bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender, the Stress Process, and Health
Authors: Longest Kyle C. , Thoits Peggy A.
Published: July 2012

Numerous studies have shown that men and women react to experiences of stressors and a lack of protective resources in different ways, with women exhibiting high levels of internalizing health outcomes (e.g., psychological distress and ill health) and men showing higher levels of externalizing outcomes (e.g., substance abuse and aggression). Although this research is valuable, the emphasis on differing outcomes by gender has prematurely shifted the focus away from the processes leading to similar health outcomes across genders. The current study uses a novel analytic approach, Fuzzy Set Qualitative Comparative Analysis (fsQCA), to examine and compare the key pathways that lead to poor physical and mental health among men and women. Analysis of data from a panel study of Indianapolis residents ( N = 532) indicates that a combination of numerous stressors with low resources consistently leads to poor mental and physical health. The specific configurations of factors that are sufficient to produce these outcomes, however, differ across men and women, with men requiring a full onslaught of stressors and a dearth of resources to experience high psychological distress or ill health and women experiencing such poor outcomes as the result of several, relatively limited combinations of these factors.
Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells
Authors: Vitali Caterina , Mingozzi Francesca , Broggi Achille , Barresi Simona , Zolezzi Francesca , Bayry Jagadeesh , Raimondi Giorgio , Zanoni Ivan , Granucci Francesca
Published: July 2012

There is evidence that dendritic cells (DCs) induce peripheral tolerance. Nevertheless, it is not known whether immature DCs in general are able to tolerize CD4+ T cells or if this is a prerogative of specialized subtypes. Here we show that, when autoantigen presentation is extended to all conventional mouse DCs, immature lymphoid tissue resident DCs are unable to induce autoantigen-specific regulatory T (iTreg) cell conversion. In contrast, this is an exclusive prerogative of steady-state migratory DCs. Because only lymph nodes host migratory DCs, iTreg cells develop and are retained solely in lymph nodes, and not in the spleen. Mechanistically, in cutaneous lymph nodes, DC-derived CCL22 contributes to the retention of iTreg cells. The importance of the local generation of iTreg cells is emphasized by their essential role in preventing autoimmunity.
Full reconstitution of human platelets in humanized mice after macrophage depletion
Authors: Hu Zheng , Yang Yong-Guang
Published: July 2012

Cotransplantation of human fetal thymic tissue and CD34+ fetal liver cells in nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) or NOD/SCID/γc−/− mice results in the development of multilineage human hematopoietic cells. In this study, we show that these humanized mice had extremely low levels of human platelets. The presence of human megakaryocytes at a normal concentration in the bone marrow suggests that human megakaryocytic differentiation occurred efficiently in these mice. Rapid increase in human platelets in blood to levels comparable with those of human peripheral blood mononuclear cells (PBMCs) after macrophage depletion indicates that mouse macrophages are responsible for the poor human platelet reconstitution in humanized mice. In support of this possibility, human platelets were rapidly rejected after infusion into untreated mice, but persisted in macrophage-depleted mice. These findings indicate that inhibition or depletion of recipient mouse macrophages may provide a useful means for evaluating human thrombopoiesis and platelet function in vivo using immunodeficient mice.
Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters
Authors: Lemonnier François , Couronné Lucile , Parrens Marie , Jaïs Jean-Philippe , Travert Marion , Lamant Laurence , Tournillac Olivier , Rousset Therese , Fabiani Bettina , Cairns Rob A. , Mak Tak , Bastard Christian , Bernard Olivier A. , de Leval Laurence , Gaulard Philippe
Published: July 2012

Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (TFH) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed TFH markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival.
Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS
Authors: Deeg H. Joachim , Scott Bart L. , Fang Min , Shulman Howard M. , Gyurkocza Boglarka , Myerson David , Pagel John M. , Platzbecker Uwe , Ramakrishnan Aravind , Radich Jerald P. , Sandmaier Brenda M. , Sorror Mohamed , Stirewalt Derek L. , Wilson Wendy A. , Storb Rainer , Appelbaum Frederick R. , Gooley Ted
Published: July 2012

Clonal cytogenetic abnormalities are a major risk factor for relapse after hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS). We determined the impact of the recently established 5-group cytogenetic classification of MDS on outcome after HCT. Results were compared with the impact of the International Prognostic Scoring System (IPSS) 3 cytogenetic risk groups, and the additional effect of a monosomal karyotype was assessed. The study included data on 1007 patients, 1-75 years old (median 45 years), transplanted from related (n = 547) or unrelated (n = 460) donors. Various conditioning regimens were used, and marrow, peripheral blood, or cord blood served as stem cell source. Both IPSS and 5-group cytogenetic risk classifications were significantly associated with post-HCT relapse and mortality, but the 5-group classification discriminated more clearly among the lowest- and highest-risk patients. A monosomal karyotype tended to further increase the rates of relapse and mortality, even after considering the IPSS or 5-group classifications. In addition, the pathologic disease category correlated with both relapse and mortality. Mortality was also impacted by patient age, donor type, conditioning regimen, platelet count, and etiology of MDS. Although mortality declined significantly in recent years, novel strategies are needed to overcome the barrier of high-risk cytogenetics.
Correlation between NIH composite skin score, patient-reported skin score, and outcome: results from the Chronic GVHD Consortium
Authors: Jacobsohn David A. , Kurland Brenda F. , Pidala Joseph , Inamoto Yoshihiro , Chai Xiaoyu , Palmer Jeanne M. , Arai Sally , Arora Mukta , Jagasia Madan , Cutler Corey , Weisdorf Daniel , Martin Paul J. , Pavletic Steven Z. , Vogelsang Georgia , Lee Stephanie J. , Flowers Mary E. D.
Published: July 2012

There are no validated criteria to measure skin response in chronic GVHD. In a prospectively assembled, multicenter cohort of patients with chronic GVHD (N = 458), we looked for correlation of change in several different scales recommended by the National Institutes of Health (NIH) Consensus with clinician and patient perception of change and overall survival. Of the clinician scales, the NIH composite 0-3 skin score was the only one that correlated with both clinician and patient perception of improvement or worsening. Of the patient-reported scales, the skin subscale of the Lee Symptom Scale was the only one that correlated with both clinician and patient perception of improvement or worsening. At study entry, NIH skin score 3 and Lee skin symptom score > 15 were both associated with worse overall survival. Worsening of NIH skin score at 6 months was associated with worse overall survival. Improvement in the Lee skin symptom score at 6 months was associated with improved overall survival. Our findings support the use of the NIH composite 0-3 skin score and the Lee skin symptom score as simple and sensitive measures to evaluate skin involvement in clinical trials as well as in the clinical monitoring of patients with cutaneous chronic GVHD.
The race for the prize: T-cell trafficking strategies for optimal surveillance
Authors: Lee Minyi , Mandl Judith N. , Germain Ronald N. , Yates Andrew J.
Published: July 2012

The initiation of T-cell responses requires rare precursors to locate a draining lymph node (dLN) and encounter dendritic cells (DCs) presenting peptide-major histocompatibility complexes (pMHCs). To locate this needle in the haystack rapidly, T cells face an optimization problem—what is the most efficient trafficking strategy for surveillance and recirculation through blood? Two extremes are scanning low numbers of DCs per node with frequent recirculation, or meticulous surveillance with infrequent recirculation. Naive T cells also require stimulation by self-pMHCs. To enable efficient location of both foreign and self, has evolution settled on an optimum time for T cells to spend surveying each lymph node? Using a data-driven mathematical model, we show the most efficient strategy for detecting antigen in a dLN depends on its abundance. Detection of low-density antigen is optimized with systemically slow transit. In contrast, at high densities or if dLN egress is restricted, rapid transit through other nodes is optimal. We argue that blood-lymph recirculation dynamics facilitate a trade-off, and are consistent with dominant roles for the very early detection of rare foreign antigens in a dLN, and the efficient accumulation of signals from systemically distributed self-antigens.
Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset
Authors: Harly Christelle , Guillaume Yves , Nedellec Steven , Peigné Cassie-Marie , Mönkkönen Hannu , Mönkkönen Jukka , Li Jianqiang , Kuball Jürgen , Adams Erin J. , Netzer Sonia , Déchanet-Merville Julie , Léger Alexandra , Herrmann Thomas , Breathnach Richard , Olive Daniel , Bonneville Marc , Scotet Emmanuel
Published: July 2012

Human peripheral Vγ9Vδ2 T cells are activated by phosphorylated metabolites (phosphoagonists [PAg]) of the mammalian mevalonate or the microbial desoxyxylulose-phosphate pathways accumulated by infected or metabolically distressed cells. The underlying mechanisms are unknown. We show that treatment of nonsusceptible target cells with antibody 20.1 against CD277, a member of the extended B7 superfamily related to butyrophilin, mimics PAg-induced Vγ9Vδ2 T-cell activation and that the Vγ9Vδ2 T-cell receptor is implicated in this effect. Vγ9Vδ2 T-cell activation can be abrogated by exposing susceptible cells (tumor and mycobacteria-infected cells, or aminobisphosphonate-treated cells with up-regulated PAg levels) to antibody 103.2 against CD277. CD277 knockdown and domain-shuffling approaches confirm the key implication of the CD277 isoform BTN3A1 in PAg sensing by Vγ9Vδ2 T cells. Fluorescence recovery after photobleaching (FRAP) experiments support a causal link between intracellular PAg accumulation, decreased BTN3A1 membrane mobility, and ensuing Vγ9Vδ2 T-cell activation. This study demonstrates a novel role played by B7-like molecules in human γδ T-cell antigenic activation and paves the way for new strategies to improve the efficiency of immunotherapies using Vγ9Vδ2 T cells.
Heparan Sulfate Proteoglycans Regulate Responses to Oocyte Paracrine Signals in Ovarian Follicle Morphogenesis
Authors: Watson Laura N. , Mottershead David G. , Dunning Kylie R. , Robker Rebecca L. , Gilchrist Robert B. , Russell Darryl L.
Published: July 2012

In the ovarian follicle, oocyte-secreted factors induce cumulus-specific genes and repress mural granulosa cell specific genes to establish these functionally distinct cell lineages. The mechanism establishing this precise morphogenic pattern of oocyte signaling within the follicle is unknown. The present study investigated a role for heparan sulphate proteoglycans (HSPG) as coreceptors mediating oocyte secreted factor signaling. In vitro maturation of cumulus oocyte complexes in the presence of exogenous heparin, which antagonizes HSPG signaling, prevented cumulus expansion and blocked the induction of cumulus-specific matrix genes, Has2 and Tnfaip6, whereas conversely, the mural granulosa-specific genes, Lhcgr and Cyp11a1, were strongly up-regulated. Heparin also blocked phosphorylation of SMAD2. Exogenous growth differentiation factor (GDF)-9 reversed these heparin effects; furthermore, GDF9 strongly bound to heparin sepharose. These observations indicate that heparin binds endogenous GDF9 and disrupts interaction with heparan sulphate proteoglycan coreceptor(s), important for GDF9 signaling. The expression of candidate HSPG coreceptors, Syndecan 1–4, Glypican 1–6, and Betaglycan, was examined. An ovulatory dose of human chorionic gonadotropin down-regulated Betaglycan in cumulus cells, and this regulation required GDF9 activity; conversely, Betaglycan was significantly increased in luteinizing mural granulosa cells. Human chorionic gonadotropin caused very strong induction of Syndecan 1 and Syndecan 4 in mural granulosa as well as cumulus cells. Glypican 1 was selectively induced in cumulus cells, and this expression appeared dependent on GDF9 action. These data suggest that HSPG play an essential role in GDF9 signaling and are involved in the patterning of oocyte signaling and cumulus cell function in the periovulatory follicle.
Estrogens Mediate Cardiac Hypertrophy in a Stimulus-Dependent Manner
Authors: Haines Christopher D. , Harvey Pamela A. , Leinwand Leslie A.
Published: July 2012

The incidence of cardiac hypertrophy, an established risk factor for heart failure, is generally lower in women compared with men, but this advantage is lost after menopause. Although it is widely believed that estrogens are cardioprotective, there are contradictory reports, including increased cardiac events in postmenopausal women receiving estrogens and enhanced cardiac protection from ischemic injury in female mice without estrogens. We exposed aromatase knockout (ArKO) mice, which produce no estrogens, to both pathologic and physiologic stimuli. This model allows an investigation into the effects of a complete, chronic lack of estrogens in male and female hearts. At baseline, female ArKO mice had normal-sized hearts but decreased cardiac function and paradoxically increased phosphorylation of many progrowth kinases. When challenged with the pathological stimulus, isoproterenol, ArKO females developed 2-fold more hypertrophy than wild-type females. In contrast, exercise-induced physiological hypertrophy was unaffected by the absence of estrogens in either sex, although running performance was blunted in ArKO females. Thus, loss of estrogen signaling in females, but not males, impairs cardiac function and sensitizes the heart to pathological insults through up-regulation of multiple hypertrophic pathways. These findings provide insight into the apparent loss of cardioprotection after menopause and suggest that caution is warranted in the long-term use of aromatase inhibitors in the setting of breast cancer prevention.
Direct Cooperation Between Androgen Receptor and E2F1 Reveals a Common Regulation Mechanism for Androgen-Responsive Genes in Prostate Cells
Authors: Altintas D. M. , Shukla M. S. , Goutte-Gattat D. , Angelov D. , Rouault J. P. , Dimitrov S. , Samarut Jacques
Published: July 2012

We have studied the regulation of ATAD2 gene expression by androgens in prostate cells. ATAD2 is a coactivator of the androgen receptor (AR) and the MYC protein. We showed that ATAD2 expression is directly regulated by AR via an AR binding sequence (ARBS) located in the distal enhancer of its regulatory region. The gene is also regulated by the E2F1 transcription factor. Using knockdown and chromatin immunoprecipitation technique approaches, we could demonstrate that AR and E2F1 functionally collaborate and physically interact between each other. From the analysis of chromatin conformation, we conclude that this cooperation results from a chromatin looping over the ATAD2 promoter region between the ARBS and E2F1 binding site in an androgen-dependent manner. Furthermore, we could show that several genes overexpressed in prostate cancer and potentially involved in several aspects of tumor development have an ARBS and an E2F1 binding site in their regulatory regions and exhibit the same mechanism of regulation by both transcription factors as ATAD2.
Association with Nitric Oxide Synthase on Insulin Secretory Granules Regulates Glucokinase Protein Levels
Authors: Markwardt Michele L. , Nkobena Andongfac , Ding Shi-Ying , Rizzo Mark A.
Published: July 2012

Glucokinase (GCK) association with insulin-secretory granules is controlled by interaction with nitric oxide synthase (NOS) and is reversed by GCK S-nitrosylation. Nonetheless, the function of GCK sequestration on secretory granules is unknown. Here we report that the S-nitrosylation blocking V367M mutation prevents GCK accumulation on secretory granules by inhibiting association with NOS. Expression of this mutant is reduced compared with a second S-nitrosylation blocking GCK mutant (C371S) that accumulates to secretory granules and is expressed at levels greater than wild type. Even so, the rate of degradation for wild type and mutant GCK proteins were not significantly different from one another, and neither mutation disrupted the ability of GCK to be ubiquitinated. Furthermore, gene silencing of NOS reduced endogenous GCK content but did not affect β-actin content. Treatment of GCK(C371S) expressing cells with short interfering RNA specific for NOS also blocked accumulation of this protein to secretory granules and reduced expression levels to that of GCK(V367M). Conversely, cotransfection of catalytically inactive NOS increased GCK-mCherry levels. Expression of GCK(C371S) in βTC3 cells enhanced glucose metabolism compared with untransfected cells and cells expressing wild type GCK, even though this mutant has slightly reduced enzymatic activity in vitro. Finally, molecular dynamics simulations revealed that V367M induces conformational changes in GCK that are similar to S-nitrosylated GCK, thereby suggesting a mechanism for V367M-inhibition of NOS association. Our findings suggest that sequestration of GCK on secretory granules regulates cellular GCK protein content, and thus cellular GCK activity, by acting as a storage pool for GCK proteins.
Aerobic scope and cardiovascular oxygen transport is not compromised at high temperatures in the toadRhinella marina
Authors: Overgaard Johannes , Andersen Jonas L , Findsen Anders , Pedersen Pil B. M. , Hansen Kasper , Ozolina Karlina , Wang Tobias
Published: July 2012

Numerous recent studies convincingly correlate the upper thermal tolerance limit of aquatic ectothermic animals to reduced aerobic scope, and ascribe the decline in aerobic scope to failure of the cardiovascular system at high temperatures. In the present study we investigate whether this "aerobic scope model" applies to an air-breathing and semi-terrestrial vertebrate Rhinella marina (formerly Bufo marinus). To quantify aerobic scope, we measured resting and maximal rate of oxygen consumption at temperatures ranging from 10 to 40°C. To include potential effects of acclimation, three groups of toads were acclimated chronically at 20, 25 and 30°C, respectively. The absolute difference between resting and maximal rate of oxygen consumption increased progressively with temperature and there was no significant decrease in aerobic scope, even at temperature immediately below the lethal limit (41-42°C). Hematological and cardio-respiratory variables were measured at rest and immediately after maximal activity at benign (30°C) and critically high (40°C) temperatures. Within this temperature interval, both resting and active heart rate increased, and there was no indication of respiratory failure, judged from high arterial oxygen saturation, PO2 and [HbO2]. With the exception of elevated resting metabolic rate for cold acclimated toads, we found few differences in the thermal responses between acclimation groups with regard to the cardio-metabolic parameters. In conclusion, we found no evidence for temperature induced cardio-respiratory failure in Rhinella marina indicating that maintenance of aerobic scope and oxygen transport is unrelated to the upper thermal limit of this air-breathing semi-terrestrial vertebrate.
Correlates of prolonged swimming performance in F2 hybrids of migratory and non-migratory threespine stickleback ecotypes
Authors: Dalziel Anne C. , Schulte Patricia M.
Published: July 2012

Determining which underlying traits contribute to differences in whole-animal performance can be difficult when many traits differ between individuals with high and low capacities. We have previously found that migratory (anadromous marine) and non-migratory (stream-resident) threespine stickleback (Gasterosteus aculeatus) populations have genetically based differences in prolonged swimming performance (Ucrit) that are associated with divergence of a number of candidate morphological and physiological traits (pectoral fin size and shape, body shape, pectoral muscle and heart size, and pectoral muscle metabolic enzyme activities). Here, we use F2 hybrid crosses to determine which traits are correlated with Ucrit when expressed in a largely randomized genetic background and a range of trait values for other divergent traits. We found that four of our 12 candidate traits were positively correlated with Ucrit in F2 hybrids and that the combined effects of ventricle mass, pectoral adductor mass, and adductor citrate synthase activity accounted for 17.9% of the variation in Ucrit. These data provide additional support for a causal role of muscle and heart size in mediating intra-specific differences in Ucrit, but indicate that many candidate morphological and biochemical traits do not have a strong effect on Ucrit when disassociated other divergent traits. However, the limited variation in Ucrit in our F2 hybrid families may have decreased our ability to detect correlations among these candidate traits and Ucrit. These data suggest that many traits, interactions among traits, and traits not measured in this study, affect prolonged swimming performance in threespine stickleback.
Functional morphology and bite performance of raptorial chelicerae of camel spiders (Solifugae)
Authors: van der Meijden Arie , Langer Franz , Boistel Renaud , Vagovic Patrik , Heethoff Michael
Published: July 2012

Solifugae are an understudied group of relatively large arachnids with well over 1.000 species distributed on almost all major continents. These highly active predators utilize their large chelicerae for feeding, defense, burrowing and mating. We investigated the differences in cheliceral morphology and performance of two ecologically divergent species from North-Africa; the cursorial Galeodes sp. and the burrowing Rhagodes melanus. Morphological data show differences in aspect ratio between the two species. Bite force measurements show Rhagodes (n=11) to be a much stronger biter than Galeodes (n=8), both in absolute maximum force (Rhagodes 5,63 N, Galeodes 2,12 N) and relative to cheliceral size. Synchrotron-μ-tomographies of one specimen for each species reveal large differences in physiological cross sectional area (PCSA) and estimated muscle stress, resulting in a much higher muscle stress in Rhagodes. The latter species also showed a longer muscle fiber length. Muscle volume and PCSA were found to differ between the two chelicerae in the two scanned specimens. Whereas Rhagodes reflects this morphological asymmetry in having a higher bite force in the right chelicera, Galeodes shows no such bias.
Induced synthesis of P450 Aromatase and 17β-estradiol by D-aspartate in frog brain
Authors: Burrone Lavina , Santillo Alessandra , Pinelli Claudia , Chieffi Baccari Gabriella , Di Fiore Maria Maddalena
Published: July 2012

D-aspartic acid is an endogenous amino acid occurring in endocrine glands as well as in nervous system of various animal phyla. Our previous studies have provided evidence that D-Aspartate plays a role in induction of estradiol synthesis in gonads. Recently, we have also demonstrated that D-aspartic acid induces P450 aromatase mRNA expression in the frog (Pelophylax esculentus) testis. P450 aromatase is the key enzyme in the estrogen synthetic pathway, which irreversibly converts testosterone into 17β-estradiol. In this study, we firstly investigated the immunolocalisation of P450 aromatase in the frog brain P. esculentus, never described in amphibians. Therefore, to test the hypothesis that D-Aspartate mediates a local synthesis of P450 aromatase in the frog brain, we administered in vivo D-Aspartate to frog male and then assessed the brain aromatase expression, sex hormone levels as well as their receptor expressions. We found that D-Aspartate enhances brain aromatase expression (mRNA and protein) through CREB pathway. Then, P450 aromatase enzyme induces 17β-estradiol production from testosterone, with consequent increase of its receptor. Therefore, the regulation of D-Aspartate-mediated P450 aromatase expression could be an important step in the control of neuroendocrine regulations of the reproductive axis. On the other hand, we found that the sites of P450 aromatase immunoreactivity in the frog brain correspond to the areas known to be involved in neurosteroid synthesis.
Annual cycles of metabolic rate are genetically determined but can be shifted by phenotypic flexibility
Authors: Versteegh Maaike A. , Helm Barbara , Gwinner Eberhard , Tieleman B. Irene
Published: July 2012

Birds have adjusted their life-history and physiological traits to the characteristics of the seasonally changing environments they inhabit. Annual cycles in physiology can result from phenotypic flexibility or from variation in its genetic basis. A key physiological trait that shows seasonal variation is basal metabolic rate (BMR). We studied genetic and phenotypic variation in the annual cycles of body mass, BMR and mass-specific BMR in three stonechat subspecies (Saxicola torquata) originating from environments that differ in seasonality, and in two hybrid lines. Birds were kept in a common garden set-up, under annually variable day length and at constant temperature. We also studied whether stonechats use the proximate environmental factor temperature as a cue for changes in metabolic rate, by keeping birds at two different temperature regimes. We found that the different subspecies kept in a common environment had different annual cycles of body mass, BMR (variance: Kazakh 4.12, European 1.31, Kenyans 1.25) and mass-specific BMR (variance: Kazakh 0.042, European 0.003, Kenyans 0.013). Annual variation in metabolic measures of hybrids was intermediate or similar to parental species. Temperature treatment did not affect the shape of the annual cycles of metabolic rate, but metabolic rate was higher in birds kept under the variable temperature regime. The distinct annual cycles in body mass and metabolic rate in stonechats subspecies kept in a common environment indicate different genetic backgrounds rather than merely a phenotypically flexible response to proximate environmental cues. Phenotypic effects of temperature are superimposed on this genetically orchestrated annual cycle.
Neuromuscular and biomechanical compensation for wing asymmetry in insect hovering flight
Authors: Fernández María José , Springthorpe Dwight , Hedrick Tyson L.
Published: July 2012

Wing damage is common in flying insects and has been studied using a variety of approaches to assess its biomechanical and fitness consequences. Results of these studies range from strong to nil effect among the variety of species, fitness measurements and damage modes studied, suggesting that not all damage modes are equal and that insects may be well adapted to compensate for some types of damage. Here, we examine the biomechanical and neuromuscular means by which flying insects compensate for asymmetric wing damage, which is expected to produce asymmetric flight forces and torques and thus destabilize the animal in addition to reducing its total wing size. We measured the kinematic and neuromuscular responses of hawkmoths (Manduca sexta) hovering in free flight with asymmetrically damaged wings via high-speed videography and extracellular neuromuscular activity recordings. The animals responded to asymmetric wing damage with asymmetric changes to wing stroke amplitude sufficient to restore symmetry in lift production. These asymmetries in stroke amplitude were significantly correlated with bilateral asymmetries in the timing of activation of the dorsal ventral muscle among and within trials. Correspondingly, the magnitude of wing asymmetry was significantly although non-linearly correlated with the magnitude of the neuromuscular response among individuals. The strongly non-linear nature of the relationship suggests that active neural compensation for asymmetric wing damage may only be necessary above a threshold, >12% asymmetry in wing second moment of area in this case, below which passive mechanisms may be adequate to maintain flight stability.
Dimiconin, a novel coagulation inhibitor from the kissing bug, Triatoma dimidiata, a vector of Chagas disease
Authors: Ishimaru Yuka , Gomez Eduardo A. , Zhang Feifei , Martini-Robles Luiggi , Iwata Hiroyuki , Sakurai Tatsuya , Katakura Ken , Hashiguchi Yoshihisa , Kato Hirotomo
Published: July 2012

Sequence analysis of Triatoma (T.) dimidiata salivary gland cDNA library resulted in the identification of two transcripts (Td60 and Td101) homologous to triabin, an inhibitor of thrombin in T. pallidipennis saliva. In the present study, a recombinant protein of Td60, designated dimiconin, was expressed in Escherichia coli and its activity was characterized. The resulting protein inhibited the intrinsic but not extrinsic blood coagulation pathway, suggesting that dimiconin is not a thrombin inhibitor. Measuring the enzymatic activity of coagulation factors using chromogenic substrates revealed that dimiconin efficiently inhibited factor XIIa (FXIIa) activity in a dose-dependent manner. In addition, pre-incubation of dimiconin with FXII effectively inhibited FXIIa activity whereas dimiconin did not affect already activated FXIIa, indicating that dimiconin inhibits the activation of FXII but not enzymatic activity of FXIIa. These results showed that dimiconin is an inhibitor of the contact phase initiated by FXII activation in the blood coagulation cascade, which differs from the bioactivity of triabin.
Electrophysiological evidence for polarization sensitivity in the camera-type eyes of the aquatic predacious insect larva,Thermonectus marmoratus(Coleoptera: Dytiscidae)
Authors: Stowasser Annette , Buschbeck Elke K.
Published: July 2012

Polarization sensitivity has most often been studied in mature insects, yet it is likely that larvae also make use of this visual modality. The aquatic larvae of the predacious diving beetle Thermonectus marmoratus are highly successful visually guided predators, with a UV-sensitive proximal retina that, according to its ultrastructure, has three distinct cell types with anatomical attributes that are consistent with polarization sensitivity. In the present study we used electrophysiological methods and single-cell staining to confirm polarization sensitivity in the proximal retinas of both principal eyes of these larvae. As expected from their microvillar orientation, cells of type T1 are most sensitive to vertically polarized light, while cells of type T2 are most sensitive to horizontally polarized light. In addition, T3 cells likely constitute a second population of cells that are most sensitive to light with vertical e-vector orientation, characterized by shallower polarization modulations, and smaller polarization sensitivity (PS) values than are typical for T1 cells. The level of PS values found in this study suggests that polarization sensitivity likely plays an important role in the visual system of these larvae. Based on their natural history and behavior, possible functions are: (1) finding water after hatching, (2) finding the shore before pupation, and (3) making prey more visible, by filtering out horizontally polarized haze, and/or using polarization features for prey detection.
Comparative utility of MRI perfusion with MSIDR and DWIBS for the characterization of breast tumors
Authors: Zhang Bing , Zhu Bin , Li Ming , Yuan Lei , Yuan Lihua , Zhang Xin , Yu Haiping , Li Chen , Lu Fangfei , Zhou Zhengyang , Zhuang Xiaoming
Published: July 2012

Background

In recent years, breast magnetic resonance imaging (MRI) has been used to evaluate the morphology and functional markers of breast lesions, which might influence local staging and surgical planning.

Purpose

To evaluate the feasibility of a one stop MRI protocol combined with diffusion-weighted imaging with background body signal suppression (DWIBS), T2*-weighted perfusion imaging (T2*-PWI) and delayed contrast-enhanced T1-weighted MRI (T1W-C+).

Material and Methods

All experiments were conducted with a 3-T clinical MRI scanner. The apparent diffusion coefficient (ADC) and detectability of lesions in DWIBS, the maximal signal intensity drop rate (MSIDR) in T2*-PWI and the intensity increasing rate (IIR) on T1W-C+ were compared between breast malignancies ( n = 29) and benign lesions ( n = 31). The time–signal curves in the T2*-PWI sequences were classified into two subtypes (a and b) according to the end of the curve. The ADC, MSIDR, the first maximal signal intensity decrease time (MSIDT), and IIR between the malignant and benign lesions were statistically analyzed by unpaired t-tests.

Results

Overall, 90% of the lesions were detected by DWIBS. There were significant differences in ADC, MSIDR, and IIR between the carcinomas and benign lesions. The Ib subtype in T2*-PWI demonstrated a specificity of 66.7% in differentiating between carcinomas and benign lesions. At a fixed specificity of 93.5%, the MSIDR, IIR, and ADC differentiated breast carcinomas from benign lesions with sensitivities of 82.8%, 44.8%, and 86.2%, respectively.

Conclusion

DWIBS might be a compensation sequence for detecting breast lesions in pre-contrast sequences. MSIDR from T2*-PWI had the best specificity index, and the two subtypes in the T2*-PWI curve were helpful in the differential diagnosis of carcinomas from benign lesions.
Clinical usefulness of adjusted D-dimer cut-off values to exclude pulmonary embolism in a community hospital emergency department patient population
Authors: Vossen Josephina A , Albrektson Joshua , Sensarma Anirban , Williams Scott C
Published: July 2012

Background

Plasma D-dimer measurement is used in the assessment of the clinical probability of pulmonary embolism (PE), in order to minimize the requirement for pulmonary computed tomography angiography (CTA).

Purpose

To evaluate whether doubling the threshold value of serum D-dimer from 500 μg/L to 1000 μg/L could safely reduce utilization of pulmonary CTA to exclude PE in our emergency department patient population.

Material and Methods

Emergency department patients evaluated for PE with a quantitative D-dimer assay and pulmonary CTA were eligible for inclusion. D-dimer values were retrospectively collected in all included patients. Pulmonary CT angiograms were reviewed and scored as positive or negative for PE. Receiver-operating characteristic (ROC) analysis was used to determine the accuracy of quantitative D-dimer measurements in differentiating between positive and negative PE patients as per CTA.

Results

A total of 237 consecutive patients underwent pulmonary CTA and had a D-dimer measurement performed. Median D-dimer level was 1007 μg/L and in 11 (5%) patients the pulmonary CT CTA was positive for PE. The ROC curve showed an area under the curve (AUC) of 0.91 ( P < 0.0001). Increasing the D-dimer threshold value of 500 μg/L to 1000 μg/L increased the specificity from 8% to 52% without changing the sensitivity.

Conclusion

Adjusting the D-dimer cut-off value for the emergency department community population and patient age increases the yield and specificity of the ELISA D-dimer assay for the exclusion of PE without reducing sensitivity.
Visually scored calcifications in thoracic arteries predict death: follow-up study after lung cancer CT screening
Authors: Vehmas Tapio
Published: July 2012

Background

Coronary arterial calcification scoring with special cardiac algorithms predicts death. However, a large number of patients undergo a non-cardiac chest CT for other reasons and the information on such arterial calcifications has so far received little attention.

Purpose

To explore whether visually detected chest atherosclerotic calcifications, which are unrelated to the indication of chest CT, predict mortality.

Material and Methods

A total of 504 men (aged 39–81 years, mean 63 years) were previously screened for lung cancer with spiral CT and later visually scored for atherosclerotic calcifications in the aorta and the origin of its great branches, and in coronary arteries. Their mortality was later checked in the national register, at a mean follow-up time of 10.4 years. Cox regression was used, adjusted for age, BMI, smoked pack-years, and asbestos exposure.

Results

One hundred and sixty deaths occurred during the follow-up, of which 57 were from cardiovascular disease. Calcifications at several sites significantly predicted all-cause and cardiovascular deaths in the enter models. In the backward model, calcifications in the aortic arch (hazard ratio HR = 1.35, 95% confidence interval 1.08–1.69, P = 0.009) and in the brachiocephalic origin (HR = 1.45, 1.15–1.82, P = 0.002) remained independent predictors of all-cause deaths. As regards cardiovascular deaths, calcifications in the left anterior descending artery (HR = 1.86, 1.29–2.67, P = 0.001) and brachiocephalic calcifications (HR = 1.65, 1.09–2.49, P = 0.018) remained independent predictors in the backward models.

Conclusion

Incidental arterial calcifications in routine chest CT should be actively reported to aid the recognition, preventive measures and medication of early atherosclerosis. The value of interventions after finding such calcifications should be further studied.
The health care experiences of Travellers compared to the general population: The All-Ireland Traveller Health Study
Authors:   for the All-Ireland Traveller Health Study Research Team, McGorrian Catherine , Frazer Kate , Daly Leslie , Moore Ronnie G , Turner Jill , Sweeney Mary Rose , Staines Anthony , Fitzpatrick Patricia , Kelleher Cecily C
Published: July 2012

Objectives:

Travellers are a minority population in Ireland and Great Britain, who have poorer health status than the general population. This study aims to investigate Traveller health service utilization and experiences of health service quality.

Methods:

Community-based census survey of all Traveller households on the island of Ireland in 2008 and 2009. Comparisons were made with survey data from a nationally representative sample of the Irish general public entitled to means-tested general medical services from the INSIGHT ′07 survey.

Results:

Valid responses were provided by 1,947 Traveller respondents (32.5% males). Travellers reported significantly higher use of hospital services including Emergency Room services (sex- and age-adjusted relative risk (RR) 2.37, 95% CI 1.99-2.82) and mental health services (adjusted RR 2.89, 95% CI 2.02-4.14). They described significantly poorer quality health care experiences than did the comparator population, with fewer Travellers expressing trust in caregivers (adjusted RR 0.51, 95% CI 0.47-0.55) and rating the quality of health service they received as being very good or excellent (adjusted RR 0.59, 95% CI 0.55-0.64). After multivariable adjustment for the dimensions of service quality, population (Traveller or INSIGHT ′07) was not associated with an overall rating of health service quality.

Conclusions:

Travellers report greater use of and adequate access to health services, but describe a consistently poorer quality health care experience. This quality gap has implications for Traveller engagement with health care professionals.
OR Forum—Intelligence Operations Research: The 2010 Philip McCord Morse Lecture
Authors: Kaplan Edward H.
Published: July 2012

This paper is the archival record of the INFORMS Philip McCord Morse Lecture delivered in 2010. It considers applications of operations research to intelligence problems in national security and counterterrorism. The phrase “intelligence operations research” can be interpreted in two different ways: as intelligence operations} research, meaning studies to characterize and improve the operations of intelligence agencies themselves, and as intelligence operations research, meaning the application of operations research methods to specific substantive intelligence problems. After defining intelligence, I review the intelligence production process (or the intelligence cycle) with reference to the intelligence community of the United States. I then consider the extent to which operations research has been deployed inside this intelligence community and summarize previous attempts to apply operations research methods to intelligence problems. I close with some suggestions for future intelligence operations research studies.
Inhaled Aztreonam Lysine for Cystic Fibrosis Pulmonary Disease–Related Outcomes
Authors: Pesaturo Kimberly A , Horton Evan R , Belliveau Paul
Published: July 2012

OBJECTIVE:

To evaluate the pharmacology, clinical efficacy, and safety of aztreonam lysine for inhalation (AZLI) for cystic fibrosis (CF)–related signs and symptoms of pulmonary disease.

DATA SOURCES:

Literature was searched in MEDLINE through PubMed and cross-referenced with EMBASE (1980-June 2012). The key search terms used were aztreonam lysine, nebulized, inhaled, and cystic fibrosis. Bibliographies of selected articles were used to identify additional references. Ongoing trials were identified through a review of Web site trial registries.

STUDY SELECTION AND DATA EXTRACTION:

Articles were limited to those written in English about studies conducted in humans. Studies included in this review examined both adult and pediatric patients with CF.

DATA SYNTHESIS:

Aztreonam lysine is an inhaled monocyclic β-lactam antibiotic approved for use in the CF population. Four completed clinical trials with peer-reviewed published data were reviewed to assess the efficacy and safety of single-course AZLI; a fifth trial assessed the safety and efficacy of repeat courses of AZLI. None of these trials compared AZLI in a head-to-head manner with tobramycin for inhalation. In patients with moderate to severe pulmonary disease, AZLI administration improved forced expiratory volume in 1 second measurements, decreased sputum bacterial Pseudomonas aeruginosa density, and improved symptoms. Adverse effects in clinical trials were generally mild and similar to those with placebo.

CONCLUSIONS:

AZLI is safe and effective for management of pulmonary-related symptoms in patients with CF who are colonized with P. aeruginosa and have moderate to severe pulmonary disease. Additional trial data comparing AZLI with tobramycin are warranted to further establish the place of AZLI in therapy.
Hemarthrosis in a Patient on Warfarin Receiving Ceftaroline: A Case Report and Brief Review of Cephalosporin Interactions with Warfarin
Authors: Bohm Nicole M , Crosby Brittany
Published: July 2012

OBJECTIVE:

To report a possible interaction between warfarin and ceftaroline, resulting in hemarthrosis, and provide readers with an understanding of mechanisms of interaction between cephalosporins and warfarin.

CASE SUMMARY:

Ceftaroline was prescribed for an 85-year-old female with a therapeutic international normalized ratio (INR) hospitalized for the treatment of cellulitis. She was subsequently readmitted with shoulder pain and a supratherapeutic INR. The patient was diagnosed with hemarthrosis, presumably related to elevated INR. Evaluation using the drug interaction probability scale for warfarin and ceftaroline yielded a score consistent with a possible or probable interaction.

DISCUSSION:

Cephalosporins may interact with warfarin through a variety of mechanisms, including potentiation of hypoprothrombinemia related to certain side chain groups, inhibition of P-glycoprotein, or alteration of gastrointestinal flora. All mechanisms reported in the medical literature as of April 2012 are briefly examined, but the latter is the most reasonable mechanism for a ceftaroline interaction with warfarin.

CONCLUSIONS:

Health care providers should consider closely monitoring patients receiving antibiotics with activity against Enterobacteriaceae and warfarin, even if no direct mechanism of interaction has been reported. Further research regarding a ceftaroline-warfarin interaction is warranted.