Zika Virus as an Emerging Neuropathogen: Mechanisms of Neurovirulence and Neuro-Immune Interactions.

Zika virus (ZIKV) is an emerging arbovirus of the genus Flaviviridae, which causes a febrile illness and has spread from across the Pacific to the Americas in a short timeframe. Convincing evidence has implicated the ZIKV to incident cases of neonatal microcephaly and a set of neurodevelopmental abnormalities referred to as the congenital Zika virus syndrome. In addition, emerging data points to an association with the ZIKV and the development of the so-called Guillain-Barre syndrome, an acute autoimmune polyneuropathy.

Temporal changes of oxidative stress markers in Escherichia coli K1-induced experimental meningitis in a neonatal rat model.

Despite advances in antimicrobial therapy and advanced critical care neonatal bacterial meningitis has a mortality rate of over 10% and induces neurological sequelae in 20-50% of cases. Escherichia coli K1 (E. coli K1) is the most common gram-negative organism causing neonatal meningitis and is the second most common cause behind group B streptococcus.

Neonatal Immune Challenge with Lipopolysaccharide Triggers Long-lasting Sex- and Age-related Behavioral and Immune/Neurotrophic Alterations in Mice: Relevance to Autism Spectrum Disorders.

Early-life challenges, particularly infections and stress, are related to neuropsychiatric disorders such as autism and schizophrenia. Here, we conducted a wide range of behavioral tests in periadolescent (postnatal day (PN) 35) and adult (PN70) Swiss mice neonatally challenged with LPS on PN5 and -7, to unveil behavioral alterations triggered by LPS exposure. Immune and neurotrophic (brain-derived neurotrophic factor-BDNF) alterations were determined in the prefrontal cortex (PFC), hippocampus (HC), and hypothalamus (HT).

RNF8 mediates histone H3 ubiquitylation and promotes glycolysis and tumorigenesis.

Disassembly of nucleosomes in which genomic DNA is packaged with histone regulates gene expression. However, the mechanisms underlying nucleosome disassembly for gene expression remain elusive. We show here that epidermal growth factor receptor activation results in the binding of the RNF8 forkhead-associated domain to pyruvate kinase M2-phosphorylated histone H3-T11, leading to K48-linked polyubiquitylation of histone H3 at K4 and subsequent proteasome-dependent protein degradation.

Validation of plastic scintillation detectors for applications in low-dose-rate brachytherapy.

Purpose: To develop a plastic scintillation detector (PSD) capable of accurately measuring dose around a low-dose-rate (LDR) iodine-125 (I) radioactive seed as a first step toward in vivo dosimetry for prostate LDR brachytherapy.

Methods: Using a GEANT4 based Monte Carlo code, photon energy distribution at any position around a realistic I source model was obtained. This energy distribution was convolved with the expected energy response from a plastic scintillator and dosimetry accuracy was evaluated.

Protein kinase activity of the glycolytic enzyme PGK1 regulates autophagy to promote tumorigenesis.

Macroautophagy/autophagy is a cellular defense response to stress conditions and is crucial for cell homeostasis maintenance. However, the precise mechanism underlying autophagy initiation, especially in response to glutamine deprivation and hypoxia, is yet to be explored. We recently discovered that PGK1 (phosphoglycerate kinase 1), a glycolytic enzyme, functions as a protein kinase, phosphorylating BECN1/Beclin 1 to initiate autophagy.

Perturbations in the apoptotic pathway and mitochondrial network dynamics in peripheral blood mononuclear cells from bipolar disorder patients.

Bipolar disorder (BD) is a severe psychiatric disorder characterized by phasic changes of mood and can be associated with progressive structural brain change and cognitive decline. The numbers and sizes of glia and neurons are reduced in several brain areas, suggesting the involvement of apoptosis in the pathophysiology of BD. Because the changes in mitochondrial dynamics are closely related with the early process of apoptosis and the specific processes of apoptosis and mitochondrial dynamics in BD have not been fully elucidated, we measured the apoptotic pathway and the expression of mitochondrial fission/fusion proteins from BD patients and healthy controls.

A systematic review of evidence for the role of inflammatory biomarkers in bipolar patients.

Bipolar disorder (BD) is a neuropsychiatric disorder that is characterized by a phasic course of affective episodes interspersed with a euthymic state. Epidemiological, clinical, genetic, post-mortem and preclinical studies have shown that inflammatory reactions and immune modulation play a pivotal role in the pathophysiology of BD. It is conceptualized that biomarkers of inflammation and immune responses should be employed to monitor the disease process in bipolar patients.

Ketamine potentiates oxidative stress and influences behavior and inflammation in response to lipolysaccharide (LPS) exposure in early life.

Immune activation (IA) during the early neonatal period is a risk factor for the development of schizophrenia. Lipopolysaccharide (LPS) injected in neonates lead to behavioral and brain changes that persist to adult life. We investigated oxidative stress, levels of cytokines, and the locomotor activity of IA in a schizophrenia animal model in which neonatal male Wistar rats were administered with an injection of LPS (50μg/kg) on postnatal day 3 and different doses of ketamine (5, 15 and 25mg/kg) for 7days during adulthood.

Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway.

PKCε, an oncogenic member of the PKC family, is aberrantly overexpressed in epithelial cancers. To date, little is known about functional interactions of PKCε with other genetic alterations, as well as the effectors contributing to its tumorigenic and metastatic phenotype. Here, we demonstrate that PKCε cooperates with the loss of the tumor suppressor Pten for the development of prostate cancer in a mouse model.

Antitumor agent 25-epi Ritterostatin GN1N induces endoplasmic reticulum stress and autophagy mediated cell death in melanoma cells.

Metastatic melanoma is the most aggressive of all skin cancers and is associated with poor prognosis owing to lack of effective treatments. 25-epi Ritterostatin GN1N is a novel antitumor agent with yet undefined mechanisms of action. We sought to delineate the antitumor mechanisms of 25-epi Ritterostatin GN1N in melanoma cells to determine the potential of this compound as a treatment for melanoma.

Delta-radiomics features for the prediction of patient outcomes in non-small cell lung cancer.

Radiomics is the use of quantitative imaging features extracted from medical images to characterize tumor pathology or heterogeneity. Features measured at pretreatment have successfully predicted patient outcomes in numerous cancer sites. This project was designed to determine whether radiomics features measured from non-small cell lung cancer (NSCLC) change during therapy and whether those features (delta-radiomics features) can improve prognostic models.

Referenceless magnetic resonance temperature imaging using Gaussian process modeling.

Purpose: During magnetic resonance (MR)-guided thermal therapies, water proton resonance frequency shift (PRFS)-based MR temperature imaging can quantitatively monitor tissue temperature changes. It is widely known that the PRFS technique is easily perturbed by tissue motion, tissue susceptibility changes, magnetic field drift, and modality-dependent applicator-induced artifacts. Here, a referenceless Gaussian process modeling (GPM)-based estimation of the PRFS is investigated as a methodology to mitigate unwanted background field changes.

Integrated transcriptome and methylome analysis in youth at high risk for bipolar disorder: a preliminary analysis.

First-degree relatives of patients with bipolar disorder (BD), particularly their offspring, have a higher risk of developing BD and other mental illnesses than the general population. However, the biological mechanisms underlying this increased risk are still unknown, particularly because most of the studies so far have been conducted in chronically ill adults and not in unaffected youth at high risk. In this preliminary study we analyzed genome-wide expression and methylation levels in peripheral blood mononuclear cells from children and adolescents from three matched groups: BD patients, unaffected offspring of bipolar parents (high risk) and controls (low risk).

Inhibition of indoleamine 2,3-dioxygenase 1/2 prevented cognitive impairment and energetic metabolism changes in the hippocampus of adult rats subjected to polymicrobial sepsis.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection that may affect the brain. We investigated the role of indoleamine 2,3-dioxygenase (IDO-1/2) inhibition on long-term memory and energetic metabolism after experimental sepsis by caecal ligation and perforation (CLP). Experimental sepsis increased the activity of complexes I, II-III and IV at 24h after CLP, and IDO-1/2 inhibition normalized the activity of these complexes in the hippocampus.

Regulation of PI3K signaling in T-cell acute lymphoblastic leukemia: a novel PTEN/Ikaros/miR-26b mechanism reveals a critical targetable role for PIK3CD.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, and T-ALL patients are prone to early disease relapse and suffer from poor outcomes. The PTEN, PI3K/AKT and Notch pathways are frequently altered in T-ALL. PTEN is a tumor suppressor that inactivates the PI3K pathway.

Attitudes Towards Prenatal Genetic Counseling, Prenatal Genetic Testing, and Termination of Pregnancy among Southeast and East Asian Women in the United States.

Recognizing the heterogeneity of the Asian population with regards to acculturation, education, health awareness, and cultural values is vital for tailoring culturally sensitive and appropriate care. Prior studies show that cultural values influence perceptions of genetics within Asian populations. The reputation of the family unit factors into decisions such as pregnancy termination and disclosure of family medical history, and the nondirective model of American genetic counseling may conflict with the historical Asian model of paternalistic health care.

Phosphoglycerate Kinase 1 Phosphorylates Beclin1 to Induce Autophagy.

Autophagy is crucial for maintaining cell homeostasis. However, the precise mechanism underlying autophagy initiation remains to be defined. Here, we demonstrate that glutamine deprivation and hypoxia result in inhibition of mTOR-mediated acetyl-transferase ARD1 S228 phosphorylation, leading to ARD1-dependent phosphoglycerate kinase 1 (PGK1) K388 acetylation and subsequent PGK1-mediated Beclin1 S30 phosphorylation.

Functional Diversity of Ciliary Proteins in Bone Development and Disease.

Purpose Of Review: The primary cilium is a non-motile microtubule-based organelle that senses a diverse range of extracellular signals. While recent studies highlight the importance of ciliary-dependent developmental signals, including Hedgehog, Wnt, and platelet-derived growth factor, it is not well understood whether and how bone morphogenetic protein (BMP) signaling, a key regulator of skeletogenesis, is involved in cilia-related bone developmental aspects and in the etiology of skeletal disorders.

Recent Findings: Increasing evidence suggests that osteoblast- or osteocyte-specific deletion of ciliary proteins leads to diverse skeletal malformations, reinforcing the idea that primary cilia are indispensable for regulating bone development and maintenance.

Increased risk of developing schizophrenia in animals exposed to cigarette smoke during the gestational period.

Cigarette smoking during the prenatal period has been investigated as a causative factor of obstetric abnormalities, which lead to cognitive and behavioural changes associated with schizophrenia. The aim of this study was to investigate behaviour and AChE activity in brain structures in adult rats exposed to cigarette smoke during the prenatal period. Pregnant rats were divided into non-PCSE (non-prenatal cigarette smoke exposure) and PCSE (prenatal cigarette smoke exposure) groups.

The Effects of Histone Deacetylase Inhibition on the Levels of Cerebral Cytokines in an Animal Model of Mania Induced by Dextroamphetamine.

Studies have suggested the involvement of inflammatory processes in the physiopathology of bipolar disorder. Preclinical evidences have shown that histone deacetylase inhibitors may act as mood-stabilizing agents and protect the brain in models of mania and depression. The aim of the present study was to evaluate the effects of sodium butyrate (SB) and valproate (VPA) on behavioral changes, histone deacetylase activity, and the levels of cytokines in an animal model of mania induced by dextroamphetamine (d-AMPH).

An exploratory study of the heterogeneity of the jealousy phenomenon and its associations with affective temperaments and psychopathological dimensions in a large Brazilian sample.

Background: Jealousy is a heterogenous emotion on a spectrum from normality to psychopathology. The relationship between different jealousy subtypes/dimensions and affective temperaments remain unknown. In addition, few large surveys have investigated the associations between jealousy subtypes and psychopathological dimensions.

Clinical Outcomes in Children and Adolescents With Bipolar Disorder and Substance Use Disorder Comorbidity.

Objective: To assess the global functioning and clinical outcomes of children and adolescents with bipolar disorder, children and adolescents with bipolar disorder and substance use disorder (SUD) comorbidity and healthy controls.

Methods: This study had a cross-sectional design. Participants were children and adolescents aged between 6 and 17 years, and data were collected between 2003 and 2015.

TRIM28 interacts with EZH2 and SWI/SNF to activate genes that promote mammosphere formation.

Histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2) is generally associated with H3K27 methylation and gene silencing, as a member of the polycomb repressor 2 (PRC2) complex. Immunoprecipitation and mass spectrometry of the EZH2-protein interactome in estrogen receptor positive, breast cancer-derived MCF7 cells revealed EZH2 interactions with subunits of chromatin remodeler SWI/SNF complex and TRIM28, which formed a complex with EZH2 distinct from PRC2. Unexpectedly, transcriptome profiling showed that EZH2 primarily activates, rather than represses, transcription in MCF7 cells and with TRIM28 co-regulates a set of genes associated with stem cell maintenance and poor survival of breast cancer patients.