Objective: Training clinician-scientists is a primary objective of many academic neurology departments, as these individuals are uniquely positioned to perform insightful clinical or laboratory-based research informed both by clinical knowledge and their own experiences caring for patients. Despite its importance, training clinician-scientists has perhaps never been so challenging. The National Institute of Neurologic Disorders and Stroke (NINDS) R25 program was designed in an attempt to support these individuals, decrease the time needed to obtain National Institutes of Health K awards, and to help educate a cohort of trainees preparing for a career in academic neurology.
View Article and Find Full Text PDFWe at the National Institute of Neurological Disorders and Stroke routinely receive questions and statements from trainees and faculty that suggest widespread beliefs about the necessity of a National Institutes of Health K99/R00 award, other prior funding, and/or specific types of publications for obtaining one's first tenure-track position in neuroscience. To address these beliefs, we examined the funding and publication history of a cohort of investigators who began their first academic faculty position between 2009 and 2019, and we interviewed several senior academic leaders with extensive experience in hiring new faculty. Our data show that <11% of newly hired faculty had a K99/R00 award and that neither prior funding nor papers in prestigious journals were necessary to obtain a tenure-track faculty position.
View Article and Find Full Text PDFObjective: To increase the number of independent National Institutes of Health (NIH)-funded neurosurgeons and to enhance neurosurgery research, the National Institute of Neurological Disorders and Stroke (NINDS) developed two national comprehensive programs (R25 [established 2009] for residents/fellows and K12 [2013] for early-career neurosurgical faculty) in consultation with neurosurgical leaders and academic departments to support in-training and early-career neurosurgeons. The authors assessed the effectiveness of these NINDS-initiated programs to increase the number of independent NIH-funded neurosurgeon-scientists and grow NIH neurosurgery research funding.
Methods: NIH funding data for faculty and clinical department funding were derived from the NIH, academic departments, and Blue Ridge Institute of Medical Research databases from 2006 to 2019.
Biomedical research training has undergone considerable change over the past several years. At its core, the goal of graduate and postdoctoral training is to provide individuals with the skills and knowledge to become outstanding scientists and expand knowledge through the scientific method. Historically, graduate school training has focused on preparation for academic positions.
View Article and Find Full Text PDFCurrent magnitude in Kv2.1 potassium channels is modulated by external [K+]. In contrast to behavior expected from the change in electrochemical driving force, outward current through Kv2.
View Article and Find Full Text PDFPotassium channels are integral membrane proteins that selectively transport K+ across the cell membrane. They are present in all mammalian cells and have a wide variety of roles in both excitable and nonexcitable cells. The phenotypic diversity required to accomplish their various roles is created by differences in conductance, the timecourse and mechanisms of different gating events, and the interaction of channels with a variety of accessory proteins.
View Article and Find Full Text PDFThe location of the tetraethylammonium (TEA) binding site in the outer vestibule of K+ channels, and the mechanism by which external TEA slows C-type inactivation, have been considered well-understood. The prevailing model has been that TEA is coordinated by four amino acid side chains at the position equivalent to Shaker T449, and that TEA prevents a constriction that underlies inactivation via a foot-in-the-door mechanism at this same position. However, a growing body of evidence has suggested that this picture may not be entirely correct.
View Article and Find Full Text PDFWe previously demonstrated that the outer vestibule of activated Kv2.1 potassium channels can be in one of two conformations, and that K(+) occupancy of a specific selectivity filter site determines which conformation the outer vestibule is in. These different outer vestibule conformations result in different sensitivities to internal and external TEA, different inactivation rates, and different macroscopic conductances.
View Article and Find Full Text PDFBackground: Many molecular studies of ion channel function rely on the ability to obtain high quality voltage clamp recordings using the patch clamp technique. For a variety of channel types studied in mammalian cell heterologous expression systems, the lack of experimenter control over expression levels severely hinders the ability to obtain a high percentage of cells with an expression level suitable for high quality recordings. Moreover, it has been nearly impossible to obtain expression levels in mammalian cells well suited for single channel recordings.
View Article and Find Full Text PDFThe Kv2.1 potassium channel contains a lysine in the outer vestibule (position 356) that markedly reduces open channel sensitivity to changes in external [K(+)]. To investigate the mechanism underlying this effect, we examined the influence of this outer vestibule lysine on three measures of K(+) and Na(+) permeation.
View Article and Find Full Text PDFWe studied the mechanism by which external acidification from pH 7.3 to 6.8 reduced current magnitude in the Kv1.
View Article and Find Full Text PDFIn Kv2.1 potassium channels, changes in external [K+] modulate current magnitude as a result of a K+-dependent interconversion between two outer vestibule conformations. Previous evidence indicated that outer vestibule conformation (and thus current magnitude) is regulated by the occupancy of a selectivity filter binding site by K+.
View Article and Find Full Text PDF