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Unmanned aerial vehicles (UAVs) represent a novel and cost effective research tool to investigate cetacean behaviour, as conventional aircraft are expensive, limited in the altitude they can fly at and potentially disturb sensitive wildlife. In addition, the aerial observation from the UAVs allows assessment of cetacean behaviour from an advantageous perspective and can collect high spatial and temporal resolution data, providing the opportunity to gather accurate data about group size, age class and subsurface behaviour. However, concerns have been raised about the potential risks of disturbance to animals caused by the UAV's visual and acoustic stimuli. Boat-based surveys were conducted to assess the short-term behavioural responses of resting bottlenose dolphins (Tursiops truncatus) to a lightweight Vertical take-off and landing (VTOL) UAV flown at 10, 25, and 40 m altitude. Changes in group swim direction and frequencies of surface and aerial behavioural events were recorded from an anchored research vessel before (control) and during the aerial survey. The number of reorientation and tail slap events increased significantly between controls and flights when the UAV was flown at 10 m over the animals. In contrast, no significant differences were detected when the aircraft was flown at 25 and 40 m altitude. However, a precautionary approach is recommended for research applications requiring lower flight altitudes, with further research recommended to assess how different cetacean species and age class may respond to the UAV presence.
Ribosome-associated quality control (RQC) provides a rescue pathway for eukaryotic cells to process faulty proteins after translational stalling of cytoplasmic ribosomes1-6. After dissociation of ribosomes, the stalled tRNA-bound peptide remains associated with the 60S subunit and extended by Rqc2 by addition of C-terminal alanyl and threonyl residues (CAT tails)7-9, whereas Vms1 catalyses cleavage and release of the peptidyl-tRNA before or after addition of CAT tails10-12. In doing so, Vms1 counteracts CAT-tailing of nuclear-encoded mitochondrial proteins that otherwise drive aggregation and compromise mitochondrial and cellular homeostasis13. Here we present structural and functional insights into the interaction of Saccharomyces cerevisiae Vms1 with 60S subunits in pre- and post-peptidyl-tRNA cleavage states. Vms1 binds to 60S subunits with its Vms1-like release factor 1 (VLRF1), zinc finger and ankyrin domains. VLRF1 overlaps with the Rqc2 A-tRNA position and interacts with the ribosomal A-site, projecting its catalytic GSQ motif towards the CCA end of the tRNA, its Y285 residue dislodging the tRNA A73 for nucleolytic cleavage. Moreover, in the pre-state, we found the ABCF-type ATPase Arb1 in the ribosomal E-site, which stabilizes the delocalized A73 of the peptidyl-tRNA and stimulates Vms1-dependent tRNA cleavage. Our structural analysis provides mechanistic insights into the interplay of the RQC factors Vms1, Rqc2 and Arb1 and their role in the protection of mitochondria from the aggregation of toxic proteins.
Central visual field (CVF) loss has been linked to poorer vision-related quality of life in eyes with open-angle glaucoma (OAG) and can occur even in early-stage OAG eyes. The present study investigated whether the detection of choroidal microvasculature dropout (CMvD) during follow-up, which may be a sign of perfusion deficiency in the optic nerve head, is associated with rapid rate of CVF loss in early-stage OAG eyes. This study included 44 Korean OAG eyes with CMvD, identified by optical coherence tomography angiography, and 44 Korean OAG eyes without CMvD matched for age and severity of visual field loss at initial presentation. The rates of mean threshold changes in global and CVF were compared in eyes with and without CMvD using a linear mixed model. Clinical variables associated with rapid rate of CVF progression were also identified using a linear mixed model. The CVF progression rate was significantly higher in eyes with CMvD than in those without CMvD (-0.584 dB/year vs. -0.190 dB/year; P < 0.001) and detection of CMvD during follow-up was an independent predictor of rapid CVF progression rate. The presence of CMvD may aid in identification of high-risk patients who may show faster CVF progression and require more aggressive treatment.
Glucocorticoids (Gcs) are widely prescribed anti-inflammatory compounds, which act through the glucocorticoid receptor (GR). Using an unbiased proteomics screen in lung tissue, we identified the membrane protein caveolin -1 (Cav1) as a direct interaction partner of the GR. In Cav1 knockout mice GR transactivates anti-inflammatory genes, including Dusp1, more than in controls. We therefore determined the role of Cav1 in modulating Gc action in two models of pulmonary inflammation. We first tested innate responses in lung. Loss of Cav1 impaired the inflammatory response to nebulized LPS, increasing cytokine/chemokine secretion from lung, but impairing neutrophil infiltration. Despite these changes to the inflammatory response, there was no Cav1 effect on anti-inflammatory capacity of Gcs. We also tested GR/Cav1 crosstalk in a model of allergic airway inflammation. Cav1 had a very mild effect on the inflammatory response, but no effect on the Gc response - with comparable immune cell infiltrate (macrophage, eosinophils, neutrophils), pathological score and PAS positive cells observed between both genotypes. Pursuing the Th2 adaptive immune response further we demonstrate that Cav1 knockout mice retained their ability to expel the intestinal nematode parasite T.muris, which requires adaptive Th2 immune response for elimination. Therefore, Cav1 regulates innate immune responses in the lung, but does not have an effect on Th2-mediated adaptive immunity in lung or gut. Although we demonstrate that Cav1 regulates GR transactivation of anti-inflammatory genes, this does not translate to an effect on suppression of inflammation in vivo.
Growth retardation is an important side effect of glucocorticoid (GC)-based drugs, which are widely used in various preparations to treat many pediatric diseases. We investigated the therapeutic effect of exogenous CNP-53, a stable molecular form of intrinsic CNP, on a mouse model of GC-induced growth retardation. We found that CNP-53 successfully restored GC-induced growth retardation when both dexamethasone (DEX) and CNP-53 were injected from 4 to 8 weeks old. Notably, CNP-53 was not effective during the first week. From 4 to 5 weeks old, neither CNP-53 in advance of DEX, nor high-dose CNP-53 improved the effect of CNP. Conversely, when CNP-53 was started at 5 weeks old, final body length at 8 weeks old was comparable to that when CNP-53 was started at 4 weeks old. As for the mechanism of resistance to the CNP effect, DEX did not impair the production of cGMP induced by CNP. CNP reduced Erk phosphorylation even under treatment with DEX, while CNP did not changed that of p38 or GSK3β. Collectively, the effect of CNP-53 on GC-induced growth retardation is dependent on age in a mouse model, suggesting adequate and deliberate use of CNP would be effective for GC-induced growth retardation in clinical settings.
Within the Australian public hospital setting, no studies have previously reported total hospital utilisation and costs (pre/postoperatively) and costed patient-level pathways for primary bariatric surgery and surgical sequelae (including secondary surgery) informed by Australia's Independent Hospital Pricing Authority's activity-based funding (ABF) model.
Although five-alpha reductase inhibitor (5-ARI) is one of standard treatment for benign prostatic hyperplasia (BPH) or alopecia, potential complications after 5-ARI have been issues recently. This study aimed to investigate the risk of depression after taking 5-ARI and to quantify the risk using meta-analysis.
Compound heterozygotes occur when different variants at the same locus on both maternal and paternal chromosomes produce a recessive trait. Here we present the tool VarCount for the quantification of variants at the individual level. We used VarCount to characterize compound heterozygous coding variants in patients with epileptic encephalopathy and in the 1000 Genomes Project participants. The Epi4k data contains variants identified by whole exome sequencing in patients with either Lennox-Gastaut Syndrome (LGS) or infantile spasms (IS), as well as their parents. We queried the Epi4k dataset (264 trios) and the phased 1000 Genomes Project data (2504 participants) for recessive variants. To assess enrichment, transcript counts were compared between the Epi4k and 1000 Genomes Project participants using minor allele frequency (MAF) cutoffs of 0.5 and 1.0%, and including all ancestries or only probands of European ancestry. In the Epi4k participants, we found enrichment for rare, compound heterozygous variants in six genes, including three involved in neuronal growth and development - PRTG (p = 0.00086, 1% MAF, combined ancestries), TNC (p = 0.022, 1% MAF, combined ancestries) and MACF1 (p = 0.0245, 0.5% MAF, EU ancestry). Due to the total number of transcripts considered in these analyses, the enrichment detected was not significant after correction for multiple testing and higher powered or prospective studies are necessary to validate the candidacy of these genes. However, PRTG, TNC and MACF1 are potential novel recessive epilepsy genes and our results highlight that compound heterozygous variants should be considered in sporadic epilepsy.
Interleukin (IL)-4 and IL-10 activate plethora of immune cells and induce the humoral immune response. However, recombinant version of horse IL-4 and IL-10 has not been investigated to understand their immunomodulating activities. This study aimed to produce recombinant horse mature IL-4 and IL-10 in Escherichia coli. Immune-modulating activities of recombinant horse IL-4 and IL-10 were investigated in peripheral blood mononuclear cells (PBMCs).
Klebsiella pneumoniae is one of the respiratory disease agents in human and chicken. This bacterium is treated by antibiotic, but this treatment may trigger antibiotic resistance. Resistance gene in K. pneumoniae may be transferred to other bacteria. One of the known resistance genes is extended-spectrum β-lactamase (ESBL). This research aimed to study K. pneumoniae isolated from chicken farms in East Java, Indonesia, by observing the antibiotic resistance pattern and detect the presence of ESBL coding gene within the isolates.
Blood proteins in birds serve as an important indicator in the evaluation of health status and represent a basis in general biochemistry allowing the identification of metabolic alterations. The objective of this study was to evaluate the protein profile in broiler chickens extended by the concentrations of serum protein fractions at different periods of fattening.
Infectious laryngotracheitis (ILT) of chickens is a substantial issue to be studied in Iraq because this disease is one of the most highly contagious respiratory diseases in the world caused by a herpesvirus. However, in Iraq, the ILT virus (ILTV) infection and disease have yet not been confirmed in layers, so farm owners do not vaccinate these layers. The current study aimed to document the detection and characterization of ILTV in layer hens from Al-Diwaniyah city, for the first time in Iraq, using molecular techniques like polymerase chain reaction (PCR) and sequencing.
Objective: We present a novel method for screening eye bank donor corneas using high definition optical coherence tomography (HD-OCT). This technology allows for the quantification of endothelial/Descemet membrane (En/DM) complex thickness ex vivo. Design: Prospective interventional study. Participants: Fifty-two corneal grafts from 27 donors were included in this study. Twenty additional control eyes and 11 eyes with Fuchs' endothelial corneal dystrophy were also evaluated for comparison. Methods: A custom built, high speed HD-OCT device (Envisu R2210, Bioptigen, Buffalo Grove, IL, USA) was used to obtain images, and custom-made graph-based segmentation software was used to automatically deconstruct corneal images into micro-layers. HD-OCT imaging was used to scan through the sealed sterile case of donor corneas stored in McCarey-Kaufman medium to image their En/DM complex through the center of the cornea. Results: This technology allowed for quantification of En/DM complex thickness in all donor corneas through the sealed sterile container used to transport graft tissue. Mean En/DM complex thickness of donor corneas was 17±4 μm. The difference between donor cornea En/DM thickness and that of control subjects (16±2 μm) was not statistically significant (p=0.3), suggesting that the transport container and media do not affect measurements. There was a significant difference between En/DM thickness of Fuchs' endothelial corneal dystrophy eyes (25±5 μm) and both donor corneas (p<0.0001) and control subjects (p<0.0001). Conclusions: We have described a new technique to measure En/DM complex thickness in eye bank donor corneas stored in a sealed sterile case. This may represent a novel adjunctive approach to screen corneal grafts for early endothelial disease.
Background: Bupivacaine (Bup) is the most commonly used local anesthetic. However, Bup induces cytotoxicity, especially in older patients. Recent reports have indicated that andrographolide (Andro) exhibits protective effects on human neurons. Nevertheless, whether Andro can inhibit Bup-induced cytotoxicity remains unclear. As such, we investigated the effect of Andro on Bup-induced cytotoxicity of SH-SY5Y cells in the present study. Methods: Western blotting was used to examine expression of Bax, Bcl2, active caspase 3, p-Akt, and p-mTOR in SH-SY5Y cells. In addition, ELISA was used to detect levels of total glutathione and reactive oxygen species in cells. Results: We found that Andro attenuated Bup-induced cytotoxicity of SH-SY5Y cells. In addition, Andro inhibited Bup-induced apoptosis via downregulating the expression of Bax and active caspase 3 and upregulating the proteins Bcl2, p-Akt, and p-mTOR in SH-SY5Y cells. Moreover, Andro alleviated Bup-induced oxidative damage in SH-SY5Y cells via downregulating the level of reactive oxygen species and upregulating of the level of total glutathione. More significantly, inhibition of Akt abolished the protective effect of Andro in Bup-treated SH-SY5Y cells. Conclusion: Our findings indicated that Andro played a neuroprotective role via preserving Akt/mTOR activity and increasing antioxidative status in Bup-treated SH-SY5Y cells. Therefore, Andro may be a potential agent for the treatment of human cytotoxicity induced by Bup.
Background: When neonatal rats suffer hypoxic-ischemic brain injury (HIBI), autophagy is over-activated in the hippocampus, and inhibition of autophagy provides neuroprotection. The aim of this study was to investigate the possible roles of autophagy and Ezh2-regulated Pten/Akt/mTOR pathway in sevoflurane post-conditioning (SPC)-mediated neuroprotection against HIBI in neonatal rats. Methods: Seven-day-old Sprague-Dawley rats underwent left common artery ligation followed by 2 h hypoxia as described in the Rice-Vannucci model. The roles of autophagy and the Ezh2-regulated Pten/Akt/mTOR signaling pathway in the neuroprotection conferred by SPC were examined by left-side intracerebroventricular injection with the autophagy activator rapamycin and the Ezh2 inhibitor GSK126. Results: SPC was neuroprotective against HIBI through the inhibition of over-activated autophagy in the hippocampus as characterized by the rapamycin-induced reversal of neuronal density, neuronal morphology, cerebral morphology, and the expression of the autophagy markers, LC3B-II and Beclin1. SPC significantly increased the expression of Ezh2, H3K27me3, pAkt, and mTOR and decreased the expression of Pten induced by HI. The Ezh2 inhibitor, GSK126, significantly reversed the SPC-induced changes in expression of H3K27me3, Pten, pAkt, mTOR, LC3B-II, and Beclin1. Ezh2 inhibition also reversed SPC-mediated attenuation of neuronal loss and behavioral improvement in the Morris water maze. Conclusion: These results indicate that SPC inhibits excessive autophagy via the regulation of Pten/Akt/mTOR signaling by Ezh2 to confer neuroprotection against HIBI in neonatal rats.
Background: The factors influencing satisfaction of the patients with implant treatments are still unclear. This study aims to evaluate the patients' satisfaction and to identify influencing factors, which will improve the medical quality of oral implantology. Materials and methods: Patients who lost single teeth and received implant treatments were enrolled in Nanjing Stomatological Hospital between February 2016 and March 2018. A questionnaire survey was performed to assess patient satisfaction and data were collected at four time points. Information included gender, age, educational level, application of bone augmentation, type of prosthetic restoration, period of teeth loss, dentist qualification, and tooth position. Meanwhile, the satisfaction of the patients was evaluated by visual analog scale. Results: A total of 373 patients completed the questionnaires. The mean of overall satisfaction score was 69.05±7.10. Lower overall satisfaction score was found in patients who received bone augmentation (P<0.001) and those with a longer period of teeth loss (P<0.05). In the bone augmentation group, the elements of pain and complication were significantly associated with a decrease in the median satisfaction score (P<0.001), and a similar result was obtained form the duration of operative time and healing response (P<0.001). On the other hand, the satisfaction scores for elements including the duration of operative time and healing response (P<0.05), aesthetics and psychology (P<0.05), and chewing function (P<0.05) decreased with an extended period of teeth loss. Meanwhile, over half of respondents were more concerned about the survival time (40.70%) and success rate (20.49%) of implants. Conclusion: Bone augmentation and the period of teeth loss are negative factors affecting patient satisfaction, and the success rate and survival time of implants are considerable aspects for patients. It is essential to raise general awareness of oral hygiene and optimize the dental implant therapeutic process.
Maintaining or improving quality of life (QoL) is a key outcome of clinical interventions in older people. Fear of falling (FoF) is associated with activity restriction as well as with poorer physical and cognitive functions and may be an important contributor to a diminished QoL. The objectives of this systematic review were to determine i) the effect of FoF on QoL in older people, ii) whether the association between these two constructs depends on the use of specific conceptualizations and measurement instruments, and iii) the role of fall events as mediating factor in this relationship. Four electronic databases (PubMed, EMBASE, CINAHL, and Cochrane Library) were searched from their inceptions to February 2018. Thirty mostly cross-sectional studies in nearly 30.000 people (weighted mean age 75.6 years (SD =6.1); 73% women) were included. FoF was associated with QoL in most studies, and this association appeared to be independent of the conceptualization of FoF. Moreover, this relationship was independent of falls people experienced which seemed to have a lower impact. FoF should be considered not only as by-product of falls and targeted interventions in parts different from those to reduce falls are likely required. Studies are needed showing that reducing FoF will lead to increased QoL.
Objective: Ageing is one of the major risks for atherosclerosis. The age-related changes of interactions between plasma lipids, oxidative stress, antioxidant defense, and glycation processes are still not established while we age. Thus, the aim of the study was to analyze such relationships in individuals at risk for atherosclerosis due to their age. Methods: Elderly and middle-aged persons with no acute disease or severe chronic disorder were assessed. Fasting plasma lipids (total cholesterol (T-C), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol, and triacylglycerols), thiobarbituric acid reacting substances (TBARS), plasma total antioxidant status (TAS), and glucose and glycated proteins (fructosamine (FA) and glycated hemoglobin (HbA1c)) were determined. An oral glucose tolerance test allowed exclusion of persons with type 2 diabetes. Results: Lipid profiles were significantly profitable, increased HDL-C especially (p<0.0001), in the elderly versus middle-aged group. Decreased TBARS and TAS were found in the elderly versus middle-aged group (p=0.0001 and p=0.00002, respectively). Increased fructosamine was found in the elderly (255±30 μmol/L) versus middle-aged (236±33 μmol/L) group (p=0.006). Multiple regression analysis showed that in the middle-aged group TBARS correlated with T-C and HDL-C, and in the elderly group with HbA1c and FA independently of other factors. Conclusion: The factors which have an impact on oxidant-antioxidant status are crucial to understanding the pathomechanisms of senescence as well as the development of chronic diseases. Healthy aging may be maintained throughout proper lipid control. Moreover, data support the premise that the balance between lipid metabolism and oxidative stress may play a role in the initial phases of glycation plasma proteins particularly among elderly persons.
Purpose: This systematic review examines intervention studies using Tai Chi in the early stages of dementia to determine the effectiveness of Tai Chi for the short-term improvement of cognitive functions for elderly persons with the disease. Methods: A keyword search was done in PubMed/MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (EMBASE), and Cochrane Library databases using keywords such as Tai Chi, Dementia*, and cognition. A secondary search strategy consisting of a manual search in the reference lists of selected articles was also used. Results: A total of nine studies were reviewed including six randomized controlled trials, two non-randomized controlled trials, and one non-randomized prospective study. The studies suggest Tai Chi has impacts on global cognitive functions, visuospatial skills, semantic memory, verbal learning/memory, and self-perception of memory. The effects of Tai Chi on overall cognition for people with mild cognitive impairment are comparable to those in control groups which engaged in exercise. Conclusion: The studies reviewed affirm the potential of Tai Chi to improve short-term cognitive function in the elderly at the onset of dementia.
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