Otoferlin Deficiency In Zebrafish Results In Defects In Balance And Hearing: Rescue Of The Balance And Hearing Phenotype With Full-length And Truncated Forms Of Mouse Otoferlin

Sensory hair cells convert mechanical motion into chemical signals. Otoferlin, a six-C2 domain transmembrane protein linked to deafness in humans, is hypothesized to play a role in exocytosis at hair cell ribbon synapses. To date however, otoferlin has been studied almost exclusively in mouse models, and no rescue experiments have been reported. Here we describe the phenotype associated with morpholino induced otoferlin knockdown in zebrafish, and report the results of rescue experiments conducted with full length and truncated forms of otoferlin. We find that expression of otoferlin occurs early in development, and is restricted to hair cells and the midbrain. Immunofluorescence microscopy reveals localization to both apical and basolateral regions of hair cells. Knockdown of otoferlin results in hearing and balance defects, as well as locomotion deficiencies. Further, otoferlin morphants had uninflated swim bladders. Rescue experiments conducted with mouse otoferlin restored hearing, balance and inflation of the swim bladder. Remarkably, truncated forms of otoferlin retaining the C-terminal C2F domain also rescued the otoferlin knockdown phenotype, while the individual N-terminal C2A domain did not. We conclude that otoferlin plays an evolutionarily conserved role in vertebrate hearing, and that truncated forms of otoferlin can rescue hearing and balance

Relationship Between Glycated Haemoglobin and Carotid Atherosclerotic Disease Among Patients with Acute Ischaemic Stroke

Objectives: This study aimed to determine the relationship between glycaemic control and carotid atherosclerotic disease among patients with acute ischaemic stroke (AIS). Methods: This retrospective cross-sectional study took place in the Neurology Department of King Fahad Hospital of University, Khobar, Saudi Arabia, from April to October 2017. Data were collected from the medical records of 244 patients with a diagnosis of AIS confirmed by computed tomography. Doppler ultrasounds of the carotid artery were performed to determine the presence of increased carotid intima media thickness (CIMT) and plaques. Results: Significantly higher mean glycated haemoglobin (HbA1c) levels were noted in cases with high CIMT values (P = 0.002), but not in cases with carotid plaques (P = 0.360). In addition, there was a significant association between diabetes mellitus (DM) and high CIMT (P = 0.045), but not with carotid plaques (P = 0.075). Finally, while dyslipidaemia and age were independently correlated with high CIMT values (P = 0.034 and 0.050 each). Conclusion: High HbA1c levels were associated with high CIMT values, but not with carotid plaques. Therefore, HbA1c levels may be useful as an indirect marker of the initial stages of carotid artery atherosclerosis. Keywords: Glycated Hemoglobin A1c; Diabetes Mellitus; Carotid Intima-Media Thickness; Atherosclerotic Plaque; Stroke

<em>Psuedomonas aeruginosa</em>-Associated Acute and Chronic Pulmonary Infections

Pseudomonas aeruginosa is highly successful in colonizing in all types of environments. P. aeruginosa colonizing in adverse environment due to the presence of its virulence factors include production of toxins, proteases hemolysins, and formation of biofilms. In man, the most common opportunist pathogen is P. aeruginosa. Metabolically P. aeruginosa is versatile. Most of the antibiotics targeted metabolically active cells and bacteria could contribute to decrease in biofilm susceptibility to the antimicrobial agents. Scientists suggested about Pseudomonas that it can be catabolized any hydrocarbon in specific time along with availability of oxygen and nitrite. If bacteria are not susceptible to one agent in three or more, it is called as multidrug-resistance strains. The antimicrobial treatments were not suitable when microorganism presented in vitro microorganism resistance to antimicrobials used for treatment of the patient which lack of treatment for 24 h after diagnosis of microbial infections. Bacteria have developed resistance against commonly used antibiotics. Treatment of Pseudomonas infections is coming harder day by day as its resistance against most of the antibiotics. Because of resistance of bacteria antibiotics, alternative methods are in consideration. These methods include use of lactic acid bacteria (LAB) and most recently nano-particles. That is why they are used as antibacterial agents

Performance Optimization of Holmium Doped Fiber Amplifiers for Optical Communication Applications in 2–2.15 μm Wavelength Range

In this paper, we address the performance optimization of Holmium doped fiber amplifier (HDFA) for optical communications in 2–2.15 μm wavelength range based on a single in-band forward pump source. The performance of the HDFA is analyzed with the help of theoretical simulations by considering an optimized length of Holmium doped fiber (HDF), doping concentration of Ho3+, and pump power. The impact of signal wavelength and power on gain, amplified spontaneous emission (ASE) noise, and noise figure (NF) of the amplifier is investigated. Furthermore, we investigate the variations in the gain of the amplifier, its output power, and NF by varying the power and wavelength of the pump source. After optimizing the parameters of the amplifier, the peak gain observed is around 56.5 dB, the 3 dB saturated output power obtained is 33.3 dBm, and the output power is 3 W at signal wavelength of 2.0321 μm for HDF having an optimized length of 12 m and pump power of 3.5 W. Minimum NF of around 8.2 dB is observed at 2.0321 μm for signal power of −5 dBm. The impact of ion-ion interaction on the performance of HDFA is also investigated. A reduction of 24.2 dB and 0.051 W is observed in peak gain and output power of HDFA, respectively by considering the ion-ion interaction

ChatterjeeParomaMolecularCellularBiologyOtoferlinDeficiencyZebrafish_FigureS1-S7.pdf

Sensory hair cells convert mechanical motion into chemical signals. Otoferlin, a six-C2 domain transmembrane protein linked to deafness in humans, is hypothesized to play a role in exocytosis at hair cell ribbon synapses. To date however, otoferlin has been studied almost exclusively in mouse models, and no rescue experiments have been reported. Here we describe the phenotype associated with morpholino induced otoferlin knockdown in zebrafish, and report the results of rescue experiments conducted with full length and truncated forms of otoferlin. We find that expression of otoferlin occurs early in development, and is restricted to hair cells and the midbrain. Immunofluorescence microscopy reveals localization to both apical and basolateral regions of hair cells. Knockdown of otoferlin results in hearing and balance defects, as well as locomotion deficiencies. Further, otoferlin morphants had uninflated swim bladders. Rescue experiments conducted with mouse otoferlin restored hearing, balance and inflation of the swim bladder. Remarkably, truncated forms of otoferlin retaining the C-terminal C2F domain also rescued the otoferlin knockdown phenotype, while the individual N-terminal C2A domain did not. We conclude that otoferlin plays an evolutionarily conserved role in vertebrate hearing, and that truncated forms of otoferlin can rescue hearing and balance

ChatterjeeParomaMolecularCellularBiologyOtoferlinDeficiencyZebrafish_TablesSA-SE.pdf

Sensory hair cells convert mechanical motion into chemical signals. Otoferlin, a six-C2 domain transmembrane protein linked to deafness in humans, is hypothesized to play a role in exocytosis at hair cell ribbon synapses. To date however, otoferlin has been studied almost exclusively in mouse models, and no rescue experiments have been reported. Here we describe the phenotype associated with morpholino induced otoferlin knockdown in zebrafish, and report the results of rescue experiments conducted with full length and truncated forms of otoferlin. We find that expression of otoferlin occurs early in development, and is restricted to hair cells and the midbrain. Immunofluorescence microscopy reveals localization to both apical and basolateral regions of hair cells. Knockdown of otoferlin results in hearing and balance defects, as well as locomotion deficiencies. Further, otoferlin morphants had uninflated swim bladders. Rescue experiments conducted with mouse otoferlin restored hearing, balance and inflation of the swim bladder. Remarkably, truncated forms of otoferlin retaining the C-terminal C2F domain also rescued the otoferlin knockdown phenotype, while the individual N-terminal C2A domain did not. We conclude that otoferlin plays an evolutionarily conserved role in vertebrate hearing, and that truncated forms of otoferlin can rescue hearing and balance

ChatterjeeParomaMolecularCellularBiologyOtoferlinDeficiencyZebrafish.pdf

Sensory hair cells convert mechanical motion into chemical signals. Otoferlin, a six-C2 domain transmembrane protein linked to deafness in humans, is hypothesized to play a role in exocytosis at hair cell ribbon synapses. To date however, otoferlin has been studied almost exclusively in mouse models, and no rescue experiments have been reported. Here we describe the phenotype associated with morpholino induced otoferlin knockdown in zebrafish, and report the results of rescue experiments conducted with full length and truncated forms of otoferlin. We find that expression of otoferlin occurs early in development, and is restricted to hair cells and the midbrain. Immunofluorescence microscopy reveals localization to both apical and basolateral regions of hair cells. Knockdown of otoferlin results in hearing and balance defects, as well as locomotion deficiencies. Further, otoferlin morphants had uninflated swim bladders. Rescue experiments conducted with mouse otoferlin restored hearing, balance and inflation of the swim bladder. Remarkably, truncated forms of otoferlin retaining the C-terminal C2F domain also rescued the otoferlin knockdown phenotype, while the individual N-terminal C2A domain did not. We conclude that otoferlin plays an evolutionarily conserved role in vertebrate hearing, and that truncated forms of otoferlin can rescue hearing and balance

Renewable biopolymer-derived carbon–nickel oxide nanocomposite as an emerging electrode material for energy storage applications

The high capacity electrode material design with rapid charging/discharging and long life capability has become a critical issue and main concern in recent years. Nickel oxide (NiO) has received much attention in the field of energy storage as a cathode electrode material owing to its layered structure with large spacing, crystal structure, and high specific surface area. In this study, the chitosan derived carbon–nickel oxide (CDC@NiO) nanocomposite was synthesized from a NiO nanoparticle precursor using a precipitation approach, and chitosan (a renewable biopolymer) was used as a carbon resource. The formation mechanism, structural behavior, and morphological properties were examined using various types of microscopic and spectroscopic characterization techniques. The design material was tested further as electrode material in an electrochemical half-cell and full cell symmetric assembly. In a three electrode system, the CDC@NiO nanocomposite exhibited satisfactory electrochemical performance with a high specific capacitance of around 1011.10 Fg−1 and better cyclic stability of 94.20% after 3000 cycles. In a two electrode symmetric supercapacitive system, the fabricated CDC@NiO delivered maximum Cs 88.30 Fg−1, stability with a higher power density of 7.84 Whkg−1 at an energy density of 133.05 Wkg−1. The fabricated CDC@NiO electrode material retains the cyclic stability of around 90% after 3500 consecutive charge/discharge cycles