Late Frasnian mass extinction: Conodont event stratigraphy, global changes, and possible causes

Several abrupt changes in conodont biofacies are documented to occur synchronously at six primary control sections across the Frasnian-Famennian boundary in Euramerica. These changes occurred within a time-span of only about 100,000 years near the end of the latest Frasnian linguiformis Zone, which is formally named to replace the Uppermost gigas Zone. The conodont-biofacies changes are interpreted to reflect a eustatic rise followed by an abrupt eustatic fall immediately preceding the late Frasnian mass extinction. Two new conodont species are named and described. Ancyrognathus ubiquitus n.sp. is recorded only just below and above the level of late Frasnian extinction and hence is a global marker for that event. Palmatolepispraetriangularis n.sp. is the long-sought Frasnian ancestor of the formerly cryptogenic species, Pa. triangularis, indicator of the earliest Famennian Lower triangularis Zone. The actual extinction event occurred entirely within the Frasnian and is interpreted to have been of brief duration-from as long as 20,000 years to as short as several days. The eustatic rise-and-fall couplet associated with the late Frasnian mass extinction is similar to eustatic couplets associated with the demise of most Frasnian (F2h) reefs worldwide about 1 m.y. earlier and with a latest Famennian mass extinction about 9.5 m.y. later. All these events may be directly or indirectly attributable to extraterrestrial triggering mechanisms. An impact of a small bolide or a near miss of a larger bolide may have caused the earlier demise of Frasnian reefs. An impact of possibly the same larger bolide in the Southern Hemisphere would explain the late Frasnian mass extinction. Global regression during the Famennian probably resulted from Southern-Hemisphere glaciation triggered by the latest Frasnian impact. Glaciation probably was the indirect cause of the latest Famennian mass extinction

Autophagy mediates degradation of nuclear lamina

Z.D. is supported by a fellow award from the Leukemia & Lymphoma Society. B.C.C. is supported by career development awards from the Dermatology Foundation, Melanoma Research Foundation, and American Skin Association. S.L.B., P.D.A. and R.M. are supported by NIA P01 grant (P01AG031862). S.L.B. is also supported by NIH R01 CA078831. R.D.G. is supported by R01 GM106023 and the Progeria Research Foundation

Crosstalk between glial and glioblastoma cells triggers the "go-or-grow" phenotype of tumor cells

Background: Glioblastoma (GBM), the most malignant primary brain tumor, leads to poor and unpredictable clinical outcomes. Recent studies showed the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. In this context, we investigated how GBM cells modulate resident glial cells, particularly their paracrine activity, and how this modulation can influence back on the malignant phenotype of GBM cells. Methods: Conditioned media (CM) of primary mouse glial cultures unexposed (unprimed) or exposed (primed) to the secretome of GL261 GBM cells were analyzed by proteomic analysis. Additionally, these CM were used in GBM cells to evaluate their impact in glioma cell viability, migration capacity and activation of tumor-related intracellular pathways. Results: The proteomic analysis revealed that the pre-exposure of glial cells to CM from GBM cells led to the upregulation of several proteins related to inflammatory response, cell adhesion and extracellular structure organization within the secretome of primed glial cells. At the functional levels, CM derived from unprimed glial cells favored an increase in GBM cell migration capacity, while CM from primed glial cells promoted cells viability. These effects on GBM cells were accompanied by activation of particular intracellular cancer-related pathways, mainly the MAPK/ERK pathway, which is a known regulator of cell proliferation. Conclusions: Together, our results suggest that glial cells can impact on the pathophysiology of GBM tumors, and that the secretome of GBM cells is able to modulate the secretome of neighboring glial cells, in a way that regulates the "go-or-grow" phenotypic switch of GBM cells.Fundação para a Ciência e Tecnologia (IF/00601/2012 to B.M.C.; IF/00111 to A.J.S; SFRH/BD/52287/2013 to A.I.O.; SFRH/BD/81495/2011 to S.I.A.; SFRH/BD/88121/2012 to J.V.C.; projects PTDC/SAU-GMG/113795/2009 to B.M.C.; PTDC/NEU-NMC/0205/2012, PTDC/NEU-SCC/7051/2014, PEst-C/SAU/LA0001/2013–2014 and UID/NEU/04539/2013 to B.M.), Liga Portuguesa Contra o Cancro (B.M.C.), Fundação Calouste Gulbenkian (B.M.C.) and Inter-University Doctoral Programme in Ageing and Chronic Disease (PhDOC; to A.I.O.). Project co-financed by Programa Operacional Regional do Norte (ON.2—O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER), Programa Operacional Factores de Competitividade (COMPETE), and by The National Mass Spectrometry Network (RNEM) under the contract REDE/1506/REM/2005info:eu-repo/semantics/publishedVersio

Profiling of Genes Related to Cross Protection and Competition for NbTOM1 by HLSV and TMV

10.1371/journal.pone.0073725PLoS ONE89-POLN

Aberrant signaling in T-cell acute lymphoblastic leukemia: biological and therapeutic implications

T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous disease with respect to phenotype, gene expression profile and activation of particular intracellular signaling pathways. Despite very significant improvements, current therapeutic regimens still fail to cure a portion of the patients and frequently implicate the use of aggressive protocols with long-term side effects. In this review, we focused on how deregulation of critical signaling pathways, in particular Notch, PI3K/Akt, MAPK, Jak/STAT and TGF-beta, may contribute to T-ALL. Identifying the alterations that affect intracellular pathways that regulate cell cycle and apoptosis is essential to understanding the biology of this malignancy, to define more effective markers for the correct stratification of patients into appropriate therapeutic regimens and to identify novel targets for the development of specific, less detrimental therapies for T-ALL

Accuracy of the new rapid test for monitoring adalimumab levels

The loss of response to adalimumab (ADL) has been related to low serum concentrations at trough. Currently, most methods commercially available for the quantification of ADL are enzyme-linked immunosorbent assay (ELISA) based, with a turnaround time of approximately 8 h, delaying the target dosage adjustment to the subsequent infusion. In this study, we aimed to evaluate the performance of the newly available rapid-test ADL quantification assay by comparing it with three established ELISA methods, using spiked samples and a set of clinical samples.info:eu-repo/semantics/publishedVersio

Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition.

Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target.This work was supported by the University of Cambridge, Cancer Research UK, Hutchison Whampoa; Cancer Research UK grants A6691 and A9892 (M.N., N.K., C.J.T., D.C.B., C.J.C., L.S.G, and M.S.); a fellowship from the Uehara Memorial Foundation (M.S.).This is the author accepted manuscript. The final version is available from the American Society for Cell Biology via http://dx.doi.org/10.1091/mbc.E15-01-000

Young people's media use and adherence to preventive measures in the “infodemic” : is it masked by political ideology?

Background: Navigating in the COVID-19 “infodemic” and adhering to preventive measures is especially challenging for young people. The use of information sources and political ideology are empirically important factors for adherence behavior. How these two are interconnected and if political ideology on its own contributes to adherence is not yet well established in young people. Objective: This study investigates what role political ideology and political extremism, use of information sources, trust and risk perception play for adhering to preventive measures in young people. Methods: Cross-sectional online survey in a representative random sample of young people aged 15–34 in two German-speaking and one Italian-speaking canton of Switzerland. The hypotheses were tested with logistic regression and multivariate regression analysis. Results: The odds for using the following information sources decreases for young people positioning themselves towards the right pole of the ideology scale: health-based sources 0.90 (CI: 0.84–0.97), news sources 0.93 (CI 0.87–0.997) and other websites 0.83 (CI: 0.75–0.92). In contrast, the odds of using broadcasting sources increases for young people positioning themselves towards the right pole of the ideology scale (OR: 1.08, CI 1.01–1.15). The odds of using social media decreases with higher political extremism (OR 0.88, CI 0.78–0.99). Political extremism was related with lower adherence to preventive measures in young people with low trust in the government, scientists, and journalists. Conclusion: Young peoples' use of information sources is associated with their political ideology and political extremism needs to be taken in account in conjunction with low trust