Modelling, inference and big data in biophysics

Letter to the editorIn recognition of the increasing importance of big data in biophysics, a new session called 'Modelling, inference, big data' is incorporated into the IUPAB/EBSA Congress on 18 July 2017 at Edinburgh, UK

Hydrologic Response and Watershed Sensitivity to Climate Warming in California's Sierra Nevada

This study focuses on the differential hydrologic response of individual watersheds to climate warming within the Sierra Nevada mountain region of California. We describe climate warming models for 15 west-slope Sierra Nevada watersheds in California under unimpaired conditions using WEAP21, a weekly one-dimensional rainfall-runoff model. Incremental climate warming alternatives increase air temperature uniformly by 2°, 4°, and 6°C, but leave other climatic variables unchanged from observed values. Results are analyzed for changes in mean annual flow, peak runoff timing, and duration of low flow conditions to highlight which watersheds are most resilient to climate warming within a region, and how individual watersheds may be affected by changes to runoff quantity and timing. Results are compared with current water resources development and ecosystem services in each watershed to gain insight into how regional climate warming may affect water supply, hydropower generation, and montane ecosystems. Overall, watersheds in the northern Sierra Nevada are most vulnerable to decreased mean annual flow, southern-central watersheds are most susceptible to runoff timing changes, and the central portion of the range is most affected by longer periods with low flow conditions. Modeling results suggest the American and Mokelumne Rivers are most vulnerable to all three metrics, and the Kern River is the most resilient, in part from the high elevations of the watershed. Our research seeks to bridge information gaps between climate change modeling and regional management planning, helping to incorporate climate change into the development of regional adaptation strategies for Sierra Nevada watersheds

Short-term reliability of inflammatory mediators and response to exercise in the heat

Prospective application of serum cytokines, lipopolysaccharide, and heat shock proteins requires reliable measurement of these biomarkers that can signify exercise-induced heat stress in hot conditions. To accomplish this, both short-term (seven day) reliability (at rest, n=12) and the acute responsiveness of each biomarker to exercise in the heat (pre and post 60 min cycling, 34.5oC and 70% RH, n=20) were evaluated. Serum was analysed for the concentration of C-reactive protein (CRP), interleukin (IL-6), heat shock protein 72 (eHSP72), immunoglobulin M (IgM) and lipopolysaccharide (LPS). Test-retest reliability was determined as the coefficient of variation (CV). Biomarkers with the least short-term within-subject variation were IL-6 (19%, ± 20%; CV, ± 95% confidence limits) and LPS (23%, ± 13%). Greater variability was observed for IgM, eHSP72 and CRP (CV range 28-38%). IL-6 exhibited the largest increase in response to acute exercise (95%, ± 11%, p = <0.001) and although CRP had a modest CV (12%, ± 7%) it increased substantially post-exercise (p = 0.02, ES; 0.78). In contrast, eHSP72 and LPS exhibited trivial changes post-exercise. It appears variation of common inflammatory markers after exercise in the heat is not always discernible from short-term (weekly) variation

Modelling, inference and big data in biophysics

Letter to the editorIn recognition of the increasing importance of big data in biophysics, a new session called 'Modelling, inference, big data' is incorporated into the IUPAB/EBSA Congress on 18 July 2017 at Edinburgh, UK

Late Pleistocene vertebrate trace fossils in the Goukamma Nature Reserve, Cape South Coast, South Africa

More than 100 Late Pleistocene trace fossil sites have been identified in aeolianites along a 275 kilometer stretch of the Cape south coast. A zone of concentration of such sites exists within the Goukamma Nature Reserve, both along the coast and along the Goukamma River. These sites provide insight into the Pleistocene fauna along the Cape south coast. Features include lion trackways, multiple elephant tracksites, a long trackway most likely attributable to Long-horned Buffalo, medium-sized carnivore tracks, avian tracks, equid tracks attributable to the giant Cape horse, numerous artiodactyl tracks, and burrow traces. The ephemeral nature of the tracksites makes regular surveys of these areas desirable, along with site documentation and trackway replication and preservation initiatives. The protected status of the area offers opportunities for geoheritage appreciation.JN

Competing in hot conditions at the Tokyo Olympic Games : Preparation strategies used by Australian race walkers

Introduction: The Tokyo 2021 Olympic Games was anticipated to expose athletes to the most challenging climatic conditions experienced in the history of the modern Olympic Games. This study documents strategies executed by Australian endurance athletes during the team holding camp and Olympic Games experiences, including (1) baseline physiological data, training data, and heat acclimation/acclimatization practices; (2) pre- and in-race cooling and nutritional strategies, and (3) Olympic Games race performance data. Methods: Six athletes (three males, three females; age 24 ± 4 years; VO2max 63.2 ± 8.7 mL⋅kg–1⋅min–1; sum of 7 skinfolds 53.1 ± 23.4 mm) were observed prior to and during the team holding camp held in Cairns, QLD, Australia. Athletes completed 6–7 weeks of intermittent heat acclimation training, utilizing a combination of 2–4 passive and active acclimation sessions per week. Active acclimation was systematically increased via exposure time, exercise intensity, temperature, and humidity. In the team holding camp, athletes undertook a further 23 heat acclimatization training sessions over 18 days in a continuous fashion. Hyperhydration (using sodium and glycerol osmolytes), and internal and external pre-and in-race cooling methods were also utilized. A low energy availability intervention was implemented with two athletes, as a strategy to periodize ideal race body composition. Race performance data and environmental conditions from the 2021 Olympic Games were also documented. Results: The highest values for aerobic capacity were 63.6 mL⋅kg–1⋅min–1 for female race walkers and 73.7 mL⋅kg–1⋅min–1 for males. Training volume for the six athletes was the highest in the second week of the team holding camp, and training intensity was lowest in the first week of the team holding camp. Performance outcomes included 6th place in the women’s 20 km event (1:30:39), which was within 2% of her 20 km personal best time, and 8th place in the men’s 50 km event (3:52:01), which was a personal best performance time. Conclusion: Periodized training, heat acclimation/acclimatization, cooling and nutritional strategies study may have contributed to the race outcomes in Olympic Games held hot, humid conditions, for the race walkers within this observational study

Exploiting the UMLS Metathesaurus for extracting and categorizing concepts representing signs and symptoms to anatomically related organ systems

AbstractObjectiveTo develop a method to exploit the UMLS Metathesaurus for extracting and categorizing concepts found in clinical text representing signs and symptoms to anatomically related organ systems. The overarching goal is to classify patient reported symptoms to organ systems for population health and epidemiological analyses.Materials and methodsUsing the concepts’ semantic types and the inter-concept relationships as guidance, a selective portion of the concepts within the UMLS Metathesaurus was traversed starting from the concepts representing the highest level organ systems. The traversed concepts were chosen, filtered, and reviewed to obtain the concepts representing clinical signs and symptoms by blocking deviations, pruning superfluous concepts, and manual review. The mapping process was applied to signs and symptoms annotated in a corpus of 750 clinical notes.ResultsThe mapping process yielded a total of 91,000 UMLS concepts (with approximately 300,000 descriptions) possibly representing physical and mental signs and symptoms that were extracted and categorized to the anatomically related organ systems. Of 1864 distinct descriptions of signs and symptoms found in the 750 document corpus, 1635 of these (88%) were successfully mapped to the set of concepts extracted from the UMLS. Of 668 unique concepts mapped, 603 (90%) were correctly categorized to their organ systems.ConclusionWe present a process that facilitates mapping of signs and symptoms to their organ systems. By providing a smaller set of UMLS concepts to use for comparing and matching patient records, this method has the potential to increase efficiency of information extraction pipelines

Control of Ascorbate Synthesis by Respiration and Its Implications for Stress Responses

We show for the first time that respiration can control ascorbate (AA) synthesis in plants. Evidence for this control is provided by (a) the localization of L-galactono-1,4-lactone dehydrogenase (GalLDH), the terminal enzyme in AA biosynthesis, with mitochondrial complex I, and its regulation by electron transport through this complex, (b) the absolute requirement of the enzyme for oxidized cytochrome c (cyt c(ox)) as substrate, and (c) the coordinated response of respiration and AA synthesis to stress induced by hormone treatment.Instituto de Fisiología VegetalFacultad de Ciencias Agrarias y Forestale

Three Dimensional N=2 Supersymmetry on the Lattice

We show how 3-dimensional, N=2 supersymmetric theories, including super QCD with matter fields, can be put on the lattice with existing techniques, in a way which will recover supersymmetry in the small lattice spacing limit. Residual supersymmetry breaking effects are suppressed in the small lattice spacing limit by at least one power of the lattice spacing a.Comment: 21 pages, 2 figures, typo corrected, reference adde

Spatiotemporal regulation of ATP and Ca2+ dynamics in vertebrate rod and cone ribbon synapses

PurposeIn conventional neurons, Ca2+ enters presynaptic terminals during an action potential and its increased local concentration triggers transient exocytosis. In contrast, vertebrate photoreceptors are nonspiking neurons that maintain sustained depolarization and neurotransmitter release from ribbon synapses in darkness and produce light-dependent graded hyperpolarizing responses. Rods transmit single photon responses with high fidelity, whereas cones are less sensitive and exhibit faster response kinetics. These differences are likely due to variations in presynaptic Ca2+ dynamics. Metabolic coupling and cross-talk between mitochondria, endoplasmic reticulum (ER), plasma membrane Ca2+ ATPase (PMCA), and Na+-Ca2+ exchanger (NCX) coordinately control presynaptic ATP production and Ca2+ dynamics. The goal of our structural and functional studies was to determine the spatiotemporal regulation of ATP and Ca2+ dynamics in rod spherules and cone pedicles.MethodsCentral retina tissue from C57BL/6 mice was used. Laser scanning confocal microscopy (LSCM) experiments were conducted on fixed-frozen vertical sections. Primary antibodies were selected for their tissue/cellular specificity and ability to recognize single, multiple or all splice variants of selected isoforms. Electron microscopy (EM) and 3-D electron tomography (ET) studies used our standard procedures on thin- and thick-sectioned retinas, respectively. Calibrated fluo-3-Ca2+ imaging experiments of dark- and light-adapted rod and cone terminals in retinal slices were conducted.ResultsConfocal microscopy showed that mitochondria, ER, PMCA, and NCX1 exhibited distinct retinal lamination patterns and differential distribution in photoreceptor synapses. Antibodies for three distinct mitochondrial compartments differentially labeled retinal areas with high metabolic demand: rod and cone inner segments, previously undescribed cone juxtanuclear mitochondria and the two plexiform layers. Rod spherule membranes uniformly and intensely stained for PMCA, whereas the larger cone pedicles preferentially stained for NCX1 at their active zones and PMCA near their mitochondria. EM and ET revealed that mitochondria in rod spherules and cone pedicles differed markedly in their number, location, size, volume, and total cristae surface area, and cristae junction diameter. Rod spherules had one large ovoid mitochondrion located near its active zone, whereas cone pedicles averaged five medium-sized mitochondria clustered far from their active zones. Most spherules had one ribbon synapse, whereas pedicles contained numerous ribbon synapses. Fluo-3 imaging studies revealed that during darkness rod spherules maintained a lower [Ca2+] than cone pedicles, whereas during light adaptation pedicles rapidly lowered their [Ca2+] below that observed in spherules.ConclusionsThese findings indicate that ATP demand and mitochondrial ATP production are greater in cone pedicles than rod spherules. Rod spherules employ high affinity/low turnover PMCA and their mitochondrion to maintain a relatively low [Ca2+] in darkness, which increases their sensitivity and signal-to-noise ratio. In contrast, cone pedicles utilize low affinity/high turnover NCX to rapidly lower their high [Ca2+] during light adaptation, which increases their response kinetics. Spatiotemporal fluo-3-Ca2+ imaging results support our immunocytochemical results. The clustering of cone pedicle mitochondria likely provides increased protection from Ca2+ overload and permeability transition. In summary, these novel studies reveal that several integrated cellular and subcellular components interact to regulate ATP and Ca2+ dynamics in rod and cone synaptic terminals. These results should provide a greater understanding of in vivo photoreceptor synaptic terminal exocytosis/endocytosis, Ca2+ overload and therapies for retinal degenerations