Holocene climate records from northern Europe improve our understanding of important North Atlantic ocean and atmospheric circulation systems to long-term insolation-driven changes, as well as more ...rapid forcing and feedback mechanisms. Here we assess Holocene climate and environmental changes in northern Norway based on the analysis of pollen, non-pollen palynomorphs, plant macrofossils, and plant wax biomarkers from a high latitude ombrotrophic bog. We define the extent and thickness of Hollabåttjønnen Bog (0.16 km2), which is located 10 km north of Tromsø. Several cores were analyzed, including a 5.16-m core that spans the last 9.5 cal ka BP. Vegetation changes from several sites were reconstructed and the distribution and hydrogen isotopic composition (δD) of n-alkanes (C21–C33) were analyzed. Our data show several distinct climate intervals that primarily indicate changes in bog surface moisture. In the early Holocene (c. 9.5–7.7 cal ka BP), wetter conditions are defined by the presence of wetland sedges and grasses, higher concentrations of mid-chain length n-alkanes, and a similarity in δD values among homologs. A dry mid-Holocene (c. 7.7–3.8 cal ka BP) is inferred from the presence of a heath shrubland, low peat accumulations rates, and significant differences between δD values of mid- and long-chain length n-alkanes. The late Holocene (c. 3.8 cal ka BP-present) is marked by the onset of wetter conditions, lateral bog expansion, and an increase in sedges and grasses. The Hollabåttjønnen Bog record is also significant because its margins were an important location for human settlement. We correlate early Holocene environmental conditions with changes in Stone Age structures recently excavated, and we identify the occurrence of coprophilous fungi, such as Sporormiella and Sordaria, likely associated with reindeer grazing activity beginning c. 1 cal ka BP. This site therefore provides important regional paleoclimate information as well as context for evaluating local prehistoric human-environment interactions.
Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from ...controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.
Abstract Research into mechanisms of haematogenous metastasis has largely become genetic in focus, attempting to understand the molecular basis of ‘seed–soil’ relationships. Preceding this biological ...mechanism is the physical process of dissemination of circulating tumour cells (CTCs) in the circulation. Patterns of metastatic spread have been previously quantified using the metastatic efficiency index, a measure quantifying metastatic incidence for a given primary-target organ pair and the relative blood flow between them. We extend this concept to take into account the reduction in CTCs which occurs in organ capillary beds connected by a realistic vascular network topology. Application to a dataset of metastatic incidence reveals that metastatic patterns depend strongly on assumptions about the existence and location of micrometastatic disease which governs CTC dynamics on the network, something which has heretofore not been considered – an oversight which precludes our ability to predict metastatic patterns in individual patients.
Historical ecology is becoming an important focus in conservation biology and offers a promising tool to help guide ecosystem management. Here, we integrate data from multiple disciplines to ...illuminate the past, present, and future of biodiversity on California’s Channel Islands, an archipelago that has undergone a wide range of land-use and ecological changes. Our analysis spans approximately 20,000 years, from before human occupation and through Native American hunter–gatherers, commercial ranchers and fishers, the US military, and other land managers. We demonstrate how long-term, interdisciplinary research provides insight into conservation decisions, such as setting ecosystem restoration goals, preserving rare and endemic taxa, and reducing the impacts of climate change on natural and cultural resources. We illustrate the importance of historical perspectives for understanding modern patterns and ecological change and present an approach that can be applied generally in conservation management planning.
Tumours are made up of a mixed population of different types of cells that include normal structures as well as ones associated with the malignancy, and there are multiple interactions between the ...malignant cells and the local microenvironment. These intercellular interactions, modulated by the microenvironment, effect tumour progression and represent a largely under-appreciated therapeutic target. We use observations of primary tumour biology from prostate cancer to extrapolate a mathematical model. Specifically, it has been observed that in prostate cancer three disparate cellular outcomes predominate: (i) the tumour remains well differentiated and clinically indolent--in this case the local stromal cells may act to restrain the growth of the cancer; (ii) early in its genesis the tumour acquires a highly malignant phenotype, growing rapidly and displacing the original stromal population (often referred to as small cell prostate cancer)--these less common aggressive tumours are relatively independent of the local microenvironment and (iii) the tumour co-opts the local stroma--taking on a classic stromagenic phenotype where interactions with the local microenvironment are critical to the cancer growth.
We present an evolutionary game theoretical construct that models the influence of tumour-stroma interactions in driving these outcomes. We consider three characteristic and distinct cellular populations: stromal cells, tumour cells that are self-reliant in terms of microenvironmental factors and tumour cells that depend on the environment for resources, but can also co-opt stroma.
Using evolutionary game theory we explore a number of different scenarios that elucidate the impact of tumour-stromal interactions on the dynamics of prostate cancer growth and progression, and how different treatments in the metastatic setting can affect different types of tumours.
The tumour microenvironment has a crucial role in selecting the traits of the tumour cells that will determine prostate cancer progression. Equally important treatments like hormone therapy affect the selection of these cancer phenotypes making it very important to understand how they impact prostate cancer's somatic evolution.
The only therapies currently available for cutaneous neurofibromas (cNF) are procedural. The goals of the Therapies Development Working Group were to (1) summarize currently available treatment ...options for cNF, (2) define key considerations for drug discovery and development generally, and specifically for cNF, and (3) outline recommendations for the successful development of medical therapies for cNF.
The subgroup reviewed published and unpublished data on procedural, drug/device, and medical treatment approaches utilized for cNFs via literature search. The team defined disease- and patient-specific factors to consider for therapies development in a series of consensus meetings.
The team identified 5 approaches entailing procedural and drug/device methods currently under study. There have been 4 clinical studies exploring various interventional therapies, from which outcomes were highly variable. The team identified 4 key factors to prioritize during the development of products for the treatment for cNF: safety, anatomic distribution of cNF, numbers of tumors to be treated, and route of administration.
The number, size, and distribution of cNF is highly variable among patients with NF1 and it is possible that different phenotypes will require different drug development paths. The nonfatal nature of the disease and relatively limited patient numbers suggest that for any product to have a higher likelihood of acceptance, it will have to (1) demonstrate an effect that is clinically meaningful, (2) have a safety profile conducive to long-term dosing, and (3) have a low manufacturing cost.
The Sierra Nevada of southern Spain is a landscape with a rich biological and cultural heritage. The range was extensively glaciated during the late Pleistocene. However, the postglacial ...paleoecologic history of the highest range in southern Europe is nearly completely unknown. Here we use sediments from a small lake above present treeline – Laguna de Río Seco at 3020 m elevation – in a paleoecological study documenting over 11,500 calendar years of vegetation, fire and climate change, addressing ecological and paleoclimatic issues unique to this area through comparison with regional paleoecological sequences. The early record is dominated by
Pinus pollen, with
Betula, deciduous
Quercus, and grasses, with an understory of shrubs. It is unlikely that pine trees grew around the lake, and fire was relatively unimportant at this site during this period. Aquatic microfossils indicate that the wettest conditions and highest lake levels at Laguna de Río Seco occurred before 7800 cal yr BP. This is in contrast to lower elevation sites, where wettest conditions occurred after ca 7800. Greater differences in early Holocene seasonal insolation may have translated to greater snowpack and subsequently higher lake levels at higher elevations, but not necessarily at lower elevations, where higher evaporation rates prevailed. With declining seasonality after ca 8000 cal yr BP, but continuing summer precipitation, lake levels at the highest elevation site remained high, but lake levels at lower elevation sites increased as evaporation rates declined. Drier conditions commenced regionally after ca 5700 cal yr BP, shown at Laguna de Río Seco by declines in wetland pollen, and increases in high elevation steppe shrubs common today (
Juniperus,
Artemisia, and others). The disappearance or decline of mesophytes, such as
Betula from ca 4000 cal yr BP is part of a regional depletion in Mediterranean Spain and elsewhere in Europe from the mid to late Holocene. On the other hand,
Castanea sativa increased in Laguna de Río Seco record after ca 4000 cal yr BP, and especially in post-Roman times, probably due to arboriculture. Though not as important at high than at low elevations, fire occurrence was elevated, particularly after ca 3700 years ago, in response to regional human population expansion. The local and regional impact of humans increased substantially after ca 2700 years ago, with the loss of
Pinus forest within the mountain range, increases in evidence of pasturing herbivores around the lake, and
Olea cultivation at lower elevations. Though human impact was not as extensive at high elevation as at lower elevation sites in southern Iberia, this record confirms that even remote sites were not free of direct human influence during the Holocene.
► We investigate high elevation vegetation change through time in southern Spain. ► Laguna de Río Seco documents regional environmental change for southern Spain. ► The early Holocene monsoonal climate ended earlier here than at lower elevations. ► Late Holocene human impact may have been limited to grazing around the lake. ► Record shows even remote sites were not free of human influence during the Holocene.
PDF
