bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Vitamin D Supplementation Versus Placebo for Urgency Urinary Incontinence: A Pilot Study
Authors: Markland Alayne D. , Tangpricha Vin , Mark Beasley T. , Vaughan Camille P. , Richter Holly E. , Burgio Kathryn L. , Goode Patricia S.
Published: December 2018

Objectives

To estimate the efficacy of vitamin D supplementation to reduce urgency urinary incontinence (UUI) episodes.

Design

Pilot, two‐arm, randomized trial conducted from 2013 to 2017. Interventions were 12 weeks of weekly oral 50,000 IU vitamin D3 or placebo.

Setting

Academic, university‐based outpatient clinic.

Participants

Community‐dwelling postmenopausal women, 50 years or older, with at least three UUI episodes on 7‐day bladder diary and serum vitamin 25‐hydroxyvitamin D (25[OH]D) of 30 ng/mL or less.

Measurements

The primary efficacy estimate was the percentage change in UUI episodes. Secondary estimates included changes in other lower urinary tract symptoms, along with exploratory subgroup analysis by race/ethnicity and obesity.

Results

We randomized 56 women (aged 50‐84 years; mean = 60.5 ± 8.2 years), 28 to vitamin D and 28 to placebo; 51 completed treatments. Mean serum 25(OH)D at baseline (21.2 ± 5.2 and 18.2 ± 5.6, P = .30) improved to 57.9 ± 16.3 ng/mL with vitamin D3 and 21.9 ± 8.2 ng/mL with placebo (P < .001). UUI episodes per 24‐hour day decreased by 43.0% with vitamin D3 compared to 27.6% with placebo (P = .22). Among black women (n = 33), UUI episodes decreased by 63.2% with vitamin D3 compared to 22.9% with placebo (P = .03). Among obese women, UUI episodes decreased by 54.1% with vitamin D compared to 32.7% with placebo (P = .29). For all women, changes in voiding frequency (P = .40), nocturia (P = .40), urgency (P = .90), incontinence severity (P = .81), and overactive bladder symptom severity (P = .47) were not different between arms.

Conclusions

Postmenopausal women with UUI and vitamin D insufficiency demonstrated a greater than 40% decrease in UUI episodes, which did not reach statistical significance compared to placebo, except in the subset of black women. The results of this pilot study support further investigation of vitamin D3 alone or in combination with other treatments for UUI, particularly for women in higher‐risk subgroups. J Am Geriatr Soc 67:570–575, 2019.
Reply to: Replacing Urine Catheters for Urinary Tract Infections: A Closer Look
Authors: Babich Tanya , Leibovici Leonard , Avni Tomer
Published: December 2018

This letter comments on the letter by Karakonstantis et al.
Replacing Urine Catheters for Urinary Tract Infections: A Closer Look
Authors: Karakonstantis Stamatis , Lydakis Charalampos
Published: December 2018

See the Reply by Babich et al.
Functional diversifications of GhERF1 duplicate genes after the formation of allotetraploid cotton
Authors: Liu Chunxiao , Zhang Tian Zhen
Published: December 2018

Whole genome duplication, a prevalent force of evolution in plants, results in massive genome restructuring in different organisms. Roles of the resultant duplicated genes are poorly understood, both functionally and evolutionarily. In the present study, differentially expressed ethylene responsive factors (GhERF1s), anchored on Chr‐A07 and Chr‐D07, were isolated from a high‐yielding cotton hybrid (XZM2) and its parents. The GhERF1 was located in the B3 subgroup of the ethylene responsive factors subfamily involved in conferring tolerance to abiotic stress. Nucleotide sequence analysis of 524 diverse accessions, together with quantitative real‐time polymerase chain reaction analysis, elucidated that de‐functionalization of GhERF1‐7A occurred due to one base insertion following formation of the allotetraploid cotton. Our quantitative trait loci and association mapping analyses highlighted a role for GhERF1‐7A in conferring high boll number per plant in modern cotton cultivars. Overexpression of GhERF1‐7A in transgenic Arabidopsis resulted in a substantial increase in the number of siliques and total seed yield. Neo‐functionalization of GhERF1‐7A was also observed in modern cultivars rather than in races and/or landraces, further supporting its role in the development of high‐yielding cotton cultivars. Both de‐ and neo‐functionalization occurred in one of the duplicate genes, thus providing new genomic insight into the evolution of allotetraploid cotton species.
Keratan sulfate (KS)‐proteoglycans and neuronal regulation in health and disease: the importance ofKS‐glycodynamics and interactive capability with neuroregulatory ligands
Authors: Melrose James
Published: December 2018

Compared to the other classes of glycosaminoglycans (GAGs), that is, chondroitin/dermatan sulfate, heparin/heparan sulfate and hyaluronan, keratan sulfate (KS), have the least known of its interactive properties. In the human body, the cornea and the brain are the two most abundant tissue sources ofKS. EmbryonicKSis synthesized as a linear poly‐N‐acetyllactosamine chain ofd‐galactose‐GlcNAc repeat disaccharides which become progressively sulfated with development, sulfation of GlcNAc is more predominant than galactose.KScontains multi‐sulfated high‐charge density, monosulfated and non‐sulfated poly‐N‐acetyllactosamine regions and thus is a heterogeneous molecule in terms of chain length and charge distribution. A recent proteomics study on cornealKSdemonstrated its interactivity with members of the Slit‐Robbo and Ephrin‐Ephrin receptor families and proteins which regulate RhoGTPase signaling and actin polymerization/depolymerization in neural development and differentiation.KSdecorates a number of peripheral nervous system/CNSproteoglycan (PG) core proteins. The astrocyteKS‐PGabakan defines functional margins of the brain and is up‐regulated following trauma. The chondroitin sulfate/KS PGaggrecan forms perineuronal nets which are dynamic neuroprotective structures with anti‐oxidant properties and roles in neural differentiation, development and synaptic plasticity. Brain phosphacan a chondroitin sulfate,KS,HNK‐1PGhave roles in neural development and repair. The intracellular microtubule and synaptic vesicleKS‐PGsMAP1B andSV2 have roles in metabolite transport, storage, and export of neurotransmitters and cytoskeletal assembly.MAP1B has binding sites for tubulin and actin through which it promotes cytoskeletal development in growth cones and is highly expressed during neurite extension. The interactive capability ofKSwith neuroregulatory ligands indicate varied roles forKS‐PGs in development and regenerative neural processes.

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Chronic adenosine A2A receptor blockade induces locomotor sensitization and potentiates striatal LTD IN GPR37‐deficient mice
Authors: Morató Xavier , Gonçalves Francisco Q. , Lopes João P. , Jauregui Olga , Soler Concepció , Fernández‐Dueñas Víctor , Cunha Rodrigo A. , Ciruela Francisco
Published: December 2018

Adenosine A2A receptors (A2AR) play a key role in modulating dopamine‐dependent locomotor activity, as heralded by the sensitization of locomotor activity upon chronic A2AR blockade, which is associated with elevated dopamine levels and altered corticostriatal synaptic plasticity. Since the orphan receptor GPR37 has been shown to modulate A2AR function in vivo, we aimed to test whether the A2AR‐mediated sensitization of locomotor activity is GPR37‐dependent and involves adaptations of synaptic plasticity. To this end, we administered a selective A2AR antagonist, SCH58261 (1 mg/kg, i.p.), daily for 14 days, and the locomotor sensitization, striatum‐dependent cued learning, and corticostriatal synaptic plasticity (i.e., long‐term depression) were compared in wild‐type and GPR37−/− mice. Notably, GPR37 deletion promoted A2AR‐associated locomotor sensitization but not striatum‐dependent cued learning revealed upon chronic SCH58261 treatment of mice. Furthermore, chronic A2AR blockade potentiated striatal long‐term depression in corticostriatal synapses of GPR37−/− but not of wild‐type mice, thus correlating well with neurochemical alterations of the adenosinergic system. Overall, these results revealed the importance of GPR37 regulating A2AR‐dependent locomotor sensitization and synaptic plasticity in the basal ganglia circuitry.

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Soluble programmed death‐1 is a useful indicator for inflammatory and fibrosis severity in chronic hepatitis B
Authors: Zhou Liang , Li Xiaoyan , Huang Xiaohui , Chen Lubiao , Gu Lin , Huang Yuehua
Published: December 2018

Elevated programmed death‐1 (PD‐1) has been found in immune cells in viral infections and plays an important role in infection persistence. The soluble form of PD‐1 (sPD‐1) is involved in tumours and viral infections. The aim of this study was to investigate the role of sPD‐1 in chronic hepatitis B (CHB). A total of two hundred and eighteen CHB patients and sixty healthy controls (HC) were enrolled. Demographic data and clinical parameters were collected. An ELISA assay was used to measure serum sPD‐1 levels, and the relationships between sPD‐1 and clinical/virological characteristics was analysed. sPD‐1 levels in CHB patients were higher (median 4.409 IQR 3.435‐5.306 pg/mL) than those of HC individuals (median 0.3665 IQR 0.2425‐0.5010 pg/mL). Among patients at various disease stages, patients with immune activity showed the highest sPD‐1 levels (median 5.138 IQR 4.329‐5.406 pg/mL). sPD‐1 concentration was associated with HBV markers (HBsAg, HBV DNA and HBeAg) and biochemical parameters (serum aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBil] and gamma glutamyl transferase [γ‐GT] levels) (all P < 0.05). sPD‐1 levels were higher in CHB patients with moderate‐to‐severe inflammation or fibrosis than in those with mild inflammation or fibrosis, regardless of ALT levels. The association between sPD‐1 and disease progression of CHB suggests that sPD‐1 could serve as a new indicator in assessing liver fibrosis. These findings may further aid in determining the initiation of antiviral treatment in patients with normal ALT levels.
Feeding ecological knowledge: the underutilised power of faecal DNA approaches for carnivore diet analysis
Authors: Monterroso Pedro , Godinho Raquel , Oliveira Teresa , Ferreras Pablo , Kelly Marcella J. , Morin Dana J. , Waits Lisette P. , Alves Paulo C. , Mills L. Scott
Published: December 2018

Accurate analyses of the diets of predators are key to understand trophic interactions and defining conservation strategies. Diets are commonly assessed through analysis of non‐invasively collected scats, and the use of faecal DNA (fDNA) analysis can reduce the species misidentifications that could lead to biased ecological inference.

We review the scientific literature since publication of the first paper on amplifying fDNA, in order to assess trends in the use of genetic non‐invasive sampling (gNIS) for predator species identification in scat‐based diet studies of North American and European terrestrial mammalian carnivores (Carnivora). We quantify error rates in morphology‐based predator species identification. We then provide an overview of how applying gNIS would improve research on trophic interactions and other areas of carnivore ecology.

We found that carnivore species identity was verified by using gNIS in only 8% of 400 studies of carnivore diets based on scats. The median percentage of false positives (i.e. samples wrongly identified as belonging to the target species) in morphology‐based studies was 18%, and was consistent regardless of species’ body size. We did not find an increasing trend in the use of gNIS over time, despite the existing technical capability to identify almost all carnivore species.

New directions for fDNA studies include employing high‐throughput sequencing (HTS) and DNA metabarcoding to identify the predator species, the individual predator, the entire assemblage of consumed items, and the microbiome of the predator and pathogens. We conclude that HTS protocols and metagenomic approaches hold great promise for elevating gNIS as a fundamental cornerstone for future research in ecology and conservation biology of mammals.
Relationship between the dietary intake, serum, and breast milk concentrations of vitamin A and vitamin E in a cohort of women over the course of lactation
Authors: da Silva Ana Gabriella Costa Lemos , de Sousa Rebouças Amanda , Mendonça Beatriz Maria Alves , Silva Danna Calina Nogueira e , Dimenstein Roberto , Ribeiro Karla Danielly da Silva
Published: December 2018

This study evaluated the nutritional status of lactating women with regard to vitamins A and E and the relationship between dietary intake and concentrations in serum and milk. A longitudinal study was conducted with 43 women at a hospital in northeastern Brazil. Blood and milk samples and food intake recalls were obtained at three moments during the breastfeeding period. Retinol and alpha‐tocopherol were analysed by high‐performance liquid chromatography. Dietary inadequacy was analysed according to the estimated average requirement, with intrapersonal variation adjusted by the multiple source method. Food intake was classified by quartiles of consumption. Serum retinol was 1.65 μmol/L, with 5% of low concentrations (<0.7 μmol/L) at the first collection. Serum alpha‐tocopherol decreased from 30.18 to 25.49 μmol/L at the third collection (P = 0.008), with an increase in the percentage frequency of deficiency (<12 μmol/L). Both vitamins maintained stable concentrations in milk at the different collection times, and the overall dietary inadequacy of vitamins A and E was 58% and 100%, respectively. There was a correlation only between vitamin A intake and serum retinol (r = 0.403, P = 0.007), and higher retinol concentrations were found in women classified in the highest consumption quartile (P = 0.031). Over the course of lactation, there was a high degree of inadequacy in vitamin intake and a reduction in serum alpha‐tocopherol, whereas its concentrations in milk remained unchanged. Dietary intake of vitamin A has been shown to influence serum retinol, which underscores the importance of adequate nutrition and monitoring of vitamin deficiency during lactation.
Effects of the sodium‐glucose cotransporter 2 inhibitor dapagliflozin on fluid distribution: A comparison study with furosemide and tolvaptan
Authors: Ohara Ken , Masuda Takahiro , Murakami Takuya , Imai Toshimi , Yoshizawa Hiromichi , Nakagawa Saki , Okada Mari , Miki Atsushi , Myoga Akihiro , Sugase Taro , Sekiguchi Chuji , Miyazawa Yasuharu , Maeshima Akito , Akimoto Tetsu , Saito Osamu , Muto Shigeaki , Nagata Daisuke
Published: December 2018

Aim

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors are an antihyperglycemic drug with diuretic properties. We recently reported that an SGLT2 inhibitor ameliorated extracellular fluid expansion with a transient increase in urinary Na+ excretion. However, the effects of SGLT2 inhibitors on fluid distribution in comparison to conventional diuretics remain unclear.

Methods

Forty chronic kidney disease patients with fluid retention (average estimated glomerular filtration rate 29.2 ± 3.2 mL/min per 1.73 m2) were divided into the SGLT2 inhibitor dapagliflozin (DAPA), loop diuretic furosemide (FR) and vasopressin V2 receptor antagonist tolvaptan (TLV). The body fluid volume was measured on days 0 and 7 using a bioimpedance analysis device.

Results

In all three groups, body weight was significantly and similarly decreased, and urine volume numerically increased for 7 days. Bioimpedance analysis showed that the changes in intracellular water were similar, but that there were significant changes in the extracellular water (ECW) (DAPA −8.4 ± 1.7, FR −12.5 ± 1.3, TLV −7.4 ± 1.5%, P = 0.048). As a result, the change in the ratio of ECW to total body water in the DAPA group was significantly smaller than that in the FR group, but numerically larger than that in the TLV group (DAPA −1.5 ± 0.5, FR −3.6 ± 0.5, TLV −0.5 ± 0.4%, P < 0.001).

Conclusion

Sodium‐glucose cotransporter 2 inhibitor DAPA predominantly decreased the ECW with a mild increase in urine volume, but the change in the ECW/total body water was smaller than that in patients treated with FR, and larger than that in patients treated with TLV, suggesting that the effects of SGLT2 inhibitors on fluid distribution may differ from those of conventional diuretics.
Phytochrome A signal transduction 1 and CONSTANS‐LIKE 13 coordinately orchestrate shoot branching and flowering in leafy Brassica juncea
Authors: Muntha Sidra Tul , Zhang Lili , Zhou Yufeng , Zhao Xuan , Hu Zhongyuan , Yang Jinghua , Zhang Mingfang
Published: December 2018

Branching is a major determinant of crop yield, and enables vigorous shoot growth and the production of a dense canopy. Phytochrome A signal transduction 1 (PAT1) positively regulates phytochrome A signal transduction in response to light, but its effects on branching remain unknown. In this study, we mapped PAT1, and revealed a previously unknown role related to branching and flowering in leafy Brassica juncea. Earlier and increased branching was observed when PAT1 expression was down‐regulated, implying that PAT1 negatively regulates shoot branching. Additionally, down‐regulated PAT1 expression reversed the inhibited branching induced by far‐red light, suggesting PAT1 is involved in the shade avoidance response. PAT1 negatively regulated branching only after bud initiation. The observed interaction between PAT1 and BRC1 implied that PAT1 influences bud outgrowth in a BRC1‐dependent manner. Biochemical and genetic evidence indicate that PAT1 directly interacts with CONSTANS‐LIKE 13 (COL13), which negatively regulates flowering, with the resulting PAT1–COL13 complex mediating shoot branching and flowering. Our findings reveal a new crosstalk modality between phytochrome signalling and flowering pathways during the regulation of shoot branching and flowering. The data presented herein may be useful for future studies involving the editing of the GRAS family transcription factor PAT1 gene to enhance crop productivity and enable earlier harvesting.
Enhanced ROS scavenging and sugar accumulation contribute to drought tolerance of naturally occurring autotetraploids in Poncirus trifoliata
Authors: Wei Tonglu , Wang Yue , Xie Zongzhou , Guo Dayong , Chen Chuanwu , Fan Qijun , Deng Xiaodong , Liu Ji‐Hong
Published: December 2018

Tetraploids have been reported to exhibit increased stress tolerance, but the underlying molecular and physiological mechanisms remain poorly understood. In this study, autotetraploid plants were identified by screening natural seedlings of trifoliate orange (Poncirus trifoliata). The tetraploids exhibited different morphology and displayed significantly enhanced drought and dehydration tolerance in comparison with the diploid progenitor. Transcriptome analysis indicated that a number of stress‐responsive genes and pathways were differentially influenced and enriched in the tetraploids, in particular those coding for enzymes related to antioxidant process and sugar metabolism. Transcript levels and activities of antioxidant enzymes (peroxidase and superoxide dismutase) and sucrose‐hydrolysing enzyme (vacuolar invertase) were increased in the tetraploids upon exposure to the drought, concomitant with greater levels of glucose but lower level of reactive oxygen species (ROS). These data indicate that the tetraploids might undergo extensive transcriptome reprogramming of genes involved in ROS scavenging and sugar metabolism, which contributes, synergistically or independently, to the enhanced stress tolerance of the tetraploid. Our results reveal that the tetraploids take priority over the diploid for stress tolerance by maintaining a more robust system of ROS detoxification and osmotic adjustment via elevating antioxidant capacity and sugar accumulation in comparison with the diploid counterpart.
Diverse Sorghum bicolor accessions show marked variation in growth and transcriptional responses to arbuscular mycorrhizal fungi
Authors: Watts‐Williams Stephanie J. , Emmett Bryan D. , Levesque‐Tremblay Veronique , MacLean Allyson M. , Sun Xuepeng , Satterlee James W. , Fei Zhangjun , Harrison Maria J.
Published: December 2018

Sorghum is an important crop grown worldwide for feed and fibre. Like most plants, it has the capacity to benefit from symbioses with arbuscular mycorrhizal (AM) fungi, and its diverse genotypes likely vary in their responses. Currently, the genetic basis of mycorrhiza‐responsiveness is largely unknown. Here, we investigated transcriptional and physiological responses of sorghum accessions, founders of a bioenergy nested association mapping panel, for their responses to four species of AM fungi. Transcriptome comparisons across four accessions identified mycorrhiza‐inducible genes; stringent filtering criteria revealed 278 genes that show mycorrhiza‐inducible expression independent of genotype and 55 genes whose expression varies with genotype. The latter suggests variation in phosphate transport and defence across these accessions. The mycorrhiza growth and nutrient responses of 18 sorghum accessions varied tremendously, ranging from mycorrhiza‐dependent to negatively mycorrhiza‐responsive. Additionally, accessions varied in the number of AM fungi to which they showed positive responses, from one to several fungal species. Mycorrhiza growth and phosphorus responses were positively correlated, whereas expression of two mycorrhiza‐inducible phosphate transporters, SbPT8 and SbPT9, correlated negatively with mycorrhizal growth responses. AM fungi improve growth and mineral nutrition of sorghum, and the substantial variation between lines provides the potential to map loci influencing mycorrhiza responses.
Donor‐derived strongyloidiasis in a Saudi pediatric kidney transplant recipient: A case report and mini‐review
Authors: Alsager Khaled , Waqar Saadia , Furrukh Hina , Alattas Nadia
Published: December 2018

S. stercoralis infection has been identified as a donor‐derived infection in cases of solid organ transplant among recipients with no prior risk factor for parasitic exposure. Worldwide and regional reports from the adult kidney transplant population highlight this indirect method of infection and caution about delayed diagnosis, severe complications, and death related to donor‐derived S. stercoralis infection. We report a deceased‐donor‐derived S. stercoralis infection in a 12‐year‐old Saudi girl who underwent kidney transplantation. This is the first pediatric case reported outside the United States of America. Although she presented with mild bouts of gastrointestinal symptoms, the need for additional immune suppression put her at risk of serious complications. A literature review highlights the importance of awareness about S. stercoralis infections and complications in kidney transplant recipients, pretransplant screening of donors based on risk assessment, and the challenges with treatment availability and duration in this vulnerable population.
Multilevel regulation of non‐photochemical quenching and state transitions by chloroplast NADPH‐dependent thioredoxin reductase
Authors: Nikkanen Lauri , Guinea Diaz Manuel , Toivola Jouni , Tiwari Arjun , Rintamäki Eevi
Published: December 2018

In natural growth habitats, plants face constant, unpredictable changes in light conditions. To avoid damage to the photosynthetic apparatus on thylakoid membranes in chloroplasts, and to avoid wasteful reactions, it is crucial to maintain a redox balance both within the components of photosynthetic electron transfer chain and between the light reactions and stromal carbon metabolism under fluctuating light conditions. This requires coordinated function of the photoprotective and regulatory mechanisms, such as non‐photochemical quenching (NPQ) and reversible redistribution of excitation energy between photosystem II (PSII) and photosystem I (PSI). In this paper, we show that the NADPH‐dependent chloroplast thioredoxin system (NTRC) is involved in the control of the activation of these mechanisms. In plants with altered NTRC content, the strict correlation between lumenal pH and NPQ is partially lost. We propose that NTRC contributes to downregulation of a slow‐relaxing constituent of NPQ, whose induction is independent of lumenal acidification. Additionally, overexpression of NTRC enhances the ability to adjust the excitation balance between PSII and PSI, and improves the ability to oxidize the electron transfer chain during changes in light conditions. Thiol regulation allows coupling of the electron transfer chain to the stromal redox state during these changes.
Function of berberine on porcine in vitro fertilization embryo development and differential expression analysis of microRNAs
Authors: Wang Jun‐Li , Zhang Chao , Liu Bing , Huang Xiao‐Meng , Dai Jia‐Ge , Tian Jian‐Hui , Gao Jian‐Ming
Published: December 2018

Contents

The effect of berberine (Ber) on in vitro fertilization (IVF) embryo development in pigs and the associated differential expression of microRNAs (miRNAs) in the embryo were investigated. NCSU‐23 embryonic culture medium was used for a control group, while NCSU‐23 embryonic culture medium added with Ber was used for a Ber group. The embryo development rates in these groups were determined, and the zygotes, 4‐ and 8‐cell embryos, and blastocysts were collected for cDNA microarray analysis. The development rates of 2‐, 4‐, 8‐cell embryos and blastocysts were significantly higher in the Ber group than those in the control group (p < 0.01). The differentially expressed miRNAs in the 8‐cell versus the 4‐cell stage in control group as well as in the 8‐cell Ber group versus the 8‐cell control group overlapped, and it was found that nine miRNAs were commonly upregulated and two of them were downregulated, while there was no overlap among the other groups. The target genes of Ber‐regulated miRNAs at the 8‐cell stage were mainly associated with the molecular pathway of nucleic acid and protein synthesis. These findings suggest that Ber may regulate the expression of miRNAs at the 8‐cell stage, which is beneficial to provide material reserves for the maternal to zygote transition of porcine embryos, thereby increasing the porcine IVF embryo development rate.
When trafficking and signaling mix: How subcellular location shapes G protein‐coupled receptor activation of heterotrimeric G proteins
Authors: Lobingier Braden T. , von Zastrow Mark
Published: December 2018

G protein‐coupled receptors (GPCRs) physically connect extracellular information with intracellular signal propagation. Membrane trafficking plays a supportive role by “bookending” signaling events: movement through the secretory pathway delivers GPCRs to the cell surface where receptors can sample the extracellular environment, while endocytosis and endolysosomal membrane trafficking provide a versatile system to titrate cellular signaling potential and maintain homeostatic control. Recent evidence suggests that, in addition to these important effects, GPCR trafficking actively shapes the cellular signaling response by altering the location and timing of specific receptor‐mediated signaling reactions. Here, we review key experimental evidence underlying this expanding view, focused on GPCR signaling mediated through activation of heterotrimeric G proteins located in the cytoplasm. We then discuss lingering and emerging questions regarding the interface between GPCR signaling and trafficking.
Sex differences in the circulatory responses to an isocapnic cold pressor test
Authors: Stone Rachel M. , Ainslie Philip N. , Kerstens Thijs P. , Wildfong Kevin W. , Tymko Michael M.
Published: December 2018

New Findings

What is the central question of this study?

Do sex differences exist in the cardiorespiratory responses to an isocapnic cold pressor test (CPT)?

What is the main finding and its importance?

During the CPT, there were no sex differences in the respiratory response; however, females demonstrated a reduced mean arterial pressure and reduced dilatation of the common carotid artery. Given that the CPT is predictive of future cardiovascular events, these data have clinical implications for improving the utility of the CPT to determine cardiovascular health risk. Sex differences should be taken into consideration when conducting and interpreting a CPT.

The cold pressor test (CPT) elicits a transient increase in sympathetic nervous activity, minute ventilation (), mean arterial pressure (MAP) and common carotid artery (CCA) diameter in healthy individuals. Although the extent of dilatation of the CCA in response to the CPT has been used as a clinical indicator of cardiovascular health status, the potential sex differences have yet to be explored. In response to a CPT, we hypothesized that elevations in and MAP and dilatation of the CCA would be attenuated in females compared with males. In 20 young, healthy participants (10 females), we measured the respiratory, cardiovascular and CCA responses during a CPT, which consisted of a 3 min immersion of the right foot into 0–1 ice water. Blood pressure (via finger photoplethysmography), heart rate (via electrocardiogram) and CCA diameter and velocity (via Duplex ultrasound) were simultaneously recorded immediately before and during the CPT. During the CPT, while controlling end‐tidal gases to baseline values, the main findings were as follows: (i) no sex differences were present in absolute or relative changes in (P = 0.801 and P = 0.179, respectively); (ii) the relative MAP and CCA diameter response were reduced in females by 51 and 55%, respectively (P = 0.008 and P = 0.029 versus males, respectively); and (iii) the relative MAP responses was positively correlated with the dilatation of the CCA in males (r = 0.42, P = 0.019), in females (r = 0.43, P = 0.019) and in males and females combined (r = 0.55, P < 0.001). Given that the CPT is used as a clinical tool to assess cardiovascular health status, sex differences should be considered in future studies.
Decrement in resting and insulin‐stimulated soleus muscle mitochondrial respiration is an early event in diet‐induced obesity in mice
Authors: Brunetta Henver Simionato , de Paula Gabriela Cristina , de Oliveira Jade , Martins Eduarda Lopes , dos Santos Gustavo Jorge , Galina Antonio , Rafacho Alex , de Bem Andreza Fabro , Nunes Everson Araújo
Published: December 2018

New Findings

What is the central question of this study?

What are the temporal responses of mitochondrial respiration and mitochondrial responsivity to insulin in soleus muscle fibres from mice during the development of obesity and insulin resistance?

What is the main finding and its importance?

Short‐ and long‐term feeding with a high‐fat diet markedly reduced soleus mitochondrial respiration and mitochondrial responsivity to insulin before any change in glycogen synthesis. Muscle glycogen synthesis and whole‐body insulin resistance were present after 14 and 28 days, respectively. Our findings highlight the plasticity of mitochondria during the development of obesity and insulin resistance.

Recently, significant attention has been given to the role of muscle mitochondrial function in the development of insulin resistance associated with obesity. Our aim was to investigate temporal alterations in mitochondrial respiration, H2O2 emission and mitochondrial responsivity to insulin in permeabilized skeletal muscle fibres during the development of obesity in mice. Male Swiss mice (5–6 weeks old) were fed with a high‐fat diet (60% calories from fat) or standard diet for 7, 14 or 28 days to induce obesity and insulin resistance. Diet‐induced obese (DIO) mice presented with reduced glucose tolerance and hyperinsulinaemia after 7 days of high‐fat diet. After 14 days, the expected increase in muscle glycogen content after systemic injection of glucose and insulin was not observed in DIO mice. At 28 days, blood glucose decay after insulin injection was significantly impaired. Complex I (pyruvate + malate) and II (succinate)‐linked respiration and oxidative phosphorylation (ADP) were decreased after 7 days of high‐fat diet and remained low in DIO mice after 14 and 28 days of treatment. Moreover, mitochondria from DIO mice were incapable of increasing respiratory coupling and ADP responsivity after insulin stimulation in all observed periods. Markers of mitochondrial content were reduced only after 28 days of treatment. The mitochondrial H2O2 emission profile varied during the time course of DIO, with a reduction of H2O2 emission in the early stages of DIO and an increased emission after 28 days of treatment. Our data demonstrate that DIO promotes transitory alterations in mitochondrial physiology during the early and late stages of insulin resistance related to obesity.
Foramen ovale blood flow and cardiac function after main pulmonary artery occlusion in fetal sheep
Authors: Lantto Juulia , Erkinaro Tiina , Haapsamo Mervi , Huhta Heikki , Voipio Hanna‐Marja , Hohimer A. Roger , Davis Lowell E. , Acharya Ganesh , Räsänen Juha
Published: December 2018

New Findings

What is the central question of this study?

At near‐term gestation, foramen ovale blood flow accounts for a significant proportion of fetal left ventricular output. Can the foramen ovale increase its volume blood flow when right ventricular afterload is increased by main pulmonary artery occlusion?

What is the main finding and its importance?

Foramen ovale volume blood flow increased during main pulmonary artery occlusion. However, this increase was attributable to an increase in fetal heart rate, because left ventricular stroke volume remained unchanged. These findings suggest that the foramen ovale has a limited capacity to increase its volume blood flow.

The foramen ovale (FO) accounts for the majority of fetal left ventricular (LV) output. Increased right ventricular afterload can cause a redistribution of combined cardiac output between the ventricles. To understand the capability of the FO to increase its volume blood flow and thus LV output, we mechanically occluded the main pulmonary artery in seven chronically instrumented near‐term sheep fetuses. We hypothesized that FO volume blood flow and LV output would increase during main pulmonary artery occlusion. Fetal cardiac function and haemodynamics were assessed by pulsed and tissue Doppler at baseline, 15 and 60 min after occlusion of the main pulmonary artery and 15 min after occlusion was released. Fetal ascending aorta and central venous pressures and blood gas values were monitored. Main pulmonary artery occlusion initially increased fetal heart rate (P < 0.05) from [mean (SD)] 158 (7) to 188 (23) beats min−1 and LV cardiac output (P < 0.0001) from 629 (198) to 776 (283) ml min−1. Combined cardiac output fell (P < 0.0001) from 1524 (341) to 720 (273) ml min−1. During main pulmonary artery occlusion, FO volume blood flow increased (P < 0.001) from 507 (181) to 776 (283) ml min−1. This increase was related to fetal tachycardia, because LV stroke volume did not change. Fetal ascending aortic blood pressure remained stable. Central venous pressure was higher (P < 0.05) during the occlusion than after it was released. During the occlusion, fetal pH decreased and increased. Left ventricular systolic dysfunction developed while LV diastolic function was preserved. Right ventricular systolic and diastolic function deteriorated after the occlusion. In conclusion, the FO has a limited capacity to increase its volume blood flow at near‐term gestation.
Ischaemia‐induced muscle metabolic abnormalities are poorly alleviated by endurance training in a mouse model of sickle cell disease
Authors: Chatel Benjamin , Messonnier Laurent A. , Vilmen Christophe , Bernard Monique , Pialoux Vincent , Bendahan David
Published: December 2018

New Findings

What is the central question of this study?

The aim of this study was to evaluate the potential beneficial effects of endurance training during an ischaemia–reperfusion protocol in a mouse model of sickle cell disease (SCD).

What is the main finding and its importance?

Endurance training did not reverse the metabolic defects induced by a simulated vaso‐occlusive crisis in SCD mice, with regard to intramuscular acidosis, mitochondrial dysfunction or anatomical properties. Our results suggest that endurance training would reduce the number of vaso‐occlusive crises rather than the complications related to vaso‐occlusive crises.

The aim of this study was to investigate whether endurance training could limit the abnormalities described in a mouse model of sickle cell disease (SCD) in response to an ischaemia–reperfusion (I/R) protocol. Ten sedentary (HbSS‐SED) and nine endurance‐trained (HbSS‐END) SCD mice were submitted to a standardized protocol of I/R of the leg, during which ATP, phosphocreatine and inorganic phosphate concentrations and intramuscular pH were measured using magnetic resonance spectroscopy. Forty‐eight hours later, skeletal muscles were harvested. Oxidative stress markers were then measured. Although the time course of protons accumulation was slightly different between trained and sedentary mice (P < 0.05), the extent of acidosis was similar at the end of the ischaemic period. The initial rate of phosphocreatine resynthesis measured at blood flow restoration, illustrating mitochondrial function, was not altered in trained mice compared with sedentary mice. Although several oxidative stress markers were not different between groups (P > 0.05), the I/R‐related increase of uric acid concentration observed in sedentary SCD mice (P < 0.05) was not present in the trained group. The spleen weight, generally used as a marker of the severity of the disease, was not different between groups (P > 0.05). In conclusion, endurance training did not limit the metabolic consequences of an I/R protocol in skeletal muscle of SCD mice, suggesting that the reduction in the severity of the disease previously demonstrated in the basal state would be attributable to a reduction of the occurrence of vaso‐occlusive crises rather than a decrease of the deleterious effects of vaso‐occlusive crises.
Simulation of Fuel Storage Hazards Associated With Petroleum
Refineries Tanks
Authors: Pourgol-Mohammad Mohammad , Pourghafari Mohammad , Alizadeh Reza , Raheli Kaleibar Mojtaba , Soleimani Morteza
Published: December 2018

Predicting of hazards associated with the damages of fuel storage tanks in petroleum refineries is critical in maintaining safety of the facilities. This study assesses the hazard of the refinery gasoline tank damage by augmented mathematical and semi-experimental methods. This research evaluates complete content release of the reservoir tank scenario in a given time, as the worst case. Environment conditions are evaluated as affecting factors on the progression of the scenario. Comparison between the results of numerical simulations for pool fire as well as vapor cloud explosion with the results of simulation based on empirical-mathematical models indicates noticeable differences between the results in the vicinity of the boundary conditions; however, with increasing the distance from the center of the accident point, this difference decreases markedly.
Cylindrical Smoothed Particle Hydrodynamics Simulations of Water Entry
Authors: Gong Kai , Shao Songdong , Liu Hua , Lin Pengzhi , Gui Qinqin
Published: December 2018

This paper presents a smoothed particle hydrodynamics (SPH) modeling technique based on the cylindrical coordinates for axisymmetrical hydrodynamic applications, thus to avoid a full three-dimensional (3D) numerical scheme as required in the Cartesian coordinates. In this model, the governing equations are solved in an axisymmetric form and the SPH approximations are modified into a two-dimensional cylindrical space. The proposed SPH model is first validated by a dam-break flow induced by the collapse of a cylindrical column of water with different water height to semi-base ratios. Then, the model is used to two benchmark water entry problems, i.e., cylindrical disk and circular sphere entry. In both cases, the model results are favorably compared with the experimental data. The convergence of model is demonstrated by comparing with the different particle resolutions. Besides, the accuracy and efficiency of the present cylindrical SPH are also compared with a fully 3D SPH computation. Extensive discussions are made on the water surface, velocity, and pressure fields to demonstrate the robust modeling results of the cylindrical SPH.
Numerical Investigation on Labyrinth Seal Leakage Flow and Its Effects on Aerodynamic Performance for a Multistage Centrifugal Compressor
Authors: Qiao Bing , Ju Yaping , Zhang Chuhua
Published: December 2018

Labyrinth seals are widely used in industrial centrifugal compressors to reduce leakage. However, no work has been conducted to numerically investigate the detailed seal leakage flow and its effects in an environment of multistage centrifugal compressor. To clarify the flow mechanism of leakage flow and the interaction mechanism between leakage and mainstream flow in multistage centrifugal compressors, the flow of the last two stages from a four-stage centrifugal compressor is studied using computational fluid dynamics (CFD) model with and without considerations of labyrinth seal leakage paths, i.e., two shroud seals, one interstage seal, and one balance piston seal. The results show that the leakage flow in shroud and hub cavities can be described as a Batchelor-type flow. The Ekman number of the cavity Batchelor flow is small and corresponds to thin boundary layers while the Rossby number is at unity order implying the importance of rotating effects. The leakage flow through the shroud, interstage, and balance piston labyrinth seals is decreased by the combined effects of throttling and diffusion flow, and has distinctive flow structures associated with the type of labyrinth seal. The influence of leakage flow on the mainstream flow can be described by suction or injection mode. The suction mode is beneficial to the improvement of mainstream flow quality while the injection mode is harmful. This work is of scientific significance to enrich the knowledge of internal fluid mechanics and of potential application value to control and design the leakage flow in real configurations of multistage centrifugal compressors.
Out With the Old, in With the New: Pelton Hydro Turbine Performance Influence Utilizing Three Different Injector Geometries
Authors: Petley S. , Židonis A. , Panagiotopoulos A. , Benzon D. , Aggidis G. A. , Anagnostopoulos J. S. , Papantonis D. E.
Published: December 2018

In previous works, the authors presented computational fluid dynamics (CFD) results, which showed that injectors with noticeably steeper nozzle and needle tip angles 110 deg & 70 deg and 150 deg & 90 deg, respectively, attain higher efficiency than the industry standard, which, according to available literature on the public domain, ranges from 80 deg to 90 deg for nozzle and 50–60 deg for needle tip angles. Moreover, experimental testing of the entire Pelton system showed that gains of about 1% in efficiency can be achieved; however there appears to be an upper limit beyond which steeper designs are no longer optimal. This study aims at providing further insight by presenting additional CFD analysis of the runner, which has been coupled with the jet profile from the aforementioned injectors. The results are compared by examining the impact the jet shape has on the runner torque profile during the bucket cycle and the influence this has on turbine efficiency. It can be concluded that the secondary velocities, which contribute to the development of more significant free-surface degradations as the nozzle and needle tip angles are increased, result in a nonoptimal jet runner interaction.
Full-Field Dependence on Inlet Modeling of Non-Isothermal Turbulent Jets Using Validated Large Eddy Simulations
Authors: Salkhordeh Sasan , Kimber Mark L.
Published: December 2018

Inlet conditions for a turbulent jet are known to affect the near field behavior but eventually lose their significance downstream. Metrics of importance are often derived from mean and fluctuating velocity components, but little has been done to explore inlet effects on transport of a scalar quantity (e.g., temperature). This paper aims to provide fundamental understanding in this regard and employs large eddy simulations (LES) of a nonisothermal round turbulent jet (Reynolds number of 16,000) with geometry and boundary conditions mimicked after a well-known experimental study. The jet inlet is first modeled with a standard Blasius profile and next by performing a simulation of the upstream flow modeled with either detached eddy simulations (DES) or LES for the second and third approaches, respectively. Only the model employing LES for both upstream nozzle and downstream jet is found to completely capture the root-mean-square (RMS) temperature behavior, namely, a distinct hump when normalized by the local mean centerline temperature at roughly five diameters downstream. Regarding the far field conditions, all three inlet conditions converge for the centerline values, but the radial distributions still portray non-negligible differences. Not surprisingly, the complete LES modeling approach agrees the best with experimental data for mean and RMS distributions, suggesting that the inlet condition plays a vital role in both the near and far field of the jet. The current effort is the very first LES study to successfully capture flow physics for a nonisothermal round turbulent jet in near and far field locations.
Tracking Fault Tolerant Control for Hybrid System: Two-Link Human Arm Application
Authors: Islem Labidi , Nadia Zanzouri , Asma Takrouni
Published: December 2018

This paper proposes a novel fault tolerant control (FTC) scheme for a class of hybrid dynamical system (HDS) subject to sensor faults. The corresponding FTC architecture is designed around a reconfiguration mechanism. It aims to compensate the effects of the sensors degradation and maintain satisfactory performances including continuous stability. Moreover, by using the linear matrix inequalities (LMI) approach, a fault estimation algorithm is fulfilled and the compromise between robustness to disturbances and sensitivity to fault is guaranteed. For the sake of trajectory tracking, a combined robust state feedback and proportional-integral-derivative control system is proposed herein. Finally, extensive simulation results conducted on two-link arm system are included to illustrate the efficiency of the designed FTC scheme.
Nonlinear Control of Turbofan Engines: An Active Set-Based Method for Performance Optimization
Authors: Wang Jiqiang , Gao Yang , Zhang Weicun , Hu Zhongzhi
Published: December 2018

The inherent nonlinear nature of engine dynamics necessitates advanced design techniques for transient control. Conventional design methodologies are either not ready to apply to large flight envelope control or failing to provide protection over a variety of physical limits. This paper proposes an active set-based method for performance optimization over large envelope while providing limit protection over all sorts of constraints. Detailed design procedures are provided, and extensive numerical investigations are presented with both robustness and implantation issues discussed. Comparisons with both conventional schedule-based control and an advanced nonlinear generalized minimum variance-based (NGMV) control are conducted to illustrate the effectiveness of the proposed method.