bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll‐interacting protein contributes to mortality following myocardial infarction through promoting inflammation and apoptosis
Authors: Wan Nian , Liu Xiaoxiong , Zhang Xiao‐Jing , Zhao Yichao , Hu Gangying , Wan Fengwei , Zhang Rui , Zhu Xueyong , Xia Hao , Li Hongliang 
Published: March 2015

Background and PurposeToll‐interacting protein (Tollip) is an endogenous inhibitor of toll‐like receptors, a superfamily that plays a pivotal role in various pathological conditions, including myocardial infarction (MI). However, the exact role of Tollip in MI remains unknown.Experimental ApproachMI models were established in Tollip knockout (KO) mice, mice with cardiac‐specific overexpression of human Tollip gene and in their Tollip+/+ and non‐transgenic controls respectively. The effects of Tollip on MI were evaluated by mortality, infarct size and cardiac function. Hypoxia‐induced cardiomyocyte damage was investigated in vitro to confirm the role of Tollip in heart damage.Key ResultsTollip expression was dramatically up‐regulated in human ischaemic hearts and infarcted mice hearts. MI‐induced mortality, infarct size and cardiac dysfunction were decreased in Tollip‐KO mice compared with Tollip+/+ controls. Ischaemic hearts from Tollip‐KO mice exhibited decreased inflammatory cell infiltration and reduced NF‐κB activation. Tollip depletion also alleviated myocardial apoptosis by down‐regulating pro‐apoptotic protein levels and up‐regulating anti‐apoptotic protein expressions in infarct border zone. Conversely, MI effects were exacerbated in mice with cardiac‐specific Tollip overexpression. This aggravated MI injury by Tollip in vivo was confirmed with in vitro assays. Inhibition of Akt signalling was associated with the detrimental effects of Tollip on MI injury; activation of Akt largely reversed the deleterious effects of Tollip on MI‐induced cardiomyocyte death.Conclusions and ImplicationsTollip promotes inflammatory and apoptotic responses after MI, leading to increased mortality and aggravated cardiac dysfunction. These findings suggest that Tollip may serve as a novel therapeutic target for the treatment of MI.
3‐Iodothyroacetic acid lacks thermoregulatory and cardiovascular effects in vivo
Authors: Hoefig Carolin S , Jacobi Simon F , Warner Amy , Harder Lisbeth , Schanze Nancy , Vennström Björn , Mittag Jens 
Published: March 2015

Background and Purpose3‐Iodothyronamine (3‐T1AM) is an endogenous thyroid hormone derivative reported to induce strong hypothermia and bradycardia within minutes upon injection in rodents. Although 3‐T1AM is rapidly converted to several other metabolites in vivo, these strong pharmacological responses were solely attributed to 3‐T1AM, leaving potential contributions of downstream products untested. We therefore examined the cardiometabolic effects of 3‐iodothyroacetic acid (TA1), the main degradation product of 3‐T1AM.Experimental ApproachWe used a sensitive implantable radiotelemetry system in C57/Bl6J mice to study the effects of TA1 on body temperature and heart rate, as well as other metabolic parameters.Key ResultsInterestingly, despite using pharmacological TA1 doses, we observed no effects on heart rate or body temperature after a single TA1 injection (50 mg·kg−1, i.p.) compared to sham‐injected controls. Repeated administration of TA1 (5 mg·kg−1, i.p. for 7 days) likewise did not alter body weight, food and water intake, heart rate, blood pressure, brown adipose tissue (BAT) thermogenesis or body temperature. Moreover, mRNA expression of tissue specific genes in heart, kidney, liver, BAT and lung was also not altered by TA1 compared to sham‐injected controls.Conclusions and ImplicationsOur data therefore conclusively demonstrate that TA1 does not contribute to the cardiovascular or thermoregulatory effects observed after 3‐T1AM administration in mice, suggesting that the oxidative deamination constitutes an important deactivation mechanism for 3‐T1AM with possible implications for cardiovascular and thermoregulatory functions.
Mechanisms of allergic disease – environmental and genetic determinants for the development of allergy
Authors: Campbell D. E. , Boyle R. J. , Thornton C. A. , Prescott S. L. 
Published: March 2015

SummaryAllergic disease can be viewed as an early manifestation of immune dysregulation. Environmental exposures including maternal inflammation, diet, nutrient balance, microbial colonization and toxin exposures can directly and indirectly influence immune programming in both pregnancy and the postnatal period. The intrauterine microclimate is critical for maternal and fetal immunological tolerance to sustain viable pregnancy, but appears susceptible to environmental conditions. Targeting aspects of the modern environment that promote aberrant patterns of immune response is logical for interventions aimed at primary prevention of allergic disease. Defining the mechanisms that underpin both natural and therapeutic acquisition of immunological tolerance in childhood will provide insights into the drivers of persistent immune dysregulation. In this review, we summarize evidence that allergy is a consequence of intrauterine and early life immune dysregulation, with specific focus on contributing environmental risk factors occurring preconception, in utero and in the early postnatal period. We explore the immunological mechanisms which underpin tolerance and persistence of allergic disease during childhood. It is likely that future investigations within these two domains will ultimately provide a road map for the primary prevention of allergic disease.
The mitogen‐activated protein kinase CgHog1 is required for iron homeostasis, adherence and virulence in Candida glabrata
Authors: Srivastava Vivek K. , Suneetha Korivi J. , Kaur Rupinder 
Published: March 2015

Candida glabrata has emerged as a major fungal pathogen over the last two decades, although our understanding of its survival strategies inside the mammalian host remains rudimentary. An important requirement for survival in vivo is the ability to acquire critical nutrients such as iron from host niches of varied iron content. In the present study, we demonstrate for the first time that C. glabrata cells respond to high external iron levels via activation of two stress‐responsive mitogen‐activated protein kinases, CgHog1 and CgSlt2, and lack of either kinase results in sensitivity to the high‐iron medium. Furthermore, we show that CgHOG1 deletion led to perturbed iron homeostasis (elevated intracellular iron content and high mitochondrial aconitase activity), reduced survival in macrophages and attenuated virulence in the murine model of disseminated candidiasis. Consistently, several genes implicated in iron acquisition and storage displayed deregulated expression in the Cghog1∆ mutant. Genome‐wide transcriptional profiling analysis revealed upregulation of genes implicated in DNA repair, RNA processing and autophagy, and downregulation of genes related to cellular respiration and organonitrogen compound metabolism under iron‐limiting conditions. In contrast, genes involved in the respiratory electron transport chain were induced under iron‐replete conditions. Gene expression microarrays also identified a set of iron‐responsive regulon in C. glabrata. Lastly, we present evidence for the iron‐regulated expression of the major adhesin‐encoding EPA1 gene, decreased histone deacetylase activity in a high‐iron environment and increased adherence of iron‐surplus‐medium‐grown C. glabrata cells to epithelial cells. Together, our findings yield novel insights into iron abundance‐based regulation of transcriptional and mitogen‐activated protein kinase signaling pathways in C. glabrata.
Methanogenesis produces strong 13C enrichment in stromatolites of Lagoa Salgada, Brazil: a modern analogue for Palaeo‐/Neoproterozoic stromatolites?
Authors: Birgel D. , Meister P. , Lundberg R. , Horath T. D. , Bontognali T. R. R. , Bahniuk A. M. , de Rezende C. E. , Vasconcelos C. , McKenzie J. A. 
Published: March 2015

AbstractHolocene stromatolites characterized by unusually positive inorganic δ13CPDB values (i.e. up to +16‰) are present in Lagoa Salgada, a seasonally brackish to hypersaline lagoon near Rio de Janeiro (Brazil). Such positive values cannot be explained by phototrophic fixation of CO2 alone, and they suggest that methanogenesis was a dominating process during the growth of the stromatolites. Indeed, up to 5 mm methane was measured in the porewater. The archaeal membrane lipid archaeol showing δ13C values between −15 and 0‰ suggests that archaea are present and producing methane in the modern lagoon sediment. Moreover, 13C‐depleted hopanoids diplopterol and 3β‐methylated C32 17β(H),21β(H)‐hopanoic acid (both −40‰) are preserved in lagoon sediments and are most likely derived from aerobic methanotrophic bacteria thriving in the methane‐enriched water column. Loss of isotopically light methane through the water column would explain the residual 13C‐enriched pool of dissolved inorganic carbon from where the carbonate constituting the stromatolites precipitated. The predominance of methanogenic archaea in the lagoon is most likely a result of sulphate limitation, suppressing the activity of sulphate‐reducing bacteria under brackish conditions in a seasonally humid tropical environment. Indeed, sulphate‐reduction activity is very low in the modern sediments. In absence of an efficient carbonate‐inducing metabolic process, we propose that stromatolite formation in Lagoa Salgada was abiotically induced, while the 13C‐enriched organic and inorganic carbon pools are due to methanogenesis. Unusually, 13C‐enriched stromatolitic deposits also appear in the geological record of prolonged periods in the Palaeo‐ and Neoproterozoic. Lagoa Salgada represents a possible modern analogue to conditions that may have been widespread in the Proterozoic, at times when low sulphate concentrations in sea water allowed methanogens to prevail over sulphate‐reducing bacteria.
Advances in non‐invasive techniques as aids to the diagnosis and monitoring of therapeutic response in plaque psoriasis: a review
Authors: Lacarrubba Francesco , Pellacani Giovanni , Gurgone Silvia , Verzì Anna Elisa , Micali Giuseppe 
Published: March 2015

AbstractPlaque psoriasis is a common, chronic, inflammatory disease with a multifactorial etiopathogenesis. Although its diagnosis is often based on clinical features, in ambiguous cases a biopsy with histopathologic confirmation may be necessary. Advanced high‐definition imaging techniques may be useful in the study of skin properties in vivo and may facilitate therapeutic monitoring. Available imaging tools vary in their resolution, depth of penetration and visual representation (horizontal, vertical, three‐dimensional), and in the type of skin structures visualized. The purpose of this review is to analyze a variety of non‐invasive techniques that may assist in establishing definitive diagnoses, as well as in the therapeutic monitoring of psoriasis. These include dermoscopy, videocapillaroscopy (VC), high‐frequency ultrasound (HFUS), reflectance confocal microscopy (RCM), laser Doppler imaging (LDI), optical coherence tomography (OCT), optical microangiography (OMAG) and multiphoton tomography (MPT). Their characteristics, indications, advantages, and limits are reviewed and discussed. Dermoscopy may be useful for a first, rapid outpatient evaluation. Videocapillaroscopy and HFUS represent the imaging techniques with the longest history of use in psoriasis. However, whereas VC is useful in both diagnosis and therapeutic monitoring, the utility of HFUS appears to be limited to the monitoring of response to therapy only. Both devices are cost‐effective and easy to use in the office setting. Both RCM and OCT allow high‐resolution microscopic imaging of psoriatic plaque in a manner comparable with that of virtual histopathology and represent more promising techniques. The utility of LDI, OMAG, and MPT in psoriasis skin imaging requires further study and validation.
Heterogeneous tumor stromal microenvironments of oral squamous cell carcinoma cells in tongue and nodal metastatic lesions in a xenograft mouse model
Authors: Shirako Youichi , Taya Yuji , Sato Kaori , Chiba Tadashige , Imai Kazushi , Shimazu Yoshihito , Aoba Takaaki , Soeno Yuuichi 
Published: March 2015

BackgroundOral squamous cell carcinoma exhibits a poor prognosis, caused by aggressive progression and early‐stage metastasis to cervical lymph nodes. Here, we developed a xenograft mouse model to explore the heterogeneity of the tumor microenvironment that may govern local invasion and nodal metastasis of tumor cells.MethodsWe transplanted five oral carcinoma cell lines into the tongues of nude mice and determined tongue tumor growth and micrometastatic dissemination by serially sectioning the tongue and lymph node lesions in combination with immunohistochemistry and computer‐assisted image analysis. Our morphometric analysis enabled a quantitative assessment of blood and lymphatic endothelial densities in the intratumoral and host stromal regions.ResultsAll cell lines tested were tumorigenic in mouse tongue. The metastatic lesion‐derived carcinoma cell lines (OSC19, OSC20, and HSC2) yielded a 100% nodal metastasis rate, whereas the primary tumor‐derived cell lines (KOSC2 and HO‐1‐u‐1) showed <40% metastatic potential. Immunohistochemistry showed that the individual cell lines gave rise to heterogeneous tumor architecture and phenotypes and that their micrometastatic lesions assimilated the immunophenotypic properties of the corresponding tongue tumors. Notably, OSC19 and OSC20 cells shared similar aggressive tumorigenicity in both the tongue and lymph node environments but displayed markedly diverse immunophenotypes and gene expression profiles.ConclusionsOur model facilitated comparing the tumor microenvironments in tongue and lymph node lesions. The results support that tumorigenicity and tumor architecture in the host tongue environment depend on the origin and properties of the carcinoma cell lines and that metastatic progression may take place through heterogeneous tumor–host interactions.
Dissociating Indifferent, Directional, and Extreme Responding in Personality Data: Applying the Three‐Process Model to Self‐ and Observer Reports
Authors: Zettler Ingo , Lang Jonas W. B. , Hülsheger Ute R. , Hilbig Benjamin E. 
Published: March 2015

AbstractResearch suggests that respondents vary in their tendency to use the response scale of typical (Likert‐style) questionnaires. We study the nature of the response process by applying a recently introduced item response theory modeling procedure, the three‐process model, to data of self‐ and observer reports of personality traits. The three‐process model captures indifferent, directional, and extreme responding. Substantively, we hypothesize that, and test whether, trait Honesty‐Humility is negatively linked to extreme responding. We applied the three‐process model to personality data of 577 dyads (self‐ and observer reports of the HEXACO Personality Inventory‐Revised; Lee & Ashton, ) of Dutch and German undergraduate respondents. First, we provide evidence that indifferent, directional, and extreme responding can be separated from each other in personality data through the use of the three‐process model. Second, we show that the various response processes show a pattern of correlations across traits and rating sources which is in line with the idea that indifferent and extreme responding are person‐specific tendencies, whereas directional responding is content‐specific. Third, we report findings supporting the hypothesis that Honesty‐Humility is negatively linked to extreme responding. In Likert‐based personality data, applying the three‐process model can unveil individual differences in the response process.
Practitioner Explanations for the Increasing Use of Restraint Measures in the Care of People With Intellectual Disabilities in Norway 2000–11
Authors: Søndenaa Erik , Dragsten Frode , Whittington Richard 
Published: March 2015

AbstractThe use of restraint measures in the care of people with an intellectual disability (ID) and challenging behavior (CB) is recognized as problematic around the world and attempts have been made to reduce reliance upon this coercive approach. In Norway, legislation was enacted to restrict the use of restraint but paradoxically since it was implemented in 1999 there has been a very large increase in the use of one form of restraint: statutory or planned interventions. This study examined professionals' explanations for this unexpected increase. ID care staff (n = 178) and local government supervisors (n = 17) completed a semi‐structured questionnaire (total n = 195). All participants were involved directly or indirectly in implementing restraint. Comparisons were made between the different levels of care staff and the supervisors. The care staff interpreted the increase as due to greater awareness of the regulations and restraint interventions. Supervisors had low expectations of a decrease in restraint rates in the future. It was felt that the new regulations on the use of restraints in the care of people with ID and CB had raised awareness of ethical issues and improved education on this topic. Future research should address possible strategies for sustaining these improvements and at the same time stabilizing or reducing the number of people receiving restrictive care.
The effect of extracorporeal photopheresis alone or in combination therapy on circulatingCD4+Foxp3+CD25−T cells in patients with leukemic cutaneous T‐cell lymphoma
Authors: Shiue Lisa H. , Couturier Jacob , Lewis Dorothy E. , Wei Caimiao , Ni Xiao , Duvic Madeleine 
Published: March 2015

AbstractPurposeExtracorporeal photopheresis (ECP) alone or in combination therapy is effective for treatment of leukemic cutaneous T‐cell lymphoma (L‐CTCL), but its mechanism(s) of action remain unclear. This study was designed to investigate the effect ofECPon regulatory T cells and CD8+T cells inL‐CTCLpatients.Experimental DesignPeripheral blood from 18 L‐CTCL patients at baseline, Day 2, 1 month, 3 month, and 6 month post‐ECP therapy was analyzed by flow cytometry for CD4+CD25+/high, CD4+Foxp3+CD25+/−, CD3+CD8+, CD3+CD8+CD69+, and CD3+CD8+IFN‐γ+T cells. Clinical responses were assessed and correlated with changes in these T‐cell subsets.ResultsTwelve of 18 patients achieved clinical responses. The average baseline number of CD4+CD25+/highT cells of PBMCs in L‐CTCL patients was normal (2.2%), but increased at 6‐month post‐therapy (4.3%,P < 0.01). The average baseline number of CD4+Foxp3+T cells out of CD4+T cells in nine evaluable patients was high (66.8 ± 13.7%), mostly CD25 negative. The levels of CD4+Foxp3+T cells in responders were higher (n = 6, 93.1 ± 5.7%) than nonresponders (n = 3, 14.2 ± 16.0%,P < 0.01), and they declined in parallel with malignant T cells. The numbers of CD3+CD8+CD69+and CD3+CD8+IFN‐γ+T cells increased at 3‐month post‐therapy in five of six patients studied.ConclusionsExtracorporeal photopheresis alone or in combination therapy might be effective inL‐CTCLpatients whose malignant T cells have a CD4+Foxp3+CD25−phenotype.
Fragment size does not matter when you are well connected: effects of fragmentation on fitness of coexisting gypsophiles
Authors: Matesanz S. , Gómez‐Fernández A. , Alcocer I. , Escudero A. 
Published: March 2015

AbstractMost habitat fragmentation studies have focused on the effects of population size on reproductive success of single species, but studies assessing the effects of both fragment size and connectivity, and their interaction, on several coexisting species are rare. In this study, we selected 20 fragments along two continuous gradients of size and degree of isolation in a gypsum landscape in central Spain. In each fragment, we selected 15 individuals of each of three dominant gypsophiles (Centaurea hyssopifolia, Lepidium subulatum and Helianthemum squamatum, 300 plants per species, 900 plants in total) and measured several reproductive traits: inflorescence number, fruit set, seed set and seed mass. We hypothesised that plant fitness would be lower on small and isolated fragments due to an interaction between fragment size and connectivity, and that response patterns would be species‐specific. Overall, fragment size had very little effect on reproductive traits compared to that of connectivity. We observed a positive effect of fragment connectivity on C. hyssopifolia fitness, mediated by the increased seed predation in plants from isolated fragments, resulting in fewer viable seeds per capitulum and lower seed set. Furthermore, seed mass was lower in plants from isolated fragments for both C. hyssopifolia and L. subulatum. In contrast, few reproductive traits of H. squamatum were affected by habitat fragmentation. We discuss the implications of species‐specific responses to habitat fragmentation for the dynamics and conservation of gypsum plant communities. Our results highlight the complex interplay among plants and their mutualistic and antagonistic visitors, and reinforce the often‐neglected role of habitat connectivity as a key component of the fragmentation process.
Conservation genetics of two island endemic Ribes spp. (Grossulariaceae) of Sardinia: survival or extinction?
Authors: Gentili R. , Fenu G. , Mattana E. , Citterio S. , De Mattia F. , Bacchetta G. 
Published: March 2015

AbstractMeasuring levels of population genetic diversity is an important step for assessing the conservation status of rare or endangered plant species and implementing appropriate conservation strategies. Populations of Ribes multiflorum subsp. sandalioticum and R. sardoum, two endangered endemic species from Sardinia, representing the whole genus on the island, were investigated using ISSR and SSR markers to determine levels and structure of genetic variability in their natural populations. Results indicated medium to low genetic diversity at the population level: Nei's gene diversity for ISSR markers ranged from 0.0840 to 0.1316; the expected heterozygosity (HE) for SSR ranged from 0.4281 to 0.7012. In addition, only one remnant population of R. sardoum showed a high level of inbreeding, in accordance with its very small size. Regarding the structure of the six R. sandalioticum populations, both principal coordinates analysis (PCoA) and STRUCTURE analysis of ISSR and SSR data highlighted low population structure, although two populations appeared to be clearly distinct from the others. The genetic pattern of the two taxa associated with their different ecological positions indicated resilience of R. sandalioticum populations in fresh and humid habitats and uncertain future resistance for the residual R. sardoum population in xeric calcareous stands. Hence, this study highlights the importance of an integrated conservation approach (genetic plus in situ and ex situ conservation studies/measures) for activating management programmes in these endemic and threatened taxa that can be considered as crop wild relatives of cultivated Ribes species.
Technology News and the US Economy: Time Variation and Structural Changes
Authors: Berg Tim Oliver 
Published: March 2015

AbstractThis article examines the time‐varying impact of technology news shocks on the US economy during the Post‐World War II period using a time‐varying parameter vector autoregression. The identification restrictions on the sign of the contemporaneous responses of observable variables are derived from a dynamic stochastic general equilibrium model and robust to parameter uncertainty. I find that the variance of news shocks has decreased over time, contributing to the Great Moderation in real activity and inflation. The importance of news shocks is, however, modest compared to technology surprise and non‐technology shocks. Finally, I obtain evidence in favor of a substantial decline in wage rigidity, while the transmission to other variables has been stable.