2,699 research outputs found
SK2 channels are required for function and long-term survival of efferent synapses on mammalian outer hair cells
Cochlear hair cells use SK2 currents to shape responses to cholinergic efferent feedback from the brain. Using SK2-/- mice, we demonstrate that, in addition to their previously defined role in modulating hair cell membrane potentials, SK2 channels are necessary for long-term survival of olivocochlear fibers and synapses. Loss of the SK2 gene also results in loss of electrically driven olivocochlear effects in vivo, and down regulation of ryanodine receptors involved in calcium-induced calcium release, the main inducer of nAChR evoked SK2 activity. Generation of double-null mice lacking both the α10 nAChR gene, loss of which results in hypertrophied olivocochlear terminals, and the SK2 gene, recapitulates the SK2-/- synaptic phenotype and gene expression, and also leads to down regulation of α9 nAChR gene expression. The data suggest a hierarchy of activity necessary to maintain early olivocochlear synapses at their targets, with SK2 serving an epistatic, upstream, role to the nAChRs.Fil: Murthy, Vidya. Tufts University; Estados UnidosFil: Maison, Stéphane F.. Massachusetts Eye and Ear Infirmary; Estados Unidos. Harvard Medical School; Estados UnidosFil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Tufts University; Estados UnidosFil: Haque, Nadeem. University of Notre Dame; Estados UnidosFil: Bond, Chris T.. Oregon Health Sciences University; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Adelman, John P.. Oregon Health Sciences University; Estados UnidosFil: Liberman, M. Charles. Massachusetts Eye and Ear Infirmary; Estados Unidos. Harvard Medical School; Estados UnidosFil: Vetter, Douglas E.. Tufts University; Estados Unido
The Influence of the Rashba spin orbit coupling on the two dimensional magnetoexcitons
Cataloged from PDF version of article.The influence of the Rashba spin-orbit coupling (RSOC) on the two-dimensional (2D) electrons and holes in a strong perpendicular magnetic field leads to different results for the Landau quantization in different spin projections. In the Landau gauge the unidimensional wave vector describing the free motion in one in-plane direction is the same for both spin projections, whereas the numbers of Landau quantization levels are different. For an electron in an s-type conduction band they differ by one, as was established earlier by Rashba (1960 Fiz. Tverd. Tela 2 1224), whereas for heavy holes in a p-type valence band influenced by the 2D symmetry of the layer they differ by three. The shifts and the rearrangements of the 2D hole Landau quantization levels on the energy scale are much larger in comparison with the case of conduction electron Landau levels. This is due to the strong influence of the magnetic field on the RSOC parameter. At sufficiently large values of this parameter the shifts and rearrangements are comparable with the hole cyclotron energy. There are two lowest spin-split Landau levels for electrons as well as four lowest ones for holes in the case of small RSOC parameters. They give rise to eight lowest energy bands of the 2D magnetoexcitons, as well as of the band-to-band quantum transitions. It is shown that three of them are dipole-active, three are quadrupole-active and two are forbidden. The optical orientation under the influence of circularly polarized light leads to optical alignment of the magnetoexcitons with different orbital momentum projections in the direction of the external magnetic field
Quantitative imaging of the Dorsal nuclear gradient reveals limitations to threshold-dependent patterning in Drosophila
The NF-κB-related transcription factor, Dorsal, forms a nuclear concentration gradient in the early Drosophila embryo, patterning the dorsal-ventral (DV) axis to specify mesoderm, neurogenic ectoderm, and dorsal ectoderm cell fates. The concentration of nuclear Dorsal is thought to determine these patterning events; however, the levels of nuclear Dorsal have not been quantified previously. Furthermore, existing models of Dorsal-dependent germ layer specification and patterning consider steady-state levels of Dorsal relative to target gene expression patterns, yet both Dorsal gradient formation and gene expression are dynamic. We devised a quantitative imaging method to measure the Dorsal nuclear gradient while simultaneously examining Dorsal target gene expression along the DV axis. Unlike observations from other insects such as Tribolium, we find the Dorsal gradient maintains a constant bell-shaped distribution during embryogenesis. We also find that some classical Dorsal target genes are located outside the region of graded Dorsal nuclear localization, raising the question of whether these genes are direct Dorsal targets. Additionally, we show that Dorsal levels change in time during embryogenesis such that a steady state is not reached. These results suggest that the multiple gene expression outputs observed along the DV axis do not simply reflect a steady-state Dorsal nuclear gradient. Instead, we propose that the Dorsal gradient supplies positional information throughout nuclear cycles 10-14, providing additional evidence for the idea that compensatory combinatorial interactions between Dorsal and other factors effect differential gene expression along the DV axis
Significant Cooperativity Between Ruthenium and Silicon in Catalytic Transformations of an Isocyanide
Elder Orphans Hiding in Plain Sight: A Growing Vulnerable Population
Adults are increasingly aging alone with multiple chronic diseases and are geographically distant from family or friends. It is challenging for clinicians to identify these individuals, often struggling with managing the growing difficulties and the complexities involved in delivering care to this population. Clinicians often may not recognize or know how to address the needs that these patients have in managing their own health. While many such patients function well at baseline, the slightest insult can initiate a cascade of avoidable negative events. We have resurrected the term elder orphan to describe individuals living alone with little to no support system. Using public data sets, including the US Census and University of Michigan’s Health and Retirement Study, we estimated the prevalence of adults 65 years and older to be around 22%. Thus, in this paper, we strive to describe and quantify this growing vulnerable population and offer practical approaches to identify and develop care plans that are consistent with each person’s goals of care. The complex medical and psychosocial issues for elder orphans significantly impact the individual person, communities, and health-care expenditures. We hope to encourage professionals across disciplines to work cooperatively to screen elders and implement policies to prevent elder orphans from hiding in plain sight
Olefin Hydroarylation Catalyzed by (Pyridyl-Indolate)Pt(II) Complexes: Catalytic Efficiencies and Mechanistic Aspects
A series of Pt(II) complexes of the type (N–N)PtPh(SR_2) (N–N = 2,2′-pyridyl-indolate) were prepared, and their performance as catalysts for the hydroarylation of olefins was assessed. Evidence that the catalysis is homogeneous and is Pt-mediated is provided by control experiments with added hindered base (2,6-di-tert-butyl-4-methylpyridine) and Hg(0). Two potential catalytic intermediates, (^tBuPyInd)PtPh(C_2H_4) and (^tBuPyInd)Pt(CH_2CH_2Ph)(C_2H_4), were synthesized, and their catalytic efficacy was explored. Additionally, decomposition and deactivation pathways, including styrene formation via β-hydride elimination and ligand reductive demetalation, were identified
Speech rhythm and language acquisition: an amplitude modulation phase hierarchy perspective.
Language lies at the heart of our experience as humans and disorders of language acquisition carry severe developmental costs. Rhythmic processing lies at the heart of language acquisition. Here, I review our understanding of the perceptual and neural mechanisms that support language acquisition, from a novel amplitude modulation perspective. Amplitude modulation patterns in infant- and child-directed speech support the perceptual experience of rhythm, and the brain encodes these rhythm patterns in part via neuroelectric oscillations. When brain rhythms align themselves with (entrain to) acoustic rhythms, speech intelligibility improves. Recent advances in the auditory neuroscience of speech processing enable studies of neuronal oscillatory entrainment in children and infants. The "amplitude modulation phase hierarchy" theoretical perspective on language acquisition is applicable across languages, and cross-language investigations adopting this novel perspective would be valuable for the field
Stress, alcohol and infection during early development: a brief review of common outcomes and mechanisms.
Although stress is an adaptive physiological response to deal with adverse conditions, its occurrence during the early stages of life, such as infancy or adolescence, can induce adaptations in multiple physiological systems, including the reproductive axis, the hypothalamic‐pituitary‐adrenal (HPA) axis, the limbic cortex and the immune system. These early changes have consequences in adult life, as seen in the physiological and behavioural responses to stress. This review highlights the impact of several stress challenges incurred at various stages of development (perinatal, juvenile, adolescent periods) and how the developmental timing of early‐life stress confers unique physiological adaptations that may persist across the lifespan. In doing so, we emphasise how intrinsic sex differences in the stress response might contribute to sex‐specific vulnerabilities, the molecular processes underlying stress in the adult, and potential therapeutic interventions to mitigate the effects of early stage stress, including the novel molecular mechanism of SUMOylation as a possible key target of HPA regulation during early‐life stress.Fil: Surkin, Pablo Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Breanhouse H. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Deak T. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Liberman AC. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Lasaga, Mercedes Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentin
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