Excavations at the Lower Palaeolithic Site at Elveden, Suffolk

The Lower Palaeolithic site at Elveden, Suffolk, was the subject of new excavations from 1995–1999. Excavations around the edge and in the centre of the former clay-pit revealed sediments infilling a lake basin that had formed in Lowestoft till, overlying Chalk, the till being attributed to the Anglian glaciation (MIS 12). The lake sediments contain pollen that can be assigned to pollen zones HoI and HoIIa of the early Hoxnian (MIS 11). Overlying grey clays contain ostracods, molluscs, vertebrates, and carbonate concretions. Together they are indicative of a fluvial environment in a temperate climate. AAR ratios (amino acid racemisation) on the molluscs also suggest correlation with MIS 11. Further indications of a fluvial context are indicated by thin spreads of lag gravel along opposite sides of the clay-pit, marking the edges of a channel. The gravel forms the raw material for the human industries which consist of handaxes, flake tools, flakes, and cores. Further artefacts are found in the overlying black clay, which is interpreted as a palaeosol that formed with the silting-up of the channel. The basin was further infilled with colluvial ‘brickearths’, which also contain artefacts that are probably derived from the underlying gravel. Further evidence of soil formation was identified in the ‘brickearth’. Coversands with periglacial involutions overlie the ‘brickearth’ at the top of the sequence. These probably formed in the last cold stage, the Devensian

Engineered carbon-nanomaterial-based electrochemical sensors for biomolecules

The study of electrochemical behavior of bioactive molecules has become one of the most rapidly developing scientific fields. Biotechnology and biomedical engineering fields have a vested interest in constructing more precise and accurate voltammetric/amperometric biosensors. One rapidly growing area of biosensor design involves incorporation of carbon-based nanomaterials in working electrodes, such as one-dimensional carbon nanotubes, two-dimensional graphene, and graphene oxide. In this review article, we give a brief overview describing the voltammetric techniques and how these techniques are applied in biosensing, as well as the details surrounding important biosensing concepts of sensitivity and limits of detection. Building on these important concepts, we show how the sensitivity and limit of detection can be tuned by including carbon-based nanomaterials in the fabrication of biosensors. The sensing of biomolecules including glucose, dopamine, proteins, enzymes, uric acid, DNA, RNA, and H2O2 traditionally employs enzymes in detection; however, these enzymes denature easily, and as such, enzymeless methods are highly desired. Here we draw an important distinction between enzymeless and enzyme-containing carbon-nanomaterial-based biosensors. The review ends with an outlook of future concepts that can be employed in biosensor fabrication, as well as limitations of already proposed materials and how such sensing can be enhanced. As such, this review can act as a roadmap to guide researchers toward concepts that can be employed in the design of next generation biosensors, while also highlighting the current advancements in the field.ope

Biologic TNF-α Inhibitors Reduce Microgliosis, Neuronal Loss, and Tau Phosphorylation in a Transgenic Mouse Model of Tauopathy

Background Tumor necrosis factor-α (TNF-α) plays a central role in Alzheimer’s disease (AD) pathology, making biologic TNF-α inhibitors (TNFIs), including etanercept, viable therapeutics for AD. The protective effects of biologic TNFIs on AD hallmark pathology (Aβ deposition and tau pathology) have been demonstrated. However, the effects of biologic TNFIs on Aβ-independent tau pathology have not been reported. Existing biologic TNFIs do not cross the blood–brain barrier (BBB), therefore we engineered a BBB-penetrating biologic TNFI by fusing the extracellular domain of the type-II human TNF-α receptor (TNFR) to a transferrin receptor antibody (TfRMAb) that ferries the TNFR into the brain via receptor-mediated transcytosis. The present study aimed to investigate the effects of TfRMAb-TNFR (BBB-penetrating TNFI) and etanercept (non-BBB-penetrating TNFI) in the PS19 transgenic mouse model of tauopathy. Methods Six-month-old male and female PS19 mice were injected intraperitoneally with saline (n = 12), TfRMAb-TNFR (1.75 mg/kg, n = 10) or etanercept (0.875 mg/kg, equimolar dose of TNFR, n = 10) 3 days/week for 8 weeks. Age-matched littermate wild-type mice served as additional controls. Blood was collected at baseline and 8 weeks for a complete blood count. Locomotion hyperactivity was assessed by the open-field paradigm. Brains were examined for phosphorylated tau lesions (Ser202, Thr205), microgliosis, and neuronal health. The plasma pharmacokinetics were evaluated following a single intraperitoneal injection of 0.875 mg/kg etanercept or 1.75 mg/kg TfRMAb-TNFR or 1.75 mg/kg chronic TfRMAb-TNFR dosing for 4 weeks. Results Etanercept significantly reduced phosphorylated tau and microgliosis in the PS19 mouse brains of both sexes, while TfRMAb-TNFR significantly reduced these parameters in the female PS19 mice. Both TfRMAb-TNFR and etanercept treatment improved neuronal health by significantly increasing PSD95 expression and attenuating hippocampal neuron loss in the PS19 mice. The locomotion hyperactivity in the male PS19 mice was suppressed by chronic etanercept treatment. Equimolar dosing resulted in eightfold lower plasma exposure of the TfRMAb-TNFR compared with etanercept. The hematological profiles remained largely stable following chronic biologic TNFI dosing except for a significant increase in platelets with etanercept. Conclusion Both TfRMAb-TNFR (BBB-penetrating) and non-BBB-penetrating (etanercept) biologic TNFIs showed therapeutic effects in the PS19 mouse model of tauopathy

Asher Lev at the Israel Museum: Stereotyping art and craft

Jesper Svartvik and Jakob Wirén (Eds.), Religious stereotyping and interreligious relations. New York: Palgrave Macmillan, 2013, reproduced with permission of Palgrave Macmillan. This extract is taken from the author's original manuscript and has not been edited. The definitive, published version of record is available here: http://www.palgrave.com/page/detail/religious-stereotyping-and-interreligious-relations-jesper-svartvik/?K=9781137344601 and http://www.palgraveconnect.com/pc/doifinder/10.1057/978113734267

Four new species of Hydnellum (Thelephorales, Basidiomycota) with a note on Sarcodon illudens

Four new Hydnellum species are described. Hydnellum roseoviolaceum sp. nov. grows in dry pine heaths on acidic, sandy soil. It is close to H. fuligineoviolaceum, another pine-associated species, but differs by smaller spores, an initially rose-coloured instead of violet flesh in fresh basidiomata and a mild taste. Hydnellum scabrosellum sp. nov. grows in coniferous forests on calcareous soil. It shares a general morphology with H. scabrosum, which also is its closest relative. It differs by having smaller and slenderer basidiomata and by the yellowish ochraceous colour of flesh and spines in dried specimens compared to the whitish or reddish brown colour seen in H. scabrosum. Hydnellum fagiscabrosum sp. nov. is another species with morphological and phylogenetic affinities to H. scabrosum. However, it is associated with trees from Fagales whereas H. scabrosum is associated with Pinaceae. Hydnellum nemorosum sp. nov. is yet another species that associates with broadleaved trees. It seems to be a rare species, morphologically reminiscent of H. fuligineoviolaceum, H. ioeides and H. scabrosum, but it is phylogenetically close to H. fennicum . Sequences from the type specimens of H. glaucopus, H. lepidum, H. scabrosum, Sarcodon illudens and S. regalis are included in the analyses. Specimens given the provisional name "Sarcodon pseudoglaucopus" in Sweden are now shown to be referable to S. illudens. The analyses further showed that S. illudens is close to H. lepidum. The new combination Hydnellum illudens is proposed. Sarcodon regalis and H. lepidum are shown to be conspecific and, although their basionyms were simultaneously published, the name S. regalis was only validated in a later publication. Hydnellum lepidum therefore takes priority and S. regalis becomes a synonym

‘Sons of athelings given to the earth’: Infant Mortality within Anglo-Saxon Mortuary Geography

FOR 20 OR MORE YEARS early Anglo-Saxon archaeologists have believed children are underrepresented in the cemetery evidence. They conclude that excavation misses small bones, that previous attitudes to reporting overlook the very young, or that infants and children were buried elsewhere. This is all well and good, but we must be careful of oversimplifying compound social and cultural responses to childhood and infant mortality. Previous approaches have offered methodological quandaries in the face of this under-representation. However, proportionally more infants were placed in large cemeteries and sometimes in specific zones. This trend is statistically significant and is therefore unlikely to result entirely from preservation or excavation problems. Early medieval cemeteries were part of regional mortuary geographies and provided places to stage events that promoted social cohesion across kinship systems extending over tribal territories. This paper argues that patterns in early Anglo-Saxon infant burial were the result of female mobility. Many women probably travelled locally to marry in a union which reinforced existing social networks. For an expectant mother, however, the safest place to give birth was with experience women in her maternal home. Infant identities were affected by personal and legal association with their mother’s parental kindred, so when an infant died in childbirth or months and years later, it was their mother’s identity which dictated burial location. As a result, cemeteries central to tribal identities became places to bury the sons and daughters of a regional tribal aristocracy

Histone arginine methylation regulates pluripotency in the early mouse embryo

It has been generally accepted that the mammalian embryo starts its development with all cells identical, and only when inside and outside cells form do differences between cells first emerge. However, recent findings show that cells in the mouse embryo can differ in their developmental fate and potency as early as the four-cell stage1,2,3,4. These differences depend on the orientation and order of the cleavage divisions that generated them2,5. Because epigenetic marks are suggested to be involved in sustaining pluripotency6,7, we considered that such developmental properties might be achieved through epigenetic mechanisms. Here we show that modification of histone H3, through the methylation of specific arginine residues, is correlated with cell fate and potency. Levels of H3 methylation at specific arginine residues are maximal in four-cell blastomeres that will contribute to the inner cell mass (ICM) and polar trophectoderm and undertake full development when combined together in chimaeras. Arginine methylation of H3 is minimal in cells whose progeny contributes more to the mural trophectoderm and that show compromised development when combined in chimaeras. This suggests that higher levels of H3 arginine methylation predispose blastomeres to contribute to the pluripotent cells of the ICM. We confirm this prediction by overexpressing the H3-specific arginine methyltransferase CARM1 in individual blastomeres and show that this directs their progeny to the ICM and results in a dramatic upregulation of Nanog and Sox2. Thus, our results identify specific histone modifications as the earliest known epigenetic marker contributing to development of ICM and show that manipulation of epigenetic information influences cell fate determination

New Suggestions for the Mechanical Control of Bone Remodeling

Bone is constantly renewed over our lifetime through the process of bone (re)modeling. This process is important for bone to allow it to adapt to its mechanical environment and to repair damage from everyday life. Adaptation is thought to occur through the mechanosensitive response controlling the bone-forming and -resorbing cells. This report shows a way to extract quantitative information about the way remodeling is controlled using computer simulations. Bone resorption and deposition are described as two separate stochastic processes, during which a discrete bone packet is removed or deposited from the bone surface. The responses of the bone-forming and -resorbing cells to local mechanical stimuli are described by phenomenological remodeling rules. Our strategy was to test different remodeling rules and to evaluate the time evolution of the trabecular architecture in comparison to what is known from μ-CT measurements of real bone. In particular, we tested the reaction of virtual bone to standard therapeutic strategies for the prevention of bone deterioration, i.e., physical activity and medications to reduce bone resorption. Insensitivity of the bone volume fraction to reductions in bone resorption was observed in the simulations only for a remodeling rule including an activation barrier for the mechanical stimulus above which bone deposition is switched on. This is in disagreement with the commonly used rules having a so-called lazy zone