bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection
Authors: Pelle Karell G , Oh Keunyoung , Buchholz Kathrin , Narasimhan Vagheesh , Joice Regina , Milner Danny A , Brancucci Nicolas MB , Ma Siyuan , Voss Till S , Ketman Ken , Seydel Karl B , Taylor Terrie E , Barteneva Natasha S , Huttenhower Curtis , Marti Matthias 
Published: February 2015

Abstract
Background
During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood.

Results
We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion.

Conclusions
This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo.
Further generalization of fixed point theorems in Menger PM-spaces
Authors: Kutbi Marwan Amin , Gopal Dhananjay , Vetro Calogero , Sintunavarat Wutiphol 
Published: February 2015

AbstractIn this work, we establish some fixed point theorems by revisiting the notion of ψ-contractive mapping in Menger PM-spaces. One of our results (namely, Theorem 2.3) may be viewed as a possible answer to the problem of existence of a fixed point for generalized type contractive mappings in M-complete Menger PM-spaces under arbitrary t-norm. Some examples are furnished to demonstrate the validity of the obtained results.
An alternative model of international migration: endogenous two sided borders and optimal legal systems
Authors: Chaabane Inaam , Gaumont Damien 
Published: February 2015

AbstractIn a 2-country and 3-period OLG model with education, we study the impact on international migration of the two sided characteristics of borders. Individuals must first “leave” their home country before “entering” the destination country. Indeed, each social planner chooses the static welfare optimal level of education, consumption, labor and capital. A unique migration flow is compatible with the market steady-state equilibrium and the maximizing social welfare solution. Difference in education generates differences in steady-state capital per capita. Consequently, both price differentials and incentives for illegal migration exist. Application to real world cases is provided.JEL ClassificationK37, D91, F22
Savings, entrepreneurial trait and self-employment: evidence from selected Ghanaian Universities
Authors: Peprah James A , Afoakwah Clifford , Koomson Isaac 
Published: February 2015

AbstractYouth unemployment is a major setback to sustainable growth. In recent times, Ghana has experienced a downward trend in youth employment in spite of several attempts made by the government to control the unemployment situation. This paper explores savings behaviour, entrepreneurial trait and the decision to be self-employed among students from selected public and private universities in Ghana. Employing the bivariate analysis and probit model on a sample of 1046 students shows that savings behaviour among the youth varies according to their programmes of study, type of institution (public and private) and family background of the students. Savings and entrepreneurial trait increase the probability of self-employment decision among university students. Policies that can address graduate unemployment should focus on helping students to save while in school. Also, incorporating entrepreneurial training into the academic programmes of these institutions has the tendency of improving the entrepreneurial traits of students and thereby, decide to be self-employed. Policy intervention needs to be designed strategically to target students into self-employment as a way of curbing youth unemployment in Ghana in order to contribute to national development.
Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity
Authors: Pandolfi J , Ferraro A , Lerner M , Serrano J R , Dueck A , Fainboim L , Arruvito L 
Published: February 2015

Abstract
Obesity is accompanied by chronic inflammation of VAT, which promotes metabolic changes, and purinergic signaling has a key role in a wide range of inflammatory diseases. Therefore, we addressed whether fat inflammation could be differentially modulated by this signaling pathway in the MUO and in individuals who remain MHO. Our results show that the necrotized VAT of both groups released greater levels of ATP compared with lean donors. Interestingly, MUO tissue SVCs showed up-regulation and engagement of the purinergic P2X7R. The extracellular ATP concentration is regulated by an enzymatic process, in which CD39 converts ATP and ADP into AMP, and CD73 converts AMP into adenosine. In VAT, the CD73 ectoenzyme was widely distributed in immune and nonimmune cells, whereas CD39 expression was restricted to immune CD45PAN+ SVCs. Although the MUO group expressed the highest levels of both ectoenzymes, no difference in ATP hydrolysis capacity was found between the groups. As expected, MUO exhibited the highest NLRP3 inflammasome expression and IL-1β production. MUO SVCs also displayed up-regulation of the A2AR, allowing extracellular adenosine to increase IL-1β local secretion. Additionally, we demonstrate that metabolic parameters and BMI are positively correlated with purinergic components in VAT. These findings indicate that purinergic signaling is a novel mechanism involved in the chronic inflammation of VAT underlying the metabolic changes in obesity. Finally, our study reveals a proinflammatory role for adenosine in sustaining IL-1β production in this tissue.
Rac1-dependent secretion of platelet-derived CCL5 regulates neutrophil recruitment via activation of alveolar macrophages in septic lung injury
Authors: Hwaiz Rundk , Rahman Milladur , Syk Ingvar , Zhang Enming , Thorlacius Henrik 
Published: February 2015

Abstract
Accumulating evidence suggest that platelets play an important role in regulating neutrophil recruitment in septic lung injury. Herein, we hypothesized that platelet-derived CCL5 might facilitate sepsis-induced neutrophil accumulation in the lung. Abdominal sepsis was induced by CLP in C57BL/6 mice. CLP increased plasma levels of CCL5. Platelet depletion and treatment with the Rac1 inhibitor NSC23766 markedly reduced CCL5 in the plasma of septic mice. Moreover, Rac1 inhibition completely inhibited proteasePAR4-induced secretion of CCL5 in isolated platelets. Immunoneutralization of CCL5 decreased CLP-induced neutrophil infiltration, edema formation, and tissue injury in the lung. However, inhibition of CCL5 function had no effect on CLP-induced expression of Mac-1 on neutrophils. The blocking of CCL5 decreased plasma and lung levels of CXCL1 and CXCL2 in septic animals. CCL5 had no effect on neutrophil chemotaxis in vitro, suggesting an indirect effect of CCL5 on neutrophil recruitment. Intratracheal challenge with CCL5 increased accumulation of neutrophils and formation of CXCL2 in the lung. Administration of the CXCR2 antagonist SB225002 abolished CCL5-induced pulmonary recruitment of neutrophils. Isolated alveolar macrophages expressed significant levels of the CCL5 receptors CCR1 and CCR5. In addition, CCL5 triggered significant secretion of CXCL2 from isolated alveolar macrophages. Notably, intratracheal administration of clodronate not only depleted mice of alveolar macrophages but also abolished CCL5-induced formation of CXCL2 in the lung. Taken together, our findings suggest that Rac1 regulates platelet secretion of CCL5 and that CCL5 is a potent inducer of neutrophil recruitment in septic lung injury via formation of CXCL2 in alveolar macrophages.
Oral Bisphosphonate Use and Risk of Postmenopausal Endometrial Cancer
Authors: Newcomb Polly A. , Passarelli Michael N. , Phipps Amanda I. , Anderson Garnet L. , Wactawski-Wende Jean , Ho Gloria Y.F. , O'Sullivan Mary Jo , Chlebowski Rowan T. 
Published: February 2015

Purpose Bisphosphonates are common medications used for the treatment of osteoporosis and are also used to reduce metastases to bone in patients with cancer. Several studies, including the Women's Health Initiative (WHI), have found that use of bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about associations with other common malignancies. This study was aimed at examining the effects of bisphosphonates on the risk of endometrial cancer. Methods We evaluated the relationship between use of oral bisphosphonates and endometrial cancer risk in a cohort of 89,918 postmenopausal women participating in the WHI. A detailed health interview was conducted at baseline, and bisphosphonate use was ascertained from an inventory of regularly used medications at baseline and over follow-up. All women had an intact uterus at the time of study entry. Results During a median follow-up of 12.5 years, 1,123 women were diagnosed with incident invasive endometrial cancer. Ever use of bisphosphonates was associated with reduced endometrial cancer risk (adjusted hazard ratio, 0.80; 95% CI, 0.64 to 1.00; P = .05), with no interactions observed with age, body mass index, or indication for use. Conclusion In this large prospective cohort of postmenopausal women, bisphosphonate use was associated with a statistically significant reduction in endometrial cancer risk.
Variation in Glucose Homeostasis Traits Associated With P2RX7 Polymorphisms in Mice and Humans
Authors: Todd Jennifer N. , Poon Wenny , Lyssenko Valeriya , Groop Leif , Nichols Brendan , Wilmot Michael , Robson Simon , Enjyoji Keiichi , Herman Mark A. , Hu Cheng , Zhang Rong , Jia Weiping , Ma Ronald , Florez Jose C. , Friedman David J. 
Published: February 2015

AbstractContext:Extracellular nucleotide receptors are expressed in pancreatic B-cells. Purinergic signaling via these receptors may regulate pancreatic B-cell function.Objective:We hypothesized that purinergic signaling might influence glucose regulation and sought evidence in human studies of glycemic variation and a mouse model of purinergic signaling dysfunction.Design:In humans, we mined genome-wide meta-analysis data sets to examine purinergic signaling genes for association with glycemic traits and type 2 diabetes. We performed additional testing in two genomic regions (P2RX4/P2RX7 and P2RY1) in a cohort from the Prevalence, Prediction, and Prevention of Diabetes in Botnia (n = 3504), which includes more refined measures of glucose homeostasis. In mice, we generated a congenic model of purinergic signaling dysfunction by crossing the naturally hypomorphic C57BL6 P2rx7 allele onto the 129SvJ background.Results:Variants in five genes were associated with glycemic traits and in three genes with diabetes risk. In the Prevalence, Prediction, and Prevention of Diabetes in Botnia study, the minor allele in the missense functional variant rs1718119 (A348T) in P2RX7 was associated with increased insulin sensitivity and secretion, consistent with its known effect on increased pore function. Both male and female P2x7-C57 mice demonstrated impaired glucose tolerance compared with matched P2x7-129 mice. Insulin tolerance testing showed that P2x7-C57 mice were also less responsive to insulin than P2x7-129 mice.Conclusions:We show association of the purinergic signaling pathway in general and hypofunctioning P2X7 variants in particular with impaired glucose homeostasis in both mice and humans.
Characterisation of detergent-insoluble membranes in pollen tubes of Nicotiana tabacum (L.)
Authors: Moscatelli Alessandra , Gagliardi Assunta , Maneta-Peyret Lilly , Bini Luca , Stroppa Nadia , Onelli Elisabetta , Landi Claudia , Scali Monica , Idilli Aurora Irene , Moreau Patrick 
Published: February 2015

ABSTRACT
Pollen tubes are the vehicle for sperm cell delivery to the embryo sac during fertilisation of Angiosperms. They provide an intriguing model for unravelling mechanisms of growing to extremes. The asymmetric distribution of lipids and proteins in the pollen tube plasma membrane modulates ion fluxes and actin dynamics and is maintained by a delicate equilibrium between exocytosis and endocytosis. The structural constraints regulating polarised secretion and asymmetric protein distribution on the plasma membrane are mostly unknown. To address this problem, we investigated whether ordered membrane microdomains, namely membrane rafts, might contribute to sperm cell delivery. Detergent insoluble membranes, rich in sterols and sphingolipids, were isolated from tobacco pollen tubes. MALDI TOF/MS analysis revealed that actin, prohibitins and proteins involved in methylation reactions and in phosphoinositide pattern regulation are specifically present in pollen tube detergent insoluble membranes. Tubulins, voltage-dependent anion channels and proteins involved in membrane trafficking and signalling were also present. This paper reports the first evidence of membrane rafts in Angiosperm pollen tubes, opening new perspectives on the coordination of signal transduction, cytoskeleton dynamics and polarised secretion.
Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytes
Authors: Kilian Nicole , Srismith Sirikamol , Dittmer Martin , Ouermi Djeneba , Bisseye Cyrille , Simpore Jacques , Cyrklaff Marek , Sanchez Cecilia P. , Lanzer Michael 
Published: February 2015

ABSTRACT
Malaria is a potentially deadly disease. However, not every infected person develops severe symptoms. Some people are protected by naturally occurring mechanisms that frequently involve inheritable modifications in their hemoglobin. The best studied protective hemoglobins are the sickle cell hemoglobin (HbS) and hemoglobin C (HbC) which both result from a single amino acid substitution in β-globin: glutamic acid at position 6 is replaced by valine or lysine, respectively. How these hemoglobinopathies protect from severe malaria is only partly understood. Models currently proposed in the literature include reduced disease-mediating cytoadherence of parasitized hemoglobinopathic erythrocytes, impaired intraerythrocytic development of the parasite, dampened inflammatory responses, or a combination thereof. Using a conditional protein export system and tightly synchronized Plasmodium falciparum cultures, we now show that export of parasite-encoded proteins across the parasitophorous vacuolar membrane is delayed, slower, and reduced in amount in hemoglobinopathic erythrocytes as compared to parasitized wild type red blood cells. Impaired protein export affects proteins targeted to the host cell cytoplasm, Maurer's clefts, and the host cell plasma membrane. Impaired protein export into the host cell compartment provides a mechanistic explanation for the reduced cytoadherence phenotype associated with parasitized hemoglobinopathic erythrocytes.
Fenofibrate in cancer: mechanisms involved in anticancer activity
Authors: Koltai Tomas 
Published: February 2015

Objective: To review the mechanisms of anti-cancer activity of fenofibrate (FF) and other Peroxisome Proliferator Activator Receptor α (PPARα) agonists based on evidences reported in the published literature.Methods: We extensively reviewed the literature concerning FF as an off target anti-cancer drug. Controversies regarding conflicting findings were also addressed.Results:The main mechanism involved in anti-cancer activity is anti-angiogenesis through down-regulation of Vascular Endothelial Growth Factor (VEGF), Vascular Endothelial Growth Factor Receptor (VEGFR) and Hypoxia Inducible factor-1 α (HIF-1α), inhibition of endothelial cell migration, up-regulation of endostatin and thrombospondin-1, but there are many other contributing mechanisms like apoptosis and cell cycle arrest, down-regulation of Nuclear Factor Kappa B (NF-kB) and Protein kinase B (Akt) and decrease of cellular energy by impairing mitochondrial function. Growth impairment is related to down-regulation of Phospho-Inositol 3 Kinase (PI3K)/Akt axis and down-regulation of the p38 map kinase (MAPK) cascade. A possible role should be assigned to FF stimulated over-expression of Tribbles Homolog-3 (TRIB3) which inhibits Akt phosphorylation. Important anti-cancer and anti-metastatic activities are due to down-regulation of MCP-1 (monocyte chemotactic protein-1), decreased Metalloprotease-9 (MMP-9) production, weak down-regulation of adhesion molecules like E selectin, intercellular adhesion molecules (ICAM) and Vascular Endothelial Adhesion Molecules (VCAM), and decreased secretion of chemokines like Interleukin-6 (IL-6), and down-regulation of cyclin D-1. There is no direct link between FF activity in lipid metabolism and anticancer activity, except for the fact that many anticancer actions are dependent from PPARα agonism. FF exhibits also PPARα independent anti-cancer activities.Conclusions: There are strong evidences indicating that FF can disrupt growth-related activities in many different cancers, due to anti-angiogenesis and anti-inflammatory effects. Therefore FF may be useful as a complementary adjunct treatment of cancer, particularly included in anti-angiogenic protocols like those currently increasingly used in glioblastoma. There are sound reasons to initiate well planned phase II clinical trials for FF as a complementary adjunct treatment of cancer.
Case Report: Radical prostatectomy without prostate biopsy in PI-RADS 5 lesions on 3T multi-parametric MRI of the prostate gland
Authors: Keller Andrew , Kua Boon 
Published: February 2015

Objective: Current practice mandates a prostate biopsy for histological confirmation of prostate cancer prior to a radical prostatectomy. Prostate biopsy, whether performed trans-rectally or trans-perineally, is an invasive procedure which typically involves an anaesthetic and has the risks of urosepsis, bleeding and haematoma. Post-biopsy inflammatory changes can also obliterate natural tissue planes thereby potentially compromising the quality of a nerve sparing procedure and increasing positive margin rates.3T-Multi-Parametric Magnetic Resonance Imaging of the Prostate (3T mpMRI-P) is gaining increasing acceptance in the identification and localisation of prostate cancer. In experienced centres, the positive predictive value has been reported to be as high as 95%.Methods: Two patients with rising and elevated age- adjusted PSAs and palpable malignant prostate nodules on Digital Rectal Examination (DRE) underwent 3T mpMRI-P. Both patients had Prostate Imaging-Reporting and Data System (PI-RADS) 5 lesions in their peripheral zones corresponding to palpable nodules. Prostate biopsies were offered but declined by both patients. Both were satisfied that there was sufficient evidence on their PSA, DRE and 3T mpMRI-P for a diagnosis of prostate cancer without prostate biopsies and both elected to proceed to a Da Vinci Robotic Assisted Laparoscopic Radical Prostatectomy (RALRP).Results: Unilateral nerve sparing RALRPs were performed on both patients without complication. Histology demonstrated Gleason 4+4=8 and 4+3=7 prostate adenocarcinomas, with tumour volumes of 14.92cc and 4.5cc respectively.Conclusions: In appropriately counselled patients who have a high pre-test probability of prostate cancer (rising and elevated PSA, malignant nodule on DRE and a corresponding PI-RADS 5 lesion on 3T mpMRI-P), it may be appropriate to proceed to a radical prostatectomy without a tissue diagnosis if the patients have strong reservations about prostate biopsy.
Psychometric properties of the Polish version of the brief version of Kutcher Adolescent Depression Scale – assessment of depression among students
Authors: Mojs Ewa , Bartkowska Weronika , Kaczmarek Łukasz , Ziarko Michał , Bujacz Aleksandra , Warchoł-Biedermann Katarzyna 
Published: February 2015

CelZaburzenia depresyjne, które należą do najczęściej występujących przewlekłych zaburzeń psychicznych, dotyczą do 15% osób przed 25 rokiem życia i mogą wiązać się z szeregiem niekorzystnych zjawisk takich jak: porzucenie nauki, uzależnienia i czyny samobójcze. Z badań wynika, że studenci stanowią grupę szczególnie obciążoną ryzykiem wystąpienia depresji. Wiadomo, że wiele przypadków depresji w tej populacji pozostaje niezdiagnozowanych i nieleczonych. Z tego powodu szczególne znaczenie ma opracowanie odpowiednich metod diagnostycznych. Skala Depresji Kutchera (wersja skrócona) jest powszechnie stosowanym testem przesiewowym do wykrywania młodych osób zagrożonych depresją. Składa się z sześciu pytań dotyczących głównych objawów depresji. Celem pracy było sprawdzenie trafności teoretycznej polskiej wersji skali do oceny depresji KADS (wersja skrócona) na próbie złożonej ze studentów metodą konfirmacyjnej analizy czynnikowej.MetodaW badaniach wzięło udział 1589 studentów w wieku 18-24 lat, którzy anonimowo i dobrowolnie wypełnili kwestionariusz KADS oraz ankietę demograficzną. Wyniki: Konfirmacyjna analiza czynnikowa wykazała dobre dopasowanie rozwiązania jednoczynnikowego do danych empirycznych. Uzyskane parametry to SB χ² (15) = 968.688, p < .001, RMSEA = .053, CFI = .958, SRMR = .029 oraz ładunki czynnikowe w przedziale od 0,40 do 0,80.WynikiKonfirmacyjna analiza czynnikowa wykazała dobre dopasowanie rozwiązania jednoczynnikowego do danych empirycznych. Uzyskane parametry to SB χ² (15) = 968.688, p < .001, RMSEA = .053, CFI = .958, SRMR = .029 oraz ładunki czynnikowe w przedziale od 0,40 do 0,80.WnioskiBadania wersji polskiej testu KADS w grupie studentów w wieku 18-24 lat wykazały, że test ten cechuje się trafnością teoretyczną i wysoką rzetelnością. Dalsze badania powinny zostać skoncentrowane na trafności kryterialnej narzędzia.