Linking modern pollen accumulation rates to biomass: Quantitative vegetation reconstruction in the western Klamath Mountains, NW California, USA

Quantitative reconstructions of vegetation abundance from sediment-derived pollen systems provide unique insights into past ecological conditions. Recently, the use of pollen accumulation rates (PAR, grains cm−2 year−1) has shown promise as a bioproxy for plant abundance. However, successfully reconstructing region-specific vegetation dynamics using PAR requires that accurate assessments of pollen deposition processes be quantitatively linked to spatially-explicit measures of plant abundance. Our study addressed these methodological challenges. Modern PAR and vegetation data were obtained from seven lakes in the western Klamath Mountains, California. To determine how to best calibrate our PAR-biomass model, we first calculated the spatial area of vegetation where vegetation composition and patterning is recorded by changes in the pollen signal using two metrics. These metrics were an assemblage-level relevant source area of pollen (aRSAP) derived from extended R-value analysis (sensu Sugita, 1993) and a taxon-specific relevant source area of pollen (tRSAP) derived from PAR regression (sensu Jackson, 1990). To the best of our knowledge, aRSAP and tRSAP have not been directly compared. We found that the tRSAP estimated a smaller area for some taxa (e.g. a circular area with a 225 m radius for Pinus) than the aRSAP (a circular area with a 625 m radius). We fit linear models to relate PAR values from modern lake sediments with empirical, distance-weighted estimates of aboveground live biomass (AGLdw) for both the aRSAP and tRSAP distances. In both cases, we found that the PARs of major tree taxa – Pseudotsuga, Pinus, Notholithocarpus, and TCT (Taxodiaceae, Cupressaceae, and Taxaceae families) – were statistically significant and reasonably precise estimators of contemporary AGLdw. However, predictions weighted by the distance defined by aRSAP tended to be more precise. The relative root-mean squared error for the aRSAP biomass estimates was 9% compared to 12% for tRSAP. Our results demonstrate that calibrated PAR-biomass relationships provide a robust method to infer changes in past plant biomass

Patterns of Suicidal Ideation and Behavior in Northern Ireland and Associations with Conflict Related Trauma

In this study, data from the World Mental Health Survey's Northern Ireland (NI) Study of Health and Stress (NISHS) was used to assess the associations between conflict- and non-conflict-related traumatic events and suicidal behaviour, controlling for age and gender and the effects of mental disorders in NI. DSM mental disorders and suicidal ideation, plans and attempts were assessed using the Composite International Diagnostic Interview (CIDI) in a multi-stage, clustered area probability household sample (N = 4,340, response rate 68.4%). The traumatic event categories were based on event types listed in the PTSD section of the CIDI. Suicidal ideation and attempts were more common in women than men, however, rates of suicide plans were similar for both genders. People with mood, anxiety and substance disorders were significantly more likely than those without to endorse suicidal ideation, plan or attempt. The highest odds ratios for all suicidal behaviors were for people with any mental disorder. However, the odds of seriously considering suicide were significantly higher for people with conflict and non-conflict-related traumatic events compared with people who had not experienced a traumatic event. The odds of having a suicide plan remain significantly higher for people with conflict-related traumatic events compared to those with only non-conflict-related events and no traumatic events. Finally, the odds of suicide attempt were significantly higher for people who have only non-conflict-related traumatic events compared with the other two categories. The results suggest that traumatic events associated with the NI conflict may be associated with suicidal ideation and plans, and this effect appears to be in addition to that explained by the presence of mental disorders. The reduced rates of suicide attempts among people who have had a conflict-related traumatic event may reflect a higher rate of single, fatal suicide attempts in this population

Lateglacial and early Holocene climates of the Atlantic margins of Europe: Stable isotope, mollusc and pollen records from Orkney, Scotland

The margins of mainland Europe, and especially those areas coming under the influence of North Atlantic weather systems, are ideally placed to record changing palaeoclimates. Cores from an infilled lake basin at Crudale Meadow in Mainland, Orkney, revealed basal deposits of calcareous mud (‘marl’) beneath sedge peat. Stable isotope, palynological and molluscan analyses allowed the establishment of palaeoenvironmental changes through the Devensian Lateglacial and the early Holocene. The δ18Omarl record exhibited the existence of possibly four climatic oscillations in the Lateglacial (one of which, within event cf. GI-1c, is not often commented upon), as well as the Preboreal Oscillation and other Holocene perturbations. The cold episodes succeeding the Preboreal Oscillation were demarcated conservatively and one of these (event C5, ∼11.0 ka) may have previously been unremarked, while the putative 9.3 and 8.2 ka events seem not to produce corresponding palynologically visible floristic changes. The events at Crudale Meadow are consistent with those recorded at other sites from Britain, Ireland and elsewhere, and can be correlated with isotopic changes shown by the Greenland ice cores. The multi-proxy approach enriches the environmental reconstructions from the site, although the synchronicity of the response of the various proxies is sometimes equivocal, depending upon the time period concerned, taphonomy, and the nature of the deposits. The site may contain the most northerly Lateglacial isotope record from northwest Europe, and it has yielded one of the best archives for the demonstration of abrupt early Holocene events within Britain

The Armadillo Repeat Protein PF16 Is Essential for Flagellar Structure and Function in Plasmodium Male Gametes

Malaria, caused by the apicomplexan parasite Plasmodium, threatens 40% of the world\u27s population. Transmission between vertebrate and insect hosts depends on the sexual stages of the life-cycle. The male gamete of Plasmodium parasite is the only developmental stage that possesses a flagellum. Very little is known about the identity or function of proteins in the parasite\u27s flagellar biology. Here, we characterise a Plasmodium PF16 homologue using reverse genetics in the mouse malaria parasite Plasmodium berghei. PF16 is a conserved Armadillo-repeat protein that regulates flagellar structure and motility in organisms as diverse as green algae and mice. We show that P. berghei PF16 is expressed in the male gamete flagellum, where it plays a crucial role maintaining the correct microtubule structure in the central apparatus of the axoneme as studied by electron microscopy. Disruption of the PF16 gene results in abnormal flagellar movement and reduced fertility, but does not lead to complete sterility, unlike pf16 mutations in other organisms. Using homology modelling, bioinformatics analysis and complementation studies in Chlamydomonas, we show that some regions of the PF16 protein are highly conserved across all eukaryotes, whereas other regions may have species-specific functions. PF16 is the first ARM-repeat protein characterised in the malaria parasite genus Plasmodium and this study opens up a novel model for analysis of Plasmodium flagellar biology that may provide unique insights into an ancient organelle and suggest novel intervention strategies to control the malaria parasite

Land management explains major trends in forest structure and composition over the last millennium in California's Klamath Mountains

For millennia, forest ecosystems in California have been shaped by fire from both natural processes and Indigenous land management, but the notion of climatic variation as a primary controller of the pre-colonial landscape remains pervasive. Understanding the relative influence of climate and Indigenous burning on the fire regime is key because contemporary forest policy and management are informed by historical baselines. This need is particularly acute in California, where 20th-century fire suppression, coupled with a warming climate, has caused forest densification and increasingly large wildfires that threaten forest ecosystem integrity and management of the forests as part of climate mitigation efforts. We examine climatic versus anthropogenic influence on forest conditions over 3 millennia in the western Klamath Mountains—the ancestral territories of the Karuk and Yurok Tribes—by combining paleoenvironmental data with Western and Indigenous knowledge. A fire regime consisting of tribal burning practices and lightning were associated with long-term stability of forest biomass. Before Euro-American colonization, the long-term median forest biomass was between 104 and 128 Mg/ha, compared to values over 250 Mg/ha today. Indigenous depopulation after AD 1800, coupled with 20th-century fire suppression, likely allowed biomass to increase, culminating in the current landscape: a closed Douglas fir–dominant forest unlike any seen in the preceding 3,000 y. These findings are consistent with precontact forest conditions being influenced by Indigenous land management and suggest large-scale interventions could be needed to return to historic forest biomass levels

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Gender and contemporary risk of adverse events in atrial fibrillation

Background and Aims: The role of gender in decision-making for oral anticoagulation in patients with atrial fibrillation (AF) remains controversial.Methods: Population cohort study using electronic healthcare records of 16,587,749 patients from UK primary care (2005-2020). Primary (composite of all-cause mortality, ischaemic stroke or arterial thromboembolism) and secondary outcomes were analysed using Cox hazard ratios (HR), adjusted for age, socioeconomic status and comorbidities.Results: 78,852 patients were included with AF, age 40-75 years, no prior stroke and no prescription of oral anticoagulants. 28,590 (36.3%) were women and 50,262 (63.7%) men. Median age was 65.7 years (interquartile range 58.5-70.9) with women being older and other differences in comorbidities. During total follow-up of 431,086 patient-years, women had a lower adjusted primary outcome rate with HR 0.89 vs men (95% CI 0.87-0.92; p&lt;0.001), and HR 0.87 after censoring for oral anticoagulation (95% CI 0.83-0.91; p&lt;0.001). This was driven by lower mortality in women (HR 0.86, 0.83-0.89; p&lt;0.001). No difference was identified between women and men for the secondary outcomes of ischaemic stroke or arterial thromboembolism (adjusted HR 1.00, 0.94-1.07; p=0.87), any stroke or any thromboembolism (1.02, 0.96-1.07; p=0.58), and incident vascular dementia (1.13, 0.97-1.32; p=0.11). Clinical risk scores were only modest predictors of outcomes, with CHA2DS2-VA (ignoring gender) superior to CHA2DS2-VASc for primary outcomes in this population (receiver operator curve area 0.651 vs 0.639; p&lt;0.001), and no interaction with gender (p=0.45).Conclusions: Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation.  <br/

Identification of 6-Benzylthioinosine as a Myeloid Leukemia Differentiation-Inducing Compound

As the pathophysiology of acute myelogenous leukemia (AML) involves a block of myeloid maturation, a desirable therapeutic strategy is to induce leukemic cell maturation to increase the efficacy and to avoid the side effects of traditional chemotherapeutics. Through a compound library screen, 6-benzylthioinosine (6BT) was identified as a promising differentiation-inducing agent. 6BT induces monocytic differentiation of myeloid leukemia cell lines such as HL-60 and OCI-AML3, as well as primary patient samples as evidenced by morphology, immunophenotyping, and nitroblue tetrazolium reduction. Not only can 6BT induce differentiation but a subset of AML cell lines such as MV4-11 and HNT34 instead undergo 6BT-mediated cell death. Despite inducing cell death in some leukemic cells, 6BT exhibits extremely low toxicity on several nonmalignant cells such as fibroblasts, normal bone marrow, and endothelial cells. This toxicity profile may relate to the function of 6BT as an inhibitor of the nucleoside transporter, ent1, which is thought to prevent it from entering many cell types. In contrast, 6BT likely enters at least some leukemic cell lines as shown by its requirement for phosphorylation for its differentiation activity. 6BT is also able to synergize with currently used myeloid differentiation agents such as ATRA and decitabine. Early studies indicate that the mechanism of action of this compound may involve ATP depletion that leads to growth inhibition and subsequent differentiation. Besides in vitro activity, 6BT also shows the ability to impair HL-60 and MV4-11 tumor growth in nude mice. 6BT is a promising new monocytic differentiation agent with apparent leukemic cell–specific activity

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference