Temozolomide resistance in glioblastoma cells occurs partly through epidermal growth factor receptor-mediated induction of connexin 43

Glioblastoma Multiforme (GBM) is an aggressive adult primary brain tumor with poor prognosis. GBM patients develop resistance to the frontline chemotherapy, temozolomide (TMZ). As the connexins (Cx) have been shown to have a complex role in GBM, we investigated the role of Cx43 in TMZ resistance. Cx43 was increased in the TMZ-resistant low passage and cell lines. This correlated with the data in The Cancer Genome Atlas. Cx43 knockdown, reporter gene assays, chromatin immunoprecipitation assay, real-time PCR and western blots verified a role for Cx43 in TMZ resistance. This occurred by TMZ-resistant GBM cells being able to activate epidermal growth factor receptor (EGFR). In turn, EGFR activated the JNK-ERK1/2-AP-1 axis to induce Cx43. The increased Cx43 was functional as indicated by gap junctional intercellular communication among the resistant GBM cells. Cell therapy could be a potential method to deliver drugs, such as anti-EGF to tumor cells. Similar strategies could be used to reverse the expression of Cx43 to sensitize GBM cells to TMZ. The studies showed the potential for targeting EGF in immune therapy. These agents can be used in conjunction with stem cell therapy to treat GBM

Intermittent reconnection and plasmoids in UV bursts in the low solar atmosphere

Magnetic reconnection is thought to drive a wide variety of dynamic phenomena in the solar atmosphere. Yet the detailed physical mechanisms driving reconnection are difficult to discern in the remote sensing observations that are used to study the solar atmosphere. In this paper we exploit the high-resolution instruments Interface Region Imaging Spectrograph (IRIS) and the new CHROMIS Fabry-Perot instrument at the Swedish 1-m Solar Telescope (SST) to identify the intermittency of magnetic reconnection and its association with the formation of plasmoids in so-called UV bursts in the low solar atmosphere. The Si IV 1403A UV burst spectra from the transition region show evidence of highly broadened line profiles with often non-Gaussian and triangular shapes, in addition to signatures of bidirectional flows. Such profiles had previously been linked, in idealized numerical simulations, to magnetic reconnection driven by the plasmoid instability. Simultaneous CHROMIS images in the chromospheric Ca II K 3934A line now provide compelling evidence for the presence of plasmoids, by revealing highly dynamic and rapidly moving brightenings that are smaller than 0.2 arcsec and that evolve on timescales of order seconds. Our interpretation of the observations is supported by detailed comparisons with synthetic observables from advanced numerical simulations of magnetic reconnection and associated plasmoids in the chromosphere. Our results highlight how subarcsecond imaging spectroscopy sensitive to a wide range of temperatures combined with advanced numerical simulations that are realistic enough to compare with observations can directly reveal the small-scale physical processes that drive the wide range of phenomena in the solar atmosphere.Comment: Accepted for publication in Astrophysical Journal Letters. Movies are available at http://folk.uio.no/rouppe/plasmoids_chromis

Prognostic stratification improvement by integrating ID1/ID3/IGJ gene expression signature and immunophenotypic profile in adult patients with B-ALL

Characteristics of pronostic groups according to EuroFlow immunophenotype. (TIFF 1364 kb

Bounds for Lepton Flavor Violation and the Pseudoscalar Higgs in the General Two Higgs Doublet Model using g−2g-2 muon factor

Current experimental data from the $g-2$ muon factor, seems to show the necessity of physics beyond the Standard Model (SM), since the difference between SM and experimental predictions is 2.6$\sigma$. In the framework of the General Two Higgs Doublet Model (2HDM), we calculate the muon anomalous magnetic moment to get lower and upper bounds for the Flavour Changing (FC) Yukawa couplings in the leptonic sector. We also obtain lower bounds for the mass of the pseudoscalar Higgs ($m_{A^0}$) as a function of the parameters of the model.Comment: 12 pages, RevTex4, 5 figures. Improved presentation, updated experimental data, amplified analysis, new figures added. Subbmited to Phys. Rev.

High expression of ID family and IGJ genes signature as predictor of low induction treatment response and worst survival in adult Hispanic patients with B-acute lymphoblastic leukemia

Table S4. Complete list of signaling pathways dysregulated in patients who achieved complete remission therapy. Signaling pathway analysis was done using MetaCore KPA using the set of 442 genes differentially expressed between good and poor response group. (XLSX 10 kb

First Trimester Examination of Fetal Anatomy: Clinical Practice Guideline by the World Association of Perinatal Medicine (WAPM) and the Perinatal Medicine Foundation (PMF)

This recommendation document follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation. We aim to bring together groups and individuals throughout the world for precise standardization to implement the ultrasound evaluation of the fetus in the first trimester of pregnancy and improve the early detection of anomalies and the clinical management of the pregnancy. The aim is to present a document that includes statements and recommendations on the standard evaluation of the fetal anatomy in the first trimester, based on quality evidence in the peer-reviewed literature as well as the experience of perinatal experts around the world.info:eu-repo/semantics/publishedVersio

Lepton Flavor Violation in the Two Higgs Doublet Model type III

We consider the Two Higgs Doublet Model (2HDM) of type III which leads to Flavour Changing Neutral Currents (FCNC) at tree level in the leptonic sector. In the framework of this model we can have, in principle, two situations: the case (a) when both doublets acquire a vacuum expectation value different from zero and the case (b) when only one of them is not zero. In addition, we show that we can make two types of rotations for the flavor mixing matrices which generates four types of lagrangians, with the rotation of type I we recover the case (b) from the case (a) in the limit $\tan \beta \to \infty$, and with the rotation of type II we obtain the case (b) from (a) in the limit $\tan \beta \to 0.$Moreover, two of the four possible lagrangians correspond to the models of types I and II plus Flavor Changing (FC) interactions. The analitical expressions of the partial lepton number violating widths $\Gamma (\mu \to eee)$ and $\Gamma (\mu \to e\gamma)$are derived for the cases (a) and (b) and both types of rotations.$$In all cases these widths go asymptotically to zero in the decoupling limit for all Higgses. We present from our analysis upper bounds for the flavour changing transition $\mu \to e,$ and we show that such bounds are sensitive to the VEV structure and the type of rotation utilized.Comment: 7 pages RevTeX4, 4 figures postscript, new section added and some new reference

Cardiovascular risk factors among Chamorros

BACKGROUND: Little is known regarding the cardiovascular disease risk factors among Chamorros residing in the United States. METHODS: The Chamorro Directory International and the CDC's Behavioral Risk Factor Surveillance System Questionnaire (BRFSS) were used to assess the health related practices and needs of a random sample of 228 Chamorros. RESULTS: Inactivity, hypertension, elevated cholesterol and diabetes mellitus were more prevalent in this Chamorro sample compared to the US average. Participants who were 50-and-older or unemployed were more likely to report hypertension, diabetes and inactivity, but they were also more likely to consume more fruits and vegetables than their younger and employed counterparts. Women were more likely to report hypertension and diabetes, whereas men were more likely to have elevated BMI and to have never had their blood cholesterol checked. CONCLUSION: The study provides data that will help healthcare providers, public health workers and community leaders identify where to focus their health improvement efforts for Chamorros and create culturally competent programs to promote health in this community

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito