represents a novel approach to target T cells in inflammation

Determinants of Self-Efficacy among Individuals who are Hard-of-Hearing

Self-efficacy plays an important role in their lives of the estimated 48 million Americans who report having some degree of hearing impairment, helping them navigate through a myriad of communication challenges. The purpose of the present study was to assess the levels of self-efficacy in this disability group by examining an array of social, psychological, spiritual, disability, and demographic variables. A total of 114 persons who identified as hard-of-hearing took part in an online survey. A hierarchical multiple regression analysis was performed to answer the research question. The proposed regression model explained 24.7% of variance in self-efficacy among individuals who are hard-of-hearing. Specifically, educational attainment, internal locus of control, spirituality/religiosity, social support, and employment status are the five significant predictors of self-efficacy. Finally, implications for rehabilitation practice and research are discussed

Operationalization, implications and correlates of the cultural deviance criterion for ICD-11 and DSM-5 prolonged grief disorder

Prolonged Grief Disorder (PGD) is included in ICD-11 and DSM-5-TR and includes a requirement of cultural deviance. This study examined endorsement rates and factors associated with endorsement of this criterion among Danish bereaved spouses (n = 425) and their adult children (n = 159) four years post-loss. In total, 7.5% (n = 44) participants endorsed this criterion. Both including and excluding the criterion, the prevalence rates for probable DSM-5-TR PGD were 1.4% (n = 8) and 1.7% (n = 10), respectively and for probable ICD-11 PGD were 1.4% (n = 8) and 2.2% (n = 13), respectively. Age and gender of the deceased, age of the bereaved, greater grief severity, and comorbid psychopathology were positively associated with endorsement of the criterion. Findings demonstrate low endorsement of the cultural deviation criterion, that its inclusion excludes several potential PGD cases, and unanticipated associations with several factors raise questions about the criterion’s validity

Spatially Extended Low Ionization Emission Regions (LIERs) at z∼0.9z\sim0.9

We present spatially resolved emission diagnostics for eight $z\sim0.9$ galaxies that demonstrate extended low ionization emission-line regions (LIERs) over kpc scales. Eight candidates are selected based on their spatial extent and emission line fluxes from slitless spectroscopic observations with the HST/WFC3 G141 and G800L grisms in the well-studied GOODS survey fields. Five of the candidates (62.5%) are matched to X-ray counterparts in the \textit{Chandra X-Ray Observatory} Deep Fields. We modify the traditional Baldwin-Philips-Terlevich (BPT) emission line diagnostic diagram to use [SII]/(H$\alpha$+[NII]) instead of [NII]/H$\alpha$ to overcome the blending of [NII] and H$\alpha$+[NII] in the low resolution slitless grism spectra. We construct emission line ratio maps and place the individual pixels in the modified BPT. The extended LINER-like emission present in all of our candidates, coupled with X-Ray properties consistent with star-forming galaxies and weak [OIII]$\lambda$5007\AA\ detections, is inconsistent with purely nuclear sources (LINERs) driven by active galactic nuclei. While recent ground-based integral field unit spectroscopic surveys have revealed significant evidence for diffuse LINER-like emission in galaxies within the local universe $(z\sim0.04)$, this work provides the first evidence for the non-AGN origin of LINER-like emission out to high redshifts.Comment: 11 pages, 1 table, 6 figures, accepted for publication in the Astrophysics Journal (ApJ

Adipokinetic hormones and their G protein-coupled receptors emerged in Lophotrochozoa

Most multicellular animals belong to two evolutionary lineages, the Proto– and Deuterostomia, which diverged 640–760 million years (MYR) ago. Neuropeptide signaling is abundant in animals belonging to both lineages, but it is often unclear whether there exist evolutionary relationships between the neuropeptide systems used by proto- or deuterostomes. An exception, however, are members of the gonadotropin-releasing hormone (GnRH) receptor superfamily, which occur in both evolutionary lineages, where GnRHs are the ligands in Deuterostomia and GnRH-like peptides, adipokinetic hormone (AKH), corazonin, and AKH/corazonin-related peptide (ACP) are the ligands in Protostomia. AKH is a well-studied insect neuropeptide that mobilizes lipids and carbohydrates from the insect fat body during flight. In our present paper, we show that AKH is not only widespread in insects, but also in other Ecdysozoa and in Lophotrochozoa. Furthermore, we have cloned and deorphanized two G protein-coupled receptors (GPCRs) from the oyster Crassostrea gigas (Mollusca) that are activated by low nanomolar concentrations of oyster AKH (pQVSFSTNWGSamide). Our discovery of functional AKH receptors in molluscs is especially significant, because it traces the emergence of AKH signaling back to about 550 MYR ago and brings us closer to a more complete understanding of the evolutionary origins of the GnRH receptor superfamily

Phenotypic Screening of Drought-Tolerant Lines for Brown Planthopper, Blast and Phytic Acid Content Assay of Rice (Oryza sativa L.)

Advanced drought tolerant lines were analysed for blast disease, brown planthopper (BPH), and phytic acid content. Thirsty lines of BC2F4 derived from OMCS2000/ IR75499-73-1 were used to screen for BPH and blast resistance. Three good resistant lines were screened against blast (45, 54, and 310) under greenhouse condition. As eight lines were identified to be resistant to BPH. The results further reveal that BC2F4-45 was the best line resistant to both BPH and blast disease. These lines will be useful in reducing grain phytic acid and improving the nutritional value of rice grain. Based on an assay for high phosphate germination stage of rice, the lowest content was found in the I5 variety (line 45). Hence, this line provides the urgent objective for breeders in cultivars of these crops to genetically enhance a healthy and functional diet. These characters will then need to be incorporated into high yield under drought stress with others such as disease and insect resistance

The number of inpatient consultations is negatively correlated with patient satisfaction in patients with prolonged hospital stays

Patient satisfaction is often measured using the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) Survey. Our aim was to examine the structural and clinical determinants of satisfaction among inpatients with prolonged lengths of stays (LOS)

Movement Interventions for Children with Autism and Developmental Disabilities: An Evidence-Based Practice Project

This review explored the following question: Are the comprehensive treatment models Makoto Therapy, Brain Gym, and Interactive Metronome effective interventions for improving occupational performance including improving executive function, academic performance, and physical coordination in children and adolescents with Autism Spectrum Disorder (ASD)? Because current research on Interactive Metronome, Brain Gym®, and Makoto Therapy fails to address children and adolescents with autism spectrum disorder, presents multiple flaws in research design, and does not measure occupational outcomes such as occupational performance, we recommend that these interventions should not be used as comprehensive treatment models in occupational therapy. We recommend that more occupational-based, methodologically-sound research involving youth with ASD be conducted before implementing these interventions in occupational therapy practice