144 research outputs found

    Artificial Modulation of the Gating Behavior of a K+ Channel in a KvAP-DNA Chimera

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    We present experiments where the gating behavior of a voltage-gated ion channel is modulated by artificial ligand binding. We construct a channel-DNA chimera with the KvAP potassium channel reconstituted in an artificial membrane. The channel is functional and the single channel ion conductivity unperturbed by the presence of the DNA. However, the channel opening probability vs. bias voltage, i.e., the gating, can be shifted considerably by the electrostatic force between the charges on the DNA and the voltage sensing domain of the protein. Different hybridization states of the chimera DNA thus lead to different response curves of the channel

    BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis

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    BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells

    Optical Control of Metabotropic Glutamate Receptors

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    G-protein coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype-specificity, spatial precision, speed and reversibility. To address this, we developed an approach for opto-chemical engineering native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized “LimGluRs”. The light-agonized “LimGluR2”, on which we focused, is fast, bistable, and supports multiple rounds of on/off switching. Light gates two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. The light-antagonized “LimGluR2block” can be used to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalize the optical control to two additional family members: mGluR3 and 6. The system works in rodent brain slice and in zebrafish in vivo, where we find that mGluR2 modulates the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease

    Photochemical activation of TRPA1 channels in neurons and animals

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    Optogenetics is a powerful research tool because it enables high-resolution optical control of neuronal activity. However, current optogenetic approaches are limited to transgenic systems expressing microbial opsins and other exogenous photoreceptors. Here, we identify optovin, a small molecule that enables repeated photoactivation of motor behaviors in wild type animals. Surprisingly, optovin's behavioral effects are not visually mediated. Rather, photodetection is performed by sensory neurons expressing the cation channel TRPA1. TRPA1 is both necessary and sufficient for the optovin response. Optovin activates human TRPA1 via structure-dependent photochemical reactions with redox-sensitive cysteine residues. In animals with severed spinal cords, optovin treatment enables control of motor activity in the paralyzed extremities by localized illumination. These studies identify a light-based strategy for controlling endogenous TRPA1 receptors in vivo, with potential clinical and research applications in non-transgenic animals, including humans

    Student Opinion Surveys: What\u27s the Use?

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    PURPOSE: The utilization and reliability of Student Opinion Surveys have sparked debates within academia for decades, as tenure and promotion decisions for faculty are often informed by these evaluations. What motivates students to accurately reflect their opinion of a faculty member’s teaching ability? Are students aware of their role in these administrative decisions? Are there differences in expectations among students, faculty, and administration as to the use of these instruments? METHODS AND MATERIALS: The authors conducted a review of literature looking for the student’s perspective on these surveys and explored possible theories to address these research questions. ANALYSES: A qualitative grounded theory method was used to analyze more than 20 research studies pertaining to Student Opinion Surveys and major themes were identified. RESULTS: There is a communication gap between students, faculty, and administration as to the purpose of Student Opinion Surveys, a misunderstanding of what students are evaluating and why, and a mistrust of survey results and their consequences; yet, these surveys continue to be used for staffing decisions based on their results. Issues of survey fatigue, concerns about confidentiality, and student cultural norms are also identified. CONCLUSIONS: Communication from faculty and administration about the purpose of the surveys is essential to ensuring accuracy and dependability of the results, while recognition of the students’ perspective is needed to develop valid and reliable instruments. Creating a shared understanding regarding the importance of Student Opinion Surveys can assist in the development of effective surveys for assessing teaching ability and ensuring student learning

    Organizational boundary regulation through social media policies

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    Digital ubiquity and penetration across spatio-temporal boundaries have exacerbated the need for a clearer understanding of where the boundaries of personal, professional, and public communication begin and end. Indeed, boundary specifications have become an iconic problematic for organizational control and employee communication in the age of social media. In response, corporations increasingly issue policies that aim to regulate when, where, how, and what employees communicate in online environments. We argue that these policies are forms of organizational boundary regulation. Drawing on a content analysis of 112 social media policies from the world’s largest corporations, we examine the boundary logics articulated in these policies to delineate corporate spheres of influence. Next, we show how boundary logics relate to directives for employee speech, self-expression, and relational engagement. We discuss how the boundary logic framework contributes to our understanding of the expansion of corporate control across multiple life domains in the digital age
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