bluuebunny/crossref_metadata_2025 huggingface dataset:
Premature replacement of μ with α immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation
Authors: Duchez Sophie , Amin Rada , Cogné Nadine , Delpy Laurent , Sirac Christophe , Pascal Virginie , Corthésy Blaise , Cogné Michel
Published: January 2010

Sequentially along B cell differentiation, the different classes of membrane Ig heavy chains associate with the Igα/Igβ heterodimer within the B cell receptor (BCR). Whether each Ig class conveys specific signals adapted to the corresponding differentiation stage remains debated. We investigated the impact of the forced expression of an IgA-class receptor throughout murine B cell differentiation by knocking in the human Cα Ig gene in place of the Sμ region. Despite expression of a functional BCR, homozygous mutant mice showed a partial developmental blockade at the pro-B/pre-BI and large pre-BII cell stages, with decreased numbers of small pre-BII cells. Beyond this stage, peripheral B cell compartments of reduced size developed and allowed specific antibody responses, whereas mature cells showed constitutive activation and a strong commitment to plasma cell differentiation. Secreted IgA correctly assembled into polymers, associated with the murine J chain, and was transported into secretions. In heterozygous mutants, cells expressing the IgA allele competed poorly with those expressing IgM from the wild-type allele and were almost undetectable among peripheral B lymphocytes, notably in gut-associated lymphoid tissues. Our data indicate that the IgM BCR is more efficient in driving early B cell education and in mucosal site targeting, whereas the IgA BCR appears particularly suited to promoting activation and differentiation of effector plasma cells.
A mutation of
Ikbkg
causes immune deficiency without impairing degradation of IκBα
Authors: Siggs Owen M. , Berger Michael , Krebs Philippe , Arnold Carrie N. , Eidenschenk Celine , Huber Christoph , Pirie Elaine , Smart Nora G. , Khovananth Kevin , Xia Yu , McInerney Gerald , Karlsson Hedestam Gunilla B. , Nemazee David , Beutler Bruce
Published: January 2010

Null alleles of the gene encoding NEMO (NF-κB essential modulator) are lethal in hemizygous mice and men, whereas hypomorphic alleles typically cause a syndrome of immune deficiency and ectodermal dysplasia. Here we describe an allele of
Ikbkg
in mice that impaired Toll-like receptor signaling, lymph node formation, development of memory and regulatory T cells, and Ig production, but did not cause ectodermal dysplasia. Degradation of IκBα, which is considered a primary requirement for NEMO-mediated immune signaling, occurred normally in response to Toll-like receptor stimulation, yet ERK phosphorylation and NF-κB p65 nuclear translocation were severely impaired. This selective loss of function highlights the immunological importance of NEMO-regulated pathways beyond IκBα degradation, and offers a biochemical explanation for rare immune deficiencies in man.
Members of the RSC Chromatin-Remodeling Complex Are Required for Maintaining Proper Nuclear Envelope Structure and Pore Complex Localization
Authors: Titus Laura C. , Dawson T. Renee , Rexer Deborah J. , Ryan Kathryn J. , Wente Susan R.
Published: January 2010

The assembly, distribution, and functional integrity of nuclear pore complexes (NPCs) in the nuclear envelope (NE) are key determinants in the nuclear periphery architecture. However, the mechanisms controlling proper NPC and NE structure are not fully defined. We used two different genetic screening approaches to identify Saccharomyces cerevisiae mutants with defects in NPC localization. The first approach examined green fluorescent protein (GFP)-Nic96 in 531 strains from the yeast Tet-promoters Hughes Collection with individual essential genes expressed from a doxycycline-regulated promoter (TetO7-orf). Under repressive conditions, depletion of the protein encoded by 44 TetO7-orf strains resulted in mislocalized GFP-Nic96. These included STH1, RSC4, RSC8, RSC9, RSC58, ARP7, and ARP9, each encoding components of the RSC chromatin remodeling complex. Second, a temperature-sensitive sth1-F793S (npa18-1) mutant was identified in an independent genetic screen for NPC assembly (npa) mutants. NPC mislocalization in the RSC mutants required new protein synthesis and ongoing transcription, confirming that lack of global transcription did not underlie the phenotypes. Electron microscopy studies showed significantly altered NEs and nuclear morphology, with coincident cytoplasmic membrane sheet accumulation. Strikingly, increasing membrane fluidity with benzyl alcohol treatment prevented the sth1-F793S NE structural defects and NPC mislocalization. We speculate that NE structure is functionally linked to proper chromatin architecture.
BEDTools: a flexible suite of utilities for comparing genomic features
Authors: Quinlan Aaron R. , Hall Ira M.
Published: January 2010

Motivation: Testing for correlations between different sets of genomic features is a fundamental task in genomics research. However, searching for overlaps between features with existing web-based methods is complicated by the massive datasets that are routinely produced with current sequencing technologies. Fast and flexible tools are therefore required to ask complex questions of these data in an efficient manner.

Results: This article introduces a new software suite for the comparison, manipulation and annotation of genomic features in Browser Extensible Data (BED) and General Feature Format (GFF) format. BEDTools also supports the comparison of sequence alignments in BAM format to both BED and GFF features. The tools are extremely efficient and allow the user to compare large datasets (e.g. next-generation sequencing data) with both public and custom genome annotation tracks. BEDTools can be combined with one another as well as with standard UNIX commands, thus facilitating routine genomics tasks as well as pipelines that can quickly answer intricate questions of large genomic datasets.

Availability and implementation: BEDTools was written in C++. Source code and a comprehensive user manual are freely available at http://code.google.com/p/bedtools

Contact:  aaronquinlan@gmail.com; imh4y@virginia.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Anti‐Obesity and Anti‐Diabetic Effects of Acacia Polyphenol in Obese Diabetic KKAy Mice Fed High‐Fat Diet
Authors: Ikarashi Nobutomo , Toda Takahiro , Okaniwa Takehiro , Ito Kiyomi , Ochiai Wataru , Sugiyama Kiyoshi
Published: January 2010

Acacia polyphenol (AP) extracted from the bark of the black wattle tree (Acacia meansii) is rich in unique catechin‐like flavan‐3‐ols, such as robinetinidol and fisetinidol. The present study investigated the anti‐obesity/anti‐diabetic effects of AP using obese diabetic KKAy mice. KKAy mice received either normal diet, high‐fat diet or high‐fat diet with additional AP for 7 weeks. After the end of administration, body weight, plasma glucose and insulin were measured. Furthermore, mRNA and protein expression of obesity/diabetic suppression‐related genes were measured in skeletal muscle, liver and white adipose tissue. As a result, compared to the high‐fat diet group, increases in body weight, plasma glucose and insulin were significantly suppressed for AP groups. Furthermore, compared to the high‐fat diet group, mRNA expression of energy expenditure‐related genes (PPARα, PPARδ, CPT1, ACO and UCP3) was significantly higher for AP groups in skeletal muscle. Protein expressions of CPT1, ACO and UCP3 for AP groups were also significantly higher when compared to the high‐fat diet group. Moreover, AP lowered the expression of fat acid synthesis‐related genes (SREBP‐1c, ACC and FAS) in the liver. AP also increased mRNA expression of adiponectin and decreased expression of TNF‐α in white adipose tissue. In conclusion, the anti‐obesity actions of AP are considered attributable to increased expression of energy expenditure‐related genes in skeletal muscle, and decreased fatty acid synthesis and fat intake in the liver. These results suggest that AP is expected to be a useful plant extract for alleviating metabolic syndrome.
Anti‐Atherogenic Activity of Ethanolic Fraction of Terminalia arjuna Bark on Hypercholesterolemic Rabbits
Authors: Subramaniam Saravanan , Subramaniam Ramachandran , Rajapandian Suja , Uthrapathi Subasini , Gnanamanickam Victor Rajamanickam , Dubey Govinda Prasad
Published: January 2010

Atherosclerosis which results from gradual deposition of lipids in medium and large arteries is a leading cause of mortality worldwide. Terminalia arjuna is a herb of Combretaceae family which contains hypolipidemic compounds and flavonoids with high antioxidative properties. This study was conducted to determine the effect of ethanolic fraction of T. arjuna on blood lipids and atherosclerosis in rabbits fed with high fat diet (HFD). Twenty New Zealand rabbits of either sex were randomly divided into five groups: the first two were normal diet group and HFD (21% fat) group and the remaining three groups received high cholesterol diet supplemented with standard drug (Atorvastatin 10 mg kg−1 body weight), T. arjuna ethanolic fraction (100 and 200 mg kg−1 body weight), respectively. The concentration of total cholesterol (TC), low density lipoprotein (LDL) cholesterol, triglycerides (TGs), very low density lipoprotein (VLDL) cholesterol and high density lipoprotein (HDL) cholesterol was determined in rabbits at the start of the experiment, at the 14th, 30th days and at the end of the study. Anti‐atherogenic index was calculated from the lipid profile of the rabbits before sacrifice. At the end of the experimental period, the aorta was removed for assessment of atherosclerotic plaques. Results show that T. arjuna significantly decreases TC, LDL and TG levels and increases HDL and lessens atherosclerotic lesion in aorta (P < .05). Hence T. arjuna extract can effectively prevent the progress of atherosclerosis. This is likely due to the effect of T. arjuna on serum lipoproteins and its antioxidant and anti‐inflammatory properties.
PCR characterization and typing of Klebsiella pneumoniae using capsular type-specific, variable number tandem repeat and virulence gene targets
Authors: Turton Jane F. , Perry Claire , Elgohari Suzanne , Hampton Catherine V.
Published: January 2010

A multiplex PCR is described which detects capsular types K1, K2, K5, K54 and K57, which are those most associated with invasive disease or pathogenicity, a further capsular type (K20), two putative virulence factors (rmpA and wcaG) and the 16S–23S internal transcribed spacer unit of Klebsiella pneumoniae, facilitating identification of this organism. wcaG encodes capsular fucose production and was associated with capsular types K1 and K54, but was also found in strains of other capsular types; 18 of the 543 isolates screened were PCR-positive for this gene. An eight-locus variable number tandem repeat (VNTR) scheme was designed, which provided discrimination at a level similar to that afforded by PFGE among a panel of 36 isolates representing 29 PFGE types. All isolates tested of the virulent K1 clone of CC23, associated with pyogenic liver abscesses, shared the same VNTR profile, which may be helpful in identifying this clone; such isolates were also PCR-positive for allS. These methods provide a rapid means of characterizing and typing isolates of this important agent of community-acquired and nosocomial infection.
The pmk1-like mitogen-activated protein kinase from Lecanicillium (Verticillium) fungicola is not required for virulence on Agaricus bisporus
Authors: Collopy Patrick D. , Amey Richard C. , Sergeant Martin J. , Challen Michael P. , Mills Peter R. , Foster Gary D. , Bailey Andy M.
Published: January 2010

In plant-pathogenic fungi, thepmk1 mitogen-activated protein kinase (MAPK) signalling pathway plays an essential role in regulating the development of penetration structures and the sensing of host-derived cues, but its role in other pathosystems such as fungal–fungal interactions is less clear. We report the use of a gene disruption strategy to investigate thepmk1-like MAPK,Lf pmk1 in the development ofLecanicillium fungicola(formerlyVerticillium fungicola) infection on the cultivated mushroomAgaricus bisporus.Lf pmk1 was isolated using a degenerate PCR-based approach and was shown to be present in a single copy by Southern blot analysis. Quantitative RT-PCR showed the transcript to be fivefold upregulated in cap lesions compared with pure culture.Agrobacterium-mediated targeted disruption was used to delete a central portion of theLf pmk1 gene. The resulting mutants showed normal symptom development as assessed byA. bisporusmushroom cap assays, sporulation patterns were normal and there were no apparent changes in overall growth rates. Our results indicate that, unlike the situation in fungal–plant pathogens, thepmk1-like MAPK pathway is not required for virulence in the fungal–fungal interaction between theL. fungicolapathogen andA. bisporushost. This observation may be of wider significance in other fungal–fungal and/or fungal–invertebrate interactions.
Capsule depolymerase overexpression reduces Bacillus anthracis virulence
Authors: Scorpio Angelo , Chabot Donald J. , Day William A. , Hoover Timothy A. , Friedlander Arthur M.
Published: January 2010

Capsule depolymerase (CapD) is aγ-glutamyl transpeptidase and a product of theBacillus anthraciscapsule biosynthesis operon. In this study, we examined the effect of modulatingcapDexpression onB. anthraciscapsule phenotype, interaction with phagocytic cells and virulence in guinea pigs. Transcriptional fusions ofcapDwere made to the genes encoding heat-shock protein 60 (hsp60) and elongation factor Tu (EFTu), and tocapA,aB. anthraciscapsule biosynthesis gene. Translation signals were altered to improve expression ofcapD, including replacing the putative ribosome-binding site with a consensus sequence and the TTG start codon with ATG. CapD was not detected by immunoblotting in lysates from wild-typeB. anthracisAmes but was detected in strains engineered with a consensus ribosome-binding site forcapD. Strains overexpressingcapDat amounts detected by immunoblotting were found to have less surface-associated capsule and released primarily lower-molecular-mass capsule into culture supernatants. Overexpression ofcapDincreased susceptibility to neutrophil phagocytic killing and adherence to macrophages and resulted in reduced fitness in a guinea pig model of infection. These data suggest thatB. anthracismay have evolved weakcapDexpression resulting in optimized capsule-mediated virulence.
The 4.5S RNA component of the signal recognition particle is required for group A Streptococcus virulence
Authors: Treviño Jeanette , Perez Nataly , Sumby Paul
Published: January 2010

The signal recognition particle (SRP) is a ribonucleoprotein complex that targets proteins for secretion in a co-translational manner. While originally thought to be essential in all bacteria, recent data show that the SRP is dispensable in at least some streptococcal species. The SRP from the human pathogen group A Streptococcus (GAS, Streptococcus pyogenes) is predicted to be composed of protein Ffh and 4.5S RNA. Deletion of ffh alters the secretion of several GAS proteins, and leads to a severe reduction in virulence. Here, we report that mutation of the gene encoding 4.5S RNA results in phenotypes both similar to and distinct from that observed following ffh mutation. Similarities include a reduction in secretion of the haemolysin streptolysin O, and attenuation of virulence as assessed by a murine soft tissue infection model. Differences include a reduction in transcript levels for the genes encoding streptolysin O and NAD-glycohydrolase, and the reduced secretion of the SpeB protease. Several differences in transcript abundance between the parental and mutant strain were shown to be dependent on the sensor-kinase-encoding gene covS. Using growth in human saliva as an ex vivo model of upper respiratory tract infection we identified that 4.5S RNA mutation leads to a 10-fold reduction in colony-forming units over time, consistent with the 4.5S RNA contributing to GAS growth and persistence during upper respiratory tract infections. Finally, we determined that the 4.5S RNA was essential for GAS to cause lethal infections in a murine bacteraemia model of infection. The data presented extend our knowledge of the contribution of the SRP to the virulence of an important Gram-positive pathogen.
Interaction of herpes simplex virus type 2 (HSV-2) glycoprotein D with the host cell surface is sufficient to induce Chlamydia trachomatis persistence
Authors: Vanover J. , Kintner J. , Whittimore J. , Schoborg R. V.
Published: January 2010

When presented with certain unfavourable environmental conditions, Chlamydia trachomatis reticulate bodies (RBs) enter into a viable, yet non-cultivable state called persistence. Previously, we established an in vitro C. trachomatis and herpes simplex virus type 2 (HSV-2) co-infection model. These data indicate that (i) viral co-infection stimulates chlamydial persistence, (ii) productive HSV replication is not required for persistence induction, and (iii) HSV-induced persistence is not mediated by any currently characterized anti-chlamydial pathway or persistence inducer. In this study we demonstrated that chlamydial infectivity, though initially suppressed, recovered within 44 h of co-infection with UV-inactivated HSV-2, demonstrating that HSV-induced persistence is reversible. Co-incubation of chemically fixed, HSV-2-infected inducer cells with viable, C. trachomatis-infected responder cells both suppressed production of infectious chlamydial progeny and stimulated formation of swollen, aberrantly shaped RBs. In addition, pre-incubation of viral particles with viral glycoprotein D (gD)-specific neutralizing antibody prevented co-infection-induced persistence. Finally, exposure of C. trachomatis-infected cells to a soluble, recombinant HSV-2 gD : Fc fusion protein decreased production of infectious EBs to a degree similar to that observed in co-infected cultures. Thus, we conclude that interaction of HSV gD with the host cell surface is sufficient to trigger a novel host anti-chlamydial response that restricts chlamydial development.
A novel redox-sensing transcriptional regulator CyeR controls expression of an Old Yellow Enzyme family protein in Corynebacterium glutamicum
Authors: Ehira Shigeki , Teramoto Haruhiko , Inui Masayuki , Yukawa Hideaki
Published: January 2010

Corynebacterium glutamicum cgR_2930 (cyeR) encodes a transcriptional regulator of the ArsR family. Its gene product, CyeR, was shown here to repress the expression of cyeR and the cgR_2931 (cye1)–cgR_2932 operon, which is located upstream of cyeR in the opposite orientation. The cye1 gene encodes an Old Yellow Enzyme family protein, members of which have been implicated in the oxidative stress response. CyeR binds to the intergenic region between cyeR and cye1. Expression of cyeR and cye1 is induced by oxidative stress, and the DNA-binding activity of CyeR is impaired by oxidants such as diamide and H2O2. CyeR contains two cysteine residues, Cys-36 and Cys-43. Whereas mutation of the former (C36A) has no effect on the redox regulation of CyeR activity, mutating the latter (C43A, C43S) abolishes the DNA-binding activity of CyeR. Cys-43 of CyeR and its C36A derivative are modified upon treatment with diamide, suggesting an important role for Cys-43 in the redox regulation of CyeR activity. It is concluded that CyeR is a redox-sensing transcriptional regulator that controls cye1 expression.
The β-ketoadipate pathway of Acinetobacter baylyi undergoes carbon catabolite repression, cross-regulation and vertical regulation, and is affected by Crc
Authors: Bleichrodt Fenja S. , Fischer Rita , Gerischer Ulrike C.
Published: January 2010

The degradation of many structurally diverse aromatic compounds inAcinetobacter baylyiis accomplished by theβ-ketoadipate pathway. In addition to specific induction of expression by certain aromatic compounds, this pathway is regulated by complex mechanisms at multiple levels, which are the topic of this study. Multiple operons feeding into theβ-ketoadipate pathway are controlled by carbon catabolite repression (CCR) caused by succinate plus acetate. The pathways under study enable the catabolism of benzoate (ben), catechol (catA),cis,cis-muconate (catB,C,I,J,F,D), vanillate (van), hydroxycinnamates (hca), dicarboxylates (dca), salicylate (sal), anthranilate (ant) and benzyl esters (are). For analysis of CCR at the transcriptional level a luciferase reporter gene cassette was introduced into the operons. The Crc (cataboliterepressioncontrol) protein is involved in repression of all operons (except forcatA), as demonstrated by the analysis of respectivecrcstrains. In addition, cross-regulation was demonstrated for thevanA,B,hcaanddcaoperons. The presence of protocatechuate caused transcriptional repression of thevanA,B- andhca-encoded funnelling pathways (vertical regulation). Thus the results presented extend the understanding both of CCR and of the effects of Crc for all aromatic degradative pathways ofA. baylyiand increase the number of operons known to be controlled by two additional mechanisms, cross-regulation and vertical regulation.
The two‐component histidine kinase Fhk1 controls stress adaptation and virulence of Fusarium oxysporum
Authors: RISPAIL NICOLAS , DI PIETRO ANTONIO
Published: January 2010

Fungal histidine kinases (HKs) have been implicated in different processes, such as the osmostress response, hyphal development, sensitivity to fungicides and virulence. Members of HK class III are known to signal through the HOG mitogen‐activated protein kinase (MAPK), but possible interactions with other MAPKs have not been explored. In this study, we have characterized fhk1, encoding a putative class III HK from the soil‐borne vascular wilt pathogen Fusarium oxysporum. Inactivation of fhk1 resulted in resistance to phenylpyrrole and dicarboximide fungicides, as well as increased sensitivity to hyperosmotic stress and menadione‐induced oxidative stress. The osmosensitivity of Δfhk1 mutants was associated with a striking and previously unreported change in colony morphology. The Δfhk1 strains showed a significant decrease in virulence on tomato plants. Epistatic analysis between Fhk1 and the Fmk1 MAPK cascade indicated that Fhk1 does not function upstream of Fmk1, but that the two pathways may interact to control the response to menadione‐induced oxidative stress.
Impacts of shellfisheries and nutrient inputs on waterbird communities in the Wash, England
Authors: Atkinson Philip W. , Maclean Ilya M.D. , Clark Nigel A.
Published: January 2010

1. Overexploited fisheries threaten many species that depend on the exploited resource. Shorebird populations are in decline globally and here we describe how changing shellfishery management and nutrient inputs have had dramatic influence on waterbird communities on an internationally important wetland.

2. Cockle Cerastoderma edule and mussel Mytilus edulis fisheries conflict with shorebirds by removing prey and increasing mortality amongst non‐target benthic invertebrates. Under intense dredging pressure, evidence suggests that benthic invertebrates such as worms, with rapid growth and short‐generation times, should predominate over species such as bivalves, with slower growth and longer generation times.

3. We investigated the change in the waterbird assemblage in the Wash, eastern England, between 1981–1982 and 2002–2003. This period was characterized by heavy fishing pressure on mussels and cockles, ultimately leading to a crash in the mussel stocks.

4. During the study period, the waterbird assemblage underwent a gradual change from one dominated by those species with a high proportion of bivalves or ‘other’ prey (e.g. crustaceans, fish) in their diet to those with a higher proportion of worms. This gradual change was punctuated by major shifts, corresponding to three winters when oystercatcher Haemotopus ostralegus mortality was 5–13 times normal winter levels.

5. Oystercatcher, knot Calidris canutus and shelduck Tadorna tadorna showed the highest levels of decline. Since the last major oystercatcher mortality event in 1996–1997, the assemblage has not shifted back to that observed prior to the major crash in the mussel stock in 1992.

6. Changes in the waterbird assemblage were significantly related to mussel and cockle stock levels and, to a lesser extent, nutrient levels. Although correlative, evidence from this study indicates that fisheries caused shifts towards a waterbird community dominated by species with a high proportion of worms in their diet.

7.
Synthesis and applications. Mechanical shellfisheries directly conflict with the nature conservation interest of sites holding internationally important waterbird populations. Removal of the mussel beds in the Wash led to major shifts in the waterbird assemblage, with a shift towards worm‐feeders. Setting annual quotas that provide sufficient food for shellfish‐eating birds is essential to maintain the favourable status of this and other internationally important wetlands where shellfish are exploited.
Haemochromatosis genotype and iron overload: association with hypertension and left ventricular hypertrophy
Authors: Ellervik C. , Tybjærg‐Hansen A. , Appleyard M. , Ibsen H. , Nordestgaard B. G.
Published: January 2010

Abstract.  Ellervik C, Tybjærg‐Hansen A, Appleyard M, Ibsen H, Nordestgaard BG (Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Herlev; Næstved Hospital, University of Copenhagen, Naestved; Copenhagen University Hospital, University of Copenhagen, Copenhagen East; Bispebjerg Hospital, Copenhagen University Hospital, University of Copenhagen, Bispebjerg; and Holbaek Hospital, Holbaek; Denmark). Haemochromatosis genotype and iron overload: association with hypertension and left ventricular hypertrophy. J Intern Med 2010; 268: 252–264.

Objective.  We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH).

Methods.  We analysed data from a cross‐sectional study of the general population including 8992 individuals from the Copenhagen City Heart Study (CCHS), a follow‐up study of 36 480 individuals from the Copenhagen General Population Study (CGPS), and a case‐only study of 3815 Scandinavians from the Losartan Intervention For End‐point Reduction in Hypertension Genetic Substudy (LIFEGEN) with LVH and hypertension.

Results.  In the CCHS, individuals with C282Y/C282Y versus wild type/wild type had an odds ratio for antihypertensive medication use of 4.8 (1.8–13; P = 0.003). In the CGPS, the corresponding hazard ratio was 1.7 (1.0–2.3; P = 0.003). Also, hazard ratios for antihypertensive medication use in the CGPS were 1.6 (1.0–2.6; P = 0.05) for transferrin saturation ≥80% vs. <50%, and 2.3 (1.3–4.2; P = 0.005) for C282Y/C282Y + transferrin saturation ≥80% vs. wild type/wild type + transferrin saturation <50%. These results were most pronounced in men above 55 years of age. We did not find any association between C282Y/C282Y or iron overload and LVH or hypertension (measured as blood pressure at a single occasion or continuous blood pressure), or LVH with hypertension in the CCHS or with severity of LVH in LIFEGEN.

Conclusions.  We found that haemochromatosis genotype C282Y/C282Y and extremely elevated transferrin saturation either separately or combined were associated with increased risk of antihypertensive medication use. Therefore, testing for haemochromatosis genotype C282Y/C282Y and extreme transferrin saturation could be considered in patients with essential hypertension.
Disruption of Nap14, a plastid‐localized non‐intrinsic ABC protein in Arabidopsis thaliana results in the over‐accumulation of transition metals and in aberrant chloroplast structures
Authors: SHIMONI‐SHOR EINAV , HASSIDIM MIRIAM , YUVAL‐NAEH NAOMI , KEREN NIR
Published: January 2010

Chloroplasts are the major sink for Fe in shoot tissues because of the requirements of the photosynthetic process and to storage in ferritins. Such requirements are common both to plastids and to their evolutionary progenitors, the cyanobacteria. Here, we examined whether iron transport mechanisms were conserved throughout the evolution of photosynthetic organisms. Comparison of the sequences of putative plastid transporters from Arabidopsis thaliana with those involved in cyanobacterial Fe transport identified two orthologs of the FutC protein, AtNAP11 and AtNAP14. To study their function, we analysed insertional mutants in the genes coding for these proteins. Both nap11/nap11 and nap14/nap14 plants exhibited severe growth defects. Significant changes in transition metal homeostasis were detected only in nap14/nap14. This mutant was found to contain ∼18 times more Fe in the shoot tissue than in wild‐type plants. The increased shoot transition metal content was accompanied by a specific loss of chloroplast structures and by a reduction in transcript levels of Fe homeostasis‐related genes. Based on these results, we propose that AtNAP14 plays an important role in plastid transition metal homeostasis. One possibility is that AtNAP14 is part of a chloroplast transporter complex. Alternatively, AtNAP14 function may be in regulating transition metal homeostasis.
How to read a nephrology systematic review
Authors: PALMER SUETONIA C , NAVANEETHAN SANKAR D , STRIPPOLI GIOVANNI FM
Published: January 2010

A systematic review provides the best summary of evidence for clinical decision‐making in nephrology by summarizing all the primary studies that evaluate a specific clinical question. By using rigorous and pre‐specified methods, conclusions about the overall effect of an intervention can be more reliable, precise and comprehensive in a systematic review than those derived from individual studies. In this article, we describe the key components of a systematic review and meta‐analysis. We summarize the features of a systematic review that should be looked for when considering the accuracy and validity of its results – particularly when applying the outcomes of a systematic review to a clinical question.
The depth of the prostatic apex is an independent predictor of positive apical margins at radical prostatectomy
Authors: Matikainen Mika P. , Von Bodman Christian J. , Secin Fernando P. , Yunis Luis Herran , Vora Kinjal , Guillonneau Bertrand , Laudone Vincent , Eastham James A. , Scardino Peter T. , Akin Oguz , Rabbani Farhang
Published: January 2010

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To determine the effect of a deep and narrow pelvis on apical positive surgical margins (PSM) at radical prostatectomy (RP), controlling for other clinical and pathological variables and surgical approach, i.e. open retropubic (RRP) vs laparoscopic (LRP), as apical dissection is expected to be more challenging at RP with a prostate situated deep in a narrow pelvis.

PATIENTS AND METHODS

From July 2003 to January 2005, 512 consecutive patients with preoperative prostate magnetic resonance imaging (MRI) underwent RRP or LRP with no previous radio‐ or hormonal therapy. An additional 74 patients with preoperative MRI undergoing RP from December 2001 to June 2007 who had an apical PSM were also included, with 586 patients comprising the study population. Bony and soft‐tissue pelvic dimensions, including interspinous distance (ISD), bony (BFW) and soft tissue (SW) pelvic width, apical prostate depth (AD) and symphysis pubis angle, were measured on preoperative MRI. The pelvic dimension index (PDI), bony width index (BWI) and soft‐tissue width index (SWI) were defined as ISD/AD, BFW/AD and SW/AD, respectively. Multivariate logistic regression was used to assess the effect of pelvic dimensions on apical PSM, controlling for surgical approach and clinical and pathological variables.

RESULTS

There was no significant difference in ISD, BFW, SW or symphysis angle between patients with and without apical PSM. The AD was significantly greater in men with an apical PSM and consequently PDI, BWI and SWI were significantly lower in men with an apical PSM. Each of PDI, AD, BWI and SWI was a significant independent predictor of apical PSM, independent of surgical approach, and other clinicopathological variables. The main limitations of the study were that it was retrospective, and the relatively few patients with apical PSM.

CONCLUSIONS

Apical prostate depth is an independent risk factor for apical PSM at RP. MRI pelvimetry might allow for preoperative planning of the approach to RP.
Laparoscopic ureterolysis with omental wrap for idiopathic retroperitoneal fibrosis
Authors: Stein Robert J. , Patel Neil S. , Quinn Kyle , Berger Milton , Koff Walter , Shah Gaurang , Aron Monish , Berger Andre K.
Published: January 2010

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To describe various approaches for ureterolysis with an omental wrap using minimally invasive techniques, as surgery for idiopathic retroperitoneal fibrosis includes tissue biopsy, ureterolysis, and intraperitonealization or omental wrap.

PATIENTS AND METHODS

Since 2006 we have performed ureterolysis in four patients diagnosed with retroperitoneal fibrosis in two institutions. The ureterolysis in two cases was bilateral, using a standard laparoscopic approach for one case and a hand‐assisted technique for the other. Unilateral ureterolysis was completed using a standard laparoscopic approach in one case and was converted to a hand‐assisted technique in the other due to difficulty with ureteric identification. An omental wrap was used after ureterolysis for all renal units.

RESULTS

A minimally invasive technique was used for all ureterolysis procedures and none required open conversion. There was fascial dehiscence after surgery at the hand‐port site in one patient, and required re‐operation for wound closure. The median (range) hospital stay for all patients was 2.5 (2–10) days and the median blood loss was 100 (50–550) mL. No patient required a blood transfusion. At a median 16.5  (12–32) months of follow‐up, there was symptomatic and radiographic success in all patients.

CONCLUSIONS

Ureterolysis can be a challenging operation depending on the extent of the retroperitoneal mass. An understanding of various laparoscopic techniques can provide the flexibility for successful completion of nearly all of these procedures using a minimally invasive approach.
Intractable haematuria: long‐term results after selective embolization of the internal iliac arteries
Authors: Liguori Giovanni , Amodeo Antonio , Mucelli Fabio Pozzi , Patel Hiten , Marco Doddi , Belgrano Emanuele , Trombetta Carlo
Published: January 2010

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To determine the feasibility and efficacy of transarterial embolization (TAE) in haemorrhagic urological emergencies, and to assess the perioperative morbidity, effect of timing of intervention on the requirement for blood transfusion, and the long‐term follow‐up.

PATIENTS AND METHODS

Between October 1997 and March 2009, 44 patients (30 men and 14 women; mean age 79 years, range 51–95) with intractable haematuria secondary to advanced pelvic tumour arising from or invading the bladder, underwent internal iliac TAE. Twenty‐four patients had transitional carcinoma of the urinary bladder, 12 adenocarcinoma of the prostate, five carcinoma of the uterus, one cancer of the vagina, two carcinoma of the rectum, three carcinoma of the kidney, two simultaneous carcinoma of prostate and bladder, one simultaneous carcinoma of prostate and kidney and one had haemorrhagic cystitis after radiotherapy.

RESULTS

TAE of the internal iliac arteries produced initial complete control of bleeding in 36 of the 44 patients (82%). At a mean (range) follow‐up of 10.5 (1–97) months TAE there was permanent control of bleeding in 19 (43%) patients. A second TAE session was use in five (11%) patients and it was successful in two of them. There were 24 patients (55%) who required a mean of 4 (1–17) transfusion units before embolization; only 13 (30%) required more blood products after TAE. The mean haematocrit level before and after TAE was 27% and 31% (P < 0001), and the respective haemoglobin level were 8.7 and 10.3 g/dL (P < 0001). During the follow‐up there were no major complications related to TAE; minor complications were post‐TAE syndrome in 12 (27%) patients, fever (11%), gluteus pain (14%), nausea (2%), and exterior genital oedema (5%). The 6‐ and 12‐month mortality rates were 66% (29 patients) and 18% (eight), respectively.

CONCLUSIONS

TAE should be considered as an alternative less‐invasive palliative measure and the treatment of choice in these situations. TAE should always be bilateral, the catheter should advance distally to the origin of the superior gluteal artery and the artery embolized with unresorbable particles. Our study confirms the efficacy and safety of TAE in patients with pelvic malignancy, and indicates that this technique should be considered before surgery. The procedure combines the benefits of a minimally invasive approach in decreasing the cost of surgery and operating time, while maintaining low blood loss and analgesia requirement.
Investigation of the association of BMP gene variants with nephropathy in Type 1 diabetes mellitus
Authors: McKnight A. J. , Pettigrew K. A. , Patterson C. C. , Kilner J. , Sadlier D. M. , Maxwell A. P. ,   the Warren 3/UK GoKinD Study Group
Published: January 2010

Diabet. Med. 27, 624–630 (2010)

Aims  Diabetic nephropathy is a leading cause of end‐stage renal disease. The transforming growth factor β–bone morphogenic protein (BMP) pathway is implicated in the pathogenesis of diabetic nephropathy. The BMP2, BMP4 and BMP7 genes are located near linkage peaks for renal dysfunction, and we hypothesize that genetic polymorphisms in these biological and positional candidate genes may be risk factors for diabetic kidney disease.

Methods  The BMP7 gene was screened, variants identified and allele frequencies determined by bidirectionally sequencing 46 individuals to facilitate selection of tag SNPs (n = 4). For BMP2 and BMP4 genes, data were downloaded for 19 single nucleotide polymorphisms (SNPs) from the International HapMap project and six tag SNPs selected.

Results  The BMP7 gene was screened for novel genetic polymorphisms, haplotypes were identified, an appropriate subset of variants selected for the investigation of common genetic risk factors, and BMP2, BMP4 and BMP7 genes assessed for association with diabetic nephropathy in 1808 individuals. Thirty‐two SNPs were identified, of which 11 were novel, including an amino‐acid changing SNP (+63639C>T). No significant differences (P > 0.2) were observed when comparing genotype or allele or haplotype frequencies between 864 individuals with Type 1 diabetes and nephropathy compared with 944 individuals with Type 1 diabetes without nephropathy, stratified by recruitment centre.

Conclusions  Common polymorphisms in these BMP genes do not strongly influence genetic susceptibility to diabetic nephropathy in White individuals with Type 1 diabetes mellitus.
CAN THE HUMAN CAPITAL APPROACH EXPLAIN LIFE‐CYCLE WAGE DIFFERENTIALS BETWEEN RACES AND SEXES?
Authors: WU HUOYING
Published: January 2010

Using data from the National Longitudinal Survey of Youth–1979 cohort (NLSY79), this paper shows the importance of postschool human capital investment in describing both gender and racial wage gaps. The empirical results suggest that male‐female wage gaps, regardless of race, are mainly caused by gender differences in the human capital production process; generally, men gain more work experience and therefore have lower marginal costs of human capital production. Black‐white lifetime wage differentials could partly result from higher implicit interest rates for blacks, while the deterioration of black males’ relative economic status as they age can be attributed to higher depreciation rates of their human capital stock. (JEL J24, J30, C61)
CLASSROOM EXPERIMENTS: NOT JUST FUN AND GAMES
Authors: DURHAM YVONNE , MCKINNON THOMAS , SCHULMAN CRAIG
Published: January 2010

The impact of classroom experiments on student performance, attitudes towards economics, and retention is examined. Experiments increase cognitive gains overall but may be more helpful in teaching some topics than others. The size of the impact varies with preferred learning style. Multimodal and kinesthetic learners are significantly affected, while read–write learners fare just as well with the traditional lecture/discussion format. Attitudes towards economics and retention of economic knowledge are also improved by classroom experiments. The results indicate that the costs of implementing experiments in the classroom may very well be offset by the benefits to students. (JEL A22, C90)
THE SUCCESS OF THE FED AND THE DEATH OF MONETARISM
Authors: KISHOR N. KUNDAN , KOCHIN LEVIS A.
Published: January 2010

We propose an explanation for the demise of monetarism in the United States. We show that optimal monetary policy would lead to zero correlation between monetary aggregates and inflation if the effect of monetary aggregates on inflation is known precisely and to negative correlations if there is coefficient uncertainty. From 1960 to 1982 the correlation of the monetary base and inflation was positive and so the variance in the growth rate of monetary base in the United States was clearly too large monetary base growth destabilized inflation. However, from 1983 to 2003 variations in monetary base growth were clearly stabilizing and could have been just right. (JEL E52, E31, E32)
EMPLOYMENT EFFECTS OF TWO NORTHWEST MINIMUM WAGE INITIATIVES
Authors: SINGELL LARRY D. , TERBORG JAMES R.
Published: January 2010

This article exploits a natural experiment initiated by Oregon and Washington voter referendums to show that the minimum wage is a blunt instrument that differentially affects low‐wage workers within and across industries. Specifically, employment growth specifications indicate that the minimum wage generates consistently negative employment effects for eating and drinking workers where the minimum is shown to be relatively binding, but not for hotel and lodging workers where the minimum is less binding. Regressions using job‐specific want‐ad data from Portland and Seattle newspapers also indicate a reduction in hiring solicitation relating to the extent that the minimum wage binds. (JEL J31, J38)
School‐based interventions promoting both physical activity and healthy eating in Europe: a systematic review within the HOPE project
Authors: De Bourdeaudhuij I. , Van Cauwenberghe E. , Spittaels H. , Oppert J.‐M. , Rostami C. , Brug J. , Van Lenthe F. , Lobstein T. , Maes L.
Published: January 2010

It is the purpose of this study to systematically review the evidence of school‐based interventions targeting dietary and physical activity behaviour in primary (6–12 years old) and secondary school (12–18 years old) children in Europe. Eleven studies (reported in 27 articles) met the inclusion criteria, six in primary school and five in secondary school children. Interventions were evaluated in terms of behavioural determinants, behaviour (diet and physical activity) and weight‐related outcomes (body mass index [BMI] or other indicators of obesity). The results suggest that combining educational and environmental components that focus on both sides of the energy balance give better and more relevant effects. Furthermore, computer‐tailored personalized education in the classroom showed better results than a generic classroom curriculum. Environmental interventions might include organized physical activities during breaks, or before and after school; improved availability of physical activity opportunities in and around the school environment; increased physical education lesson time; improved availability or accessibility of healthy food options; and restricted availability and accessibility of unhealthy food options. More high‐quality studies are needed to assess obesity‐related interventions in Europe.
Sociolinguistic Variation in the Speech of Learners of Chinese as a Second Language
Authors: Li Xiaoshi
Published: January 2010

With Chinese native‐speaker data as the baseline, this study investigates the use of the morphosyntactic particle DE by learners of Chinese as a second language. The general patterns are as follows: (a) DE tends to be deleted more in informal speech than in formal settings; (b) higher proficiency and longer residence in China—more interactions with native speakers—promote DE deletion; and (c) females tend to adopt more formal language style and use DE more than males. The study also found that teachers and textbooks use DE much more often than native speakers. Learners’ patterns of DE use closely follow those of their teachers and textbooks, suggesting the necessity of explicit instruction in sociolinguistic variants in L2 classrooms.
Prevalence and risk factors for postpartum depression among women with preterm and low‐birth‐weight infants: a systematic review
Authors: Vigod SN , Villegas L , Dennis C‐L , Ross LE
Published: January 2010

Please cite this paper as: Vigod S, Villegas L, Dennis C‐L, Ross L. Prevalence and risk factors for postpartum depression among women with preterm and low‐birth‐weight infants: a systematic review. BJOG 2010;117:540–550.

Background  Although much is known about the risk factors for postpartum depression (PPD), the role of giving birth to a preterm or low‐birth‐weight infant has not been reviewed systematically.

Objective  To review systematically the prevalence and risk factors for PPD among women with preterm infants.

Search strategy  Medline, CINAHL, EMBASE, PsycINFO and the Cochrane Library were searched from their start dates to August 2008 using keywords relevant to depression and prematurity.

Selection criteria  Peer‐reviewed articles were eligible for inclusion if a standardised assessment of depression was administered between delivery and 52 weeks postpartum to mothers of preterm infants.

Data collection and analysis  Data on either the prevalence of PPD or mean depression score in the target population and available comparison groups were extracted from the 26 articles included in the review. Risk factors for PPD were also extracted where reported.

Main results  The rates of PPD were as high as 40% in the early postpartum period among women with premature infants. Sustained depression was associated with earlier gestational age, lower birth weight, ongoing infant illness/disability and perceived lack of social support. The main limitation was that most studies failed to consider depression in pregnancy as a confounding variable.

Author’s conclusions  Mothers of preterm infants are at higher risk of depression than mothers of term infants in the immediate postpartum period, with continued risk throughout the first postpartum year for mothers of very‐low‐birth‐weight infants. Targeted clinical interventions to identify and prevent PPD in this vulnerable obstetric population are warranted.