bluuebunny/crossref_metadata_2025 huggingface dataset:
sTREM‐1 and LBP in Central Venous Catheter–associated Bloodstream Infections in Pediatric Intestinal Failure
Authors: Kevan Emily N. , Simmons Julia R. , Kocoshis Samuel A. , Cohen Mitchell B. , Rudolph Jeffrey A.
Published: June 2011

Objective:

Central venous catheter–associated bloodstream infections (CVC‐BSIs) are a major cause of morbidity and mortality in the pediatric intestinal failure (IF) population. We assessed plasma lipopolysaccharide‐binding protein (LBP) and soluble triggering receptor expressed on myeloid cells‐1 (sTREM‐1) as biomarkers for CVC‐BSI. We hypothesized that sTREM‐1 and LBP rise with BSI and decline following treatment, and that baseline LBP is higher in the IF population than in controls.

Patients and Methods:

Patients younger than 4 years were recruited from the IF registry at Cincinnati Children's Hospital. LBP and sTREM‐1 levels were measured on 22 patients with IF at baseline, 17 patients with IF with BSIs, and 11 healthy controls.

Results:

Mean sTREM‐1 level (pg/mL) and LBP level (μg/mL) rose with CVC‐BSI over baseline (115.0 ± 51.2 vs 85.9 ± 27.6, P = 0.011 and 79.8 ± 45.4 vs 20.5 ± 11.3, P < 0.001, respectively) and declined following antibiotic therapy (115.0 ± 51.2 vs 77.9 ± 29.8, P = 0.003 and 79.8 ± 45.4 vs 26.2 ± 10.8, P < 0.001, respectively). Receiver operating characteristic curves showed that neither sTREM‐1 nor LBP is sufficient to predict bacteremia versus fever without bacteremia (area under these curves = 0.57 and 0.82, respectively). Baseline LBP was higher in hospitalized patients than in outpatients (27.5 ± 8.7 vs 13.5 ± 9.2, P = 0.002), patients with previous BSIs versus those without (23.5 ± 10.4 vs 10.1 ± 8.3, P = 0.016), and those listed for transplantation versus those not listed (29.6 ± 9.8 vs 16.2 ± 9.5, P = 0.033).

Conclusions:

sTREM‐1 and LBP rise with CVC‐BSI in IF and decline after treatment; however, neither distinguishes infection from nonbacteremic febrile episodes. Baseline LBP may be a marker of disease severity in IF.
Abdominal Pain–Predominant Functional Gastrointestinal Diseases in Children and Adolescents
Authors: Devanarayana Niranga Manjuri , Mettananda Sachith , Liyanarachchi Chathurangi , Nanayakkara Navoda , Mendis Niranjala , Perera Nimnadi , Rajindrajith Shaman
Published: June 2011

Background and Objective:

Functional gastrointestinal disorders (FGD) are common among children, but little is known regarding their prevalence in developing countries. We assessed the prevalence of abdominal pain–predominant FGD, in addition to the predisposing factors and symptomatology, in Sri Lankan children.

Patients and Methods:

A cross‐sectional survey was conducted among a randomly selected group of 10‐ to 16‐year‐olds in 8 randomly selected schools in 4 provinces in Sri Lanka. A validated, self‐administered questionnaire was completed by children independently in an examination setting. FGD were diagnosed using Rome III criteria.

Results:

A total of 2180 questionnaires were distributed and 2163 (99.2%) were included in the analysis (1189 [55%] boys, mean age 13.4 years, standard deviation 1.8 years). Of them, 270 (12.5%) had at least 1 abdominal pain–predominant FGD. Irritable bowel syndrome (IBS) was seen in 107 (4.9%), functional dyspepsia in 54 (2.5%), functional abdominal pain in 96 (4.4%), and abdominal migraine (AM) in 21 (1.0%) (2 had AM and functional dyspepsia, 6 had AM and IBS). Extraintestinal symptoms were more common among affected children (P < 0.05). Abdominal pain–predominant FGD were higher in girls and those exposed to stressful events (P < 0.05). Prevalence negatively correlated with age (r = −0.05, P = 0.02).

Conclusions:

Abdominal pain–predominant FGD affects 12.5% of children ages 10 to 16 years and constitutes a significant health problem in Sri Lanka. IBS is the most common FGD subtype present. Abdominal pain–predominant FGD are higher in girls and those exposed to emotional stress. Prevalence of FGD decreased with age. Extraintestinal symptoms are more frequent in affected children.
Biochemical Parameters and Anthropometry Predict NAFLD in Obese Children
Authors: Maffeis Claudio , Banzato Claudia , Rigotti Francesca , Nobili Valerio , Valandro Silvia , Manfredi Riccardo , Morandi Anita
Published: June 2011

The aim of the present study was to build a predictive model of nonalcoholic fatty liver disease (NAFLD) in obese children. Fifty‐six obese 10‐year‐old children underwent blood tests for biochemical measures and magnetic resonance imaging for NAFLD diagnosis. A model combining waist‐to‐height ratio, homeostasis model assessment of insulin resistance, adiponectin, and alanine aminotransferase was accurate in predicting NAFLD (AUROC = 0.94 [95% confidence interval 0.89–0.99], P < 10−5). When adiponectin was not included in the model, the discrimination accuracy was still good (AUROC = 0.88 [95% confidence interval 0.79–0.97], P < 10−5). In conclusion, a predictive equation combining routinely available variables may allow physicians to identify obese children at the highest risk of NAFLD.
Early Developing Celiac Disease in Children With Cerebral Palsy
Authors: Stenberg Reidun , Kaukinen Katri , Bengtsson Mats , Lindberg Eva , Dahle Charlotte
Published: June 2011

Objectives:

We have reported on increased levels of antibodies against gliadin and/or transglutaminase 2 (TG2) in children with cerebral palsy (CP) but without having increased prevalence of celiac disease (CD). The aim of the present study was to evaluate whether these children have mucosal signs of early developing CD, human leukocyte antigen (HLA)‐DQ2/DQ8, and antibodies against deamidated gliadin peptides (DGP).

Patients and Methods:

Stored blood samples from 16 children with CP were analyzed regarding HLA‐DQ2/DQ8 and anti‐DGP antibodies. HLA‐DQ2/DQ8 were analyzed by polymerase chain reaction sequence‐specific oligonucleotide probes. Anti‐DGP antibodies were analyzed with enzyme‐linked immunosorbent assay. Small‐bowel biopsies from 15 of these children were available for immunohistochemistry regarding IgA colocalized with TG2, densities of α/β+ and γ/δ+ intraepithelial lymphocytes.

Results:

Mucosal immunoglobulin A (IgA) deposits colocalized with TG2 were found in the small‐bowel biopsy from 1 patient with serum IgA‐class anti‐TG2 antibodies, HLA‐DQ2, and gastrointestinal complaints. Another 2 children had slightly increased numbers of mucosal α/β+ and/or γ/δ+ intraepithelial lymphocytes. In total, 10 of 16 children were HLA‐DQ2 and/or DQ8‐positive. Anti‐DGP antibodies were detected in sera from 4 of 16 children.

Conclusions:

In the present study, 1 child with CP had IgA colocalizing with TG2 in the small‐bowel mucosa, suggesting CD at an early stage. Although the majority of children with CP and elevated levels of CD‐related seromarkers are HLA‐DQ2 and/or DQ8‐positive, they have neither classical nor early developing CD.
Human endogenous retrovirus transcription profiles of the kidney and kidney-derived cell lines
Authors: Haupt Sonja , Tisdale Michele , Vincendeau Michelle , Clements Mary Anne , Gauthier David T. , Lance Raymond , Semmes O. John , Turqueti-Neves Adriana , Noessner Elfriede , Leib-Mösch Christine , Greenwood Alex D.
Published: June 2011

The human genome comprises approximately 8–9 % of human endogenous retroviruses (HERVs) that are transcribed with tissue specificity. However, relatively few organs have been examined in detail for individual differences in HERV transcription pattern, nor have tissue-to-cell culture comparisons been frequently performed. Using an HERV-specific DNA microarray, a core HERV transcription profile was established for the human kidney comparing 10 tissue samples. This core represents HERV groups expressed uniformly or nearly so in non-tumour kidney tissue. The profiles obtained from non-tumour tissues were compared to 10 renal tumour tissues (renal cell carcinoma, RCC) derived from the same individuals and additionally, to 22 RCC cell lines. No RCC cell line or tumour-specific differences were observed, suggesting that HERV transcription is not altered in RCC. However, when comparing tissue transcription to cell line transcription, there were consistent differences. The differences were irrespective of cancer state and included cell lines derived from non-tumour kidney tissue, suggesting that a specific alteration of HERV transcription occurs when establishing cell lines. In contrast to previous publications, all known HERV-derived tumour antigens, including those identified in RCC, were expressed both in multiple RCC cell lines and several non-tumour tissue-derived cell lines, a result that contrasts with findings from patient samples. The results establish the core kidney transcription pattern of HERVs and reveal differences between cell culture lines and tissue samples.
Predicting antigenic sites on the foot-and-mouth disease virus capsid of the South African Territories types using virus neutralization data
Authors: Maree F. F. , Blignaut B. , Esterhuysen J. J. , de Beer T. A. P. , Theron J. , O’Neill H. G. , Rieder E.
Published: June 2011

Foot-and-mouth disease virus (FMDV) outer capsid proteins 1B, 1C and 1D contribute to the virus serotype distribution and antigenic variants that exist within each of the seven serotypes. This study presents phylogenetic, genetic and antigenic analyses of South African Territories (SAT) serotypes prevalent in sub-Saharan Africa. Here, we show that the high levels of genetic diversity in the P1-coding region within the SAT serotypes are reflected in the antigenic properties of these viruses and therefore have implications for the selection of vaccine strains that would provide the best vaccine match against emerging viruses. Interestingly, although SAT1 and SAT2 viruses displayed similar genetic variation within each serotype (32 % variable amino acids), antigenic disparity, as measured by r1-values, was less pronounced for SAT1 viruses compared with SAT2 viruses within our dataset, emphasizing the high antigenic variation within the SAT2 serotype. Furthermore, we combined amino acid variation and the r1-values with crystallographic structural data and were able to predict areas on the surface of the FMD virion as antigenically relevant. These sites were mostly consistent with antigenic sites previously determined for types A, O and C using mAbs and escape mutant studies. Our methodology offers a quick alternative to determine antigenic relevant sites for FMDV field strains.
On the form of the space‐time domain reflection function for a simple flat‐lying interface
Authors: Thomson C.J.
Published: June 2011

A description is given of the function R(x, t) forming the kernel of the space‐time domain reflection operator for scalar waves illuminating a single interface in two space dimensions. This reflection function is closely related to migration common‐image gathers and it can be thought of as the set of all plane‐wave reflection coefficients after Fourier synthesis over wavenumber, or slowness, and frequency.

R(x, t) is a generalized function with a complicated form at the origin, or around it when smoothing is applied. Much can be inferred from knowledge of the plane‐wave coefficients themselves and a simple scalar‐ or acoustic‐wave case without density variation displays the essential features. The theoretical predictions are visualized by smoothed numerical examples obtained using a discrete Fourier transform method. The space‐time form of the reflection function for a low‐contrast boundary is also considered, as is, briefly, the transmission function.

Among the characteristics of R(x, t) are that it is essentially V shaped in the (x, t) plane, with linear arms given by the wave cones for the two media involved. These arms carry  signals, where H(t) is the Heaviside step function. The time dependence along x = 0 is also relatively simple, being like the delta derivative δ′(t). At or around the origin R(x, t) is intricate due to the fine balancing of its plane‐wave components. This intricacy makes the corresponding reflection operator capable of analysing an arbitrary incident wave to give the reflected wave, including such effects as total reflection and head waves and the reflection of short horizontal wavelength evanescent waves due to a point source very close to the interface.

The results provide a baseline for understanding common‐image gathers used in migration, including those associated with reverse‐time migration and full‐waveform inversion. Clarity about the space‐time form of the reflection operator will hopefully advance the goal of unifying imaging, amplitude‐versus‐offset analysis and waveform inversion. Application to the time‐domain numerical modelling of waves is also conceivable.
The form of the reflection operator and extended image gathers for a dipping plane reflector in two space dimensions
Authors: Thomson C.J.
Published: June 2011

The reflection operator for a simple flat‐lying interface can be thought of as the set of all its plane‐wave reflection coefficients or as the set of virtual surveys with sources and receivers along the interface. When there is dip, however, it is necessary to include the varying effects of propagation between the virtual‐survey level and the interface.

Hence, step one in this paper is to derive the reflection operator for a dipping plane interface as observed at a datum level some distance away. The key assumption is that the aperture at the datum level is sufficient to characterize the reflector properties around a particular point. This translates into an assumption that the dip is moderate, though no explicit small‐angle approximation is required.

The second step is to find the apparent reflection operator that would relate data that have been extrapolated from the datum towards and possibly beyond the reflector using an assumed migration velocity. This apparent reflection operator is closely related to extended common‐image gathers. The apparent reflection operator may be analysed asymptotically in terms of rays and other signals, shedding light on the structure of extended image gathers.

In keeping with the virtual‐survey idea, the results are considered in a subsurface space‐time or slowness‐time domain at various extrapolation levels around the interface. An important distinction is drawn between using subsurface midpoint‐offset coordinates and the wavefield coordinates of the incident and reflected waves. The latter reveal more clearly the effects of dip, because they lead to a more asymmetric apparent reflection operator. Properties such as an up‐dip shift of a traveltime minimum and its associated curvature theoretically provide information about the reflector location and dip and the migration‐velocity error.

The space‐time form of the reflection operator can be highly intricate around the offset‐time origin and it was described for a simple flat interface in a background paper. To avoid a layer of mathematics, the reflection‐operator formulas presented here are in the intermediate space‐frequency domain. They are analysed by considering their stationary‐phase and branch‐point high‐frequency contributions.

There is no Born‐like assumption of weak reflector contrast and so wide‐angle, total reflection and head‐wave effects are included. Snell’s law is an explicit part of the theory. It is hoped that the work will therefore be a step towards the goal of unifying amplitude‐versus‐offset, imaging and waveform inversion.
Spermatogonial stem cells alone are not sufficient to re‐initiate spermatogenesis in the rat testis following adjudin‐induced infertility
Authors: Mok K‐W. , Mruk D. D. , Lee W. M. , Cheng C. Y.
Published: June 2011

The blood–testis barrier (BTB) is a unique ultrastructure in the testis, which creates a specialized microenvironment in the seminiferous epithelium known as the apical (or adluminal) compartment for post‐meiotic germ‐cell development and for maintenance of an immunological barrier. In this study, we have demonstrated unequivocally that a functional and intact BTB is crucial for the initiation of spermatogenesis, in particular, the differentiation of spermatogonial stem cells (SSCs). It was shown that adult rats (∼300 g body weight, b.w.) treated with adjudin at 50 (low‐dose) or 250 (high‐dose) mg/kg b.w. by gavage led to germ‐cell depletion from the seminiferous tubules and that >98% of the tubules were devoid of germ cells by ∼2 week and rats became infertile in both groups after the sperm reserve in the epididymis was exhausted. While the population of SSC/spermatogonia in the seminiferous tubules from both groups was similar to that of normal rats, only rats from the low‐dose group were capable of re‐initiating spermatogenesis; and by 20 weeks, greater than 75% of the tubules displayed normal spermatogenesis and the fertility of these rats rebounded. Detailed analysis by dual‐labelled immunofluorescence analysis and a functional BTB integrity assay revealed that in both treatment groups, the BTB was disrupted from week 6 to week 12. However, the disrupted BTB ‘resealed’ in the low‐dose group, but not in the high‐dose group. Our findings illustrate that SSC/spermatogonia failed to differentiate into spermatocytes beyond Aaligned spermatogonia in the high‐dose group with a disrupted BTB. In short, these findings illustrate the critical significance of the BTB for re‐initiation of spermatogenesis besides SSC and spermatogonia.
Exploring variation in pressure ulcer prevalence in Sweden and the USA: benchmarking in action
Authors: Gunningberg Lena , Donaldson Nancy , Aydin Carolyn , Idvall Ewa
Published: June 2011

Aim  To compare overall unit‐level pressure ulcer (PU) prevalence, hospital‐acquired pressure ulcer (HAPU) prevalence and prevention strategies, as well as nurse staffing and workload in two hospitals in Sweden with data from the USA.

Methods  Medical and surgical units in a university hospital and a general hospital in Sweden were compared with 207 hospitals in the USA participating in the Collaborative Alliance for Nursing Outcomes (CALNOC) benchmarking registry. All adult inpatients in university hospital (n = 630), general hospital (n = 253) and CALNOC hospitals (n = 3506) were included in the study. Outcome indicators were pressure ulcer prevalence for all types (PU) and HAPU prevalence, specifically. Process indicators were risk assessment and PU prevention strategies. Structure indicators were nurse staffing (hours of care, and skill mix) and workload (admissions, discharges and transfers).

Results  The prevalence of PU (categories 1–4) was 17.6% (university hospital) and 9.5% (general hospital) compared with 6.3–6.7% in the CALNOC sample. The prevalence of full thickness HAPU (categories 3 and 4) was 2.7% (university hospital) and 2.0% (general hospital) compared with 0–0.5% in the CALNOC sample. Risk and skin assessment varied between 6% and 60% in the Swedish hospitals compared with 100% in the CALNOC sample. Total hours per patient day were 8.4 in both Swedish hospitals and 9.5 to 9.8 in the CALNOC hospitals

Conclusions  The findings suggest a link between processes of care and outcomes that is exciting to observe internationally and suggest the opportunity to expedite performance improvement through global benchmarking. Using HAPU as a complement to point prevalence of PU in Sweden has revealed this indicator as a more valid measure for patient care quality.
Evaluation of the physicians' approach to the diagnosis and treatment of patients with antituberculosis drug‐induced hepatotoxicity
Authors: Thongraung Wilawan , Sittidach Maneerat , Khwansuwan Panatda , Sariyasuntorn Kanitha , Wongsampan Sirinart
Published: June 2011

Objectives  To describe the practices of physicians on the diagnosis and treatment of antituberculosis drug‐induced hepatotoxicity (ATH), and to evaluate the concordance between these practices and the American Thoracic Society (ATS) 2006 guidelines.

Methods  Information was reviewed on 670 new cases of tuberculosis patients aged not less than 15 years and registered at the outpatient clinics of a large hospital in southern Thailand during October 2006 to September 2009. The patient was identified as having ATH if: (1) he/she was diagnosed as transaminitis, hepatitis or hepatotoxicity from antituberculosis (anti‐TB) drugs; (2) their treatment regimen was subsequently modified by their attending physicians; and (3) their liver enzyme decreased after withdrawal of the suspected anti‐TB drugs. Compliance with the ATS guidelines was considered on diagnosis, initial management, selection of alternative regimens, and a reintroduction strategy.

Results  The prevalence of ATH was 6.7%. The proportion of patients diagnosed as ATH in accordance with the ATS 2006 guidelines was 73.8%. For the initial management, isoniazid, rifampicin and pyrazinamide were concurrently stopped in 55.0% of patients. While waiting for normalization of liver enzymes, 28 patients (70.0%) were treated with alternative regimens and 12 patients (30.0%) took no drug. Only 47.5% of the ATH patients received a regimen in accordance with ATS guidelines, including three less hepatotoxic drugs (ethambutol, ofloxacin and streptomycin). Of 34 patients who discontinued the treatment, anti‐TB drugs were reintroduced sequentially in 30 patients (88.2%). Of these, only 23.4% were firstly rechallenged with rifampicin as suggested by the ATS guidelines.

Conclusions  The practice of physicians on the diagnosis and management of ATH varied. The practices of physicians on the diagnosis and rechallenged method were in high compliance with the ATS guidelines. For the initial management and selection of alternative regimens, the physicians' compliance was not good.
Caregivers' difficulties in activating long‐term mental illness patients with low self‐esteem
Authors: ERDNER A. , MAGNUSSON A.
Published: June 2011

Accessible summary

Caregivers have knowledge about the importance of activities for the self‐esteem of patients with mental illness.

The caregivers do not apply their knowledge about activities and its importance for self‐esteem. They expect others to take care of this.

Caregivers in psychiatric care should be supported to implement their knowledge about activities in the care of patients with mental illness.

The aim of the study was to describe psychiatric caregivers' perceptions of self‐esteem and activities for patients with long‐term mental illness. The study design used a qualitative approach, based on an open lifeworld perspective. A total of 13 caregivers at four psychiatric hospital units in a large Swedish city were interviewed about their views on patients' physical activity and/or other pastimes, as well as their self‐esteem and its bearing on the patients' well‐being. According to the caregivers, it is up to the patients themselves to decide what they wish to occupy themselves with. In the same time the caregivers' opinions are that patients have difficulties to occupy themselves. The caregivers believe that patients' disability is based in a lack of self‐esteem, commitment and capacity to realize their wishes. The caregivers in this study argue that activities are valuable for self‐esteem and physical health of people with long‐term mental illness. The caregivers consider that it is the patient's responsibility to initiate their needs of activities. This means that the caregivers do not use their knowledge about the importance of activities for the patient's health. Search terms: activity, caregivers, mental illness.
The periplasmic membrane proximal domain of MacA acts as a switch in stimulation of ATP hydrolysis by MacB transporter
Authors: Modali Sita D. , Zgurskaya Helen I.
Published: June 2011

Escherichia coli MacAB‐TolC is a tripartite macrolide efflux transporter driven by hydrolysis of ATP. In this complex, MacA is the periplasmic membrane fusion protein that stimulates the activity of MacB transporter and establishes the link with the outer membrane channel TolC. The molecular mechanism by which MacA stimulates MacB remains unknown. Here, we report that the periplasmic membrane proximal domain of MacA plays a critical role in functional MacA–MacB interactions and stimulation of MacB ATPase activity. Binding of MacA to MacB stabilizes the ATP‐bound conformation of MacB, whereas interactions with both MacB and TolC affect the conformation of MacA. A single G353A substitution in the C‐terminus of MacA inactivates MacAB‐TolC function by changing the conformation of the membrane proximal domain of MacA and disrupting the proper assembly of the MacA‐MacB complex. We propose that MacA acts in transport by promoting MacB transition into the closed ATP‐bound conformation and in this respect, is similar to the periplasmic solute‐binding proteins.
Simultaneous silencing of endo‐β‐1,4 xylanase genes reveals their roles in the virulence of Magnaporthe oryzae
Authors: Nguyen Quoc Bao , Itoh Kenji , Van Vu Ba , Tosa Yukio , Nakayashiki Hitoshi
Published: June 2011

Due to functional redundancy, it is often difficult to genetically analyse the biological function of fungal cell wall‐degrading enzymes that belong to a gene family. To overcome this difficulty, we used RNAi to knock‐down (KD) multiple xylanase genes to elucidate their roles in the pathogenicity of the blast fungus, Magnaporthe oryzae. To obtain the maximum average efficiency of gene silencing for the xylanase genes, we used the ‘building blocks method’, in which a 40 bp sequence was chosen from an endoxylanase gene, and 10 such sequences from 10 endoxylanases were combined to make an artificial RNAi trigger by synthetic DNA. Quantitative RT‐PCR analysis revealed that the transcript levels of all the expressed xylanase genes were significantly reduced in KD mutants with the artificial RNAi trigger. Even though the KD mutants did not completely lose their pathogenicity to host plants, the number of lesions, rate of penetration and extent of infected cells were all reduced in KD mutant‐infected leaves. The degree of pathogenicity reduction was associated with the silencing levels of xylanase mRNA and enzymatic activity in the KD mutants. Cytological analysis indicated that xylanases play significant roles in both vertical penetration and horizontal expansion of M. oryzae in infected plants.
LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study
Authors: Sharma S. , Bandopadhyay R. , Lashley T. , Renton A. E. M. , Kingsbury A. E. , Kumaran R. , Kallis C. , Vilariño‐Güell C. , O'Sullivan S. S. , Lees A. J. , Revesz T. , Wood N. W. , Holton J. L.
Published: June 2011

S. Sharma, R. Bandopadhyay, T. Lashley, A. E. M. Renton, A. E. Kingsbury, R. Kumaran, C. Kallis, C. Vilariño‐Güell, S. S. O'Sullivan, A. J. Lees, T. Revesz, N. W. Wood and J. L. Holton (2011) Neuropathology and Applied Neurobiology37, 777–790

LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study

Aims: Mutations in the gene encoding leucine‐rich repeat kinase‐2 (LRRK2) have been established as a common genetic cause of Parkinson's disease (PD). The distribution of LRRK2 mRNA and protein in the human brain has previously been described, although it has not been reported in PD cases with the common LRRK2 G2019S mutation. Methods: To further elucidate the role of LRRK2 in PD, we determined the localization of LRRK2 mRNA and protein in post‐mortem brain tissue from control, idiopathic PD (IPD) and G2019S positive PD cases. Results: Widespread neuronal expression of LRRK2 mRNA and protein was recorded and no difference was observed in the morphological localization of LRRK2 mRNA or protein between control, IPD and G2019S positive PD cases. Using quantitative real‐time polymerase chain reaction, we demonstrated that there is no regional variation in LRRK2 mRNA in normal human brain, but we have identified differential expression of LRRK2 mRNA with significant reductions recorded in limbic and neocortical regions of IPD cases compared with controls. Semi‐quantitative analysis of LRRK2 immunohistochemical staining demonstrated regional variation in staining intensity, with weak LRRK2 immunoreactivity consistently recorded in the striatum and substantia nigra. No clear differences were identified in LRRK2 immunoreactivity between control, IPD and G2019S positive PD cases. LRRK2 protein was identified in a small proportion of Lewy bodies. Conclusions: Our data suggest that widespread dysregulation of LRRK2 mRNA expression may contribute to the pathogenesis of IPD.
Elemental formula annotation of polar and lipophilic metabolites using 13C, 15N and 34S isotope labelling, in combination with high‐resolution mass spectrometry
Authors: Giavalisco Patrick , Li Yan , Matthes Annemarie , Eckhardt Aenne , Hubberten Hans‐Michael , Hesse Holger , Segu Shruthi , Hummel Jan , Köhl Karin , Willmitzer Lothar
Published: June 2011

The unbiased and comprehensive analysis of metabolites in any organism presents a major challenge if proper peak annotation and unambiguous assignment of the biological origin of the peaks are required. Here we provide a comprehensive multi‐isotope labelling‐based strategy using fully labelled 13C, 15N and 34S plant tissues, in combination with a fractionated metabolite extraction protocol. The extraction procedure allows for the simultaneous extraction of polar, semi‐polar and hydrophobic metabolites, as well as for the extraction of proteins and starch. After labelling and extraction, the metabolites and lipids were analysed using a high‐resolution mass spectrometer providing accurate MS and all‐ion fragmentation data, providing an unambiguous readout for every detectable isotope‐labelled peak. The isotope labelling assisted peak annotation process employed can be applied in either an automated database‐dependent or a database‐independent analysis of the plant polar metabolome and lipidome. As a proof of concept, the developed methods and technologies were applied and validated using Arabidopsis thaliana leaf and root extracts. Along with a large repository of assigned elemental compositions, which is provided, we show, using selected examples, the accuracy and reliability of the developed workflow.
A novel NDUFV1 gene mutation in complex I deficiency in consanguineous siblings with brainstem lesions and Leigh syndrome
Authors: Vilain C , Rens C , Aeby A , Balériaux D , Van Bogaert P , Remiche G , Smet J , Van Coster R , Abramowicz M , Pirson I
Published: June 2011

Vilain C, Rens C, Aeby A, Balériaux D, Van Bogaert P, Remiche G, Smet J, Van Coster R, Abramowicz M, Pirson I. A novel NDUFV1 gene mutation in complex I deficiency in consanguineous siblings with brainstem lesions and Leigh syndrome.

Although deficiency of complex I of the mitochondrial respiratory chain is a frequent cause of encephalopathy in children, only a few mutations have been reported in each of its subunits. In the absence of families large enough for conclusive segregation analysis and of robust functional testing, it is difficult to unequivocally show the causality of the observed mutations and to delineate genotype–phenotype correlations, making additional observations necessary. We observed two consanguineous siblings with an early‐onset encephalopathy, medulla, brainstem and mesencephalon lesions on brain magnetic resonance imaging and death before 8 months of age, caused by a complex I deficiency. We used a homozygosity mapping approach and identified a missense mutation in the NDUFV1 gene. The mutation, p.Arg386His, affects a highly conserved residue, contiguous to a cysteine residue known to coordinate an Fe ion. This observation adds to our understanding of complex I deficiency disease. It validates the important role of Arg386 and therefore supports the current molecular model of iron–sulfur clusters in NDUFV1.
Genetically‐modified pig mesenchymal stromal cells: xenoantigenicity and effect on human T‐cell xenoresponses
Authors: Ezzelarab Mohamed , Ezzelarab Corin , Wilhite Tyler , Kumar Goutham , Hara Hidetaka , Ayares David , Cooper David K. C.
Published: June 2011

Ezzelarab M, Ezzelarab C, Wilhite T, Kumar G, Hara H, Ayares D, Cooper DKC. Genetically‐modified pig mesenchymal stromal cells: xenoantigenicity and effect on human T‐cell xenoresponses. Xenotransplantation 2011; 18: 183–195. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  Mesenchymal stromal cells (MSC) are being investigated as immunomodulatory therapy in the field of transplantation, particularly islet transplantation. While MSC can regenerate across species barriers, the immunoregulatory influence of genetically modified pig MSC (pMSC) on the human and non‐human primate T‐cell responses has not been studied.

Methods:  Mesenchymal stromal cells from wild‐type (WT), α1,3‐galactosyltransferase gene knockout (GTKO) and GTKO pigs transgenic for the human complement‐regulatory protein CD46 (GTKO/CD46) were isolated and tested for differentiation. Antibody binding and T‐cell responses to WT and GTKO pMSC in comparison with GTKO pig aortic endothelial cells (pAEC) were investigated. The expression of swine leukocyte antigen (SLA) class II (SLA II) was tested. Costimulatory molecules CD80 and CD86 mRNA levels were measured. Human T‐cell proliferation and the production of pro‐inflammatory cytokines in response to GTKO and GTKO/CD46 pMSC in comparison with human MSC (hMSC) were evaluated.

Results:  α1,3‐galactosyltransferase gene knockout and GTKO/CD46 pMSC isolation and differentiation were achieved in vitro. Binding of human antibodies and T‐cell responses were lower to GTKO than those to WT pMSC. Human and baboon (naïve and sensitized) antibody binding were significantly lower to GTKO pMSC than to GTKO pAEC. Before activation, <1% of GTKO pMSC expressed SLA II, compared with 2.5% of GTKO pAEC. After pig interferon‐gamma (pIFN‐γ) activation, 99% of GTKO pAEC upregulated SLA II expression, compared with 49% of GTKO pMSC. Only 3% of GTKO pMSC expressed CD80 compared with 80% of GTKO pAEC without activation. After pIFN‐γ activation, GTKO pAEC upregulated CD86 mRNA level stronger than GTKO pMSC. The human CD4+ T‐cell response to GTKO pMSC was significantly weaker than that to GTKO pAEC, even after pIFN‐γ activation. More than 99% of GTKO/CD46 pMSC expressed hCD46. Human peripheral blood mononuclear cells and CD4+T‐cell responses to GTKO and GTKO/CD46 pMSC were comparable with those to hMSC, and all were significantly lower than to GTKO pAEC. GTKO/CD46 pMSC downregulated human T‐cell proliferation as efficiently as hMSC. The level of proinflammatory cytokines IL‐2, IFN‐γ, TNF‐α, and sCD40L correlated with the downregulation of T‐cell proliferation by all types of MSC.

Conclusion:  Genetically modified pMSC is significantly less immunogenic than WT pMSC. GTKO/CD46 pMSC downregulates the human T‐cell responses to pig antigens as efficiently as human MSC, which can be advantageous for therapeutic cell xenotransplantation.
Histology‐directed matrix‐assisted laser desorption/ionization analysis reveals tissue origin and p53 status of primary liver cancers
Authors: Jeon Young Eun , Lee Seok Cheol , Paik Seung Sam , Lee Kyeong Geun , Jin So Young , Kim Hyo Rim , Yoo Chong Woo , Park Hye Min , Han Sang Yun , Choi Dong Ho , Kim Hark Kyun
Published: June 2011

To date, protein profiles for hepatocellular carcinomas and cholangiocarcinomas have not been systematically evaluated and compared with each other in an unbiased way. Thirty‐six hepatocellular carcinomas and adjacent normal tissue samples were analyzed using histology‐directed, matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Four cholangiocarcinomas and adjacent normal tissue samples were also evaluated. Tissue samples were sectioned at 10 µm, with 1–3 sections thaw‐mounted on a conductive indium tin oxide‐coated glass slide. Sinapinic acid was manually deposited on areas of each tissue section enriched by epithelial cells, either tumor or normal, and mass spectra were acquired using a MALDI‐time of flight instrument. According to class prediction analysis, average prediction accuracy in test sets (composed of 18 hepatocellular carcinoma–normal pairs) ranged from 93.0 to 95.8%. Cholangiocarcinomas and hepatocellular carcinomas had different protein profiles, as evidenced by average prediction accuracy of >95% in the test set for all classifiers. Permutation P‐values for 0.632 + bootstrap cross validated misclassification rates (at feature selection P < 0.001) were less than 0.05 for predicting p53 immunostaining status. We conclude that MALDI MS profiles may be useful in assisting with the diagnosis and the differential diagnosis of primary liver cancers.
Molecular pathology of tumor‐initiating cells: Lessons from Philadelphia chromosome‐positive leukemia
Authors: Naka Kazuhito , Hoshii Takayuki , Tadokoro Yuko , Hirao Atsushi
Published: June 2011

Recent improvements in cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor‐initiating cells (TIC). This discovery has led to the ‘cancer stem cell hierarchy’ concept, which holds that tumors are organized as a hierarchy of malignant tissues sustained by such TIC. However, this concept remains controversial. In this review, we examine recent advances in cancer stem cell research that have been generated from studies of Philadelphia (Ph) chromosome‐positive leukemia. The abnormal Ph chromosome, which arises from a translocation creating the BCR‐ABL1 fusion gene, is most commonly associated with chronic myelogenous leukemia (CML) and precursor B cell acute lymphoblastic leukemia (B‐ALL). Examination of the pathophysiology of these diseases has provided interesting insights into not only the hierarchy of leukemia stem cells but also their clonal evolution. Both shared and unique regulatory mechanisms affecting normal and CML stem cell behavior have been identified. On the other hand, genetic diversity in specific clones of Ph+ B‐ALL that drive clonal evolution has recently come to light. Our expanding knowledge of the biology of TIC contributes to the progress of cancer research, and may open the door to new concepts in cancer therapy.
Diabetes UK evidence‐based nutrition guidelines for the prevention and management of diabetes
Authors: Dyson P. A. , Kelly T. , Deakin T. , Duncan A. , Frost G. , Harrison Z. , Khatri D. , Kunka D. , McArdle P. , Mellor D. , Oliver L. , Worth J. ,   on behalf of Diabetes UK Nutrition Working Group
Published: June 2011

Diabet. Med. 28, 1282–1288 (2011)

This article summarizes the Diabetes UK evidence‐based guidelines for the prevention of Type 2 diabetes and nutritional management of diabetes. It describes the development of the recommendations and highlights the key changes from previous guidelines.

The nutrition guidelines include a series of recommendations for the prevention of Type 2 diabetes, nutritional management of Type 1 and Type 2 diabetes, weight management, management of microvascular and macrovascular disease, hypoglycaemia management, and additional considerations such as nutrition support, end‐of‐life care, disorders of the pancreas, care of the older person with diabetes, nutrition provided by external agencies and fasting. The evidence‐based recommendations were graded using the Scottish Intercollegiate Guidelines Network methodology and, in a small number of topic areas, where strong evidence was lacking, the recommendations were reached by consensus.

The Diabetes UK 2011 guidelines place an emphasis on carbohydrate management and a more flexible approach to weight loss, unlike previous guidelines which were expressed in terms of recommendations for individual nutrient intakes. Additionally, the guidelines for alcohol have been aligned to national recommendations.

The full evidence‐based nutrition guidelines for the prevention and management of diabetes are available from: http://www.diabetes.org.uk/nutrition‐guidelines
Criminal Sittings – Rape in the Colony, New Zealand, 1862
Authors: ERAI MICHELLE
Published: June 2011

In 1862 His Honor, Justice Johnston, issued his instructions to the jury of the New Zealand Supreme Court for two simultaneous rape trials – the alleged rape of a European woman by two Māori men, and an alleged “assault with intent to commit a rape” of a Māori woman by a European man. This article argues that those instructions should be read within an historiographical critique of British colonial expansion, print capitalism and violence. Drawing on feminist postcolonial theorizing the question posed here, is, “What is the historical, ideological context for a newspaper reporting of the possible rape of a Māori woman in 1862?
AGGREGATE EMPLOYMENT DYNAMICS AND (PARTIAL) LABOUR MARKET REFORMS
Authors: Jiménez‐Rodríguez Rebeca , Russo Giuseppe
Published: June 2011

European labour markets have undergone several important innovations over the last three decades. Most countries have reformed their labour markets since the mid‐1990s, with the liberalization of fixed‐term contracts and temporary work agencies being the common elements to such reforms. This paper investigates the existence of a change in the dynamic behaviour of the aggregate employment for major European Union countries – France, Germany, Italy and Spain. According to our results, partial labour market reforms have made the response of the aggregate employment to output shocks larger and quite comparable to that found for the UK – the most flexible labour market in Europe since the Thatcher reforms.
Ambivalent or Indifferent? Examining the Validity of an Objective Measure of Partisan Ambivalence
Authors: Thornton Judd R.
Published: June 2011

This article examines the validity of an objective measure of partisan ambivalence. More generally, it draws attention to the idea that measurement is an active step taken by the researcher and therefore should be subjected to empirical examination. It is also argued that treating a variable at a higher level of measurement than warranted will cause a valid measure to cease to be so, and that the appropriate level of a variable is determined not by the underlying concept or the measurement procedure, but by the researcher. I demonstrate the measure examined can distinguish between various attitudinal states, but only at the nominal level. This is largely driven by individuals who offer no responses to open‐ended questions, who are termed indifferent. Furthermore, different coding schemes result in different conclusions. For example, the finding that indifferent individuals are less likely to rely on partisanship than ambivalent individuals when evaluating candidates is obscured when treating the measure as interval. The findings suggest the measure should be coded to account for indifferent individuals, and that even well developed measures of clearly defined concepts need to be subjected to empirical examination.
FOR LACK OF ANYTHING BETTER? INTERNATIONAL ORGANIZATIONS AND GLOBAL CORPORATE CODES
Authors: BACCARO LUCIO , MELE VALENTINA
Published: June 2011

This paper analyses the two most important international programmes for the voluntary regulation of corporate behaviour: the OECD Guidelines for Multinational Corporations and the UN Global Compact. It argues that international organizations adopted them mostly for reasons of political feasibility: by imposing minimal constraints on constituents the codes circumvented the most pressing problems of political acceptability associated with standard setting. It finds no clear evidence, however, that the network solutions adopted are technically more effective than traditional forms of regulation. The paper concludes that while it is unlikely that corporate behaviour will change simply as a result of participation in these programmes, if the programmes increase their ability to consistently discriminate between good and bad performers, the resulting ‘soft’ sanctioning power has the potential to alter corporate behaviour in the long run.
The Changing Meaning of Community Space: Two Models of NGO Management of Community Gardens in New York City
Authors: EIZENBERG EFRAT
Published: June 2011

This article examines two different models of space management, devised by NGOs to confront the marketization of public space in New York City through privatizing the land of community gardens. The Trust for Public Land promotes a model that emphasizes community ownership, while the New York Restoration Project promotes a model that emphasizes the preservation of land. The article compares the two models of NGO management of community gardens particularly through the lens of community participation, sense of ownership and control over space, and argues that both models transform the meaning of public space in ways that undermine its opportunity to develop as an autonomous community space.

L'étude porte sur deux modèles de gestion spatiale conçus par des ONG face à la commercialisation de l'espace public de la ville de New York via la privatisation des terrains occupés par les jardins communautaires. D'un côté, le modèle du Trust for Public Land prône la propriété communautaire, de l'autre, celui du New York Restoration Project privilégie la préservation des terrains. La comparaison des modèles des deux ONG pour l'administration des jardins communautaires s'effectue à travers le prisme de la participation communautaire, du sens de la propriété et de la maîtrise des espaces. Il en résulte que, l'un comme l'autre, ils transforment la signification de l'espace public d'une façon qui compromet la possibilité d'un aménagement en tant qu'espace communautaire autonome.
The Economics of Marriage
Authors: Cigno Alessandro
Published: June 2011

In a separate-property jurisdiction, marriage may induce domestic cooperation, and enhance efficiency in the production of children, because it may lend credibility to the prospective main earner’s promise to compensate the main childcarer at some future date, when the children will no longer be economically dependent on them. In a community-property jurisdiction, marriage will induce domestic cooperation, and enhance efficiency in the production of children, because it rules out strategic behavior. Whatever the matrimonial property regime, reducing the cost or difficulty of obtaining a divorce will have no permanent effect on the divorce rate. In separate-property jurisdiction, it will encourage marriage, and induce more married women to specialize in market work. Couples should be allowed to choose the matrimonial property regime.
Ungleichheiten bei der Geburt: Einige Ursachen und Folgen
Authors: Currie Janet
Published: June 2011

Recent research shows that health at birth is affected by many factors, including maternal education, behaviors, and participation in social programs. In turn, endowments at birth are predictive of adult outcomes, and of the outcomes of future generations. Exposure to environmental pollution is one potential determinant of health at birth that has received increasing attention. A large literature outside of economics advocates for “Environmental Justice,” and argues that poor and minority families are disproportionately exposed to environmental hazards. I provide new evidence on this question, showing that children born to less educated and minority mothers are more likely to be exposed to pollution in utero and that white, college educated mothers are particularly responsive to changes in environmental amenities. I estimate that differences in exposure to toxic releases may explain 6% of the gap in incidence of low birth weight between infants of white college educated mothers and infants of black high school dropout mothers.