bluuebunny/crossref_metadata_2025 huggingface dataset:
A Structure–Conduct–Performance Perspective of How Strategic Supply Chain Integration Affects Firm Performance
Authors: Ralston Peter M. , Blackhurst Jennifer , Cantor David E. , Crum Michael R.
Published: October 2014

There are several factors that affect a firm's ability to successfully integrate internally and externally for organizational improvement. This study seeks to understand the relationship between a firm's strategy, its supply chain integration efforts, and firm performance. Leveraging the theoretical lens of structure–conduct–performance from the industrial organization economics literature, and utilizing both archival and survey data, we describe how firms may align their internal and external supply chain integration strategies with customers and suppliers. In doing so, these internal and external integration strategies affect the firm's ability to respond to customer demand, which then impacts operational and financial performance. Our work provides theoretical and empirical evidence of these relationships and thus extends prior strategic supply chain integration literature.
Relationship Between Degenerative Joint Disease, Pain, and Bartonella spp. Seroreactivity in Domesticated Cats
Authors: Tomas A. , Pultorak E.L. , Gruen M.E. , Breitschwerdt E.B. , Lascelles B.D.X.
Published: October 2014

Background

Recently, a potential association was identified between Bartonella exposure and arthritides in mammalian species other than cats.

Hypothesis/Objectives

We hypothesized that Bartonella exposure is associated with more severe degenerative joint disease (DJD) and a greater burden of DJD‐associated pain in client‐owned cats.

Animals

Ninety‐four client‐owned cats (6 months to 20 years old), ranging from clinically unaffected to severely lame because of DJD.

Methods

Using physical examination and radiography, pain and radiographic scores were assigned to each part of the bony skeleton. Sera were tested for Bartonella henselae, B. koehlerae, and B. vinsonii subsp. berkhoffii (genotypes I, II, and III) antibodies using immunofluorescence antibody assays. Variables were categorized and logistic regression used to explore associations.

Results

Seropositivity to Bartonella was identified in 33 (35.1%) cats. After multivariate analysis controlling for age, total DJD score (OR, 0.51; 95% CI, 0.26–0.97; P = .042), appendicular pain score (OR, 0.33; 95% CI, 0.17–0.65; P = .0011), and total pain score (OR, 0.35; 95% CI, 0.17–0.72; P = .0045) were significantly inversely associated with Bartonella seroreactivity status, indicating that cats with higher DJD and pain scores were less likely to be Bartonella seropositive.

Conclusions and Clinical Importance

Based upon this preliminary study, Bartonella spp. seropositivity was associated with decreased severity of DJD and decreased DJD‐associated pain in cats. Additional studies are needed to verify these findings, and if verified, to explore potential mechanisms.
Antiarrhythmic and Electrophysiologic Effects of Flecainide on Acutely Induced Atrial Fibrillation in Healthy Horses
Authors: Haugaard M.M. , Pehrson S. , Carstensen H. , Flethøj M. , Hesselkilde E.Z. , Præstegaard K.F. , Diness J.G. , Grunnet M. , Jespersen T. , Buhl R.
Published: October 2014

Background

Only few pharmacologic compounds have been validated for treatment of atrial fibrillation (AF) in horses. Studies investigating the utility and safety of flecainide to treat AF in horses have produced conflicting results, and the antiarrhythmic mechanisms of flecainide are not fully understood.

Objectives

To study the potential of flecainide to terminate acutely induced AF of short duration (≥15 minutes), to examine flecainide‐induced changes in AF duration and AF vulnerability, and to investigate the in vivo effects of flecainide on right atrial effective refractory period, AF cycle length, and ventricular depolarization and repolarization.

Animals

Nine Standardbred horses. Eight received flecainide, 3 were used as time‐matched controls, 2 of which also received flecainide.

Methods

Prospective study. The antiarrhythmic and electrophysiologic effects of flecainide were based on 5 parameters: ability to terminate acute pacing‐induced AF (≥15 minutes), and drug‐induced changes in atrial effective refractory period, AF duration, AF vulnerability, and ventricular depolarization and repolarization times. Parameters were assessed at baseline and after flecainide by programmed electrical stimulation methods.

Results

Flecainide terminated all acutely induced AF episodes (n = 7); (AF duration, 21 ± 5 minutes) and significantly decreased the AF duration, but neither altered atrial effective refractory period nor AF vulnerability significantly. Ventricular repolarization time was prolonged between 8 and 20 minutes after initiation of flecainide infusion, but no ventricular arrhythmias were detected.

Conclusions and Clinical Importance

Flecainide had clear antiarrhythmic properties in terminating acute pacing‐induced AF, but showed no protective properties against immediate reinduction of AF. Flecainide caused temporary prolongation in the ventricular repolarization, which may be a proarrhythmic effect.
Conservation genomics of anadromous Atlantic salmon across its North American range: outlier loci identify the same patterns of population structure as neutral loci
Authors: Moore Jean‐Sébastien , Bourret Vincent , Dionne Mélanie , Bradbury Ian , O'Reilly Patrick , Kent Matthew , Chaput Gérald , Bernatchez Louis
Published: October 2014

Anadromous Atlantic salmon (Salmo salar) is a species of major conservation and management concern in North America, where population abundance has been declining over the past 30 years. Effective conservation actions require the delineation of conservation units to appropriately reflect the spatial scale of intraspecific variation and local adaptation. Towards this goal, we used the most comprehensive genetic and genomic database for Atlantic salmon to date, covering the entire North American range of the species. The database included microsatellite data from 9142 individuals from 149 sampling locations and data from a medium‐density SNP array providing genotypes for >3000 SNPs for 50 sampling locations. We used neutral and putatively selected loci to integrate adaptive information in the definition of conservation units. Bayesian clustering with the microsatellite data set and with neutral SNPs identified regional groupings largely consistent with previously published regional assessments. The use of outlier SNPs did not result in major differences in the regional groupings, suggesting that neutral markers can reflect the geographic scale of local adaptation despite not being under selection. We also performed assignment tests to compare power obtained from microsatellites, neutral SNPs and outlier SNPs. Using SNP data substantially improved power compared to microsatellites, and an assignment success of 97% to the population of origin and of 100% to the region of origin was achieved when all SNP loci were used. Using outlier SNPs only resulted in minor improvements to assignment success to the population of origin but improved regional assignment. We discuss the implications of these new genetic resources for the conservation and management of Atlantic salmon in North America.
The NOTCH3ECD cascade hypothesis of cerebral autosomal‐dominant arteriopathy with subcortical infarcts and leukoencephalopathy disease
Authors: Joutel Anne
Published: October 2014

Background

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, with an autosomal dominant mode of transmission, is an archetypal small vessel disease of the brain that has emerged as the most common heritable cause of stroke and vascular dementia worldwide.

Aims and methods

Here we review the current knowledge on the pathogenesis of this disease.

Results

The disease is caused by highly stereotyped missense mutations that alter the number of cysteine residues in the extracellular domain of NOTCH3, a transmembrane receptor that undergoes a series of proteolytic cleavages on ligand binding that release the extracellular domain, and ultimately enable the intracellular domain to translocate to the nucleus, where it acts as a transcriptional activator. NOTCH3 is predominantly expressed in vascular smooth muscle cells, and is critical for the structure and function of small vessels of the brain. Mutations differentially affect NOTCH3 transcriptional activity; however, it is still debated whether a reduction in NOTCH3 activity might contribute to the disease process. In contrast, all disease associated NOTCH3 mutations are associated with an early accumulation, aggregation and deposition of the extracellular domain at the plasma membrane of smooth muscle cells, in extracellular deposits called granular osmiophilic material. Importantly, recent work identified a novel mechanism in which excess of the extracellular domain of NOTCH3 promotes the abnormal recruitment of proteins of the extracellular matrix that might cause multifactorial toxicity in the brain vessels.

Conclusion

Recent studies lend support to a NOTCH3ECD cascade hypothesis in in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy that posits that the deposition of NOTCH3 extracellular domain in the brain vessels initiates a sequence of events that ultimately lead to stroke and dementia.
Chronic inflammatory demyelinating polyneuropathy triggered by interferon‐α for chronic hepatitis B virus infection
Authors: Sakaguchi Hideya , Yamashita Satoshi , Ueda Akihiko , Sada Hiromi , Ikeda Tokunori , Hirahara Tomoo , Honda Shoji , Kimura En , Yamashita Taro , Maeda Yasushi , Hirano Teruyuki , Uchino Makoto
Published: October 2014

Interferon‐α has been widely used for treatment of chronic hepatitis and some malignancies. Several autoimmune diseases have been reported to be induced by interferon‐α, but chronic inflammatory demyelinating polyneuropathy is rare. Here, we report a chronic hepatitis B patient who developed chronic inflammatory demyelinating polyneuropathy after receiving interferon‐α treatment. After withdrawal of interferon‐α, neurological symptoms continued to progress, but the symptoms improved after intravenous immunoglobulin treatment. This case provides further immunological insight into the correlation between chronic inflammatory demyelinating polyneuropathy and interferon‐α.
Spinocerebellar ataxia type 6: Lessons from faithful knock‐in mouse models
Authors: Watase Kei
Published: October 2014

Spinocerebellar ataxia type 6 is a dominantly inherited neurodegenerative disorder characterized by slowly progressive ataxia, slurred speech and nystagmus. The molecular pathogenesis of spinocerebellar ataxia type 6 has attracted considerable attention, because it is caused by the small expansion of a CAG trinucleotide repeat encoding a polyglutamine tract within the Cav2.1 voltage‐gated Ca++ channel. To recreate the characteristics of spinocerebellar ataxia type 6, we produced several lines of knock‐in mice carrying normal or mutant CAG repeat tracts in the Cacna1a locus. The mice expressing a hyperexpanded polyglutamine (Sca684Q) developed late‐onset progressive motor impairment and neuronal inclusion formation in the cytoplasm of cerebellar Purkinje cells. The electrophysiological analysis of the Sca684Q Purkinje cells showed that the repeat expansion did not affect the intrinsic properties of the channel. MPI‐118Q knock‐in mice, which expressed a hyperexpanded channel at modestly enhanced levels because of the insertion of a splice‐site mutation, recapitulated many features of spinocerebellar ataxia type 6, including selective Purkinje cell degeneration. An analysis of the cytoplasmic neuronal inclusions showed the lysosomal localization of accumulated mutant Cav2.1 channels. The lack of cathepsin B, a major lysosomal cysteine proteinase, increased the loss of the Purkinje cells and was accompanied by an acceleration of neuronal inclusion formation in this model. These results suggest that the spinocerebellar ataxia type 6 mutation exerts its neurotoxicity through a mechanism associated with age‐dependent accumulation of the expanded polyglutamine protein, and the pathogenesis of spinocerebellar ataxia type 6 involves the endolysosomal degradation pathway.
Cardioembolic stroke in the cardiac variant of Fabry disease
Authors: Nishimura Kazutaka , Uehara Toshiyuki , Ishibashi‐Ueda Hatsue , Anzai Toshihisa , Toyoda Kazunori
Published: October 2014

We describe herein the case of a 71‐year‐old man with the cardiac variant of Fabry disease presenting with cardioembolic stroke. Stroke is one of the most well‐known manifestations of Fabry disease, and lacunar stroke is a widely recognized etiology. However, little is known about stroke in patients with the cardiac variant of Fabry disease. The cardiac variant of Fabry disease should be considered as a potential cardiac source of embolic stroke.
Perpetuating ‘New Public Management’ at the expense of nurses' patient education: a discourse analysis
Authors: Bergh Anne‐Louise , Friberg Febe , Persson Eva , Dahlborg‐Lyckhage Elisabeth
Published: October 2014

This study aimed to explore the conditions for nurses' daily patient education work by focusing on managers' way of speaking about the patient education provided by nurses in hospital care. An explorative, qualitative design with a social constructionist perspective was used. Data were collected from three focus group interviews and analysed by means of critical discourse analysis. Discursive practice can be explained by the ideology of hegemony. Due to a heavy workload and lack of time, managers could ‘see’ neither their role as a supporter of the patient education provided by nurses, nor their role in the development of nurses' pedagogical competence. They used organisational, financial, medical and legal reasons for explaining their failure to support nurses' provision of patient education. The organisational discourse was an umbrella term for ‘things’ such as cost‐effectiveness, which were prioritised over patient education. There is a need to remove managerial barriers to the professional development of nurses' patient education. Managers should be responsible for ensuring and overseeing that nurses have the prerequisites necessary for providing patient education as well as for enabling continuous reflective dialogue and opportunities for learning in practice.
Genome‐wide association mapping and biochemical markers reveal that seed ageing and longevity are intricately affected by genetic background and developmental and environmental conditions in barley
Authors: NAGEL MANUELA , KRANNER ILSE , NEUMANN KERSTIN , ROLLETSCHEK HARDY , SEAL CHARLOTTE E. , COLVILLE LOUISE , FERNÁNDEZ‐MARÍN BEATRIZ , BÖRNER ANDREAS
Published: October 2014

Globally, over 7.4 million accessions of crop seeds are stored in gene banks, and conservation of genotypic variation is pivotal for breeding. We combined genetic and biochemical approaches to obtain a broad overview of factors that influence seed storability and ageing in barley (Hordeum vulgare). Seeds from a germplasm collection of 175 genotypes from four continents grown in field plots with different nutrient supply were subjected to two artificial ageing regimes. Genome‐wide association mapping revealed 107 marker trait associations, and hence, genotypic effects on seed ageing. Abiotic and biotic stresses were found to affect seed longevity. To address aspects of abiotic, including oxidative, stress, two major antioxidant groups were analysed. No correlation was found between seed deterioration and the lipid‐soluble tocochromanols, nor with oil, starch and protein contents. Conversely, the water‐soluble glutathione and related thiols were converted to disulphides, indicating a strong shift towards more oxidizing intracellular conditions, in seeds subjected to long‐term dry storage at two temperatures or to two artificial ageing treatments. The data suggest that intracellular pH and (bio)chemical processes leading to seed deterioration were influenced by the type of ageing or storage. Moreover, seed response to ageing or storage treatment appears to be significantly influenced by both maternal environment and genetic background.
Photoisomerization of cis‐1,2‐di(1‐Methyl‐2‐naphthyl)ethene at 77 K in Glassy Media
Authors: Redwood Christopher , Ratheesh Kumar V. K. , Hutchinson Stuart , Mallory Frank B. , Mallory Clelia W. , Clark Ronald J. , Dmitrenko Olga , Saltiel Jack
Published: October 2014

cis‐1,2‐Di(1‐methyl‐2‐naphthyl)ethene, c‐1,1, undergoes photoisomerization in methylcyclohexane, isopentane and diethyl ether/isopentane/ethanol glasses at 77 K. On 313 nm excitation the fluorescence of c‐1,1 is replaced by fluorescence from t‐1,1. Singular value decomposition reveals that the spectral matrices behave as two component systems suggesting conversion of a stable c‐1,1 conformer to a stable t‐1,1 conformer. However, the fluorescence spectra are λexc dependent. Analysis of global spectral matrices shows that c‐1,1 is a mixture of two conformers, each of which gives one of four known t‐1,1 conformers. The λexc dependence of the c‐1,1 fluorescence spectrum is barely discernible. Structure assignments to the resolved fluorescence spectra are based on the principle of least motion and on calculated geometries, energy differences and spectra of the conformers. The relative shift of the c‐1,1 conformer spectra is consistent with the shift of the calculated absorption spectra. The calculated structure of the most stable conformer of c‐1,1 agrees well with the X‐ray crystal structure. Due to large deviations of the naphthyl groups from the ethenic plane in the conformers of both c‐ and t‐1,1 isomers, minimal motion of these bulky substituents accomplishes cis → trans interconversion by rotation about the central bond.
Systemic jasmonic acid modulation in mycorrhizal tomato plants and its role in induced resistance against Alternaria alternata
Authors: Nair A. , Kolet S. P. , Thulasiram H. V. , Bhargava S.
Published: October 2014

Tomato plants colonised with the arbuscular mycorrhizal (AM) fungus Glomus fasciculatum show systemic induced resistance to the foliar pathogen Alternaria alternata, as observed in interactions of other AM‐colonised plants with a range of pathogens. The role of jasmonic (JA) and salicylic (SA) acid in expression of this mycorrhiza‐induced resistance (MIR) against A. alternata was studied by measuring: (i) activity of enzymes reported to be involved in their biosynthesis, namely lipoxygenase (LOX) and phenylammonia lyase (PAL); and (ii) levels of methyl jasmonate (MeJA) and SA. Transcript abundance of some defence genes associated with JA and SA response pathways were also studied. Both LOX and PAL activity increased twofold in response to pathogen application to control plants. AM‐colonised plants had three‐fold higher LOX activity compared to control plants, but unlike controls, this did not increase further in response to pathogen application. Higher LOX activity in AM‐colonised plants correlated with four‐fold higher MeJA in leaves of AM‐colonised plants compared to controls. Treatment of plants with the JA biosynthesis inhibitor salicylhydroxamic acid (SHAM) led to 50% lower MeJA in both control and AM‐colonised plants and correlated with increased susceptibility to A. alternata, suggesting a causal role for JA in expression of MIR against the pathogen. Genes involved in JA biosynthesis (OPR3) and response (COI1) showed six‐ and 42‐fold higher expression, respectively, in leaves of AM‐colonised plants compared to controls. AM‐colonised plants also showed increased expression of the SA response gene PR1 and that of the wound‐inducible polypeptide prosystemin. Our results suggest that the systemic increase in JA in response to AM colonisation plays a key role in expression of MIR against A. alternata.
Vote as you Think: Determinants of Consistent Decision Making in Direct Democracy
Authors: Lanz Simon , Nai Alessandro
Published: October 2014

This study investigates the conditions under which Swiss citizens take consistent decisions, that is, decisions that reflect their argument‐based opinions, during direct‐democratic ballots. In line with recent work on cognitive political behavior, we expect the drivers of consistent voting to be found at the individual and contextual level. At the individual level, we argue that political knowledge positively affects consistent decisions. At the contextual level, we anticipate a positive effect for campaign intensity, complexity and negativism. We estimate hierarchical logistic models based on VOX survey data (1999‐2005) and original data that captures the nature of political campaigns. Our results support our expectations for the situational level and (partially) for the individual factors.
Rice SNF2 family helicase ENL1 is essential for syncytial endosperm development
Authors: Hara Tomomi , Katoh Hirokazu , Ogawa Daisuke , Kagaya Yasuaki , Sato Yutaka , Kitano Hidemi , Nagato Yasuo , Ishikawa Ryo , Ono Akemi , Kinoshita Tetsu , Takeda Shin , Hattori Tsukaho
Published: October 2014

The endosperm of cereal grains represents the most important source of human nutrition. In addition, the endosperm provides many investigatory opportunities for biologists because of the unique processes that occur during its ontogeny, including syncytial development at early stages. Rice endospermless 1 (enl1) develops seeds lacking an endosperm but carrying a functional embryo. The enl1 endosperm produces strikingly enlarged amoeboid nuclei. These abnormal nuclei result from a malfunction in mitotic chromosomal segregation during syncytial endosperm development. The molecular identification of the causal gene revealed that ENL1 encodes an SNF2 helicase family protein that is orthologous to human Plk1‐Interacting Checkpoint Helicase (PICH), which has been implicated in the resolution of persistent DNA catenation during anaphase. ENL1‐Venus (enhanced yellow fluorescent protein (YFP)) localizes to the cytoplasm during interphase but moves to the chromosome arms during mitosis. ENL1‐Venus is also detected on a thread‐like structure that connects separating sister chromosomes. These observations indicate the functional conservation between PICH and ENL1 and confirm the proposed role of PICH. Although ENL1 dysfunction also affects karyokinesis in the root meristem, enl1 plants can grow in a field and set seeds, indicating that its indispensability is tissue‐dependent. Notably, despite the wide conservation of ENL1/PICH among eukaryotes, the loss of function of the ENL1 ortholog in Arabidopsis (CHR24) has only marginal effects on endosperm nuclei and results in normal plant development. Our results suggest that ENL1 is endowed with an indispensable role to secure the extremely rapid nuclear cycle during syncytial endosperm development in rice.
Stoichiometry and novel gating mechanism within the cystic fibrosis transmembrane conductance regulator channel
Authors: Qian Feng , Li Tao , Yang Fei , Liu Lian
Published: October 2014

New Findings

What is the central question of this study?

We aimed to demonstrate the possibility that the cystic fibrosis transmembrane conductance regulator (CFTR) forms higher‐order multimers during channel pore formation and/or channel gating using functional evidence.

What is the main finding and its importance?

The majority of our electrophysiological data suggested that the CFTR channel pore is formed by transmembrane domains of only one CFTR molecule as a monomer. However, we also observed functional upregulation of CFTR activation in patches, which implies interprotein interactions among CFTR molecules. Our findings will help to resolve many contradictions among previous reports regarding whether CFTR is a monomer or a multimer.

Despite its fundamental importance to the molecular mechanism underlying cystic fibrosis, many details of the structural basis for the cystic fibrosis transmembrane conductance regulator (CFTR) remain unknown. In addition, the possible interactions among the CFTR proteins have not been clearly demonstrated. In order to identify whether the CFTR channel pore is formed as a monomer or a multimer, we analysed the single‐channel properties in patches of cell membrane that coexpressed selected CFTR mutants having significantly different single‐channel properties. No hybrid channel opening patterns were observed. We therefore propose that the CFTR channel pore is indeed composed of a monomer. However, we also observed that coexisting CFTR monomers in the cell membrane facilitated the activation of individual CFTR channels. The functional upregulation of this CFTR channel opening probability and the different gating behaviour suggest dynamic conformational changes among the interacting CFTR proteins within the multimeric CFTR complex. Our findings regarding the CFTR monomer channel pore and the novel synergistic gating behaviour within the CFTR channel complex will help to resolve the remaining contradictions among previous studies regarding whether CFTR is a monomer or a multimer.
Enhanced pan‐peroxisome proliferator‐activated receptor gene and protein expression in adipose tissue of diet‐induced obese mice treated with telmisartan
Authors: Penna‐de‐Carvalho Aline , Graus‐Nunes Francielle , Rabelo‐Andrade Júlia , Mandarim‐de‐Lacerda Carlos Alberto , Souza‐Mello Vanessa
Published: October 2014

New Findings

What is the central question of this study?

Telmisartan, an antihypertensive, has beneficial side‐effects through its peroxisome proliferator‐activated receptor (PPAR) β/δ agonism in white adipose tissue, besides its well‐known property of partial PPARγ agonism. Here, we investigated a potential pan‐PPAR role of this drug in the white and brown adipose tissues.

What is the main finding and its importance?

Telmisartan enhanced pan‐PPAR gene and protein expression in adipose tissue (white and brown) in obese mice, with downstream effects that resulted in the management of insulin resistance, anti‐inflammatory adipokine profile and thermogenesis induction. These findings are relevant and should be explored as new targets for controlling obesity and comorbidities through pan‐PPAR‐related effects.

Telmisartan has previously been used to target obesity, showing peroxisome proliferator‐activated receptor (PPAR) β/δ‐related effects in white adipose tissue (WAT). We sought to evaluate whether telmisartan enhances gene and protein expression of all PPAR isoforms in WAT and brown adipose tissue (BAT), as well as their downstream effects upon insulin resistance, adipokine profile and adaptive thermogenesis. Male C57BL/6 mice were fed standard chow (SC; 10% lipids) or high‐fat diet (HF; 50% lipids) for 10 weeks. Animals were then randomly allocated into the following four groups: SC, SC‐T, HF and HF‐T. Telmisartan [10 mg (kg diet)−1] was administered for 4 weeks in the diet. Animals in the HF group were overweight and exhibited hypertension, insulin resistance, decreased energy expenditure, a pro‐inflammatory adipokine profile and abnormal fat pad mass distribution. Animals in the HF group showed decreased expression of PPARα, β/δ and γ in WAT and BAT, resulting in impaired glucose uptake and insufficient thermogenesis. Due to the improvement in the adipokine profile and enhanced insulin sensitivity with adequate insulin‐stimulated glucose uptake after treatment with telmisartan, the activation of all PPAR isoforms in WAT was beneficial. In BAT, telmisartan induced sustained sympathetic activation, because the β3‐adrenergic receptor was induced by PPARβ/δ, while uncoupling protein 1 was induced by PPARα to promote thermogenesis. Telmisartan exerted anti‐obesity effects through higher pan‐PPAR gene and protein expression. Upon PPARα, β/δ and γ (pan‐PPAR) agonism in adipose tissue of obese mice, telmisartan ameliorates inflammation and insulin resistance, as well as inducing non‐shivering thermogenesis. Our results point to new therapeutic targets for the control of obesity and comorbidities through pan‐PPAR‐related effects.
Distinct roles of L‐ and T‐type voltage‐dependent Ca2+ channels in regulation of lymphatic vessel contractile activity
Authors: Lee Stewart , Roizes Simon , von der Weid Pierre‐Yves
Published: October 2014

Key points

Lymph transport is promoted by lymphatic pumping, a robust phasic contractile activity of the collecting lymphatic vessels. This contractile function, critical for tissue fluid homeostasis and immune cell transport to lymph nodes, is regulated by the amount of lymph entering the vessels and subsequent distension of the vessel wall.

While lymphatic pumping relies on influx of Ca2+ through voltage‐dependent Ca2+ channels, characterization of these channels and details of their contribution to the regulation of stretch‐activated contractions are lacking.

Here we report the expression of L‐ and T‐type Ca2+ channels in rat mesenteric lymphatic vessels and their differential role in regulating strength and frequency of lymphatic contractions.

This study fosters our knowledge on the mechanisms that drive stretch‐activated lymphatic contractions. It may help in providing a basis to developing agents able to enhance lymphatic function, which could be of therapeutic benefit during lymphatic impairment such as lymphoedema.

Lymph drainage maintains tissue fluid homeostasis and facilitates immune response. It is promoted by phasic contractions of collecting lymphatic vessels through which lymph is propelled back into the blood circulation. This rhythmic contractile activity (i.e. lymphatic pumping) increases in rate with increase in luminal pressure and relies on activation of nifedipine‐sensitive voltage‐dependent Ca2+ channels (VDCCs). Despite their importance, these channels have not been characterized in lymphatic vessels. We used pressure‐ and wire‐myography as well as intracellular microelectrode electrophysiology to characterize the pharmacological and electrophysiological properties of L‐type and T‐type VDCCs in rat mesenteric lymphatic vessels and evaluated their particular role in the regulation of lymphatic pumping by stretch. We complemented our study with PCR and confocal immunofluorescence imaging to investigate the expression and localization of these channels in lymphatic vessels. Our data suggest a delineating role of VDCCs in stretch‐induced lymphatic vessel contractions, as the stretch‐induced increase in force of lymphatic vessel contractions was significantly attenuated in the presence of L‐type VDCC blockers nifedipine and diltiazem, while the stretch‐induced increase in contraction frequency was significantly decreased by the T‐type VDCC blockers mibefradil and nickel. The latter effect was correlated with a hyperpolarization. We propose that activation of T‐type VDCCs depolarizes membrane potential, regulating the frequency of lymphatic contractions via opening of L‐type VDCCs, which drive the strength of contractions.
Ageing and muscular dystrophy differentially affect murine pharyngeal muscles in a region‐dependent manner
Authors: Randolph Matthew E. , Luo Qingwei , Ho Justin , Vest Katherine E. , Sokoloff Alan J. , Pavlath Grace K.
Published: October 2014

Key points

Millions of elderly individuals have dysphagia, a debilitating and life‐threatening condition in which the ability to swallow is impaired.

Several muscles surround the three regions of the pharynx, which are essential for proper swallowing, yet the effects of ageing and disease on these muscles are not well understood.

We demonstrate that the fibre size of murine pharyngeal muscles is differentially affected by ageing and muscular dystrophy depending on their location within the pharynx.

Using a mouse model of an age‐associated dysphagic disease (oculopharyngeal muscular dystrophy), we show that overexpression of wild‐type polyadenylate binding nuclear protein 1 in muscle tissue prevents age‐related dysphagia and age‐related muscle atrophy of laryngopharyngeal muscles.

These results demonstrate that mice are an excellent model for studying mechanisms of ageing and disease on pharyngeal muscle physiology, and such studies could lead to new therapies for individuals with dysphagia.

The inability to swallow, or dysphagia, is a debilitating and life‐threatening condition that arises with ageing or disease. Dysphagia results from neurological or muscular impairment of one or more pharyngeal muscles, which function together to ensure proper swallowing and prevent the aspiration of food or liquid into the lungs. Little is known about the effects of age or disease on pharyngeal muscles as a group. Here we show ageing affected pharyngeal muscle growth and atrophy in wild‐type mice depending on the particular muscle analysed. Furthermore, wild‐type mice also developed dysphagia with ageing. Additionally, we studied pharyngeal muscles in a mouse model for oculopharyngeal muscular dystrophy, a dysphagic disease caused by a polyalanine expansion in the RNA binding protein, PABPN1. We examined pharyngeal muscles of mice overexpressing either wild‐type A10 or mutant A17 PABPN1. Overexpression of mutant A17 PABPN1 differentially affected growth of the palatopharyngeus muscle dependent on its location within the pharynx. Interestingly, overexpression of wild‐type A10 PABPN1 was protective against age‐related muscle atrophy in the laryngopharynx and prevented the development of age‐related dysphagia. These results demonstrate that pharyngeal muscles are differentially affected by both ageing and muscular dystrophy in a region‐dependent manner. These studies lay important groundwork for understanding the molecular and cellular mechanisms that regulate pharyngeal muscle growth and atrophy, which may lead to novel therapies for individuals with dysphagia.
Evidence for cyclooxygenase‐dependent sweating in young males during intermittent exercise in the heat
Authors: Fujii Naoto , McGinn Ryan , Stapleton Jill M. , Paull Gabrielle , Meade Robert D. , Kenny Glen P.
Published: October 2014

Key points

Previous studies implicate nitric oxide (NO) in the control of sweating during exercise in the heat; however, it is unclear whether cyclooxygenase (COX) is also involved.

We demonstrated that exercise‐induced sweating at a moderate heat production (400 W, ∼40% was similarly reduced when COX and NO synthase were inhibited separately and in combination.

Alternatively, inhibiting COX and/or NO synthase did not influence exercise‐induced sweating at a high heat production (700 W, ∼70%

We show that both COX and NO are involved in sweating during exercise at moderate heat production and that the effects may not be independent. However, roles for COX and NO are less evident when heat production is elevated.

The results lead to better understanding of the mechanisms of sweating and indicate that COX inhibitors (e.g. aspirin) may impair core body temperature regulation and thereby increase the risk of heat‐related illness.

Our recent work implicated nitric oxide (NO) in the control of sweating during intermittent exercise; however, it is unclear if cyclooxygenase (COX) is also involved. On separate days, ten healthy young (24 ± 4 years) males cycled in the heat (35°C). Two 30 min exercise bouts were performed at either a moderate (400 W, moderate heat load) or high (700 W, high heat load) rate of metabolic heat production and were followed by 20 and 40 min of recovery, respectively. Forearm sweating (ventilated capsule) was evaluated at four skin sites that were continuously perfused via intradermal microdialysis with: (1) lactated Ringer solution (Control), (2) 10 mm ketorolac (a non‐selective COX inhibitor), (3) 10 mm NG‐nitro‐l‐arginine methyl ester (l‐NAME; a non‐selective NO synthase inhibitor) or (4) a combination of 10 mm ketorolac + 10 mm
l‐NAME. During the last 5 min of the first exercise at moderate heat load, forearm sweating (mg min−1 cm−2) was equivalently reduced with ketorolac (0.54 ± 0.08), l‐NAME (0.55 ± 0.07) and ketorolac+l‐NAME (0.56 ± 0.08) compared to Control (0.67 ± 0.06) (all P < 0.05). Similar results were obtained for the second exercise at moderate heat load (all P < 0.05). However, forearm sweating was similar between the four sites during exercise at high heat load and during recovery regardless of exercise intensity (all P > 0.05). We show that (1) although both COX and NO modulate forearm sweating during intermittent exercise bouts in the heat at a moderate heat load, the effects are not additive, and (2) the contribution of both enzymes to forearm sweating is less evident during intermittent exercise when the heat load is high and during recovery.
Functional changes in deep dorsal horn interneurons following spinal cord injury are enhanced with different durations of exercise training
Authors: Rank M. M. , Flynn J. R. , Battistuzzo C. R. , Galea M. P. , Callister R. , Callister R. J.
Published: October 2014

Key points

Exercise training after spinal cord injury (SCI) enhances collateral sprouting from axons near the injury and is thought to promote intraspinal circuit reorganisation that effectively bridges the SCI. The effects of exercise training, and its duration, on interneurons in these de novo intraspinal circuits are poorly understood.

In an adult mouse hemisection model of SCI, we used whole‐cell patch‐clamp electrophysiology to examine changes in the intrinsic and synaptic properties of deep dorsal horn interneurons in the vicinity of a SCI in response to the injury, and after 3 and 6 weeks of treadmill exercise training.

SCI alone exerted powerful effects on the intrinsic and synaptic properties of interneurons near the lesion.

Importantly, synaptic activity, both local and descending, was preferentially enhanced by exercise training, suggesting that exercise promotes synaptic plasticity in spinal cord interneurons that are ideally placed to form new intraspinal circuits after SCI.

Following incomplete spinal cord injury (SCI), collaterals sprout from intact and injured axons in the vicinity of the lesion. These sprouts are thought to form new synaptic contacts that effectively bypass the lesion epicentre and contribute to improved functional recovery. Such anatomical changes are known to be enhanced by exercise training; however, the mechanisms underlying exercise‐mediated plasticity are poorly understood. Specifically, we do not know how SCI alone or SCI combined with exercise alters the intrinsic and synaptic properties of interneurons in the vicinity of a SCI. Here we use a hemisection model of incomplete SCI in adult mice and whole‐cell patch‐clamp recording in a horizontal spinal cord slice preparation to examine the functional properties of deep dorsal horn (DDH) interneurons located in the vicinity of a SCI following 3 or 6 weeks of treadmill exercise training. We examined the functional properties of local and descending excitatory synaptic connections by recording spontaneous excitatory postsynaptic currents (sEPSCs) and responses to dorsal column stimulation, respectively. We find that SCI in untrained animals exerts powerful effects on intrinsic, and especially, synaptic properties of DDH interneurons. Plasticity in intrinsic properties was most prominent at 3 weeks post SCI, whereas synaptic plasticity was greatest at 6 weeks post injury. Exercise training did not markedly affect intrinsic membrane properties; however, local and descending excitatory synaptic drive were enhanced by 3 and 6 weeks of training. These results suggest exercise promotes synaptic plasticity in spinal cord interneurons that are ideally placed to form new intraspinal circuits after SCI.
Geoacoustic inversion of ship radiated noise in shallow water using data from a single hydrophone
Authors: Crocker Steven E. , Nielsen Peter L. , Miller James H. , Siderius Martin
Published: October 2014

The Centre for Maritime Research and Experimentation conducted a geoacoustic inverse experiment in the Mediterranean Sea in the summer of 2012. Among the objectives was to employ an autonomous underwater vehicle to collect acoustic data to invert for properties of the seafloor. Inversion results for the compression wave speed in the bottom and the source spectrum of the R/V Alliance during a close approach to the bottom moored vehicle are presented. The estimated wave speed was 1529 m/s (σ=10). The source spectrum of the Alliance was estimated across more than six octaves of frequency.
Spinner dolphins (Stenella longirostris GRAY, 1828) acoustic parameters recorded in the Western South Atlantic Ocean
Authors: Moron Juliana R. , Andriolo Artur , Rossi-Santos Marcos
Published: October 2014

Spinner dolphins bioacoustics were study only in Fernando de Noronha Archipelago region in the Western South Atlantic Ocean. Our study aimed to describe the acoustic parameters of this species recorded approximately 3500 km south of Fernando de Noronha Archipelago. An one-element hydrophone was towed 250 m behind the vessel R/V Atlântico Sul over the continental shelf break. Continuous mono recording was performed with the hydrophone passing signals to a digital Fostex® FR-2 LE, recording at 96 kHz/24 bits. A group of approximate 400 dolphins were recorded on June 3, 2013, at 168.9 km shore distance (27o 24’29”S, 46o50’05”W). The wav-files were analyzed through the spectrogram configured as DFT 512 samples, 50% overlap and Hamming window of 1024 points generated by software Raven Pro 1.4. The preliminary results of 10 min recording allowed the extraction of 693 whistles that were classified in contours shapes as: upsweep (42%), chirp (17.3%), downsweep (14%), sinusoidal (10.5%), convex (5.9%), constant (5.4%), and concave (4.9%). Minimum frequencies ranged from 3.32 kHz to 23.30 kHz (mean = 10.88 kHz); maximum frequencies ranged from 6.61 kHz to 35.34 kHz (mean = 15.77 kHz); whistle duration ranged from 0.03 s to 2.58 s (mean = 0.68 s). These results are important to understand populations and/or species distributed in different ocean basins.
A new method for detection of North Atlantic right whale up-calls
Authors: Esfahanian Mahdi , Zhuang Hanqi , Erdol Nurgun
Published: October 2014

A study of detecting North Atlantic Right Whale (NARW) up-calls has been conducted with measurements from passive acoustic monitoring devices. Denoising and normalization algorithms are applied to remove local variance and narrowband noise in order to isolate the NARW up-calls in spectrograms. The resulting spectrograms, after binarization, are treated with a region detection procedure called the Moor-Neighbor algorithm to find continuous objects that are candidates of up-call contours. After selected properties of each detected object are computed, they are compared with a pair of low and high empirical thresholds to estimate the probability of the detected object being an up-call; therefore, those objects that are determined with certainty to be non up-calls are discarded. The final stage in the proposed call detection method is to separate true up-calls from the rest of potential up-calls with classifiers such as linear discriminate analysis (LDA), Naïve Bayes, and decision tree. Experimental results using the data set obtained by Cornell University show that the proposed method can achieve accuracy to 96%.
Spatio-temporal distribution of beaked whales in southern California waters
Authors: Baumann-Pickering Simone , Trickey Jennifer S. , Roch Marie A. , Wiggins Sean M.
Published: October 2014

Cuvier’s beaked whales are the dominant beaked whales offshore of southern California. Their abundance, distribution, and seasonality are poorly understood. Insights on the spatio-temporal distribution of both Cuvier’s and a rare beaked whale with signal type BW43, likely Perrin’s beaked whale, have been derived from long-term autonomous recordings of beaked whale echolocation clicks. Acoustic recordings were collected at 18 sites offshore of southern California since 2006, resulting in a total of ~26 years of recordings. About 23,000 acoustic encounters with Cuvier’s beaked whales were detected. In contrast, there were ~100 acoustic encounters of the BW43 signal type. Cuvier’s beaked whales were predominantly detected at deeper, more southern, and farther offshore sites, and there appears to be a seasonal pattern to their presence, with lower probability of detection during summer and early fall. The BW43 signal type had higher detection rates in the central basins, indicating a possible difference in habitat preference and niche separation between the two species. Further investigation is needed to reveal if these distribution patterns are purely based on bathymetric preference, driven by water masses that determine prey species composition and distribution, or possibly by anthropogenic activity.
Robustness of perceptual features used for passive acoustic classification of cetaceans to the ocean environment
Authors: Binder Carolyn , Hines Paul C.
Published: October 2014

Passive acoustic monitoring (PAM) is used to study cetaceans in their habitats, which cover diverse underwater environments. It is well known that properties of the ocean environment can be markedly different between regions, which can result in distinct propagation characteristics. These can in turn lead to differences in the time-frequency characteristics of a recorded signal and may impact the accuracy of PAM systems. To develop an automatic PAM system capable of operating under numerous environmental conditions, one must account for the impact of propagation conditions. A prototype aural classifier developed at Defence R&D Canada has successfully been used for inter-species discrimination of cetaceans. The aural classifier achieves accurate results by using perceptual signal features that model the features employed by the human auditory system. The current work uses a combination of at-sea experiments and pulse propagation modeling to examine the robustness of the perceptual features with respect to propagation effects. Preliminary results will be presented from bowhead and humpback vocalizations that were transmitted over 1–20 km ranges during a two-day sea trial in the Gulf of Mexico. Insight gained from experimental results will be augmented with model results. [Work supported by the U.S. Office of Naval Research.]
Passive acoustic monitoring on the seasonal species composition of cetaceans from a marine observatory
Authors: Lin Tzu-Hao , Yu Hsin-Yi , Chen Chi-Fang , Chou Lien-Siang
Published: October 2014

Information on the species diversity of cetaceans can help us to understand the community ecology of marine top predators. Passive acoustic monitoring has been widely applied in the cetacean research, however, species identification based on tonal sounds remains challenging. In order to examine the seasonal changing pattern of species diversity, we applied an automatic detection and classification algorithm on acoustic recordings collected from the marine cable hosted observatory off the northeastern Taiwan. Representative frequencies of cetacean tonal sounds were detected. Statistical features were extracted based on the distribution of representative frequency and were used to classify four cetacean groups. The correct classification rate was 72.2% based on the field recordings collected from onboard surveys. Analysis on one-year recordings revealed that the species diversity was highest in winter and spring. Short finned pilot whales and Risso’s dolphins were the most common species, they mainly occurred in winter and summer. False killer whales were mostly detected in winter and spring. Spinner dolphins, spotted dolphins, and Fraser’s dolphins were mainly detected in summer. Bottlenose dolphins represent the least common species. In the future, the biodiversity, species-specific habitat use, and inter-specific interaction of cetaceans can be investigated through an underwater acoustic monitoring network.