Upper Palaeolithic settlements in Buran-Kaya 3 (Crimea, Ukraine): new interdisciplinary researches of the layers 5-2, 6-1 and 6-2

Грот Буран Кая 3 (Крым, Украина) содержит уникальную стратиграфию литологических и культурных отложений, включающую индустрии среднего и верхнего палеолита. В частности, в слоях 5-2, 6-1, и 6-2 был обнаружен кремневый и костяной инвентарь, относящийся к эпиграветту. Эти же слои содержат многочисленные фаунистические остатки, а также антропологический материал. В данной статье публикуются некоторые результаты междисциплинарных исследований: техникотипологический анализ кремневого и костяного инвентаря; зооархеологическое изучение останков крупных млекопитающих; исследование технологии нанесения орнамента на кости; анализ палеоантропологических материалов. На основании полученных данных предлагается функциональная интерпретация стоянки, а также производится сравнение культурных характеристик эпиграветта Буран Каи 3 и памятников соседних территорий

Upper Palaeolithic settlements in Buran-Kaya 3 (Crimea, Ukraine): new interdisciplinary researches of the layers 5-2, 6-1 and 6-2

Грот Буран Кая 3 (Крым, Украина) содержит уникальную стратиграфию литологических и культурных отложений, включающую индустрии среднего и верхнего палеолита. В частности, в слоях 5-2, 6-1, и 6-2 был обнаружен кремневый и костяной инвентарь, относящийся к эпиграветту. Эти же слои содержат многочисленные фаунистические остатки, а также антропологический материал. В данной статье публикуются некоторые результаты междисциплинарных исследований: техникотипологический анализ кремневого и костяного инвентаря; зооархеологическое изучение останков крупных млекопитающих; исследование технологии нанесения орнамента на кости; анализ палеоантропологических материалов. На основании полученных данных предлагается функциональная интерпретация стоянки, а также производится сравнение культурных характеристик эпиграветта Буран Каи 3 и памятников соседних территорий

Development of a PbWO4 Detector for Single-Shot Positron Annihilation Lifetime Spectroscopy at the GBAR Experiment

We have developed a PbWO4 (PWO) detector with a large dynamic range to measure the intensity of a positron beam and the absolute density of the ortho-positronium (o-Ps) cloud it creates. A simulation study shows that a setup based on such detectors may be used to determine the angular distribution of the emission and reflection of o-Ps to reduce part of the uncertainties of the measurement. These will allow to improve the precision in the measurement of the cross-section for the (anti)hydrogen formation by (anti)proton-positronium charge exchange and to optimize the yield of antihydrogen ion which is an essential parameter in the GBAR experiment

Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells

Citrobacter rodentium Subverts ATP Flux and Cholesterol Homeostasis in Intestinal Epithelial Cells In Vivo.

The intestinal epithelial cells (IECs) that line the gut form a robust line of defense against ingested pathogens. We investigated the impact of infection with the enteric pathogen Citrobacter rodentium on mouse IEC metabolism using global proteomic and targeted metabolomics and lipidomics. The major signatures of the infection were upregulation of the sugar transporter Sglt4, aerobic glycolysis, and production of phosphocreatine, which mobilizes cytosolic energy. In contrast, biogenesis of mitochondrial cardiolipins, essential for ATP production, was inhibited, which coincided with increased levels of mucosal O2 and a reduction in colon-associated anaerobic commensals. In addition, IECs responded to infection by activating Srebp2 and the cholesterol biosynthetic pathway. Unexpectedly, infected IECs also upregulated the cholesterol efflux proteins AbcA1, AbcG8, and ApoA1, resulting in higher levels of fecal cholesterol and a bloom of Proteobacteria. These results suggest that C. rodentium manipulates host metabolism to evade innate immune responses and establish a favorable gut ecosystem

Novel de novo EEF1A2 missense mutations causing epilepsy and intellectual disability.

BACKGROUND: Exome sequencing has led to the discovery of mutations in novel causative genes for epilepsy. One such gene is EEF1A2, encoding a neuromuscular specific translation elongation factor, which has been found to be mutated de novo in five cases of severe epilepsy. We now report on a further seven cases, each with a different mutation, of which five are newly described. METHODS: New cases were identified and sequenced through the Deciphering Developmental Disabilities project, via direct contact with neurologists or geneticists, or recruited via our website. RESULTS: All the mutations cause epilepsy and intellectual disability, but with a much wider range of severity than previously identified. All new cases share specific subtle facial dysmorphic features. Each mutation occurs at an evolutionarily highly conserved amino acid position indicating strong structural or functional selective pressure. CONCLUSIONS: EEF1A2 should be considered as a causative gene not only in cases of epileptic encephalopathy but also in children with less severe epilepsy and intellectual disability. The emergence of a possible discernible phenotype, a broad nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth may help in identifying patients with mutations in EEF1A2

Policy design for the Anthropocene

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordToday, more than ever, ‘Spaceship Earth’ is an apt metaphor as we chart the boundaries for a safe planet1. Social scientists both analyse why society courts disaster by approaching or even overstepping these boundaries and try to design suitable policies to avoid these perils. Because the threats of transgressing planetary boundaries are global, long-run, uncertain and interconnected, they must be analysed together to avoid conflicts and take advantage of synergies. To obtain policies that are effective at both international and local levels requires careful analysis of the underlying mechanisms across scientific disciplines and approaches, and must take politics into account. In this Perspective, we examine the complexities of designing policies that can keep Earth within the biophysical limits favourable to human life.Stockholm Resilience CentreBECC - Biodiversity and Ecosystem services in a Changing ClimateMistra Carbon Exi

On the zero-Hopf bifurcation of the Lotka-Volterra systems in R3

Here we study the Lotka-Volterra systems in R3, i.e. the differential systems of the form dxi/dt = xi(ri - Σ3j=1 aijxj), i = 1, 2, 3. It is known that some of these differential systems can have at least four periodic orbits bifurcating from one of their equilibrium points. Here we prove that there are some of these differential systems exhibiting at least six periodic orbits bifurcating from one of their equilibrium points. The tool for proving this result is the averaging theory of third order

The Spectrin Cytoskeleton Is Crucial for Adherent and Invasive Bacterial Pathogenesis

Various enteric bacterial pathogens target the host cell cytoskeletal machinery as a crucial event in their pathogenesis. Despite thorough studies detailing strategies microbes use to exploit these components of the host cell, the role of the spectrin-based cytoskeleton has been largely overlooked. Here we show that the spectrin cytoskeleton is a host system that is hijacked by adherent (Entropathogenic Escherichia coli [EPEC]), invasive triggering (Salmonella enterica serovar Typhimurium [S. Typhimurium]) and invasive zippering (Listeria monocytogenes) bacteria. We demonstrate that spectrin cytoskeletal proteins are recruited to EPEC pedestals, S. Typhimurium membrane ruffles and Salmonella containing vacuoles (SCVs), as well as sites of invasion and comet tail initiation by L. monocytogenes. Spectrin was often seen co-localizing with actin filaments at the cell periphery, however a disconnect between the actin and spectrin cytoskeletons was also observed. During infections with S. Typhimurium ΔsipA, actin-rich membrane ruffles at characteristic sites of bacterial invasion often occurred in the absence of spectrin cytoskeletal proteins. Additionally, early in the formation of L. monocytogenes comet tails, spectrin cytoskeletal elements were recruited to the surface of the internalized bacteria independent of actin filaments. Further studies revealed the presence of the spectrin cytoskeleton during SCV and Listeria comet tail formation, highlighting novel cytoplasmic roles for the spectrin cytoskeleton. SiRNA targeted against spectrin and the spectrin-associated proteins severely diminished EPEC pedestal formation as well as S. Typhimurium and L. monocytogenes invasion. Ultimately, these findings identify the spectrin cytoskeleton as a ubiquitous target of enteric bacterial pathogens and indicate that this cytoskeletal system is critical for these infections to progress

Variation in RNA expression and genomic DNA content acquired during cell culture

Specific chromosomal abnormalities are increasingly recognised to be associated with particular tumour subtypes. These cytogenetic abnormalities define the sites of specific genes, the alteration of which is implicated in the neoplastic process. We used comparative genomic hybridisation (CGH) to examine DNA from different breast and ovarian cancer cell lines for variations in DNA sequence copy number compared with the same normal control. We also compared different sources of the MCF7 breast line by both CGH and cDNA expression arrays. Some of the differences between the subcultures were extensive and involved large regions of the chromosome. Differences between the four subcultures were observed for gains of 2q, 5p, 5q, 6q, 7p, 7q, 9q, 10p, 11q, 13q, 14c, 16q, 18p and 20p, and losses of 4q, 5p, 5q, 6q, 7q, 8p, 11p, 11q, 12q, 13q, 15q, 19p, 19q, 20p, 21q, 22q and Xp. However, few variations were found between two subcultures examined, 5 months apart, from the same initial source. The RNA arrays also demonstrated considerable variation between the three different subcultures, with only 43% of genes expressed at the same levels in all three. Moreover, the patterns of the expressed genes did not always reflect our observed CGH aberrations. These results demonstrate extensive genomic instability and variation in RNA expression during subculture and provide supportive data for evidence that cell lines do evolve in culture, thereby weakening the direct relevance of such cultures as models of human cancer. This work also reinforces the concern that comparisons of published analyses of cultures of the same name may be dangerous