bluuebunny/crossref_metadata_2025 huggingface dataset:
PrfA regulation offsets the cost of Listeria virulence outside the host
Authors: Vasanthakrishnan Radhakrishnan B. , de las Heras Aitor , Scortti Mariela , Deshayes Caroline , Colegrave Nick , Vázquez‐Boland José A.
Published: July 2015

Virulence traits are essential for pathogen fitness, but whether they affect microbial performance in the environment, where they are not needed, remains experimentally unconfirmed. We investigated this question with the facultative pathogen Listeria monocytogenes and its PrfA virulence regulon. PrfA‐regulated genes are activated intracellularly (PrfA ‘ON’) but shut down outside the host (PrfA ‘OFF’). Using a mutant PrfA regulator locked ON (PrfA*) and thus causing PrfA‐controlled genes to be constitutively activated, we show that virulence gene expression significantly impairs the listerial growth rate (μ) and maximum growth (A) in rich medium. Deletion analysis of the PrfA regulon and complementation of a L. monocytogenes mutant lacking all PrfA‐regulated genes with PrfA* indicated that the growth reduction was specifically due to the unneeded virulence determinants and not to pleiotropic regulatory effects of PrfA ON. No PrfA*‐associated fitness disadvantage was observed in infected eukaryotic cells, where PrfA‐regulated virulence gene expression is critical for survival. Microcosm experiments demonstrated that the constitutively virulent state strongly impaired L. monocytogenes performance in soil, the natural habitat of these bacteria. Our findings provide empirical proof that virulence carries a significant cost to the pathogen. They also experimentally substantiate the assumed, although not proven, key role of virulence gene regulation systems in suppressing the cost of bacterial virulence outside the host.
MetaKosovo: Local and International Narratives
Authors: Musliu Vjosa , Orbie Jan
Published: July 2015

This article: Problematizes the concept of ‘home’ and ‘hospitality’ in the case of unfinished states in terms of sovereignty. Argues that the concept of home is always preconditioned by the differences of host and guest; in cases where these two are intermingled/confused/unclear, the concept of home changes too. Looks at local and international narratives on Kosovo as a struggle of conceptual ownerships. Asserts that international and local narratives are always already both subject and object, yet fully neither at the same time, they exist and are destroyed by their own, and their subjectivity therefore lies in their autoimmunity, which makes them intrinsically undecidable. States that the Serbs and the Albanians have reached a historical point on their claim on Kosovo, where they share Kosovo as a state beyond ‘home’ (beyond sovereignty); for the Serbs, Kosovo as their previous ‘home’ is beyond remedy, for the Albanians Kosovo as their new/legitimate ‘home’ is beyond reach.

This article examines local narratives on Kosovo and their role in crafting and articulating interpretations of Kosovo and international missions. Using the concept of ‘home’, as used and conceptualised by Jacques Derrida, the article reverses the order of who is ‘guest’ and ‘host’ in Kosovo and how that defines the local narratives on the subject. In the first part, attention is paid solely to letting local narratives deconstruct themselves, while in the second part we let them deconstruct the international narrative on Kosovo. The aim of the article is to present Kosovo as a battleground of division and commonality among the narratives and at the same time as an ‘impossible’ ‘home’ of all its narratives. In conclusion, some thoughts pave the way for the idea of ‘renegotiating’ the concept of ‘home’ with particular focus on ‘home’ in interventions and missions and its ultimate influence on the ethics of intervention.
Hard and Soft Densification Policies in the Paris City‐Region
Authors: Touati‐Morel Anastasia
Published: July 2015

This essay is concerned with the planning and densification of suburbs, which present a huge challenge insofar as they form a large area of urbanized land that remains underexploited due to low residential density. Drawing on current research in the Paris city‐region, the essay focuses specifically on the difficulty in implementing densification policies in low‐rise suburban areas. It examines the varying degrees of densification fostered by these policies, and builds upon recent urban studies literature on suburban change to trace how suburban areas are being transformed through regulations, instruments and market dynamics associated with densification processes. What kinds of densification policy are being implemented and what are the socio‐economic, political and cultural determinants of each type of regulatory approach? This essay will attempt to answer this question via an analysis of the densification policies being put in place in the municipalities of the Paris city‐region. It will offer in turn a typology of these different policies. It shows that densification is an instrument that can be used to address local political concerns which vary greatly depending on the economic, social and geographical position of municipalities within larger urban areas.
Cosmopolitics: towards a new articulation of politics, science and critique
Authors: Saito Hiro
Published: July 2015

This paper explores howUlrichBeck's world‐risk‐society theory (WRST) andBrunoLatour'sActor‐NetworkTheory (ANT) can be combined to advance a theory of cosmopolitics. On the one hand,WRSThelps to examine ‘cosmopolitan politics’, how actors try to inject cosmopolitanism into existing political practices and institutions anchored in the logic of nationalism. On the other hand,ANTsheds light on ‘cosmological politics’, how scientists participate in the construction of reality as a reference point for political struggles. By combining theWRSTandANTperspectives, it becomes possible to achieve a more comprehensive understanding of cosmopolitics that takes into account both political and ontological dimensions. The proposed synthesis ofWRSTandANTalso calls for a renewal of critical theory by making social scientists aware of their performative involvement in cosmopolitics. This renewal prompts social scientists to explore how they can pragmatically support certain ideals of cosmopolitics through continuous dialogues with their objects of study, actors who inhabit different nations and different cosmoses.
Use of homogenisation pressure to improve quality and functionality of probiotic fermented milks containing Lactobacillus rhamnosus BFE 5264
Authors: Patrignani Francesca , Serrazanetti Diana I. , Mathara Julius Maina , Siroli Lorenzo , Gardini Fausto , Holzapfel Wilhelm H. , Lanciotti Rosalba
Published: July 2015

The effects of 60‐MPa milk homogenisation treatment were investigated on the viability of the probiotic strain Lactobacillus rhamnosus BFE5264, when used as yoghurt co‐starter, as well as on the aroma profile, texture and microstructure of the resulting set‐type fermented milks. The results demonstrated that the combined use of homogenisation pressure and co‐inoculation of the probiotic strain with the traditional yoghurt starters allowed the reduction in the product coagulation time, the increase of the probiotic strain viability and the improvement of the product volatile molecule profiles. The rheological indices and the microstructure results indicated the positive effects of the milk homogenisation treatment on the product viscosity index and exopolysaccharide production.
Fetal sex dependency of maternal vascular adaptation to pregnancy: a prospective population‐based cohort study
Authors: Broere‐Brown ZA , Schalekamp‐Timmermans S , Hofman A , Jaddoe VWV , Steegers EAP
Published: July 2015

Objective

To investigate fetal sex dependency of maternal vascular adaptation to pregnancy as assessed by uteroplacental vascular resistance and maternal blood pressure.

Design

Prospective population‐based cohort study.

Setting

Rotterdam, the Netherlands.

Population

In total, 8224 liveborn singleton pregnancies were included.

Methods

Maternal vascular adaptation was assessed in all trimesters of pregnancy. Pregnancies were stratified into being either complicated by the placental syndrome (i.e. pre‐eclampsia, fetal growth restriction or preterm birth, n = 1229) or uncomplicated (n = 6995).

Main outcome measures

First trimester: blood pressures. Second trimester: blood pressures, pulsatility index of the uterine artery (PI‐UtA). Third trimester: blood pressures, PI‐UtA, presence of notching in the uterine artery.

Results

In women carrying a male fetus PI‐UtA was higher than in women with a female fetus in the total group (second trimester P < 0.001, third trimester P = 0.005). Effect estimates differed between women with or without the placental syndrome. In the total group, women with a male fetus more often showed notching in the Doppler resistance pattern (odds ratio 1.42, 95% confidence interval 1.17–1.72). Different blood pressure patterns were observed between pregnant women with a male fetus and pregnant women with a female fetus and between complicated pregnancies and uncomplicated pregnancies.

Conclusion

Fetal sex is significantly associated with maternal vascular adaptation to pregnancy with differential effects in uncomplicated pregnancies and in pregnancies complicated by the placental syndrome.

Tweetable abstract

Fetal sex is significantly associated with maternal vascular adaptation to pregnancy.
Associational Patterns of Scavenger Beetles to Decomposition Stages
Authors: Zanetti Noelia I. , Visciarelli Elena C. , Centeno Nestor D.
Published: July 2015

Beetles associated with carrion play an important role in recycling organic matter in an ecosystem. Four experiments on decomposition, one per season, were conducted in a semirural area in Bahía Blanca, Argentina. Melyridae are reported for the first time of forensic interest. Apart from adults and larvae of Scarabaeidae, thirteen species and two genera of other coleopteran families are new forensic records in Argentina. Diversity, abundance, and species composition of beetles showed differences between stages and seasons. Our results differed from other studies conducted in temperate regions. Four guilds and succession patterns were established in relation to decomposition stages and seasons. Dermestidae (necrophages) predominated in winter during the decomposition process; Staphylinidae (necrophiles) in Fresh and Bloat stages during spring, summer, and autumn; and Histeridae (necrophiles) and Cleridae (omnivores) in the following stages during those seasons. Finally, coleopteran activity, diversity and abundance, and decomposition rate change with biogeoclimatic characteristics, which is of significance in forensics.
Nocturnal Oviposition Behavior of Forensically Important Diptera in Central England
Authors: Barnes Kate M. , Grace Karon A. , Bulling Mark T.
Published: July 2015

Timing of oviposition on a corpse is a key factor in entomologically based minimum postmortem interval (mPMI) calculations. However, there is considerable variation in nocturnal oviposition behavior of blow flies reported in the research literature. This study investigated nocturnal oviposition in central England for the first time, over 25 trials from 2011 to 2013. Liver‐baited traps were placed in an urban location during control (diurnal), and nocturnal periods and environmental conditions were recorded during each 5‐h trial. No nocturnal activity or oviposition was observed during the course of the study indicating that nocturnal oviposition is highly unlikely in central England.
Transmission ecology of rodent‐borne diseases: New frontiers
Authors: BORDES Frédéric , BLASDELL Kim , MORAND Serge
Published: July 2015

Rodents are recognized reservoir hosts for many human zoonotic pathogens. The current trends resulting from anthropocene defaunation suggest that in the future they, along with other small mammals, are likely to become the dominant mammals in almost all human‐modified environments. Recent intricate studies on bat‐borne emerging diseases have highlighted that many gaps exist in our understanding of the zoonotic transmission of rodent‐borne pathogens. This has emphasized the need for scientists interested in rodent‐borne diseases to integrate rodent ecology into their analysis of rodent‐borne pathogen transmission in order to identify in more detail the mechanisms of spillover and chains of transmission. Further studies are required to better understand the true impact of rodent abundance and the importance of pathogen sharing and circulation in multi‐host– multi‐pathogen communities. We also need to explore in more depth the roles of generalist and abundant species as the potential links between pathogen‐sharing, co‐infections and disease transmission.
SPARROW Modeling of Nitrogen Sources and Transport in Rivers and Streams of California and Adjacent States, U.S.
Authors: Saleh Dina , Domagalski Joseph
Published: July 2015

The SPARROW (SPAtially Referenced Regressions On Watershed attributes) model was used to evaluate the spatial distribution of total nitrogen (TN) sources, loads, watershed yields, and factors affecting transport and decay in the stream network of California and portions of adjacent states for the year 2002. The two major TN sources to local catchments on a mass basis were fertilizers and manure (51.7%) and wastewater discharge (15.9%). Other sources contributed < 12%. Fertilizer use is widespread in the Central Valley region of California, and also important in several other regions because of the diversity of California agriculture. Precipitation, sand content of surficial soils, wetlands, and tile drains were important for TN movement to stream reaches. Median streamflow in the study area is about 0.04 m3/s. Aquatic losses of nitrogen were found to be most important in intermittent and small to medium sized streams (0.2‐14 m3/s), while larger streams showed less loss, and therefore are important for TN transport. Nitrogen loss in reservoirs was found to be insignificant, possibly because most of the larger ones are located upstream of nitrogen sources. The model was used to show loadings, sources, and tributary inputs to several major rivers. The information provided by the SPARROW model is useful for determining both the major sources contributing nitrogen to streams and the specific tributaries that transport the load.
An Analysis of the Effects of Land Use and Land Cover on Flood Losses along the Gulf of Mexico Coast from 1999 to 2009
Authors: Brody Samuel D. , Highfield Wesley E. , Blessing Russell
Published: July 2015

Major coastal flooding events over the last decade have led decision makers in the United States to favor structural engineering solutions as a means to protect vulnerable coastal communities from the adverse impacts of future storms. While a resistance‐based approach to flood mitigation involving large‐scale construction works may be a central component of a regional flood risk reduction strategy, it is equally important to consider the role of land use and land cover (LULC) patterns in protecting communities from floods. To date, little observational research has been conducted to quantify the effects of various LULC configurations on the amount of property damage occurring across coastal regions over time. In response, we statistically examine the impacts of LULC on observed flood damage across 2,692 watersheds bordering the Gulf of Mexico. Specifically, we analyze statistical linear regression models to isolate the influence of multiple LULC categories on over 372,000 insured flood losses claimed under the National Flood Insurance Program per year from 2001 to 2008. Results indicate that percent increase in palustrine wetlands is the equivalent to, on average, a $13,975 reduction in insured flood losses per year, per watershed. These and other results provide important insights to policy makers on how protecting specific types of LULC can help reduce adverse impacts to local communities.
Reducing Fertilizer‐Nitrogen Losses from Rowcrop Landscapes: Insights and Implications from a Spatially Explicit Watershed Model
Authors: McLellan Eileen , Schilling Keith , Robertson Dale
Published: July 2015

We present conceptual and quantitative models that predict changes in fertilizer‐derived nitrogen delivery from rowcrop landscapes caused by agricultural conservation efforts implemented to reduce nutrient inputs and transport and increase nutrient retention in the landscape. To evaluate the relative importance of changes in the sources, transport, and sinks of fertilizer‐derived nitrogen across a region, we use the spatially explicit SPAtially Referenced Regression On Watershed attributes watershed model to map the distribution, at the small watershed scale within the Upper Mississippi‐Ohio River Basin (UMORB), of: (1) fertilizer inputs; (2) nutrient attenuation during delivery of those inputs to the UMORB outlet; and (3) nitrogen export from the UMORB outlet. Comparing these spatial distributions suggests that the amount of fertilizer input and degree of nutrient attenuation are both important in determining the extent of nitrogen export. From a management perspective, this means that agricultural conservation efforts to reduce nitrogen export would benefit by: (1) expanding their focus to include activities that restore and enhance nutrient processing in these highly altered landscapes; and (2) targeting specific types of best management practices to watersheds where they will be most valuable. Doing so successfully may result in a shift in current approaches to conservation planning, outreach, and funding.
Evaluating Geomorphic Change in Constructed Two‐Stage Ditches
Authors: D'Ambrosio Jessica L. , Ward Andrew D. , Witter Jonathan D.
Published: July 2015

Straight, trapezoidal‐shaped surface drainage channels efficiently drain the soil profile, but their deviations from natural fluvial conditions drive the need for frequent maintenance. Ecological and socioeconomic impacts of drainage ditch maintenance activities can be significant, leading to harmful algal blooms and increased sedimentation. We developed a two‐stage ditch design that is more consistent with fluvial form and process. The approach has potential to enhance ecological services while meeting drainage needs essential for agricultural production. We studied geomorphic change of the inset channel, benches and banks of seven two‐stage ditches in Ohio, Indiana, and Michigan. Three to 10 years after construction, inset channel changes reflected natural adjustments, but not all ditches had reached their quasi‐equilibrium state. Ditches had experienced both degradation and aggradation on the benches at a rate of 0.5‐13 mm/yr. Aggradation on the benches was not likely to threaten tile drain outlets. Localized scour was observed on the banks at some sites, but at all but one site changes were not statistically significant. Except for the removal of woody vegetation, none of the ditches required routine maintenance since construction. Two‐stage ditches can be a stable, viable option for drainage ditch management if designed and installed properly on the landscape.
Systemic lupus erythematosus observations of travel burden: A qualitative inquiry
Authors: Williams Edith M. , Ortiz Kasim , Flournoy‐Floyd Minnjuan , Bruner Larisa , Kamen Diane
Published: July 2015

Aims

Explorations of travel impediments among patients suffering from rheumatic diseases have been very limited. Research has consistently indicated a shortage of rheumatologists, resulting in patients potentially having to travel long distances for care. The purpose of our study was to explore how systemic lupus erythematosus (SLE) patients experience travel issues differentially by race and socio‐economic status.

Methods

We conducted semi‐structured interviews and a brief demographic survey with 10 patients diagnosed with SLE. Interview transcripts were coded and analyzed using NVivo Analysis Software to facilitate the reporting of recurrent themes and supporting quotations, and an initial codebook was independently developed by two researchers on the study team and then verified together.

Results

Patients described three major areas of concern with respect to travel burden in accessing their rheumatologists: reliance on caregivers; meeting financial priorities; and pain and physical limitations.

Conclusions

Our data suggest general traveling challenges interfering with medical appointment compliance for several participants and the importance of socio‐economic issues when considering travel issues. This study highlights an important area with implications for adherence to medical appointments and participation in research among patients with SLE.
A retrospective study on 158 Thai patients with juvenile idiopathic arthritis followed in a single center over a 15‐year period
Authors: Vilaiyuk Soamarat , Soponkanaporn Sirisucha , Jaovisidha Suphaneewan , Benjaponpitak Suwat , Manuyakorn Wiparat
Published: July 2015

Aim

To determine the outcomes of juvenile idiopathic arthritis (JIA) in Thai children.

Methods

A retrospective cohort study. All JIA patients in a rheumatology clinic, Ramathibodi Hospital, between July 1997 and December 2012 were enrolled. The patient data were reviewed from medical records. At the most recent follow‐up visit, patient outcomes were assessed in three aspects: disease status, functional outcomes and structural damage.

Results

Of 168 patients, 158 (94.0%) were assessed in disease status and functional outcomes, with 114 patients (67.9%) assessed in three aspects over 4 years of disease. The most common JIA category was systemic JIA (SJIA) (33.8%), followed by enthesitis‐related arthritis (ERA) (24.8%), oligoarthritis (18.5%), rheumatoid factor (RF)‐negative polyarthritis (15.3%), RF‐positive polyarthritis (7.6%) and one undifferentiated arthritis. SJIA had the highest remission rate due to early diagnosis and prompt treatment compared to other categories, whereas RF‐positive polyarthritis carried the worst prognosis in three aspects, followed by ERA. Moreover, ERA patients had the highest failure rate in conventional therapy, half of whom had combined treatment with biologic agents and presence of human leukocyte antigen (HLA)‐B27 was a predictor for biologic treatment in ERA patients. In addition, disease duration > 2 years or failure of conventional therapy was a predictor of structural bone damage.

Conclusions

SJIA had the highest remission rate, whereas RF‐positive polyarthritis had the worst outcome in three aspects. Prolonged disease duration or failure of conventional therapy was a predictor of structural bone damage, while HLA‐B27 was a predictor for biologic treatment in ERA patients.
Anti‐centromere antibody‐positive Sjögren's syndrome: A distinct clinical subgroup?
Authors: Lee Kyung‐Eun , Kang Ji‐Hyoun , Lee Jeong‐Won , Wen Lihui , Park Dong‐Jin , Kim Tae‐Jong , Park Yong‐Wook , Lee Shin‐Seok
Published: July 2015

Aim

To investigate whether patients with Sjögren's syndrome (SS) can be distinguished based on the positivity of anti‐centromere antibody (ACA), and if so, whether the subgroups differ in their clinical and laboratory features.

Methods

Eleven patients with ACA‐positive and 71 patients ACA‐negative SS were examined. All patients had minor salivary gland biopsy; sociodemographic data, glandular and extraglandular manifestations, and laboratory findings, including autoantibodies, complement and immunoglobulin levels, were analyzed. European League Against Rheumatism SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured.

Results

The prevalence of ACA among SS patients was 13.4%. ACA‐positive SS patients had a higher prevalence of Raynaud's phenomenon, sclerodactyly and autoimmune thyroiditis and a lower prevalence of anti‐SSA/Ro and anti‐SSB/La antibodies compared to ACA‐negative patients. Disease activity was higher in ACA‐positive patients than in ACA‐negative patients, but the damage index did not differ between the two groups. None of the patients who originally had ACA evolved to having full‐blown systemic sclerosis.

Conclusion

Patients with SS who have ACA differ from classic SS patients in several clinical and laboratory parameters. ACA should be considered one of the pathogenically relevant autoantibodies for SS.
The association between CTLA‐4 (+49 A/G) polymorphism and susceptibility to ankylosing spondylitis: a meta‐analysis
Authors: Wu Jian , Zhang Liang , Zhou Yixin
Published: July 2015

Aim

The objective of the present meta‐analysis was to investigate whether or not cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) polymorphisms are associated with ankylosing spondylitis (AS) susceptibility.

Methods

A systematic search was conducted from the PubMed, ENBASE, and Springer link database up to April 2014. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of association between CTLA‐4 (+49 A/G) and AS risk. A subgroup analysis based on geographic region and a sensitivity analysis were also conducted.

Results

Five studies were eligible for meta‐analysis, including 918 cases and 845 controls. The results showed that no significant association was found between AS and CTLA‐4 (+49 A/G) for the additive model (G vs. A), dominant model (GG + AG vs. AA), co‐dominant model (GG vs. AA, AG vs. AA) and recessive model (GG vs. AG + AA). The OR was 1.09 (95% CI, 0.87–1.38), 1.16 (95% CI, 0.89–1.51), 1.05 (95% CI, 0.75–1.46), 1.15 (95% CI, 0.86–1.52) and 0.99 (95% CI, 0.79–1.23), respectively. Although subgroup analysis demonstrated no association between CTLA‐4 (+49 A/G) polymorphisms and susceptibility to AS in Europe and Taiwan, an association was found in Iran through both the co‐dominant and dominant models. Exclusion of any individual study did not alter the significance of the final outcome, excepting the result by omitting the study by Huang et al.

Conclusions

The present results suggest that the CTLA‐4 may not be a major susceptibility locus in humans with AS. The relationship between them may be affected by different geographic populations.
Expression of Pax8 is decreased and bortezomib does not increase the iodine uptake in thyroid carcinoma cells
Authors: Wang Huan‐jun , Yao Jin‐ming , Zhang Zhong‐wen , Zhao Jun‐yu , Shang Hong‐xia , Liao Lin , Dong Jian‐jun
Published: July 2015

Fundamental treatment for papillary thyroid carcinoma (PTC) involves total or subtotal thyroidectomy. Iodine‐131 (131I) is routinely utilized to target remnant thyroid cancer and metastasis after thyroidectomy. The effectiveness of other therapeutic modalities remains unsatisfactory; thus, these patients have a poor prognosis. The manner in which the ability of 131I uptake can be improved is vital for their prognosis. Bortezomib has been used as a re‐differentiation agent for the treatment of patients with multiple myeloma; however, little is reported about the role of bortezomib in thyroid cancer. To evaluate the therapeutic potential of bortezomib in a human PTC cell line, expression of paired‐box 8 (Pax8) protein was determined using Western blot in PTC, normal thyroid, and anaplastic/undifferentiated thyroid carcinoma (ATC) cells. The expression of Pax8 protein in PTC cells pretreated with bortezomib was determined using the same method. Iodine uptake was determined using 131I radioactivity assay. The level of Pax8 protein in normal thyroid cells was significantly higher than in PTC (P < 0.05) and ATC cells (P < 0.05); its expression in PTC cells was also significantly higher than in ATC cells (P < 0.05). The PTC cells in the bortezomib‐treated group showed a higher expression of Pax8 protein than the control group (P < 0.05). These findings indicate that bortezomib can increase the expression of Pax8, but does not significantly increase the iodine uptake of PTC cells.
To Comply or Not to Comply: Understanding the Discretion in Reporting Public Float and SEC Regulations
Authors: Gao Feng
Published: July 2015

This paper documents how firms exercise discretion in defining affiliates and reporting public float in response to Securities and Exchange Commission regulations. I find that firms with higher expected compliance costs under section 404 of the Sarbanes‐Oxley Act of 2002 tend to classify more shares as affiliated and report lower public float. In contrast, firms issuing seasoned equity are less likely to underreport public float, possibly due to favorable regulatory treatment for large issuers. These incentives are weakened when future regulatory changes render float less important.
Abnormal Accruals and Managerial Intent: Evidence from the Timing of Merger Announcements and Completions
Authors: Louis Henock , Sun Amy X.
Published: July 2015

We examine acquiring managers' opportunistic reporting behavior around stock‐for‐stock acquisitions. Using the timing of merger announcements and completions to infer managerial intent, we show that acquirers with the most inflated earnings tend to announce mergers on Fridays, and that they manage earnings several quarters before the merger announcement date. Friday announcers exhibit a stronger negative association between pre‐merger announcement abnormal accruals and post‐merger announcement market performance than non‐Friday announcers. This effect is driven mainly by mergers that are completed relatively quickly after they are announced. Overall, the evidence supports the notion that some acquiring managers inflate earnings prior to announcing the mergers, and time the merger announcements to exploit investor inattention.
IGF‐1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging
Authors: Toth Peter , Tarantini Stefano , Ashpole Nicole M. , Tucsek Zsuzsanna , Milne Ginger L. , Valcarcel‐Ares Noa M. , Menyhart Akos , Farkas Eszter , Sonntag William E. , Csiszar Anna , Ungvari Zoltan
Published: July 2015

Aging is associated with marked deficiency in circulating IGF‐1, which has been shown to contribute to age‐related cognitive decline. Impairment of moment‐to‐moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of age‐related cognitive impairment. To establish the link between IGF‐1 deficiency and cerebromicrovascular impairment, neurovascular coupling mechanisms were studied in a novel mouse model of IGF‐1 deficiency (Igf1f/f‐TBG‐Cre‐AAV8) and accelerated vascular aging. We found that IGF‐1‐deficient mice exhibit neurovascular uncoupling and show a deficit in hippocampal‐dependent spatial memory test, mimicking the aging phenotype. IGF‐1 deficiency significantly impaired cerebromicrovascular endothelial function decreasing NO mediation of neurovascular coupling. IGF‐1 deficiency also impaired glutamate‐mediated CBF responses, likely due to dysregulation of astrocytic expression of metabotropic glutamate receptors and impairing mediation of CBF responses by eicosanoid gliotransmitters. Collectively, we demonstrate that IGF‐1 deficiency promotes cerebromicrovascular dysfunction and neurovascular uncoupling mimicking the aging phenotype, which are likely to contribute to cognitive impairment.
Calpain‐mediated cleavage of DARPP‐32 in Alzheimer's disease
Authors: Cho Kwangmin , Cho Mi‐Hyang , Seo Jung‐Han , Peak Jongjin , Kong Kyoung‐Hye , Yoon Seung‐Yong , Kim Dong‐Hou
Published: July 2015

Toxicity induced by aberrant protein aggregates in Alzheimer's disease (AD) causes synaptic disconnection and concomitant progressive neurodegeneration that eventually impair cognitive function. cAMP‐response element‐binding protein (CREB) is a transcription factor involved in the molecular switch that converts short‐term to long‐term memory. Although disturbances in CREB function have been suggested to cause memory deficits in both AD and AD animal models, the mechanism of CREB dysfunction is still unclear. Here, we show that the dopamine‐ and cAMP‐regulated phosphoprotein 32 kDa (DARPP‐32), a key inhibitor of protein phosphate‐1 (PP‐1) that regulates CREB phosphorylation, is cleaved by activated calpain in both AD brains and neuronal cells treated with amyloid‐β or okadaic acid, a protein phosphatase‐2A inhibitor that induces tau hyperphosphorylation and neuronal death. We found that DARPP‐32 is mainly cleaved at Thr153 by calpain and that this cleavage of DARPP‐32 reduces CREB phosphorylation via loss of its inhibitory function on PP1. Our results suggest a novel mechanism of DARPP‐32–CREB signalling dysregulation in AD.
Cannabis use among Swedish men in adolescence and the risk of adverse life course outcomes: results from a 20 year‐follow‐up study
Authors: Danielsson Anna‐Karin , Falkstedt Daniel , Hemmingsson Tomas , Allebeck Peter , Agardh Emilie
Published: July 2015

Aims

To examine associations between cannabis use in adolescence (at age 18) and unemployment and social welfare assistance in adulthood (at age 40) among Swedish men.

Design

Longitudinal cohort study.

Setting and Participants

A total of 49 321 Swedish men born in 1949–51, who were conscripted to compulsory military service at 18–20 years of age.

Measurements

All men answered two detailed questionnaires at conscription and were subject to examinations of physical aptitude psychological functioning and medical status. By follow‐up in national databases, information on unemployment and social welfare assistance was obtained.

Findings

Individuals who used cannabis at high levels in adolescence had increased risk of future unemployment and of receiving social welfare assistance. Adjusted for all confounders (social background, psychological functioning, health behaviours, educational level, psychiatric diagnoses), an increased relative risk (RR) of unemployment remained in the group reporting cannabis use > 50 times [RR = 1.26, 95% confidence interval (CI) = 1.04–1.53] only. For social welfare assistance, RR in the group reporting cannabis use 1–10 times was 1.15 (95% CI = 1.06–1.26), RR for 11–50 times was 1.21 (95% CI = 1.04–1.42) and RR for > 50 times was 1.38 (95% CI = 1.19–1.62).

Conclusions

Heavy cannabis use among Swedish men in late adolescence appears to be associated with unemployment and being in need of social welfare assistance in adulthood. These associations are not explained fully by other health‐related, social or behavioural problems.
Early‐onset neonatal group B streptococcus sepsis following national risk‐based prevention guidelines
Authors: Darlow Brian A. , Voss Lesley , Lennon Diana R. , Grimwood Keith
Published: July 2015

Background

Neonatal infection with group B streptococcus (GBS) is an important cause of infant mortality. Intrapartum antibiotics reduce early‐onset GBS sepsis, but recommendations vary as to whether they should be offered following antenatal screening or based on risk factors alone. We aimed to determine the incidence of early‐onset GBS sepsis in New Zealand five years after the publication of national risk‐based GBS prevention guidelines.

Materials and Methods

Prospective surveillance of early‐onset GBS sepsis (defined as infection in the first 48 h of life) was undertaken between April 2009 and March 2011 through the auspices of the New Zealand Paediatric Surveillance Unit as part of a survey of infection presenting in the first week of life.

Results

There were 29 cases of confirmed early‐onset GBS sepsis, including one case of meningitis, giving an incidence rate of 0.23 per 1000 (95% CI 0.16–0.33) live births. Three infants (10.3%) died. In 16 cases (55%), a maternal risk factor qualifying the mother for intrapartum antibiotics was present, but only five (31%) received this intervention. A retrospective review of the major hospital laboratory databases for this period identified two additional cases. A secondary sensitivity analysis taking account of these cases provided an estimated national incidence of 0.26 (95% CI 0.18–0.37) per 1000 live births.

Conclusions

Ten years after a similar survey and five years after promoting a single, risk‐based prevention protocol nationally, the incidence of early‐onset GBS disease in New Zealand has more than halved, but opportunities remain to further reduce the rate.
Prevalence of celiac disease in patients with severe food allergy
Authors: Pillon R. , Ziberna F. , Badina L. , Ventura A. , Longo G. , Quaglia S. , De Leo L. , Vatta S. , Martelossi S. , Patano G. , Not T. , Berti I.
Published: July 2015

The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy.
The Construction of Public and Domestic Spheres in the Preclassic Maya Lowlands
Authors: Inomata Takeshi , MacLellan Jessica , Burham Melissa
Published: July 2015

There exists a significant theoretical imbalance in the archaeological study of domestic and public domains. Although the domestic has been an important focus of theoretical discussion, there is not an adequate archaeological theory on the public, and the study of the public is often confused with that of elite strategies. We believe that this theoretical imbalance strongly shapes interpretations of early Maya society, leading to the problematic assumption that the domestic existed before the public. Jürgen Habermas's concept of public sphere provides a logical starting point for the exploration of this issue. At the lowland Maya site of Ceibal, Guatemala, a public ceremonial complex was built around 1000 B.C.E. when some groups began to adopt a sedentary and agricultural way of life, but some populations probably maintained residential mobility and a mixed economy for the next few centuries. During this period of profound social change, the new public sphere probably served as an arena of negotiation between diverse groups through communal rituals. The construction of minor temples and the disappearance of figurines several centuries later signal a transformation of domestic ritual through its integration into a more homogeneous system of ritual practice rooted in earlier public rites. [public sphere, political process, Maya, archaeology]
Analysis of Medieval and Post‐Medieval Glass Fragments from the Dubrovnik Region (Croatia)
Authors: Topić N. , Bogdanović Radović I. , Fazinić S. , Skoko Ž.
Published: July 2015

Dubrovnik was an important trade city throughout the medieval and post‐medieval time period, maintaining its own glass production from the 14th to the 16th century. Unfortunately, Dubrovnik glass discoveries have not been well investigated up until now, except via archival data in large data analyses. In the following work, we will shed new light on the glass material found in this region, which has diverse origins, chronology, typology and style. Medieval and post‐medieval glass finds (10th/12th–18th centuries) discovered during archaeological excavations in Dubrovnik and the Dubrovnik region were analysed using particle‐induced X‐ray emission (PIXE) and particle‐induced gamma‐ray emission (PIGE), which revealed three main compositional groups: natron glass, plant‐ash glass and potash glass. This demonstrates the important commercial links present between Dubrovnik and other major glass‐making centres.
Ultrasonographic imaging of abomasal milk clotting and abomasal diameter in healthy and diarrheic calves
Authors: Kirchner Daniela , Schwedhelm Lea , Wenge Julia , Steinhöfel Ilka , Heinrich Christian , Coenen Manfred , Bachmann Lisa
Published: July 2015

In case of diarrhea calves are treated with oral rehydration solutions (ORS), which are known to increase abomasalpHand inhibit milk clottingin vitro. Nevertheless, recent studies have shown thatORSwithHCO3‐≤ 62 mmol/L do not interfere with abomasal milk clotting in healthy calves. However, in diarrheic calves, feedingORSand milk simultaneously may disturb abomasal curd formation and exacerbate diarrhea due to faster abomasal passage of ingesta. Therefore, the aim of the present study was to ultrasonographically examine abomasal milk clotting and diameter after feeding milk and milk replacer (MR) with and withoutORSto healthy and diarrheic calves. Abomasal curd formation and diameter in healthy and diarrheic calves were ultrasonographically imaged before and after feeding milk,MRandORSprepared in milk orMR. Feeding mixtures of milk orMRwithORSdid not cause any remarkable differences in the ultrasonographic images of abomasal content. Moreover, abomasal milk clotting was not disturbed due to diarrhea. Statistically significant differences of abomasal diameter after feeding between healthy and diarrheic calves indicated that abomasal emptying is delayed in diarrheic calves. Hence, further studies are needed to determine reasons for decelerated abomasal passage in calves suffering from diarrhea.
Is Minocycline an Antiviral Agent? A Review of Current Literature
Authors: Nagarakanti Sandhya , Bishburg Eliahu
Published: July 2015

Minocycline is a second‐generation semi‐synthetic derivative of tetracycline and has well‐known anti‐bacterial effects. The drug possesses anti‐inflammatory, anti‐oxidant, anti‐apoptotic and immunomodulatory effects. The drug is widely used in bacterial infections and non‐infectious conditions such as acne, dermatitis, periodontitis and neurodegenerative conditions. Minocycline was shown to have antiviral activity in vitro and also against different viruses in some animal models. Some studies have been done on human patients infected with Human Immunodeficiency Virus. We have review the available data regarding minocycline activity as an antiviral agent.
A Model-Based Initial Guess for Estimating Parameters in Systems of Ordinary Differential Equations
Authors: Dattner Itai
Published: July 2015

The inverse problem of parameter estimation from noisy observations is a major challenge in statistical inference for dynamical systems. Parameter estimation is usually carried out by optimizing some criterion function over the parameter space. Unless the optimization process starts with a good initial guess, the estimation may take an unreasonable amount of time, and may converge to local solutions, if at all. In this article, we introduce a novel technique for generating good initial guesses that can be used by any estimation method. We focus on the fairly general and often applied class of systems linear in the parameters. The new methodology bypasses numerical integration and can handle partially observed systems. We illustrate the performance of the method using simulations and apply it to real data.
Baicalein ameliorates renal interstitial fibrosis by inducing myofibroblast apoptosis in vivo and in vitro
Authors: Wang Wei , Zhou Pang‐hu , Xu Chang‐geng , Zhou Xiang‐jun , Hu Wei , Zhang Jie
Published: July 2015

Objective

To investigate the anti‐fibrotic effects of baicalein and its influence on myofibroblasts in vivo and in vitro.

Materials and Methods

An in vivo unilateral ureteric obstruction (UUO) mouse model and an in vitro transforming growth factor β1 (TGF‐β1) activated normal rat kidney (NRK)‐49F cell model were established. Baicalein treatment was then investigated in these models to assess its anti‐fibrotic effects and potential mechanisms of action.

Results

Baicalein attenuated renal fibrosis by ameliorating kidney injury, reducing deposition of fibronectin and collagen type 1, and inducing apoptosis in myofibroblasts in the UUO mouse model. Baicalein also induced apoptosis of TGF‐β1‐activated myofibroblasts in vitro in a dose‐dependent manner. Furthermore, baicalein triggered a cascade of mitochondrion‐associated apoptosis by upregulating cleaved‐caspase‐3, Bcl2‐associated X protein (Bax), and cleaved‐caspase‐9 while downregulating the protein expression of B‐cell lymphoma 2 (Bcl‐2). Additionally, down‐regulation of phosphorylated protein kinase B (pAkt) was found in the baicalein‐induced pro‐apoptotic components.

Conclusions

The present findings show that baicalein can ameliorate tubulointerstitial fibrosis by inducing myofibroblast apoptosis through the mitochondrion‐associated intrinsic pathway, which may be mediated by the inhibition of the phosphoinositide‐3‐kinase/Akt (PI3k/Akt) pathway.
Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation
Authors: Huo Zhi‐Jun , Wang Shi‐Jiang , Wang Zhi‐Qi , Zuo Wen‐Shu , Liu Ping , Pang Bo , Liu Kai
Published: July 2015

The present study was performed to investigate the therapeutic performance of polymer‐lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib‐loaded polymer‐lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide‐co‐glycolide]‐D‐a‐tocopheryl polyethylene glycol 1000 succinate [PLGA–TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE‐PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF‐7 cancer cells in a time‐ and concentration‐dependent manner. Moreover, LPT‐loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib‐loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers.
p53 activated by AND gate genetic circuit under radiation and hypoxia for targeted cancer gene therapy
Authors: Ding Miao , Li Rong , He Rong , Wang Xingyong , Yi Qijian , Wang Weidong
Published: July 2015

Radio‐activated gene therapy has been developed as a novel therapeutic strategy against cancer; however, expression of therapeutic gene in peritumoral tissues will result in unacceptable toxicity to normal cells. To restrict gene expression in targeted tumor mass, we used hypoxia and radiation tolerance features of tumor cells to develop a synthetic AND gate genetic circuit through connecting radiation sensitivity promoter cArG6, heat shock response elements SNF1, HSF1 and HSE4 with retroviral vector plxsn. Their construction and dynamic activity process were identified through downstream enhanced green fluorescent protein and wtp53 expression in non‐small cell lung cancer A549 cells and in a nude mice model. The result showed that AND gate genetic circuit could be activated by lower required radiation dose (6 Gy) and after activated, AND gate could induce significant apoptosis effects and growth inhibition of cancer cells in vitro and in vivo. The radiation‐ and hypoxia‐activated AND gate genetic circuit, which could lead to more powerful target tumoricidal activity represented a promising strategy for both targeted and effective gene therapy of human lung adenocarcinoma and low dose activation character of the AND gate genetic circuit implied that this model could be further exploited to decrease side‐effects of clinical radiation therapy.