bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Ultramorphological Assessment of Apoptosis on CEMss Induced by Linoleic Acid‐Rich Fraction from Typhonium flagelliforme Tuber
Authors: Mohan Syam , Bustamam Ahmad , Ibrahim Siddig , Al-Zubairi Adel S. , Aspollah Mohammed , Abdullah Rasedee , Elhassan Manal Mohamed
Published: February 2010

The plant Typhonium flagelliforme, commonly known as “rodent tuber” in Malaysia, is often used as a health supplement and traditional remedy for alternative cancer therapies, including leukemia. This study aimed to evaluate in vitro anti‐leukemic activity of dichloromethane extract/fraction number 7 (DCM/F7) from T. flagelliforme tuber on human T4 lymphoblastoid (CEMss) cell line. The DCM extract of tuber has been fractionated by column chromatography. The obtained fractions were evaluated for its cytotoxicity toward CEMss cells as well as human primary blood lymphocytes (PBLs). Assessment of apoptosis produced by the most active fraction was evaluated by various microscopic techniques and further confirmation of apoptosis was done by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Phytochemical screening was done by gas chromatography‐mass spectrometry (GC‐MS). The results shows that 7 out of 12 fractions showed significant cytotoxicity against the selected cell line CEMss, in which fractions DCM/F7, DCM/F11 and DCM/F12 showed exceptional activity with 3, 5 and 6.2 μg ml−1, respectively. Further studies in the non‐cancerous PBL exhibited significant selectivity of DCM/F7 compared to other fractions. Cytological observations showed chromatin condensation, cell shrinkage, abnormalities of cristae, membrane blebbing, cytoplasmic extrusions and formation of apoptotic bodies as confirmed collectively by double‐staining of acridine orange (AO)/propidium iodide (PI), SEM and TEM. In addition, DCM/F7 has increased the cellular DNA breaks on treated cells. GC‐MS revealed that DCM/F7 contains linoleic acid, hexadecanoic acid and 9‐hexadecanoic acid. The present results indicate that T. flagelliforme possess a valuable anti‐leukemic effect and was able to produce distinctive morphological features of cell death that corresponds to apoptosis.
Examination of transcriptional networks reveals an important role for TCFAP2C, SMARCA4, and EOMES in trophoblast stem cell maintenance
Authors: Kidder Benjamin L. , Palmer Stephen
Published: February 2010

Trophoblast stem cells (TS cells), derived from the trophectoderm (TE) of blastocysts, require transcription factors (TFs) and external signals (FGF4, INHBA/NODAL/TGFB1) for self-renewal. While many reports have focused on TF networks that regulate embryonic stem cell (ES cell) self-renewal and pluripotency, little is know about TF networks that regulate self-renewal in TS cells. To further understand transcriptional networks in TS cells, we used chromatin immunoprecipitation with DNA microarray hybridization (ChIP-chip) analysis to investigate targets of the TFs—TCFAP2C, EOMES, ETS2, and GATA3—and a chromatin remodeling factor, SMARCA4. We then evaluated the transcriptional states of target genes using transcriptome analysis and genome-wide analysis of histone H3 acetylation (AcH3). Our results describe previously unknown transcriptional networks in TS cells, including TF occupancy of genes involved in ES cell self-renewal and pluripotency, co-occupancy of TCFAP2C, SMARCA4, and EOMES at a significant number of genes, and transcriptional regulatory circuitry within the five factors. Moreover, RNAi depletion of Tcfap2c, Smarca4, and Eomes transcripts resulted in a loss of normal colony morphology and down-regulation of TS cell–specific genes, suggesting an important role for TCFAP2C, SMARCA4, and EOMES in TS cell self-renewal. Through genome-wide mapping and global expression analysis of five TF target genes, our data provide a comprehensive analysis of transcriptional networks that regulate TS cell self-renewal.
The human fungal pathogenParacoccidioides brasiliensis(Onygenales: Ajellomycetaceae) is a complex of two species: phylogenetic evidence from five mitochondrial markers
Authors: Salgado‐Salazar Catalina , Jones Leandro R. , Restrepo Ángela , McEwen Juan G.
Published: February 2010

Paracoccidioides brasiliensisis the aetiological agent of paracoccidioidomycosis, the most important systemic mycosis in Latin America. In order to study the diversity ofP. brasiliensismitochondrial genes, to evaluate previous taxonomic proposals, and to explore the hypothesis that the previously described “divergent isolate” B30 (also called Pb01) could represent a newP. brasiliensisspecies, we undertook a molecular phylogenetic analysis based on five mitochondrial markers. Mitochondrial sequences of 59P. brasiliensisisolates obtained from clinical and environmental samples, and the orthologous genes from outgroup species, are reported and analysed using parsimony and Bayesian methods. The combined data set comprised 2364 characters, of which 426 were informative. One of the studied strains presented a 376‐nt insertion at the apocytochromeb(cob) gene. The corresponding sequence had a high similarity (79%) with an intron found in theNeurospora crassa cobgene. Interestingly, this intron is absent in the previously published sequence of theP. brasiliensismitochondrial genome. Our trees were moderately congruent with the previousP. brasiliensistaxonomic proposals. Furthermore, we identified a new monophyletic group of strains withinP. brasiliensis. Nevertheless, the phylogenetic species recognition (PSR) analyses described here suggested that these groups of strains could represent geographical variants rather than differentParacoccidioidescryptic species. In addition, and as previously proposed by other authors, these analyses supported the existence of a new specie ofParacoccidioides, which includes the previously described, divergent isolate B30/Pb01. This is the first report providing evidence, independent of nuclear markers, for the split of this important human pathogen into two species. We support the formal description of the B30/Pb01 as new specie. ©The Willi Hennig Society 2010.
Pharmacological interaction with sunitinib is abolished by a germ‐line mutation (1291T>C) of BCRP/ABCG2 gene
Authors: Kawahara Haruka , Noguchi Kohji , Katayama Kazuhiro , Mitsuhashi Junko , Sugimoto Yoshikazu
Published: February 2010

Sunitinib malate (Sutent, SU11248) is a small‐molecule multitargeted tyrosine kinase inhibitor (TKI) used for the treatment of renal cell carcinoma and imatinib‐resistant gastrointestinal stromal tumors. Some TKIs can overcome multidrug resistance conferred by ATP‐binding cassette transporter, P‐glycoprotein (P‐gp)/ABCB1, multidrug resistance‐associated protein 1 (MRP1)/ABCC1, and breast cancer resistance protein (BCRP)/ABCG2. Here, we analyzed the effects of sunitinib on P‐gp and on wild‐type and germ‐line mutant BCRPs. Sunitinib remarkably reversed BCRP‐mediated and partially reversed P‐gp‐mediated drug resistance in the respective transfectants. The in vitro vesicle transport assay indicated that sunitinib competitively inhibited BCRP‐mediated estrone 3‐sulfate transport and P‐gp‐mediated vincristine transport. These inhibitory effects of sunitinib were further analyzed in Q141K‐, R482G‐, R482S‐, and F431L‐variant BCRPs. Intriguingly, the F431L‐variant BCRP, which is expressed by a germ‐line mutant allele 1291T>C, was almost insensitive to both sunitinib‐ and fumitremorgin C (FTC)‐mediated inhibition in a cell proliferation assay. Sunitinib and FTC did not inhibit 125I‐iodoarylazidoprazosin‐binding to F431L‐BCRP. Thus, residue Phe‐431 of BCRP is important for the pharmacological interaction with sunitinib and FTC. Collectively, this is the first report showing a differential effect of a germ‐line variation of the BCRP/ABCG2 gene on the pharmacological interaction between small‐molecule TKIs and BCRP. These findings would be useful for improving our understanding of the pharmaceutical effects of sunitinib in personalized chemotherapy. (Cancer Sci 2010; 00: 000–000)
Gastritis OLGA‐staging and gastric cancer risk: a twelve‐year clinico‐pathological follow‐up study
Authors: RUGGE M. , DE BONI M. , PENNELLI G. , DE BONA M. , GIACOMELLI L. , FASSAN M. , BASSO D. , PLEBANI M. , GRAHAM D. Y.
Published: February 2010

Aliment Pharmacol Ther 31, 1104–1111

Background  Intestinal‐type gastric cancer (GC) still ranks among the high‐incidence, highly lethal malignancies. Atrophic gastritis is the cancerization field in which GC develops. The current histological reporting formats for gastritis do not include any (atrophy‐based) ranking of GC risk.

Aim  To test the gastritis OLGA‐staging (Operative Link for Gastritis Assessment) in prognosticating neoplastic progression.

Methods  Ninety‐three Italian patients were followed up for more than 12 years (range: 144–204 months). Clinical examinations, pepsinogen serology, endoscopy and histology (also assessing Helicobacter pylori status) were performed both at enrolment (T1) and at the end of the follow‐up (T2).

Results  All invasive or intra‐epithelial gastric neoplasia were consistently associated with high‐risk (III/IV) OLGA stages. There was a significant inverse correlation between the mean pepsinogen ratio and the OLGA stage (test for trend; P < 0.001). OLGA‐staging at T1 predicted both the OLGA stage (Kaplan–Maier log‐rank test, P = 0.001) and the neoplasia at T2 (Kaplan–Maier log‐rank test, P = 0.001).

Conclusions  This long‐term follow‐up study provides the first evidence that gastritis OLGA‐staging conveys relevant information on the clinico‐pathological outcome of gastritis and therefore for patient management. According to OLGA‐staging and H. pylori‐status, gastritis patients could be confidently stratified and managed according to their different cancer risks.
Does calcium supplementation increase cardiovascular risk?
Authors: Reid Ian R , Bolland Mark J. , Grey Andrew
Published: February 2010

Calcium supplementation is widely used for the prevention of osteoporosis in postmenopausal women and in men. While there has been ongoing debate regarding its effectiveness in fracture prevention, the underlying assumption has been that, even if it was not particularly effective, at least it was safe. The recent finding of the Auckland Calcium Study that myocardial infarctions were more common in women randomised to calcium calls this assumption into question, and consideration of vascular event data from other calcium trials does not refute the Auckland findings. Meta‐analyses of these data will be necessary to settle this matter. It is already accepted that calcium supplements increase vascular risk in patients with renal compromise, even in those not yet requiring dialysis. Also, there is substantial epidemiological evidence that serum calcium levels in the upper part of the normal range are a risk factor for vascular disease, and that calcium supplements acutely elevate serum calcium – a combination of findings that lends plausibility to supplementation increasing vascular risk. As there are reasonable grounds for doubting the safety of calcium supplements, and as the evidence for their efficacy in fracture prevention remains marginal, we suggest that there should be a reappraisal of their role in the management of osteoporosis, with a greater emphasis on agents known to prevent fractures.
ORIGINAL ARTICLE: Postpartum thyroid dysfunction and the long‐term risk of hypothyroidism: results from a 12‐year follow‐up study of women with and without postpartum thyroid dysfunction
Authors: Stuckey B G A , Kent G N , Ward L C , Brown S J , Walsh J P
Published: February 2010

Background  The long‐term risk of hypothyroidism following postpartum thyroid dysfunction (PPTD) is uncertain. Most previous studies have been small, short‐term or have lacked a control group.

Objective  To ascertain the long‐term risk of hypothyroidism in women following PPTD.

Design and participants  A 12‐year longitudinal study of 409 women (including 71 with PPTD) who previously participated in a PPTD prevalence study.

Measurements  The primary outcome measure was hypothyroidism (defined as TSH greater than 4 mU/l or on thyroxine replacement) at follow‐up. Outcomes in women with and without PPTD were compared by logistic regression. Receiver operating characteristic analysis was used to determine the optimal cut‐off for baseline TSH as a predictor of hypothyroidism in the cohort.

Results  At follow‐up, hypothyroidism was present in 27 of 71 women who had PPTD at baseline (38%) and 14 of 338 women without PPTD (4%). From multivariate analysis, odds ratios (with 95% confidence intervals) for hypothyroidism were – 4·8 (1·6, 14·1) for PPTD; 8·2 (2·8, 24·6) for positive thyroid peroxidase antibodies (TPOAb); 9·7 (2·6, 37·0) for the hypothyroid phase of PPTD and 51·4 (19·2, 137·5) for hypothyroid PPTD with positive TPOAb. A baseline TSH above 2·6 mU/l was the optimal cut‐off for predicting hypothyroidism (sensitivity 76%, specificity 86%).

Conclusions  PPTD is a strong predictor of hypothyroidism in the long‐term. Women who present with postpartum hypothyroidism or have positive TPOAb are at particularly high risk, suggesting that close long‐term follow‐up is advisable if thyroxine replacement is not instituted at an early stage.
The growth hormone insulin‐like growth factor 1 axis in children and adolescents with inflammatory bowel disease and growth retardation
Authors: Wong S. C. , Smyth A. , McNeill E. , Galloway P. J. , Hassan K. , McGrogan P. , Ahmed S. F.
Published: February 2010

Context  There is scarce knowledge about the growth hormone (GH) insulin‐like growth factor‐1 (IGF1) axis in children & adolescents with inflammatory bowel disease (IBD) and growth retardation.

Objective  To describe the pattern of GH and IGF1 secretion in children & adolescents with IBD.

Design  A retrospective review of 28 patients (23 M) of IBD (25 Crohn’s Disease and three Ulcerative Colitis) and growth retardation who had investigation of the GH/IGF‐1 axis. Height velocity (HV) and serum IGF1 were converted to standard deviation score (SDS); to account for delayed puberty in girls over 11 years and boys over 12 years, HV and serum IGF1 SDS were adjusted for bone age.

Results  Median (range) age and Ht SDS at the time of endocrine evaluation was 14·3 years (7·7,17·0) and −2·0(−3·6,−0·9), respectively. Median HVSDS over the prior 12 months was −2·2(−7·7,2·8). Median peak serum GH on insulin tolerance test (ITT) was 5·8 mcg/l (1·3, 24·0), and median serum IGF1 SDS was −0·9(−3·1, 0·1). Five of 28 (18%) had a peak serum GH of >12 mcg/l. Overall, four had biochemical evidence of functional GH deficiency (peak GH < 3 mcg/l and IGF1 SDS < 0) and 11 children had biochemical evidence suggesting GH resistance (peak GH > 6 mcg/l and IGF1 SDS < 0). However, only one child had a peak serum GH > 6 mcg/l and a very low IGF1 SDS of <−2·0. There was a negative association between peak serum GH and Ht SDS (r = −0·49, P = 0·008), but there was no association with HV and there was no association between IGF1 SDS and Ht or HV SDS. IGF1 SDS showed a negative association with erythrocyte sedimentation rate (r = −0·41, P = 0·04).

Conclusion  Growth retardation in children and adolescents with IBD is commonly associated with a range of biochemical abnormalities ranging from functional GH deficiency to GH resistance. In these children, poor relationship between systemic markers of growth and height velocity point to an important role of growth factors at the target organ level in modulating growth in children with IBD. The value of assessing the GH/IGF‐1 axis and whether it predicts subsequent response to growth‐promoting therapy requires further exploration.
Identification and characterization of circadian clock genes in the pea aphid Acyrthosiphon pisum
Authors: Cortés T. , Ortiz‐Rivas B. , Martínez‐Torres D.
Published: February 2010

The molecular basis of circadian clocks is highly evolutionarily conserved and has been best characterized in Drosophila and mouse. Analysis of the Acyrthosiphon pisum genome revealed the presence of orthologs of the following genes constituting the core of the circadian clock in Drosophila: period (per), timeless (tim), Clock, cycle, vrille, and Pdp1. However, the presence in A. pisum of orthologs of a mammal‐type in addition to a Drosophila‐type cryptochrome places the putative aphid clockwork closer to the ancestral insect system than to the Drosophila one. Most notably, five of these putative aphid core clock genes are highly divergent and exhibit accelerated rates of change (especially per and tim orthologs) suggesting that the aphid circadian clock has evolved to adapt to (unknown) aphid‐specific needs. Additionally, with the exception of jetlag (absent in the aphid) other genes included in the Drosophila circadian clock repertoire were found to be conserved in A. pisum. Expression analysis revealed circadian rhythmicity for some core genes as well as a significant effect of photoperiod in the amplitude of oscillations.
Genomic evidence for complementary purine metabolism in the pea aphid, Acyrthosiphon pisum, and its symbiotic bacterium Buchnera aphidicola
Authors: Ramsey J. S. , MacDonald S. J. , Jander G. , Nakabachi A. , Thomas G. H. , Douglas A. E.
Published: February 2010

The purine salvage pathway recycles purines to nucleotides, promoting efficient utilization of purine nucleotides. Exceptionally among animals with completely sequenced genomes, the pea aphid lacks key purine recycling genes that code for purine nucleoside phosphorylase and adenosine deaminase, indicating that the aphid can neither metabolize nucleosides to the corresponding purines, nor adenosine to inosine. Purine metabolism genes in the symbiotic bacterium Buchnera complement aphid genes, and Buchnera can meet its nucleotide requirement from aphid‐derived guanosine. Buchnera demand for nucleosides may have relaxed the selection for purine recycling in the aphid, leading to the loss of key aphid purine salvage genes. Further, the coupled purine metabolism of aphid and Buchnera could contribute to the dependence of the pea aphid on this symbiosis.
The pea aphid phylome: a complete catalogue of evolutionary histories and arthropod orthology and paralogy relationships for Acyrthosiphon pisum genes
Authors: Huerta‐Cepas J. , Marcet‐Houben M. , Pignatelli M. , Moya A. , Gabaldón T.
Published: February 2010

Phylogenetic analyses serve many purposes, including the establishment of orthology relationships, the prediction of protein function and the detection of important evolutionary events. Within the context of the sequencing of the genome of the pea aphid, Acyrthosiphon pisum, we undertook a phylogenetic analysis for every protein of this species. The resulting phylome includes the evolutionary relationships of all predicted aphid proteins and their homologues among 13 other fully‐sequenced arthropods and three out‐group species. Subsequent analyses have revealed multiple gene expansions that are specific to aphids and have served to transfer functional annotations to 4058 pea aphid genes that display one‐to‐one orthology relationships with Drosophila melanogaster annotated genes. All phylogenies and alignments are accessible through the PhylomeDB database. Here we provide a description of this dataset and provide some examples on how can it be exploited.
Neuropeptide and neurohormone precursors in the pea aphid, Acyrthosiphon pisum
Authors: Huybrechts J. , Bonhomme J. , Minoli S. , Prunier‐Leterme N. , Dombrovsky A. , Abdel‐Latief M. , Robichon A. , Veenstra J. A. , Tagu D.
Published: February 2010

Aphids respond to environmental changes by developing alternative phenotypes with differing reproductive modes. Parthenogenetic reproduction occurs in spring and summer, whereas decreasing day lengths in autumn provoke the production of sexual forms. Changing environmental signals are relayed by brain neuroendocrine signals to the ovarioles. We combined bioinformatic analyses with brain peptidomics and cDNA analyses to establish a catalogue of pea aphid neuropeptides and neurohormones. 42 genes encoding neuropeptides and neurohormones were identified, of which several were supported by expressed sequence tags and/or peptide mass analyses. Interesting features of the pea aphid peptidome are the absence of genes coding for corazonin, vasopressin and sulfakinin and the presence of 10 different genes coding insulin related peptides, one of which appears to be very abundantly expressed.
Analysis of meiosis and cell cycle genes of the facultatively asexual pea aphid, Acyrthosiphon pisum(Hemiptera: Aphididae)
Authors: Srinivasan D. G. , Fenton B. , Jaubert‐Possamai S. , Jaouannet M.
Published: February 2010

Phenotypic plasticity in response to environmental change is a common phenomenon, yet is poorly understood at the genetic and molecular level. Aphids exhibit a reproductive plasticity whereby seasonal changes result in asexual or sexual reproduction. To investigate the genetic basis of this reproductive plasticity, we assessed the meiosis and cell cycle gene repertoire in the genome of the pea aphid, Acyrthosiphon pisum. Aphids possess meiotic recombination genes and G1‐to‐S phase transition regulatory genes in gene copy numbers similar to other metazoans. However, mitotic and meiotic regulatory genes have duplicated, and several paralogues exhibit differential expression between reproductive morphs. Together, this suggests that cell cycle plasticity may be important in the evolution and mechanism of aphid reproductive plasticity.
Chromatin‐remodelling proteins of the pea aphid, Acyrthosiphon pisum (Harris)
Authors: Rider Jr S. D. , Srinivasan D. G. , Hilgarth R. S.
Published: February 2010

Aphids display extraordinary developmental plasticity in response to environmental cues. These differential responses to environmental changes may be due in part to changes in gene expression patterns. To understand the molecular basis for aphid developmental plasticity, we attempted to identify the chromatin‐remodelling machinery in the recently sequenced pea aphid genome. We find that the pea aphid possesses a complement of metazoan histone modifying enzymes with greater gene family diversity than that seen in a number of other arthropods. Several genes appear to have undergone recent duplication and divergence, potentially enabling greater combinatorial diversity among the chromatin‐remodelling complexes. The abundant aphid chromatin modifying enzymes may facilitate the phenotypic plasticity necessary to maintain the complex life cycle of the aphid.
Comparative analysis of detoxification enzymes in Acyrthosiphon pisum and Myzus persicae
Authors: Ramsey J. S. , Rider D. S. , Walsh T. K. , De Vos M. , Gordon K. H. J. , Ponnala L. , Macmil S. L. , Roe B. A. , Jander G.
Published: February 2010

Herbivorous insects use detoxification enzymes, including cytochrome P450 monooxygenases, glutathione S‐transferases, and carboxy/cholinesterases, to metabolize otherwise deleterious plant secondary metabolites. Whereas Acyrthosiphon pisum (pea aphid) feeds almost exclusively from the Fabaceae, Myzus persicae (green peach aphid) feeds from hundreds of species in more than forty plant families. Therefore, M. persicae as a species would be exposed to a greater diversity of plant secondary metabolites than A. pisum, and has been predicted to require a larger complement of detoxification enzymes. A comparison of M. persicae cDNA and A. pisum genomic sequences is partially consistent with this hypothesis. There is evidence of at least 40% more cytochrome P450 genes in M. persicae than in A. pisum. In contrast, no major differences were found between the two species in the numbers of glutathione S‐transferases, and carboxy/cholinesterases. However, given the incomplete M. persicae cDNA data set, the number of identified detoxification genes in this species is likely to be an underestimate.
A functional DNA methylation system in the pea aphid, Acyrthosiphon pisum
Authors: Walsh T. K. , Brisson J. A. , Robertson H. M. , Gordon K. , Jaubert‐Possamai S. , Tagu D. , Edwards O. R.
Published: February 2010

Methylation of cytosine is one of the main epigenetic mechanisms involved in controlling gene expression. Here we show that the pea aphid (Acyrthosiphon pisum) genome possesses homologues to all the DNA methyltransferases found in vertebrates, and that 0.69% (±0.25%) of all cytosines are methylated. Identified methylation sites are predominantly restricted to the coding sequence of genes at CpG sites. We identify twelve methylated genes, including genes that interact with juvenile hormone, a key endocrine signal in insects. Bioinformatic prediction using CpG ratios for all predicted genes suggest that a large proportion of genes are methylated within the pea aphid.
Who's the Expert? Rethinking authority in the face of intellectual disability
Authors: Carlson L.
Published: February 2010

This article poses the question, ‘Who is the expert?’ in relation to people with intellectual disabilities. It begins with an exploration of what it means to assert moral authority in relation to people with IDs, and makes the argument that ‘experts’ who draw moral boundaries, define conceptions of the ‘good’ and quality of life for people must consider how to occupy this position responsibly. It then considers a second form of authority –epistemic authority– and explores the moral responsibility that accompanies the practice of putting forth knowledge claims about ID. This involves acknowledging three potential problems: distancing, oppression and dehumanization. The article concludes with questions that point towards greater interdisciplinary dialogue regarding authority, responsibility and the role of the expert.
From autonomy to relationships: productive engagement with uncertainty
Authors: Clegg J. , Lansdall‐Welfare R.
Published: February 2010

This paper argues that we are at a point of change in ID services, that new ideas and different frames of reference are required to take services forward in the 21st century. We describe how contemporary thinking in architecture, philosophy and organisational theory can assist in generating service principles for specialist services that allow us to better address the continuing isolation that is the experience of many people with ID, and the moral judgements that can limit service possibilities. We do not seek to offer a rigid blueprint for any particular service but one that allows for agency from its participants and relationships between them.
A large cohort study of GJB2 mutations in Japanese hearing loss patients
Authors: Tsukada K , Nishio S , Usami S ,   the Deafness Gene Study Consortium
Published: February 2010

Tsukada K, Nishio S, Usami S, and the Deafness Gene Study Consortium. A large cohort study of GJB2 mutations in Japanese hearing loss patients.

GJB2 is the gene most frequently associated with hereditary hearing loss, and the GJB2 mutation spectrums vary among different ethnic groups. In this study, the mutation spectrum as well as clinical features of patients with GJB2 mutations as found in more than 1000 Japanese hearing loss families are summarized. The present results show that the frequency of GJB2 mutations in the Japanese population with hearing loss is 14.2% overall and 25.2% in patients with congenital hearing loss. c.235delC was the most frequent allele (49.8%), was associated with a more severe phenotype, and was mainly found in patients who were diagnosed by the age of 3. In contrast, the second most frequent was p.V37I (16.5%), which has a milder phenotype and was mainly found in patients diagnosed at a higher age. Additional clinical features in hearing loss patients with GJB2 mutations in this study were the near absence of tinnitus, vestibular dysfunction and inner ear malformations.
Somatic mosaicism in Cornelia de Lange syndrome: a further contributor to the wide clinical expressivity?
Authors: Castronovo P , Delahaye‐Duriez A , Gervasini C , Azzollini J , Minier F , Russo S , Masciadri M , Selicorni A , Verloes A , Larizza L
Published: February 2010

Castronovo P, Delahaye‐Duriez A, Gervasini C, Azzollini J, Minier F, Russo S, Masciadri M, Selicorni A, Verloes A, Larizza L. Somatic mosaicism in Cornelia de Lange syndrome: a further contributor to the wide clinical expressivity?

Cornelia de Lange syndrome (CdLS) is a rare, congenital syndrome characterized by growth retardation, dysmorphic face, mental retardation and limb reduction defects. Clinical manifestations of CdLS can be extremely variable. Mutations in NIPBL, SMC1A and SMC3 genes, encoding for a regulator and two subunits of the cohesin complex, respectively, are found in 60–65% of CdLS patients. We report on a male with CdLS who is mosaic for the c.2827delA mutation in the NIPBL gene. Allele quantitation by pyrosequencing showed the presence of the mutation in about 10% and 33% of DNA samples from peripheral blood and buccal smears, respectively. The patient shows a complex phenotype: growth and psychomotor retardation are characteristic of the severe forms of CdLS, while the absence of severe limb reduction defects and major malformations are typical of the mild phenotype. He also has depigmentation areas following Blashko lines, an unusual finding in CdLS, which has been associated with mosaicism in other genetic conditions. This case represents the first evidence of somatic mosaicism in CdLS and explains the mild phenotype in the patient as compared to that predicted by a truncating mutation. Besides confirming the clinical and genetic heterogeneity of CdLS, this case also raises the likely underestimated mutation rate of known genes and points to the complexity of addressing genotype–phenotype correlations.
Late‐onset venous outflow obstruction treated by placement of a Foley balloon catheter in living donor liver transplantation using a left lobe
Authors: Nomura Ryohei , Ishizaki Yoichi , Sugo Hiroyuki , Yoshimoto Jiro , Imamura Hiroshi , Kawasaki Seiji
Published: February 2010

Nomura R, Ishizaki Y, Sugo H, Yoshimoto J, Imamura, H, Kawasaki S. Late‐onset venous outflow obstruction treated by placement of a Foley balloon catheter in living donor liver transplantation using a left lobe.  Clin Transplant 2010: 24: 723–725. © 2010 John Wiley & Sons A/S.

Abstract:  A 60‐yr‐old man having hepatitis C virus‐associated liver cirrhosis and hepatocellular carcinoma underwent living donor liver transplantation using a left liver graft. On post‐operative day 20, the patient developed a large amount of ascites and hypovolemic shock because of decreased venous return. Emergency laparotomy revealed that fixation of the round ligament to the abdominal wall was loose, and free movement of the graft into the right subphrenic space had caused twisting the hepatic vein. After upward traction of the round ligament, two Foley balloon catheters were inserted into the right subphrenic space to maintain the graft in the midline portion. The catheters with the balloons were removed on day 30 after re‐operation. This method is easy, simple and inexpensive for the treatment of hepatic venous outflow block after partial liver transplantation.
Genetic basis of differential opsin gene expression in cichlid fishes
Authors: CARLETON K. L. , HOFMANN C. M. , KLISZ C. , PATEL Z. , CHIRCUS L. M. , SIMENAUER L. H. , SOODOO N. , ALBERTSON R. C. , SER J. R.
Published: February 2010

Visual sensitivity can be tuned by differential expression of opsin genes. Among African cichlid fishes, seven cone opsin genes are expressed in different combinations to produce diverse visual sensitivities. To determine the genetic architecture controlling these adaptive differences, we analysed genetic crosses between species expressing different complements of opsin genes. Quantitative genetic analyses suggest that expression is controlled by only a few loci with correlations among some genes. Genetic mapping identifies clear evidence of trans‐acting factors in two chromosomal regions that contribute to differences in opsin expression as well as one cis‐regulatory region. Therefore, both cis and trans regulation are important. The simple genetic architecture suggested by these results may explain why opsin gene expression is evolutionarily labile, and why similar patterns of expression have evolved repeatedly in different lineages.
Evolution of avian clutch size along latitudinal gradients: do seasonality, nest predation or breeding season length matter?
Authors: GRIEBELER E. M. , CAPRANO T. , BÖHNING‐GAESE K.
Published: February 2010

Birds display a latitudinal gradient in clutch size with smaller clutches in the tropics and larger in the temperate region. Three factors have been proposed to affect this pattern: seasonality of resources (SR), nest predation and length of the breeding season (LBS). Here, we test the importance of these factors by modelling clutch size evolution within bird populations under different environmental settings. We use an individual‐based ecogenetic simulation model that combines principles from population ecology and life history theory. Results suggest that increasing SR from the tropics to the poles by itself or in combination with a decreasing predation rate and LBS can generate the latitudinal gradient in clutch size. Annual fecundity increases and annual adult survival rate decreases from the tropics to the poles. We further show that the annual number of breeding attempts that (together with clutch size) determines total annual egg production is an important trait to understand latitudinal patterns in these life history characteristics. Field experiments that manipulate environmental factors have to record effects not only on clutch size, but also on annual number of breeding attempts. We use our model to predict the outcome of such experiments under different environmental settings.
Inheritance pattern of aluminum tolerance in pea
Authors: Singh D. , Choudhary A. K.
Published: February 2010

With 1 figure and 4 tables

An understanding of the inheritance of aluminum (Al) tolerance is important to breed for Al tolerant genotypes of pea (Pisum sativum L.). Therefore, an investigation was undertaken to infer genes governing Al tolerance in pea. To study the inheritance of Al tolerance, tolerant lines ‘Azad P1’ and ‘PC‐55‐11‐1‐2’ were crossed with sensitive lines ‘PC‐493‐5’ and ‘PSM‐2’. Parental, F1, F2 and backcross generations were grown in a nutrient solution containing 30 ppm of Al for haematoxylin staining and root regrowth and classified for tolerance by staining of root tips and root regrowth. The F1 hybrids responded similarly to the tolerant parents indicating dominance of Al tolerance over sensitivity. Segregation for tolerance vs. sensitivity in F2 fitted well with the 3 : 1 ratio expected for a single gene. The backcrosses involving dominant parents showed the dominant reaction on all the plants while those involving susceptible parents segregated into one tolerant to one sensitive ratio. Experimental results showed that Al tolerance is a monogenic dominant trait that can be easily transferred to desirable lines through backcross breeding programme.
Facial porokeratosis: A series of six patients
Authors: Gutierrez Ericson L , Galarza Carlos , Ramos Willy , Tello Mercedes , De Paz Patricia Chávez , Bobbio Lucia , Barquinero Alicia , Ronceros Gerardo , Ortega‐Loayza Alex G
Published: February 2010

Porokeratosis is a disorder of epidermal keratinization characterized by annular plaques with an atrophic centre and hyperkeratotic edges, and includes a heterogeneous group of disorders that are mostly inherited in an autosomal dominant fashion. Facial porokeratosis is rare and is not well documented. We present six cases of facial porokeratosis seen over a period of 15 years in a hospital in Lima, Peru. In most of the cases, porokeratosis was found in younger women without any significant past medical history. Oral isotretinoin showed moderate improvement in two of our patients.
ZJM‐289, a novel nitric oxide donor, alleviates the cerebral ischaemic–reperfusion injury in rats
Authors: Zhuang Pei , Ji Hui , Zhang Yi‐Hua , Min Zhen‐Li , Ni Qing‐Gui , You Ran
Published: February 2010

1. Current studies indicate that nitric oxide (NO) plays a dual role as both a protective and pathogenic factor in focal cerebral ischaemia depending on the level, location, source and environment. The present study hypothesized that the NO donor ZJM‐289 could inhibit cerebral ischaemia–reperfusion (I/R) injury and investigated the mechanism of the beneficial events.

2. Adult male rats were randomly divided into four groups: (i) sham operated; (ii) I/R (ischaemia for 90 min and reperfusion for 24 h) treated with vehicle; (iii) I/R treated with 0.1 mmol/kg body weight ZJM‐289; and (iv) I/R treated with 0.2 mmol/kg body weight ZJM‐289. We evaluated the changes in brain infarction, brain‐water content, neurological deficits and histopathology. Western blot analysis was used to study the expression of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) in the brain after I/R. The levels of NO and cyclic guanosine monophosphate (cGMP) were also determined.

3. ZJM‐289 reduced infarct volume and brain‐water content in ischemic brains and promoted functional recovery. Western blotting showed significant inhibition of nNOS in ZJM‐289 treated rats compared with untreated rats. However, eNOS expression in the ischemic brain was enhanced in the ZJM‐289 groups. The cGMP and NO levels increased in the ZJM‐289 groups after I/R. The study showed that ZJM‐289 could alleviate cerebral injury after I/R through inhibition of nNOS and stimulation of the NO/soluble guanylate cyclase/cGMP pathway. Therefore, a suitable NO donor might be an effective candidate for the treatment of acute stroke by neuroprotection.
Bellwether Citizens: The Regulation of Male Clients of Sex Workers
Authors: Brooks‐Gordon Belinda
Published: February 2010

Dangerous and discriminatory new provisions against sex workers' clients have repeatedly been put before parliament in England and Wales. Female ministers keen to punish clients of sex workers eagerly supported the Bill. However, while sex work has become a rights issue it is no longer just about women's rights. Diverse and multiple sexualities and working practices see gay, trans or bisexual workers selling sex to a diverse range of lesbian, gay, trans, and straight clients who may be able‐bodied or disabled. This article critically examines the regulation of clients of sex workers, explores the current legislation against them, and reviews recent research evidence. The ideas that inform policy will be discussed along with the various policy approaches. The latest move to criminalize clients in the Policing and Crime Bill 2009 will be discussed along with the spectre of trafficking, used to scapegoat clients by a government which has undermined civil liberties and the fundamental concepts of a free society.

[A]nyone indulging in sexual activity is entitled to a degree of privacy especially if it is on private property and between consenting adults (paid or unpaid)

                          Mr Justice Eady1
Industrial Relations Climate, Employee Voice and Managerial Attitudes to Unions: An Australian Study
Authors: Pyman Amanda , Holland Peter , Teicher Julian , Cooper Brian K.
Published: February 2010

This article examines how employee voice arrangements and managerial attitudes to unions shape employees' perceptions of the industrial relations climate, using data from the 2007 Australian Worker Representation and Participation Survey (AWRPS) of 1,022 employees. Controlling for a range of personal, job and workplace characteristics, regression analyses demonstrate that employees' perceptions of the industrial relations climate are more likely to be favourable if they have access to direct‐only voice arrangements. Where management is perceived by employees to oppose unions (in unionized workplaces), the industrial relations climate is more likely to be reported as poor. These findings have theoretical implications, and significant practical implications for employers, employees, unions and the government.
NARRATIVE AND MEANING IN SCIENCE AND RELIGION
Authors: Teske John A.
Published: February 2010

Differences of understanding in science and in religion can be explored via the distinction between paradigmatic and narrative modes of explanation. Although science is inclusive of the paradigmatic, I propose that in explaining the behavior of complex adaptive systems, and in the human sciences in particular, narratives may well constitute the best scientific explanations. Causal relationships may be embedded within, and expressions of higher‐order constraints provided by, complex system dynamics, best understood via the temporal organization of intentionalities that constitute narrative. Complex adaptive systems, out of which intentions emerge, have behavioral trajectories that are in principle unique, contingent, and nondeterministic even in stable states and unpredictable across phase transitions. Given such unpredictability, the only explanation can be an interpretive story that retrospectively retraces the actual changes in dynamics. Without narrative, personality traits and human actions are incomprehensible. Such phenomena do not permit a reduction of purposive acts to nonpurposive elements or of reasons to the causes they constrain. Causality does not exhaust meaning. Given the role of narratives in human lives, religion and mythology provide larger stories within which individual stories make sense. Differences between narrative and historical truth suggest how we can be constituted by what we imagine ourselves to be.
GAPS IN THE ARGUMENT: A DISCUSSION OF CERTAIN ASPECTS OF COSMOLOGY
Authors: Ruse Michael
Published: February 2010

In this discussion review of Robert John Russell's collection of essays I agree with him about the necessity of human existence given the claims of Christian theology. I look in detail at his suggestions for speaking to this issue, especially his thesis of NIODA—noninterventionist objective divine action. I end up disagreeing with the suggestion and argue that in respects Russell is tackling the science‐religion relationship in the wrong way.
ROBERT J. RUSSELL'S ESCHATOLOGICAL THEOLOGY IN THE CONTEXT OF COSMOLOGY
Authors: Drees Willem B.
Published: February 2010

The main title of Robert J. Russell's Cosmology from Alpha to Omega: The Creative Mutual Interaction of Theology and Science catches the substance of the essays; the subtitle his methodological vision. The mutualis modest as far as the influence from theology on science goes; in no way is Russell curtailing the pursuit of science. Driven by intellectual honesty, he holds that in the end religious convictions will have to stand the test of compatibility with scientific knowledge. And as a Christian he believes core beliefs of Christianity, reformulated as needed, will be able to stand this test. The essays address the origin and contingency of our universe in relation to belief in creation, and his proposal for noninterventionist objective divine action. For him a stumbling block is natural evil; the evolutionary intelligibility of evil falls short of what would be desirable theologically. As steps toward an adequate eschatology Russell seeks to develop a more complex understanding of temporality, and proposes to understand the resurrection of Jesus as the First Instantiation of a New Law of the New Creation. This area is more in tension with current science, but that could be expected when one moves from creation to redemption. Within his self‐imposed boundaries, these essays are well informed and well argued, and together they provide a sincere and sustained research program.
THE NATURE OF EMBODIMENT: RELIGION AND SCIENCE IN DIALOGUE
Authors: Pederson Ann Milliken
Published: February 2010

What is embodiment? And how does this notion apply not only to science qua science but also to the conversation between religion and science? I offer a descriptive analysis of an embodied conversation between religion, science, ethics, and technology. The domain of embodiment is one in which the participants practice humility in the face of others, become aware of their own limitations and finitude, bear witness to the other's finiteness and limitations, take account of the sociocultural atmosphere, and acknowledge the ethical weight of the conversation for all involved. I offer examples of how this tangled knot of emergent practices is put into play, examples that expand upon some notions of what conversations between religion and science should be like.
Neurocognitive stability in Asperger syndrome, ADHD, and reading and writing disorder: a pilot study
Authors: Nydén Agneta , Billstedt Eva , Hjelmquist Erland , Gillberg Christopher
Published: February 2010

Boys with Asperger syndrome (n=20), attention‐deficit‐hyperactivity disorder (n=20), and reading and writing disorder (n=20) were followed up and retested on several neuropsychological measures 1 to 2 years after initial assessments. Wechsler Intelligence Scale for Children (WISC‐III) Full Scale, Verbal, and Performance IQ scores remained stable for all diagnostic groups. Kaufman factors and ‘fluid’ and ‘crystallized’ abilities were also stable measures. Subtest stability over time, was slightly more variable. There was a tendency for the group with Asperger syndrome to deteriorate over time with respect to logical reasoning abilities. Measures of executive function/attention (‘go‐no‐go’ and ‘conflict’ tests) showed good test‐retest stability in all diagnostic groups. This is the first study of its kind.
An UNC‐49 GABA receptor subunit from the parasitic nematode Haemonchus contortus is associated with enhanced GABA sensitivity in nematode heteromeric channels
Authors: Siddiqui Salma Z. , Brown David D. R. , Rao Vijayaraghava T. S. , Forrester Sean G.
Published: February 2010

J. Neurochem. (2010) 113, 1113–1122.

We have identified two genes from the parasitic nematode Haemonchus contortus, Hco‐unc‐49B and Hco‐unc‐49C that encode two GABA‐gated chloride channel subunits. Electrophysiological analysis revealed that this channel has properties similar to those of the UNC‐49 channel from the free‐living nematode Caenorhabditis elegans. For example, the Hco‐UNC‐49B subunit forms a functional homomeric channel that responds to GABA and is highly sensitive to picrotoxin. Hco‐UNC‐49C alone does not respond to GABA but can assemble with Hco‐UNC‐49B to form a heteromeric channel with a lower sensitivity to picrotoxin. However, we did find that the Hco‐UNC‐49B/C heteromeric channel is significantly more responsive to agonists compared to the Hco‐UNC‐49B homomeric channel, which is the opposite trend to what has been found previously for the C. elegans channel. To investigate the subunit requirements for high agonist sensitivity, we generated cross‐assembled channels by co‐expressing the H. contortus subunits with UNC‐49 subunits from C. elegans (Cel‐UNC‐49). Co‐expressing Cel‐UNC‐49B with Hco‐UNC‐49C produced a heteromeric channel with a reduced sensitivity to GABA compared to that of the Cel‐UNC‐49B homomeric channel. In contrast, co‐expressing Hco‐UNC‐49B with Cel‐UNC‐49C produced a heteromeric channel that, like the Hco‐UNC‐49B/C heteromeric channel, exhibits an increased sensitivity to GABA. These results suggest that the Hco‐UNC‐49B subunit is the key determinant for the high agonist sensitivity of heteromeric channels.