bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of Solanum tuberosum to Myzus persicae infestation at different stages of foliage maturity
Authors: Alvarez Adriana E. , Alberti D'Amato Anahí M. , Tjallingii W. Fred , Dicke Marcel , Vosman Ben
Published: October 2013

Young leaves of the potato Solanum tuberosum L. cultivar Kardal contain resistance factors to the green peach aphid Myzus persicae (Sulzer) (Hemiptera: Aphididae) and normal probing behavior is impeded. However, M. persicae can survive and reproduce on mature and senescent leaves of the cv. Kardal plant without problems. We compared the settling of M. persicae on young and old leaves and analyzed the impact of aphids settling on the plant in terms of gene expression. Settling, as measured by aphid numbers staying on young or old leaves, showed that after 21 h significantly fewer aphids were found on the young leaves. At earlier time points there were no difference between young and old leaves, suggesting that the young leaf resistance factors are not located at the surface level but deeper in the tissue. Gene expression was measured in plants at 96 h postinfestation, which is at a late stage in the interaction and in compatible interactions this is long enough for host plant acceptance to occur. In old leaves of cv. Kardal (compatible interaction), M. persicae infestation elicited a higher number of differentially regulated genes than in young leaves. The plant response to aphid infestation included a larger number of genes induced than repressed, and the proportion of induced versus repressed genes was larger in young than in old leaves. Several genes changing expression seem to be involved in changing the metabolic state of the leaf from source to sink.
TheD1‐D2 region of the large subunit ribosomalDNAas barcode for ciliates
Authors: Stoeck T. , Przybos E. , Dunthorn M.
Published: October 2013

Ciliates are a major evolutionary lineage within the alveolates, which are distributed in nearly all habitats on our planet and are an essential component for ecosystem function, processes and stability. Accurate identification of these unicellular eukaryotes through, for example, microscopy or mating type reactions is reserved to few specialists. To satisfy the demand for aDNAbarcode for ciliates, which meets the standard criteria forDNAbarcodes defined by the Consortium for the Barcode of Life (CBOL), we here evaluated theD1‐D2 region of the ribosomalDNAlarge subunit (LSU‐rDNA). Primer universality for the phylumCiliophora was testedin silicowith available database sequences as well as in the laboratory with 73 ciliate species, which represented nine of 12 ciliate classes. Primers tested in this study were successful for all tested classes. To test the ability of theD1‐D2 region to resolve conspecific and congeneric sequence divergence, 63Parameciumstrains were sampled from 24 mating species. The average conspecificD1‐D2 variation was 0.18%, whereas congeneric sequence divergence averaged 4.83%. In pairwise genetic distance analyses, we identified aD1‐D2 sequence divergence of <0.6% as an ideal threshold to discriminateParameciumspecies. Using this definition, only 3.8% of all conspecific and 3.9% of all congeneric sequence comparisons had the potential of false assignments. Neighbour‐joining analyses inferred monophyly for all taxa but for twoParamecium octaureliastrains. Here, we present a protocol for easyDNAamplification of single cells and voucher deposition. In conclusion, the presented data pinpoint theD1‐D2 region as an excellent candidate for an official CBOL barcode for ciliated protists.
Separating mortality and emigration: modelling space use, dispersal and survival with robust‐design spatial capture–recapture data
Authors: Ergon Torbjørn , Gardner Beth
Published: October 2013

Capture–recapture (CR) techniques are commonly used to gain information about population dynamics, demography and life‐history traits of populations. However, traditional CR models cannot separate mortality from emigration. Recently developed spatial–capture–recapture (SCR) models explicitly incorporate spatial information into traditional CR models, thus allowing for individuals' movements to be modelled explicitly.

In this paper, we extend SCR models using robust‐design data to allow for both processes in which individuals can disappear from the population, mortality and dispersal, to be estimated separately. We formulate a general robust‐design spatial capture–recapture (RD‐SCR) model, explore the properties of the model in a simulation study and compare the results to a Cormack–Jolly–Seber model and a non‐spatial robust‐design model with temporary emigration. In the case study, we fit several versions of the general model to data on field voles (Microtus agrestis) and compare the results with those from the non‐spatial models fitted to the same data. We also evaluate assumptions of the fitted models with a series of simulation‐based posterior predictive goodness‐of‐fit checks that are applicable to the SCR models in general and the RD‐SCR model in particular.

The simulation results show that the model preforms well under a wide range of dispersal distances. Our model outperforms the traditional CR models in terms of both accuracy and precision for survival. The case study showed that adult females have an c. 3·5 times higher mortality rate than adult males. Males have larger home ranges and disperse longer distances than females, but both males and females mostly move their activity centres within their previous home range between trapping sessions at 3‐week intervals.

Our RD‐SCR model has several advantages compared to other approaches to estimate ‘true’ survival instead of only ‘apparent’ survival. Additionally, the model extracts information about space use and dispersal distributions that are relevant for behavioural studies as well as studies of life‐history variation, population dynamics and management. The model can be widely applied due to the flexible framework, and other variations of the model could easily be implemented.
Estimating true instead of apparent survival using spatial Cormack–Jolly–Seber models
Authors: Schaub Michael , Royle J. Andrew
Published: October 2013

Survival is often estimated from capture–recapture data using Cormack–Jolly–Seber (CJS) models, where mortality and emigration cannot be distinguished, and the estimated apparent survival probability is the product of the probabilities of true survival and of study area fidelity. Consequently, apparent survival is lower than true survival unless study area fidelity equals one. Underestimation of true survival from capture–recapture data is a main limitation of the method.

We develop a spatial version of the CJS model that allows estimation of true survival. Besides the information about whether a specific individual was encountered at a given occasion, it is often recorded where the encounter occurred. Thus, information is available about the fraction of dispersal that occurs within the study area, and we use it to model dispersal and estimate true survival. Our model is formulated hierarchically and consists of survival, dispersal and observation submodels, assuming that encounters are possible anywhere within a study area.

In a simulation study, our new spatial CJS model produced accurate estimates of true survival and dispersal behaviour for various sizes and shapes of the study area, even if emigration is substantial. However, when the information about dispersal is scarce due to low survival, low recapture probabilities and high emigration, the estimators are positively biased. Moreover, survival estimates are sensitive to the assumed dispersal kernel.

We applied the spatial CJS model to a data set of adult red‐backed shrikes (Lanius collurio). Apparent survival of males (c. 0·5) estimated with the CJS model was larger than in females (c. 0·4), but the application of the spatial CJS model revealed that both sexes had similar survival probabilities (c. 0·6). The mean breeding dispersal distance in females was c. 700 m, while males dispersed only c. 250 m between years.

Spatial CJS models enable study of dispersal and survival independent of study design constraints such as imperfect detection and size of the study area provided that some of the dispersing individuals remain in the study area. We discuss possible extensions of our model: alternative dispersal models and the inclusion of covariates and of a habitat suitability map.
Thymic metastasis of breast cancer 22 years after surgery: A case report
Authors: Fujioka Shinji , Nakamura Hiroshige , Miwa Ken , Takagi Yuzo , Yurugi Yohei , Taniguchi Yuji , Ishiguro Kiyosuke
Published: October 2013

We report a rare case of thymic metastasis of breast cancer. A 68‐year‐old woman, who had undergone surgery for cancer in her right breast and had been free of recurrence for 22 years, was noted to have an abnormal shadow on a chest X‐ray at a regular medical checkup. Further workup, including chest CT, revealed a 22 × 18‐mm mass in the anterior mediastinum. Fluorine‐18‐fluorodeoxyglucose‐PET showed increased fluorine‐18‐fluorodeoxyglucose uptake that was highly suggestive of thymoma. Thoracoscopic thymothymectomy was performed. The tumor had invaded the pericardium, which was also resected. A small nodule was found in the right lung, and it was also resected. The intraoperative frozen‐section diagnosis was breast cancer metastasis to the thymus and lung. The pathological diagnosis was luminal A solid tubular carcinoma (strongly estrogen receptor and progesterone receptor positive, HER2 negative) with an MIB‐1 index of less than 5%. After surgery, the patient was treated with an aromatase inhibitor. As of August 2013, she has been free of recurrence for more than 36 months. It is extremely rare for breast cancer to metastasize to the thymus more than 20 years after surgery.
Neuroangiostrongyliasis due to Angiostrongylus cantonensis in gang‐gang cockatoos (Callocephalon fimbriatum)
Authors: Reece RL , Perry RA , Spratt DM
Published: October 2013

Case report

Four gang‐gang cockatoos from an aviary in Sydney displayed severe neurological signs. Three were necropsied and histopathology of the brains and spinal cords revealed migrating nematodes, which were identified as Angiostrongylus cantonensis. The migrating larval nematodes created tracts of malacia in the brain, but elicited little inflammatory cell infiltration. However, adult nematodes that had emerged onto the meningeal surface of the spinal cord evoked a marked non‐suppurative reaction. Detailed histological examination of other tissues revealed larvae embedded in arterioles in the gastrointestinal serosa, lung and heart, which were associated with a significant granulomatous response. The latter lesions were consistent with our understanding of the pathogenesis of infection with this parasite, but have not been previously described, probably as a result of limited sampling.

Conclusions

Angiostrongylus cantonensis is still present in the Sydney area and can cause significant disease in exposed animals, including birds. It also highlights potential human health problems.
Incidence of calf scours and associated risk factors in southernNewSouthWales beef herds
Authors: Lievaart JJ , Charman NR , Scrivener C , Morton A , Allworth MB
Published: October 2013

Objective

The aim of this study was to identify the incidence of morbidity and mortality associated with calf scours in beef calves between birth and 14 days of age. Farm characteristics, animal factors and management practices were also assessed for any association with calf scours being present on the farm.

Methods

A questionnaire and return address envelope were distributed to 721 farms with at least 50 head of beef cattle in theHume area ofNewSouthWales,Australia.

Results

In total, 147 (20.4%) farmers responded to the survey, of which 76 (51.7%) indicated calf scours did occur on their farm. On average, farmers estimated the morbidity of calf scours was 4.5%, but only 0.2% of all calves died as a result of scours. Affected herds were more likely to have multiple breeds and a higher proportion of cows with mismothering problems or weak calves compared with unaffected herds. These differences were confirmed with regression analysis. A large proportion of farmers with affected herds reported the loss of many calves from ‘unexplained’ or ‘sudden’ death within the first 14 days of life.

Conclusions

The incidence of calf morbidity was lower and mortality was within the same range compared with other studies on beef farms around the world. The high percentage of farms reporting losses from ‘unexplained’ or ‘sudden’ death of calves requires further monitoring and diagnostic and economic investigations.
Maternal Magnesium Sulphate Exposure Predicts Neonatal Magnesium Blood Concentrations
Authors: Sherwin Catherine M.T. , Balch Alfred , Campbell Sarah C. , Fredrickson Jeunesse , Clark Erin A.S. , Varner Michael , Stockmann Chris , Korgenski E. Kent , Bonkowsky Joshua L. , Spigarelli Michael G.
Published: October 2013

Tocolytic use of magnesium sulphate is associated with excess neonatal mortality and has been proposed to follow a dose–response relationship. This study aimed to define the correlation between maternal and neonatal magnesium blood concentrations. Magnesium blood concentrations were retrospectively obtained for mother–neonate pairs who were cared for at an Intermountain Healthcare facility from January 2009 to October 2011. Complete data were available for 231 mother–neonate pairs. Mean (±SD) maternal and neonatal magnesium concentrations were 5.43 ± 1.69 and 2.98 ± 0.94 mg/dL, respectively. Maternal and neonatal magnesium concentrations were highly correlated (p < 0.001). In univariate analyses, residual unexplained variability was high (r2 = 0.19). However, further multivariate analyses revealed that caesarian section, severe pre‐eclampsia and Apgar score at 5 min. were significantly associated with neonatal magnesium concentrations (p < 0.05 for all). Maternal magnesium concentrations correlate with neonatal exposure. This finding suggests that maternal monitoring deserves further evaluation as a marker of foetal toxicity.
How we manage the haematological aspects of major obstetric haemorrhage
Authors: Allard Shubha , Green Laura , Hunt Beverley J.
Published: October 2013

Major obstetric haemorrhage (MOH) remains an important medical challenge worldwide, contributing to significant maternal morbidity and mortality. Prompt and appropriate management is essential if we are to improve outcomes and reduce substandard care that may result in adverse consequences. This review describes the current understanding of the pathophysiological aspects of MOH together with the principles of transfusion and haemostatic therapy, with emphasis on a coordinated multidisciplinary approach. We also highlight the current lack of evidence available from randomized controlled trials to inform best practice and the need to prioritize research in this key clinical area.
Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity
Authors: Gandhi Anita K. , Mendy Derek , Waldman Michelle , Chen Gengxin , Rychak Emily , Miller Karen , Gaidarova Svetlana , Ren Yan , Wang Maria , Breider Michael , Carmel Gilles , Mahmoudi Afshin , Jackson Pilgrim , Abbasian Mahan , Cathers Brian E. , Schafer Peter H. , Daniel Tom O. , Lopez‐Girona Antonia , Thakurta Anjan , Chopra Rajesh
Published: October 2013

Cereblon, a member of the cullin 4 ring ligase complex (CRL4), is the molecular target of the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide and is required for the antiproliferative activity of these agents in multiple myeloma (MM) and immunomodulatory activity in T cells. Cereblon's central role as a target of lenalidomide and pomalidomide suggests potential utility as a predictive biomarker of response or resistance to IMiD therapy. Our studies characterized a cereblon monoclonal antibody CRBN65, with high sensitivity and specificity in Western analysis and immunohistochemistry that is superior to commercially available antibodies. We identified multiple cereblon splice variants in both MM cell lines and primary cells, highlighting challenges with conventional gene expression assays given this gene complexity. Using CRBN65 antibody and TaqMan quantitative reverse transcription polymerase chain reaction assays, we showed lack of correlation between cereblon protein and mRNA levels. Furthermore, lack of correlation between cereblon expression in MM cell lines and sensitivity to lenalidomide was shown. In cell lines made resistant to lenalidomide and pomalidomide, cereblon protein is greatly reduced. These studies show limitations to the current approaches of cereblon measurement that rely on commercial reagents and assays. Standardized reagents and validated assays are needed to accurately assess the role of cereblon as a predictive biomarker.
Prenatal exposure to acid‐suppressive drugs and the risk of allergic diseases in the offspring: a cohort study
Authors: Mulder B. , Schuiling‐Veninga C. C. M. , Bos H. J. , De Vries T. W. , Jick S. S. , Hak E.
Published: October 2013

Background

Recent studies reported increased risks for the development of asthma in children after prenatal exposure to acid‐suppressive drugs. As a result of common pathogenesis, associations could also be present for other allergic diseases.

Methods

Using the prescription database IADB.nl, we conducted a cohort study amongst 33 536 children in the Netherlands, with a maximum follow‐up of 8 years. Maternal exposure was defined as ≥1 dispensed prescription for proton pump inhibitors (PPIs) and/or Histamine 2‐antagonists (H2As) during pregnancy. Children were considered to have a drug‐treated allergic disease if they received either ≥2 prescriptions for dermal (atopic dermatitis), inhaled (asthma) or nasal (allergic rhinitis) steroids within a 12‐month period. Clustered Cox proportional hazard regression was used to estimate crude and adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI).

Results

The aHR for the development of any allergic disease was 1.37 (95% CI: 1.14–1.66) for children exposed to PPIs or H2As. Prenatal exposure to PPIs and/or H2As was associated with atopic dermatitis, asthma and allergic rhinitis with aHRs of 1.32 (95% CI 1.06–1.64), 1.57 (95% CI 1.20–2.05) and 2.40 (95% CI 1.42–4.04), respectively. The aHR for the development of two or more (aHR 2.13 95% CI: 1.43–3.19) and three allergic diseases (aHR 5.18 95% CI: 2.16–12.42) were even more elevated after prenatal exposure to PPIs or H2As.

Conclusion

Prenatal exposure to PPIs and H2As appeared associated with an increased risk for the development of atopic dermatitis, asthma and allergic rhinitis in the offspring, especially with the development of multiple allergic diseases. Because our study has limitations inherent to observational studies, prospective studies are now warranted to confirm our findings.
Incidence of nosocomial pneumonia and risk of recurrence after antimicrobial therapy in critically ill lung and heart–lung transplant patients
Authors: Dudau Daniela , Camous Julien , Marchand Séverine , Pilorge Catherine , Rézaiguia‐Delclaux Saïda , Libert Jean‐Marie , Fadel Elie , Stéphan François
Published: October 2013

Little is known about the resolution of symptoms of nosocomial pneumonia (NosoP) after lung and heart–lung transplantation. The aim of this study was to describe the clinical response to antimicrobial therapy in (ICU) patients with NosoP after lung or heart–lung transplantation. Between January 2008 and August 2010, 79 lung or heart–lung transplantations patients were prospectively studied. NosoPwas confirmed by quantitative cultures of bronchoalveolar lavage or endotracheal aspirates. Clinical variables, sequential organ failure assessment (SOFA) score, and radiologic score were recorded from start of therapy until day 9. Thirty‐five patients (44%) experienced 64 episodes of NosoP in ICU. Fourteen patients (40%) had NosoP recurrence. Most frequently isolated organisms were Enterobacteriaceae (30%), Pseudomonas aeruginosa (25%), and Staphylococcus aureus (20%). Sequential organ failure assessment (SOFA) score improved significantly at day 6 and C‐reactive protein level at day 9. SOFA and radiologic scores differed significantly between patients with and without NosoP recurrence at day 3 and 9. The ICU mortality rate did not differ between patients with and without NosoP recurrence, and free of NosoP (14.3%, 9.5%, 11.4%, respectively) (p = 0.91). Severities of illness and lung injury were the two major risk factors for NosoP recurrence. Occurrence of NosoP has no impact on ICU mortality.
Breastfeeding and child neurodevelopment – a role for gut microbiota?
Authors: Parletta Natalie
Published: October 2013

This commentary is on the original article by Julvez et al. on pages 148–156 of this issue.
GOVERNMENT DEBT‐THRESHOLD CONTRACTS
Authors: GERSBACH HANS
Published: October 2013

Politicians tend to push the amount of public debt beyond socially desirable levels in order to increase their reelection chances. We develop a model that provides a new explanation for this behavior: office holders undertake debt‐financed public projects, but postpone the timing of part of the output to the next term. This makes it difficult to replace them. As a consequence, the office holders' reelection chances rise—as does public debt. As a potential remedy for this inefficiency, we allow candidates for public office to offer government debt‐threshold contracts. Such a contract contains an upper limit for government debt and the sanction that an office holder violating this limit cannot stand for reelection. We show that such competitively offered contracts contain low debt levels that limit debt financing and improve the citizens' welfare. When negative macroeconomic events occur, government debt‐threshold contracts may be violated, and the economy is stabilized. (JEL: D7, D82, H4)
Beyond realism in climate change experiments: gradient approaches identify thresholds and tipping points
Authors: Kreyling Juergen , Jentsch Anke , Beier Claus
Published: October 2013

Experimental evidence for impacts of increased climatic variability and extremes on ecosystems is urgently needed. The constraint in our knowledge, however, is not caused by the uncertainty in the applied climate scenarios. We need mechanistic understanding from experiments challenging ecological thresholds coupled with ecosystem models to allow for meaningful up‐scaling.
Challenges associated with the diagnosis and treatment of parasitic encephalitis
Authors: Lacombe V. A.
Published: October 2013

See also article by Wilford et al.
3′–UTR‐dependent regulation of mRNA turnover is critical for differential distribution patterns of cyclic gene mRNAs
Authors: Nitanda Yasuhide , Matsui Takaaki , Matta Tatsuro , Higami Aya , Kohno Kenji , Nakahata Yasukazu , Bessho Yasumasa
Published: October 2013

Somite segmentation, a prominent periodic event in the development of vertebrates, is instructed by cyclic expression of several genes, including Hes7 and Lunatic fringe (Lfng). Transcriptional regulation accounts for the cyclic expression. In addition, because the expression patterns vary in a cycle, rapid turnover of mRNAs should be involved in the cyclic expression, although its contribution remains unclear. Here, we demonstrate that 3′–UTR‐dependent rapid turnover of Lfng and Hes7 plays a critical role in their dynamic expression patterns. The regions active in the transcription of Lfng and Hes7 are wholly overlapped in the posterior presomitic mesoderm (PSM) of the mouse embryo. However, their distribution patterns are slightly different; Hes7 mRNA shows a broader distribution pattern than Lfng mRNA in the posterior PSM. Lfng mRNA is less stable than Hes7 mRNA, where their 3′–UTRs are responsible for the different stability. Using transgenic mice expressing Venus under the control of the Hes7 promoter, which leads to cyclic transcription in the PSM, we reveal that the Lfng 3′–UTR provides the narrow distribution pattern of Lfng mRNA, whereas the Hes7 3′–UTR contributes the relatively broad distribution pattern of Hes7 mRNA. Thus, we conclude that 3′–UTR‐dependent mRNA stability accounts for the differential distribution patterns of Lfng and Hes7 mRNA. Our findings suggest that 3′–UTR‐dependent regulation of mRNA turnover plays a crucial role in the diverse patterns of mRNA distribution during development.
T‐cell immunoglobulin and mucin domain 2 (TIM‐2) is a target of ADAM10‐mediated ectodomain shedding
Authors: Dewitz Christin , Möller‐Hackbarth Katja , Schweigert Olga , Reiss Karina , Chalaris Athena , Scheller Jürgen , Rose‐John Stefan
Published: October 2013

T‐cell immunoglobulin and mucin domain (TIM)‐2 is expressed on activated B cells. Here, we provide evidence that murine TIM‐2 is a target of ADAM10‐mediated ectodomain shedding, resulting in the generation of a soluble form of TIM‐2. We identified ADAM10 but not ADAM17 as the major sheddase of TIM‐2, as shown by pharmacological ADAM10 inhibition and with ADAM10‐deficient and ADAM17‐deficient murine embryonic fibroblasts. Ionomycin‐induced or 2′(3′)‐O‐(4‐benzoylbenzoyl) ATP triethylammonium salt‐induced shedding of TIM‐2 was abrogated by deletion of 10 juxtamembrane amino acids from the stalk region but not by deletion of two further N‐terminally located blocks of 10 amino acids, indicating a membrane‐proximal cleavage site. TIM‐2 lacking the intracellular domain was cleaved after ionomycin or 2′ (3′)‐O‐(4‐benzoylbenzoyl) ATP triethylammonium salt treatment, indicating that this domain was not involved in the regulation of ectodomain shedding. Moreover, TIM‐2 shedding was negatively controlled by calmodulin. Shed and soluble TIM‐2 interacted with H‐ferritin. In summary, we describe TIM‐2 as a novel target for ADAM10‐mediated ectodomain shedding, and reveal the involvement of ADAM proteases in cellular iron homeostasis.
The COP9 signalosome is involved in the regulation of lipid metabolism and of transition metals uptake in Saccharomyces cerevisiae
Authors: Licursi Valerio , Salvi Chiara , De Cesare Virginia , Rinaldi Teresa , Mattei Benedetta , Fabbri Claudia , Serino Giovanna , Bramasole Laylan , Zimbler Jacob Z. , Pick Elah , Barnes Brett M. , Bard Martin , Negri Rodolfo
Published: October 2013

The COP9 signalosome (CSN) is a highly conserved eukaryotic protein complex which regulates the cullin RING family of ubiquitin ligases and carries out a deneddylase activity that resides in subunit 5 (CSN5). Whereas CSN activity is essential for the development of higher eukaryotes, several unicellular fungi including the budding yeast Saccharomyces cerevisiae can survive without a functional CSN. Nevertheless, the budding yeast CSN is biochemically active and deletion mutants of each of its subunits exhibit deficiency in cullins deneddylation, although the biological context of this activity is still unknown in this organism. To further characterize CSN function in budding yeast, we present here a transcriptomic and proteomic analysis of a S. cerevisiae strain deleted in the CSN5/RRI1 gene (hereafter referred to as CSN5), coding for the only canonical subunit of the complex. We show that Csn5 is involved in modulation of the genes controlling amino acid and lipid metabolism and especially ergosterol biosynthesis. These alterations in gene expression correlate with the lower ergosterol levels and increased intracellular zinc content which we observed in csn5 null mutant cells. We show that some of these regulatory effects of Csn5, in particular the control of isoprenoid biosynthesis, are conserved through evolution, since similar transcriptomic and/or proteomic effects of csn5 mutation were previously observed in other eukaryotic organisms such as Aspergillus nidulans, Arabidopsis thaliana and Drosophila melanogaster. Our results suggest that the diverged budding yeast CSN is more conserved than was previously thought.
Use of a modified Gurson model for the failure behaviour of the clinched joint on Al6061 sheet
Authors: Xu F. , Zhao S. D. , Han X. L.
Published: October 2013

This paper discusses the ductile fracture behaviour of the clinched joint on Alloy 6061 sheets. Failure behaviour of the clinched joint is associated with the nucleation, growth and coalescence of voids within the microstructure. Various corrections to the original Gurson model are proposed to allow for instability and final fracture of the material. This paper is concerned with the application of the modified Gurson–Tvergaard–Needleman damage developed by Ken Nahshon and Zhenyu Xue. The results of the tension tests are compared with those of numerical analysis to obtain the initial void volume fraction f0 and the shear damage coefficients kw. The modified Gurson–Tvergaard–Needleman model is used to describe the failure behaviour and the shear strength of the clinched joint. Good agreement is shown between the experiment results and the numerical results on the location of fracture and the maximum failure load.
A model‐data comparison of Holocene timberline changes in the Swiss Alps reveals past and future drivers of mountain forest dynamics
Authors: Schwörer Christoph , Henne Paul D. , Tinner Willy
Published: October 2013

Mountain vegetation is strongly affected by temperature and is expected to shift upwards with climate change. Dynamic vegetation models are often used to assess the impact of climate on vegetation and model output can be compared with paleobotanical data as a reality check. Recent paleoecological studies have revealed regional variation in the upward shift of timberlines in the Northern and Central European Alps in response to rapid warming at the Younger Dryas/Preboreal transition ca. 11 700 years ago, probably caused by a climatic gradient across the Alps. This contrasts with previous studies that successfully simulated the early Holocene afforestation in the (warmer) Central Alps with a chironomid‐inferred temperature reconstruction from the (colder) Northern Alps. We use LandClim, a dynamic landscape vegetation model to simulate mountain forests under different temperature, soil and precipitation scenarios around Iffigsee (2065 m a.s.l.) a lake in the Northwestern Swiss Alps, and compare the model output with the paleobotanical records. The model clearly overestimates the upward shift of timberline in a climate scenario that applies chironomid‐inferred July‐temperature anomalies to all months. However, forest establishment at 9800 cal. BP at Iffigsee is successfully simulated with lower moisture availability and monthly temperatures corrected for stronger seasonality during the early Holocene. The model‐data comparison reveals a contraction in the realized niche of Abies alba due to the prominent role of anthropogenic disturbance after ca. 5000 cal. BP, which has important implications for species distribution models (SDMs) that rely on equilibrium with climate and niche stability. Under future climate projections, LandClim indicates a rapid upward shift of mountain vegetation belts by ca. 500 m and treeline positions of ca. 2500 m a.s.l. by the end of this century. Resulting biodiversity losses in the alpine vegetation belt might be mitigated with low‐impact pastoralism to preserve species‐rich alpine meadows.
Stroke Prevention in New Zealand: Can We Do Better?
Authors: Feigin Valery L. , Krishnamurthi Rita , Barber P. Alan , Arroll Bruce
Published: October 2013

There are approximately 45 000 stroke survivors in New Zealand and this number is projected to increase to 50 000 survivors, with annual costs to the health system exceeding $700 million by 2015 if no effective primary stroke prevention strategies are introduced. However, development of evidence-based stroke prevention strategies requires answering several research questions. In this article, we summarize some key research questions that are particularly pertinent to stroke prevention in New Zealand.
A novel Zap70 mutation with reduced protein stability demonstrates the rate‐limiting threshold for Zap70 in T‐cell receptor signalling
Authors: Cauwe Bénédicte , Tian Lei , Franckaert Dean , Pierson Wim , Staats Kim A. , Schlenner Susan M. , Liston Adrian
Published: October 2013

Loss of ζ‐associated protein 70 (Zap70) results in severe immunodeficiency in humans and mice because of the critical role of Zap70 in T‐cell receptor (TCR) signalling. Here we describe a novel mouse strain generated by N‐ethyl‐N‐nitrosourea mutagenesis, with the reduced protein stability (rps) mutation in Zap70. The A243V rps mutation resulted in decreased Zap70 protein and a reduced duration of TCR‐induced calcium responses, equivalent to that induced by a 50% decrease in catalytically active Zap70. The reduction of signalling through Zap70 was insufficient to substantially perturb thymic differentiation of conventional CD4 and CD8 T cells, although Foxp3+ regulatory T cells demonstrated altered thymic production and peripheral homeostasis. Despite the mild phenotype, the Zap70A243V variant lies just above the functional threshold for TCR signalling competence, as T cells relying on only a single copy of the Zap70rps allele for TCR signalling demonstrated no intracellular calcium response to TCR stimulation. This addition to the Zap70 allelic series indicates that a rate‐limiting threshold for Zap70 protein levels exists at which signalling capacity switches from nearly intact to effectively null.
Epstein–Barr virus antibodies mark systemic lupus erythematosus and scleroderma patients negative for anti‐DNA
Authors: Fattal Ittai , Shental Noam , Molad Yair , Gabrielli Armando , Pokroy‐Shapira Elisheva , Oren Shirly , Livneh Avi , Langevitz Pnina , Pauzner Rachel , Sarig Ofer , Gafter Uzi , Domany Eytan , Cohen Irun R.
Published: October 2013

Systemic lupus erythematosus (SLE) is an autoimmune disease that can attack many different body organs; the triggering event is unknown. SLE has been associated with more than 100 different autoantibody reactivities – anti‐dsDNA is prominent. Nevertheless, autoantibodies to dsDNA occur in only two‐thirds of SLE patients. We previously reported the use of an antigen microarray to characterize SLE serology. We now report the results of an expanded study of serology in SLE patients and scleroderma (SSc) patients compared with healthy controls. The analysis validated and extended previous findings: two‐thirds of SLE patients reacted to a large spectrum of self‐molecules that overlapped with their reactivity to dsDNA; moreover, some SLE patients manifested a deficiency of natural IgM autoantibodies. Most significant was the finding that many SLE patients who were negative for autoantibodies to dsDNA manifested abnormal antibody responses to Epstein–Barr virus (EBV): these subjects made IgG antibodies to EBV antigens to which healthy subjects did not respond or they failed to make antibodies to EBV antigens to which healthy subjects did respond. This observation suggests that SLE may be associated with a defective immune response to EBV. The SSc patients shared many of these serological abnormalities with SLE patients, but differed from them in increased IgG autoantibodies to topoisomerase and centromere B; 84% of SLE patients and 58% of SSc patients could be detected by their abnormal antibodies to EBV. Hence an aberrant immune response to a ubiquitous viral infection such as EBV might set the stage for an autoimmune disease.
CD49a promotes T‐cell‐mediated hepatitis by driving T helper 1 cytokine and interleukin‐17 production
Authors: Chen Yonglin , Peng Hui , Chen Yongyan , Wei Haiming , Sun Rui , Tian Zhigang
Published: October 2013

It is becoming increasingly clear that the T‐cell‐mediated immune response is important in many diseases. In this study, we used concanavalin A (Con A) ‐induced hepatitis to investigate the role of CD49a in the molecular and cellular mechanism of the T‐cell‐mediated immune response. We found that CD49a−/− mice had significantly reduced levels of serum alanine aminotransferase and were protected from Con A‐induced hepatitis. CD49a deficiency led to decreased production of interferon‐γ (IFN‐γ) and interleukin‐17A (IL‐17A) after Con A injection. Furthermore, we found that hepatic CD4+ T cells and invariant natural killer T cells up‐regulated CD49a expression, along with enhanced activation after Con A injection, leading to production of inflammatory cytokines by these T cells. Blockade of CD49a in vivo ameliorated Con A‐induced hepatitis with reduced production of IFN‐γ and IL‐17A. Hence, CD49a promoted Con A‐induced hepatitis through enhancing inflammatory cytokine production (IFN‐γ and IL‐17A) by CD4+ T and invariant natural killer T cells. The protective effect of CD49a blockade antibody suggested a new target therapeutic molecule for intervention of T‐cell‐mediated liver injury.
Introducing a Comprehensive Data Reduction and Uncertainty Propagation Algorithm for U‐Th Geochronometry with Extraction Chromatography and Isotope Dilution MC‐ICP‐MS
Authors: Pourmand Ali , Tissot François L. H. , Arienzo Monica , Sharifi Arash
Published: October 2013

We present an open‐source algorithm in Mathematica application (Wolfram Research) with a transparent data reduction and Monte Carlo simulation of systematic and random uncertainties for U‐Th geochronometry by multi‐collector ICP‐MS. Uranium and thorium were quantitatively separated from matrix elements through a single U/TEVA extraction chromatography step. A rigorous calibrator‐sample bracketing routine was adopted using CRM‐112A and IRMM‐035 standard solutions, doped with an IRMM‐3636a 233U/236U ‘double‐spike’ to account for instrumental mass bias and deviations of measured isotope ratios from certified values. The mean of 234U/238U and 230Th/232Th in the standard solutions varied within 0.42 and 0.25‰ (permil) of certified ratios, respectively, and were consistent with literature values within uncertainties. Based on multiple dissolutions with lithium metaborate flux fusion, U and Th concentrations in USGS BCR‐2 CRM were updated to 1739 ± 2 and 5987 ± 50 ng g−1 (95% CI), respectively. The measurement reproducibility of our analytical technique was evaluated by analysing six aliquots of an in‐house reference material, prepared by homogenising a piece of speleothem (CC3A) from Cathedral Cave, Utah, which returned a mean age of 21483 ± 63 years (95% CI, 2.9‰). Replicate analysis of ten samples from CC3A was consistent with ages previously measured at the University of Minnesota by single‐collector ICP‐MS within uncertainties.
Micromechanics of ITZ‐Aggregate Interaction in Concrete Part II: Strength Upscaling
Authors: Königsberger Markus , Pichler Bernhard , Hellmich Christian
Published: October 2013

Cracking in concrete typically starts in the immediate vicinity around the aggregates, i.e., in the region of the so‐called interfacial transition zones (ITZs), but the process is still not fully understood. Notably, crushing of concrete in compression results in fragments with interesting aggregate surface textures. Part of the aggregate surfaces is cleanly separated from the ITZ, while another part of the aggregate surfaces remains covered with a thin layer of cement paste. This suggests two different types of failure: ITZ‐aggregate separation and ITZ failure; which we here study based on the continuum micromechanics approach of the companion paper (part I). It provides access to both traction vectors acting on aggregate surfaces and three‐dimensional stress states within representative ITZ volumes for loading states below the elastic limit of concrete. When inserting these microtractions and microstresses into Rankine‐type strength criteria for the aggregate‐ITZ interface and for the ITZ, respectively, the micromechanics model allows for upscaling this microscopic failure behavior to concrete‐level criteria for crack onset. Comparing the latter to corresponding experimental results, reveals that under tension‐dominated loading both ITZ failure and ITZ‐aggregate separation appear to be realistic, while under compression‐dominated loading ITZ failure appears as the more likely mechanism. Also, comparing model and experiments shows that the ITZ‐aggregate separation strength amounts to at least half of the internal ITZ cohesion strength, but may be much larger than the latter.
Smoking in young adult African Americans
Authors: Jones Pamela R. , Cohen Marlene Z. , McIlvain Helen E. , Siahpush Mohammad , Scott Alexis , Okafor Kingsley
Published: October 2013

Aim

The aim of this study was to describe factors that influence decisions of young African Americans to start smoking.

Background

Young adult African Americans have a high risk for becoming regular smokers, but little is understood about their smoking. This knowledge is needed because understanding young adults' smokers will help develop effective tobacco cessation and prevention strategies.

Design

Qualitative study.

Method

The study consisted of 22 in‐depth interviews with African Americans between the ages of 19–25. Data were collected between 2009–2010. Smokers, former smokers and non‐smokers were included.

Results/findings

Results indicated that smoking identity of young adults was influenced by their limited and discounted knowledge of health risks and the stigma associated with the type of tobacco smoked. The importance of cost was discussed as was the effect of smoking on relationships and vice versa. Marijuana was the primary reason they started smoking tobacco. Their transition into adulthood and views of smoking, adulthood and success all influenced smoking. Additionally, self‐reflection on personal choices around smoking was important and may be useful in effective smoking cessation programmes for this group.

Conclusion

Nurses are in an ideal position to promote effective smoking cessation in young adults. Direct, culturally relevant messages are needed that fit into the context of the young adults' lives by addressing concurrent use of marijuana, self‐esteem and success in life.
Cardiac Sarcoidosis: Electrophysiological Outcomes on Long‐Term Follow‐Up and the Role of the Implantable Cardioverter‐Defibrillator
Authors: MOHSEN AMR , JIMENEZ ALEJANDRO , HOOD ROBERT E. , DICKFELD TIMM , SALIARIS ANASTASIOS , SHOROFSKY STEPHEN , SABA MAGDI M.
Published: October 2013

Cardiac Sarcoidosis

Objectives

The objectives of this study were to identify the predictors of life‐threatening ventricular arrhythmias in patients with cardiac sarcoidosis (CS) and to evaluate the role of the implantable cardioverter‐defibrillator (ICD) in this patient population.

Background

ICD implantation is a class IIA recommendation for patients with CS. However, some indications for ICD implantation in CS patients are still unclear and not enough data are available to establish predictors of malignant ventricular tachyarrhythmias in this group of patients.

Methods

We retrospectively identified all consecutive patients who were diagnosed with CS, during the period from March 2002 to April 2010. Cardiac rhythm devices were regularly interrogated and clinical data recorded during follow‐up visits.

Results

Thirty‐three patients (17 male) with CS were identified. The mean age was 53 ± 11. The mean left ventricular ejection fraction (LVEF) was 41 ± 18%. Thirty patients received an ICD. Twelve patients (36.3%) had sustained ventricular arrhythmias. Eleven patients received appropriate therapies and 9 patients received inappropriate shocks, representing 36.7% and 30.0% of the ICD population, respectively. Patients who received appropriate ICD therapies were younger with mean age 47.4 ± 7.8, and had a lower mean LVEF 33.0 ± 12.0 compared to those who did not receive ICD therapies (P = 0.0301 and 0.0341, respectively). There were no other demographic, clinical, electrocardiographic, electrophysiological, or imaging markers that predicted the future occurrence of appropriate ICD therapies in our cohort of patients.

Conclusions

CS is strongly associated with malignant ventricular arrhythmias. No specific predictors of such tachyarrhythmias emerged, other than young age and low LVEF.
Comparative effect of lurasidone and blonanserin on cortical glutamate, dopamine, and acetylcholine efflux: role of relative serotonin (5‐HT)2A and DA D2 antagonism and 5‐HT1A partial agonism
Authors: Huang Mei , Panos John J. , Kwon Sunoh , Oyamada Yoshihiro , Rajagopal Lakshmi , Meltzer Herbert Y.
Published: October 2013

Atypical antipsychotic drugs (AAPDs) have been suggested to be more effective in improving cognitive impairment in schizophrenia than typical APDs, a conclusion supported by differences in receptor affinities and neurotransmitter efflux in the cortex and the hippocampus. More potent serotonin (5‐HT)2A than dopamine (DA) D2 receptors antagonism, and direct or indirect 5‐HT1A agonism, characterize almost all AAPDs. Blonanserin, an AAPD, has slightly greater affinity for D2 than 5‐HT2A receptors. Using microdialysis and ultra performance liquid chromatography‐mass spectrometry/mass spectrometry, we compared the abilities of the typical APD, haloperidol, three AAPDs, blonanserin, lurasidone, and olanzapine, and a selective 5‐HT1A partial agonist, tandospirone, and all, except haloperidol, were found to ameliorate the cognitive deficits produced by the N‐methyl‐d‐aspartate antagonist, phencyclidine, altering the efflux of neurotransmitters and metabolites in the rat cortex and nucleus accumbens. Blonanserin, lurasidone, olanzapine, and tandospirone, but not haloperidol, increased the efflux of cortical DA and its metabolites, homovanillic acid and 3,4‐dihydroxyphenylacetic acid. Olanzapine and lurasidone increased the efflux of acetylcholine; lurasidone increased glutamate as well. None of the compounds significantly altered the efflux of 5‐HT or its metabolite, 5‐hydroxyindole acetic acid, or GABA, serine, and glycine. The ability to increase cortical DA efflux was the only shared effect of the compounds which ameliorates the deficit in cognition in rodents following phencyclidine.

image

Abnormalities in dopaminergic, glutamatergic, gamma‐aminobutyric acid (GABAergic), cholinergic, and noradrenergic activity in the medial prefrontal cortex and hippocampus have been implicated in the pathophysiology of the cognitive impairment in schizophrenia. Using in vivo microdialysis and UPLC‐MS/MS assay method, the effect of multiple antipsychotics with different binding properties on the efflux of neurotransmitters including acetylcholine (ACh), dopamine (DA), and metabolites, serotonin, serine, glycine, glutamate (Glu) and GABA in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) have been studied in rats. Related mechanisms of receptors and neurotransmitter efflux have been discussed.