bluuebunny/crossref_metadata_2025_split huggingface dataset:
MIR29B regulates expression of MLLT11 (AF1Q), an MLL fusion partner, and low MIR29B expression associates with adverse cytogenetics and poor overall survival in AML
Authors: Xiong Yin , Li Zejuan , Ji Min , Tan Aik‐Choon , Bemis Judson , Tse Jove‐Victor , Huang Gang , Park Jino , Ji Chunyan , Chen Jianjun , Bemis Lynne T. , Bunting Kevin D. , Tse William 
Published: April 2011

Summary MLLT11, an MLL fusion partner, is a poor prognostic biomarker for paediatric acute myeloid leukaemia (AML), adult normal cytogenetics AML, and adult myelodysplastic syndrome. MLLT11 is highly regulated during haematopoietic progenitor differentiation and development but its regulatory mechanisms have not been defined. In this study, we demonstrate by transfection experiments that MIR29B directly regulates MLLT11 expression in vitro. MIR29B expression level was also inversely related to MLLT11 expression in a cohort of 56 AML patients (P < 0·05). AML patients with low MIR29B/elevated MLLT11 expression had poor overall survival (P = 0·038). Therefore, MIR29B may be a potential prognostic biomarker for AML patients.
How I manage venous thromboembolism in pregnancy
Authors: Arya Roopen 
Published: April 2011

SummaryIn pregnancy, the combination of altered coagulation factors, stasis and vascular damage heightens the thrombotic risk and venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality. In women presenting with pregnancy‐related VTE, the wellbeing of both mother and fetus must be considered, necessitating a multidisciplinary approach. The risk of VTE is present throughout the pregnancy and is maximal during the postpartum period. Diagnosis may be difficult because the symptoms might mimic those of pregnancy and prospectively validated diagnostic protocols are lacking. Compression ultrasound is the test of choice for deep vein thrombosis and perfusion scan and computerized tomography pulmonary angiography are the imaging options for diagnosis of pulmonary embolism. Low molecular weight heparin does not cross the placenta and is a safe and effective treatment for the majority of cases of pregnancy‐related VTE. This review provides a practical approach to diagnosis and treatment of VTE in pregnancy.
Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin‐deficient hypopituitary male patients
Authors: Behan Lucy‐Ann , Rogers Bairbre , Hannon Mark J. , O’Kelly Patrick , Tormey William , Smith Diarmuid , Thompson Christopher J. , Agha Amar 
Published: April 2011

SummaryBackground  The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15–30 mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens.Objective  Primarily to define the hydrocortisone regimen which results in a 24 h cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL).Design  Ten male hypopituitary patients with severe ACTH deficiency (basal cortisol <100 nm and peak response to stimulation <400 nm) were enrolled in a prospective, randomized, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24 h serum cortisol sampling and QoL assessment with the Short Form 36 (SF36) and the Nottingham Health Profile (NHP) questionnaires. Free cortisol was calculated using Coolen’s equation. All results were compared to those of healthy, matched controls.Results  Corticosteroid binding globulin (CBG) was significantly lower across all dose regimens compared to controls (P < 0·05). The lower dose regimen C (10 mg mane/5 mg tarde) produced a 24 h free cortisol profile (FCP) which most closely resembled that of controls. Both regimen A(20 mg mane/10 mg tarde) and B(10 mg mane/10 mg tarde) produced supraphysiological post‐absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (P < 0·001).Conclusions  The lower dose of hydrocortisone (10 mg/5 mg) produces a more physiological cortisol profile, without compromising QoL, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.
Mechanisms for maintaining cell shape in rod‐shaped Gram‐negative bacteria
Authors: Furchtgott Leon , Wingreen Ned S. , Huang Kerwyn Casey 
Published: April 2011

SummaryFor the rod‐shaped Gram‐negative bacterium Escherichia coli, changes in cell shape have critical consequences for motility, immune system evasion, proliferation and adhesion. For most bacteria, the peptidoglycan cell wall is both necessary and sufficient to determine cell shape. However, how the synthesis machinery assembles a peptidoglycan network with a robustly maintained micron‐scale shape has remained elusive. To explore shape maintenance, we have quantified the robustness of cell shape in three Gram‐negative bacteria in different genetic backgrounds and in the presence of an antibiotic that inhibits division. Building on previous modelling suggesting a prominent role for mechanical forces in shape regulation, we introduce a biophysical model for the growth dynamics of rod‐shaped cells to investigate the roles of spatial regulation of peptidoglycan synthesis, glycan‐strand biochemistry and mechanical stretching during insertion. Our studies reveal that rod‐shape maintenance requires insertion to be insensitive to fluctuations in cell‐wall density and stress, and even a simple helical pattern of insertion is sufficient for over sixfold elongation without significant loss in shape. In addition, we demonstrate that both the length and pre‐stretching of newly inserted strands regulate cell width. In sum, we show that simple physical rules can allow bacteria to achieve robust, shape‐preserving cell‐wall growth.
A mitochondrial GABA permease connects the GABA shunt and the TCA cycle, and is essential for normal carbon metabolism
Authors: Michaeli Simon , Fait Aaron , Lagor Kelly , Nunes‐Nesi Adriano , Grillich Nicole , Yellin Ayelet , Bar Dana , Khan Munziba , Fernie Alisdair R. , Turano Frank J. , Fromm Hillel 
Published: April 2011

SummaryIn plants, γ‐aminobutyric acid (GABA) accumulates in the cytosol in response to a variety of stresses. GABA is transported into mitochondria, where it is catabolized into TCA cycle or other intermediates. Although there is circumstantial evidence for mitochondrial GABA transporters in eukaryotes, none have yet been identified. Described here is an Arabidopsis protein similar in sequence and topology to unicellular GABA transporters. The expression of this protein complements a GABA‐transport‐deficient yeast mutant. Thus the protein was termed AtGABP to indicate GABA‐permease activity. In vivo localization of GABP fused to GFP and immunobloting of subcellular fractions demonstrate its mitochondrial localization. Direct [3H]GABA uptake measurements into isolated mitochondria revealed impaired uptake into mitochondria of a gabp mutant compared with wild‐type (WT) mitochondria, implicating AtGABP as a major mitochondrial GABA carrier. Measurements of CO2 release, derived from radiolabeled substrates in whole seedlings and in isolated mitochondria, demonstrate impaired GABA‐derived input into the TCA cycle, and a compensatory increase in TCA cycle activity in gabp mutants. Finally, growth abnormalities of gabp mutants under limited carbon availability on artificial media, and in soil under low light intensity, combined with their metabolite profiles, suggest an important role for AtGABP in primary carbon metabolism and plant growth. Thus, AtGABP‐mediated transport of GABA from the cytosol into mitochondria is important to ensure proper GABA‐mediated respiration and carbon metabolism. This function is particularly essential for plant growth under conditions of limited carbon.
Gene transfer of the adaptor Lnk (SH2B3) prevents porcine endothelial cell activation and apoptosis: implication for xenograft’s cytoprotection
Authors: Chatelais Mathias , Devallière Julie , Galli Cesare , Charreau Béatrice 
Published: April 2011

Chatelais M, Devallière J, Galli C, Charreau B. Gene transfer of the adaptor Lnk (SH2B3) prevents porcine endothelial cell activation and apoptosis: implication for xenograft’s cytoprotection. Xenotransplantation 2011; 18: 108–120. © 2011 John Wiley & Sons A/S.Abstract:  Background:  Targeting protective gene expression to porcine endothelium by genetic modification of the donor could improve xenograft survival by controlling cell activation and death. We previously found that, in endothelial cells (EC), the molecular adaptor Lnk (SH2B3) is a negative regulator of cytokine signaling. We also have shown that Lnk is upregulated in pig EC (PAEC) in response to tumor necrosis factor‐α (TNF) and xenoreactive natural antibodies (XNA) binding. The present study investigated whether ectopic expression of human Lnk using gene transfer may be efficient to control signaling pathways associated with inflammation and apoptosis in porcine aortic endothelial cells (PAEC).Methods:  Endothelial cells cultures were established from WT and Gal−/− pigs and transduced with a recombinant adenovirus encoding human Lnk. Phenotype and functions of transduced PAEC expressing Lnk were analyzed by flow cytometry, western blot and XNA and complement‐dependent assays. The regulatory functions of Lnk toward inflammation were assessed in TNF‐activated EC, and the protective functions were tested toward TNF‐induced apoptosis and anoïkis. Apoptosis assays included DNA content analysis and caspase‐3/7 activity.Results:  First, we found that as a result of adenoviral transduction, human Lnk was efficiently and similarly expressed in EC from WT or Gal−/− pigs. Lnk expression or EC transduction caused no significant change in the binding of XNA (IgG and IgM) to PAEC and has no effect on complement activation and C5b‐9 formation. We demonstrated that expression of human Lnk efficiently inhibits TNF signaling in PAEC and decreases VCAM‐1 induction by 46.3 ± 1.2% compared to controls (n = 6, **P < 0.01). Furthermore, expression of Lnk was associated with a significant decrease in the percentage of caspase‐3/7‐dependent apoptosis caused by TNF in the presence of actinomycin D and also reduces cell death by anoïkis by 25.0 ± 1.9% compared to controls (n = 5, **P < 0.01).Conclusions:  Together, these findings indicate that the signaling adaptor Lnk is effective to reduce PAEC activation and apoptosis. Thus, Lnk is a potential candidate for the modulation of signaling pathways to protect vascular EC from inflammation in xenotransplantation.
Microbiological safety of porcine islets: comparison with source pig
Authors: Abrahante Juan E. , Martins Kyra , Papas Klearchos K. , Hering Bernhard J. , Schuurman Henk‐Jan , Murtaugh Michael P. 
Published: April 2011

Abrahante JE, Martins K, Papas KK, Hering BJ, Schuurman H‐J, Murtaugh MP. Microbiological safety of porcine islets: comparison with source pig. Xenotransplantation 2011; 18: 88–93. © 2011 John Wiley & Sons A/S.Abstract:  Background:  Pig islet donors intended for clinical xenotransplantation for the treatment of diabetes must meet stringent conditions. Among others, viruses with the potential to cross the species barrier should be excluded from the herd: this list includes encephalomyocarditis virus (EMCV), hepatitis E virus (HEV), porcine cytomegalovirus (PCMV) and porcine γ‐lymphotropic herpesvirus (PLHV). As an islet product is isolated from the pancreas and then subjected to culture before implantation, the question is raised whether islets could be negative even if the animal itself is positive for a distinct pathogen.Methods:  To answer this question, sensitive quantitative real‐time PCR assays were established for EMCV, HEV, PCMV and PLHV. Twelve adult animals from a high‐hygienic herd were then evaluated; testing tissues, where the virus is expected to reside in latent infection, testing islets immediately after isolation, and then isolated islets after a 7‐day culture.Results:  None of the tissues tested positive for EMCV, HEV or PLHV. PCMV was observed in spleen tissue from six animals: three of these six animals were positive for isolated islets, and two of these three cases were also positive for islets after culture. Older animals in particular showed positivity, and within a given litter not all animals were PCMV positive.Conclusions:  These data fit with spread through the herd by horizontal transmission, not in utero infection. PCMV has to be excluded from the herd to ensure that islets for transplantation are negative for PCMV.
Evaluation of 15 caespitose bamboo EST‐SSR markers for cross‐species/genera transferability and ability to identify interspecies hybrids
Authors: Dong Wen‐Juan , Wu Miao‐Dan , Lin Yuan , Zhou Ming‐Bing , Tang Ding‐Qin 
Published: April 2011

With 1 figure and 1 tableAbstractPublic sequence databases provide a convenient and inexpensive resource for the rapid development of microsatellite markers. We analysed 3406 publically available expressed sequence tags (ESTs) from caespitose bamboo species (Bambusa edulis and B. oldhamii) and found 245 non‐redundant simple sequence repeats (SSRs) in 205 EST contigs that were used to develop 15 EST‐SSR markers. The transferability of the markers was 59.6% among 14 additional caespitose bamboo species (4 within the same genus and 10 in other genera) and Phyllostachys pubescens. The successfully transferred markers showed 51.4% polymorphism. Markers BOM01 and BOM02 transferred successfully to most of the caespitose bamboo species showed rich polymorphism, and are therefore potentially valuable as species‐specific alleles for the identification of caespitose bamboo interspecies hybrids.
A study on relative importance of additive, epistasis and unmapped QTL for Aluminium tolerance at seedling stage in soybean
Authors: Korir Paul C. , Qi Bo , Wang Yufeng , Zhao Tuanjie , Yu Deyue , Chen Shouyi , Gai Junyi 
Published: April 2011

With 3 figures and 6 tablesAbstractThe relative importance of quantitative trait locus (QTL) types controlling aluminium (Al) tolerance in a recombinant inbred line population of soybean was assessed under greenhouse sand culture in 2 years. Three growth‐related indicators for Al‐tolerance, namely relative total plant dry weight (RTDW), relative shoot dry weight (RSDW) and relative root dry weight (RRDW) were analysed for genetic architecture. RTDW showed relatively higher correlations and shared marker regions with RSDW and RRDW. Four additive QTL, four epistatic QTL pairs and collective unmapped QTL were identified for RTDW, with respective contributions of 22.30%, 14.86% and 40.64%, in a total genetic contribution of 77.80% to phenotypic variation, while QTL × Environment contribution was relatively negligible. Similar results were found for RSDW and RRDW. Altogether, seven additive QTL, eleven epistatic QTL pairs and collective unmapped QTL were involved with Al‐tolerance. Among them, one major QTL linked to marker region GMKF046‐Sat_128 on B1 was shared by the three traits. The results imply that the three QTL types are all relevant and should be comprehensively utilized for the improvement of Al‐tolerance in soybean.
Relationships between blood levels of fat soluble vitamins and disease etiology and severity in adults awaiting liver transplantation
Authors: Abbott‐Johnson Winsome , Kerlin Paul , Clague Alan , Johnson Helen , Cuneo Ross 
Published: April 2011

AbstractBackground and Aims:  Although malnutrition is common in liver disease, there are limited data on fat soluble vitamins in various diseases. The aims of this study were to: (i) determine fat soluble vitamin levels in patients assessed for liver transplantation; (ii) compare levels between different disease etiologies (hepatocellular and cholestatic) and between subgroups of hepatocellular disease; and (iii) assess the multivariate contribution to vitamin levels of etiology and various indicators of disease severity.Methods:  This was a cross‐sectional study of 107 inpatients awaiting liver transplantation, mean age 47 years. Biochemical parameters included plasma retinol, 25‐hydroxycholecalciferol, and vitamin E. Biochemical (albumin, bilirubin and zinc) and clinical indicators (Child‐Pugh and Model of End Stage Liver Disease [MELD] scores) of disease severity were determined.Results:  Deficiencies of retinol (< 1.0 µmol/L), 25‐hydroxycholecalciferol (< 50 nmol/L) and vitamin E (< 11 µmol/L) were present in 75%, 66% and 3%, respectively, of patients. Concentrations of retinol and vitamin E were lower in hepatocellular than cholestatic disease but 25‐hydroxycholecalciferol concentrations were similar. Child–Pugh score was higher in hepatocellular than cholestatic disease. Concentrations of retinol were lower in alcoholic liver disease (ALD) than hepatitis and Child–Pugh score was higher in ALD. For the whole group, levels of retinol, 25‐hydroxycholecalciferol and vitamin E were negatively related to Child–Pugh score, MELD score and bilirubin, and positively related to albumin. When Child–Pugh scores were controlled for, retinol was lower in the hepatocellular group.Conclusions:  There was a high prevalence of fat soluble vitamin deficiencies with vitamin levels being related to disease severity. Retinol was lower in the hepatocellular group.
Diagnostic accuracy of endoscopic ultrasound‐guided fine needle aspiration for suspected pancreatic malignancy in relation to the size of lesions
Authors: Uehara Hiroyuki , Ikezawa Kenji , Kawada Natsuko , Fukutake Nobuyasu , Katayama Kazuhiro , Takakura Rena , Takano Yasuna , Ishikawa Osamu , Takenaka Akemi 
Published: April 2011

AbstractBackground and Aim:  Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is an accurate method for cytological confirmation of pancreatic malignancy, but it has been unknown whether its diagnostic accuracy for pancreatic lesions was affected by their size, location, or size of needles. Our aim was to investigate the accuracy of EUS‐FNA for suspected pancreatic malignancy in relation to these factors, especially to the size of lesions.Methods:  In a tertiary referral center, EUS‐FNAs for 120 suspected pancreatic malignancies in 115 patients based on other imaging studies were evaluated retrospectively.Results:  Overall accuracy of EUS‐FNA was 96% (115/120), with sensitivity of 95% (76/80), specificity of 98% (39/40), positive predictive value of 99% (76/77), and negative predictive value of 91% (39/43). Accuracies for lesions less than 10 mm, 11–20 mm, 21–30 mm, and more than 31 mm were 96%, 95%, 96%, and 100%, respectively; those for lesions in the head, the body, and the tail of the pancreas were 96%, 95%, and 95%, respectively. Accuracies for 22‐gauge and 25‐gauge needle were 93% and 98%, respectively.Conclusion:  EUS‐FNA was accurate in the evaluation of suspected pancreatic malignancy regardless of its size, location, or size of needles. It was useful also in the confirmation of small pancreatic malignancies less than 10 mm.
Understanding global patterns in amphibian geographic range size: does Rapoport rule?
Authors: Whitton Felix J. S. , Purvis Andy , Orme C. David L. , Olalla‐Tárraga Miguel Á. 
Published: April 2011

ABSTRACTAim Species geographic ranges are the ‘fundamental units’ of macroecology. Range size is a major correlate of extinction risk in many groups, and is also critical in studies of biotic responses to climate change. Despite this, there is a lack of studies exploring the role of environmental, historical and anthropogenic processes in determining large‐scale patterns in range size. We perform the first global analysis of putative drivers of range size variation in any group, choosing amphibians as our study taxon. Our aims are to disentangle the many hypothesized causes of range size variation and evaluate support for ‘Rapoport's rule’, the observation that range size correlates with latitude.Location Global.Methods We develop a global map of gridded median range size using the International Union for Conservation of Nature (IUCN) distribution maps. From this we perform spatial and non‐spatial regressions to explore relationships between range size and nine hypothesized variables in six biogeographic realms. We use information‐theoretic model selection to compare multiple competing variables, simultaneously evaluating the relative support for each one.Results Current climate – environmental water and energy, and temperature seasonality – is consistently highly ranked in spatial and non‐spatial analyses. Human impacts and other environmental measures (topographic and landscape complexity, effective area, climate extremes) show mixed support, and glacial history is consistently unimportant. Our findings add further evidence to the view that Rapoport's rule is a regional, not global, phenomenon.Main conclusions The primary importance of temperature seasonality may explain why Rapoport's rule is largely restricted to northern latitudes, as this is where seasonality is most pronounced. More generally, the dominance of contemporary climate in our analyses (even when accounting for space) has stark implications for the future status of amphibians. Changes in climate will almost certainly interact with the anthropogenic processes already threatening a third of amphibians globally, with the effects being most keenly felt by species with a restricted range.
Forecasting species ranges by statistical estimation of ecological niches and spatial population dynamics
Authors: Pagel Jörn , Schurr Frank M. 
Published: April 2011

ABSTRACTAim  The study and prediction of species–environment relationships is currently mainly based on species distribution models. These purely correlative models neglect spatial population dynamics and assume that species distributions are in equilibrium with their environment. This causes biased estimates of species niches and handicaps forecasts of range dynamics under environmental change. Here we aim to develop an approach that statistically estimates process‐based models of range dynamics from data on species distributions and permits a more comprehensive quantification of forecast uncertainties.Innovation  We present an approach for the statistical estimation of process‐based dynamic range models (DRMs) that integrate Hutchinson's niche concept with spatial population dynamics. In a hierarchical Bayesian framework the environmental response of demographic rates, local population dynamics and dispersal are estimated conditional upon each other while accounting for various sources of uncertainty. The method thus: (1) jointly infers species niches and spatiotemporal population dynamics from occurrence and abundance data, and (2) provides fully probabilistic forecasts of future range dynamics under environmental change. In a simulation study, we investigate the performance of DRMs for a variety of scenarios that differ in both ecological dynamics and the data used for model estimation.Main conclusions  Our results demonstrate the importance of considering dynamic aspects in the collection and analysis of biodiversity data. In combination with informative data, the presented framework has the potential to markedly improve the quantification of ecological niches, the process‐based understanding of range dynamics and the forecasting of species responses to environmental change. It thereby strengthens links between biogeography, population biology and theoretical and applied ecology.