bluuebunny/crossref_metadata_2025 huggingface dataset:
The neuropathology of kuru and variant Creutzfeldt–Jakob disease
Authors: McLean Catriona A
Published: October 2008

A comparison of the pathological profiles of two spongiform encephalopathies with a similar presumptive route of infection was performed. Archival kuru and recent variant Creutzfeldt–Jakob disease (vCJD) cases reveal distinct lesional differences, particularly with respect to prion protein, suggesting that the strain of agent is important in determining the phenotype. Genotype analysis of the polymorphism on codon 129 reveals (in conjunction with updated information from more kuru cases) that all three genotypes (VV, MV and MM (where M is methionine and V is valine)) are detected in kuru with some preference for MM homozygosity. The presence of valine does not therefore appear to determine peripheral selection of PrP
CJD
. vCJD remains restricted to date to MM homozygosity on codon 129. It remains to be determined whether this genotype is dictating a shorter incubation period.
Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease
Authors: Brandner Sebastian , Whitfield Jerome , Boone Ken , Puwa Anderson , O'Malley Catherine , Linehan Jacqueline M , Joiner Susan , Scaravilli Francesco , Calder Ian , P. Alpers Michael , Wadsworth Jonathan D.F , Collinge John
Published: October 2008

While the neuropathology of kuru is well defined, there are few data concerning the distribution of disease-related prion protein in peripheral tissues. Here we report the investigation of brain and peripheral tissues from a kuru patient who died in 2003. Neuropathological findings were compared with those seen in classical (sporadic and iatrogenic) Creutzfeldt–Jakob disease (CJD) and variant CJD (vCJD). The neuropathological findings of the kuru patient showed all the stereotypical changes that define kuru, with the occurrence of prominent PrP plaques throughout the brain. Lymphoreticular tissue showed no evidence of prion colonization, suggesting that the peripheral pathogenesis of kuru is similar to that seen in classical CJD rather than vCJD. These findings now strongly suggest that the characteristic peripheral pathogenesis of vCJD is determined by prion strain type alone rather than route of infection.
The impact of single substitutions on multiple sequence alignments
Authors: Klaere Steffen , Gesell Tanja , von Haeseler Arndt
Published: October 2008

We introduce another view of sequence evolution. Contrary to other approaches, we model the substitution process in two steps. First we assume (arbitrary) scaled branch lengths on a given phylogenetic tree. Second we allocate a Poisson distributed number of substitutions on the branches. The probability to place a mutation on a branch is proportional to its relative branch length. More importantly, the action of a single mutation on an alignment column is described by a doubly stochastic matrix, the so-called one-step mutation matrix. This matrix leads to analytical formulae for the posterior probability distribution of the number of substitutions for an alignment column.
Empirical evaluation of a prior for Bayesian phylogenetic inference
Authors: Yang Ziheng
Published: October 2008

The Bayesian method of phylogenetic inference often produces high posterior probabilities (PPs) for trees or clades, even when the trees are clearly incorrect. The problem appears to be mainly due to large sizes of molecular datasets and to the large-sample properties of Bayesian model selection and its sensitivity to the prior when several of the models under comparison are nearly equally correct (or nearly equally wrong) and are of the same dimension. A previous suggestion to alleviate the problem is to let the internal branch lengths in the tree become increasingly small in the prior with the increase in the data size so that the bifurcating trees are increasingly star-like. In particular, if the internal branch lengths are assigned the exponential prior, the prior meanμ0should approach zero faster thanbut more slowly than 1/n, wherenis the sequence length. This paper examines the usefulness of this data size-dependent prior using a dataset of the mitochondrial protein-coding genes from the baleen whales, with the prior mean fixed atμ0=0.1n−2/3. In this dataset, phylogeny reconstruction is sensitive to the assumed evolutionary model, species sampling and the type of data (DNA or protein sequences), but Bayesian inference using the default prior attaches high PPs for conflicting phylogenetic relationships. The data size-dependent prior alleviates the problem to some extent, giving weaker support for unstable relationships. This prior may be useful in reducing apparent conflicts in the results of Bayesian analysis or in making the method less sensitive to model violations.
Basing population genetic inferences and models of molecular evolution upon desired stationary distributions of DNA or protein sequences
Authors: Choi Sang Chul , Redelings Benjamin D , Thorne Jeffrey L
Published: October 2008

Models of molecular evolution tend to be overly simplistic caricatures of biology that are prone to assigning high probabilities to biologically implausible DNA or protein sequences. Here, we explore how to construct time-reversible evolutionary models that yield stationary distributions of sequences that match given target distributions. By adopting comparatively realistic target distributions, evolutionary models can be improved. Instead of focusing on estimating parameters, we concentrate on the population genetic implications of these models. Specifically, we obtain estimates of the product of effective population size and relative fitness difference of alleles. The approach is illustrated with two applications to protein-coding DNA. In the first, a codon-based evolutionary model yields a stationary distribution of sequences, which, when the sequences are translated, matches a variable-length Markov model trained on human proteins. In the second, we introduce an insertion–deletion model that describes selectively neutral evolutionary changes to DNA. We then show how to modify the neutral model so that its stationary distribution at the amino acid level can match a profile hidden Markov model, such as the one associated with the Pfam database.
The genetic code can cause systematic bias in simple phylogenetic models
Authors: Whelan Simon
Published: October 2008

Phylogenetic analysis depends on inferential methodology estimating accurately the degree of divergence between sequences. Inaccurate estimates can lead to misleading evolutionary inferences, including incorrect tree topology estimates and poor dating of historical species divergence. Protein coding sequences are ubiquitous in phylogenetic inference, but many of the standard methods commonly used to describe their evolution do not explicitly account for the dependencies between sites in a codon induced by the genetic code. This study evaluates the performance of several standard methods on datasets simulated under a simple substitution model, describing codon evolution under a range of different types of selective pressures. This approach also offers insights into the relative performance of different phylogenetic methods when there are dependencies acting between the sites in the data. Methods based on statistical models performed well when there was no or limited purifying selection in the simulated sequences (low degree of dependency between sites in a codon), although more biologically realistic models tended to outperform simpler models. Phylogenetic methods exhibited greater variability in performance for sequences simulated under strong purifying selection (high degree of the dependencies between sites in a codon). Simple models substantially underestimate the degree of divergence between sequences, and underestimation was more pronounced on the internal branches of the tree. This underestimation resulted in some statistical methods performing poorly and exhibiting evidence for systematic bias in tree inference. Amino acid-based and nucleotide models that contained generic descriptions of spatial and temporal heterogeneity, such as mixture and temporal hidden Markov models, coped notably better, producing more accurate estimates of evolutionary divergence and the tree topology.
Bayesian inference of fine-scale recombination rates using population genomic data
Authors: Wang Ying , Rannala Bruce
Published: October 2008

Recently, several statistical methods for estimating fine-scale recombination rates using population samples have been developed. However, currently available methods that can be applied to large-scale data are limited to approximated likelihoods. Here, we developed a full-likelihood Markov chain Monte Carlo method for estimating recombination rate under a Bayesian framework. Genealogies underlying a sampling of chromosomes are effectively modelled by using marginal individual single nucleotide polymorphism genealogies related through an ancestral recombination graph. The method is compared with two existing composite-likelihood methods using simulated data. Simulation studies show that our method performs well for different simulation scenarios. The method is applied to two human population genetic variation datasets that have been studied by sperm typing. Our results are consistent with the estimates from sperm crossover analysis.
Fast, accurate and simulation-free stochastic mapping
Authors: Minin Vladimir N , Suchard Marc A
Published: October 2008

Mapping evolutionary trajectories of discrete traits onto phylogenies receives considerable attention in evolutionary biology. Given the trait observations at the tips of a phylogenetic tree, researchers are often interested where on the tree the trait changes its state and whether some changes are preferential in certain parts of the tree. In a model-based phylogenetic framework, such questions translate into characterizing probabilistic properties of evolutionary trajectories. Current methods of assessing these properties rely on computationally expensive simulations. In this paper, we present an efficient, simulation-free algorithm for computing two important and ubiquitous evolutionary trajectory properties. The first is the mean number of trait changes, where changes can be divided into classes of interest (e.g. synonymous/non-synonymous mutations). The mean evolutionary reward, accrued proportionally to the time a trait occupies each of its states, is the second property. To illustrate the usefulness of our results, we first employ our simulation-free stochastic mapping to execute a posterior predictive test of correlation between two evolutionary traits. We conclude by mapping synonymous and non-synonymous mutations onto branches of an HIV intrahost phylogenetic tree and comparing selection pressure on terminal and internal tree branches.
Subclassification of non‐solid‐type papillary thyroid carcinoma identification of high‐risk group in common type
Authors: Bai Yanhua , Kakudo Kennichi , Li Yaqiong , Liu Zhiyan , Ozaki Takashi , Ito Yasuhiro , Kihara Minoru , Miyauchi Akira
Published: October 2008

Two hundred and sixty‐three cases of primary human papillary thyroid carcinoma (PTC) were analyzed. All cases met the following parameters: tumor size ≥ 10 mm, no distant metastasis at presentation, and no coexistence of other histological type. The histological features of the solid/trabecular component, encapsulation, tall/columnar cell component and loss of polarity/cohesiveness were utilized to subclassify the 263 cases of PTC into five groups: solid type (15.6%), encapsulated group (9.5%), tall/columnar cell group (7.2%), micropapillary/discohesive group (19.8%) and not‐otherwise‐specified group (47.9%). We focused on the latter four non‐solid groups and compared their prognosis with the solid type. The tall/columnar cell group showed the worst disease‐free survival rate (DFS) analyzed by the Kaplan–Meier method, followed by the micropapillary/discohesive group. The not‐otherwise‐specified group and encapsulated group showed a better DFS rate than the solid type. Cancer‐related death was noted in the tall/columnar cell group (21.1%) and micropapillary/discohesive group (3.8%), but not in the other groups. The four non‐solid histological groups were further categorized into two prognostic groups: high‐risk group (including tall/columnar cell group and micropapillary/discohesive group); and low‐risk group (including encapsulated group and not‐otherwise‐specified group). Their 10‐year disease‐free survival rates were 78.7% and 93.1%, respectively. In the present study, histological grouping was significantly correlated with prognosis in the multivariate analysis according to the Cox proportional hazards regression model in addition to clinical parameters of extrathyroid invasion and gross lymph node metastasis, which predicts the patient outcome in terms of tumor recurrence and cancer‐related death more precisely. (Cancer Sci 2008; 99: 1908–1915)
Novel centrosome protein, TCC52, is a cancer‐testis antigen
Authors: Li Sichen , Hu Xiaohua , Cui Shuang , He Dacheng
Published: October 2008

A novel centrosome protein, TCC52, was identified as a cancer‐testis (CT) antigen. The TCC52 gene was tissue‐restricted in normal tissues but highly expressed in lung cancer tissues and some cancer cell lines. Immunoglobulin G antibody specific to TCC52 was detected in serum samples from patients with prostate cancer (59.4%, 69/116), cholangiocarcinoma (17.6%, 6/34), laryngeal cancer (8%, 8/100) and lung cancer (5.6%, 4/71) in patients, rather than from healthy donors. Based on its restricted expression pattern and immunogenicity in some types of tumor, TCC52, as a novel CT antigen, would be a promising candidate for cancer immunotherapy. (Cancer Sci 2008; 99: 2274–2279)
Frequent alterations of hMLH1 and RBSP3/HYA22 at chromosomal 3p22.3 region in early and late‐onset breast carcinoma: clinical and prognostic significance
Authors: Sinha Satyabrata , Singh Ratnesh K. , Alam Neyaz , Roy Anup , Roychoudhury Susanta , Panda Chinmay Kumar
Published: October 2008

Young age can be an independent prognostic factor for adverse prognosis in women with breast carcinoma (BC). In younger women, BC exhibited more aggressive pathological features than older women, indicating differences in biology. Frequent alterations in chromosomal (chr.) 3p22.3 in different malignancies indicated the existence of multiple candidate tumor suppressor genes (TSG) in this region, yet its association with BC remains unclear. In an effort to understand the differences in molecular pathogenesis in two age groups of BC, detailed analysis of alterations at chr.3p22.3 region was carried out in 47 early onset (group‐A: ≤40 years) and 59 late‐onset (group‐A: >40 years) BC samples. Deletion mapping of the four candidate TSG, hMLH1, APRG1, ITGA9 and RBSP3/HYA22, located within 1 Mb of chr.3p22.3 showed high deletion in hMLH1 and RBSP3/HYA22 genes. Frequent methylation was also observed in these genes and significantly associated with their deletion. Quantitative messenger RNA (mRNA) expression and immunohistochemical analysis showed down‐regulation of these genes. Alterations (deletion/methylation) of hMLH1 were significantly associated with RBSP3/HYA22 in group‐A (P = 0.02). Significant poor survival in group‐A patients with alterations in hMLH1 and RBSP3/HYA22 and the same in group‐B patients with hMLH1 alterations indicated their importance as prognostic markers. Differential association of alterations of these genes with higher histological grades, more advanced stages and positive lymph node involvement were also seen. Thus, the present study suggests hMLH1 and RBSP3/HYA22 to be candidate TSG associated with development of both early and late‐onset BC undergoing frequent genetic and epigenetic alteration and having significant prognostic implications. (Cancer Sci 2008; 99: 1984–1991)
Study of oncogenic transformation in ex vivo expanded mesenchymal cells, from paediatric bone marrow
Authors: Choumerianou D. M. , Dimitriou H. , Perdikogianni C. , Martimianaki G. , Riminucci M. , Kalmanti M.
Published: October 2008

Abstract.  Objectives: Mesenchymal stromal cells (MSCs) have attracted considerable interest in both the scientific and clinical fields. In order to obtain a sufficient cell number for application, their in vitro expansion is necessary, but during this process their characteristics may be altered and cells may acquire oncogenic properties. We have investigated properties of MSC that may be related to oncogenesis, a critical parameter that has to be evaluated prior to MSC clinical use. Materials and methods: We studied the expression of p53, p16, RB, H‐RAS and human telomerase reverse transcriptase (hTERT) in MSCs from bone marrow of children diagnosed with idiopathic thrombocytopenic purpura (ITP) and autoimmune neutropenia. The same cells were seeded in soft agar to confirm their anchorage dependence and were karyotypically analysed. Finally, MSCs were subcutaneously transplanted into SCID mice and their ectopic osteogenic as well as tumorigenic potential was evaluated. Results: We have shown that MSCs derived from bone marrow of children with ITP and autoimmune neutropenia do not undergo transformation, the cells expressed normal levels of p53, p16, RB and H‐RAS. Expression of hTERT was undetectable, chromosome content remained stable, and their anchorage dependence was confirmed. In an in vivo model, when MSCs were subcutaneously transplanted into SCID mice, no tumorigenesis was observed. Conclusions: These findings suggest that MSCs from bone marrow of children do not have oncogenic properties and, therefore, represent validate candidates for applications in regenerative medicine.
Higher constitutive IL15Rα expression and lower IL-15 response threshold in coeliac disease patients
Authors: Bernardo D , Garrote J A , Allegretti Y , León A , Gómez E , Bermejo-Martin J F , Calvo C , Riestra S , Fernández-Salazar L , Blanco-Quirós A , Chirdo F , Arranz E
Published: October 2008

The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific. We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15Rα mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15Rα mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0·0334, on GCD P = 0·0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15Rα expression was only triggered in non-CD controls (P = 0·0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFNγ (P = 0·0313, P = 0·0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine.
Anomalous mandibular premolars: a mandibular first premolar with three roots and a mandibular second premolar with a C‐shaped canal system
Authors: Cleghorn B. M. , Christie W. H. , Dong C. C. S.
Published: October 2008

Aim  To describe unusual variations in the root morphology and root canal systems of mandibular first and second premolar teeth extracted for orthodontic reasons.

Summary  Normally mandibular first and second premolar teeth have single roots with single canals. A 15‐year‐old patient presented for orthodontic treatment and two mandibular premolar teeth were examined post‐extraction. The mandibular first premolar exhibited three distinct, separate roots and the mandibular second premolar exhibited a C‐shaped root canal system. The coronal morphology of each of the mandibular premolars revealed dimensions and anatomy within normal limits. The incidence of a three‐rooted mandibular first premolar is approximately 0.2%.

Key learning points • Thorough clinical and radiographic interpretation is important in recognizing anomalous root and root canal systems.

• The most common forms of root and canal systems and its aberrations must be understood to realize variations from normal do occur.

• Successful root canal treatment requires an accurate diagnosis of the root canal system using all available aids.

• Value of microcomputed tomography in the study of anatomy ex vivo and cone‐beam tomography in clinical endodontics of complex premolar cases is increasing.
Effect of remaining dentine structure and thermal‐mechanical aging on the fracture resistance of bovine roots with different post and core systems
Authors: Marchi G. M. , Mitsui F. H. O. , Cavalcanti A. N.
Published: October 2008

Aim  To evaluate the influence of remaining dentine thickness around post and core systems and the thermo‐mechanical stresses on fracture resistance of bovine roots.

Methodology  This study involved 288 bovine incisor roots with standardized dimensions. Roots were randomly distributed into 24 groups (n = 12) according to root conditions [intact, semi‐weakened, or weakened] and post and core systems [custom cast core, composite resin core, prefabricated metallic post, or prefabricated carbon fibre post], submitted or not to thermomechanical aging [5000 thermal cycles and 100 000 mechanical cycles at a 135‐degree angle to the long axis of the root]. Specimens were submitted to a tangential compressive load (135° angle) at a crosshead speed of 0.5 mm min−1 until failure. Fracture resistance data were analyzed using 3‐way anova and Tukey test: α = 5%.

Results  Roots restored with composite resin cores demonstrated no resistance to mechanical aging. No statistically significant difference was observed between aged and nonaged specimens involving all post‐systems. Roots restored with custom cast cores had the highest fracture strength, followed by prefabricated metallic posts and carbon fibre posts, regardless of root conditions and thermomechanical aging. The remaining dentine thickness affected significantly roots restored with custom cast cores; weakened roots had a lower fracture resistance.

Conclusions  Although custom cast cores had a higher fracture resistance when compared to the other techniques, the results were highly dependent on remaining dentine thickness. Prefabricated posts performed in a similar manner in intact, semi‐weakened and weakened roots reinforced with composite resin.
Insomnia and long sleep duration are risk factors for later work disability. The Hordaland Health Study
Authors: SIVERTSEN BØRGE , ØVERLAND SIMON , PALLESEN STÅLE , BJORVATN BJØRN , NORDHUS INGER HILDE , MÆLAND JOHN GUNNAR , MYKLETUN ARNSTEIN
Published: October 2008

Both insomnia and sleep duration have previously been linked with a range of adverse outcomes, but no studies have explored their relative effect on subsequent work disability. The aim of the present study was to investigate the contribution of insomnia versus sleep duration to later long‐term work disability. Using a historical cohort design with 4‐year follow‐up, data on insomnia, sleep duration and potential confounders were gathered from 6599 working persons (40–45 years). The outcome was award of disability pension, as registered in the National Insurance Administration. After controlling for baseline exposure to disability and sick leave, insomnia was a strong predictor of permanent work disability [odds ratio (OR) = 4.56], and this effect remained significant after controlling for sleep duration, as well as for other possible confounders (OR = 1.88). Short sleep duration was not significantly associated with subsequent work disability, while long sleep duration (>8.5 h) did predict work disability (OR = 2.96), also in the fully adjusted model (OR = 2.14).The present study demonstrates that both insomnia and long sleep duration are strong and independent risk factors for subsequent work disability.
Managing conflict between humans and wildlife: trends in licensed operations to resolve problems with badgers Meles meles in England
Authors: DELAHAY R. J. , DAVISON J. , POOLE D. W. , MATTHEWS A. J. , WILSON C. J. , HEYDON M. J. , ROPER T. J.
Published: October 2008

Successful wildlife management needs to be underpinned by frequent evaluation of the problems arising and the management techniques used to resolve them. The aims of this review were: (i) to investigate spatial and temporal patterns in the occurrence and characteristics of badger–human conflict in England; and (ii) to determine which factors influence the success of management actions. Licences are required before interfering with badgers or setts, so we carried out analyses of records of applications received by Defra and data from follow‐up monitoring of management actions.

The number of licence applications rose significantly during the recording period (1994–2004), with an increasing proportion coming from the east of England and from urban, as opposed to rural, areas. Damage problems caused by setts were the most frequent sources of conflict in both urban and rural areas. However, the majority of rural problems related to agricultural land, whereas buildings and gardens were most affected in urban areas. A higher proportion of problems involved outlier setts in urban areas compared with rural areas.

The use of one‐way gates to exclude badgers from part or all of a problem sett was the commonest management action proposed by Defra Wildlife Advisers, with total sett closure more common in urban, compared with rural, areas. Follow‐up monitoring revealed that the success of action varied in relation to the type of sett causing a problem, the type of management action undertaken and the land use (urban or rural) at the problem location, with total closure of an urban main sett being the least successful strategy. This review provides an assessment of current trends in conflict occurrence and will help in the development of management techniques.
The diverse CheC‐type phosphatases: chemotaxis and beyond
Authors: Muff Travis J. , Ordal George W.
Published: October 2008

A new class of protein phosphatases has emerged in the study of bacterial/archaeal chemotaxis, the CheC‐type phosphatases. These proteins are distinct and unrelated to the well‐known CheY‐P phosphatase CheZ, though they have convergently evolved to dephosphorylate the same target. The family contains a common consensus sequence D/S‐X3‐E‐X2‐N‐X22‐P that defines the phosphatase active site, of which there are often two per protein. Three distinct subgroups make up the family: CheC, FliY and CheX. Further, the CheC subgroup can be divided into three classes. Bacillus subtilis CheC typifies the first class and might function as a regulator of CheD. Class II CheCs likely function as phosphatases in systems other than chemotaxis. Class III CheCs are found in the archaeal class Halobacteria and might function as class I CheCs. FliY is the main phosphatase in the B. subtilis chemotaxis system. CheX is quite divergent from the rest of the family, forms a dimer and some may function outside chemotaxis. A model for the evolution of the family is discussed.
The ribosomal stalk is required for ribosome binding, depurination of the rRNA and cytotoxicity of ricin A chain in Saccharomyces cerevisiae
Authors: Chiou Jia‐Chi , Li Xiao‐Ping , Remacha Miguel , Ballesta Juan P. G. , Tumer Nilgun E.
Published: October 2008

Ribosome inactivating proteins (RIPs) like ricin, pokeweed antiviral protein (PAP) and Shiga‐like toxins 1 and 2 (Stx1 and Stx2) share the same substrate, the α‐sarcin/ricin loop, but differ in their specificities towards prokaryotic and eukaryotic ribosomes. Ricin depurinates the eukaryotic ribosomes more efficiently than the prokaryotic ribosomes, while PAP can depurinate both types of ribosomes. Accumulating evidence suggests that different docking sites on the ribosome might be used by different RIPs, providing a basis for understanding the mechanism underlying their kingdom specificity. Our previous results demonstrated that PAP binds to the ribosomal protein L3 to depurinate the α‐sarcin/ricin loop and binding of PAP to L3 was critical for its cytotoxicity. Here, we used surface plasmon resonance to demonstrate that ricin toxin A chain (RTA) binds to the P1 and P2 proteins of the ribosomal stalk in Saccharomyces cerevisiae. Ribosomes from the P protein mutants were depurinated less than the wild‐type ribosomes when treated with RTA in vitro. Ribosome depurination was reduced when RTA was expressed in the ΔP1 and ΔP2 mutants in vivo and these mutants were more resistant to the cytotoxicity of RTA than the wild‐type cells. We further show that while RTA, Stx1 and Stx2 have similar requirements for ribosome depurination, PAP has different requirements, providing evidence that the interaction of RIPs with different ribosomal proteins is responsible for their ribosome specificity.
A new function of Trypanosoma brucei mitochondrial topoisomerase II is to maintain kinetoplast DNA network topology
Authors: Lindsay Megan E. , Gluenz Eva , Gull Keith , Englund Paul T.
Published: October 2008

The mitochondrial genome of Trypanosoma brucei, called kinetoplast DNA, is a network of topologically interlocked DNA rings including several thousand minicircles and a few dozen maxicircles. Kinetoplast DNA synthesis involves release of minicircles from the network, replication of the free minicircles and reattachment of the progeny. Here we report a new function of the mitochondrial topoisomerase II (TbTOP2mt). Although traditionally thought to reattach minicircle progeny to the network, here we show that it also mends holes in the network created by minicircle release. Network holes are not observed in wild‐type cells, implying that this mending reaction is normally efficient. However, RNAi of TbTOP2mt causes holes to persist and enlarge, leading to network fragmentation. Remarkably, these network fragments remain associated within the mitochondrion, and many appear to be appropriately packed at the local level, even as the overall kinetoplast organization is dramatically altered. The deficiency in mending holes is temporally the earliest observable defect in the complex TbTOP2mt RNAi phenotype.
Electrochemical detection of neurotransmitters in the gut wall
Authors: Vanden Berghe P.
Published: October 2008

Abstract Cells interact with each other by releasing signalling molecules, which can activate or inactivate target cells. In order to understand how coordination results from this communication, accurate measurements of these signalling molecules are prerequisite. Several different techniques exist to monitor and quantify these compounds, including enzymatic and histochemical assays, electrophysiological and optical recordings. However, there has been little use of electrochemical recordings in gastroenterological research, although these are very fast and sensitive. Electrochemical techniques rely on the simple fact that electroactive molecules can be oxidized at a given potential. The currents, elicited by the oxidation, are directly proportional to the concentration of the compound. In the current issue ofNeurogastroenterology and Motility, electrochemical detection was successfully applied to measure nitric oxide (NO) from intestinal preparations. Although there are some important specificity, timing and spatial aspects to consider, this direct NO‐probing technique is definitely a great asset to the field of gastrointestinal research and advances our understanding of NO signalling in the intestinal wall.
The Vallo di Diano and Auletta extensional basins in the southern Apennines (Italy): a simple model for a complex setting
Authors: Amicucci Laura , Barchi Massimiliano R. , Montone Paola , Rubiliani Nicola
Published: October 2008

The aim of this paper was to provide a significant case‐history concerning the evolution of a segmented system of extensional faults and related basins, investigated by a set of seismic reflection profiles. We investigated two kinematically linked semi‐grabens, developed at the hangingwall of two opposite‐dipping normal faults: the Vallo di Diano and Auletta basins, located in the southern Apennines, one of the most seismically active regions of the Italian peninsula. Our interpretation suggests that the Pliocene–Quaternary tectonic history consists of a single extensional phase, where the major NW–SE trending normal faults, generating the basins, and the strike‐slip and transtensional faults connecting adjacent normal fault segments, simultaneously act, being part of the same extensional system. We also conclude that major normal faults, bordering the basins, should be considered as potential seismogenic sources in the seismic hazard evaluation.
Plate tectonics, flood basalts and the evolution of Earth’s oceans
Authors: Korenaga Jun
Published: October 2008

The chemical composition of the bulk silicate Earth (BSE) indicates that the present‐day thermal budget of Earth is likely to be characterized by a significant excess of surface heat loss over internal heat generation, indicating an important role of secular cooling in Earth’s history. When combined with petrological constraints on the degree of secular cooling, this thermal budget places a tight constraint on permissible heat‐flow scaling for mantle convection, along with implications for the operation of plate tectonics on Earth, the history of mantle plumes and flood basalt magmatism, and the origin and evolution of Earth’s oceans. In the presence of plate tectonics, hotter mantle may have convected more slowly because it generates thicker dehydrated lithosphere, which could slow down subduction. The intervals of globally synchronous orogenies are consistent with the predicted variation of plate velocity for the last 3.6 Gyr. Hotter mantle also produces thicker, buoyant basaltic crust, and the subductability of oceanic lithosphere is a critical factor regarding the emergence of plate tectonics before the Proterozoic. Moreover, sluggish convection in the past is equivalent to reduced secular cooling, thus suggesting a more minor role of mantle plumes in the early Earth. Finally, deeper ocean basins are possible with slower plate motion in the past, and Earth’s oceans in the Archean is suggested to have had about twice as much water as today, and the mantle may have started as dry and have been gradually hydrated by subduction. The global water cycle may thus be dominated by regassing, rather than degassing, pointing towards the impact origin of Earth’s oceans, which is shown to be supported by the revised composition of the BSE.
How much residual plasma may cause TRALI?
Authors: Win N. , Chapman C. E. , Bowles K. M. , Green A. , Bradley S. , Edmondson D. , Wallis J. P.
Published: October 2008

summary Although passive infusion of plasma‐rich components containing white blood cell (WBC) antibodies are responsible for majority of the reported transfusion‐related acute lung injury (TRALI) cases, the minimum volume of residual plasma, which might trigger TRALI, is not known. We report three cases of TRALI where the implicated donor component contained between 10 and 20 mL of residual plasma. Two cases were related to transfusion of red blood cells prepared in optimal additive solution, and the other was related to transfusion of pooled buffy coat platelets. In the latter case, WBC antibodies that matched the patient’s human leucocyte antigen (HLA) antigens were only found in one buffy coat donor (female) who contributed a buffy coat for pooled platelets preparation. Plasma prepared from pooling platelets was collected from a male donor. Laboratory investigation confirmed that in all three cases, the donors’ serum contained three to four different HLA class 1‐specific and class 11‐specific antibodies that matched with the patient’s HLA type. Our cases suggest that the residual plasma volume as small as 10–20 mL containing donor derived WBC antibodies may cause TRALI. The risk of TRALI remains, despite providing pooled platelets suspended in male donor plasma. The significance of multiple HLA antigen/antibody matching between donor and recipient in immune TRALI warrants further study.
Paroxysmal nocturnal haemoglobinuria presenting as cerebral venous sinus thrombosis
Authors: Misra U. K. , Kalita J. , Bansal V. , Nair P. P.
Published: October 2008

summary Paroxysmal nocturnal haemoglobinuria (PNH) is associated with anaemia, intravascular haemolysis and venous thrombosis. Cerebral venous sinus thrombosis (CVST) is a late but serious complication of PNH. We for the first time report a young man who presented with CVST and was diagnosed to have PNH after 11 months. We highlight the reasons for delay in the diagnosis and discuss the special issues in the management.
Association Between Leptin, LH and its Receptor and Luteinization and Progesterone Accumulation (P4) in Bovine Granulosa Cell In Vitro
Authors: Montaño E , Olivera M , Ruiz‐Cortés ZT
Published: October 2008

Contents

A full understanding of the cellular events that occur during in vitro luteinization of bovine granulosa cells, stimulated by LH and by leptin, is a complex goal that has not been completely achieved. The aim of this work was to study the effects of leptin, LH and leptin + LH on progesterone accumulation (P4) and on the expression of LH receptors (LHR) in bovine granulosa cells in culture. The results confirm that this in vitro model is representative of functional and morphological luteinization/differentiation. The pattern of expression of LHR with time of incubation was an important marker of in vitro luteinization, with 50–90% of cells expressing LHR by 96 h in culture. Cytoplasmic lipidic droplets were highly abundant in granulosa cells, suggesting a sufficient source of precursors for steroid hormone synthesis: P4 accumulation ranged between 40 and 550 ng/ml. In addition, a positive correlation (r = 0.58, p < 0.05) between the expression of LHR and accumulation of P4 throughout the time of incubation was observed. The expression of LHR was inhibited by LH and leptin + LH treatment. In conclusion, we found an inverse modulation between the expression of LHR and the concentration of LH, and the expression of LHR could be regulated by P4 produced by the luteinized granulosa cells. These findings are contributing to elucidate further the panoply of interactions during the differentiation of granulosa cells into luteal cells in vitro.
Visual function and performance with blue‐light blocking filters in age‐related macular degeneration
Authors: Kiser Ava K , Deschler Emily K , Dagnelie Gislin
Published: October 2008

Abstract

Purpose:  Some dispute has occurred over the use of blue‐light‐attenuating intraocular lenses in age‐related macular degeneration (AMD), as they may reduce scotopic vision. This study aimed to determine if a blue blocking filter would affect performance during eye–hand coordination and mobility tasks in scotopic illumination, psychophysically measured scotopic sensitivity or colour discrimination in AMD patients.

Methods:  Scotopic measures performed with and without a blue‐attenuating filter included a mobility obstacle course, manipulation of cylindrical blocks and a psychophysical dark‐adapted full‐field flash test. A navy and blue sock colour sorting task evaluated photopic colour discrimination. Subjects were 22 bilateral pseudophakes with early AMD and visual acuity >6/24.

Results:  On average with the filter, there was a 13% increase in time during the block test. The differences in time and number of bumps with versus without the filter were not significant for the mobility course. Performance with and without the filter was well correlated for the blocks (r = 0.70), flash test (r = 0.83) and mobility (r = 0.66), and the regression slopes were not significantly different from unity. 77% of subjects misidentified at least one navy sock as black with the filter compared with 9% without, with a significant increase in such misidentifications with the filter.

Conclusions:  The difference in scotopic visual function or performance with versus without a blue‐blocking filter most likely does not produce a clinically significant effect or risk; however, detection of navy colour may be impaired.
Retinal arterial abnormalities correlate with brain white matter lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy
Authors: Liu Yang , Wu Yuan , Xie Sheng , Luan Xing‐hua , Yuan Yun
Published: October 2008

Abstract

Purpose:  The aim of this study is to determine the relationship between retinal abnormalities and brain white matter hyper‐intensities (WMH) in symptomatic patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL).

Methods:  Fifteen patients with CADASIL and fifteen age‐matched healthy control individuals were enrolled in this study. Ophthalmological examinations were performed on all subjects and all patients with CADASIL underwent cerebral MRI scanning. Retinal artery abnormalities were graded according to the Keith‐Wagener‐Barker hypertensive retinopathy classification. WMH were classified as punctuate (Grade 1), nodular or early confluent (Grade 2) and diffusly confluent (Grade 3). Partial correlation was used to assess the relationship between retinal abnormalities and WMH, controlling for age.

Results:  Retinal arteriole narrowing existed in 15 cases and 2 controls, with Grade 2 and Grade 3 being the most common grading of retinal artery narrowing in patients with CADASIL. All patients had WMH on MRI, rated as Grade 1 in one patient, Grade 2 in five patients and Grade 3 in nine patients. The correlation coefficient of retinal arteriole narrowing and WMH was 0.546 (P < 0.05).

Conclusion:  Retinal arteriole narrowing may be associated with the severity of the cerebral lesions in CADASIL.
The quality of reporting of diagnostic accuracy studies in diabetic retinopathy screening: a systematic review
Authors: Zafar Atif , Khan Ghulam Ishaq , Siddiqui MA Rehman
Published: October 2008

Abstract

Purpose:  Diabetic retinopathy (DR) is a common cause of blindness among the working age group in the developed world. To identify potentially treatable DR, systematic screening is recommended. The aim of this study was to evaluate the quality of reporting of diagnostic accuracy studies in DR screening.

Methods:  We conducted a systematic literature survey in which a highly sensitive MEDLINE search was performed. The aim was to identify reports of diagnostic accuracy for DR screening published during 1995–2006. Two reviewers appraised all selected papers independently. The Standards for Reporting of Diagnostic Accuracy (STARD) checklist was used to evaluate the quality of reporting of each publication. For every manuscript, each item was scored as completely reported (score = 2), partly reported (score = 1) or not reported (score = 0). We calculated the total number of reported STARD items per article, summary scores for each STARD item and the average number of reported STARD items per year.

Results:  A total of 5887 citations were identified from Medline search. Seventy‐six fulfilled the criteria for inclusion. The mean score ± SD of articles included in our study was 19.8 ± 6.5 out of a maximum of 50. The mean number ± SD of fully reported items among included studies was 8 ± 3.3. Only 9 (11.8%) manuscripts completely reported at least 50% of the STARD items. Descriptions of key aspects of the methodology were frequently missing. Only 8% (6/76) of the manuscripts had a flow chart describing flow of participants within a study.

Conclusion:  The quality of reporting of diagnostic‐accuracy studies for DR screening is suboptimal. Adherence to STARD guidelines may improve the quality of reporting of DR screening studies.
Ocular response analyser to assess hysteresis and corneal resistance factor in low tension, open angle glaucoma and ocular hypertension
Authors: Shah Sunil , Laiquzzaman Mohammad , Mantry Sanjay , Cunliffe Ian
Published: October 2008

Abstract

Purpose: The aim of this study is to compare the hysteresis and corneal resistance factor (CRF) in normal tension glaucoma (NTG), primary open angle glaucoma (POAG) and ocular hypertension (OHT) eyes measured by the ocular response analyser (ORA).

Methods: This is a prospective, cross‐sectional and comparative clinical trial. The setting was a teaching hospital in Birmingham, England. Patients: 216 eyes with POAG, 68 eyes with NTG and 199 eyes with OHT. Observational procedures: Goldmann applanation tonometry and intraocular pressure (IOP), hysteresis and CRF measured by ORA and central corneal thickness (CCT) by ultrasonic pachymetery. The main outcome measures were IOP, CCT, hysteresis and CRF.

Results: The hysteresis in NTG, POAG and OHT eyes was 9.0 ± 1.9, 9.9 ± 2.1 and 10.2 ± 2.0 mmHg; CRF was 9.1 ± 2.2, 10.6 ± 2.0 and 12.0 ± 2.0 mmHg; IOP by Goldmann applanation tonometry and ORA was 14.7 ± 2.8 and 15.3 ± 4.2 mmHg, 16.7 ± 4.0 and 16.9 ± 4.6 mmHg and 20.5 ± 4.1 and 20.0 ± 4.5 mmHg; CCT was 526.5 ± 42.2, 537.0 ± 36.0 and 563.4 ± 35.9 µm, respectively. The difference for CRF, IOP and CCT for NTG, POAG and OHT eyes was statistically significant.

Conclusion: Hysteresis and CRF were highest in OHT eyes. These factors may prove to be useful measurements of ocular rigidity and may help to understand role of the corneal rigidity in monitoring the progress of conditions such as NTG, POAG and OHT.
Distinct subsets of nucleus accumbens neurons encode operant responding for ethanol versus water
Authors: Robinson Donita L. , Carelli Regina M.
Published: October 2008

Subsets of nucleus accumbens (NAc) neurons process information about operant responses for drugs as well as natural rewards (food and water) by excitations and inhibitions in firing rate time‐locked to the operant response. The degree to which ensembles of neurons exhibit similar firing patterns when encoding cues and operant responses across different reinforcer conditions will provide critical information regarding the functional organization of this nucleus. The present experiment evaluated the relative contribution of subsets of accumbens neurons that encode distinct features of lever press responding for ethanol vs. water. Electrophysiological recordings (n = 153 neurons) were made in the accumbens of rats trained on concurrent reinforcement schedules for ethanol and water throughout a self‐administration session. During operant responding, 52% of neurons exhibited patterned discharges characterized by significant increases or decreases in firing rate of ± 1 s relative to lever presses for ethanol and/or water. Of these phasic cells, 85% discriminated between presses for ethanol and water (i.e. exhibited firing patterns unique to one reinforcer type), while 15% exhibited identical firing patterns relative to lever presses for both reinforcers. Notably, the data revealed that both high ethanol preference and spatially distinct lever positions contributed to the reinforcer specificity. Together, these data demonstrate that subsets of NAc neurons encode conditioned and instrumental aspects of ethanol vs. water reinforcement in well‐trained rats, and that reinforcer preference and spatial cues are important components of this differential information processing.