The HCN domain is required for HCN channel cell-surface expression and couples voltage- and cAMP-dependent gating mechanisms

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are major regulators of synaptic plasticity, and rhythmic activity in the heart and brain. Opening of HCN channels requires membrane hyperpolarization and is further facilitated by intracellular cyclic nucleotides (cNMPs). In HCN channels, membrane hyperpolarization is sensed by the membrane-spanning voltage sensor domain (VSD) and the cNMP-dependent gating is mediated by the intracellular cyclic nucleotide-binding domain (CNBD) connected to the pore-forming S6 transmembrane segment via the C-linker. Previous functional analysis of HCN channels has suggested a direct or allosteric coupling between the voltage- and cNMP-dependent activation mechanisms. However, the specifics of this coupling remain unclear. The first cryo-EM structure of an HCN1 channel revealed that a novel structural element, dubbed the HCN domain (HCND), forms a direct structural link between the VSD and C-linker/CNBD. In this study, we investigated the functional significance of the HCND. Deletion of the HCND prevented surface expression of HCN2 channels. Based on the HCN1 structure analysis, we identified R237 and G239 residues on the S2 of the VSD that form direct interactions with I135 on the HCND. Disrupting these interactions abolished HCN2 currents. We also identified three residues on the C-linker/CNBD (E478, Q382 and H559) that form direct interactions with residues R154 and S158 on the HCND. Disrupting these interactions affected both voltage- and cAMP-dependent gating of HCN2 channels. These findings indicate that the HCND is necessary for the cell-surface expression of HCN channels, and provides a functional link between voltage- and cAMP-dependent mechanisms of HCN channel gating

A developmental approach to diversifying neuroscience through effective mentorship practices: perspectives on cross-identity mentorship and a critical call to action.

Many early-career neuroscientists with diverse identities may not have mentors who are more advanced in the neuroscience pipeline and have a congruent identity due to historic biases, laws, and policies impacting access to education. Cross-identity mentoring relationships pose challenges and power imbalances that impact the retention of diverse early career neuroscientists, but also hold the potential for a mutually enriching and collaborative relationship that fosters the mentee\u27s success. Additionally, the barriers faced by diverse mentees and their mentorship needs may evolve with career progression and require developmental considerations. This article provides perspectives on factors that impact cross-identity mentorship from individuals participating in Diversifying the Community of Neuroscience (CNS)-a longitudinal, National Institute of Neurological Disorders and Stroke (NINDS) R25 neuroscience mentorship program developed to increase diversity in the neurosciences. Participants in Diversifying CNS were comprised of 14 graduate students, postdoctoral fellows, and early career faculty who completed an online qualitative survey on cross-identity mentorship practices that impact their experience in neuroscience fields. Qualitative survey data were analyzed using inductive thematic analysis and resulted in four themes across career levels: (1) approach to mentorship and interpersonal dynamics, (2) allyship and management of power imbalance, (3) academic sponsorship, and (4) institutional barriers impacting navigation of academia. These themes, along with identified mentorship needs by developmental stage, provide insights mentors can use to better support the success of their mentees with diverse intersectional identities. As highlighted in our discussion, a mentor\u27s awareness of systemic barriers along with active allyship are foundational for their role

Zebrafish as a model organism for studying Alzheimer\u27s disease–focusing on the role of ADAM10a

Current models suggest that Alzheimer’s disease is caused by the self-aggregation of Aβ peptide fragments in the brain, resulting from the cleavage of Amyloid Precursor Protein (APP). In humans, α-secretase proteolytically cleaves APP precluding the formation of Aβ, thus inhibiting Alzheimer’s disease. Zebrafish was shown to posses a homolog to the human α-secretase, ADAM10a. This study shows that ADAM10a is crucial for embryogenesis. My results show that knocking down ADAM10a leads to mortality during gastrulation. In addition, ADAM10a knockdown leads to a decrease in the number and length of axons and dendrites, consistent with an increase in neuronal apoptosis. I propose zebrafish ADAM10a as a potential target to study the role of Aβ peptides in Alzheimer’s disease pathogenicity

The development of pedagogic professional abilities from the Marxist Philosophy in the initial formation of the Pedagogy-psychology career

The presentation has a purpose to base the development of pedagogical, investigative and communicative professional abilities in the career of Pedagogy-psychology, as well as the system of educational tasks from the Marxist Philosophy. The results of the diagnostic revealed cognitive inadequacies and lacks of development of professional abilities when not being integrated with the knowledge of the Marxist Philosophy, it determined an inadequate formative process in the professors in formation. It was used for it methods of investigation of theoretical level, empiric and statistical level that with the determination of dimensions and indicators facilitated the valuation of the system of applied educational tasks. The practical significance is contributed from the system of educational task and as a scientific novelty it is possible to structure this system with their respective didactic demands that allow the students to develop these abilities to apply in a creative way those philosophical contents

Autoestima como factor afectivo que interviene en el fenomeno de la velarizacion de la consonante velar sorda /t/ posicion final de palabra, al momento del discurso oral en estudiantes del idioma Ingles como lengua extranjera en el tercer nivel del curso del Instituto natural learning languages, c.a.

En el Instituto Natural Learning Languages, C.A., se observó que una gran parte de los estudiantes que se encuentran en el tercer nivel de dicho curso, tienden a presentar dificultades para producir ciertos sonidos del idioma inglés como /t/ en posición final, lo cual difícilmente ocurre en español. Esta situación se observa al momento del discurso oral (/light/ – /like/). Lo antes descrito podría significar un problema que obstaculizaría la comunicación. El objetivo de la presente investigación es Establecer la intervención del factor afectivo autoestima en el fenómeno de la velarización de consonantes oclusivas en posición final, específicamente de la consonante velar sorda /t/ en el discurso oral, en estudiantes del idioma inglés en el tercer nivel del curso del Instituto “Natural Learning Languages, C.A.”. El enfoque es cuantitativo y el tipo de investigación descriptivo. La Unidad social son 6 estudiantes escogidos de manera intencional. Las técnicas de recolección de datos utilizadas fueron observación escala de Rosenberg y pruebas de lectura

Análisis y diseño de un monopolo impreso para UWB

In the present paper describes a method to obtain a printed rectangular monopole antenna designed for Ultra Wide band that meets predetermined requirements from optimization.The obtained band width covers the frequency range defined by the Federal Communications Commission(FCC) for Ultra Wide band (3.1-10.6 GHz).To harness the band wid the xcellent reached,further shows ascaling procedurefor design in gother antenna with smaller lower frequency (847 MHz) that can be usedin numerous applications, such as mobile phones,GPS, Bluetooth, Wi-Fi and WiMax.With the implementation of this efficient design method, known as «Scale Method», is achieved by significant time savings in the necessary processdesign and simulation. We presenta comparisonbetween the results obtainedby simulating thescaleddesignandthe measurements obtained from the prototype built.En el presente trabajo se expone un método para obtener una antena tipo monopolo rectangular impreso diseñado para Ultra Wideband que cumple con los requerimientos preestablecidos luego de su optimización. El ancho de banda obtenido cubre el intervalo de frecuencias definido por la Comisión Federal de las Comunicaciones (FCC) para los sistemas Ultra Wideband (3.1-10.6 GHz). Se muestra además un procedimiento de escalamiento para aprovechar el excelente ancho de banda alcanzado, para diseñar otra antena con menor frecuencia inferior (847 MHz) que puede ser utilizada en numerosas aplicaciones, como por ejemplo la telefonía móvil, GPS, Bluetooth, Wi-Fi y WiMax. Con la aplicación de este método de diseño eficiente, conocido como «Método de Escala»,se logra un significativo ahorro de tiempo en el necesario proceso de diseño y simulación. Se presenta una comparación entre los resultados obtenidos mediante la simulación del diseño escalado y las mediciones obtenidas del prototipo construido

Identificación de las poblaciones de fitonematodos y nematodos de vida libre en el cultivo de plátano variedad Hartón enano (AAB), en el departamento de León, ciclo agrícola postrera 2012

Tesis (Ing. en Agroecología Tropical)-Universidad Nacional Autónoma de Nicaragua, LeónUNAN-Leó