bluuebunny/crossref_metadata_2025 huggingface dataset:
Leg muscles that mediate stability: mechanics and control of two distal extensor muscles during obstacle negotiation in the guinea fowl
Authors: Daley Monica A. , Biewener Andrew A.
Published: April 2011

Here, we used an obstacle treadmill experiment to investigate the neuromuscular control of locomotion in uneven terrain. We measuredin vivofunction of two distal muscles of the guinea fowl, lateral gastrocnemius (LG) and digital flexor-IV (DF), during level running, and two uneven terrains, with 5 and 7 cm obstacles. Uneven terrain required one step onto an obstacle every four to five strides. We compared both perturbed and unperturbed strides in uneven terrain to level terrain. When the bird stepped onto an obstacle, the leg became crouched, both muscles acted at longer lengths and produced greater work, and body height increased. Muscle activation increased on obstacle strides in the LG, but not the DF, suggesting a greater reflex contribution to LG. In unperturbed strides in uneven terrain, swing pre-activation of DF increased by 5 per cent compared with level terrain, suggesting feed-forward tuning of leg impedance. Across conditions, the neuromechanical factors in work output differed between the two muscles, probably due to differences in muscle–tendon architecture. LG work depended primarily on fascicle length, whereas DF work depended on both length and velocity during loading. These distal muscles appear to play a critical role in stability by rapidly sensing and responding to altered leg–ground interaction.
Speed adaptation in a powered transtibial prosthesis controlled with a neuromuscular model
Authors: Markowitz Jared , Krishnaswamy Pavitra , Eilenberg Michael F. , Endo Ken , Barnhart Chris , Herr Hugh
Published: April 2011

Control schemes for powered ankle–foot prostheses would benefit greatly from a means to make them inherently adaptive to different walking speeds. Towards this goal, one may attempt to emulate the intact human ankle, as it is capable of seamless adaptation. Human locomotion is governed by the interplay among legged dynamics, morphology and neural control including spinal reflexes. It has been suggested that reflexes contribute to the changes in ankle joint dynamics that correspond to walking at different speeds. Here, we use a data-driven muscle–tendon model that produces estimates of the activation, force, length and velocity of the major muscles spanning the ankle to derive local feedback loops that may be critical in the control of those muscles during walking. This purely reflexive approach ignores sources of non-reflexive neural drive and does not necessarily reflect the biological control scheme, yet can still closely reproduce the muscle dynamics estimated from biological data. The resulting neuromuscular model was applied to control a powered ankle–foot prosthesis and tested by an amputee walking at three speeds. The controller produced speed-adaptive behaviour; net ankle work increased with walking speed, highlighting the benefits of applying neuromuscular principles in the control of adaptive prosthetic limbs.
Spring-like leg behaviour, musculoskeletal mechanics and control in maximum and submaximum height human hopping
Authors: Bobbert Maarten F. , Richard Casius L. J.
Published: April 2011

The purpose of this study was to understand how humans regulate their ‘leg stiffness’ in hopping, and to determine whether this regulation is intended to minimize energy expenditure. ‘Leg stiffness’ is the slope of the relationship between ground reaction force and displacement of the centre of mass (CM). Variations in leg stiffness were achieved in six subjects by having them hop at maximum and submaximum heights at a frequency of 1.7 Hz. Kinematics, ground reaction forces and electromyograms were measured. Leg stiffness decreased with hopping height, from 350 N m−1kg−1at 26 cm to 150 N m−1kg−1at 14 cm. Subjects reduced hopping height primarily by reducing the amplitude of muscle activation. Experimental results were reproduced with a model of the musculoskeletal system comprising four body segments and nine Hill-type muscles, with muscle stimulation STIM(t) as only input. Correspondence between simulated hops and experimental hops was poor when STIM(t) was optimized to minimize mechanical energy expenditure, but good when an objective function was used that penalized jerk of CM motion, suggesting that hopping subjects are not minimizing energy expenditure. Instead, we speculated, subjects are using a simple control strategy that results in smooth movements and a decrease in leg stiffness with hopping height.
Neuromuscular strategies for the transitions between level and hill surfaces during walking
Authors: Gottschall Jinger S. , Nichols T. Richard
Published: April 2011

Despite continual fluctuations in walking surface properties, humans and animals smoothly transition between terrains in their natural surroundings. Walking transitions have the potential to influence dynamic balance in both the anterior–posterior and medial–lateral directions, thereby increasing fall risk and decreasing mobility. The goal of the current manuscript is to provide a review of the literature that pertains to the topic of surface slope transitions between level and hill surfaces, as well as report the recent findings of two experiments that focus on the neuromuscular strategies of surface slope transitions. Our results indicate that in anticipation of a change in surface slope, neuromuscular patterns during level walking prior to a hill are significantly different from the patterns during level walking without the future change in surface. Typically, the changes in muscle activity were due to co-contraction of opposing muscle groups and these changes correspond to modifications in head pitch. In addition, further experiments revealed that the neck proprioceptors may be an initial source of feedback for upcoming surface slope transitions. Together, these results illustrate that in order to safely traverse varying surfaces, transitions strides are functionally distinct from either level walking or hill walking independently.
The influence of propofol or desflurane on postoperative cognitive dysfunction in patients undergoing coronary artery bypass surgery*
Authors: Royse C. F. , Andrews D. T. , Newman S. N. , Stygall J. , Williams Z. , Pang J. , Royse A. G.
Published: April 2011

We investigated the influence of either propofol or desflurane on the incidence of postoperative cognitive dysfunction in a randomised trial of 180 patients undergoing coronary artery bypass surgery. The primary outcome was incidence of postoperative cognitive dysfunction at 3 months, defined as ≥ 1 SD deterioration in two or more of 12 neurocognitive tests. Secondary outcomes included early postoperative cognitive dysfunction (between days three and seven), delirium on day one, morbidity and length of hospital stay. Early postoperative cognitive dysfunction was significantly higher with propofol compared with desflurane (56/84 (67.5%) vs 41/83 (49.4%), respectively, p = 0.018), but this effect was not seen at 3 months (10/87 (11.2%) vs 9/90 (10.0%), respectively. There was no difference in delirium (7/89 (7.9%) vs 12/91 (13.2%), respectively, length of hospital stay (median (IQR [range]) 7 (6‐9 [4‐15]) vs 6 (5‐7 [5‐16) days, respectively or other morbidities. Desflurane was associated with reduced early cognitive dysfunction.
A comparison of low vs conventional‐dose heparin for minimal cardiopulmonary bypass in coronary artery bypass grafting surgery
Authors: Fromes Y. , Daghildjian K. , Caumartin L. , Fischer M. , Rouquette I. , Deleuze P. , Bical O. M.
Published: April 2011

The biocompatibility of minimal extracorporeal circuits has improved; however, anticoagulation is still required. We compared standard high‐dose anticoagulation with a low‐dose heparin regimen in a retrospective study of patients who underwent coronary bypass surgery using minimal cardiopulmonary bypass. One hundred patients who received 300 IU.kg−1 heparin were compared with 68 patients who received heparin according to an individually adjusted activated coagulation time target of 300 s, resulting in a mean (SD) heparin dose of 145 (30) IU.kg−1. There were no thromboembolic events in either group; however, patients in the low‐dose group had lower 24‐hour mean (SD) postoperative blood loss than the conventional group (545 (61) vs 680 (88) ml, p = 0.001) and a reduced rate of transfusion of allogeneic blood (15% patients transfused vs 32%, p = 0.01). An individually tailored low‐dose heparin regimen for minimal cardiopulmonary bypass is safe and may be associated with reduced bleeding and lower transfusion requirements.
Paediatric drug development: are population models predictive of pharmacokinetics across paediatric populations?
Authors: Cella Massimo , Zhao Wei , Jacqz‐Aigrain Evelyne , Burger David , Danhof Meindert , Pasqua Oscar Della
Published: April 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• In paediatric development, initial estimation of the paediatric dose is obtained by extrapolation. This is usually performed using the dosing regimen in another population as reference. However, no consensus on dose selection methodologies has been reached so far.

• The paradigm compound identified to illustrate these concepts is a nucleoside reverse transcriptase inhibitor (NRTI) used to treat HIV infection. The recommended paediatric dose of abacavir is 8 mg kg−1 twice daily up to a maximum of 300 mg twice daily.

WHAT THIS STUDY ADDS

• Our findings show that the use of a population model may not suffice to predict parameter distributions and drug exposure across paediatric populations.

• Estimation of covariate effects is critical, but not sufficient to extrapolate pharmacokinetics from a reference population to another population.

• Covariate‐parameter correlations may not remain constant beyond the range of observations. Exponential relationships used by allometry do not correct for these discrepancies.

AIMS To assess the predictive value of a model‐based approach for dose selection across paediatric populations in early clinical drug development.

METHODS Abacavir was selected as a paradigm compound using data across a wide age range. Abacavir pharmacokinetics (PK) in children were analysed separately from infants and toddlers. Two independent models were obtained, and systemic exposure (AUC) was then simulated across populations based on the estimates from each model. Drug exposures in infants and toddlers were predicted using pharmacokinetic parameter distributions obtained from children, and the other way around.

RESULTS The pharmacokinetic models (a two‐compartment PK model for infants and toddlers and a one compartment PK model for children) accurately described the exposure in the population from which they were built. However, neither model predicted exposure in a different population: in infants, the median AUC (95%‐CI) was estimated at 7.03 (6.72, 7.48) µg ml−1 h, whilst it was predicted at 5.75 (4.82, 6.26) µg ml−1 h; in children, the estimated median AUC was 6.96 (5.85, 7.91) µg ml−1 h, whilst the predicted value was 6.45 (5.80, 7.01) µg ml−1 h.

CONCLUSIONS These findings suggest that the assumption of an identical (linear or nonlinear) correlation between pharmacokinetic parameters and demographic factors may not hold true across age groups. Whilst the use of modelling enables accurate characterization of pharmacokinetic properties, extrapolations based on such parameter estimates may have limited value due to differences in the impact of developmental growth across populations.
Serum concentrations and clinical effects of atorvastatin in patients taking grapefruit juice daily
Authors: Reddy Patrick , Ellington David , Zhu Yiliang , Zdrojewski Immo , Parent Sarah J. , Harmatz Jerold S. , Derendorf Hartmut , Greenblatt David J. , Browne, Jr Kevin
Published: April 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• In previous studies of healthy volunteers, administration of atorvastatin with very large quantities of grapefruit juice increases exposure to atorvastatin by a mean factor of 3.3. However more typical quantities of grapefruit juice increased exposure only by a factor of 1.3. The effects of customary doses of grapefruit juice on the efficacy and safety of atorvastatin in patients requiring treatment with this drug have not been established.

WHAT THIS STUDY ADDS

• The present study is the first to evaluate changes in the lipid‐lowering efficacy of atorvastatin, as well as subjective and laboratory assessments of safety, in a series of hyperlipidaemic patients on stable doses of atorvastatin who co‐ingested typical quantities of grapefruit juice. The findings indicate a small elevation of serum atorvastatin concentrations due to grapefruit juice, but no meaningful enhancement of lipid‐lowering effects, and no evidence of adverse liver or muscle effects.

AIM To determine whether customary exposure to grapefruit juice (GFJ) alters serum concentrations, effectiveness, and potential adverse effects of atorvastatin in patients requiring the medication.

METHODS Patients receiving extended treatment with atorvastatin (10, 20 or 40 mg day−1) at a stable dose received 300 ml day−1 of 100% GFJ for a period of 90 days. One cohort of patients (arm A, n= 60) continued on their current dose of atorvastatin; the second cohort (arm B, n= 70) reduced the daily dose by 50%. Serum atorvastatin, lipid profile, liver functions, and creatine phosphokinase (CPK) were measured at baseline and at 30, 60, and 90 days after starting GFJ.

RESULTS In Arm A patients, co‐ingestion of GFJ significantly elevated serum atorvastatin by 19% to 26% compared with baseline. Changes in lipid profile relative to baseline were negligible. There were no adverse effects on liver function tests or CPK. In arm B patients, serum atorvastatin declined by 12% to 25% compared to baseline, with a small but significant unfavourable effect in serum lipid profile. There were no adverse effects on liver function tests or CPK.

CONCLUSION In patients on extended stable atorvastatin treatment, addition of daily GFJ in typical quantities slightly elevates serum atorvastatin concentrations, but has no meaningful effect on the serum lipid profile, and causes no detectable adverse liver or muscle effects. Reduction of atorvastatin dosage when moderate amounts of GFJ are co‐ingested does not appear to be necessary.
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

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

In 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

Background  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

For 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

In 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 table

Public 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 tables

The 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

Background 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

Background 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

Aim 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

Aim  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.
Cryptic niche conservatism among evolutionary lineages of an invasive lizard
Authors: Schulte Ulrich , Hochkirch Axel , Lötters Stefan , Rödder Dennis , Schweiger Silke , Weimann Thomas , Veith Michael
Published: April 2011

Aim There is increasing evidence that the quality and breadth of ecological niches vary among individuals, populations, evolutionary lineages and therefore also across the range of a species. Sufficient knowledge about niche divergence among clades might thus be crucial for predicting the invasion potential of species. We tested for the first time whether evolutionary lineages of an invasive species vary in their climate niches and invasive potential. Furthermore, we tested whether lineage‐specific models show a better performance than combined models.

Location Europe.

Methods We used species distribution models (SDMs) based on climatic information at native and invasive ranges to test for intra‐specific niche divergence among mitochondrial DNA (mtDNA) clades of the invasive wall lizardPodarcis muralis. Using DNA barcoding, we assigned 77 invasive populations in Central Europe to eight geographically distinct evolutionary lineages. Niche similarity among lineages was assessed and the predictive power of a combination of clade‐specific SDMs was compared with a combined SDM using the pooled records of all lineages.

Results We recorded eight different invasive mtDNA clades in Central Europe. The analysed clades had rather similar realized niches in their native and invasive ranges, whereas inter‐clade niche differentiation was comparatively strong. However, we found only a weak correlation between geographic origin (i.e. mtDNA clade) and invasive occurrences. Clades with narrow realized niches still became successful invaders far outside their native range, most probably due to broader fundamental niches. The combined model using data for all invasive lineages achieved a much better prediction of the invasive potential.

Conclusions Our results indicate that the observed niche differentiation among evolutionary lineages is mainly driven by niche realization and not by differences in the fundamental niches. Such cryptic niche conservatism might hamper the success of clade‐specific niche modelling. Cryptic niche conservatism may in general explain the invasion success of species in areas with apparently unsuitable climate.
The effect of cross‐listing on insider trading returns
Authors: Chang Millicent , Corbitt Ross
Published: April 2011

Holding privileged positions within firms, insiders can acquire excessive private benefits based on their informational advantage. The bonding hypothesis suggests that this can be prevented when a firm is cross‐listed on an exchange with higher regulatory and legal costs compared with its home exchange. When cross‐listed insiders buy and sell shares, the returns earned are lower than in domestic firms. This difference is attributable to the increased shareholder protection in cross‐listed firms that constrains the extraction of private benefits, such that when cross‐listed insiders trade, they trade for non‐informational reasons.
The Post‐Industrial Regime of Production/Consumption and the Rural Gentrification of the New West Archipelago
Authors: Hines J. Dwight
Published: April 2011

Abstract:  The contemporary American West is undergoing a round of rapid restructuring, which has been characterized as the shift from landscapes of production to landscapes of consumption. Here I propose that a more effective description of current changes, which allows us to retain focus on the relevant inter‐ and intra‐class‐based dynamics of an ongoing capitalist‐Modernity, is as a result of the transition from the prior dominance of a regime of production/consumption of commodities/natural resources to the increasing ascendancy of the production/consumption of “experiences”. The rising dominance of this regime is, in large part, the result of the locally dramatic in‐migration by ex‐urban members of the post‐industrial middle class to the “amenity‐rich” counties of the region. This process of rural gentrification exacerbates preexisting social, geographic, and environmental disparities within the region, creating an “archipelago” of changing communities commonly referred to as the “New” West. Drawing on almost two years of ethnographic research from one such “island” community in south‐central Montana, I describe local‐level change between the relative primacy of the two regimes of production/consumption.
Reasons patients give to use or not to use immunomodulating agents for multiple sclerosis
Authors: Visser L. H. , van der Zande A.
Published: April 2011

Background:  Variations in the treatment of multiple sclerosis (MS) occur. This study was performed to obtain insight into the reasons why patients with MS use or do not use immunomodulating treatment (DMT).

Methods:  We held a survey on the use of DMT in a group of 1572 patients with MS.

Results:  Response rate was 89%. Of the patients, 31% were never on DMT, 21% had stopped DMT, 30% were still on the first DMT, and 18% had changed. The treatment‐naive patients were significantly older, had a longer duration of disease, and had a lower number of relapses per year (P < 0.0001). The most important reasons not to start the treatment of MS were the severity and phase of the disease (too mild or PP), possible side effects, the advice of the neurologist, and uncertainty about the effect of DMT. Fifteen percent of the patients stated that when choosing treatment, the information definitely had not been sufficient to make a proper choice. Reasons to stop or switch DMT were mainly side effects (primarily influenza‐like symptoms or injection site reactions), especially in RR‐MS, and the uncertainty of action or failure of DMT, especially in SP‐MS. According to the opinion of the patients, the neurologist had the most decisive role in starting or changing DMT, whilst the patient was primarily responsible in deciding to stop DMT.

Conclusions:  Disease‐modifying therapy in MS is not well standardized in the Netherlands, because of the heterogeneous disease course and the variable doctors’ and patients’ expectations of the (side) effects of DMT.
Neuroglobin attenuates Alzheimer‐like tau hyperphosphorylation by activating Akt signaling
Authors: Chen Li‐Ming , Xiong Yan‐Si , Kong Fan‐Li , Qu Min , Wang Qun , Chen Xiao‐Qian , Wang Jian‐Zhi , Zhu Ling‐Qiang
Published: April 2011

J. Neurochem. (2012) 120, 157–164.

Neuroglobin (Ngb) is a recently identified member of hemoglobin family, distributed mainly in central and peripheral nervous systems. Recent studies suggest that Ngb can protect neural cells from β‐amyloid‐induced toxicity in Alzheimer disease (AD). Hyperphosphorylation of tau is another characterized pathological hallmark in the AD brains; however, it is not reported whether Ngb also affects tau phosphorylation. In this study, we found that the level of Ngb was significantly reduced in Tg2576 mice (a recognized mouse model of AD) and TgMAPt mice, and the level of Ngb was negatively correlated with tau phosphorylation. Over‐expression of Ngb attenuates tau hyperphosphorylation at multiple AD‐related sites induced by up‐regulation of glycogen synthase kinase‐3β (GSK‐3β), a crucial tau kinase. While Ngb activates Akt and thus inhibits GSK‐3β, simultaneously inhibition of Akt abolishes the effects of Ngb on GSK‐3β inhibition and tau hyperphosphorylation. Our data indicate that Ngb may attenuate tau hyperphosphorylation through activating Akt signaling pathway, implying a therapeutic target for AD.
Show the data, don't conceal them
Authors: Drummond GB , Vowler SL
Published: April 2011

Data presentation and statistical analysis in scientific writing are agreed to be in need of improvement, despite the profusion of advice and instruction. Recent evidence supports the need for better planning and analysis of animal experiments. This series of short articles aims to provide advice in small easily digested pieces, on a variety of topics, both basic and more specialized, that are relevant to readers of the journal. The present article encourages authors to present data clearly, preferably as a dot plot, so that the distribution of the values can be recognized. The use of different measures of distribution of a population, and different measures of precision of an estimate is contrasted.
The SLC36 family of proton‐coupled amino acid transporters and their potential role in drug transport
Authors: Thwaites David T , Anderson Catriona MH
Published: April 2011

Members of the solute carrier (SLC) 36 family are involved in transmembrane movement of amino acids and derivatives. SLC36 consists of four members. SLC36A1 and SLC36A2 both function as H+‐coupled amino acid symporters. SLC36A1 is expressed at the luminal surface of the small intestine but is also commonly found in lysosomes in many cell types (including neurones), suggesting that it is a multipurpose carrier with distinct roles in different cells including absorption in the small intestine and as an efflux pathway following intralysosomal protein breakdown. SLC36A1 has a relatively low affinity (Km 1–10 mM) for its substrates, which include zwitterionic amino and imino acids, heterocyclic amino acids and amino acid‐based drugs and derivatives used experimentally and/or clinically to treat epilepsy, schizophrenia, bacterial infections, hyperglycaemia and cancer. SLC36A2 is expressed at the apical surface of the human renal proximal tubule where it functions in the reabsorption of glycine, proline and hydroxyproline. SLC36A2 also transports amino acid derivatives but has a narrower substrate selectivity and higher affinity (Km 0.1–0.7 mM) than SLC36A1. Mutations in SLC36A2 lead to hyperglycinuria and iminoglycinuria. SLC36A3 is expressed only in testes and is an orphan transporter with no known function. SLC36A4 is widely distributed at the mRNA level and is a high‐affinity (Km 2–3 µM) transporter for proline and tryptophan. We have much to learn about this family of transporters, but from current knowledge, it seems likely that their function will influence the pharmacokinetic profiles of amino acid‐based drugs by mediating transport in both the small intestine and kidney.

LINKED ARTICLES This article is part of a themed section on Transporters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2011.164.issue‐7