Energetic Adaptations Research Articles

#4904 EPAC1- MEDIATED CAMP SIGNALLING PROMOTES CELLULAR ENERGY ADAPTATIONS IN PODOCYTES TO PROTECT FROM GLOMERULONEPHRITIS

Abstract Background and Aims Many efforts are made to identify new therapeutic targets to slow down, prevent or even reverse Chronic Kidney Disease (CKD) progression. One of the therapeutic approaches is activating the renoprotective cAMP pathway, especially by stimulation of its downstream effector, the protein kinase A (PKA). PKA was considered as the unique cAMP effector, however, the exchange factor directly activated by cAMP 1 (EPAC1) has been recently identified as a novel, PKA-independent, mediator of cAMP signalling. EPAC1 is a guanidine exchange factor that promotes the exchange of GDP for GTP regulating important cellular functions. Epac1 activation exerts a renoprotective effect during acute kidney injury, via maintenance of epithelial adhesion and protection from oxidative stress. However, the role of EPAC1 in CKD remains poorly understood. Here we aim to determine the role of EPAC1 in CKD progression. Method Nephrotoxic serum glomerulonephritis (NTS-GN) is induced in genetically modified mice with total and conditional EPAC1 deletion. Then isolated glomeruli from mice with conditional EPAC1 deletion in podocytes are analysed by RNA-sequencing. The main metabolic energy pathways are studied in podocytes in vitro under oxidative stress exposure in the presence or absence of an EPAC1 agonist. Results Following the induction of NTS-GN, mice with genetic deletion of EPAC1 show aggravated renal disease, characterized by increased proteinuria, glomerular damage, tissue inflammation and fibrosis compared to wild-type mice. Conversely, pharmacological activation of EPAC1, with the agonist 8-pCPT-2-OMe-cAMP, delays NTS-GN progression. Since in human and wild type mouse kidney tissues we observe EPAC1 expression in podocytes, mice with conditional deletion of EPAC1 in podocytes (Nphs2Cre:epac) are generated. Similar to the whole-body knockout, mice with EPAC1 deletion in podocytes show increased renal damage and worsened disease progression compared to control mice. RNA-sequencing analysis of glomeruli isolated from these mice show that gene expression of proteins linked to the pathway of glycolysis are abolished in early stage of NTS-GN (day 4). These data suggest that EPAC1-mediated activation of glycolysis in podocytes is essential to limit GN progression. This is substantiated by the in vitro experiments in podocytes, in which EPAC1 activation under oxidative stress promotes glycolysis with cellular energy production independently from mitochondrial respiration. The EPAC1-mediated glycolysis protected podocytes by increasing cell viability, decreasing LDH release and activating the AKT pathway. Conclusion Our results suggest a protective role of podocytes-derived EPAC1 against the development of GN through cellular energetic adaptations based on metabolic switch to glycolysis. Activating the cAMP-EPAC1 signalling axis could represent a therapeutic option to delay the development of CKD. Further investigations are needed to define its relevance in human CKD.

Mitochondrial responses to brain death in solid organ transplant.

Mitochondrial dynamics are central to the pathophysiology of cellular damage and inflammatory responses. In the context of solid organ transplantation, mitochondria are implicated in immune activation in donor organs that occurs after brain death, as they are critical to the regulation of cellular stress response, cell death, and display energetic adaptations through the adjustment of respiratory capacity depending on the cellular milieu. Mitochondrial damage activates mitochondrial systems of fission, fusion, biogenesis, and mitochondrial autophagy, or mitophagy. The mechanistic pathways as well as therapies targeting mitochondrial physiology have been studied as plausible ways to mitigate the negative effects of brain death on donor organs, though there is no summative evaluation of the multiple efforts across the field. This mini-review aims to discuss the interplay of donor brain death, mitochondrial dynamics, and impact on allograft function as it pertains to heart, lung, liver, and kidney transplants.

Mechanisms of mitochondrial respiratory adaptation.

Mitochondrial energetic adaptations encompass a plethora of conserved processes that maintain cell and organismal fitness and survival in the changing environment by adjusting the respiratory capacity of mitochondria. These mitochondrial responses are governed by general principles of regulatory biology exemplified by changes in gene expression, protein translation, protein complex formation, transmembrane transport, enzymatic activities and metabolite levels. These changes can promote mitochondrial biogenesis and membrane dynamics that in turn support mitochondrial respiration. The main regulatory components of mitochondrial energetic adaptation include: the transcription coactivator peroxisome proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC1α) and associated transcription factors; mTOR and endoplasmic reticulum stress signalling; TOM70-dependent mitochondrial protein import; the cristae remodelling factors, including mitochondrial contact site and cristae organizing system (MICOS) and OPA1; lipid remodelling; and the assembly and metabolite-dependent regulation of respiratory complexes. These adaptive molecular and structural mechanisms increase respiration to maintain basic processes specific to cell types and tissues. Failure to execute these regulatory responses causes cell damage and inflammation or senescence, compromising cell survival and the ability to adapt to energetically demanding conditions. Thus, mitochondrial adaptive cellular processes are important for physiological responses, including to nutrient availability, temperature and physical activity, and their failure leads to diseases associated with mitochondrial dysfunction such as metabolic and age-associated diseases and cancer.

Human Musculoskeletal and Energetic Adaptations to Unilateral Robotic Knee Gait Assistance.

This paper aims to analyse the human musculoskeletal and energetic adaptation mechanisms when physically interacting with a unilateral knee orthosis during treadmill walking. Test subjects participated in two walking trials, whereby the orthosis was controlled to deliver five predefined torque profiles of different duration (as % of a gait cycle). The adaptations to assistive torques of different duration were analysed in terms of gait parameters, metabolic effort, and muscle activity. Orthotic assistance's kinematic effects remain local to the assisted leg and joint, unlike the muscles spanning the knee joint, which engage in a balancing-out action to retain stability. Duration of assistive torque significantly affects only the timing of the knee joint's peak flexion angle in the stance phase, while the observed joint kinematics and muscle activity demonstrate different recovery times upon changing robotic support (washout effects). Human body adaptations to external robotic knee joint assistance during walking take place on multiple levels and to a different extent in a joint effort to keep the gait stable. This paper provides important insights into the human body's multiple adaptation mechanisms in the presence of external robotic assistance.

Field metabolic rates of giant pandas reveal energetic adaptations

Knowledge of energy expenditure informs conservation managers for long term plans for endangered species health and habitat suitability. We measured field metabolic rate (FMR) of free-roaming giant pandas in large enclosures in a nature reserve using the doubly labeled water method. Giant pandas in zoo like enclosures had a similar FMR (14,182 kJ/day) to giant pandas in larger field enclosures (13,280 kJ/day). In winter, giant pandas raised their metabolic rates when living at − 2.4 °C (36,108 kJ/day) indicating that they were below their thermal neutral zone. The lower critical temperature for thermoregulation was about 8.0 °C and the upper critical temperature was about 28 °C. Giant panda FMRs were somewhat lower than active metabolic rates of sloth bears, lower than FMRs of grizzly bears and polar bears and 69 and 81% of predicted values based on a regression of FMR versus body mass of mammals. That is probably due to their lower levels of activity since other bears actively forage for food over a larger home range and pandas often sit in a patch of bamboo and eat bamboo for hours at a time. The low metabolic rates of giant pandas in summer, their inability to acquire fat stores to hibernate in winter, and their ability to raise their metabolic rate to thermoregulate in winter are energetic adaptations related to eating a diet composed almost exclusively of bamboo. Differences in FMR of giant pandas between our study and previous studies (one similar and one lower) appear to be due to differences in activity of the giant pandas in those studies.

Abstract 8956: Association of Serum Irisin Levels with Inflammatory, Biochemical, and Cardiac Imaging Parameters in Patients With Chronic Heart Failure versus Controls

Chronic heart failure (CHF) remains one of the most important causes of morbidity and mortality globally. Metabolic and energetic maladaptation has proven to play a critical in the progression of this condition. In this regard, evidence from preclinical studies has shown that irisin, a recently discovered adipomyokine involved in metabolic control, can induce positive cardioprotective effects by improving cardiac remodeling, cardiomyocyte viability, calcium delivery, and reduction of inflammatory mediators. However, data on the clinical associations between irisin levels and inflammatory and functional imaging parameters are scarce in CHF patients. 32 subjects diagnosed with CHF and 32 healthy controls were evaluated in a cross-sectional study. Serum irisin levels were significantly lower in patients with CHF (4.92, IQR [5.4] ng/ml) than controls (6.45, IQR [3.58] ng/ml). We identified a positive correlation between irisin levels and LVEF (R=0.3), fraction shortening (R=0.4), and body fat percentage (R=0.4). In contrast, a negative correlation between irisin levels and BNP (R=-0.4), insulin levels (R=-0.1), and HOMA index (R=-0.2) was reported. Subjects with CHF showed higher levels of TNF-α (22.05 IQR [12.28] pg/ml) and IL-12p70 (5.58 IQR [4.47] pg/ml) in comparison with controls (9.77 IQR [6.24] and 3.05 [1.90] pg/ml ), while controls showed higher levels of IL-10 (16.27 IQR [10.82] pg/ml) in comparison with CHF cases (7.51 IQR [8.47] pg/ml). However, we did not observe significant correlations between irisin levels and inflammatory cytokines. Irisin levels are possibly reduced in patients with CHF due to the intrinsic energetic and metabolic adaptations that occur as a result of the reduction of cardiac output. Reduced irisin levels play a synergic role with the effects of proinflammatory mediators by hazarding the cardiomyocyte viability, adaptation to ventricular remodeling, and response to fibrosis. This additional damage continues compromising cardiac dynamical parameters creating a vicious cycle.

Abstract 506: Enhanced Mitochondrial Calcium Uptake During Chronic β-adrenergic Stimulation Causes Maladaptive Remodeling and Impaired Left Ventricular Function Independent of Cyclophilin D-mediated Mitochondrial Permeability Transition

The mitochondrial calcium uniporter (MCU) forms the pore of the mitochondrial calcium uniporter channel (mtCU) and is required for rapid mitochondrial Ca 2+ ( m Ca 2+ ) uptake. MCU is necessary to increase cardiac energetics to fuel an increase in cardiac contractility during acute sympathetic stimulation. However, little is known about how MCU-dependent Ca 2+ flux may contribute to the heart’s adaptations to chronic stress. We therefore compared mice with adult cardiomyocyte (ACM)-specific loss ( Mcu fl/fl ; Mcu-cKO) or gain (CAG-CAT-MCU; MCU-Tg) of MCU function to examine the role of MCU-dependent m Ca 2+ uptake in a model of chronic catecholamine overload. In vitro characterization of ACMs confirmed that MCU overexpression enhanced and Mcu deletion inhibited acute m Ca 2+ uptake. Neither loss nor gain of MCU function altered baseline contractile function in vivo . In αMHC-MCM control mice, fractional shortening was transiently increased after 2 days of isoproterenol infusion. This initial increase in contractility was attenuated in MCU-cKO mice. In contrast, MCU-Tg mice exhibited decreased fractional shortening at 7 and 14 days of isoproterenol infusion. This detrimental effect on contractile function was associated with increased LV dilation, HW/BW ratio, and lung edema. MCU-Tg cardiomyocytes in vitro exhibited increased ROS production and a trend towards increased cell death upon elevation of cytosolic Ca 2+ with ionomycin. These data prompted us to test the hypothesis that isoproterenol-induced contractile dysfunction in MCU-Tg hearts is caused by cardiomyocyte dropout due to m Ca 2+ overload and mitochondrial permeability transition. However, genetic deletion of the mPTP component cyclophilin D did not prevent the decline in contractile function, diminish cardiomyocyte death, or attenuate LV remodeling in MCU-Tg animals during chronic isoproterenol infusion. We conclude that although mtCU-dependent m Ca 2+ uptake is essential for early energetic adaptations to high adrenergic load, under conditions of chronic adrenergic stress it is maladaptive and predisposes to heart failure. Our data suggest that this maladaptive response occurs via mechanisms independent of cyclophilin D-mediated permeability transition.

Energetic adaptations: Metabolic control of endocytic membrane traffic.

Endocytic membrane traffic controls the access of myriad cell surface proteins to the extracellular milieu, and thus gates nutrient uptake, ion homeostasis, signaling, adhesion and migration. Coordination of the regulation of endocytic membrane traffic with a cell's metabolic needs represents an important facet of maintenance of homeostasis under variable conditions of nutrient availability and metabolic demand. Many studies have revealed intimate regulation of endocytic membrane traffic by metabolic cues, from the specific control of certain receptors or transporters, to broader adaptation or remodeling of the endocytic membrane network. We examine how metabolic sensors such as AMP-activated protein kinase, mechanistic target of rapamycin complex 1 and hypoxia inducible factor 1 determine sufficiency of various metabolites, and in turn modulate cellular functions that includes control of endocytic membrane traffic. We also examine how certain metabolites can directly control endocytic traffic proteins, such as the regulation of specific protein glycosylation by limiting levels of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) produced by the hexosamine biosynthetic pathway. From these ideas emerge a growing appreciation that endocytic membrane traffic is orchestrated by many intrinsic signals derived from cell metabolism, allowing alignment of the functions of cell surface proteins with cellular metabolic requirements. Endocytic membrane traffic determines how cells interact with their environment, thus defining many aspects of nutrient uptake and energy consumption. We examine how intrinsic signals that reflect metabolic status of a cell regulate endocytic traffic of specific proteins, and, in some cases, exert broad control of endocytic membrane traffic phenomena. Hence, endocytic traffic is versatile and adaptable and can be modulated to meet the changing metabolic requirements of a cell.

Metabolic cost adaptations during training with a soft exosuit assisting the hip joint

Different adaptation rates have been reported in studies involving ankle exoskeletons designed to reduce the metabolic cost of their wearers. This work aimed to investigate energetic adaptations occurring over multiple training sessions, while walking with a soft exosuit assisting the hip joint. The participants attended five training sessions within 20 days. They walked carrying a load of 20.4 kg for 20 minutes with the exosuit powered and five minutes with the exosuit unpowered. Percentage change in net metabolic cost between the powered and unpowered conditions improved across sessions from −6.2 ± 3.9% (session one) to −10.3 ± 4.7% (session five), indicating a significant effect associated with training. The percentage change at session three (−10.5 ± 4.5%) was similar to the percentage change at session five, indicating that two 20-minute sessions may be sufficient for users to fully adapt and maximize the metabolic benefit provided by the exoskeleton. Retention was also tested measuring the metabolic reduction five months after the last training session. The percent change in metabolic cost during this session (−10.1 ± 3.2%) was similar to the last training session, indicating that the adaptations resulting in reduced metabolic cost are preserved. These outcomes are relevant when evaluating exoskeletons’ performance on naïve users, with a specific focus on hip extension assistance.

Abstract 277: Enhanced Mitochondrial Calcium Uptake Promotes Deleterious Remodeling and Impaired Left Ventricular Function During Chronic Adrenergic Stimulation

The mitochondrial calcium uniporter (MCU) constitutes the pore-forming unit of the mitochondrial calcium uniporter channel (mtCU) and is necessary for mitochondrial Ca 2+ ( m Ca 2+ ) uptake. We previously reported that MCU is required to increase cardiac energetics and contractility in response to acute β-adrenergic stimulation. However, deletion of MCU has no detrimental effect on basal cardiac function or metabolism. While these findings support a role for MCU-dependent Ca 2+ flux in functional adaptations to acute stress, little is known about the involvement of MCU in cardiac responses to sustained stress. We compared mice with adult, cardiomyocyte (ACM)-specific loss ( Mcu fl/fl ; Mcu -cKO) or gain (CAG-CAG-MCU; MCU-Tg) of MCU function to explore the role of m Ca 2+ uptake in a model of chronic catecholamine overload. Biophysical characterization confirmed that MCU overexpression enhanced and MCU deletion inhibited ACM m Ca 2+ uptake. Neither loss nor gain of MCU had a significant impact on baseline contractile function. In αMHC-MCM control mice, fractional shortening was transiently increased after 2 days of isoproterenol infusion (Fig 1). This early increase in contractility was attenuated in Mcu -cKO mice. MCU-Tg mice exhibited decreased fractional shortening at 7 and 14 days of isoproterenol infusion. This detrimental effect on LV function was associated with increased LV dilation, HW/BW ratio, and lung edema as compared to αMHC-MCM controls. These data suggest that although mtCU-dependent m Ca 2+ uptake is essential for early energetic adaptations to high adrenergic load, under conditions of chronic adrenergic stress it is maladaptive and predisposes to heart failure.

Effects of swim training on energetic and performance in women masters’ swimmers

The aim of this study was to analyze and compare the changes of performance and energetic profile of female masters swimmers over a season, in three distinct time periods (TP): December (TP 1 ), March (TP 2 ) and June (TP 3 ). Eleven female masters swimmers performed an all-out 200 m freestyle to evaluate the swimmers’ energetic adaptations. The 200 m freestyle performance, the total energy expenditure ( E tot ) and the partial contribution of aerobic energy source (% Aer ), partial contribution of anaerobic lactic energy source (% AnL ) and partial contribution of anaerobic alactic energy source (% AnAl ) contributions were estimated or assessed. Female masters swimmers improved significantly the 200 m freestyle performance over a season. However, a non-significant improvement was found on their energetic profile. Hence, one might speculate that performance improvement might be related to other performance determinants, such as, technical enhancement. Aerobic metabolism was the major contributor for E tot whereas anaerobic alactic was the second major contributor.

Effects of High-Intensity Training on Anaerobic and Aerobic Contributions to Total Energy Release During Repeated Supramaximal Exercise in Obese Adults.

BackgroundStudying relative anaerobic and aerobic metabolism contributions to total energy release during exercise may be valuable in understanding exercise energetic demands and the energetic adaptations that occur in response to acute or chronic exercise in obese adults. The aim of the present study is to evaluate the effects of 6 weeks of high-intensity training (HIT) on relative anaerobic and aerobic contributions to total energy release and on peak power output during repeated supramaximal cycling exercises (SCE) in obese adults.MethodsTwenty-four obese adults (body mass index = ± 33 kg.m−2) were randomized into a control group (n = 12) and an HIT group (n = 12). Accumulated oxygen deficits (ml.min−1) and anaerobic and aerobic contributions (%) were measured in all groups before and after training via repeated SCE. In addition, the peak power output performed during SCE was determined using the force-velocity test.ResultsBefore HIT, anaerobic contributions to repeated SCE did not differ between the groups and decreased significantly during the third and fourth repetitions. After HIT, anaerobic contributions increased significantly in the HIT group (+11 %, p < 0.01) and were significantly higher than those of the control group (p < 0.01). Moreover, the peak power obtained during SCE increased significantly in the HIT group (+110 W.kg−1, p < 0.01) and correlated positively with increases in anaerobic contributions (r = 0.9, p < 0.01).ConclusionsIn obese adults, HIT increased anaerobic contributions to energy release which were associated with peak power enhancement in response to repeated SCE. Consequently, HIT may be an appropriate approach for improving energy contributions and muscle power among obese adults.

Energetic adaptations to larval export within the brackish-water palaemonine shrimp, Palaemonetes varians

Decapod crustaceans have repeatedly colonised brackish, freshwater, and terrestrial environments. Many decapods, which inhabit brackish and freshwater habitats, export larvae into estuarine and coastal areas where conditions for larval development may be better. In this study, we assess the starvation resistance, biochemical composition and respiration rate during larval development, and the effects of temperature on these factors within the brackish living palaemonine shrimp, Palaemonetes varians. Our results demonstrate that P. varians is highly resistant to starvation and may be considered facultative lecithotrophic in its first and second larval instars and planktotrophic from its third instar. This high starvation resistance is associated with a relatively large size, high carbon content (~45%) and C:N ratio (~4.2), and visible yolk reserves at hatching. These energy reserves are interpreted as an adaptation to the exportation of larvae from peripheral adult environments into mid and lower estuarine waters. Respiration rates varied with the moult cycle and were similar between fed and unfed larvae, suggesting that starved larvae do not suppress their metabolism as an energy saving strategy. Despite higher respiration rates at higher temperatures, energy loss throughout development (estimated from respiration rates) increased with decreasing temperature, whilst larval growth and development rates decreased with increasing temperature. High energy reserves at hatching, as within Palaemonetes varians, is an important life history adaptation in the colonisation of brackish and freshwaters, initially enabling the exportation of larvae from adult environments and eventually enabling lecithotrophy and direct development.

Dietary and flight energetic adaptations in a salivary gland transcriptome of an insectivorous bat.

We hypothesized that evolution of salivary gland secretory proteome has been important in adaptation to insectivory, the most common dietary strategy among Chiroptera. A submandibular salivary gland (SMG) transcriptome was sequenced for the little brown bat, Myotis lucifugus. The likely secretory proteome of 23 genes included seven (RETNLB, PSAP, CLU, APOE, LCN2, C3, CEL) related to M. lucifugus insectivorous diet and metabolism. Six of the secretory proteins probably are endocrine, whereas one (CEL) most likely is exocrine. The encoded proteins are associated with lipid hydrolysis, regulation of lipid metabolism, lipid transport, and insulin resistance. They are capable of processing exogenous lipids for flight metabolism while foraging. Salivary carboxyl ester lipase (CEL) is thought to hydrolyze insect lipophorins, which probably are absorbed across the gastric mucosa during feeding. The other six proteins are predicted either to maintain these lipids at high blood concentrations or to facilitate transport and uptake by flight muscles. Expression of these seven genes and coordinated secretion from a single organ is novel to this insectivorous bat, and apparently has evolved through instances of gene duplication, gene recruitment, and nucleotide selection. Four of the recruited genes are single-copy in the Myotis genome, whereas three have undergone duplication(s) with two of these genes exhibiting evolutionary ‘bursts’ of duplication resulting in multiple paralogs. Evidence for episodic directional selection was found for six of seven genes, reinforcing the conclusion that the recruited genes have important roles in adaptation to insectivory and the metabolic demands of flight. Intragenic frequencies of mobile- element-like sequences differed from frequencies in the whole M. lucifugus genome. Differences among recruited genes imply separate evolutionary trajectories and that adaptation was not a single, coordinated event.

Saving energy during hard times: energetic adaptations of Shetland pony mares.

Recent results suggest that wild Northern herbivores reduce their metabolism during times of low ambient temperature and food shortage in order to reduce their energetic needs. It is, however, not known whether domesticated animals are also able to reduce their energy expenditure. We exposed 10 Shetland pony mares to different environmental conditions (summer and winter) and to two food quantities (60% and 100% of maintenance energy requirement) during low winter temperatures to examine energetic and behavioural responses. In summer, ponies showed a considerably higher field metabolic rate (FMR; 63.4±15.0 MJ day(-1)) compared with food-restricted and control animals in winter (24.6±7.8 and 15.0±1.1 MJ day(-1), respectively). During summer, locomotor activity, resting heart rate and total water turnover were considerably elevated (P<0.001) compared with winter. Animals on a restricted diet (N=5) compensated for the decreased energy supply by reducing their FMR by 26% compared with control animals (N=5). Furthermore, resting heart rate, body mass and body condition score were lower (29.2±2.7 beats min(-1), 140±22 kg and 3.0±1.0 points, respectively) than in control animals (36.8±41 beats min(-1), 165±31 kg, 4.4±0.7 points; P<0.05). While the observed behaviour did not change, nocturnal hypothermia was elevated. We conclude that ponies acclimatize to different climatic conditions by changing their metabolic rate, behaviour and some physiological parameters. When exposed to energy challenges, ponies, like wild herbivores, exhibited hypometabolism and nocturnal hypothermia.

Amor y autoridad. Ejercicios legítimos del poder de las policías mujeres en su trabajo

Pensar los modos de ejercicio de la autoridad por parte de las mujeres en la policía bonaerense lleva a reflexionar sobre la asociación entre las cualidades y relaciones personales y el poder formalizado puesto en escena en los espacios laborales. Los vínculos, sentimientos y experiencias afectivas introducen orientaciones particulares al devenir de la profesión policial de las personas, especialmente para las mujeres. Ese plus amoroso es vivido, algunas veces, como una obligación personal y, otras, como una estrategia que permite capitalizar las habilidades laborales. El análisis de esta asociación particular es un aporte al estudio de las significaciones y experiencias alrededor de los complejos procesos de ingreso y jerarquización de mujeres en las policías. Porque además de exigir enérgicas adaptaciones a las policías mujeres, provocó modificaciones en la forma de ejercer la profesión más allá del género. Este artículo no pierde de vista cómo se conjugan clivajes sociales diferentes en la dinámica de las relaciones de poder. Los datos analizados han sido construidos con trabajo de campo etnográfico en comisarías de la Policía de la Provincia de Buenos Aires.

Lipid dynamics and feeding of dominant Antarctic calanoid copepods in the eastern Weddell Sea in December

Lipid content, fatty acid composition, and feeding activity of the dominant Antarctic copepods, Calanoides acutus, Calanus propinquus, and Metridia gerlachei, were studied at a quasi-permanent station in the eastern Weddell Sea in December 2003. During 3 weeks of the spring phytoplankton development, total lipid levels of females and copepodite stages V (CVs) of C. acutus were almost doubled. Meanwhile, only a slight increase in total lipid content occurred in M. gerlachei, and no clear trend was observed in lipids of C. propinquus females. The pronounced increase of lipids in C. acutus was due to an accumulation of wax esters. The proportion of wax esters in the lipids of M. gerlachei was clearly lower, while triacylglycerols played a more important role. In C. propinquus, triacylglycerols were the only neutral lipid class. There were no pronounced changes in the feeding activity of M. gerlachei, whereas the feeding activity of C. acutus had rapidly increased with the development of the phytoplankton bloom in December, which explains its rapid lipid accumulation. The combination of gut content and fatty acid trophic marker analyses showed that C. acutus was feeding predominantly on diatoms. The typical diatom fatty acid marker, 16:1(n-7), slightly decreased and the tracer for flagellates, 18:4(n-3), increased in females and CVs of C. acutus. This shift indicates the time, when the significance of flagellates started to increase. The three copepod species exhibited different patterns of lipid accumulation in relation to their trophic niches and different duration of their active phases. The investigations filled a crucial data gap in the seasonal lipid dynamics of dominant calanoid copepods in the Weddell Sea in December and support earlier hypotheses on their energetic adaptations and life cycle strategies.

The effect of walking speed on muscle function and mechanical energetics

Modulating speed over a large range is important in walking, yet understanding how the neuromotor patterns adapt to the changing energetic demands of different speeds is not well understood. The purpose of this study was to identify functional and energetic adaptations in individual muscles in response to walking at faster steady-state speeds using muscle-actuated forward dynamics simulations. The simulation data were invariant with speed as to whether muscles contributed to trunk support, forward propulsion or leg swing. Trunk support (vertical acceleration) was provided primarily by the hip and knee extensors in early stance and the plantar flexors in late stance, while trunk propulsion (horizontal acceleration) was provided primarily by the soleus and rectus femoris in late stance, and these muscle contributions all systematically increased with speed. The results also highlighted the importance of initiating and controlling leg swing as there was a dramatic increase at the higher walking speeds in iliopsoas muscle work to accelerate the leg in pre- and early swing, and an increase in the biarticular hamstring muscle work to decelerate the leg in late swing. In addition, walking near self-selected speeds (1.2 m/s) improves the utilization of elastic energy storage and recovery in the uniarticular ankle plantar flexors and reduces negative fiber work, when compared to faster or slower speeds. These results provide important insight into the neuromotor mechanisms underlying speed regulation in walking and provide the foundation on which to investigate the influence of walking speed on various neuromotor measures of interest in pathological populations.

Potential applications of urinary C‐peptide of insulin for comparative energetics research

The study of comparative energetics offers a valuable way to identify broad ecological principles and assess the functional significance of energetic adaptations during the course of evolution. Yet, the quantification of energetic status for nonhuman primates under natural conditions remains one of the most challenging aspects of comparative energetics research. Here, we report on the development of a noninvasive field method for measuring energetic status in great apes, humans, and possibly other nonhuman primates. Specifically, we have explored measurement of a urinary metabolite of insulin (C-peptide) as a physiological marker of energetic condition in chimpanzees and orangutans. We performed three validation studies and successfully measured C-peptide in urine samples from captive chimpanzees, wild chimpanzees, and wild orangutans. Urinary C-peptide measures gave indications of being a reliable signal of energetic status in both species. For chimpanzees and orangutans in the wild, baseline urinary C-peptide levels were higher during periods of fruit abundance than periods of low fruit availability. Urinary C-peptide levels were also higher for well-fed captive chimpanzees compared with wild chimpanzees. Although sample size was small, top-ranking male chimpanzees showed higher C-peptide levels in the wild than low-ranking males only during the period of fruit abundance. These preliminary results indicate that further development of the urinary C-peptide method could expand opportunities to quantify energetic condition for great apes in the wild and generate new data for comparative research. We highlight specific applications for studying great ape reproduction as well as the nutritional ecology of human foragers.

Mitochondrial DNA G10398A polymorphism imparts maternal Haplogroup N a risk for breast and esophageal cancer

Mitochondria are the major source of Reactive Oxygen Species (ROS) and mtDNA G10398A (Ala → Thr) polymorphism, proposed to be involved in increased ROS production, has been shown in association with invasive breast cancer in African–American (AA) women [J.A. Canter, A.R. Kallianpur, F.F. Parl, R.C. Millikan, Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African–American women, Cancer Res. 65 (2005) 8028–8033] and prostate cancer in AA men [M.P. Mims, T.G. Hayes, S. Zheng, S.M. Leal, A. Frolov, M.M. Ittmann, et al., Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African–American women, Cancer Res. 66 (2006) 1880; author reply 1880–1881]. The role of mitochondria, however, in cancer development has been in question recently [A. Salas, Y.G. Yao, V. Macaulay, A. Vega, A. Carracedo, H.J. Bandelt, A critical reassessment of the role of mitochondria in tumorigenesis, PLoS Med. 2 (2005) e296], which has made it pertinent to analyze the data and test the hypotheses by conducting fresh case-control studies. This study, therefore, makes an attempt to validate the exclusive presence of mtG10398A (Ala → Thr) polymorphism in a haplotype constituting mtDNA haplogroup N and its sublineages, imparting this group a higher risk for breast cancer, based on the re-analyses of ∼1000 complete human mtDNA sequences worldwide and collated information on 2334 individuals belonging to 18 regions in India. The conclusion drawn of mt10398A allele providing a risk towards cancer is confirmed in a case-control comparison study of 124 sporadic breast cancer patients and 273 controls; and 55 squamous cell carcinoma of esophagus, ESCC, and 163 controls, matched for age, ethnicity and sex from north India. It is further apparent from the study that such a mtDNA polymorphism background provides a higher risk for the cancers of the tissues which could be affected by environmental insults directly as in the ESCC, observed with a high acquired (somatic) rate of mutation in p53 when compared to the breast cancer, suggesting that the mtDNA variants that arose as energetic adaptations, influence our health differentially under different environment conditions and a given genetic background of the mt genome.