Railways are an environmentally friendly means of transport well suited to modern society. However, noise and vibration are key obstacles to further development of the railway networks for high-speed ...intercity traffic, for freight and for suburban metros and light-rail. All too often noise problems are dealt with inefficiently due to lack of understanding of the problem.
This book brings together coverage of the theory of railway noise and vibration with practical applications of noise control technology at source to solve noise and vibration problems from railways. Each source of noise and vibration is described in a systematic way: Rolling noise, curve squeal, bridge noise, aerodynamic noise, ground vibration and ground-borne noise, and vehicle interior noise.
Railways are frequently promoted as one of the most sustainable modes of transport. However, their impact will in practice be significantly affected by the ways in which they are designed, ...constructed, and used. This book provides a comprehensive overview of the issues involved in planning, engineering and operating sustainable railway systems.
Tran inneholder også miljøgifter Bjørke-Monsen, Anne-Lise; Huber, Sandra; Averina, Maria ...
Tidsskrift for den Norske Lægeforening,
2021, Volume:
141, Issue:
4
Journal Article
Background & Aims The molecular biology of hepatitis B virus (HBV) has been extensively studied but the exact role of the hepatitis B X protein (HBx) in the context of natural HBV infections remains ...unknown. Methods Primary human hepatocytes and differentiated HepaRG cells allowing conditional trans complementation of HBx were infected with wild type (HBV(wt)) or HBx deficient (HBV(x−)) HBV particles and establishment of HBV replication was followed. Results We observed that cells inoculated with HBx-deficient HBV particles (HBV(x−)) did not lead to productive HBV infection contrary to cells inoculated with wild type HBV particles (HBV(wt)). Although equal amounts of nuclear covalently closed circular HBV-DNA (cccDNA) demonstrated comparable uptake and nuclear import, active transcription was only observed from HBV(wt) genomes. Trans-complementation of HBx was able to rescue transcription from the HBV(x−) genome and led to antigen and virion secretion, even weeks after infection. Constant expression of HBx was necessary to maintain HBV antigen expression and replication. Finally, we demonstrated that HBx is not packaged into virions during assembly but is expressed after infection within the new host cell to allow epigenetic control of HBV transcription from cccDNA. Conclusions Our results demonstrate that HBx is required to initiate and maintain HBV replication and highlight HBx as the key regulator during the natural infection process.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The NACHT-, leucine-rich-repeat- (LRR), and pyrin domain-containing protein 3 (NLRP3) is emerging to be a critical intracellular inflammasome sensor of membrane integrity and a highly important ...clinical target against chronic inflammation. Here, we report that an endogenous, stimulus-responsive form of full-length mouse NLRP3 is a 12- to 16-mer double-ring cage held together by LRR-LRR interactions with the pyrin domains shielded within the assembly to avoid premature activation. Surprisingly, this NLRP3 form is predominantly membrane localized, which is consistent with previously noted localization of NLRP3 at various membrane organelles. Structure-guided mutagenesis reveals that trans-Golgi network dispersion into vesicles, an early event observed for many NLRP3-activating stimuli, requires the double-ring cages of NLRP3. Double-ring-defective NLRP3 mutants abolish inflammasome punctum formation, caspase-1 processing, and cell death. Thus, our data uncover a physiological NLRP3 oligomer on the membrane that is poised to sense diverse signals to induce inflammasome activation.
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•Full-length mouse NLRP3 forms oligomeric double-ring cages•Pyrin domains are hidden within the cages to avoid premature activation•NLRP3 cages are membrane bound and use the membrane as an oligomerization scaffold•The cages control dispersion of the trans-Golgi network to allow NLRP3 activation
Formation of a membrane-bound, double-ring cage structure controls activation of the murine NLRP3 protein, thus clarifying the native oligomeric form in cells and the structural basis of the early activation steps leading to inflammasome assembly and IL-1-family cytokine processing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aberrant expression of microRNAs (miRNAs) and the enzymes that control their processing have been reported in multiple biological processes including primary and metastatic tumours, but the ...mechanisms governing this are not clearly understood. Here we show that TAp63, a p53 family member, suppresses tumorigenesis and metastasis, and coordinately regulates Dicer and miR-130b to suppress metastasis. Metastatic mouse and human tumours deficient in TAp63 express Dicer at very low levels, and we found that modulation of expression of Dicer and miR-130b markedly affected the metastatic potential of cells lacking TAp63. TAp63 binds to and transactivates the Dicer promoter, demonstrating direct transcriptional regulation of Dicer by TAp63. These data provide a novel understanding of the roles of TAp63 in tumour and metastasis suppression through the coordinate transcriptional regulation of Dicer and miR-130b and may have implications for the many processes regulated by miRNAs.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Broadly, tissue regeneration is achieved in two ways: by proliferation of common differentiated cells and/or by deployment of specialized stem/progenitor cells. Which of these pathways applies is ...both organ- and injury-specific. Current models in the lung posit that epithelial repair can be attributed to cells expressing mature lineage markers. By contrast, here we define the regenerative role of previously uncharacterized, rare lineage-negative epithelial stem/progenitor (LNEP) cells present within normal distal lung. Quiescent LNEPs activate a ΔNp63 (a p63 splice variant) and cytokeratin 5 remodelling program after influenza or bleomycin injury in mice. Activated cells proliferate and migrate widely to occupy heavily injured areas depleted of mature lineages, at which point they differentiate towards mature epithelium. Lineage tracing revealed scant contribution of pre-existing mature epithelial cells in such repair, whereas orthotopic transplantation of LNEPs, isolated by a definitive surface profile identified through single-cell sequencing, directly demonstrated the proliferative capacity and multipotency of this population. LNEPs require Notch signalling to activate the ΔNp63 and cytokeratin 5 program, and subsequent Notch blockade promotes an alveolar cell fate. Persistent Notch signalling after injury led to parenchymal 'micro-honeycombing' (alveolar cysts), indicative of failed regeneration. Lungs from patients with fibrosis show analogous honeycomb cysts with evidence of hyperactive Notch signalling. Our findings indicate that distinct stem/progenitor cell pools repopulate injured tissue depending on the extent of the injury, and the outcomes of regeneration or fibrosis may depend in part on the dynamics of LNEP Notch signalling.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
La trata de personas con fines de explotación sexual es una de las más complejas manifestaciones de violencia contra la mujer, debido a la confluencia de violencia física, psicológica, sexual, ...económica y su conexidad con otros delitos que vulneran la libertad y la vida. Las organizaciones criminales trafican con la vida y la dignidad de las personas sometiéndolas a una moderna forma de esclavitud, situación que afecta profundamente a la mujer en el goce de sus derechos y la posibilidad de una vida libre. Se plantean interrogantes acerca de la protección adecuada de los derechos de las víctimas en la sociedad contemporánea, frente a la aparición de carácter permanente de nuevos grupos y sus modalidades operativas. Una de estas interrogantes consiste en determinar si la figura del femicidio es aplicable al homicidio cometido en el contexto de trata de personas, pues el Código Penal argentino solo contempla el femicidio íntimo. Con el objetivo de despejar estas inquietudes, se formularán conclusiones que propician la revisión de los aspectos negativos que la normativa actual presenta, como así también se aportarán fundamentos, en aras de incentivar futuras reformas legislativas, que aborden esta modalidad de trata en toda su extensión. Para ello, se efectuará un análisis cualitativo de la normativa de la República Argentina, los tratados signados: Convención sobre la Eliminación de todas las formas de Discriminación contra la Mujer (CEDAW, por sus siglas en inglés), Belém do Pará y precedentes de la Corte Interamericana de Derechos Humanos (Corte IDH).
O funcionamento do trato gastrointestinal (TGI) tem grande relação com o estado geral do organismo humano. O equilíbrio entre microrganismos benéficos e patógenos, assim como suas interações, são ...capazes de determinar a saúde do hospedeiro. Fatores internos e externos ao indivíduo podem determinar o equilíbrio do ecossistema bacteriano. Se bem equilibrado, o organismo se mantém protegido e saudável. Se houver um desequilíbrio, pode aumentar o número de patógenos que se manifestam por meio de sinais e sintomas em todo o organismo, caracterizando um estado de disbiose intestinal. Objetivo: Avaliar a disbiose intestinal em estudantes do Curso de Nutrição de uma Universidade da Grande Florianópolis. Materiais e métodos: Estudo descritivo, transversal de caráter quantitativo. Os dados foram obtidos por meio da aplicação do Questionário de Rastreamento Metabólico adaptado aos sintomas gastrointestinais e escala de Bristol aplicados em 128 estudantes do curso de Nutrição de uma Universidade da Grande Florianópolis. Resultados: 29,69% apresentaram sintomas de disbiose e 16,41% tipo de fezes com risco para disbiose. Os principais sintomas apresentados foram arrotos e/ou gases intestinais (82,82%), seguido de inchaço/distensão abdominal (80,47%) e dor estomacal/intestinal (60,94%). O tipo de fezes mais frequente foi o tipo 3 (46,88%). Conclusão: É baixa a prevalência de sinais e sintomas de disbiose intestinal nos estudantes do curso de Nutrição, provavelmente por já adotarem práticas alimentares saudáveis em sua rotina, contribuindo para a saúde da microbiota.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cellular mRNAs exist in messenger ribonucleoprotein (mRNP) complexes, which undergo transitions during the lifetime of the mRNAs and direct posttranscriptional gene regulation. A final ...posttranscriptional step in gene expression is the turnover of the mRNP, which involves degradation of the mRNA and recycling of associated proteins. How tightly associated protein components are released from degrading mRNPs is unknown. Here, we demonstrate that the ATPase activity of the RNA helicase Upf1 allows disassembly of mRNPs undergoing nonsense-mediated mRNA decay (NMD). In the absence of Upf1 ATPase activity, partially degraded NMD mRNA intermediates accumulate in complex with NMD factors and concentrate in processing bodies. Thus, disassembly and completion of turnover of mRNPs undergoing NMD requires ATP hydrolysis by Upf1. This uncovers a previously unappreciated and potentially regulated step in mRNA decay and raises the question of how other mRNA decay pathways release protein components of substrate mRNPs.
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► Completion of nonsense-mediated mRNA decay (NMD) requires Upf1 ATPase activity ► Partially degraded NMD mRNP intermediates accumulate in the absence of Upf1 ATPase ► NMD mRNP intermediates are resistant to 5′-to-3′ exonucleolytic decay ► NMD mRNP intermediates accumulate in processing bodies
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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