329 research outputs found

    Components of the Ubiquitin Proteasome System are Required for the Nonapoptotic Death of the C. Elegans Linker Cell

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    Cell death is a major cell fate that promotes tissue sculpting and morphogenesis during animal development. Many developmental cell-culling events cannot be accounted for solely by caspase-dependent apoptosis, yet, alternate pathways are poorly understood. Direct evidence that caspase-independent non-apoptotic cell death pathways operate during animal development is provided by studies of the C. elegans linker cell. Genetic studies of linker cell death have led to the identification of genes that promote this process, including pqn-41, which encodes a glutamine-rich protein, as well as tir-1/TIRdomain and sek-1/MAPKK, which may function in the same pathway as pqn-41. The let- 7 microRNA and its indirect target, the Zn-finger transcription factor LIN-29, also promote linker cell death, and may act early in the process. Our work suggests that components of the ubiquitin proteasome system (UPS) act to promote linker cell death. We show that LET-70, an E2 ubiquitin-conjugating enzyme, is required cell-autonomously for linker cell death. LET-70 levels, as well as those of ubiquitin and some proteasome components, increase just before linker cell death initiation. This rise is dependent on an MLL-type histone methyltransferase complex and a MAPK cascade, whose activities are required for linker cell death. The E3 ligase components SIAH-1, RBX-1, and CUL-3 are also required for linker cell death and appear to act in the same pathway as let-70. We also identify the PLZF transcription factor EOR-1, and its accessory protein, EOR-2 as major regulators of linker cell death. Our studies suggest that EOR-1/2, as well as all known regulators of the linker cell death pathway may act upstream of UPS components to promote cell death. Our studies reveal that activation of the ubiquitin proteasome system is an important event promoting linker cell death. Given the morphological similarities between linker cell death and non-apoptotic developmental and pathological cell death in vertebrates, we raise the possibility that the proteasome may be a key mediator of vertebrate cell death

    Changing the Tide: An Internet/Video Exercise and Low Fat Diet Intervention with Middle School Students

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    The rising tide of obesity erodes the health of youths and many times results in adult obesity. The purpose of this investigation was to examine the effectiveness of an eight-session health promotion/transtheoretical model Internet/video-delivered intervention to increase physical activity and reduce dietary fat among low-income, culturally diverse, seventh-grade students. Those who completed more than half the sessions increased exercise, t(103) = −1.99, p = .05, and decreased the percentage of dietary fat, t(87) = 2.73, p = .008. Responses to the intervention by stage of change, race, and income are examined

    Den ideella vÀgen till det ideala beteendet

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    Denna studie hade som syfte att undersöka ett antal viktiga faktorer inom ideella organisationer vilka antas vara relaterade till Organizational Citizenship Behavior (OCB) samt i vilken grad dessa faktorer kunde förutsÀga OCB. De undersökta variablerna var VÀlmÄende, Beslutstilar, Centralisering, Kontroll över arbetet, Autonomi och Engagemang. Ytterligare ett syfte var att undersöka sambandet mellan beslutstilar och OCB. Deltagarna bestod av individer med en beslutsfattande position inom svenska studentkÄrer. Deltagarna rekryterades via e-post och svarade pÄ ett webbaserat frÄgeformulÀr. Resultaten pekade pÄ att engagemang och centralisering var de bÀsta prediktorerna för OCB. VÀlmÄende visade sig inte ha nÄgon större effekt i att predicera OCB. Beslutstilar hade inte heller nÄgon större effekt pÄ OCB. Ett antal alternativa förklaringar till resultaten redovisas

    Cost-Effectiveness of Primary versus Secondary Prophylaxis with Pegfilgrastim in Women with Early-Stage Breast Cancer Receiving Chemotherapy

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    AbstractObjectiveProphylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. We estimated the incremental cost-effectiveness of G-CSF pegfilgrastim primary (starting in cycle 1 and continuing in subsequent cycles of chemotherapy) versus secondary (only after an FN event) prophylaxis in women with early-stage breast cancer receiving myelosuppressive chemotherapy with a ≄20% FN risk.MethodsA decision-analytic model was constructed from a health insurer's perspective with a lifetime study horizon. The model considers direct medical costs and outcomes related to reduced FN and potential survival benefits because of reduced FN-related mortality. Inputs for the model were obtained from the medical literature. Sensitivity analyses were conducted across plausible ranges in parameter values.ResultsThe incremental cost-effectiveness ratio (ICER) of pegfilgrastim as primary versus secondary prophylaxis was 48,000/FNepisodeavoided.AddingsurvivalbenefitfromavoidingFNmortalityyieldedanICERof48,000/FN episode avoided. Adding survival benefit from avoiding FN mortality yielded an ICER of 110,000/life-year gained (LYG) or $116,000/quality-adjusted life-year (QALY) gained. The most influential factors included FN case-fatality, FN relative risk reduction from primary prophylaxis, and age at diagnosis.ConclusionsCompared with secondary prophylaxis, the cost-effectiveness of pegfilgrastim as primary prophylaxis may be equivalent or superior to other commonly used supportive care interventions for women with breast cancer. Further assessment of the direct impact of G-CSF on short- and long-term survival is needed to substantiate these findings

    Pulping and pretreatment affect the characteristics of bagasse inks for 3D printing

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    Bagasse is an underutilized agro-industrial residue with great potential as raw material for the production of cellulose nanofibrils (CNF) for a range of applications. In this study, we have assessed the suitability of bagasse for production of CNF for three-dimensional (3D) printing. First, pulp fibers were obtained from the bagasse raw material using two fractionation methods, i.e. soda and hydrothermal treatment combined with soda. Second, the pulp fibers were pretreated by TEMPO-mediated oxidation using two levels of oxidation for comparison purposes. Finally, the CNF were characterized in detail and assessed as inks for 3D printing. The results show that CNF produced from fibers obtained by hydrothermal and soda pulping were less nanofibrillated than the corresponding material produced by soda pulping. However, the CNF sample obtained from soda pulp was cytotoxic, apparently due to a larger content of silica particles. All the CNF materials were 3D printable. We conclude that the noncytotoxic CNF produced from hydrothermally and soda treated pulp can potentially be used as inks for 3D printing of biomedical devices.Fil: Chinga Carrasco, Gary. RISE PFI; NoruegaFil: Ehman, Nanci Vanesa. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Nordeste. Instituto de Materiales de Misiones. Universidad Nacional de Misiones. Facultad de Ciencias Exactas QuĂ­micas y Naturales. Instituto de Materiales de Misiones; ArgentinaFil: Pettersson, Jennifer. RISE Bioscience and Materials; SueciaFil: Vallejos, MarĂ­a Evangelina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Nordeste. Instituto de Materiales de Misiones. Universidad Nacional de Misiones. Facultad de Ciencias Exactas QuĂ­micas y Naturales. Instituto de Materiales de Misiones; ArgentinaFil: Felissia, Fernando Esteban. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Nordeste. Instituto de Materiales de Misiones. Universidad Nacional de Misiones. Facultad de Ciencias Exactas QuĂ­micas y Naturales. Instituto de Materiales de Misiones; ArgentinaFil: Hakansson, Joakim. RISE Bioscience and Materials; SueciaFil: Area, Maria Cristina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Nordeste. Instituto de Materiales de Misiones. Universidad Nacional de Misiones. Facultad de Ciencias Exactas QuĂ­micas y Naturales. Instituto de Materiales de Misiones; Argentin

    Myc controls a distinct transcriptional program in fetal thymic epithelial cells that determines thymus growth

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    Interactions between thymic epithelial cells (TEC) and developing thymocytes are essential for T cell development, but molecular insights on TEC and thymus homeostasis are still lacking. Here we identify distinct transcriptional programs of TEC that account for their age-specific properties, including proliferation rates, engraftability and function. Further analyses identify Myc as a regulator of fetal thymus development to support the rapid increase of thymus size during fetal life. Enforced Myc expression in TEC induces the prolonged maintenance of a fetal-specific transcriptional program, which in turn extends the growth phase of the thymus and enhances thymic output; meanwhile, inducible expression of Myc in adult TEC similarly promotes thymic growth. Mechanistically, this Myc function is associated with enhanced ribosomal biogenesis in TEC. Our study thus identifies age-specific transcriptional programs in TEC, and establishes that Myc controls thymus size

    Effects of triclosan in breast milk on the infant fecal microbiome

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    Triclosan is frequently used for its antimicrobial properties and has been detected in human serum, urine, and breast milk. Animal and molecular studies have shown that triclosan exerts a wide range of adverse health effects at both high (ppm) and low (ppb) concentrations. Since triclosan is of growing concern to human and environmental health, there is a need to improve extraction procedures and to study additional effects from triclosan exposure. In this study, we have improved triclosan extraction from breast milk by using salt (MgSO4) to reduce emulsion formation and increase water polarity and water (~80%) to enhance the overall extraction efficiency (~3.5 fold). This extraction method was applied to breast milk samples collected from donors who i) recorded their use of triclosan-containing personal care products and ii) provided matching infant stool samples. Of the participants who had detectable amounts of triclosan in their breast milk, nine (75%) of them reported daily use of triclosan-containing personal care products. Levels of triclosan in breast milk were compared to the donor\u27s infant\u27s fecal microbiome. We found that the bacterial diversity in the fecal microbiome of the infants exposed to breast milk with detectable triclosan levels differed compared to their peers exposed to milk containing non-detectable amounts. This finding implies that exogenous chemicals are impacting microbiome diversity

    Towards a Global Tree Assessment

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    Although trees have high economic, cultural and ecological value, increasing numbers of species are potentially at risk of extinction because of forest loss and degradation as a result of human activities, including overharvesting, fire and grazing. Emerging threats include climate change and its interaction with the spread of pests and diseases. The impact of such threats on the conservation status of trees is poorly understood. Here we highlight the need to conduct a comprehensive conservation assessment of the world's tree species, building on previous assessments undertaken for the IUCN Red List. We suggest that recent developments in plant systematics, online databases, remote sensing data and associated analytical tools offer an unprecedented opportunity to conduct such an assessment. We provide an overview of how a Global Tree Assessment could be achieved in practice, through participative, open-access approaches to data sharing and evaluation

    Fish investigations in the Barents Sea winter 2020

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    This report presents the main results from the surveys in January-March 2020. The surveys were performed with the Norwegian research vessels “Helmer Hanssen” and “Johan Hjort” and the Russian research vessel “Vilnyus”. Annual survey reports since 1981 are listed in Appendix 1, and names of scientific participants are given in Appendix 3.publishedVersio
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