TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke

<p>Abstract</p> <p>Background</p> <p>TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging.</p> <p>Methods</p> <p>We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia.</p> <p>Results</p> <p>TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes.</p> <p>Conclusions</p> <p>We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial scar formation and the immune response to stroke.</p

P-parity of charmed particles from associative photoproduction of D and D^*-mesons

We suggest to measure the triple polarization correlations in the exclusive associative charm particle photoproduction, vector gamma + vector p --> vector Lambda_c^{++} bar{D^0} with linearly polarized photons, as a method to determine the P-parity of the charmed D-meson. The dependence of these correlations on the parity P(N Lambda_c D) can be predicted in model independent way. The t-dependence of the differential cross section for vector meson photoproduction, gamma + p --> Lambda_c^{++} bar{D^{*0}}, in a model based on D-exchange, is also sensitive to P(N Lambda_c D).Comment: 11 pages, 1 figur

Threshold J/ψ−J/\psi- production in nucleon-nucleon collisions

We analyze $J/\psi-$ production in nucleon-nucleon collisions near threshold in the framework of a general model independent formalism, which can be applied to any reaction $N+N\to N+N+V^0$, where $V^0=\omega$, $\phi$, or $J/\psi$. Such reactions show large isotopic effects: a large difference for $pp$- and $pn$-collisions, which is due to the different spin structure of the corresponding matrix elements. The analysis of the spin structure and of the polarization observables is based on symmetry properties of the strong interaction. Using existing experimental data on the different decays of $J/\psi-$meson, we suggest a model for $N+N\to N+N+J/\psi$, based on $t-$channel $\eta+\pi$-exchanges. We predict polarization phenomena for the $n+p\to n+p+J/\psi$-reaction and the ratio of cross sections for $np$ and $pp$-collisions. For the processes $\eta(\pi)+N\to N+J/\psi$ we apply two different approaches: vector meson exchange and local four-particle interaction. In both cases we find larger $J/\psi$-production in $np$-collisions, with respect to $pp$-collisions.Comment: 17 pages, 6 figure

Soluble CD40L and cardiovascular risk in asymptomatic low-grade carotid stenosis

Background and Purpose-We investigated whether soluble CD40L (sCD40L) may predict the risk of cardiovascular (CV) events in patients with asymptomatic carotid plaques. Methods-Forty-two patients with asymptomatic low-grade carotid stenosis (ALCS) and 21 controls without any carotid stenosis were enrolled. All subjects had at least a major cardiovascular risk factor (CRF). Plasma levels of C-reactive protein (CRP), IL-6, and sCD40L were measured. Subjects were reviewed every 12 months (median follow-up, 8 years). Results-ALCS patients had higher (P<0.0001) CRP, IL-6, and sCD40L than controls. Fourteen patients experienced a CV event. Cox regression analysis showed that only high sCD40L levels (P=0.003) independently predicted cardiovascular risk. Conclusions-High levels of sCD40L may predict the risk of CV events in ALCS

Genomic insights into <i>Vibrio cholerae</i> O1 responsible for cholera epidemics in Tanzania between 1993 and 2017

BackgroundTanzania is one of seven countries with the highest disease burden caused by cholera in Africa. We studied the evolution of Vibrio cholerae O1 isolated in Tanzania during the past three decades.Methodology/principal findingsGenome-wide analysis was performed to characterize V. cholerae O1 responsible for the Tanzanian 2015-2017 outbreak along with strains causing outbreaks in the country for the past three decades. The genomes were further analyzed in a global context of 590 strains of the seventh cholera pandemic (7PET), as well as environmental isolates from Lake Victoria. All Tanzanian cholera outbreaks were caused by the 7PET lineage. The T5 sub-lineage (ctxB3) dominated outbreaks until 1997, followed by the T10 atypical El Tor (ctxB1) up to 2015, which were replaced by the T13 atypical El Tor of the current third wave (ctxB7) causing most cholera outbreaks until 2017 with T13 being phylogenetically related to strains from East African countries, Yemen and Lake Victoria. The strains were less drug resistant with approximate 10-kb deletions found in the SXT element, which encodes resistance to sulfamethoxazole and trimethoprim. Nucleotide deletions were observed in the CTX prophage of some strains, which warrants further virulence studies. Outbreak strains share 90% of core genes with V. cholerae O1 from Lake Victoria with as low as three SNPs difference and a significantly similar accessory genome, composed of genomic islands namely the CTX prophage, Vibrio Pathogenicity Islands; toxin co-regulated pilus biosynthesis proteins and the SXT-ICE element.Conclusion/significanceCharacterization of V. cholerae O1 from Tanzania reveals genetic diversity of the 7PET lineage composed of T5, T10 and T13 sub-lineages with introductions of new sequence types from neighboring countries. The presence of these sub-lineages in environmental isolates suggests that the African Great Lakes may serve as aquatic reservoirs for survival of V. cholerae O1 favoring continuous human exposure

Pennsylvania Folklife Vol. 18, No. 4

• Discord in the Garden • The Folk Festival Seminars: Crafts and Customs of the Year • What to Read on the Amish • Soup\u27s On! • Festival Highlights • Folk Festival Program • Folk Festival Geisinger • Four Interviews with Powwowers • The First Historian of the Pennsylvania Germans • The Public Sale Sixty Years Ago • The Long Shingle • Quilts and Quilting: Folk-Cultural Questionnaire No. 12https://digitalcommons.ursinus.edu/pafolklifemag/1036/thumbnail.jp

Apaf-1 and caspase-9 do not act as tumor suppressors in myc-induced lymphomagenesis or mouse embryo fibroblast transformation

Based on experiments with cultured fibroblasts, the apoptosis regulators caspase-9 and Apaf-1 are hypothesized to function as tumor suppressors. To investigate their in vivo role in lymphomagenesis, an IgH enhancer-driven c-myc transgene was crossed onto Apaf-1−/− and caspase-9−/− mice. Due to perinatal lethality, Eμ-myc transgenic Apaf-1−/− or caspase-9−/− fetal liver cells were used to reconstitute lethally irradiated recipient mice. Surprisingly, no differences were seen in rate, incidence, or severity of lymphoma with loss of Apaf-1 or caspase-9, and Apaf-1 was not a critical determinant of anticancer drug sensitivity of c-myc–induced lymphomas. Moreover, loss of Apaf-1 did not promote oncogene-induced transformation of mouse embryo fibroblasts. Thus, Apaf-1 and caspase-9 do not suppress c-myc–induced lymphomagenesis and embryo fibroblast transformation

The reaction Δ+N→N+N+ϕ\Delta+N\to N+N+\phi in ion-ion collisions

We study the threshold $\phi$-meson production in the process $\Delta+N\to N+N+\phi$, which appears as a possible important mechanism in high energy nuclei-nuclei collisions. The isotopic invariance of the strong interaction and the selection rules due to P-parity and total angular momentum result in a general and model independent parametrization of the spin structure of the matrix element in terms of three partial amplitudes. In the framework of one-pion exchange model these amplitudes can be derived in terms of the two threshold partial amplitudes for the process $\pi+N\to N+\phi$. We predict the ratio of cross sections for $\phi-$meson production in $pp$- and $\Delta N$-collisions and the polarization properties of the $\phi$-meson, in $\Delta+N\to N+N+\phi$, as a function of a single parameter, which characterizes the relative role of transversal and longitudinal $\phi$-meson polarizations in the process $\pi+N\to N+\phi$.Comment: 10 pages 3 figure

Switchable zero-bias anomaly in individual C₆₀ molecules contacted with tunable aluminum electrodes

We report the observation of strong resonances at zero bias in the differential conductance through Al–C₆₀–Al junctions with tunable electrode distance, measured above T = 10 K. The conductance value at resonance ranges from a few percent up to eighty percent of the quantum of conductance. The resonances may disappear or reoccur completely and discontinuously upon very small changes of the electrode distance. However, once they are formed they are very robust with respect to changes of the electrode distance. We discuss similarities and differences to the common theories of the Kondo screening of a spontaneous spin polarization of the C₆₀ molecule. We deduce Kondo temperatures in the range from 35 to 160 K and demonstrate that the temperature dependence is in agreement with the scaling behavior of the Kondo effect in the temperature range of our experiment