bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pittsburgh Fatigability Scale for Older Adults: Development and Validation
Authors: Glynn Nancy W. , Santanasto Adam J. , Simonsick Eleanor M. , Boudreau Robert M. , Beach Scott R. , Schulz Richard , Newman Anne B.
Published: December 2014

Objectives

To describe the development of the Pittsburgh Fatigability Scale (PFS) and establish its reliability and concurrent and convergent validity against performance measures.

Design

Cross‐sectional.

Setting

University of Pittsburgh, Pittsburgh, Pennsylvania.

Participants

Scale development sample: 1,013 individuals aged 60 and older from two registries; validation sample: 483 adults aged 60 and older from the Baltimore Longitudinal Study of Aging (BLSA).

Measurements

The scale development sample and BLSA participants self‐administered an initial 26‐item perceived fatigability scale. BLSA participants also completed measures of performance fatigability (perceived exertion from a standard treadmill task and performance deterioration from a fast‐paced long‐distance corridor walk), a 6‐m usual‐paced corridor walk, and five timed chair stands.

Results

Principal components analysis with varimax rotation reduced the 26‐item scale to the 10‐item PFS. The PFS showed strong internal consistency (Cronbach's alpha 0.88) and excellent test–retest reliability (intraclass correlation 0.86). In the validation sample, PFS scores, adjusted for age, sex, and race, were greater for those with high performance fatigability, slow gait speed, worse physical function, and lower fitness, with differences between high and low fatigability ranging from 3.2 to 5.1 points (P < .001).

Conclusion

The 10‐item PFS physical fatigability score is a valid and reliable measure of perceived fatigability in older adults and can serve as an adjunct to performance‐based fatigability measures for identifying older adults at risk of mobility limitation in clinical and research settings.
Porosity imaged by a vector projection algorithm correlates with fractal dimension measured on 3D models obtained by microCT
Authors: CHAPPARD DANIEL , STANCU IZABELA‐CRISTINA
Published: December 2014

Porosity is an important factor to consider in a large variety of materials. Porosity can be visualized in bone or 3D synthetic biomaterials by microcomputed tomography (microCT). Blocks of porous poly(2‐hydroxyethyl methacrylate) were prepared with polystyrene beads of different diameter (500, 850, 1160 and 1560 μm) and analysed by microCT. On each 2D binarized microCT section, pixels of the pores which belong to the same image column received the same pseudo‐colour according to a look up table. The same colour was applied on the same column of a frontal plane image which was constructed line by line from all images of the microCT stack. The fractal dimension Df of the frontal plane image was measured as well as the descriptors of the 3D models (porosity, 3D fractal dimension D3D, thickness, density and separation of material walls. Porosity, thickness Df and D3D increased with the size of the porogen beads. A linear correlation was observed between Df and D3D. This method provides quantitative and qualitative analysis of porosity on a single frontal plane image of a porous object.
Side‐chain interactions in the regulatory domain of human glutamate dehydrogenase determine basal activity and regulation
Authors: Mastorodemos Vasileios , Kanavouras Konstantinos , Sundaram Shobana , Providaki Maria , Petraki Zoe , Kokkinidis Michael , Zaganas Ioannis , Logothetis Diomedes E. , Plaitakis Andreas
Published: December 2014

Glutamate Dehydrogenase (GDH) is central to the metabolism of glutamate, a major excitatory transmitter in mammalian central nervous system (CNS). hGDH1 is activated by ADP and L‐leucine and powerfully inhibited by GTP. Besides this housekeeping hGDH1, duplication led to an hGDH2 isoform that is expressed in the human brain dissociating its function from GTP control. The novel enzyme has reduced basal activity (4–6% of capacity) while remaining remarkably responsive to ADP/L‐leucine activation. While the molecular basis of this evolutionary adaptation remains unclear, substitution of Ser for Arg443 in hGDH1 is shown to diminish basal activity (< 2% of capacity) and abrogate L‐leucine activation. To explore whether the Arg443Ser mutation disrupts hydrogen bonding between Arg443 and Ser409 of adjacent monomers in the regulatory domain (‘antenna’), we replaced Ser409 by Arg or Asp in hGDH1. The Ser409Arg‐1 change essentially replicated the Arg443Ser‐1 mutation effects. Molecular dynamics simulation predicted that Ser409 and Arg443 of neighboring monomers come in close proximity in the open conformation and that introduction of Ser443‐1 or Arg409‐1 causes them to separate with the swap mutation (Arg409/Ser443) reinstating their proximity. A swapped Ser409Arg/Arg443Ser‐1 mutant protein, obtained in recombinant form, regained most of the wild‐type hGDH1 properties. Also, when Ser443 was replaced by Arg443 in hGDH2 (as occurs in hGDH1), the Ser443Arg‐2 mutant acquired most of the hGDH1 properties. Hence, side‐chain interactions between 409 and 443 positions in the ‘antenna’ region of hGDHs are crucial for basal catalytic activity, allosteric regulation, and relative resistance to thermal inactivation.

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Glutamate dehydrogenase (GDH) is central to the metabolism of the excitatory transmitter glutamate, and links it with carbohydrate metabolism in energy homeostasis and cell signaling. The isoform hGDH2, in contrast to hGDH1, is dissociated from GTP (guanosine triphosphate) control, has a reduced basal activity, but remains highly responsive to ADP/L‐leucine activation. Substitution of Serine (Ser) for arginine (Arg443) in hGDH1 diminishes basal activity (< 2% of capacity) and abrogates L‐leucine activation. We provide evidence that side‐chain interactions between 409 and 443 positions in the regulatory domain of GDH are crucial for basal catalytic activity, allosteric regulation, and relative resistance to thermal inactivation.
Substantially elevating the levels of αB‐crystallin in spinal motor neurons of mutant SOD1 mice does not significantly delay paralysis or attenuate mutant protein aggregation
Authors: Xu Guilian , Fromholt Susan , Ayers Jacob I. , Brown Hilda , Siemienski Zoe , Crosby Keith W. , Mayer Christopher A. , Janus Christopher , Borchelt David R.
Published: December 2014

There has been great interest in enhancing endogenous protein maintenance pathways such as the heat‐shock chaperone response, as it is postulated that enhancing clearance of misfolded proteins could have beneficial disease modifying effects in amyotrophic lateral sclerosis and other neurodegenerative disorders. In cultured cell models of mutant SOD1 aggregation, co‐expression of αB‐crystallin (αB‐crys) has been shown to inhibit the formation of detergent‐insoluble forms of mutant protein. Here, we describe the generation of a new line of transgenic mice that express αB‐crys at > 6‐fold the normal level in spinal cord, with robust increases in immunoreactivity throughout the spinal cord grey matter and, specifically, in spinal motor neurons. Surprisingly, spinal cords of mice expressing αB‐crys alone contained 20% more motor neurons per section than littermate controls. Raising αB‐crys by these levels in mice transgenic for either G93A or L126Z mutant SOD1 had no effect on the age at which paralysis developed. In the G93A mice, which showed the most robust degree of motor neuron loss, the number of these cells declined by the same proportion as in mice expressing the mutant SOD1 alone. In paralyzed bigenic mice, the levels of detergent‐insoluble, misfolded, mutant SOD1 were similar to those of mice expressing mutant SOD1 alone. These findings indicate that raising the levels of αB‐crys in spinal motor neurons by 6‐fold does not produce the therapeutic effects predicted by cell culture models of mutant SOD1 aggregation.

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Enhancing the protein chaperone function may present a therapeutic approach to amyotrophic lateral sclerosis caused by mutations in SOD1, and other neurodegenerative disorders characterized by cytosolic protein aggregation. Previous studies in cell models suggested that the chaperone known as αB‐crystallin (αB‐crys) can prevent mutant SOD1 aggregation. We report that transgenic expression of αB‐crys at > 6‐fold the normal level in spinal cords of mice expressing mutant SOD1 produces no therapeutic benefit.
Why and How Do Employees Break and Bend Confidential Information Protection Rules?
Authors: Hannah David R. , Robertson Kirsten
Published: December 2014

Organizations cannot function effectively if their employees do not follow organizational rules and policies. In this paper, we explore why and how employees in two high‐tech organizations often broke or bent rules designed to protect their employers' confidential information (CI). The CI protection rules sometimes imposed requirements that disrupted employees' work, forcing employees to choose between CI rule compliance and doing their work effectively and efficiently. Employees in these situations often broke the rules or bent them in ways that enabled employees to meet some of the rules' requirements, while also satisfying other expectations that they faced. We discuss implications of our findings for practice and for future organizational scholarship on rule following.
Preparation and evaluation of a novel biodegradable long-acting intravitreal implant containing ligustrazine for the treatment of proliferative vitreoretinopathy
Authors: Zhang Xuemei , Wei Junhua , Ma Pengkai , Mu Hongjie , Wang Aiping , Zhang Leiming , Wu Zimei , Sun Kaoxiang
Published: December 2014

Objectives

It is challenging to deliver the therapeutic drug effectively to the posterior ocular disease location with optimized exposure and long-term effects when treating proliferative vitreoretinopathy (PVR). The objective of this study is to develop a novel biodegradable and long-acting ocular implant for PVR therapy with ligustrazine as the active ingredient.

Methods

The ligustrazine implants were prepared with poly(DL-lactide-co-glycolide) using a hot-melting extrusion. The physicochemical properties of the implants were characterized. The effectiveness of the selected ligustrazine implants was evaluated in a PVR rabbit model. Furthermore, the in-vitro drug release profile and pharmacokinetics were compared, and in-vitro/in-vivo correlations were evaluated.

Key findings

The optimal implants had an ideal zero-order in-vitro drug release profile, which was correlated with the in-vivo drug absorption fraction in the vitreous bodies of the rabbits. The sustained-release ligustrazine implants significantly reduced the development of PVR in the animal model.

Conclusions

Ligustrazine implants can be used to treat posterior ocular disease in rabbit animal models, and it provides more choices for medical research on posterior ocular disease.
Lemnalol attenuates mast cell activation and osteoclast activity in a gouty arthritis model
Authors: Lee Hsin-Pai , Lin Yen-You , Duh Chang-Yih , Huang Shi-Ying , Wang Hui-Min , Wu Shu-Fen , Lin Sung-Chun , Jean Yen-Hsuan , Wen Zhi-Hong
Published: December 2014

Objectives

In this study, we investigated the effects of a soft coral-derived anti-inflammatory compound, lemnalol, on mast cell (MC) function and osteoclast activity in rats with monosodium urate (MSU) crystal-induced gouty arthritis.

Methods

In this study, we examined the therapeutic effects of lemnalol on intra-articular injection of MSU induces gouty arthritis with the measurement of ankle oedema. Toluidine blue staining were used to analyse the infiltration and the percentage degranulation MCs. Immunohistochemical analysis showed CD117, transforming growth factor beta 1 (TGF-β1), matrix metalloproteinase 9 (MMP-9), the osteoclast markers cathepsin K and tartrate-resistant acid phosphatase (TRAP) protein expression in ankle tissue.

Key findings

We found that both infiltration and degranulation of MCs increased at 24 h after MSU injection in the ankle joint. Immunohistochemical analysis showed that MSU induced upregulation of TGF-β1, MMP-9, the osteoclast markers cathepsin K and TRAP in ankle tissues. Administration of lemnalol ameliorated MSU-induced TGF-β1, MMP-9, cathepsin K and TRAP protein expression.

Conclusions

Taken together, our results show that MSU-induced gouty arthritis is accompanied by osteoclast-related protein upregulation and that lemnalol treatment may be beneficial for the attenuation of MC infiltration and degranulation and for suppressing osteoclast activation in gouty arthritis.
Dissolution of mesalazine modified release tablets under standard and bio-relevant test conditions
Authors: Garbacz Grzegorz , Rappen Gerd-Martin , Koziolek Mirko , Weitschies Werner
Published: December 2014

Objectives

For the treatment of inflammatory bowel disease, the development of pH responsive modified release dosage forms is one of the most common approaches to achieve targeted drug delivery. In this study, the dissolution behaviour of eight different modified release (MR) products containing 800 mg mesalazine was investigated.

Methods

The performance of the products was compared under simulated fasted state conditions using the paddle apparatus as well as the dissolution stress test device mimicking mechanical stress events of bio-relevant intensity.

Key findings

The dissolution behaviour of the eight tested different pH-responsive MR tablets containing 800 mg mesalazine was dependent on the test conditions. Phases of mechanical stress with physiological intensity influenced the dissolution characteristics and caused in some cases accelerated drug release indicating possible dose dumping.

Conclusion

The study demonstrates that besides the investigation of the pH dependency of drug release, the characterisation of the mechanical robustness of the dosage forms is an essential factor determining the dissolution characteristics of such pH-dependent targeted modified release tablets. The susceptibility of 800 mg mesalazine MR tablets towards mechanical stress may be one reason for undesired drug delivery in vivo.
Cross-linked human serum albumin dimer has the potential for use as a plasma-retaining agent for the fatty acid-conjugated antidiabetic drugs
Authors: Taguchi Kazuaki , Chuang Victor Tuan Giam , Yamasaki Keishi , Urata Yukino , Tanaka Ryota , Anraku Makoto , Seo Hakaru , Kawai Keiichi , Maruyama Toru , Komatsu Teruyuki , Otagiri Masaki
Published: December 2014

Objectives

The half-life of fatty acid-conjugated antidiabetic drugs are prolonged through binding to albumin, but this may not occur in diabetic patients with nephropathy complicated with hypoalbuminemia. We previously showed that human serum albumin (HSA) dimerized at the protein's Cys34 by 1,6-bis(maleimido)hexane has longer half-life than the monomer under high permeability conditions. The aim of this study was to investigate the superior ability of this HSA dimer as a plasma-retaining agent for fatty acid conjugated antidiabetic drugs.

Methods

The diabetic nephropathy rat model was prepared by administering a single injection of streptozotocin (STZ) intravenously, and the pharmacokinetic properties of HSA monomer and dimer were evaluated. Site-specific fluorescent probe displacement experiments were performed using warfarin and dansylsarcosine as site I and site II specific fluorescent probes, respectively.

Key findings

The half-life of the HSA dimer in STZ-induced diabetic nephropathy model rats was 1.5 times longer than the HSA monomer. The fluorescent probe displacement experiment results for HSA monomer and dimer were similar, where fatty acid-conjugated antidiabetic drugs displaced dansylsarcosine but not warfarin in a concentration-dependent manner.

Conclusions

The HSA dimer shows potential for use as a plasma-retaining agent for antidiabetic drugs due to its favourable pharmacokinetic properties.
Recombinant protein subunit vaccine synthesis in microbes: a role for yeast?
Authors: Bill Roslyn M
Published: December 2014

Objectives

Recombinant protein subunit vaccines are formulated using protein antigens that have been synthesized in heterologous host cells. Several host cells are available for this purpose, ranging from Escherichia coli to mammalian cell lines. This article highlights the benefits of using yeast as the recombinant host.

Key findings

The yeast species, Saccharomyces cerevisiae and Pichia pastoris, have been used to optimize the functional yields of potential antigens for the development of subunit vaccines against a wide range of diseases caused by bacteria and viruses. Saccharomyces cerevisiae has also been used in the manufacture of 11 approved vaccines against hepatitis B virus and one against human papillomavirus; in both cases, the recombinant protein forms highly immunogenic virus-like particles.

Advances in our understanding of how a yeast cell responds to the metabolic load of producing recombinant proteins will allow us to identify host strains that have improved yield properties and enable the synthesis of more challenging antigens that cannot be produced in other systems. Yeasts therefore have the potential to become important host organisms for the production of recombinant antigens that can be used in the manufacture of subunit vaccines or in new vaccine development.
Z
eyheria montana Mart. (Bignoniaceae) as source of antioxidant and immunomodulatory compounds with beneficial effects on intestinal inflammation
Authors: Seito Leonardo Noboru , Sforcin José Maurício , Bastos Jairo Kenupp , Di Stasi Luiz Claudio
Published: December 2014

Objectives

Z eyheria montana is a medicinal plant used in Brazilian folk medicine for treating skin affections, ulcers, inflammation and diarrhoea, and as an antisyphilitic and antiblenorrhagic agent, but little is known about its mechanisms of action. Herein, a bio-guided assay was carried out to further evaluate its antioxidant and immunomodulatory effects, and the possible benefits on experimental intestinal inflammation.

Methods

Extracts, partitions, fractions and isolated compounds were tested for inhibition of lipid peroxidation. Isolated compounds were tested in vitro for its antioxidant and immunomodulatory action prior to in-vivo evaluation in trinitrobenzenesulfonic acid-induced rat colitis.

Key findings

Two major compounds were identified in the leaf dichloromethane extract: 3′-hydroxy-5,7,4′-trimethoxyflavone and 6-hydroxy-5,7-dimethoxyflavone, which exhibited an antioxidant activity. The compounds protected the colonic glutathione levels in more than 90% despite the absence of protection against the gross macroscopic colonic damage. In addition, the compounds inhibited IL-1ß secretion by macrophages in 91.5% and 72.7% respectively, whereas both reduced IL-6 secretion in about 44.5%.

Conclusions

The major active compounds from Z. montana leaves exerted antioxidant and immunomodulatory effects, endorsing the use of Z. montana in folk medicine as an anti-inflammatory agent. However, further investigation is still needed regarding medicinal plants and the identification of candidate compounds for the treatment of the inflammatory bowel diseases.
Antioxidant activity of Tween-20 and Tween-80 evaluated through different in-vitro tests
Authors: Pérez-Rosés Renato , Risco Ester , Vila Roser , Peñalver Pedro , Cañigueral Salvador
Published: December 2014

Objectives

This study aimed to evaluate the possible antioxidant activity of Tween-20 and Tween-80, two amphipathic nonionic surfactants commonly used as solubilizers and stabilizers, whose pharmacological effects have been ignored to a large degree.

Methods

Antioxidant activity was investigated in vitro measuring the scavenging activity on the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH●), the production of reactive oxygen species (ROS) in activated human neutrophils using flow cytometry and the myeloperoxidase (MPO) inhibitory activity.

Key findings

Tween-20 and Tween-80 did not show scavenging activity on DPPH●, while produced a decrease of the ROS production in human neutrophils, being Tween-20 more active than Tween-80. Moreover, Tween-80 and Tween-20 were found to significantly stimulate MPO enzymatic activity.

Conclusions

Our findings raise concerns with regard to the indiscriminate use of Tween-20 and Tween-80 in clinical and laboratory testing, since they could influence the results that are assigned to the tested substance.
Restoration of Cerebral and Systemic Microvascular Architecture in APP/PS1 Transgenic Mice Following Treatment with Liraglutide™
Authors: Kelly Patricia , McClean Paula L. , Ackermann Maximilian , Konerding Moritz A. , Hölscher Christian , Mitchell Christopher A.
Published: December 2014

Objective

Cerebral microvascular impairments occurring in AD may reduce Aβ peptide clearance and impact upon circulatory ultrastructure and function. We hypothesized that microvascular pathologies occur in organs responsible for systemic Aβ peptide clearance in a model of AD and that Liraglutide (Victoza®) improves vessel architecture.

Methods

Seven‐month‐old APP/PS1 and age‐matched wild‐type mice received once‐daily intraperitoneal injections of either Liraglutide or saline (n = 4 per group) for eight weeks. Casts of cerebral, splenic, hepatic, and renal microanatomy were analyzed using SEM.

Results

Casts from wild‐type mice showed regularly spaced microvasculature with smooth lumenal profiles, whereas APP/PS1 mice revealed evidence of microangiopathies including cerebral microanuerysms, intracerebral microvascular leakage, extravasation from renal glomerular microvessels, and significant reductions in both splenic sinus density (p = 0.0286) and intussusceptive microvascular pillars (p = 0.0412). Quantification of hepatic vascular ultrastructure in APP/PS1 mice revealed that vessel parameters (width, length, branching points, intussusceptive pillars and microaneurysms) were not significantly different from wild‐type mice. Systemic administration of Liraglutide reduced the incidence of cerebral microanuerysms and leakage, restored renal microvascular architecture and significantly increased both splenic venous sinus number (p = 0.0286) and intussusceptive pillar formation (p = 0.0129).

Conclusion

Liraglutide restores cerebral, splenic, and renal architecture in APP/PS1 mice.
The Bacterial signal transduction protein GlnB regulates the committed step in fatty acid biosynthesis by acting as a dissociable regulatory subunit of acetyl‐CoA carboxylase
Authors: Gerhardt Edileusa C.M. , Rodrigues Thiago E. , Müller‐Santos Marcelo , Pedrosa Fabio O. , Souza Emanuel M. , Forchhammer Karl , Huergo Luciano F.
Published: December 2014

Biosynthesis of fatty acids is one of the most fundamental biochemical pathways in nature. In bacteria and plant chloroplasts, the committed and rate‐limiting step in fatty acid biosynthesis is catalyzed by a multi‐subunit form of the acetyl‐CoA carboxylase enzyme (ACC). This enzyme carboxylates acetyl‐CoA to produce malonyl‐CoA, which in turn acts as the building block for fatty acid elongation. In Escherichia coli, ACC is comprised of three functional modules: the biotin carboxylase (BC), the biotin carboxyl carrier protein (BCCP) and the carboxyl transferase (CT). Previous data showed that both bacterial and plant BCCP interact with signal transduction proteins belonging to the PII family. Here we show that the GlnB paralogues of the PII proteins from E. coli and Azospirillum brasiliense, but not the GlnK paralogues, can specifically form a ternary complex with the BC‐BCCP components of ACC. This interaction results in ACC inhibition by decreasing the enzyme turnover number. Both the BC‐BCCP‐GlnB interaction and ACC inhibition were relieved by 2‐oxoglutarate and by GlnB uridylylation. We propose that the GlnB protein acts as a 2‐oxoglutarate‐sensitive dissociable regulatory subunit of ACC in Bacteria.
Invited review: Frontotemporal dementia caused by microtubule‐associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging
Authors: Ghetti Bernardino , Oblak Adrian L. , Boeve Bradley F. , Johnson Keith A. , Dickerson Bradford C. , Goedert Michel
Published: December 2014

Hereditary frontotemporal dementia associated with mutations in the microtubule‐associated protein tau gene (MAPT) is a protean disorder. Three neuropathologic subtypes can be recognized, based on the presence of inclusions made of tau isoforms with three and four repeats, predominantly three repeats and mostly four repeats. This is relevant for establishing a correlation between structural magnetic resonance imaging and positron emission tomography using tracers specific for aggregated tau. Longitudinal studies will be essential to determine the evolution of anatomical alterations from the asymptomatic stage to the various phases of disease following the onset of symptoms.
ERK and p38MAPK pathways regulate myosin light chain phosphatase and contribute to Ca2+ sensitization of intestinal smooth muscle contraction
Authors: Ihara E. , Yu Q. , Chappellaz M. , MacDonald J. A.
Published: December 2014

Background

Mitogen‐activated protein kinases (MAPKs), including extracellular signal‐regulated protein kinase (ERK) and p38MAPK, are known regulators of smooth muscle contractility. The contraction of smooth muscle is mainly regulated by the phosphorylation of regulatory light chains of myosin II (LC20), which is driven by the balance between myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP). We hypothesized that one possible mechanism for MAPK‐dependent modulation of intestinal smooth muscle contractility is via the regulation of MLCP activity.

Methods

Contractile responses to carbachol (CCh) and effects of MAPK inhibitors on CCh‐induced contractions were assessed with isolated rat ileal longitudinal smooth muscle strips. Biochemical assessments of MLCP activity and myosin phosphatse targeting subunit (MYPT1) and CPI‐17 phosphorylations were completed.

Key Results

Treatment of ileal smooth muscle with PD98059 (10 μM; MEK inhibitor) or SB203580 (10 μM; p38MAPK inhibitor) significantly inhibited CCh‐induced contractile force. Decreased MLCP activity was observed during sustained contractions induced by CCh; the MLCP activity was recovered by treatment with PD98059 and SB203580. However, MYPT1 (Thr697 and Thr855) and CPI‐17 (Thr38) phosphorylations were not affected. Application of ML‐7 (MLCK inhibitor) during CCh‐induced sustained contraction elicited an MLCP‐dependent relaxation, the rate of which was accelerated by application of PD98059 and SB203580 with proportional changes in LC20 phosphorylation levels but not MYPT1 phosphorylation (Thr697 or Thr855).

Conclusions & Inferences

ERK and p38MAPK contribute to CCh‐induced sustained contraction in a LC20 phosphorylation dependent manner. Moreover, both kinases inhibit MLCP activity possibly by a novel mechanism.
Characterization of ghrelin‐sensitive neurons in the lumbosacral defecation center in rats
Authors: Naitou K. , Shiina T. , Sugita R. , Nakamori H. , Shimizu Y.
Published: December 2014

Background

Ghrelin is involved in the regulation of somatic growth, feeding behavior and energy homeostasis. Ghrelin stimulates neuropeptide Y (NPY) neurons and activates intracellular AMP‐activated protein kinase (AMPK) in the hypothalamus. These NPY neurons also express the leptin receptor and leptin inhibits ghrelin‐induced activation of NPY neurons. In the spinal cord, we have demonstrated colokinetic action of ghrelin. However, the precise characteristics of the ghrelin‐sensitive neurons remain to be clarified. The aim of this study was firstly to confirm that the action of ghrelin is mediated via a neurogenic pathway in the spinal cord, and secondly to characterize the ghrelin‐sensitive neurons by comparing with hypothalamic ghrelin‐sensitive neurons.

Methods

Rats were anesthetised with alpha‐chloralose and ketamine, and colorectal intraluminal puressure and expelled volume were recorded in vivo. Drugs were applied intrathecally.

Key Results

Ghrelin caused enhancement of propulsive contractions. Tetrodotoxin completely blocked the colokinetic effect of ghrelin. An AMPK activator, aminoimidazole carboxamide ribonucleotide, failed to mimic the ghrelin effect. Leptin had no effect on the spontanious contractions and did not exert a suppressive effect on the ghrelin‐enhanced colorectal motility. An NPY Y1 receptor antagonist did not affect the action of ghrelin. NPY had no effect on the colorectal motility.

Conclusions & Inferences

This study showed that intrathecal injection of ghrelin stimulates colorectal motility by acting on ghrelin‐sensitive neurons in the lumbosacral defecation center. The characteristics of ghrelin‐sensitive neurons in the spinal cord are quite different from those of ghrelin‐sensitive neurons in the hypothalamus.
Corticotrophin‐releasing factor 1 activation in the central amygdale and visceral hyperalgesia
Authors: Taché Y.
Published: December 2014

Corticotropin‐releasing factor (CRF)‐CRF1 receptor in the brain plays a key role in stress‐related alterations of behavior including anxiety/depression, and autonomic and visceral functions. In particular, CRF1 signaling mediates hypersensitivity to colorectal distension (CRD) in various models (early life adverse events, repeated psychological stress, chronic high anxiety, postcolonic inflammation, or repeated nociceptive CRD). So far, knowledge of brain sites involved is limited. A recent article demonstrates in rats that CRF microinjected into the central amygdala (CeA) induces a hyperalgesic response to CRD and enhances the noradrenaline and dopamine levels at this site. The visceral and noradrenaline, unlike dopamine, responses were blocked by a CRF1 antagonist injected into the CeA. Here, we review the emerging role that CRF‐CRF1 signaling plays in the CeA to induce visceral hypersensitivity. In the somatic pain field, CRF in the CeA was shown to induce pain sensitization. This is mediated by the activation of postsynaptic CRF1 receptors and protein kinase A signaling that increases N‐methyl‐d‐aspartate receptor neurotransmission. In addition, the activation of tetraethylamonium‐sensitive ion channels such as Kv3 accelerates repolarization and firing rate. Whether facilitation of pain transmission underlies CRF action in the CeA‐induced visceral hypersensitivity will need to be delineated. CRF1 signaling in the CeA is also an important component of the neuronal circuitry inducing anxiety‐like behavior and positioned at the interphase of the reciprocal relationship between pain and affective state. The hyperactivity of this system may represent the neuroanatomical and biochemical substrate contributing to the coexpression of hypersensitivity to CRD and mood disorders in subsets of irritable bowel syndrome patients.
Characterization of two CENH3 genes and their roles in wheat evolution
Authors: Yuan Jing , Guo Xiang , Hu Jing , Lv Zhenling , Han Fangpu
Published: December 2014

Wheat evolution is complex as a result of successive rounds of allopolyploidization and continuous selection during domestication.

Diploid and tetraploid wheat species (Triticum spp.) were used as model systems in which to study the role of centromere‐specific histone H3 variant (CENH3) in wheat evolution.

We characterized two types of CENH3 genes, named αCENH3 and βCENH3, each of which has three slightly different copies derived from the AA, BB and DD genomes. Specific antibodies were raised against the two CENH3 proteins and were co‐localized to centromeres with subtle differences. In most tetraploid wheat species, CENH3 genes are more highly expressed from the AA genome. In wild tetraploids, βCENH3 has a much lower expression level than αCENH3, while in cultivated tetraploids βCENH3 transcripts are enhanced to near αCENH3 levels. Comparison of the CENH3 proteins in wild and cultivated tetraploids revealed that the histone folding domain (HFD) of only βCENH3 is under positive selection, especially in the region responsible for targeting of CENH3 to the centromere.

Taken together, positive selection of βCENH3 and its increased expression in tetraploid cultivars are indicative of adaptive evolution. Furthermore, the differences in localization between αCENH3 and βCENH3 observed using fiber fluorescence in situ hybridization (FISH) and immunodetection and in developmental phenotypes resulting from virus‐reduced gene silencing imply their functional diversification during wheat evolution.
Relatedness is a poor predictor of negative plant–soil feedbacks
Authors: Mehrabi Zia , Tuck Sean L.
Published: December 2014

Understanding the mechanisms underlying negative plant–soil feedbacks remains a critical challenge in plant ecology. If closely related species are more similar, then phylogeny could be used as a predictor for plant species interactions, simplifying our understanding of how plant–soil feedbacks structure plant communities, underlie invasive species dynamics, or reduce agricultural productivity.

Here, we test the utility of phylogeny for predicting plant–soil feedbacks by undertaking a hierarchical Bayesian meta‐analysis on all available pairwise plant–soil feedback experiments conducted over the last two decades, including 133 plant species in 329 pairwise interactions.

We found that the sign and magnitude of plant–soil feedback effects were not explained by the phylogenetic distance separating interacting species. This result was consistent across different life forms, life cycles, provenances, and phylogenetic scales.

Our analysis shows that, contrary to widespread assumption, relatedness is a poor predictor of plant–soil feedback effects.
Exposure of barley plants to low Pi leads to rapid changes in root respiration that correlate with specific alterations in amino acid substrates
Authors: Alexova Ralitza , Nelson Clark J. , Jacoby Richard P. , Millar A. Harvey
Published: December 2014

The majority of inorganic phosphate (Pi) stress studies in plants have focused on the response after growth has been retarded. Evidence from transcript analysis, however, shows that a Pi‐stress specific response is initiated within minutes of transfer to low Pi and in crop plants precedes the expression of Pi transporters and depletion of vacuolar Pi reserves by days.

In order to investigate the physiological and metabolic events during early exposure to low Pi in grain crops, we monitored the response of whole barley plants during the first hours following Pi withdrawal.

Lowering the concentration of Pi led to rapid changes in root respiration and leaf gas exchange throughout the early phase of the light course. Combining amino and organic acid analysis with 15N labelling we show a root‐specific effect on nitrogen metabolism linked to specific substrates of respiration as soon as 1 h following Pi withdrawal; this explains the respiratory responses observed and was confirmed by stimulation of respiration by exogenous addition of these respiratory substrates to roots.

The rapid adjustment of substrates for respiration in roots during short‐term Pi‐stress is highlighted and this could help guide roots towards Pi‐rich soil patches without compromising biomass accumulation of the plant.
Relaxed selection when you least expect it: why declining bird populations might fail to respond to phenological mismatches
Authors: Day Emma , Kokko Hanna
Published: December 2014

Ongoing climate change threatens to cause mismatches between the phenology of many organisms and their resources. Populations of migratory birds may need to undergo ‘evolutionary rescue’ if resource availability moves to earlier dates in the year, as shifted arrival dates at the breeding grounds may be required for persistence under new environmental schedules. Here we show a counterintuitive process that can reduce the strength of selection for early arrival when the resource peaks earlier. This happens when two processes combine to determine selection for early arrival: breeding success is higher if a bird does not miss the resource peak, but this occurs together with a ‘zero‐sum game’ where birds acquire good territories ahead of their competitors if they arrive early. The latter process can relax if the population has experienced a recent decline. Therefore, climate change can have two opposing effects: its direct effect on breeding success strengthens selection for early arrival, but this combines with an indirect effect of relaxed selection due to population declines, if territoriality is a significant determinant of population dynamics and fitness. We show that the latter process can predominate, and this can cause a failure for a population to adapt to a new schedule under changing environmental conditions.
Modelling demand for liquefied petroleum gas (LPG) in Ghana: current dynamics and forecast
Authors: Mensah Justice Tei
Published: December 2014

Gas is fast becoming an integral component of the energy mix in Ghana and holds huge prospects for the future. However, there is still great uncertainty surrounding the size of this potential market and often results in supply shortfalls. The recurrent shortages in the supply of liquefied petroleum gas (LPG) for domestic and industrial consumption pose a great challenge to the goal of promoting access and utilisation of modern and efficient energy to engender sustainable development in Ghana. As a result, this paper investigates the long‐ and short‐run demand drivers of LPG in Ghana and presents a 10‐year forecast of future trends in the demand using the autoregressive distributed lag and partial adjustment model techniques. Results identify income, price and urbanisation as the main drivers of demand. Projections from all three scenarios reveal that demand for LPG will reach a minimum of 5.9 million metric tons by the year 2022. This result has serious implications on both demand and supply side management, and thus calls for stringent efforts to attract the requisite infrastructure to ensure stable and reliable supply of LPG to meet domestic and industrial demands.
Impact of economic and non‐economic factors on gasoline demand: a varying parameter model for Sweden and the UK
Authors: Karimu Amin
Published: December 2014

This paper investigated the impact of price, income and non‐economic factors on gasoline demand using a structural time series model. The results indicated that non‐economic factors did have an impact on gasoline demand and also one of the largest contributors to changes in gasoline demand in both countries, especially after the 1990s. The results from the time‐varying parameter model indicated that both price and income elasticities were varying over time, but the variations were insignificant for both Sweden and the UK. The estimated gasoline trend also showed a similar pattern for the two countries, increasing continuously up to 1990 and taking a downturn thereafter.
Modelling oil price volatility before, during and after the global financial crisis
Authors: Salisu Afees A.
Published: December 2014

In this paper, we evaluate the comparative performance of volatility models for oil price using daily returns of crude oil price. The innovations of this paper are in three folds: (i) we consider two prominent oil prices namely Brent and West Texas Intermediate (WTI); (ii) we analyse these prices across three subsamples namely periods before, during and after the global financial crisis; and (iii) we also analyse the comparative performance of both symmetric and asymmetric volatility models for these oil prices. We find inconsistent patterns in the performance of the volatility models over the subsamples. On the average, however, we find evidence of leverage effects in both oil prices and therefore, investors in the oil market react to news. Specifically, we find that bad news in the oil market increased volatility in crude oil price than good news. We also find high level of persistence in the volatility of WTI and Brent although the latter appears more persistent than the former while the period of global financial crisis recorded the highest level of persistence in both prices. Also, we find that during the global financial crisis, risk averse investors shifted assets from the oil market to other less risky assets.
Propofol–ketamine or propofol–remifentanil for deep sedation and analgesia in pediatric patients undergoing burn dressing changes: a randomized clinical trial
Authors: Seol Tai‐Kyung , Lim Jin‐Kyu , Yoo Eun‐Kyung , Min Seong‐Won , Kim Chong‐Soo , Hwang Jin‐Young
Published: December 2014

Objective

In this study, we compared the propofol–ketamine and propofol–remifentanil combinations for deep sedation and analgesia during pediatric burn wound dressing changes.

Methods

Fifty pediatric patients aged 12–36 months, undergoing burn wound dressing changes, were randomly assigned to receive propofol–remifentanil (group PR) or propofol–ketamine (group PK) for deep sedation and analgesia. Patients in the group PR received 2 mg·kg−1 propofol and 0.1 μg·kg−1 remifentanil, and 0.05 μg·kg−1·min−1 remifentanil was infused continuously until the end of the procedure. Patients in the group PK received 2 mg·kg−1 propofol and 1 mg·kg−1 ketamine, and the same volume of isotonic saline was infused continuously until the end of the procedure. Additional propofol with remifentanil or ketamine was administered when required. Hemodynamic variables, drug requirements, occurrence of patient movement, surgeon's satisfaction score, recovery time, and the incidence of adverse events were recorded throughout the procedure and recovery.

Results

Recovery time was significantly shorter in the group PR compared to that in the group PK (10.3 [9.1–11.5] min vs 22.5 [20.3–25.6] min, median [interquartile range], respectively; P < 0.001). No significant hypotension or bradycardia occurred throughout the procedure. No significant differences were observed in terms of drug requirements, occurrence of patient movement, surgeon's satisfaction, incidence of respiratory depression, hypoxia, or nausea and vomiting

Conclusions

The combinations of propofol–ketamine and propofol–remifentanil were effective for sedation and analgesia in pediatric patients undergoing burn dressing changes, but the propofol–remifentanil combination provided faster recovery compared to the propofol–ketamine combination.
Tardive dyskinesia (syndrome): Current concept and modern approaches to its management
Authors: Lerner Paul P. , Miodownik Chanoch , Lerner Vladimir
Published: December 2014

Tardive dyskinesia is a serious, disabling and potentially permanent, neurological hyperkinetic movement disorder that occurs after months or years of taking psychotropic drugs. The pathophysiology of tardive dyskinesia is complex, multifactorial and still not fully understood. A number of drugs were tried for the management of this motor disturbance, yet until now no effective and standard treatment has been found. It is very disappointing to realize that the introduction of antipsychotics from the second generation has not significantly decreased the prevalence and incidence of tardive dyskinesia. Therefore, the management of this motor disturbance remains an actual topic as well as a challenge for clinicians. This review summarizes recent relevant publications concerning the treatment of tardive dyskinesia.
Effects of organic matter addition on phosphorus availability to flooded and nonflooded rice in a P‐deficient tropical soil: a greenhouse study
Authors: Rakotoson T. , Six L. , Razafimanantsoa M. P. , Rabeharisoa L. , Smolders E.
Published: December 2014

Addition of organic matter (OM) to flooded soils stimulates reductive dissolution of Fe(III) minerals, thereby mobilizing associated phosphate (P). Hence, OM management has the potential to overcome P deficiency. This study assessed if OM applications increases soil or mineral fertilizer P availability to rice under anaerobic (flooded) condition and if that effect is different relative to that in aerobic (nonflooded) soils. Rice was grown in P‐deficient soil treated with combinations of addition of mineral P (0, 26 mg P/kg), OM (0, ~9 g OM/kg as rice straw + cattle manure) and water treatments (flooded vs nonflooded) in a factorial pot experiment. The OM was either freshly added just before flooding or incubated moist in soil for 6 months prior to flooding; blanket N and K was added in all treatments. Fresh addition of OM promoted reductive dissolution of Fe(III) minerals in flooded soils, whereas no such effect was found when OM had been incubated for 6 months before flooding. Yield and shoot P uptake largely increased with mineral P addition in all soils, whereas OM addition increased yield and P uptake only in flooded soils following fresh OM addition. The combination of mineral P and OM gave the largest yield and P uptake. Addition of OM just prior to soil flooding increased P uptake but was insufficient to overcome P deficiency in the absence of mineral P. Larger applications of OM are unlikely to be more successful in flooded soils due to side effects, such as Fe toxicity.
Climate Variability and the Occurrence of Human Puumala Hantavirus Infections in Europe: A Systematic Review
Authors: Roda Gracia J. , Schumann B. , Seidler A.
Published: December 2014

Hantaviruses are distributed worldwide and are transmitted by rodents. In Europe, the infection usually manifests as a mild form of haemorrhagic fever with renal syndrome (HFRS) known as nephropathia epidemica (NE), which is triggered by the virus species Puumala. Its host is the bank vole (Myodes glareolus). In the context of climate change, interest in the role of climatic factors for the disease has increased. A systematic review was conducted to investigate the association between climate variability and the occurrence of human Puumala hantavirus infections in Europe. We performed a literature search in the databases MEDLINE, EMBASE and Web of Science. Studies that investigated Puumala virus infection and climatic factors in any European country with a minimum collection period of 2 years were included. The selection of abstracts and the evaluation of included studies were performed by two independent reviewers. A total of 434 titles were identified in the databases, of which nine studies fulfilled the inclusion criteria. The majority of studies were conducted in central Europe (Belgium, France and Germany), while only two came from the north (Sweden) and one from the south (Bosnia). Strong evidence was found for a positive association between temperature and NE incidence in central Europe, while the evidence for northern Europe so far appears insufficient. Results regarding precipitation were contradictory. Overall, the complex relationships between climate and hantavirus infections need further exploration to identify specific health risks and initiate appropriate intervention measures in the context of climate change.
Homotopical systole and hyperbolicity
Authors: Elsner Tomasz , Januszkiewicz Tadeusz
Published: December 2014

We provide a condition for systolic complexes implying hyperbolicity, which is weaker than 7‐systolicity.
Single Crystal Perovskites Analyzed Using X-ray Photoelectron Spectroscopy: 5. NdGaO3(110)
Authors: Haasch Richard T. , Breckenfeld Eric , Martin Lane W.
Published: December 2014

X-ray photoelectron spectroscopy (XPS) was used to analyze a commercially available NdGaO3 (110) bulk single crystal. XP spectra were obtained using incident monochromatic Al Kα radiation at 0.83401 nm. A survey spectrum together with Ga 2p, Nd 3d, O 1s, C 1s, Nd 4p3/2, Ga 3s, Nd 4d, Ga 3p, Nd 5s, O 2s, Ga 3d and Nd 5p core level spectra and the valence band are presented. The spectra indicate the principle core level photoelectron and Auger electron signals and show only minor carbon contamination. Making use of the O 1s, Nd 4d, Ga 3p lines and neglecting the components related to surface contaminants, XPS quantitative analysis reveals an altered stoichiometry of the air-exposed crystal surface of Nd1.13GaO2.17.