bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Virologic Failure in an HIV Clinic
Authors: Robbins Gregory K. , Johnson Kristin L. , Chang Yuchiao , Jackson Katherine E. , Sax Paul E. , Meigs James B. , Freedberg Kenneth A.
Published: February 2010

Background . We sought to use data captured in the electronic health record (EHR) to develop and validate a prediction rule for virologic failure among patients being treated for infection with human immunodeficiency virus (HIV).

Methods . We used EHRs at 2 Boston tertiary care hospitals, Massachusetts General Hospital and Brigham and Women's Hospital, to identify HIV-infected patients who were virologically suppressed (HIV RNA level ⩽400 copies/mL) on antiretroviral therapy (ART) during the period from 1 January 2005 through 31 December 2006. We used a multivariable logistic model with data from Massachusetts General Hospital to derive a 1-year virologic failure prediction rule. The model was validated using data from Brigham and Women's Hospital. We then simplified the scoring scheme to develop a clinical prediction rule.

Results . The 1-year virologic failure prediction model, using data from 712 patients from Massachusetts General Hospital, demonstrated good discrimination (C statistic, 0.78) and calibration (X2=6.6; P=.58). The validation model, based on 362 patients from Brigham and Women's Hospital, also showed good discrimination (C statistic, 0.79) and calibration (X2=1.9; P=.93). The clinical prediction rule included 7 predictors (suboptimal adherence, CD4 cell count <100 cells/µL, drug and/or alcohol abuse, highly ART experienced, missed ⩾1 appointment, prior virologic failure, and suppressed ⩽12 months) and appropriately stratified patients in the validation data set into low-, medium-, and high-risk groups, with 1-year virologic failure rates of 3.0%, 13.0%, and 28.6%, respectively.

Conclusions . A risk score based on 7 variables available in the EHR predicts HIV virologic failure at 1 year and could be used for targeted interventions to improve outcomes in HIV infection.
Preventive Effect of Pine Bark Extract (Flavangenol) on Metabolic Disease in Western Diet‐Loaded Tsumura Suzuki Obese Diabetes Mice
Authors: Shimada Tsutomu , Kosugi Mitsutaka , Tokuhara Daisuke , Tsubata Masahito , Kamiya Tomoyasu , Sameshima Mayu , Nagamine Rika , Takagaki Kinya , Miyamoto Ken-ichi , Aburada Masaki
Published: February 2010

It is known that the metabolic syndrome has a multi‐factorial basis involving both genetic and environmental risk factors. In this study, Tsumura Suzuki Obese Diabetes (TSOD) mice, a mouse model of multi‐factorial, hereditary, obese type II diabetes, were given a Western diet (WTD) as an environmental factor to prepare a disease model (TSOD‐WTD) and to investigate the preventive effects of Pine bark extract (Flavangenol) against obesity and various features of metabolic disease appearing in this animal model. In contrast to control Tsumura Suzuki Non‐obesity (TSNO) mice, TSOD mice were obese and suffered from other metabolic complications. WTD‐fed TSOD mice developed additional features such as hyperinsulinemia, abnormal glucose/lipid metabolism and fatty liver. The treatment with Flavangenol had a suppressive effect on increase in body weight and accumulation of visceral and subcutaneous fat, and also showed preventive effects on symptoms related to insulin resistance, abnormal glucose/lipid metabolism and hypertension. Flavangenol also increased the plasma concentration of adiponectin and decreased the plasma concentration of TNF‐α. We next investigated the effect of Flavangenol on absorption of meal‐derived lipids. Flavangenol suppressed absorption of neutral fat in an olive‐oil‐loading test (in vivo) and showed an inhibitory effect on pancreatic lipase (in vitro). The above results suggest that Flavangenol has a preventive effect on severe metabolic disease due to multiple causes that involve both genetic and environmental risk factors. The mechanism of action might involve a partial suppressive effect of meal‐derived lipids on absorption.
KIOM‐4 Protects against Oxidative Stress‐Induced Mitochondrial Damage in Pancreatic β‐cells via Its Antioxidant Effects
Authors: Kang Kyoung Ah , Kim Jin Sook , Zhang Rui , Piao Mei Jing , Maeng Young Hee , Kang Mi Young , Lee In Kyung , Kim Bum Joon , Hyun Jin Won
Published: February 2010

The protective effect of KIOM‐4, a mixture of plant extracts, was examined against streptozotocin (STZ)‐induced mitochondrial oxidative stress in rat pancreatic β‐cells (RINm5F). KIOM‐4 scavenged superoxide and hydroxyl radicals generated by xanthine/xanthine oxidase and Fenton reaction (FeSO4/H2O2), respectively, in a cell‐free chemical system. In addition, a marked increase in mitochondrial reactive oxygen species (ROS) was observed in STZ‐induced diabetic cells; this increase was attenuated by KIOM‐4 treatment. Mitochondrial manganese superoxide dismutase (Mn SOD) activity and protein expression were down‐regulated by STZ treatment and up‐regulated by KIOM‐4 treatment. In addition, NF‐E2 related factor 2 (Nrf2), a transcription factor for Mn SOD, was up‐regulated by KIOM‐4. KIOM‐4 prevented STZ‐induced mitochondrial lipid peroxidation, protein carbonyl and DNA modification. Moreover, KIOM‐4 treatment restored the loss of mitochondrial membrane potential (Δψ) that was induced by STZ treatment, and inhibited the translocation of cytochrome c from the mitochondria to the cytosol. In addition, KIOM‐4 treatment elevated the level of ATP, succinate dehydrogenase activity and insulin level, which were reduced by STZ treatment. These results suggest that KIOM‐4 exhibits a protective effect through its antioxidant effect and the attenuation of mitochondrial dysfunction in STZ‐induced diabetic cells.
Autophagy in unicellular eukaryotes
Authors: Kiel Jan A. K. W.
Published: February 2010

Cells need a constant supply of precursors to enable the production of macromolecules to sustain growth and survival. Unlike metazoans, unicellular eukaryotes depend exclusively on the extracellular medium for this supply. When environmental nutrients become depleted, existing cytoplasmic components will be catabolized by (macro)autophagy in order to re-use building blocks and to support ATP production. In many cases, autophagy takes care of cellular housekeeping to sustain cellular viability. Autophagy encompasses a multitude of related and often highly specific processes that are implicated in both biogenetic and catabolic processes. Recent data indicate that in some unicellular eukaryotes that undergo profound differentiation during their life cycle (e.g. kinetoplastid parasites and amoebes), autophagy is essential for the developmental change that allows the cell to adapt to a new host or form spores. This review summarizes the knowledge on the molecular mechanisms of autophagy as well as the cytoplasm-to-vacuole-targeting pathway, pexophagy, mitophagy, ER-phagy, ribophagy and piecemeal microautophagy of the nucleus, all highly selective forms of autophagy that have first been uncovered in yeast species. Additionally, a detailed analysis will be presented on the state of knowledge on autophagy in non-yeast unicellular eukaryotes with emphasis on the role of this process in differentiation.
Peroxisome diversity and evolution
Authors: Gabaldón Toni
Published: February 2010

Peroxisomes are organelles bounded by a single membrane that can be found in all major groups of eukaryotes. A single evolutionary origin of this cellular compartment is supported by the presence, in diverse organisms, of a common set of proteins implicated in peroxisome biogenesis and maintenance. Their enzymatic content, however, can vary substantially across species, indicating a high level of evolutionary plasticity. Proteomic analyses have greatly expanded our knowledge on peroxisomes in some model organisms, including plants, mammals and yeasts. However, we still have a limited knowledge about the distribution and functionalities of peroxisomes in the vast majority of groups of microbial eukaryotes. Here, I review recent advances in our understanding of peroxisome diversity and evolution, with a special emphasis on peroxisomes in microbial eukaryotes.
Rewiring and regulation of cross-compartmentalized metabolism in protists
Authors: Ginger Michael L. , McFadden Geoffrey I. , Michels Paul A. M.
Published: February 2010

Plastid acquisition, endosymbiotic associations, lateral gene transfer, organelle degeneracy or even organelle loss influence metabolic capabilities in many different protists. Thus, metabolic diversity is sculpted through the gain of new metabolic functions and moderation or loss of pathways that are often essential in the majority of eukaryotes. What is perhaps less apparent to the casual observer is that the sub-compartmentalization of ubiquitous pathways has been repeatedly remodelled during eukaryotic evolution, and the textbook pictures of intermediary metabolism established for animals, yeast and plants are not conserved in many protists. Moreover, metabolic remodelling can strongly influence the regulatory mechanisms that control carbon flux through the major metabolic pathways. Here, we provide an overview of how core metabolism has been reorganized in various unicellular eukaryotes, focusing in particular on one near universal catabolic pathway (glycolysis) and one ancient anabolic pathway (isoprenoid biosynthesis). For the example of isoprenoid biosynthesis, the compartmentalization of this process in protists often appears to have been influenced by plastid acquisition and loss, whereas for glycolysis several unexpected modes of compartmentalization have emerged. Significantly, the example of trypanosomatid glycolysis illustrates nicely how mathematical modelling and systems biology can be used to uncover or understand novel modes of pathway regulation.
The evolution, metabolism and functions of the apicoplast
Authors: Lim Liting , McFadden Geoffrey Ian
Published: February 2010

The malaria parasite,Plasmodium falciparum, harbours a relict plastid known as the ‘apicoplast’. The discovery of the apicoplast ushered in an exciting new prospect for drug development against the parasite. The eubacterial ancestry of the organelle offers a wealth of opportunities for the development of therapeutic interventions. Morphological, biochemical and bioinformatic studies of the apicoplast have further reinforced its ‘plant-like’ characteristics and potential as a drug target. However, we are still not sure why the apicoplast is essential for the parasite's survival. This review explores the origins and metabolic functions of the apicoplast. In an attempt to decipher the role of the organelle within the parasite we also take a closer look at the transporters decorating the plastid to better understand the metabolic exchanges between the apicoplast and the rest of the parasite cell.
Review article: the modern management of hepatic encephalopathy
Authors: BAJAJ J. S.
Published: February 2010

Aliment Pharmacol Ther 31, 537–547

Background  Hepatic encephalopathy, both overt and minimal, forms a continuum of cognitive change in cirrhosis. Strategies to diagnose and treat hepatic encephalopathy have evolved considerably.

Aim To examine the updated diagnostic and treatment strategies for hepatic encephalopathy.

Methods  Techniques for the clinical, psychometric and neurophysiological evaluation of hepatic encephalopathy are reviewed. The methods reviewed include pure clinical scales (West‐Haven), psychometric tests (PSE‐syndrome test), neurophysiological tests (EEG, Critical flicker frequency, CFF) and computerized tests (Inhibitory control test, ICT).

Results  Clinical scales are limited, whereas psychometric tests (specifically PSE‐syndrome test), CFF and ICT can be used to diagnose minimal hepatic encephalopathy. However, there is no single test that can capture the entire spectrum of cognitive impairment. Treatment options and goals depend on the acuity of hepatic encephalopathy. In‐patient management should concentrate on supportive care, precipitating factor reversal and lactulose and/or rifaximin therapy. Out‐patient therapy should aim to prevent recurrences, and both lactulose and rifaximin have evidence to support their use.

Conclusions  Diagnostic techniques for hepatic encephalopathy range from simple scales to sophisticated tools. Treatment options depend on the stage of hepatic encephalopathy. The future challenge is to evaluate cognitive function as a continuum with clinically relevant outcomes and to develop well‐tolerated and inexpensive treatments for hepatic encephalopathy.
Clinical trial: irsogladine maleate, a mucosal protective drug, accelerates gastric ulcer healing after treatment for eradication ofHelicobacter pyloriinfection – the results of a multicentre, double‐blind, randomized clinical trial (IMPACT study)
Authors: HIRAISHI H. , HARUMA K. , MIWA H. , GOTO H.
Published: February 2010

Aliment Pharmacol Ther 31, 824–833

Background Helicobacter pylorieradication therapy alone is not sufficient to heal all gastric ulcers.

Aim To verify the efficacy of treatment with irsogladine maleate between the termination and assessment of treatment for eradicatingH. pyloriin a double‐blind study.

MethodsThree hundred and twenty‐two patients with a singleH. pylori‐positive gastric ulcer were given eradication treatment, then assigned randomly to a treatment group [given 4 mg/day irsogladine maleate (n = 150)] or a control group [given a placebo (n = 161)]. The gastric ulcer healing rates were compared after 7 weeks of treatment.

Results The healing rate was significantly higher in the irsogladine maleate group (83.0%) than in the placebo group (72.2%; χ2test,P = 0.0276). In the subgroup analysis of cases of eradication failure, the gastric ulcer healing rate was significantly higher in the irsogladine maleate group (57.9%) than in the placebo group (26.1%; χ2test,P = 0.0366).

Conclusions Irsogladine maleate was effective for treating gastric ulcer afterH. pylorieradication. The high healing rates observed in patients with or without successful eradication demonstrate the usefulness of irsogladine maleate treatment regardless of the outcome of eradication.
Relative importance of abnormalities of CCK and 5‐HT (serotonin) in Giardia‐induced post‐infectious irritable bowel syndrome and functional dyspepsia
Authors: DIZDAR V. , SPILLER R. , SINGH G. , HANEVIK K. , GILJA O. H. , EL‐SALHY M. , HAUSKEN T.
Published: February 2010

Aliment Pharmacol Ther 31, 883–891

Background  Post‐infectious irritable bowel syndrome (PI‐IBS) and functional dyspepsia (FD) have been described after both Campylobacter jejuni gastroenteritis and Giardia infection. After C. jejuni, there is increased rectal serotonin (5‐HT)‐containing EC cells and postprandial plasma 5‐HT, while a pilot study suggested increased plasma cholecystokinin (CCK) after Giardia infection.

Aim  To determine changes in plasma and duodenal mucosal 5‐HT and CCK in Giardia‐induced PI‐IBS.

Methods  A total of 32 patients previously infected with Giardia and 19 who had recovered fully (controls) completed symptom questionnaires. Endoscopic duodenal biopsies were obtained from all subjects and immunohistochemically stained for CCK, 5‐HT and CgA containing entero‐endocrine cells and mast cells. 5‐HT content was also assessed. Twenty‐one of 32 patients and 19 controls consumed a high‐carbohydrate meal, while fasting and postprandial plasma CCK and 5‐HIAA were measured.

Results  Post‐infectious irritable bowel syndrome patients had increased numbers of CCK cells (P = 0.02), but lower numbers of EC cells (P = 0.009). Plasma CCK did not differ significantly between the groups, but correlated significantly with postprandial dyspepsia scores (r = 0.5, P = 0.05). PI‐IBS patients had significantly lower plasma 5‐HIAA, before and after meal (P = 0.05) as well as more dyspepsia (P < 0.0001) compared with recovered subjects.

Conclusions  Post‐infectious bowel dysfunction following Giardia infection is associated with increased duodenal mucosal CCK. Postprandial dyspeptic symptoms correlate better with CCK than measures of 5‐HT metabolism.
Lactose intolerance in patients with chronic functional diarrhoea: the role of small intestinal bacterial overgrowth
Authors: ZHAO J. , FOX M. , CONG Y. , CHU H. , SHANG Y. , FRIED M. , DAI N.
Published: February 2010

Aliment Pharmacol Ther 31, 892–900

Background  Many studies report a high prevalence of lactose intolerance in patients with functional, gastrointestinal disease.

Aim  To evaluate the role of small intestinal bacterial overgrowth (SIBO) in condition of lactose intolerance and the mechanism by which SIBO may impact lactose tolerance in affected patients.

Methods  Consecutive out‐patients with chronic functional diarrhoea (CFD) and healthy controls underwent a validated 20 g lactose hydrogen breath test (HBT). Patients completed also a 10 g lactulose HBT with concurrent assessment of small bowel transit by scintigraphy.

Results  Lactose malabsorption was present in 27/31 (87%) patients with CFD and 29/32 (91%) healthy controls (P = 0.708). From the patient group 14/27 (52%) had lactose intolerance and 13/27 (48%) experienced no symptoms (lactose malabsorption controls). Only 5 (17%) healthy controls reported symptoms (P < 0.01). The oro‐caecal transit time was similar between patient groups with or without symptoms (P = 0.969). SIBO was present in 11 (41%) subjects and was more prevalent in lactose intolerance than in lactose malabsorption [9/14 (64%) vs. 2/13 (15%), P = 0.018]. Symptom severity was similar in lactose intolerance patients with and without SIBO (P = 0.344).

Conclusions  Small intestinal bacterial overgrowth increases the likelihood of lactose intolerance in patients with CFD as a direct result of lactose fermentation in the small intestine, independent of oro‐caecal transit time and visceral sensitivity.
Clinical trial: maintenance intermittent therapy with rabeprazole 20 mg in patients with symptomatic gastro‐oesophageal reflux disease – a double‐blind, placebo‐controlled, randomized study
Authors: FASS R. , DELEMOS B. , NAZARENO L. , KAO R. , XIANG J. , LU Y.
Published: February 2010

Aliment Pharmacol Ther 31, 950–960

Background  Optimal long‐term management of symptomatic gastro‐oesophageal reflux disease (sGERD) patients has not been established.

Aim  To determine the clinical value of maintenance intermittent treatment with rabeprazole 20 mg vs. placebo in patients with sGERD.

Methods  This multicentre, US study enrolled patients with sGERD (≥3‐month history of GERD symptoms and ≥4 days/week of heartburn during a 2‐week placebo run‐in) without oesophageal erosions. Patients with complete heartburn control after 4 weeks of open‐label rabeprazole 20 mg daily treatment were randomized to 6‐month, double‐blind, maintenance intermittent treatment (7‐ to 14‐day courses when heartburn recurred) with rabeprazole 20 mg or placebo.

Results  The primary efficacy end point, mean percentage of heartburn‐free days, was significantly greater with rabeprazole vs. placebo: 82.58% and 62.17% (ITT; P < 0.0001) [per protocol 86.74% rabeprazole vs. 74.93% placebo (P < 0.0254)]. Compared with placebo group, the rabeprazole group also experienced a significantly higher percentage of heartburn‐free daytime (84.06% vs. 63.39%; P < 0.0001) and nighttime (95.41% vs. 90.25%; P = 0.0021) periods, had significantly fewer discontinuations because of insufficient heartburn control (6.3% vs. 36.3%; P < 0.0001) and took fewer antacid tablets daily (0.58 vs. 1.16; P = 0.0021).

Conclusion  Intermittent use of rabeprazole may be an effective maintenance treatment strategy for patients with sGERD and warrants further investigation. This trial was registered with http://clinicaltrials.gov under the number NCT00165841.
Effects of a single dose of rabeprazole 20 mg and pantoprazole 40 mg on 24‐h intragastric acidity and oesophageal acid exposure: a randomized study in gastro‐oesophageal reflux disease patients with a history of nocturnal heartburn
Authors: MINER P. , DELEMOS B. , XIANG J. , LOCOCO J. , IENI J.
Published: February 2010

Aliment Pharmacol Ther 31, 991–1000

Background  Nocturnal heartburn is common in patients with gastro‐oesophageal reflux disease (GERD).

Aim  To compare the effects of single doses of rabeprazole 20 mg and pantoprazole 40 mg on 24‐h intragastric acidity and oesophageal acid exposure (OAE).

Methods  A total of 52 subjects with GERD and a ≥6‐month history of heartburn were randomized into a blinded, 2 × 2 crossover trial. Subjects’ intragastric pH was monitored in two 48‐h study periods with 6‐ to 13‐day washout between periods. Patients received placebo on day 1, a single dose of rabeprazole 20 mg or pantoprazole 40 mg on day 2, and standardized meals throughout.

Results  The mean percentage time with intragastric pH >4 was significantly greater with rabeprazole vs. pantoprazole for the 24‐h postdose interval (44.0% vs. 32.8%; P < 0.001). Significant differences were observed in the daytime (51.0% vs. 42.2%; P < 0.001) and nighttime (32.0% vs. 16.9%; P < 0.001). Rabeprazole was also significantly superior in other intragastric pH parameters. There was no statistical difference for OAE between treatments.

Conclusions  In GERD patients with nocturnal heartburn, rabeprazole 20 mg was significantly more effective than pantoprazole 40 mg in percentage time with intragastric pH >4 during the nighttime, daytime, and 24‐h periods. Differences between treatments in OAE were not demonstrated. This trial is registered with http://clinicaltrials.gov, number NCT00237367.
Tectonic controls on Cenozoic foreland basin development in the north‐eastern Andes, Colombia
Authors: Parra Mauricio , Mora Andrés , Jaramillo Carlos , Torres Vladimir , Zeilinger Gerold , Strecker Manfred R.
Published: February 2010

In order to evaluate the relationship between thrust loading and sedimentary facies evolution, we analyse the progradation of fluvial coarse‐grained deposits in the retroarc foreland basin system of the northern Andes of Colombia. We compare the observed sedimentary facies distribution with the calculated one‐dimensional (1D) Eocene to Quaternary sediment‐accumulation rates in the Medina wedge‐top basin and with a three‐dimensional (3D) sedimentary budget based on the interpretation of ∼1800 km of industry‐style seismic reflection profiles and borehole data. Age constraints are derived from a new chronostratigraphic framework based on extensive fossil palynological assemblages. The sedimentological data from the Medina Basin reveal rapid accumulation of fluvial and lacustrine sediments at rates of up to ∼500 m my−1during the Miocene. Provenance data based on gravel petrography and paleocurrents reveal that these Miocene fluvial systems were sourced from Upper Cretaceous and Paleocene sedimentary units exposed to the west in the Eastern Cordillera. Peak sediment‐accumulation rates in the upper Carbonera Formation and the Guayabo Group occur during episodes of coarse‐grained facies progradation in the early and late Miocene proximal foredeep. We interpret this positive correlation between sediment accumulation and gravel deposition as the direct consequence of thrust activity along the Servitá–Lengupá faults. This contrasts with one class of models relating gravel progradation in more distal portions of foreland basin systems to episodes of tectonic quiescence.
Interleukin-2 inhibits polarization to T helper type 1 cells and prevents mouse acute graft-versus-host disease through up-regulating suppressors of cytokine signalling-3 expression of naive CD4+ T cells
Authors: Zhao J , Zhang T , He H , Xie Y
Published: February 2010

T helper type 1 (Th1)-type polarization plays a critical role in the pathophysiology of acute graft-versus-host disease (aGVHD). The differentiation of T cells into this subtype is dictated by the nature of the donor naive CD4+ T cell–host antigen presenting cell (APC) interaction. Suppressors of cytokine signalling (SOCS) are a family of molecules that act as negative regulators for cytokine signalling, which regulate the negative cytokine signalling pathway through inhibiting the cytokine-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Studies have shown that SOCS proteins are key physiological regulators of both innate and adaptive immunity. These molecules are essential for T cell development and differentiation. SOCS-3 can inhibit polarization to Th1 and contribute to polarization to Th2. In this study, we found that interleukin (IL)-2 pre-incubation of C57BL/6 naive CD4+ T cells could up-regulate the expression of SOCS-3. Naive CD4+ T cells constitutively expressed low levels of SOCS-3 mRNA. SOCS-3 mRNA began to rise after 4 h, and reached peak level at 6 h. At 8 h it began to decrease. High expression of SOCS-3 mRNA induced by IL-2 could inhibit the proliferation of naive CD4+ T cells following stimulation with allogeneic antigen. IL-2-induced high SOCS-3 expression in naive CD4+ T cells could inhibit polarization to Th1 with stimulation of allogeneic antigens. We have demonstrated that IL-2-induced high SOCS-3 expression in naive CD4+ T cells could reduce the incidence of aGVHD between major histocompatibility complex (MHC) completely mismatched donor and host when high SOCS3 expression of CD4+T cells encounter allogeneic antigen in time. These results show that IL-2-induced high SOCS-3 expression can inhibit aGVHD through inhibiting proliferation and polarization to Th1 with the stimulation of allogeneic antigen.
Infant CD4 C868T polymorphism is associated with increased human immunodeficiency virus (HIV-1) acquisition
Authors: Choi R Y , Farquhar C , Juno J , Mbori-Ngacha D , Lohman-Payne B , Vouriot F , Wayne S , Tuff J , Bosire R , John-Stewart G , Fowke K
Published: February 2010

The C868T single nucleotide polymorphism (SNP) in the CD4 receptor encodes an amino acid change that could alter its structure and influence human immunodeficiency virus (HIV-1) infection risk. HIV-1-infected pregnant women in Nairobi were followed with their infants for 1 year postpartum. Among 131 infants, those with the 868T allele were more likely than wild-type infants to acquire HIV-1 overall [hazard ratio (HR) = 1.92, 95% confidence interval (CI) 1.05, 3.50, P = 0.03; adjusted HR = 2.03, 95% CI 1.03, 3.98, P = 0.04], after adjusting for maternal viral load. This SNP (an allele frequency of ∼15% in our cohort) was associated with increased susceptibility to mother-to-child HIV-1 transmission, consistent with a previous study on this polymorphism among Nairobi sex workers.
Dynamics and regulation of the southern brook trout (Salvelinusfontinalis) population in an Appalachian stream
Authors: GROSSMAN GARY D. , RATAJCZAK ROBERT E. , WAGNER C. MICHAEL , PETTY J. TODD
Published: February 2010

1. We used information theoretic statistics [Akaike’s Information Criterion (AIC)] and regression analysis in a multiple hypothesis testing approach to assess the processes capable of explaining long‐term demographic variation in a lightly exploited brook trout population in Ball Creek, NC. We sampled a 100‐m‐long second‐order site during both spring and autumn 1991–2004, using three‐pass electrofishing.

2. Principle component analysis indicated that the site had lower average velocity, greater amounts of depositional substrata and lower amount of erosional substrata during the 1999–2002 drought than in non‐drought years. In addition, drought years had lower flows, and lower variation in flows, than non‐drought years.

3. Both young‐of‐the‐year (YOY) and adult densities varied by an order of magnitude during the study. AIC analysis conducted on regressions ofper capitarate of increase versus various population and habitat parameters for the population, adults and YOY, for both spring and autumn data sets, indicated that simple density dependence almost always was the only interpretable model with Akaike weights (wi) ranging from 0.262 to 0.836.

4. Growth analyses yielded more variable results, with simple density dependence being the only interpretable model for both adult spring data (wi = 0.999) and YOY autumn data (wi = 0.905), and positive density dependence (wi = 0.636) and simple density independence (wi = 0.241) representing interpretable models for spring YOY data.

5. We detected a significant stock–recruitment relationship between both spring and autumn densities of adults in year t and autumn YOY density in yeart + 1. Finally, spring YOY density was positively correlated with both autumn YOY density and spring mean YOY standard length (SL), suggesting that processes affecting recruitment show residual effects at least in the first year of life. This population appears to be regulated primarily by density‐dependent processes, although high flows also negatively affected mean SLs of YOY.
Genetic evidence for Dnmt3a‐dependent imprinting during oocyte growth obtained by conditional knockout with Zp3‐Cre and complete exclusion of Dnmt3b by chimera formation
Authors: Kaneda Masahiro , Hirasawa Ryutaro , Chiba Hatsune , Okano Masaki , Li En , Sasaki Hiroyuki
Published: February 2010

In the male and female germ‐lines of mice, both of the two de novo DNA methyltransferases Dnmt3a and Dnmt3b are expressed. By the conditional knockout experiments using the Tnap‐Cre gene, we previously showed that deletion of Dnmt3a in primordial germ cells disrupts paternal and maternal imprinting, however, Dnmt3b mutants did not show any defect. Here, we have knocked out Dnmt3a after birth in growing oocytes by using the Zp3‐Cre gene and obtained genetic evidence that de novo methylation by Dnmt3a during the oocyte growth stage is indispensable for maternal imprinting. We also carried out DNA methylation analysis in the mutant oocytes and embryos and found that hypomethylation of imprinted genes in Dnmt3a‐deficient oocytes was directly inherited to the embryos, but repetitive elements were re‐methylated during development. Furthermore, we show that Dnmt3b‐deficient cells can contribute to the male and female germ‐lines in chimeric mice and can produce normal progeny, establishing that Dnmt3b is dispensable for mouse gametogenesis and imprinting. Finally, Dnmt3‐related protein Dnmt3L is not only essential for methylation of imprinted genes but also enhances de novo methylation of repetitive elements in growing oocytes.
Prophylaxis in haemophilia with inhibitors: update from international experience
Authors: CARCAO M. , LAMBERT T.
Published: February 2010

Summary.  An antibody response to therapeutically administered factor VIII (FVIII) can occur in up to 30% of patients with haemophilia, resulting in the production of inhibitors that neutralize FVIII coagulant activity. Immune tolerance induction (ITI) therapy can be used to eradicate inhibitors in these patients, allowing them to continue with factor replacement therapy. Patients with inhibitors (prior to initiation of ITI, while on ITI or those who fail ITI) experience more difficulty in treating bleeds than those patients who do not develop inhibitors. Increasingly, prophylaxis with bypassing therapy is being employed in patients who develop inhibitors. Two bypassing agents, a plasma‐derived activated prothrombin complex concentrate [aPCC (FEIBA®; Baxter AG, Vienna, Austria)] and NovoSeven® [recombinant factor VIIa (rFVIIa); NovoNordisk, Denmark] are potentially available for prophylaxis in patients with haemophilia who have developed inhibitors. Results from recent retrospective studies demonstrate the efficacy and safety of both aPCC and rFVIIa in decreasing the frequency of bleeding episodes in patients with haemophilia and inhibitors. In this article, we highlight a number of ongoing studies that aim to identify patients who should be placed on prophylaxis with bypassing agents.
Interleukin‐17 and its target genes: mechanisms of interleukin‐17 function in disease
Authors: Onishi Reiko M. , Gaffen Sarah L.
Published: February 2010

Interleukin‐17 (IL‐17) has emerged as a central player in the mammalian immune system. Although this cytokine exerts a host‐defensive role in many infectious diseases, it promotes inflammatory pathology in autoimmunity and other settings. A myriad of studies have focused on how IL‐17‐producing cells are generated. However, the means by which IL‐17 achieves its effects, either for the benefit or the detriment of the host, are due in large part to the induction of new gene expression. Whereas many IL‐17 target genes are common to different disease states, in some cases the effects of IL‐17 differ depending on the target cell, infectious site or pathogen. Gene products induced by IL‐17 include cytokines (IL‐6, granulocyte‐colony‐stimulating factor, tumour necrosis factor‐α), chemokines (CXCL1, CXCL2, CCL20, among many others), inflammatory effectors (acute‐phase protesins, complement) and antimicrobial proteins (defensins, mucins). Different cell types appear to respond differently to IL‐17 in terms of target gene expression, with notable differences seen in mesenchymal and epithelial cells compared with cells of haematopoietic origin. Here, we summarize the major IL‐17 target genes that mediate this cytokine’s activities in both autoimmune and chronic diseases as well as during various types of infections.
Immunological synapse: a multi‐protein signalling cellular apparatus for controlling gene expression
Authors: Padhan Kartika , Varma Rajat
Published: February 2010

The interaction of T cells with antigen‐presenting cells is the hallmark of adaptive immunity. In vitro studies have described the formation of an immunological synapse between these cells, and intra‐vital imaging has described in great detail the dynamics of these interactions. The immunological synapse has become a paradigm to study signals exchanged between the two cells. A wealth of information has been amassed regarding the localization of signalling molecules, their kinetics and the transcription factors they activate. We continue to discover mechanisms that cause receptors and signalling molecules to compartmentalize in the cell; however, the emerging challenge lies in understanding how the immunological synapse contributes to differentiation. Here, we review some of the transcription factors activated downstream of T‐cell receptor signalling and discuss mechanisms by which antigen dose and affinity may influence differentiation. Antigen affinity might change the kind of transcription factors that are activated whereas antigen dose is likely to influence the temporal dynamics of the transcription factors. The immunological synapse is therefore likely to influence differentiation by modulating the trafficking of transcription factors and by promoting asymmetric cell division, an emerging concept.
Phosphorylation of phosducin‐like protein BDM‐1 by protein kinase 2 (CK2) is required for virulence and Gβ subunit stability in the fungal plant pathogen Cryphonectria parasitica
Authors: Salamon Joanna A. , Acuña Rachel , Dawe Angus L.
Published: February 2010

Phosducin‐like proteins are conserved regulatory components of G‐protein signalling pathways, which mediate many physiological processes. Identified throughout eukaryotic genomes, they are thought to serve as regulators of Gβγ assembly. Cryphonectria parasitica, a plant pathogen and causative agent of chestnut blight, contains three Gα, one Gβ, one Gγ subunits and phosducin‐like protein BDM‐1 that have important roles in pigmentation, sporulation and virulence. Deletion of either Gβ subunit or BDM‐1 produces identical phenotypes. Additionally, we report that the Gβ subunit is not detectable in absence of BDM‐1. Given that the regulatory role of phosducin‐like proteins may be influenced by protein kinase 2 (CK2), we confirmed that BDM‐1 is a phosphoprotein that can be targeted by CK2 in vitro. Mutagenesis of the five putative CK2 sites revealed that native phosphorylation likely occurs at two locations. Strains bearing a single or double serine to alanine substitutions at those sites were significantly less virulent with only minor phenotypic changes from vegetative colonies. Therefore, CK2 activity appears to mediate key signals that are required for virulence, but not for vegetative growth. Expression of selected CK2 mutants resulted in reduced accumulation of the Gβ subunit, suggesting that phosphorylation of BDM‐1 influences Gβ stability.
Human sewage identified as likely source of white pox disease of the threatened Caribbean elkhorn coral, Acropora palmata
Authors: Sutherland Kathryn Patterson , Porter James W. , Turner Jeffrey W. , Thomas Brian J. , Looney Erin E. , Luna Trevor P. , Meyers Meredith K. , Futch J. Carrie , Lipp Erin K.
Published: February 2010

Caribbean elkhorn coral, Acropora palmata, has been decimated in recent years, resulting in the listing of this species as threatened under the United States Endangered Species Act. A major contributing factor in the decline of this iconic species is white pox disease. In 2002, we identified the faecal enterobacterium, Serratia marcescens, as an etiological agent for white pox. During outbreaks in 2003 a unique strain of S. marcescens was identified in both human sewage and white pox lesions. This strain (PDR60) was also identified from corallivorious snails (Coralliophila abbreviata), reef water, and two non‐acroporid coral species, Siderastrea siderea and Solenastrea bournoni. Identification of PDR60 in sewage, diseased Acropora palmata and other reef invertebrates within a discrete time frame suggests a causal link between white pox and sewage contamination on reefs and supports the conclusion that humans are a likely source of this disease.
Transcriptional studies of the hrpM/opgH gene in Pseudomonas syringae during biofilm formation and in response to different environmental challenges
Authors: Penaloza‐Vazquez Alejandro , Sreedharan Aswathy , Bender Carol L.
Published: February 2010

Pseudomonas syringae pv. syringae strain FF5 is a phytopathogen that causes a rapid dieback on ornamental pear trees. In the present study, the transcriptional expression of hrpM/opgH, algD, hrpR and rpoD was evaluated in P. syringae FF5 and FF5.M2 (hrpM/opgH mutant). The temporal expression of these genes was evaluated during biofilm formation, the hypersensitive reaction (HR) on tobacco plants, and when the bacteria were subjected to different environmental stresses. The results indicate that mutations in hrpM negatively impair several traits including biofilm formation, the ability to cause disease in host plants and the HR in non‐host plants, and the expression of hrpR, a regulatory gene modulating the latter two traits. Furthermore, FF5.M2 was decreased in swarming motility and unable to respond to different environmental challenges. Interestingly, FF5.M2 showed an exponential increase in the expression of algD, which is the first gene to be transcribed during the biosynthesis of the alginate, a virulence factor in P. syringae. The expression of both hrpM and algD were required for biofilm formation, and hrpM was expressed earlier than algD during biofilm development. These findings indicate that hrpM expression is required for several traits in P. syringae and plays an important role in how this bacterium responds to environmental challenges.
Do high ferritin levels confer lower cardiovascular risk in men with Type 2 diabetes?
Authors: Hermans M. P. , Ahn S. A. , Amoussou‐Guenou K. D. , Balde N. M. , Rousseau M. F.
Published: February 2010

Diabet. Med. 27, 417–422 (2010)

Aims  High ferritin levels are associated with insulin resistance and liver steatosis, both thought of as emerging cardiovascular risk factors. The association between ferritin and cardiovascular disease is poorly documented in cardiometabolic states with higher cardiovascular risk, such as diabetes and metabolic syndrome. We therefore characterized a cohort of males with Type 2 diabetes mellitus (T2DM) according to ferritin levels and prevalent macroangiopathy.

Methods  The presence of overall macroangiopathy, peripheral and/or coronary artery disease was documented in 424 consecutive T2DM males, who were divided according to ferritin quartiles (Q) as follows: QI–III, normal ferritin (NF; n = 318), mean ± 1 sd ferritin 133 ± 72 ng/ml; and QIV patients, high ferritin (HF; n = 106), ferritin 480 ± 228 ng/ml.

Results  Age, age at diabetes diagnosis, smoking, ethanol intake, body mass index, waist circumference, blood pressure and presence of metabolic syndrome did not differ between groups. However, the prevalence of macroangiopathy was unexpectedly much lower in patients with high ferritin, as follows: 25% vs. 43% for overall macroangiopathy; 7% vs. 16% for peripheral artery disease; and 16% vs. 31% for coronary artery disease (P = 0.0009, P = 0.0140 and P = 0.0035, respectively, vs. NF patients). Insulin resistance index and prevalence of liver steatosis were higher in HF compared with NF patients as follows: 2.17% vs. 1.89% and 78% vs. 64% (P = 0.0345 and P = 0.0059, respectively). Liver enzymes (aspartate aminotransferase, alanine aminotransferase and γ‐glutamyl transferase) were significantly higher in HF, by 33%, 42% and 72%, respectively (all P < 0.0002), suggesting a higher prevalence of steatohepatitis. Glycated haemoglobin, low‐density lipoprotein‐cholesterol, high‐density lipoprotein‐cholesterol, triglycerides, urate, high‐sensitivity C‐reactive protein and albuminuria were not different between groups.

Conclusions  Our results demonstrate that T2DM males with high ferritin levels exhibit a markedly decreased prevalence of macroangiopathy, despite more severe insulin resistance and higher markers of steatohepatitis. High ferritin levels and/or steatosis may thus paradoxically confer a lowered cardiovascular risk in diabetic males.
The Absence of Knowledge in Australian Curriculum Reforms
Authors: YATES LYN , COLLINS CHERRY
Published: February 2010

This article draws on a study of Australian curriculum shifts between 1975 and 2005 to take up two themes of this special issue: the question about what conceptions of knowledge are now at work; and the consideration of global influences and national specificities in the reformulations of curriculum. It discusses two important approaches to curriculum in Australia in recent times, the ‘Statements and Profiles’ activity of the early 1990s, and the ‘Essential Learnings’ formulations of the past decade. The global tendencies we see at work in these two major approaches are, first, an increasing emphasis on externally managing and auditing student progress as a key driver of how curriculum policies are being constructed; and, secondly, a growing emphasis on approaching curriculum aims in terms of what students should be able to do rather than what they should know. We argue that in the contexts we discuss here, these approaches offered a way of marrying 1970s progressive views on child development and knowledge‐as‐process (views widely held by influential curriculum professionals in Australia) with late 20th century technologies of micro‐management and instrumental agendas favoured by politicians — but that many questions about knowledge were left off the agenda.
Institutional Contexts and International Performances in Schooling: comparing patterns and trends over time in international surveys
Authors: HOFMAN W.H. ADRIAAN , HOFMAN ROELANDE H. , GRAY JOHN M.
Published: February 2010

15 European countries were classified into four types in an international comparative study. The country profiles are based on indicators of the key concepts' funding, governance and choice. This research attempts to answer the question of how the quality of schooling of these types of education systems progressed as from 1995 and what explanations an expert panel of educationalists and researchers can provide for the outcomes. We observe significant differences between the performance trends of the four types of education systems. Also, comparisons between the different years show relatively high and significant correlations, especially between the original sample of countries in 1995 and future performances in TIMSS and PISA measurements.
DO RENT‐SEEKING GROUPS ANNOUNCE THEIR SHARING RULES?
Authors: BAIK KYUNG HWAN , LEE DONGRYUL
Published: February 2010

We study collective rent seeking between two groups in which each group has the option of releasing or not its sharing‐rule information. First, we show that the case where both groups release their sharing‐rule information never occurs in equilibrium; when the players are unevenly matched, one group releases its sharing‐rule information and the other does not. Then, we select the Pareto‐superior equilibrium when the players are unevenly matched. We show that, in this selected equilibrium, the underdog releases its sharing‐rule information, and the favorite does not; thus, the underdog becomes the leader, and the favorite the follower (JEL D72).
Humanitarian presence and urban development: new opportunities and contrasts in Goma, DRC
Authors: Büscher Karen , Vlassenroot Koen
Published: February 2010

This paper examines the impact of the presence of international humanitarian organisations on local urban transformation processes in the city of Goma, Democratic Republic of the Congo (DRC). Rather than evaluating the direct effects of humanitarian interventions and strategies, it focuses on the indirect but profound effects of the presence of this ‘humanitarian sector’. It argues that the international humanitarian presence became a significant factor in the recent shaping and reshaping of the city's profile and has reinforced competition over the urban political and socioeconomic space. The paper evaluates the direct and indirect impact of the international humanitarian presence on the local urban economy and the larger political economy of war in eastern DRC. It analyses how this presence has reinforced processes of spatial reconfiguration, how it has influenced urban planning, and how it has affected dynamics of gentrification and marginalisation on the urban spatial level.
On the invisibility of the emasculated (Respond to this article at http://www.therai.org.uk/at/debate)
Authors: Wassersug Richard
Published: February 2010

Castrating a male by destroying his testicles is a practice that most people assume ended a century or so ago with the collapse of the Chinese and Ottoman Empires and the death of the last castrato in the Vatican choir. However, because advanced prostate cancer is treated by either chemical or surgical castration, there are probably more castrated men alive today than ever before in history. Castration is also used in the western world as either a step in the sexual reassignment of male to female (MtF) transsexuals or rarely to treat recidivist sexual predators. In addition, some men desire emasculation who are neither cancer patients, MtF transsexuals, nor sexual predators. In this essay I argue that the public association of castration with sexual predators and deviant behaviour is so great that men, who require it as a medical treatment for cancer or who seek it for other reasons typically hide from public view. One consequence of the shame associated with castration is that those, who desire emasculation but do not have a diagnosis of cancer, too often subject themselves to risky and illegal amateur surgeries outside the medical system. I argue that for whatever reason a male seeks castration, the overall invisibility of the emasculated in modern society is a disservice. It minimizes the public's understanding of the magnitude of the impact of castration on cancer patients and it inhibits those in need of medical treatment from getting it in an appropriate and timely fashion.