Chemokines in the balance: Maintenance of homeostasis and protection at CNS barriers

In the adult central nervous system (CNS), chemokines and their receptors are involved in developmental, physiological and pathological processes. Although most lines of investigation focus on their ability to induce the migration of cells, recent studies indicate that chemokines also promote cellular interactions and activate signaling pathways that maintain CNS homeostatic functions. Many homeostatic chemokines are expressed on the vasculature of the blood brain barrier including CXCL12, CCL19, CCL20, and CCL21. While endothelial cell expression of these chemokines is known to regulate the entry of leukocytes into the CNS during immunosurveillance, new data indicate that CXCL12 is also involved in diverse cellular activities including adult neurogenesis and neuronal survival, having an opposing role to the homeostatic chemokine, CXCL14, which appears to regulate synaptic inputs to neural precursors. Neuronal expression of CX3CL1, yet another homeostatic chemokine that promotes neuronal survival and communication with microglia, is partly regulated by CXCL12. Regulation of CXCL12 is unique in that it may regulate its own expression levels via binding to its scavenger receptor CXCR7/ACKR3. In this review, we explore the diverse roles of these and other homeostatic chemokines expressed within the CNS, including the possible implications of their dysfunction as a cause of neurologic disease

The Transit Light Curve Project. VI. Three Transits of the Exoplanet TrES-2

Of the nearby transiting exoplanets that are amenable to detailed study, TrES-2 is both the most massive and has the largest impact parameter. We present z-band photometry of three transits of TrES-2. We improve upon the estimates of the planetary, stellar, and orbital parameters, in conjunction with the spectroscopic analysis of the host star by Sozzetti and co-workers. We find the planetary radius to be 1.222 +/- 0.038 R_Jup and the stellar radius to be 1.003 +/- 0.027 R_Sun. The quoted uncertainties include the systematic error due to the uncertainty in the stellar mass (0.980 +/- 0.062 M_Sun). The timings of the transits have an accuracy of 25s and are consistent with a uniform period, thus providing a baseline for future observations with the NASA Kepler satellite, whose field of view will include TrES-2.Comment: 15 pages, including 2 figures, accepted Ap

The Transit Light Curve Project. VIII. Six Occultations of the Exoplanet TrES-3

We present photometry of the exoplanet host star TrES-3 spanning six occultations (secondary eclipses) of its giant planet. No flux decrements were detected, leading to 99%-confidence upper limits on the planet-to-star flux ratio of 0.00024, 0.0005, and 0.00086 in the i, z, and R bands respectively. The corresponding upper limits on the planet's geometric albedo are 0.30, 0.62, and 1.07. The upper limit in the i band rules out the presence of highly reflective clouds, and is only a factor of 2-3 above the predicted level of thermal radiation from the planet.Comment: To appear in AJ [14 pages

Entering the Thicket - Mandamus Review of Texas District Court Witness Disclosure Orders.

In the absence of statutory authorization of interlocutory appeal, the writ of mandamus usually is the sole convenient remedy for an egregious trial court decision prior to judgment. The increasing number of mandamus petitions which annually invade the Texas appellate courts reflects the importance of the writ of mandamus. While once described as the “extraordinary” remedy, it is not uncommon for proceedings in a trial court to cease while a party seeks mandamus review of a controversial discovery ruling. One type of discovery rule which has not escaped mandamus review is the admission or exclusion of the testimony of witnesses whom a party has failed to disclose in response to a discovery request. In the decision of Mother Frances Hospital v. Coats, a Texas court of appeals determined, at least in some cases, mandamus is an appropriate remedy for an erroneous trial court witness disclosure order. This opinion could offer litigants an escape valve from pre-trial witness disclosure orders which threaten the effective presentation of a claim or defense. Conversely this opinion could trigger even more mandamus petitions to the appellate courts, thus contributing to the “thicket” of review mechanisms which interrupt trial processes. Having “entered the thicket” to control or correct even one trial court witness disclosure order, the Texas appellate courts will soon be asked to review in mandamus proceedings on more such orders. Some petitions undoubtedly will attempt to implicate the appellate courts in routine questions more appropriately left to the trial court’s discretion, while other petitions will seek appellate intervention in the erroneous exclusion of critical trial witnesses. The appellate courts must tolerate some abuse of mandamus procedures to ensure, in cases where mandamus is necessary, trial proceedings are fair and equitable to all parties

Characterization of cytoskeletal and junctional proteins expressed by cells cultured from human arachnoid granulation tissue

BACKGROUND: The arachnoid granulations (AGs) are projections of the arachnoid membrane into the dural venous sinuses. They function, along with the extracranial lymphatics, to circulate the cerebrospinal fluid (CSF) to the systemic venous circulation. Disruption of normal CSF dynamics may result in increased intracranial pressures causing many problems including headaches and visual loss, as in idiopathic intracranial hypertension and hydrocephalus. To study the role of AGs in CSF egress, we have grown cells from human AG tissue in vitro and have characterized their expression of those cytoskeletal and junctional proteins that may function in the regulation of CSF outflow. METHODS: Human AG tissue was obtained at autopsy, and explanted to cell culture dishes coated with fibronectin. Typically, cells migrated from the explanted tissue after 7–10 days in vitro. Second or third passage cells were seeded onto fibronectin-coated coverslips at confluent densities and grown to confluency for 7–10 days. Arachnoidal cells were tested using immunocytochemical methods for the expression of several common cytoskeletal and junctional proteins. Second and third passage cultures were also labeled with the common endothelial markers CD-31 or VE-cadherin (CD144) and their expression was quantified using flow cytometry analysis. RESULTS: Confluent cultures of arachnoidal cells expressed the intermediate filament protein vimentin. Cytokeratin intermediate filaments were expressed variably in a subpopulation of cells. The cultures also expressed the junctional proteins connexin43, desmoplakin 1 and 2, E-cadherin, and zonula occludens-1. Flow cytometry analysis indicated that second and third passage cultures failed to express the endothelial cell markers CD31 or VE-cadherin in significant quantities, thereby showing that these cultures did not consist of endothelial cells from the venous sinus wall. CONCLUSION: To our knowledge, this is the first report of the in vitro culture of arachnoidal cells grown from human AG tissue. We demonstrated that these cells in vitro continue to express some of the cytoskeletal and junctional proteins characterized previously in human AG tissue, such as proteins involved in the formation of gap junctions, desmosomes, epithelial specific adherens junctions, as well as tight junctions. These junctional proteins in particular may be important in allowing these arachnoidal cells to regulate CSF outflow

Photometric Follow-up Observations of the Transiting Neptune-Mass Planet GJ 436b

This paper presents multi-band photometric follow-up observations of the Neptune-mass transiting planet GJ 436b, consisting of 5 new ground-based transit light curves obtained in May 2007. Together with one already published light curve we have at hand a total of 6 light curves, spanning 29 days. The analysis of the data yields an orbital period P = 2.64386+-0.00003 days, mid-transit time T_c [HJD] =2454235.8355+-0.0001, planet mass M_p = 23.1+-0.9 M_{\earth} = 0.073+-0.003 M_{Jup}, planet radius R_p = 4.2+-0.2 R_{\earth} = 0.37+-0.01 R_{Jup} and stellar radius R_s = 0.45+-0.02 R_{\sun}. Our typical precision for the mid transit timing for each transit is about 30 seconds. We searched the data for a possible signature of a second planet in the system through transit timing variations (TTV) and variation of the impact parameter. The analysis could not rule out a small, of the order of a minute, TTV and a long-term modulation of the impact parameter, of the order of +0.2 year^{-1}.Comment: V2: Replaced with accepted versio