74 research outputs found
Gene expression profiling of DBA/2J mice cochleae treated with l-methionine and valproic acid
No full textAbstractDBA/2J mice, which have homozygous mutations in Cdh23 and Fscn2, are characterized by early onset hearing loss at as early as three-weeks of age (Noben-Trauth et al., 2003 [1]) and are an animal model for progressive hearing loss research. Recently, it has been reported that epigenetic regulatory pathways likely play an important role in hearing loss (Provenzano and Domann, 2007 [2]; Mutai et al., 2009 [3]; Waldhaus et al., 2012 [4]). We previously reported that DBA/2J mice injected subcutaneously with a combination of epigenetic modifying reagents, l-methionine (MET) as methyl donor and valproic acid (VPA) as a pan-histone deacetylases (Hdac) inhibitor, showed a significant attenuation of progressive hearing loss by measuring their auditory brainstem response (ABR) thresholds (Mutai et al., 2015 [5]). Here we present genome wide expression profiling of the DBA/2J mice cochleae, with and without treatment of MET and VPA, to identify the genes involved in the reduction of progressive hearing loss. The raw and normalized data were deposited in NCBI's Gene Expression Omnibus (GEO ID: GSE62173) for ease of reproducibility and reanalysis
Correction:An exploration of mortality risk factors in non-severe pneumonia in children using clinical data from Kenya. [BMC Med. 15, (2017) (201)] DOI: 10.1186/s12916-017-0963-9
No full textThe original article [1] contains an omission in the Acknowledgements sub-section of the Declarations. The authors would like to acknowledge the work of the following members of the Clinical Information Network Author Group: David Githanga, Fred Were, Philip Ayieko, Grace Irimu, Sam Akech, Samuel Ng'arng'ar, Barnabas Kigen, Rachel Inginia, Nick Aduro, Grace Ochieng, Beatrice Mutai, Francis Kanyingi, Lydia Thuranira, Sam Otido, Magdalene Kuria, Peris Njiiri, Kigondu Rutha, Charles Nzioki, Martin Chabi, Supa Tonje, Joan Ondere, Caren Emadau, Cecelia Mutiso, Loice Mutai, Christine Manyasi, David Kimutai, Celia Muturi, Agnes Mithamo, Anne Kamunya, Alice Kariuki, Grace Wachira, Melab Musabi, Sande Charo, Naomi Muinga, Mercy Chepkirui, Wycliffe Nyachiro, Boniface Makone, Thomas Julius, George Mbevi, Morris Ogero, Susan Gachau, and James Wafula.</p
TMC and EVER genes belong to a larger novel family, the TMC gene family encoding transmembrane proteins
No full textAbstract Background Mutations in the transmembrane cochlear expressed gene 1 (TMC1) cause deafness in human and mouse. Mutations in two homologous genes, EVER1 and EVER2 increase the susceptibility to infection with certain human papillomaviruses resulting in high risk of skin carcinoma. Here we report that TMC1, EVER1 and EVER2 (now TMC6 and TMC8) belong to a larger novel gene family, which is named TMC for trans membrane channel-like gene family. Results Using a combination of iterative database searches and reverse transcriptase-polymerase chain reaction (RT-PCR) experiments we assembled contigs for cDNA encoding human, murine, puffer fish, and invertebrate TMC proteins. TMC proteins of individual species can be grouped into three subfamilies A, B, and C. Vertebrates have eight TMC genes. The majority of murine TMC transcripts are expressed in most organs; some transcripts, however, in particular the three subfamily A members are rare and more restrictively expressed. Conclusion The eight vertebrate TMC genes are evolutionary conserved and encode proteins that form three subfamilies. Invertebrate TMC proteins can also be categorized into these three subfamilies. All TMC genes encode transmembrane proteins with intracellular amino- and carboxyl-termini and at least eight membrane-spanning domains. We speculate that the TMC proteins constitute a novel group of ion channels, transporters, or modifiers of such.</p
PREVALENCE AND RISK FACTORS OF NEONATAL JAUNDICE AMONG NEONATES 0-28 DAYS OLD, IN KIAMBU LEVEL 5 HOSPITALS, KIAMBU COUNTY, KENYA
No full textAbstract: Neonatal jaundice (NNJ) is the yellowish discoloration of the skin, mucous membrane, and sclera due excessive bilirubin deposition. Jaundice remains the leading cause of hospital readmission among the neonates in their first 2 weeks of life. Its mortality stands at 7% globally, despite various therapeutic and preventive measures put in place. The purpose of this study is to determine the prevalence and risk factors of neonatal jaundice in Kiambu county hospital. An analytical cross-sectional study design has been used in this study. Simple random sampling technique was used to obtain the study participants and 270 participants were recruited into the study. Data collected were analyzed using the Statistical Package for the Social sciences (SPSS) version 28 through descriptive and inferential statistical tests. Out of 270 neonates in this study, 43.33% representing 117 neonates were diagnosed with neonatal Jaundice. Neonatal factors including; birth weight p=0.015, gestational age p<0.001, difficulty in breastfeeding p=0.001, duration of sunlight exposure p<0.001, and neonatal sepsis<0.001 were statistically significant. Statistically significant maternal factors include; use of alcohol during pregnancy p=0.005, antenatal infections p=0.003, and mode of delivery p=0.026. The maternal knowledge of neonatal jaundice was assessed as being adequate for most of the caregivers of the neonates. In conclusion, the prevalence of neonatal Jaundice in Kiambu County hospital was relatively high at 43.33%. The associated risk factors include neonatal gestational age, neonatal sepsis, difficulty breastfeeding, duration of sunlight exposure, maternal antenatal infections, mode of delivery, and use of alcohol during pregnancy. Rigorous maternal education on prevention of neonatal jaundice is recommended during the antenatal, intrapartum and postnatal period. Further research on prevalence and risk factors associated with neonatal jaundice in other county referral hospitals in Kenya is recommended.
Keywords: Neonatal jaundice (NNJ), yellowish discoloration. sunlight exposure, maternal antenatal infections.
Title: PREVALENCE AND RISK FACTORS OF NEONATAL JAUNDICE AMONG NEONATES 0-28 DAYS OLD, IN KIAMBU LEVEL 5 HOSPITALS, KIAMBU COUNTY, KENYA
Author: Rodney Mutai, Mose Francis, Nathan Okworo, Eric Boaz Kipkorir, Gloria Towett
International Journal of Novel Research in Life Sciences
ISSN 2394-966X
Vol. 10, Issue 4, July 2023 - August 2023
Page No: 26-47
Novelty Journals
Website: www.noveltyjournals.com
Published Date: 16-August-2023
DOI: https://doi.org/10.5281/zenodo.8252362
Paper Download Link (Source)
https://www.noveltyjournals.com/upload/paper/PREVALENCE%20AND%20RISK%20FACTORS-16082023-5.pdfInternational Journal of Novel Research in Life Sciences, ISSN 2394-966X, Novelty Journals, Website: www.noveltyjournals.co
<it>In silico </it>modeling of the pore region of a KCNQ4 missense mutant from a patient with hearing loss
No full textAbstract Background Mutation of the voltage-gated potassium channel KCNQ4 causes DFNA2-type nonsyndromic autosomal dominant sensorineural hearing loss. KCNQ4 is expressed predominantly in the auditory sensory outer hair cells, which are critical for sound amplification. Results We sequenced KCNQ4 from Japanese patients with sensorineural hearing loss, and identified a novel missense mutation encoding a Tyr270His located at the N-terminus of the highly conserved pore helix sequence. As this patient was not accessible to us and information about them was limited, we used molecular modeling to investigate whether this novel mutation is hypothetically pathogenic. A careful examination of an in silico structural model of the KCNQ4 pore region revealed that the Tyr270His mutation caused an alteration in the electrostatic surface potential of the pore helix. Conclusion We propose two possible means by which the Tyr270His mutation causes hearing loss: a positively charged His270 side chain might enhance the helix dipole moment of the pore helix, thereby destabilizing the helix and/or the pore region, or it might disturb transport of K+ through the channel by electrostatic repulsion.</p
Solid-State Photoluminescence of Diphenylnaphthalenes Studied by Photophysical Measurements and Crystallographic Analysis
No full textThanks to recent developments in spectrophotometric instruments, the spectra, quantum yields (Φf), and lifetimes (τf) of photoluminescence from organic and inorganic compounds can be readily determined not only in solution but also in the solid state. It is known that naphthalene emits fluorescence in solution, but not in the solid state. In a previous paper, we reported that solid-state emission can be seen from biaryl compounds comprised of chromophores that show no emission in the solid state. In this work, we prepared diphenylnaphthalenes (DPNs), and the spectra and the Φf and τf values of fluorescence were determined in solution and the solid state, as well as the crystallographic features. The 2,6-Diphenylnphthalene (26DPN) showed solid-state emission in the wavelength region for longer than those in solution, while the emission spectra of the others in the solid state were similar to those in solution. The crystal structure of 26DPN belonged to a herringbone motif, whereas those of the others were column-stacked structures. Based on these spectroscopic and crystallographic facts, the relationship between the crystal motif and the emission features in the solid state is discussed
A Novel Animal Model of Hearing Loss Caused by Acute Endoplasmic Reticulum Stress in the Cochlea
No full textMany stimuli such as ischemia, hypoxia, heat shock, amino acid starvation, and gene mutation, exhibit a cellular response called endoplasmic reticulum (ER) stress. ER stress induces expression of a series of genes, leading to cell survival or apoptosis. Previously, we found that in an animal model of hearing loss caused by acute mitochondrial dysfunction, several ER stress markers including C/EBP homologous protein were induced in the cochlear lateral wall. To elucidate the mechanism of hearing loss caused by ER stress, we established a novel animal model of hearing loss by perilymphatic perfusion of tunicamycin, an ER stress activator that inhibits N-acetylglucosamine transferases. Subacute and progressive hearing loss was observed at all sound frequencies studied, and stimulation of ER stress marker genes was noted in the cochlea. The outer hair cells were the most sensitive to ER stress in the cochlea. Electron microscopic analysis demonstrated degeneration of the subcellular organelles of the inner hair cells and nerve endings of the spiral ganglion cells. This newly established animal model of hearing loss from ER stress will provide additional insight into the mechanism of sensorineural hearing loss. Keywords:: endoplasmic reticulum stress, tunicamycin, hearing loss, animal mode
Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.
No full textVarious factors that are important for proper hearing have been identified, including serum levels of zinc. Here we investigated whether epigenetic regulatory pathways, which can be modified by environmental factors, could modulate hearing. RT-PCR detected expression of genes encoding DNA methyltransferase and histone deacetylase (Hdac) in the postnatal as well as adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive hearing loss, were injected subcutaneously with one or a combination of the following reagents: L-methionine as a methyl donor, valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative factors involved in age-related hearing loss. The mice were treated from ages 4 to 12 weeks (N ≥ 5), and auditory brainstem response (ABR) thresholds were measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of L-methionine and valproic acid (M+V) significantly reduced the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents individually produced no such effect. Microarray analyses detected 299 gene probes that were significantly up- or down-regulated in the cochleae of mice treated with M+V compared with the control vehicle-treated mice. Quantitative RT-PCR confirmed significant up-regulation of a zinc importer gene, Zip4, in the cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and spiral ganglion. Finally, mice treated with the Zip4 inducer (-)-epigallocatechin-3-O-gallate showed a significant reduction in the increase of the ABR threshold at 32 kHz and up-regulation of Zip4 expression in the cochlea. This study suggests that epigenetic regulatory pathways can modify auditory function and that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian hearing
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