bluuebunny/crossref_metadata_2025_split huggingface dataset:
EMT Transition Alters Interstitial Fluid Flow–Induced Signaling in ERBB2-Positive Breast Cancer Cells
Authors: Tchafa Alimatou M. , Ta Mi , Reginato Mauricio J. , Shieh Adrian C. 
Published: January 2015

Abstract
A variety of biophysical forces are altered in the tumor microenvironment (TME) and these forces can influence cancer progression. One such force is interstitial fluid flow (IFF)—the movement of fluid through the tissue matrix. IFF was previously shown to induce invasion of cancer cells, but the activated signaling cascades remain poorly understood. Here, it is demonstrated that IFF induces invasion of ERBB2/HER2-expressing breast cancer cells via activation of phosphoinositide-3-kinase (PI3K). In constitutively activate ERBB2-expressing cells that have undergone epithelial-to-mesenchymal transition (EMT), IFF-mediated invasion requires the chemokine receptor CXCR4, a gradient of its ligand CXCL12, and activity of the PI3K catalytic subunits p110α and β. In wild-type ERBB2-expressing cells, IFF-mediated invasion is chemokine receptor–independent and requires only p110α activation. To test whether cells undergoing EMT alter their signaling response to IFF, TGFβ1 was used to induce EMT in wild-type ERBB2-expressing cells, resulting in IFF-induced invasion dependent on CXCR4 and p110β.
Implications: This study identifies a novel signaling mechanism for interstitial flow–induced invasion of ERBB2-expressing breast cancer cells, one that depends on EMT and acts through a CXCR4–PI3K pathway. These findings suggest that the response of cancer cells to interstitial flow depends on EMT status and malignancy. Mol Cancer Res; 13(4); 755–64. ©2015 AACR.
Low-dose decitabine promotes megakaryocyte maturation and platelet production in healthy controls and immune thrombocytopenia
Authors: Zhou Hai , Hou Yu , Liu Xuena , Qiu Jihua , Feng Qi , Wang Yawen , Zhang Xu , Min Yanan , Shao Linlin , Liu Xinguang , Li Guosheng , Li Lizhen , Yang Lei , Xu Shuqian , Ni Heyu , Peng Jun , Hou Ming 
Published: January 2015

SummaryImpaired megakaryocyte maturation and insufficient platelet production have been shown to participate in the pathogenesis of immune thrombocytopenia (ITP). Our previous study demonstrated that low expression of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in megakaryocytes contributed to impaired platelet production in ITP. Decitabine (DAC), a demethylating agent, is known to promote cell differentiation and maturation at low doses. However, whether decitabine is potential in promoting megakaryocyte maturation and platelet release in ITP is unclear. In this study, we evaluated the effect of DAC on megakaryocyte maturation and platelet release in the presence of ITP plasma that has been shown to cause impaired megakaryocyte maturation and platelet production. We observed that low-dose DAC (10 nM) could significantly increase the number of mature polyploid (≥ 4N) megakaryocytes in cultures with plasma from healthy controls and more than one-half of ITP patients in vitro. Furthermore, the number of platelets released from these megakaryocytes significantly increased compared with those untreated with DAC. In these megakaryocytes, DAC significantly enhanced TRAIL expression via decreasing its promoter methylation status. These findings demonstrate that low-dose DAC can promote megakaryocyte maturation and platelet production and enhance TRAIL expression in megakaryocytes in healthy controls and ITP. The potential therapeutic role of low-dose DAC may be beneficial for thrombocytopenic disorders.H. Z. and Y. H. contributed equally to this work.
Diversity and impact of rare variants in genes encoding the platelet G protein-coupled receptors
Authors: Jones Matthew L. , Norman Jane E. , Morgan Neil V. , Mundell Stuart J. , Lordkipanidzé Marie , Lowe Gillian C. , Daly Martina E. , Simpson Michael A. , Drake Sian , Watson Steve P. , Mumford Andrew D. 
Published: January 2015

SummaryPlatelet responses to activating agonists are influenced by common population variants within or near G protein-coupled receptor (GPCR) genes that affect receptor activity. However, the impact of rare GPCR gene variants is unknown. We describe the rare single nucleotide variants (SNVs) in the coding and splice regions of 18 GPCR genes in 7,595 exomes from the 1,000-genomes and Exome Sequencing Project databases and in 31 cases with inherited platelet function disorders (IPFDs). In the population databases, the GPCR gene target regions contained 740 SNVs (318 synonymous, 410 missense, 7 stop gain and 6 splice region) of which 70 % had global minor allele frequency (MAF) < 0.05 %. Functional annotation using six computational algorithms, experimental evidence and structural data identified 156/740 (21 %) SNVs as potentially damaging to GPCR function, most commonly in regions encoding the transmembrane and C-terminal intracellular receptor domains. In 31 index cases with IPFDs (Gi-pathway defect n=15; secretion defect n=11; thromboxane pathway defect n=3 and complex defect n=2) there were 256 SNVs in the target regions of 15 stimulatory platelet GPCRs (34 unique; 12 with MAF< 1 % and 22 with MAF≥ 1 %). These included rare variants predicting R122H, P258T and V207A substitutions in the P2Y12 receptor that were annotated as potentially damaging, but only partially explained the platelet function defects in each case. Our data highlight that potentially damaging variants in platelet GPCR genes have low individual frequencies, but are collectively abundant in the population. Potentially damaging variants are also present in pedigrees with IPFDs and may contribute to complex laboratory phenotypes.
Self‐Controlled Case‐Series Study to Verify the Effect of Adherence to Beta‐Blockers in Secondary Prevention of Myocardial Infarction
Authors: Di Bartolomeo Stefano , Marino Massimiliano , Guastaroba Paolo , Valent Francesca , De Palma Rossana 
Published: January 2015

Background

Beta‐blockers (
BB
) are recommended in secondary prevention of acute myocardial infarction (
AMI
), but adherence to prescription medication is a recognized problem. Most literature on the consequences of poor adherence to prescribed
BB
is limited by the possibility of “healthy adherer bias” and better‐designed studies have been advocated.

Methods and Results

We investigated the association between adherence to
BB
prescription and risk of subsequent
AMI
s using the self‐controlled case series design, which allows improved control of interpersonal confounding, being based on intrapersonal comparisons. From all the 30 089 patients hospitalized for
AMI
in the years 2009–2011 in an Italian region we selected those that suffered subsequent
AMI
s at days 31 to 365 from discharge (1328), and then the 1207 that had at least one
BB
prescription collected at any of the regional pharmacies. Using information on prescriptions, each individual's observation time was then divided into periods exposed or unexposed to
BB
and the relative
AMI
incidence rate ratios (
IRR
) of
BB
exposure were estimated by conditional
P
oisson regression. The
IRR
(rate of recurrent
AMI
in exposed versus unexposed periods) was 0.79 (95%
CI
0.69 to 0.90,
P
=0.001). Various sensitivity analyses confirmed the robustness to possible failure of assumptions, ie, considering only first recurrences (
IRR
0.76, 95%
CI
0.66 to 0.88,
P
<0.001), excluding cardiovascular fatalities (
IRR
0.76, 95%
CI
0.65 to 0.89,
P
<0.001), and excluding individuals with long hospital admissions (
IRR
0.60, 95%
CI
0.43 to 0.83,
P
=0.002).

Conclusions

Adherence to recommended
BB
therapy was associated with a 20% reduction of recurrent
AMI
s, consistently with previous research, but with decreased concerns about healthy‐adherer bias.
Cytomegalovirus in pediatric systemic lupus erythematosus: prevalence and clinical manifestations
Authors: Rozenblyum E V , Levy D M , Allen U , Harvey E , Hebert D , Silverman E D 
Published: January 2015

Cytomegalovirus (CMV) is a beta-herpesvirus and antibodies to this virus are common in patients with systemic lupus erythematosus (SLE). However, few studies have examined the relationship between CMV infection and SLE. Objectives Our objectives were: 1) to determine the prevalence of CMV infection at the time of SLE diagnosis, and 2) to determine the risk factors for CMV infection. Methods A database review of 670 patients with pediatric SLE (pSLE) seen over a 20-year period identified seven patients with a CMV infection detected at the time of diagnosis of SLE. CMV was diagnosed by serology, urine and bronchoalveolar lavage. Clinical manifestations, laboratory findings, virology studies and treatments were reviewed. Results CMV infection was detected in seven patients at the time of SLE diagnosis (1.04% of total cohort): six were female: mean age was 13 years. Predominant features included non-Caucasian ethnicity ( p < 0.01 as compared to total SLE cohort), persistent fevers on prednisone in seven and nephrotic syndrome in four. Laboratory findings included: anemia in seven, lymphopenia in five, elevated liver enzymes in four, with anti-dsDNA and anti-RNP antibodies present in six and five, respectively. Six patients received ganciclovir and CMV hyperimmune globulin (Cytogam®) with the continuation of prednisone during CMV treatment. Six of seven fully recovered without sequelae (one without treatment) but one patient died with active CMV infection. Conclusions There were 1.04% of patients with pSLE who developed CMV infection. All were of non-Caucasian ethnicity. Persistent fever despite prednisone, with concomitant anemia, may be additional clues to CMV infection in pSLE. We suggest all patients have routine testing for CMV immunity at initial presentation of pSLE.
Coercion in nursing homes
Authors: Gjerberg Elisabeth , Lillemoen Lillian , Pedersen Reidar , Førde Reidun 
Published: January 2015

Background: Studies have demonstrated the extensive use of coercion in Norwegian nursing homes, which represents ethical, professional as well as legal challenges to the staff. We have, however, limited knowledge of the experiences and views of nursing home patients and their relatives. Objectives: The aim of this study is to explore the perspectives of nursing home patients and next of kin on the use of coercion; are there situations where the use of coercion can be defended, and if so, under which circumstances? Methods: The data are based on individual interviews with 35 patients living in six nursing homes and seven focus group interviews with 60 relatives. Ethical considerations: Participation was based on written informed consent, and the study was approved by the Regional Committees for Medical and Health Research Ethics. Results: More than half of the patients and the majority of the relatives accepted the use of coercion, trusting the staff to act in the patient’s best interest. However, the acceptance of coercion is strongly related to the patients’ lack of understanding, to prevent health risks and to preserve the patient’s dignity. Conclusion: The majority of nursing home patients and relatives accepted the use of coercion in specific situations, while at the same time they emphasised the need to try alternative strategies first. There is still a need for good qualitative research on the use of coercion in nursing homes, especially with a closer focus on the perspectives and experiences of nursing home patients.
Psychosocial experiences of chronic illness in individuals with an intellectual disability
Authors: Flynn Samantha , Hulbert-Williams Nicholas , Hulbert-Williams Lee , Bramwell Ros 
Published: January 2015

Background: Increased life expectancy has led to an increase in diagnoses of chronic illness in people with an intellectual disability; despite this increase, research about the psychological impact is rare. This review explored the psychosocial experiences of chronic illness in adults with an intellectual disability, revealing potential predictors and moderators of these experiences. Methods: Online databases were systematically searched to identify relevant literature, using predefined inclusion criteria. Of the 25,058 titles initially identified, 4 were included, that is, those collecting data on people with an intellectual disability and diagnosed with cancer ( n = 2), chronic pain ( n = 1) and diabetes ( n = 1). Results: Narrative synthesis of the data identified six themes, namely, (1) delayed diagnosis, (2) information, communication and understanding, (3) negative psychological consequences, (4) negative physical consequences, (5) social perception and (6) social support. Conclusions: There are unmet needs within this population, including a lack of assistance in understanding their illness. A substantial gap in the literature should be addressed through further empirical work.
AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice
Authors: Crudele Julie M. , Finn Jonathan D. , Siner Joshua I. , Martin Nicholas B. , Niemeyer Glenn P. , Zhou Shangzhen , Mingozzi Federico , Lothrop Clinton D. , Arruda Valder R. 
Published: January 2015

Key Points
Liver-restricted expression of FIX-Padua induces immune tolerance to the transgene in hemophilia B inhibitor dog models. Long-term toxicity studies show no increased risk of thrombogenicity of FIX-Padua in mice and dogs.
Current and potential geographical distribution of Platymeris biguttatus (Linnaeus, 1767) with description of nymphs
Authors: Chłond Dominik , Bugaj-Nawrocka Agnieszka , Junkiert Łukasz 
Published: January 2015

AbstractBackgroundThe description ofPlatymeris biguttatus(Linnaeus 1767) nymphal instars as well as the prediction of the potentially suitable ecological niche was the main goal of this study. Our research was based on 258 specimens ofP. biguttatusspecies of museum collections. A set of 23 environmental predictor variables covering Africa was used at ecological niche modeling - a method performed using the Maxent software to prepare potential distribution maps for this species.ResultsThe results suggested the most suitable areas seen as potentially suitable ecological niche forP. biguttatusin Africa. A jackknife test showed that temperature seasonality and percentage of tree cover were among the most important environmental variables affecting the distribution of the species. The analysis of climate preferences shows that most of the potentially suitable niches for this species were located in the area of tropical savanna climate, with a small participation of tree vegetation.ConclusionsP. biguttatuswas only known to be widely distributed in the tropical part of continental Africa. Thanks to the ecological niche modeling methods and the museum data on the occurrence of the species, we introduced new information about potentially suitable ecological niches and the possible range of distribution.
Establishment of a microsatellite set for noninvasive paternity testing in free-ranging Macaca mulatta tcheliensis in Mount Taihangshan area, Jiyuan, China
Authors: Wang Bai-Shi , Wang Zhen-Long , Tian Jun-Dong , Cui Zhen-Wei , Lu Ji-Qi 
Published: January 2015

Abstract

Background
Within multi-male and multi-female mammalian societies, paternity assignment is crucial for evaluating male reproductive success, dominance hierarchy, and inbreeding avoidance. It is, however, difficult to determine paternity because of female promiscuity during reproduction. Noninvasive molecular techniques (e.g., fecal DNA) make it possible to match the genetic father to his offspring. In the current study, a troop of free-ranging Taihangshan macaques (Macaca mulatta tcheliensis) in Mt. Taihangshan area, Jiyuan, China, was selected for studying the paternity. We successfully screened a set of microsatellite loci from fecal DNA and evaluated the efficiency of these loci for paternity testing using clearly recorded data of maternity.

Results
The results showed that: 1) ten loci out of 18 candidate microsatellite loci were amplified successfully in the fecal samples of Taihangshan macaques. The error probability in maternity assignments and paternity testing was very low as indicated by their power of discrimination (0.70 to 0.95), power of exclusion (0.43 to 0.84), and the values of polymorphic information content ranging from 0.52 to 0.82; 2) the combined probability of exclusion in paternity testing for ten qualified loci was as high as 99.999%, and the combined probability of exclusion reached 99.99% when the seven most polymorphic loci were adopted; 3) the offspring were assigned to their biological mother correctly and also matched with their genetic father.

Conclusions
We concluded that the ten polymorphic microsatellite loci, especially a core set of seven most polymorphic loci, provided an effective and reliable tool for noninvasive paternity testing in free-ranging rhesus macaques.
Membrane dynamics in autophagosome biogenesis
Authors: Carlsson Sven R. , Simonsen Anne 
Published: January 2015

Bilayered phospholipid membranes are vital to the organization of the living cell. Based on fundamental principles of polarity, membranes create borders allowing defined spaces to be encapsulated. This compartmentalization is a prerequisite for the complex functional design of the eukaryotic cell, yielding localities that can differ in composition and operation. During macroautophagy, cytoplasmic components become enclosed by a growing double bilayered membrane, which upon closure creates a separate compartment, the autophagosome. The autophagosome is then primed for fusion with endosomal and lysosomal compartments, leading to degradation of the captured material. A large number of proteins have been found to be essential for autophagy, but little is known about the specific lipids that constitute the autophagic membranes and the membrane modeling events that are responsible for regulation of autophagosome shape and size. In this Commentary, we review the recent progress in our understanding of the membrane shaping and remodeling events that are required at different steps of the autophagy pathway.
This article is part of a Focus on Autophagosome biogenesis. For further reading, please see related articles: ‘ERES: sites for autophagosome biogenesis and maturation?’ by Jana Sanchez-Wandelmer et al. (J. Cell Sci. 128, 185-192) and ‘WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome’ by Tassula Proikas-Cezanne et al. (J. Cell Sci. 128, 207-217).
WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome
Authors: Proikas-Cezanne Tassula , Takacs Zsuzsanna , Dönnes Pierre , Kohlbacher Oliver 
Published: January 2015

Autophagy is a pivotal cytoprotective process that secures cellular homeostasis, fulfills essential roles in development, immunity and defence against pathogens, and determines the lifespan of eukaryotic organisms. However, autophagy also crucially contributes to the development of age-related human pathologies, including cancer and neurodegeneration. Macroautophagy (hereafter referred to as autophagy) clears the cytoplasm by stochastic or specific cargo recognition and destruction, and is initiated and executed by autophagy related (ATG) proteins functioning in dynamical hierarchies to form autophagosomes. Autophagosomes sequester cytoplasmic cargo material, including proteins, lipids and organelles, and acquire acidic hydrolases from the lysosomal compartment for cargo degradation. Prerequisite and essential for autophagosome formation is the production of phosphatidylinositol 3-phosphate (PtdIns3P) by phosphatidylinositol 3-kinase class III (PI3KC3, also known as PIK3C3) in complex with beclin 1, p150 (also known as PIK3R4; Vps15 in yeast) and ATG14L. Members of the human WD-repeat protein interacting with phosphoinositides (WIPI) family play an important role in recognizing and decoding the PtdIns3P signal at the nascent autophagosome, and hence function as autophagy-specific PtdIns3P-binding effectors, similar to their ancestral yeast Atg18 homolog. The PtdIns3P effector function of human WIPI proteins appears to be compromised in cancer and neurodegeneration, and WIPI genes and proteins might present novel targets for rational therapies. Here, we summarize the current knowledge on the roles of the four human WIPI proteins, WIPI1–4, in autophagy.
This article is part of a Focus on Autophagosome biogenesis. For further reading, please see related articles: ‘ERES: sites for autophagosome biogenesis and maturation?’ by Jana Sanchez-Wandelmer et al. (J. Cell Sci. 128, 185-192) and ‘Membrane dynamics in autophagosome biogenesis’ by Sven R. Carlsson and Anne Simonsen (J. Cell Sci. 128, 193-205).
Synchronized Activation of π-Conjugated Molecules toward Self-Assembly: Precisely Controlling the Hysteresis of the Metastable State along Microflow
Authors: Numata Munenori , Kozawa Tomohiro , Nogami Rie , Tanaka Kaori , Sanada Yusuke , Sakurai Kazuo 
Published: January 2015

Abstract
In this article, we have demonstrated that π–π stacking interactions can be synchronized through the rapid hydration of π-conjugated molecules, generating a sort of metastable state. The self-assembly process of the group of molecules activated with the same timing was directly correlated to the spatial pathway along the microflow channel. Various micrometer-sized molecular architectures having desired molecular packing, therefore, can be created through the precise regulation of the flowing self-assembly field in a top-down fashion, where the hysteresis of the spatial pathway was recorded in the resultant assemblies.
Genetic Markers for Western Corn Rootworm Resistance to Bt Toxin
Authors: Flagel Lex E , Swarup Shilpa , Chen Mao , Bauer Christopher , Wanjugi Humphrey , Carroll Matthew , Hill Patrick , Tuscan Meghan , Bansal Raman , Flannagan Ronald , Clark Thomas L , Michel Andrew P , Head Graham P , Goldman Barry S 
Published: January 2015

Abstract
Western corn rootworm (WCR) is a major maize (Zea mays L.) pest leading to annual economic losses of more than 1 billion dollars in the United States. Transgenic maize expressing insecticidal toxins derived from the bacterium Bacillus thuringiensis (Bt) are widely used for the management of WCR. However, cultivation of Bt-expressing maize places intense selection pressure on pest populations to evolve resistance. Instances of resistance to Bt toxins have been reported in WCR. Developing genetic markers for resistance will help in characterizing the extent of existing issues, predicting where future field failures may occur, improving insect resistance management strategies, and in designing and sustainably implementing forthcoming WCR control products. Here, we discover and validate genetic markers in WCR that are associated with resistance to the Cry3Bb1 Bt toxin. A field-derived WCR population known to be resistant to the Cry3Bb1 Bt toxin was used to generate a genetic map and to identify a genomic region associated with Cry3Bb1 resistance. Our results indicate that resistance is inherited in a nearly recessive manner and associated with a single autosomal linkage group. Markers tightly linked with resistance were validated using WCR populations collected from Cry3Bb1 maize fields showing significant WCR damage from across the US Corn Belt. Two markers were found to be correlated with both diet (R2 = 0.14) and plant (R2 = 0.23) bioassays for resistance. These results will assist in assessing resistance risk for different WCR populations, and can be used to improve insect resistance management strategies.