bluuebunny/crossref_metadata_2025 huggingface dataset:
An evaluation of models of bare soil evaporation formulated with different land surface boundary conditions and assumptions
Authors: Smits Kathleen M. , Ngo Viet V. , Cihan Abdullah , Sakaki Toshihiro , Illangasekare Tissa H.
Published: November 2012

Bare soil evaporation is a key process for water exchange between the land and the atmosphere and an important component of the water balance. However, there is no agreement on the best modeling methodology to determine evaporation under different atmospheric boundary conditions. Also, there is a lack of directly measured soil evaporation data for model validation to compare these methods to establish the validity of their mathematical formulations. Thus, a need exists to systematically compare evaporation estimates using existing methods to experimental observations. The goal of this work is to test different conceptual and mathematical formulations that are used to estimate evaporation from bare soils to critically investigate various formulations and surface boundary conditions. Such a comparison required the development of a numerical model that has the ability to incorporate these boundary conditions. For this model, we modified a previously developed theory that allows nonequilibrium liquid/gas phase change with gas phase vapor diffusion to better account for dry soil conditions. Precision data under well‐controlled transient heat and wind boundary conditions were generated, and results from numerical simulations were compared with experimental data. Results demonstrate that the approaches based on different boundary conditions varied in their ability to capture different stages of evaporation. All approaches have benefits and limitations, and no one approach can be deemed most appropriate for every scenario. Comparisons of different formulations of the surface boundary condition validate the need for further research on heat and vapor transport processes in soil for better modeling accuracy.
Regional parameter estimation for the unified land model
Authors: Livneh Ben , Lettenmaier Dennis P.
Published: November 2012

Key Points

Resampling calibration data leads to improved spatial representation

PCA is a viable method to regionalize calibrated data

Globally available data offer a means to transfer geophysical information
Water availability and vulnerability of 225 large cities in the United States
Authors: Padowski Julie C. , Jawitz James W.
Published: November 2012

This study presents a quantitative national assessment of urban water availability and vulnerability for 225 U.S. cities with population greater than 100,000. Here, the urban assessments account for not only renewable water flows, but also the extracted, imported, and stored water that urban systems access through constructed infrastructure. These sources represent important hydraulic components of the urban water supply, yet are typically excluded from water scarcity assessments. Results from this hydraulic‐based assessment were compared to those obtained using a more conventional method that estimates scarcity solely based on local renewable flows. The inclusion of hydraulic components increased the mean availability to cities, leading to a significantly lower portion of the total U.S. population considered “at risk” for water scarcity (17%) than that obtained from the runoff method (47%). Water vulnerability was determined based on low‐flow conditions, and smaller differences were found for this metric between at‐risk populations using the runoff (66%) and hydraulic‐based (54%) methods. The large increase in the susceptible population between the scarcity measures evaluated using the hydraulic method may better reconcile the seeming contradiction in the United States between perceptions of natural water abundance and widespread water scarcity. Additionally, urban vulnerability measures developed here were validated using a media text analysis. Vulnerability assessments that included hydraulic components were found to correlate with the frequency of urban water scarcity reports in the popular press while runoff‐based measures showed no significant correlation, suggesting that hydraulic‐based assessments provide better context for understanding the nature and severity of urban water scarcity issues.
AVHRR‐NDVI‐based crop coefficients for analyzing long‐term trends in evapotranspiration in relation to changing climate in the U.S. High Plains
Authors: Mutiibwa Denis , Irmak Suat
Published: November 2012

Key Points

Evaluating changes in ET fluxes in response to regional climate change

Estimation of crop coefficient from satellite acquired NDVI

Development of spatial ET surfaces from non‐energy balance models
Kinetic analysis of Arabidopsis glucosyltransferase UGT74B1 illustrates a general mechanism by which enzymes can escape product inhibition
Authors: Kopycki Jakub , Wieduwild Elizabeth , Kohlschmidt Janine , Brandt Wolfgang , Stepanova Anna N. , Alonso Jose M. , Pedras M. Soledade C. , Abel Steffen , Grubb C. Douglas
Published: November 2012

Plant genomes encode numerous small molecule glycosyltransferases which modulate the solubility, activity, immunogenicity and/or reactivity of hormones, xenobiotics and natural products. The products of these enzymes can accumulate to very high concentrations, yet somehow avoid inhibiting their own biosynthesis. Glucosyltransferase UGT74B1 (UDP-glycosyltransferase 74B1) catalyses the penultimate step in the core biosynthetic pathway of glucosinolates, a group of natural products with important functions in plant defence against pests and pathogens. We found that mutation of the highly conserved Ser284 to leucine [wei9-1 (weak ethylene insensitive)] caused only very mild morphological and metabolic phenotypes, in dramatic contrast with knockout mutants, indicating that steady state glucosinolate levels are actively regulated even in unchallenged plants. Analysis of the effects of the mutation via a structural modelling approach indicated that the affected serine interacts directly with UDP-glucose, but also predicted alterations in acceptor substrate affinity and the kcat value, sparking an interest in the kinetic behaviour of the wild-type enzyme. Initial velocity and inhibition studies revealed that UGT74B1 is not inhibited by its glycoside product. Together with the effects of the missense mutation, these findings are most consistent with a partial rapid equilibrium ordered mechanism. This model explains the lack of product inhibition observed both in vitro and in vivo, illustrating a general mechanism whereby enzymes can continue to function even at very high product/precursor ratios.
Fibroblast growth factor 2 induces the precocious development of endothelial cell networks in bovine luteinising follicular cells
Authors: Laird Mhairi , Woad Kathryn J. , Hunter Morag G. , Mann George E. , Robinson Robert S.
Published: November 2012

The transition from follicle to corpus luteum represents a period of intense angiogenesis; however, the exact roles of angiogenic factors during this time remain to be elucidated. Thus, the roles of vascular endothelial growth factor (VEGF) A, fibroblast growth factor (FGF) 2 and LH in controlling angiogenesis were examined in the present study. A novel serum-free luteinising follicular angiogenesis culture system was developed in which progesterone production increased during the first 5 days and was increased by LH (P < 0.01). Blockade of signalling from FGF receptors (SU5402; P < 0.001) and, to a lesser extent, VEGF receptors (SU1498; P < 0.001) decreased the development of endothelial cell (EC) networks. Conversely, FGF2 dose-dependently (P < 0.001) induced the precocious transition of undeveloped EC islands into branched networks associated with a twofold increase in the number of branch points (P < 0.001). In contrast, VEGFA had no effect on the area of EC networks or the number of branch points. LH had no effect on the area of EC networks, but it marginally increased the number of branch points (P < 0.05) and FGF2 production (P < 0.001). Surprisingly, progesterone production was decreased by FGF2 (P < 0.01) but only on Day 5 of culture. Progesterone production was increased by SU5402 (P < 0.001) and decreased by SU1498 (P < 0.001). These results demonstrate that FGF and VEGF receptors play a fundamental role in the formation of luteal EC networks in vitro, which includes a novel role for FGF2 in induction of EC sprouting.
Active multilayer mirrors for reflectance tuning at extreme ultraviolet (EUV) wavelengths
Authors: Bayraktar Muharrem , Wessels Werner A , Lee Chris J , van Goor Fred A , Koster Gertjan , Rijnders Guus , Bijkerk Fred
Published: November 2012

We propose an active multilayer mirror structure for extreme ultraviolet (EUV) wavelengths, which can be adjusted to compensate for reflectance changes. The multilayer structure tunes the reflectance via an integrated piezoelectric layer that can change its dimension due to an externally applied voltage. Here, we present design and optimization of the mirror structure for maximum reflectance tuning. In addition, we present preliminary results showing that the deposition of piezoelectric thin films with the requisite layer smoothness and crystal structure is possible. Finally piezoelectric coefficient measurement (d
33 = 60 pm V−1) of the film is presented.
Fan-shaped body neurons are involved in period-dependent regulation of long-term courtship memory in Drosophila
Authors: Sakai Takaomi , Inami Show , Sato Shoma , Kitamoto Toshihiro
Published: November 2012

In addition to its established function in the regulation of circadian rhythms, the Drosophila gene period (per) also plays an important role in processing long-term memory (LTM). Here, we used courtship conditioning as a learning paradigm and revealed that (1) overexpression and knocking down of per in subsets of brain neurons enhance and suppress LTM, respectively, and (2) suppression of synaptic transmission during memory retrieval in the same neuronal subsets leads to defective LTM. Further analysis strongly suggests that the brain region critical for per-dependent LTM regulation is the fan-shaped body, which is involved in sleep-induced enhancement of courtship LTM.
Chlamydomonas reinhardtii Chloroplasts Contain a Homodimeric Pyruvate:Ferredoxin Oxidoreductase That Functions with FDX1
Authors: van Lis Robert , Baffert Carole , Couté Yohann , Nitschke Wolfgang , Atteia Ariane
Published: November 2012

Eukaryotic algae have long been known to live in anoxic environments, but interest in their anaerobic energy metabolism has only recently gained momentum, largely due to their utility in biofuel production. Chlamydomonas reinhardtii figures remarkably in this respect, because it efficiently produces hydrogen and its genome harbors many genes for anaerobic metabolic routes. Central to anaerobic energy metabolism in many unicellular eukaryotes (protists) is pyruvate:ferredoxin oxidoreductase (PFO), which decarboxylates pyruvate and forms acetyl-coenzyme A with concomitant reduction of low-potential ferredoxins or flavodoxins. Here, we report the biochemical properties of the homodimeric PFO of C. reinhardtii expressed in Escherichia coli. Electron paramagnetic resonance spectroscopy of the recombinant enzyme (Cr-rPFO) showed three distinct [4Fe-4S] iron-sulfur clusters and a thiamine pyrophosphate radical upon reduction by pyruvate. Purified Cr-rPFO exhibits a specific decarboxylase activity of 12 µmol pyruvate min−1 mg−1 protein using benzyl viologen as electron acceptor. Despite the fact that the enzyme is very oxygen sensitive, it localizes to the chloroplast. Among the six known chloroplast ferredoxins (FDX1–FDX6) in C. reinhardtii, FDX1 and FDX2 were the most efficient electron acceptors from Cr-rPFO, with comparable apparent K  m values of approximately 4 µm. As revealed by immunoblotting, anaerobic conditions that lead to the induction of CrPFO did not increase levels of either FDX1 or FDX2. FDX1, being by far the most abundant ferredoxin, is thus likely the partner of PFO in C. reinhardtii. This finding postulates a direct link between CrPFO and hydrogenase and provides new opportunities to better study and engineer hydrogen production in this protist.
One Divinyl Reductase Reduces the 8-Vinyl Groups in Various Intermediates of Chlorophyll Biosynthesis in a Given Higher Plant Species, But the Isozyme Differs between Species
Authors: Wang Pingrong , Wan Chunmei , Xu Zhengjun , Wang Pingyu , Wang Wenming , Sun Changhui , Ma Xiaozhi , Xiao Yunhua , Zhu Jianqing , Gao Xiaoling , Deng Xiaojian
Published: November 2012

Divinyl reductase (DVR) converts 8-vinyl groups on various chlorophyll intermediates to ethyl groups, which is indispensable for chlorophyll biosynthesis. To date, five DVR activities have been detected, but adequate evidence of enzymatic assays using purified or recombinant DVR proteins has not been demonstrated, and it is unclear whether one or multiple enzymes catalyze these activities. In this study, we systematically carried out enzymatic assays using four recombinant DVR proteins and five divinyl substrates and then investigated the in vivo accumulation of various chlorophyll intermediates in rice (Oryza sativa), maize (Zea mays), and cucumber (Cucumis sativus). The results demonstrated that both rice and maize DVR proteins can convert all of the five divinyl substrates to corresponding monovinyl compounds, while both cucumber and Arabidopsis (Arabidopsis thaliana) DVR proteins can convert three of them. Meanwhile, the OsDVR (Os03g22780)-inactivated 824ys mutant of rice exclusively accumulated divinyl chlorophylls in its various organs during different developmental stages. Collectively, we conclude that a single DVR with broad substrate specificity is responsible for reducing the 8-vinyl groups of various chlorophyll intermediates in higher plants, but DVR proteins from different species have diverse and differing substrate preferences, although they are homologous.
Dinuclear oxofluorometallates as a new structural type of d
0 transition metal oxofluoride compound
Authors: Udovenko Anatoly A. , Laptash Natalia M.
Published: November 2012

Five isomorphous d
0 transition metal oxofluoride compounds A
3[M
2O
x
F11 − x
]·(AF)0.333 (A = K, Rb, NH4; M = Nb, Mo, W; x = 2, 4) have been synthesized from acid fluoride solutions, and their crystal structures have been determined by single-crystal X-ray diffraction. The basic structural building units are dinuclear M
2
X
11 (dimers) formed from NbOF5 or Mo(W)O2F4 octahedra connected by the fluorine bridging atom. In the Nb2O2F9 dimer, the O atoms occupy apical corners. In the M
2O4F7 (M = Mo, W) dimers two O atoms are also apically placed, whereas the other two O atoms are statistically disordered in equatorial planes. The arrangement of dimers is so that the hexagonal tunnels containing `free' fluoride ions are formed. During the irradiation process the orthorhombic structure of K3Nb2O2F9·(KF)0.333 transforms into a pseudo-trigonal one with a = 23.15 Å, which is the [101] diagonal of the orthorhombic unit cell. The other four trigonal crystals are merohedral twins.
Mode-crystallography analysis and magnetic structures of SrLnFeRuO6 (Ln = La, Pr, Nd) disordered perovskites
Authors: Iturbe-Zabalo E. , Fabelo O. , Gateshki M. , Igartua J. M.
Published: November 2012

The crystal and magnetic structures of SrLnFeRuO6 (Ln = La, Pr, Nd) double perovskites have been investigated. All compounds crystallize with an orthorhombic Pbnm structure at room temperature. These materials show complete chemical disorder of Fe and Ru cations for all compounds. The distortion of the structure, relative to the ideal cubic perovskite, has been decomposed into distortion modes. It has been found that the primary modes of the distortion are octahedral tilting modes: R
+
4 and M
+
3. The crystal structure of SrPrFeRuO6 has been studied from room temperature up to 1200 K by neutron powder diffraction. There is a structural phase transition from orthorhombic (space group Pbnm) to trigonal (space group R\bar{3}c) at T = 1075 K. According to group theory no second-order transition is possible between these symmetries. Magnetic ordering for all the compounds is described by the magnetic propagation vector (0,0,0). SrPrFeRuO6 shows ferrimagnetic order below ca 475 K, while SrLaFeRuO6 (below ca 450 K) and SrNdFeRuO6 (below ca 430 K) exhibit canted-antiferromagnetic order. The magnetic moments at low temperatures are m(Fe/Ru) = 1.88 (3)μB for SrLaFeRuO6 (2 K), m(Pr) = 0.46 (4)μB and m(Fe/Ru) = 2.24μB for SrPrFeRuO6 (2 K), and m(Fe/Ru) = 1.92μB for SrNdFeRuO6 (10 K).
Horses and hippos: WhyItalian government bills change in the legislative arena, 1987–2006
Authors: Pedrazzani Andrea , Zucchini Francesco
Published: November 2012

Scholars interested in legislative processes pay relatively little attention to the changes made to bills in parliamentary democracies. On the one hand, comparative research has often described parliamentary institutions as ineffectualvis‐à‐viscabinets throughout the lawmaking process; on the other hand, for a long time the rational choice literature has focused more on the formal rules regulating amendatory activity than on amendatory activity itself. Hence, very few studies have tried to explain how much government bills are altered in parliament and why. This article investigates the changes made to governmental legislation inItaly. Taking the modifications occurring during the legislative process as the dependent variable, a number of explanatory hypotheses derived from both existing scholarship and original arguments are discussed and tested. This also allows the identification of some usually unobserved aspects of the decision‐making process within the cabinet. The findings can also be relevant for comparative research sinceItaly has been characterised during the period under scrutiny (1987–2006) by two distinct electoral systems, two extremely different party systems (pivotal and alternational), governments with various ideological orientations and range, and both partisan and technical ministers.
Use of allograft for portomesenteric vein interposition in radical resection of pancreatic tumor
Authors: Zhang Qiyi , Yan Sheng , Wang Weilin , Shen Yan , Zhang Min , Ding Yuan , Zheng Shusen
Published: November 2012

Aim

To develop a clinical strategy for the interposition of portomesenteric vein (PMV) by means of allograft in pancreatic surgery.

Patients and Methods

Between January 2004 and September 2011, nine patients had PMV interposition using allograft for massive vascular involvement by pancreatic tumour during pancreaticoduodenectomy. Their clinical outcomes were reviewed.

Results

After anastomosis of the allografts, three of which were fresh portal venous allografts, and six of which were cryopreserved iliac arterial allografts harvested from cadaveric donors, follow‐up Doppler ultrasonography revealed neither thrombosis nor stenosis.

Conclusions

The allografts might provide a feasible and clinically‐attractive option in PMV interposition in the radical resection of pancreatic tumours.
History lessons in medical education: A current necessity?
Authors: Sugand Kapil , Metcalfe David , Arya Donna , Akhtar Kash
Published: November 2012

Aim

To explore and discuss the necessity of integrating the history of medicine within the medical curriculum.

Methods

International peer‐reviewed academic journals, PubMed and MedLine databases and secondary sources were explored to review historical events that revolutionalized the practice of medicine, surgery, pharmaceuticals and robotics, among others.

Results

Numerous case studies have been presented in chronological order, which have made a sustainable impact on clinical practice. The profiles of pioneers and the historical events that led to a chain reaction of advancement in the history of medicine have been discussed, with a view to their impact on future achievements. History should still play an integral role within undergraduate and postgraduate medical education.
Maxillary sinus unilateral aplasia as an incidental finding following cone‐beam computed (volumetric) tomography
Authors: Steier Liviu , Steier Gabriela , Doğramacı Esma J , Rossi‐Fedele Giampiero
Published: November 2012

This paper presents a case of maxillary sinus unilateral aplasia, an uncommon condition in adults, diagnosed as an incidental finding during cone‐beam computed tomography (CBCT) examination for an endodontic case analysis. The patient was referred to a specialist endodontic practice for management of an upper right central incisor tooth. A CBCT scan was performed. The images of the left maxillary sinus showed a total lack of pneumatisation, prompting the diagnosis of aplasia. The patient's otolaryngologist was made aware of the findings. Clinical evaluation of volumetric images should be performed by an adequately trained dentist or radiologist so the maximum amount of information is gathered for the patient. This requires a systematic approach to ensure that no relevant information is missed and should include the paranasal sinuses and other surrounding structures as incidental findings can be observed during CBCT analysis.
The effect of propofol on patient reaction time and its relationship with loss of verbal contact before induction of anaesthesia*
Authors: Anderson K. J. , Allam S. , Chapman R. , Kenny G. N. C.
Published: November 2012

Increasing the calculated plasma concentration of propofol has been shown to increase choice reaction time and visual and auditory response times. We studied the relationship of reaction to a vibrating handset as the effect‐site target‐controlled propofol concentration was incrementally increased in 20 patients during sedation, before induction of general anaesthesia. The reaction time increased, initially slowly and then more rapidly, as the calculated effect‐site concentration of propofol increased, until the reaction to the vibrating handset was lost at a mean (SD) propofol effect‐site concentration of 2.0 (0.6) μg.ml−1. The loss of response to verbal contact occurred at a propofol effect‐site concentration of 2.4 (0.5) μg.ml−1. Reaction time may be of use clinically to warn of impending loss of verbal contact.
Patient‐maintained propofol sedation using reaction time monitoring: a volunteer safety study*
Authors: Allam S. , Anderson K. J. , O’Brien C. , Macpherson J. A. , Gambhir S. , Leitch J. A. , Kenny G. N. C.
Published: November 2012

Previous volunteer studies of an effect‐site controlled, patient‐maintained sedation system using propofol have demonstrated a risk of over‐sedation. We have incorporated a reaction‐time monitor into the handset of the patient‐maintained sedation system to add an individualised patient‐feedback mechanism. This study assessed if such reaction‐time feedback modification would reduce the risk of over‐sedation in 20 healthy volunteers deliberately attempting to over‐administer themselves propofol. All the volunteers successfully sedated themselves without reaching any unsafe endpoints. All volunteers maintained verbal contact throughout, in accordance with the definition of conscious sedation. The mean (SD) lowest SpO2 was 97 (1.7) % when breathing room air and no volunteer required supplementary oxygen. The mean (SD) maximum effect‐site propofol concentration reached was 1.7 (0.4) μg.ml−1. The present system was found to be safer than its predecessors, allowing conscious sedation, but preventing over‐sedation.
Maternal mortality in Sweden 1988–2007: more deaths than officially reported
Authors: Esscher Annika , Högberg Ulf , Haglund Bengt , Essën Birgitta
Published: November 2012

Objective

To obtain more accurate calculations of maternal and pregnancy‐related mortality ratios in Sweden from 1988 to 2007 by using information from national registers and death certificates.

Design

A national register‐based study, supplemented by a review of death certificates.

Setting

Sweden, 1988–2007.

Population

The deaths of 27 957 women of reproductive age (15–49 years).

Methods

The Swedish Cause of Death Register, Medical Birth Register, and National Patient Register were linked. All women with a diagnosis related to pregnancy in at least one of these registers within 1 year prior to death were identified. Death certificates were reviewed to ascertain maternal deaths. Maternal mortality ratio (the number of maternal deaths/100 000 live births, excluding and including suicides), and pregnancy‐related mortality ratio (number of deaths within 42 days after termination of pregnancy, irrespective of cause of death/100 000 live births) were calculated.

Main outcome measures

Direct and indirect maternal deaths and pregnancy‐related deaths.

Results

The maternal mortality ratio in Sweden, based on the current method of identifying maternal deaths, was 3.6. After linking registers and reviewing death certificates, we identified 64% more maternal deaths, resulting in a ratio of 6.0 (or 6.5 if suicides are included). The pregnancy‐related mortality ratio was 7.3. A total of 478 women died within a year after being recorded with a diagnosis related to pregnancy.

Conclusions

By including the 123 cases of maternal death identified in this study, the mean maternal mortality ratio from 1988 to 2007 was 64% higher than reported to the World Health Organization.
Sequential urodynamic assessment before and after laparoscopic sacrocolpopexy
Authors: Kummeling Maxime T.M. , Rietbergen John B.W. , Withagen MariËlla I.J. , Mannaerts Guido H.H. , van der Weiden Robin M.F.
Published: November 2012

Objective

Controversial data are available as to whether to perform a simultaneous abdominal or vaginal colposuspension operation in laparoscopic sacrocolpopexy procedures. We wanted to evaluate the effect of a modified laparoscopic operation technique on urodynamic parameters and lower urinary tract symptoms.

Design

Prospective single center cohort study.

Setting

Teaching hospital.

Population

Forty‐nine consecutive patients who underwent a modified laparoscopic sacrocolpopexy/hysteropexy operation using bone anchor fixation and synthetic mesh, performed by the same laparoscopic surgeons.

Methods

Pre‐ and postoperative multichannel urodynamic evaluation and validated questionnaires. The same urologist, blinded to the results of the questionnaire survey, interpreted all urodynamic evaluations.

Main outcome measures

The effects of surgery on pelvic anatomy and patient satisfaction, urodynamic observations and diagnoses and symptom scores in validated questionnaires.

Results

Forty‐two patients consented to pre‐ and postoperative urodynamic evaluation. Laparoscopic sacrocolpopexy successfully corrected vaginal vault prolapse in all 42 patients with urodynamic evaluation six months after surgery. The bladder volume at first desire to void was significantly increased and the maximal detrusor pressure at voiding phase was significantly decreased. In the questionnaires, irritative and storage voiding symptoms were significantly decreased.

Conclusions

The results of the study demonstrate that there are no adverse urodynamic findings following this modified technique for laparoscopic sacrocolpopexy. The statistically significant urodynamic improvements are in accordance with the scores on the Urogenital Distress Inventory questionnaires. These results do not support a simultaneous routine prophylactic colposuspension procedure.
The beta 1 tubulin R307H single nucleotide polymorphism is associated with treatment failures in immune thrombocytopenia (ITP)
Authors: Basciano Paul A. , Bussel James , Hafeez Zeeshan , Christos Paul J. , Giannakakou Paraskevi
Published: November 2012

Predictive biomarkers are needed in immune thrombocytopenia (ITP). Single nucleotide polymorphisms (SNPs) in beta 1 tubulin are potential candidates, as beta 1 tubulin is integral for platelet production and function, and SNPs in beta 1 tubulin have been associated with distinct phenotypes in platelets. We investigated the most prevalent beta 1 tubulin SNP (R307H) as a biomarker in patients with ITP via a retrospective chart review. Allelic frequencies between a group of 191 ITP patients and a healthy control group showed no difference, suggesting no direct aetiological role for the SNP in ITP. However, over similar periods of follow‐up, both heterozygote and homozygote minor allele ITP patients were treated with significantly more treatment modalities and had significantly higher risk of failure to immune‐modulatory therapies [relative risk (RR) = 1·5, 95% confidence interval (CI) = 1·1–2·1; P = 0·01]; with rituximab, in particular, ITP patients with the SNP experienced a 58% failure rate (RR = 1·6, 95%CI = 1·03–2·5; P = 0·04). Analysis of the absolute immature platelet fraction (A‐IPF) as a marker of platelet production showed that SNP patients had significantly higher median A‐IPFs compared to non‐SNP patients when complete responses were achieved using immune modulatory therapies. The data suggest that the beta 1 tubulin R307H SNP has potential for use as a biomarker in ITP and may affect platelet turnover.
Stability of human mesenchymal stem cells during in vitro culture: considerations for cell therapy
Authors: Binato R. , de Souza Fernandez T. , Lazzarotto‐Silva C. , Du Rocher B. , Mencalha A. , Pizzatti L. , Bouzas L. F. , Abdelhay E.
Published: November 2012

Ex vivo expansion and manipulation of human mesenchymal stem cells are important approaches to immunoregulatory and regenerative cell therapies. Although these cells show great potential for use, issues relating to their overall nature emerge as problems in the field. The need for extensive cell quantity amplification in vitro to obtain sufficient cell numbers for use, poses a risk of accumulating genetic and epigenetic abnormalities that could lead to sporadic malignant cell transformation. In this study, we have examined human mesenchymal stem cells derived from bone marrow, over extended culture time, using cytogenetic analyses, mixed lymphocyte reactions, proteomics and gene expression assays to determine whether the cultures would retain their potential for use in subsequent passages. Results indicate that in vitro cultures of these cells demonstrated chromosome variability after passage 4, but their immunomodulatory functions and differentiation capacity were maintained. At the molecular level, changes were observed from passage 5 on, indicating initiation of differentiation. Together, these results lead to the hypothesis that human mesenchymal stem cells cultures can be used successfully in cell therapy up to passage 4. However, use of cells from higher passages would have to be analysed case by case.
Living vs. deceased donor liver transplantation for hepatocellular carcinoma: a systematic review and meta‐analysis
Authors: Grant Robert C. , Sandhu Lakhbir , Dixon Peter R. , Greig Paul D. , Grant David R. , McGilvray Ian D.
Published: November 2012

Experimental studies suggest that the regenerating liver provides a “fertile field” for the growth of hepatocellular carcinoma (HCC). However, clinical studies report conflicting results comparing living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) for HCC. Thus, disease‐free survival (DFS) and overall survival (OS) were compared after LDLT and DDLT for HCC in a systematic review and meta‐analysis. Twelve studies satisfied eligibility criteria for DFS, including 633 LDLT and 1232 DDLT. Twelve studies satisfied eligibility criteria for OS, including 637 LDLT and 1050 DDLT. Altogether, there were 16 unique studies; 1, 2, and 13 of these were rated as high, medium, and low quality, respectively. Studies were heterogeneous, non‐randomized, and mostly retrospective. The combined hazard ratio was 1.59 (95% confidence interval [CI]: 1.02–2.49; I2 = 50.07%) for DFS after LDLT vs. DDLT for HCC, and 0.97 (95% CI: 0.73–1.27; I2 = 5.68%) for OS. This analysis provides evidence of lower DFS after LDLT compared with DDLT for HCC. Improved study design and reporting is required in future research to ascribe the observed difference in DFS to study bias or biological risk specifically associated with LDLT.
Impaired induction of long‐term potentiation‐like plasticity in patients with high‐functioning autism and Asperger syndrome
Authors: JUNG NIKOLAI H , JANZARIK WIBKE G , DELVENDAHL IGOR , MÜNCHAU ALEXANDER , BISCALDI MONICA , MAINBERGER FLORIAN , BÄUMER TOBIAS , RAUH REINHOLD , MALL VOLKER
Published: November 2012

Aim  We aimed to investigate the induction of long‐term potentiation (LTP)‐like plasticity by paired associative stimulation (PAS) in patients with high‐functioning autism and Asperger syndrome (HFA/AS).

Method  PAS with an interstimulus interval between electrical and transcranial magnetic stimulation of 25 ms (PAS25) was performed in patients with HFA/AS (n=9; eight males, one female; mean age 17y 11mo, SD 4y 5mo) and in typically developing age‐matched volunteers (n=9; five males, four females; mean age 22y 4mo, SD 5y 2mo). The amplitude of motor‐evoked potentials was measured before PAS25, immediately after stimulation, and 30 minutes and 60 minutes later. A PAS protocol adapted to individual N20 latency (PASN20+2) was performed in six additional patients with HFA/AS. Short‐interval intracortical inhibition was measured using paired‐pulse stimulation.

Results  In contrast to the typically developing participants, the patients with HFA/AS did not show a significant increase in motor‐evoked potentials after PAS25. This finding could also be demonstrated after adaptation for N20 latency. Short‐interval intracortical inhibition of patients with HFA/AS was normal compared with the comparison group and did not correlate with PAS effect.

Interpretation  Our results show a significant impairment of LTP‐like plasticity induced by PAS in individuals with HFA/AS compared with typically developing participants. This finding is in accordance with results from animal studies as well as human studies. Impaired LTP‐like plasticity in patients with HFA/AS points towards reduced excitatory synaptic connectivity and deficits in sensory‐motor integration in these patients.
Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1
Authors: WALSH KARIN S , VÉLEZ JORGE I , KARDEL PETER G , IMAS DANIEL M , MUENKE MAXIMILIAN , PACKER ROGER J , CASTELLANOS FRANCISCO X , ACOSTA MARIA T
Published: November 2012

Aim  Difficulties in neurocognition and social interaction are the most prominent causes of morbidity and long‐term disability in children with neurofibromatosis type 1 (NF1). Symptoms of attention‐deficit–hyperactivity disorder (ADHD) have also been extensively recognized in NF1. However, systematic evaluation of symptoms of autism spectrum disorder (ASD) in children with NF1 has been limited.

Method  We present a retrospective, cross‐sectional study of the prevalence of symptoms of ASD and ADHD and their relationship in a consecutive series of 66 patients from our NF1 clinic. The Social Responsiveness Scale and the Vanderbilt ADHD Diagnostic Parent Rating Scale were used to assess symptoms of ASD and ADHD.

Results  Sixty‐six participants (42 males, 24 females) were included in this study. Mean age at assessment was 10 years 11 months (SD 5y 4mo). Forty percent of our NF1 sample had raised symptom levels reaching clinical significance on the Social Responsiveness Scale (T ≥ 60), and 14% reached levels consistent with those seen in children with ASDs (T ≥ 75). These raised levels were not explained by NF1 disease severity or externalizing/internalizing behavioral disorders. There was a statistically significant relationship between symptoms of ADHD and ASD (χ2=9.11, df=1, p=0.003, φ=0.56). Particularly salient were the relationships between attention and hyperactivity deficits, with impairments in social awareness and social motivation.

Interpretation  We found that symptoms of ASD in our NF1 population were raised, consistent with previous reports. Further characterization of the specific ASD symptoms and their impact on daily function is fundamental to the development and implementation of effective interventions in this population, which will probably include a combination of medical and behavioral approaches.
Synaptic plasticity and non‐invasive brain stimulation in autism spectrum disorders
Authors: ENTICOTT PETER G , OBERMAN LINDSAY M
Published: November 2012

This commentary is on the original article by Jung et al. on pages 83–89 of this issue
Influence of estuary conditions on the recovery rate of coded‐wire‐tagged Chinook salmon (Oncorhynchus tshawytscha) in an ocean fishery
Authors: Zeug Steven C. , Cavallo Bradley J.
Published: November 2012

Chinook salmon (Oncorhynchus tschawytscha) populations within the highly modified San Francisco Estuary, California, have seen precipitous declines in recent years. To better understand this decline, a decade of coded‐wire tag release and recovery data for juvenile salmon was combined with physicochemical data to construct models that represented alternative hypotheses of estuarine conditions that influence tag recovery rate in the ocean. An information theoretic approach was used to evaluate the weight of evidence for each hypothesis and model averaging was performed to determine the level of support for variables that represented individual hypotheses. A single best model was identified for salmon released into the Sacramento River side of the estuary, whereas two competitive models were selected for salmon released into the San Joaquin River side of the estuary. Model averaging found that recovery rates were greatest for San Joaquin River releases when estuary water temperatures were lower, and salmon were released at larger sizes. Recovery rate of Sacramento releases was greatest during years with better water quality. There was little evidence that large‐scale water exports or inflows influenced recovery rates in the ocean during this time period. These results suggest that conceptual models of salmon ecology in estuaries should be quantitatively evaluated prior to implementation of recovery actions to maximise the effectiveness of management and facilitate the recovery of depressed Chinook populations.
Positive climate feedbacks of soil microbial communities in a semi‐arid grassland
Authors: Nie Ming , Pendall Elise , Bell Colin , Gasch Caley K. , Raut Swastika , Tamang Shanker , Wallenstein Matthew D.
Published: November 2012

Soil microbial communities may be able to rapidly respond to changing environments in ways that change community structure and functioning, which could affect climate–carbon feedbacks. However, detecting microbial feedbacks to elevated CO2 (eCO2) or warming is hampered by concurrent changes in substrate availability and plant responses. Whether microbial communities can persistently feed back to climate change is still unknown. We overcame this problem by collecting microbial inocula at subfreezing conditions under eCO2 and warming treatments in a semi‐arid grassland field experiment. The inoculant was incubated in a sterilised soil medium at constant conditions for 30 days. Microbes from eCO2 exhibited an increased ability to decompose soil organic matter (SOM) compared with those from ambient CO2 plots, and microbes from warmed plots exhibited increased thermal sensitivity for respiration. Microbes from the combined eCO2 and warming plots had consistently enhanced microbial decomposition activity and thermal sensitivity. These persistent positive feedbacks of soil microbial communities to eCO2 and warming may therefore stimulate soil C loss.
Chronic catchment nitrogen enrichment and stoichiometric constraints on the bioavailability of dissolved organic matter from leaf leachate
Authors: MINEAU MADELEINE M. , RIGSBY CHAD M. , ELY DAMON T. , FERNANDEZ IVAN J. , NORTON STEPHEN A. , OHNO TSUTOMU , VALETT H. MAURICE , SIMON KEVIN S.
Published: November 2012

1. Chronic nitrogen (N) deposition may alter the bioavailability of dissolved organic matter (DOM) in streams by multiple pathways. Elevated N deposition may alter the nutrient stoichiometry of DOM as well as nutrient availability in stream water.

2. We evaluated the influence of a decadal‐scale experimental N enrichment on the relative importance of DOM nutrient content and inorganic nutrient availability on the bioavailability of DOM. We measured the consumption of dissolved organic carbon (DOC) and changes in nutrient concentration, DOM components and enzyme activity in a bottle incubation assay with different DOM and nutrient treatments. To evaluate the effect of DOM stoichiometry, we used leaf leachates of different carbon/N/phosphorus (C : N :P) ratio, made from leaf litter sourced in the reference and N‐enriched catchments at the Bear Brook Watershed in Maine (BBWM). We also manipulated the concentration of inorganic N and P to compare the effect of nutrient enrichment with DOM stoichiometry.

3. DOC from the N‐enriched catchment was consumed 14% faster than that from the reference catchment. However, mean DOC consumption for both leachates was more than doubled by the simultaneous addition of N and P, compared to controls, while the addition of N or P alone increased consumption by 42 and 23%, respectively. The effect of N and/or P enrichment consistently had a greater effect than DOM source for all response variables considered.

4. We subsequently conducted DOC uptake measurements using leaf leachate addition under ambient and elevated N and P in the streams draining the reference and N‐enriched catchments at BBWM. In both streams, DOC uptake lengths were shorter when N and P were elevated.

5. Although both DOM stoichiometry and inorganic nutrient availability affect DOM bioavailability, N and P co‐limitation appears to be the dominant driver of reach‐scale processing of DOM.
Climate‐induced shift in hydrological regime alters basal resource dynamics in a wilderness river ecosystem
Authors: DAVIS J. M. , BAXTER C. V. , MINSHALL G. W. , OLSON N. F. , TANG C. , CROSBY B. T.
Published: November 2012

1. We integrated a 20‐year ecological data set from a sparsely inhabited, snowmelt‐dominated catchment with hydrologic models to predict the effects of hydrologic shifts on stream biofilm.

2.  We used a stepwise multiple regression to assess the relationship between hydrology and biofilm ash‐free dry mass (AFDM) and chlorophyll‐a (chl‐a) under recent climate conditions. Biofilm AFDM was significantly related to the timing of peak streamflow, and chl‐a was significantly related to the timing of median streamflow. We applied these results to output from the variable infiltration capacity hydrologic model, which predicted hydrology under a baseline scenario (+0 °C) and a range of warming scenarios expected with climate change (+1, +2 or +3 °C).

3.  When compared to the baseline, the results indicated that earlier peakflows predicted under warming scenarios may lead to earlier initiation of biofilm growth. This may increase biofilm AFDM during the summer by up to 103% (±29) in the +3 °C scenario. Moreover, interannual variability of AFDM was predicted to increase up to 300%. Average chl‐a during the summer increased by up to 90% (±15) in the +3 °C scenario; however, its response was not significantly different from baseline in most years.

4.  Because hydrologic change may alter the temporal dynamics of biofilm growth, it may affect the seasonal dynamics of biofilm quality (i.e. chl‐a‐to‐AFDM ratio). The results indicated that hydrologic shifts may increase biofilm quality during the spring, but may decrease it during the summer. Thus, we provide evidence that predicted hydrologic shifts in snowmelt‐dominated streams may alter the quantity and quality of an important basal resource. However, the magnitudes of these predictions are likely to be affected by other environmental changes that are occurring with climate change (e.g. increased wildfire activity and stream warming).
CtIP‐ and ATR‐dependent FANCJ phosphorylation in response to DNA strand breaks mediated by DNA replication
Authors: Sakasai Ryo , Sakai Akiko , Iimori Makoto , Kiyonari Shinichi , Matsuoka Kazuaki , Kakeji Yoshihiro , Kitao Hiroyuki , Maehara Yoshihiko
Published: November 2012

FANCJ, also called BACH1/BRIP1, is a 5′‐3′ DEAH helicase, whose mutations are known as a risk factor for Fanconi anemia and also breast and ovarian cancer. FANCJ is thought to contribute to DNA double‐strand break (DSB) repair and S‐phase checkpoint through binding to multiple partner proteins, such as BRCA1 and TopBP1, but its molecular regulation remains unclear. We focused on DNA damage‐induced phosphorylation of FANCJ and found that reagents that cause DSB or replication fork stalling induce FANCJ hyperphosphorylation. In particular, camptothecin (CPT) induced rapid and efficient FANCJ hyperphosphorylation that was largely dependent on TopBP1 and ATM‐Rad3 related (ATR) kinase. Furthermore, DNA end resection that exposes single‐strand DNA at the DSB site was required for hyperphosphorylation. Interestingly, upon CPT treatment, a dramatic increase in the FANCJ–TopBP1 complex was observed, and this increase was not alleviated even when ATR‐dependent hyperphosphorylation was suppressed. These results suggest that FANCJ function may be modulated by hyperphosphorylation in a DNA end resection‐ and ATR‐dependent manner and by FANCJ–TopBP1 complex formation in response to replication‐coupled DSBs.
Recent developments in uterine mesenchymal neoplasms
Authors: Chiang Sarah , Oliva Esther
Published: November 2012

Smooth muscle and endometrial stromal tumours represent the two most common uterine mesenchymal neoplasms that may present diagnostic dilemmas for the practising surgical pathologist. Recent changes in morphological and staging criteria, as well as the discovery of new immunohistochemical markers, have improved the diagnosis and classification of these tumours. We highlight the difficulty in distinguishing tumour cell necrosis from infarct‐type necrosis and the limited utility of p16 immunohistochemical expression in the diagnosis of leiomyosarcoma. We also discuss the controversial use of mitotic activity and necrosis as prognostic factors in endometrial stromal sarcomas. Emerging genetic information has also greatly expanded our understanding of ‘sarcomagenesis’ in both tumour types and may provide insight into potential therapeutic targets for the treatment of leiomyosarcoma and endometrial stromal sarcomas, harboring MED12 (mediator complex subunit 12) mutations and recurrent gene rearrangements, respectively. In this review, we discuss the core updates in the diagnosis and classification of uterine leiomyosarcomas and endometrial stromal sarcomas, highlighting new and important molecular genetic findings that may drive pathogenesis.
Triploidy alters brain morphology in pre‐smolt Atlantic salmon Salmo salar: possible implications for behaviour
Authors: Fraser T. W. K. , Fjelldal P. G. , Skjæraasen J. E. , Hansen T. , Mayer I.
Published: November 2012

Total brain mass and the volumes of five specific brain regions in diploid and triploid Atlantic salmon Salmo salar pre‐smolts were measured using digital images. There were no significant differences (P > 0·05) in total brain mass when corrected for fork length, or the volumes of the optic tecta or hypothalamus when corrected for brain mass, between diploids and triploids. There was a significant effect (P < 0·01) of ploidy on the volume of the olfactory bulb, with it being 9·0% larger in diploids compared with triploids. The cerebellum and telencephalon, however, were significantly larger, 17 and 8% respectively, in triploids compared with diploids. Sex had no significant effect (P > 0·05) on total brain mass or the volumes of any measured brain region. As the olfactory bulbs, cerebellum and telencephalon are implicated in a number of functions, including foraging ability, aggression and spatial cognition, these results may explain some of the behavioural differences previously reported between diploids and triploids.