bluuebunny/crossref_metadata_2025 huggingface dataset:
Enteral glutamine differentially regulates Nrf 2 along the villus‐crypt axis of the intestine to enhance glutathione levels
Authors: Venoji Raghupathy , Amirtharaj Gnanaraj Jayakumar , Kini Archana , Vanaparthi Sivakumar , Venkatraman Aparna , Ramachandran Anup
Published: June 2015

Background and Aim:

Glutamine is an important energy source for the intestinal epithelium, and its supplementation protects intestinal epithelial cells by induction of glutathione. However, mechanisms of glutathione induction in cells at various stages of differentiation along the crypt to villus axis are not well understood. This study examined induction of glutathione in response to glutamine along the intestinal villus–crypt axis and evaluated regulatory mediators involved in the process.

Methods:

Animals were administered 4% glutamine in feed for 7 days, following which enterocytes at various stages of differentiation were isolated and glutathione levels and signaling mediators involved in its regulation were studied.

Results:

In control animals, glutathione levels were higher in the intestinal crypt than in the villus or middle region. This was accompanied by elevated expression of the modifier subunit of glutathione synthetase (GCLM) and the transcription factor Nrf2 when compared with cells from the villus and middle regions. These levels were further enhanced by glutamine throughout the intestine, although the effects were more dramatic in the crypt. In parallel to glutathione induction, glutamine supplementation also altered actin dynamics and proliferation in cells of the crypt.

Conclusions:

These results suggest that the variation of glutathione levels along the villus–crypt axis in the intestine is due to gradients in expression of mediators such as glutamate cysteine ligase modifier subunit and Nrf2. The protective effects of glutamine supplementation seem to be most pronounced in the crypt, where it upregulates proliferation, glutathione levels and alters actin dynamics.
Time and space profiling of NMDA receptor co‐agonist functions
Authors: Mothet Jean‐Pierre , Le Bail Matildé , Billard Jean‐Marie
Published: June 2015

The N‐Methyl D‐Aspartic acid (NMDA) receptors (NMDAR) are key tetrameric ionotropic glutamate receptors that transduce glutamatergic signals throughout the central nervous system (CNS) and spinal cord. Although NMDARs are diverse in their subunit composition, subcellular localization, and biophysical and pharmacological properties, their activation always requires the binding of a co‐agonist that has long been thought to be glycine. However, intense research over the last decade has challenged this classical model by showing that another amino acid, d‐serine, is the preferential co‐agonist for a subset of synaptic NMDARs in many areas of the adult brain. Nowadays, a totally new picture of glutamatergic synapses at work is emerging where both glycine and d‐serine are involved in a complex interplay to regulate NMDAR functions in the CNS following time and space constraints. The purpose of this review was to highlight the particular role of each co‐agonist in modulating NMDAR‐dependent activities in healthy and diseased brains. We have herein integrated our most advanced knowledge of how glycine and d‐serine may orchestrate synapse dynamics and drive neuronal network activity in a time‐ and synapse‐specific manner and how changes in synaptic availability of these amino acids may contribute to cognitive impairments such as those associated with healthy aging, epilepsy, and schizophrenia.

image

The N‐Methyl D‐Aspartic acid (NMDA) subtype of glutamate receptors are central to many physiological functions and are linked to brain disorders. Their functions require glutamate and a co‐agonist d‐serine or glycine. After years of intense research and controversy on the identity of the amino acid that serves as the right co‐agonist, we are just entering a new era of consensus where glycine and d‐serine are teaming up to regulate the function of different subsets of NMDA receptors and at different synapses during different time windows of brain development.
The innervation of the muscle spindle: a personal history
Authors: Banks Robert W.
Published: June 2015

I present a brief review of current understanding of the innervation of the mammalian muscle spindle, from a personal historical perspective. The review begins with comparative studies on the numbers of spindle afferents and considers how their relative abundance may best be assessed. This is followed by an examination of the distribution and some functional properties of the motor innervation. The primary ending is the subject of the final section, in particular, I look at what can be learned from serial sectioning and volumetric reconstruction, and present new results on a model and simulations concerning sensory terminal deformation during stretch.
A non‐toxigenic but morphologically and phylogenetically distinct new species of Pseudo‐nitzschia, P. sabit sp. nov. (Bacillariophyceae)
Authors: Teng Sing Tung , Lim Po Teen , Lim Hong Chang , Rivera‐Vilarelle María , Quijano‐Scheggia Sonia , Takata Yoshinobu , Quilliam Michael A. , Wolf Matthias , Bates Stephen S. , Leaw Chui Pin
Published: June 2015

A new species of Pseudo‐nitzschia (Bacillariophyceae) is described from plankton samples collected from Port Dickson (Malacca Strait, Malaysia) and Manzanillo Bay (Colima, Mexico). The species possesses a distinctive falcate cell valve, from which they form sickle‐like colonies in both environmental samples and cultured strains. Detailed observation of frustules under TEM revealed ultrastructure that closely resembles P. decipiens, yet the new species differs by the valve shape and greater ranges of striae and poroid densities. The species is readily distinguished from the curve‐shaped P. subcurvata by the presence of a central interspace. The morphological distinction is further supported by phylogenetic discrimination. We sequenced and analyzed the nuclear ribosomal RNA genes in the LSU and the second internal transcribed spacer, including its secondary structure, to infer the phylogenetic relationship of the new species with its closest relatives. The results revealed a distinct lineage of the new species, forming a sister cluster with its related species, P. decipiens and P. galaxiae, but not with P. subcurvata. We examined the domoic acid (DA) production of five cultured strains from Malaysia by Liquid chromatography‐mass spectrometry (LC‐MS), but they showed no detectable DA. Here, we present the taxonomic description of the vegetative cells, document the sexual reproduction, and detail the molecular phylogenetics of Pseudo‐nitzschia sabit sp. nov.
Expression of anti‐Porphyromonas gingivalis peptidylarginine deiminase immunoglobulin G and peptidylarginine deiminase‐4 in patients with rheumatoid arthritis and periodontitis
Authors: Shimada A. , Kobayashi T. , Ito S. , Okada M. , Murasawa A. , Nakazono K. , Yoshie H.
Published: June 2015

Background and Objective

Autoimmunity against citrullinated proteins through peptidylarginine deiminase (PAD) may be involved in the pathophysiology of rheumatoid arthritis (RA). The present study evaluated the serum levels of antibodies to citrullinated proteins and to Porphyromonas gingivalis PAD (PPAD), and the endogenous expression of PAD‐4, in individuals with and without RA, as well as before and after periodontal treatment.

Material and Methods

The study participants consisted of 52 patients with RA (RA group) and 26 age‐, gender‐ and smoking status‐matched healthy controls (non‐RA group). Of the 52 patients, 26 were randomly assigned to receive oral hygiene instruction and supragingival scaling (RA subgroup). After periodontal and rheumatologic assessments, the serum levels of anti‐cyclic citrullinated peptide (CCP) immunoglobulin G (IgG), anti‐PPAD IgG and PAD‐4 were determined using ELISA.

Results

The serum levels of anti‐CCP IgG and anti‐PPAD IgG were significantly higher in the RA group than in the non‐RA group (p < 0.001 and p = 0.03). A significant, positive correlation was observed between the serum levels of anti‐PPAD IgG and anti‐CCP IgG (p = 0.04), but not between the serum levels of PAD‐4 and anti‐CCP IgG. Multiple logistic regression analyses revealed a significant association between anti‐PPAD IgG responses and RA after adjustment for age, gender and smoking (p = 0.004). Supragingival scaling significantly improved the periodontal condition and disease activity of RA (p < 0.05), but failed to decrease the serum levels of anti‐CCP IgG, anti‐PPAD IgG and PAD‐4 after 2 mo of treatment.

Conclusion

These results might suggest an association between anti‐PPAD IgG and anti‐CCP IgG responses, implicating a role for PPAD in protein citrullination in patients with RA and periodontitis.
Osteogenic potential of dualblocks cultured with human periodontal ligament stem cells: in vitro and synchrotron microtomography study
Authors: Manescu A. , Giuliani A. , Mohammadi S. , Tromba G. , Mazzoni S. , Diomede F. , Zini N. , Piattelli A. , Trubiani O.
Published: June 2015

Background and Objective

In the present study, the early stages of in vitro bone formation in collagenated porcine scaffolds cultured with human periodontal ligament cells were investigated. The comparison between the osteogenic potential of this structure in basal and differentiating culture media was explored to predict the mechanism of its biological behavior as graft in human defect. Results were validated by synchrotron radiation X‐Ray phase contrast computed microtomography (micro‐CT). As the periodontal disease plays a key role in systemic and oral diseases, it is crucial to find advanced therapeutic clinical interventions to repair periodontal defects. This has been recently explored using cells and tissues developed in vitro that should ideally be immunologically, functionally, structurally and mechanically identical to the native tissue.

Material and Methods

In vitro cultures of human periodontal ligament cells, easily obtained by scraping of alveolar crestal and horizontal fibers of the periodontal ligament, were seeded on to collagenated porcine blocks constituted by natural cancellous and cortical bone. 3D images were obtained by synchrotron radiation micro‐CT and processed with a phase‐retrieval algorithm based on the transport of intensity equation.

Results

Starting from the second week of culture, newly formed mineralized bone was detected in all the scaffolds, both in basal and differentiating media. Bone mineralization was proved to occur preferentially in the trabecular portion and in differentiating media.

Conclusion

The chosen method, supported by phase contrast micro‐CT analysis, successfully and quantitatively monitored the early stages of bone formation and the rate of the bioscaffold resorption in basal and differentiating culture media.
Sleep deprivation impairs inhibitory control during wakefulness in adult sleepwalkers
Authors: Labelle Marc‐Antoine , Dang‐Vu Thien Thanh , Petit Dominique , Desautels Alex , Montplaisir Jacques , Zadra Antonio
Published: June 2015

Sleepwalkers often complain of excessive daytime somnolence. Although excessive daytime somnolence has been associated with cognitive impairment in several sleep disorders, very few data exist concerning sleepwalking. This study aimed to investigate daytime cognitive functioning in adults diagnosed with idiopathic sleepwalking. Fifteen sleepwalkers and 15 matched controls were administered the Continuous Performance Test and Stroop Colour‐Word Test in the morning after an overnight polysomnographic assessment. Participants were tested a week later on the same neuropsychological battery, but after 25 h of sleep deprivation, a procedure known to precipitate sleepwalking episodes during subsequent recovery sleep. There were no significant differences between sleepwalkers and controls on any of the cognitive tests administered under normal waking conditions. Testing following sleep deprivation revealed significant impairment in sleepwalkers' executive functions related to inhibitory control, as they made more errors than controls on the Stroop Colour‐Word Test and more commission errors on the Continuous Performance Test. Sleepwalkers' scores on measures of executive functions were not associated with self‐reported sleepiness or indices of sleep fragmentation from baseline polysomnographic recordings. The results support the idea that sleepwalking involves daytime consequences and suggest that these may also include cognitive impairments in the form of disrupted inhibitory control following sleep deprivation. These disruptions may represent a daytime expression of sleepwalking's pathophysiological mechanisms.
Pb‐Pb dating of individual chondrules from the CBa chondrite Gujba: Assessment of the impact plume formation model
Authors: Bollard Jean , Connelly James N. , Bizzarro Martin
Published: June 2015

The CB chondrites are metal‐rich meteorites with characteristics that sharply distinguish them from other chondrite groups. Their unusual chemical and petrologic features and a young formation age of bulk chondrules dated from the CBa chondrite Gujba are interpreted to reflect a single‐stage impact origin. Here, we report high‐precision internal isochrons for four individual chondrules of the Gujba chondrite to probe the formation history of CB chondrites and evaluate the concordancy of relevant short‐lived radionuclide chronometers. All four chondrules define a brief formation interval with a weighted mean age of 4562.49 ± 0.21 Myr, consistent with its origin from the vapor‐melt impact plume generated by colliding planetesimals. Formation in a debris disk mostly devoid of nebular gas and dust sets an upper limit for the solar protoplanetary disk lifetime at 4.8 ± 0.3 Myr. Finally, given the well‐behaved Pb‐Pb systematics of all four chondrules, a precise formation age and the concordancy of the Mn‐Cr, Hf‐W, and I‐Xe short‐lived radionuclide relative chronometers, we propose that Gujba may serve as a suitable time anchor for these systems.
Petrology and geochemistry of Northwest Africa 5480 diogenite and evidence for a basin‐forming event on Vesta
Authors: Yamaguchi A. , Barrat J. A. , Shirai N. , Ebihara M.
Published: June 2015

We performed a petrological and geochemical study of an olivine diogenite, Northwest Africa (NWA) 5480. NWA 5480 is a crystalline stone, but shows a heterogeneous texture. Olivine aggregates and grains of olivine and chromite display resorption textures set in a crystalline pyroxene matrix. Large olivine aggregates are penetrated by pyroxene matrix. Flow textures are observed near olivine aggregates. Olivine, chromite, and pyroxene show minor chemical zoning, implying relatively rapid cooling. NWA 5480 contains a significant amount of platinum group elements with chondritic relative proportions. All this evidence supports that NWA 5480 is an impact‐melt breccia from a target composed of olivine and pyroxene‐rich lithologies. Such impact melt would have formed by melting crustal materials, possibly during one of the impacts that formed the South Pole basins on Vesta.
Geographic and temporal dynamics of a global radiation and diversification in the killer whale
Authors: Morin Phillip A. , Parsons Kim M. , Archer Frederick I. , Ávila‐Arcos María C. , Barrett‐Lennard Lance G. , Dalla Rosa Luciano , Duchêne Sebastián , Durban John W. , Ellis Graeme M. , Ferguson Steven H. , Ford John K. , Ford Michael J. , Garilao Cristina , Gilbert M. Thomas P. , Kaschner Kristin , Matkin Craig O. , Petersen Stephen D. , Robertson Kelly M. , Visser Ingrid N. , Wade Paul R. , Ho Simon Y. W. , Foote Andrew D.
Published: June 2015

Global climate change during the Late Pleistocene periodically encroached and then released habitat during the glacial cycles, causing range expansions and contractions in some species. These dynamics have played a major role in geographic radiations, diversification and speciation. We investigate these dynamics in the most widely distributed of marine mammals, the killer whale (Orcinus orca), using a global data set of over 450 samples. This marine top predator inhabits coastal and pelagic ecosystems ranging from the ice edge to the tropics, often exhibiting ecological, behavioural and morphological variation suggestive of local adaptation accompanied by reproductive isolation. Results suggest a rapid global radiation occurred over the last 350 000 years. Based on habitat models, we estimated there was only a 15% global contraction of core suitable habitat during the last glacial maximum, and the resources appeared to sustain a constant global effective female population size throughout the Late Pleistocene. Reconstruction of the ancestral phylogeography highlighted the high mobility of this species, identifying 22 strongly supported long‐range dispersal events including interoceanic and interhemispheric movement. Despite this propensity for geographic dispersal, the increased sampling of this study uncovered very few potential examples of ancestral dispersal among ecotypes. Concordance of nuclear and mitochondrial data further confirms genetic cohesiveness, with little or no current gene flow among sympatric ecotypes. Taken as a whole, our data suggest that the glacial cycles influenced local populations in different ways, with no clear global pattern, but with secondary contact among lineages following long‐range dispersal as a potential mechanism driving ecological diversification.
Macro‐Hysteresis Test for Brazilian Exports of Manufactured Products: A threshold Panel Approach
Authors: Kannebley Júnior Sérgio , Martins Baroni João Paulo , de Prince Diogo
Published: June 2015

This study tests for macro‐hysteresis in Brazilian exports of manufactured products using a panel model with threshold parameters according to Hansen. To test hysteresis, the threshold variables are built based on studies by Parslei and Wei, and Penkova. There is evidence of asymmetrical responses, with more pronounced increases in the price elasticity of demand during periods of high depreciation of the exchange rate compared with periods of more pronounced currency appreciation. We also estimate the relative price intervals that correspond to the inaction band.
Locked‐in syndrome caused by bilateral midbrain infarctions with occlusion of the intracranial vertebral artery
Authors: Uemura Masahiro , Takeshima Akari , Akaiwa Yasuhisa , Ninomiya Itaru , Tazawa Ayako , Harigai Toru , Okamoto Kouichirou , Shimohata Takayoshi , Nishizawa Masatoyo
Published: June 2015

Bilateral cerebral peduncles are rarely simultaneously infarcted unless the basilar artery is involved. A 60‐year‐old man developed locked‐in syndrome because of bilateral cerebral peduncle infarctions with right intracranial vertebral artery occlusion. Dysarthria occurred a day before admission. His neurological condition rapidly deteriorated, and he subsequently became quadriplegic. His left vertebral artery showed a posterior inferior cerebellar artery end pattern, and anastomosis between the anterior and posterior circulations through the hypoplastic right P1 and fine left posterior communicating artery was insufficient; therefore, severe hypoperfusion and multiple infarctions in the distribution of the posterior circulation were induced by right intracranial vertebral artery occlusion. These findings highlight the fact that large‐artery atherosclerosis represents an important cause of mesencephalic infarctions. Several neurological manifestations are caused by intracranial vertebral artery occlusion, and when collateral flow to the posterior circulation is insufficient, intracranial vertebral artery occlusion results in bilateral cerebral peduncle infarctions and locked‐in syndrome without basilar artery occlusion.
An autopsy case of familial amyotrophic lateral sclerosis with a TARDBP Q343R mutation
Authors: Okamoto Koichi , Fujita Yukio , Hoshino Eri , Tamura Yuhji , Fukuda Toshio , Hasegawa Masato , Takatama Masamitsu
Published: June 2015

We describe a Japanese autopsy case of familial amyotrophic lateral sclerosis (FALS) with a TARDBP Q343R mutation. This male patient developed dysarthria at the age of 52 years, and bulbar symptoms progressed, with weakness and atrophy in the extremities. His mental status was normal, but he became bedridden, received artificial respiratory support at 54 years of age, and gradually acquired a locked‐in state and died at 58 years of age. Microscopically, marked diffuse myelin pallor was observed in the anterolateral columns of the spinal cord. The remaining anterior horn cells contained Bunina bodies and phosphorylation‐dependent transactivation response DNA‐binding protein of 43 kDa (pTDP‐43)‐positive neuronal cytoplasmic inclusions (NCIs). Glial cytoplasmic inclusions (GCIs) were also observed. The number of ubiquitin‐ and p62‐positive inclusions was markedly lower than that of pTDP‐43‐positive inclusions. NCIs and many fine dot‐like pTDP‐43‐positive granules in the neuropil were mainly seen in the temporal and motor cortices, and striatum. NCIs were rare in hippocampal granular cells. Immunoblotting of samples from the cerebral cortex using an anti‐pTDP‐43 antibody was slightly different from previous TDP‐43 pathological subtypes.
An autopsy case of refractory epilepsy due to unilateral polymicrogyria in a 65‐year‐old man: Histogenesis of four‐layered polymicrogyric cortex
Authors: Miki Yasuo , Tanji Kunikazu , Mori Fumiaki , Sakamoto Namiko , Wakabayashi Koichi
Published: June 2015

Polymicrogyria (PMG) is a complex malformation accompanied with abnormal cortical laminations (two‐, four‐ or six‐layered cortex), and horizontally oriented myelinated fiber layer is evident in four‐layered PMG in older individuals. Here we report a 65‐year‐old man with refractory epilepsy, in whom postmortem examination revealed four‐layered PMG in the left hemisphere. We carried out a histological and immunohistochemical study to clarify the nature of the myelinated band in four‐layered PMG cortex. The myelinated band contained no or only few neurons. GFAP‐ and aquaporin‐1‐immunoreactive astrocytes were found in the subcortical white matter as well as in the myelinated band. By contrast, GFAP‐ and aquaporin‐1‐immunoreactive astrocytes were not found in the band of Baillarger. These findings suggest that the myelinated band in PMG cortex is not the band of Baillarger and that the immunohistochemical characteristics of astrocytes in the myelinated band in PMG cortex are similar to those of the subcortical white matter. Previous studies suggest that PMG is not a cell migration disorder but a post‐migration malformation. Taken together, it is likely that the myelinated band in PMG cortex represents abnormality of axonal growth or myelination after migration has terminated.
Quality of patient information leaflets for Down syndrome screening: A comparison between the UK and Thailand
Authors: Saiklang Parvinee , Skirton Heather
Published: June 2015

Prenatal screening tests can help to estimate the possibility of a pregnant woman having a baby with trisomy 21 (Down syndrome). As these tests are optional, it is essential that women are provided with appropriate verbal and written information to enable them to make an informed choice. In this study, we assessed the content and quality of Down syndrome screening information leaflets used by health professionals to provide information to pregnant women in the UK (26 leaflets) and Thailand (11 leaflets). We collected leaflets from health institutions and the Internet, and compared the topics covered in each one against recommendations for patient information on this topic. We also assessed the quality of each leaflet using the DISCERN Genetics tool. While the quality‐rating score of the UK leaflets was significantly higher than the Thai leaflets, none of the leaflets included all the recommended topics; some contained erroneous material. In both countries, the quality of information can be improved to provide accurate information to women and their partners, which is essential to ensure prospective parents can make informed choices during pregnancy.
Competition for canopy cover between accessions of Phalaris minor that are susceptible and resistant to ACCase inhibiting herbicides
Authors: Torres‐García Jesús R. , Núñez‐Farfán Juan , Uscanga‐Mortera Ebandro , Trejo Carlos , Conde‐Martínez Víctor , Kohashi‐Shibata Josuú , Martínez‐Moreno David , Velazquéz‐Marquez Sabina
Published: June 2015

Herbicide resistance has the potential to impose fitness costs in plants. In Mexico, Phalaris minor Retz. has evolved resistance to acetyl‐coa carboxylase (ACCase) inhibiting herbicides. However, it is unknown whether these changes may involve other ecological costs for resistant individuals under non‐selective conditions. The aim of this study was to determine whether the evolution of resistance has reduced the ability of P. minor to compete for resources at the seedling stage. De Wit's replacement series experiments (susceptible:resistant 100:0, 50:50, 0:100) were performed under two initial conditions. In the first experiment, we examined the effect of differences in germination time between resistant and susceptible genotypes on canopy cover. In the second experiment, germination was synchronized, and all the replacement series began at the same time. Delayed germination of resistant accessions reduced their ability to compete for canopy space, competition intensity index, and relative productivity in relation to susceptible accessions. When germination was synchronized, the resistant accessions had the same canopy cover and productivity as susceptible accessions. The delayed germination may cause displacement of resistant individuals in the absence of the selective factor (herbicide).
Ghrelin enhancer, rikkunshito, improves postprandial gastric motor dysfunction in an experimental stress model
Authors: Harada Y. , Ro S. , Ochiai M. , Hayashi K. , Hosomi E. , Fujitsuka N. , Hattori T. , Yakabi K.
Published: June 2015

Background

Functional dyspepsia (FD) is one of the most common disorders of gastrointestinal (GI) diseases. However, no curable treatment is available for FD because the detailed mechanism of GI dysfunction in stressed conditions remains unclear. We aimed to clarify the association between endogenous acylated ghrelin signaling and gastric motor dysfunction and explore the possibility of a drug with ghrelin signal‐enhancing action for FD treatment.

Methods

Solid gastric emptying (GE) and plasma acylated ghrelin levels were evaluated in an urocortin1 (UCN1) ‐induced stress model. To clarify the role of acylated ghrelin on GI dysfunction in the model, exogenous acylated ghrelin, an endogenous ghrelin enhancer, rikkunshito, or an α2‐adrenergic receptor (AR) antagonist was administered. Postprandial motor function was investigated using a strain gauge force transducer in a free‐moving condition.

Key Results

Exogenous acylated ghrelin supplementation restored UCN1‐induced delayed GE. Alpha2‐AR antagonist and rikkunshito inhibited the reduction in plasma acylated ghrelin and GE in the stress model. The action of rikkunshito on delayed GE was blocked by co‐administration of the ghrelin receptor antagonist. UCN1 decreased the amplitude of contraction in the antrum while increasing it in the duodenum. The motility index of the antrum but not the duodenum was significantly reduced by UCN1 treatment, which was improved by acylated ghrelin or rikkunshito.

Conclusions & Inferences

The UCN1‐induced gastric motility dysfunction was mediated by abnormal acylated ghrelin dynamics. Supplementation of exogenous acylated ghrelin or enhancement of endogenous acylated ghrelin secretion by rikkunshito may be effective in treating functional GI disorders.
Self‐reported lactose intolerance in clinic patients with functional gastrointestinal symptoms: prevalence, risk factors, and impact on food choices
Authors: Zheng X. , Chu H. , Cong Y. , Deng Y. , Long Y. , Zhu Y. , Pohl D. , Fried M. , Dai N. , Fox M.
Published: June 2015

Background

Many patients complain of abdominal symptoms with dairy products; however, clinical and psychosocial factors associated with self‐reported lactose intolerance (SLI) have not been assessed in large studies. In particular, data are lacking from lactase deficient populations. This prospective cohort study assessed the prevalence of, and risk factors for, SLI in Chinese patients attending a gastroenterology clinic.

Methods

Consecutive patients completed questionnaires to assess digestive health (Rome III), psychological state (HADS), life event stress (LES), food intake, and quality‐of‐life (SF‐8). A representative sample completed genetic studies and hydrogen breath testing (HBT) at the clinically relevant dose of 20 g lactose.

Key Results

SLI was present in 411/910 (45%) clinic patients with functional abdominal symptoms. The genotype in all subjects was C/C‐13910. A small number of novel SNPs in lactase promoter region were identified, including C/T‐13908 which appeared to confer lactase persistence. Over half of the patients (54%) completed the 20 g lactose HBT with 58% (285/492) reporting typical symptoms. Positive and negative predictive values of SLI for abdominal symptoms during HBT were 60% and 44%, respectively. Psychological state and stress were not associated with SLI in clinic patients. SLI impacted on physical quality‐of‐life and was associated with reduced ingestion of dairy products, legumes, and dried fruit (p ≤ 0.05).

Conclusions & Inferences

In a lactase deficient population, approximately half of patients attending clinic with functional gastrointestinal symptoms reported intolerance to dairy products; however, SLI did not predict findings on 20 g lactose HBT. Independent of psychosocial factors, SLI impacted on quality‐of‐life and impacted on food choices with restrictions not limited to dairy products.
Targeting tachykinin receptors for the treatment of functional gastrointestinal disorders with a focus on irritable bowel syndrome
Authors: Corsetti M. , Akyuz F. , Tack J.
Published: June 2015

Background

Tachykinins (TKs) are a family of endogenous peptides widely expressed in the central and in the peripheral nervous systems as well as in the gastrointestinal (GI) tract. They act as full agonists at three different membrane receptors neurokinin (NK) 1, NK2, and NK3, which are G protein‐coupled receptors and in the GI tract are expressed both on neurons and effector cells.

Purpose

This article reviews the literature concerning the role of TKs in the GI tract function in physiological and pathological conditions and their potential relevance in the treatment of functional GI disorders with particular reference to irritable bowel syndrome (IBS). The efficacy of NK1 antagonists in chemotherapy‐induced and postoperative nausea and vomiting is well established. While pharmacodynamic studies have reported conflicting and negative results concerning the effects of NK1 and of NK3 antagonists, respectively, on the GI tract function in humans, clinical studies applying the NK3 antagonist talnetant in IBS‐D were negative. Pharmacodynamic studies applying NK2 antagonists have suggested a role for antagonism of NK2 receptors in modulation of GI chemical‐induced altered motility and of stress‐induced altered bowel habits. Clinical studies and in particular a recently completed Phase 2 study have reported that the NK2 antagonist ibodutant is effective and safe in treating symptoms of D‐IBS, especially in females.
Chloride‐inducible transient apoplastic alkalinizations induce stomata closure by controlling abscisic acid distribution between leaf apoplast and guard cells in salt‐stressed Vicia faba
Authors: Geilfus Christoph‐Martin , Mithöfer Axel , Ludwig‐Müller Jutta , Zörb Christian , Muehling Karl H.
Published: June 2015

Chloride stress causes the leaf apoplast transiently to alkalize, an event that is presumed to contribute to the ability of plants to adapt to saline conditions. However, the initiation of coordinated processes downstream of the alkalinization is unknown. We hypothesize that chloride‐inducible pH dynamics are a key chemical feature modulating the compartmental distribution of abscisic acid (ABA) and, as a consequence, affecting stomata aperture.

Apoplastic pH and stomata aperture dynamics in intact Vicia faba leaves were monitored by microscopy‐based ratio imaging and porometric measurements of stomatal conductance. ABA concentrations in leaf apoplast and guard cells were compared with pH dynamics by gas‐chromatography‐mass‐spectrometry (GC‐MS) and liquid‐chromatography–tandem‐mass spectrometry (LC‐MS/MS).

Results demonstrate that, upon chloride addition to roots, an alkalizing factor that initiates the pH dynamic propagates from root to leaf in a way similar to xylem‐distributed water. In leaves, it induces a systemic transient apoplastic alkalinization that causes apoplastic ABA concentration to increase, followed by an elevation of endogenous guard cell ABA.

We conclude that the transient alkalinization, which is a remote effect of chloride stress, modulates the compartmental distribution of ABA between the leaf apoplast and the guard cells and, in this way, is instrumental in inducing stomata closure during the beginning of salinity.
Catecholamines and acetylcholine are key regulators of the interaction between microbes and the immune system
Authors: Islas Weinstein Leon , Revuelta Alberto , Pando Rogelio Hernandez
Published: June 2015

Recent studies suggest that catecholamines (CAs) and acetylcholine (ACh) play essential roles in the crosstalk between microbes and the immune system. Host cholinergic afferent fibers sense pathogen‐associated molecular patterns and trigger efferent cholinergic and catecholaminergic pathways that alter immune cell proliferation, differentiation, and cytokine production. On the other hand, microbes have the ability to produce and degrade ACh and also regulate autogenous functions in response to CAs. Understanding the role played by these neurotransmitters in host–microbe interactions may provide valuable information for the development of novel therapies.
Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin‐4 channelopathies: a decade later
Authors: Pittock Sean J. , Lucchinetti Claudia F.
Published: June 2015

The discovery of AQP4‐IgG (a pathogenic antibody that targets the astrocytic water channel aquaporin‐4), as the first sensitive and specific biomarker for any inflammatory central nervous system demyelinating disease (IDD), has shifted emphasis from the oligodendrocyte and myelin to the astrocyte as a central immunopathogenic player. Neuromyelitis optica (NMO) spectrum disorders (SDs) represent an evolving spectrum of IDDs extending beyond the optic nerves and spinal cord to include the brain (especially in children) and, rarely, muscle. NMOSD typical brain lesions are located in areas that highly express the target antigen, AQP4, including the circumventricular organs (accounting for intractable nausea and vomiting) and the diencephalon (accounting for sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Magnetic resonance imaging brain abnormalities fulfill Barkoff criteria for multiple sclerosis in up to 10% of patients. As the spectrum broadens, the importance of highly specific assays that detect pathogenic AQP4‐IgG targeting extracellular epitopes of AQP4 cannot be overemphasized. The rapid evolution of our understanding of the immunobiology of AQP4 autoimmunity necessitates continuing revision of NMOSD diagnostic criteria. Here, we describe scientific advances that have occurred since the discovery of NMO‐IgG in 2004 and review novel targeted immunotherapies. We also suggest that NMOSDs should now be considered under the umbrella term autoimmune aquaporin‐4 channelopathy.
The impact of bariatric surgery on quality of life: a systematic review and meta‐analysis
Authors: Lindekilde N. , Gladstone B. P. , Lübeck M. , Nielsen J. , Clausen L. , Vach W. , Jones A.
Published: June 2015

This study aims to review the obesity literature in order to assess the impact of bariatric surgery on quality of life and the between‐study variation by examining the standardized mean magnitude of effect in change in the levels of quality of life. The following databases EMBASE, PubMed, PsycINFO, CINAHL, the Cochrane Library and Web of Science were systematically searched for studies examining change in quality of life in adults receiving bariatric surgery for obesity. Seventy‐two studies were included with a total of 9,433 participants treated for obesity with bariatric surgery. The average impact of bariatric surgery on quality of life corresponded to an effect size of 0.88 (95% CI: 0.80–0.96), indicating that bariatric surgery has a significant positive influence on quality of life in general. The impact varied considerably across studies with bariatric surgery showing a significantly greater positive influence on physical quality of life compared to mental quality of life. Bariatric surgery is effective in improving quality of life, especially when looking at physical well‐being. Greater focus on the psychological well‐being of the person undergoing surgery for obesity may lead to a better post‐surgery prognosis for more people.
Radiofrequency Ablation with an Enhanced‐Irrigation Flexible‐Tip Catheter versus a Standard‐Irrigation Rigid‐Tip Catheter
Authors: HUSSEIN AYMAN A. , OBERTI CARLOS , WAZNI OUSSAMA M. , HEGRENES JAMI A. , SRAL JOHN A. , LOPEZ JOHN , KOWALEWSKI WILLIAM , KATTAR JACQUELINE , KANJ MOHAMED , LINDSAY BRUCE , SALIBA WALID
Published: June 2015

Background

The flexible‐tip irrigated ablation catheter Cool Flex™ (St. Jude Medical, St. Paul, MN, USA) was introduced to enhance cooling of the catheter‐tissue interface and to conform to endocardial surface with better contact. Little is known about the performance of such catheter design compared to the widely used rigid‐tip catheters.

Methods

In a thigh muscle preparation, ablation using the flexible‐tip and rigid‐tip catheters was performed in seven pigs across a range of ablation settings and catheter orientation. Postprocedure, the thigh muscle was stained with 2,3,5‐triphenyltetrazolium‐chloride injected into the femoral artery. The muscle was excised, fixed with formalin, and examined grossly.

Results

A total of 196 lesions (95 flexible tip, 101 rigid tip) were evaluated. The flexible‐tip catheter was associated with enhanced cooling of catheter‐tissue interface (31.1 ± 3.3°C vs 36.3 ± 3.7°C, P = 0.0001) in both perpendicular and nonperpendicular catheter orientations. This allowed more energy delivery (37.3 ± 8.9 W vs 33.7 ± 8.1 W, P = 0.004) to targeted tissue and resulted in larger lesions (median 194.7 [interquartile range: 113.1–333.8] mm3 vs 170.9 [88.7–261.6] mm3, P = 0.03) than the rigid‐tip catheter with larger maximum diameter (11.1 ± 2.6 mm vs 10.3 ± 2.1 mm, P = 0.03) and larger diameter at tissue surface (10.3 ± 2.4 mm vs 9.6 ± 1.7 mm, P = 0.01). Catheter orientation during ablation affected the efficiency of rigid‐tip but not the flexible‐tip catheter. The use of the flexible‐tip catheter was associated with significantly less char formation on tissue (none vs 5.1% with rigid tip, P = 0.009).

Conclusion

The Cool Flex™ catheter performed better than a rigid‐tip catheter with enhanced cooling, larger ablation lesions, and no charring of targeted tissue.
Jasmonate in plant defence: sentinel or double agent?
Authors: Yan Chun , Xie Daoxin
Published: June 2015

Plants and their biotic enemies, such as microbial pathogens and herbivorous insects, are engaged in a desperate battle which would determine their survival–death fate. Plants have evolved efficient and sophisticated systems to defend against such attackers. In recent years, significant progress has been made towards a comprehensive understanding of inducible defence system mediated by jasmonate (JA), a vital plant hormone essential for plant defence responses and developmental processes. This review presents an overview of JA action in plant defences and discusses how microbial pathogens evade plant defence system through hijacking the JA pathway.
Safety Stock, Excess Capacity or Diversification: Trade‐Offs under Supply and Demand Uncertainty
Authors: Chaturvedi Aadhaar , Martínez‐de‐Albéniz Victor
Published: June 2015

Firms mitigate uncertainty in demand and supply by carrying safety stock, planning for excess capacity and diversifying supply sources. In this study, we provide a framework to jointly optimize these three levers in a periodic review infinite horizon setting, and in particular we examine how one can reduce inventory and capacity investments through proper diversification strategies. Observing that a modified base‐stock inventory policy is optimal, we find that the capacity‐diversification problem is well behaved and characterize the optimal mix of safety stock, excess capacity and extra number of supply sources. We find that higher supply uncertainty results in higher safety stock, more excess capacity, and higher diversification. But safety stock and diversification are non‐monotonic in demand uncertainty. Our results can be extended to situations in which suppliers are heterogeneous, and can be used to develop effective heuristics.
Optimal Coordination in Distributed Software Development
Authors: Xia Hao , Dawande Milind , Mookerjee Vijay
Published: June 2015

The construction of a software system requires not only individual coding effort from team members to realize the various functionalities, but also adequate team coordination to integrate the developed code into a consistent, efficient, and bug‐free system. On the one hand, continuous coding without adequate coordination can cause serious system inconsistencies and faults that may subsequently require significant corrective effort. On the other hand, frequent integrations can be disruptive to the team and delay development progress. This tradeoff motivates the need for a good coordination policy. Both the complexity and the importance of coordination is accentuated in distributed software development (DSD), where a software project is developed by multiple, geographically‐distributed sub‐teams. The need for coordination in DSD exists both within one sub‐team and across different sub‐teams. The latter type of coordination involves communication across spatial boundaries (different locations) and possibly temporal boundaries (different time zones), and is a major challenge that DSD faces. In this study, we model both inter‐ and intra‐sub‐team coordination in DSD based on the characteristics of the systems being developed by the sub‐teams, the deadline for completion, and the nature of division adopted by the sub‐teams with respect to development and integration activities. Our analysis of optimal coordination policies in DSD shows that integration activities by one sub‐team not only benefit that sub‐team (as is the case in co‐located development) but can also help the other sub‐teams by providing greater visibility, thereby resulting in a higher integration frequency relative to co‐located development. Analytical results are presented to demonstrate how the characteristics of the projects and the sub‐teams, and the efficiency of communication across the sub‐teams, affect coordination and productivity. We also investigate the pros and cons of using specialized integration sub‐teams and find that their advantage decreases as the project schedule becomes tighter. Decentralized decisions and asymmetric subsystems are also discussed.
Managing R&D Project Shifts in High‐Tech Organizations: A Multi‐Method Study
Authors: Chandrasekaran Aravind , Linderman Kevin , Sting Fabian J. , Benner Mary J.
Published: June 2015

High‐tech organizations maintain a portfolio of R&D projects that address problems with different levels of complexity. These projects use different strategies to search for technological solutions. Projects refining existing products, processes, and technologies, for instance, employ a local search strategy to improve performance, while projects developing new products, processes, and technologies employ a distant search strategy. However, projects can shift in their levels of complexity due to exogenous technological changes, and failure to change search strategy in turn can negatively impact project performance. This study first develops grounded theory via case studies to understand how high‐tech organizations manage R&D projects when complexity shifts. The case data come from 142 informants in 12 R&D projects at three high‐tech business units. A cross‐case comparison shows that three interconnected mechanisms positioned at multiple levels within the organization enable high‐tech organizations to identify such shifts and adjust the project's search. We refer to this strategy as responsive search. We then conduct agent‐based simulation experiments to examine the conditions under which the responsive search outperforms other canonical search strategies. Overall, this study sheds light on the underexplored question of how to make mid‐project corrections by effectively identifying and managing shifts in project complexity.
Taxonomy, morphology, and genetic variation of Nitella flexilis var. bifurcata (Charales, Characeae) from Japan
Authors: Sakayama Hidetoshi , Kai Atsushi , Nishiyama Mio , Watanabe Makoto M. , Kato Syou , Ito Motomi , Nozaki Hisayoshi , Kawai Hiroshi
Published: June 2015

The taxonomic status of Nitella flexilis var. bifurcata (Charales, Characeae), which is endemic to Japan, has remained unclear because there have been no records since its description in 1964, and the detailed morphology of fully mature individuals as well as its molecular phylogeny have not been studied. Recently, we collected a fully mature N. flexilis var. bifurcata from two lakes near the type locality in Japan. The morphological characteristics of the thalli agreed well with that in the original description of the taxon, with distinctive fertile and sterile branchlets that divided twice and unicellular dactyls. Scanning electron microscopy showed that the fine oospore structure of N. flexilis var. bifurcata was different from that of related taxa. In addition, molecular phylogenetic and haplotype network analyses using the chloroplast rbcL DNA sequences and the intergenic spacer regions between atpB and rbcL genes demonstrated that N. flexilis var. bifurcata and N. flexilis var. flexilis were distinct.
Intracellular nitrite accumulation: The cause of growth inhibition of Microcystis aeruginosa exposure to high nitrite level
Authors: Chen Weimin , Liu Hao
Published: June 2015

The aim of the present study is to test the role of intracellular nitrite in external nitrite suppressing algal growth. We examined the growth of Microcystis aeruginosa at different nitrite levels under high nitrate conditions and without nitrate conditions. There were higher intracellular nitrite and lower Pmchla, Rd chla, αchl, maximum cell density and specific growth rate in high nitrate group than nitrate absence group at 5 mg NO2−‐N L−1. At 10 and 15 mg NO2−‐N L−1, Pmchla, Rd chla, αchl, maximum cell densities and specific growth rates in the high nitrate group became higher than those of the nitrate absence group, while a lower intracellular nitrite in the high nitrate group than nitrate absence group was observed. In addition, the intracellular nitrite and the growth of M. aeruginosa in the high nitrate group did not change from 5 to 10 mg NO2−‐N L−1. In the nitrite uptake experiment, with nitrite concentration increasing from 5 to 15 mg NO2−‐N L−1, maximum nitrite uptake rate of alga increased, and half‐saturation constant of alga decreased. These results indicate that external nitrite inhibited algal growth through stimulating intracellular nitrite rise, which resulted from overexpression of nitrite transporter.