bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoalveolarisation contributes to compensatory lung growth following pneumonectomy in mice
Authors: Fehrenbach H. , Voswinckel R. , Michl V. , Mehling T. , Fehrenbach A. , Seeger W. , Nyengaard J. R. 
Published: November 2007

Regeneration of the gas exchange area by induction of neoalveolarisation would greatly improve therapeutic options in destructive pulmonary diseases. Unilateral pneumonectomy is an established model to remove defined portions of gas exchange area and study mechanisms of compensatory lung growth. The question of whether new alveoli are added to the residual lung after pneumonectomy in mice was addressed.Left-sided pneumonectomy was performed in 11 adult C57BL/6 mice. Alveolar numbers were analysed in lungs fixed at days 6 and 20 after pneumonectomy and in 10 age-matched controls using design-based stereology based on a physical fractionator. Post-fixation lung volume was determined by fluid displacement.Complete restoration of lung volume was observed 20 days after pneumonectomy. Alveolar numbers were significantly increased by 33% in residual right lungs at day 20 in comparison with control right lungs. In control left lungs, an average of 471±162×103 alveoli was estimated, 49% of which were regenerated by residual lungs at day 20. Of the newly formed alveoli seen at day 20, 74% were already present at day 6.The present data demonstrate that, in addition to growth in size of existing alveoli, neoalveolarisation contributes to restoration of the gas exchange area in adult mice and is induced early after pneumonectomy.
The role of the UPS in cystic fibrosis
Authors: Turnbull Emma L , Rosser Meredith FN , Cyr Douglas M 
Published: November 2007

AbstractCF is an inherited autosomal recessive disease whose lethality arises from malfunction of CFTR, a single chloride (Cl-) ion channel protein. CF patients harbor mutations in theCFTRgene that lead to misfolding of the resulting CFTR protein, rendering it inactive and mislocalized. Hundreds of CF-related mutations have been identified, many of which abrogate CFTR folding in the endoplasmic reticulum (ER). More than 70% of patients harbor the ΔF508 CFTR mutation that causes misfolding of the CFTR proteins. Consequently, mutant CFTR is unable to reach the apical plasma membrane of epithelial cells that line the lungs and gut, and is instead targeted for degradation by the UPS. Proteins located in both the cytoplasm and ER membrane are believed to identify misfolded CFTR for UPS-mediated degradation. The aberrantly folded CFTR protein then undergoes polyubiquitylation, carried out by an E1-E2-E3 ubiquitin ligase system, leading to degradation by the 26S proteasome. This ubiquitin-dependent loss of misfolded CFTR protein can be inhibited by the application of ‘corrector’ drugs that aid CFTR folding, shielding it from the UPS machinery. Corrector molecules elevate cellular CFTR protein levels by protecting the protein from degradation and aiding folding, promoting its maturation and localization to the apical plasma membrane. Combinatory application of corrector drugs with activator molecules that enhance CFTR Cl-ion channel activity offers significant potential for treatment of CF patients.Publication history:Republished from Current BioData's Targeted Proteins database (TPdb;http://www.targetedproteinsdb.com).
The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias
Authors: Davies Janet E , Sarkar Sovan , Rubinsztein David C 
Published: November 2007

AbstractHuntington's disease and several of the spinocerebellar ataxias are caused by the abnormal expansion of a CAG repeat within the coding region of the disease gene. This results in the production of a mutant protein with an abnormally expanded polyglutamine tract. Although these disorders have a clear monogenic cause, each polyglutamine expansion mutation is likely to cause the dysfunction of many pathways and processes within the cell. It has been proposed that the ubiquitin proteasome system is impaired in polyglutamine expansion disorders and that this contributes to pathology. However, this is controversial with some groups demonstrating decreased proteasome activity in polyglutamine expansion disorders, some showing no change in activity and others demonstrating an increase in proteasome activity. It remains unknown whether the ubiquitin proteasome system is a feasible therapeutic target in these disorders. Here we review the conflicting results obtained from different assays performed in a variety of different systems.Publication history:Republished from Current BioData's Targeted Proteins database (TPdb;http://www.targetedproteinsdb.com).
Randomised controlled comparison of the Health Survey Short Form (SF-12) and the Graded Chronic Pain Scale (GCPS) in telephone interviews versus self-administered questionnaires. Are the results equivalent?
Authors: Lungenhausen Margitta , Lange Stefan , Maier Christoph , Schaub Claudia , Trampisch Hans J , Endres Heinz G 
Published: November 2007

Abstract

Background
The most commonly used survey methods are self-administered questionnaires, telephone interviews, and a mixture of both. But until now evidence out of randomised controlled trials as to whether patient responses differ depending on the survey mode is lacking. Therefore this study assessed whether patient responses to surveys depend on the mode of survey administration. The comparison was between mailed, self-administered questionnaires and telephone interviews.

Methods
A four-armed, randomised controlled two-period change-over design. Each patient responded to the same survey twice, once in written form and once by telephone interview, separated by at least a fortnight. The study was conducted in 2003/2004 in Germany. 1087 patients taking part in the German Acupuncture Trials (GERAC cohort study), who agreed to participate in a survey after completing acupuncture treatment from an acupuncture-certified family physician for headache, were randomised. Of these, 823 (664 women) from the ages of 18 to 83 (mean 51.7) completed both parts of the study. The main outcome measure was the comparison of the scores on the 12-Item Short-Form Health Survey (SF-12) and the Graded Chronic Pain Scale (GCPS) questionnaire for the two survey modes.

Results
Computer-aided telephone interviews (CATI) resulted in significantly fewer missing data (0.5%) than did mailed questionnaires (2.8%; p < 0.001). The analysis of equivalence revealed a difference between the survey modes only for the SF-12 mental scales. On average, reported mental status score was 3.5 score points (2.9 to 4.0) lower on the self-administered questionnaire compared to the telephone interview. The order of administration affected results. Patients who responded to the telephone interview first reported better mental health in the subsequent paper questionnaire (mean difference 2.8 score points) compared to those who responded to the paper questionnaire first (mean difference 4.1 score points).

Conclusion
Despite the comparatively high cost of telephone interviews, they offer clear advantages over mailed self-administered questionnaires as regards completeness of data. Only items concerning mental status were dependent on the survey mode and sequence of administration. Items on physical status were not affected. Normative data for standardized telephone questionnaires could contribute to a better comparability with the results of the corresponding standardized paper questionnaires.
Structural analysis of the carboxy terminal PH domain of pleckstrin bound to D-myo-inositol 1,2,3,5,6-pentakisphosphate
Authors: Jackson Sean G , Zhang Yi , Haslam Richard J , Junop Murray S 
Published: November 2007

Abstract

Background
Pleckstrin homology (PH) domains are one of the most prevalent domains in the human proteome and represent the major phosphoinositide-binding module. These domains are often found in signaling proteins and function predominately by targeting their host proteins to the cell membrane. Inositol phosphates, which are structurally similar to phosphoinositides, are not only known to play a role as signaling molecules but are also capable of being bound by PH domains.

Results
In the work presented here it is shown that the addition of commercial myo-inositol hexakisphosphate (IP6) inhibited the binding of the carboxy terminal PH domain of pleckstrin (C-PH) to phosphatidylinositol 3,4-bisphosphate with an IC50 of 7.5 μM. In an attempt to characterize this binding structurally, C-PH was crystallized in the presence of IP6 and the structure was determined to 1.35 Å. Examination of the resulting electron density unexpectedly revealed the bound ligand to be D-myo-inositol 1,2,3,5,6-pentakisphosphate.

Conclusion
The discovery of D-myo-inositol 1,2,3,5,6-pentakisphosphate in the crystal structure suggests that the inhibitory effects observed in the binding studies may be due to this ligand rather than IP6. Analysis of the protein-ligand interaction demonstrated that this myo-inositol pentakisphosphate isomer interacts specifically with protein residues known to be involved in phosphoinositide binding. In addition to this, a structural alignment of other PH domains bound to inositol phosphates containing either four or five phosphate groups revealed that the majority of phosphate groups occupy conserved locations in the binding pockets of PH domains. These findings, taken together with other recently reported studies suggest that myo- inositol pentakisphosphates could act to regulate PH domain-phosphoinositide interactions by directly competing for binding, thus playing an important role as signaling molecules.
Inorganic pyrophosphate generation by transforming growth factor-beta-1 is mainly dependent on ANK induction by Ras/Raf-1/extracellular signal-regulated kinase pathways in chondrocytes
Authors: Cailotto Frederic , Bianchi Arnaud , Sebillaud Sylvie , Venkatesan Narayanan , Moulin David , Jouzeau Jean-Yves , Netter Patrick 
Published: November 2007

AbstractANK is a multipass transmembrane protein transporter thought to play a role in the export of intracellular inorganic pyrophosphate and so to contribute to the pathophysiology of chondrocalcinosis. As transforming growth factor-beta-1 (TGF-β1) was shown to favor calcium pyrophosphate dihydrate deposition, we investigated the contribution of ANK to the production of extracellular inorganic pyrophosphate (ePPi) by chondrocytes and the signaling pathways involved in the regulation of Ank expression by TGF-β1. Chondrocytes were exposed to 10 ng/mL of TGF-β1, and Ank expression was measured by quantitative polymerase chain reaction and Western blot. ePPi was quantified in cell supernatants. RNA silencing was used to define the respective roles of Ank and PC-1 in TGF-β1-induced ePPi generation. Finally, selective kinase inhibitors and dominant-negative/overexpression plasmid strategies were used to explore the contribution of several signaling pathways to Ank induction by TGF-β1. TGF-β1 strongly increased Ank expression at the mRNA and protein levels, as well as ePPi production. Using small interfering RNA technology, we showed that Ank contributed approximately 60% and PC-1 nearly 20% to TGF-β1-induced ePPi generation. Induction of Ank by TGF-β1 required activation of the extracellular signal-regulated kinase (ERK) pathway but not of p38-mitogen-activated protein kinase or of protein kinase A. In line with the general protein kinase C (PKC) inhibitor calphostin C, Gö6976 (a Ca2+-dependent PKC inhibitor) diminished TGF-β1-induced Ank expression by 60%, whereas a 10% inhibition was observed with rottlerin (a PKCδ inhibitor). These data suggest a regulatory role for calcium in TGF-β1-induced Ank expression. Finally, we demonstrated that the stimulatory effect of TGF-β1 on Ank expression was inhibited by the suppression of the Ras/Raf-1 pathway, while being enhanced by their constitutive activation. Transient overexpression of Smad 7, an inhibitory Smad, failed to affect the inducing effect of TGF-β1 on Ank mRNA level. These data show that TGF-β1 increases ePPi levels, mainly by the induction of the Ank gene, which requires activation of Ras, Raf-1, ERK, and Ca2+-dependent PKC pathways in chondrocytes.
Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa
Authors: Loscher Carol J , Hokamp Karsten , Kenna Paul F , Ivens Alasdair C , Humphries Peter , Palfi Arpad , Farrar G Jane 
Published: November 2007

Abstract
Background
The role played by microRNAs (miRs) as common regulators in physiologic processes such as development and various disease states was recently highlighted. Retinitis pigmentosa (RP) linked to RHO (which encodes rhodopsin) is the most frequent form of inherited retinal degeneration that leads to blindness, for which there are no current therapies. Little is known about the cellular mechanisms that connect mutations within RHO to eventual photoreceptor cell death by apoptosis.

Results
Global miR expression profiling using miR microarray technology and quantitative real-time RT-PCR (qPCR) was performed in mouse retinas. RNA samples from retina of a mouse model of RP carrying a mutant Pro347Ser RHO transgene and from wild-type retina, brain and a whole-body representation (prepared by pooling total RNA from eight different mouse organs) exhibited notably different miR profiles. Expression of retina-specific and recently described retinal miRs was semi-quantitatively demonstrated in wild-type mouse retina. Alterations greater than twofold were found in the expression of nine miRs in Pro347Ser as compared with wild-type retina (P < 0.05). Expression of miR-1 and miR-133 decreased by more than 2.5-fold (P < 0.001), whereas expression of miR-96 and miR-183 increased by more than 3-fold (P < 0.001) in Pro347Ser retinas, as validated by qPCR. Potential retinal targets for these miRs were predicted in silico.

Conclusion
This is the first miR microarray study to focus on evaluating altered miR expression in retinal disease. Additionally, novel retinal preference for miR-376a and miR-691 was identified. The results obtained contribute toward elucidating the function of miRs in normal and diseased retina. Modulation of expression of retinal miRs may represent a future therapeutic strategy for retinopathies such as RP.
MADS-complexes regulate transcriptome dynamics during pollen maturation
Authors: Verelst Wim , Twell David , de Folter Stefan , Immink Richard , Saedler Heinz , Münster Thomas 
Published: November 2007

Abstract
Background
Differentiation processes are responsible for the diversity and functional specialization of the cell types that compose an organism. The outcome of these processes can be studied at molecular, physiologic, and biochemical levels by comparing different cell types, but the complexity and dynamics of the regulatory processes that specify the differentiation are largely unexplored.

Results
Here we identified the pollen-specific MIKC* class of MADS-domain transcription factors as major regulators of transcriptome dynamics during male reproductive cell development in Arabidopsis thaliana. Pollen transcript profiling of mutants deficient in different MIKC* protein complexes revealed that they control a transcriptional switch that directs pollen maturation and that is essential for pollen competitive ability. We resolved the functional redundancy among the MIKC* proteins and uncovered part of the underlying network by identifying the non-MIKC* MADS-box genes AGL18 and AGL29 as downstream regulators of a subset of the MIKC* MADS-controlled genes.

Conclusion
Our results provide a first, unique, and compelling insight into the complexity of a transcription factor network that directs cellular differentiation during pollen maturation, a process that is essential for male reproductive fitness in flowering plants.
Early events in the recognition of danger signals after tissue injury
Authors: Kaczorowski David J , Mollen Kevin P , Edmonds Rebecca , Billiar Timothy R 
Published: November 2007

AbstractThe systemic inflammatory response observed in the setting of overwhelming infection bears striking similarities to that observed in the setting of severe traumatic injury from a clinical and physiologic standpoint. Recent observations have demonstrated that these disparate clinical entities share common mediators on a molecular level. TLRs, specifically TLR4, and the endogenous molecule high-mobility group box 1 are among the mediators that are known to play a role in inflammation in the setting of sepsis. Evidence is accumulating that demonstrates that these mediators also play a role in the host response to tissue injury. Here, we highlight findings from the 7th World Conference on Trauma, Shock, Inflammation and Sepsis in Munich, Germany, in the context of this growing body of literature.
Dispensing errors in community pharmacy: frequency, clinical significance and potential impact of authentication at the point of dispensing
Authors: Franklin Bryony Dean , O'Grady Kara 
Published: November 2007

Abstract

Objective
Our aims were to explore the nature of dispensing errors in community pharmacy, and investigate the potential impact of authentication at the point of dispensing using barcodes or radio-frequency identification tags. Objectives were to develop a dispensing error definition for use in the community setting, to describe the incidence, types and clinical significance of dispensing errors in UK community pharmacies and to assess the likely impact of authentication at the point of dispensing.

Setting
Eleven UK community pharmacies.

Method
A definition of a dispensing error was developed using the Delphi technique. A research pharmacist checked dispensed items awaiting collection and compared them against the original prescription to identify dispensing errors. An expert panel assessed the potential clinical significance of the errors identified. We then predicted the likely impact of three different systems of authentication at the point of dispensing: (a) stand-alone; (b) linked to patient medication records (PMR); and (c) linked to electronic transfer of prescriptions (ETP).

Key findings
We found a content error in 49 (1.7%) of 2859 dispensed items, and a labelling error in 46 (1.6%). The majority (67%) were of minor clinical significance. We estimated that a stand-alone system would prevent about one in five content errors and very few labelling errors, a PMR-linked system would prevent one-quarter of content errors and one-third of labelling errors, and an ETP-linked system would prevent nearly half of content and labelling errors. While none of the three systems would have prevented the one serious error identified, 22–60% of moderate errors could have been prevented, depending on the system used.

Conclusion
Content errors were identified in 1.7% of dispensed items, and labelling errors in 1.6%. Authentication at the point of dispensing could prevent a significant proportion of these, particularly if the system were linked to PMR or ETP. An experimental study is now needed.
A descriptive study of anxiolytic and hypnotic prescribing according to age and sex
Authors: Kairuz Therése E , Truter Ilse 
Published: November 2007

Abstract

Objective
Benzodiazepines are primarily indicated for the treatment of anxiety states and as hypnotics. Their inappropriate use often relates to duration and manner of use. Few studies have attempted to assess the prevalence of benzodiazepine prescribing in South Africa. The primary aim of the study was to examine the prevalence of sedative/hypnotic prescribing according to patient age and sex in a primary care setting. Setting South African private healthcare patients.

Method
An exposure cohort drug utilisation study was conducted. Prescription data were obtained from a South African private medical aid administrator. Descriptive statistics were used in the data analysis.

Key findings
Prescription records (n = 27 080) of 8084 patients in 2004 who were prescribed one or more benzodiazepines were retrospectively analysed. The average age of patients receiving benzodiazepines was 43.17 years (standard deviation (SD) 14.42 years). Benzodiazepine prescribing was more common in females (55.64% of patients were female). There was an increase in prescriptions per patient with increasing age, peaking at an older age among females. Diazepam (13.36%), zopiclone (13.19%) and oxazepam (12.03%) were the most frequently prescribed active ingredients. The majority of benzodiazepine hypnotics were prescribed in quantities of up to 14 units (tablets or capsules), while the benzodiazepine-related drugs zolpidem and zopiclone were prescribed in quantities of up to 30 units. Anxiolytics were often prescribed in quantities of 20 to 30 units.

Conclusion
Anxiolytics were prescribed in greater quantities than hypnotics. An increase in anxiolytic/hypnotic prescriptions and quantities of tablets/capsules occurred with increasing age. The trends and differences that were detected in the prescribing of benzodiazepines warrant further investigation in larger patient populations, especially with respect to the choice of agent, duration of treatment and patient age.
Influence of solid lipid microparticle carriers on skin penetration of the sunscreen agent, 4-methylbenzylidene camphor
Authors: Scalia Santo , Mezzena Matteo , Iannuccelli Valentina 
Published: November 2007

Abstract
The objective of this study was to prepare lipid microparticles (LMs) loaded with the sunscreen agent, 4-methylbenzylidene camphor (4-MBC), to achieve decreased skin penetration of this UV filter. The microparticles were produced by the melt dispersion technique using tristearin as lipidic material and hydrogenated phosphatidylcholine as the surfactant. The obtained microparticles were characterized by scanning electron microscopy and differential scanning calorimetry. Release of 4-MBC from the LMs was found to be slower than its dissolution rate. The influence of the LMs' carrier system on percutaneous penetration was evaluated after their introduction in a model topical formulation (emulsion). In-vitro measurements were performed with cellulose acetate membranes in Franz diffusion cells. The 4-MBC release and diffusion was decreased by 66.7–77.3% with the LM formulation, indicating that the retention capacity of the microparticles was maintained after incorporation into the emulsion. In-vivo human skin penetration of 4-MBC was investigated by tape stripping, a technique for selectively removing the upper cutaneous layers. The amount of sunscreen penetrating into the stratum corneum was greater for the emulsion containing non-encapsulated 4-MBC (36.55% of the applied dose) compared with the formulation with the sunscreen-loaded microparticles (24.57% of the applied dose). The differences between the two formulations were statistically significant in the first (2–4) horny layer strips. Moreover, the LMs' effect measured in-vivo was less pronounced than in-vitro. The increased 4-MBC retention on the skin surface achieved by its incorporation in the LMs should enhance its efficacy and reduce the potential toxicological risk associated with skin penetration.
Radical-scavenging polyphenols: new strategies for their synthesis
Authors: Bovicelli Paolo 
Published: November 2007

Abstract
New strategies for the synthesis of polyphenols, compounds with antioxidant properties contained in every kind of plants, are discussed. Syntheses of different classes of polyphenols, namely ubiquinones, present in many natural systems in which electron-transfer mechanisms are involved, hydroxy-tyrosol, one of the main components of the phenol fraction in olives, and flavonoids, widespread in the plant kingdom, were approached by simple and environmentally sustainable methods.