bluuebunny/crossref_metadata_2025_split 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

ObjectivesTo describe the development of the Pittsburgh Fatigability Scale (PFS) and establish its reliability and concurrent and convergent validity against performance measures.DesignCross‐sectional.SettingUniversity of Pittsburgh, Pittsburgh, Pennsylvania.ParticipantsScale 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).MeasurementsThe 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.ResultsPrincipal 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).ConclusionThe 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

SummaryPorosity 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

AbstractGlutamate 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

AbstractThere 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

ABSTRACTOrganizations 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.

Summary
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

Abstract

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

Abstract

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

AbstractObjectiveCerebral 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.MethodsSeven‐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.ResultsCasts 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).ConclusionLiraglutide 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

SummaryBiosynthesis 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.