Human Dental Microwear From Ohalo II (22,500–23,500 cal BP), Southern Levant

Dietary hardness and abrasiveness are inferred from human dental microwear at Ohalo II, a late Upper Palaeolithic site (22,500–23,500 cal BP) in the southern Levant. Casts of molar grinding facets from two human skeletons were examined with a scanning electron microscope. The size and frequency of microwear was measured, counted, and compared to four prehistoric human groups from successive chronological periods in the same region: pre-pottery Neolithic A, Chalcolithic (this study); Natufian, pre-pottery Neolithic B (Mahoney: Am J Phys Anthropol 130 (2006) 308–319). The Ohalo molars had a high frequency of long narrow scratches, and a few small pits, suggesting a tough abrasive diet that required more shearing rather than compressive force while chewing. These results imply that the diet of the two late Upper Palaeolithic hunter-gatherers did not focus on very hard foods. Aquatic foods with adherent contaminants, as well as grit from plant grinding tools seemed likely causal agents. The size of the pits and scratches on the Ohalo molars were most similar to microwear from the pre-pot- tery Neolithic A period, though they also compared well to the Chalcolithic period. These results contrasted with the larger pits and scratches from the Natufian hunter-gath- erers and pre-pottery Neolithic B farmers, implying that there is no simple increase or decrease in dietary hard- ness and abrasiveness across the late Upper Palaeolithic to Chalcolithic development in the Southern Levant

Metabolic networking in Brunfelsia calycina petals after flower opening

Brunfelsia calycina flowers change colour from purple to white due to anthocyanin degradation, parallel to an increase in fragrance and petal size. Here it was tested whether the production of the fragrant benzenoids is dependent on induction of the shikimate pathway, or if they are formed from the anthocyanin degradation products. An extensive characterization of the events taking place in Brunfelsia flowers is presented. Anthocyanin characterization was performed using ultraperfomance liquid chromatography–quadrupole time of flight–tandem mass specrometry (UPLC-QTOF-MS/MS). Volatiles emitted were identified by headspace solid phase microextraction–gas chromatography–mass spectrometry (HS-SPME-GC-MS). Accumulated proteins were identified by 2D gel electrophoresis. Transcription profiles were characterized by cross-species hybridization of Brunfelsia cDNAs to potato cDNA microarrays. Identification of accumulated metabolites was performed by UPLC-QTOF-MS non-targeted metabolite analysis. The results include characterization of the nine main anthocyanins in Brunfelsia flowers. In addition, 146 up-regulated genes, 19 volatiles, seven proteins, and 17 metabolites that increased during anthocyanin degradation were identified. A multilevel analysis suggests induction of the shikimate pathway. This pathway is the most probable source of the phenolic acids, which in turn are precursors of both the benzenoid and lignin production pathways. The knowledge obtained is valuable for future studies on degradation of anthocyanins, formation of volatiles, and the network of secondary metabolism in Brunfelsia and related species

Hominin reactions to herbivore distribution in the Lower Palaeolithic of the Southern Levant

We explore the relationship between the edaphic potential of soils and the mineral properties of the underlying geology as a means of mapping the differential productivity of different areas of the Pleistocene landscape for large herbivores. These factors strongly control the health of grazing animals irrespective of the particular types of vegetation growing on them, but they have generally been neglected in palaeoanthropological studies in favour of a more general emphasis on water and vegetation, which provide an incomplete picture. Taking the Carmel-Galilee-Golan region as an example, we show how an understanding of edaphic potential provides insight into how animals might have exploited the environment. In order to simplify the analysis, we concentrate on the Lower Palaeolithic period and the very large animals that dominate the archaeofaunal assemblages of this period. Topography and the ability of soils to retain water also contribute to the differential productivity and accessibility of different regions and to patterns of seasonal movements of the animals, which are essential to ensure a supply of healthy fodder throughout the year, especially for large animals such as elephants, which require substantial regions of good grazing and browsing. Other animals migrating in groups have similar needs. The complex topography of the Southern Levant with frequent sudden and severe changes in gradient, and a wide variety of landforms including rocky outcrops, cliffs, gorges, and ridges, places major limits on these patterns of seasonal movements. We develop methods of mapping these variables, based on the geology and our substantial field experience, in order to create a framework of landscape variation that can be compared with the locations and contents of archaeological sites to suggest ways in which early hominins used the variable features of the landscape to target animal prey, and we extend the analysis to the consideration of smaller mammals that were exploited more intensively after the disappearance of the elephants. We consider some of the ways in which this regional-scale approach can be further tested and refined, and advocate the development of such studies as an essential contribution to understanding the wider pattern of hominin dispersal

A clinical evaluation of an ex vivo organ culture system to predict patient response to cancer therapy

IntroductionEx vivo organ cultures (EVOC) were recently optimized to sustain cancer tissue for 5 days with its complete microenvironment. We examined the ability of an EVOC platform to predict patient response to cancer therapy.MethodsA multicenter, prospective, single-arm observational trial. Samples were obtained from patients with newly diagnosed bladder cancer who underwent transurethral resection of bladder tumor and from core needle biopsies of patients with metastatic cancer. The tumors were cut into 250 μM slices and cultured within 24 h, then incubated for 96 h with vehicle or intended to treat drug. The cultures were then fixed and stained to analyze their morphology and cell viability. Each EVOC was given a score based on cell viability, level of damage, and Ki67 proliferation, and the scores were correlated with the patients’ clinical response assessed by pathology or Response Evaluation Criteria in Solid Tumors (RECIST).ResultsThe cancer tissue and microenvironment, including endothelial and immune cells, were preserved at high viability with continued cell division for 5 days, demonstrating active cell signaling dynamics. A total of 34 cancer samples were tested by the platform and were correlated with clinical results. A higher EVOC score was correlated with better clinical response. The EVOC system showed a predictive specificity of 77.7% (7/9, 95% CI 0.4–0.97) and a sensitivity of 96% (24/25, 95% CI 0.80–0.99).ConclusionEVOC cultured for 5 days showed high sensitivity and specificity for predicting clinical response to therapy among patients with muscle-invasive bladder cancer and other solid tumors

A Historiometric Examination of Machiavellianism and a New Taxonomy of Leadership

Although researchers have extensively examined the relationship between charismatic leadership and Machiavellianism (Deluga, 2001; Gardner & Avolio, 1995; House & Howell, 1992), there has been a lack of investigation of Machiavellianism in relation to alternative forms of outstanding leadership. Thus, the purpose of this investigation was to examine the relationship between Machiavellianism and a new taxonomy of outstanding leadership comprised of charismatic, ideological, and pragmatic leaders. Using an historiometric approach, raters assessed Machiavellianism via the communications of 120 outstanding leaders in organizations across the domains of business, political, military, and religious institutions. Academic biographies were used to assess twelve general performance measures as well as twelve general controls and five communication specific controls. The results indicated that differing levels of Machiavellianism is evidenced across the differing leader types as well as differing leader orientation. Additionally, Machiavellianism appears negatively related to performance, though less so when type and orientation are taken into account.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

A Spatial Distribution Study of Faunal Remains from Two Lower Magdalenian Occupation Levels in El Mirón Cave, Cantabria, Spain

Abstract: Human behaviour can be reconstructed by analysing specific activities and campsite organization using spatial analysis. The dense occupation layers of the Lower Cantabrian Magdalenian in the Northern Spain reveal varied aspects of Upper Palaeolithic lifeways, including evidence of specific localized activities. The outer vestibule of El Mirón cave has a particularly rich and intact Lower Magdalenian occupation horizon, Levels 15–17. The excavations in the outer vestibule “Cabin” area of the site revealed excellent bone preservation. Artefacts and faunal remains were individually recorded and sediments water-screened to yield a large sample of archaeological finds and spatial data. Zooarchaeological analysis provided the taxonomic, anatomic and taphonomic determination of the faunal individual finds. Smaller animal remains were categorized and counted; special attention was given to the identification of anthropogenic modifications such as burnt bones or bone flakes. These small refuse items are considered to be useful, in situ indicators of localized activities. The spatial distribution analysis of this dense and complex palimpsest of El Mirón Lower Cantabrian Magdalenian layers required GIS based methods including density analysis, heatmaps and cluster analysis. Based on the spatial distribution of Level 15 and 16 faunal remains, different activity areas were identified comprising hearth, working and dropping zones. These results imply the deliberately segregated use of space within the Lower Cantabrian Magdalenian site area, in which bone-processing activities played a central rol

Monoaminergic and histaminergic strategies and treatments in brain diseases

The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems. Later, some dramatic side effects associated with older medicines were shown to disappear with new chemical compounds targeting the origin of the therapeutic benefit more specifically. The increased knowledge regarding the function and interaction of the monoaminergic systems in the brain resulting from in vivo neurochemical and neurophysiological studies indicated new monoaminergic targets that could achieve the efficacy of the older medicines with fewer side-effects. Yet, this accumulated knowledge regarding monoamines did not produce valuable strategies for diseases where no monoaminergic drug has been shown to be effective. Here, we emphasize the new therapeutic and monoaminergic-based strategies for the treatment of psychiatric diseases. We will consider three main groups of diseases, based on the evidence of monoamines involvement (schizophrenia, depression, obesity), the identification of monoamines in the diseases processes (Parkinson's disease, addiction) and the prospect of the involvement of monoaminergic mechanisms (epilepsy, Alzheimer's disease, stroke). In most cases, the clinically available monoaminergic drugs induce widespread modifications of amine tone or excitability through neurobiological networks and exemplify the overlap between therapeutic approaches to psychiatric and neurological conditions. More recent developments that have resulted in improved drug specificity and responses will be discussed in this review.peer-reviewe

Late Quaternary sea-level change and early human societies in the central and eastern Mediterranean Basin : an interdisciplinary review

This article reviews key data and debates focused on relative sea-level changes since the Last Interglacial (approximately the last 132,000 years) in the Mediterranean Basin, and their implications for past human populations. Geological and geomorphological landscape studies are critical to archaeology. Coastal regions provide a wide range of resources to the populations that inhabit them. Coastal landscapes are increasingly the focus of scholarly discussions from the earliest exploitation of littoral resources and early hominin cognition, to the inundation of the earliest permanently settled fishing villages and eventually, formative centres of urbanisation. In the Mediterranean, these would become hubs of maritime transportation that gave rise to the roots of modern seaborne trade. As such, this article represents an original review of both the geo-scientific and archaeological data that specifically relate to sea-level changes and resulting impacts on both physical and cultural landscapes from the Palaeolithic until the emergence of the Classical periods. Our review highlights that the interdisciplinary links between coastal archaeology, geomorphology and sea-level changes are important to explain environmental impacts on coastal human societies and human migration. We review geological indicators of sea level and outline how archaeological features are commonly used as proxies for measuring past sea levels, both gradual changes and catastrophic events. We argue that coastal archaeologists should, as a part of their analyses, incorporate important sea-level concepts, such as indicative meaning. The interpretation of the indicative meaning of Roman fishtanks, for example, plays a critical role in reconstructions of late Holocene Mediterranean sea levels. We identify avenues for future work, which include the consideration of glacial isostatic adjustment (GIA) in addition to coastal tectonics to explain vertical movements of coastlines, more research on Palaeolithic island colonisation, broadening of Palaeolithic studies to include materials from the entire coastal landscape and not just coastal resources, a focus on rescue of archaeological sites under threat by coastal change, and expansion of underwater archaeological explorations in combination with submarine geomorphology. This article presents a collaborative synthesis of data, some of which have been collected and analysed by the authors, as the MEDFLOOD (MEDiterranean sea-level change and projection for future FLOODing) community, and highlights key sites, data, concepts and ongoing debates