31 research outputs found

    Nodal quasiparticle meltdown in ultra-high resolution pump-probe angle-resolved photoemission

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    High-TcT_c cuprate superconductors are characterized by a strong momentum-dependent anisotropy between the low energy excitations along the Brillouin zone diagonal (nodal direction) and those along the Brillouin zone face (antinodal direction). Most obvious is the d-wave superconducting gap, with the largest magnitude found in the antinodal direction and no gap in the nodal direction. Additionally, while antinodal quasiparticle excitations appear only below TcT_c, superconductivity is thought to be indifferent to nodal excitations as they are regarded robust and insensitive to TcT_c. Here we reveal an unexpected tie between nodal quasiparticles and superconductivity using high resolution time- and angle-resolved photoemission on optimally doped Bi2_2Sr2_2CaCu2_2O8+δ_{8+\delta}. We observe a suppression of the nodal quasiparticle spectral weight following pump laser excitation and measure its recovery dynamics. This suppression is dramatically enhanced in the superconducting state. These results reduce the nodal-antinodal dichotomy and challenge the conventional view of nodal excitation neutrality in superconductivity.Comment: 7 pages, 3 figure. To be published in Nature Physic

    The Stem Species of Our Species: A Place for the Archaic Human Cranium from Ceprano, Italy

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    One of the present challenges in the study of human evolution is to recognize the hominin taxon that was ancestral to Homo sapiens. Some researchers regard H. heidelbergensis as the stem species involved in the evolutionary divergence leading to the emergence of H. sapiens in Africa, and to the evolution of the Neandertals in Europe. Nevertheless, the diagnosis and hypodigm of H. heidelbergensis still remain to be clarified. Here we evaluate the morphology of the incomplete cranium (calvarium) known as Ceprano whose age has been recently revised to the mid of the Middle Pleistocene, so as to test whether this specimen may be included in H. heidelbergensis. The analyses were performed according to a phenetic routine including geometric morphometrics and the evaluation of diagnostic discrete traits. The results strongly support the uniqueness of H. heidelbergensis on a wide geographical horizon, including both Eurasia and Africa. In this framework, the Ceprano calvarium – with its peculiar combination of archaic and derived traits – may represent, better than other penecontemporaneous specimens, an appropriate ancestral stock of this species, preceding the appearance of regional autapomorphic features

    A framework for evolutionary systems biology

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    <p>Abstract</p> <p>Background</p> <p>Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects.</p> <p>Results</p> <p>Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions <it>in silico</it>. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism.</p> <p>Conclusion</p> <p>EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications.</p

    Pan-cancer analysis of whole genomes

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    Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

    The feasibility of a role for community health workers in integrated mental health care for perinatal depression: a qualitative study from Surabaya, Indonesia.

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    BACKGROUND: Indonesian maternal health policies state that community health workers (CHWs) are responsible for detection and referral of pregnant women and postpartum mothers who might suffer from mental health problems (task-sharing). The documents have been published for a while, however reports on the implementation are hardly found which possibly resulted from feasibility issue within the health system. AIMS: To examine the feasibility of task-sharing in integrated mental health care to identify perinatal depression in Surabaya, Indonesia. METHODS: Semi-structured interviews were conducted with 62 participants representing four stakeholder groups in primary health care: program managers from the health office and the community, health workers and CHWs, mental health specialists, and service users. Questions on the feasibility were supported by vignettes about perinatal depression. WHO's health systems framework was applied to analyse the data using framework analysis. RESULTS: Findings indicated the policy initiative is feasible to the district health system. A strong basis within the health system for task-sharing in maternal mental health rests on health leadership and governance that open an opportunity for training and supervision, financing, and intersectoral collaboration. The infrastructure and resources in the city provide potential for a continuity of care. Nevertheless, feasibility is challenged by gaps between policy and practices, inadequate support system in technologies and information system, assigning the workforce and strategies to be applied, and the lack of practical guidelines to guide the implementation. CONCLUSION: The health system and resources in Surabaya provide opportunities for task-sharing to detect and refer cases of perinatal depression in an integrated mental health care system. Participation of informal workforce might facilitate in closing the gap in the provision of information on perinatal mental health

    Myo5b knockout mice as a model of microvillus inclusion disease

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    Inherited MYO5B mutations have recently been associated with microvillus inclusion disease (MVID), an autosomal recessive syndrome characterized by intractable, life-threatening, watery diarrhea appearing shortly after birth. Characterization of the molecular mechanisms underlying this disease and development of novel therapeutic approaches is hampered by the lack of animal models. In this study we describe the phenotype of a novel mouse model with targeted inactivation of Myo5b. Myo5b knockout mice show perinatal mortality, diarrhea and the characteristic mislocalization of apical and basolateral plasma membrane markers in enterocytes. Moreover, in transmission electron preparations, we observed microvillus atrophy and the presence of microvillus inclusion bodies. Importantly, Myo5b knockout embryos at day 20 of gestation already display all these structural defects, indicating that they are tissue autonomous rather than secondary to environmental cues, such as the long-term absence of nutrients in the intestine. Myo5b knockout mice closely resemble the phenotype of MVID patients and constitute a useful model to further investigate the underlying molecular mechanism of this disease and to preclinically assess the efficacy of novel therapeutic approaches

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    Keywords: We present a femtosecond time-resolved optical spectroscopy (TRS) as an experimental tool to probe the changes in the low energy electronic density of states as a result of short and long range charge density wave order. In these experiments, a femtosecond laser pump pulse excites electron-hole pairs via an interband transition in the material. These hot carriers rapidly release their energy via electron-electron and electron-phonon collisions reaching states near the Fermi energy within 10-100 fs. The presence of an energy gap in the quasiparticle excitation spectrum inhibits the final relaxation step and photoexcited carriers accumulate above the gap. The relaxation and recombination processes of photoexcited quasiparticles are monitored by measuring the time evolution of the resulting photoinduced absorption. This way, the studies of carrier relaxation dynamics give direct information of the temperature-dependent changes in the low energy density of states. Here we present the application of the femtosecond time-resolved optical spectroscopy for studying changes in the low energy electronic density of states in low dimensional charge density wave systems associated with various charge density wave (CDW) transitions and review some recent experiments on quasi 1D and 2D CDW compounds. 1
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