Clonal Neoantigen: Emerging "Mechanism-based" Biomarker of Immunotherapy Response.

Clonal mutations represent the initiating molecular defects related to cellular transition of a normal phenotype to a malignant phenotype. Molecular genomic assessment utilizing next generation and whole exome sequencing is now being increasingly applied to biomarker determination to refine the use of targeted immune therapies. Case examples followed by retrospective study assessment have convincingly demonstrated clonal neoantigens provide a relevant predictor of response to checkpoint inhibition.

Network based analysis identifies TP53m-BRCA1/2wt-homologous recombination proficient (HRP) population with enhanced susceptibility to Vigil immunotherapy.

Thus far immunotherapy has had limited impact on ovarian cancer. Vigil (a novel DNA-based multifunctional immune-therapeutic) has shown clinical benefit to prolong relapse-free survival (RFS) and overall survival (OS) in the BRCA wild type and HRP populations. We further analyzed molecular signals related to sensitivity of Vigil treatment.

RNA-seq analysis to identify novel roles of scleraxis during embryonic mouse heart valve remodeling.

Heart valve disease affects up to 30% of the population and has been shown to have origins during embryonic development. Valvulogenesis begins with formation of endocardial cushions in the atrioventricular canal and outflow tract regions. Subsequently, endocardial cushions remodel, elongate and progressively form mature valve structures composed of a highly organized connective tissue that provides the necessary biomechanical function throughout life.

Longitudinal transcriptomic dysregulation in the peripheral blood of transgenic Huntington's disease monkeys.

Background: Huntington's Disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the polyglutamine (polyQ) region of the Huntingtin (HTT) gene. The clinical features of HD are characterized by cognitive, psychological, and motor deficits. Molecular instability, a core component in neurological disease progression, can be comprehensively evaluated through longitudinal transcriptomic profiling.

MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function.

Schizophrenia is characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of 854 miRNAs in prefrontal cortical tissue from 100 control, schizophrenic, and bipolar subjects.

Myocardial alternative RNA splicing and gene expression profiling in early stage hypoplastic left heart syndrome.

Hypoplastic Left Heart Syndrome (HLHS) is a congenital defect characterized by underdevelopment of the left ventricle and pathological compensation of the right ventricle. If untreated, HLHS is invariably lethal due to the extensive increase in right ventricular workload and eventual failure. Despite the clinical significance, little is known about the molecular pathobiological state of HLHS.

Placental microRNA expression in pregnancies complicated by preeclampsia.

Objective: The role of posttranscription regulation in preeclampsia is largely unknown. We investigated preeclampsia-related placental microRNA (miRNA) expression using microarray and confirmatory quantitative real-time polymerase chain reaction experiments.

Study Design: Placental expressions of characterized and novel miRNAs (1295 probes) were measured in samples collected from 20 preeclampsia cases and 20 controls.

Striatal microRNA controls cocaine intake through CREB signalling.

Cocaine addiction is characterized by a gradual loss of control over drug use, but the molecular mechanisms regulating vulnerability to this process remain unclear. Here we report that microRNA-212 (miR-212) is upregulated in the dorsal striatum of rats with a history of extended access to cocaine. Striatal miR-212 decreases responsiveness to the motivational properties of cocaine by markedly amplifying the stimulatory effects of the drug on cAMP response element binding protein (CREB) signalling.

Matrix metalloproteinase 9 expression: new regulatory elements.

Retinal ganglion cells apoptosis is linked to matrix metalloproteinase 9 (MMP-9) controlled changes of extracellular matrix. Abnormal expression of MMP-9 is associated with glaucomatous alterations. Thus, the knowledge of MMP-9 regulation is important for the understanding the pathogenesis of glaucoma.

MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction.

N-methyl-D-aspartate (NMDA) glutamate receptors are regulators of fast neurotransmission and synaptic plasticity in the brain. Disruption of NMDA-mediated glutamate signaling has been linked to behavioral deficits displayed in psychiatric disorders such as schizophrenia. Recently, noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators of neuronal functions.

Wasp gene expression supports an evolutionary link between maternal behavior and eusociality.

The presence of workers that forgo reproduction and care for their siblings is a defining feature of eusociality and a major challenge for evolutionary theory. It has been proposed that worker behavior evolved from maternal care behavior. We explored this idea by studying gene expression in the primitively eusocial wasp Polistes metricus.

The occurrence and distribution of Salmonella enteritidis and other serovars on California egg laying premises: a comparison of two sampling methods and two culturing techniques.

Between the summer of 1998 and the winter of 2000, Salmonella analysis was performed on 2128 single and 532 pooled manure drag swabs obtained from 133 California commercial egg laying farms. The isolation of Salmonella from all rows and from all flocks using single or pooled swabs was 80% and 92%, respectively. Hence, there was no statistical difference between single vs.

Descriptive study of California egg layer premises and analysis of risk factors for Salmonella enterica serotype enteritidis as characterized by manure drag swabs.

This cross-sectional, double-blind study reports the prevalence of Salmonella enterica serotype enteritidis (SE) on California egg layer premises using single vs. pooled manure drag swabs and presents a description of egg production and management systems in the state and an initial analysis of risk factors for SE. The study included 91% of all known eligible egg premises in California, representing the majority of eggs produced in the state.