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here is little understanding of couple communication surrounding covert contraceptive use decisions, research should focus on characterizing content and context of couple communication particularly in cases of disagreement over fertility decisions.The present study employed structured diagnostic interviews to assess the construct validity of the brief version of the Multidimensional Schizotypy Scale (MSS-B), which was developed to assess positive, negative, and disorganized dimensions of schizotypy. It was hypothesized that the MSS-B subscales would be associated with differential patterns of symptoms and impairment, comparable to findings for the full-length MSS. A total of 177 young adults completed structured diagnostic interviews assessing symptoms and impairment. As hypothesized, MSS-B positive schizotypy was significantly associated with interview ratings of positive (psychotic-like) symptoms, as well as schizotypal and paranoid personality disorder traits. MSS-B negative schizotypy was associated with interview ratings of negative symptoms, as well as schizoid, paranoid, and schizotypal traits. Furthermore, negative schizotypy predicted Cluster A personality disorder diagnoses. MSS-B disorganized schizotypy was associated with interview ratings of disorganized symptoms. All three schizotypy dimensions were associated with impaired functioning. This was the first study to evaluate the validity of the MSS-B using interview measures, and the pattern of findings for each MSS-B subscale was closely comparable to the findings for the full-length MSS. Contrary to our hypothesis, cannabis use was largely unassociated with psychotic-like symptoms and did not moderate the expression of the schizotypy dimensions. The MSS-B has good psychometric properties, high concordance with the full-length MSS, and good construct validity. Thus, it appears to be a promising brief alternative to traditional schizotypy measures.Sickle cell disease (SCD) impacts liver and kidney function as well as skin integrity. These complications, as well as the hyperinflammatory state of SCD, could affect serum albumin. Serum albumin has key roles in antioxidant, anti-inflammatory and antithrombotic pathways and maintains vascular integrity. https://www.selleckchem.com/products/ins018-055-ism001-055.html In SCD, these pathways modulate disease severity and clinical outcomes. We used three independent SCD adult cohorts to assess clinical predictors of serum albumin as well its association with mortality. In 2553 SCD adult participants, the frequency of low ( less then 35 g/L) serum albumin was 5%. Older age and lower hemoglobin (P less then 0.001) were associated with lower serum albumin in all three cohorts. In age and hemoglobin adjusted analysis, higher liver enzymes (P less then 0.05) were associated with lower serum albumin. In two of the three cohorts, lower kidney function as measured by Glomerular Filtration Rate (P less then 0.001) was associated with lower serum albumin. Lower serum albumin predicted higher risk of tricuspid regurgitation velocity ≥ 2.5 m/s (OR = 1.1 per g/L, P ≤0.01). In all three cohorts, patients with low serum albumin had higher mortality (adjusted HR ≥2.9, P ≤0.003). This study confirms the role of serum albumin as a biomarker of disease severity and prognosis in patients with SCD. Albumin as a biomarker and possible mediator of SCD severity should be studied further.Kaposi's sarcoma (KS), caused by Kaposi's sarcoma-associated herpesvirus (KSHV), is a highly angioproliferative disseminated tumor of endothelial cells commonly found in AIDS patients. We have recently shown that KSHV-encoded viral interferon regulatory factor 1 (vIRF1) mediates KSHV-induced cell motility (PLoS Pathog. 2019 Jan 30;15(1)e1007578). However, the role of vIRF1 in KSHV-induced cellular transformation and angiogenesis remains unknown. Here, we show that vIRF1 promotes angiogenesis by upregulating sperm associated antigen 9 (SPAG9) using two in vivo angiogenesis models including the chick chorioallantoic membrane assay (CAM) and the matrigel plug angiogenesis assay in mice. Mechanistically, vIRF1 interacts with transcription factor Lef1 to promote SPAG9 transcription. vIRF1-induced SPAG9 promotes the interaction of mitogen-activated protein kinase kinase 4 (MKK4) with JNK1/2 to increase their phosphorylation, resulting in enhanced VEGFA expression, angiogenesis, cell proliferation and migration. Finally, genetic deletion of ORF-K9 from KSHV genome abolishes KSHV-induced cellular transformation and impairs angiogenesis. Our results reveal that vIRF1 transcriptionally activates SPAG9 expression to promote angiogenesis and tumorigenesis via activating JNK/VEGFA signaling. These novel findings define the mechanism of KSHV induction of the SPAG9/JNK/VEGFA pathway and establish the scientific basis for targeting this pathway for treating KSHV-associated cancers.The diamondback moth, Plutella xylostella, is a cosmopolitan pest and the first species to develop field resistance to toxins from the gram-positive bacterium Bacillus thuringiensis (Bt). Although previous work has suggested that mutations of ATP-binding cassette transporter subfamily C2 (ABCC2) or C3 (ABCC3) genes can confer Cry1Ac resistance, here we reveal that P. xylostella requires combined mutations in both PxABCC2 and PxABCC3 to achieve high-level Cry1Ac resistance, rather than simply a mutation of either gene. We identified natural mutations of PxABCC2 and PxABCC3 that concurrently occurred in a Cry1Ac-resistant strain (Cry1S1000) of P. xylostella, with a mutation (RA2) causing the mis-splicing of PxABCC2 and another mutation (RA3) leading to the premature termination of PxABCC3. Genetic linkage analysis showed that RA2 and RA3 were tightly linked to Cry1Ac resistance. Introgression of RA2 and RA3 enabled a susceptible strain (G88) of P. xylostella to obtain high resistance to Cry1Ac, confirming that these genes confer resistance. To further support the role of PxABCC2 and PxABCC3 in Cry1Ac resistance, frameshift mutations were introduced into PxABCC2 and PxABCC3 singly and in combination in the G88 strain with CRISPR/Cas9 mediated mutagenesis. Bioassays of CRISPR-based mutant strains, plus genetic complementation tests, demonstrated that the deletion of PxABCC2 or PxABCC3 alone provided 8,000-fold resistance to Cry1Ac, suggesting the redundant/complementary roles of PxABCC2 and PxABCC3. This work advances our understanding of Bt resistance in P. xylostella by demonstrating mutations within both PxABCC2 and PxABCC3 genes are required for high-level Cry1Ac resistance.
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