If we want to improve young voter engagement, there are lessons that can be learned from the US Presidential campaigns

The 2016 US Presidential election is in full-flow, with Hilary Clinton and Bernie Sanders fighting for the Democratic nomination, and Donald Trump still the frontrunner for the Republicans. Here, Josie Torrice looks at the lessons that can be learned from the campaign in terms of increasing the engagement of young voters, who are considerably less likely to vote than their older counterparts

Chemical-Scale Studies on the Role of a Conserved Aspartate in Preorganizing the Agonist Binding Site of the Nicotinic Acetylcholine Receptor

The nicotinic acetylcholine receptor and related Cys-loop receptors are ligand-gated ion channels that mediate fast synaptic transmission throughout the central and peripheral nervous system. A highly conserved aspartate residue (D89) that is near the agonist binding site but does not directly contact the ligand plays a critical part in receptor function. Here we probe the role of D89 using unnatural amino acid mutagenesis coupled with electrophysiology. Homology modeling implicates several hydrogen bonds involving D89. We find that no single hydrogen bond is essential to proper receptor function. Apparently, the side chain of D89 establishes a redundant network of hydrogen bonds; these bonds preorganize the agonist binding site by positioning a critical tryptophan residue that directly contacts the ligand. Earlier studies of the D89N mutant led to the proposal that a negative charge at this position is essential for receptor function. However, we find that receptors with neutral side chains at position 89 can function well, if the side chain is less perturbing than the amide of asparagine (nitro or keto groups allow function) or if a compensating backbone mutation is introduced to relieve unfavorable electrostatics

Fighting Human Trafficking and Exploitation through the power of local policy and programs: Analysis and Recommendations

While the United States has made great strides since 2000 to combat human trafficking federally, there is still much to be done. This capstone project provides a comprehensive understanding of key terms related to human trafficking. These terms are then used to provide context to the reality of the issue of human trafficking and exploitation in our world today, and specifically the United States. Although human trafficking legislation has made swift advances at the federal level since 2000 and states have followed suit in creating their own policies, local municipalities and communities have an immense amount of power in creating policy in which they can provide prevention, intervention and aftercare services to trafficked persons

Probing the role of the cation–π interaction in the binding sites of GPCRs using unnatural amino acids

We describe a general application of the nonsense suppression methodology for unnatural amino acid incorporation to probe drug–receptor interactions in functional G protein-coupled receptors (GPCRs), evaluating the binding sites of both the M2 muscarinic acetylcholine receptor and the D2 dopamine receptor. Receptors were expressed in Xenopus oocytes, and activation of a G protein-coupled, inward-rectifying K^+ channel (GIRK) provided, after optimization of conditions, a quantitative readout of receptor function. A number of aromatic amino acids thought to be near the agonist-binding site were evaluated. Incorporation of a series of fluorinated tryptophan derivatives at W6.48 of the D2 receptor establishes a cation–π interaction between the agonist dopamine and W6.48, suggesting a reorientation of W6.48 on agonist binding, consistent with proposed “rotamer switch” models. Interestingly, no comparable cation–π interaction was found at the aligning residue in the M2 receptor

¿Estamos todos de acuerdo con la Asignación Universal por Hijo? Entre el liberalismo y la recuperación del Estado

En el presente trabajo propongo exponer descriptivamente algunas herramientas conceptuales que nos posibiliten comprender el actual consenso de todo el espectro político entorno a una política social como la Asignación Universal por Hijo (AUH). Se buscará reconstruir los contextos y antecedentes de la AUH y las diversas justificaciones que se pueden encontrar en distintas tradiciones teórico-políticas. Desde distintos posicionamientos ideológicos se puede brindar un consentimiento a la AUH, así sea vista únicamente como una política de asistencia focalizada en los grupos más vulnerables para paliar la pobreza, como que se la valore como un piso de ingresos que apunta a garantizar un ingreso “universal” para la niñez. La propuesta es recuperar aportes de algunos clásicos del pensamiento político para matizar las diversas miradas que existen sobre la AUH

Two Neuronal Nicotinic Acetylcholine Receptors, α4β4 and α7, Show Differential Agonist Binding Modes

Nicotinic acetylcholine receptors (nAChRs) are pentameric, neurotransmitter-gated ion channels responsible for rapid excitatory neurotransmission in the central and peripheral nervous systems, resulting in skeletal muscle tone and various cognitive effects in the brain. These complex proteins are activated by the endogenous neurotransmitter ACh as well as by nicotine and structurally related agonists. Activation and modulation of nAChRs has been implicated in the pathology of multiple neurological disorders, and as such, these proteins are established therapeutic targets. Here we use unnatural amino acid mutagenesis to examine the ligand binding mechanisms of two homologous neuronal nAChRs: the α4β4 and α7 receptors. Despite sequence identity among the residues that form the core of the agonist-binding site, we find that the α4β4 and α7 nAChRs employ different agonist-receptor binding interactions in this region. The α4β4 receptor utilizes a strong cation-π interaction to a conserved tryptophan (TrpB) of the receptor for both ACh and nicotine, and nicotine participates in a strong hydrogen bond with a backbone carbonyl contributed by TrpB. Interestingly, we find that the α7 receptor also employs a cation-π interaction for ligand recognition, but the site has moved to a different aromatic amino acid of the agonist-binding site depending on the agonist. ACh participates in a cation-π interaction with TyrA, whereas epibatidine participates in a cation-π interaction with TyrC2

¿Estamos todos de acuerdo con la Asignación Universal por Hijo? Entre el liberalismo y la recuperación del Estado

En el presente trabajo propongo exponer descriptivamente algunas herramientas conceptuales que nos posibiliten comprender el actual consenso de todo el espectro político entorno a una política social como la Asignación Universal por Hijo (AUH). Se buscará reconstruir los contextos y antecedentes de la AUH y las diversas justificaciones que se pueden encontrar en distintas tradiciones teórico-políticas. Desde distintos posicionamientos ideológicos se puede brindar un consentimiento a la AUH, así sea vista únicamente como una política de asistencia focalizada en los grupos más vulnerables para paliar la pobreza, como que se la valore como un piso de ingresos que apunta a garantizar un ingreso “universal” para la niñez. La propuesta es recuperar aportes de algunos clásicos del pensamiento político para matizar las diversas miradas que existen sobre la AUH

Dis-putas : Discursos, normativas y resistencias. Experiencia en AMMAR Córdoba

Esta tesina intenta dar cuenta de reflexiones y aprendizajes de todo un año de trabajo de las estudiantes de practicas de intervención del 5 año de la carrera de Trabajo Social con AMMAR Córdoba. Desarrolla una aproximación teórica a los debates en torno a las sexualidades las discusiones en torno al género, el papel de los movimientos feministas en instalar la cuestión de las mujeres en el espacio público y las disputas en torno a su regulación del trabajo sexual. Describiendo, además, los actuales debates que atraviesan la realidad del trabajo sexual y las diferentes perspectivas en pugna. Se recupera la historia de organización y lucha del colectivo de mujeres trabajadoras sexuales nucleadas en AMMAR Córdoba, desde una mirada de la participación y empoderamiento ciudadano desarrollamos las particularidades de este colectivo y los desafíos a los que se enfrenta

cholangiocarcinomas new insights from the discovery of stem cell niches in peribiliary glands of the biliary tree

Peribiliary glands (PBGs) are located in the large intrahepatic and extrahepatic bile ducts. Although they were described many years ago, their functions have been elucidated only in the last couple of years when our group demonstrated that PBGs are niches of multipotent stem/progenitor cells of endodermal origin. These cells express genes of multipotency and can be rapidly differentiatedin vitrointo hepatocytes, cholangiocytes, and endocrine pancreatic cells. PBGs share common features, in terms of stem/progenitor cell niches, with pancreatic duct glands and colon crypts, glandular structures representing in the adult life the endodermal remnants of fetal life. PBG stem/progenitor cells participate in the renewal of surface biliary epithelium and are active players in chronic pathologies of the biliary tree as well as in cholangiocarcinomas (CCA). Specifically, a large amount of recent evidence indicates that the pure mucin-CCA originates from PBGs; this could explain the similarities with pancreatic ductal adenocarcinoma and colorectal cancer, which also originate from transformed gland cells. In this paper, we summarized our recent findings concerning structure and functions of PBGs with the implications for liver pathophysiology and, specifically, for cancers of the biliary tree

Reduced ratio of protective versus proinflammatory cytokine responses to commensal bacteria in HLA-B27 transgenic rats

Germ-free HLA-B27 transgenic (TG) rats do not develop colitis, but colonization with specific pathogen-free (SPF) bacteria induces colitis accompanied by immune activation. To study host-dependent immune responses to commensal caecal bacteria we investigated cytokine profiles in mesenteric lymph node (MLN) cells from HLA-B27 TG versus nontransgenic (non-TG) littermates after in vitro stimulation with caecal bacterial lysates (CBL). Supernatants from CBL-stimulated unseparated T- or B- cell-depleted MLN cells from HLA-B27 TG and non-TG littermates were analysed for IFN-γ, IL-12, TNF, IL-10 and TGF-β production. Our results show that unfractionated TG MLN cells stimulated with CBL produced more IFN-γ, IL-12 and TNF than did non-TG MLN cells. In contrast, CBL-stimulated non-TG MLN cells produced more IL-10 and TGF-β. T cell depletion abolished IFN-γ and decreased IL-12 production, but did not affect IL-10 and TGF-β production. Conversely, neither IL-10 nor TGF-β was produced in cultures of B cell-depleted MLN. In addition, CD4+ T cells enriched from MLN of HLA-B27 TG but not from non-TG rats produced IFN-γ when cocultured with CBL-pulsed antigen presenting cells from non-TG rats. Interestingly, IL-10 and TGF-β, but not IFN-γ, IL-12 and TNF were produced by MLN cells from germ-free TG rats. These results indicate that the colitis that develops in SPF HLA-B27 TG rats is accompanied by activation of IFN-γ-producing CD4+ T cells that respond to commensal bacteria. However, B cell cytokine production in response to components of commensal intestinal microorganisms occurs in the absence of intestinal inflammation