bluuebunny/crossref_metadata_2025 huggingface dataset:
Marked changes in neuropeptide expression accompany broadcast spawnings in the gastropod Haliotis asinina
Authors: York Patrick S , Cummins Scott F , Degnan Sandie M , Woodcroft Ben J , Degnan Bernard M
Published: May 2012

Introduction

A huge diversity of marine species reproduce by synchronously spawning their gametes into the water column. Although this species-specific event typically occurs in a particular season, the precise time and day of spawning often can not be predicted. There is little understanding of how the environment (e.g. water temperature, day length, tidal and lunar cycle) regulates a population’s reproductive physiology to synchronise a spawning event. The Indo-Pacific tropical abalone,Haliotis asinina, has a highly predictable spawning cycle, where individuals release gametes on the evenings of spring high tides on new and full moons during the warmer half of the year. These calculable spawning events uniquely allow for the analysis of the molecular and cellular processes underlying reproduction. Here we characterise neuropeptides produced inH. asininaganglia that are known in egg-laying molluscs to control vital aspects of reproduction.

Results

We demonstrate that genes encoding APGWamide, myomodulin, the putative proctolin homologue whitnin, FMRFamide, a schistosomin-like peptide (SLP), a molluscan insulin-related peptide (MIP) and a haliotid growth-associated peptide (HGAP) all are differentially expressed in the anterior ganglia during the two week spawning cycle in both male and female abalone. Each gene has a unique and sex-specific expression profile. Despite these differences, expression levels in most of the genes peak at or within 12 h of the spawning event. In contrast, lowest levels of transcript abundance typically occurs 36 h before and 24 h after spawning, with differences in peak and low expression levels being most pronounced in genes orthologous to known molluscan reproduction neuromodulators.

Conclusions

Exploiting the predictable semi-lunar spawning cycle of the gastropodH. asinina, we have identified a suite of evolutionarily-conserved, mollusc-specific and rapidly-evolving neuropeptides that appear to contribute to the regulation of spawning. Dramatic increases and decreases in ganglionic neuropeptide expression levels from 36 h before to 24 h after the broadcast spawning event are consistent with these peptides having a regulatory role in translating environmental signals experienced by a population into a synchronous physiological output, in this case, the release of gametes.
Clinical application of computerized evaluation and re-education biofeedback prototype for sensorimotor control of the hand in stroke patients
Authors: Hsu Hsiu-Yun , Lin Cheng-Feng , Su Fong-Chin , Kuo Huan-Ting , Chiu Haw-Yen , Kuo Li-Chieh
Published: May 2012

Background

Hemianaesthesia patients usually exhibit awkward and inefficient finger movements of the affected hands. Conventionally, most interventions emphasize the improvement of motor deficits, but rarely address sensory capability and sensorimotor control following stroke. Thus it is critical for stroke patients with sensory problems to incorporate appropriate strategies for dealing with sensory impairment, into traditional hand function rehabilitation programs. In this study, we used a custom-designed computerized evaluation and re-education biofeedback (CERB) prototype to analyze hand grasp performances, and monitor the training effects on hand coordination for stroke patients with sensory disturbance and without motor deficiency.

Methods

The CERB prototype was constructed to detect momentary pinch force modulation for 14 sub-acute and chronic stroke patients with sensory deficiency and 14 healthy controls. The other ten chronic stroke patients (ranges of stroke period: 6–60 months) were recruited to investigate the effects of 4-weeks computerized biofeedback treatments on the hand control ability. The biofeedback procedures provide visual and auditory cues to the participants when the interactive force of hand-to-object exceeded the target latitude in a pinch-up-holding task to trigger optimal motor strategy. Follow-up measurements were conducted one month after training. The hand sensibility, grip forces and results of hand functional tests were recorded and analyzed.

Results

The affected hands of the 14 predominant sensory stroke patients exhibited statistically significant elevation in the magnitude of peak pinch force (p = 0.033) in pinching and lifting-up tasks, and poor results for hand function tests (p = 0.005) than sound hands did. In addition, the sound hands of patients were less efficient in force modulation (p = 0.009) than the hands of healthy subjects were. Training with the biofeedback system produced significant improvements in grip force modulation (p = 0.020) and better performances in the subtests of pin insertion (p = 0.019), and lifting of lightweight objects (p = 0.005).

Conclusions

The CERB prototype can provide momentary and interactive information for quantitative assessing and re-educating force modulation appropriately for stroke patients with sensory deficits. Furthermore, the patients could transfer the learned strategy to improve hand function.
Transient Receptor Potential Melastatin 8 (TRPM8) Channels are Involved in Body Temperature Regulation
Authors: Gavva Narender R , Davis Carl , Lehto Sonya G , Rao Sara , Wang Weiya , Zhu Dawn XD
Published: May 2012

Background:

Transient receptor potential cation channel subfamily M member 8 (TRPM8) is activated by cold temperature in vitro and has been demonstrated to act as a ‘cold temperature sensor’ in vivo. Although it is known that agonists of this ‘cold temperature sensor’, such as menthol and icilin, cause a transient increase in body temperature (Tb), it is not known if TRPM8 plays a role in Tb regulation. Since TRPM8 has been considered as a potential target for chronic pain therapeutics, we have investigated the role of TRPM8 in Tb regulation.

Results:

We characterized five chemically distinct compounds (AMG0635, AMG2850, AMG8788, AMG9678, and Compound 496) as potent and selective antagonists of TRPM8 and tested their effects on Tb in rats and mice implanted with radiotelemetry probes. All five antagonists used in the study caused a transient decrease in Tb (maximum decrease of 0.98°C). Since thermoregulation is a homeostatic process that maintains Tb about 37°C, we further evaluated whether repeated administration of an antagonist attenuated the decrease in Tb. Indeed, repeated daily administration of AMG9678 for four consecutive days showed a reduction in the magnitude of the Tb decrease Day 2 onwards.

Conclusions:

The data reported here demonstrate that TRPM8 channels play a role in Tb regulation. Further, a reduction of magnitude in Tb decrease after repeated dosing of an antagonist suggests that TRPM8's role in Tb maintenance may not pose an issue for developing TRPM8 antagonists as therapeutics.
Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides
Authors: El-Mesery ME , Al-Gayyar MM , Salem HA , Darweish MM , El-Mowafy AM
Published: May 2012

Background

The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA), claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP) in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP), lipid peroxidation (measured as malondialdehyde; MDA) and leukocytic count (LC). Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein.

Results

EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg). Interestingly, DHA (125 mg/kg) markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85) and leukocytosis (r = 0.89), thus attesting to a diagnostic/prognostic role for CRP.

On the other hand, a single CP dose (10 mg/kg) induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold), a rise in serum creatinine/urea levels (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying causal relationships.

Conclusion

DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels (thus implying a diagnostic/prognostic role for CRP). Further, this study is the first to reveal that DHA can obliterate the lethal CP-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing leukocytosis, systemic inflammation, and oxidative stress.
Whole-liver radiotherapy for end-stage colorectal cancer patients with massive liver metastases and advanced hepatic dysfunction
Authors: Yeo Seung-Gu , Kim Dae Yong , Kim Tae Hyun , Kim Sun Young , Hong Yong Sang , Jung Kyung Hae
Published: May 2012

Background

To investigate whether whole-liver radiotherapy (RT) is beneficial in end-stage colorectal cancer with massive liver metastases and severe hepatic dysfunction.

Methods

Between June 2004 and July 2008, 10 colorectal cancer patients, who exhibited a replacement of over three quarters of their normal liver by metastatic tumors and were of Child-Pugh class B or C in liver function with progressive disease after undergoing chemotherapy, underwent whole-liver RT. RT was administered using computed tomography-based three-dimensional planning and the median dose was 21 Gy (range, 21-30) in seven fractions. Improvement in liver function tests, defined as a decrease in the levels within 1 month after RT, symptom palliation, toxicity, and overall survival were analyzed retrospectively.

Results

Levels of alkaline phosphatase, total bilirubin, aspartate transaminase, and alanine transaminase improved in 8, 6, 9, and all 10 patients, respectively, and the median reduction rates were 42%, 68%, 50%, and 57%, respectively. Serum carcinoembryonic antigen level decreased after RT in three of four assessable patients. For all patients, pain levels decreased and acute toxicity consisted of nausea/vomiting of grade ≤ 2. Further chemotherapy became possible in four of 10 patients. Mean survival after RT was 80 ± 80 days (range, 20-289); mean survival for four patients who received post-RT chemotherapy was 143 ± 100 days (range, 65-289), versus 38 ± 16 days (range, 20-64) for the six patients who did not receive post-RT chemotherapy (p = 0.127).

Conclusions

Although limited by small case number, this study demonstrated a possible role of whole-liver RT in improving hepatic dysfunction and delaying mortality from hepatic failure for end-stage colorectal cancer patients with massive liver metastases. Further studies should be followed to confirm these findings.
Anti-oxidative effects of the biennial flower of Panax notoginseng against H2O2-induced cytotoxicity in cultured PC12 cells
Authors: Choi Roy Chi-Yan , Jiang Zhiyong , Xie Heidi Qun , Cheung Anna Wing-Han , Lau David Tai-Wai , Fu Qiang , Dong Tina Tingxia , Chen Jijun , Wang Zhengtao , Tsim Karl Wah-Keung
Published: May 2012

Background

Radix notoginseng is used in Chinese medicine to improve blood circulation and clotting; however, the pharmacological activities of other parts of Panax notoginseng have yet to be explored. The present study reports the anti-oxidative effects of various parts of Panax notoginseng.

Methods

Various parts of Panax notoginseng, including the biennial flower, stem-leaf, root-rhizome, fiber root and sideslip, were used to prepare extracts and analyzed for their anti-oxidation effects, namely suppressing xanthine oxidase activity, H2O2-induced cytotoxicity and H2O2-induced ROS formation.

Results

Among various parts of the herb (biennial flower, stem-leaf, root-rhizome, fiber root and sideslip), the water extract of the biennial flower showed the strongest effects in (i) inhibiting the enzymatic activity of xanthine oxidase and (ii) protecting neuronal PC12 cells against H2O2-induced cytotoxicity. Only the water extracts demonstrated such anti-oxidative effects while the ethanol extracts did not exert significant effects in suppressing xanthine oxidase and H2O2-induced neuronal cytotoxicity.

Conclusions

The present study demonstrates the biennial flower of Panax notoginseng to have neuroprotection effect on cultured neurons and the underlying protection mechanism may involve anti-oxidation.
Psychological and weight-related characteristics of patients with anorexia nervosa-restricting type who later develop bulimia nervosa
Authors: Nishimura Hiroki , Komaki Gen , Ando Tetsuya , Nakahara Toshihiro , Oka Takakazu , Kawai Keisuke , Nagata Toshihiko , Nishizono Aya , Okamoto Yuri , Okabe Kenjiro , Koide Masanori , Yamaguchi Chikara , Saito Satoshi , Ohkuma Kazuyoshi , Nagata Katsutaro , Naruo Tetsuro , Takii Masato , Kiriike Nobuo , Ishikawa Toshio ,   Japanese Genetic Research Group for Eating Disorders
Published: May 2012

Background

Patients with anorexia nervosa-restricting type (AN-R) sometimes develop accompanying bulimic symptoms or the full syndrome of bulimia nervosa (BN). If clinicians could predict who might change into the bulimic sub-type or BN, preventative steps could be taken. Therefore, we investigated anthropometric and psychological factors possibly associated with such changes.

Method

All participants were from a study by the Japanese Genetic Research Group for Eating Disorders. Of 80 patients initially diagnosed with AN-R, 22 changed to the AN-Binge Eating/Purging Type (AN-BP) and 14 to BN for some period of time. The remaining 44 patients remained AN-R only from the onset to the investigation period. Variables compared by ANOVA included anthropometric measures, personality traits such as Multiple Perfectionism Scale scores and Temperament and Character Inventory scores, and Beck Depression Inventory-II scores.

Results

In comparison with AN-R only patients, those who developed BN had significantly higher current BMI (p < 0.05) and maximum BMI in the past (p < 0.05). They also scored significantly higher for the psychological characteristic of parental criticism (p < 0.05) and lower in self-directedness (p < 0.05), which confirms previous reports, but these differences disappeared when the depression score was used as a co-variant. No significant differences were obtained for personality traits or depression among the AN-R only patients irrespective of their duration of illness.

Conclusion

The present findings suggest a tendency toward obesity among patients who cross over from AN-R to BN. Low self-directedness and high parental criticism may be associated with the development of BN by patients with AN-R, although the differences may also be associated with depression.
Mansonia africana and Mansonia uniformis are Vectors in the transmission of Wuchereria bancrofti lymphatic filariasis in Ghana
Authors: Ughasi Josephine , Bekard Hilaria Esiawonam , Coulibaly Maimouna , Adabie-Gomez Delphina , Gyapong John , Appawu Maxwell , Wilson Michael David , Boakye Daniel Adjei
Published: May 2012

Background

Recent data from Ghana indicates that after seven rounds of annual mass drug administration (MDA) there is still sustained transmission albeit at low levels in certain areas where Anopheles melas, An. gambiae s.s., Mansonia and Culex species are the main biting mosquitoes. Anopheles gambiae s.l. and An. funestus are the known vectors in Ghana and a recent report indicated that An. melas could transmit at low level microfilaraemia. However, because An. melas is not found everywhere there was the need to determine whether any of the other culicine species could also be playing a role in the transmission of LF.

Methods

Indoor mosquitoes collected once a month for three months using pyrethrum spray catches in six communities within the Kommenda-Edina-Eguafo-Abirem (KEEA) District, Central Region of Ghana were morphologically identified, dissected and examined for the presence of W. bancrofti. Additionally, stored mosquito samples collected during previous years in 8 communities from the Gomoa District also in the Central Region were similarly processed. The identities of all W. bancrofti parasites found were confirmed using an established PCR method.

Results

A total of 825 indoor resting mosquitoes comprising of 501 Anopheles species, 239 Mansonia species, 84 Culex species and 1 Aedes species were dissected and examined for the presence of W. bancrofti. Mansonia africana had infection and infectivity rates of 2.5%. and 2.1% respectively. Anopheles gambiae s.l. had an infection rate of 0.4% and a similar infectivity rate. None of the Culex sp. and Aedes sp were found with infection. From the stored mosquitoes the infection and infectivity rates for M. africana were 7.6% (N = 144) and 2.8% respectively whilst the corresponding rates for M. uniformis were 2.9% (N = 244) and 0.8%.

Conclusions

This is the first report of Mansonia species as vectors of lymphatic filariasis (LF) in Ghana and in West Africa since that of 1958 in Guinea. The revelation of a hitherto unrecognised vector which is possibly more efficient in transmission than the recognised ones has a profound implication for elimination of lymphatic filariasis programmes in the sub-region.
Effect of dietary stable isotopic ratios of carbon and nitrogen on the extent of their incorporation into tissues of rats
Authors: Lv Wentao , Ju Tingting , Dong Bing , Yu Boyang , Yin Jingdong
Published: May 2012

This study was conducted to investigate the effect of different dietary ratios of 13 C to 12 C or 15 N to 14 N on their relative incorporation into tissues. Eighty male rats were used in two 21-day feeding trials in which they were fed diets with either high δ13C levels (δ13C = −13.89‰ and δ15N = 2.37‰ in experiment 1 and δ13C = −19.34‰ and δ15N = 4.73‰ in experiment 2) or low δ13C levels (δ13C = −17.90‰ and δ15N = 3.08‰ in experiment 1 and δ13C = −21.76‰ and δ15N = 0.53‰ in experiment 2), meanwhile, the dietary δ15N levels were designed to two ranks. Blood, liver, adipose and muscle tissues were collected on day 0, 3, 7, 14, and 21 for determination of 13 C, 12 C, 15 N and 14 N isotopes. Rat growth rate, antioxidant capacity and metabolic parameters were also assessed. The results indicate that adipose tissue tend to deplete 13 C before the stable isotopic ratios achieved final equilibrium. Therefore, feeds with different isotopic signatures had different incorporation rates into tissues. Low dietary 13 C levels decreased tissue δ13C values whereas high dietary 13 C levels did not alter tissue δ13C values during the 21-d experiment. Blood δ15N values were a reliable parameter in assessing the relative contribution of dietary nitrogen to tissues. This study revealed a relationship between dietary isotopic signatures and their incorporation rates into rat tissues. However, more studies are needed to illustrate the mechanism through which dietary isotopic ratios influence the extent of isotopic incorporation into the tissues.
Mycophenolic acid counteracts B cell proliferation and plasmablast formation in patients with systemic lupus erythematosus
Authors: Eickenberg Sebastian , Mickholz Eva , Jung Elisabeth , Nofer Jerzy-Roch , Pavenstädt Herrmann , Jacobi Annett M
Published: May 2012

Introduction

Clinical trials revealed a high efficacy of mycophenolate mofetil (MMF) in inducing and maintaining remission in patients with class III-V-lupus nephritis. Also extrarenal manifestations respond to MMF treatment. However, few attempts have been undertaken to delineate its mechanism of action in systemic lupus erythematosus (SLE) a disease characterized by enhanced B cell activation.

Methods

Clinical and paraclinical parameters of 107 patients with SLE were recorded consecutively and analyzed retrospectively. Patients were divided into treatment groups (MMF: n = 39, azathioprine (AZA) n = 30 and controls without immunosuppressive therapy n = 38). To further delineate the effect of mycophenolic acid (MPA) on naive and memory B cells in vitro assays were performed.

Results

Although patients taking AZA flared more frequently than patients on MMF or controls, the analysis of clinical parameters did not reveal significant differences. However, profound differences in paraclinical parameters were found. B cell frequencies and numbers were significantly higher in patients taking MMF compared to those on AZA but lower numbers and frequencies of plasmablasts were detected compared to AZA-treated patients or controls. Notably, MMF treatment was associated with a significantly higher frequency and number of transitional B cells as well as naive B cells compared to AZA treatment. Differences in T cell subsets were not significant. MPA abrogated in vitro proliferation of purified B cells completely but had only moderate impact on B cell survival.

Conclusions

The thorough inhibition of B cell activation and plasma cell formation by MMF might explain the favorable outcomes of previous clinical trials in patients with SLE, since enhanced B cell proliferation is a hallmark of this disease.
Expression profiling of cancerous and normal breast tissues identifies microRNAs that are differentially expressed in serum from patients with (metastatic) breast cancer and healthy volunteers
Authors: van Schooneveld Eleni , Wouters Maartje CA , Van der Auwera Ilse , Peeters Dieter J , Wildiers Hans , Van Dam Peter A , Vergote Ignace , Vermeulen Peter B , Dirix Luc Y , Van Laere Steven J
Published: May 2012

Introduction

MicroRNAs (miRNAs) are a group of small noncoding RNAs involved in the regulation of gene expression. As such, they regulate a large number of cellular pathways, and deregulation or altered expression of miRNAs is associated with tumorigenesis. In the current study, we evaluated the feasibility and clinical utility of circulating miRNAs as biomarkers for the detection and staging of breast cancer.

Methods

miRNAs were extracted from a set of 84 tissue samples from patients with breast cancer and eight normal tissue samples obtained after breast-reductive surgery. After reverse transcription and preamplification, 768 miRNAs were profiled by using the TaqMan low-density arrays. After data normalization, unsupervised hierarchical cluster analysis (UHCA) was used to investigate global differences in miRNA expression between cancerous and normal samples. With fold-change analysis, the most discriminating miRNAs between both tissue types were selected, and their expression was analyzed on serum samples from 20 healthy volunteers and 75 patients with breast cancer, including 16 patients with untreated metastatic breast cancer. miRNAs were extracted from 200 μl of serum, reverse transcribed, and analyzed in duplicate by using polymerase chain reaction (qRT-PCR).

Results

UHCA showed major differences in miRNA expression between tissue samples from patients with breast cancer and tissue samples from breast-reductive surgery (P < 0.0001). Generally, miRNA expression in cancerous samples tends to be repressed when compared with miRNA expression in healthy controls (P = 0.0685). The four most discriminating miRNAs by fold-change (miR-215, miR-299-5p, miR-411, and miR-452) were selected for further analysis on serum samples. All miRNAs at least tended to be differentially expressed between serum samples from patients with cancer and serum samples from healthy controls (miR-215, P = 0.094; miR-299-5P, P = 0.019; miR-411, P = 0.002; and miR-452, P = 0.092). For all these miRNAs, except for miR-452, the greatest difference in expression was observed between serum samples from healthy volunteers and serum samples from untreated patients with metastatic breast cancer.

Conclusions

Our study provides a basis for the establishment of miRNAs as biomarkers for the detection and eventually staging of breast cancer through blood-borne testing. We identified and tested a set of putative biomarkers of breast cancer and demonstrated that altered levels of these miRNAs in serum from patients with breast cancer are particularly associated with the presence of metastatic disease.
Estrogen-Induced Memory Enhancements Are Blocked by Acute Bisphenol A in Adult Female Rats: Role of Dendritic Spines
Authors: Inagaki T. , Frankfurt M. , Luine V.
Published: May 2012

Acute effects of bisphenol (BPA), an environmental chemical, on estradiol (17α or β-E2)-dependent recognition memory and dendritic spines in the medial prefrontal cortex and hippocampus were investigated in adult female rats. Ovariectomized rats received BPA 30 min before or immediately after a sample trial (viewing objects), and retention trials were performed 4 h later. Retention trials tested discrimination between old and new objects (visual memory) or locations (place memory). When given immediately after the sample trial, BPA, 1–400 μg/kg, did not alter recognition memory, but 1 and 40 μg/kg BPA, respectively, blocked 17β-E2-dependent increases in place and visual memory. When ovariectomized rats were tested with 17α-E2, 1 μg/kg BPA blocked place memory, but up to 40 μg did not block visual memory. BPA, given to cycling rats at 40 μg/kg, blocked visual, but not place, memory during proestrus when 2 h intertrial delays were given. Spine density was assessed at times of memory consolidation (30 min) and retention (4 h) after 17β-E2 or BPA + 17β-E2. In prefrontal cortex, BPA did not alter E2-dependent increases. In the hippocampus, BPA blocked E2 increases in basal spines at 4 h and was additive with E2 at 30 min. Thus, these novel data show that doses of BPA, below the current Environmental Protection Agency safe limit of 50 μg/kg, rapidly alter neural functions dependent on E2 in adult female rats.
Hyperandrogenism Sensitizes Leukocytes to Hyperglycemia to Promote Oxidative Stress in Lean Reproductive-Age Women
Authors: González Frank , Nair K. Sreekumaran , Daniels Janice K. , Basal Eati , Schimke Jill M. , Blair Hilary E.
Published: May 2012

Context:

Hyperandrogenism and oxidative stress are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate oxidative stress.

Objective:

The purpose of this study was to determine the effect of oral androgen administration on fasting and glucose-stimulated leukocytic reactive oxygen species (ROS) generation, reduced nicotinamide adenine dinucleotide phosphate oxidase p47phox subunit gene expression, and plasma thiobarbituric acid-reactive substances (TBARS) in lean healthy reproductive-age women.

Participants, Design, and Setting:

Sixteen lean healthy ovulatory reproductive-age women were treated with 130 mg dehydroepiandrosterone (DHEA) or placebo (n = 8 each) for 5 d in this randomized, controlled, double-blind study that was performed at an an academic medical center.

Main Outcome Measures:

Leukocytic ROS generation, p47phox gene expression, and plasma TBARS were quantified in the fasting state and 2 h after glucose ingestion, before and after treatment.

Results:

Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any prooxidant markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-sulfate, increased the percent change in glucose-challenged p47phox RNA content, and increased the percent change in fasting and glucose-challenged ROS generation from mononuclear cells and polymorphonuclear cells, p47phox protein content, and plasma TBARS.

Conclusion:

Elevation of circulating androgens comparable to what is present in PCOS increases leukocytic ROS generation, p47phox gene expression, and plasma TBARS to promote oxidative stress in lean healthy reproductive-age women. Thus, hyperandrogenemia activates and sensitizes leukocytes to glucose in this population.
The cystic fibrosis-associated ΔF508 mutation confers post-transcriptional destabilization on the C. elegans ABC transporter PGP-3
Authors: He Liping , Skirkanich Jennifer , Moronetti Lorenza , Lewis Rosemary , Lamitina Todd
Published: May 2012

Membrane proteins comprise ~30% of the proteome. During the early stages of maturation, this class of proteins can experience localized misfolding in distinct cellular compartments, such as the cytoplasm, endoplasmic reticulum (ER) lumen, and ER membrane. ER quality control (ERQC) mechanisms monitor folding and determine whether a membrane protein is appropriately folded or is misfolded and warrants degradation. ERQC plays critical roles in human diseases, such as cystic fibrosis, where deletion of a single amino acid (F508) results in the misfolding and degradation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Cl- channel. We introduced the ΔF508 mutation into C. elegans PGP-3, a 12 transmembrane ABC transporter with 15% identity to CFTR. When expressed in intestinal epithelial cells, PGP-3wt was stable and efficiently trafficked to the apical plasma membrane through a COPII-dependent mechanism. However, PGP-3ΔF508 was post-transcriptionally destabilized, resulting in reduced total and apical membrane protein levels. Genetic or physiological activation of the osmotic stress response pathway, which causes accumulation of the chemical chaperone glycerol, stabilized PGP-3ΔF508. Efficient degradation of PGP-3ΔF508 required the function of several C. elegans endoplasmic reticulum-associated degradation (ERAD) homologs, suggesting that destabilization occurs through an ERAD-type mechanism. Our studies show that the ΔF508 mutation causes post-transcriptional destabilization and degradation of PGP-3 in C. elegans epithelial cells. This model, combined with the power of C. elegans genetics, provides a new opportunity to genetically dissect metazoan ERQC.
Aerobic and anaerobic metabolism in oxygen minimum layer fishes: the role of alcohol dehydrogenase
Authors: Torres Joseph J. , Grigsby Michelle D. , Clarke M. Elizabeth
Published: May 2012

Zones of minimum oxygen form at intermediate depth in all the world’s oceans as a result of global circulation patterns that keep the water at oceanic mid-depths out of contact with the atmosphere for hundreds of years. In areas where primary production is very high, the microbial oxidation of sinking organic matter results in very low oxygen concentrations at mid-depths. Such is the case with the Arabian Sea, with O2 concentrations reaching zero at 200 m and remaining very low (<0.1 ml O2 l–1) for hundreds of meters below this depth, and in the California borderland, where oxygen levels reach 0.2 ml O2 l–1 at 700 m with severely hypoxic (<1.0 ml O2 l–1) waters at depths 300 m above and below that. Despite the very low oxygen, mesopelagic fishes (primarily lanternfishes: Mytophidae) inhabiting the Arabian Sea and California borderland perform a daily vertical migration into the low-oxygen layer, spending daylight hours in the oxygen minimum zone and migrating upward into normoxic waters at night. To find out how fishes were able to survive their daily sojourns into the minimum zone, we tested the activity of four enzymes, one (lactate dehydrogenase, LDH) that served as a proxy for anaerobic glycolysis with a conventional lactate endpoint, a second (citrate synthase, CS) that is indicative of aerobic metabolism, a third (malate dehydrogenase) that functions in the Krebs’ cycle and as a bridge linking mitochondrion and cytosol, and a fourth (alcohol dehydrogenase, ADH) that catalyzes the final reaction in a pathway where pyruvate is reduced to ethanol. Ethanol is a metabolic product easily excreted by fish, preventing lactate accumulation. The ADH pathway is rarely very active in vertebrate muscle; activity has previously been seen only in goldfish and other cyprinids capable of prolonged anaerobiosis. Activity of the enzyme suite in Arabian Sea and California fishes was compared with that of ecological analogs in the same family and with the same lifestyle but living in systems with much higher oxygen concentrations: the Gulf of Mexico and the Southern Ocean. ADH activities in the Arabian Sea fishes were similar to those of goldfish, far higher than those of confamilials from the less severe minimum in the Gulf of Mexico, suggesting that the Arabian Sea fishes are capable of exploiting the novel ethanol endpoint to become competent anaerobes. In turn, the fishes of California exhibited a higher ADH activity than their Antarctic relatives. It was concluded that ADH activity is more widespread in fishes than previously believed and that it may play a role in allowing vertically migrating fishes to exploit the safe haven afforded by severe oxygen minima.
Muscular strategy shift in human running: dependence of running speed on hip and ankle muscle performance
Authors: Dorn Tim W. , Schache Anthony G. , Pandy Marcus G.
Published: May 2012

Humans run faster by increasing a combination of stride length and stride frequency. In slow and medium-paced running, stride length is increased by exerting larger support forces during ground contact, whereas in fast running and sprinting, stride frequency is increased by swinging the legs more rapidly through the air. Many studies have investigated the mechanics of human running, yet little is known about how the individual leg muscles accelerate the joints and centre of mass during this task. The aim of this study was to describe and explain the synergistic actions of the individual leg muscles over a wide range of running speeds, from slow running to maximal sprinting. Experimental gait data from nine subjects were combined with a detailed computer model of the musculoskeletal system to determine the forces developed by the leg muscles at different running speeds. For speeds up to 7 m s–1, the ankle plantarflexors, soleus and gastrocnemius, contributed most significantly to vertical support forces and hence increases in stride length. At speeds greater than 7 m s–1, these muscles shortened at relatively high velocities and had less time to generate the forces needed for support. Thus, above 7 m s–1, the strategy used to increase running speed shifted to the goal of increasing stride frequency. The hip muscles, primarily the iliopsoas, gluteus maximus and hamstrings, achieved this goal by accelerating the hip and knee joints more vigorously during swing. These findings provide insight into the strategies used by the leg muscles to maximise running performance and have implications for the design of athletic training programs.
An experimental exploration of the incorporation of hydrogen isotopes from dietary sources into avian tissues
Authors: Wolf Nathan , Newsome Seth D. , Fogel Marilyn L. , del Rio Carlos Martínez
Published: May 2012

The analysis of hydrogen stable isotopes (∂D) is a potentially powerful tool for studying animal ecology. Unlike other stable isotopes used in ecological research, however, we are less familiar with the physiological processes that influence the incorporation of hydrogen isotopes from dietary resources to animal tissues. Here we present the results of a controlled feeding experiment utilizing Japanese quail (Cortunix japonica) that was designed to: (1) estimate the relative contributions of diet to the ∂D signatures of blood plasma, red blood cells, intestine, liver, muscle and feathers; (2) investigate possible differences among these same tissues in diet to tissue discrimination; and (3) explore the differences in incorporation dynamics between deuterium (2H) and a well-studied isotope, 13C, for blood plasma solids and red blood cells. Tissues differed in both the relative contribution of diet to tissue ∂D and diet to tissue discrimination. The average residence time of both hydrogen and carbon was significantly lower in plasma solids than in red blood cells. The average residence time of hydrogen was significantly lower than that of carbon in plasma solids, but not in red blood cells. Although the average residence times of hydrogen and carbon were positively correlated, the correlation was weak. Hence the incorporation of carbon seems to be a poor predictor of that of hydrogen.
A vitellogenin polyserine cleavage site: highly disordered conformation protected from proteolysis by phosphorylation
Authors: Havukainen Heli , Underhaug Jarl , Wolschin Florian , Amdam Gro , Halskau Øyvind
Published: May 2012

Vitellogenin (Vg) is an egg-yolk precursor protein in most oviparous species. In honeybee (Apis mellifera), the protein (AmVg) also affects social behavior and life-span plasticity. Despite its manifold functions, the AmVg molecule remains poorly understood. The subject of our structure-oriented AmVg study is its polyserine tract — a little-investigated repetitive protein segment mostly found in insects. We previously reported that AmVg is tissue specifically cleaved in the vicinity of this tract. Here, we show that, despite its potential for an open, disordered structure, AmVg is unexpectedly resistant to trypsin/chymotrypsin digestion at the tract. Our findings suggest that multiple phosphorylation plays a role in this resilience. Sequence variation is highly pronounced at the polyserine region in insect Vgs. We demonstrate that sequence differences in this region can lead to structural variation, as NMR and circular dichroism (CD) evidence assign different conformational propensities to polyserine peptides from the honeybee and the jewel wasp Nasonia vitripennis; the former is extended and disordered and the latter more compact and helical. CD analysis of the polyserine region of bumblebee Bombus ignitus and wasp Pimpla nipponica supports a random coil structure in these species. The spectroscopic results strengthen our model of the AmVg polyserine tract as a flexible domain linker shielded by phosphorylation.
Thermal games in crayfish depend on establishment of social hierarchies
Authors: Tattersall Glenn J. , Luebbert Joshua P. , LePine Olivia K. , Ormerod Kiel G. , Mercier A. Joffre
Published: May 2012

An unequal resource distribution is commonly seen in dominance hierarchies, in which the individual with the higher status is more successful in obtaining the resource. One possible resource is preferred temperature. When situations allow, ectotherms regulate their body temperature by behaviourally selecting different environmental conditions, achieving, when possible, a preferred temperature. Using a shuttlebox, the preferred temperature for Procambarus clarkii was determined to be 23.9°C with upper and lower voluntary escape temperatures of 25.9 and 21.8°C, respectively. If this preferred temperature zone (21.8–25.9°C) was valued as a resource, given the choice between a preferred temperature and a non-preferred temperature, crayfish should compete over the preferred temperature, with the dominant individual of dyadic pairs achieving the preferred temperature more often than the subordinate. Using a dual-choice experimental tank, competition over a binary temperature choice between rank-established paired crayfish was determined under both warm and cold challenge conditions (warm vs preferred temperature and cold vs preferred temperature, respectively). In naive pairings, similar levels of competition over the preferred temperature occurred in both warm and cold challenge trials, as predicted by game theory. In established pairings, however, dominant crayfish gained significantly greater access to preferred temperature in both warm and cold challenge conditions. These results demonstrate that crayfish engage in a cost–benefit assessment during their initial agonistic contests over temperature, but as hierarchies mature, these thermal games are decided by the dominant animal gaining primary access to the temperature resource.
The visual control of landing and obstacle avoidance in the fruit flyDrosophila melanogaster
Authors: van Breugel Floris , Dickinson Michael H.
Published: May 2012

Landing behavior is one of the most critical, yet least studied, aspects of insect flight. In order to land safely, an insect must recognize a visual feature, navigate towards it, decelerate, and extend its legs in preparation for touchdown. Although previous studies have focused on the visual stimuli that trigger these different components, the complete sequence has not been systematically studied in a free-flying animal. Using a real-time 3D tracking system in conjunction with high speed digital imaging, we were able to capture the landing sequences of fruit flies (Drosophila melanogaster) from the moment they first steered toward a visual target, to the point of touchdown. This analysis was made possible by a custom-built feedback system that actively maintained the fly in the focus of the high speed camera. The results suggest that landing is composed of three distinct behavioral modules. First, a fly actively turns towards a stationary target via a directed body saccade. Next, it begins to decelerate at a point determined by both the size of the visual target and its rate of expansion on the retina. Finally, the fly extends its legs when the visual target reaches a threshold retinal size of approximately 60 deg. Our data also let us compare landing sequences with flight trajectories that, although initially directed toward a visual target, did not result in landing. In these ‘fly-by’ trajectories, flies steer toward the target but then exhibit a targeted aversive saccade when the target subtends a retinal size of approximately 33 deg. Collectively, the results provide insight into the organization of sensorimotor modules that underlie the landing and search behaviors of insects.
The formation and functional consequences of heterogeneous mitochondrial distributions in skeletal muscle
Authors: Pathi B. , Kinsey S. T. , Howdeshell M. E. , Priester C. , McNeill R. S. , Locke B. R.
Published: May 2012

Diffusion plays a prominent role in governing both rates of aerobic metabolic fluxes and mitochondrial organization in muscle fibers. However, there is no mechanism to explain how the non-homogeneous mitochondrial distributions that are prevalent in skeletal muscle arise. We propose that spatially variable degradation with dependence on O2 concentration, and spatially uniform signals for biogenesis, can account for observed distributions of mitochondria in a diversity of skeletal muscle. We used light and transmission electron microscopy and stereology to examine fiber size, capillarity and mitochondrial distribution in fish red and white muscle, fish white muscle that undergoes extreme hypertrophic growth, and four fiber types in mouse muscle. The observed distributions were compared with those generated using a coupled reaction-diffusion/cellular automata (CA) mathematical model of mitochondrial function. Reaction-diffusion analysis of metabolites such as oxygen, ATP, ADP and PCr involved in energy metabolism and mitochondrial function were considered. Coupled to the reaction-diffusion approach was a CA approach governing mitochondrial life cycles in response to the metabolic state of the fiber. The model results were consistent with the experimental observations and showed higher mitochondrial densities near the capillaries because of the sometimes steep gradients in oxygen. The present study found that selective removal of mitochondria in the presence of low prevailing local oxygen concentrations is likely the primary factor dictating the spatial heterogeneity of mitochondria in a diversity of fibers. The model results also suggest decreased diffusional constraints corresponding to the heterogeneous mitochondrial distribution assessed using the effectiveness factor, defined as the ratio of the reaction rate in the system with finite rates of diffusion to that in the absence of any diffusion limitation. Thus, the non-uniform distribution benefits the muscle fiber by increasing the energy status and increasing sustainable metabolic rates.
How well do muscle biomechanics predict whole-animal locomotor performance? The role of Ca2+ handling
Authors: Seebacher Frank , Pollard Samuel R. , James Rob S.
Published: May 2012

It is important to determine the enabling mechanisms that underlie locomotor performance to explain the evolutionary patterns and ecological success of animals. Our aim was to determine the extent to which calcium (Ca2+) handling dynamics modulate the contractile properties of isolated skeletal muscle, and whether the effects of changing Ca2+ handling dynamics in skeletal muscle are paralleled by changes in whole-animal sprint and sustained swimming performance. Carp (Cyprinus carpio) increased swimming speed by concomitant increases in tail-beat amplitude and frequency. Reducing Ca2+ release from the sarcoplasmic reticulum (SR) by blocking ryanodine receptors with dantrolene decreased isolated peak muscle force and was paralleled by a decrease in tail-beat frequency and whole-animal sprint performance. An increase in fatigue resistance following dantrolene treatment may reflect the reduced depletion of Ca2+ stores in the SR associated with lower ryanodine receptor (RyR) activity. Blocking RyRs may be detrimental by reducing force production and beneficial by reducing SR Ca2+ depletion so that there was no net effect on critical sustained swimming speed (Ucrit). In isolated muscle, there was no negative effect on force production of blocking Ca2+ release via dihydropyridine receptors (DHPRs) with nifedipine. Nifedipine decreased fatigue resistance of isolated muscle, which was paralleled by decreases in tail-beat frequency and Ucrit. However, sprint performance also decreased with DHPR inhibition, which may indicate a role in muscle contraction of the Ca2+ released by DHPR into the myocyte. Inhibiting sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity with thapsigargin decreased fatigue resistance, suggesting that SERCA activity is important in avoiding Ca2+ store depletion and fatigue. We have shown that different molecular mechanisms modulate the same muscle and whole-animal traits, which provides an explanatory model for the observed variations in locomotor performance within and between species.