Microglia cells protect neurons by direct engulfment of invading neutrophil granulocytes: a new mechanism of CNS immune privilege

Microglial cells maintain the immunological integrity of the healthy brain and can exert protection from traumatic injury. During ischemic tissue damage such as stroke, peripheral immune cells acutely infiltrate the brain and may exacerbate neurodegeneration. Whether and how microglia can protect from this insult is unknown. Polymorphonuclear neutrophils (PMNs) are a prominent immunologic infiltrate of ischemic lesions in vivo. Here, we show in organotypic brain slices that externally applied invading PMNs massively enhance ischemic neurotoxicity. This, however, is counteracted by additional application of microglia. Time-lapse imaging shows that microglia exert protection by rapid engulfment of apoptotic, but, strikingly, also viable, motile PMNs in cell culture and within brain slices. PMN engulfment is mediated by integrin- and lectin-based recognition. Interference with this process using RGDS peptides and N-acetyl-glucosamine blocks engulfment of PMNs and completely abrogates the neuroprotective function of microglia. Thus, engulfment of invading PMNs by microglia may represent an entirely new mechanism of CNS immune privilege

Hybrid adiabatic quantum computing for tomographic image reconstruction -- opportunities and limitations

Our goal is to reconstruct tomographic images with few measurements and a low signal-to-noise ratio. In clinical imaging, this helps to improve patient comfort and reduce radiation exposure. As quantum computing advances, we propose to use an adiabatic quantum computer and associated hybrid methods to solve the reconstruction problem. Tomographic reconstruction is an ill-posed inverse problem. We test our reconstruction technique for image size, noise content, and underdetermination of the measured projection data. We then present the reconstructed binary and integer-valued images of up to 32 by 32 pixels. The demonstrated method competes with traditional reconstruction algorithms and is superior in terms of robustness to noise and reconstructions from few projections. We postulate that hybrid quantum computing will soon reach maturity for real applications in tomographic reconstruction. Finally, we point out the current limitations regarding the problem size and interpretability of the algorithm

Improving Refrigerant Flammability Limit Test Methods Based on ASTM E681

An improved test method for refrigerant flammability limit measurements is presented. Such measurements are essential for determining the lower flammability limits of refrigerants, and thus their safety classifications. Predicated on expert interviews and experiments, several changes to ASTM E681 and related standards are recommended, as follows. The 12 L glass vessel should be replaced with transparent polycarbonate (or other transparent plastic) to eliminate etching by HF and to facilitate vessel penetrations. The orientation of the electrode supports and the temperature probe should be changed from vertical to horizontal to prevent flame quenching. Venting should not occur before the flame stops propagating near the vessel wall. All penetrations should be removed from the rubber stopper, it should be weighted for a total mass of 2.5 kg, and the initial pressure should be 90 kPa absolute. The flame angle should be plotted versus refrigerant concentration, whereby a least-squares line determines the flammability limit at a flame angle of 90°. Finally, the vessel pressure should be measured during each test to evaluate the pressure rise during flame propagation and to help identify the onset of venting. These changes are relatively easy to implement and they improve the test precision and reproducibility without significantly changing previously established flammability limits

Aβ Mediated Diminution of MTT Reduction—An Artefact of Single Cell Culture?

The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) reduction assay is a frequently used and easily reproducible method to measure beta-amyloid (Aβ) toxicity in different types of single cell culture. To our knowledge, the influence of Aβ on MTT reduction has never been tested in more complex tissue. Initially, we reproduced the disturbed MTT reduction in neuron and astroglia primary cell cultures from rats as well as in the BV2 microglia cell line, utilizing four different Aβ species, namely freshly dissolved Aβ (25-35), fibrillar Aβ (1-40), oligomeric Aβ (1-42) and oligomeric Aβ (1-40). In contrast to the findings in single cell cultures, none of these Aβ species altered MTT reduction in rat organotypic hippocampal slice cultures (OHC). Moreover, application of Aβ to acutely isolated hippocampal slices from adult rats and in vivo intracerebroventricular injection of Aβ also did not influence the MTT reduction in the respective tissue. Failure of Aβ penetration into the tissue cannot explain the differences between single cells and the more complex brain tissue. Thus electrophysiological investigations disclosed an impairment of long-term potentiation (LTP) in the CA1 region of hippocampal slices from rat by application of oligomeric Aβ (1-40), but not by freshly dissolved Aβ (25-35) or fibrillar Aβ (1-40). In conclusion, the experiments revealed a glaring discrepancy between single cell cultures and complex brain tissue regarding the effect of different Aβ species on MTT reduction. Particularly, the differential effect of oligomeric versus other Aβ forms on LTP was not reflected in the MTT reduction assay. This may indicate that the Aβ oligomer effect on synaptic function reflected by LTP impairment precedes changes in formazane formation rate or that cells embedded in a more natural environment in the tissue are less susceptible to damage by Aβ, raising cautions against the consideration of single cell MTT reduction activity as a reliable assay in Alzheimer's drug discovery studies

First Measurement of the Transverse Spin Asymmetries of the Deuteron in Semi-Inclusive Deep Inelastic Scattering

First measurements of the Collins and Sivers asymmetries of charged hadrons produced in deep-inelastic scattering of muons on a transversely polarized 6-LiD target are presented. The data were taken in 2002 with the COMPASS spectrometer using the muon beam of the CERN SPS at 160 GeV/c. The Collins asymmetry turns out to be compatible with zero, as does the measured Sivers asymmetry within the present statistical errors.Comment: 6 pages, 2 figure

Gluon polarization in the nucleon from quasi-real photoproduction of high-pT hadron pairs

We present a determination of the gluon polarization Delta G/G in the nucleon, based on the helicity asymmetry of quasi-real photoproduction events, Q^2<1(GeV/c)^2, with a pair of large transverse-momentum hadrons in the final state. The data were obtained by the COMPASS experiment at CERN using a 160 GeV polarized muon beam scattered on a polarized 6-LiD target. The helicity asymmetry for the selected events is = 0.002 +- 0.019(stat.) +- 0.003(syst.). From this value, we obtain in a leading-order QCD analysis Delta G/G=0.024 +- 0.089(stat.) +- 0.057(syst.) at x_g = 0.095 and mu^2 =~ 3 (GeV}/c)^2.Comment: 10 pages, 3 figure

Measurement of the Spin Structure of the Deuteron in the DIS Region

We present a new measurement of the longitudinal spin asymmetry A_1^d and the spin-dependent structure function g_1^d of the deuteron in the range 1 GeV^2 < Q^2 < 100 GeV^2 and 0.004< x <0.7. The data were obtained by the COMPASS experiment at CERN using a 160 GeV polarised muon beam and a large polarised 6-LiD target. The results are in agreement with those from previous experiments and improve considerably the statistical accuracy in the region 0.004 < x < 0.03.Comment: 10 pages, 6 figures, subm. to PLB, revised: author list, Fig. 4, details adde

Cell Transplant

Human induced pluripotent stem cells (hiPSCs) are a most appealing source for cell replacement therapy in acute brain lesions. We evaluated the potential of hiPSC therapy in stroke by transplanting hiPSC-derived neural progenitor cells (NPCs) into the postischemic striatum. Grafts received host tyrosine hydroxylase-positive afferents and contained developing interneurons and homotopic GABAergic medium spiny neurons that, with time, sent axons to the host substantia nigra. Grafting reversed stroke-induced somatosensory and motor deficits. Grafting also protected the host substantia nigra from the atrophy that follows disruption of reciprocal striatonigral connections. Graft innervation by tyrosine hydoxylase fibers, substantia nigra protection, and somatosensory functional recovery were early events, temporally dissociated from the slow maturation of GABAergic neurons in the grafts and innervation of substantia nigra. This suggests that grafted hiPSC-NPCs initially exert trophic effects on host brain structures, which precede integration and potential pathway reconstruction. We believe that transplantation of NPCs derived from hiPSCs can provide useful interventions to limit the functional consequences of stroke through both neuroprotective effects and reconstruction of impaired pathways

Monte Carlo Simulations indicate that Chromati: Nanostructure is accessible by Light Microscopy

A long controversy exists about the structure of chromatin. Theoretically, this structure could be resolved by scattering experiments if one determines the scattering function - or equivalently the pair distribution function - of the nucleosomes. Unfortunately, scattering experiments with live cells are very difficult and limited to only a couple of nucleosomes

Kidney Pathology Precedes and Predicts the Pathological Cascade of Cerebrovascular Lesions in Stroke Prone Rats

INTRODUCTION: Human cerebral small vessel disease (CSVD) has been hypothesized to be an age-dependent disease accompanied by similar vascular changes in other organs. SHRSP feature numerous vascular risk factors and may be a valid model of some aspects of human CSVD. Here we compare renal histopathological changes with the brain pathology of spontaneously hypertensive stroke-prone rats (SHRSP). MATERIAL AND METHODS: We histologically investigated the brains and kidneys of 61 SHRSP at different stages of age (12 to 44 weeks). The brain pathology (aggregated erythrocytes in capillaries and arterioles, microbleeds, microthromboses) and the kidney pathology (aggregated erythrocytes within peritubular capillaries, tubular protein cylinders, glomerulosclerosis) were quantified separately. The prediction of the brain pathology by the kidney pathology was assessed by creating ROC-curves integrating the degree of kidney pathology and age of SHRSP. RESULTS: Both, brain and kidney pathology, show an age-dependency and proceed in definite stages whereas an aggregation of erythrocytes in capillaries and arterioles, we parsimoniously interpreted as stases, represent the initial finding in both organs. Thus, early renal tubulointerstitial damage characterized by rather few intravasal erythrocyte aggregations and tubular protein cylinders predicts the initial step of SHRSPs' cerebral vascular pathology marked by accumulated erythrocytes. The combined increase of intravasal erythrocyte aggregations and protein cylinders accompanied by glomerulosclerosis and thrombotic renal microangiopathy in kidneys of older SHRSP predicts the final stages of SHRSPs' cerebrovascular lesions marked by microbleeds and thrombotic infarcts. CONCLUSION: Our results illustrate a close association between structural brain and kidney pathology and support the concept of small vessel disease to be an age-dependent systemic pathology. Further, an improved joined nephrologic and neurologic diagnostic may help to identify patients with CSVD at an early stage