Acid treatment biasing to C/N, δ13C and δ15N of organic matter: A Molecular insight

(DIPPI-C) - Development of Isotopic Proxies for Palaeoenvironmental Interpretation: a Carbon PerspectiveIt is known that acid treatment methods employed to remove inorganic carbon (IC) from sample material prior to analysis for C/N, δ13C and δ15N cause non-linear, unpredictable biasing to the organic matter (OM) fraction. Consequently, measured C/N, δ13C and δ15N have an uncertainty much greater than instrument precision: uncertainties for C/N are reported in the range of 1 – 100, for δ13C in the range of 0.2 – 6.8 ‰ and for δ15N in the range of 0.2 – 1.5 ‰, in both modern and palaeo environmental materials. Brodie et al (2011) extended this investigation to a down-core lake sedimentary archive (Lake Tianyang, South China) and noted the potential for uncertainties to preclude “common” interpretations of the data (e.g., C/N values a s a n OM p rovenance tool; δ 13C as a proxy for changes in C3 and C4 vegetation). It is evident that the size of uncertainty between sample horizons varies considerably implying a differential relative reaction to acid treatment down-core (i.e., as the type, relative amount and physical state of organic and inorganic components change). We are now investigating this biasing at the molecular level by employing 13C-NMR and GCIRMS techniques on a suite of modern and palaeo environmental materials and on a lake sedimentary archive. This will provide an important insight into the effect of acid treatment on organic compounds (i.e. removal from the sample, breakdown of compounds and partial removal) and associated isotopic fractionation. From an improved understanding of the type of compounds most susceptible to alteration/removal during the acid treatment processes it will be possible to consider refinements to the acid pre-treatment process and provide information on the relative down-core changes in those compounds susceptible to change (which we may be able to glean environmental information from).postprintThe 1st DIPPI-C Workshop, Durham, UK., 8-10 May 2012. In Abstract Bok of the 1st DIPPI-C Workshop, 2012, p. 1

Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal dominant Parkinson disease (PD), while polymorphic LRRK2 variants are associated with sporadic PD. PD-linked mutations increase LRRK2 kinase activity and induce neurotoxicity in vitro and in vivo. The small GTPase Rab8a is a LRRK2 kinase substrate and is involved in receptor-mediated recycling and endocytic trafficking of transferrin, but the effect of PD-linked LRRK2 mutations on the function of Rab8a is poorly understood. Here, we show that gain-of-function mutations in LRRK2 induce sequestration of endogenous Rab8a to lysosomes in overexpression cell models, while pharmacological inhibition of LRRK2 kinase activity reverses this phenotype. Furthermore, we show that LRRK2 mutations drive association of endocytosed transferrin with Rab8a-positive lysosomes. LRRK2 has been nominated as an integral part of cellular responses downstream of proinflammatory signals and is activated in microglia in postmortem PD tissue. Here, we show that iPSC-derived microglia from patients carrying the most common LRRK2 mutation, G2019S, mistraffic transferrin to lysosomes proximal to the nucleus in proinflammatory conditions. Furthermore, G2019S knock-in mice show a significant increase in iron deposition in microglia following intrastriatal LPS injection compared to wild-type mice, accompanied by striatal accumulation of ferritin. Our data support a role of LRRK2 in modulating iron uptake and storage in response to proinflammatory stimuli in microglia

Oxygen isotopes in tree rings show good coherence between species and sites in Bolivia

A tree ring oxygen isotope (δ18OTR) chronology developed from one species (Cedrela odorata) growing in a single site has been shown to be a sensitive proxy for rainfall over the Amazon Basin, thus allowing reconstructions of precipitation in a region where meteorological records are short and scarce. Although these results suggest there should be large-scale (> 100 km) spatial coherence of δ18OTR records in the Amazon, this has not been tested. Furthermore, it is of interest to investigate whether other, possibly longer -lived, species similarly record interannual variation of Amazon precipitation, and can be used to develop climate sensitive isotope chronologies. In this study, we measured δ18O in tree rings from seven lowland and one highland tree species from Bolivia. We found that cross-dating with δ18OTR gave more accurate tree ring dates than using ring width. Our “isotope cross-dating approach” is confirmed with radiocarbon “bomb-peak” dates, and has the potential to greatly facilitate development of δ18OTR records in the tropics, identify dating errors, and check annual ring formation in tropical trees. Six of the seven lowland species correlated significantly with C. odorata, showing that variation in δ18OTR has a coherent imprint across very different species, most likely arising from a dominant influence of source water δ18O on δ18OTR. In addition we show that δ18OTR series cohere over large distances, within and between species. Comparison of two C. odorata δ18OTR chronologies from sites several hundreds of kilometres apart showed a very strong correlation (r = 0.80, p < 0.001, 1901–2001), and a significant (but weaker) relationship was found between lowland C. odorata trees and a Polylepis tarapacana tree growing in the distant Altiplano (r = 0.39, p < 0.01, 1931–2001). This large-scale coherence of δ18OTR records is probably triggered by a strong spatial coherence in precipitation δ18O due to large-scale controls. These results highlight the strength of δ18OTR as a precipitation proxy, and open the way for temporal and spatial expansion of precipitation reconstructions in South America

Diet and food strategies in a southern al-Andalusian urban environment during Caliphal period, ecija, Sevilla

The Iberian medieval period is unique in European history due to the widespread socio-cultural changes that took place after the arrival of Arabs, Berbers and Islam in 711 AD. Recently, isotopic research has been insightful on dietary shifts, status, resource availability and the impact of environment. However, there is no published isotopic research exploring these factors in southern Iberian populations, and as the history of this area differs to the northern regions, this leaves a significant lacuna in our knowledge. This research fills this gap via isotopic analysis of human (n = 66) and faunal (n = 13) samples from the 9th to the 13th century Écija, a town renowned for high temperatures and salinity. Stable carbon (δ13C) and nitrogen (δ15N) isotopes were assessed from rib collagen, while carbon (δ13C) values were derived from enamel apatite. Human diet is consistent with C3 plant consumption with a very minor contribution of C4 plants, an interesting feature considering the suitability of Écija to C4 cereal production. δ15N values vary among adults, which may suggest variable animal protein consumption or isotopic variation within animal species due to differences in foddering. Consideration of δ13C collagen and apatite values together may indicate sugarcane consumption, while moderate δ15N values do not suggest a strong aridity or salinity effect. Comparison with other Iberian groups shows similarities relating to time and location rather than by religion, although more multi-isotopic studies combined with zooarchaeology and botany may reveal subtle differences unobservable in carbon and nitrogen collagen studies alone.OLC is funded by Plan Galego I2C mod.B (ED481D 2017/014). The research was partially funded by the projects “Galician Paleodiet” and by Consiliencia network (ED 431D2017/08) Xunta de GaliciaS

Evaluation of the Indications for Sentinel Node Biopsy in Early-Stage Melanoma with the Advent of Adjuvant Systemic Therapy: An International, Multicenter Study

Background Patients presenting with early-stage melanoma (AJCC pT1b-pT2a) reportedly have a relatively low risk of a positive SNB (~5–10%). Those patients are usually found to have low-volume metastatic disease after SNB, typically reclassified to AJCC stage IIIA, with an excellent prognosis of ~90% 5-year survival. Currently, adjuvant systemic therapy is not routinely recommended for most patients with AJCC stage IIIA melanoma. The purpose was to assess the SN-positivity rate in early-stage melanoma and to identify primary tumor characteristics associated with high-risk nodal disease eligible for adjuvant systemic therapy Methods An international, multicenter retrospective cohort study from 7 large-volume cancer centers identified 3,610 patients with early primary cutaneous melanomas 0.8–2.0 mm in Breslow thickness (pT1b-pT2a; AJCC 8th edition). Patient demographics, primary tumor characteristics, and SNB status/details were analyzed. Results The overall SNB-positivity rate was 11.4% (412/3610). Virtually all SNB-positive patients (409/412; 99.3%) were reclassified to AJCC stage IIIA. Multivariate analysis identified age, T-stage, mitotic rate, primary site and subtype, and lymphovascular invasion as independent predictors of sentinel node status. A mitotic rate of >1/mm2 was associated with a significantly increased SN-positivity rate and was the only significant independent predictor of high-risk SNB metastases (>1 mm maximum diameter). Conclusions The new treatment paradigm brings into question the role of SNB for patients with early-stage melanoma. The results of this large international cohort study suggest that a reevaluation of the indications for SNB for some patients with early-stage melanoma is required

A flexible mathematical model platform for studying branching networks : experimentally validated using the model actinomycete, Streptomyces coelicolor

Branching networks are ubiquitous in nature and their growth often responds to environmental cues dynamically. Using the antibiotic-producing soil bacterium Streptomyces as a model we have developed a flexible mathematical model platform for the study of branched biological networks. Streptomyces form large aggregates in liquid culture that can impair industrial antibiotic fermentations. Understanding the features of these could aid improvement of such processes. The model requires relatively few experimental values for parameterisation, yet delivers realistic simulations of Streptomyces pellet and is able to predict features, such as the density of hyphae, the number of growing tips and the location of antibiotic production within a pellet in response to pellet size and external nutrient supply. The model is scalable and will find utility in a range of branched biological networks such as angiogenesis, plant root growth and fungal hyphal networks

Insight dimensions and cognitive function in psychosis: a longitudinal study

BACKGROUND: It has been reported that lack of insight is significantly associated with cognitive disturbance in schizophrenia. This study examines the longitudinal relationships between insight dimensions and cognitive performance in psychosis. METHODS: Participants were 75 consecutively admitted inpatients with schizophrenia, affective disorder with psychotic symptoms or schizoaffective disorder. Assessments were conducted at two time points during the study: at the time of hospital discharge after an acute psychotic episode and at a follow-up time that occurred more than 6 months after discharge. A multidimensional approach of insight was chosen and three instruments for its assessment were used: the Scale to Assess Unawareness of Mental Disorder (SUMD), three items concerning insight on the Assessment and Documentation in Psychopathology (AMDP) system and the Insight and Treatment Attitudes Questionnaire. The neuropsychological battery included a wide range of tests that assessed global cognitive function, attention, memory, and executive functions. RESULTS: After conducting adequate statistical correction to avoid Type I bias, insight dimensions and cognitive performance were not found to be significantly associated at cross-sectional and longitudinal assessments. In addition, baseline cognitive performance did not explain changes in insight dimensions at follow-up. Similar results were found in the subset of patients with schizophrenia (n = 37). The possibility of a Type II error might have increased due to sample attrition at follow-up. CONCLUSION: These results suggest that lack of insight dimensions and cognitive functioning may be unrelated phenomena in psychosis

Modelling the impact of women’s education on fertility in Malawi

Many studies have suggested that there is an inverse relationship between education and number of children among women from sub-Saharan Africa countries, including Malawi. However, a crucial limitation of these analyses is that they do not control for the potential endogeneity of education. The aim of our study is to estimate the role of women’s education on their number of children in Malawi, accounting for the possible presence of endogeneity and for nonlinear effects of continuous observed confounders. Our analysis is based on micro data from the 2010 Malawi Demographic Health Survey, and uses a flexible instrumental variable regression approach. The results suggest that the relationship of interest is affected by endogeneity and exhibits an inverted U-shape among women living in rural areas of Malawi, whereas it exhibits an inverse (nonlinear) relationship for women living in urban areas

Does Lack of Multinutrient Supplementation During Early Pregnancy Increase Vulnerability to Alcohol-Related Preterm or Small-for-Gestational-Age Births?

The objective of this study was to assess whether women who do not take multinutrient supplements during early pregnancy are more susceptible to the effects of low-to-moderate alcohol consumption on preterm birth and small-for-gestational-age birth (SGA) compared to women who do take multinutrients. This analysis included 800 singleton live births to mothers from a cohort of pregnant women recruited for a population-based cohort study conducted in the Kaiser Permanente Medical Care Program in Northern California. Participants were recruited in their first trimester of pregnancy and information about their alcohol use and supplement intake during pregnancy was collected. Preterm birth (n = 53, 7%) was defined as a delivery prior to 37 completed weeks of gestation and SGA birth (n = 124, 16%) was defined as birth weight less than the 10th percentile for the infant’s gestational age and sex compared to US singleton live births. A twofold increase in the odds of SGA birth attributed to low-to-moderate alcohol intake was found among multinutrient supplement non-users (95% CI: 1.1, 5.3). Yet, among multinutrient supplement users, there was no increased risk of an SGA birth for women who drank low-to-moderately compared to women who abstained (aOR: 0.97, 95% CI: 0.6, 1.6). Similar results emerged for preterm birth. Our findings provide marginal evidence that multinutrient supplementation during early pregnancy may modify the risk of SGA births and preterm birth associated with alcohol consumption during pregnancy and may have important implications for pregnant women and women of child-bearing age. However, future research needs to be conducted