Interaction of yeast eIF4G with spliceosome components Implications in pre-mRNA processing events

International audienceAs evidenced from mammalian cells the eukaryotic translation initiation factor eIF4G has a putative role in nuclear RNA metabolism. Here we investigate whether this role is conserved in the yeast Saccharomyces cerevisiae. Using a combination of in vitro and in vivo methods, we show that, similar to mammalian eIF4G, yeast eIF4G homologues, Tif4631p and Tif4632p, are present both in the nucleus and the cytoplasm. We show that both eIF4G proteins interact efficiently in vitro with UsnRNP components of the splicing machinery. More specifically, Tif4631p and Tif4632p interact efficiently with U1 snRNA in vitro. In addition, Tif4631p and Tif4632p associate with protein components of the splicing machinery, namely Snu71p and Prp11p. To further delineate these interactions, we map the regions of Tif4631p and Tif4632p that are important for the interaction with Prp11p and Snu71p and we show that addition of these regions to splicing reactions in vitro has a dominant inhibitory effect. The observed interactions implicate eIF4G in aspects of pre-mRNA processing. In support of this hypothesis, deletion of one of the eIF4G isoforms results in accumulation of un-spliced precursors for a number of endogenous genes, in vivo. In conclusion these observations are suggestive of the involvement of yeast eIF4G in pre-mRNA metabolism

End-To-End Modeling Reveals Species-Specific Effects of Large-Scale Coastal Restoration On Living Resources Facing Climate Change

Coastal erosion and wetland loss are affecting Louisiana to such an extent that the loss of land between 1932 and 2016 was close to 5,000 km2. To mitigate this decline, coastal protection and restoration projects are being planned and implemented by the State of Louisiana, United States. The Louisiana Coastal Master Plan (CMP) is an adaptive management approach that provides a suite of projects that are predicted to build or maintain land and protect coastal communities. Restoring the coast with this 50-year large-scale restoration and risk reduction plan has the potential to change the biomass and distribution of economically and ecologically important fisheries species in this region. However, not restoring the coast may have negative impacts on these species due to the loss of habitat. This research uses an ecosystem model to evaluate the effects of plan implementation versus a future without action (FWOA) on the biomass and distribution of fisheries species in the estuaries over 50 years of model simulations. By simulating effects using a spatially-explicit ecosystem model, not only can the changes in biomass in response to plan implementation be evaluated, but also the distribution of species in response to the planned restoration and risk reducation projects. Simulations are performed under two relative sea level rise (SLR) scenarios to understand the effects of climate change on project performance and subsequent fisheries species biomass and distribution. Simulation output of eight economically important fisheries species shows that the plan mostly results in increases in species biomass, but that the outcomes are species-specific and basin-specific. The SLR scenarios highly affects the amount of wetland habitat maintained after 50 years (with higher levels of wetland loss under increased SLR) and, subsequently, the biomass of species depending on that habitat. Species distribution results can be used to identify expected changes for specific species on a regional basis. By making this type of information available to resource managers, precautionary measures of ecosystem management and adaptation can be implemented

Ambiguous Tests of General Relativity on Cosmological Scales

There are a number of approaches to testing General Relativity (GR) on linear scales using parameterized frameworks for modifying cosmological perturbation theory. It is sometimes assumed that the details of any given parameterization are unimportant if one uses it as a diagnostic for deviations from GR. In this brief report we argue that this is not necessarily so. First we show that adopting alternative combinations of modifications to the field equations significantly changes the constraints that one obtains. In addition, we show that using a parameterization with insufficient freedom significantly tightens the apparent theoretical constraints. Fundamentally we argue that it is almost never appropriate to consider modifications to the perturbed Einstein equations as being constraints on the effective gravitational constant, for example, in the same sense that solar system constraints are. The only consistent modifications are either those that grant near-total freedom, as in decomposition methods, or ones which map directly to a particular part of theory space

ELR510444 Inhibits Tumor Growth and Angiogenesis by Abrogating HIF Activity and Disrupting Microtubules in Renal Cell Carcinoma

Background: Hypoxia-inducible factor (HIF) is an attractive therapeutic target for renal cell carcinoma (RCC) as its high expression due to the loss of von Hippel-Lindau (VHL) promotes RCC progression. Considering this, we hypothesized that ELR510444, a novel orally available small molecule inhibitor of HIF activity, would reduce angiogenesis and possess significant activity in RCC. The mechanism of action and therapeutic efficacy of ELR510444 were investigated in in vitro and in vivo models of RCC. Principal Findings: ELR510444 decreased HIF-1a and HIF-2a levels, reduced RCC cell viability and clonogenic survival, and induced apoptosis. VHL-deficient RCC cells were more sensitive to ELR510444-mediated apoptosis and restoration of VHL promoted drug resistance. Higher concentrations of ELR51044 promoted apoptosis independently of VHL status, possibly due to the microtubule destabilizing properties of this agent. ELR510444 significantly reduced tumor burden in the 786-O and A498 RCC xenograft models. These effects were associated with increased necrosis and apoptosis and inhibition of angiogenesis. Conclusions: ELR510444 is a promising new HIF inhibitor that reduced RCC cell viability, induced apoptosis, and diminished tumor burden in RCC xenograft models. ELR510444 also destabilized microtubules suggesting that it possesses vascula

The Grizzly, March 4, 1983

Zeta Chi Suspended: Fraternity Disciplined for Pledging Violations • Symposium Topics Discussed • New Forum Committee to Revise System • Letters to the Editor: Alumnus Responds to Grizzly Policy • Committee Reviews Appeals Procedure • Meistersingers Tour • Exam Schedule • Woodcuts at Myrin • Stravinsky Program Ends Winterfest • Lantern Deadline Approaches • Lewis on Wall Street • Alpha Sigma Nu Tops GPAs • Roving Reporter: The Administration is Proposing to put a Live-in Dean in 97 of New Men\u27s Dorm • Pre-Legal Society Resurrected • Swimmers Perform Beyond Expectation • Bear Blades Blaze to Victory • Gymnasts Draw No. 2 Ratinghttps://digitalcommons.ursinus.edu/grizzlynews/1096/thumbnail.jp

The Grizzly, February 4, 1983

Trouble at Cutillo\u27s: Frats Earn Reputation as Animals • Drinking Concerns Richter • Economics Council Sponsors Entrepreneur-Related Forum • President\u27s Corner • Wismer Tries Again • Pfacelift at Pfahler • Bear Blades Burnished Beat Wilmington Twice • Serendipity Celebration Features Films • Writing Center Welcomes Students • Who\u27s Who in Who\u27s Who? • Commentary: Speak Up for Coed Housing • Didja Ever Wonder • Wrestlers Earn Split • Lewis on Wall Street • Disruptive Fans Cause Flare-up at Widener • Top Individual Efforts Mark Gymnastics Team • Interview: Chupein Named to All-League Team • Lady Hoops Still Struggling • Men\u27s Basketball Find Road a Bit Bumpy • Swimmers Maul Terrors of Western Marylandhttps://digitalcommons.ursinus.edu/grizzlynews/1092/thumbnail.jp

The communication of a secondary care diagnosis of autoimmune hepatitis to primary care practitioners: a population-based study

Background Autoimmune Hepatitis is a chronic liver disease which affects young people and can result in liver failure leading to death or transplantation yet there is a lack of information on the incidence and prevalence of this disease and its natural history in the UK. A means of obtaining this information is via the use of clinical databases formed of electronic primary care records. How reliably the diagnosis is coded in such records is however unknown. The aim of this study therefore was to assess the proportion of consultant hepatologist diagnoses of Autoimmune Hepatitis which were accurately recorded in General Practice computerised records. Methods Our study population were patients with Autoimmune Hepatitis diagnosed by consultant hepatologists in the Queens Medical Centre, Nottingham University Hospitals (UK) between 2004 and 2009. We wrote to the general practitioners of these patients to obtain the percentage of patients who had a valid READ code specific for Autoimmune Hepatitis. Results We examined the electronic records of 51 patients who had biopsy evidence and a possible diagnosis of Autoimmune Hepatitis. Forty two of these patients had a confirmed clinical diagnosis of Autoimmune Hepatitis by a consultant hepatologist: we contacted the General Practitioners of these patients obtaining a response rate of 90.5% (39/42 GPs). 37/39 of these GPs responded with coding information and 89% of these patients (33/37) used Read code J638.00 (Autoimmune Hepatitis) to record a diagnosis. Conclusions The diagnosis of Autoimmune Hepatitis made by a Consultant Hepatologist is accurately communicated to and electronically recorded by primary care in the UK. As a large proportion of cases of Autoimmune Hepatitis are recorded in primary care, this minimises the risk of introducing selection bias and therefore selecting cases using these data will be a valid method of conducting population based studies on Autoimmune Hepatitis

Cutting cardiovascular risk in barbershops

http://dx.doi.org/10.1016/j.jomh.2009.07.00

Domesticating the ‘troubled family’: Racialised sexuality and the postcolonial governance of family life in the UK

This article examines how the UK’s Troubled Families Programme (TFP) works as a strategy of domestication which produces and delimits certain forms of ‘family life’. Drawing upon critical geographies of home and empire, the article explores how the TFP works to manage the troubled family as part of a longer history of regulating unruly households in the name of national health and civilisation. Viewing the TFP as part of the production of heteronormative order, highlights how the policy remobilises and reconfigures older forms of colonial rule which work to demarcate between civility/savagery, the developable/undevelopable. In examining the postcolonial dimension of neoliberal social policy, the article stresses how the TFP relies on racializing and sexualised logics of socio-biological control borrowed from imperial eugenics. Reading the TFP in this way contributes to our understanding of neoliberal rule. That the troubled family can be either domesticated or destroyed (through benefit sanctions and eviction) equally reveals the extent to which domesticity works as a key site for the production of both ‘worthy’ and ‘surplus’ life