Genres: Thriller Running Time: 106 min. Directed by: Francis Annan Starring: Daniel Radcliffe, Ian Hart Synopsis: Based on the real-life prison break of two political captives, Escape From Pretoria is a race-against-time thriller set in the tumultuous apartheid days of South Africa.

It certainly wasn’t big, and probably didn’t bang – and the surprises in the conventional story of the universe's origins don’t end there

It certainly wasn’t big, and probably didn’t bang – and the surprises in the conventional story of the universe's origins don’t end there

ABSTRACT

Human noroviruses (HuNoVs) are the leading cause of nonbacterial gastroenteritis worldwide. Histo-blood group antigen (HBGA) expression is an important susceptibility factor for HuNoV infection based on controlled human infection models and epidemiologic studies that show an association of secretor status with infection caused by several genotypes. The fucosyltransferase 2 gene (FUT2) affects HBGA expression in intestinal epithelial cells; secretors express a functional FUT2 enzyme, while nonsecretors lack this enzyme and are highly resistant to infection and gastroenteritis caused by many HuNoV strains. These epidemiologic associations are confirmed by infections in stem cell-derived human intestinal enteroid (HIE) cultures. GII.4 HuNoV does not replicate in HIE cultures derived from nonsecretor individuals, while HIEs from secretors are permissive to infection. However, whether FUT2 expression alone is critical for infection remains unproven, since routinely used secretor-positive transformed cell lines are resistant to HuNoV replication. To evaluate the role of FUT2 in HuNoV replication, we used CRISPR or overexpression to genetically manipulate FUT2 gene function to produce isogenic HIE lines with or without FUT2 expression. We show that FUT2 expression alone affects both HuNoV binding to the HIE cell surface and susceptibility to HuNoV infection. These findings indicate that initial binding to a molecule(s) glycosylated by FUT2 is critical for HuNoV infection and that the HuNoV receptor is present in nonsecretor HIEs. In addition to HuNoV studies, these isogenic HIE lines will be useful tools to study other enteric microbes where infection and/or disease outcome is associated with secretor status.

IMPORTANCE Several studies have demonstrated that secretor status is associated with susceptibility to human norovirus (HuNoV) infection; however, previous reports found that FUT2 expression is not sufficient to allow infection with HuNoV in a variety of continuous laboratory cell lines. Which cellular factor(s) regulates susceptibility to HuNoV infection remains unknown. We used genetic manipulation of HIE cultures to show that secretor status determined by FUT2 gene expression is necessary and sufficient to support HuNoV replication based on analyses of isogenic lines that lack or express FUT2. Fucosylation of HBGAs is critical for initial binding and for modification of another putative receptor(s) in HIEs needed for virus uptake or uncoating and necessary for successful infection by GI.1 and several GII HuNoV strains.

Maintenance of the proteome, ensuring the proper locations, proper conformations, appropriate concentrations, etc., is essential to preserve the health of an organism in the face of environmental insults, infectious diseases, and the challenges associated with aging. Maintaining the proteome is even more difficult in the background of inherited mutations that render a given protein and others handled by the same proteostasis machinery misfolding prone and/or aggregation prone. Maintenance of the proteome or maintaining proteostasis requires the orchestration of protein synthesis, folding, trafficking, and degradation by way of highly conserved, interacting, and competitive proteostasis pathways. Each subcellular compartment has a unique proteostasis network compromising common and specialized proteostasis maintenance pathways. Stress-responsive signaling pathways detect the misfolding and/or aggregation of proteins in specific subcellular compartments using stress sensors and respond by generating an active transcription factor. Subsequent transcriptional programs up-regulate proteostasis network capacity (i.e., ability to fold and degrade proteins in that compartment). Stress-responsive signaling pathways can also be linked by way of signaling cascades to nontranscriptional means to reestablish proteostasis (e.g., by translational attenuation). Proteostasis is also strongly influenced by the inherent kinetics and thermodynamics of the folding, misfolding, and aggregation of individual proteins, and these sequence-based attributes in combination with proteostasis network capacity together influence proteostasis. In this review, we will focus on the growing body of evidence that proteostasis deficits leading to human pathology can be reversed by pharmacologic adaptation of proteostasis network capacity through stress-responsive signaling pathway activation. The power of this approach will be exemplified by focusing on the ATF6 arm of the unfolded protein response stress responsive-signaling pathway that regulates proteostasis network capacity of the secretory pathway.

Selon Pierre Karl Péladeau, la crise du coronavirus pourrait permettre d’établir les bases du retour d’une équipe de hockey professionnelle à Québec.

Le Québec en dehors de la grande région de Montréal s’apprête à rouvrir les écoles et les garderies, et plusieurs inquiétudes persistent.

Notre journaliste est retournée travailler comme préposée dans une RI deux ans après avoir sonné l’alarme sur les conditions de ces établissements.

En 2017, je me suis plongée dans la peau d’une préposée aux bénéficiaires. Cette fois, le travail est le même, mais le contexte est bien différent.

It appears that this act of God had a little help from man, and was an accident waiting to happen.

In our dystopian future we might all be buying power by the watt-hour from a cart in the market.

The Secretary-General of the OECD will be in South Africa on 4th March 2013 on an Official Visit. On this occasion, he will present the 2013 OECD Economic Survey of South Africa together with Mr. Pravin Jamnadas Gordhan, Minister of Finance.

A new data set from Silicon Valley Bank (SVB) details how startups are reacting to the post-unicorn era as COVID-19-related disruptions upset the global economy and remake the risk tolerance of private investors. What SVB’s new report shows is unsurprising: venture capital deal volumes are falling, startups are tapping existing debt capacities to add cash […]

Uber Eats is pulling out of a clutch of markets — shuttering its on-demand food offering in the Czech Republic, Egypt, Honduras, Romania, Saudi Arabia, Uruguay and Ukraine. It’s also transferring its Uber Eats business operations in the United Arab Emirates (UAE) to Careem, its wholly owned ride-hailing subsidiary that’s mostly focused on the Middle […]

Nottingham Forest striker Ben Brereton has agreed personal terms with Blackburn Rovers ahead of a proposed £6million transfer, Sportsmail understands.

Blackburn Rovers have completed the loan signing of Nottingham Forest striker Ben Brereton on an initial loan which can be made permanent on January 1, 2019.

Kate, 27, covers Health magazine in a pair of denim shorts and a button-down shirt that she wore open and tied around her waist to expose her stomach.

Oscar Pistorius faces being jailed in the same high security prison as a notorious Czech prisoner on trial for torture. The athlete is due to discover his fate on Tuesday when he is sentenced.

The disgraced former Paralympian (right) is said to be well-looked after in prison because guards are terrified of the public and legal backlash should he come to any harm while serving his sentence.

With its drab, yellow walls, metal bed, this cramped two metre squared cell at Kgosi Mampuru II jail in Pretoria is where Oscar Pistorius spent 23 hours a day for killing model Reeva Steenkamp

In the caption, the power sisters even credited the man who did the retouching for the photograph in a rare move.

A primary school principal who threatened to expel a five-year-old boy because of his long hair will have to let him attend classed for the time being. 

The contestants on Netflix dating show Too Hot to Handle aren't exactly known for their intellectual gifts.

This re-telling of Mahabharata from the perspective of Shakuni delves into how the heir of Gandhara used the Padavas and the Kauravas as pawns in an intricate and clever power play that culminated in an epic battle of 18 days.

Finance Minister Nirmala Sitharaman insisted that the Indian National Congress and Rahul Gandhi should introspect why they "fail to play a constructive role in cleaning up the system".

Cham : Palgrave Macmillan, 2019.

New York, NY : Oxford University Press, 2020.

Cham : Springer, 2019.

Hayden Library - PN6790.J34 P87313 2015

Hayden Library - PN6790.J33 T378513 2017

Hayden Library - PN6728.E73 B37 2018

Hayden Library - PN6790.J34 M6613 2018

Australia. Parliament. Joint Standing Committee on Electoral Matters, author, issuing body

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Davies, Martin et.al., author

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Gerschel, Antoine

Dewey Library - GB1201.R58 2019

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Hayden Library - PQ3949.C44 C3413 2017

Westerner

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Hayden Library - QB843.B55 G83 2017

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