bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of cyclase-associated protein in regulating actin filament dynamics – more than a monomer-sequestration factor
Authors: Ono Shoichiro
Published: August 2013

Dynamic reorganization of the actin cytoskeleton is fundamental to a number of cell biological events. A variety of actin-regulatory proteins modulate polymerization and depolymerization of actin and contribute to actin cytoskeletal reorganization. Cyclase-associated protein (CAP) is a conserved actin-monomer-binding protein that has been studied for over 20 years. Early studies have shown that CAP sequesters actin monomers; recent studies, however, have revealed more active roles of CAP in actin filament dynamics. CAP enhances the recharging of actin monomers with ATP antagonistically to ADF/cofilin, and also promotes the severing of actin filaments in cooperation with ADF/cofilin. Self-oligomerization and binding to other proteins regulate activities and localization of CAP. CAP has crucial roles in cell signaling, development, vesicle trafficking, cell migration and muscle sarcomere assembly. This Commentary discusses the recent advances in our understanding of the functions of CAP and its implications as an important regulator of actin cytoskeletal dynamics, which are involved in various cellular activities.
Cut via CrebA transcriptionally regulates the COPII secretory pathway to direct dendrite development inDrosophila
Authors: Chandramouli Iyer Srividya , Ramachandran Iyer Eswar P. , Meduri Ramakrishna , Rubaharan Myurajan , Kuntimaddi Aravinda , Karamsetty Madhu , Cox Daniel N.
Published: August 2013

Dendrite development is critical in the formation of functional neural networks. Recent studies have provided insights into the involvement of secretory transport in dendritogenesis, raising the question of how the secretory pathway may be under regulation to direct dendritic elaboration. Here, we identify a functional link between transcriptional regulatory programs and the COPII secretory machinery in driving dendrite morphogenesis in Drosophila dendritic arborization (da) sensory neurons. MARCM analyses and gain-of-function studies reveal cell-autonomous requirements for the COPII coat protein Sec31 in mediating da neuron dendritic homeostasis. We demonstrate that the homeodomain protein Cut transcriptionally regulates Sec31 in addition to other components of COPII secretory transport to promote dendrite elaboration, accompanied by increased satellite secretory endoplasmic reticulum (ER) and Golgi outposts primarily localized at dendritic branch points. We further establish a novel functional role for the transcription factor CrebA in regulating dendrite development and show that Cut initiates a gene expression cascade via CrebA that coordinately affects the COPII machinery to mediate dendritic morphology.
Meeting Report – Building a Centrosome
Authors: Baffet Alexandre D. , Martin Carol-Anne , Scarfone Ilaria , Daly Owen M. , David Ahuvit , Tibelius Alexandra , Lattao Ramona , Hussain Muhammad S. , Woodruff Jeffrey B.
Published: August 2013

Located in the 16th century Wiston House in West Sussex, UK, the ‘Building a Centrosome’ Workshop was organised by The Company of Biologists and chaired by Fanni Gergely and David Glover (University of Cambridge). Held in March 2013, the Workshop gathered together many of the leaders in the field of centrosome biology, as well as postdocs and students who were given the opportunity to meet and interact with many of the scientists who inspired their early careers. The diverse range of speakers provided a multi-disciplinary forum for the exchange of ideas, and gave fresh impetus to tackling outstanding questions related to centrosome biology. Here, we provide an overview of the meeting and highlight the main themes that were discussed.
Wie die Sublimatkur der Syphilis zur Verödungstherapie der Varizen führte
Authors: Hach W.
Published: August 2013

Die Behandlung der Syphilis mit Quecksilberpräparaten wie Sublimat setzte sich von Beginn an bis zur Einführung der Antibiose nach dem 2. Weltkrieg fort. Dabei gab es unterschiedliche Wege der Applikation. Zunächst standen die Injunktionskur, Bäder und verschiedene Pillenzubereitungen im Vordergrund, um eine Salivation zur Ausscheidung der Krankheitsgifte zu erreichen. Mit Erfin-dung der Luer´schen und der Pravaz´schen Spritzen konnten auch subkutane und schließlich intravenöse Injektionen von Sublimat durchgeführt werden. Häufige Thrombosen an den Armvenen führten zu dem Ausweg, die Einspritzung an Krampfadern vorzunehmen. Der Verödungseffekt brachte Paul Linser auf den Gedanken der Verödungstherapie. Von seinem Mitarbeiter Karl Linser wurde das erste Sklerosierungsmittel ohne Quecksilber, die hochprozentige Kochsalzlö-sung, erfunden.
Compliance und Non-Compliance bei der Behandlung chronischer Wunden
Authors: Risse A.
Published: August 2013

Einleitung: „Compliance” bezeichnet die Einhaltung von ärztlich verordneten Verhaltensmaßregeln durch Patienten. In den meisten Fällen beinhalten derartige Verhaltensmaßregeln eine mehr oder weniger intensive Lebensstiländerung des Patienten.

Diskussion: Versuche, Menschen zu Lebensstiländerungen zu bewegen, haben sich als überwiegend erfolglos herausgestellt. „Non-Compliance” resultiert in schlechten Therapieergebnissen. Diese führen zu verschiedenen Reaktionen seitens der Therapeuten in einem Spektrum zwischen Frustration und Aggression. Häufig ist der Begriff der „Non-Compliance” negativ kodiert und impliziert zudem eine freie Willensbildung des Patienten bzw. dessen mangelnden Willen zu gesundheitsadäquatem Verhalten.
Supply Chain Optimization and Planning in Heracles General Cement Company
Authors: Dikos George , Spyropoulou Stavroula
Published: August 2013

Heracles General Cement Company, a member of Lafarge Group, is the largest producer of cement in Greece. In 2005, the corporation decided to improve the efficiency of its supply chain. To help manage this process, we developed a platform for supply chain optimization and planning (SCOP) using mathematical programming. Today, Heracles management uses SCOP to guide its supply chain operations, determine optimal operational response policies to fluctuations in demand and production, perform mid- and long-term planning, evaluate what-if scenarios, address network optimization problems, and identify the best tactics for implementing strategic decisions. SCOP has enabled Heracles to improve its global performance in supply chain management and achieve substantial savings at the operational and strategic levels.
Robust Portfolio Control with Stochastic Factor Dynamics
Authors: Glasserman Paul , Xu Xingbo
Published: August 2013

Portfolio selection is vulnerable to the error-amplifying effects of combining optimization with statistical estimation and model error. For dynamic portfolio control, sources of model error include the evolution of market factors and the influence of these factors on asset returns. We develop portfolio control rules that are robust to this type of uncertainty, applying a stochastic notion of robustness to uncertainty in model dynamics. In this stochastic formulation, robustness reflects uncertainty about the probability law generating market data, and not just uncertainty about model parameters. We analyze both finite- and infinite-horizon problems in a model in which returns are driven by factors that evolve stochastically. The model incorporates transaction costs and leads to simple and tractable optimal robust controls for multiple assets. We illustrate the performance of the controls on historical data. As one would expect, in-sample tests show no evidence of improved performance through robustness—evaluating performance on the same data used to estimate a model leaves no room to capture model uncertainty. However, robustness does improve performance in out-of-sample tests in which the model is estimated on a rolling window of data and then applied over a subsequent time period. By acknowledging uncertainty in the estimated model, the robust rules lead to less aggressive trading and are less sensitive to sharp moves in underlying prices.
Chronic peritonitis in adult cattle
Authors: Scott Phil
Published: August 2013

Primary peritonitis is generally caused by haematogenous spread, but is uncommon in cattle. Peritonitis more commonly results from compromise to the gut wall which allows toxins, and following perforation gut contents, to leak into the peritoneal cavity. Other causes of peritonitis include traumatic perforation of the reticulum and uterus. The ability of the omentum to envelope perforated gut and leaked contents is remarkable which masks clinical signs making diagnosis difficult. Fibrinous adhesions to hepatic abscesses at the capsular surface are not uncommon and again prove difficult to diagnose and are rarely reported.
Reverse shoulder arthroplasty in patients with pre-operative impairment of the deltoid muscle
Authors: Lädermann A. , Walch G. , Denard P. J. , Collin P. , Sirveaux F. , Favard L. , Edwards T. B. , Kherad O. , Boileau P.
Published: August 2013

The indications for reverse shoulder arthroplasty (RSA) continue to be expanded. Associated impairment of the deltoid muscle has been considered a contraindication to its use, as function of the RSA depends on the deltoid and impairment of the deltoid may increase the risk of dislocation. The aim of this retrospective study was to determine the functional outcome and risk of dislocation following the use of an RSA in patients with impaired deltoid function. Between 1999 and 2010, 49 patients (49 shoulders) with impairment of the deltoid underwent RSA and were reviewed at a mean of 38 months (12 to 142) post-operatively. There were nine post-operative complications (18%), including two dislocations. The mean forward elevation improved from 50° (sd 38; 0° to 150°) pre-operatively to 121° (sd 40; 0° to 170°) at final follow-up (p < 0.001). The mean Constant score improved from 24 (sd 12; 2 to 51) to 58 (sd 17; 16 to 83) (p < 0.001). The mean Single Assessment Numeric Evaluation score was 71 (sd 17; 10 to 95) and the rate of patient satisfaction was 98% (48 of 49) at final follow-up.

These results suggest that pre-operative deltoid impairment, in certain circumstances, is not an absolute contraindication to RSA. This form of treatment can yield reliable improvement in function without excessive risk of post-operative dislocation.

Cite this article: Bone Joint J 2013;95-B:1106–13.
Charnley low-friction arthroplasty in patients 35 years of age or younger
Authors: Lampropoulou-Adamidou K. , Georgiades G. , Vlamis J. , Hartofilakidis G.
Published: August 2013

We evaluated the outcome of 41 consecutive Charnley low-friction arthroplasties (LFAs) performed by a single surgeon in 28 patients aged ≤ 35 years at operation between 23 and 36 years previously. There were 20 women and eight men with a mean age of 32 years (23 to 35) at surgery. Two patients (three hips) were lost to follow-up at 12 and 17 years post-operatively, respectively, and one patient (one hip) died at 13 years post-operatively. These patients were excluded from the final evaluation. The survival rate of the acetabular components was 92.7% (95% confidence interval (CI) 88.7 to 96.7) at ten years, 67.1% (95% CI 59.75 to 74.45) at 20 years and 53.2% (95% CI 45.3 to 61.1) at 25 years. For the femoral component the survival was 95.1% (95% CI 91.8 to 98.5) at ten years, 77.1% (95% CI 73.9 to 80.3) at 20 years and 68.2% (95% CI 60.7 to 75.8) at 25 years. The results indicate that the Charnley LFA remains a reasonable choice in the treatment of young patients and can serve for comparison with newer techniques and implants.

Cite this article: Bone Joint J 2013;95-B:1052–6.
A new radiological method to detect dorsally penetrating screws when using volar locking plates in distal radial fractures
Authors: Haug L. C. , Glodny B. , Deml C. , Lutz M. , Attal R.
Published: August 2013

Penetration of the dorsal screw when treating distal radius fractures with volar locking plates is an avoidable complication that causes lesions of the extensor tendon in between 2% and 6% of patients. We examined axial fluoroscopic views of the distal end of the radius to observe small amounts of dorsal screw penetration, and determined the ideal angle of inclination of the x-ray beam to the forearm when making this radiological view.

Six volar locking plates were inserted at the wrists of cadavers. The actual screw length was measured under direct vision through a dorsal approach to the distal radius. Axial radiographs were performed for different angles of inclination of the forearm at the elbow.

Comparing axial radiological measurements and real screw length, a statistically significant correlation could be demonstrated at an angle of inclination between 5° and 20°. The ideal angle of inclination required to minimise the risk of implanting over-long screws in a dorsal horizon radiological view is 15°.

Cite this article: Bone Joint J 2013;95-B:1101–5.
Controversies in the management of congenital pseudarthrosis of the tibia and fibula
Authors: Khan T. , Joseph B.
Published: August 2013

Congenital pseudarthrosis of the tibia (CPT) is a rare but well recognised condition. Obtaining union of the pseudarthrosis in these children is often difficult and may require several surgical procedures. The treatment has changed significantly since the review by Hardinge in 1972, but controversies continue as to the best form of surgical treatment. This paper reviews these controversies.

Cite this article: Bone Joint J 2013;95-B:1027–34.
Modular neck femoral stems
Authors: Krishnan H. , Krishnan S. P. , Blunn G. , Skinner J. A. , Hart A. J.
Published: August 2013

Following the recall of modular neck hip stems in July 2012, research into femoral modularity will intensify over the next few years. This review aims to provide surgeons with an up-to-date summary of the clinically relevant evidence. The development of femoral modularity, and a classification system, is described. The theoretical rationale for modularity is summarised and the clinical outcomes are explored. The review also examines the clinically relevant problems reported following the use of femoral stems with a modular neck.

Joint replacement registries in the United Kingdom and Australia have provided data on the failure rates of modular devices but cannot identify the mechanism of failure. This information is needed to determine whether modular neck femoral stems will be used in the future, and how we should monitor patients who already have them implanted.

Cite this article: Bone Joint J 2013;95-B:1011–21.
Cost-effectiveness in the management of Dupuytren’s contracture
Authors: Baltzer H. , Binhammer P. A.
Published: August 2013

In Canada, Dupuytren's contracture is managed with partial fasciectomy or percutaneous needle aponeurotomy (PNA). Injectable collagenase will soon be available. The optimal management of Dupuytren’s contracture is controversial and trade-offs exist between the different methods. Using a cost-utility analysis approach, our aim was to identify the most cost-effective form of treatment for managing Dupuytren’s contracture it and the threshold at which collagenase is cost-effective. We developed an expected-value decision analysis model for Dupuytren’s contracture affecting a single finger, comparing the cost-effectiveness of fasciectomy, aponeurotomy and collagenase from a societal perspective. Cost-effectiveness, one-way sensitivity and variability analyses were performed using standard thresholds for cost effective treatment ($50 000 to $100 000/QALY gained). Percutaneous needle aponeurotomy was the preferred strategy for managing contractures affecting a single finger. The cost-effectiveness of primary aponeurotomy improved when repeated to treat recurrence. Fasciectomy was not cost-effective. Collagenase was cost-effective relative to and preferred over aponeurotomy at $875 and $470 per course of treatment, respectively.

In summary, our model supports the trend towards non-surgical interventions for managing Dupuytren’s contracture affecting a single finger. Injectable collagenase will only be feasible in our publicly funded healthcare system if it costs significantly less than current United States pricing.

Cite this article: Bone Joint J 2013;95-B:1094–1100.
New and updated reviews published by the Cochrane collaboration
Authors: Das A.
Published: August 2013

Things have not been quiet in the Cochrane Collaboration in the four months since the last 'Cochrane Corner', with the publication of six new or updated reviews summarised here, all conducted with the bulletproof Collaboration's methodology representing the pinnacle of evidence relevant to orthopaedic surgeons.
Architectural Conservation as a Tool for Cultural Continuity: A Focus on the Religious Built Environment of Islam
Authors: Khan Hasan-Uddin
Published: August 2013

Architectural historic preservation has been used as a means to express or represent national, Islamic and even ethnic identity; and often this is linked to tourism or used to serve political ends, particularly in nation building. This article investigates agency and utility in the conservation and restoration of religious built environments in different societies in the Islamic world and its meaning to these societies today. It concludes that conservation should be interpreted more broadly than the physical continuity of historic structures; it should also enable the continuity of non-material aspects of culture and thus embody the relationship between faith and the built environment.
Ornamented Facades and Panoramic Views: The Impact of Tourism Development on al-Salt’s Historic Urban Landscape
Authors: Khirfan Luna
Published: August 2013

This article discusses a series of tourism development projects for historic al-Salt in Jordan that began in the 1990s. A critical analysis of these projects reveals how their emphasis on tourism development results in superficial treatments that overlook the distinctive nature of the city’s morphology and the productive relationship between architectural elements and cultural, economic and political processes. Thus, using al-Salt in Jordan as a case study, this article reveals how preservation efforts can be rejected by a local community, particularly when the specifics of social, cultural, political and economic identity are not considered. According to the findings, these historical specificities contribute to shaping the city’s distinctive urban morphology. As such, al-Salt’s rehabilitation was reduced to superficial beautification and surface treatments that prioritize a fleeting visual experience for tourists but fail to address the fundamental aspects of rehabilitating the historic urban landscape.
Book Reviews
Authors: Baydar Gülsüm , Kargon Jeremy , DeLancey Mark Dike , Holden Stacy , Demerdash Nancy
Published: August 2013

Turkey, Modern Architectures in History Series, Sibel Bozdoğan and Esra Akcan, (2012) London: Reaktion Books, 344 pp., 226 illus., ISBN 9781861898784, $29.95 (paperback)

Architecture in Translation: Germany, Turkey, and the Modern House, Esra Akcan, (2012) Durham, NC and London: Duke University Press, 392 pp., 142 illus., ISBN 9780822353089, $24.95 (paperback)

Solomon’s Temple: Myth, Conflict, and Faith, Alan Balfour, (2012) Chichester: Wiley-Blackwell, 328 pp., 58 b/w illus., 32 colour plates, ISBN 9780470674956, $84.95 (cloth)

Making and Remaking Mosques in Senegal, Islam in Africa Series, vol. 13, Cleo Cantone, (2012) Leiden and Boston: Brill, xliv + 408 pp., 122 b/w illus., 39 colour illus., 6 maps, 6 figs, ISBN 9789004203372, $182 (cloth)

The Future of Historic Cities

The Aga Khan Historic Cities Programme: Strategies for Urban Regeneration, Philip Jodidio (ed.), (2011) London and New York: Prestel, 339 pp., 300 illus., ISBN 9783791344065, $75.00 (cloth)

The Medina: The Restoration and Conservation of Historic Islamic Cities, Marcello Balbo (ed.), (2012) New York: I.B. Tauris, viii + 285 pp., ISBN 9781848857131, $100.00 (cloth)

Heritage and Sustainability in the Islamic Built Environment, Bashir A. Kazimee (ed.), (2012) Billerica, MA: WIT Press, xv + 213 pp., 300 illus., ISBN 9781845646240, $192.00 (cloth)

Fès, La Fabrication D’une Ville Nouvelle (1912–1956), Charlotte Jelidi, (2012) Lyon, France: ENS Éditions, 270 pp., 34 illus., ISBN 9782847882391,  €27.00 (paperback)
Conference Precis
Authors: Madar Heather , DelPlato Joan , Meshkani Taraneh
Published: August 2013

‘Harems Imagined and Real’, Panel at the Annual College Art Association Conference, New York, February 16, 2013

‘From Tehran to Tahrir: Public Space Redefined’, Center for Global Communication Studies at the Annenberg School for Communication, University of Pennsylvania, February 8, 2013
Progress in mitochondrial epigenetics
Authors: Manev Hari , Dzitoyeva Svetlana
Published: August 2013

Mitochondria, intracellular organelles with their own genome, have been shown capable of interacting with epigenetic mechanisms in at least four different ways. First, epigenetic mechanisms that regulate the expression of nuclear genome influence mitochondria by modulating the expression of nuclear-encoded mitochondrial genes. Second, a cell-specific mitochondrial DNA content (copy number) and mitochondrial activity determine the methylation pattern of nuclear genes. Third, mitochondrial DNA variants influence the nuclear gene expression patterns and the nuclear DNA (ncDNA) methylation levels. Fourth and most recent line of evidence indicates that mitochondrial DNA similar to ncDNA also is subject to epigenetic modifications, particularly by the 5-methylcytosine and 5-hydroxymethylcytosine marks. The latter interaction of mitochondria with epigenetics has been termed ‘mitochondrial epigenetics’. Here we summarize recent developments in this particular area of epigenetic research. Furthermore, we propose the term ‘mitoepigenetics’ to include all four above-noted types of interactions between mitochondria and epigenetics, and we suggest a more restricted usage of the term ‘mitochondrial epigenetics’ for molecular events dealing solely with the intra-mitochondrial epigenetics and the modifications of mitochondrial genome.
Long antisense non-coding RNAs and the epigenetic regulation of gene expression
Authors: Vadaie Nadia , Morris Kevin V.
Published: August 2013

Shortly after the completion of the human genome project in 2003, the Encode project was launched. The project was set out to identify the functional elements in the human genome, and unexpectedly it was found that >80% of the genome is transcribed. The Encode project identified those transcribed regions of the genome to be encoded by non-coding RNAs (ncRNAs). With only 2% of the genome carrying gene-encoding proteins, the conundrum was then, what is the function, if any, of these non-coding regions of the genome? These ncRNAs included both short and long RNAs. The focus of this review will be on antisense long non-coding RNAs (lncRNAs), as these transcripts have been observed to play a role in gene expression of protein-coding genes. Some lncRNAs have been found to regulate protein-coding gene transcription at the epigenetic level, whereby they suppress transcription through the recruitment of protein complexes to target loci in the genome. Conversely, there are lncRNAs that have a positive role in gene expression with less known about mechanism, and some lncRNAs have been shown to be involved in post-transcriptional processes. Additionally, lncRNAs have been observed to regulate their own expression in a positive feedback loop by functioning as a decoy. The biological significance of lncRNAs is only just now becoming evident, with many lncRNAs found to play a significant role in several human diseases.
MicroRNA biogenesis and variability
Authors: García-López Jesús , Brieño-Enríquez Miguel A. , del Mazo Jesús
Published: August 2013

MicroRNAs (miRNAs) are cell-endogenous small noncoding RNAs that, through RNA interference, are involved in the posttranscriptional regulation of mRNAs. The biogenesis and function of miRNAs entail multiple elements with different alternative pathways. These confer a high versatility of regulation and a high variability to generate different miRNAs and hence possess a broad potential to regulate gene expression. Here we review the different mechanisms, both canonical and noncanonical, that generate miRNAs in animals. The ‘miRNome’ panorama enhances our knowledge regarding the fine regulation of gene expression and provides new insights concerning normal, as opposed to pathological, cell differentiation and development.
Changes in COX-2 and oxidative damage factors during differentiation of human mesenchymal stem cells to hepatocyte-like cells is associated with downregulation of P53 gene
Authors: Khajeniazi Safoura , Allameh Abdolamir , Soleimani Masoud , Mortaz Esmaeil
Published: August 2013

Differentiation of human mesenchymal stem cells (MSCs) to metabolically active hepatocytes depends on different regulatory factors. Trans-differentiation of stem cells into specific cell lineage in the presence of specific stimuli is associated with the molecular and cellular damage. The aim of the present study was to examine the role of P53 in the regulation of cyclooxygenase-2 (COX-2) expression and the generation of protein and lipid oxidation during trans-differentiation of MSCs into hepatocyte-like cells. During the 3-week differentiation process of MSCs to hepatocyte-like cells we found that expression liver-specific markers was associated with increased levels of lipid peroxidation and protein carbonyl formation. Expression of P53 and COX-2 at mRNA and protein levels were evaluated in MSCs before and after differentiation on days 7, 14 and 21. We showed that the up-regulation of COX-2 was associated with augmentation of the rate of cell proliferation, morphological and biochemical changes of hepatocytes-like cells. However, in parallel the P53 at the mRNA level was down-regulated, and at protein levels accumulation in the nuclei was reduced during the hepatogenic differentiation time. Our results may suggest a P53-COX-2 pathway in the regulation of hepatogenic differentiation of stem cells, which is linked to differentiation-dependent molecular oxidative damage.
The active form of goat insulin-like peptide 3 (INSL3) is a single-chain structure comprising three domains B-C-A, constitutively expressed and secreted by testicular Leydig cells
Authors: Siqin  , Minagawa Itaru , Okuno Mitsutoshi , Yamada Kimihiko , Sugawara Yasushi , Nagura Yoshio , Hamano Koh-Ichi , Park Enoch Y. , Sasada Hiroshi , Kohsaka Tetsuya
Published: August 2013

Relaxin-like factor (RLF), also called insulin-like peptide 3 (INSL3), is a member of the insulin/relaxin gene family and is produced by testicular Leydig cells. While the understanding of its effects is growing, very little is known about the structural and functional properties of native INSL3. Here, we demonstrate that native INSL3 isolated from goat testes is a single-chain structure with full biological activity, and is constitutively expressed and secreted by Leydig cells. Using a series of chromatography steps, native INSL3 was highly purified as a single 12-kDa peak as revealed by SDS-PAGE. MS/MS analysis provided 81% sequence coverage and revealed a distinct single-chain structure consisting of the B-, C-, and A-domains deduced previously from the INSL3 cDNA sequence. Moreover, the N-terminal peptide was six amino acid residues longer than predicted. Native INSL3 exhibited full bioactivity in HEK-293 cells expressing the receptor for INSL3. Immunoelectron microscopy and Western blot analysis revealed that INSL3 was secreted by Leydig cells through the constitutive pathway into blood and body fluids. We conclude, therefore, that goat INSL3 is constitutively secreted from Leydig cells as a B-C-A single-chain structure with full biological activity.
Cathepsin K: a unique collagenolytic cysteine peptidase
Authors: Novinec Marko , Lenarčič Brigita
Published: August 2013

Cathepsin K has emerged as a promising target for the treatment of osteoporosis in recent years. Initially identified as a papain-like cysteine peptidase expressed in high levels in osteoclasts, the important role of this enzyme in bone metabolism was highlighted by the finding that mutations in the CTSK gene cause the rare recessive disorder pycnodysostosis, which is characterized by severe bone anomalies. At the molecular level, the physiological role of cathepsin K is reflected by its unique cleavage pattern of type I collagen molecules, which is fundamentally different from that of other endogenous collagenases. Several cathepsin K inhibitors have been developed to reduce the excessive bone matrix degradation associated with osteoporosis, with the frontrunner odanacatib about to successfully conclude Phase 3 clinical trials. Apart from osteoclasts, cathepsin K is expressed in different cell types throughout the body and is involved in processes of adipogenesis, thyroxine liberation and peptide hormone regulation. Elevated activity of cathepsin K has been associated with arthritis, atherosclerosis, obesity, schizophrenia, and tumor metastasis. Accordingly, its activity is tightly regulated via multiple mechanisms, including competitive inhibition by endogenous macromolecular inhibitors and allosteric regulation by glycosaminoglycans. This review provides a state-of-the-art description of the activity of cathepsin K at the molecular level, its biological functions and the mechanisms involved in its regulation.
Functional ribosome biogenesis is a prerequisite for p53 destabilization: impact of chemotherapy on nucleolar functions and RNA metabolism
Authors: Burger Kaspar , Eick Dirk
Published: August 2013

The production and processing of ribosomal RNA is a complex and well-coordinated nucleolar process for ribosome biogenesis. Progress in understanding nucleolar structure and function has lead to the unexpected discovery of the nucleolus as a highly sensitive sensor of cellular stress and an important regulator of the tumor suppressor p53. Inhibition of ribosomal RNA metabolism has been shown to activate a signaling pathway for p53 induction. This review elucidates the potential of classical and recently developed chemotherapeutic drugs to stabilize p53 by inhibiting nucleolar functions.
Die Wirkungen der „Physikalischen Gefäßtherapie BEMER®“, eines physikalischen Stimulationsverfahrens präkapillärer Mikrogefäße bei gestörter Mikrozirkulation auf Schlaf, Schmerz und Lebensqualität von Patienten mit unterschiedlichen Krankheitsbildern unter Verwendung von 3 wissenschaftlich validierten Skalen
Authors: Bohn Wolfgang , Hess Lorenzo , Burger Ralph
Published: August 2013

Im Rahmen der gesetzlich vorgeschriebenen Marktbeobachtung von zertifizierten Medizinprodukten wurde über den Zeitraum April 2011 bis März 2013 eine Auswertung von 658 validen Patienten-Fragebögen vorgenommen. Die Fragen bestanden im Wesentlichen aus 3 wissenschaftlich anerkannten Skalen zur Beurteilung der Veränderungen von Schlaf, Schmerz und Lebensqualität von Patienten, die über 6 Wochen die „Physikalische Gefäßtherapie BEMER®“ wegen unterschiedlicher Erkrankungen angewendet hatten. Das Ergebnis zeigt eindeutig, dass es in allen abgefragten Bereichen unabhängig von den Grunderkrankungen zu signifikanten Verbesserungen durch die Anwendung dieser komplementären Therapieoption kommt.
Adult height in girls with Turner syndrome treated from before 6 years of age with a fixed per kilogram GH dose
Authors: Wasniewska Malgorzata , Aversa Tommaso , Mazzanti Laura , Guarneri Maria Pia , Matarazzo Patrizia , De Luca Filippo , Lombardo Fortunato , Messina Maria Francesca , Valenzise Mariella
Published: August 2013

Objective

To evaluate adult height (AH) in 25 girls with Turner syndrome (TS) who were treated from before 6 years of age for 10.0±1.7 years with a fixed GH dose of 0.33 mg/kg per week.

Patients and design

After a 6-month pretreatment assessment all patients were measured 6-monthly under therapy to assess height SDS (H-SDS) and height velocity (HV) until AH achievement.

Results

Following initial acceleration, HV declined after the first 4 years of therapy. At the end of the sixth year of therapy, H-SDS gain was 1.9±1.1. Thereafter, H-SDS gain from baseline decreased, becoming 0.9±0.9 SDS at AH achievement. Bone maturation velocity did not significantly change throughout the prepubertal period. According to Lyon standards for TS, mean AH SDS was significantly higher than pretreatment H-SDS (P<0.0001), with a mean H-SDS change of 0.9±0.9. However, the prevalence of patients with AH <−2 SDS (according to Sempé standards) was close to those recorded at the start of therapy (16/25 vs 18/25). No significant differences in terms of AH were found between patients with either X monosomy or X-chromosomal abnormalities and between girls with either spontaneous or induced puberty.

Conclusions

We infer that the therapeutic regimen adopted in this prospective study is sufficient to induce a significant growth acceleration during the first year, but the response waned after 6 years of treatment.
Testosterone and cardiometabolic risk in the general population – the impact of measurement method on risk associations: a comparative study between immunoassay and mass spectrometry
Authors: Haring Robin , Baumeister Sebastian E , Nauck Matthias , Völzke Henry , Keevil Brian G , Brabant Georg , Wallaschofski Henri
Published: August 2013

Objective

Low total testosterone (TT) serum concentrations in men have been associated with various cardiometabolic risk factors. But given error-prone immunoassays used for TT assessment, upcoming mass spectrometry methods question the validity of these risk associations. Thus, we performed the first comparative study quantifying potential differences in the association of TT with cardiometabolic risk factors between the two methods.

Methods

We used data from 1512 men aged 20–81 years, recruited for the cross-sectional population-based Study of Health in Pomerania (SHIP), Germany. TT concentrations were repeatedly measured by chemiluminescent immunoassay (CLIA, Immulite 2500) and liquid chromatography–tandem mass spectrometry (LC–MS/MS). We tested for significant differences between coefficients from CLIA- and LC–MS/MS-based multiple linear regression models associating TT with major cardiometabolic risk factors including adiposity, lipid metabolism, blood pressure, diabetic status, and inflammation.

Results

TT measurements by CLIA and LC–MS/MS yielded a Pearson correlation coefficient of 0.84. Only three of the ten tested associations for TT with cardiometabolic risk factor showed significant differences between the two measurement methods: in comparison to LC–MS/MS, CLIA-based TT assessment significantly underestimated risk associations of TT with waist circumference (β: −0.54 vs −0.63), BMI (β: −0.19 vs −0.22), and serum glucose levels (β: −0.006 vs −0.008).

Conclusion

In this comparative study, the CLIA platform showed a reasonable measurement error and yielded comparable risk associations, providing little support to measure TT concentrations in men from the general population exclusively by LC–MS/MS.
Gamma knife surgery for patients with volumetric classification of nonfunctioning pituitary adenomas: a systematic review and meta-analysis
Authors: Chen Yong , Li Zhi Feng , Zhang Fei Xiang , Li Jian Xian , Cai Lin , Zhuge Qi Chuan , Wu Zhe Bao
Published: August 2013

Objective

The aim of this study was to scrutinize the literature to determine the efficacy and safety of gamma knife surgery (GKS) for the treatment of nonfunctioning pituitary adenomas (NFPAs) with volumetric classification.

Methods

Electronic databases including MedLine, PubMed, and Cochrane Central were searched. The literature related to patients with NFPAs treated with GKS was collected. Eligible studies reported on the rate of tumor control (RTC), the rate of radiosurgery-induced optic neuropathy injury (RRIONI), the rate of radiosurgery-induced endocrinological deficits (RRIED), and other parameters.

Results

A total of 17 studies met the criteria. Based on the tumor volume, NFPAs were divided into three groups: the RTC of group I (93 patients) with tumor volumes <2 ml was 99% (95% CI 96–100%), the RRIONI was 1% (95% CI 0–4%), and the RRIED was 1% (95% CI 0–4%). The RTC of group II (301 patients) with volumes from 2 to 4 ml was 96% (95% CI 92–99%), the RRIONI was 0 (95% CI 0–2%), and RRIED was 7% (95% CI 2–14%). The RTC of group III (531 patients) with volumes larger than 4 ml was 91% (95% CI 89–94%), the RRIONI was 2% (95% CI 0–5%), and the RRIED was 22% (95% CI 14–31%). There were significant differences in the RTC and in the RRIED among the three groups (P<0.001), indicating that there were higher RRIED and lower RTC with the increase of tumor volume.

Conclusions

NFPAs, according to tumor volume classification, need stratification for GKS treatment. GKS is the optimal choice for the treatment of group II NFPAs. Patients with residual tumor volumes of <4 ml will benefit most from GKS treatment.
Impaired mammary gland T cell population during early lactation in hypoprolactinemic lactation-deficient rats
Authors: Mackern-Oberti Juan Pablo , Valdez Susana Ruth , Vargas-Roig Laura María , Jahn Graciela Alma
Published: August 2013

Mammary stroma is composed of various cell types, including migratory leukocytes. Although mammary antibody-secreting cells have been extensively studied, reports focusing on mammary T cells are scarce. It is thought that the recruitment mechanism of leukocytes to the mammary gland (MG) is controlled by pregnancy- and lactation-specific stimuli. But whether prolactin (PRL) modulates the T-cell population in MG is still unknown. Our aim was to study the relationship between PRL levels and T and B cells during early lactation (L2, day 2post partum) and mid-lactation (L12, day 12 of lactation). In order to investigate whether PRL is associated with homing events to MG, female Sprague Dawley (SD) and SD-derived desmoglein 4−/−hairless (phenotype with lactation deficit, OFAhr/hr) rats were killed during estrus, pregnancy, andpost partum, and blood, MG, and corpora lutea were obtained to perform fluorescent-activated cell sorting (FACS), real-time PCR, and histological and RIA studies. Serum PRL levels were lower in OFAhr/hrrats than in SD rats during early lactation. MG of OFAhr/hrrats showed less secretory material compared with SD rats. FACS analysis showed lower percentage of MG CD3+ cells in OFAhr/hrrats compared with SD rats on L2 and L12. OFAhr/hrrats showed higher absolute numbers of circulating CD3+ cells compared with SD rats on L2 but not on L12. These results show that T-cell population in MG is affected in early lactating OFAhr/hrrats and strongly suggest that serum PRL levels may be involved in the homing events to MG, probably helping antibody-secreting cells and protecting the gland during lactation development.
The Composition, Functions, and Regulation of the Budding Yeast Kinetochore
Authors: Biggins Sue
Published: August 2013

The propagation of all organisms depends on the accurate and orderly segregation of chromosomes in mitosis and meiosis. Budding yeast has long served as an outstanding model organism to identify the components and underlying mechanisms that regulate chromosome segregation. This review focuses on the kinetochore, the macromolecular protein complex that assembles on centromeric chromatin and maintains persistent load-bearing attachments to the dynamic tips of spindle microtubules. The kinetochore also serves as a regulatory hub for the spindle checkpoint, ensuring that cell cycle progression is coupled to the achievement of proper microtubule–kinetochore attachments. Progress in understanding the composition and overall architecture of the kinetochore, as well as its properties in making and regulating microtubule attachments and the spindle checkpoint, is discussed.
Lamarck, Evolution, and the Inheritance of Acquired Characters
Authors: Burkhardt Richard W
Published: August 2013

Scientists are not always remembered for the ideas they cherished most. In the case of the French biologist Jean-Baptiste Lamarck, his name since the end of the nineteenth century has been tightly linked to the idea of the inheritance of acquired characters. This was indeed an idea that he endorsed, but he did not claim it as his own nor did he give it much thought. He took pride instead in advancing the ideas that (1) nature produced successively all the different forms of life on earth, and (2) environmentally induced behavioral changes lead the way in species change. This article surveys Lamarck’s ideas about organic change, identifies several ironies with respect to how his name is commonly remembered, and suggests that some historical justice might be done by using the adjective “Lamarckian” to denote something more (or other) than a belief in the inheritance of acquired characters.
Configuring the caller in ambiguous encounters: Volunteer handling of calls to Samaritans emotional support services
Authors: Pollock Kristian , Moore John , Coveney Catherine , Armstrong Sarah
Published: August 2013

This paper discusses volunteer strategies for handling and assessing calls to Samaritans emotional support services for the suicidal and despairing. It presents findings from the qualitative components of a two year mixed methods study based on an online caller survey, branch observations and interviews with volunteers and callers throughout the UK. A thematic analysis of the qualitative data analysis was undertaken using the principle of constant comparison. Many calls fell beyond the primary remit of a crisis service, and called for rapid attribution and assessment. Uncertainty about identifying ‘good’ calls and recognizing those which were not caused difficulty, frustration and negative attribution towards some callers. This paper presents our analysis of volunteers’ accounts of how they configure the caller in intrinsically uncertain and ambiguous encounters, and how such strategies relate to the formal principles of unconditional support and non-judgemental active listening espoused by the organization. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License
Sam Rivers
Authors: Rodwan, Jr. John G.
Published: August 2013

‘Sam Rivers: Jazz’s Forgotten Man’ examines the life and work of Sam Rivers and explores the reasons for his relative lack of renown. Though admired by fellow musicians, Rivers never received the level of recognition achieved by Miles Davis or Cecil Taylor, with whom he played and recorded. Factors unrelated to his work itself—such as where he chose to live, when he started recording as a leader, his arrangements with record labels and interactions with younger musicians—largely determined his neglect, which is reflected in music critics’ and historians’ scant discussion of him. The essay considers how a saxophonist compared to John Coltrane can go unappreciated and largely unknown.
Dental Stem Cells and their Applications in Dental Tissue Engineering
Authors: Lymperi S , Ligoudistianou C , Taraslia V , Kontakiotis E , Anastasiadou E
Published: August 2013

Tooth loss or absence is a common condition that can be caused by various pathological circumstances. The replacement of the missing tooth is important for medical and aesthetic reasons. Recently, scientists focus on tooth tissue engineering, as a potential treatment, beyond the existing prosthetic methods. Tooth engineering is a promising new therapeutic approach that seeks to replace the missing tooth with a bioengineered one or to restore the damaged dental tissue. Its main tool is the stem cells that are seeded on the surface of biomaterials (scaffolds), in order to create a biocomplex. Several populations of mesenchymal stem cells are found in the tooth. These different cell types are categorized according to their location in the tooth and they demonstrate slightly different features. It appears that the dental stem cells isolated from the dental pulp and the periodontal ligament are the most powerful cells for tooth engineering. Additional research needs to be performed in order to address the problem of finding a suitable source of epithelial stem cells, which are important for the regeneration of the enamel. Nevertheless, the results of the existing studies are encouraging and strongly support the belief that tooth engineering can offer hope to people suffering from dental problems or tooth loss.
Assessment of Knowledge of Dental Staff at a Saudi Arabian University Regarding the Prophylaxis for Infective Endocarditis
Authors: Bhayat Ahmed , Jarab Fadi , Mansuri Samir , Ahmad Mohammad Sami , Mahrous Mohamed Saad
Published: August 2013

The use of prophylactic antibiotics for the prevention of infective endocarditis following dental procedures has long been debated and there is still confusion regarding its efficacy. As a result, the prophylactic treatment varies considerably amongst different countries across the world and amongst different dental practitioners.

Aim:

To evaluate the knowledge of dental staff regarding the guidelines for the prevention of infective endocarditis.

Methods:

This was a cross sectional analytical study which included all staff members. A self administered questionnaire was used and responses were “graded” according to the American Heart Association (AHA) guidelines.

Results:

The response rate was 87% (N=39) and 97% reported to use the AHA guidelines; 66% reported their knowledge was based on previous training and scientific journals. Of those cardiac conditions and dental procedures which required prophylaxis; 47% and 65% chose the correct option, respectively. Penicillin was prescribed as the drug of choice by the majority of respondents.

Conclusions:

Although almost all staff reported the use of the AHA guidelines, many were not following them. The study emphasizes the need for continuous education and evaluation of this critical aspect of dentistry.
The influence of packaging materials protective properties and applying modified atmosphere on packed dried apricot quality changes
Authors: Randjelovic Dobrila , Lazic Vera , Tepic Aleksandra , Mosic Ivana
Published: August 2013

The influence of protective properties of packaging materials and modified
atmosphere on quality changes of dried apricot is shown in this paper. In our
investigation, we used four different characteristic combinations of
packaging materials with different barrier properties for packaging of dried
apricot: polyester-polyethylene (PET/PE), paper-polyethylene (PAP/PE),
paper-aluminum-polyethylene (PAP/Al/PE), polyester-aluminum-polyethylene
(PET/Al/PE) and two different atmospheric conditions: normal and modified.
Modified atmosphere was made in laboratory conditions: CO2 about 30%, N2
about 60%, and the rest is O2. Over the 12-month storage period, the changes
in the water content, water activity (aw) and overall polyphenol content were
monitored in the packed product.