The Open AUC Project

Progress in analytical ultracentrifugation (AUC) has been hindered by obstructions to hardware innovation and by software incompatibility. In this paper, we announce and outline the Open AUC Project. The goals of the Open AUC Project are to stimulate AUC innovation by improving instrumentation, detectors, acquisition and analysis software, and collaborative tools. These improvements are needed for the next generation of AUC-based research. The Open AUC Project combines on-going work from several different groups. A new base instrument is described, one that is designed from the ground up to be an analytical ultracentrifuge. This machine offers an open architecture, hardware standards, and application programming interfaces for detector developers. All software will use the GNU Public License to assure that intellectual property is available in open source format. The Open AUC strategy facilitates collaborations, encourages sharing, and eliminates the chronic impediments that have plagued AUC innovation for the last 20 years. This ultracentrifuge will be equipped with multiple and interchangeable optical tracks so that state-of-the-art electronics and improved detectors will be available for a variety of optical systems. The instrument will be complemented by a new rotor, enhanced data acquisition and analysis software, as well as collaboration software. Described here are the instrument, the modular software components, and a standardized database that will encourage and ease integration of data analysis and interpretation software

Identification of Networks of Co-Occurring, Tumor-Related DNA Copy Number Changes Using a Genome-Wide Scoring Approach

Tumorigenesis is a multi-step process in which normal cells transform into malignant tumors following the accumulation of genetic mutations that enable them to evade the growth control checkpoints that would normally suppress their growth or result in apoptosis. It is therefore important to identify those combinations of mutations that collaborate in cancer development and progression. DNA copy number alterations (CNAs) are one of the ways in which cancer genes are deregulated in tumor cells. We hypothesized that synergistic interactions between cancer genes might be identified by looking for regions of co-occurring gain and/or loss. To this end we developed a scoring framework to separate truly co-occurring aberrations from passenger mutations and dominant single signals present in the data. The resulting regions of high co-occurrence can be investigated for between-region functional interactions. Analysis of high-resolution DNA copy number data from a panel of 95 hematological tumor cell lines correctly identified co-occurring recombinations at the T-cell receptor and immunoglobulin loci in T- and B-cell malignancies, respectively, showing that we can recover truly co-occurring genomic alterations. In addition, our analysis revealed networks of co-occurring genomic losses and gains that are enriched for cancer genes. These networks are also highly enriched for functional relationships between genes. We further examine sub-networks of these networks, core networks, which contain many known cancer genes. The core network for co-occurring DNA losses we find seems to be independent of the canonical cancer genes within the network. Our findings suggest that large-scale, low-intensity copy number alterations may be an important feature of cancer development or maintenance by affecting gene dosage of a large interconnected network of functionally related genes

Trends in popularity of some morphological traits of purebred dogs in Australia.

Background The morphology of dogs can provide information about their predisposition to some disorders. For example, larger breeds are predisposed to hip dysplasia and many neoplastic diseases. Therefore, longitudinal trends in popularity of dog morphology can reveal potential disease pervasiveness in the future. There have been reports on the popularity of particular breeds and behavioural traits but trends in the morphological traits of preferred breeds have not been studied. Methods This study investigated trends in the height, dog size and head shape (cephalic index) of Australian purebred dogs. One hundred eighty-one breeds derived from Australian National Kennel Council (ANKC) registration statistics from 1986 to 2013 were analysed. Weighted regression analyses were conducted to examine trends in the traits by using them as outcome variables, with year as the explanatory variable and numbers of registered dogs as weights. Linear regression investigated dog height and cephalic index (skull width/skull length), and multinomial logistic regression studied dog size. Results The total number of ANKC registration had decreased gradually from 95,792 in 1986 to 66,902 in 2013. Both weighted minimal height (p = 0.014) and weighted maximal height (p < 0.001) decreased significantly over time, and the weighted cephalic index increased significantly (p < 0.001). The odds of registration of medium and small breeds increased by 5.3 % and 4.2 %, respectively, relative to large breeds (p < 0.001) and by 12.1 % and 11.0 %, respectively, relative to giant breeds (p < 0.001) for each 5-year block of time. Conclusions Compared to taller and larger breeds, shorter and smaller breeds have become relatively popular over time. Mean cephalic index has increased, which indicates that Australians have gradually favoured breeds with shorter and wider heads (brachycephalic). These significant trends indicate that the dog morphological traits reported here may potentially influence how people select companion dogs in Australia and provide valuable predictive information on the pervasiveness of diseases in dogs. Keywords: Purebred dogs, Dog popularity, Dog height, Dog size, Cephalic index, Brachycephalic Disease, predisposition, Australia. Plain English Summary Some diseases in dogs are related to certain physical characteristics. For example, larger breeds have a higher risk of getting hip dysplasia and certain neoplastic diseases while breeds with wider and shorter heads, such as Pug and French bulldog, are more likely to experience breathing problems and dystocia. Therefore, if we know the trends in popularity of dogs of a certain morphology, we may be able to predict disease pervasiveness. The study aimed to investigate the trends in the height, dog size and head shape of Australian purebred dogs. The numbers of dogs registered within the 181 breeds in Australian National Kennel Council (ANKC) every year from 1986 to 2013 were obtained and analysed. The total number of ANKC registration had decreased from 95,792 in 1986 to 66,902 in 2013. Compared to taller and larger breeds, shorter and smaller breeds have become relatively popular over time. Also, the data suggest that Australians increasingly favour dogs with shorter and wider heads for whose welfare veterinarians often express concern [1, 2]. The results indicate that dog height, dog size and dog head shape may potentially influence how people select companion dogs in Australia and provide valuable predictive information on trends in disease prevalence, enabling the veterinary profession and industry to prepare for potential future caseloads

EFFECTS OF QUENCHING THIRST VERSUS FULL FLUID REPLENISHMENT ON MOOD AND COGNITIVE CHANGES AFTER MILD HYPOHYDRATION

Brian Hack, Hyun Gyu Suh, Mindy Millard-Stafford, FACSM. Georgia Institute of Technology, Atlanta, GA. Dehydration impairs mood and sustained attention; however, evidence regarding the time course that rehydration reverses such effects is limited. Furthermore, whether assuaging thirst reverses cognitive deficits is unclear. Our purpose was to examine effects of partial rehydration (quenching thirst) compared to full rehydration (restoring fluid balance) on cognitive changes induced by exercise-induced dehydration. METHODS: Fifteen physically active men (age: 23.6±4.4 y; weight: 73.7±7.9 kg) participated in a dehydration-rehydration protocol. Mild-hypohydration [-1.7±0.3% change in body mass (%ΔBM)] was achieved via cycling in the heat (35°C; 40%RH) followed by 30 min rehydration (restoring \u3e100% BM). Flanker cognitive task and Brunel Mood scale were administered at baseline (BASE), dehydration (DEH), partial rehydration replacing 50% BM loss (PAR), and immediately following full fluid replacement (FULL0) through 180 min (FULL180). RESULTS: DEH increased (P\u3c0.05) thirst from BASE (4.6 ± 0.7 to 6.2 ± 0.6 cm) but PAR (3.5 ± 1.5 cm) attenuated thirst with no additional changes through FULL180 (3.5 ± 1.6 cm). Plasma osmolality decreased (P\u3c0.05) from DEH to FULL0 (296.5 ± 3.6 to 294.5 ± 2.8 mmol/kg) but continued lower by FULL60 (291.0 ± 3.0 mmol/kg). Copeptin also decreased (P\u3c0.05) from DEH to FULL0 (22.1 ± 9.1 to 14.5 ± 7.3 pmol/L) and continued lower by FULL60 (7.7 ± 3.5 pmol/L). Compared to DEH, FULL0 restored (P\u3c0.05) %ΔBM (0.1 ± 0.3%) similar to BASE. However, %ΔBM became lower (P\u3c0.05) than BASE by FULL60 (-0.5 ± 0.3%) through FULL180 (-1.0 ± 0.4%) although %ΔBM remained above DEH. Flanker incongruent reaction time decreased (P\u3c0.05) from BASE (0.46±0.02s) due to DEH (0.42 ± 0.02s) and persisted through FULL180 (0.42 ± 0.02s). Accuracy (%correct) decreased (P\u3c0.05) from BASE (93.7 ± 4.7%) to DEH (87.0 ± 6.7%) and remained lower through FULL180 (87.6 ± 4.0%). Fatigue ratings decreased (P\u3c.05) from DEH (6.9 ± 3.1) with PAR (4.7 ± 2.6) and remained lower through FULL180 (3.2 ± 3.5) similar to BASE (3.1 ± 1.7). CONCLUSION: Partial rehydration attenuated thirst and improved perceived fatigue but did not reverse cognitive changes. Fully restoring fluid balance after dehydration also did not reverse cognitive changes. Effects of fluid imbalance versus thirst on cognitive deficits remains unclear. Funded by a grant from The Coca-Cola Company, Atlanta, GA

ASSESSMENT OF EXERCISE-INDUCED DEHYDRATION AND REHYDRATION: EFFECTIVENESS OF USING PREDICTION EQUATIONS FOR PLASMA OSMOLALITY

Chiagoziem K. Ohamadike, Lia Teng, HyunGyu Suh, Mindy L. Millard-Stafford, FACSM. Georgia Institute of Technology, Atlanta, GA. ASSESSMENT OF EXERCISE-INDUCED DEHYDRATION AND REHYDRATION: EFFECTIVENESS OF USING PREDICTION EQUATIONS FOR PLASMA OSMOLALITY BACKGROUND: Plasma osmolality (POsm) is a gold standard for assessing hydration status; however, osmometers are primarily found in research labs and therefore POsm is not typically measured in clinical or athletic settings. PURPOSE: To compare the accuracy in assessment of dehydration versus rehydration states following the ingestion of oral rehydration solution (ORS) between published equations estimating POsm from Na+, K+, glucose, and blood urea nitrogen (BUN) versus direct measured POsm. METHODS: Seventeen healthy men cycled 90 min in the heat losing ~2.5% body mass and then ingested Pedialyte ORS ([Na+] = 42.6 mmol/L; [K+] = 30.9 mmol/L) replacing 100% of sweat loss over 30 min (~2 liters). Blood samples were collected at dehydration, then 30, 60, and 90 min post rehydration. POsm was directly measured with 50 µl samples (Micro Osmette osmometer, Precision System Inc). These values were compared to three highly cited equations estimating POsm (mmol/L): 1) 2 x (Na++ K+) + BUN+ Glucose (Gerich, Diabetes, 1971); 2) 1.86 x (Na+ + K+) + (1.15 x Glucose) + BUN + 14 (Hooper, British Medical Journal Open, 2015); and 3) 2 x Na+ + Glucose + BUN (Worthley, Anaesthesia and Intensive Care, 1987). RESULTS: All estimation equations were significantly correlated with measured POsm (p \u3c 0.0001, R2ranging from 0.64-0.72). At dehydration and 90 min post-rehydration, measured POsm was 294.6 ± 3.4 and 285.0 ± 3.1 mosmol/L, respectively. At dehydration, Worthley was lower (p \u3c 0.05) than the other equations and measured POsm (mean osmole gap = -3.4 mosmol/L). Conversely, at 90 min post rehydration, Gerich and Hooper equations were higher than Worthley and measured POsm (mean osmol gaps = -4.9 and -3.7 mosmol/L). CONCLUSION: Dehydration due to sweat losses in the heat results in underestimation of POsm when using equations excluding plasma K+ (e.g. Worthley). However, rehydration is not accurately assessed with equations including K+(e.g. Hooper and Gerich) when ORS is ingested to fully restore fluid balance. Therefore, selection of an appropriate published equation to estimate POsm depends on the nature of dehydration and/or fluid replenishment. Supported by a grant from Einsof Biohealth, Miami, FL