Anthropogenic sound exposure-induced stress in captive dolphins and implications for cetacean health

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Yang, W.-C., Chen, C.-F., Chuah, Y.-C., Zhuang, C.-R., Chen, I.-H., Mooney, T. A., Stott, J., Blanchard, M., Jen, I.-F., & Chou, L.-S. Anthropogenic sound exposure-induced stress in captive dolphins and implications for cetacean health. Frontiers in Marine Science, 8,(2021): 606736, https://doi.org/10.3389/fmars.2021.606736.Many cetaceans are exposed to increasing pressure caused by anthropogenic activities in their marine environment. Anthropogenic sound has been recognized as a possible stressor for cetaceans that may have impacts on health. However, the relationship between stress, hormones, and cytokines secretion in cetaceans is complex and not fully understood. Moreover, the effects of stress are often inconsistent because the character, intensity, and duration of the stressors are variable. For a better understanding of how anthropogenic sounds affect the psychophysiology of cetaceans, the present study compared the changes of cortisol concentration and cytokine gene transcriptions in blood samples and behaviors of captive bottlenose dolphins (Tursiops truncatus) after sound exposures. The sound stimuli were 800 Hz pure-tone multiple impulsive sound for 30 min at three different sound levels (estimated mean received SPL: 0, 120, and 140 dB re 1 μPa) that likely cause no permanent and temporary hearing threshold shift in dolphins. Six cytokine genes (IL-2Rα, IL-4, IL-10, IL-12, TNF-α, and IFN-γ) were selected for analysis. Cortisol levels and IL-10 gene transcription increased and IFNγ/IL-10 ratio was lower after a 30-min high-level sound exposure, indicating the sound stimuli used in this study could be a stressor for cetaceans, although only minor behavior changes were observed. This study may shed light on the potential impact of pile driving-like sounds on the endocrine and immune systems in cetaceans and provide imperative information regarding sound exposure for free-ranging cetaceans.This work was supported by the Ministry of Science and Technology in Taiwan (MOST 108-2313-B-002-021 and MOST 109-2628-B-002-028)

Spinocerebellar ataxia type 8 larger triplet expansion alters histone modification and induces RNA foci

<p>Abstract</p> <p>Background</p> <p>Spinocerebellar ataxia type 8 (SCA8) involves the expression of an expanded CTG/CAG combined repeats (CR) from opposite strands producing CUG expansion transcripts (ataxin 8 opposite strand, ATXN8OS) and a polyglutamine expansion protein (ataxin 8, ATXN8). The pathogenesis of SCA8 is complex and the spectrum of clinical presentations is broad.</p> <p>Results</p> <p>Using stably induced cell models expressing 0, 23, 88 and 157 CR, we study the role of ATXN8OS transcripts in SCA8 pathogenesis. In the absence of doxycycline, the stable ATXN8OS CR cell lines exhibit low levels of ATXN8OS expression and a repeat length-related increase in staurosporine sensitivity and in the number of annexin positive cells. A repeat length-dependent repression of ATXN8OS expression was also notable. Addition of doxycycline leads to 25~50 times more ATXN8OS RNA expression with a repeat length-dependent increase in fold of ATXN8OS RNA induction. ChIP-PCR assay using anti-dimethyl-histone H3-K9 and anti-acetyl-histone H3-K14 antibodies revealed increased H3-K9 dimethylation and reduced H3-K14 acetylation around the ATXN8OS cDNA gene in 157 CR line. The repeat length-dependent increase in induction fold is probably due to the increased RNA stability as demonstrated by monitoring ATXN8OS RNA decay in cells treated with the transcriptional inhibitor, actinomycin D. In cells stably expressing ATXN8OS, RNA FISH experiments further revealed ribonuclear foci formation in cells carrying expanded 88 and 157 CR.</p> <p>Conclusion</p> <p>The present study demonstrates that the expanded CUG-repeat tracts are toxic to human cells and may affect ATXN8OS RNA expression and stability through epigenetic and post-transcriptional mechanisms.</p

Antinociceptive effects of morphine and naloxone in mu-opioid receptor knockout mice transfected with the MORS196A gene

<p>Abstract</p> <p>Background</p> <p>Opioid analgesics such as morphine and meperidine have been used to control moderate to severe pain for many years. However, these opioids have many side effects, including the development of tolerance and dependence after long-term use, which has limited their clinical use. We previously reported that mutations in the mu-opioid receptors (MOR) S196L and S196A rendered them responsive to the opioid antagonist naloxone without altering the agonist phenotype. In MORS196A knock-in mice, naloxone and naltrexone were antinociceptive but did not cause tolerance or physical dependence. In this study we delivery this mutated MOR gene into pain related pathway to confirm the possibility of <it>in vivo </it>transfecting MORS196A gene and using naloxone as a new analgesic agent.</p> <p>Methods</p> <p>The MOR-knockout (MOR-KO) mice were used to investigate whether morphine and naloxone could show antinociceptive effects when MORS196A gene was transfected into the spinal cords of MOR-KO mice. Double-stranded adeno-associated virus type 2 (dsAAV2) was used to deliver the MORS196A-enhanced green fluorescence protein (EGFP) gene by microinjected the virus into the spinal cord (S2/S3) dorsal horn region. Tail-flick test was used to measure the antinociceptive effect of drugs.</p> <p>Results</p> <p>Morphine (10 mg/kg, s.c.) and naloxone (10 mg/kg, s.c.) had no antinociceptive effects in MOR-KO mice before gene transfection. However, two or three weeks after the MOR-S196A gene had been injected locally into the spinal cord of MOR-KO mice, significant antinociceptive effects could be induced by naloxone or morphine. On the other hand, only morphine but not naloxone induced significant tolerance after sub-chronic treatment.</p> <p>Conclusion</p> <p>Transfecting the MORS196A gene into the spinal cord and systemically administering naloxone in MOR-KO mice activated the exogenously delivered mutant MOR and provided antinociceptive effect without causing tolerance. Since naloxone will not activate natural MOR in normal animals or humans, it is expected to produce fewer side effects and less tolerance and dependence than traditional opioid agonists do.</p

Excited-state optically detected magnetic resonance of spin defects in hexagonal boron nitride

Negatively charged boron vacancy (VB-) centers in hexagonal boron nitride (hBN) are promising spin defects in a van der Waals crystal. Understanding the spin properties of the excited state (ES) is critical for realizing dynamic nuclear polarization. Here, we report zero-field splitting in the ES of DES = 2160 MHz and an optically detected magnetic resonance (ODMR) contrast of 12% at cryogenic temperature. The ES has a g-factor similar to the ground state. The ES photodynamics is further elucidated by measuring the level anti-crossing of the VB- defects under varying external magnetic fields. In contrast to nitrogen vacancy (NV-) centers in diamond, the emission change caused by excited-state level anti-crossing (ESLAC) is more prominent at cryo-temperature than at room temperature. Our results provide important information for utilizing the spin defects of hBN in quantum technology

Pyk2 activates the NLRP3 inflammasome by directly phosphorylating ASC and contributes to inflammasome-dependent peritonitis

The inflammasome adaptor protein, ASC, contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, caspase-1. Here, we report that the cytosolic tyrosine kinases, FAK and Pyk2, are differentially involved in NLRP3 and AIM2 inflammasome activation. The inhibition of FAK and Pyk2 with RNA interference or chemical inhibitors dramatically abolished ASC oligomerization, caspase-1 activation, and IL-1β secretion in response to NLRP3 or AIM2 stimulation. Pyk2 is phosphorylated by the kinase Syk and relocalizes to the ASC specks upon NLRP3 inflammasome activation. Pyk2, but not FAK, could directly phosphorylate ASC at Tyr146, and only the phosphorylated ASC could participate in speck formation and trigger IL-1β secretion. Moreover, the clinical-trial-tested Pyk2/FAK dual inhibitor PF-562271 reduced monosodium urate-mediated peritonitis, a disease model used for studying the consequences of NLRP3 activation. Our results suggest that although Pyk2 and FAK are involved in inflammasome activation, only Pyk2 directly phosphorylates ASC and brings ASC into an oligomerization-competent state by allowing Tyr146 phosphorylation to participate ASC speck formation and subsequent NLRP3 inflammation

Methicillin-resistant Staphylococcus aureus in Taiwan

We found a virulent closely related clone (Panton-Valentine leukocidin–positive, SCCmec V:ST59) of methicillin-resistant Staphylococcus aureus in inpatients and outpatients in Taiwan. The isolates were found mostly in wounds but were also detected in blood, ear, respiratory, and other specimens; all were susceptible to ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole