bluuebunny/crossref_metadata_2025 huggingface dataset:
MOLECULAR RECOGNITION OF THE DISORDERED DIHYDROPYRIDINE RECEPTOR II–III LOOP BY A CONSERVED SPRY DOMAIN OF THE TYPE 1 RYANODINE RECEPTOR
Authors: Tae Han‐Shen , Norris Nicole C , Cui Yanfang , Karunasekara Yamuna , Board Philip G , Dulhunty Angela F , Casarotto Marco G
Published: November 2008

The dihydropyridine receptor (DHPR) II–III loop is an intrinsically unstructured region made up of α‐helical and β‐turn secondary structure elements with the N and C termini in close spatial proximity.

The DHPR II–III loop interacts in vitro with a ryanodine receptor (RyR) 1 SPRY domain through α‐helical segments located in the A and B regions. Mutations within the A and B regions in the DHPR II–III loop alter the binding affinity to the SPRY2 domain.

The A and C peptides derived from DHPR II–III loop show negative cooperativity in binding to the SPRY2 domain.

The SPRY2 domain of the RyR1 (1085–1208) forms a β‐sheet sandwich structure flanked by variable loop regions. An acidic loop region of SPRY2 (1107–1121) forms part of a negatively charged cleft that is implicated in the binding of the DHPR II–III loop.

The mutant E1108A located in the negatively charged loop of SPRY2 reduces the binding affinity to the DHPR II–III loop.
Expression of nerve growth factor and tyrosine kinase receptor A and correlation with perineural invasion in pancreatic cancer
Authors: Ma Jun , Jiang Yumei , Jiang Yuhua , Sun Yan , Zhao Xueming
Published: November 2008

Background and Aim:  Perineural invasion (PNI) is one of the most common routes of invasion in pancreatic cancer and the exact mechanism is still not clear. The aim of the present study was to investigate the effect of nerve growth factor (NGF) and tyrosine kinase receptor A (TrkA) on PNI and to clarify the possible mechanism of PNI in pancreatic cancer.

Methods:  Expressions of NGF/TrkA were examined in 51 human primary pancreatic cancer using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT‐PCR). The molecular findings were correlated with PNI, clinicopathological parameters and expression of Ki‐67.

Results:  Immunohistochemical analysis indicated that the presence and kind of PNI are prognostic parameters (P = 0.002,, P = 0.004). Tumors with high NGF expression exhibited more frequent presence of PNI (P = 0.033). NGF expression was significantly correlated with metastasis of lymph nodes and involvement of surgical margins (P = 0.006, 0.015). TrkA expression was significantly correlated with degree of PNI (P = 0.017). Negative correlations were found between expression of NGF/TrkA and Ki‐67. As shown by RT‐PCR, mRNA levels of NGF/TrkA with PNI were significantly higher than that without PNI.

Conclusions:  In pancreatic cancer, overexpression of NGF may contribute to PNI by prompting the hyperplasia of nerves, restraining the apoptosis of tumor cells and specifically combining NGF and TrkA.
Is there a link between food and intestinal microbes and the occurrence of Crohn's disease and ulcerative colitis?
Authors: Asakura Hitoshi , Suzuki Kenji , Kitahora Tetsuji , Morizane Toshio
Published: November 2008

The pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) is not fully understood. The interaction between intestinal environmental factors of food and intestinal microbes and the immunological system of hosts seems to be an important aspect. We have reviewed the relationship of the daily consumption of dietary animal meat and fats, dairy products, sugar, and other factors that may be linked to the occurrence of CD and UC from the literature and Japanese epidemiological data. In the present study, we reviewed the association between food and intestinal microbes and other factors contributing to the occurence of inflammatory bowel disease (IBD) from epidemiological data and case‐control studies of IBD in the literature that appeared on Medline, and assessed the reports of intestinal microbes involved in the occurrence of IBD. We found several papers describing the positive association of animal meat and sweets and sugar with the occurrence of CD and UC. An analysis of Japanese epidemiological data suggested that the registered number of patients with CD or UC started to increase more than 20 years after an increased daily consumption of dietary animal meat and fats, and milk and dairy products, and after a decreased consumption of rice. Many studies implied a positive role of intestinal microbes in the occurrence of IBD. Intestinal environmental factors, such as Westernized food and intestinal microbes, seem to be involved in the increased occurrence of IBD.
Gastroesophageal reflux disease: An Asian perspective
Authors: Wu Justin CY
Published: November 2008

The prevalence of gastroesophageal reflux disease (GERD) ranges from 2.5% to 7.1% in most population‐based studies in Asia. There is evidence that GERD and its complications are rising, coinciding with a decline in Helicobacter pylori (H. pylori) infection. Asian GERD patients share similar risk factors and pathophysiological mechanisms with their Western counterparts. Possible causes for the lower prevalence of GERD include less obesity and hiatus hernia, a lesser degree of esophageal dysmotility, a high prevalence of virulent strains of H. pylori, and low awareness. Owing to the lack of precise translation for ‘heartburn’ in most Asian languages, reflux symptoms are often overlooked or misinterpreted as dyspepsia or chest pain. Furthermore, a symptom‐based diagnosis with a therapeutic trial of the proton pump inhibitor (PPI) may be hampered by the high prevalence of H. pylori‐related disease. The risk stratification for prompt endoscopy, use of a locally‐validated, diagnostic symptom questionnaire, and response to H. pylori‘test and treat’ help improve the accuracy of the PPI test for diagnoses. PPI remain the gold standard treatment, and ‘on‐demand’ PPI have been shown to be a cost‐effective, long‐term treatment. The clinical course of GERD is benign in most patients in Asia. The risk of progression from non‐erosive reflux disease to erosive esophagitis is low, and treatment response to a conventional dose of PPI is generally higher. Although H. pylori eradication may lead to more resilient GERD in a subset of patients, the benefits of H. pylori eradication outweigh the risks, especially in Asian populations with a high incidence of gastric cancer.
Expression of pro‐ and anti‐inflammatory cytokines in relation to apoptotic genes in Egyptian liver disease patients associated with HCV‐genotype‐4
Authors: Zekri Abdel‐Rahman N , Bahnassy Abeer A , Abdel‐Wahab Sabrin A , Khafagy Medhat M , Loutfy Samah A , Radwan Hessam , Shaarawy Sabry M
Published: November 2008

Background:  Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide strongly linked to hepatitis C virus (HCV) infection. However, the exact pathogenetic mechanisms are still unclear.

Methods:  We assessed the expression of apoptosis genes (GSK3‐B, AKT‐1, Bcl‐2), inflammatory cytokines (TNFα, TNF‐RI, TNF‐RII, IL‐6, IL‐6R), anti‐inflammatory IL‐10, CRP and αFP by reverse transcription—polymerase chain reaction (RT‐PCR) in 33 HCC, 25 chronic hepatitis and 16 asymptomatic HCV carrier positive for HCV subjects. Also, pooled normal liver tissues and HepG2 cells were used as controls.

Results:  Hepatocellular carcinoma and liver disease (LD) showed reduced expression of GSK‐3β, TNFα, TNF‐R I, TNF‐RII, IL‐10 and overexpression of IL‐6R and CRP with no significant difference between the two groups. AFP was expressed in HCC only (33%). AKT, BCL2 and IL‐6 showed normal, reduced and overexpression in studied patients with a significant difference between AFP, AKT overexpression (67% and 30%), BCL2 overexpression (49% and 10%) and reduced IL‐6 in between HCC and LD. The morphologically normal tissues adjacent to tumors showed aberrant expression of AKT, IL‐6, CRP, TNFα and TNFRI. A significant relation was observed between cirrhosis and GSK‐3β, AKT and IL‐6 (P = 0.0018, P = 0.018, P = 0.0001; respectively).

Conclusions:  Aberrant expressions of AKT, GSK3‐B, and BCL2 are common events in HCV‐associated LD and HCC. AKT, GSK3‐B and IL‐6 are significantly associated with cirrhosis and could be used as biomarkers for both early detection and molecular target therapy for the prevention of HCC development. TNFRII, GSK3‐B and s‐AFP could be used as prognostic factors that can predict the clinical outcome of HCC patients.
Stress concentration factors of a general triaxial ellipsoidal cavity
Authors: CHIANG CHUN‐RON
Published: November 2008

The equivalent inclusion method is applied to solve the stress concentration problem concerning the disturbing effect of a general triaxial ellipsoidal cavity on an otherwise uniform normal stress state. Several useful solutions in simple form for limiting cases are derived and numerical results for general cases are obtained. These findings show the general features of the stress concentration factors around the base equator of the cavity. It is found that (1) when Poisson's ratio of the material is zero, the stress concentration factor does not vary along the equator of the cavity; (2) When the aspect ratio c/b of the cavity is very small, the stress concentration factor is also constant along the equator; (3) In general, the variation of stress concentration factors around the equator is less than 0.17 regardless of Poisson's ratio of the material. Thus, it is concluded that the stress concentration factor may be treated as constant around the equator of an ellipsoidal cavity with only a slight error.
Feeding by short‐snouted weevils on seedlings of seven tree species planted beneath Norway spruce at differing stand densities
Authors: Löf M. , Welander N. T.
Published: November 2008

1 Short‐snouted weevils, including Strophosoma spp. and related species, may damage tree seedlings. We investigated the damage caused by these weevils feeding on seedlings of seven tree species planted in clear‐cuts and under shelterwoods with three densities (control, dense, and sparse).

2 There were no pronounced differences in damage caused by short‐snouted weevils in the various shelterwood densities. Most feeding occurred in the clear‐cuts during the first year, whereas more seedlings were damaged in the shelterwoods of all densities in the second year. In the third year, virtually no feeding occurred in either the clear‐cuts or shelterwoods. We cannot explain this pattern of damage, but a fallow period of 2 years seems to prevent short‐snouted weevil damage.

3 We determined the general feeding preferences for short‐snouted weevils to be cherry, lime > beech, oak, spruce > maple, ash. However, although Strophosoma mellanogrammum [Correction added after online publication 8 December 2008: Strophosoma melanogrammum corrected to Strophosoma mellanogrammum] was observed feeding on seedlings, no full short‐snouted weevil inventory was conducted, so caution must be exercised when drawing conclusions from this study regarding weevil damage patterns and feeding preferences.

4 Short‐snouted weevils can sometimes occur in large numbers and may destroy entire reforestation projects, but in our study their influence on seedling growth and survival was minor.
Recombinant aryl hydrocarbon receptors for bioassay of aryl hydrocarbon receptor ligands in transgenic tobacco plants
Authors: Kodama Susumu , Okada Kumiko , Akimoto Keiko , Inui Hideyuki , Ohkawa Hideo
Published: November 2008

Dioxin residues widely contaminate soil and agricultural products at low concentrations and may accumulate in organisms at the top of food chains owing to their physicochemical properties. In this study, we have developed novel, dioxin‐inducible, reporter gene expression systems regulated by recombinant aryl hydrocarbon receptors (AhRs). The recombinant AhRs, referred to as XDVs, consist of the DNA‐binding domain of the bacterial repressor protein LexA, a 90‐kDa heat shock protein‐ and ligand‐binding regulatory domain from mouse AhR, and the transactivation domain of herpes simplex virus regulatory protein VP16. Transgenic tobacco plants carrying XDVs absorb various AhR ligands, including 3‐methylcholanthrene, β‐naphthoflavone and indigo from solid medium and vermiculite, and show dose‐ and time‐dependent expression of theβ‐glucuronidasereporter gene. The results clearly suggest that XDVs are functional transcription factors that respond to AhR ligands, and that the XDV‐mediated reporter gene expression system is applicable to bioassays for dioxin residues in the environment.
BUYER‐SUPPLIER PARTNERING IN UK DEFENCE PROCUREMENT: LOOKING BEYOND THE POLICY RHETORIC
Authors: SANDERSON JOE
Published: November 2008

This article looks beyond the rhetoric in recent UK defence procurement policy to discuss factors that might impact on the practical implementation of buyer‐supplier partnering. Various explanations of the difficulty of creating a partnership are identified. The principal explanation explored is that the likelihood of successful partnering is a function of the power relation between a buyer and a supplier. It is argued that partnering is most likely to occur under circumstances of interdependence when each party is highly dependent upon and vulnerable to the other. A case study from naval shipbuilding is used to examine the plausibility of this power explanation. None of the power relations in the supply network discussed is primarily characterized by interdependence and there is no evidence of partnering. This suggests that while the MoD and its suppliers may use the language of partnering, they often find it difficult to translate this into meaningful action.
BUREAUCRACIES REMEMBER, POST‐BUREAUCRATIC ORGANIZATIONS FORGET?
Authors: POLLITT CHRISTOPHER
Published: November 2008

The paper examines the hypothesis that post‐bureaucratic forms of organization perform less well than traditional bureaucracies with respect both to organizational memory and learning from experience. First, the paper discusses the meanings of the main terms and concepts to be used in the argument, and delimits its domain. Second, it identifies a series of mechanisms that are likely to bring about memory loss. Third, it examines the empirical literature in search of evidence to confirm or disconfirm the existence and effects of these mechanisms. Fourth, it reflects on its own limitations. Finally, it sets out some broad conclusions concerning the state of organizational memories in the public sector. The aim is to develop new theory, identify relevant generative mechanisms, set this model alongside such evidence as is available, and suggest lines for further research.

The new men of the Empire are the ones who believe in fresh starts, new chapters, clean pages; I struggle on with the old story, hoping that, before it is finished, it will reveal to me why it was that I thought it worth the trouble. (J. M. Coetzee,Waiting for the Barbarians, 1980, p. 26)
Luther and the Girls: Religious Denomination and the Female Education Gap in Nineteenth‐century Prussia*
Authors: Becker Sascha O. , Woessmann Ludger
Published: November 2008

Martin Luther urged each town to have a girls' school so that girls would learn to read the Gospel, thereby evoking a surge of building girls' schools in Protestant areas. Using county‐ and town‐level data from the first Prussian census of 1816, we show that a larger share of Protestants decreased the gender gap in basic education. This result holds when using only the exogenous variation in Protestantism due to a county's or town's distance to Wittenberg, the birthplace of the Reformation. Similar results are found for the gender gap in literacy among the adult population in 1871.
Gender Differences in Educational Attainment: Evidence on the Role of Tracking from a Finnish Quasi‐experiment
Authors: Pekkarinen Tuomas
Published: November 2008

In this paper we study the relationship between the timing of tracking of pupils into vocational and academic secondary education and gender differences in educational attainment and income. It is argued that in a comprehensive system, where students are tracked into vocational and academic schools relatively late (age 15–16), girls are more likely to choose the academic track than boys. We exploit the Finnish comprehensive school reform of the 1970s to analyse this hypothesis. This changed the Finnish school system from a selective to a comprehensive structure and postponed tracking from the age of 10–11 to 15–16. Since the reform was not implemented at the same time throughout the country, we can observe members of the same cohorts under both systems. The shift to a comprehensive system was found to increase gender differences in the probability of choosing an academic secondary education and of continuing onto academic tertiary education. Moreover, the reform decreased the gender wage gap in adult income by four percentage points.
Inter‐agency Cooperation and New Approaches to Employability
Authors: Lindsay Colin , McQuaid Ronald W. , Dutton Matthew
Published: November 2008

This article examines the role of inter‐agency cooperation, which is one form of ‘partnership’, in new approaches to employability in the UK. The article articulates a ‘model for effective partnership working’ on employability. This model is applied first in a general review of employability policy and then to discuss case study research on the recent ‘Pathways to Work’ and ‘Working Neighbourhoods’ pilots. It is argued that successful partnerships need a clear strategic focus based on a necessity for inter‐agency cooperation and institutional arrangements that allow for shared ownership, trust and mutualism, and flexibility in resource‐sharing. While some of these factors are apparent in UK employability services, an over‐reliance on contractualism and centralized organizational structures may undermine partnership‐based approaches. Many of the success factors associated with effective partnership working appeared to be in place, even though the role of the Public Employment Service was fundamentally different in each case (as a key actor in implementing the first pilot, but largely withdrawing from the implementation role in the second). The article concludes by outlining the relevance of this model and the case study findings to discussions of the future development of employability policies and related partnership working.
Social and Family Policies in Italy: Not Totally Frozen but Far from Structural Reforms
Authors: Naldini Manuela , Saraceno Chiara
Published: November 2008

This article analyses the main shifts in the political and public discourse about families, children, elderly people, care needs and women‐friendly policies in Italy over the last two decades. It shows that while family and gender relationships have become an ideologically highly charged public issue, policies at the practical level have remained largely stagnant, marginal and fragmentary. At the same time, important institutional changes (such as the constitutional reform of 2001, which introduced a form of federalism) have created new problems of governance. The authors argue that in the face of inadequate policies, the recourse of individuals and families to old (family solidarity) and new (migrant labour) solutions may cause new tensions and inequalities.
Back to Work after Incapacity Benefit: Differences between Ethnic Minority and Native Dutch Workers
Authors: Snel Erik , Linder Frank
Published: November 2008

Contemporary pleas for an activating welfare state and social security system emphasize that getting benefit claimants back to work is more important than providing income compensation for social risks connected with unemployment or illness. The Dutch system of incapacity benefits, however, is far removed from this normative ideal of a proactive social security system. Resumption of work after a spell of incapacity benefit is the exception rather than the rule. This article examines possible ethnic differences in resumption of work following incapacity benefit. We use a unique register data file from Statistics Netherlands that contains information about all incapacity benefit claimants in the Netherlands in 1999. In the analysis we follow these benefit claimants for three years and examine what their labour market position was in 2002. We find that resumption of work after incapacity benefit is even more the exception for migrant workers with a Turkish or Moroccan ethnic background. Contrary to our assumption, this difference from native Dutch workers cannot be explained by unfavourable personal characteristics of Turkish or Moroccan benefit claimants – their personal characteristics (gender, age, low educational level) appear to be rather favourable for resumption of work. In the current literature, these differences in outcomes between ethnic groups are often attributed to certain ‘ethnic‐specific’ or cultural factors. This article argues that we should be careful of explaining different outcomes between ethnic groups by (alleged) cultural phenomena. There are other explanations possible such as differences in work motivation, lack of ‘transition facilities’ in companies and differential treatment by employers or social security officials.
RESPONSIBILITY AND RATIONAL ABILITIES: DEFENDING AN ASYMMETRICAL VIEW*
Authors: NELKIN DANA K.
Published: November 2008

Abstract: In this paper, I defend a view according to which one is responsible for one's actions to the extent that one has the ability to do the right thing for the right reasons. The view is asymmetrical in requiring the ability to do otherwise when one acts badly or for bad reasons, but no such ability in cases in which one acts well for good ones. Despite its intuitive appeal, the view's asymmetry makes it a target of both of the main camps in the debate over responsibility. In addressing objections, I explore the relationship between fairness and responsibility, and the nature of the ability to do otherwise.
BLAME AND RESPONSIVENESS TO MORAL REASONS: ARE PSYCHOPATHS BLAMEWORTHY?
Authors: TALBERT MATTHEW
Published: November 2008

Abstract:  Many philosophers believe that people who are not capable of grasping the significance of moral considerations are not open to moral blame when they fail to respond appropriately to these considerations. I contend, however, that some morally blind, or ‘psychopathic,’ agents are proper targets for moral blame, at least on some occasions. I argue that moral blame is a response to the normative commitments and attitudes of a wrongdoer and that the actions of morally blind agents can express the relevant blame‐grounding attitudes insofar as these agents possess the capacity to make judgments about non‐moral reasons.
Predictors of the scleroderma phenotype in fibroblasts from systemic sclerosis patients
Authors: Qi Q , Guo Q , Tan G , Mao Y , Tang H , Zhou C , Zeng F
Published: November 2008

Background  Fibroblasts from skin lesions generally exhibit the scleroderma phenotype in the early stage of in vitro culture, and act as one of the most important samples to investigate systemic sclerosis. However, not all cell lines from patients show the scleroderma phenotype, and little prospective evidence can be relied on to predict the phenotype of fibroblasts from systemic sclerosis patients.

Objective  This study aims to find the predictive factors related to fibroblast phenotypes.

Methods  Fibroblast lines from 15 patients with systemic sclerosis were established through explant culture, with their scleroderma phenotypes being determined by real‐time reverse transcription–polymerase chain reaction (RT‐PCR) of procollagen transcription. Logistic regression analysis was used to analyse the clinical data of these patients. Haematoxylin–eosin staining was performed to observe histopathological differences. Expression of methylation‐related factors was detected by real‐time reverse transcription‐polymerase chain reaction.

Results  Eight of the 15 fibroblast cell lines from patients with systemic sclerosis exhibited the scleroderma phenotype. Logistic regression analysis yielded an equation (Y = –9.718 + 2.525X1) in which X1 significantly represents the Valentini Disease Activity Index. Histopathology results demonstrated that the scleroderma phenotype was positively correlated with leucocyte infiltration. Further laboratory observations showed increased expression of Dnmt1 in the positive phenotype fibroblasts and a positive correlation between elevations of Dnmt1 and the maintenance period of the scleroderma phenotype.

Conclusions  The results of this study suggest that the Valentini Disease Activity Index and expression of Dnmt1 may act as indicators of the scleroderma phenotype in fibroblasts. Additionally, these data also imply that epigenetic factors, such as Dnmt1, may be involved in the maintenance of the scleroderma phenotype. Our analyses may be beneficial to the research in systemic sclerosis.

Conflicts of interest

None declared
Population Structure in Contemporary Sweden—A Y‐Chromosomal and Mitochondrial DNA Analysis
Authors: Lappalainen T. , Hannelius U. , Salmela E. , Von Döbeln U. , Lindgren C. M. , Huoponen K. , Savontaus M.‐L. , Kere J. , Lahermo P.
Published: November 2008

A population sample representing the current Swedish population was analysed for maternally and paternally inherited markers with the aim of characterizing genetic variation and population structure. The sample set of 820 females and 883 males were extracted and amplified from Guthrie cards of all the children born in Sweden during one week in 2003. 14 Y‐chromosomal and 34 mitochondrial DNA SNPs were genotyped. The haplogroup frequencies of the counties closest to Finland, Norway, Denmark and the Saami region in the north exhibited similarities to the neighbouring populations, resulting from the formation of the Swedish nation during the past millennium. Moreover, the recent immigration waves of the 20th century are visible in haplogroup frequencies, and have led to increased diversity and divergence of the major cities. Signs of genetic drift can be detected in several counties in northern as well as in southern Sweden. With the exception of the most drifted subpopulations, the population structure in Sweden appears mostly clinal. In conclusion, our study yielded valuable information of the structure of the Swedish population, and demonstrated the usefulness of biobanks as a source of population genetic research. Our sampling strategy, nonselective on the current population rather than stratified according to ancestry, is informative for capturing the contemporary variation in the increasingly panmictic populations of the world.
Association of a Polymorphism in the Intron 7 of the SREBF1 Gene with Osteonecrosis of the Femoral Head in Koreans
Authors: Lee H.‐J. , Choi S.‐J. , Hong J. M. , Lee W. K. , Baek J.‐I. , Kim S.‐Y. , Park E. K. , Kim S.‐Y. , Kim T.‐H. , Kim U.‐K.
Published: November 2008

Reduction or disruption of the blood supply to the bone is involved in the pathogenesis of osteonecrosis of the femoral head (ONFH). An altered lipid metabolism is one of the major risk factors for ONFH. Sterol regulatory element binding protein, SREBF1 activates genes regulating lipid biosynthesis. The aim of this study was to examine the association between the polymorphisms of the SREBF1 gene and ONFH susceptibility in the Korean population. The SREBF1 gene in 24 unrelated Korean individuals was sequenced and two polymorphisms were detected. Two variants, IVS6 − 48 C > T and IVS7 + 117 A > G, were genotyped in 423 ONFH patients and 348 controls. The genotype frequency of IVS7 + 117 A > G in ONFH patients was significantly different from that of the control group with P value < 0.0001 (Adjusted OR; 6.88, 95% CI; 3.74‐12.67). Moreover, the IVS7 + 117 A > G genotype showed an association with men, and further analysis stratified by etiological factors indicated that the genotype data was significantly associated with a high risk for patients with alcohol‐induced ONFH (P < 0.0001). We found that the IVS7 + 117 A > G polymorphism of the SREBF1 gene is associated with an increased risk of ONFH in the Korean population.
Facial asymmetry in young healthy subjects evaluated by statistical shape analysis
Authors: Ercan Ilker , Ozdemir Senem Turan , Etoz Abdullah , Sigirli Deniz , Tubbs R. Shane , Loukas Marios , Guney Ibrahim
Published: November 2008

Statistical shape analysis, a relatively a new method for biological research, compares body forms by using specific landmarks determined by anatomical prominences. In this study, we aimed to identify normal facial asymmetry between the right and the left sides of the face. Facial landmark data were collected from two‐dimensional digital images of 321 young healthy subjects (150 males and 171 females). These data were analysed using Euclidean distance matrix analysis. The number of significantly asymmetric linear distances between the two halves of the face was greater in females than in males. We found that the left side of the face was most commonly dominant in both males and females. Such data may be useful in establishing a database for future similar studies.
Loss of translation elongation factor (eEF1A2) expression in vivo differentiates between Wallerian degeneration and dying‐back neuronal pathology
Authors: Murray Lyndsay M. , Thomson Derek , Conklin Annalijn , Wishart Thomas M. , Gillingwater Thomas H.
Published: November 2008

Wallerian degeneration and dying‐back pathology are two well‐known cellular pathways capable of regulating the breakdown and loss of axonal and synaptic compartments of neurons in vivo. However, the underlying mechanisms and molecular triggers of these pathways remain elusive. Here, we show that loss of translation elongation factor eEF1A2 expression in lower motor neurons and skeletal muscle fibres in homozygous Wasted mice triggered a dying‐back neuropathy. Synaptic loss at the neuromuscular junction occurred in advance of axonal pathology and by a mechanism morphologically distinct from Wallerian degeneration. Dying‐back pathology in Wasted mice was accompanied by reduced expression levels of the zinc finger protein ZPR1, as found in other dying‐back neuropathies such as spinal muscular atrophy. Surprisingly, experimental nerve lesion revealed that Wallerian degeneration was significantly delayed in homozygous Wasted mice; morphological assessment revealed that ~80% of neuromuscular junctions in deep lumbrical muscles at 24 h and ~50% at 48 h had retained motor nerve terminals following tibial nerve lesion. This was in contrast to wild‐type and heterozygous Wasted mice where < 5% of neuromuscular junctions had retained motor nerve terminals at 24 h post‐lesion. These data show that eEF1A2 expression is required to prevent the initiation of dying‐back pathology at the neuromuscular junction in vivo. In contrast, loss of eEF1A2 expression significantly inhibited the initiation and progression of Wallerian degeneration in vivo. We conclude that loss of eEF1A2 expression distinguishes mechanisms underlying dying‐back pathology from those responsible for Wallerian degeneration in vivo and suggest that eEF1A2‐dependent cascades may provide novel molecular targets to manipulate neurodegenerative pathways in lower motor neurons.
The fatty acid levels and physicochemical properties of herby brined cheese, a traditional Turkish cheese
Authors: TEMIZ HASAN , TARAKCI ZEKAI , AYKUT UMUT , TURHAN SADETTIN
Published: November 2008

In this study, some gross chemical compositions and fatty characteristics of herby cheeses were investigated. In the present study, the cheeses used as materials were collected from 10 different plants. The cheeses were made from sheep milk, cow's milk or a mixture of them, and stored in brine at 7–8°C and analysed for some proximate chemical compositions and fatty acid composition after 150 days of ripening. Capric acid, palmitic acid, oleic acid, short‐chain fatty acids, medium‐chain fatty acids, long‐chain fatty acids, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids and other fatty acids as g in 100 g fatty acids were determined.
Novel role for the δ‐opioid receptor in hypoxic preconditioning in rat retinas
Authors: Peng Pai‐Huei , Huang Ho‐Shiang , Lee Yih‐Jing , Chen Yih‐Sharng , Ma Ming‐Chieh
Published: November 2008

δ‐Opioid receptor (DOR) is an oxygen‐sensitive protein whose function in the rat retina is unknown. We examined whether DOR is involved in hypoxic preconditioning (HPC)‐mediated retinoprotection following intraocular pressure (IOP) elevation. Rats were exposed to intermittent hypoxia (10% oxygen) to induce HPC. Unilateral retinal ischemia/reperfusion injury was induced by elevating IOP to 100 mmHg for 1 h. HPC attenuated the loss of neuronal marker expression and increased pro‐apoptotic caspase 3 activity in the IOP retina. Excess superoxide production and 8‐iso‐prostaglandin F2α accumulation caused by enhanced oxidant protein expression and reduced antioxidant enzyme level after IOP elevation were largely abrogated by HPC. HPC markedly increased the expression of hypoxia‐inducible factor‐1α (HIF‐1α) and DOR, but intravitreal administration of HIF‐1α‐specific small interfering RNA abrogated the up‐regulation of DOR. This suggested that DOR functions downstream of HIF‐1α. However, the endogenous content of leucine enkephalin in retinas was not affected by HPC or IOP. Treatment of retinas with the DOR antagonist naltrindole attenuated the HPC‐induced protection and activation of extracellular signal‐regulated kinase. These results suggest a novel mechanism of HPC‐mediated retinoprotection whereby HIF‐1α induces the expression of DOR, and DOR‐mediated activation of extracellular signal‐regulated kinase triggers cellular events that correct the redox imbalance in the post‐ischemic retina.
Hydrogen sulfide evokes neurite outgrowth and expression of high‐voltage‐activated Ca2+ currents in NG108‐15 cells: involvement of T‐type Ca2+ channels
Authors: Nagasawa Keita , Tarui Takeshi , Yoshida Shigeru , Sekiguchi Fumiko , Matsunami Maho , Ohi Ai , Fukami Kazuki , Ichida Seiji , Nishikawa Hiroyuki , Kawabata Atsufumi
Published: November 2008

We investigated if stimulation of T‐type Ca2+ channels with sodium hydrosulfide (NaHS), a donor of hydrogen sulfide (H2S), could cause neuronal differentiation of NG108‐15 cells. Like dibutyryl cyclic AMP (db‐cAMP), treatment with NaHS at 1.5–13.5 mM for 16 h enhanced neurite outgrowth in a concentration‐dependent manner. Synergistic neuritogenic effect was obtained in the cells stimulated with NaHS in combination with db‐cAMP at subeffective concentrations. Exposure to NaHS or db‐cAMP for 2 days resulted in enhancement of expression of high‐voltage‐activated currents consisting of N‐, P/Q‐, L‐ and also other types, but not of T‐type currents. Mibefradil, a pan‐T‐type channel blocker, abolished the neuritogenesis induced by NaHS, but not by db‐cAMP. The NaHS‐evoked neuritogenesis was also completely blocked by pretreatment with BAPTA/AM, a chelator of intracellular Ca2+, and by zinc chloride at a concentration known to selectively inhibit Cav3.2 isoform of T‐type Ca2+ channels, but not Cav3.1 or Cav3.3. Further, l‐ascorbate, recently proven to selectively inhibit Cav3.2, abolished the neuritogenic effect of NaHS, but not db‐cAMP. Our data thus demonstrate that NaHS/H2S is a novel inducer of neuronal differentiation in NG108‐15 cells, as characterized by neuritogenesis and expression of high‐voltage‐activated currents, and suggest the involvement of T‐type Ca2+ channels, especially Cav3.2.
Pancreas β‐cells morphology, liver antioxidant enzymes and liver oxidative parameters in alloxan‐resistant and alloxan‐susceptible Wistar rats: a viable model system for the study of concepts into reactive oxygen species
Authors: Behr Guilherme Antônio , Da Silva Evandro Gomes , Ferreira Amâncio Romanelli , Cerski Carlos Thadeu Schmidt , Dal‐Pizzol Felipe , Moreira José Cláudio Fonseca
Published: November 2008

The aim of this study was to investigate biochemical and antioxidant parameters in alloxan‐resistant (ALR) and alloxan‐susceptible (ALS) rats. Diabetes was induced in 60‐day‐old male Wistar rats by a single intraperitonial injection of alloxan (AL, 150 mg/kg). Ten days after induction, a group of rats showed a significant decrease in glycemia. This group was named alloxan‐resistant group. Susceptible rats showed a remarkable increase in the plasma lipid content, blood glucose and HbA1. Glycogen content in the liver decreased significantly in the ALS group (2.08 ± 0.41 mg%) compared with ALR group (4.22 ± 0.18). Aspartate aminotransferase and alanine aminotransferase activities were quantified in the plasma. Interestingly, ALR rats showed a decrease in both activities (42.1 ± 6.11 and 21.7 ± 5.54 U/mL) when compared with ALS rats (59.1 ± 6.55 and 58.1 ± 7.28 U/mL). The TBARS index was significantly increased in the ALS liver (0.38 ± 0.08 nm/mg protein) when compared with the ALR liver (0.18 ± 0.04). Superoxide dismutase and catalase activities in the ALR (230 ± 13 and 131 ± 15 U/mg protein) liver showed a marked increase when compared with the ALS liver (148 ± 13 and 68 ± 5 U/mg protein). The immunohistochemical and hematoxilin–eosin analysis also revealed that pancreatic islets of ALR rats display a different morphology amongst the groups. These results suggest an increased regenerative or recovery process in the ALR rat pancreatic islets and an increased hepatic antioxidant defenses in these group of alloxan‐resistant rats.
An insight on the neuropharmacological activity ofTelescopium telescopium– a mollusc from the Sunderban mangrove
Authors: Samanta S.K. , Manisenthil Kumar K.T. , Roy Amrita , Karmakar S. , Lahiri Shawon , Palit G. , Vedasiromoni J.R. , Sen T.
Published: November 2008

The present study was carried out to evaluate the biological properties of the tissue extract of a marine snailTelescopium telescopium, collected from the coastal regions of West Bengal India. On extensive pharmacological screening, it was found that the biological extract ofT. telescopium(TTE) produced significant central nervous system (CNS)‐depressant activity as observed from the reduced spontaneous motility, potentiation of pentobarbitone induced sleeping time, hypothermia and respiratory depression with transient apnoea. The extract significantly decreased both residual curiosity and also muscle coordination. The fraction, obtained following saturation with 60–80% ammonium sulphate (80S), was also found to demonstrate predominant CNS‐depressant activity. It was observed that both TTE and the 80S fraction significantly altered the brain noradrenaline and homovanillic acid levels without affecting the brain gamma amino butyric acid (GABA) concentration. Based on the present observations, it can be suggested that the CNS‐depressant effects produced by TTE and 80S could be attributable to modified catecholamine metabolism in the brain.
The Hill equation: a review of its capabilities in pharmacological modelling
Authors: Goutelle Sylvain , Maurin Michel , Rougier Florent , Barbaut Xavier , Bourguignon Laurent , Ducher Michel , Maire Pascal
Published: November 2008

The Hill equation was first introduced by A.V. Hill to describe the equilibrium relationship between oxygen tension and the saturation of haemoglobin. In pharmacology, the Hill equation has been extensively used to analyse quantitative drug–receptor relationships. Many pharmacokinetic–pharmacodynamic models have used the Hill equation to describe nonlinear drug dose–response relationships. Although the Hill equation is widely used, its many properties are not all well known. This article aims at reviewing the various properties of the Hill equation. The descriptive aspects of the Hill equation, in particular mathematical and graphical properties, are examined, and related to Hill’s original work. The mechanistic aspect of the Hill equation, involving a strong connection with the Guldberg and Waage law of mass action, is also described. Finally, a probabilistic view of the Hill equation is examined. Here, we provide some new calculation results, such as Fisher information and Shannon entropy, and we introduce multivariate probabilistic Hill equations. The main features and potential applications of this probabilistic approach are also discussed. Thus, within the same formalism, the Hill equation has many different properties which can be of great interest for those interested in mathematical modelling in pharmacology and biosciences.
Evaluation of chalcones – a flavonoid subclass, for, their anxiolytic effects in rats using elevated plus maze and open field behaviour tests
Authors: Jamal Huma , Ansari Wajid Hussain , Rizvi Shamim Jahan
Published: November 2008

The clinical applications of benzodiazepines as anxiolytics are limited because of their unwanted side effects. Therefore, the development of new pharmacological agents is well justified. Eight variably substituted chalcones were investigated for their effects on central nervous system if they have anxiolytic effects in rats. Anxiolytic effects of chalcones were also compared with standard anxiolytic drug (diazepam, DZP). Rats were injected intraperitoneally with chalcones, their derivatives and DZP for 3 days. Chalcones and their derivatives were injected at the dose of 25 mg/kg body weight and DZP was injected at the dose of 1 and 2 mg/kg body weight. Rats were then subjected to various anxiety paradigms including the open field behaviour and elevated plus maze tests. In addition, their effects on rota rod performance and grip strength were also examined. Variably substituted chalcones and DZP showed differential pattern of activities.
Can positron emission tomography facilitate paediatric drug development?
Authors: Zimmer Luc
Published: November 2008

Advances in paediatric clinical pharmacology are interdependent with a better understanding of the influence of growth on drug disposition and action. In this field, there is an increasing need for non‐invasive drug monitoring approaches. This paper aims to discuss the role of positron emission tomography in such practice. This molecular imaging technique enables the determination of the distribution of a drug radiolabelled with a positron‐emitting radionuclide. Able to directly assess both pharmacokinetic and pharmacodynamic events in humans, positron emission tomography provides a new perspective on paediatric drug research. Although placing this technique in a unique position to potentially contribute to the process of drug development and evaluation in paediatrics, several ethical and methodological aspects should be considered.
Muscle precursor cells isolated from aged rats exhibit an increased tumor necrosis factor‐α response
Authors: Lees Simon J. , Zwetsloot Kevin A. , Booth Frank W.
Published: November 2008

Improving muscle precursor cell (MPC, muscle‐specific stem cells) function during aging has been implicated as a key therapeutic target for improving age‐related skeletal muscle loss. MPC dysfunction during aging can be attributed to both the aging MPC population and the changing environment in skeletal muscle. Previous reports have identified elevated levels of tumor necrosis factor‐α (TNF‐α) in aging, both circulating and locally in skeletal muscle. The purpose of the present study was to determine if age‐related differences exist between TNF‐α‐induced nuclear factor‐kappa B (NF‐κB) activation and expression of apoptotic gene targets. MPCs isolated from 32‐month‐old animals exhibited an increased NF‐κB activation in response to 1, 5, and 20 ng mL−1 TNF‐α, compared to MPCs isolated from 3‐month‐old animals. No age differences were observed in the rapid canonical signaling events leading to NF‐κB activation or in the increase in mRNA levels for TNF receptor 1, TNF receptor 2, TNF receptor‐associated factor 2 (TRAF2), or Fas (CD95) observed after 2 h of TNF‐α stimulation. Interestingly, mRNA levels for TRAF2 and the cell death‐inducing receptor, Fas (CD95), were persistently upregulated in response to 24 h TNF‐α treatment in MPCs isolated from 32‐month‐old animals, compared to 3‐month‐old animals. Our data indicate that age‐related differences may exist in the regulatory mechanisms responsible for NF‐κB inactivation, which may have an effect on TNF‐α‐induced apoptotic signaling. These findings improve our understanding of the interaction between aged MPCs and the changing environment associated with age, which is critical for the development of potential clinical interventions aimed at improving MPC function with age.
A Review of Methods to Estimate Creep Damage in Low‐Alloy Steel Power Station Steam Pipes
Authors: Maharaj C. , Dear J. P. , Morris A.
Published: November 2008

Abstract:  For large complex structures, such as power stations, refineries and other processing plants, cost‐effective operation is essential. With power stations, failures of components without prior warning can have serious consequences for personnel on‐site and be extremely expensive in terms of both losses in generation revenue and repair costs. The ability to monitor and assess the evolution of damage is critical to maximise plant availability and to minimise the risk of failures that pose a threat to personnel safety. This paper relates to the methods used to estimate creep damage in service‐aged low‐alloy steel steam piping. Welds and the extrados of bends in steam pipes are a particular problem with regard to measuring for the onset and progression of creep failure. Existing techniques will be discussed with respect to traditional site‐based, sample extraction and assessment. Emerging strain‐monitoring techniques will also be described and evaluated that include point‐to‐point measurement and two‐dimensional mapping of creep strain across the weld zone and other creep‐susceptible components of power station steam piping.
Investigation of the Bulge Test Response of Molybdenum Thin Films at Room Temperature and at 100 °C
Authors: Walter M. E. , Schneider A. S. , Wübben T. , Richter G. , Arzt E.
Published: November 2008

Abstract:  It is well known that mechanical properties of materials are dependent on the volume of material that is deformed. This size effect has been investigated for metal nanostructures and thin films. However, to date there are no known studies of how confined geometries affect properties of BCC metals. The current investigation began with the aim of shedding new light on this open question. Because it allows for isothermal tensile tests of thin films in a temperature regime from cryogenic to elevated temperatures, the approach taken is that of bulge testing. Molybdenum was chosen as a starting material because of its insensitivity to oxidation at temperatures below 300 °C. After describing the coating procedure and the parameters associated with the coating process, the coating microstructure is presented. Qualitative results for investigation of the oxidation of Mo thin films are also presented. We then describe the method to obtain free‐standing thin films. Finally, the apparatus for performing bulge tests and several stress–strain curves is presented. Due to limitations with the measurement equipment, for the current round of experiments, it was not possible to test the Molybdenum films at temperatures high enough to induce a brittle‐to‐ductile transition.