Disruption of the Toxoplasma gondii Parasitophorous Vacuole by IFNγ-Inducible Immunity-Related GTPases (IRG Proteins) Triggers Necrotic Cell Death

Toxoplasma gondii is a natural intracellular protozoal pathogen of mice and other small mammals. After infection, the parasite replicates freely in many cell types (tachyzoite stage) before undergoing a phase transition and encysting in brain and muscle (bradyzoite stage). In the mouse, early immune resistance to the tachyzoite stage is mediated by the family of interferon-inducible immunity-related GTPases (IRG proteins), but little is known of the nature of this resistance. We reported earlier that IRG proteins accumulate on intracellular vacuoles containing the pathogen, and that the vacuolar membrane subsequently ruptures. In this report, live-cell imaging microscopy has been used to follow this process and its consequences in real time. We show that the rupture of the vacuole is inevitably followed by death of the intracellular parasite, shown by its permeability to cytosolic protein markers. Death of the parasite is followed by the death of the infected cell. The death of the cell has features of pyronecrosis, including membrane permeabilisation and release of the inflammatory protein, HMGB1, but caspase-1 cleavage is not detected. This sequence of events occurs on a large scale only following infection of IFNγ-induced cells with an avirulent strain of T. gondii, and is reduced by expression of a dominant negative mutant IRG protein. Cells infected by virulent strains rarely undergo necrosis. We did not find autophagy to play any role in the key steps leading to the death of the parasite. We conclude that IRG proteins resist infection by avirulent T. gondii by a novel mechanism involving disruption of the vacuolar membrane, which in turn ultimately leads to the necrotic death of the infected cell

Management of brainstem haemorrhages

Among spontaneous intracranial haemorrhages, primary non-traumatic brainstem haemorrhages are associated with the highest mortality rate. Patients classically present with rapid neurological deterioration. Previous studies have found that the severity of initial neurological symptoms and hydrocephalus are predictors of poor outcomes. In addition, radiological parameters aim to classify brainstem haematomas according to volume, extension and impact on prognosis. However, previous studies have failed to agree on a differentiated radiological classification for outcome and functional recovery. Electrophysiology, including motor, auditory and somatosensory evoked potentials, is used to estimate the extent of the initial injury and predict functional recovery. The current management of brainstem haematomas remains conservative, focusing on initial close neurocritical care monitoring. Surgical treatment concepts exist, but similarly to general intracranial haemorrhage management, they continue to be controversial and have not been sufficiently investigated. This is especially the case for haematomas in the posterior fossa, as these are excluded from most current clinical trials. Existing studies were mostly carried out before the present millennium began, and limitations are evident in the adaptation of those results and recommendations to current management, with today’s technological and diagnostic possibilities. We therefore recommend the re-evaluation of brainstem haemorrhages in the modern neurosurgical and intensive care environment

Structural Color 3D Printing By Shrinking Photonic Crystals

The rings, spots and stripes found on some butterflies, Pachyrhynchus weevils, and many chameleons are notable examples of natural organisms employing photonic crystals to produce colorful patterns. Despite advances in nanotechnology, we still lack the ability to print arbitrary colors and shapes in all three dimensions at this microscopic length scale. Commercial nanoscale 3D printers based on two-photon polymerization are incapable of patterning photonic crystal structures with the requisite ~300 nm lattice constant to achieve photonic stopbands/ bandgaps in the visible spectrum and generate colors. Here, we introduce a means to produce 3D-printed photonic crystals with a 5x reduction in lattice constants (periodicity as small as 280 nm), achieving sub-100-nm features with a full range of colors. The reliability of this process enables us to engineer the bandstructures of woodpile photonic crystals that match experiments, showing that observed colors can be attributed to either slow light modes or stopbands. With these lattice structures as 3D color volumetric elements (voxels), we printed 3D microscopic scale objects, including the first multi-color microscopic model of the Eiffel Tower measuring only 39-microns tall with a color pixel size of 1.45 microns. The technology to print 3D structures in color at the microscopic scale promises the direct patterning and integration of spectrally selective devices, such as photonic crystal-based color filters, onto free-form optical elements and curved surfaces

Origin of the butterfly magnetoresistance in a Dirac nodal-line system

We report a study on the magnetotransport properties and on the Fermi surfaces (FS) of the ZrSi(Se,Te) semimetals. Density Functional Theory (DFT) calculations, in absence of spin orbit coupling (SOC), reveal that both the Se and the Te compounds display Dirac nodal lines (DNL) close to the Fermi level $\varepsilon_F$ at symmorphic and non-symmorphic positions, respectively. We find that the geometry of their FSs agrees well with DFT predictions. ZrSiSe displays low residual resistivities, pronounced magnetoresistivity, high carrier mobilities, and a butterfly-like angle-dependent magnetoresistivity (AMR), although its DNL is not protected against gap opening. As in Cd$_3$As$_2$, its transport lifetime is found to be 10$^2$ to 10$^3$ times larger than its quantum one. ZrSiTe, which possesses a protected DNL, displays conventional transport properties. Our evaluation indicates that both compounds most likely are topologically trivial. Nearly angle-independent effective masses with strong angle dependent quantum lifetimes lead to the butterfly AMR in ZrSiSe

The association of patient age with postoperative morbidity and mortality following resection of intracranial tumors

INTRODUCTION The postoperative functional status of patients with intracranial tumors is influenced by patient-specific factors, including age. RESEARCH QUESTION This study aimed to elucidate the association between age and postoperative morbidity or mortality following the resection of brain tumors. MATERIAL AND METHODS A multicenter database was retrospectively reviewed. Functional status was assessed before and 3-6 months after tumor resection by the Karnofsky Performance Scale (KPS). Uni- and multivariable linear regression were used to estimate the association of age with postoperative change in KPS. Logistic regression models for a ≥10-point decline in KPS or mortality were built for patients ≥75 years. RESULTS The total sample of 4864 patients had a mean age of 56.4 ​± ​14.4 years. The mean change in pre-to postoperative KPS was -1.43. For each 1-year increase in patient age, the adjusted change in postoperative KPS was -0.11 (95% CI -0.14 - - 0.07). In multivariable analysis, patients ≥75 years had an odds ratio of 1.51 to experience postoperative functional decline (95%CI 1.21-1.88) and an odds ratio of 2.04 to die (95%CI 1.33-3.13), compared to younger patients. DISCUSSION Patients with intracranial tumors treated surgically showed a minor decline in their postoperative functional status. Age was associated with this decline in function, but only to a small extent. CONCLUSION Patients ≥75 years were more likely to experience a clinically meaningful decline in function and about two times as likely to die within the first 6 months after surgery, compared to younger patients

Permutable entire functions satisfying algebraic differential equations

It is shown that if two transcendental entire functions permute, and if one of them satisfies an algebraic differential equation, then so does the other one.Comment: 5 page