Infiltrative microgliosis: activation and long-distance migration of subependymal microglia following periventricular insults

BACKGROUND: Subventricular microglia (SVMs) are positioned at the interface of the cerebrospinal fluid and brain parenchyma and may play a role in periventricular inflammatory reactions. However, SVMs have not been previously investigated in detail due to the lack of a specific methodology for their study exclusive of deeper parenchymal microglia. METHODS: We have developed and characterized a novel model for the investigation of subventricular microglial reactions in mice using intracerebroventricular (ICV) injection of high-dose rhodamine dyes. Dynamic studies using timelapse confocal microscopy in situ complemented the histopathological analysis. RESULTS: We demonstrate that high-dose ICV rhodamine dye injection resulted in selective uptake by the ependyma and ependymal death within hours. Phagocytosis of ependymal debris by activated SVMs was evident by 1d as demonstrated by the appearance of rhodamine-positive SVMs. In the absence of further manipulation, labelled SVMs remained in the subventricular space. However, these cells exhibited the ability to migrate several hundred microns into the parenchyma towards a deafferentation injury of the hippocampus. This "infiltrative microgliosis" was verified in situ using timelapse confocal microscopy. Finally, supporting the disease relevance of this event, the triad of ependymal cell death, SVM activation, and infiltrative microgliosis was recapitulated by a single ICV injection of HIV-1 tat protein. CONCLUSIONS: Subependymal microglia exhibit robust activation and migration in periventricular inflammatory responses. Further study of this population of microglia may provide insight into neurological diseases with tendencies to involve the ventricular system and periventricular tissues

S22RS SGR No. 1 (Dead week)

A Resolution To Urge and Request LSU to extend Concentrated Study Period, also known as Dead Week from five (5) days to seven (7) days to now begin on Monday instead of Wednesda

An Unusual Transmission Spectrum for the Sub-Saturn KELT-11b Suggestive of a Sub-Solar Water Abundance

We present an optical-to-infrared transmission spectrum of the inflated sub-Saturn KELT-11b measured with the Transiting Exoplanet Survey Satellite (TESS), the Hubble Space Telescope (HST) Wide Field Camera 3 G141 spectroscopic grism, and the Spitzer Space Telescope (Spitzer) at 3.6 $\mu$m, in addition to a Spitzer 4.5 $\mu$m secondary eclipse. The precise HST transmission spectrum notably reveals a low-amplitude water feature with an unusual shape. Based on free retrieval analyses with varying molecular abundances, we find strong evidence for water absorption. Depending on model assumptions, we also find tentative evidence for other absorbers (HCN, TiO, and AlO). The retrieved water abundance is generally $\lesssim 0.1\times$ solar (0.001--0.7$\times$ solar over a range of model assumptions), several orders of magnitude lower than expected from planet formation models based on the solar system metallicity trend. We also consider chemical equilibrium and self-consistent 1D radiative-convective equilibrium model fits and find they too prefer low metallicities ($[M/H] \lesssim -2$, consistent with the free retrieval results). However, all the retrievals should be interpreted with some caution since they either require additional absorbers that are far out of chemical equilibrium to explain the shape of the spectrum or are simply poor fits to the data. Finally, we find the Spitzer secondary eclipse is indicative of full heat redistribution from KELT-11b's dayside to nightside, assuming a clear dayside. These potentially unusual results for KELT-11b's composition are suggestive of new challenges on the horizon for atmosphere and formation models in the face of increasingly precise measurements of exoplanet spectra.Comment: Accepted to The Astronomical Journal. 31 pages, 20 figures, 7 table

Immunohistochemical assessment of protein phosphorylation state: the dream and the reality

The development of phosphorylation state-specific antibodies (PSSAs) in the 1980s, and their subsequent proliferation promised to enable in situ analysis of the activation states of complex intracellular signaling networks. The extent to which this promise has been fulfilled is the topic of this review. I review some applications of PSSAs primarily in the assessment of solid tumor signaling pathway activation status. PSSAs have received considerable attention for their potential to reveal cell type-specific activation status, provide added prognostic information, aid in the prediction of response to therapy, and most recently, demonstrate the efficacy of kinase-targeted chemotherapies. However, despite some successes, many studies have failed to demonstrate added value of PSSAs over general antibody immunohistochemistry. Moreover, there is still a large degree of uncertainty about the interpretation of complex and heterogeneous staining patterns in tissue samples and their relationship to the actual phosphorylation states in vivo. The next phase of translational research in applications of PSSAs will entail the hard work of antibody validation, gathering of detailed information about epitope-specific lability, and implementation of methods for standardization

SUMOylation of nuclear actin

Actin, a major component of the cytoplasm, is also abundant in the nucleus. Nuclear actin is involved in a variety of nuclear processes including transcription, chromatin remodeling, and intranuclear transport. Nevertheless, the regulation of nuclear actin by posttranslational modifications has not been investigated. We now show that nuclear actin is modified by SUMO2 and SUMO3 and that computational modeling and site-directed mutagenesis identified K68 and K284 as critical sites for SUMOylating actin. We also present a model for the actin–SUMO complex and show that SUMOylation is required for the nuclear localization of actin

Balloon dilation of mitral stenosis in adult patients: Postmortem and percutaneous mitral valvuloplasty studies

Preliminary reports have documented the utility of percutaneous balloon valvuloplasty of the mitral valve in adult patients with mitral stenosis, but the mechanism of successful valve dilation and the effect of mitral valvuloplasty on cardiac performance have not been studied in detail. Accordingly, mitral valvuloplasty was performed in five postmortem specimens and in 18 adult patients with rheumatic mitral stenosis, using either one (25 mm) or two (18 and 20 mm) dilation balloons. Postmortem balloon dilation resulted in increased valve orifice area in all five postmortem specimens, secondary to separation of fused commissures and fracture of nodular calcium within the mitral leaflets. In no case did balloon dilation result in tearing of valve leaflets, disruption of the mitral ring or liberation of potentially embolic debris.Percutaneous mitral valvuloplasty in 18 patients with severe mitral stenosis (including 9 with a heavily calcified valve) resulted in an increase in cardiac output (4.3 ± 1.1 to 5.1 ± 1.5 liters/min, p < 0.01) and mitral valve area (0.9 ± 0.2 to 1.6 ± 0.4 cm2, p < 0.0001), and a decrease in mean mitral pressure gradient (15 ± 5 to 9 ± 4 mm Hg, p < 0.0001), pulmonary capillary wedge pressure (23 ± 7 to 18 ± 7 mm Hg, p < 0.0001) and mean pulmonary artery pressure (36 ± 12 to 33 ± 12 mm Hg, p < 0.01). Left ventriculography before and after valvuloplasty in 14 of the 18 patients showed a mild (≤1 +) increase in mitral regurgitation in five patients and no change in the remainder. Embolic phenomena were not observed in any patient.Serial radionuclide ventriculography showed an increase in left ventricular peak filling rate (2.20 ± 1.20 to 2.50 ± 1.20 end-diastolic volumes per second [EDV/s], p < 0.05). Serial echocardiography/phonocardiography showed improvement in mitral valve excursion (11 ± 6 to 14 ± 6 mm, p < 0.001), mitral EF slope (7 ± 4 to 13 ± 5, p < 0.001), left atrial diameter (5.7 ± 0.9 to 5.3 ± 0.8 cm, p < 0.001), S2-opening snap interval (0.07 ± 0.03 to 0.08 ± 0.02 second, p < 0.02) and mitral valve area (0.9 ± 0.2 to 1.5 ± 0.4 cm2, p < 0.0001). All patients were discharged from the hospital with de- creased symptoms after valvuloplasty.It is concluded that percutaneous mitral valvuloplasty can be performed in adult patients with mitral stenosis, including patients with calcific disease, and can result in significant improvement in valvular function. The mechanisms of successful dilation include commissural separation and fracture of nodular calcium