bluuebunny/crossref_metadata_2025 huggingface dataset:
Positive affect measured using ecological momentary assessment and survival in older men and women
Authors: Steptoe Andrew , Wardle Jane
Published: November 2011

Links between positive affect (PA) and health have predominantly been investigated by using measures of recollected emotional states. Ecological momentary assessment is regarded as a more precise measure of experienced well-being. We analyzed data from the English Longitudinal Study of Aging, a representative cohort of older men and women living in England. PA was assessed by aggregating momentary assessments over a single day in 3,853 individuals aged 52 to 79 y who were followed up for an average of 5 y. Respondents in the lowest third of PA had a death rate of 7.3%, compared with 4.6% in the medium-PA group and 3.6% in the high-PA group. Cox proportional-hazards regression showed a hazard ratio of 0.498 (95% confidence interval, 0.345–0.721) in the high-PA compared with the low-PA group, adjusted for age and sex. This was attenuated to 0.646 (95% confidence interval, 0.436–0.958) after controlling for demographic factors, negative affect, depressed mood, health indicators, and health behaviors. Negative affect and depressed mood were not related to survival after adjustment for covariates. These findings indicate that experienced PA, even over a single day, has a graded relationship with survival that is not caused by baseline health status or other covariates. Momentary PA may be causally related to survival, or may be a marker of underlying biological, behavioral, or temperamental factors, although reverse causality cannot be conclusively ruled out. The results endorse the value of assessing experienced affect, and the importance of evaluating interventions that promote happiness in older populations.
Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host
Salmonella
Authors: Spanò Stefania , Liu Xiaoyun , Galán Jorge E.
Published: November 2011

Unlike broad-host
Salmonella
serovars, which cause self-limiting disease,
Salmonella enterica
serovar Typhi can infect only humans causing typhoid fever, a life-threatening systemic disease. The molecular bases for these differences are presently unknown. Here we show that the GTPase Rab29 (Rab7L1) distinguishes the intracellular vacuole of human-adapted and broad-host
Salmonella
serovars. A screen to identify host factors required for the export of typhoid toxin, which is exclusively encoded by the human-specific
Salmonella enterica
serovars Typhi (
S
. Typhi) and Paratyphi (
S
. Paratyphi) identified Rab29. We found that Rab29 is recruited to the
S
. Typhi-containing vacuole but not to vacuoles containing broad-host
Salmonella
. We observed that in cells infected with broad-host
Salmonella
Rab29 is specifically cleaved by the proteolytic activity of GtgE, a unique type III secretion effector protein that is absent from
S
. Typhi. An
S
. Typhi strain engineered to express GtgE and therefore able to cleave Rab29 exhibited increased intracellular replication in human macrophages. These findings indicate significant differences in the intracellular biology of human-adapted and broad-host
Salmonella
and show how subtle differences in the assortment of effector proteins encoded by highly related pathogens can have a major impact in their biology.
Quantitative assessment of
Plasmodium falciparum
sexual development reveals potent transmission-blocking activity by methylene blue
Authors: Adjalley Sophie H. , Johnston Geoffrey L. , Li Tao , Eastman Richard T. , Ekland Eric H. , Eappen Abraham G. , Richman Adam , Sim B. Kim Lee , Lee Marcus C. S. , Hoffman Stephen L. , Fidock David A.
Published: November 2011

Clinical studies and mathematical models predict that, to achieve malaria elimination, combination therapies will need to incorporate drugs that block the transmission of
Plasmodium falciparum
sexual stage parasites to mosquito vectors. Efforts to measure the activity of existing antimalarials on intraerythrocytic sexual stage gametocytes and identify transmission-blocking agents have, until now, been hindered by a lack of quantitative assays. Here, we report an experimental system using
P. falciparum
lines that stably express gametocyte-specific GFP-luciferase reporters, which enable the assessment of dose- and time-dependent drug action on gametocyte maturation and transmission. These studies reveal activity of the first-line antimalarial dihydroartemisinin and the partner drugs lumefantrine and pyronaridine against early gametocyte stages, along with moderate inhibition of mature gametocyte transmission to
Anopheles
mosquitoes. The other partner agents monodesethyl-amodiaquine and piperaquine showed activity only against immature gametocytes. Our data also identify methylene blue as a potent inhibitor of gametocyte development across all stages. This thiazine dye almost fully abolishes
P. falciparum
transmission to mosquitoes at concentrations readily achievable in humans, highlighting the potential of this chemical class to reduce the spread of malaria.
Altered axonal targeting and short-term plasticity in the hippocampus of Disc1 mutant mice
Authors: Kvajo Mirna , McKellar Heather , Drew Liam J. , Lepagnol-Bestel Aude-Marie , Xiao Lan , Levy Rebecca J. , Blazeski Richard , Arguello P. Alexander , Lacefield Clay O. , Mason Carol A. , Simonneau Michel , O'Donnell James M. , MacDermott Amy B. , Karayiorgou Maria , Gogos Joseph A.
Published: November 2011

Carefully designed animal models of genetic risk factors are likely to aid our understanding of the pathogenesis of schizophrenia. Here, we study a mouse strain with a truncating lesion in the endogenous
Disc1
ortholog designed to model the effects of a schizophrenia-predisposing mutation and offer a detailed account of the consequences that this mutation has on the development and function of a hippocampal circuit. We uncover widespread and cumulative cytoarchitectural alterations in the dentate gyrus during neonatal and adult neurogenesis, which include errors in axonal targeting and are accompanied by changes in short-term plasticity at the mossy fiber/CA3 circuit. We also provide evidence that cAMP levels are elevated as a result of the
Disc1
mutation, leading to altered axonal targeting and dendritic growth. The identified structural alterations are, for the most part, not consistent with the growth-promoting and premature maturation effects inferred from previous RNAi-based
Disc1
knockdown. Our results provide support to the notion that modest disturbances of neuronal connectivity and accompanying deficits in short-term synaptic dynamics is a general feature of schizophrenia-predisposing mutations.
Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients
Authors: Staquicini Fernanda I. , Cardó-Vila Marina , Kolonin Mikhail G. , Trepel Martin , Edwards Julianna K. , Nunes Diana N. , Sergeeva Anna , Efstathiou Eleni , Sun Jessica , Almeida Nalvo F. , Tu Shi-Ming , Botz Gregory H. , Wallace Michael J. , O’Connell David J. , Krajewski Stan , Gershenwald Jeffrey E. , Molldrem Jeffrey J. , Flamm Anne L. , Koivunen Erkki , Pentz Rebecca D. , Dias-Neto Emmanuel , Setubal João C. , Cahill Dolores J. , Troncoso Patricia , Do Kim-Ahn , Logothetis Christopher J. , Sidman Richard L. , Pasqualini Renata , Arap Wadih
Published: November 2011

Molecules differentially expressed in blood vessels among organs or between damaged and normal tissues, are attractive therapy targets; however, their identification within the human vasculature is challenging. Here we screened a peptide library in cancer patients to uncover ligand-receptors common or specific to certain vascular beds. Surveying ∼2.35 × 10
6
motifs recovered from biopsies yielded a nonrandom distribution, indicating that systemic tissue targeting is feasible. High-throughput analysis by similarity search, protein arrays, and affinity chromatography revealed four native ligand-receptors, three of which were previously unrecognized. Two are shared among multiple tissues (integrin α4/annexin A4 and cathepsin B/apolipoprotein E3) and the other two have a restricted and specific distribution in normal tissue (prohibitin/annexin A2 in white adipose tissue) or cancer (RAGE/leukocyte proteinase-3 in bone metastases). These findings provide vascular molecular markers for biotechnology and medical applications.
A chemical-genetic screen to unravel the genetic network of
CDC28/CDK1
links ubiquitin and Rad6–Bre1 to cell cycle progression
Authors: Zimmermann Christine , Chymkowitch Pierre , Eldholm Vegard , Putnam Christopher D. , Lindvall Jessica M. , Omerzu Manja , Bjørås Magnar , Kolodner Richard D. , Enserink Jorrit M.
Published: November 2011

Cyclin-dependent kinases (CDKs) control the eukaryotic cell cycle, and a single CDK, Cdc28 (also known as Cdk1), is necessary and sufficient for cell cycle regulation in the budding yeast
Saccharomyces cerevisiae
. Cdc28 regulates cell cycle-dependent processes such as transcription, DNA replication and repair, and chromosome segregation. To gain further insight into the functions of Cdc28, we performed a high-throughput chemical-genetic array (CGA) screen aimed at unraveling the genetic network of
CDC28
. We identified 107 genes that strongly genetically interact with
CDC28
. Although these genes serve multiple cellular functions, genes involved in cell cycle regulation, transcription, and chromosome metabolism were overrepresented.
DOA1
, which is involved in maintaining free ubiquitin levels, as well as the
RAD6
–
BRE1
pathway, which is involved in transcription, displayed particularly strong genetic interactions with
CDC28
. We discovered that
DOA1
is important for cell cycle entry by supplying ubiquitin. Furthermore, we found that the
RAD6
–
BRE1
pathway functions downstream of
DOA1
/ubiquitin but upstream of
CDC28
, by promoting transcription of cyclins. These results link cellular ubiquitin levels and the Rad6–Bre1 pathway to cell cycle progression.
Gating charge interactions with the S1 segment during activation of a Na
+
channel voltage sensor
Authors: DeCaen Paul G. , Yarov-Yarovoy Vladimir , Scheuer Todd , Catterall William A.
Published: November 2011

Voltage-gated Na
+
channels initiate action potentials during electrical signaling in excitable cells. Opening and closing of the pore of voltage-gated ion channels are mechanically linked to voltage-driven outward movement of the positively charged S4 transmembrane segment in their voltage sensors. Disulfide locking of cysteine residues substituted for the outermost T0 and R1 gating-charge positions and a conserved negative charge (E43) at the extracellular end of the S1 segment of the bacterial Na
+
channel NaChBac detects molecular interactions that stabilize the resting state of the voltage sensor and define its conformation. Upon depolarization, the more inward gating charges R2 and R3 engage in these molecular interactions as the S4 segment moves outward to its intermediate and activated states. The R4 gating charge does not disulfide-lock with E43, suggesting an outer limit to its transmembrane movement. These molecular interactions reveal how the S4 gating charges are stabilized in the resting state and how their outward movement is catalyzed by interaction with negatively charged residues to effect pore opening and initiate electrical signaling.
Alternatively spliced domains interact to regulate BK potassium channel gating
Authors: Johnson Brandon E. , Glauser Dominique A. , Dan-Glauser Elise S. , Halling D. Brent , Aldrich Richard W. , Goodman Miriam B.
Published: November 2011

Most human genes contain multiple alternative splice sites believed to extend the complexity and diversity of the proteome. However, little is known about how interactions among alternative exons regulate protein function. We used the
Caenorhabditis elegans slo
-1
large-conductance calcium and voltage-activated potassium (BK) channel gene, which contains three alternative splice sites (A, B, and C) and encodes at least 12 splice variants, to investigate the functional consequences of alternative splicing. These splice sites enable the insertion of exons encoding part of the regulator of K
+
conductance (RCK)1 Ca
2+
coordination domain (exons A1 and A2) and portions of the RCK1–RCK2 linker (exons B0, B1, B2, C0, and C1). Exons A1 and A2 are used in a mutually exclusive manner and are 67% identical. The other exons can extend the RCK1–RCK2 linker by up to 41 residues. Electrophysiological recordings of all isoforms show that the A1 and A2 exons regulate activation kinetics and Ca
2+
sensitivity, but only if alternate exons are inserted at site B or C. Thus, RCK1 interacts with the RCK1–RCK2 linker, and the effect of exon variation on gating depends on the combination of alternate exons present in each isoform.
WORK ORIENTATIONS IN FLUX?
Authors: Turunen Teemu
Published: November 2011

In this article, subjective work goals are studied comparatively among employees in five European countries: Finland, Germany, Great Britain, Spain, and Sweden. Inglehart (2008), West European Politics 31) has claimed that a cultural shift from survival values to self-expression values also brings changing values concerning work in advanced western societies. Inglehart's thesis is tested empirically in this article by using pooled data from World Values Surveys and European Values Studies collected in 1990–1999/2000. The results do not show a clear shift from survival values to self-expression values in work goals, which contradicts Inglehart's thesis. However, there was some support for Inglehart's claims in the data. The results also pointed to differences, as well as some similarities, between these European countries regarding work goals. Advanced western countries should not then be treated as a homogenous category in future research on work goals. The support for intrinsic work goals was also analysed using four independent variables: birth cohort, gender, social class, and job satisfaction. Social class was the main individual determinant of intrinsic work goals in most of the research countries. Higher social classes valued intrinsic work goals more than lower social classes did.
Counsellors’ experiences of working with male victims of female‐perpetrated domestic abuse
Authors: Hogan Kevin F. , Hegarty John R. , Ward Tony , Dodd Lorna J.
Published: November 2011

Aim:To provide an understanding of counsellors’ experiences of working with male victims of female‐perpetrated domestic abuse. This topic has been virtually unexplored within counselling literature.Method:A qualitative design was adopted to address the objective of this research. Semi‐structured interviews were conducted with six counsellors. Snowball sampling was used to identify suitable participants. Three were males and three females, and all had experience of working with male victims of female‐perpetrated domestic abuse. Results were analysed using Interpretative Phenomenological Analysis (IPA).Findings:Ten over‐arching themes emerged from the transcripts, including a distinct lack of recognition of male victimisation, which was seen as hampering counsellors’ work with clients. Participants, particularly female counsellors, also drew on the significance of their gender. Furthermore, counsellors described changes in their perceptions of women within modern society. A central feature of participants’ accounts was a sense of privilege in sharing clients’ experiences. However, participants described the work as challenging, and employed both personal and professional strategies to help them cope with work‐related difficulties.Discussion:Findings offer an initial understanding as to the experiences of counsellors that have worked with male victims. This may be helpful in leading to the development of more effective strategies employed by counsellors and counselling agencies in successfully working with male victims, whilst increasing awareness of male victimisation.
Prospective study of sport dropout: A motivational analysis as a function of age and gender
Authors: Guzmán Jose Francisco , Kingston Kieran
Published: November 2011

Introduction: This paper aimed to analyse the predictive ability of a self‐determination theory (SDT) based model describing competitive sport dropout, and variance as a function of age and gender. Variables included in the model were: psychological need satisfaction, self‐determined motivation, perceived conflict between sport and study, intention to practise sport, and dropout.

Methods: A prospective study was performed over a period of 19 months. Variables considered as predictors of sport dropout were measured initially, and after 19 months persistence or dropout was assessed. The sample consisted of 857 athletes aged 11–19 (mean value 15.3; standard deviation = 1.77), 680 males and 177 females.

Results: Structural equation modelling illustrated support for an “alternative” model that incorporated a direct relationship between psychological need satisfaction and intention to practise sport. Analysis of invariance showed that the model was consistent as a function of age and gender, i.e. no differences were found in regression weights. MANOVA, however, revealed some group differences with respect to the dependent variables. Specifically, in terms of engagement, although assessed at the start of the study, those athletes who persisted at 19 months demonstrated greater need satisfaction, self‐determined motivation and intention to practise sport than those who dropped out. Age related differences were also identified: with increased age self‐determined motivation and intention to practise sport decreased, while there were no differences in need satisfaction or perceived conflict between sport and study. There were no differences related to gender.

Discussion: The results support previous studies that had used SDT to predict sport dropout, specifically those that had reported an inverse relationship between self‐determined motivation and perceived conflict between activities. Further, it suggests that other variables (emotional) may play a specific role in predicting intention to continue engagement with sport.

Conclusion: The major contribution of the study is in validating a motivational model predicting sport dropout which incorporates perceived conflict and the direct effect of psychological need satisfaction on the intention to practise sport. The invariance of regression weights between age and gender groups suggests that the relationships proposed in the model are universal.
Left ventricular oxidant and antioxidant markers induced by lifestyle modification in rats exposed to lead acetate
Authors: Dabidi Roshan Valiollah , Ranjbar Shima , Hosseinzadeh Mahdi , Myers Jonathan
Published: November 2011

Responses of the left ventricle oxidant/antioxidant markers such as glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA) and protein carbonyls (PCs) induced by lifestyle modification, including turmeric supplementation and exercise training, were investigated in rats during chronic exposure to lead acetate. Forty male rats were randomly divided into five groups: (1) lead acetate; (2) turmeric; (3) endurance training; (4) training + turmeric; and (5) sham‐operated groups. Enzyme activities were determined in rat hearts after receiving 20 mg·kg−1 of lead acetate (groups 1 to 4) and 30 mg·kg−1 turmeric (groups 2 and 4) for 8 weeks, three times a week. In addition, the rats in groups 3 and 4 performed treadmill running at a speed of 15 to 22 m·min−1 for 25 to 64 min, five times a week for 8 weeks. One way ANOVA analyses indicated that administration of lead evoked a significant increase in MDA and PC and significant decreases in GPx and SOD activity in the left ventricular homogenates. However, endurance training and\or turmeric supplementation resulted in a significant decrease in MDA and PC levels and significantly increased levels of GPx and SOD. These results suggest that lifestyle modification may have a cardioprotective effect by ameliorating lead‐induced cardiotoxicity.
Functional Equivalence and Spatial Path Memory
Authors: Lyon Don R. , Gunzelmann Glenn
Published: November 2011

Loomis, Klatzky, Avraamides, Lippa and Golledge (2007) suggest that, when it comes to spatial information, verbal description and perceptual experience are nearly functionally equivalent with respect to the cognitive representations they produce. We tested this idea for the case of spatial memory for complex paths. Paths consisted entirely of unit-length segments followed by 90-degree turns, thus assuring that a path could be described with equal precision using either an egocentric verbal description or a virtual self-motion experience. The verbal description was analogous to driving directions (e.g., turn left and go one block, then turn right, etc.) except in three dimensions (allowing rotation followed by up or down movement). Virtual self-motion was depicted as first-person travel through a 3D grid of featureless corridors. Comparison of these two conditions produced a result that may be surprising to some, but nevertheless appears to support the notion of functional equivalence: Virtual self-motion does not produce better path memory than verbal description, when care is taken to present equally precise path information. This result holds for even very complex paths and despite evidence from proximity-based interference that the memory representation of the path is spatial.
Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells
Authors: Hickman Heather D. , Li Lily , Reynoso Glennys V. , Rubin Erica J. , Skon Cara N. , Mays Jacqueline W. , Gibbs James , Schwartz Owen , Bennink Jack R. , Yewdell Jonathan W.
Published: November 2011

Naive antiviral CD8+ T cells are activated in the draining LN (DLN) by dendritic cells (DCs) presenting viral antigens. However, many viruses infect LN macrophages, which participate in initiation of innate immunity and B cell activation. To better understand how and why T cells select infected DCs rather than macrophages, we performed intravital microscopy and ex vivo analyses after infecting mice with vaccinia virus (VV), a large DNA virus that infects both LN macrophages and DCs. Although CD8+ T cells interact with both infected macrophages and DCs in the LN peripheral interfollicular region (PIR), DCs generate more frequent and stable interactions with T cells. VV infection induces rapid release of CCR5-binding chemokines in the LN, and administration of chemokine-neutralizing antibodies diminishes T cell activation by increasing T cell localization to macrophages in the macrophage-rich region (MRR) at the expense of PIR DCs. Similarly, DC ablation increases both T cell localization to the MRR and the duration of T cell–macrophage contacts, resulting in suboptimal T cell activation. Thus, virus-induced chemokines in DLNs enable antiviral CD8+ T cells to distinguish DCs from macrophages to optimize T cell priming.
REG-γ associates with and modulates the abundance of nuclear activation-induced deaminase
Authors: Uchimura Yasuhiro , Barton Lance F. , Rada Cristina , Neuberger Michael S.
Published: November 2011

Activation-induced deaminase (AID) acts on the immunoglobulin loci in activated B lymphocytes to initiate antibody gene diversification. The abundance of AID in the nucleus appears tightly regulated, with most nuclear AID being either degraded or exported back to the cytoplasm. To gain insight into the mechanisms regulating nuclear AID, we screened for proteins interacting specifically with it. We found that REG-γ, a protein implicated in ubiquitin- and ATP-independent protein degradation, interacts in high stoichiometry with overexpressed nuclear AID as well as with endogenous AID in B cells. REG-γ deficiency results in increased AID accumulation and increased immunoglobulin class switching. A stable stoichiometric AID–REG-γ complex can be recapitulated in co-transformed bacteria, and REG-γ accelerates proteasomal degradation of AID in in vitro assays. Thus, REG-γ interacts, likely directly, with nuclear AID and modulates the abundance of this antibody-diversifying but potentially oncogenic enzyme.
Ideal games and Ramsey sets
Authors: Di Prisco Carlos , Mijares José , Uzcátegui Carlos
Published: November 2011

It is shown that Matet’s characterization of the Ramsey property relative to a selective co-ideal

H

\mathcal {H}

, in terms of games of Kastanas, still holds if we consider semiselectivity instead of selectivity. Moreover, we prove that a co-ideal

H

\mathcal {H}

is semiselective if and only if Matet’s game-theoretic characterization of the

H

\mathcal {H}

-Ramsey property holds. This lifts Kastanas’s characterization of the classical Ramsey property to its optimal setting, from the point of view of the local Ramsey theory, and gives a game-theoretic counterpart to a theorem of Farah, asserting that a co-ideal

H

\mathcal {H}

is semiselective if and only if the family of

H

\mathcal {H}

-Ramsey subsets of

N

[
∞
]

\mathbb {N}^{[\infty ]}

coincides with the family of those sets having the abstract

H

\mathcal {H}

-Baire property. Finally, we show that under suitable assumptions, for every semiselective co-ideal

H

\mathcal H

all sets of real numbers are

H

\mathcal H

-Ramsey.
Analysis of model replication origins inDrosophilareveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex
Authors: Liu Jun , McConnell Kristopher , Dixon Michael , Calvi Brian R.
Published: November 2011

Epigenetic regulation exerts a major influence on origins of DNA replication during development. The mechanisms for this regulation, however, are poorly defined. We showed previously that acetylation of nucleosomes regulates the origins that mediate developmental gene amplification during Drosophila oogenesis. Here we show that developmental activation of these origins is associated with acetylation of multiple histone lysines. Although these modifications are not unique to origin loci, we find that the level of acetylation is higher at the active origins and quantitatively correlated with the number of times these origins initiate replication. All of these acetylation marks were developmentally dynamic, rapidly increasing with origin activation and rapidly declining when the origins shut off and neighboring promoters turn on. Fine-scale analysis of the origins revealed that both hyperacetylation of nucleosomes and binding of the origin recognition complex (ORC) occur in a broad domain and that acetylation is highest on nucleosomes adjacent to one side of the major site of replication initiation. It was surprising to find that acetylation of some lysines depends on binding of ORC to the origin, suggesting that multiple histone acetyltransferases may be recruited during origin licensing. Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development.
TIP: A probabilistic method for identifying transcription factor target genes from ChIP-seq binding profiles
Authors: Cheng Chao , Min Renqiang , Gerstein Mark
Published: October 2011

Motivation: ChIP-seq and ChIP-chip experiments have been widely used to identify transcription factor (TF) binding sites and target genes. Conventionally, a fairly ‘simple’ approach is employed for target gene identification e.g. finding genes with binding sites within 2 kb of a transcription start site (TSS). However, this does not take into account the number of sites upstream of the TSS, their exact positioning or the fact that different TFs appear to act at different characteristic distances from the TSS.

Results: Here we propose a probabilistic model called target identification from profiles (TIP) that quantitatively measures the regulatory relationships between TFs and target genes. For each TF, our model builds a characteristic, averaged profile of binding around the TSS and then uses this to weight the sites associated with a given gene, providing a continuous-valued ‘regulatory’ score relating each TF and potential target. Moreover, the score can readily be turned into a ranked list of target genes and an estimate of significance, which is useful for case-dependent downstream analysis.

Conclusion: We show the advantages of TIP by comparing it to the ‘simple’ approach on several representative datasets, using motif occurrence and relationship to knock-out experiments as metrics of validation. Moreover, we show that the probabilistic model is not as sensitive to various experimental parameters (including sequencing depth and peak-calling method) as the simple approach; in fact, the lesser dependence on sequencing depth potentially utilizes the result of a ChIP-seq experiment in a more ‘cost-effective’ manner.

Contact:  mark.gerstein@yale.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Human Leukocyte Antigen Class I and II Alleles and Overall Survival in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma
Authors: Lu Yani , Abdou Amr M. , Cerhan James R. , Morton Lindsay M. , Severson Richard K. , Davis Scott , Cozen Wendy , Rothman Nathaniel , Bernstein Leslie , Chanock Stephen , Hartge Patricia , Wang Sophia S.
Published: November 2011

Genetic variation in the 6p21 chromosomal region, including human leukocyte antigen (HLA) genes and tumor necrosis factor (TNF), has been linked to both etiology and clinical outcomes of lymphomas. We estimated the effects ofHLAclass I (A, B, and C), class IIDRB1alleles, and the ancestral haplotype (AH) 8.1 (HLAA*01-B*08-DRB1*03-TNF-308A) on overall survival (OS) among patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in a population-based study of non-Hodgkin lymphoma. During a median followup of 89 months, 31% (52 of 166) DLBCL and 28% (46 of 165) FL patients died. Using multivariate Cox regression models, we observed statistically significant associations between genetic variants and survival:HLA-Cw*07:01was associated with poorer OS among DLBCL patients (Hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.01–3.05);HLA-A*01:01was associated with poorer OS (HR = 2.23, 95% CI = 1.24–4.01), andHLA-DRB1*13(HR = 0.12, 95% CI = 0.02–0.90) andHLA-B Bw4(HR = 0.36, 95% CI = 0.20–0.63) with better OS among FL patients. These results support a role forHLAin the prognosis of DLBCL and FL and represent a promising class of prognostic factors that warrants further evaluation.
Advantages and Disadvantages of Hyperbaric Oxygen Treatment in Mice with Obesity Hyperlipidemia and Steatohepatitis
Authors: Tsuneyama Koichi , Chen Yen-Chen , Fujimoto Makoto , Sasaki Yoshiyuki , Suzuki Wataru , Shimada Tsutomu , Iizuka Seiichi , Nagata Mitsunobu , Aburada Masaki , Chen Shao-Yuan
Published: November 2011

The effect of hyperbaric oxygen treatment (HBOT) was examined using MSG mice, which are an animal model of obesity, hyperlipidemia, diabetes, and nonalcoholic fatty liver disease. Nineteen MSG male mice were divided into HBOT treated and control groups at 12 weeks of ages. The HBOT group was treated with hyperbaric oxygen from 12 to 14 weeks (first phase) and then from 16 to 18 weeks (second phase). Interestingly, the body weight of the HBOT group was significantly lower (P<0.01) than that of the control group. In contrast, the serum lipid level did not show significant changes between the two groups. As for the effects of increasing oxidative stress, the liver histology of the HBOT group showed severer cellular damage and aberrant TNF-α expression. HBOT has the advantage of improving obesity in patients with metabolic syndrome, but the fault of causing organ damage by increasing oxidative stress.
Problem of Foreign Body in GI Tract
Authors: Daneshbod Yahya , Talei Abdolrasoul , Negahban Shahrzad , Soleimanpour Hossein , Aledavoud Azita , Bagheri Neda , Khanlari Mahsa , Daneshbod Khosrow
Published: November 2011

Most foreign bodies pass through the gastrointestinal tract uneventful. We report of a case of inadvertently ingested foreign body, which by endoscopy simulated a polyp and on biopsy reported as cancer, so the patient underwent an unnecessary major operation. This report emphasizes the importance of resemblance of foreign bodies with gastrointestinal neoplasm, and endoscopists, surgeons and pathologists should consider this entity in their daily practice.
Preparation of Drosophila Eye Specimens for Transmission Electron Microscopy
Authors: Wolff Tanya
Published: November 2011

Transmission electron microscopy (TEM) allows for high-magnification ultrastructural analysis of the Drosophila eye. The fixation protocol described here works well for Drosophila eye tissue, including larval imaginal discs and pupal and adult retinas.
Time-Lapse Imaging of Membrane Traffic in Living Cells
Authors: Snapp Erik Lee , Lajoie Patrick
Published: November 2011

Eukaryotic cells are composed of an intricate system of internal membranes that are organized into different compartments—including the endoplasmic reticulum (ER), the nuclear envelope, the Golgi complex (GC), lysosomes, endosomes, caveolae, mitochondria, and peroxisomes—that perform specialized tasks within the cell. The localization and dynamics of intracellular compartments are now being studied in living cells because of the availability of green fluorescent protein (GFP)-fusion proteins and recent advances in fluorescent microscope imaging systems. This protocol describes the use of the confocal laser-scanning microscope (CLSM) for time-lapse imaging of one or more fluorescent markers.
The Optical Trapping Dumbbell Assay for Nonprocessive Motors or Motors That Turn around Filaments
Authors: Spudich James A. , Rice Sarah E. , Rock Ronald S. , Purcell Thomas J. , Warrick Hans M.
Published: November 2011

In vitro motility assays enabled the analysis of coupling between ATP hydrolysis and movement of myosin along actin filaments or kinesin along microtubules. Single-molecule assays using laser trapping have been used to obtain more detailed information about kinesins, myosins, and processive DNA enzymes. The combination of in vitro motility assays with laser-trap measurements has revealed detailed dynamic structural changes associated with the ATPase cycle. This protocol describes the preparation of biotin–actin filaments and coverslips coated with polystyrene beads. These are then used in optical trapping dumbbell assays to study interactions between motors and filaments.
The ‘F‐words’ in childhood disability: I swear this is how we should think!
Authors: Rosenbaum P. , Gorter J. W.
Published: November 2011

The 21st century is witnessing a sea change in our thinking about ‘disability’. Nowhere are these developments more apparent than in the field of childhood disability, where traditional biomedical concepts are being incorporated into – but expanded considerably by – new ways of formulating ideas about children, child development, social‐ecological forces in the lives of children with chronic conditions and their families, and ‘points of entry’ for professionals to be helpful. In this paper, we have tried to package a set of ideas, grounded in the World Health Organization's International Classification of Functioning, Disability and Health (the ICF), into a series of what we have called ‘F‐words’ in child neurodisability – function, family, fitness, fun, friends and future. We hope this will be an appealing way for people to incorporate these concepts into every aspect of clinical service, research and advocacy regarding disabled children and their families.
Effects of incorporating cowpea in a subtropical grass pasture on forage production and quality and the performance of cows and calves
Authors: Vendramini J.M.B , Arthington J. D. , Adesogan A. T.
Published: November 2011

The increasing cost of N fertilizer has stimulated an interest in sourcing protein from warm‐season legumes among beef cattle producers in the tropical/subtropical areas of the world. The objective of this study was to evaluate effects of two strategies of incorporating cowpea [Vigna unguiculata (L.) Walp.] into bahiagrass (Paspalum notatum Flügge) pastures on the herbage characteristics and performance of grazing cow–calf pairs. The study was conducted in Ona, Florida, USA, from May to August in 2007 and 2008. Experimental units were 1·0 ha. Treatments were bahiagrass pasture alone (control), 50:50 bahiagrass–cowpea pasture (cowpea), bahiagrass pasture with a cowpea creep grazing area (0·1 ha, creep grazing) and bahiagrass pasture with a creep‐fed concentrate [(creep feeding; 10 g kg−1 body weight (BW)]. The cowpea pastures had lower herbage mass [HM, 1·8 vs. 3·7 t ha−1] and herbage allowance [HA, 0·8 vs. 1·4 kg DM kg−1 live weight (LW)] compared with the other treatments. Cowpea had greater CP (CP, 160 g kg−1) and in vitro digestible organic matter (IVDOM), (600 g kg−1) than bahiagrass (110 and 490 g kg−1 respectively); however, cowpea HM was only 0·9 t ha−1 in May and 0·7 t ha−1 in June, but it did not persist in July and August. Calves receiving the creep feeding treatments had greater average daily gain (0·8 vs. 0·7 kg d−1) than calves in other treatments. Further research is necessary to exploit the superior nutritive value of cowpea in grazing systems in the south‐eastern USA.
An alternative rotational stocking management designed to favour butterflies in permanent grasslands
Authors: Farruggia A. , Dumont B. , Scohier A. , Leroy T. , Pradel P. , Garel J.‐P.
Published: November 2011

Grassland butterflies are on the decline throughout Europe. We tested an ‘alternative rotational stocking’ (ARS) strategy based on theoretical and practical aspects of grassland ecology, designed to increase butterfly diversity while also meeting farmers’ production objectives. This management strategy implies taking animals away from one subplot of the rotation during the main flowering period. Its feasibility and benefits on butterfly diversity were tested by comparing ARS with continuous stocking (CS) in plots grazed by cattle at the same stocking rate: high in 2005 and 2006 then lenient in 2007 and 2008. At the high stocking rate, butterfly abundance (21·9 vs. 8·3, P < 0·01) and butterfly species richness (7·4 vs. 3·7, P < 0·001) were significantly higher in ARS than in CS plots, matching the increase in pasture flowering intensity and sward structural diversity. ARS was led according to the pre‐planned schedule in 2005, but in 2006, the number of heifer grazing days in ARS was reduced by 19% because of unfavourable spring grass growth. At the lenient stocking rate, ARS was less beneficial for butterflies (abundance: 17·4 vs. 13·0, P < 0·10; species richness: 5·9 vs. 5·2, P = 0·35) but would present less risk for farmers in terms of providing livestock with sufficient forage. Alternative rotational stocking thus has potential to be integrated into grassland‐based systems, but would require earlier grazing on the excluded subplot of the rotation in the event of unfavourable grass growth during spring.
The effect of a major road on bat activity and diversity
Authors: Berthinussen Anna , Altringham John
Published: November 2011

1. It is well known that roads can have a significant impact, usually negative, on species and ecosystems. However, despite their protected status in many countries, little research has been done into the effects of roads on bats. With a view to making more informed management recommendations, we address the simple question: are bat activity and diversity (as measured with ultrasonic detectors) correlated with distance from a major road?

2. Broadband acoustic surveys were conducted on 20 walked transects perpendicular to the M6, a major road in Cumbria (UK), with bat activity recorded at eight spot checks per transect at different distances from the road. Climatic and habitat variables were also recorded, and the relationships between bat activity and these variables were investigated using generalised estimated equations (GEE) and ordinal logistic regression.

3. Total bat activity, the number of species and the activity of Pipistrellus pipistrellus (the most abundant species) were all positively correlated with distance from the road. Total activity increased more than threefold between 0 and 1600 m from the road. These effects were found to be consistent over 2 years.

4. Synthesis and applications. This study is one of the first to show that roads have a major negative impact on bat foraging activity and diversity and is broadly applicable to insectivorous bat communities worldwide. Mitigation requires that roads are made more permeable to bats through the use of effective crossings, such as underpasses and overpasses, and that habitat is improved within 1 km of major roads. Because the effectiveness of current mitigation measures is unknown, well‐designed monitoring of mitigation is essential.
Modelling large‐scale relationships between changes in woodland deer and bird populations
Authors: Newson Stuart E. , Johnston Alison , Renwick Anna R. , Baillie Stephen R. , Fuller Robert J.
Published: November 2011

1. There is increasing evidence from local studies carried out in several parts of the world to suggest that increases in the abundance of deer may be depressing population levels of breeding woodland bird populations that are associated with dense understorey habitats. We examine whether habitat modification by deer is likely to be a factor contributing to recent large‐scale population declines of woodland birds in lowland England.

2. Novel analytical methods are applied to extensive national bird and deer monitoring data, to examine whether populations of 11 woodland bird species that are associated with dense understorey habitats in lowland England may have been depressed following increases in the abundance of three widespread and abundant deer species: Reeves’ muntjac Muntiacus reevesi, roe deer Capreolus capreolus and fallow deer Dama dama. An additional four woodland bird species that are not specifically associated with understorey habitats are included as controls.

3. For five of the 11 understorey species considered, there is evidence that increases in deer are associated with large‐scale depression of abundance or population declines in lowland England. Of these species, we suggest that the impacts of deer are likely to have been greatest for two species of conservation concern, common nightingale Luscinia megarhynchos and willow tit Poecile montanus.

4. Synthesis and applications. Large‐scale analyses of extensive national monitoring data provide evidence for a negative association between three widespread and abundant deer species and several woodland bird populations that are associated with dense understorey habitats. These findings are consistent with those from small‐scale experimental studies and indicate that deer‐related habitat modification may be affecting some bird species on far larger scales than previously appreciated. Mainly through their effects on understorey vegetation, high deer populations are now likely to be affecting woodland biodiversity over large parts of lowland England and deer management plans, involving integrated exclusion and culling of deer, need to be co‐ordinated on large scales. It is suggested that such management plans could most usefully target areas that still support relatively high populations of species that are sensitive to deer. Knowledge about the form of relationships between deer abundance and habitat quality for birds and other biodiversity is an important knowledge gap that needs to be addressed if sound, collaborative deer management plans are to be developed.
Scaling down distribution maps from atlas data: a test of different approaches with virtual species
Authors: Bombi Pierluigi , D’Amen Manuela
Published: November 2011

Aim  Conservation managers are increasingly looking for modelled projections of species distributions to inform management strategies; however, the coarse resolution of available data usually compromises their helpfulness. The aim of this paper is to delineate and test different approaches for converting coarse‐grain occurrence data into high‐resolution predictions, and to clarify the conceptual circumstances affecting the accuracy of downscaled models.

Location  We used environmental data from a real landscape, southern Africa, and simulated species distributions within this landscape.

Methods  We built 10 virtual species at a resolution of 5 arcmin, and for each species we simulated atlas range maps at four decreasing resolutions (15, 30, 60, 120 arcmin). We tested the ability of three downscaling strategies to produce high‐resolution predictions using two modelling techniques: generalized linear models and generalized boosted models. We calibrated reference models with high‐resolution data and we compared the relative reduction of predictive performance in the downscaled models by using a null model approach. We also estimated the applicability of downscaling procedures to different situations by using distribution data for Mediterranean reptiles.

Results  All reference models achieved high performance measures. For all strategies, we observed a reduction of predictive performance proportional to the degree of downscaling. The differences in evaluation indices between reference models and downscaled projections obtained from atlases at 15 and 30 arcmin were never statistically significant. The accuracy of projections scaled down from 60 arcmin largely depended on the combination of approach and algorithm adopted. Projections scaled down from 120 arcmin gave misleading results in all cases.

Main conclusions  Moderate levels of downscaling allow for reasonably accurate results, regardless of the technique used. The most general effect of scaling down coarse‐grain data is the reduction of model specificity. The models can successfully delineate a species’ environmental association up until a 12‐fold downscaling, although with an increasing approximation that causes the overestimation of true distributions. We suggest appropriate procedures to mitigate the commission error introduced by downscaling at intermediate levels (approximately 12‐fold). Reductions of grain size > 12‐fold are discouraged.
Pressure ulcers: knowledge and attitude of nurses and nursing assistants in Belgian nursing homes
Authors: Demarré Liesbet , Vanderwee Katrien , Defloor Tom , Verhaeghe Sofie , Schoonhoven Lisette , Beeckman Dimitri
Published: November 2011

Aims.  To gain insight into the knowledge and attitudes of nurses and nursing assistants and to study the correlation between knowledge, attitudes and the compliance with the pressure ulcer prevention guidelines provided to residents at risk of pressure ulcers in nursing homes.

Background.  There is a lack of evidence on knowledge and attitudes of nurses and nursing assistants towards pressure ulcer prevention in nursing homes.

Design.  A cross‐sectional multi‐centre study.

Methods.  A convenience sample of nine Belgian nursing homes, representing 18 wards was chosen in the study. In total, 145 nurses and nursing assistants were included. The compliance with the guidelines was evaluated in 615 residents, and data were collected using validated instruments.

Results.  Fully compliant prevention was found in only 6·9% of the residents at risk. The mean knowledge score of the nurses was 29·3 vs. 28·7% for the nursing assistants. The overall attitude score was 74·5%, and attitude scores were significantly different between nurses and nursing assistants. Nurses showed to have a more positive attitude towards pressure ulcer prevention than nursing assistants, respectively 78·3 and 72·3%. A more positive attitude was a significant predictor of pressure ulcer prevention compliance with the guidelines provided to residents at risk of pressure ulcers in nursing homes.

Conclusions.  Knowledge about pressure ulcer prevention of both nurses and nursing assistants in nursing homes was low. Attitudes were a significant predictor of the application of fully compliant prevention in residents at risk.

Relevance to clinical practice.  Pressure ulcer prevention is an important aspect in daily care for residents at risk in nursing homes. These insights will contribute to evidence‐based practice in this area of care and will form the basis for the development of an education strategy for pressure ulcer prevention and management in nursing homes.