Carbon nanotube array as a van der Waals two-dimensional hyperbolic material

We use an ab-initio approach to design and study a novel two-dimensional material - a planar array of carbon nanotubes separated by an optimal distance defined by the van der Waals interaction. We show that the energy spectrum for an array of quasi-metallic nanotubes is described by a strongly anisotropic hyperbolic dispersion and formulate a model low-energy Hamiltonian for its semi-analytical treatment. Periodic-potential-induced lifting of the valley degeneracy for an array of zigzag narrow-gap nanotubes leads to the band gap collapse. In contrast, the band gap is opened in an array of gapless armchair tubes. These unusual spectra, marked by pronounced van Hove singularities in the low-energy density of states, open the opportunity for interesting physical effects and prospective optoelectronic applications

Compositional variation of thin PZT films near morphotropic phase boundary: experiment and simulation

The work was partly supported by the Ministry for Education and Science (Russian Federation) (Grant No 16.2811.2017/4.6) and RFBR (Grant No 16-02-00632)

SORL1 mutation in a Greek family with Parkinson's disease and dementia

Whole exome sequencing and linkage analysis were performed in a three generational pedigree of Greek origin with a broad phenotypic spectrum spanning from Parkinson’s disease and Parkinson’s disease dementia to dementia of mixed type (Alzheimer disease and vascular dementia). We identified a novel heterozygous c.G1135T (p.G379W) variant in SORL1 which segregated with the disease in the family. Mutation screening in sporadic Greek PD cases identified one additional individual with the mutation, sharing the same 12.8Mb haplotype. Our findings provide support for SORL1 mutations resulting in a broad range of additional phenotypes and warrants further studies in neurodegenerative diseases beyond AD

Relevance of biomarkers across different neurodegenerative

Background: The panel of fluid- and imaging-based biomarkers available for neurodegenerative disease research is growing and has the potential to close important gaps in research and the clinic. With this growth and increasing use, appropriate implementation and interpretation are paramount. Various biomarkers feature nuanced differences in strengths, limitations, and biases that must be considered when investigating disease etiology and clinical utility. For example, neuropathological investigations of Alzheimer’s disease pathogenesis can fall in disagreement with conclusions reached by biomarker-based investigations. Considering the varied strengths, limitations, and biases of different research methodologies and approaches may help harmonize disciplines within the neurodegenerative disease field. Purpose of review: Along with separate review articles covering fluid and imaging biomarkers in this issue of Alzheimer’s Research and Therapy, we present the result of a discussion from the 2019 Biomarkers in Neurodegenerative Diseases course at the University College London. Here, we discuss themes of biomarker use in neurodegenerative disease research, commenting on appropriate use, interpretation, and considerations for implementation across different neurodegenerative diseases. We also draw attention to areas where biomarker use can be combined with other disciplines to understand issues of pathophysiology and etiology underlying dementia. Lastly, we highlight novel modalities that have been proposed in the landscape of neurodegenerative disease research and care

Drosophila S2 Cells Are Non-Permissive for Vaccinia Virus DNA Replication Following Entry via Low pH-Dependent Endocytosis and Early Transcription

Vaccinia virus (VACV), a member of the chordopox subfamily of the Poxviridae, abortively infects insect cells. We have investigated VACV infection of Drosophila S2 cells, which are useful for protein expression and genome-wide RNAi screening. Biochemical and electron microscopic analyses indicated that VACV entry into Drosophila S2 cells depended on the VACV multiprotein entry-fusion complex but appeared to occur exclusively by a low pH-dependent endocytic mechanism, in contrast to both neutral and low pH entry pathways used in mammalian cells. Deep RNA sequencing revealed that the entire VACV early transcriptome, comprising 118 open reading frames, was robustly expressed but neither intermediate nor late mRNAs were made. Nor was viral late protein synthesis or inhibition of host protein synthesis detected by pulse-labeling with radioactive amino acids. Some reduction in viral early proteins was noted by Western blotting. Nevertheless, synthesis of the multitude of early proteins needed for intermediate gene expression was demonstrated by transfection of a plasmid containing a reporter gene regulated by an intermediate promoter. In addition, expression of a reporter gene with a late promoter was achieved by cotransfection of intermediate genes encoding the late transcription factors. The requirement for transfection of DNA templates for intermediate and late gene expression indicated a defect in viral genome replication in VACV-infected S2 cells, which was confirmed by direct analysis. Furthermore, VACV-infected S2 cells did not support the replication of a transfected plasmid, which occurs in mammalian cells and is dependent on all known viral replication proteins, indicating a primary restriction of DNA synthesis

Multiple Phosphatidylinositol 3-Kinases Regulate Vaccinia Virus Morphogenesis

Poxvirus morphogenesis is a complex process that involves the successive wrapping of the virus in host cell membranes. We screened by plaque assay a focused library of kinase inhibitors for those that caused a reduction in viral growth and identified several compounds that selectively inhibit phosphatidylinositol 3-kinase (PI3K). Previous studies demonstrated that PI3Ks mediate poxviral entry. Using growth curves and electron microscopy in conjunction with inhibitors, we show that that PI3Ks additionally regulate morphogenesis at two distinct steps: immature to mature virion (IMV) transition, and IMV envelopment to form intracellular enveloped virions (IEV). Cells derived from animals lacking the p85 regulatory subunit of Type I PI3Ks (p85α−/−β−/−) presented phenotypes similar to those observed with PI3K inhibitors. In addition, VV appear to redundantly use PI3Ks, as PI3K inhibitors further reduce plaque size and number in p85α−/−β−/− cells. Together, these data provide evidence for a novel regulatory mechanism for virion morphogenesis involving phosphatidylinositol dynamics and may represent a new therapeutic target to contain poxviruses

Исследование клинической эффективности дженерика латанопроста 0,005% в составе комбинированной терапии первичной открытоугольной глаукомы

PURPOSE: To assess hypotensive efficiency and conduct a compositional analysis of different samples of generic latanoprost 0,005% (Prolatan, “Sentiss Rus”, India) in combined treatment of primary open-angle glaucoma (POAG) patients.METHODS: The study included patients with different stages of POAG. Initially, patients received a separate combination therapy that included beta-blockers and prostaglandins. After prostaglandin discontinuation and a subsequent 2-week wash-out period, during which the patients received only beta-blockers monotherapy, latanoprost 0.005% analogue Prolatan (“Sentiss Rus”, India) was added to treatment. IOP was measured at the baseline level, after the wash-out period and 1, 2 and 3 months after the beginning of the new drug administration. Different samples of generic latanoprost 0.005% (Prolatan, “Sentiss Rus”, India) were analyzed in a certified laboratory by means of reverse phase highly efficient liquid chromatography using «Milichrom A-02» with an ultraviolet detector.RESULTS: The study included 25 patients (45 eyes) with POAG. The average age of patients was 65.7±9.2 years. Baseline IOP in patients with basic therapy by non-fixed combination of beta-blockers and prostaglandin analogues was 19.47±2.08 mm Hg. After 3 months of combined therapy with latanoprost 0.005% analogue Prolatan level of IOP was 18.07±1.78 mm Hg. Comparison of baseline IOP level with post drug replacement therapy IOP level showed a statistically significant difference (p<0.05). The results of chromatography showed that different samples of generic latanoprost 0.005% (Prolatan, “Sentiss Rus”, India) are identical in composition and contain three peaks, each consisting of several components.CONCLUSION: Obtained data allows us to recommend the use of generic forms of latanoprost 0.005% in combination therapy of patients with different stages of POAG.ЦЕЛЬ. Изучить гипотензивную эффективность и компонентный состав разных образцов дженерика латанопроста 0,005% Пролатан («Сентисс Рус», Индия), входящего в состав комбинированной гипотензивной инстилляционной терапии у пациентов с первичной открытоугольной глаукомой (ПОУГ).МЕТОДЫ. В исследование были включены пациенты с разными стадиями ПОУГ, ранее получавшие раздельную комбинированную инстилляционную терапию, включающую бета-адреноблокаторы и простагландины. После отмены препарата простагландинового ряда и последовавшего за этим 2-недельного периода «вымывания», в течение которого пациенты получали только монотерапию бета-адреноблокаторами, в дополнение к ним был назначен аналог латанопроста 0,005% Пролатан («Сентисс Рус», Индия). Уровень офтальмотонуса измеряли при базовом исследовании, после окончания периода «вымывания», через 1, 2 и 3 месяца новой инстилляционной комбинированной терапии. Исследование образцов медицинских препаратов проводили методом обращенно-фазовой высокоэффективной жидкостной хроматографии с использованием прибора «Милихром А-02» с ультрафиолетовым детектором.РЕЗУЛЬТАТЫ. В исследование были включены 25 пациентов (45 глаза). Средний возраст больных составил 65,7±9,2 года. На фоне базовой терапии, включающей нефиксированную комбинацию бета-адреноблокатора и препарата простагландинового ряда, уровень внутриглазного давления (ВГД, Pt) составил 19,47±2,08 мм рт.ст. Через 3 месяца применения комбинированной инстилляционной терапии с аналогом дженерика латанопроста 0,005% уровень офтальмотонуса составил 18,07±1,78 мм рт.ст. При сравнении исходных показателей офтальмотонуса, полученных при использовании базовой терапии, с показателями уровня ВГД на фоне инстилляции препаратов «замены» были установлены статистически значимые различия (р<0,05). Результаты хроматографии показали, что разные образцы препарата латанопроста 0,005% (Пролатан, «Сентисс Рус», Индия) совершенно одинаковы по составу и содержат по 3 пика, каждый из которых состоит из нескольких компонентов.ЗАКЛЮЧЕНИЕ. Полученные результаты позволяют рекомендовать использование дженерика латанопроста 0,005% (Пролатан, «Сентисс Рус», Индия) в комбинированной терапии у больных глаукомой с разными стадиями заболевания

Decreased expression of the Augmenter of Liver Regeneration results in increased apoptosis and oxidative damage in human-derived glioma cells

The mammalian growth factor erv1-like (GFER) gene encodes a sulfhydryl oxidase enzyme, named Augmenter of Liver Regeneration (ALR). Recently it has been demonstrated that ALR supports cell proliferation acting as an anti-apoptotic factor. This effect is determined by ALR ability to support the anti-apoptotic gene expression and to preserve cellular normoxic conditions. We recently demonstrated that the addition of recombinant ALR (rALR) in the culture medium of H2O2-treated neuroblastoma cells reduces the lethal effects induced by the hydrogen peroxide. Similar data have been reported in the regenerating liver tissue from partially hepatectomized rats treated with rALR. The purpose of the present study was to evaluate the effect of the GFER inhibition, via the degradation of the complementary mRNA by the specific siRNA, on the behaviour of the apoptosis (apoptotic gene and caspase expression and apoptotic cell number) and of the oxidative stress-induced parameters (reactive oxygen species (ROS), clusterin expression and mitochondrial integrity) in T98G glioma cells. The results revealed a reduction of (i) ALR, (ii) clusterin and (iii) bcl-2 and an increase of (iv) caspase-9, activated caspase-3, ROS, apoptotic cell number and mitochondrial degeneration. These data confirm the anti-apoptotic role of ALR and its anti-oxidative properties, and shed some light on the molecular pathways through which ALR modulates its biological effects

Molecular dynamics simulations of the growth of poly(chloro-para-xylylene) films

Parylene C, poly(chloro-para-xylylene) is the most widely used member of the parylene family due to its excellent chemical and physical properties. In this work we analyzed the formation of the parylene C film using molecular mechanics and molecular dynamics methods. A five unit chain is necessary to create a stable hydrophobic cluster and to adhere to a covered surface. Two scenarios were deemed to take place. The obtained results are consistent with a polymer film scaling growth mechanism and contribute to the description of the dynamic growth of the parylene C polymer