The development of cochlear implants for the treatment of patients with profound hearing loss has advanced considerably in the last few decades, particularly in the field of speech comprehension. However, attempts to provide not only sound decoding but also spatial hearing are limited by our understanding of circuit adaptations in the absence of auditory input. Here we investigate the lateral superior olive (LSO), a nucleus involved in interaural level difference (ILD) processing in the auditory brainstem using a mouse model of congenital deafness (the dn/dn mouse). An electrophysiological investigation of principal neurons of the LSO from the dn/dn mouse reveals a higher than normal proportion of single spiking (SS) neurons, and an increase in the hyperpolarisation-activated I(h) current. However, inhibitory glycinergic input to the LSO appears to develop normally both pre and postsynaptically in dn/dn mice despite the absence of auditory nerve activity. In combination with previous electrophysiological findings from the dn/dn mouse, we also compile a simple Hodgkin and Huxley circuit model in order to investigate possible computational deficits in ILD processing resulting from congenital hearing loss. We find that the predominance of SS neurons in the dn/dn LSO may compensate for upstream modifications and help to maintain a functioning ILD circuit in the dn/dn mouse. This could have clinical repercussions on the development of stimulation paradigms for spatial hearing with cochlear implants.
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http://dx.doi.org/10.1016/j.heares.2011.01.012 | DOI Listing |
Diabetol Metab Syndr
July 2024
Department of Nephrology, The Second Clinical Medical College), Zhujiang Hospital of Southern Medical University, No. 253, Middle Industrial Avenue, Haizhu District, Guangzhou, 510280, Guangdong Province, People's Republic of China.
Background: Diabetic nephropathy is a major secondary cause of end-stage renal disease. Apelin plays an important role in the development of DN. Understanding the exact mechanism of Apelin can help expand the means of treating DN.
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March 2024
Department of Internal Medicine and Geriatrics, University Medicine Greifswald, Germany (D.T., M.K., M.A., M.G.).
Background: Small arteries exhibit resting tone, a partially contracted state that maintains arterial blood pressure. In arterial smooth muscle cells, potassium channels control contraction and relaxation. Perivascular adipose tissue (PVAT) has been shown to exert anticontractile effects on the blood vessels.
View Article and Find Full Text PDFmedRxiv
January 2024
Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney,caused by variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative (DN) mode-of-action, wherein an increased level of AFF3 resulted in pathological effects.
Methods: Evolutionary constraints suggest that other mode-of-inheritance could be at play.
Sci Rep
January 2023
Department of Physiology, McGill University, 368 Bellini Life Sciences Complex, 3649 Promenade Sir William Osler, Montreal, QC, H3G 0B1, Canada.
Myb-like SWIRM and MPN domains 1 (MYSM1) is a chromatin binding protein with deubiquitinase (DUB) catalytic activity. Rare MYSM1 mutations in human patients result in an inherited bone marrow failure syndrome, highlighting the biomedical significance of MYSM1 in the hematopoietic system. We and others characterized Mysm1-knockout mice as a model of this disorder and established that MYSM1 regulates hematopoietic function and leukocyte development in such models through different mechanisms.
View Article and Find Full Text PDFBioengineered
January 2022
Department of Nephrology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, P.R China.
Mitochondrial injury-triggered podocyte apoptosis is a major risk factor for diabetic nephropathy (DN). However, the detailed relationship between mitochondrial homeostasis and podocyte apoptosis remains unclear. The present study aimed to explore the role and functional mechanism of germacrone in DN in type I diabetes (type I DN).
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