Late Würm and Early-Middle Holocene environmental change and human activities in the Northern Apennines, Italy

An enhanced radiocarbon-dated pollen-stratigraphical record from Rovegno (Liguria, 812m asl), northern Apennines (Italy), has provided a history of vegetation succession from before 17,056-16,621 cal yrs BP to the present day. The record indicates the transition from open Pinus woodland to Artemisia dominated grassland, and finally Juniperus shrubland during the late Würm. This is succeeded by Betula and Pinus woodland, and the expansion of thermophilous taxa, namely Abies, Corylus and Quercus during the Late Würm Lateglacial Interstadial. The ‘Younger Dryas’ is possibly represented by an increase in Betula and Artemisia. During the early Holocene, mixed coniferous-deciduous woodland is dominant with Quercus, as well as Abies, Fagus and Corylus. Fagus woodland becomes established sometime before 6488-6318 cal yrs BP, but never becomes a major component of the woodland cover. Throughout the middle Holocene, Abies woodland fl uctuates, with marked declines between 6488-6318 cal yrs BP and 5287-4835 cal yrs BP, although the cause remains uncertain. Finally, the paper evaluates the application of non-pollen palynomorphs, especially coprophilous fungal spores, at Prato Spilla ‘A’ (Emilia Romagna) and concludes that greater caution must be used when interpreting middle Holocene human activity based upon pollen data alone

The lives and deaths of young medieval women: the osteological evidence

Written sources from the medieval period focus mainly on the activities of adults, particularly males and often those from the wealthier sections of society. Recent scholarship has attempted to redress this balance by giving attention to medieval women and children, but we are still limited by what we can learn about the daily lives of all members of medieval English society. Osteology, the study of human skeletal remains, suffers from no such bias and can provide substantial and detailed information on growth, health and daily life of the general population. This paper presents the results of a new analysis of the skeletal remains of over 300 medieval girls and young women aged at between 14 and 25 years from a number of English cemetery sites. We incorporate data from the published archaeological literature as well as documentary evidence to provide new insights into the lives and deaths of young medieval women.

Thin place exhibition

Thin Place is an interdisciplinary project which aims to find connections between the fields of art, archaeology, astrophysics, astrology, alternative therapy, poetry and theology. The nature of this project goes beyond the exhibition and incorporates a symposium, catalogue and education programme which will attempt to dissolve the boundaries that separate fields of knowledge and, in so doing, create a thin place at Oriel Myrddin. The five exhibiting artists and the other contributors to this project have produced work that is concerned with or responds to two particular locations: West Wales and the West of Ireland. In ancient times it was believed that the West was where departed souls easily entered Otherworlds. This is because the delineation between worlds was more permeable along these coasts. Archaeological excavations reveal that West Wales and the West of Ireland were thought by some to be ‘thin places.’ In considering the notion of a ‘thin place’, this exhibition addresses the ways in which we value our relationship with Place, particularly in landscapes where human and non-human relationships are well established.

1,8-cineol potentiates IRF3-mediated antiviral response in human stem cells and an ex vivo model of rhinosinusitis

Common cold is one of the most frequent human inflammatory diseases caused by viruses and can facilitate bacterial super-infections resulting in sinusitis or pneumonia. The active ingredient of the drug Soledum, 1,8-cineole, is commonly applied for treating inflammatory diseases of the respiratory tract. However, the potential of 1,8-cineole for treating primary viral infections of the respiratory tract remains unclear. In the present study, we demonstrate for the first time that 1,8-cineole potentiates Poly(I:C)-induced activity of the anti-viral transcription factor Interferon Regulatory Factor 3, while simultaneously reducing pro-inflammatory NF-κB-activity in human cell lines, inferior turbinate stem cells (ITSCs) and ex vivo cultivated human nasal mucosa. Co-treatment of cell lines with Poly(I:C) and 1,8-cineole resulted in significantly increased IRF3 reporter gene activity compared to Poly(I:C) alone, whereas NF-κB-activity was reduced. Accordingly, 1,8-cineole- and Poly(I:C)-treatment led to increased nuclear translocation of IRF3 in ITSCs and a human ex vivo model of rhinosinusitis compared to the Poly(I:C)-treated approach. Nuclear translocation of IRF3 was significantly increased in ITSCs and slice cultures treated with LPS and 1,8-cineole compared to the LPS-treated cells mimicking bacterial infection. Our findings strongly suggest that 1,8-cineole potentiates the antiviral activity of IRF3 in addition to its inhibitory effect on pro-inflammatory NF-κB-signalling and may thus broaden its field of application.

Paleoamerican Morphology in the Context of European and East Asian Late Pleistocene Variation: Implications for Human Dispersion Into the New World

Early American crania show a different morphological pattern from the one shared by late Native Americans. Although the origin of the diachronic morphological diversity seen on the continents is still debated, the distinct morphology of early Americans is well documented and widely dispersed. This morphology has been described extensively for South America, where larger samples are available. Here we test the hypotheses that the morphology of Early Americans results from retention of the morphological pattern of Late Pleistocene modern humans and that the occupation of the New World precedes the morphological differentiation that gave rise to recent Eurasian and American morphology. We compare Early American samples with European Upper Paleolithic skulls, the East Asian Zhoukoudian Upper Cave specimens and a series of 20 modern human reference crania. Canonical Analysis and Minimum Spanning Tree were used to assess the morphological affinities among the series, while Mantel and Dow-Cheverud tests based on Mahalanobis Squared Distances were used to test different evolutionary scenarios. Our results show strong morphological affinities among the early series irrespective of geographical origin, which together with the matrix analyses results favor the scenario of a late morphological differentiation of modern humans. We conclude that the geographic differentiation of modern human morphology is a late phenomenon that occurred after the initial settlement of the Americas. Am J Phys Anthropol 144:442-453, 2011. (c) 2010 Wiley-Liss, Inc.

Smad5 regulates Akt2 expression and insulin-induced glucose uptake in L6 myotubes

Insulin-induced glucose uptake by skeletal muscle results from Akt2 activation and is severely impaired during insulin resistance Recently, we and others have demonstrated that BMP9 improves glucose homeostasis in diabetic and non-diabetic rodents. However, the mechanism by which BMP9 modulates insulin action remains unknown. Here we demonstrate that Smad5. a transcription factor activated by BMP9, and Akt2. are upregulated in differentiated L6 myotubes. Smad5, rather than Smad1/8, is downregulated ""in vivo"" and ""in vitro"" by dexamethasone Smad5 knockdown decreased Akt2 expression and serine phosphorylation and insulin-induced glucose uptake, and increased the expression of the lipid phosphatase Ship2. Additionally, binding of Smad5 to Akt2 gene is decreased in dexamethasone-treated rats and Increased in L6 myotubes compared to myoblasts The present study indicates that Smad5 regulates glucose uptake in skeletal muscle by controlling Akt2 expression and phosphorylation These finding reveals Smad5 as a potential target for the therapeutic of type 2 diabetes. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Pivotal Role for Platelet-Activating Factor Receptor in CD36 Expression and oxLDL Uptake by Human Monocytes/Macrophages

The uptake of oxLDL by CD36 is not regulated by intracellular levels of cholesterol, leading to macrophage differentiation into foam cells which play a major role in atherosclerosis. Furthermore, oxLDL competes with PAF in macrophages for binding to PAF receptors (PAFR). Here we investigated the involvement of PAFR in CD36 expression and uptake of oxLDL by human monocytes/macrophages. Adherent peripheral blood mononuclear cells were treated with PAFR-antagonists (WEB2170, CV3988); inhibitors of ERK1/2 (PD98059), p38 (SB203580), JNK (SP600125) or diluents, before stimulation with oxLDL or PAF. After 24 h, uptake of FITC oxLDL and expression of CD36 was determined by flow cytometry and phosphorylation of MAP-kinases by Western blot. It was shown that the uptake of oxLDL was reduced by PAFR antagonists. CD36 expression was up-regulated by oxLDL, an effect reversed by PAFR antagonists. The up-regulation of CD36 and oxLDL uptake both required MAP-kinases activation. The oxLDL induced ERK1/2 and JNK but not p38 phosphorylation was reversed by PAFR-antagonists suggesting that oxLDL signalling involves PAFR dependent and independent pathways. In macrophages from PAFR(-/-) mice, oxLDL was unable to up-regulate CD36 expression and the oxLDL uptake was reduced compared to wild type. These results suggest that oxLDL interacts with PAFR in macrophages to increase CD36 expression and oxLDL uptake. Whereas pharmacological intervention at the level of PAFR would be beneficial in atherosclerosis remains to be determined. Copyright (C) 2011 S. Karger AG, Basel

Extensive microsatellite diversity in the human malaria parasite Plasmodium vivax

The population structure of Plasmodium vivax remains elusive. The markers of choice for large-scale population genetic studies of eukaryotes, short tandem repeats known as microsatellites, have been recently reported to be less polymorphic in R vivax. Here we investigate the microsatellite diversity and geographic structure in P vivax, at both local and global levels, using 14 new markers consisting of tri- or tetranucleotide repeats. The local-level analysis, which involved 50 field isolates from Sri Lanka, revealed unexpectedly high diversity (average virtual heterozygosity [H-E], 0.807) and significant multilocus linkage disequilibrium in this region of low malaria endemicity. Multiple-clone infections occurred in 60% of isolates sampled in 2005. The global-level analysis of field isolates or monkey-adapted strains identified 150 unique haplotypes among 164 parasites from four continents. Individual P. vivax isolates could not be unambiguously assigned to geographic populations. For example, we found relatively low divergence among parasites from Central America, Africa, Southeast Asia and Oceania, but substantial differentiation between parasites from the same continent (South Asia and Southeast Asia) or even from the same country (Brazil). Parasite relapses, which may extend the duration of P. vivax carriage in humans, are suggested to facilitate the spread of strains across continents, breaking down any pre-existing geographic structure. (C) 2008 Elsevier B.V. All rights reserved.

The importance of human FcyRI in mediating protection to malaria

The success of passive immunization suggests that antibody-based therapies will be effective at controlling malaria. We describe the development of fully human antibodies specific for Plasmodium falciparum by antibody repertoire cloning from phage display libraries generated from immune Gambian adults. Although these novel reagents bind with strong affinity to malaria parasites, it remains unclear if in vitro assays are predictive of functional immunity in humans, due to the lack of suitable animal models permissive for P. falciparum. A potentially useful solution described herein allows the antimalarial efficacy of human antibodies to be determined using rodent malaria parasites transgenic for P. falciparum antigens in mice also transgenic for human Fc-receptors. These human IgG1s cured animals of an otherwise lethal malaria infection, and protection was crucially dependent on human FcγRI. This important finding documents the capacity of FcγRI to mediate potent antimalaria immunity and supports the development of FcγRI-directed therapy for human malaria.

Intense exercise up-regulates Na+, K+ -ATPase isoform mRNA, but not protein expression in human skeletal muscle

Characterization of expression of, and consequently also the acute exercise effects on, Na+,K+-ATPase isoforms in human skeletal muscle remains incomplete and was therefore investigated. Fifteen healthy subjects (eight males, seven females) performed fatiguing, knee extensor exercise at 40% of their maximal work output per contraction. A vastus lateralis muscle biopsy was taken at rest, fatigue and 3 and 24 h postexercise, and analysed for Na+,K+-ATPase 1, 2, 3, ß1, ß2 and ß3 mRNA and crude homogenate protein expression, using Real-Time RT-PCR and immunoblotting, respectively. Each individual expressed gene transcripts and protein bands for each Na+,K+-ATPase isoform. Each isoform was also expressed in a primary human skeletal muscle cell culture. Intense exercise (352 ± 69 s; mean ±S.E.M.) immediately increased 3 and ß2 mRNA by 2.4- and 1.7-fold, respectively (P < 0.05), whilst 1 and 2 mRNA were increased by 2.5- and 3.5-fold at 24 h and 3 h postexercise, respectively (P < 0.05). No significant change occurred for ß1 and ß3 mRNA, reflecting variable time-dependent responses. When the average postexercise value was contrasted to rest, mRNA increased for 1, 2, 3, ß1, ß2 and ß3 isoforms, by 1.4-, 2.2-, 1.4-, 1.1-, 1.0- and 1.0-fold, respectively (P < 0.05). However, exercise did not alter the protein abundance of the 1–3 and ß1–ß3 isoforms. Thus, human skeletal muscle expresses each of the Na+,K+-ATPase 1, 2, 3, ß1, ß2 and ß3 isoforms, evidenced at both transcription and protein levels. Whilst brief exercise increased Na+,K+-ATPase isoform mRNA expression, there was no effect on isoform protein expression, suggesting that the exercise challenge was insufficient for muscle Na+,K+-ATPase up-regulation.

Human Sulfotransferases and Their Role in Chemical Metabolism

Sulfonation is an important reaction in the metabolism of numerous xenobiotics, drugs, and endogenous compounds. A supergene family of enzymes called sulfotransferases (SULTs) catalyze this reaction. In most cases, the addition of a sulfonate moiety to a compound increases its water solubility and decreases its biological activity. However, many of these enzymes are also capable of bioactivating procarcinogens to reactive electrophiles. In humans three SULT families, SULT1, SULT2, and SULT4, have been identified that contain at least thirteen distinct members. SULTs have a wide tissue distribution and act as a major detoxification enzyme system in adult and the developing human fetus. Nine crystal structures of human cytosolic SULTs have now been determined, and together with site-directed mutagenesis experiments and molecular modeling, we are now beginning to understand the factors that govern distinct but overlapping substrate specificities. These studies have also provided insight into the enzyme kinetics and inhibition characteristics of these enzymes. The regulation of human SULTs remains as one of the least explored areas of research in the field, though there have been some
recent advances on the molecular transcription mechanism controlling the individual SULT promoters. Interindividual variation in sulfonation capacity may be important in determining an individual’s response to xenobiotics, and recent studies have begun to suggest roles for SULT polymorphism in disease susceptibility. This review aims to provide a summary of our present understanding of the function of human cytosolic sulfotransferases.

Valuing local built heritage in a global setting : identity & visual perceptions of cultural built heritage in Northern Ireland

‘In these troubled times with the world in search of its bearings and way ward minds using the terms “culture” and “civilization” in an attempt to turn human beings against one another, there is an urgent need to remember how fundamental cultural diversity is to humanity itself’ (UNESCO 2002). The progressive idea of culture can be used in regressive ways by extremists who used it occasionally to pursue the politics of xenophobia and exclusion. The hypothesis that different communities can share the same culture but have different visual perception of their built environment might seems contradictory. It is essential to describe what is meant by the ‘same culture’. The ever evolving changes of definition and re-definition of the word has not yet settled. This paper adopts the descriptive definition of culture while challenging its interpretation. The descriptive definition refers to ‘all the characteristics activities by a people’. While this description is generally accepted, the interpretation of what ‘a people’ means is divisive. It is not clear how Eliot defines ‘a people’. Is the term genetically prescribed or is ‘a people’ place related? And what about the moral and religious orientation? This paper argues that culture is basically place related and the forces that shape a culture of a ‘people’ are deeply embedded in the environmental forces that also shape other aspects of the place making and its identity. The paper addresses the questions of conflicts, value systems, and culture definitions and the inseparable links with architecture aesthetics.

Local built heritage in Northern Ireland is taken as a case study. Unlike many parts of the world, visual perceptions in Northern Ireland is well recognised with iconic as well as formal representations. The population is well aware of the signified as well as the signifiers. The boundaries between iconology and formalism theories are very blurred in the Northern Ireland context. This paper examines how the two communities visually perceive their shared built heritage and the extent of overlapping between the understanding of iconic and formalist visual representations in the built environment. The paper takes the buildings of the successful economic ventures of the shirt industry in the 19th century as a case study. The case study provides an insight of how a signified value of a successful economic regeneration initiative that is deeply imbedded in the social structure and within the urban fabric can overcome divisive visual perception. The paper examines the possibility of building upon the historical success of the shirt industry to promote architectural cultural dialogue in which cultural built heritage in Derry is able to facilitate knowledge creation and social capital in different arenas.

Piecing together the puzzle of graduate employment : factors that shape the graduate work expectations of human resource management students

Providing graduates with a set of skills and attributes relevant to their future employment remains a key topic in both higher education policy and research. This paper reports findings from a pilot study of human resource management (HRM) students' perceptions of the graduate work experience. Specifically, it focuses on how these perceptions are shaped, driven by a concern for the uncertainty - and even fear - expressed by the study's participants in relation to their future workplace experiences. The influences of three key factors in shaping participants' expectations are discussed: the graduate recruitment experience, previous work experiences and 'graduate work folklore' from the stories of family and friends. With these influences not always providing students with a realistic picture of their future work experience, we conclude that educators need to improve the opportunities for practical experience and industry knowledge through work placements, stronger links with industry and increased exposure to the practicalities of work within the curriculum.

Research on human embryos and cloning : difficulties of legislating in a changing environment and model approaches to regulation

It is difficult to regulate rapidly changing fields of science. New technologies are not anticipated and legislation becomes inadequate. Legislative definitions are also problematic. This article begins with consideration of such difficulties in the context of research on human embryos and cloning. It considers problems with past legislative definitions in Australia, the new regulatory regime, and whether that regime now sets clear boundaries. It is found that problems still exist – some terms are not adequately defined and boundaries for research prove unclear. Three regulatory approaches are therefore discussed. Legislation based on strict definitions is compared to a legislative model that leaves terms undefined. The third model – which combines framework legislation with the oversight of a regulatory authority – is seen as most suitable. However, problems with this model are recognised and suggestions made regarding how to ensure the “framework” remains workable and effective.