Substrate selection in endoplasmic reticulum protein quality control

Protein folding and maturation is a complex and error-prone process. Errors in this process may lead to deleterious effects ranging from non-functional single proteins to large-scale protein aggregation leading to cell death. It is essential for cellular function that protein misfolding does not occur unchecked, and therefore numerous chaperone systems exist within the cell. For the thousands of proteins which traffic through the secretory pathway, the primary site of folding and maturation is the endoplasmic reticulum (ER). Multiple chaperone pathways within the ER, generally termed ER protein quality control, must support the proper maturation process of these thousands of substrates. While some simple secretory pathway proteins may be able to fold with minimal chaperone engagement, more complex proteins may commonly misfold even under native conditions, which is especially important for multi-cellular organisms which have larger and more complex secretory pathway proteomes. The chaperone pathways within the ER engage substrates based generally on features those substrates possess. These include hydrophobic regions, free cysteines, and N-glycans. However, which substrates are selected by each of these pathways is not well understood on a systematic level. The work presented here examines the chaperone selection process for a substrate which possess all features and demonstrates that substrate features do not dictate chaperone pathway engagement. As such, an understanding of which substrates are engaged by which pathway under endogenous conditions requires experimental determination. The N-glycan based chaperone pathway was next examined, and the substrates which heavily engage this process under endogenous conditions were described. This information allows for a previously lacking understanding of the folding and maturation process of many proteins and therefore presents possible interventions for the diseases and cellular functions associated with these proteins

Inheritability of the Right of Publicity Upon the Death of the Famous

After tracing the evolution of the right of publicity, this Recent Development focuses on these recent decisions confronting the issue of descendibility. This Recent Development then concludes that the right of publicity should be inheritable for a designated period of time and that inheritability should not depend upon previous exploitation of the right

The Role of Genomics in Tracking the Evolution of Influenza A Virus

Influenza A virus causes annual epidemics and occasional pandemics of short-term respiratory infections associated with considerable morbidity and mortality. The pandemics occur when new human-transmissible viruses that have the major surface protein of influenza A viruses from other host species are introduced into the human population. Between such rare events, the evolution of influenza is shaped by antigenic drift: the accumulation of mutations that result in changes in exposed regions of the viral surface proteins. Antigenic drift makes the virus less susceptible to immediate neutralization by the immune system in individuals who have had a previous influenza infection or vaccination. A biannual reevaluation of the vaccine composition is essential to maintain its effectiveness due to this immune escape. The study of influenza genomes is key to this endeavor, increasing our understanding of antigenic drift and enhancing the accuracy of vaccine strain selection. Recent large-scale genome sequencing and antigenic typing has considerably improved our understanding of influenza evolution: epidemics around the globe are seeded from a reservoir in East-Southeast Asia with year-round prevalence of influenza viruses; antigenically similar strains predominate in epidemics worldwide for several years before being replaced by a new antigenic cluster of strains. Future in-depth studies of the influenza reservoir, along with large-scale data mining of genomic resources and the integration of epidemiological, genomic, and antigenic data, should enhance our understanding of antigenic drift and improve the detection and control of antigenically novel emerging strains

Investigation of Anaerobic Digestion of the Aqueous Phase from Hydrothermal Carbonization of Mixed Municipal Solid Waste

In 2017, the United States Environmental Protection Agency (EPA) reported that Americans generated over 268 million tons of municipal solid waste (MSW). The majority (52%) of this waste ends up in landfills, which are the third largest source of anthropogenic methane emissions. Improvements in terms of waste management and energy production could be solved by integrating MSW processing with hydrothermal carbonization (HTC) and anaerobic digestion (AD) for converting organic carbon of MSW to fuels. The objectives of this study were to (a) investigate HTC experiments at varying temperatures and residence times (b) evaluate aqueous phase and solids properties, and (c) perform AD bench scale bottle test on the aqueous phase. A mixture of different feedstock representing MSW was used. HTC at 280 °C and 10 min yielded the highest total organic carbon (TOC) of 8.16 g/L with biogas yields of 222 mL biogas/g TOC. Results showed that AD of the aqueous phase from a mixed MSW feedstock is feasible. The integrated approach shows organic carbon recovery of 58% (hydrochar and biogas). This study is the first of its kind to investigate varying temperature and times for a heterogeneous feedstock (mixed MSW), and specifically evaluating HTC MSW aqueous phase anaerobic biodegradability

Theoretical analysis for the apparent discrepancy between pbarp and pp data in charged particle forward-backward multiplicity correlations

The strength of charged particle forward-backward multiplicity correlation in pbar+p and p+p collisions at s^1/2 = 200 GeV is studied by PYTHIA 6.4 and compared to the UA5 and STAR data correspondingly. It is turned out that a factor of 3-4 apparent discrepancy between UA5 and STAR data can be attributed to the differences in detector acceptances and observing bin interval in both experiments. A mixed event method is introduced and used to calculate the statistical correlation strength and the dynamical correlation strengths stemming from the charge conservation, four- momentum conservation, and decay, respectively. It seems that the statistical correlation is much larger than dynamical one and the charge conservation, four-momentum conservation and decay may account for most part of the dynamical correlation. In addition, we have also calculated the correlation strength by fitting the charged particle multiplicity distribution from PYTHIA to the Negative Binomial Distribution and found that the result agrees well with the correlation strength calculated by mixed events.Comment: 5 pages, 4 figure

Household demographic determinants of Ebola epidemic risk

A salient characteristic of Ebola, and some other infectious diseases such as Tuberculosis, is intense transmission among small groups of cohabitants and relatively limited indiscriminate transmission in the wider population. Here we consider a mathematical model for an Ebola epidemic in a population structured into households of equal size. We show that household size, a fundamental demographic unit, is a critical factor that determines the vulnerability of a community to epidemics, and the effort required to control them. Our analysis is based on the household reproduction number, but we also consider the basic reproduction number, intrinsic growth rate and final epidemic size. We show that, when other epidemiological parameters are kept the same, all of these quantifications of epidemic growth and size are increased by larger households and more intense within-household transmission. We go on to model epidemic control by case detection and isolation followed by household quarantine. We show that, if household quarantine is ineffective, the critical probability with which cases must be detected to halt an epidemic increases significantly with each increment in household size and may be a very challenging target for communities composed of large households. Effective quarantine may, however, mitigate the detrimental impact of large household sizes. We conclude that communities composed of large households are fundamentally more vulnerable to epidemics of infectious diseases primarily transmitted by close contact, and any assessment of control strategies for these epidemics should take into account the demographic structure of the population

Functionalised Microscale Nanoband Edge Electrode (MNEE) Arrays; the systematic quantitative study of hydrogels grown on nanoelectrode biosensor arrays for enhanced sensing in biological media

We demonstrate a hydrogel-coated nanoelectrode array biosensor that is resistant to biofouling.</p