bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of High Molecular Weight Glutenins on Viscoelastic Properties of Intact Wheat Kernel and Relation to Functional Properties of Wheat Dough
Authors: Figueroa J. D. C. , Maucher Tanja , Reule W. , Peña R. J.
Published: March 2009

High and low molecular weight glutenin subunits (HMW‐GS and LMW‐GS, respectively) are the main factors determining the viscoelastic properties of wheat dough. The mechanical and viscoelastic properties of 29 samples of wheat kernels differing in HMW‐GS were evaluated with load‐compression tests. Samples were grouped by genotypes differing in HMW‐GS composition (allelic variants: Glu‐A1: null, 1, 2*; Glu‐B1: 7, 7+8, 7+9, 13+16, and 17+18; Glu‐D1: 5+10, 2+12). Groups representing Glu‐A1 1 and 2*; Glu‐B1 7, 7+9 and 17+18; and Glu‐D1 5+10 generally possessed hard grain and showed the largest kernel elasticity values, while those representing subunits Glu‐A1 null; Glu‐B1 7+8; and Glu‐D1 2+12 had soft kernels and showed lower elastic work values. Genotypes possessing HMW‐GS 1, 17+18 and 5+10 gave large SDS‐sedimentation values and better dough viscoelastic properties than those with allelels: null, 7+8, and 2+12. Kernel hardness showed significant correlation with the dough‐strength‐related parameters: SDS‐sedimentation; dough mixing time; and the alveographic parameters, W and P. There was a negative correlation between kernel plastic work and dough mixing time and the dough tenacity/extensibility parameters, P/L. The significant relationship between sedimentation tests and kernel elastic work seems to indicate that elastic work is related to genotype (protein composition). The general tendency was that higher values in kernel elastic work and size corresponded to better dough rheological quality. Mechanical properties of the kernel were significantly related to the elastic behavior measured in a single wheat kernel. The use of the compression test on individual kernels is easy, rapid and nondestructive and therefore seems to show potential use as a rapid tool in breeding to improve wheat quality.
Comparison of Waxy vs. Nonwaxy Wheats in Fuel Ethanol Fermentation
Authors: Zhao R. , Wu X. , Seabourn B. W. , Bean S. R. , Guan L. , Shi Y.‐C. , Wilson J. D. , Madl R. , Wang D.
Published: March 2009

Fermentation performance of eight waxy, seven nonwaxy soft, and 15 nonwaxy hard wheat cultivars was compared in a laboratory dry‐grind procedure. With nitrogen supplements in the mash, the range of ethanol yields was 368–447 L/ton. Nonwaxy soft wheat had an average ethanol yield of 433 L/ton, higher than nonwaxy hard and waxy wheat. Conversion efficiencies were 91.3–96.2%. Despite having higher levels of free sugars in grain, waxy wheat had higher conversion efficiency than nonwaxy wheat. Although there was huge variation in the protein content between nonwaxy hard and soft wheat, no difference in conversion efficiency was observed. Waxy cultivars had extremely low peak viscosity during liquefaction. Novel mashing properties of waxy cultivars were related to unique pasting properties of starch granules. With nitrogen supplementation, waxy wheat had a faster fermentation rate than nonwaxy wheat. Fermentation rates for waxy cultivars without nitrogen supplementation and nonwaxy cultivars with nitrogen supplementation were comparable. Ethanol yield was highly related to both total starch and protein content, but total starch was a better predictor of ethanol yield. There were strong negative relationships between total starch content of grain and both yield and protein content of distillers dried grains with solubles (DDGS).
Isolation and Characterization of High‐Purity Starch Isolates from Regular, Waxy, and High‐Amylose Hulless Barley Grains
Authors: Gao Jun , Vasanthan Thava , Hoover Ratnajothi
Published: March 2009

Recovering starch from barley is problematic typically due to interference from β‐glucan (the soluble fiber component), which becomes highly viscous in aqueous solution. Dry fractionation techniques tend to be inefficient and often result in low yields. Recently, a protocol was developed in our laboratory for recovering β‐glucan from barley in which sieving whole barley flour in a semiaqueous (50% ethanol) medium allowed separation of the starch and fiber fractions without activating the viscosity of the β‐glucan. In this report, we investigate an aqueous method which further purifies the crude starch component recovered from this process. Six hulless barley (HB) cultivars representing two each of waxy, regular, and high‐amylose cultivars were fractionated into primarily starch, fiber, and protein components. Starch isolates primarily had large granules with high purity (>98%) and yield range was 22–39% (flour dry weight basis). More importantly, the β‐glucan extraction efficiency was 77–90%, meaning that it was well separated from the starch component during processing. Physicochemical evaluation of the starch isolates, which were mainly composed of large granules, showed properties that are typical of the barley genotypes.
Bmi-1 cooperates with Foxg1 to maintain neural stem cell self-renewal in the forebrain
Authors: Fasano Christopher A. , Phoenix Timothy N. , Kokovay Erzsebet , Lowry Natalia , Elkabetz Yechiel , Dimos John T. , Lemischka Ihor R. , Studer Lorenz , Temple Sally
Published: March 2009

Neural stem cells (NSCs) persist throughout life in two forebrain areas: the subventricular zone (SVZ) and the hippocampus. Why forebrain NSCs self-renew more extensively than those from other regions remains unclear. Prior studies have shown that the polycomb factor Bmi-1 is necessary for NSC self-renewal and that it represses the cell cycle inhibitors p16, p19, and p21. Here we show that overexpression of Bmi-1 enhances self-renewal of forebrain NSCs significantly more than those derived from spinal cord, demonstrating a regional difference in responsiveness. We show that forebrain NSCs require the forebrain-specific transcription factor Foxg1 for Bmi-1-dependent self-renewal, and that repression of p21 is a focus of this interaction. Bmi-1 enhancement of NSC self-renewal is significantly greater with increasing age and passage. Importantly, when Bmi-1 is overexpressed in cultured adult forebrain NSCs, they expand dramatically and continue to make neurons even after multiple passages, when control NSCs have become restricted to glial differentiation. Together these findings demonstrate the importance of Bmi-1 and Foxg1 cooperation to maintenance of NSC multipotency and self-renewal, and establish a useful method for generating abundant forebrain neurons ex vivo, outside the neurogenic niche.
A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome
Authors: Jans Judith , Gladden John M. , Ralston Edward J. , Pickle Catherine S. , Michel Agnès H. , Pferdehirt Rebecca R. , Eisen Michael B. , Meyer Barbara J.
Published: March 2009

In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X-gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the Caenorhabditis elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites (recruitment elements on X) recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12-base-pair (bp) consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites (dependent on X) lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and noncompensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X-gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome.
Regulated degradation of FANCM in the Fanconi anemia pathway during mitosis
Authors: Kee Younghoon , Kim Jung Min , D'Andrea Alan
Published: March 2009

The 13 Fanconi anemia (FA) proteins cooperate in a common DNA repair pathway. Eight of these proteins are assembled into a multisubunit E3 ligase called the FA core complex. During S phase, the FA core complex is loaded by the FANCM protein into chromatin where it monoubiquitinates its substrates. In mitosis, the FA core complex is released from FANCM by an unknown mechanism. Here we show that FANCM is hyperphosphorylated and degraded during mitosis. β-TRCP and Plk1 are the key regulators of FANCM degradation. Nondegradable mutant forms of FANCM retain the FA core complex in the chromatin and disrupt the FA pathway. Our data provide a novel mechanism for the cell cycle-dependent regulation of the FA pathway.
Pattern formation via small RNA mobility
Authors: Chitwood Daniel H. , Nogueira Fabio T.S. , Howell Miya D. , Montgomery Taiowa A. , Carrington James C. , Timmermans Marja C.P.
Published: March 2009

MicroRNAs and trans-acting siRNAs (ta-siRNAs) have important regulatory roles in development. Unlike other developmentally important regulatory molecules, small RNAs are not known to act as mobile signals during development. Here, we show that low-abundant, conserved ta-siRNAs, termed tasiR-ARFs, move intercellularly from their defined source of biogenesis on the upper (adaxial) side of leaves to the lower (abaxial) side to create a gradient of small RNAs that patterns the abaxial determinant AUXIN RESPONSE FACTOR3. Our observations have important ramifications for the function of small RNAs and suggest they can serve as mobile, instructive signals during development.
Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome
Authors: Schwaiger Michaela , Stadler Michael B. , Bell Oliver , Kohler Hubertus , Oakeley Edward J. , Schübeler Dirk
Published: March 2009

Duplication of eukaryotic genomes during S phase is coordinated in space and time. In order to identify zones of initiation and cell-type- as well as gender-specific plasticity of DNA replication, we profiled replication timing, histone acetylation, and transcription throughout the Drosophila genome. We observed two waves of replication initiation with many distinct zones firing in early-S phase and multiple, less defined peaks at the end of S phase, suggesting that initiation becomes more promiscuous in late-S phase. A comparison of different cell types revealed widespread plasticity of replication timing on autosomes. Most occur in large regions, but only half coincide with local differences in transcription. In contrast to confined autosomal differences, a global shift in replication timing occurs throughout the single male X chromosome. Unlike in females, the dosage-compensated X chromosome replicates almost exclusively early. This difference occurs at sites that are not transcriptionally hyperactivated, but show increased acetylation of Lys 16 of histone H4 (H4K16ac). This suggests a transcription-independent, yet chromosome-wide process related to chromatin. Importantly, H4K16ac is also enriched at initiation zones as well as early replicating regions on autosomes during S phase. Together, our study reveals novel organizational principles of DNA replication of the Drosophila genome and suggests that H4K16ac is more closely correlated with replication timing than is transcription.
Geographical structure and differential natural selection among North European populations
Authors: McEvoy Brian P. , Montgomery Grant W. , McRae Allan F. , Ripatti Samuli , Perola Markus , Spector Tim D. , Cherkas Lynn , Ahmadi Kourosh R. , Boomsma Dorret , Willemsen Gonneke , Hottenga Jouke J. , Pedersen Nancy L. , Magnusson Patrik K.E. , Kyvik Kirsten Ohm , Christensen Kaare , Kaprio Jaakko , Heikkilä Kauko , Palotie Aarno , Widen Elisabeth , Muilu Juha , Syvänen Ann-Christine , Liljedahl Ulrika , Hardiman Orla , Cronin Simon , Peltonen Leena , Martin Nicholas G. , Visscher Peter M.
Published: March 2009

Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from FST-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association.
Systematic review: impaired drug absorption related to the co‐administration of antisecretory therapy
Authors: LAHNER E. , ANNIBALE B. , DELLE FAVE G.
Published: March 2009

Background  Due to suppression of gastric acidity during antisecretory therapy, an impaired absorption of co‐administered drugs may occur.

Aim  To review evidence of impaired drug absorption related to the use of co‐administered PPIs or H2RAs.

Methods  Systematic search of MEDLINE/EMBASE/SCOPUS databases (1980–September 2008) for English articles with keywords: drug malabsorption and absorption, stomach, anti‐secretory/acid inhibitory drugs, histamine H2 antagonists, PPIs, gastric acid, pH, hypochlorhydria, gastric hypoacidity. From 2126 retrieved articles, 16 randomized crossover studies were identified investigating impaired absorption of nine different drugs in association with co‐administration of PPIs or H2RAs. Information on investigated drug, study type, features of investigated subjects, study design, type of intervention, and study results were extracted.

Results  The identified studies investigated the absorption kinetics of nine drugs. Acid suppression reduced absorption of ketoconazole, itraconazole, atazanavir, cefpodoxime, enoxacin and dipyridamole (median Cmax reduction by 66.5%). An increased absorption of nifedipine and digoxin (median AUC increase by 10%) and a 2‐fold‐increase in alendronate bioavailability were observed.

Conclusions  Gastric pH appears relevant for absorption of some cardiovascular or infectious disease agents. Antisecretory treatment may significantly modify the absorption of co‐administered drugs.
Small‐intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease
Authors: PANDE C. , KUMAR A. , SARIN S. K.
Published: March 2009

Background  Small‐intestinal bacterial overgrowth (SIBO) is known to be present in patients with cirrhosis, predisposing to various complications.

Aim  To determine the frequency of SIBO in cirrhotics and correlate with severity of cirrhosis.

Methods  Small‐intestinal bacterial overgrowth was determined by glucose–hydrogen breath test (GHBT). A basal breath‐hydrogen >20 ppm or a rise by ≥12 ppm above baseline following glucose administration was taken as positive test. Prevalence of SIBO in cirrhotics was compared with healthy controls and correlated with severity of cirrhosis.

Results  Of the 53 cirrhotics, 26 (49%) had SIBO, compared to one (8%) control (P = 0.010). The prevalence of SIBO increased with severity of cirrhosis (Child–Pugh A 20%, B 52% and C 73%; P = 0.013). On multivariate analysis, SIBO was independently associated with serum bilirubin and ascites. The best cut‐off of serum bilirubin was ≥2 mg/dL [AUROC 0.77 (95% CI 0.64–0.90)] predicting SIBO with sensitivity 65%, specificity 81%, positive predictive value 77%, negative predictive value 71% and accuracy 74%. Patients having combination of ascites and serum bilirubin ≥2 mg/dL had 82% chance, while patients having neither had only 10% chance of having SIBO.

Conclusions  Small‐intestinal bacterial overgrowth was prevalent in about half of cirrhotics. Its frequency increased with increase in severity of cirrhosis. Ascites and raised serum bilirubin reliably predicted presence of SIBO.
Targeted inhibition of interleukin‐6 with CNTO 328 sensitizes pre‐clinical models of multiple myeloma to dexamethasone‐mediated cell death
Authors: Voorhees Peter M. , Chen Qing , Small George W. , Kuhn Deborah J. , Hunsucker Sally A. , Nemeth Jeffrey A. , Orlowski Robert Z.
Published: March 2009

Interleukin (IL)‐6‐mediated signalling attenuates the anti‐myeloma activity of glucocorticoids (GCs). We therefore sought to evaluate whether CNTO 328, an anti‐IL‐6 monoclonal antibody in clinical development, could enhance the apoptotic activity of dexamethasone (dex) in pre‐clinical models of myeloma. CNTO 328 potently increased the cytotoxicity of dex in IL‐6‐dependent and ‐independent human myeloma cell lines (HMCLs), including a bortezomib‐resistant HMCL. Isobologram analysis revealed that the CNTO 328/dex combination was highly synergistic. Addition of bortezomib to CNTO 328/dex further enhanced the cytotoxicity of the combination. Experiments with pharmacologic inhibitors revealed a role for the p44/42 mitogen‐activated protein kinase pathway in IL‐6‐mediated GC resistance. Although CNTO 328 alone induced minimal cell death, it potentiated dex‐mediated apoptosis, as evidenced by increased activation of caspases‐8, ‐9 and ‐3, Annexin‐V staining and DNA fragmentation. The ability of CNTO 328 to sensitize HMCLs to dex‐mediated apoptosis was preserved in the presence of human bone marrow stromal cells. Importantly, the increased activity of the combination was also seen in plasma cells from patients with GC‐resistant myeloma. Taken together, our data provide a strong rationale for the clinical development of the CNTO 328/dex regimen for patients with myeloma.
Discovering the genetics underlying foetal haemoglobin production in adults
Authors: Thein Swee Lay , Menzel Stephan
Published: March 2009

Sickle cell disease (SCD) and β thalassaemia, caused by lesions that affect the HBB (β globin gene), form the most common human genetic disorders world‐wide, and represent a major public health problem. Inter‐individual variation in foetal haemoglobin (HbF) expression is a known and heritable disease modifier; high HbF levels are correlated with reduced morbidity and mortality in both diseases. This review traces our progress in the understanding of the persistence of HbF in adults as a quantitative trait and the genetic approaches used in teasing out the loci contributing to its variability in normal populations and in patients with haemoglobinopathies. Three major loci – Xmn1‐HBG2 single nucleotide polymorphism, HBS1L‐MYB intergenic region on chromosome 6q, and BCL11A– contribute 20–50% of the trait variance in patients with sickle cell anaemia and healthy European Caucasians. It is likely that the remaining trait variance is due to numerous other loci, many contributing modest effects. Identification of the three major loci has not yet been translated into new therapeutic approaches for HbF reactivation but an immediate application would be an improved prediction of one’s ability to produce HbF, which in turn, may improve prediction of disease severity.
The Germinal centre‐derived lymphomas seen through their cellular microenvironment
Authors: Carbone Antonino , Gloghini Annunziata , Cabras Antonello , Elia Giuliano
Published: March 2009

The human lymph node is a complex tissue resulting from the microenvironmental organisation of different cell populations linked by topographical and/or functional relationships. Germinal centres (GCs) of lymphoid follicles contain a meshwork of follicular dendritic cells in addition to B‐cells and some CD4+ T cells. Moreover, there is a sharp demarcation around the whole follicle centre, which is highlighted by fibroblastic reticulum cells. On the whole, GC exerts a role in B cell physiology and malignancy. In GC‐derived lymphomas, gene expression profiling studies have raised the possibility that survival of the affected patients may be associated with signatures preferentially expressed in non‐malignant T cells and macrophages and/or dendritic cells. Immunohistological analyses in lymphoma biopsy samples have confirmed that the biological behaviour and tumour progression may be influenced by the tumour microenvironment. This review will examine GC‐derived lymphomas, including follicular lymphomas, Hodgkin lymphomas and angioimmunoblastic T‐cell lymphoma, through their integrated cellular microenvironment, highlighting those findings which may serve as a useful surrogate marker for tumour diagnosis or tumour progression, together with key molecules involved in tumour development.
Haemoglobin oxygen saturation is a determinant of cerebral artery blood flow velocity in children with sickle cell anaemia
Authors: Quinn Charles T. , Variste Jennifer , Dowling Michael M.
Published: March 2009

Steady‐state haemoglobin (Hb) desaturation is a common finding in sickle cell anaemia (Hb SS) that could predispose to stroke by limiting oxygen delivery to the brain. To determine its association with the risk of overt stroke, we examined the relationship between daytime Hb saturation measured by pulse oximetry (SpO2) and cerebral artery blood flow velocity measured by transcranial Doppler ultrasonography (TCD), an established risk factor for overt stroke in Hb SS. We studied 181 children using multivariate models to control for known determinants of TCD velocity, including age, haematocrit, and a measure of stenosis. We found that SpO2 correlated significantly and inversely with TCD velocity in both the right and left middle cerebral arteries. Hb desaturation was associated with increased cerebral artery blood flow velocities and increased odds of abnormal TCD velocities, hence increased risk of stroke. About 5% of the variation in TCD velocity could be ascribed to Hb saturation while controlling for other determinants of TCD velocity. In conclusion, Hb saturation is a determinant of TCD velocity and a risk factor for stroke in children with Hb SS.
Translational Mini-Review Series on Vaccines for HIV: Harnessing innate immunity for HIV vaccine development
Authors: Rhee E G , Barouch D H
Published: March 2009

Innate immunity is critical for shaping vaccine-elicited adaptive immune responses. Several classes of immune sensors, including Toll-like receptors, retinoic acid-inducible gene-I-like receptors, nucleotide-binding oligomerization domain-like receptors and cytosolic DNA receptors mediate important innate immune pathways and provide potential targets for novel adjuvant development. Understanding how innate immunity modulates adaptive immune responses will probably be important for optimizing vaccine candidates. Here, we review recent advances in innate immunity, focusing upon their potential applications in developing adjuvants and vectors for HIV vaccines.
Congenital hypopituitarism: clinical, molecular and neuroradiological correlates
Authors: Mehta Ameeta , Hindmarsh Peter C. , Mehta Hiten , Turton James P.G. , Russell‐Eggitt Isabelle , Taylor David , Chong W.K. , Dattani Mehul T.
Published: March 2009

Objective  Recent studies have suggested that mutations in genes encoding several hypothalamo–pituitary (H–P) transcription factors result in hypopituitarism [isolated GH deficiency (IGHD) and combined pituitary hormone deficiency (CPHD)], which may in turn be related to the neuroanatomy revealed by magnetic resonance (MR) imaging. Although studies have focused on patients with either optic nerve hypoplasia (ONH) or isolated hypopituitarism with normal optic nerves, few studies have compared the two groups. We aimed to relate the clinical phenotype of a large cohort (n = 170) of children with congenital hypopituitarism including septo‐optic dysplasia (SOD) attending a single centre to the neuroradiological and genetic findings.

Design  Clinical, biochemical, MR imaging and molecular data were analysed retrospectively in 170 patients with or ‘at‐risk’ (with ONH) of hypopituitarism to determine predictors of hypopituitarism.

Results  The presence of ONH was significantly associated with an absent septum pellucidum [odds ratio (OR) 31·5, 95% confidence intervals (CI) 7·3–136·6, P < 0·001], an abnormal corpus callosum (OR 10·5, 95% CI 3·8–28·6, P < 0·001) and stalk abnormalities (OR 2·3, 95% CI 1·2–4·2, P = 0·009). The risk of hypopituitarism was 27·2 times greater in patients with an undescended posterior pituitary (95% CI 3·6–205·1, P < 0·001). Anterior pituitary hypoplasia (OR 3·1, 95% CI 1·3–7·0, P = 0·006) and an absent pituitary stalk (P < 0·001) were also significantly associated with hypopituitarism. With respect to the type or severity of hypopituitarism, CPHD was more often associated with an abnormal corpus callosum (OR 6·1, 95% CI 1·4–27·4, P = 0·008) and stalk abnormalities (OR 2·8, 95% CI 1·3–6·1, P = 0·006). Male to female ratio was significantly greater in patients with normal optic nerves (3·3:1) as compared with those with ONH (1·2:1). The prevalence of diabetes insipidus, thyrotrophin and ACTH deficiencies was significantly greater in patients with ONH as compared with ‘idiopathic’ hypopituitarism. Mutations in pituitary transcription factors and genes regulating GH secretion were rare (5/170) in this cohort of patients with sporadic hypopituitarism.

Conclusion  Our data suggest that individuals presenting with ONH are at high risk for neuroradiologic and endocrine abnormalities. The neuroradiologic features are predictive not only of the presence, but also of the type, of hypopituitarism. The association of midline abnormalities with hypopituitarism in this cohort suggests a common developmental origin for these features, the aetiology of which remains unidentified in the majority of cases.
Should macroprolactin be measured in all hyperprolactinaemic sera?
Authors: Joseph McKenna T.
Published: March 2009

Macroprolactin is a nonbioactive prolactin isoform usually composed of a monomer of prolactin and a IgG molecule which has a prolonged clearance rate similar to that of the immunoglobulins. Macroprolactinaemia, hyperprolactinaemia entirely accounted for by the presence of macroprolactin, is estimated to account for approximately 10% of all hyperprolactinaemia coming to clinical attention in the United Kingdom and the United States. Failure to recognize that macroprolactinaemia can explain hyperprolactinaemia, leads to unnecessary investigation, incorrect diagnosis and inappropriate treatment. Screening of hyperprolactinaemic sera for the presence of misleading concentrations of macroprolactin is readily performed in biochemistry laboratories although the procedures have not been automated. The most widely employed method is to treat the hyperprolactinaemic sera with polyethylene glycol which precipitates out high‐molecular weight constituents including immunoglobulins. Re‐assay of the sera for prolactin will then identify those sera which yield values within the relevant normal range indicative of macroprolactinaemia and not true hyperprolactinaemia. The case for the routine screening of all hyperprolactinaemic sera for macroprolactin is compelling. The consequences of failure to recognize macroprolactinaemia are significant, the problem is frequently encountered, the means of addressing it are immediately available and it is cost effective.
Increased C‐reactive protein levels in overweight and obese women taking exogenous hormones: the United Kingdom Women’s Heart Study (UKWHS)
Authors: Kwok See , Canoy Dexter , Ashton William D. , Lowe Gordon D. O. , Wood David , Humphries Stephen E. , Charlton‐Menys Valentine , Durrington Paul N.
Published: March 2009

Objective  Women’s cardiovascular risk factors, including inflammatory markers such as C‐reactive protein (CRP) which is emerging as a major association with cardiovascular disease (CVD) risk, can be influenced by the oral contraceptive (OC) pill in premenopausal and hormone replacement (HR) in postmenopausal women and by central adiposity which is associated with a heightened inflammatory state. The interaction between central obesity and different hormone use in both pre and postmenopausal women has not previously been reported in a study spanning the whole age range associated with hormone use.

Design  Observational, cross‐sectional study.

Patients  Only healthy women were included in this study.

Measurements  A total of 21,310 women aged 30–64 employed by Marks & Spencer participated. They completed a health questionnaire and were screened for CVD risk factors including blood pressure, weight, height, waist and hip circumference, lipids and lipoproteins, CRP and fibrinogen.

Results  Compared with non‐users, women who took the OC or HR had significantly higher CRP levels. This was more marked than effects on other CVD risk factors. It was further compounded by the independent effect of increased waist circumference. The CRP increase was greatest (more than twice that of nonhormone users) in premenopausal women with the highest quartile of waist circumference who took the combined contraceptive pill.

Conclusions  Women who received first the combined OC and then HR may be exposed over much of their life to high CRP levels aggravated by central obesity. The health consequences of this require further investigation.
Dual‐gear approach for calibrating electric fishing capture efficiency and abundance estimates
Authors: CARRIER P. , ROSENFELD J. S. , JOHNSON R. M.
Published: March 2009

Abstract  Electric fishing depletion systematically underestimates fish abundance in streams. Electric fishing mark‐recapture estimates are unbiased, but only when performed over several days to allow marked fish to recover from electric fishing. A mark‐recapture procedure that can be performed in 1 day and produces unbiased population estimates is described. It involves minnow trapping, marking and releasing juvenile salmonids in a stop‐netted reach, followed by electric fishing the reach 1 h after release of marked fish. Recapture of marked fish during electric fishing can form the basis of a dual‐gear mark‐recapture population estimate, or an unbiased estimate of electric fishing capture efficiency. The marking technique did not affect short‐term catchability of the target species (P = 0.823), and provided unbiased estimates of capture efficiency (0.38–0.40) that were similar to those documented by other researchers. However, local validation to confirm equal catchability of marked and unmarked fish, as described in this study, is recommended.
A safe hydraulic architecture as wood anatomical explanation for the difference in distribution of the mangroves Avicennia and Rhizophora
Authors: Robert Elisabeth M R , Koedam Nico , Beeckman Hans , Schmitz Nele
Published: March 2009

Wood anatomical characteristics are an important source of information about how trees are coping with the conflicting requirements of optimal hydraulic conductivity and safety. In this study we compared the vessel characteristics of Avicennia marina and Rhizophora mucronata to contribute to a better understanding of the difference in distribution of these two mangrove species.

Density, grouping and diameters of vessels together with vessel element length of A. marina trees growing on seven different study sites in Gazi Bay (Kenya) were measured and compared with the vessel characteristics of R. mucronata of the same research area. Furthermore, the relation of environmental factors related to the water relations of mangrove trees to the wood anatomy of both species was tested.

Vessel density of both species and vessel grouping of A. marina are higher with higher salinity. In addition, A. marina was shown to have a higher vessel density, a higher vessel grouping, smaller vessel diameters and shorter vessel element lengths as compared to R. mucronata.

As the vessel characteristics of A. marina are related to protection against cavitation or the effects of cavitation, we can infer that this species has a water transport system which can be considered safer under water limiting conditions than that of R. mucronata.

The contrast in the safety of the water transport system between the two mangrove species studied is reflected in their distribution at local scale, over the land‐sea ecotone, and it may also explain the wide latitudinal distribution of A. marina as compared to R mucronata.

This conclusion emphasizes the importance of the anatomy of the water transport system for survival under diverse environmental conditions. In general it is shown that dominant species of a single ecosystem can deal with the stressful conditions they live in by contrasting ecological strategies.
Life history correlates of oxidative damage in a free‐living mammal population
Authors: Nussey Daniel H. , Pemberton Josephine M. , Pilkington Jill G. , Blount Jonathan D.
Published: March 2009

Reactive oxygen species, produced as a by‐product of normal metabolism, can cause intracellular damage and negatively impact on cell function. Such oxidative damage has been proposed as an evolutionarily important cost of growth and reproduction and as a mechanistic explanation for organismal senescence, although few tests of these ideas have occurred outside the laboratory.

Here, we examined correlations between a measure of phospholipid oxidative damage in plasma samples and age, growth rates, parasite burden and investment in reproduction in a population of wild Soay sheep on St. Kilda, Scotland.

We found that, amongst females of different ages, lambs had significantly elevated levels of oxidative damage compared to all other age classes and there was no evidence of increasing damage with age amongst adult sheep.

Amongst lambs, levels of oxidative damage increased significantly with increasing growth rates over the first 4 months of life. Neither mean damage nor the effect of growth rate on damage differed between male and female lambs.

Amongst adult female sheep, there was no evidence that body mass, current parasite burden or metrics of recent and past reproductive effort significantly predicted oxidative damage levels.

This study is the first to examine age variation in an assay of oxidative damage and correlations between oxidative damage, growth and reproduction in a wild mammal. Our results suggest strong links between early conditions and oxidative damage in lambs, but also serve to highlight the limitations of cross‐sectional data for studies examining associations between oxidative stress, ageing and life history in free‐living populations.
Linking movement behaviour, dispersal and population processes: is individual variation a key?
Authors: Hawkes Colin
Published: March 2009

Movement behaviour has become increasingly important in dispersal ecology and dispersal is central to the development of spatially explicit population ecology. The ways in which the elements have been brought together are reviewed with particular emphasis on dispersal distance distributions and the value of mechanistic models.

There is a continuous range of movement behaviours and in some species, dispersal is a clearly delineated event but not in others. The biological complexities restrict conclusions to high‐level generalizations but there may be principles that are common to dispersal and other movements.

Random walk and diffusion models when appropriately elaborated can provide an understanding of dispersal distance relationships on spatial and temporal scales relevant to dispersal. Leptokurtosis in the relationships may be the result of a combination of factors including population heterogeneity, correlation, landscape features, time integration and density dependence. The inclusion in diffusion models of individual variation appears to be a useful elaboration. The limitations of the negative exponential and other phenomenological models are discussed.

The dynamics of metapopulation models are sensitive to what appears to be small differences in the assumptions about dispersal. In order to represent dispersal realistically in population models, it is suggested that phenomenological models should be replaced by those based on movement behaviour incorporating individual variation.

The conclusions are presented as a set of candidate principles for evaluation. The main features of the principles are that uncorrelated or correlated random walk, not linear movement, is expected where the directions of habitat patches are unpredictable and more complex behaviour when organisms have the ability to orientate or navigate. Individuals within populations vary in their movement behaviour and dispersal; part of this variation is a product of random elements in movement behaviour and some of it is heritable. Local and metapopulation dynamics are influenced by population heterogeneity in dispersal characteristics and heritable changes in dispersal propensity occur on time‐scales short enough to impact population dynamics.
Facing inadequacy and being good enough: psychiatric care providers' narratives about experiencing and coping with troubled conscience
Authors: DAHLQVIST V. , SÖDERBERG A. , NORBERG A.
Published: March 2009

The aim of this study is to illuminate the meaning of encounters with a troubled conscience among psychiatric therapists. Psychiatric care involves ethical dilemmas which may affect conscience. Conscience relates to keeping or losing a sense of personal integrity when making judgments about one's actions. Ten psychiatric therapists were interviewed in June 2006. The interviews were tape‐recorded, transcribed verbatim and interpreted using a phenomenological‐hermeneutic method. Two themesFacing inadequacyandStruggling to view oneself as being ‘good enough’are presented. In the therapists interviewed, awareness of their use of power, a sense of powerlessness and a sense of blame gave rise to feelings of betrayals and shameful inadequacy. By sharing their inadequacy with co‐workers, they managed to endure the sense of their inadequacy which otherwise would have threatened to paralyse them. Finding consolation in sharing wearing feelings, becoming realistic and attesting their worthiness, they reached reconciliation and found confirmation of being good enough. The findings are interpreted in light of Lögstrup's ethics of trust, according to which conscience alerts us to silent but radical ethical demand and the risk of self‐deception.
ADHD in the college student: a block in the road
Authors: MEAUX J. B. , GREEN A. , BROUSSARD L.
Published: March 2009

Older adolescents with Attention Deficit Hyperactivity Disorder (ADHD) often struggle as they make the transition to college. Loss of parental supervision and structure, variable course schedules and the freedom and distractions of campus life can lead to health‐risk behaviours for the college student with ADHD. The purpose of this study was to determine factors that help, as well as hinder, college students with ADHD as they learn to cope with everyday challenges of life and academics once they leave the structure and support of their parents' home. Investigators conducted semi‐structured qualitative interviews with 15 college students with ADHD. Follow‐up interviews confirmed and validated information obtained during initial interviews. In‐depth qualitative analysis of transcribed interviews resulted in identification of three global themes: gaining insight about ADHD, managing life and utilizing sources of support. Each global theme contains factors that hinder, as well as factors that help the college student with ADHD. The factors that college students described as helping and hindering their transition to college can serve as the basis for interventions to educate and empower younger adolescents with ADHD well in advance of their transition to college.
Using and understanding consumer satisfaction to effect an improvement in mental health service delivery
Authors: BRUNERO S. , LAMONT S. , FAIRBROTHER G.
Published: March 2009

Consumer satisfaction is today, widely accepted as a measure of the level and quality of service received by consumers. The aim of this survey‐based study is to explore consumer satisfaction with quality of care, staff, environment and discharge in a south eastern Sydney adult acute inpatient mental health unit. A cross‐sectional analysis is pursued in order to identify aspects of the patient stay, which form an associative relationship with an overall rating of consumer satisfaction on a 10‐point scale. During the survey period, there were 182 discharges. Seventy questionnaires (38.5%) were returned from this group. The survey results highlight a number of areas of identified need, enabling the service to prioritize organizational systems around meeting these needs. Multiple regression analysis identified three items in the survey, which were independently significant associates of overall consumer satisfaction. They included being happy with the service provided by the consumer support worker, having support for services on discharge and feeling safe and secure on the ward. The model containing these three items accounted for 50% of the variation in overall satisfaction. Two primary interventions have been developed because survey administration which, it is hoped, will address issues raised in the survey. The interventions were the development of an admission and discharge pathway and a ward‐based psychosocial intervention programme, which includes the involvement of consumer support workers.
Locked doors in acute inpatient psychiatry: a literature review
Authors: VAN DER MERWE M. , BOWERS L. , JONES J. , SIMPSON A. , HAGLUND K.
Published: March 2009

Many acute inpatient psychiatric wards in the UK are permanently locked, although this is contrary to the current Mental Health Act Code of Practice. To conduct a literature review of empirical articles concerning locked doors in acute psychiatric inpatient wards, an extensive literature search was performed in SAGE Journals Online, EBM Reviews, British Nursing Index, CINAHL, EMBASE Psychiatry, International Bibliography of the Social Sciences, Ovid MEDLINE(R), PsycINFO and Google, using the search terms ‘open$’, ‘close$’, ‘$lock$’, ‘door’, ‘ward’, ‘hospital’, ‘psychiatr’, ‘mental health’, ‘inpatient’ and ‘asylum’. A total of 11 empirical papers were included in the review. Both staff and patients reported advantages (e.g. preventing illegal substances from entering the ward and preventing patients from absconding and harming themselves or others) and disadvantages (e.g. making patients feel depressed, confined and creating extra work for staff) regarding locked doors. Locked wards were associated with increased patient aggression, poorer satisfaction with treatment and more severe symptoms. The limited literature available showed the urgent need for research to determine the real effects of locked doors in inpatient psychiatry.
Global gene regulation by Fusarium transcription factors Tri6 and Tri10 reveals adaptations for toxin biosynthesis
Authors: Seong Kye‐Yong , Pasquali Matias , Zhou Xiaoying , Song Jongwoo , Hilburn Karen , McCormick Susan , Dong Yanhong , Xu Jin‐Rong , Kistler H. Corby
Published: March 2009

Trichothecenes are isoprenoid mycotoxins produced in wheat infected with the filamentous fungus Fusarium graminearum. Some fungal genes for trichothecene biosynthesis (Tri genes) are known to be under control of transcription factors encoded by Tri6 and Tri10. Tri6 and Tri10 deletion mutants were constructed in order to discover additional genes regulated by these factors in planta. Both mutants were greatly reduced in pathogenicity and toxin production and these phenotypes were largely restored by genetic complementation with the wild‐type gene. Transcript levels for over 200 genes were altered ≥ twofold for Δtri6 or Δtri10 mutants including nearly all known Tri genes. Also reduced were transcript levels for enzymes in the isoprenoid biosynthetic pathway leading to farnesyl pyrophosphate, the immediate molecular precursor of trichothecenes. DNA sequences 5′ to isoprenoid biosynthetic genes were enriched for the Tri6p DNA binding motif, YNAGGCC, in F. graminearum but not in related species that do not produce trichothecenes. To determine the effect of trichothecene metabolites on gene expression, cultures were treated with trichodiene, the first metabolic intermediate specific to the trichothecene biosynthetic pathway. A total of 153 genes were upregulated by added trichodiene and were significantly enriched for genes likely involved in cellular transport. Differentially regulated genes will be targeted for functional analysis to discover additional factors involved in toxin biosynthesis, toxin resistance and pathogenesis.
The cell cycle as a therapeutic target against Trypanosoma brucei: Hesperadin inhibits Aurora kinase‐1 and blocks mitotic progression in bloodstream forms
Authors: Jetton Neal , Rothberg Karen G. , Hubbard James G. , Wise John , Li Yan , Ball Haydn L. , Ruben Larry
Published: March 2009

Aurora kinase family members co‐ordinate a range of events associated with mitosis and cytokinesis. Anti‐cancer therapies are currently being developed against them. Here, we evaluate whether Aurora kinase‐1 (TbAUK1) from pathogenic Trypanosoma brucei might be targeted in anti‐parasitic therapies as well. Conditional knockdown of TbAUK1 within infected mice demonstrated its essential contribution to infection. An in vitro kinase assay was developed which used recombinant trypanosome histone H3 as a substrate. Tandem mass spectroscopy identified a novel phosphorylation site in the carboxyl‐tail of recombinant trypanosome histone H3. Hesperadin, an inhibitor of human Aurora B, prevented the phosphorylation of substrate with IC50 of 40 nM. Growth of cultured bloodstream forms was also sensitive to Hesperadin (IC50 of 50 nM). Hesperadin blocked nuclear division and cytokinesis but not other aspects of the cell cycle. Consequently, growth arrested cells accumulated multiple kinetoplasts, flagella and nucleoli, similar to the effects of RNAi‐dependent knockdown of TbAUK1 in cultured bloodstream forms cells. Molecular models predicted high‐affinity binding of Hesperadin to both conserved and novel sites in TbAUK1. Collectively, these data demonstrate that cell cycle progression is essential for infections with T. brucei and that parasite Aurora kinases can be targeted with small‐molecule inhibitors.
RNase E autoregulates its synthesis in Escherichia coli by binding directly to a stem‐loop in the rne 5′ untranslated region
Authors: Schuck Alyssa , Diwa Alexis , Belasco Joel G.
Published: March 2009

RNase E autoregulates its production in Escherichia coli by governing the decay rate of rne (RNase E) mRNA. It does so by a mechanism that is dependent in part on hp2, a cis‐acting stem‐loop within the rne 5′ untranslated region. In principle, hp2 could function either as a cleavage site for RNase E or as a binding site for that protein or an ancillary factor. Here we show that the effector region at the top of hp2 is cleaved poorly by RNase E yet binds the catalytic domain of that ribonuclease with a sequence specificity reflecting its efficacy in feedback regulation. These findings suggest that hp2 controls RNase E synthesis by binding to RNase E and expediting cleavage elsewhere within the rne transcript.