bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of IL-6 and CCL5 (RANTES) in human respiratory epithelial (A549) cells by clinical isolates of respiratory syncytial virus is strain specific
Authors: Levitz Ruth , Wattier Rachel , Phillips Pamela , Solomon Alexandra , Lawler Jessica , Lazar Isaac , Weibel Carla , Kahn Jeffrey S
Published: September 2012

Background

Respiratory syncytial virus (RSV) is the major respiratory pathogen of infants and young children. During each seasonal epidemic, multiple strains of both subgroup A and B viruses circulate in the community. Like other RNA viruses, RSV genome replication is prone to errors that results in a heterogeneous population of viral strains some of which may possess differences in virulence. We sought to determine whether clinical isolates of RSV differ in their capacity to induce inflammatory cytokines IL-6 and CCL5 (previously known as RANTES [regulated upon activation, normal T-cell expressed and secreted protein]), which are known to be induced in vitro and in vivo in response to RSV, during infection of A549 cells.

Results

Screening of subgroup A and B isolates revealed heterogeneity among strains to induce IL-6 and CCL5. We chose two subgroup B strains, New Haven (NH)1067 and NH1125, for further analysis because of their marked differences in cytokine inducing properties and because subgroup B strains, in general, are less genetically heterogeneous as compared to subgroup A strains. At 12 and 24 hours post infection RSV strains, NH1067 and NH1125 differed in their capacity to induce IL-6 by an order of magnitude or more. The concentrations of IL-6 and CCL5 were dependent on the dose of infectious virus and the concentration of these cytokines induced by NH1125 was greater than that of those induced by NH1067 when the multiplicity of infection of NH1067 used was as much as 10-fold higher than that of NH1125. The induction of IL-6 was dependent on viable virus as infection with UV-inactivated virus did not induce IL-6. The difference in IL-6 induction most likely could not be explained by differences in viral replication kinetics. The intracellular level of RSV RNA, as determined by quantitative RT-PCR, was indistinguishable between the 2 strains though the titer of progeny virus produced by NH1125 was greater than that produced by NH1067 at 16, 24 and 36 hours but essentially equal at 48 and 72 hours. Full genome sequencing of the 2 strains revealed 193 polymorphisms and 4 insertions in NH1067when compared to NH1125 (2 single base insertions in non-coding regions and 2 duplications of 3 and 60 bases in the RSV G gene). Of the polymorphisms, 147 occurred in coding regions and only 30 resulted in amino acid changes in 7 of the RSV genes.

Conclusions

These data suggest that RSV strains may not be homogeneous with regard to pathogenesis or virulence. Identification of the genetic polymorphisms associated with variations in cytokine induction may lead to insights into RSV disease and to the development of effective antiviral agents and vaccines.
Novel and unexpected bacterial diversity in an arsenic-rich ecosystem revealed by culture-dependent approaches
Authors: Delavat François , Lett Marie-Claire , Lièvremont Didier
Published: September 2012

Background

Acid Mine Drainages (AMDs) are extreme environments characterized by very acid conditions and heavy metal contaminations. In these ecosystems, the bacterial diversity is considered to be low. Previous culture-independent approaches performed in the AMD of Carnoulès (France) confirmed this low species richness. However, very little is known about the cultured bacteria in this ecosystem. The aims of the study were firstly to apply novel culture methods in order to access to the largest cultured bacterial diversity, and secondly to better define the robustness of the community for 3 important functions: As(III) oxidation, cellulose degradation and cobalamine biosynthesis.

Results

Despite the oligotrophic and acidic conditions found in AMDs, the newly designed media covered a large range of nutrient concentrations and a pH range from 3.5 to 9.8, in order to target also non-acidophilic bacteria. These approaches generated 49 isolates representing 19 genera belonging to 4 different phyla. Importantly, overall diversity gained 16 extra genera never detected in Carnoulès. Among the 19 genera, 3 were previously uncultured, one of them being novel in databases. This strategy increased the overall diversity in the Carnoulès sediment by 70% when compared with previous culture-independent approaches, as specific phylogenetic groups (e.g.the subclassActinobacteridaeor the orderRhizobiales) were only detected by culture. Cobalamin auxotrophy, cellulose degradation and As(III)-oxidation are 3 crucial functions in this ecosystem, and a previous meta- and proteo-genomic work attributed each function to only one taxon. Here, we demonstrate that other members of this community can also assume these functions, thus increasing the overall community robustness.

Conclusions

This work highlights that bacterial diversity in AMDs is much higher than previously envisaged, thus pointing out that the AMD system is functionally more robust than expected. The isolated bacteria may be part of the rare biosphere which remained previously undetected due to molecular biases. No matter their current ecological relevance, the exploration of the full diversity remains crucial to decipher the function and dynamic of any community. This work also underlines the importance to associate culture-dependent and -independent approaches to gain an integrative view of the community function.

Reviewers

This paper was reviewed by Sándor Pongor, Eugene V. Koonin and Brett Baker (nominated by Purificacion Lopez-Garcia).
Increased numbers of P63-positive/CD117-positive cells in advanced adenoid cystic carcinoma give a poorer prognosis
Authors: Zhou Quan , Chang Hong , Zhang Hongkai , Han Yiding , Liu Honggang
Published: September 2012

Objectives

This study consisted of two parts. One part was to analyze the survival rates of adenoid cystic carcinoma (ACC) in Chinese and explain the difference between our data and the literature. The other was to analyze the relationship between the expression of CD117 and the histological grade and the prognosis.

Methods

A retrospective study of 80 ACC patients was performed. Clinical data were collected, and p63, CD117 were detected by immunohistochemical staining.

Results

Eighty patients received follow-ups 3 to 216 months after initial diagnosis. ACC occurred in the lacrimal gland (26.3%, n = 21), nasal cavity and parasinus (33.8%, n = 27) and other sites (40.0%, n = 33). The 5-year and 10-year survival rates were 66.41% and 10.16%, respectively. Over expression of CD117 was detected in p63-negative cells in 94.3% of cases and in p63-positive cells in 45.8%. The expression of CD117 in p63-positive cells was significantly associated with the histological grade (P<0.001) and prognosis (P = 0.037) in patients in the advanced stage.

Conclusions

ACC had a good 5-year survival but poor 10-year survival in Chinese, which differed from the occidental data. More p63+/CD117+ cells were associated with a higher histological grade and poorer outcome.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1701457278762097
Clinical governance implementation in a selected teaching emergency department: a systems approach
Authors: Heyrani Ali , Maleki Mohammadreza , Marnani Ahmad Barati , Ravaghi Hamid , Sedaghat Mojtaba , Jabbari Mosadegh , Farsi Davood , Khajavi Abdoljavad , Abdi Zhaleh
Published: September 2012

Background

Clinical governance (CG) is among the different frameworks proposed to improve the quality of healthcare. Iran, like many other countries, has put healthcare quality improvement in its top health policy priorities. In November 2009, implementation of CG became a task for all hospitals across the country. However, it has been a challenge to clarify the notion of CG and the way to implement it in Iran. The purpose of this action research study is to understand how CG can be defined and implemented in a selected teaching emergency department (ED).

Methods/design

We will use Soft Systems Methodology for both designing the study and inquiring into its content. As we considered a complex problem situation regarding the quality of care in the selected ED, we initially conceptualized CG as a cyclic set of purposeful activities designed to explore the situation and find relevant changes to improve the quality of care. Then, implementation of CG will conceptually be to carry out that set of purposeful activities. The activities will be about: understanding the situation and finding out relevant issues concerning the quality of care; exploring different stakeholders’ views and ideas about the situation and how it can be improved; and defining actions to improve the quality of care through structured debates and development of accommodations among stakeholders. We will flexibly use qualitative methods of data collection and analysis in the course of the study. To ensure the study rigor, we will use different strategies.

Discussion

Successful implementation of CG, like other quality improvement frameworks, requires special consideration of underlying complexities. We believe that addressing the complex situation and reflections on involvement in this action research will make it possible to understand the concept of CG and its implementation in the selected setting. By describing the context and executed flexible methods of implementation, the results of this study would contribute to the development of implementation science and be employed by boards and executives governing other clinical settings to facilitate CG implementation.
The role of prophylactic ibuprofen and N-acetylcysteine on the level of cytokines in periapical exudates and the post-treatment pain
Authors: Ehsani Maryam , Moghadamnia Ali-Akbar , Zahedpasha Samir , Maliji Ghorban , Haghanifar Sina , Mir Seyyed Mohsen Aghajanpour , Kani Narges Mousavi
Published: September 2012

Background

Periapical lesions are inflammatory diseases that result in periapical bone destruction because of host defensive–microbial disturbances.

Objective

To evaluate the role of prophylactic ibuprofen and N-acetylcysteine (NAC) on the levels of tumor necrosis factor alpha (TNF- α), interleukin- 6(IL-6) and IL-17 and post-treatment pain level in chronic periapical lesions.

Materials and methods

Eighty patients with chronic apical lesions less than 1 cm were randomly assigned to receive NAC tablets (400 mg), ibuprofen tablets (400 mg), NAC (400 mg)/ibuprofen (200 mg) combination and placebo 90 minutes prior to sampling. Periapical exudates were collected from root canals. TNF- α, IL-6 and IL-17 levels were determined by ELISA and post-treatment pain was assessed using a visual analog scale (VAS).

Results

There was a significant difference in IL-6 level between ibuprofen group and placebo (p = 0.019). Significant difference in IL-17 level was observed between NAC/ibuprofen combination group and placebo (p = 0.043). Four hours after treatment, a significant difference was observed in VAS pain score between ibuprofen group and placebo (p = 0.017). Eight hours post-treatment, VAS pain score for NAC group was statistically lower than placebo group (p = 0.033). After 12 hours VAS pain score showed a significant decrease in NAC group compared to placebo (p = 0.049).

Conclusion

The prophylactic ibuprofen and NAC failed to clearly reflect their effect on cytokines levels in exudates of chronic periapical lesions. On the other hand it seems that NAC can be a substitute for ibuprofen in the management of post endodontic pain.
Structured self monitoring of blood glucose in Iranian people with type 2 diabetes; A cost consequence analysis
Authors: Aghili Rokhsareh , Khamseh Mohammad E , Malek Mojtaba , Yarahmadi Shahin , Farshchi Amir
Published: September 2012

Background

Self-Monitoring of Blood Glucose (SMBG) is considered as a key factor in management of people with diabetes which is a growing and cost demanding health problem. The purpose of this study was to investigate the effect of comprehensive patient management using structured SMBG on metabolic control as well as its cost consequence analysis.

Methods

Sixty subjects were recruited in an observational study for a period of 6 months. They were provided with the ACCU-CHEK 360° View tool to fill in the values of the 7-point blood glucose profiles in three consecutive days during the study on a monthly basis. Changes in metabolic control were assessed by HbA1c and lipid profile measurement at the beginning and at the end of the study. In addition, cost consequence analysis was done considering different level of health care professionals with or without insurance coverage. The Average Cost Effectiveness Ratio (ACER) as well as Cost saving analysis were calculated and compared.

Results

The analysis showed significant reduction in HbA1c during the 6-month period in all subjects (P = 0.000). Furthermore, a positive effect was observed on lipid profile. The cost of endocrinologist’s visit in private sector was estimated to be 265.76 USD while this figure was149.15 USD for general practitioner in public sector with insurance coverage. Total complications and mortality cost saving was 154.8 USD. The lowest ACER was calculated for intervention with general practitioner in public sector with insurance coverage.

Conclusion

Structured SMBG results in significant improvement of glycemic status. Moreover, it is more cost saving in public sector with insurance coverage. It seems that general practitioner visits with insurance coverage is the most affordable option for people with type 2 diabetes.
From the Editors—Copulas, Group Preferences, Multilevel Defenders, Sharing Rewards, and Communicating Analytics
Authors: Keller L. Robin , Kophazi Kelly M.
Published: September 2012

We review the past year and this Editor-in-Chief's editorship for the last six annual volumes in this issue's “From the Editors” column, which is coauthored with Managing Editor Kelly M. Kophazi, and then we preview this issue's research articles. Our first article, by Dorota Kurowicka is on “Conditionalization of Copula-Based Models.” The next three papers address groups or teams. First is “A Note on a Group Preference Axiomatization with Cardinal Utility,” by Luis C. Dias and Paula Sarabando. Next, Andrew Samuel and Seth D. Guikema address “Resource Allocation for Homeland Defense: Dealing with the Team Effect.” Then, Arthur Carvalho and Kate Larson present a way for “Sharing Rewards Among Strangers Based on Peer Evaluations.” Finally, Jeffrey M. Keisler and Patrick S. Noonan provide guidance for decision analysis practice in “Communicating Analytic Results: A Tutorial for Decision Consultants.”
(2R,3R)-1,4-Dimethoxy-1,1,4,4-tetraphenylbutane-2,3-diol: Valuable reagent in the asymmetric synthesis of organoboronates
Authors: Berg C. Annette , Eichenauer Nils C. , Pietruszka Jörg
Published: September 2012

Tartrate-derived (2R,3R)-1,4-dimethoxy-1,1,4,4-tetraphenylbutane-2,3-diol has found diverse applications in asymmetric organic synthesis. Among these, its utilization as a protecting group for boronic acids has been investigated extensively. Besides being extraordinarily stable and thus allowing a plethora of transformations, it enables access to various diastereo- and enantiomerically pure organoboron reagents and versatile intermediates in asymmetric synthesis.
Multifunctional organic polymeric catalysts and reagents
Authors: Lu Jinni , Toy Patrick H.
Published: September 2012

A series of polystyrenes bearing multiple different functional groups has been synthesized, and these materials have been used as catalysts and reagents in a variety of organic reactions. Polymers functionalized with various combinations of amine, phenol, phosphine, and thiourea groups have been prepared in both non-cross-linked (soluble) and cross-linked (insoluble) formats. Reactions catalyzed by these polymers include Morita–Baylis–Hillman (MBH), alkyne to 1,3-diene isomerization, and decarboxylative Doebner–Knoevenagel reactions. Furthermore, Wittig and tandem Wittig/reduction reactions have been performed using heterogeneous polymeric reagents possessing a combination of amine and phosphine groups.
Particle swarm optimization technique for the optimal design of shell and tube heat exchangers
Authors: Lahiri Sandip Kumar , Khalfe Nadeem Muhammed , Wadhwa Shiv Kumar
Published: September 2012

Owing to the wide utilization of heat exchangers in industrial processes, their cost minimization is an important target for both designers and users. Traditional design approaches are based on iterative procedures which gradually change the design and geometric parameters until given heat duty and set of geometric and operational constraints are satisfied.Although well proven, this kind of approach is time consuming and may not lead to cost effective design. The present study explores the use of non-traditional optimization technique: calledParticle swarm optimization (PSO), for design optimization of shell and tube heat exchangers from economic point of view. The optimization procedure involves the selection of the major geometric parameters such as tube diameters, tubelength, bafflespacing, number of tube passes, tubelayout, type of head, baffle cutetc and minimization of total annual cost is considered as design target. The presented PSO technique is conceptually simple, has only a few parameters and is easy to implement.Furthermore, the PSO algorithm explores the good quality solutions quickly, giving the designer more degrees of freedom in the final choice with respect to traditional methods. The methodology takes into account the geometric and operational constraints typically recommended by design codes. Three different case studies are presented to demonstrate the effectiveness and accuracy of proposed algorithm . The PSO method leads to a design of a heat exchanger with a reduced cost of heat exchanger as compare to cost obtained by previously reported GA approach.
Proposals for the mitigation of the environmental impact of clinical laboratories
Authors: Lopez Joseph B. , Badrick Tony
Published: September 2012

Laboratories should be aware of the carbon footprint resulting from their activities and take steps to mitigate it as part of their societal responsibilities. Once committed to a mitigation programme, they should announce an environmental policy, secure the support of senior management, initiate documentation, institute a staff training programme, schedule environmental audits and appoint an environmental manager. Laboratories may aspire to be accredited to one of the standards for environmental management, such as the ISO 14000. As environmental and quality issues are linked, the improvement in the environmental management of an organisation will ultimately lead to improved quality system performance. Indeed, environmental management could conceivably come under overall quality management. Although there will be initial costs, good environmental practices can bring savings. Environmental improvement should be based on the 3R concept to reduce, reuse and recycle. Several policy initiatives may be introduced. These include a green purchasing policy for equipment, laboratory furniture and reagents as well as the management of packaging wastes. There are several ways to reduce energy, water usage and wastage. A reduction of test numbers and collection tubes should be attempted. Paper management involves all aspects of 3R. The recycling of solvents and general wastes should be practised where feasible. The construction new laboratories or renovations to existing ones are opportunities to make them more environmentally-friendly. The advocacy of policies to associates and the inclusion of environmentally-friendly conditions on contractors are integral parts of the programme.
Variation of serum and urinary neutrophil gelatinase associated lipocalin (NGAL) after strenuous physical exercise
Authors: Lippi Giuseppe , Sanchis-Gomar Fabian , Salvagno Gian Luca , Aloe Rosalia , Schena Federico , Guidi Gian Cesare
Published: September 2012

Strenuous exercise may trigger acute complications, such as exertional rhabdomyolysis and gastrointestinal complaint. As less is known about the potential renal impairment after long distance running, we assessed creatinine and neutrophil gelatinase associated lipocalin (NGAL) in serum (sNGAL) and urine (uNGAL) before and after an ultramarathon.

The study population consisted of 16 trained male athletes who ran a 60 km ultramarathon. Blood and spot urine samples were collected 20 min before and immediately after the run. Creatinine was assessed by Jaffe assay on Beckman Coulter AU5800 and renal function was expressed as estimated glomerular filtration rate (eGFR) by MDRD formula. NGAL was measured by fully-automated immunoassay NGAL Test™ on AU 5800.

Serum and urinary creatinine increased significantly by 38% and 78%, respectively. The eGFR contextually decreased by 31%. sNGAL, uNGAL and uNGAL/creatinine ratio increased by 1.6-fold, 7.7-fold and 2.9-fold. In six of 16 athletes (38%), the acute post-exercise increase of serum creatinine met the criteria of acute kidney injury. No significant relationship was found between pre-exercise, post-exercise values and post-exercise variation of sNGAL, uNGAL and uNGAL/creatinine ratio. A significant correlation was found between pre- and post-exercise changes of serum creatinine and sNGAL, but not with either uNGAL or uNGAL/creatinine ratio.

The acute variations of serum creatinine and uNGAL attest that renal impairment is likely to develop after long distance running. The uNGAL seems more independent from creatinine variation and extra-renal sources, and thereby more reliable for monitoring the renal involvement in these types of kidney impairment.
Testing for lupus anticoagulants – fresh or frozen?
Authors: Froom Paul , Barak Mira
Published: September 2012

There are no previous studies reporting the effect of using frozen-thawed plasma on lupus anticoagulant ratios in kits with the combined screen and confirm assay.

In the following study we chose patients with elevated dilute Russel’s viper venom test (dRVVT) normalized ratios and compared the test results of fresh to frozen-thawed plasma. Platelet counts ranged from 2 to 7×10

There were 13 out of 14 dRVVT test normalized ratios that decreased after freezing (p<0.001), leading to the misclassification of six of 14 patients with high values that decreased into the reference interval.

The major finding of this study is that testing frozen-thawed plasma with platelet counts <10,000/μL (10
Determinants of the essential one-carbon metabolism metabolites, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid
Authors: Smith Desirée E.C. , Smulders Yvo M. , Blom Henk J. , Popp Julius , Jessen Frank , Semmler Alexander , Farkas Melinda , Linnebank Michael
Published: September 2012

Disturbances in the levels of one-carbon (1C) metabolism metabolites have been associated with a wide variety of neuropsychiatric diseases. Cerebrospinal fluid (CSF) levels of homocysteine (Hcy) and the other 1C metabolites, nor their interrelatedness and putative determinants, have been studied extensively in a healthy population.

Plasma and CSF samples from 100 individuals free from neuropsychiatric diseases were analyzed (55 male, 45 female; age 50±17 years). In blood, we measured plasma Hcy, serum folate and serum vitamin B12. In CSF, we measured total Hcy, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and 5-methyltetrahydrofolate (5-methylTHF). Highly selective analytical methods like liquid chromatography combined with either mass spectrometry or fluorescence detection were used.

CSF Hcy was inversely correlated with CSF 5-methylTHF and positively with plasma Hcy, independent of serum folate status. CSF SAH correlated with age, lower CSF 5-methylTHF and higher CSF Hcy. CSF 5-methylTHF showed independent negative correlations with age and positive correlations with serum folate. CSF SAM did not correlate with any of the 1C metabolites.

Aging is characterized by a reduction in CSF 5-methylTHF levels and increased CSF levels of the potentially neurotoxic transmethylation inhibitor SAH. CSF 5-methylTHF, which is itself determined in part by systemic folate status, is a powerful independent determinant of CSF levels of Hcy and SAH.
Neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular disease: a systematic review
Authors: Cruz Dinna N. , Gaiao Sergio , Maisel Alan , Ronco Claudio , Devarajan Prasad
Published: September 2012

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury (AKI). Recently, elevated NGAL levels have also been reported in heart failure, coronary heart disease, and stroke. Other studies demonstrate that NGAL is upregulated in failing myocardium and in atherosclerotic plaque. Our aim was to synthesize the current evidence on NGAL and cardiovascular disease (CVD), and to clarify the prognostic significance of systemic NGAL levels in CVD.

We performed a systematic review to identify experimental and human studies on NGAL and CVD. We excluded articles which specifically dealt with AKI or renal endpoints.

We identified 22 studies, including both animal and human data. NGAL is highly expressed in the heart, both in failing myocardium and myocarditis, and is also expressed in atherosclerotic plaques. Areas of co-localization of NGAL and matrix metalloproteinase (MMP)-9 exhibited increased MMP-9 proteolytic activity. Systemic NGAL levels correlated with renal function and severity of CVD in several, but not all, studies. An association between elevated systemic NGAL levels and clinical outcomes (e.g., death, hospital readmissions) were reported in six CVD studies, but these had limited adjustment for potential confounders.

There is ample literature to support a putative role of NGAL in the pathophysiology of CVD, but at present there is insufficient data regarding the clinical utility of systemic NGAL levels in the management of CVD. Available evidence regarding NGAL as a predictor of outcomes in CVD is very limited.
Locally finitely presented categories with no flat objects
Authors: Estrada Sergio , Saorín Manuel
Published: September 2012

If X is a quasi-compact and quasi-separated scheme, the
category
Qcoh(X) of quasi-coherent sheaves on X is locally finitely presented. Therefore categorical flat quasi-coherent sheaves in
the sense of Stenström (1968) naturally arise. But there is also the standard
definition
of flatness in
Qcoh(X) from the stalks. So it makes sense to wonder the relationship (if
any) between these two notions. In this paper we show that there are
plenty of
locally finitely presented categories having no other categorical flats than
the zero object. As particular instance, we show that Qcoh(𝐏
n
(R)) has no other
categorical flat objects than zero, where R is any commutative ring.
Functional and structural insights into astacin metallopeptidases
Authors: Gomis-Rüth F. Xavier , Trillo-Muyo Sergio , Stöcker Walter
Published: September 2012

The astacins are a family of multi-domain metallopeptidases with manifold functions in metabolism. They are either secreted or membrane-anchored and are regulated by being synthesized as inactive zymogens and also by co-localizing protein inhibitors. The distinct family members consist of N-terminal signal peptides and pro-segments, zinc-dependent catalytic domains, further downstream extracellular domains, transmembrane anchors, and cytosolic domains. The catalytic domains of four astacins and the zymogen of one of these have been structurally characterized and shown to comprise compact ∼200-residue zinc-dependent moieties divided into an N-terminal and a C-terminal sub-domain by an active-site cleft. Astacins include an extended zinc-binding motif (HEXXHXXGXXH) which includes three metal ligands and groups them into the metzincin clan of metallopeptidases. In mature, unbound astacins, a conserved tyrosine acts as an additional zinc ligand, which is swung out upon substrate or inhibitor binding in a ‘tyrosine switch’ motion. Other characteristic structural elements of astacin catalytic domains are three large α-helices and a five-stranded β-sheet, as well as two or three disulfide bonds. The N-terminal pro-segments are variable in length and rather unstructured. They inhibit the catalytic zinc following an ‘aspartate-switch’ mechanism mediated by an aspartate embedded in a conserved motif (FXGD). Removal of the pro-segment uncovers a deep and extended active-site cleft, which in general shows preference for aspartate residues in the specificity pocket (S1′). Furthermore, astacins undergo major rearrangement upon activation within an ‘activation domain,’ and show a slight hinge movement when binding substrates or inhibitors. In this review, we discuss the overall architecture of astacin catalytic domains and their involvement in function and zymogenic activation.
Structural analysis of the C-terminal domain of the spliceosomal helicase Prp22
Authors: Kudlinzki Denis , Schmitt Andreas , Christian Henning , Ficner Ralf
Published: September 2012

Splicing of pre-mRNA requires the activity of at least eight different DEAD/H-box proteins that are involved in distinct steps of the splicing process. These proteins are driving the spliceosomal machinery by ATP-dependent unwinding of dsRNA and/or disrupting protein-RNA complexes. The spliceosomal DEAH-box proteins Prp2, Prp16, Prp22 and Prp43 share homologous C-terminal domains (CTD). We have determined the crystal structure of the CTD of human Prp22 by means of MAD. The fold of the human Prp22-CTD closely resembles that of the yeast Prp43-CTD. The similarity of these helicase-associated CTDs to the winged-helix and ratchet domains of the DNA helicase Hel308 suggests an analogous function in dsRNA binding and unwinding. Here, we also demonstrate that the CTD has a significant impact on the ATPase activity of yPrp22 in vitro. Homology modeling of the CTDs of hPrp2, hPrp16 and hPrp43 suggests that the CTDs of spliceosomal helicases contain conserved positively charged patches on their surfaces representing a common RNA-binding surface as well as divergent regions most likely mediating specific interactions with different proteins of the spliceosome.
β-Trefoil inhibitors – from the work of Kunitz onward
Authors: Renko Miha , Sabotič Jerica , Turk Dušan
Published: September 2012

Protein protease inhibitors are the tools of nature in controlling proteolytic enzymes. They come in different shapes and sizes. The β-trefoil protease inhibitors that come from plants, first discovered by Kunitz, were later complemented with representatives from higher fungi. They inhibit serine (families S1 and S8) and cysteine proteases (families C1 and C13) as well as other hydrolases. Their versatility is the result of the plasticity of the loops coming out of the stable β-trefoil scaffold. For this reason, they display several different mechanisms of inhibition involving different positions of the loops and their combinations. Natural diversity, as well as the initial successes in de novo protein engineering, makes the β-trefoil proteins a promising starting point for the generation of strong, specific, multitarget inhibitors capable of inhibiting multiple types of hydrolytic enzymes and simultaneously interacting with different protein, carbohydrate, or DNA molecules. This pool of knowledge opens up new possibilities for the exploration of their naturally occurring as well as modified properties for applications in many fields of medicine, biotechnology, and agriculture.
Withaferin A binds covalently to the N-terminal domain of annexin A2
Authors: Ozorowski Gabriel , Ryan Christopher M. , Whitelegge Julian P. , Luecke Hartmut
Published: September 2012

Annexin A2 (AnxA2), a 38-kDa member of the Ca2+-binding annexin family, has been implicated in numerous cancer pathways. Withaferin A (WithfA), a natural plant compound, has been reported previously to bind covalently to Cys133 of the AnxA2 core domain leading to a reduction of the invasive capabilities of cancer cells by altering their cytoskeleton. We show here that AnxA2 has an inhibitory effect on actin polymerization, and a modification with WithfA significantly increases this inhibitory role of AnxA2. Using mass spectrometry and single-site mutants, we localized the WithfA-AnxA2 interaction to the N-terminal domain of AnxA2 where WithfA binds covalently to Cys9. Whereas binding to F-actin filaments has been mapped to the C terminus of AnxA2, our results suggest that the N-terminal domain modified by WithfA may also play a role in the AnxA2-actin interaction. The binding of WithfA may regulate the AnxA2-mediated actin dynamics in two distinct ways: (i) the increase of F-actin bundling activity by the Anx2/p11 heterotetramer and (ii) the decrease of actin polymerization as a result of the increased affinity of AnxA2 to the barbed end of actin microfilaments. We demonstrate the susceptibility of Cys9 of AnxA2 to chemical modifications and exclude Cys133 as a binding site for WithfA.
Structural basis of [NiFe] hydrogenase maturation by Hyp proteins
Authors: Watanabe Satoshi , Sasaki Daisuke , Tominaga Taiga , Miki Kunio
Published: September 2012

[NiFe] hydrogenases catalyze reversible hydrogen production/consumption. The active site of [NiFe] hydrogenases contains a complex NiFe(CN)2CO center, and the biosynthesis/maturation of these enzymes is a complex and dynamic process, primarily involving six Hyp proteins (HypABCDEF). HypA and HypB are involved in the Ni insertion, whereas the other four Hyp proteins (HypCDEF) are required for the biosynthesis, assembly and insertion of the Fe(CN)2CO group. Over the last decades, a large number of functional and structural studies on maturation proteins have been performed, revealing detailed functions of each Hyp protein and the framework of the maturation pathway. This article will focus on recent advances in structural studies of the Hyp proteins and on mechanistic insights into the [NiFe] hydrogenase maturation.
No end in sight: the development of protein crystallography in Martinsried
Authors: Stubbs Milton T. , Baumann Ulrich
Published: September 2012

No abstract available.
Implementation of the Secondary 2 Program of Project P.A.T.H.S.: observations based on the co-walker scheme
Authors: Shek Daniel T.L. , Yu Lu , Ho Vicky Y.T.
Published: September 2012

The present study examined the implementation quality of the Tier 1 Program of Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) at Secondary 2 level in the third year of the initial phase of the project in Hong Kong. Classroom observations of 222 units in 148 schools were conducted under the co-walker scheme. Results generally showed that the overall level of program adherence was high and different dimensions of program delivery were positively correlated amongst themselves. Instructors’ use of positive and supportive feedback, degree of achievement of the objectives, and lesson preparation significantly predicted both the overall implementation quality and perceived success of the program. While instructors’ interactive delivery method and their familiarity with the students predicted overall implementation quality, student participation and involvement, and opportunity for reflection were predictive of implementation success. In conjunction with other evaluation findings, the present study lends further support to the high implementation quality of Project P.A.T.H.S. in Hong Kong.
A stakeholder-collaborative evaluation of intervention for students with greater psychosocial needs
Authors: Shek Daniel T.L. , Yu Lu
Published: September 2012

The Tier 2 Program of Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong was designed and implemented by school social workers targeting adolescents with greater psychosocial needs. Based on the responses of 237 participants, 48 program implementers wrote down five conclusions on the program effectiveness in their reports submitted to the funding body. Based on a stakeholder-collaborative approach involving secondary data analyses, results showed that most conclusions were positive regarding participants’ perceptions of the program, instructors and their perceived program effectiveness, although there were also conclusions reflecting difficulties encountered and suggestions for improvements. In conjunction with the previous evaluation findings, the present study suggests that the Tier 2 Program was well received by the stakeholders and the program was beneficial to the development of the program participants.
Impact of Project P.A.T.H.S. on adolescent developmental outcomes in Hong Kong: findings based on seven waves of data
Authors: Shek Daniel T.L. , Ma Cecilia M.S.
Published: September 2012

The present study examined the longitudinal impact of Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) on adolescent developmental outcomes in Hong Kong. Using a longitudinal randomized group design, seven waves of data were collected from 24 experimental schools (n=4049 at wave 1) in which students participated in the Tier 1 Program of Project P.A.T.H.S. and 24 control schools (n=3797 at wave 1). Results based on individual growth curve modeling generally showed that, relative to the control participants, participants in the experimental group had: (a) a higher level of positive development; (b) a lower level of substance abuse; and (c) a lower level of delinquent behavior. Participants who regarded the program to be beneficial also showed higher levels of positive development and lower levels of problem behavior than did the control school students. The present findings suggest that Project P.A.T.H.S. is effective in promoting positive development and preventing adolescent problem behavior in Chinese adolescents in Hong Kong.
Genomic advances for gene discovery in hereditary hearing loss
Authors: Avraham Karen B. , Kanaan Moien
Published: September 2012

High-throughput sequencing is changing the face of genetic diagnosis and counseling. While in the past, it would take on average 1 to 5 years to identify a mutation leading to deafness, today, the genetic basis for deafness can be determined within months in a child or adult with inherited hearing loss. Obstacles and challenges still remain, but the field is changing at a dramatic rate, making gene discovery a much easier and more efficient task than in the past.
H∀Mcast - Evaluierung einer systemzentrierten
Middleware-Komponente für einen universellen Multicast-Dienst im Future
Internet
Authors: Meiling Sebastian , Charousset Dominik , Schmidt Thomas C. , Wählisch Matthias
Published: September 2012

Das Internet hat die globale Kommunikation durch eine einzelne,
adaptive Abstraktionsschicht revolutioniert. IP verbindet heute
Millionen von Anwendungen, welche wiederum über die Socket API an die
bisherige IP-Schicht gebunden sind. Eine Veränderung dieser
`Verbindungsschicht' ist in der Praxis nur schwer erreichbar. In
diesem Beitrag präsentieren wir den H∀Mcast-Ansatz einer
Multi-Service-Architektur für ein Future Internet auf höherem
Abstraktionsniveau. Für das Publish/Subscribe Modell eines
universellen Multicast-Dienstes integrieren wir heterogene
Netzwerktechnologien unter einer transparenten Anwendungsschnittstelle
mit abstraktem Namensschema und einer systemzentrierten
Middleware-Komponente. Eine gründliche Evaluierung der
Leistungsdaten unseres H∀Mcast-Prototypen kann in diesem Beitrag zeigen,
dass die entstehenden Anforderungen auf gegenwärtigen Endsystemen
problemlos bewältigt werden können.
Messung und Optimierung der Interaktionsgüte (Quality of
Interaction) zeitverzögerter CSCW-Anwendungen
Authors: Donick Mario , Daher Robil , Schwelgengräber Wiebke , Krohn Martin , Tavangarian Djamshid
Published: September 2012

Zeitverzögerungen in Kommunikationsnetzen, z.B. interplanetaren Netzen
(IPNs), zeigen sich als Leistungseinbußen. Dies ist messbar bei technischen
Ressourcen und Diensten (z.B. niedrigen Datenübertragungsraten und
Verbindungsabbrüchen) und wird von menschlichen Akteuren wahrgenommen (z.B.
als erfolgloser Kooperationsversuch in CSCW-Anwendungen). In diesem Beitrag
zeigen wir, wie mittels des Konzepts Quality of Interaction (QoI,
Interaktionsgüte) die Bewertung technischer Ressourcen und Dienste
hinsichtlich des Interaktionserfolgs auf Anwendungsebene durchgeführt werden
kann, um Leistungseinbußen aufzudecken und QoI auf einem optimalen Niveau zu
halten. Dabei ist QoI eine Ergänzung zu Quality of Service (QoS) und Quality
of Experience (QoE, [1,2]).
A “New” Anarchism? – On Bifurcation and Transformation of Contemporary Anarchist Thought and Praxis
Authors: Vodovnik Žiga
Published: September 2012

The article reflects main discrepancies between basic coordinates of classic anarchist thought and coordinates of contemporary anarchism, as it developed within the “post-Seattle” alter-globalization movement. The article ascertains that the anarchist renaissance within the alter-globalization movement is not fostered only by classical anarchism, but also by ideational currents that in the past had represented its main counterpoint. The question that the author addresses is therefore: Is it possible to talk about a “new” anarchism? Following a thorough examination of the alter-globalization movement, its genealogy and the main ideational currents within the movement, the author concludes, that a “new” or “post-ideological” anarchism does not offer important innovations only on the level of political praxis, but also on the level of theoretical paradigms. In the last part of the article, the author affirms these findings with an outline of redefinition of violence, political power, nation state and democracy within (contemporary) anarchism.
Principals or Beginners? The Regions and the Local Railway System (1997–2011)
Authors: Giulio Marco Di
Published: September 2012

This article analyzes the implementation of the Italian railway reforms, with a focus on the process of regionalization started in 1997. Indeed, this sector represents a relevant challenge for the Italian legacy in the field, traditionally regulated by the bureaucratic structure of the Italian Railways, under direct ministerial control since 1905. However, after 10 years of implementation, Regions seem to have not yet enough financial resources and administrative capacity to deal with this policy. In addition, the national incumbent (FS) initiated a successful lobbying campaign to restrict the market condition at regional level in order to protect its own domain. As a result, the regionalization process appears to be dominated by national actors and highly politicized dynamics which undermine the creation of a stable and accountable regulatory framework.
Women’s Substantive Representation in the Belgian Chamber of Representatives: Testing the Added Value of a ‘Claims-making’ Approach
Authors: Erzeel Silvia
Published: September 2012

Studies of women’s representation have often explored the link between women’s descriptive and women’s substantive representation in parliament, analyzing whether female representatives bring a unique – and often feminist– contribution to the representation of women’s interests. Recent studies however propose to apply a claim-based framework, leaving open how, why and by whom women’s substantive representation occurs (Celis et al. 2008). In this article, we put this new claim-based approach to the empirical test. More in particular, we consider its added value by studying the variety of claims made about women in the Belgian Chamber of Representatives (1995–2007). We conclude that a claim-based framework indeed brings additional actors and perspectives to the fore, but that there are limits as to which claims can be formulated and by whom.
Adsorption of Solvent Cations on Au(111) and Au(100) in Alkylimidazolium-Based Ionic Liquids – Worm-Like versus Micelle-Like Structures
Authors: Su Yu-Zhuan , Yan Jia-Wei , Li Mian-Gang , Xie Zhao-Xiong , Mao Bing-Wei , Tian Zhong-Qun
Published: September 2012

By employing high resolution in-situ STM, the adsorption of alkylimidazolium-based cations of EMI
+
, PMI
+
, BMI
+
and OMI
+
on Au(111) and Au(100) surfaces are investigated systematically. The cation adsorption on both Au(111) and Au(100) are composed of double rows arising from counter-facing imidazolium-based cation pairs. On Au(100), the double rows associated with the four cations show micelle-like appearance along the two √ 2 directions of the Au(100) surface lattice units. The width of the double rows varies depending on the side chain length of the cations, but is constrained by the periodicity along the √ 2 directions. Anions of BF
4
-
, PF
6
-
, CF3SO
3
-
and Tf2N
-
do not influence the micelle-like adsorption structure. On Au(111), the double rows are formed only when the terraces are etched to several atoms wide. Most likely, the underneath Au surface experiences restructuring to accommodate the double row structure, and the worm-like orientation of the double rows is the consequence of strain release. Both the micelle-like and worm-like adsorption structures would be lifted upon cathodic potential excursions when the surfaces are driven to undergo ordinary Au(100)-hex and Au(111)-(√ 3 × 22) reconstructions. These results reveal that the ordered micelle-like structure on Au(100) and the irregular worm-like structure on Au(111) are of the same nature.
Improving patient safety in perioperative care for major surgeries
Authors: Horváth Alexandra , Reusz Géza , Gál János , Csomós Ákos
Published: September 2012

The Helsinki Declaration was created and signed by the European Board of Anaesthesiology (EBA) and the European Society of Anaesthesiology (ESA). It was initiated in June 2010, and it implies a European consensus on those medical practices which improve patient safety and provide higher quality perioperative care. Authors focus on four elements of this initiative, which can be easily implemented, and provide almost instant benefit: use of preoperative checklist, prevention of perioperative infections, goal-directed fluid therapy and perioperative nutrition. The literature review emphasizes that well organized perioperative care plays the most important role in improving patient safety. Orv. Hetil., 2012, 153, 1447–1455.
Demand‐driven resource investment in annual seed production by a perennial angiosperm precludes resource limitation
Authors: Ida Takashi Y. , Harder Lawrence D. , Kudo Gaku
Published: September 2012

The limits on annual seed production have long been characterized as restriction by either pollination success or resource provision to seed development. This expected dichotomy between pollen and resource limitation is based on the assumption that reproductive resources are fixed, which is reasonable for semelparous species. In contrast, iteroparity can ease the constraints on reproductive output per breeding season, if resources can be either mobilized from past storage or borrowed against future performance. For perennial plants, these options allow enhanced reproductive investment in response to unusually good pollination, so that annual seed production may not be pollen or resource limited. We assessed demand‐governed reproductive investment by manipulating both resource supply capacity (partial defoliation) and resource demand (pollination quality: fully self‐pollination, fully cross‐pollination, or combinations of partial self‐ and cross‐pollination within the inflorescence) for a forest herb,Stenanthium occidentale, which is subject to strong pre‐dispersal inbreeding depression. Insensitivity to partial defoliation indicated that reproductive output was not source regulated. Instead, demand by developing seeds governs resource distribution, as demonstrated by elevated photosynthate translocation to fruits on fully cross‐pollinated plants and the ability of completely defoliated plants to produce seeds. Such contingent resource allocation eliminates a simple dichotomy between pollen receipt and resource availability as limits on annual seed production. Instead, such flexible reproductive investment allows iteroparous perennials to participate maximally in current reproduction (as determined by ovule production) following superior pollination, or to conserve resources for future reproduction following poor pollination.