bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized trial comparing repetitive transcranial magnetic stimulation given 3 days/week and 5 days/week for the treatment of major depression: is efficacy related to the duration of treatment or the number of treatments?
Authors: Galletly C. , Gill S. , Clarke P. , Burton C. , Fitzgerald P. B. 
Published: September 2011

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been shown to be an effective treatment for depression. However, there has been little research to determine optimal parameters for treatment.MethodThis study compared two rTMS treatment regimes for the treatment of major depression. Seventy-seven participants were randomized to either spaced or daily treatment. Spaced rTMS was given 3 days/week for 6 weeks (18 treatments in total) and daily rTMS was given 5 days/week for 4 weeks (20 treatments in total). All participants were assessed at baseline and after 4 weeks of treatment. Participants in the spaced treatment group were also assessed after 6 weeks of treatment. All participants were treated at 110% of the resting motor threshold with high-frequency rTMS (10 Hz) to the left dorsolateral prefrontal cortex (DLPFC) followed by low-frequency rTMS to the right DLPFC.ResultsParticipants in the daily treatment group showed more improvement by week 4 than those in the spaced treatment group; however, both groups had similar improvement by treatment completion. There was significant improvement in both groups in ratings of depression and anxiety, with no significant differences between groups.ConclusionsOur study indicates that the efficacy of rTMS is related to the number of treatments given and that spacing the treatments neither improves nor reduces efficacy.
Elder Abuse and Neglect in Canada: The Glass is Still Half Full
Authors: McDonald Lynn 
Published: September 2011

RÉSUMÉCet article examine les développements dans le domaine de la maltraitance et de la négligence des aînés depuis la publication deElder Abuse and Neglect in Canada(Butterworths, 1991). Les arguments présentés ici sont de deux ordres : d’abord, nous n’avons aucune idée de la taille ou de la nature du problèmes de la violence et de la négligence dans la communauté ou dans les institutions et, d’autre part, nous ne savons pas comment résoudre ces problèmes ou leurs questions connexes qui ont été masqués par la rhétorique et le recyclage de l’information pendant les 20 dernières années. C’est le temps d’avancer au-delà de la « phase de sensibilisation ». Ce à quoi nous devons nous attaquer à l’avenir est aussi évident aujourd’hui qu’il ne l’était il y a 20 ans. Notre connaissance est incomplète parce qu’il nous manque le type d’enquêtes dont le besoin se fait le plus urgent: les études de prévalence dans la communauté et les institutions, un développement théoriquement solide, et des essais cliniques randomisé pour tester à la fois nos interventions socialement et juridiquement.
Semi-automatic ESOL error annotation
Authors: Andersen Øistein E. 
Published: September 2011

AbstractManual error annotation of learner corpora is time-consuming and error-prone, whereas existing automatic techniques cannot reliably detect and correct all types of error. This paper shows that the two methods can successfully complement each other: automatic detection and partial correction of trivial errors relieves the human annotator from the laborious task of incessantly marking up oft-committed mistakes and enables him or her to focus on errors which cannot or cannot yet be handled mechanically, thus enabling more consistent annotation with considerably less manual time and effort expended.
Structure and dynamics of a conformationally constrained nitroxide side chain and applications in EPR spectroscopy
Authors: Fleissner Mark R. , Bridges Michael D. , Brooks Evan K. , Cascio Duilio , Kálai Tamás , Hideg Kálmán , Hubbell Wayne L. 
Published: September 2011

A disulfide-linked nitroxide side chain (R1) is the most widely used spin label for determining protein topology, mapping structural changes, and characterizing nanosecond backbone motions by site-directed spin labeling. Although the internal motion of R1 and the number of preferred rotamers are limited, translating interspin distance measurements and spatial orientation information into structural constraints is challenging. Here, we introduce a highly constrained nitroxide side chain designated RX as an alternative to R1 for these applications. RX is formed by a facile cross-linking reaction of a bifunctional methanethiosulfonate reagent with pairs of cysteine residues at
i
and
i
+ 3 or
i
and
i
+ 4 in an α-helix, at
i
and
i
+ 2 in a β-strand, or with cysteine residues in adjacent strands in a β-sheet. Analysis of EPR spectra, a crystal structure of RX in T4 lysozyme, and pulsed electron-electron double resonance (ELDOR) spectroscopy on an immobilized protein containing RX all reveal a highly constrained internal motion of the side chain. Consistent with the constrained geometry, interspin distance distributions between pairs of RX side chains are narrower than those from analogous R1 pairs. As an important consequence of the constrained internal motion of RX, spectral diffusion detected with ELDOR reveals microsecond internal motions of the protein. Collectively, the data suggest that the RX side chain will be useful for distance mapping by EPR spectroscopy, determining spatial orientation of helical segments in oriented specimens, and measuring structural fluctuations on the microsecond time scale.
Crystal structure of QscR, aPseudomonas aeruginosaquorum sensing signal receptor
Authors: Lintz Mario J. , Oinuma Ken-Ichi , Wysoczynski Christina L. , Greenberg Everett Peter , Churchill Mair E. A. 
Published: September 2011

Acyl-homoserine lactone (AHL) quorum sensing controls gene expression in hundreds of Proteobacteria including a number of plant and animal pathogens. Generally, the AHL receptors are members of a family of related transcription factors, and although they have been targets for development of antivirulence therapeutics there is very little structural information about this class of bacterial receptors. We have determined the structure of the transcription factor, QscR, bound to N-3-oxo-dodecanoyl-homoserine lactone from the opportunistic human pathogenPseudomonas aeruginosaat a resolution of 2.55 Å. The ligand-bound QscR is a dimer with a unique symmetric “cross-subunit” arrangement containing multiple dimerization interfaces involving both domains of each subunit. The QscR dimer appears poised to bind DNA. Predictions about signal binding and dimerization contacts were supported by studies of mutant QscR proteins in vivo. The acyl chain of the AHL is in close proximity to the dimerization interfaces. Our data are consistent with an allosteric mechanism of signal transmission in the regulation of DNA binding and thus virulence gene expression.
Pre‐emptive rituximab based on viraemia and T cell reconstitution: a highly effective strategy for the prevention of Epstein–Barr virus‐associated lymphoproliferative disease following stem cell transplantation
Authors: Worth Austen , Conyers Rachel , Cohen Jonathon , Jagani Mamta , Chiesa Robert , Rao Kanchana , Goulden Nicholas , Veys Paul , Amrolia Persis J. 
Published: September 2011

SummaryThis study investigated the efficacy of a pre‐emptive strategy based on the combination of Epstein–Barr virus (EBV) viraemia and poor T cell reconstitution in preventing post‐transplant lymphoproliferative disease (PTLD) following T cell depleted stem cell transplant (SCT). EBV viral load and immune reconstitution were prospectively monitored in 70 consecutive children undergoing SCT following reduced intensity conditioning with alemtuzumab. Patients who developed significant EBV viraemia (>40 000 copies/ml blood) were treated pre‐emptively with rituximab if they were within 3 months of SCT or their CD3 count was <0·3 × 109/l. Of 20/70 patients who developed significant EBV viraemia, 13 received pre‐emptive rituximab. The incidence of PTLD was significantly reduced in the pre‐emptive cohort compared to historical controls (1·4% vs. 21·7%, P = 0·003). This difference was more marked among viraemic patients (2·7% vs. 62·5%P < 0·0001). Patients treated with rituximab demonstrated significantly delayed B cell reconstitution at 1 year post‐SCT but this was not associated with an increase in infectious mortality. In 6/6 patients >3 months post‐SCT who had a CD3 count >0·3 × 109/l, reduced immunosuppression only resulted in successful resolution of EBV viraemia without PTLD. This strategy is safe and highly effective in preventing PTLD following T cell depleted SCT, and directs rituximab therapy to patients at highest risk of this complication.
The effect of azithromycin on the maturation and function of murine bone marrow-derived dendritic cells
Authors: Iwamoto S , Kumamoto T , Azuma E , Hirayama M , Ito M , Amano K , Ido M , Komada Y 
Published: September 2011

SummaryDendritic cells (DCs) are professional antigen-presenting cells capable of initiating primary/adaptive immune responses and tolerance. DC functions are regulated by their state of maturation. However, the molecular pathways leading to DC development and maturation remain poorly understood. We attempted to determine whether inhibition of nuclear factor kappa B (NF-κB), which is one of the pivotal pathways underlying these processes, could induce immunophenotypic and functional changes in lipopolysaccharide-induced mature DCs derived from murine bone marrow. A comparative in vitro study of five clinically used drugs that are known to inhibit NF-κB demonstrated that azithromycin, a macrolide antibiotic, significantly inhibited expression of co-stimulatory molecules (CD40 and CD86) and major histocompatibility complex (MHC) class II by DCs. It also reduced Toll-like receptor 4 expression, interleukin-12 production and the allostimulatory capacity of DCs. These data suggest that azithromycin, as not only an NF-κB inhibitor but also an antibiotic, has potential as a novel drug for manipulation of allogeneic responses.
Increased LCAT activity and hyperglycaemia decrease the antioxidative functionality of HDL
Authors: Kappelle Paul J. W. H. , de Boer Jan Freark , Perton Frank G. , Annema Wijtske , de Vries Rindert , Dullaart Robin P. F. , Tietge Uwe J. F. 
Published: September 2011

Eur J Clin Invest 2012; 42 (5): 487–495AbstractBackground  Type 2 diabetes mellitus increases the risk of atherosclerotic cardiovascular disease. Antioxidative properties of high density lipoprotein (HDL) are important for atheroprotection. This study investigated whether the antioxidative functionality of HDL is altered in type 2 diabetes mellitus and aimed to identify potential determinants of this parameter.Materials and methods  In a cross‐sectional study, we investigated 74 patients with type 2 diabetes and 75 control subjects. Antioxidative properties of HDL were measured and expressed as either (i) HDL antioxidative capacity or (ii) HDL antioxidation index after multiplying HDL antioxidative capacity results with individual plasma HDL cholesterol concentrations. Lecithin:cholesterol acyltransferase (LCAT) and paraoxonase‐1 (PON‐1) activities were determined.Results  HDL antioxidative capacity was similar in patients with diabetes and controls, while the HDL antioxidation index was decreased in patients with diabetes (P = 0·005) owing to lower plasma HDL cholesterol (P < 0·001). LCAT activity was higher and PON‐1 activity lower in type 2 diabetes mellitus (each P < 0·001). In the combined subjects, HDL antioxidative capacity was inversely related to LCAT activity (P < 0·01). The HDL antioxidation index correlated negatively with blood glucose (P < 0·001), HbA1c and LCAT activity (each P < 0·01), and positively with PON‐1 activity (P < 0·01). Multiple linear regression analysis demonstrated that high LCAT activity was associated with both decreased HDL antioxidation capacity (P < 0·05) and index (P < 0·001) independent of diabetes status, glycaemic control and PON‐1.Conclusions  Overall, the antioxidative functionality of HDL is impaired in type 2 diabetes mellitus mostly because of lower HDL cholesterol. Hyperglycaemia, increased LCAT activity and lower PON‐1 activity likely contribute to impaired antioxidative functionality of HDL.
Pinniped taxonomy: review of currently recognized species and subspecies, and evidence used for their description
Authors: BERTA Annalisa , CHURCHILL Morgan 
Published: September 2011

ABSTRACT
Pinnipeds are charismatic but difficult to study, and taxonomy is poorly understood. An accurate taxonomic framework is essential for studies of biogeography, ecology and conservation.
Morphologic and genetic criteria used to recognize pinniped species and subspecies are evaluated individually for all taxa in the three families: Otariidae (sea lions and fur seals), Odobenidae (walruses) and Phocidae (seals). We advocate a pragmatic approach that, in general, follows the Evolutionary Species Concept and ‘diagnosability’ criterion for subspecies delimitations.
Of the 33 species, all have at least two lines of evidence to distinguish them, and of the 29 subspecies, 24 have at least one line of evidence, but five have inadequate support. We present a composite phylogeny for pinnipeds.
We propose that the genus Arctocephalus be limited to Arctocephalus pusillus, and we resurrect the name Arctophoca for at least six species and subspecies.
We recommend large sample sizes and broad, random sampling in further research on pinniped taxonomy. Taxa should be described based on robust statistical analysis, not by arbitrary division of characters, and molecular research should include analysis of mtDNA and nuDNA.
Finally, we offer suggestions for further taxonomic research (on hybridization in otariids, and to allow consideration of life history data in sampling) in an effort to improve our understanding of pinniped diversity. Even for taxa which are already protected, better understanding of their taxonomy can only enhance their conservation status and facilitate efforts to protect their habitats.
The trafficking protein SYP121 of Arabidopsis connects programmed stomatal closure and K+ channel activity with vegetative growth
Authors: Eisenach Cornelia , Chen Zhong‐Hua , Grefen Christopher , Blatt Michael R. 
Published: September 2011

SummaryThe vesicle‐trafficking protein SYP121 (SYR1/PEN1) was originally identified in association with ion channel control at the plasma membrane of stomatal guard cells, although stomata of the Arabidopsis syp121 loss‐of‐function mutant close normally in ABA and high Ca2+. We have now uncovered a set of stomatal phenotypes in the syp121 mutant that reduce CO2 assimilation, slow vegetative growth and increase water use efficiency in the whole plant, conditional upon high light intensities and low relative humidity. Stomatal opening and the rise in stomatal transpiration of the mutant was delayed in the light and following Ca2+‐evoked closure, consistent with a constitutive form of so‐called programmed stomatal closure. Delayed reopening was observed in the syp121, but not in the syp122 mutant lacking the homologous gene product; the delay was rescued by complementation with wild‐type SYP121 and was phenocopied in wild‐type plants in the presence of the vesicle‐trafficking inhibitor Brefeldin A. K+ channel current that normally mediates K+ uptake for stomatal opening was suppressed in the syp121 mutant and, following closure, its recovery was slowed compared to guard cells of wild‐type plants. Evoked stomatal closure was accompanied by internalisation of GFP‐tagged KAT1 K+ channels in both wild‐type and syp121 mutant guard cells, but their subsequently recycling was slowed in the mutant. Our findings indicate that SYP121 facilitates stomatal reopening and they suggest that K+ channel traffic and recycling to the plasma membrane underpins the stress memory phenomenon of programmed closure in stomata. Additionally, they underline the significance of vesicle traffic for whole‐plant water use and biomass production, tying SYP121 function to guard cell membrane transport and stomatal control.
Subcellular localization of the Hpa RxLR effector repertoire identifies a tonoplast‐associated protein HaRxL17 that confers enhanced plant susceptibility
Authors: Caillaud Marie‐Cécile , Piquerez Sophie J. M. , Fabro Georgina , Steinbrenner Jens , Ishaque Naveed , Beynon Jim , Jones Jonathan D. G. 
Published: September 2011

SummaryFilamentous phytopathogens form sophisticated intracellular feeding structures called haustoria in plant cells. Pathogen effectors are likely to play a role in the establishment and maintenance of haustoria in addition to their better‐characterized role in suppressing plant defence. However, the specific mechanisms by which these effectors promote virulence remain unclear. To address this question, we examined changes in subcellular architecture using live‐cell imaging during the compatible interaction between the oomycete Hyaloperonospora arabidopsidis (Hpa) and its host Arabidopsis. We monitored host‐cell restructuring of subcellular compartments within plant mesophyll cells during haustoria ontogenesis. Live‐cell imaging highlighted rearrangements in plant cell membranes upon infection, in particular to the tonoplast, which was located close to the extra‐haustorial membrane surrounding the haustorium. We also investigated the subcellular localization patterns of Hpa RxLR effector candidates (HaRxLs) in planta. We identified two major classes of HaRxL effector based on localization: nuclear‐localized effectors and membrane‐localized effectors. Further, we identified a single effector, HaRxL17, that associated with the tonoplast in uninfected cells and with membranes around haustoria, probably the extra‐haustorial membrane, in infected cells. Functional analysis of selected effector candidates in planta revealed that HaRxL17 enhances plant susceptibility. The roles of subcellular changes and effector localization, with specific reference to the potential role of HaRxL17 in plant cell membrane trafficking, are discussed with respect to Hpa virulence.
AtIRE1A/AtIRE1B and AGB1 independently control two essential unfolded protein response pathways in Arabidopsis
Authors: Chen Yani , Brandizzi Federica 
Published: September 2011

SummaryThe endoplasmic reticulum (ER) has the ability to maintain the balance between demand for and synthesis of secretory proteins. To ensure protein‐folding homeostasis in the ER, cells invoke signaling pathways known as the unfolded protein response (UPR). To initiate UPR, yeasts largely rely on a conserved sensor, IRE1. In metazoans, there are at least three independent UPR signalling pathways. Some UPR transducers have been identified in plants, but no genetic interaction among them has yet been examined. The Arabidopsis genome encodes two IRE1 sequence homologs, AtIRE1A and AtIRE1B. Here we provide evidence that AtIRE1A and AtIRE1B have overlapping functions that are essential for the plant UPR. A double mutant of AtIRE1A and AtIRE1B, atire1a atire1b, showed reduced ER stress tolerance and a compromised UPR activation phenotype. We have also established that Arabidopsis AGB1, a subunit of the ubiquitous heterotrimeric GTP‐binding protein family, and AtIRE1A/AtIRE1B independently control two essential plant UPR pathways. By demonstrating that atire1a atire1b has a short root phenotype that is enhanced by an agb1 loss‐of‐function mutation, we have identified a role for UPR transducers in organ growth regulation.
Allelic and phenotypic heterogeneity in 49 Italian patients with the muscle form of CPT‐II deficiency
Authors: Fanin M , Anichini A , Cassandrini D , Fiorillo C , Scapolan S , Minetti C , Cassanello M , Donati MA , Siciliano G , D'Amico A , Lilliu F , Bruno C , Angelini C 
Published: September 2011

Fanin M, Anichini A, Cassandrini D, Fiorillo C, Scapolan S, Minetti C, Cassanello M, Donati MA, Siciliano G, D’Amico A, Lilliu F, Bruno C, Angelini C. Allelic and phenotypic heterogeneity in 49 Italian patients with the muscle form of CPT‐II deficiency.As genotype–phenotype correlations require the study of large patient populations, we investigated 49 Italian patients (33 unreported) with the muscle form of carnitine‐palmitoyl‐transferase‐II (CPT‐II) deficiency and CPT2 gene mutations. CPT enzyme activity below 25% of controls would lead to the development of muscle symptoms, and CPT activity below 15% would cause a relatively severe phenotype of the muscle form. Of the 15 different mutations found, 6 are novel (40%). A functional significance of mutations could be derived only for the two homozygous missense mutations found: both the p.S113L and the p.R631C (recurring in four unrelated patients from a genetic isolate) alleles caused a severe CPT enzyme defect (15% and 7%, respectively) and a relatively severe clinical phenotype of the muscle form. We identified three genotypes (homozygous p.R631C, homozygous p.S113L, and heterozygous null mutations) usually associated with a relatively severe and often life‐threatening condition, which should be considered both in the clinical management of newly diagnosed patients (to prevent symptoms) and in their possible inclusion in therapeutic trials. We confirmed the existence of symptomatic heterozygous patient(s), through a family study, providing an important issue when offering genetic counseling and suggesting the crucial role of polymorphisms or environmental factors in determining the phenotype.
Detection of Rhagoletis indifferens (Dipt., Tephritidae) larvae using brown sugar flotation and hot water methods
Authors: Yee W. L. 
Published: September 2011

AbstractThe brown sugar flotation and hot water methods are accepted procedures for detecting larval western cherry fruit fly, Rhagoletis indifferens Curran, in sweet cherry [Prunus avium (L.) L.] and could be included in a systems approach, a combination of all steps involved in cherry production, for showing the absence of larvae in fruit. The methods require crushing cherries and then submerging them in brown sugar solution or hot water to extract the larvae. Larvae are visually detected when they float to the surface of the brown sugar solution or sink in the hot water. The objective of this study was to test the efficacy of these two methods. Both methods detected at least one larva in all 288 moderately to heavily infested cherry samples. The brown sugar flotation and hot water methods detected 89.6–94.7% and 83.0–85.9% of total larvae, respectively, from cherry samples on each of three dates. Significantly higher percentages of 1st instars were detected using the brown sugar than hot water method on two dates, of 3rd instars on one date and of total larvae on two dates. Percent detection of 3rd instars was higher than that of 1st instars using both methods. For both methods, greater percentages of split whole cherries with seeds and non‐split cherries had larvae than split whole cherries with no seeds and halved cherries. Results show that both methods were equally efficacious in detecting the presence of R. indifferens larvae in cherry samples, but brown sugar flotation was more efficacious than the hot water method in detecting a higher percentage of total larvae present and could be integrated into a systems approach for R. indifferens.