Critical role of actin in modulating BBB permeability

Abstract A major obstacle in the treatment of degenerative manifestations and debilitating diseases in the central nervous system (CNS) lies in the impediment of drug delivery into these tissues. The impediment is due to a membrane barrier referred to as the blood -brain barrier (BBB). It is known that the BBB is a unique membranous structure in brain capillaries that tightly segregates the brain from systemic blood circulation. It is imperative to have a thorough understanding of the molecular components and their integrated function of this barrier to develop effective therapeutics for CNS disorders and diseases. Although there are other cell and biochemical properties that underlie this barrier function, it is well established that the barrier is mainly made up of the physical elements of tight junction (TJ) complex. The major constituents of TJ, such as occludin, claudins, zonula occludens (ZOs) and junctional adhesion molecule (JAM) have been subjects of intensive studies and reviews. However, after examining currently proposed models, we have come to believe that a cytoskeletal componentactin may play a critical role in interacting TJ molecular constituents and modulating functional TJ complex. In this review, we will discuss the correlation of temporal and spatial distribution and remodeling of actin filaments with altering integrity of TJ complexes in various systems and present a hypothesis to depict its potential role in modulating BBB permeability.

Simulation of the global contrail radiative forcing: A sensitivity analysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96352/1/grl29839.pd

Component analysis of errors in satellite-based precipitation estimates

Satellite-based precipitation estimates have great potential for a wide range of critical applications, but their error characteristics need to be examined and understood. In this study, six (6) high-resolution, satellite-based precipitation data sets are evaluated over the contiguous United States against a gauge-based product. An error decomposition scheme is devised to separate the errors into three independent components, hit bias, missed precipitation, and false precipitation, to better track the error sources associated with the satellite retrieval processes. Our analysis reveals the following. (1) The three components for each product are all substantial, with large spatial and temporal variations. (2) The amplitude of individual components sometimes is larger than that of the total errors. In such cases, the smaller total errors are resulting from the three components canceling one another. (3) All the products detected strong precipitation (\u3e40 mm/d) well, but with various biases. They tend to overestimate in summer and underestimate in winter, by as much as 50% in either season, and they all miss a significant amount of light precipitation (\u3c10 mm/d), up to 40%. (4) Hit bias and missed precipitation are the two leading error sources. In summer, positive hit bias, up to 50%, dominates the total errors for most products. (5) In winter, missed precipitation over mountainous regions and the northeast, presumably snowfall, poses a common challenge to all the data sets. On the basis of the findings, we recommend that future efforts focus on reducing hit bias, adding snowfall retrievals, and improving methods for combining gauge and satellite data. Strategies for future studies to establish better links between the errors in the end products and the upstream data sources are also proposed

Primordial large-scale electromagnetic fields from Gravitoelectromagnetic Inflation

We investigate the origin and evolution of primordial electric and magnetic fields in the early universe, when the expansion is governed by a cosmological constant $\Lambda_0$. Using the gravitoelectromagnetic inflationary formalism with $A_0=0$, we obtain the power of spectrums for large-scale magnetic fields and the inflaton field fluctuations during inflation. A very important fact is that our formalism is {\em naturally non-conformally invariant}.Comment: Accepted for publication in Physics Letters

LuxO controls luxR expression in Vibrio harveyi : evidence for a common regulatory mechanism in Vibrio

Quorum-sensing control of luminescence in Vibrio harveyi , which involves an indirect autoinducer-mediated phosphorelay signal transduction system, contrasts with the prototypical quorum-sensing system of Vibrio fischeri , in which the autoinducer and the transcriptional activator LuxR directly activate lux operon expression. In V. harveyi , a regulator not homologous to V. fischeri LuxR and also designated LuxR (LuxR vh ), binds specifically to the lux operon promoter region and activates the expression of luminescence. A direct connection has not been identified previously between V. harveyi LuxR vh and the autoinducer-mediated phosphorelay system. Here, we demonstrate by mobility shift assays and measurement of luxR vh mRNA levels with luxO + and luxO – cells that the central response regulator of the V. harveyi phosphorelay system (LuxO) represses the level of LuxR vh . Expression of a luxR vh -bearing plasmid strongly stimulated luminescence of a luxO – mutant but had no effect on luminescence of wild-type luxO + cells, indicating tight regulation of luxR vh by LuxO. Furthermore, luxO null mutants of V. fischeri MJ-1 and two autoinducer mutants, MJ-211 ( luxI – ) and MJ-215 ( luxI – ainS – ), emitted more light and exhibited more elevated levels of litR , a newly identified V. harveyi luxR vh homologue, than their luxO + counterparts. These results suggest that activity of the autoinducer-mediated phosphorelay system is coupled to LuxR vh /LitR control of luminescence through LuxO in V. harveyi and V. fischeri . The presence of homologues of V. harveyi LuxR vh , LuxO and other phosphorelay system proteins in various Vibrio species and the control of LuxR vh and its homologues by LuxO identified here in V. harveyi and V. fischeri and recently in Vibrio cholerae suggest that the luxO–luxR vh couple is a central feature of this quorum-sensing system in members of the genus Vibrio .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72700/1/j.1365-2958.2003.03453.x.pd

The Search for a Primordial Magnetic Field

Magnetic fields appear wherever plasma and currents can be found. As such, they thread through all scales in Nature. It is natural, therefore, to suppose that magnetic fields might have been formed within the high temperature environments of the big bang. Such a primordial magnetic field (PMF) would be expected to arise from and/or influence a variety of cosmological phenomena such as inflation, cosmic phase transitions, big bang nucleosynthesis, the cosmic microwave background (CMB) temperature and polarization anisotropies, the cosmic gravity wave background, and the formation of large-scale structure. In this review, we summarize the development of theoretical models for analyzing the observational consequences of a PMF. We also summarize the current state of the art in the search for observational evidence of a PMF. In particular we review the framework needed to calculate the effects of a PMF power spectrum on the CMB and the development of large scale structure. We summarize the current constraints on the PMF amplitude $B_\lambda$ and the power spectral index $n_B$ and discuss prospects for better determining these quantities in the near future.Comment: 40 pages, 13 figures, Accepted for Physics Reports 23 Feb 2012. Available online 3 March 2012. In press, corrected proo

2003 AAPP Monograph Series

It is significant that the African American Professors Program (AAPP) at the University of South Carolina is producing the third edition of its annual monograph series at this time-the fifth anniversary of AAPP. The program graciously accepts the challenge of putting into place a requirement for the scholars to produce quality research papers worthy of publication. This provides widespread visibility for them and enhances their curriculum vitae concurrently. Scholars who have contributed manuscripts for this monograph are to be commended for adding this additional responsibility to their academic workload. Writing across disciplines adds to the intellectual diversity of these papers. From neophytes, relatively speaking, to an array of very experienced individuals, the chapters have been researched and comprehensively written. Founded in 1997 through the Department of Educational Leadership and Policies in the College of Education, AAPP was designed to address the underrepresentation of African American professors on college and university campuses. Its mission is to expand the pool of these professors in critical academic and research areas. Sponsored by the University of South Carolina, the W. K. Kellogg Foundation, and the South Carolina General Assembly, the program recruits students with bachelor\u27s, master\u27s, and doctoral degrees for disciplines in which African Americans currently are underrepresented. An important component of the program is the mentoring experience that is provided. Each student is assigned to a mentor/professor who guides the student through a selected academic program and provides various learning experiences. When possible, the mentor serves as chair of the student\u27s doctoral committee. The mentor also provides opportunities for the student to team teach, conduct research, and co-author publications. Students have the advantage of attending committee, faculty, and professional meetings, as well as engaging in a range of activities that characterize professional life in academia. Scholars enrolled in the program also are involved in programmatic and institutional workshops, independent research, and program development. The continuation of this monograph series is seen as responding to a window of opportunity to be sensitive to an academic expectation of graduates as they pursue career placement and, at the same time, one that allows for the dissemination of AAPP products to a broader community. The importance of this monograph series has been voiced by one of our 2002 AAPP graduates, Dr. Shundelle LaTjuan Dogan, a recent Harvard Administrative Fellow at Harvard University and now Program Officer for the Southern Education Foundation, Atlanta, Georgia. Dr. Dogan wrote: One thing in particular that I want to thank you for is having the African American Professors Program scholars publish articles for the monograph. I have to admit that writing the articles seemed like extra work at the time. However, in my recent interview process, organizations have asked me for samples of my writing. Including an article from a published monograph helped to make my portfolio much more impressive. You were right on target in having us do the monograph series. We hope that you will read this monograph of the African American Professors Program with enthusiasm or enlightenment. John McFadden, Ph.D. The Benjamin Elijah Mays Professor Director, African American Professors Program University of South Carolinahttps://scholarcommons.sc.edu/mcfadden_monographs/1006/thumbnail.jp