The Stroke-Induced Increase of Somatostatin-Expressing Neurons is Inhibited by Diabetes: A Potential Mechanism at the Basis of Impaired Stroke Recovery

Type 2 diabetes (T2D) hampers recovery after stroke, but the underling mechanisms are mostly unknown. In a recently published study (Pintana et al. in Clin Sci (Lond) 133(13):1367\u20131386, 2019), we showed that impaired recovery in T2D was associated with persistent atrophy of parvalbumin+ interneurons in the damaged striatum. In the current work, which is an extension of the abovementioned study, we investigated whether somatostatin (SOM)+ interneurons are also affected by T2D during the stroke recovery phase. C57Bl/6j mice were fed with high-fat diet or standard diet (SD) for 12\ua0months and subjected to 30-min transient middle cerebral artery occlusion (tMCAO). SOM+ cell number/density in the striatum was assessed by immunohistochemistry 2 and 6\ua0weeks after tMCAO in peri-infarct and infarct areas. This was possible by establishing a computer-based quantification method that compensates the post-stroke tissue deformation and the irregular cell distribution. SOM+ interneurons largely survived the stroke as seen at 2\ua0weeks. Remarkably, 6\ua0weeks after stroke, the number of SOM+ interneurons increased (vs. contralateral striatum) in SD-fed mice in both peri-infarct and infarct areas. However, this increase did not result from neurogenesis. T2D completely abolished this effect specifically in the in the infarct area. The results suggest that the up-regulation of SOM expression in the post-stroke phase could be related to neurological recovery and T2D could inhibit this process. We also present a new and precise method for cell counting in the stroke-damaged striatum that allows to reveal accurate, area-related effects of stroke on cell number

Grazing protozoa and the evolution of the Escherichia coli O157:H7 Shiga toxin-encoding prophage

Humans play little role in the epidemiology of Escherichia coli O157:H7, a commensal bacterium of cattle. Why then does E. coli O157:H7 code for virulence determinants, like the Shiga toxins (Stxs), responsible for the morbidity and mortality of colonized humans? One possibility is that the virulence of these bacteria to humans is coincidental and these virulence factors evolved for and are maintained for other roles they play in the ecology of these bacteria. Here, we test the hypothesis that the carriage of the Stx-encoding prophage of E. coli O157:H7 increases the rate of survival of E. coli in the presence of grazing protozoa, Tetrahymena pyriformis. In the presence but not the absence of Tetrahymena, the carriage of the Stx-encoding prophage considerably augments the fitness of E. coli K-12 as well as clinical isolates of E. coli O157 by increasing the rate of survival of the bacteria in the food vacuoles of these ciliates. Grazing protozoa in the environment or natural host are likely to play a significant role in the ecology and maintenance of the Stx-encoding prophage of E. coli O157:H7 and may well contribute to the evolution of the virulence of these bacteria to colonize humans

Low-lying level structure of 56^{56}Cu and its implications on the rp process

The low-lying energy levels of proton-rich $^{56}$Cu have been extracted using in-beam $\gamma$-ray spectroscopy with the state-of-the-art $\gamma$-ray tracking array GRETINA in conjunction with the S800 spectrograph at the National Superconducting Cyclotron Laboratory at Michigan State University. Excited states in $^{56}$Cu serve as resonances in the $^{55}$Ni(p,$\gamma$)$^{56}$Cu reaction, which is a part of the rp-process in type I x-ray bursts. To resolve existing ambiguities in the reaction Q-value, a more localized IMME mass fit is used resulting in $Q=639\pm82$~keV. We derive the first experimentally-constrained thermonuclear reaction rate for $^{55}$Ni(p,$\gamma$)$^{56}$Cu. We find that, with this new rate, the rp-process may bypass the $^{56}$Ni waiting point via the $^{55}$Ni(p,$\gamma$) reaction for typical x-ray burst conditions with a branching of up to $\sim$40$\%$. We also identify additional nuclear physics uncertainties that need to be addressed before drawing final conclusions about the rp-process reaction flow in the $^{56}$Ni region.Comment: 8 pages, accepted for Phys. Rev.

Multi-scale evolution of Kelvin–Helmholtz waves at the earth's magnetopause during southward IMF periods

At the Earth's low-latitude magnetopause, the Kelvin–Helmholtz instability (KHI), driven by the velocity shear between the magnetosheath and magnetosphere, has been frequently observed during northward interplanetary magnetic field (IMF) periods. However, the signatures of the KHI have been much less frequently observed during southward IMF periods, and how the KHI develops under southward IMF has been less explored. Here, we performed a series of realistic 2D and 3D fully kinetic simulations of a KH wave event observed by the Magnetospheric Multiscale (MMS) mission at the dusk-flank magnetopause during southward IMF on September 23, 2017. The simulations demonstrate that the primary KHI bends the magnetopause current layer and excites the Rayleigh–Taylor instability (RTI), leading to penetration of high-density arms into the magnetospheric side. This arm penetration disturbs the structures of the vortex layer and produces intermittent and irregular variations of the surface waves which significantly reduces the observational probability of the periodic KH waves. The simulations further demonstrate that in the non-linear growth phase of the primary KHI, the lower-hybrid drift instability (LHDI) is induced near the edge of the primary vortices and contributes to an efficient plasma mixing across the magnetopause. The signatures of the large-scale surface waves by the KHI/RTI and the small-scale fluctuations by the LHDI are reasonably consistent with the MMS observations. These results indicate that the multi-scale evolution of the magnetopause KH waves and the resulting plasma transport and mixing as seen in the simulations may occur during southward IM

First-principle based multi-channel integrated modelling in support to the design of the Divertor Tokamak Test facility

An intensive integrated modelling work of main scenarios of the new tokamak DTT (Divertor Tokamak Test facility) with the Single Null divertor configuration has been performed using first-principle quasi-linear transport models, in support to the design of the device and to the definition of its scientific work-programme. First results of this integrated modelling work on DTT (R0= 2.14 m, a= 0.65 m) are presented here along with outcome of the gyrokinetic simulations used to validate the reduced models in the DTT range of parameters. As a result of this work, the heating mix was defined, the size of device was increased to R0= 2.19 m and a= 0.70 m, the use of pellets for fuelling has been advised and reference profiles for diagnostic design, estimates of neutron yields and fast particle losses have become available.</p

Prognosis of screen-detected breast cancers: results of a population based study

BACKGROUND: The reduced mortality rate from breast carcinoma among women offered screening mammography is demonstrated after 15–20 years of follow-up. However, the assessment of 5-year overall and event-free survival could represent an earlier measure of the efficacy of mammography screening program (MSP). METHODS: All cases of breast cancer diagnosed in the Province of Modena between years 1996 and 2000 in women aged 50 to 69 years, were identified through the Modena Cancer Registry (MCR). Stage of disease and treatment information were obtained from clinical records. All the events occurring up to June 30, 2003 were retrieved by experienced monitors. Five-year overall and event-free survival were the principal end-points of the study. RESULTS: During a 5-year period, 587 primary breast cancers were detected by the MSP and 471 primary breast cancers were diagnosed out of the MSP. The screen-detected breast cancers were smaller, more likely node negative, with low histological grade, low proliferative activity and positive receptors status. Furthermore, the breast cancer diagnosed through the MSP more frequently received a conservative surgery. The 5-year survival rate was 94% in the screen-detected group, versus 84% in the other group (p = 0.0001). The rate of 5-year event-free survival was 89% and 75% for the MSP participants and not participants, respectively (p = 0.0001). CONCLUSIONS: Our data confirm a favourable outcome of screen-detected breast cancers in terms of five-year overall and event-free survival, which reflect the good quality assurance parameters of the MSP. Finally, a cancer registry should be implemented in every area covered by screening programs

Multi-scale evolution of Kelvin–Helmholtz waves at the Earth's magnetopause during southward IMF periods

At the Earth's low-latitude magnetopause, the Kelvin-Helmholtz instability (KHI), driven by the velocity shear between the magnetosheath and magnetosphere, has been frequently observed during northward interplanetary magnetic field (IMF) periods. However, the signatures of the KHI have been much less frequently observed during southward IMF periods, and how the KHI develops under southward IMF has been less explored. Here, we performed a series of realistic 2D and 3D fully kinetic simulations of a KH wave event observed by the Magnetospheric Multiscale (MMS) mission at the dusk-flank magnetopause during southward IMF on September 23, 2017. The simulations demonstrate that the primary KHI bends the magnetopause current layer and excites the Rayleigh-Taylor instability (RTI), leading to penetration of high-density arms into the magnetospheric side. This arm penetration disturbs the structures of the vortex layer and produces intermittent and irregular variations of the surface waves which significantly reduces the observational probability of the periodic KH waves. The simulations further demonstrate that in the non-linear growth phase of the primary KHI, the lower-hybrid drift instability (LHDI) is induced near the edge of the primary vortices and contributes to an efficient plasma mixing across the magnetopause. The signatures of the large-scale surface waves by the KHI/RTI and the small-scale fluctuations by the LHDI are reasonably consistent with the MMS observations. These results indicate that the multi-scale evolution of the magnetopause KH waves and the resulting plasma transport and mixing as seen in the simulations may occur during southward IMF

Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy

Thermodynamic theory of epitaxial ferroelectric thin films with dense domain structures

A Landau-Ginsburg-Devonshire-type nonlinear phenomenological theory is presented, which enables the thermodynamic description of dense laminar polydomain states in epitaxial ferroelectric thin films. The theory explicitly takes into account the mechanical substrate effect on the polarizations and lattice strains in dissimilar elastic domains (twins). Numerical calculations are performed for PbTiO3 and BaTiO3 films grown on (001)-oriented cubic substrates. The "misfit strain-temperature" phase diagrams are developed for these films, showing stability ranges of various possible polydomain and single-domain states. Three types of polarization instabilities are revealed for polydomain epitaxial ferroelectric films, which may lead to the formation of new polydomain states forbidden in bulk crystals. The total dielectric and piezoelectric small-signal responses of polydomain films are calculated, resulting from both the volume and domain-wall contributions. For BaTiO3 films, strong dielectric anomalies are predicted at room temperature near special values of the misfit strain.Comment: 19 pages, 8 figure