Expression Profiles of Mitochondrial Genes in the Frontal Cortex and the Caudate Nucleus of Developing Humans and Mice Selectively Bred for High and Low Fear

A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC) and the caudate nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115) and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A greater number of the genes in the PFC (91%) than the genes in the CN (62%) showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1), mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3). In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05). However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.

Validity of dietary questionnaires in Sri Lankan adults and the association of dietary intake with obesity

Traditionally, infectious diseases and under-nutrition have been considered major health problems in Sri Lanka with little attention paid to obesity and associated non-communicable diseases (NCDs). However, the recent Sri Lanka Diabetes and Cardiovascular Study (SLDCS) reported the epidemic level of obesity, diabetes and metabolic syndrome. Moreover, obesity-associated NCDs is the leading cause of death in Sri Lanka and there is an exponential increase in hospitalization due to NCDs adversely affecting the development of the country. Despite Sri Lanka having a very high prevalence of NCDs and associated mortality, little is known about the causative factors for this burden. It is widely believed that the global NCD epidemic is associated with recent lifestyle changes, especially dietary factors. In the absence of sufficient data on dietary habits in Sri Lanka, successful interventions to manage these serious health issues would not be possible. In view of the current situation the dietary survey was undertaken to assess the intakes of energy, macro-nutrients and selected other nutrients with respect to socio demographic characteristics and the nutritional status of Sri Lankan adults especially focusing on obesity. Another aim of this study was to develop and validate a culturally specific food frequency questionnaire (FFQ) to assess dietary risk factors of NCDs in Sri Lankan adults. Data were collected from a subset of the national SLDCS using a multi-stage, stratified, random sampling procedure (n=500). However, data collection in the SLDCS was affected by the prevailing civil war which resulted in no data being collected from Northern and Eastern provinces. To obtain a nationally representative sample, additional subjects (n=100) were later recruited from the two provinces using similar selection criteria. Ethical Approval for this study was obtained from the Ethical Review Committee, Faculty of Medicine, University of Colombo, Sri Lanka and informed consent was obtained from the subjects before data were collected. Dietary data were obtained using the 24-h Dietary Recall (24HDR) method. Subjects were asked to recall all foods and beverages, consumed over the previous 24-hour period. Respondents were probed for the types of foods and food preparation methods. For the FFQ validation study, a 7-day weight diet record (7-d WDR) was used as the reference method. All foods recorded in the 24 HDR were converted into grams and then intake of energy and nutrients were analysed using NutriSurvey 2007 (EBISpro, Germany) which was modified for Sri Lankan food recipes. Socio-demographic details and body weight perception were collected from interviewer-administrated questionnaire. BMI was calculated and overweight (BMI ≥23 kg.m-2), obesity (BMI ≥25 kg.m-2) and abdominal obesity (Men: WC ≥ 90 cm; Women: WC ≥ 80 cm) were categorized according to Asia-pacific anthropometric cut-offs. The SPSS v. 16 for Windows and Minitab v10 were used for statistical analysis purposes. From a total of 600 eligible subjects, 491 (81.8%) participated of whom 34.5% (n=169) were males. Subjects were well distributed among different socio-economic parameters. A total of 312 different food items were recorded and nutritionists grouped similar food items which resulted in a total of 178 items. After performing step-wise multiple regression, 93 foods explained 90% of the variance for total energy intake, carbohydrates, protein, total fat and dietary fibre. Finally, 90 food items and 12 photographs were selected. Seventy-seven subjects completed (response rate = 65%) the FFQ and 7-day WDR. Estimated mean energy intake (SD) from FFQ (1794±398 kcal) and 7DWR (1698±333 kcal, P<0.001) was significantly different due to a significant overestimation of carbohydrate (~10 g/d, P<0.001) and to some extent fat (~5 g/d, NS). Significant positive correlations were found between the FFQ and 7DWR for energy (r = 0.39), carbohydrate (r = 0.47), protein (r = 0.26), fat (r =0.17) and dietary fiber (r = 0.32). Bland-Altman graphs indicated fairly good agreement between methods with no relationship between bias and average intake of each nutrient examined. The findings from the nutrition survey showed on average, Sri Lankan adults consumed over 14 portions of starch/d; moreover, males consumed 5 more portions of cereal than females. Sri Lankan adults consumed on average 3.56 portions of added sugars/d. Moreover, mean daily intake of fruit (0.43) and vegetable (1.73) portions was well below minimum dietary recommendations (fruits 2 portions/d; vegetables 3 portions/d). The total fruit and vegetable intake was 2.16 portions/d. Daily consumption of meat or alternatives was 1.75 portions and the sum of meat and pulses was 2.78 portions/d. Starchy foods were consumed by all participants and over 88% met the minimum daily recommendations. Importantly, nearly 70% of adults exceeded the maximum daily recommendation for starch (11portions/d) and a considerable proportion consumed larger numbers of starch servings daily, particularly men. More than 12% of men consumed over 25 starch servings/d. In contrast to their starch consumption, participants reported very low intakes of other food groups. Only 11.6%, 2.1% and 3.5% of adults consumed the minimum daily recommended servings of vegetables, fruits, and fruits and vegetables combined, respectively. Six out of ten adult Sri Lankans sampled did not consume any fruits. Milk and dairy consumption was extremely low; over a third of the population did not consume any dairy products and less than 1% of adults consumed 2 portions of dairy/d. A quarter of Sri Lankans did not report consumption of meat and pulses. Regarding protein consumption, 36.2% attained the minimum Sri Lankan recommendation for protein; and significantly more men than women achieved the recommendation of ≥3 servings of meat or alternatives daily (men 42.6%, women 32.8%; P<0.05). Over 70% of energy was derived from carbohydrates (Male:72.8±6.4%, Female:73.9±6.7%), followed by fat (Male:19.9±6.1%, Female:18.5±5.7%) and proteins (Male:10.6±2.1%, Female:10.9±5.6%). The average intake of dietary fiber was 21.3 g/day and 16.3 g/day for males and females, respectively. There was a significant difference in nutritional intake related to ethnicities, areas of residence, education levels and BMI categories. Similarly, dietary diversity was significantly associated with several socio-economic parameters among Sri Lankan adults. Adults with BMI ≥25 kg.m-2 and abdominally obese Sri Lankan adults had the highest diet diversity values. Age-adjusted prevalence (95% confidence interval) of overweight, obesity, and abdominal obesity among Sri Lankan adults were 17.1% (13.8-20.7), 28.8% (24.8-33.1), and 30.8% (26.8-35.2), respectively. Men, compared with women, were less overweight, 14.2% (9.4-20.5) versus 18.5% (14.4-23.3), P = 0.03, less obese, 21.0% (14.9-27.7) versus 32.7% (27.6-38.2), P < .05; and less abdominally obese, 11.9% (7.4-17.8) versus 40.6% (35.1-46.2), P < .05. Although, prevalence of obesity has reached to epidemic level body weight misperception was common among Sri Lankan adults. Two-thirds of overweight males and 44.7% of females considered themselves as in "about right weight". Over one third of both male and female obese subjects perceived themselves as "about right weight" or "underweight". Nearly 32% of centrally obese men and women perceived that their waist circumference is about right. People who perceived overweight or very overweight (n = 154) only 63.6% tried to lose their body weight (n = 98), and quarter of adults seek advices from professionals (n = 39). A number of important conclusions can be drawn from this research project. Firstly, the newly developed FFQ is an acceptable tool for assessing the nutrient intake of Sri Lankans and will assist proper categorization of individuals by dietary exposure. Secondly, a substantial proportion of the Sri Lankan population does not consume a varied and balanced diet, which is suggestive of a close association between the nutrition-related NCDs in the country and unhealthy eating habits. Moreover, dietary diversity is positively associated with several socio-demographic characteristics and obesity among Sri Lankan adults. Lastly, although obesity is a major health issue among Sri Lankan adults, body weight misperception was common among underweight, healthy weight, overweight, and obese adults in Sri Lanka. Over 2/3 of overweight and 1/3 of obese Sri Lankan adults believe that they are in "right weight" or "under-weight" categories.

Improved healing of large segmental defects in the rat femur by reverse dynamization in the presence of bone morphogenetic protein-2

Background Large segmental defects in bone do not heal well and present clinical challenges. This study investigated modulation of the mechanical environment as a means of improving bone healing in the presence of bone morphogenetic protein (BMP)-2. Although the influence of mechanical forces on the healing of fractures is well established, no previous studies, to our knowledge, have described their influence on the healing of large segmental defects. We hypothesized that bone-healing would be improved by initial, low-stiffness fixation of the defect, followed by high-stiffness fixation during the healing process. We call this reverse dynamization. Methods A rat model of a critical-sized femoral defect was used. External fixators were constructed to provide different degrees of stiffness and, importantly, the ability to change stiffness during the healing process in vivo. Healing of the critical-sized defects was initiated by the implantation of 11 mg of recombinant human BMP (rhBMP)-2 on a collagen sponge. Groups of rats receiving BMP-2 were allowed to heal with low, medium, and high-stiffness fixators, as well as under conditions of reverse dynamization, in which the stiffness was changed from low to high at two weeks. Healing was assessed at eight weeks with use of radiographs, histological analysis, microcomputed tomography, dual x-ray absorptiometry, and mechanical testing. Results Under constant stiffness, the low-stiffness fixator produced the best healing after eight weeks. However, reverse dynamization provided considerable improvement, resulting in a marked acceleration of the healing process by all of the criteria of this study. The histological data suggest that this was the result of intramembranous, rather than endochondral, ossification. Conclusions Reverse dynamization accelerated healing in the presence of BMP-2 in the rat femur and is worthy of further investigation as a means of improving the healing of large segmental bone defects. Clinical Relevance These data provide the basis of a novel, simple, and inexpensive way to improve the healing of critical-sized defects in long bones. Reverse dynamization may also be applicable to other circumstances in which bonehealing is problematic.

Randomized trial of a clinic-based, community-supported, lifestyle intervention to improve physical activity and diet : The North Carolina enhanced WISEWOMAN project

Objective To determine if a clinic-based behavioral intervention program for low-income mid-life women that emphasizes use of community resources will increase moderate intensity physical activity (PA) and improve dietary intake. Methods Randomized trial conducted from May 2003 to December 2004 at one community health center in Wilmington, NC. A total of 236 women, ages 40–64, were randomized to receive an Enhanced Intervention (EI) or Minimal Intervention (MI). The EI consisted of an intensive phase (6 months) including 2 individual counseling sessions, 3 group sessions, and 3 phone calls from a peer counselor followed by a maintenance phase (6 months) including 1 individual counseling session and 7 monthly peer counselor calls. Both phases included efforts to increase participants' use of community resources that promote positive lifestyle change. The MI consisted of a one-time mailing of pamphlets on diet and PA. Outcomes, measured at 6 and 12 months, included the comparison of moderate intensity PA between study groups as assessed by accelerometer (primary outcome) and questionnaire, and dietary intake assessed by questionnaire and serum carotenoids (6 months only). Results For accelerometer outcomes, follow-up was 75% at 6 months and 73% at 12 months. Though moderate intensity PA increased in the EI and decreased in the MI, the difference between groups was not statistically significant (p = 0.45; multivariate model, p = 0.08); however, moderate intensity PA assessed by questionnaire (92% follow-up at 6 months and 75% at 12 months) was greater in the EI (p = 0.01; multivariate model, p = 0.001). For dietary outcomes, follow-up was 90% for questionnaire and 92% for serum carotenoids at 6 months and 74% for questionnaire at 12 months. Dietary intake improved more in the EI compared to the MI (questionnaire at 6 and 12 months, p < 0.001; serum carotenoid index, p = 0.05; multivariate model, p = 0.03). Conclusion The EI did not improve objectively measured PA, but was associated with improved self-reported and objective measures of dietary intake.

Monocyte chemoattractant protein-1 and nitric oxide promote adipogenesis in a model that mimics obesity

Objective: An increasing body of evidence is emerging linking adipogenesis and inflammation. Obesity, alone or as a part of the metabolic syndrome, is characterized by a state of chronic low-level inflammation as revealed by raised plasma levels of inflammatory cytokines and acute-phase proteins. If inflammation can, in turn, increase adipose tissue growth, this may be the basis for a positive feedback loop in obesity. We have developed a tissue engineering model for growing adipose tissue in the mouse that allows quantification of increases in adipogenesis. In this study, we evaluated the adipogenic potential of the inflammogens monocyte chemoattractant protein (MCP)-I and zymosan-A (Zy) in a murine tissue engineering model. Research Methods and Procedures: MCP-I and Zy were added to chambers filled with Matrigel and fibroblastgrowth factor 2. To analyze the role of inducible nitric oxide synthase (iNOS), the iNOS inhibitor aminoguanidine was added to the chamber. Results: Our results show that MCP-I generated proportionally large quantities of new adipose tissue. This neoadipogenesis was accompanied by an ingrowth of macrophages and could be mimicked by Zy. Aminoguanidine significantly inhibited the formation of adipose tissue. Discussion: Our findings demonstrate that low-grade inflammation and iNOS expression are important factors in adipogenesis, Because fat neoformation in obesity and the metabolic syndrome is believed to be mediated by macrophage-derived proinflammatory cytokines, this adipose tissue engineering system provides a model that could potentially be used to further unravel the pathogenesis of these two metabolic disorders.

Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GR βgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin- aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet.

F9 fimbriae of uropathogenic Escherichia coli are expressed at low temperature and recognise Galβ1-3GlcNAc-containing glycans

Uropathogenic Escherichia coli (UPEC) is the leading causative agent of urinary tract infections (UTI) in the developed world. Among the major virulence factors of UPEC, surface expressed adhesins mediate attachment and tissue tropism. UPEC strains typically possess a range of adhesins, with type 1 fimbriae and P fimbriae of the chaperone-usher class the best characterised. We previously identified and characterised F9 as a new chaperone-usher fimbrial type that mediates biofilm formation. However, the regulation and specific role of F9 fimbriae remained to be determined in the context of wild-type clinical UPEC strains. In this study we have assessed the distribution and genetic context of the f9 operon among diverse E. coli lineages and pathotypes and demonstrated that f9 genes are significantly more conserved in a UPEC strain collection in comparison to the well-defined E. coli reference (ECOR) collection. In the prototypic UPEC strain CFT073, the global regulator protein H-NS was identified as a transcriptional repressor of f9 gene expression at 37°C through its ability to bind directly to the f9 promoter region. F9 fimbriae expression was demonstrated at 20°C, representing the first evidence of functional F9 fimbriae expression by wild-type E. coli. Finally, glycan array analysis demonstrated that F9 fimbriae recognise and bind to terminal Galβ1-3GlcNAc structures.

A high and low fear phenotype mouse model

Fear-related illnesses such as post-traumatic stress disorder (PTSD) impose a tremendous burden on individual quality of life, families, and the national economy. In the military population, 17-20% of services members returning from deployment are diagnosed with PTSD. While treatments have improved for PTSD and are helpful for some, many people continue to suffer despite therapy. The aim of this research is to examine fear memory behaviourally and at the cellular level in the amygdala by using a unique inter-cross strain of high and low fear phenotype mice. An extended outcross C57BL/6J x DBA/2J (F8) are selected for high or low Pavlovian fear memory to context and cue. On presentation of either the original learning context or the cue (tone) mice display high or low levels of freezing as a behavioural measure of fear. In order to identify key aspects of the cellular basis of this difference in fear memory behaviour we are making measurements of protein levels and neuron numbers of a known pathway involved in the consolidation of a long term fear memory (pMAPK). Ongoing studies aim to determine if high fear behaviour is associated with differential signalling in the lateral amygdala compared to low fear behaviour. Additionally, by blocking this pathway in the lateral amygdala (LA), we aim to reduce fear behaviour following Pavlovian fear conditioning. This research will help to unravel the cellular mechanisms underlying high fear behaviour and advance the field toward targeted treatment and improved outcomes, ultimately improving human quality of life.

Imaging intracellular protein dynamics by spinning disk confocal microscopy

The palette of fluorescent proteins (FPs) has grown exponentially over the past decade, and as a result, live imaging of cells expressing fluorescently tagged proteins is becoming more and more mainstream. Spinning disk confocal (SDC) microscopy is a high-speed optical sectioning technique and a method of choice to observe and analyze intracellular FP dynamics at high spatial and temporal resolution. In an SDC system, a rapidly rotating pinhole disk generates thousands of points of light that scan the specimen simultaneously, which allows direct capture of the confocal image with low-noise scientific grade-cooled charge-coupled device cameras, and can achieve frame rates of up to 1000 frames per second. In this chapter, we describe important components of a state-of-the-art spinning disk system optimized for live cell microscopy and provide a rationale for specific design choices. We also give guidelines of how other imaging techniques such as total internal reflection microscopy or spatially controlled photoactivation can be coupled with SDC imaging and provide a short protocol on how to generate cell lines stably expressing fluorescently tagged proteins by lentivirus-mediated transduction.

Wing morphology, echolocation calls, diet and emergence time of black-bearded tomb bats (Taphozous melanopogon, Emballonuridae) from southwest China

We studied the wing morphology, echolocation calls, diet and emergence time of the black-bearded tomb bat (Taphozous melanopogon) from May to October 2006 in Guangxi Province, southwest China. Taphozous melanopogon has wings with high aspect ratio, high loading and pointed wing-tip shape-characteristics associated with fast flight in open space. This species usually produces low-intensity, low frequency, and frequency-modulated (FM) calls usually containing up to four harmonics, with most energy in the second (or sometimes third) harmonic. The diet of this species consists mostly of Lepidoptera and Hemiptera. Timing of evening emergence is correlated with the time of sunset. This is the first study to describe the flight and echolocation behavior of this species in China, and opens the way for future studies of its biology.

Echolocation calls, wing shape, diet and phylogenetic diagnosis of the endemic Chinese bat Myotis pequinius

We describe the echolocation calls, flight morphology and diet of the endemic Chinese bat Myotis pequinius Thomas, 1908. Orientation calls are broadband, and reach low terminal frequencies. Diet comprised 80% beetles by volume. Wing shape and call design suggest that the bats fly in cluttered habitats, and the possession of moderately long ears and the dietary composition imply they forage at least sometimes by gleaning. Myotis pequinius resembles a larger Oriental version of the western Palaearctic species M. nattereri. Phylogenetic analysis based on sequences of the cytochrome b gene of mitochondrial DNA (1,140 base pairs) from a range of Palaearctic Myotis species confirmed that M. pequinius is close to the nattereri group, and is a sister-species to the eastern Palaearctic M. bombinus. One bat sequenced from China could not be identified from available species descriptions. It was smaller than M. pequinius, and also differed from it in sequence divergence by 6.7%, suggesting the existence of additional, cryptic taxonomic diversity in this group. Our phylogenetic analysis also supports the recognition of M. schaubi as a species distinct from M. nattereri in Transcaucasia and south-western Asia. Myotis nattereri tschuliensis is more closely related to M. schaubi than to M. nattereri, and is best considered either as a subspecies of M. schaubi, or possibly as a distinct species.

High and low fear phenotypes show differences in phosphorylated (p44/42 ERK) MAPK-expressing neurons in the lateral amygdala

Post traumatic stress disorder (PTSD) is a serious medical condition effecting both military and civilian populations. While its etiology remains poorly understood it is characterized by high and prolonged levels of fear responding. One biological unknown is whether individuals expressing high or low conditioned fear memory encode the memory differently and if that difference underlies fear response. In this study we examined cellular mechanisms that underlie high and low conditioned fear behavior by using an advanced intercrossed mouse line (B6D2F1) selected for high and low Pavlovian fear response. A known requirement for consolidation of fear memory, phosphorylated mitogen activated protein kinase (p44/42 (ERK) MAPK (pMAPK)) in the lateral amygdala (LA) is a reliable marker of fear learning-related plasticity. In this study, we asked whether high and low conditioned fear behavior is associated with differential pMAPK expression in the LA and if so, is it due to an increase in neurons expressing pMAPK or increased pMAPK per neuron. To examine this, we quantified pMAPK-expressing neurons in the LA at baseline and following Pavlovian fear conditioning. Results indicate that high fear phenotype mice have more pMAPK-expressing neurons in the LA. This finding suggests that increased endogenous plasticity in the LA may be a component of higher conditioned fear responses and begins to explain at the cellular level how different fear responders encode fear memories. Understanding how high and low fear responders encode fear memory will help identify novel ways in which fear-related illness risk can be better predicted and treated.

Socioeconomic inequalities in diet and bodyweight: Evidence, causes, and intervention options

Diets low in fruits, vegetables, and whole grains, and high in saturated fat, salt, and sugar are the major contributors to the burden of chronic diseases globally. Previous research, and studies in this issue of Public Health Nutrition (PHN), show that unhealthy diets are more commonly observed among socioeconomically disadvantaged groups, and are key contributors to their higher rates of chronic disease. Most research examining socioeconomic inequalities in diet and bodyweight has been descriptive, and has focused on identifying the nature, extent, and direction of the inequalities. These types of studies are clearly necessary and important. We need however to move beyond description of the problem and focus much more on the question of why inequalities in diet and bodyweight exist. Furthering our understanding of this question will provide the necessary evidence-base to develop effective interventions to reduce the inequalities. The challenge of tackling dietary inequalities however doesn’t finish here: a maximally effective approach will also require equity-based policies that address the unequal population-distribution of social and economic resources, which is the fundamental root-cause of dietary and bodyweight inequalities.

Resistance exercise with low glycogen increases p53 phosphorylation and PGC-1α mRNA in skeletal muscle

Purpose We determined the effect of reduced muscle glycogen availability on cellular pathways regulating mitochondrial biogenesis and substrate utilization after a bout of resistance exercise. Methods Eight young, recreationally trained men undertook a glycogen depletion protocol of one-leg cycling to fatigue (LOW), while the contralateral (control) leg rested (CONT). Following an overnight fast, subjects completed 8 sets of 5 unilateral leg press repetitions (REX) at 80 % 1 Repetition Maximum (1RM) on each leg. Subjects consumed 500 mL protein/CHO beverage (20 g whey + 40 g maltodextrin) upon completion of REX and 2 h later. Muscle biopsies were obtained at rest and 1 and 4 h after REX in both legs. Results Resting muscle glycogen was higher in the CONT than LOW leg (~384 ± 114 vs 184 ± 36 mmol kg−1 dry wt; P < 0.05), and 1 h and 4 h post-exercise (P < 0.05). Phosphorylation of p53Ser15 increased 1 h post-exercise in LOW (~115 %, P < 0.05) and was higher than CONT at this time point (~87 %, P < 0.05). p38MAPKThr180/Tyr182 phosphorylation increased 1 h post-exercise in both CONT and LOW (~800–900 %; P < 0.05) but remained above rest at 4 h only in CONT (~585 %, P < 0.05; different between legs P < 0.05). Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) mRNA was elevated 4 h post-exercise in LOW (~200 %, P < 0.05; different between legs P < 0.05). There were no changes in Fibronectin type III domain-containing protein 5 (FNDC5) mRNA for CONT or LOW legs post-exercise. Conclusion Undertaking resistance exercise with low glycogen availability may enhance mitochondrial-related adaptations through p53 and PGC-1α-mediated signalling.

Acute inflammatory response to low-, moderate- and high-load resistance exercise in women with breast cancer-related lymphoedema

Background Resistance exercise is emerging as a potential adjunct therapy to aid in the management of breast cancer-related lymphedema (BCRL). However, the mechanisms underlying the relationships between the acute and long-term benefits of resistance exercise on BCRL are not well understood. Purpose. To examine the acute inflammatory response to upper-body resistance exercise in women with BCRL and to compare these effects between resistance exercises involving low-, moderate- and high-loads. The impact on lymphoedema status and associated symptoms was also compared. Methods Twenty-one women aged 62 ± 10 years with mild to severe BCRL participated in the study. Participants completed a low-load (15-20 repetition maximum), moderate-load (10-12 repetition maximum) and high-load (6-8 repetition maximum) exercise sessions consisting of three sets of six upper-body resistance exercises. Sessions were completed in a randomized order separated by a seven to 10 day wash-out period. Venous blood samples were obtained to assess markers of exercise-induced muscle damage and inflammation (creatine kinase [CK], C-reactive protein [CRP], interleukin-6 [IL-6] and tumour necrosis factor-alpha [TNF-α]). Lymphoedema status was assessed using bioimpedance spectroscopy and arm circumferences, and associated symptoms were assessed using visual analogue scales (VAS) for pain, heaviness and tightness. Measurements were conducted before and 24 hours after the exercise sessions. Results No significant changes in CK, CRP, IL-6 and TNF-α were observed following the low-, moderate- or high-load resistance exercise sessions. There were no significant changes in arm swelling or symptom severity scores across the three resistance exercise conditions. Conclusions The magnitude of acute exercise-induced inflammation following upper-body resistance exercise in women with BCRL does not vary between resistance exercise loads. Given these observations, moderate- to high-load resistance training is recommended for this patient population as these loads prompt superior physiological and functional benefits.