bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infection Dynamics and Immune Response in a Newly Described
Drosophila
-Trypanosomatid Association
Authors: Hamilton Phineas T. , Votýpka Jan , Dostálová Anna , Yurchenko Vyacheslav , Bird Nathan H. , Lukeš Julius , Lemaitre Bruno , Perlman Steve J. 
Published: September 2015

ABSTRACT

Trypanosomatid parasites are significant causes of human disease and are ubiquitous in insects. Despite the importance of
Drosophila melanogaster
as a model of infection and immunity and a long awareness that trypanosomatid infection is common in the genus, no trypanosomatid parasites naturally infecting
Drosophila
have been characterized. Here, we establish a new model of trypanosomatid infection in
Drosophila
—
Jaenimonas drosophilae
, gen. et sp. nov. As far as we are aware, this is the first
Drosophila
-parasitic trypanosomatid to be cultured and characterized. Through experimental infections, we find that
Drosophila falleni
, the natural host, is highly susceptible to infection, leading to a substantial decrease in host fecundity.
J. drosophilae
has a broad host range, readily infecting a number of
Drosophila
species, including
D. melanogaster
, with oral infection of
D. melanogaster
larvae resulting in the induction of numerous immune genes. When injected into adult hemolymph,
J. drosophilae
kills
D. melanogaster
, although interestingly, neither the Imd nor the Toll pathway is induced and Imd mutants do not show increased susceptibility to infection. In contrast, mutants deficient in drosocrystallin, a major component of the peritrophic matrix, are more severely infected during oral infection, suggesting that the peritrophic matrix plays an important role in mediating trypanosomatid infection in
Drosophila
. This work demonstrates that the
J. drosophilae
-
Drosophila
system can be a powerful model to uncover the effects of trypanosomatids in their insect hosts.

IMPORTANCE
Trypanosomatid parasites are ubiquitous in insects and are significant causes of disease when vectored to humans by blood-feeding insects. In recent decades,
Drosophila
has emerged as the predominant insect model of infection and immunity and is also known to be infected by trypanosomatids at high rates in the wild. Despite this, there has been almost no work on their trypanosomatid parasites, in part because
Drosophila
-specific trypanosomatids have been resistant to culturing. Here, we present the first isolation and detailed characterization of a trypanosomatid from
Drosophila
, finding that it represents a new genus and species,
Jaenimonas drosophilae
. Using this parasite, we conducted a series of experiments that revealed many of the unknown aspects of trypanosomatid infection in
Drosophila
, including host range, transmission biology, dynamics of infection, and host immune response. Taken together, this work establishes
J. drosophilae
as a powerful new opportunity to study trypanosomatid infections in insects.
Body mass index in early and middle adult life: prospective associations with myocardial infarction, stroke and diabetes over a 30-year period: the British Regional Heart Study
Authors: Owen Christopher G , Kapetanakis Venediktos V , Rudnicka Alicja R , Wathern Andrea K , Lennon Lucy , Papacosta Olia , Cook Derek G , Wannamethee S Goya , Whincup Peter H 
Published: September 2015

ObjectivesAdiposity in middle age is an established risk factor for cardiovascular disease and type 2 diabetes; less is known about the impact of adiposity from early adult life. We examined the effects of high body mass index (BMI) in early and middle adulthood on myocardial infarction (MI), stroke and diabetes risks.DesignA prospective cohort study.Participants7735 men with BMI measured in middle age (40–59 years) and BMI ascertained at 21 years from military records or participant recall.Primary and secondary outcome measures30-year follow-up data for type 2 diabetes, MI and stroke incidence; Cox proportional hazards models were used to examine the effect of BMI at both ages on these outcomes, adjusted for age and smoking status.ResultsAmong 4846 (63%) men (with complete data), a 1 kg/m2higher BMI at 21 years was associated with a 6% (95% CI 4% to 9%) higher type 2 diabetes risk, compared with a 21% (95% CI 18% to 24%) higher diabetes risk for a 1 kg/m2higher BMI in middle age (hazard ratio (HR) 1.21, 95% CI 1.18 to 1.24). Higher BMI in middle age was associated with a 6% (95% CI 4% to 8%) increase in MI and a 4% (95% CI 1% to 7%) increase in stroke; BMI at 21 years showed no associations with MI or stroke risk.ConclusionsHigher BMI at 21 years of age is associated with later diabetes incidence but not MI or stroke, while higher BMI in middle age is strongly associated with all outcomes. Early obesity prevention may reduce later type 2 diabetes risk, more than MI and stroke.
Relationship between implementing interpersonal communication and mass education campaigns in emergency settings and use of reproductive healthcare services: evidence from Darfur, Sudan
Authors: Adam Izzeldin Fadl , Nakamura Keiko , Kizuki Masashi , Al Rifai Rami , Vanching Urnaa 
Published: September 2015

Objectives(1) To examine changes in women's awareness and utilisation of reproductive healthcare services in emergency settings following provision of interpersonal communication (IPC) and mass education campaigns, and (2) to describe factors associated with reproductive healthcare service use in internally displaced person (IDP) camps.SettingThree camps containing 88 984 IDPs in Darfur, Sudan.Participants640 women aged 15−49 who had experienced pregnancy in the camp during the previous 2 years were enrolled in each of two independent cross-sectional surveys 26 months apart.InterventionsIPC and mass education campaigns where community health workers disseminated information by home/shelter visits, clinic sessions, public meetings and other means to raise awareness and promote reproductive healthcare service use.Primary outcome measuresAwareness of the existence of antenatal care (ANC) and tetanus toxoid (TT) vaccination services, reception of ANC and TT vaccination, place of delivery and use of postnatal care (PNC).ResultsThe percentage of women who received home visits, and attended in-clinic sessions and public meetings increased from 61.6% to 86.7%, from 43.0% to 68.8%, and from 3.8% to 39.8%, respectively, between the initial and follow-up surveys. More women were aware of ANC (OR 18.6, 95% CI 13.1 to 26.5) and TT vaccination (OR 3.2, 95% CI 2.4 to 4.4) in the follow-up than the initial survey, after multivariable adjustment. More women received ≥3 ANC visits (OR 8.8, 95% CI 6.4 to 12.0) and ≥3 doses of TT (OR 2.5, 95% CI 1.9 to 3.3), delivered at a healthcare facility (OR 5.4, 95% CI 4.0 to 7.4) and received a PNC visit (OR 5.5, 95% CI 4.0 to 7.7) in the follow-up than in the initial survey, after multivariable adjustment.ConclusionsAwareness about and utilisation of reproductive healthcare services were higher in the follow-up survey. An integrated IPC and mass education campaign is effective for improving women's reproductive health in emergency settings.
Systematic review of the measurement properties of self-report physical activity questionnaires in healthy adult populations
Authors: Silsbury Zoë , Goldsmith Robert , Rushton Alison 
Published: September 2015

ObjectiveThis systematic review evaluated the measurement properties of current self-report physical activity questionnaires (SRPAQs) completed within healthy adult populations.DesignTwo reviewers independently searched seven electronic databases and hand searched for articles investigating measurement properties of a SRPAQ evaluating physical activity over the previous 6 months. Articles published from 1 May 2001 to 4 December 2014 were systematically screened and eligible studies were not limited to English language sources. Articles investigating specific race, gender or socioeconomic populations were excluded.Results10 studies investigating 10 SRPAQs were included. The methodological quality of the included studies was evaluated using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) and ranged from ‘poor’ to ‘good’. The Recent Physical Activity Questionnaire, International Physical Activity Questionnaires and Physical Activity Assessment Tool demonstrated good/excellent test–retest reliability (intra-class coefficient (ICC)=0.76, p<0.0001; r=0.627–0.91; r=0.618, p<0.001, respectively), but variable criterion validity (r=0.67, p<0.0001; r=−0.02–0.43; r=0.392, p<0.01, respectively). The single-item measure showed significant criterion validity against an accelerometer (for moderate to vigorous physical activity (MVPA) k=0.23, 95% CI 0.05 to 0.41; and physical activity ≥10 min bouts 0.39 (95% CI 0.14 to 0.64). Construct validity of the six-point scale and Human Activity Profile varied significantly with age, marital status and presence of comorbidities (p<0.05, <0.01, <0.000 and p<0.05, <0.05, <0.000, respectively). The 1 week Godlin-Shephard recall demonstrated ‘moderate’ validity with the gold standard measure of accelerometry (r=0.43).ConclusionsInconclusive evidence exists. Further investigation of criterion validity of the short-form International Physical Activity Questionnaire is required, as it demonstrated excellent test–retest reliability.PROSPERO numberCRD42012002484.
Search for associated production of Higgs with Z boson in the noncommutative Standard Model at linear colliders
Authors: Selvaganapathy J. , Das Prasanta Kumar , Konar Partha 
Published: September 2015

We study the associated Higgs production with [Formula: see text] boson at future linear colliders in the framework of the minimal noncommutative standard model. Using the Seiberg–Witten map, we calculate the production cross-section considering all orders of the noncommutative parameter [Formula: see text]. We consider the effect of earth’s rotation on the orientation of [Formula: see text] with respect to the laboratory frame and thus on the total cross-section, its azimuthal distribution and rapidity distribution for the machine energy ranging from 0.5 TeV to 3 TeV corresponding to the noncommutative scale [Formula: see text].
Colored knot polynomials: HOMFLY in representation [2, 1]
Authors: Mironov A. , Morozov A. , Morozov An. , Sleptsov A. 
Published: September 2015

This paper starts a systematic description of colored knot polynomials, beginning from the first non-(anti)symmetric representation [Formula: see text]. The project involves several steps: (i) parametrization of big families of knots á la [A. Mironov and A. Morozov, arXiv:1506.00339], (ii) evaluating Racah/mixing matrices for various numbers of strands in various representations á la [A. Mironov, A. Morozov and An. Morozov, J. High Energy Phys. 03, 034 (2012), arXiv:1112.2654], (iii) tabulating and collecting the results at http://www.knotebook.org . In this paper, we discuss only the representation [Formula: see text] and construct all necessary ingredients that allow one to evaluate knot/links represented by three-strand closed parallel braids with inserted double-fat fingers. In particular, it is used to evaluate knots from a 7-parametric family. This family contains over 80% of knots with up to 10 intersections, but does not include mutants.
Src Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer
Authors: Jain Shalini , Wang Xiao , Chang Chia-Chi , Ibarra-Drendall Catherine , Wang Hai , Zhang Qingling , Brady Samuel W. , Li Ping , Zhao Hong , Dobbs Jessica , Kyrish Matt , Tkaczyk Tomasz S. , Ambrose Adrian , Sistrunk Christopher , Arun Banu K. , Richards-Kortum Rebecca , Jia Wei , Seewaldt Victoria L. , Yu Dihua 
Published: September 2015

Abstract
Preventing breast cancer will require the development of targeted strategies that can effectively block disease progression. Tamoxifen and aromatase inhibitors are effective in addressing estrogen receptor–positive (ER+) breast cancer development, but estrogen receptor–negative (ER−) breast cancer remains an unmet challenge due to gaps in pathobiologic understanding. In this study, we used reverse-phase protein array to identify activation of Src kinase as an early signaling alteration in premalignant breast lesions of women who did not respond to tamoxifen, a widely used ER antagonist for hormonal therapy of breast cancer. Src kinase blockade with the small-molecule inhibitor saracatinib prevented the disorganized three-dimensional growth of ER− mammary epithelial cells in vitro and delayed the development of premalignant lesions and tumors in vivo in mouse models developing HER2+ and ER− mammary tumors, extending tumor-free and overall survival. Mechanistic investigations revealed that Src blockade reduced glucose metabolism as a result of an inhibition in ERK1/2–MNK1–eIF4E–mediated cap-dependent translation of c-Myc and transcription of the glucose transporter GLUT1, thereby limiting energy available for cell growth. Taken together, our results provide a sound rationale to target Src pathways in premalignant breast lesions to limit the development of breast cancers. Cancer Res; 75(22); 4863–75. ©2015 AACR.
The MYC–WDR5 Nexus and Cancer
Authors: Thomas Lance R. , Foshage Audra M. , Weissmiller April M. , Tansey William P. 
Published: September 2015

Abstract
The MYC oncogenes encode a family of transcription factors that feature prominently in cancer. MYC proteins are overexpressed or deregulated in a majority of malignancies and drive tumorigenesis by inducing widespread transcriptional reprogramming that promotes cell proliferation, metabolism, and genomic instability. The ability of MYC to regulate transcription depends on its dimerization with MAX, which creates a DNA-binding domain that recognizes specific sequences in the regulatory elements of MYC target genes. Recently, we discovered that recognition of target genes by MYC also depends on its interaction with WDR5, a WD40-repeat protein that exists as part of several chromatin-regulatory complexes. Here, we discuss how interaction of MYC with WDR5 could create an avidity-based chromatin recognition mechanism that allows MYC to select its target genes in response to both genetic and epigenetic determinants. We rationalize how the MYC–WDR5 interaction provides plasticity in target gene selection by MYC and speculate on the biochemical and genomic contexts in which this interaction occurs. Finally, we discuss how properties of the MYC–WDR5 interface make it an attractive point for discovery of small-molecule inhibitors of MYC function in cancer cells. Cancer Res; 75(19); 4012–5. ©2015 AACR.
MEK Inhibitor Selumetinib (AZD6244; ARRY-142886) Prevents Lung Metastasis in a Triple-Negative Breast Cancer Xenograft Model
Authors: Bartholomeusz Chandra , Xie Xuemei , Pitner Mary Kathryn , Kondo Kimie , Dadbin Ali , Lee Jangsoon , Saso Hitomi , Smith Paul D. , Dalby Kevin N. , Ueno Naoto T. 
Published: September 2015

AbstractPatients with triple-negative breast cancer (TNBC) have a poor prognosis because TNBC often metastasizes, leading to death. Among patients with TNBC, those with extracellular signal-regulated kinase 2 (ERK2)-overexpressing tumors were at higher risk of death than those with low-ERK2-expressing tumors (hazard ratio, 2.76; 95% confidence interval, 1.19–6.41). The MAPK pathway has been shown to be a marker of breast cancer metastasis, but has not been explored as a potential therapeutic target for preventing TNBC metastasis. Interestingly, when we treated TNBC cells with the allosteric MEK inhibitor selumetinib, cell viability was not reduced in two-dimensional culture. However, in three-dimensional culture, selumetinib changed the mesenchymal phenotype of TNBC cells to an epithelial phenotype. Cells that undergo epithelial–mesenchymal transition (EMT) are thought to contribute to the metastatic process. EMT leads to generation of mesenchymal-like breast cancer cells with stem cell–like characteristics and a CD44+CD24−/low expression pattern. We tested the hypothesis that targeted inhibition of the MAPK pathway by selumetinib inhibits acquisition of the breast cancer stem cell phenotype and prevents lung metastasis of TNBC. TNBC cells treated with selumetinib showed inhibition of anchorage-independent growth, an indicator of in vivo tumorigenicity (P &lt; 0.005), and decreases in the CD44+CD24−/low fraction, ALDH1 activity, and mammosphere-forming efficiency. Mice treated with selumetinib formed significantly fewer lung metastases than control mice injected with vehicle (P &lt; 0.05). Our data demonstrate that MEK inhibitors can inhibit breast cancer stem cells and may have clinical potential for the prevention of metastasis in certain cases in which tumors are MAPK dependent. Mol Cancer Ther; 14(12); 2773–81. ©2015 AACR.
Synthesis of an Endogenous Steroidal Na Pump Inhibitor Marinobufagenin, Implicated in Human Cardiovascular Diseases, Is Initiated by CYP27A1 via Bile Acid Pathway
Authors: Fedorova Olga V. , Zernetkina Valentina I. , Shilova Victoria Y. , Grigorova Yulia N. , Juhasz Ondrej , Wei Wen , Marshall Courtney A. , Lakatta Edward G. , Bagrov Alexei Y. 
Published: September 2015

Background—
The bioactive steroid, marinobufagenin, is an endogenous Na/K-ATPase bufadienolide inhibitor that is synthesized by adrenocortical and placental cells. Marinobufagenin binding to Na/K-ATPase initiates profibrotic cell signaling, and heightened marinobufagenin levels are implicated in the pathogenesis of hypertension, preeclampsia, and chronic kidney disease. Steroids are derived from cholesterol through the traditional steroidogenesis pathway initiated by enzyme CYP11A1, and via the acidic bile acid pathway, which is controlled by enzyme CYP27A1. The mechanism of marinobufagenin biosynthesis in mammals, however, remains unknown.

Methods and Results—

Here, we show that post-transcriptional silencing of the
CYP27A1
gene in human trophoblast and rat adrenocortical cells reduced the expression of CYP27A1 mRNA by 70%, reduced total bile acids 2-fold, and marinobufagenin levels by 67% when compared with nontreated cells or cells transfected with nontargeting siRNA. In contrast, silencing of the
CYP11A1
gene did not affect marinobufagenin production in either cell culture, but suppressed production of progesterone 2-fold in human trophoblast cells and of corticosterone by 90% in rat adrenocortical cells when compared with cells transfected with nontargeting siRNA. In vivo, in a high-salt administration experiment, male and female Dahl salt-sensitive rats became hypertensive after 4 weeks on a high-NaCl diet, their plasma marinobufagenin levels doubled, and adrenocortical CYP27A1 mRNA and protein increased 1.6-fold and 2.0-fold.

Conclusions—
Therefore, the endogenous steroidal Na/K-ATPase inhibitor, marinobufagenin, is synthesized in mammalian placenta and adrenal cortex from cholesterol through the novel acidic bile acid pathway. These findings will help to understand the role of marinobufagenin in highly prevalent human cardiovascular diseases.
Left Ventricular Structure and Risk of Cardiovascular Events: A Framingham Heart Study Cardiac Magnetic Resonance Study
Authors: Tsao Connie W. , Gona Philimon N. , Salton Carol J. , Chuang Michael L. , Levy Daniel , Manning Warren J. , O'Donnell Christopher J. 
Published: September 2015

Background

Elevated left ventricular mass index (
LVMI
) and concentric left ventricular (
LV
) remodeling are related to adverse cardiovascular disease (
CVD
) events. The predictive utility of
LV
concentric remodeling and
LV
mass in the prediction of
CVD
events is not well characterized.

Methods and Results

Framingham Heart Study Offspring Cohort members without prevalent
CVD
(n=1715, 50% men, aged 65±9 years) underwent cardiovascular magnetic resonance for
LVMI
and geometry (2002–2006) and were prospectively followed for incident
CVD
(myocardial infarction, coronary insufficiency, heart failure, stroke) or
CVD
death. Over 13 808 person‐years of follow‐up (median 8.4, range 0.0 to 10.5 years), 85
CVD
events occurred. In multivariable‐adjusted proportional hazards regression models, each 10‐g/m
2
increment in
LVMI
and each 0.1 unit in relative wall thickness was associated with 33% and 59% increased risk for
CVD
, respectively (
P
=0.004 and
P
=0.009, respectively). The association between
LV
mass/
LV
end‐diastolic volume and incident
CVD
was borderline significant (
P
=0.053). Multivariable‐adjusted risk reclassification models showed a modest improvement in
CVD
risk prediction with the incorporation of cardiovascular magnetic resonance
LVMI
and measures of
LV
concentricity (C‐statistic 0.71 [95%
CI
0.65 to 0.78] for the model with traditional risk factors only, improved to 0.74 [95%
CI
0.68 to 0.80] for the risk factor model additionally including
LVMI
and relative wall thickness).

Conclusions

Among adults free of prevalent
CVD
in the community, greater
LVMI
and
LV
concentric hypertrophy are associated with a marked increase in adverse incident
CVD
events. The potential benefit of aggressive primary prevention to modify
LV
mass and geometry in these adults requires further investigation.
Optimizating Clot Retrieval in Acute Stroke
Authors: Haussen Diogo C. , Rebello Leticia C. , Nogueira Raul G. 
Published: September 2015

Background and Purpose—
We aimed to investigate the safety and efficacy of the Push and Fluff technique (PFT) as compared with the standard unsheathing technique for closed-cell stent retrievers in acute ischemic stroke.

Methods—
Acute ischemic stroke thrombectomy database was analyzed (September 2010 to January 2015) with the Trevo Retriever as a primary strategy. The PFT was compared with our internal standard unsheathing technique and with the Trevo Versus Merci Retrievers for Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke 2 (TREVO2) trial. Additionally, a silicon flow model was used to compare cell size/configuration, wall apposition/device diameter, and degree of foreshortening/device length across the 2 techniques.

Results—

One hundred fifty-one out of 662 patients qualified for the study. The PFT (n=71) was associated with higher rates of first-pass reperfusion (54% versus 35%,
P
=0.03; 54% versus 32.6%,
P
<0.01), lower number of passes (1.3±0.8 versus 1.8±1.0,
P
<0.01; 1.7±1.0 versus 2.4±1.6,
P
<0.01), and higher rates of modified treatment in cerebral ischemia-3 reperfusion (58% versus 40%,
P
=0.03; 58% versus 14%,
P
<0.01) as compared with the standard unsheathing technique (n=81) and the TREVO2 Trevo arm (n=88), respectively. No differences in hemorrhagic complications were observed across the groups. The in vitro model indicated that, compared with standard unsheathing technique, PFT resulted in improved wall apposition (device diameter, 75% larger) and cell size (mean area, 51% larger) at the cost of a mild degree of foreshortening (25% length reduction).

Conclusions—
The PFT is safe and leads to optimization of wall apposition and cell size/configuration, resulting in higher chances of first-pass reperfusion, lower number of passes, and better rates of complete reperfusion.