Mechanisms for Temperature Modulation of Feeding in Goldfish and Implications on Seasonal Changes in Feeding Behavior and Food Intake

In fish models, seasonal change in feeding is under the influence of water temperature. However, the effects of temperature on appetite control can vary among fish species and the mechanisms involved have not been fully characterized. Using goldfish (Carassius auratus) as a model, seasonal changes in feeding behavior and food intake were examined in cyprinid species. In our study, foraging activity and food consumption in goldfish were found to be reduced with positive correlation to the gradual drop in water temperature occurring during the transition from summer (28.4 ± 2.2°C) to winter (15.1 ± 2.6°C). In goldfish with a 4-week acclimation at 28°C, their foraging activity and food consumption were notably higher than their counterparts with similar acclimation at 15°C. When compared to the group at 28°C during summer, the attenuation in feeding responses at 15°C during the winter also occurred with parallel rises of leptin I and II mRNA levels in the liver. Meanwhile, a drop in orexin mRNA along with concurrent elevations of CCK, MCH, POMC, CART, and leptin receptor (LepR) transcript expression could be noted in brain areas involved in feeding control. In short-term study, goldfish acclimated at 28°C were exposed to 15°C for 24 h and the treatment was effective in reducing foraging activity and food intake. The opposite was true in reciprocal experiment with a rise in water temperature to 28°C for goldfish acclimated at 15°C. In parallel time-course study with lowering of water temperature from 28 to 15°C, short-term exposure (6–12 h) of goldfish to 15°C could also increase leptin I and II mRNA levels in the liver. Similar to our seasonality study, transcript level of orexin was reduced along with up-regulation of CCK, MCH, POMC, CART, and LepR gene expression in different brain areas. Our results, as a whole, suggest that temperature-driven regulation of leptin output from the liver in conjunction with parallel modulations of orexigenic/anorexigenic signals and leptin responsiveness in the brain may contribute to the seasonal changes of feeding behavior and food intake observed in goldfish

Ocular myasthenia gravis saccades as a measure of extraocular muscle function

BACKGROUND: It is important to understand the pathophysiology of ocular myasthenia gravis (OMG) to improve treatment. AIM: To use modern video-oculography to characterise saccadic eye movements in patients with OMG, including anti-AChR, anti-MuSK, anti-LRP4, and seronegative OMG. METHODS: In total, 21 patients with OMG and five age-matched healthy control subjects underwent video-oculography. Participants performed a sequence of horizontal saccades (3 minutes each) at ±5°, ± 10°, and ±20°, followed by 3 minutes of saccades directed at randomly presented targets at ±5°, ± 10°, and ±15°. We recorded the direction, amplitude, duration, peak, and average velocity of each saccade for each task for each participant. RESULTS: Saccadic amplitude, duration, and average velocity were all lower in OMG patients than in control subjects (p < 0.021). Saccadic amplitude and velocity decreased over time, but this decrease was similar in OMG patients and control subjects. Fixation drift and ocular disparity tended to be greater in OMG patients than in control subjects. Saccadic intrusions occurred more frequently in OMG patients than in control subjects (p < 0.001). No significant effects of time or group by time on fixation drift or ocular disparity were found. DISCUSSION: Saccadic velocities in OMG patients differed from those in normal control subjects, which suggests that OMG affects fast-twitch fibres, although fast-twitch fibres were still able to generate “twitch” or “quiver” movements in the presence of even severe ophthalmoplegia. Slow-twitch muscle fibres involved in gaze holding were also affected, accounting for increased fixation drift following saccades. Our objective finding of increased fixation drift and a larger number of saccadic intrusions mirror our anecdotal experience of patients with OMG who report significant diplopia despite minimal ophthalmoplegia on examination. Such microsaccades may be a surrogate for compensation of a gaze-holding deficit in MG

Ethnic dissimilarity predicts belonging motive frustration and reduced organizational attachment

Some empirical studies show negative consequences of being demographically different from one’s group, but the underlying psychological mechanisms are not well understood. To address this gap, we investigated the role of the belonging and distinctiveness motives in individuals’ experiences of being ethnically dissimilar from their group. We propose that ethnic dissimilarity satisfies group members’ need for distinctiveness whereas it frustrates members’ need for belonging, and this frustration reduces their organizational attachment. An experimental study showed that ethnic dissimilarity led to heightened arousal of the belonging motive, indicating that this motive was frustrated. In a naturalistic study of real-life student groups, ethnic dissimilarity was associated with frustrated belonging, which in turn was associated with reduced organizational attachment. This paper contributes to the literature on demographic dissimilarity in groups by closely examining the effect of demographic dissimilarity on group members’ fundamental motives and reactions to group membership

Quantification of injury burden using multiple data sources: a longitudinal study

Quantification of injury burden is vital for injury prevention, as it provides a guide for setting policies and priorities. This study generated a set of Hong Kong specific disability weights (DWs) derived from patient experiences and hospital records. Patients were recruited from the Accident and Emergency Department (AED) of three major trauma centers in Hong Kong between September 2014 and December 2015 and subsequently interviewed with a focus on health-related quality of life at most three times over a 12-month period. These patient-reported data were then used for estimation of DWs. The burden of injury was determined using the mortality and inpatient data from 2001 to 2012 and then compared with those reported in the UK Burden of Injury (UKBOI) and global burden of diseases (GBD) studies. There were 22,856 mortality cases and 817,953 morbidity cases caused by injuries, in total contributing to 1,027,641 disability-adjusted life years (DALYs) in the 12-year study timeframe. Estimates for DALYs per 100,000 in Hong Kong amounted to 1192, compared with 2924 in UKBOI and 3459 in GBD. Our findings support the use of multiple data sources including patient-reported data and hospital records for estimation of injury burden

Measure Twice: Promise of Liquid Biopsy in Pediatric High-Grade Gliomas

Purpose To review and critique the current state of liquid biopsy in pHGG. Materials and Methods Published literature was reviewed for articles related to liquid biopsy in pediatric glioma and adult glioma with a focus on high-grade gliomas. Results This review discusses the current state of liquid biomarkers of pHGG and their potential applications for liquid biopsy development. Conclusions While nascent, the progress toward identifying circulating analytes of pHGG primes the field of neuro-oncoogy for liquid biopsy development

Inferring Loss-of-Heterozygosity from Unpaired Tumors Using High-Density Oligonucleotide SNP Arrays

Loss of heterozygosity (LOH) of chromosomal regions bearing tumor suppressors is a key event in the evolution of epithelial and mesenchymal tumors. Identification of these regions usually relies on genotyping tumor and counterpart normal DNA and noting regions where heterozygous alleles in the normal DNA become homozygous in the tumor. However, paired normal samples for tumors and cell lines are often not available. With the advent of oligonucleotide arrays that simultaneously assay thousands of single-nucleotide polymorphism (SNP) markers, genotyping can now be done at high enough resolution to allow identification of LOH events by the absence of heterozygous loci, without comparison to normal controls. Here we describe a hidden Markov model-based method to identify LOH from unpaired tumor samples, taking into account SNP intermarker distances, SNP-specific heterozygosity rates, and the haplotype structure of the human genome. When we applied the method to data genotyped on 100 K arrays, we correctly identified 99% of SNP markers as either retention or loss. We also correctly identified 81% of the regions of LOH, including 98% of regions greater than 3 megabases. By integrating copy number analysis into the method, we were able to distinguish LOH from allelic imbalance. Application of this method to data from a set of prostate samples without paired normals identified known regions of prevalent LOH. We have developed a method for analyzing high-density oligonucleotide SNP array data to accurately identify of regions of LOH and retention in tumors without the need for paired normal samples

BEAMing and Droplet Digital PCR Analysis of Mutant IDH1 mRNA in Glioma Patient Serum and Cerebrospinal Fluid Extracellular Vesicles

Development of biofluid-based molecular diagnostic tests for cancer is an important step towards tumor characterization and real-time monitoring in a minimally invasive fashion. Extracellular vesicles (EVs) are released from tumor cells into body fluids and can provide a powerful platform for tumor biomarkers because they carry tumor proteins and nucleic acids. Detecting rare point mutations in the background of wild-type sequences in biofluids such as blood and cerebrospinal fluid (CSF) remains a major challenge. Techniques such as BEAMing (beads, emulsion, amplification, magnetics) PCR and droplet digital PCR (ddPCR) are substantially more sensitive than many other assays for mutant sequence detection. Here, we describe a novel approach that combines biofluid EV RNA and BEAMing RT-PCR (EV-BEAMing), as well droplet digital PCR to interrogate mutations from glioma tumors. EVs from CSF of patients with glioma were shown to contain mutant IDH1 transcripts, and we were able to reliably detect and quantify mutant and wild-type IDH1 RNA transcripts in CSF of patients with gliomas. EV-BEAMing and EV-ddPCR represent a valuable new strategy for cancer diagnostics, which can be applied to a variety of biofluids and neoplasms

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P &lt; 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification