bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Mitochondrial Oxidative Phosphorylation in the Liver Is Associated With Obesity and Insulin Resistance
Authors: Buchner David A. , Yazbek Soha N. , Solinas Paola , Burrage Lindsay C. , Morgan Michael G. , Hoppel Charles L. , Nadeau Joseph H.
Published: September 2010

Obesity is the result of excess energy intake relative to expenditure, however little is known about why some individuals are more prone to weight gain than others. Inbred strains of mice also vary in their susceptibility to obesity and therefore represent a valuable model to study the genetics and physiology of weight gain and its co‐morbidities such as type 2 diabetes. C57BL/6J mice are susceptible to obesity and insulin resistance when fed an obesogenic diet, whereas A/J mice are resistant despite increased caloric intake. Analysis of B6‐ and A/J‐derived chromosome substitution strains and congenic strains revealed a complex genetic and physiological basis for this phenotype. To improve our understanding of the molecular mechanisms underlying susceptibility to metabolic disease we analyzed global gene expression patterns in 6C1 and 6C2 congenic strains. 6C1 is susceptible whereas 6C2 is resistant to diet‐induced obesity. In addition, we demonstrate that 6C1 is glucose intolerant and insulin resistant relative to 6C2. Pathway analysis of global gene expression patterns in muscle, adipose, and liver identified expression level differences between 6C1 and 6C2 in pathways related to basal transcription factors, endocytosis, and mitochondrial oxidative phosphorylation (OxPhos). The OxPhos expression differences were subtle but evident in each complex of the electron transport chain and were associated with a marked increase in mitochondrial oxidative capacity in the livers of the obese strain 6C1 relative to the obesity‐resistant strain 6C2. These data suggests the importance of hepatic mitochondrial function in the development of obesity and insulin resistance.
Lifestyle Intervention Leading to Moderate Weight Loss Normalizes Postprandial Triacylglycerolemia Despite Persisting Obesity
Authors: Maraki Maria I. , Aggelopoulou Niki , Christodoulou Nektarios , Anastasiou Costas A. , Toutouza Marina , Panagiotakos Demosthenes B. , Kavouras Stavros A. , Magkos Faidon , Sidossis Labros S.
Published: September 2010

Obesity is associated with impaired postprandial triacylglycerolemia, an independent risk factor for cardiovascular disease. Given that obesity is hard to treat, efforts should focus on treating its comorbidities. We aimed to investigate whether moderate weight loss normalizes postprandial triacylglycerol (TAG) concentrations, in the absence of the acute effects of negative energy balance. For this purpose, postprandial lipemia was investigated in eight obese but otherwise healthy, sedentary men (age: 41.3 ± 4.1 years, BMI: 36.5 ± 1.6 kg·m−2), once before and again after a 10% weight loss followed by ≥4 weeks of weight maintenance, and was compared with that of eight age‐matched healthy lean men (BMI: 24.7 ± 0.6 kg·m−2). Dietary intervention consisted of reduced carbohydrate and saturated fat intake and increased monounsaturated fat intake. Obese volunteers were advised to increase physical activity using pedometers to record daily activity. Postprandial triacylglycerolemia after weight loss was reduced by 27–46% (P < 0.05), and became similar to that of lean men despite persisting obesity (BMI after weight loss: 32.9 ± 1.5 kg·m−2). Reduction in postprandial TAG responses was inversely correlated with the decrease in postprandial insulin sensitivity index (ISI) after weight loss (r = −0.714, P = 0.047). We conclude that moderate weight loss induced by a low‐carbohydrate and saturated fat diet and a slight increase in daily physical activity normalizes postprandial triacylglycerolemia in obese men, independently of acute diet‐induced negative energy balance, and possibly through enhancement of insulin action.
A Common Haplotype in NAPEPLD Is Associated With Severe Obesity in a Norwegian Population‐Based Cohort (the HUNT Study)
Authors: Wangensteen Teresia , Akselsen Hanne , Holmen Jostein , Undlien Dag , Retterstøl Lars
Published: September 2010

Obesity has a strong genetic etiology involving numerous identified metabolic pathways and others not yet examined. We investigated the association between severe obesity and genetic variation in selected candidate genes, including three drug‐related genes: cannabinoid receptor 1 (CNR1), N‐acyl phosphatidylethanolamine phospholipase D (NAPEPLD), and gastric lipase (LIPF); and three genes related to inflammation: nicotinamide phosphoribosyltransferase, six‐transmembrane epithelial antigen of the prostate 4 (STEAP4) and interleukin 18 (IL‐18). Subjects were 1,632 individuals with severe obesity (BMI ≥35 kg/m2) and 3,379 controls (BMI 20–24.9 kg/m2) that took part in a Norwegian population based cohort study. Tagging single‐nucleotide polymorphisms (SNPs) of the coding region of these genes were analyzed. SNP‐haplotypes for each gene were constructed in order to analyze allelic, genotypic, and haplotypic association to obesity. A single SNPs rs17605251 in NAPEPLD was nominally associated with BMI ≥35 kg/m2 (P = 0.035). A common haplotype in NAPEPLD was associated with BMI ≥35 kg/m2, after correction for multiple testing. The allele frequency was 56.8% in cases and 60.3% in controls, giving an odds ratio (OR) of 0.87 (95% confidence interval (CI) 0.79, 0.95; P = 0.0016). Homozygosity for this haplotype was protective against obesity (OR 0.79 (CI 0.70–0.91); P = 0.00059). The SNP rs7913071 in LIPF was associated with obesity, but the association lost statistical significance after correction for multiple testing. The CNR1, IL‐18, STEAP4, and nicotinamide phosphoribosyltransferase genes were not associated with obesity. In conclusion a common haplotype in NAPEPLD, an enzyme involved in endocannabinoid synthesis, was protective against obesity.
Engineered hydrogen-bonded polymer multilayers: from assembly to biomedical applications
Authors: Such Georgina K. , Johnston Angus P. R. , Caruso Frank
Published: September 2010

In thistutorial review, developments in hydrogen-bonded LbL materials are discussed, with an emphasis on loading and release of cargo for biomedical applications.
Caloric restriction increases free radicals and inducible nitric oxide synthase expression in mice infected withSalmonellaTyphimurium
Authors: Trujillo-Ferrara José , Campos-Rodríguez Rafael , Lara-Padilla Eleazar , Ramírez-Rosales Daniel , Correa Basurto José , Miliar Garcia Angel , Reyna Garfias Humberto , Zamorano Ulloa Rafael , Rosales-Hernández Martha C.
Published: September 2010

It is well known that CR (caloric restriction) reduces oxidative damage to proteins, lipids and DNA, although the underlying mechanism is unclear. However, information concerning the effect of CR on the host response to infection is sparse. In this study, 6-month-old mice that were fed AL (ad libitum) or with a CR diet were infected with Salmonella serovar Typhimurium. EPR (electron paramagnetic resonance; also known as ESR (electron spin resonance)) was used to identify FRs (free radicals). These results were subsequently correlated with SOD (superoxide dismutase) catalytic activity, iNOS [inducible NOS (nitric oxide synthase) or NOSII] expression and NO (nitric oxide) content. EPR analysis of liver samples demonstrated that there was a higher quantity of FRs and iron–nitrosyl complex in infected mice provided with a CR diet as compared with those on an AL diet, indicating that CR was beneficial by increasing the host response to Salmonella Typhimurium. Furthermore, in infected mice on the CR diet, NOSII expression was higher, NO content was greater and spleen colonization was lower, compared with mice on the AL diet. No changes in SOD activity were detected, indicating that the NO produced participated more in the formation of iron–nitrosyl complexes than peroxynitrite. These results suggest that CR exerts a protective effect against Salmonella Typhimurium infection by increasing NO production.
A common polymorphism in theABCB11gene is associated with advanced fibrosis in hepatitis C but not in non-alcoholic fatty liver disease
Authors: Iwata Rika , Baur Katharina , Stieger Bruno , Mertens Joachim C. , Daly Ann K. , Frei Pascal , Braun Julia , Vergopoulos Athanasios , Stickel Felix , Sabrane Karim , Martin Ina V. , Schmitt Johannes , Goetze Oliver , Day Chris P. , Müllhaupt Beat , Geier Andreas ,   the Swiss Hepatitis C Cohort Study Group
Published: September 2010

Chronic HCV (hepatitis C virus)-associated cirrhosis represents a major indication for liver transplantation. Bile acids contribute to hepatic stellate cell activation as a key event in fibrogenesis. The aim of the present study was to investigate the role of bile acids and polymorphisms in bile acid level-regulating genes on fibrosis progression. A total of 206 subjects with chronic HCV infection were included for ABCB11 (ATP-binding cassette, subfamily B, member II) 1331T>C and NR1H4 (nuclear receptor) −1G>T genotyping, 178 of which were analysed for fibrosis stage. Exclusion criteria were HBV (hepatitis B virus) or HIV coinfection, alcohol >40 g/day and morbid obesity. A total of 358 patients with NAFLD (non-alcoholic fatty liver disease) were genotyped for comparison with a non-viral liver disease. Caucasian individuals (n = 110), undergoing liver resection for focal hepatic metastasis, served as controls. The ABCB11 1331C allele was significantly overrepresented in HCV patients compared with controls {allelic frequency 62.9%; OR (odds ratio), 1.41 [95% CI (confidence interval), 1.012–1.965]}. Median plasma bile acid levels were not significantly increased in the CC compared with TT genotype [7.2 (1–110) μmol/l compared with 3.5 (1–61) μmol/l; values are medians (range). A significant association between the presence of cirrhosis and ABCB11 genotype (CC compared with CT or TT, P=0.047) was observed in the χ2 test and independent of other risk factors of age, gender, body mass index and disease duration in multivariate analysis (P = 0.010). No such association could be observed in fatty liver patients with regard to advanced fibrosis (F≥2). The common ABCB11 1331CC genotype, which is present in 40% of HCV patients and renders the carrier susceptible to increased bile acid levels, is associated with cirrhosis.
Airway fire due to diathermy during tracheostomy in an intensive care patient
Authors: Rogers S. A. , Mills K. G. , Tufail Z.
Published: September 2010

We describe a case of airway fire in an 83‐year‐old, critically ill patient. The fire occurred during a surgical tracheostomy under general anaesthesia, following ignition of the tracheal tube by diathermy. After debridement of the burnt tissue and treatment with intravenous antibiotics and glucocorticoids, the patient's respiratory function worsened initially. The patient eventually recovered without long‐term sequelae and was discharged from the intensive care unit. The circumstances of this and other similar incidents are reviewed, as are the suggested methods for preventing this frightening occurrence.
Wood Protection Properties of Quaternary Ammonium Arylspiroborate Esters Derived from Naphthalene 2,3-Diol, 2,2'-Biphenol and 3-Hydroxy-2-naphthoic Acid
Authors: Carr Jenny M. , Duggan Peter J. , Humphrey David G. , Platts James A. , Tyndall Edward M.
Published: September 2010

In continuation of a program aimed at developing a boron-based, high performing and environmentally benign wood preservative suitable for outdoor use, three lipophilic tetra-n-butylammonium spiroborates, tetra-n-butylammonium bis[naphthalene-2,3-diolato(2-)-O,O′]borate 4, tetra-n-butylammonium bis[2,2′-biphenolato(2-)-O,O′]borate 5 and tetra-n-butylammonium bis[3-hydroxy-2-naphthoato(2-)-O,O′]borate 6 were prepared and tested. The higher molecular weight and lipophilicity of these borates compared with related borates previously examined correlates, in the case of 5 and 6, with significantly enhanced leach resistance while termiticidal activity has been maintained. The racemic spiroborate derived from 2,2′-biphenol 5, in particular, appears to be close to an optimum balance between ease of synthesis, solubility, hydrolytic stability and termiticidal activity.
Biodegradable PEG Hydrogels Cross-linkedUsing Biotin-Avidin Interactions
Authors: Liu Yingkai , Liu Jingquan , Xu Jiangtao , Feng Shengyu , Davis Thomas P.
Published: September 2010

Poly(ethylene glycol) (PEG) hydrogels are water-swellable, non-toxic, non-immunogenic, and biocompatible. In this paper, we describe the generation of biodegradable PEG hydrogels by cross-linking biotinylated PEG oligomers containing intrinsic disulfide bonds via biotin-avidin interactions. The biotinylated PEG oligomers were synthesized by the condensation reaction between PEG and 3,3′-dithiodipropionic acid, followed by the reaction with biotin. This methodology obviates the need for potentially toxic chemical cross-linking agents that are usually used in the common preparation of hydrogels. Therefore it may be particularly useful in biomedical or pharmaceutical applications.
Liver iron status and associated haematological parameters in relation to fetal growth and pregnancy outcome in rapidly growing adolescent sheep carrying a singleton lamb derived by embryo transfer
Authors: Luther Justin , Aitken Raymond , Milne John , McArdle Harry , Gambling Lorraine , Reynolds Lawrence , Redmer Dale , Wallace Jacqueline
Published: September 2010

Maternal and fetal liver iron concentrations and associated haematology parameters were determined in an adolescent sheep paradigm characterised by rapid maternal growth, premature delivery and feto–placental growth restriction. Singleton-bearing dams were offered a control or high dietary intake to induce normal or growth-restricted pregnancies, respectively. Pregnancies were terminated on Day 90 or 130 of gestation or progressed to term. Relative blood volume increased (P < 0.05) and liver iron concentration decreased (P < 0.003) from mid to late gestation in control, but not in high-intake dams. At 90 and 130 days gestation, liver iron concentrations were reduced (P < 0.001) in high-intake dams but fetal liver iron was independent of dam nutrition. High intakes leading to poor pregnancy outcome at term were characterised by increased maternal haematocrit, haemoglobin, total plasma protein, albumin (all P < 0.001) and serum iron (P < 0.05), and by reduced oestradiol 17β (P < 0.001) at Day 130. Thus, high dietary intakes that promote rapid maternal growth and adiposity are associated with early depletion of maternal liver iron stores and a relative failure of normal blood volume expansion, which may, in turn, underlie the reduction in uteroplacental blood flows and fetal nutrient delivery previously established for this paradigm.
Quantitative analysis of the intensity of zona pellucida birefringence of oocytes during IVF cycles
Authors: Cheng Junping , Huang Li , He Bing , Lu Fenghua , Wang Xiaoli , Wu Zhengsan , Shi Deshun
Published: September 2010

To determine whether the age of the female patient, oocyte maturation stage, pronuclei, embryonic quality and/or cycle outcome are related to the intensity of the zona pellucida birefringence (ZPB) in oocytes during IVF procedures, a retrospective study was conducted on 214 IVF cycles using a polarisation imaging system. A negative correlation was found between ZPB intensity and the age of female patients (r = –0.44; P < 0.0001). For oocytes at different maturation stages, the ZPB score was higher at the germinal vesicle stage (20.77 ± 1.88) than at MI (10.99 ± 1.35; P < 0.001), and higher at MI than at MII (7.91 ± 0.65; P < 0.05). For the pronuclei (PN) of fertilised oocytes, the ZPB score of oocytes with 3PN was significantly higher than that of oocytes with 1PN or 0PN (7.94 ± 0.78 v. 5.57 ± 1.51 and 4.45 ± 0.85, respectively; P < 0.001). However, there were no differences in ZPB scores between oocytes with 2PN and 3PN. Neither embryo quality on Day 3 nor the clinical results could be predicted on the basis of the ZPB score (P > 0.05).
Impact of surface chemistry
Authors: Somorjai Gabor A. , Li Yimin
Published: September 2010

The applications of molecular surface chemistry in heterogeneous catalyst technology, semiconductor-based technology, medical technology, anticorrosion and lubricant technology, and nanotechnology are highlighted in this perspective. The evolution of surface chemistry at the molecular level is reviewed, and the key roles of surface instrumentation developments for in situ studies of the gas–solid, liquid–solid, and solid–solid interfaces under reaction conditions are emphasized.
Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations
Authors: Schubert Heidi L. , Zhai Qianting , Sandrin Virginie , Eckert Debra M. , Garcia-Maya Mitla , Saul Louise , Sundquist Wesley I. , Steiner Roberto A. , Hill Christopher P.
Published: September 2010

HIV-1 and other enveloped viruses can be restricted by a host cellular protein called BST2/tetherin that prevents release of budded viruses from the cell surface. Mature BST2 contains a small cytosolic region, a predicted transmembrane helix, and an extracellular domain with a C-terminal GPI anchor. To advance understanding of BST2 function, we have determined a 2.6 Å crystal structure of the extracellular domain of the bacterially expressed recombinant human protein, residues 47–152, under reducing conditions. The structure forms a single long helix that associates as a parallel dimeric coiled coil over its C-terminal two-thirds, while the N-terminal third forms an antiparallel four-helix bundle with another dimer, creating a global tetramer. We also report the 3.45 Å resolution structure of BST2(51-151) prepared by expression as a secreted protein in HEK293T cells. This oxidized construct forms a dimer in the crystal that is superimposable with the reduced protein over the C-terminal two-thirds of the molecule, and its N terminus suggests pronounced flexibility. Hydrodynamic data demonstrated that BST2 formed a stable tetramer under reducing conditions and a dimer when oxidized to form disulfide bonds. A mutation that selectively disrupted the tetramer (L70D) increased protein expression modestly but only reduced antiviral activity by approximately threefold. Our data raise the possibility that BST2 may function as a tetramer at some stage, such as during trafficking, and strongly support a model in which the primary functional state of BST2 is a parallel disulfide-bound coiled coil that displays flexibility toward its N terminus.
Electrical transport and magnetic properties of reactive sputtered polycrystalline Ti1−xCrxN films
Authors: Mi W B , Ye T Y , Wang X C , Tan H , Bai H L
Published: September 2010

The magnetoresistance (MR) and magnetic properties of (2 0 0) preferentially oriented Ti1−x
Cr
x
N films have been investigated systematically. All the films are ferromagnetic. The Curie temperature of the films is above 305 K, which is much higher than the previously reported value of 140 K in the Ti1−x
Cr
x
N systems. MR shows a weak saturation trend with the applied magnetic field, and increases significantly with a decrease in temperature below 50 K following the relation log |MR| = a − bT
1/2. The MR–T curves are fitted using MR = P
2/(1 + P
2) with the spin polarization P of
, where the fitted P
0 is 55% at x = 0.14. The enhanced coercivity and low-temperature MR are related to the pinned surface moments of the Cr-doped TiN grains.
Stationary measures and equidistribution for orbits of nonabelian semigroups on the torus
Authors: Bourgain Jean , Furman Alex , Lindenstrauss Elon , Mozes Shahar
Published: September 2010

Let

ν
\nu

be a probability measure on

S
L

d

(

Z

)

\mathrm {SL}_d(\mathbb {Z})

satisfying the moment condition

E

ν

(
‖
g

‖
ϵ

)
>
∞

\mathbb {E}_\nu (\|g\|^\epsilon )>\infty

for some

ϵ
\epsilon

. We show that if the group generated by the support of

ν
\nu

is large enough, in particular if this group is Zariski dense in

S
L

d

\mathrm {SL}_d

, for any irrational

x
∈

T

d

x \in \mathbb {T}^d

the probability measures

ν

∗
n

∗

δ
x

\nu ^{* n} * \delta _x

tend to the uniform measure on

T

d

\mathbb {T}^d

. If in addition

x
x

is Diophantine generic, we show this convergence is exponentially fast.
Appendix and erratum to “Massey products for elliptic curves of rank 1”
Authors: Balakrishnan Jennifer , Kedlaya Kiran , Kim Minhyong
Published: September 2010

The paper Massey products for elliptic curves of rank

1
1

, J. Amer. Math. Soc. 23 (2010), 725-747, contained an error in the final explicit formula because of a mistake in Hodge theory and in analysing the structure of an integral model for a ramified cover of an elliptic curve. This paper corrects that error and includes a collection of numerical examples illustrating the main theorem.
The fundamental group of random 2-complexes
Authors: Babson Eric , Hoffman Christopher , Kahle Matthew
Published: September 2010

We study Linial-Meshulam random22-complexesY(n,p)Y(n,p), which are22-dimensional analogues of Erdős-Rényi random graphs. We find the threshold for simple connectivity to bep=n−1/2p = n^{-1/2}. This is in contrast to the threshold for vanishing of the first homology group, which was shown earlier by Linial and Meshulam to bep=2log⁡n/np = 2 \log n / n.

We use a variant of Gromov’s local-to-global theorem for linear isoperimetric inequalities to show that whenp=O(n−1/2−ϵp = O( n^{-1/2 -\epsilon }), the fundamental group is word hyperbolic. Along the way we classify the homotopy types of sparse22-dimensional simplicial complexes and establish isoperimetric inequalities for such complexes. These intermediate results do not involve randomness and may be of independent interest.
Good formal structures for flat meromorphic connections, II: Excellent schemes
Authors: Kedlaya Kiran
Published: September 2010

Given a flat meromorphic connection on an excellent scheme over a field of characteristic zero, we prove existence of good formal structures after blowing up; this extends a theorem of Mochizuki for algebraic varieties. The argument combines a numerical criterion for good formal structures from a previous paper, with an analysis based on the geometry of an associated valuation space (Riemann-Zariski space). We obtain a similar result over the formal completion of an excellent scheme along a closed subscheme. If we replace the excellent scheme by a complex analytic variety, we obtain a similar but weaker result in which the blowup can only be constructed in a suitably small neighborhood of a prescribed point.
On relative and bi-relative algebraic 𝐾-theory of rings of finite characteristic
Authors: Geisser Thomas , Hesselholt Lars
Published: September 2010

We consider unital associative rings in which a fixed prime number

p
p

is nilpotent. It was proved long ago by Weibel that for such rings, the relative

K
K

-groups associated with a nilpotent extension and the bi-relative

K
K

-groups associated with a pull-back square are

p
p

-primary torsion groups. However, the question of whether these groups can contain a

p
p

-divisible torsion subgroup has remained an open and intractable problem. In this paper, we answer this question in the negative. In effect, we prove the stronger statement that the groups in question are always

p
p

-primary torsion groups of bounded exponent.
Nuclear Organization and Dynamics of 7SK RNA in Regulating Gene Expression
Authors: Prasanth Kannanganattu V. , Camiolo Matthew , Chan Grace , Tripathi Vidisha , Denis Laurence , Nakamura Tetsuya , Hübner Michael R. , Spector David L.
Published: September 2010

Noncoding RNAs play important roles in various aspects of gene regulation. We have identified 7SK RNA to be enriched in nuclear speckles or interchromatin granule clusters (IGCs), a subnuclear domain enriched in pre-mRNA processing factors. 7SK RNA, in association with HEXIM 1 and 2, is involved in the inhibition of transcriptional elongation by RNA polymerase II. Inhibition occurs via sequestration of the active P-TEFb kinase complex (CDK 9 and Cyclin T1/T2a/b or K) that is involved in phosphorylating the C-terminal domain of RNA polymerase II. Our results demonstrate that knock-down of 7SK RNA, by specific antisense oligonucleotides, results in the mislocalization of nuclear speckle constituents in a transcription-dependent manner, and the transcriptional up-regulation of a RNA polymerase II transcribed reporter gene locus. Furthermore, 7SK RNA transiently associates with a stably integrated reporter gene locus upon transcriptional down-regulation and its presence correlates with the efficient displacement of P-TEFb constituents from the locus. Our results suggest that 7SK RNA plays a role in modulating the available level of P-TEFb upon transcriptional down-regulation by sequestering its constituents in nuclear speckles.
A simple and fast method to determine the parameters for fuzzy c–means cluster analysis
Authors: Schwämmle Veit , Jensen Ole Nørregaard
Published: September 2010

Motivation: Fuzzy c-means clustering is widely used to identify cluster structures in high-dimensional datasets, such as those obtained in DNA microarray and quantitative proteomics experiments. One of its main limitations is the lack of a computationally fast method to set optimal values of algorithm parameters. Wrong parameter values may either lead to the inclusion of purely random fluctuations in the results or ignore potentially important data. The optimal solution has parameter values for which the clustering does not yield any results for a purely random dataset but which detects cluster formation with maximum resolution on the edge of randomness.

Results: Estimation of the optimal parameter values is achieved by evaluation of the results of the clustering procedure applied to randomized datasets. In this case, the optimal value of the fuzzifier follows common rules that depend only on the main properties of the dataset. Taking the dimension of the set and the number of objects as input values instead of evaluating the entire dataset allows us to propose a functional relationship determining the fuzzifier directly. This result speaks strongly against using a predefined fuzzifier as typically done in many previous studies. Validation indices are generally used for the estimation of the optimal number of clusters. A comparison shows that the minimum distance between the centroids provides results that are at least equivalent or better than those obtained by other computationally more expensive indices.

Contact:  veits@bmb.sdu.dk

Supplementary information:  Supplementary data are available at Bioinformatics online.
A statistical framework for Illumina DNA methylation arrays
Authors: Kuan Pei Fen , Wang Sijian , Zhou Xin , Chu Haitao
Published: September 2010

Motivation: The Illumina BeadArray is a popular platform for profiling DNA methylation, an important epigenetic event associated with gene silencing and chromosomal instability. However, current approaches rely on an arbitrary detection P-value cutoff for excluding probes and samples from subsequent analysis as a quality control step, which results in missing observations and information loss. It is desirable to have an approach that incorporates the whole data, but accounts for the different quality of individual observations.

Results: We first investigate and propose a statistical framework for removing the source of biases in Illumina Methylation BeadArray based on several positive control samples. We then introduce a weighted model-based clustering called LumiWCluster for Illumina BeadArray that weights each observation according to the detection P-values systematically and avoids discarding subsets of the data. LumiWCluster allows for discovery of distinct methylation patterns and automatic selection of informative CpG loci. We demonstrate the advantages of LumiWCluster on two publicly available Illumina GoldenGate Methylation datasets (ovarian cancer and hepatocellular carcinoma).

Availability:  R package LumiWCluster can be downloaded from http://www.unc.edu/~pfkuan/LumiWCluster

Contact:  pfkuan@bios.unc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
‘La Mémoire de la Shoah’: The Contentious Case of Soazig Aaron's
Le Non de Klara
Authors: Cairns Lucille
Published: September 2010

Soazig Aaron's
Le Non de Klara
(2002) is a prize-winning novel about an Auschwitz survivor and has been greatly lauded, by Jorge Semprún among others. This article attempts to convey the novel's status as a literary artefact of high aesthetic quality and to interrogate the complex ethical questions the work mobilizes. Two diametrically opposed responses to the novel are considered. The first holds that, while the non-Jewish Aaron (a pseudonym) may have the right as a creative writer to simulate the voice of a Jewish survivor of Auschwitz, the Jewish reader may still be troubled by the fact that this survivor rejects her Jewish identity and is, moreover, constructed in morally ambiguous terms. The second view is that Aaron's attempt imaginatively to cross a Jewish–Gentile hiatus via textual introjection and empathy is artistically justifiable and morally exemplary, and that her use of artifice to accede to ‘truth’ is entirely legitimate.
Savage Poetry: Torture and Cruelty in Mirbeau and Barbey d'Aurevilly
Authors: Thompson Hannah
Published: September 2010

Octave Mirbeau's
Le Jardin des supplices
and Barbey d'Aurevilly's
L'Ensorcelée
and
Les Diaboliques
depict a range of cruel attacks on the human body. These examples of violence, hitherto neglected by critical readers of the texts, have much to tell us not only about the authors' approach to violence, but also about the relationships between author, reader, and text that such representations of violence foreground. The notion of readerly pleasure theorized by Roland Barthes and linked to identity formation by Emma Wilson is associated with the witnessing or experiencing of pain in these texts. The reader is problematically positioned as both sadist, vicariously enjoying the suffering he or she is forced to witness, and masochist, taking pleasure in the authors' manipulations of them. These depictions of violated bodies ask whether and by what means violence can be represented in language, and this discussion leads to an analysis of the impact that such representations of violence have on the reader's experience of a text.
Recruitment dynamics of the Gulf of Riga herring stock: density-dependent and environmental effects
Authors: Raid Tiit , Kornilovs Georgs , Lankov Ain , Nisumaa Anne-Marin , Shpilev Heli , Järvik Ahto
Published: September 2010

Raid, T., Kornilovs, G., Lankov, A., Nisumaa, A-M., Shpilev, H., and Järvik, A. 2010. Recruitment dynamics of the Gulf of Riga herring stock: density-dependent and environmental effects. – ICES Journal of Marine Science, 67: 1914–1920. The Gulf of Riga and open-sea stocks of the Baltic herring have displayed remarkably consistent inverse recruitment and stock development patterns since the 1970s: the open-sea stocks steadily declined, whereas the Gulf stock increased rapidly in the early 1990s, reaching a peak abundance in the early 2000s and exceeding the level of the 1970s by a factor of 2–3. The increase was accompanied by a decline in the mean weight-at-age and the condition factor. The estimated decline (by 30–40%) in the average annual consumption rate per individual and changes observed in the zooplankton community suggest that density-dependent effects may have increased since the 1970s. The current period of high stock sizes is also characterized by greater recruitment variability. Historical fecundity investigations have established that the average egg production per individual has decreased in all age groups by 20–50%, along with a decrease in mean weight and condition. Yet, the effect on recruitment has been low so far, because lower fecundity has been compensated by the greater abundance and population fecundity has been maintained at the original level. Recruitment appears to be more influenced by environmental conditions than by spawning-stock biomass.
Minimally Invasive Measurement of Cardiac Output during Surgery and Critical Care
Authors: Peyton Philip J. , Chong Simon W.
Published: September 2010

When assessing the accuracy and precision of a new technique for cardiac output measurement, the commonly quoted criterion for acceptability of agreement with a reference standard is that the percentage error (95% limits of agreement/mean cardiac output) should be 30% or less. We reviewed published data on four different minimally invasive methods adapted for use during surgery and critical care: pulse contour techniques, esophageal Doppler, partial carbon dioxide rebreathing, and transthoracic bioimpedance, to assess their bias, precision, and percentage error in agreement with thermodilution. An English language literature search identified published papers since 2000 which examined the agreement in adult patients between bolus thermodilution and each method. For each method a meta-analysis was done using studies in which the first measurement point for each patient could be identified, to obtain a pooled mean bias, precision, and percentage error weighted according to the number of measurements in each study. Forty-seven studies were identified as suitable for inclusion: N studies, n measurements: mean weighted bias [precision, percentage error] were: pulse contour N = 24, n = 714: -0.00 l/min [1.22 l/min, 41.3%]; esophageal Doppler N = 2, n = 57: -0.77 l/min [1.07 l/min, 42.1%]; partial carbon dioxide rebreathing N = 8, n = 167: -0.05 l/min [1.12 l/min, 44.5%]; transthoracic bioimpedance N = 13, n = 435: -0.10 l/min [1.14 l/min, 42.9%]. None of the four methods has achieved agreement with bolus thermodilution which meets the expected 30% limits. The relevance in clinical practice of these arbitrary limits should be reassessed.
Sugammadex and Neostigmine Dose-finding Study for Reversal of Shallow Residual Neuromuscular Block
Authors: Schaller Stefan J. , Fink Heidrun , Ulm Kurt , Blobner Manfred
Published: September 2010

Introduction

Sugammadex effectively and rapidly reverses deep to moderate rocuronium-induced neuromuscular block. However, the required dose of sugammadex for smaller degrees of residual block is unknown. Therefore we investigated the efficacy of sugammadex and neostigmine at a train-of-four (TOF) ratio of 0.5.

Methods

After ethics committee (Munich, Germany) approval and written informed consent were obtained, 99 patients were anesthetized with propofol, remifentanil, and rocuronium. Neuromuscular monitoring was performed by calibrated electromyography. At recovery of the TOF ratio to 0.5, patients randomly received sugammadex (0.0625, 0.125, 0.25, 0.5, or 1.0 mg/kg), neostigmine (5, 8, 15, 25, or 40 μg/kg), or saline. The time between study drug injection, at TOF ratio of 0.5, and postoperative TOF ratio of 0.9 was measured. The dose-response relationship was analyzed with a biexponential model using the dose as the independent variable and the logarithm of the recovery time as the dependent variable. Effective doses were interpolated from regression models.

Results

Sugammadex, 0.22 mg/kg, is able to reverse a TOF ratio of 0.5 to 0.9 or higher in an average time of 2 min. Within 5 min, 95% of patients reach this TOF ratio. Neostigmine, 34 μg/kg, is able to reverse a TOF ratio of 0.5 to 0.9 or higher within 5 min. No recurarization was observed.

Conclusions

Sugammadex, 0.22 mg/kg, and neostigmine, 34 μg/kg, effectively and comparably reverse a rocuronium-induced shallow residual neuromuscular block at a TOF ratio of 0.5.
Does Central Venous Oxygen Saturation-directed Fluid Therapy Affect Postoperative Morbidity after Colorectal Surgery?
Authors: Jammer Ib , Ulvik Atle , Erichsen Christian , Lødemel Olav , Østgaard Gro
Published: September 2010

Background

The optimal amount and method for monitoring intravenous fluid in surgical patients is unresolved. Central venous oxygen saturation (Scvo2) has been used to guide therapy and predict outcome in high-risk and intensive-care patients. The aim of this prospective, randomized trial was to compare the rate of postoperative complications in patients receiving fluid therapy guided by Scvo2 and those treated with a traditional effluent fluid scheme.

Methods

Patients undergoing open colorectal and lower intestinal surgery (n = 241) were randomized to the Scvo2 group or the control group. The Scvo2 group received perioperatively crystalloid infusion 100 ml/h. When Scvo2 was less than 75%, a bolus of 3 ml/kg hydroxyethyl starch was given. The bolus was repeated if Scvo2 increased by 1 percentage point or more. The control group was maintained with crystalloid 800 ml/h and given extra fluid if there were clinical signs of hypovolemia. The participating surgeon, unaware of the group allocation, registered complications within day 30.

Results

Until 8:00 am on the first postoperative day, the Scvo2 group had received 3,869 ± 992 ml (mean ± SD) intravenous fluid compared with 6,491 ± 1,649 ml in the control group. Increase in weight was 0.8 ± 1.8 kg and 2.5 ± 1.6 kg in the two groups, respectively. The postoperative complication rate was 42% in both groups.

Conclusion

Clinical outcomes among patients receiving Scvo2-guided perioperative fluid therapy were similar to those for patients treated with a traditional fluid regimen. Limitations in study design prevent full interpretation of these findings, and further large trials of this treatment algorithm are still required.
Lower Isoflurane Concentration Affects Spatial Learning and Neurodegeneration in Adult Mice Compared with Higher Concentrations
Authors: Valentim Ana M. , Di Giminiani Pierpaolo , Ribeiro Patrícia O. , Rodrigues Paula , Olsson I. Anna S. , Antunes Luís M.
Published: September 2010

Background

Volatile anesthetics such as isoflurane are widely used in clinical and research contexts. Concerns have been raised that the effects of these drugs on the central nervous system may result in long-term impairment after surgery or general anesthesia. Hence, this study aimed to detect how different isoflurane concentrations influence spatial learning and cell death in adult mice.

Methods

Fifty-two C57BL/6 mice were randomly divided in four groups. Mice in three groups were exposed to different concentrations of isoflurane (1, 1.5, and 2%) for 1 h; the control group was not exposed to anesthesia. Five mice per group were killed 3 h after anesthesia to perform histopathologic and immunohistochemical analyses (hematoxylin-eosin staining; caspase-3 activation). Eight mice per group were used for behavioral tests (open field, T-maze spontaneous alternation, and water maze) on subsequent days.

Results

There were no differences between groups in the T-maze spontaneous alternation test or in the open field (no confounding effects of stress or locomotion). The group anesthetized with 1% isoflurane performed worse in the water maze task on day 1 (550.4 ±162.78 cm) compared with the control group (400.1 ± 112.88 cm), 1.5% isoflurane (351.9 ± 150.67 cm), and 2% isoflurane (364.5 ± 113.70 cm; P ≤ 0.05) and on day 3 (305.0 ± 81.75 cm) compared with control group (175.13 ± 77.00 cm) and 2% isoflurane (204.11 ± 85.75 cm; P ≤ 0.038). In the pyramidal cell layer of the region cornu ammonis 1 of the hippocampus, 1% isoflurane showed a tendency to cause more neurodegeneration (apoptosis) (61.4 ± 26.40, profiles/mm) than the group with 2% of isoflurane (20.6 ± 17.77, profiles/mm; P = 0.051).

Conclusion

Low isoflurane concentration (1%) caused spatial learning impairment and more neurodegeneration compared with higher isoflurane concentrations. Results for mice receiving the latter concentrations were similar to those of control mice.
Peripheral and Intestinal CD4+ T Cells With a Regulatory Phenotype in Pediatric Patients With Inflammatory Bowel Disease
Authors: La Scaleia Raffaella , Morrone Stefania , Stoppacciaro Antonella , Scarpino Stefania , Antonelli Manila , Bianchi Elettra , Di Nardo Giovanni , Oliva Salvatore , Viola Franca , Cucchiara Salvatore , Santoni Angela , Palmieri Gabriella , Uccini Stefania
Published: September 2010

Objectives:

Regulatory T cells (TR cells) play a crucial role in the regulation of intestinal inflammation. To examine the pathogenetic relevance of TR cells in inflammatory bowel disease (IBD), we evaluated their frequency in peripheral blood and inflamed and noninflamed mucosae of pediatric patients with IBD and age‐matched controls without IBD; we also characterized the immune profile of the inflammatory infiltrate in the different phases of the disease.

Patients and Methods:

Circulating TR cells were investigated on peripheral blood mononuclear cells by fluorescence‐activated cell sorting analysis; mucosal TR cells and inflammatory cell populations were investigated by immunohistochemistry on bioptic specimens. FOXP3 messenger RNA expression levels were confirmed using real‐time polymerase chain reaction.

Results:

FOXP3+ TR cells were significantly increased in the intestinal lesions of patients with active IBD, and returned to normal levels in posttherapy remission phase. At variance, circulating TR cell frequency was elevated in patients with IBD independently of disease activity, as it persisted in the remission phase. A selective imbalance in the frequency of CD4+ T and natural killer cell subsets characterized the abundant inflammatory infiltrate of active intestinal lesions, and also persisted, at a lower level, in noninflamed mucosae of patients in the remission phase.

Conclusions:

TR cell frequency is differently regulated in mucosal tissues and at the systemic level during the distinct phases of pediatric IBD. The inactive stage of pediatric IBD is characterized by an incomplete normalization of the immune profile, independently of the clinical efficacy of the therapy. The pediatric, early‐onset condition may represent a privileged observatory to dissect the immune‐mediated pathogenetic mechanisms at the basis of the disease.
Value of Ultrasound‐guided Percutaneous Liver Biopsy in Children Following Liver Transplantation
Authors: Sornsakrin Marijke , Helmke Knut , Briem‐Richter Andrea , Ganschow Rainer
Published: September 2010

Objectives:

Pediatric liver transplant recipients often need to undergo liver biopsies for the detection and specification of complications such as acute or chronic graft rejection, infection, or drug toxicity. Complications resulting from liver biopsy are rare. The aim of our single‐center retrospective study was to report on liver biopsy–related complications and, moreover, to assess the significance of histological findings in correlation with the suspected diagnosis.

Patients and Methods:

Overall, 120 liver biopsies from 67 children were performed and analyzed. All of the biopsies were performed with ultrasound guidance using midazolam and ketamine.

Results:

The overall incidence of complications was 5.0%, but most of these complications were mild. In 2 cases, however, the complications were severe and required surgical intervention in addition to further medical treatment.

In about 92% of the cases, liver histology confirmed the previously suspected diagnosis based on clinical and clinical laboratory indications.

Conclusions:

We concluded that postliver transplantation liver biopsy in children seldom provides unexpected results and, even using ultrasound guidance, has led, albeit rarely, to serious complications. We therefore now accept potential delay in treatment and reserve liver biopsy for patients who fail to respond to therapy based on clinical judgment.
Comparative Analysis of the Properties of Bifidobacterial Isolates From Fecal Samples of Mother–Infant Pairs
Authors: Takahashi Hidenori , Mikami Katsunaka , Nishino Ryou , Matsuoka Takashi , Kimura Moto , Koga Yasuhiro
Published: September 2010

Objectives:

The aim of the study was to evaluate the possibility of Bifidobacterium breve transfer from the mother to her infant during the perinatal period.

Materials and Methods:

Hundred isolates of B breve and 80 isolates of Bifidobacterium longum were collected from paired fecal samples of mothers and their infants. Bacterial DNA from the samples was comparatively analyzed by random amplification of polymorphic DNA. The growth of the bacteria was examined in vitro.

Results:

The analysis of diversity in B breve population showed that infant‐derived isolates had significantly less diversity than mother‐derived isolates. The analysis of the similarity between these samples revealed that the number of shared type isolates tended to be higher in infants than in their mothers. In the isolates of B longum, however, no such difference was found in the diversity between mother‐ and infant‐derived isolates. Examination of the growth of B breve strains revealed that the shared type strains have a significantly higher growth than nonshared strains both in the presence of galactooligosaccharides and at a higher redox potential.

Conclusions:

These results suggested that subpopulations of B breve strains in the mothers may be transferred to their infants. Such populations may become dominant in the gut of infants at an early time after birth, during which time the transmission of the bifidobacteria of environmental origin is not yet established. B breve strain possessing a higher growth advantage in these conditions may be advantageous for colonization in the infant gut.
Interspecific symbiont transfection confers a novel ecological trait to the recipient insect
Authors: Tsuchida Tsutomu , Koga Ryuichi , Matsumoto Shogo , Fukatsu Takema
Published: September 2010

In Japan, pea aphids
Acyrthosiphon pisum
mainly feed on vetch and clover, and many aphid clones produce more progeny on vetch than on clover. In this context, particular genotypes of the facultative symbiont
Regiella insecticola
enhance reproduction of infected pea aphids specifically on clover, thereby broadening the suitable food plant range of the insect. A species that is sympatric to
A. pisum
, vetch aphids
Megoura crassicauda
, are commonly found on vetch but not on clover. Laboratory rearing of
M. crassicauda
strains revealed active reproduction on vetch but substantially no reproduction on clover. Experimental transfection of
Regiella
from
A. pisum
to
M. crassicauda
by haemolymph injection established stable and heritable infection in the recipients, although no
Regiella
infection has been detected in natural populations of
M. crassicauda
. Different strains of
Regiella
-transfected
M. crassicauda
grew and reproduced on vetch, but exhibited lower fitness in comparison with corresponding uninfected aphid strains. Strikingly, the
Regiella
-transfected
M. crassicauda
exhibited improved survival and some reproduction on clover. These results suggest that
Regiella
has the potential to confer an ecological trait, adaptation to clover, on novel insect hosts, and also account for why
Regiella
is able to infect
M. crassicauda
but is scarcely found in these aphid populations.