Stratigraphic,chronological and behavioural contexts of Pleistocene Homo sapiens from Middle Awash,Ethiopia

Clarifying the geographic, environmental and behavioural contexts in which the emergence of anatomically modern Homo sapiens occurred has proved difficult, particularly because Africa lacked adequate geochronological, palaeontological and archaeological evidence. The discovery of anatomically modern Homo sapiens fossils at Herto, Ethiopia, changes this. Here we report on stratigraphically associated Late Middle Pleistocene artefacts and fossils from fluvial and lake margin sandstones of the Upper Herto Member of the Bouri Formation, Middle Awash, Afar Rift, Ethiopia. The fossils and artefacts are dated between 160,000 and 154,000 years ago by precise age determinations using the 40Ar/39Ar method. The archaeological assemblages contain elements of both Acheulean and Middle Stone Age technocomplexes. Associated faunal remains indicate repeated, systematic butchery of hippopotamus carcasses. Contemporary adult and juvenile Homo sapiens fossil crania manifest bone modifications indicative of deliberate mortuary practices.     

Electron cryo-microscopy shows how strong binding of myosin to actin releases nucleotide

Muscle contraction involves the cyclic interaction of the myosin cross-bridges with the actin filament, which is coupled to steps in the hydrolysis of ATP. While bound to actin each cross-bridge undergoes a conformational change, often referred to as the "power stroke", which moves the actin filament past the myosin filaments; this is associated with the release of the products of ATP hydrolysis and a stronger binding of myosin to actin. The association of a new ATP molecule weakens the binding again, and the attached cross-bridge rapidly dissociates from actin. The nucleotide is then hydrolysed, the conformational change reverses, and the myosin cross-bridge reattaches to actin. X-ray crystallography has determined the structural basis of the power stroke, but it is still not clear why the binding of actin weakens that of the nucleotide and vice versa. Here we describe, by fitting atomic models of actin and the myosin cross-bridge into high-resolution electron cryo-microscopy three-dimensional reconstructions, the molecular basis of this linkage. The closing of the actin-binding cleft when actin binds is structurally coupled to the opening of the nucleotide-binding pocket.     

Organization of cell assemblies in the hippocampus

Neurons can produce action potentials with high temporal precision. A fundamental issue is whether, and how, this capability is used in information processing. According to the 'cell assembly' hypothesis, transient synchrony of anatomically distributed groups of neurons underlies processing of both external sensory input and internal cognitive mechanisms. Accordingly, neuron populations should be arranged into groups whose synchrony exceeds that predicted by common modulation by sensory input. Here we find that the spike times of hippocampal pyramidal cells can be predicted more accurately by using the spike times of simultaneously recorded neurons in addition to the animals location in space. This improvement remained when the spatial prediction was refined with a spatially dependent theta phase modulation. The time window in which spike times are best predicted from simultaneous peer activity is 10-30 ms, suggesting that cell assemblies are synchronized at this timescale. Because this temporal window matches the membrane time constant of pyramidal neurons, the period of the hippocampal gamma oscillation and the time window for synaptic plasticity, we propose that cooperative activity at this timescale is optimal for information transmission and storage in cortical circuits.     

Temporal effects of ACTH,indomethacin and 7-oxa-13-prostynoic acid upon glucocorticoid production by the human adrenal

Summary Indomethacin or 7-oxa-13-prostynoic acid does not alter basal adrenal cortisol output. Preincubation in either, depresses subsequent ACTH-stimulated cortisol output below ACTH alone and controls. Either inhibitor following ACTH preincubation blunts normal ACTH-stimulated cortisol production.     

Labelling of ribosomal RNA peaks in the liver of rats after administration of tritiated fluorouracil

Zusammenfassung Nach i.p. Injektion von 5-Fluorouracil-³H wurde bei Ratten zu verschiedenen Zeiten die RNS-Neubildung der Leber bestimmt. Die Resultate sprechen dafür, dass Fluorouracil in die ribosomale RNA der Leber eingebaut wird.

---

---

This work was supported by grants from the Swedish Medical Research Council (Project No. K68-12X-623-04), the Swedish Cancer Society (Project No. 95-K68-02X), the Faculty of Medicine, University of Uppsala, Sweden, and the Swedish Society for Medical Research.     

Philosophical Issues and their Implications for the Systems Architect

Many system architects select their system methodologies without explicit consideration of the philosophical perspectives that impact their decisions. This paper describes how the concepts of ontology and epistemology apply in systems science. Ontology is how we specify terms of reference for existence, allowing us to understand the theory of existence via an ‘existence framework’. Epistemology, the theory of knowledge, allows us to explore new models and theories of knowledge acquisition so the best system-based methodologies can be deployed to solve complex system problems. After introducing these concepts, the paper presents system science issues and assesses the impact of ontological, axiological and epistemological perspectives on system methodology selection, research, system design and deployment. An ontological viewpoint such as realism, as an objective view is contrasted versus nationalism, a personal perceptional view. An epistemological viewpoint is explored comparing knowledge as a product of sensory perception or rational reflection. The paper’s significant contribution is that it helps system architects understand that their philosophical views of systems science impact their system methodology choices.     

Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation

The embryonic pyruvate kinase M2 (PKM2) isoform is highly expressed in human cancer. In contrast to the established role of PKM2 in aerobic glycolysis or the Warburg effect, its non-metabolic functions remain elusive. Here we demonstrate, in human cancer cells, that epidermal growth factor receptor (EGFR) activation induces translocation of PKM2, but not PKM1, into the nucleus, where K433 of PKM2 binds to c-Src-phosphorylated Y333 of β-catenin. This interaction is required for both proteins to be recruited to the CCND1 promoter, leading to HDAC3 removal from the promoter, histone H3 acetylation and cyclin D1 expression. PKM2-dependent β-catenin transactivation is instrumental in EGFR-promoted tumour cell proliferation and brain tumour development. In addition, positive correlations have been identified between c-Src activity, β-catenin Y333 phosphorylation and PKM2 nuclear accumulation in human glioblastoma specimens. Furthermore, levels of β-catenin phosphorylation and nuclear PKM2 have been correlated with grades of glioma malignancy and prognosis. These findings reveal that EGF induces β-catenin transactivation via a mechanism distinct from that induced by Wnt/Wingless and highlight the essential non-metabolic functions of PKM2 in EGFR-promoted β-catenin transactivation, cell proliferation and tumorigenesis.