Role of Astrocyte Network in Edema after Juvenile Traumatic Brain Injury

Juvenile traumatic brain injury (jTBI) is the leading cause of death and disability in young children and adolescents. Despite its lasting detrimental effects on the developing brain, no pharmacological treatment exists. One of the pathological hallmarks of jTBI is edema. Astrocytes play a key role in the edema process, and have been hypothesized that numerous astrocyte networks allow communication and propagation of edema and secondary injury spread. Two key astrocyte proteins are hypothesized to have a central role in the edema process: Aquaporin 4 (AQP4) and Connexin 43 (Cx43). AQP4 is expressed extensively in astrocyte endfeet, which surrounds the blood vessels as part of the blood brain barrier (BBB). Cx43 is central in astrocyte to astrocyte connection and communication. We hypothesized that AQP4 acted as one of the potential passageway of water into the astrocyte, whereas Cx43 acted as the bridge between astrocytes once inside the brain. By blocking these strategically located pathways, we hypothesized that edema would decrease post-jTBI. In order to achieve specific inhibitions of APQ4 or Cx43, we utilized small interference RNA (siRNA), which is also an endogenous mechanism. We observed that after jTBI both AQP4 and Cx43 was significantly upregulated, edema was prominent, and reactive astrogliosis occurred. When siAQP4 was administered after jTBI, there was functional improvement, decreased edema, and decreased reactive astrogliosis. When siCx43 was administered, there was functional improvement and decreased reactive astrogliosis, but the level of edema did not change. From these findings, it can be seen that (1) AQP4 and Cx43 are upregulated acutely after jTBI, (2) both siAQP4 and siCx43 have therapeutic potentials after jTBI leading to functional recovery, (3) although both target astrocyte endfeet proteins, the mechanism of action seem to be different and AQP4 may play a more direct role in the edema process than Cx43. Future studies could focus on (1) a more clinically relevant delivery of siRNA for jTBI, (2) elucidating the mechanism behind functional improvement of siCx43, and (3) the relationship between AQP4 and Cx43 regarding astrocyte pathology after jTBI

On the Relevance of Social Media Platforms in Predicting The Volume and Patterns of Web Defacement Attacks

Social media platforms are commonly employed by law enforcement agencies for collecting Open Source Intelligence (OSNIT) on criminals, and assessing the risk they pose to the environment the live in. However, since no prior research has investigated the relationships between hackers’ use of social media platforms and their likelihood to generate cyber-attacks, this practice is less common among Information Technology Teams. Addressing this empirical gap, we draw on the social learning theory and estimate the relationships between hackers’ use of Facebook, Twitter, and YouTube and the frequency of web defacement attacks they generate in different times (weekdays vs. weekends) and against different targets (USA vs. non-USA websites). To answer our research questions, we use hackers’ reports of web defacement they generated (available on http://www.zone-h.org), and complement with an independent data collection we launched to identify these hackers’ use of different social media platforms. Results from a series of Negative Binomial Regression analyses reveal that hackers’ use of social media platforms, and specifically Twitter and Facebook, significantly increases the frequency of web defacement attacks they generate. However, while using these social media platforms significantly increases the volume of web defacement attacks these hackers generate during weekdays, it has no association with the volume of web defacement they launch over weekends. Finally, although hackers’ use of both Facebook and Twitter accounts increase the frequency of attacks they generate against non-USA websites, the use of Twitter only increases significantly the volume of web defacement attacks against USA websites

Small Interference RNA Targeting Connexin-43 Improves Motor Function and Limits Astrogliosis After Juvenile Traumatic Brain Injury

International audienceJuvenile traumatic brain injury (jTBI) is the leading cause of death and disability for children and adolescents worldwide, but there are no pharmacological treatments available. Aquaporin 4 (AQP4), an astrocytic perivascular protein, is increased after jTBI, and inhibition of its expression with small interference RNA mitigates edema formation and reduces the number of reactive astrocytes after jTBI. Due to the physical proximity of AQP4 and gap junctions, coregulation of AQP4 and connexin 43 (Cx43) expressions, and the possibility of water diffusion via gap junctions, we decided to address the potential role of astrocytic gap junctions in jTBI pathophysiology. We evaluated the role of Cx43 in the spread of the secondary injuries via the astrocyte network, such as edema formation associated with blood-brain barrier dysfunctions, astrogliosis, and behavioral outcome. We observed that Cx43 was altered after jTBI with increased expression in the perilesional cortex and in the hippocampus at several days post injury. In a second set of experiments, cortical injection of small interference RNA against Cx43 decreased Cx43 protein expression, improved motor function recovery, and decreased astrogliosis but did not result in differences in edema formation as measured via T2-weighted imaging or diffusion-weighted imaging at 1 day or 3 days. Based on our findings, we can speculate that while decreasing Cx43 has beneficial roles, it likely does not contribute to the spread of edema early after jTBI

Making the great transformation, November 13, 14, and 15, 2003

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This Conference took place during November 13, 14, and 15, 2003. Co-organized by Cutler Cleveland and Adil Najam.The conference discussants and participants analyze why transitions happen, and why they matter. Transitions are those wide-ranging changes in human organization and well being that can be convincingly attributed to a concerted set of choices that make the world that was significantly and recognizably different from the world that becomes. Transition scholars argue that that history does not just stumble along a pre-determined path, but that human ingenuity and entrepreneurship have the ability to fundamentally alter its direction. However, our ability to ‘will’ such transitions remains in doubt. These doubts cannot be removed until we have a better understanding of how transitions work

Timelike Boundary Liouville Theory

The timelike boundary Liouville (TBL) conformal field theory consisting of a negative norm boson with an exponential boundary interaction is considered. TBL and its close cousin, a positive norm boson with a non-hermitian boundary interaction, arise in the description of the $c=1$ accumulation point of $c<1$ minimal models, as the worldsheet description of open string tachyon condensation in string theory and in scaling limits of superconductors with line defects. Bulk correlators are shown to be exactly soluble. In contrast, due to OPE singularities near the boundary interaction, the computation of boundary correlators is a challenging problem which we address but do not fully solve. Analytic continuation from the known correlators of spatial boundary Liouville to TBL encounters an infinite accumulation of poles and zeros. A particular contour prescription is proposed which cancels the poles against the zeros in the boundary correlator d(\o) of two operators of weight \o^2 and yields a finite result. A general relation is proposed between two-point CFT correlators and stringy Bogolubov coefficients, according to which the magnitude of d(\o) determines the rate of open string pair creation during tachyon condensation. The rate so obtained agrees at large \o with a minisuperspace analysis of previous work. It is suggested that the mathematical ambiguity arising in the prescription for analytic continuation of the correlators corresponds to the physical ambiguity in the choice of open string modes and vacua in a time dependent background.Comment: 28 pages, 1 figure, v2 reference and acknowledgement adde

Concert recording 2015-11-19

[Track 01]. Partita. Prelude ; [Track 02]. Capriccio ; [Track 03]. Sarabande ; [Track 04]. Bourree ; [Track 05]. Schezo / Arthur Butterworth -- [Track 06]. Introduction and dance / J.E. Barat -- [Track 07]. Concert pierce no. 1 / Joseph Turrin -- [Track 08]. Sonata. Allegro ; [Track 09]. Aria / Bruce Broughton -- [Track 10]. Variations on the Carnival of Venice / J.B. Arban -- [Track 11]. Concerto for bass tuba. Allegro moderato ; [Track 12]. Romanza / Ralph Vaughan Williams -- [Track 13]. Concerto, op. 114 / Derek Bourgeois -- [Track 14]. Milori blue. Simply ; [Track 15]. Presto / Jonathan Newman

Measuring Gas Accretion and Angular Momentum near Simulated Supermassive Black Holes

Using cosmological simulations with a dynamic range in excess of 10 million, we study the transport of gas mass and angular momentum through the circumnuclear region of a disk galaxy containing a supermassive black hole (SMBH). The simulations follow fueling over relatively quiescent phases of the galaxy's evolution (no mergers) and without feedback from active galactic nuclei (AGNs), as part of the first stage of using state-of-the-art, high-resolution cosmological simulations to model galaxy and black hole co-evolution. We present results from simulations at different redshifts (z=6, 4, and 3) and three different black hole masses (30 million, 90 million, and 300 million solar masses; at z=4), as well as a simulation including a prescription that approximates optically thick cooling in the densest regions. The interior gas mass throughout the circumnuclear disk shows transient and chaotic behavior as a function of time. The Fourier transform of the interior gas mass follows a power law with slope -1 throughout the region, indicating that, in the absence of the effects of galaxy mergers and AGN feedback, mass fluctuations are stochastic with no preferred timescale for accretion over the duration of each simulation (~ 1-2 Myr). The angular momentum of the gas disk changes direction relative to the disk on kiloparsec scales over timescales less than 1 Myr, reflecting the chaotic and transient gas dynamics of the circumnuclear region. Infalling clumps of gas, which are driven inward as a result of the dynamical state of the circumnuclear disk, may play an important role in determining the spin evolution of an SMBH, as has been suggested in stochastic accretion scenarios.Comment: 13 pages, 10 figures; accepted to ApJ; corrected minor typos and reference error

Looking ahead: forecasting and planning for the longer-range future, April 1, 2, and 3, 2005

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's spring Conference that took place during April 1, 2, and 3, 2005.The conference allowed for many highly esteemed scholars and professionals from a broad range of fields to come together to discuss strategies designed for the 21st century and beyond. The speakers and discussants covered a broad range of subjects including: long-term policy analysis, forecasting for business and investment, the National Intelligence Council Global Trends 2020 report, Europe’s transition from the Marshal plan to the EU, forecasting global transitions, foreign policy planning, and forecasting for defense

Palmitoylation-dependent association with CD63 targets the Ca2+ sensor synaptotagmin VII to lysosomes

Posttranslational lipid modifications promote association of Syt VII with the tetraspanin CD63, determining its exit from the Golgi and targeting to lysosomes

Outcome of hospitalised heart failure in Japan and the United Kingdom stratified by plasma N-terminal pro-B-type natriuretic peptide

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Background: Mortality subsequent to a hospitalisation for heart failure is reported to be much lower in Japan than in the United Kingdom (UK). This could reflect differences in disease severity or in management. Accordingly, we directly compared patient backgrounds and outcomes between Japan and UK. Methods: Consecutive patients admitted to academic hospitals in the UK and Japan with heart failure had a common set of variables, including plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), collected during admission. Mortality during hospitalisations, at 90 and 180 days was recorded and stratified by quintile of NT-proBNP. Results: Overall, 935 patients were enrolled; 197 from UK and 738 from Japan. Median (interquartile range) age [UK: 78 (71–88) vs. Japan: 78 (70–84) years; p = 0.947], glomerular filtration rate [UK: 49 (34–68) vs. Japan: 49 (33–65) ml/min/1.73 m2; p = 0.209] and plasma NT-proBNP [UK: 4957 (2278–10,977) vs. Japan: 4155 (1972–9623) ng/l; p = 0.186] were similar, but systolic blood pressure was lower in the UK [118 (105–131) vs. 137 (118–159) mmHg; p < 0.001]. Patients with a higher plasma NT-proBNP had a worse prognosis in both countries; in-hospital and post-discharge mortality rates were higher in the UK even after adjusting for prognostic variables including NT-proBNP. Conclusions: This analysis suggests that either unobserved differences in patient characteristics or differences in care (formal or informal) rather than greater heart failure severity may account for the worse outcome of heart failure in the UK compared to Japan