Spatial control of irreversible protein aggregation

Liquid cellular compartments spatially segregate from the cytoplasm and can regulate aberrant protein aggregation, a process linked to several medical conditions, including Alzheimer's and Parkinson's diseases. Yet the mechanisms by which these droplet-like compartments affect protein aggregation remain unknown. Here, we combine kinetic theory of protein aggregation and liquid-liquid phase separation to study the spatial control of irreversible protein aggregation in the presence of liquid compartments. We find that, even for weak interactions between the compartment constituents and the aggregating monomers, aggregates are strongly enriched inside the liquid compartment relative to the surrounding cytoplasm. We show that this enrichment is caused by a positive feedback mechanism of aggregate nucleation and growth which is mediated by a flux maintaining the phase equilibrium between the compartment and the cytoplasm. Our model predicts that the compartment volume that maximizes aggregate enrichment in the compartment is determined by the reaction orders of aggregate nucleation. The underlying mechanism of aggregate enrichment could be used to confine cytotoxic protein aggregates inside droplet-like compartments suggesting potential new avenues against aberrant protein aggregation. Our findings could also represent a common mechanism for the spatial control of irreversible chemical reactions in general

Editorial.

Welcome to the third issue of our journal . We are delighted to feature in this issue two peer-reviewed papers looking in detail at some of the outcomes of the ring-fenced money used for researcher development in the UK under the guise of Roberts funding. In her paper looking at impact of the training provided by this funding on late stage doctoral student researchers, Walsh and colleagues draw our attention to detailed analysis of impact via a variety of evaluation approaches. She also alerts us to the question of whether such development programmes should run alongside the traditional apprenticeship style training of such students. The second paper by Heading and colleagues provides a detailed example of a development programme event in information management and provides further evidence for impact of such training. Bai and Hudson move the focus to the research –teaching nexus and highlight the difficulty for TEFL staff in Chinese HEIs to develop a research strand in their careers. The importance in developing research capacity, providing support and mentoring to such staff is shown to be pivotal in their development. Finally conceptions of research from a variety of viewpoints are analyzed by Pitcher. Pitcher considers how the PhD itself, alongwith how the knowledge and outcomes of PhD research are perceived. In a preliminary survey of students on these matters, Pitcher highlights the importance of alignment with these concepts between student and supervisor thus avoiding difficulties between apprentice and supervisor as the research progresses which might inhibit development

Parvovirus B19 infection in pediatric transplant patients

Evidence of recent parvovirus virus infection (as determined by the presence of a positive IgM antibody titer) without other identified causes of anemia was found in 5 of 26 pediatric solid-organ transplant recipients evaluated for moderate-to-severe anemia between June 1990 and July 1991. Anemia tended to be chronic (median duration of anemia at the time of diagnosis was 12 weeks) and was associated with normal red blood cell indices in the absence of reticulocytes. The median age of the children at the time of presentation with anemia due to parvovirus was 1.8 years at a median time of 8 months after transplantation. Four of the 5 children were treated with i.v. immunoglobulin because of persistance of anemia requiring blood transfusions. A response characterized by an increase in reticulocyte count and normalization of hemoglobin was seen in each of these patients 2-4 weeks after treatment. The remaining patient experienced a spontaneous recovery from her anemia. Parvovirus infection should be included in the differential diagnosis of solid-organ transplant recipients presenting with severe anemia associated with low or absent reticulocytes

Amplification of simian retroviral sequences from human recipients of baboon liver transplants

Investigations into the use of baboons as organ donors for human transplant recipients, a procedure called xenotransplantation, have raised the specter of transmitting baboon viruses to humans and possibly establishing new human infectious diseases. Retrospective analysis of tissues from two human transplant recipients with end-stage hepatic disease who died 70 and 27 days after the transplantation of baboon livers revealed the presence of two simian retroviruses of baboon origin, simian foamy virus (SFV) and baboon endogenous virus (BaEV), in multiple tissue compartments. The presence of baboon mitochondrial DNA was also detected in these same tissues, suggesting that xenogeneic 'passenger leukocytes' harboring latent or active viral infections had migrated from the xenografts to distant sites within the human recipients. The persistence of SFV and BaEV in human recipients throughout the posttransplant period underscores the potential infectious risks associated with xenotransplantation

Ariel - Volume 8 Number 4

Executive Editor James W. Lockard Jr. Issues Editor Neeraj K. Kanwal Business Manager Neeraj K. Kanwal University News Martin Trichtinger World News Doug Hiller Opinions Elizabeth A. McGuire Features Patrick P. Sokas Sports Desk Shahab S. Minassian Managing Editor Edward H. Jasper Managing Associate Brenda Peterson Photography Editor Robert D. Lehman, Jr. Graphics Christine M. Kuhnl

Phase shifts of synchronized oscillators and the systolic/diastolic blood pressure relation

We study the phase-synchronization properties of systolic and diastolic arterial pressure in healthy subjects. We find that delays in the oscillatory components of the time series depend on the frequency bands that are considered, in particular we find a change of sign in the phase shift going from the Very Low Frequency band to the High Frequency band. This behavior should reflect a collective behavior of a system of nonlinear interacting elementary oscillators. We prove that some models describing such systems, e.g. the Winfree and the Kuramoto models offer a clue to this phenomenon. For these theoretical models there is a linear relationship between phase shifts and the difference of natural frequencies of oscillators and a change of sign in the phase shift naturally emerges.Comment: 8 figures, 9 page

Transiting Exoplanet Survey Satellite (TESS) Flight Dynamics Commissioning Results and Experiences

The Transiting Exoplanet Survey Satellite (TESS) will perform the first-ever spaceborne all-sky exoplanet transit survey and is the first primary-mission application of a lunar-resonant orbit. Launched on April 18, 2018, TESS completed a two-month commissioning phase consisting of three phasing loops followed by a lunar flyby and a final maneuver to achieve resonance. During the mission orbit, no further station-keeping maneuvers are planned or required. NASA Goddard Space Flight Center is performing flight dynamics operations for the mission. This paper covers the design, implementation, and results from TESS commissioning, including the projected performance of the final mission orbit

2003 Manifesto on the California Electricity Crisis

The authors, an ad-hocgroup of professionals with experience in regulatory and energy economics, share a common concern with the continuing turmoil facing the electricity industry ("the industry") in California. Most ofthe authorsendorsed the first California Electricity Manifesto issued on January 25, 2001. Almost two years have passed since that first Manifesto. While wholesale electric prices have moderated and California no longer faces the risk of blackouts, in many ways the industry is in worse shape now than it was at the start of 2001. As a result, the group of signatories continues to have a deep concern with the conflicting policy directions being pursued for the industry at both the State and Federal levels of government and the impact the uncertainties associated with these conflicting policies will have, long term, on the economy of California. Theauthorshave once again convened under the auspices of the Institute of Management, Innovation and Organization at the University of California, Berkeley, to put forward ourtheir ideas on a basic set of necessary policies to move the industry forward for the benefit of all Californians and the nation. The authors point out that theydo not pretend to be "representative." They do bring, however, a very diverse range of backgrounds and expertise.Technology and Industry, Regulatory Reform