PrEPárate: Evaluation of a Community-Driven PrEP Social Marketing Intervention Tailored to Latino/a/x Individuals.

Latino/a/x sexual minority men (SMM) and transgender women remain disproportionately impacted by HIV, with higher HIV incidence and lower uptake of pre-exposure prophylaxis (PrEP) than their non-Hispanic White peers. Disparities in PrEP uptake among Latino/a/x populations have been found to be due to structural, social, and personal barriers. Social marketing interventions have been shown to effectively address barriers and increase PrEP uptake in other populations, and thus offer potential as a tool to increase PrEP uptake for Latino/a/x populations.

Tcf-1 promotes genomic instability and T cell transformation in response to aberrant β-catenin activation.

Understanding the mechanisms promoting chromosomal translocations of the rearranging receptor loci in leukemia and lymphoma remains incomplete. Here we show that leukemias induced by aberrant activation of β-catenin in thymocytes, which bear recurrent translocations, depend on Tcf-1. The DNA double strand breaks (DSBs) in the site of the translocation are Rag-generated, whereas the DSBs are not.

Wnt-β-catenin activation epigenetically reprograms T cells in inflammatory bowel disease and dysplastic progression.

The diversity of regulatory T (T) cells in health and in disease remains unclear. Individuals with colorectal cancer harbor a subpopulation of RORγt T cells with elevated expression of β-catenin and pro-inflammatory properties. Here we show progressive expansion of RORγt T cells in individuals with inflammatory bowel disease during inflammation and early dysplasia.

TCF-1 and HEB cooperate to establish the epigenetic and transcription profiles of CD4CD8 thymocytes.

Thymocyte development requires a complex orchestration of multiple transcription factors. Ablating either TCF-1 or HEB in CD4CD8 thymocytes elicits similar developmental outcomes including increased proliferation, decreased survival, and fewer late Tcra rearrangements. Here, we provide a mechanistic explanation for these similarities by showing that TCF-1 and HEB share ~7,000 DNA-binding sites genome wide and promote chromatin accessibility.

Kinase-Dependent and -Independent Roles for PTK6 in Colon Cancer.

Unlabelled: Disruption of the gene encoding Protein Tyrosine Kinase 6 (Ptk6) delayed differentiation and increased growth in the mouse intestine. However, Ptk6-null mice were also resistant to azoxymethane-induced colon tumorigenesis. To further explore functions of PTK6 in colon cancer, expression of epithelial and mesenchymal markers, as well as proliferation, migration, and xenograft tumor growth, was examined in human colon tumor cell lines with knockdown or overexpression of PTK6.

Toward molecular genetic dissection of neural circuits for emotional and motivational behaviors.

How does the brain process the emotional meaning of sensory stimuli and in turn drive behavior?Studies in the mammalian systems have identified various brain regions and neurotransmitter systems that are critical for emotional and motivational behaviors and have implicated their involvement in neuropsychiatric disorders including anxiety, depression, schizophrenia, and addiction. Despite these significant advancements, the precise neural circuitry underlying emotional and motivational behaviors remains to be understood at molecular and cellular levels. In this review, we discuss how the vertebrate model organism zebrafish can help us gain insights into the underlying circuitry.

Conditioned place preference behavior in zebrafish.

This protocol describes conditioned place preference (CPP) in zebrafish following a single exposure to a substance. In the CPP paradigm, animals show a preference for an environment that has previously been associated with a substance (drug), thus indicating the positive-reinforcing qualities of that substance. The test tank consists of two visually distinct compartments separated by a central alley.

Identification of a brain center whose activity discriminates a choice behavior in zebrafish.

The ability to make choices and carry out appropriate actions is critical for individual survival and well-being. Choice behaviors, from hard-wired to experience-dependent, have been observed across the animal kingdom. Although differential engagement of sensory neuronal pathways is a known mechanism, neurobiological substrates in the brain that underlie choice making downstream of sensory perception are not well understood.

Differences of acute versus chronic ethanol exposure on anxiety-like behavioral responses in zebrafish.

Zebrafish, a vertebrate model organism amenable to high throughput screening, is an attractive system to model and study the mechanisms underlying human diseases. Alcoholism and alcoholic medical disorders are among the most debilitating diseases, yet the mechanisms by which ethanol inflicts the disease states are not well understood. In recent years zebrafish behavior assays have been used to study learning and memory, fear and anxiety, and social behavior.

Corticotropin-releasing factor critical for zebrafish camouflage behavior is regulated by light and sensitive to ethanol.

The zebrafish camouflage response is an innate "hard-wired" behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin-releasing factor (CRF) as a critical component of the camouflage response pathway.

Preference for ethanol in zebrafish following a single exposure.

Ethanol is one of the most widely abused drugs in the world. Its addictive property is believed to primarily stem from its ability to influence the brain reinforcement pathway evolved for mediating natural rewards. Although dopamine is a known component of the reinforcement pathway, clear molecular and cellular compositions of this pathway and its sensitivity to ethanol remain not well understood.

Use of zebrafish as a model to understand mechanisms of addiction and complex neurobehavioral phenotypes.

Despite massive research efforts the exact pathogenesis and pathophysiology of addiction and neuropsychiatric disorders such as anxiety, schizophrenia and autism remain largely unknown. Animal models can serve as tools to understand the etiology and pathogenesis of these disorders. In recent years researchers are turning to zebrafish as it allows easy access to all developmental stages and imaging of pathological processes as well as automated behavioral quantification coupled with large scale screening and mutagenesis strategies.

Ethanol-modulated camouflage response screen in zebrafish uncovers a novel role for cAMP and extracellular signal-regulated kinase signaling in behavioral sensitivity to ethanol.

Ethanol, a widely abused substance, elicits evolutionarily conserved behavioral responses in a concentration-dependent manner in vivo. The molecular mechanisms underlying such behavioral sensitivity to ethanol are poorly understood. While locomotor-based behavioral genetic screening is successful in identifying genes in invertebrate models, such complex behavior-based screening has proven difficult for recovering genes in vertebrates.

Correlates of response to Olanzapine in a North Indian Schizophrenia sample.

Olanzapine is widely used for the treatment of schizophrenia and is considered a first line medication in India. Along with other factors, the variation in response and side effects to this agent may be accounted for by genetic differences among patients. Olanzapine was administered for 6 weeks to Indian subjects with schizophrenia or schizoaffective disorder (DSM-IV, n=130), as part of an open label study.

Green tea catechins inhibit angiogenesis through suppression of STAT3 activation.

Previous studies indicate that green tea extract may inhibit breast cancer progression by blocking angiogenesis, although the molecular mechanisms are not well defined. We demonstrate that administration of Polyphenon E (Poly E), a standardized green tea extract, inhibited MDA-MB231 breast cancer and human dermal microvascular endothelial (HMVEC) cell migration and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9). In addition, Poly E inhibited VEGF-induced neovascularization in vivo.

Inhibition of mammary tumorigenesis in the C3(1)/SV40 mouse model by green tea.

Previous studies show inhibitory effects of green tea in chemically induced mammary tumors or human tumor explants, but not in spontaneous tumor models that are more representative of human breast cancer. The C3(1)/SV40 mouse model is particularly suited for breast cancer prevention studies because it produces spontaneous ductal adenocarcinomas and a predictable time course for mammary tumorigenesis through a multistage progression similar to that occurring in humans. We therefore used this model to test the chemoprotective effects of green tea.

Patterning the zebrafish diencephalon by the conserved zinc-finger protein Fezl.

The forebrain constitutes the most anterior part of the central nervous system, and is functionally crucial and structurally conserved in all vertebrates. It includes the dorsally positioned telencephalon and eyes, the ventrally positioned hypothalamus, and the more caudally located diencephalon [from rostral to caudal: the prethalamus, the zona limitans intrathalamica (ZLI), the thalamus and the pretectum]. Although antagonizing Wnt proteins are known to establish the identity of the telencephalon and eyes, it is unclear how various subdivisions are established within the diencephalon--a complex integration center and relay station of the vertebrate brain.

Cellular events preceding acetaminophen cataractogenesis studied by confocal fluorescence microscopy.

Acetaminophen (APAP) is biotransformed by hepatic cytochrome P450 (CYP) enzymes to the cataractogenic metabolite N-acetyl-p-benzoquinone imine (NAPQI). In the previous studies in which NAPQI was injected into the anterior chamber of mouse eye, we observed mitochondrial dysfunction and disturbances in Ca2+ homeostasis in the lens epithelium, and activation of the nonlysosomal neutral protease calpain. In this work we investigated whether intraperitoneal injection of APAP elicits similar cellular responses in the lens epithelium prior to the onset of lens opacity development.