• The action of octopamine on muscles of Drosophila melanogaster larvae

      Ormerod, Kiel G; Hadden, Julia K; Lylah D, Deady; Joffre, Mercier; Jacob, Krans (2012-10)
      Octopamine (OA) and tyramine (TA) play important roles in homeostatic mechanisms, behavior, and modulation of neuromuscular junctions in arthropods. However, direct actions of these amines on muscle force production that are distinct from effects at the neuromuscular synapse have not been well studied. We utilize the technical benefits of the Drosophila larval preparation to distinguish the effects of OA and TA on the neuromuscular synapse from their effects on contractility of muscle cells. In contrast to the slight and often insignificant effects of TA, the action of OA was profound across all metrics assessed. We demonstrate that exogenous OA application decreases the input resistance of larval muscle fibers, increases the amplitude of excitatory junction potentials (EJPs), augments contraction force and duration, and at higher concentrations (10(-5) and 10(-4) M) affects muscle cells 12 and 13 more than muscle cells 6 and 7. Similarly, OA increases the force of synaptically driven contractions in a cell-specific manner. Moreover, such augmentation of contractile force persisted during direct muscle depolarization concurrent with synaptic block. OA elicited an even more profound effect on basal tonus. Application of 10(-5) M OA increased synaptically driven contractions by ≈ 1.1 mN but gave rise to a 28-mN increase in basal tonus in the absence of synaptic activation. Augmentation of basal tonus exceeded any physiological stimulation paradigm and can potentially be explained by changes in intramuscular protein mechanics. Thus we provide evidence for independent but complementary effects of OA on chemical synapses and muscle contractility.
    • Variability in the Insect and Plant Adhesins, Mad1 and Mad2, within the Fungal Genus Metarhizium Suggest Plant Adaptation as an Evolutionary Force

      Bidochka, Michael J. (PLOS ON, 2013-03)
      Several species of the insect pathogenic fungus Metarhizium are associated with certain plant types and genome analyses suggested a bifunctional lifestyle; as an insect pathogen and as a plant symbiont. Here we wanted to explore whether there was more variation in genes devoted to plant association (Mad2) or to insect association (Mad1) overall in the genus Metarhizium. Greater divergence within the genus Metarhizium in one of these genes may provide evidence for whether host insect or plant is a driving force in adaptation and evolution in the genus Metarhizium. We compared differences in variation in the insect adhesin gene, Mad1, which enables attachment to insect cuticle, and the plant adhesin gene, Mad2, which enables attachment to plants. Overall variation for the Mad1 promoter region (7.1%), Mad1 open reading frame (6.7%), and Mad2 open reading frame (7.4%) were similar, while it was higher in the Mad2 promoter region (9.9%). Analysis of the transcriptional elements within the Mad2 promoter region revealed variable STRE, PDS, degenerative TATA box, and TATA box-like regions, while this level of variation was not found for Mad1. Sequences were also phylogenetically compared to EF-1a, which is used for species identification, in 14 isolates representing 7 different species in the genus Metarhizium. Phylogenetic analysis demonstrated that the Mad2 phylogeny is more congruent with 59 EF-1a than Mad1. This would suggest that Mad2 has diverged among Metarhizium lineages, contributing to clade- and species-specific variation, while it appears that Mad1 has been largely conserved. While other abiotic and biotic factors cannot be excluded in contributing to divergence, these results suggest that plant relationships, rather than insect host, have been a major driving factor in the divergence of the genus Metarhizium.
    • Structure-function relationships of tachykinin peptides from octopus venoms

      Ruder, Tim; Ormerod, Kiel; Brust, Andreas; Abid Ali, Syed; Manchadi, Mary-Louise Roy; Ventura, Sabatino; Undheim, Eivind AB; Mercier, Joffre; King, Glenn F.; Alewood, Paul F.; et al. (Elsevier, 2013-04)
    • Post-hatch heat warms adult beaks: irreversible physiological plasticity in Japanese quail

      Tattersall, Glenn (Royal Society Publishing, 2013-08)
      Across taxa, the early rearing environment contributes to adult morphological and physiological variation. For example, in birds, environmental temperature plays a key role in shaping bill size and clinal trends across latitudinal/thermal gradients. Such patterns support the role of the bill as a thermal window and in thermal balance. It remains unknown whether bill size and thermal function are reversibly plastic. We raised Japanese quail in warm (308C) or cold (158C) environments and then at a common intermediate temperature. We predicted that birds raised in cold temperatures would develop smaller bills than warm-reared individuals, and that regulation of blood flow to the bill in response to changing temperatures would parallel the bill’s role in thermal balance. Cold-reared birds developed shorter bills, although bill size exhibited ‘catch-up’ growth once adults were placed at a common temperature. Despite having lived in a common thermal environment as adults, individuals that were initially reared in the warmth had higher bill surface temperatures than coldreared individuals, particularly under cold conditions. This suggests that blood vessel density and/or the control over blood flow in the bill retained a memory of early thermal ontogeny. We conclude that post-hatch temperature reversibly affects adult bill morphology but irreversibly influences the thermal physiological role of bills and may play an underappreciated role in avian energetics
    • Evaporative respiratory cooling augments pit organ thermal detection in rattlesnakes

      Tattersall, Glenn (Springer, 2013-12)
      Rattlesnakes use their facial pit organs to sense external thermal fluctuations. A temperature decrease in the heat-sensing membrane of the pit organ has the potential to enhance heat flux between their endothermic prey and the thermal sensors, affect the optimal functioning of thermal sensors in the pit membrane and reduce the formation of thermal ‘‘afterimages’’, improving thermal detection. We examined the potential for respiratory cooling to improve strike behaviour, capture, and consumption of endothermic prey in the South American rattlesnake, as behavioural indicators of thermal detection. Snakes with a higher degree of rostral cooling were more accurate during the strike, attacking warmer regions of their prey, and relocated and consumed their prey faster. These findings reveal that by cooling their pit organs, rattlesnakes increase their ability to detect endothermic prey; disabling the pit organs caused these differences to disappear. Rattlesnakes also modify the degree of rostral cooling by altering their breathing pattern in response to biologically relevant stimuli, such as a mouse odour. Our findings reveal that low humidity increases their ability to detect endothermic prey, suggesting that habitat and ambush sites election in the wild may be influenced by external humidity levels as well as temperature.
    • Group-invariant solutions of semilinear Schrodinger equations in multi-dimensions

      Anco, Stephen C. (AIP Publishing, 2013-12)
      Symmetry group methods are applied to obtain all explicit group-invariant radial solutions to a class of semilinear Schr¨odinger equations in dimensions n = 1. Both focusing and defocusing cases of a power nonlinearity are considered, including the special case of the pseudo-conformal power p = 4/n relevant for critical dynamics. The methods involve, first, reduction of the Schr¨odinger equations to group-invariant semilinear complex 2nd order ordinary differential equations (ODEs) with respect to an optimal set of one-dimensional point symmetry groups, and second, use of inherited symmetries, hidden symmetries, and conditional symmetries to solve each ODE by quadratures. Through Noether’s theorem, all conservation laws arising from these point symmetry groups are listed. Some group-invariant solutions are found to exist for values of n other than just positive integers, and in such cases an alternative two-dimensional form of the Schr¨odinger equations involving an extra modulation term with a parameter m = 2−n = 0 is discussed.
    • Potential Urinary Protein Biomarker Candidates for the Accurate Detection of Prostate Cancer among Benign Prostatic Hyperplasia Patients

      Haj-Ahmad, Yousef (Springer, 2014-01)
      Globally, Prostate cancer (PCa) is the most frequently occurring non-cutaneous cancer, and is the second highest cause of cancer mortality in men. Serum prostate specific antigen (PSA) has been the standard in PCa screening since its approval by the American Food & Drug Administration (FDA) in 1994. Currently, PSA is used as an indicator for PCa - patients with a serum PSA level above 4ng/mL will often undergo prostate biopsy to confirm cancer. Unfortunately fewer than similar to 30% of these men will biopsy positive for cancer, meaning that the majority of men undergo invasive biopsy with little benefit. Despite PSA's notoriously poor specificity (33%), there is still a significant lack of credible alternatives. Therefore an ideal biomarker that can specifically detect PCa at an early stage is urgently required. The aim of this study was to investigate the potential of using deregulation of urinary proteins in order to detect Prostate Cancer (PCa) among Benign Prostatic Hyperplasia (BPH). To identify the protein signatures specific for PCa, protein expression profiling of 8 PCa patients, 12 BPH patients and 10 healthy males was carried out using LC-MS/MS. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This approach revealed that significant the down-regulation of Fibronectin and TP53INP2 was a characteristic event among PCa patients. Fibronectin mRNA down-regulation, was identified as offering improved specificity (50%) over PSA, albeit with a slightly lower although still acceptable sensitivity (75%) for detecting PCa. As for TP53INP2 on the other hand, its down-regulation was moderately sensitive (75%), identifying many patients with PCa, but was entirely non-specific (7%), designating many of the benign samples as malignant and being unable to accurately identify more than one negative.
    • Inhibition of human lung cancer cell proliferation and survival by wine

      Barron, Carly; Moore, Jesse; Tsakiridis, Theodoros; Pickering, Gary; Tsiani, Evangelia (BioMed Central, 2014-01)
      Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events.
    • Potential Urinary miRNA Biomarker Candidates for the Accurate Detection of Prostate Cancer among Benign Prostatic Hyperplasia Patients

      Haj-Ahmad, Yousef (Springer, 2014-01)
      MicroRNAs (miRNAs) are a class of short (similar to 22nt), single stranded RNA molecules that function as post-transcriptional regulators of gene expression. MiRNAs can regulate a variety of important biological pathways, including: cellular proliferation, differentiation and apoptosis. Profiling of miRNA expression patterns was shown to be more useful than the equivalent mRNA profiles for characterizing poorly differentiated tumours. As such, miRNA expression "signatures" are expected to offer serious potential for diagnosing and prognosing cancers of any provenance. The aim of this study was to investigate the potential of using deregulation of urinary miRNAs in order to detect Prostate Cancer (PCa) among Benign Prostatic Hyperplasia (BPH). To identify the miRNA signatures specific for PCa, miRNA expression profiling of 8 PCa patients, 12 BPH patients and 10 healthy males was carried out using whole genome expression profiling. Differential expression of two individual miRNAs between healthy males and BPH patients was detected and found to possibly target genes related to PCa development and progression. The sensitivity and specificity of miR-1825 for detecting PCa among BPH individuals was found to be 60% and 69%, respectively. Whereas, the sensitivity and specificity of miR-484 were 80% and 19%, respectively. Additionally, the sensitivity and specificity for miR-1825/484 in tandem were 45% and 75%, respectively. The proposed PCa miRNA signatures may therefore be of great value for the accurate diagnosis of PCa and BPH. This exploratory study has identified several possible targets that merit further investigation towards the development and validation of diagnostically useful, non-invasive, urine-based tests that might not only help diagnose PCa but also possibly help differentiate it from BPH.
    • Identification of renin progenitors in the mouse bone marrow that give rise to B-cell leukaemia

      Liang, Ping (2014-02)
      cell of origin and triggering events for leukaemia are mostly unknown. Here we show that the bone marrow contains a progenitor that expresses renin throughout development and possesses a B-lymphocyte pedigree. This cell requires RBP-J to differentiate. Deletion of RBP-J in these renin-expressing progenitors enriches the precursor B-cell gene programme and constrains lymphocyte differentiation, facilitated by H3K4me3 activating marks in genes that control the pre-B stage. Mutant cells undergo neoplastic transformation, and mice develop a highly penetrant B-cell leukaemia with multi-organ infiltration and early death. These reninexpressing cells appear uniquely vulnerable as other conditional models of RBP-J deletion do not result in leukaemia. The discovery of these unique renin progenitors in the bone marrow and the model of leukaemia described herein may enhance our understanding of normal and neoplastic haematopoiesis.
    • Complete Genome Sequence of Erwinia amylovora Bacteriophage

      Yagubi, AI (American Society for Microbiology, 2014-07)
      The complete genome of an Erwinia amylovora bacteriophage, vB_EamM_Ea35-70 (Ea35-70), is 271,084 bp, encodes 318 putative proteins, and contains one tRNA. Comparative analysis with other Myoviridae genomes suggests that Ea35-70 is related to the Phikzlikevirus genus within the family Myoviridae, since 26% of Ea35-70 proteins share homology to proteins in Pseudomonas phage φKZ.
    • New conserved vorticity integrals for moving surfaces in multi-dimensional fluid flow

      Anco, Stephen C. (Springer Basel, 2014-09)
      For inviscid fluid flow in any n-dimensional Riemannian manifold, new conserved vorticity integrals generalizing helicity, enstrophy, and entropy circulation are derived for lower-dimensional surfaces that move along fluid streamlines. Conditions are determined for which the integrals yield constants of motion for the fluid. In the case when an inviscid fluid is isentropic, these new constants of motion generalize Kelvin’s circulation theorem from closed loops to closed surfaces of any dimension.
    • The Relationship Between Body Temperature, Heart Rate, Breathing Rate, and Rate of Oxygen Consumption, in the Tegu Lizard (Tupinambis merianae) at Various Levels of Activity

      Piercy, Joanna; Rogers, Kip; Reichert, Michelle; Andrade, Denis V; Abe, Augusto S; Tattersall, Glenn J; Milsom, William K (2015)
      The present study determined whether EEG and/or EMG recordings could be used to reliably define activity states in the Brazilian black and white tegu lizard (Tupinambis merianae) and then examined the interactive effects of temperature and activity states on strategies for matching O2 supply and demand. In a first series of experiments, the rate of oxygen consumption (V˙O2), breathing frequency (f R), heart rate (f H), and EEG and EMG (neck muscle) activity were measured in different sleep/wake states (sleeping, awake but quiet, alert, or moving). In general, metabolic and cardio-respiratory changes were better indictors of the transition from sleep to wake than were changes in the EEG and EMG. In a second series of experiments, the interactive effects of temperature (17, 27 and 37 °C) and activity states on f R, tidal volume (V T), the fraction of oxygen extracted from the lung per breath (FIO2–FEO2), f H, and the cardiac O2 pulse were quantified to determine the relative roles of each of these variables in accommodating changes in V˙O2. The increases in oxygen supply to meet temperature- and activity-induced increases in oxygen demand were produced almost exclusively by increases in f H and f R. Regression analysis showed that the effects of temperature and activity state on the relationships between f H, f R and V˙O2 was to extend a common relationship along a single curve, rather than separate relationships for each metabolic state. For these lizards, the predictive powers of f R and f H were maximized when the effects of changes in temperature, digestive state and activity were pooled. However, the best r 2 values obtained were 0.63 and 0.74 using f R and f H as predictors of met abolic rate, respectively.
    • Daily and annual cycles in thermoregulatory behaviour and cardio‑respiratory physiology of black and white tegu lizards

      Sanders, Colin E; Tattersall, Glenn J; Reichert, Michelle; Andrade, Denis V; Abe, Augusto S; Milsom, William K (2015)
      This study was designed to determine the manner in which metabolism is suppressed during dormancy in black and white tegu lizards (Tupinambis merianae). To this end, heart rate (f H), respiration rate (f R), and deep body temperature (T b) were continuously monitored in outdoor enclosures by radio-telemetry for nine months. There was a continuous decline in nighttime breathing and heart rate, at constant T b, throughout the late summer and fall suggestive of an active metabolic suppression that developed progressively at night preceding the entrance into dormancy. During the day, however, the tegus still emerged to bask. In May, when the tegus made a behavioural commitment to dormancy, T b (day and night) fell to match burrow temperature, accompanied by a further reduction in f H and f R. Tegus, under the conditions of this study, did arouse periodically during dormancy. There was a complex interplay between changes in f H and T b associated with the direct effects of temperature and the indirect effects of thermoregulation, activity, and changes in metabolism. This interplay gave rise to a daily hysteresis in the f H/T b relationship reflective of the physiological changes associated with warming and cooling as preferred T b alternated between daytime and nighttime levels. The shape of the hysteresis curve varied with season along with changes in metabolic state and daytime and nighttime body temperature preferences.
    • Cell-selective modulation of the Drosophila neuromuscular system by a neuropeptide

      Ormerod, Kiel G.; Krans, Jacob L.; Mercier, Joffre (2015-03)
      Neuropeptides can modulate physiological properties of neurons in a cell-specific manner. The present work examines whether a neuropeptide can also modulate muscle tissue in a cell-specific manner, using identified muscle cells in third instar larvae of fruit flies. DPKQDFMRFa, a modulatory peptide in the fruit fly Drosophila melanogaster, has been shown to enhance transmitter release from motor neurons and to elicit contractions by a direct effect on muscle cells. We report that DPKQDFMRFa causes a nifedipine-sensitive drop in input resistance in some muscle cells (6 and 7) but not others (12 and 13). The peptide also increased the amplitude of nerve-evoked contractions and compound excitatory junctional potentials (EJPs) to a greater degree in muscle cells 6 and 7 than 12 and 13. Knocking down FMRFa receptor (FR) expression separately in nerve and muscle indicate that both presynaptic and postsynaptic FR expression contributed to the enhanced contractions, but EJP enhancement was due mainly to presynaptic expression. Muscle-ablation showed that DPKQDFMRFa induced contractions and enhanced nerve-evoked contractions more strongly in muscle cells 6 and 7 than cells 12 and 13. In situ hybridization indicated that FR expression was significantly greater in muscle cells 6 and 7 than 12 and 13. Taken together, these results indicate that DPKQDFMRFa can elicit cell-selective effects on muscle fibres. The ability of neuropeptides to work in a cell-selective manner on neurons and muscle cells may help explain why so many peptides are encoded in invertebrate and vertebrate genomes.
    • Infrared thermography: A non-invasive window into thermal physiology

      Tattersall, Glenn J (2016)
      Infrared thermography is a non-invasive technique that measures mid to long-wave infrared radiation emanating from all objects and converts this to temperature. As an imaging technique, the value of modern infrared thermography is its ability to produce a digitized image or high speed video rendering a thermal map of the scene in false colour. Since temperature is an important environmental parameter influencing animal physiology and metabolic heat production an energetically expensive process, measuring temperature and energy exchange in animals is critical to understanding physiology, especially under field conditions. As a non-contact approach, infrared thermography provides a non-invasive complement to physiological data gathering. One caveat, however, is that only surface temperatures are measured, which guides much research to those thermal events occurring at the skin and insulating regions of the body. As an imaging technique, infrared thermal imaging is also subject to certain uncertainties that require physical modeling, which is typically done via built-in software approaches. Infrared thermal imaging has enabled different insights into the comparative physiology of phenomena ranging from thermogenesis, peripheral blood flow adjustments, evaporative cooling, and to respiratory physiology. In this review, I provide background and guidelines for the use of thermal imaging, primarily aimed at field physiologists and biologists interested in thermal biology. I also discuss some of the better known approaches and discoveries revealed from using thermal imaging with the objective of encouraging more quantitative assessment.
    • Seasonal reproductive endothermy in tegu lizards

      Tattersall, Glenn J; Leite, Cleo A.C.; Sanders, Colin E; Cadena, Viviana; Andrade, Denis V; Abe, Augusto S; Milsom, William K (2016)
      With some notable exceptions, small ectothermic vertebrates are incapable of endogenously sustaining a body temperature substantially above ambient temperature. This view was challenged by our observations of nighttime body temperatures sustained well above ambient (up to 10°C) during the reproductive season in tegu lizards (~2 kg). This led us to hypothesize that tegus have an enhanced capacity to augment heat production and heat conservation. Increased metabolic rates and decreased thermal conductance are the same mechanisms involved in body temperature regulation in those vertebrates traditionally acknowledged as “true endotherms” : the birds and mammals. The appreciation that a modern ectotherm the size of the earliest mammals can sustain an elevated body temperature through metabolic rates approaching that of endotherms enlightens the debate over endothermy origins, providing support for the parental care model of endothermy, but not for the assimilation capacity model of endothermy. It also indicates that, contrary to prevailing notions, ectotherms can engage in facultative endothermy, providing a physiological analog in the evolutionary transition to true endothermy.
    • Reptile thermogenesis and the origins of endothermy

      Tattersall, Glenn J (2016)
      Extant endotherms have high rates of metabolism, elevated body temperatures, usually tight control over body temperature, and a reasonable scope for further increases in metabolism through locomotor activity. Vertebrate ectotherms, on the other hand, rely on behavioural thermoregulation and cardiovascular adjustments to facilitate warming, and generally lack specific biochemical and cellular mechanisms for sustained, elevated metabolism. Nevertheless, the ancestral condition to endothermy is thought to resemble that of many extant reptiles, which raises the question of the origins and selection pressures relevant to the transitional state. Numerous hypotheses have emerged to explain the multiple origins of endothermy in vertebrates, including thermoregulatory, locomotory, and reproductive activity as possible drivers for these sustained and elevated metabolic rates. In this article, I discuss recent evidence for facultative endothermy in an extant lepidosaur, the tegu lizard. Since lepidosaurs are a sister group to the archosaurs, understanding how a novel form of endothermy evolved will open up opportunities to test the compatibility or incompatibility of the various endothermy hypotheses, with potential to elucidate and resolve long contentious ideas in evolutionary physiology.
    • Novel energy savings to multiple stressors in birds: The ultradian regulation of body temperature

      Tattersall, Glenn J; Rousesel, Damien; Voituron, Yann; Teulier, Loic (Royal Society Publishing, 2016-09-28)
      This study aimed to examine thermoregulatory responses in birds facing two commonly experienced stressors, cold and fasting. Logging devices allowing long-term and precise access to internal body temperature were placed within the gizzards of ducklings acclimated to cold (CA) (5°C) or thermoneutrality (TN) (25°C). The animals were then examined under three equal 4-day periods: ad libitum feeding, fasting and re-feeding. Through the analysis of daily as well as short-term, or ultradian, variations of body temperature, we showed that while ducklings at TN show only a modest decline in daily thermoregulatory parameters when fasted, they exhibit reduced surface temperatures from key sites of vascular heat exchange during fasting. The CA birds, on the other hand, significantly reduced their short-term variations of body temperature while increasing long-term variability when fasting. This phenomenon would allow the CA birds to reduce the energetic cost of body temperature maintenance under fasting. By analysing ultradian regulation of body temperature, we describe a means by which an endotherm appears to lower thermoregulatory costs in response to the combined stressors of cold and fasting.
    • The evolution of the avian bill as a thermoregulatory organ

      Tattersall, Glenn J; Arnaout, Bassel; Symonds, Matthew R. E. (Cambridge Philosophical Society, 2016-10-06)
      The avian bill is a textbook example of how evolution shapes morphology in response to changing environments. Bills of seed-specialist finches in particular have been the focus of intense study demonstrating how climatic fluctuations acting on food availability drive bill size and shape. The avian bill also plays an important but under-appreciated role in body temperature regulation, and therefore in energetics. Birds are endothermic and rely on numerous mechanisms for balancing internal heat production with biophysical constraints of the environment. The bill is highly vascularised and heat exchange with the environment can vary substantially, ranging from around 2% to as high as 400% of basal heat production in certain species. This heat exchange may impact how birds respond to heat stress, substitute for evaporative water loss at elevated temperatures or environments of altered water availability, or be an energetic liability at low environmental temperatures. As a result, in numerous taxa, there is evidence for a positive association between bill size and environmental temperatures, both within and among species. Therefore, bill size is both developmentally flexible and evolutionarily adaptive in response to temperature. Understanding the evolution of variation in bill size however, requires explanations of all potential mechanisms. The purpose of this review, therefore, is to promote a greater understanding of the role of temperature on shaping bill size over spatial gradients as well as developmental, seasonal, and evolutionary timescales.