Ordered and periodic chaos of the bounded one dimensinal multibarrier potential

Numerical analysis indicates that there exists an unexpected new ordered chaos for the bounded one-dimensional multibarrier potential. For certain values of the number of barriers, repeated identical forms (periods) of the wavepackets result upon passing through the multibarrier potential.Comment: 16 pages, 9 figures, 1 Table. Some former text removed and other introduce

Identification of a Core Amino Acid Motif within the α Subunit of GABAARs that Promotes Inhibitory Synaptogenesis and Resilience to Seizures

The fidelity of inhibitory neurotransmission is dependent on the accumulation of γ-aminobutyric acid type A receptors (GABAARs) at the appropriate synaptic sites. Synaptic GABAARs are constructed from α(1-3), β(1-3), and γ2 subunits, and neurons can target these subtypes to specific synapses. Here, we identify a 15-amino acid inhibitory synapse targeting motif (ISTM) within the α2 subunit that promotes the association between GABAARs and the inhibitory scaffold proteins collybistin and gephyrin. Using mice in which the ISTM has been introduced into the α1 subunit (Gabra1-2 mice), we show that the ISTM is critical for axo-axonic synapse formation, the efficacy of GABAergic neurotransmission, and seizure sensitivity. The Gabra1-2 mutation rescues seizure-induced lethality in Gabra2-1 mice, which lack axo-axonic synapses due to the deletion of the ISTM from the α2 subunit. Taken together, our data demonstrate that the ISTM plays a critical role in promoting inhibitory synapse formation, both in the axonic and somatodendritic compartments

Wild-Type, but Not Mutant N296H, Human Tau Restores Aβ-Mediated Inhibition of LTP in Tau−/− mice

Microtubule associated protein tau (MAPT) is involved in the pathogenesis of Alzheimer’s disease and many forms of frontotemporal dementia (FTD). We recently reported that Aβ-mediated inhibition of hippocampal long-term potentiation (LTP) in mice requires tau. Here, we asked whether expression of human $MAPT$ can restore Aβ-mediated inhibition on a mouse $Tau−/−$ background and whether human tau with an FTD-causing mutation (N296H) can interfere with Aβ-mediated inhibition of LTP. We used transgenic mouse lines each expressing the full human $MAPT$ locus using bacterial artificial chromosome technology. These lines expressed all six human tau protein isoforms on a $Tau−/−$ background. We found that the human wild-type $MAPT$ H1 locus was able to restore Aβ$_{42}$-mediated impairment of LTP. In contrast, Aβ$_{42}$ did not reduce LTP in slices in two independently generated transgenic lines expressing tau protein with the mutation N296H associated with frontotemporal dementia (FTD). Basal phosphorylation of tau measured as the ratio of AT8/Tau5 immunoreactivity was significantly reduced in N296H mutant hippocampal slices. Our data show that human $MAPT$ is able to restore Aβ$_{42}$-mediated inhibition of LTP in $Tau−/−$ mice. These results provide further evidence that tau protein is central to Aβ-induced LTP impairment and provide a valuable tool for further analysis of the links between Aβ, human tau and impairment of synaptic function.MVC was supported by a Wellcome Trust OXION Training Fellowship and an equipment grant from Alzheimer’s Research UK. MVC is funded by the Institute for Life Sciences University of Southampton. RW-M was supported by a Wellcome Trust Research Career Development Fellowship (073141/Z/03/Z), CurePSP and the Alzheimer’s Society; FD held a Wellcome Trust DPhil in Neuroscience (075406/Z/04/A), and CMP is funded by the Gerald Kerkut Trust and IfLS. We thank Hana N. Dawson and Michael P. Vitek for Tau−/− mice. We thank Jenny Dworzak for her participation at an early phase of this project

The green tea polyphenol (-)-epigallocatechin gallate prevents the aggregation of tau protein into toxic oligomers at substoichiometric ratios

The accumulation of amyloid-beta (Abeta) and tau aggregates is a pathological hallmark of Alzheimer's disease. Both polypeptides form fibrillar deposits, but several lines of evidence indicate that Abeta and tau form toxic oligomeric aggregation intermediates. Depleting such structures could thus be a powerful therapeutic strategy. We generated a fragment of tau (His-K18DeltaK280) that forms stable, toxic, oligomeric tau aggregates in vitro. We show that (-)-epigallocatechin gallate (EGCG), a green tea polyphenol that was previously found to reduce Abeta aggregation, inhibits the aggregation of tau K18DeltaK280 into toxic oligomers at ten- to hundred-fold substoichiometric concentrations, thereby rescuing toxicity in neuronal model cells

Acute mental stress drives vascular inflammation and promotes plaque destabilization in mouse atherosclerosis

Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.Aims: Mental stress substantially contributes to the initiation and progression of human disease, including cardiovascular conditions. We aim to investigate the underlying mechanisms of these contributions since they remain largely unclear. Methods and results: Here, we show in humans and mice that leucocytes deplete rapidly from the blood after a single episode of acute mental stress. Using cell-tracking experiments in animal models of acute mental stress, we found that stress exposure leads to prompt uptake of inflammatory leucocytes from the blood to distinct tissues including heart, lung, skin, and, if present, atherosclerotic plaques. Mechanistically, we found that acute stress enhances leucocyte influx into mouse atherosclerotic plaques by modulating endothelial cells. Specifically, acute stress increases adhesion molecule expression and chemokine release through locally derived norepinephrine. Either chemical or surgical disruption of norepinephrine signalling diminished stress-induced leucocyte migration into mouse atherosclerotic plaques. Conclusion: Our data show that acute mental stress rapidly amplifies inflammatory leucocyte expansion inside mouse atherosclerotic lesions and promotes plaque vulnerability.publishersversionPeer reviewe

Archaeological Ethnography, Heritage Management, and Community Archaeology: A Pragmatic Approach from Crete

This article examines the introduction of archaeological ethnography as an approach to establish positioned research and bring context-specific and reflexive considerations into community archaeology projects. It considers recent cri-tiques of heritage management in archaeology and the role of archaeologists as experts in it, contending that smaller and less prominent sites exist in different contexts and pose different problems than large-scale projects usually addressed in the literature. We describe how the ‘Three Peak Sanctuaries of Central Crete’ project, investigating prehistoric Minoan ritual sites, involves communities and stakeholders and what demands the latter pose on experts in the field. Archae-ological work is always already implicated in local development projects which create and reproduce power hierarchies. It is therefore important that archaeol-ogists maintain their critical distance from official heritage discourses, as they are materialized in development programmes, while at the same time engaging with local expectations and power struggles; they also have to critically address and position their own assumptions. We use examples from our community archae-ology project to propose that these goals can be reached through archaeological ethnographic fieldwork that should precede any archaeological project to inform its methodological decisions, engage stakeholders, and collaboratively shape heritage management strategies

The Long-Term Evolution of Social Organization

This chapter outlines how the ‘innovation innovation’ transformed the world of our distant ancestors into that in which we live today. It focuses on the relationship between people and the material world, as it is the material world that has been most drastically, and measurably, transformed over the last several tens of thousands of years. In view of what we know about such distant periods, and in view of the space allot-ted to us here, it will not surprise the reader that we do so in the form of a narrative that is only partly underpinned by substantive data. We emphasize this because we do not want to hide from the reader the speculative nature of the story that follows. Yet we firmly believe that, in very general terms, this scenario is correct, and that further research will vindicate us.We first give examples of the kinds of abstractions, and the hierarchy of conceptual dimensions necessary for prehistoric human beings and their ancestors, to conquer matter, i.e. to conceptually understand, transmit and apply the operations needed to master the making of a range of objects made out of stone, bone, wood, clay and other materials. Some of the abstractions that had to be conceived in this domain re-semble those that Read et al. (http://www.escholarship.org/uc/item/2798j162) refer to, while others apply to this domain alone, and had to be truly ‘invented’. It is then argued that such ‘identification of conceptual dimensions’ is a process that underlies all human activity, and we look a little closer at how that process relates to invention and innovation.Lastly, we shift our attention to the role of innovation, information processing and communication in the emergence of social institutions, and in the structural transformation of human societies as they grow in size and complexity. In particular, we look at the role that problem solving and invention play in creating more and more complex societies, encompassing increasing numbers of people, more and more diverse institutions, and an – ultimately seemingly all-encompassing – appropriation of the natural environment. To illustrate this development we will focus on the origins and growth of urban systems

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Peer reviewe

Persistent Place-Making in Prehistory: the Creation, Maintenance, and Transformation of an Epipalaeolithic Landscape

Most archaeological projects today integrate, at least to some degree, how past people engaged with their surroundings, including both how they strategized resource use, organized technological production, or scheduled movements within a physical environment, as well as how they constructed cosmologies around or created symbolic connections to places in the landscape. However, there are a multitude of ways in which archaeologists approach the creation, maintenance, and transformation of human-landscape interrelationships. This paper explores some of these approaches for reconstructing the Epipalaeolithic (ca. 23,000–11,500 years BP) landscape of Southwest Asia, using macro- and microscale geoarchaeological approaches to examine how everyday practices leave traces of human-landscape interactions in northern and eastern Jordan. The case studies presented here demonstrate that these Epipalaeolithic groups engaged in complex and far-reaching social landscapes. Examination of the Early and Middle Epipalaeolithic (EP) highlights that the notion of “Neolithization” is somewhat misleading as many of the features we use to define this transition were already well-established patterns of behavior by the Neolithic. Instead, these features and practices were enacted within a hunter-gatherer world and worldview