Early-Holocene greening of the Afro-Asian dust belt changed sources of mineral dust in West Asia

Production, transport and deposition of mineral dust have significant impacts on different components of the Earth systems through time and space. In modern times, dust plumes are associated with their source region(s) using satellite and land -based measurements and trajectory analysis of air masses through time. Reconstruction of past changes in the sources of mineral dust as related to changes in climate, however, must rely on the knowledge of the geochemical and mineralogical composition of modern and paleodust, and that of their potential source origins. In this contribution, we present a 13,000-yr record of variations in radiogenic Sr-Nd-Hf isotopes and Rare Earth Element (REE) anomalies as well as dust grain size from an ombrotrophic (rain fed) peat core in NW Iran as proxies of past changes in the sources of dust over the interior of West Asia. Our data shows that although the grain size of dust varies in a narrow range through the entire record, the geochemical fingerprint of dust particles deposited during the low flux, early Holocene period (11,700-6,000 yr BP) is distinctly different from aerosols deposited during high dust flux periods of the Younger Dryas and the mid-late Holocene (6,000-present). Our findings indicate that the composition of mineral dust deposited at the study site changed as a function of prevailing atmospheric circulation regimes and land exposure throughout the last deglacial period and the Holocene. Simulations of atmospheric circulation over the region show the Northern Hemisphere Summer Westerly Jet was displaced poleward across the study area during the early Holocene when Northern Hemisphere insolation was higher due to the Earth\u27s orbital configuration. This shift, coupled with lower dust emissions simulated based on greening of the Afro-Asian Dust Belt during the early Holocene likely led to potential sources in Central Asia dominating dust export to West Asia during this period. In contrast, the dominant western and southwest Asian and Eastern African sources have prevailed during the mid-Holocene to modern times. (C) 2017 Elsevier B.V. All rights reserved

Climate Action In Megacities 3.0

"Climate Action in Megacities 3.0" (CAM 3.0) presents major new insights into the current status, latest trends and future potential for climate action at the city level. Documenting the volume of action being taken by cities, CAM 3.0 marks a new chapter in the C40-Arup research partnership, supported by the City Leadership Initiative at University College London. It provides compelling evidence about cities' commitment to tackling climate change and their critical role in the fight to achieve global emissions reductions

Amino Alkynylisoquinoline and Alkynylnaphthyridine Compounds Potently Inhibit Acute Myeloid Leukemia Proliferation in Mice

B ackground: Acute myeloid leukemia (AML) remains one of the most lethal, rarely cured cancers, despite decades of active development of AML therapeutics. Currently, the 5-year survival of AML patients is about 30% and for elderly patients, the rate drops to b10%. About 30% of AML patients harbor an activating mutation in the tyrosine kinase domain (TKD) of Fms-Like Tyrosine kinase 3 (FLT3) or a FLT3 internal tandem duplication (FLT3-ITD). In- hibitors of FLT3, such as Rydapt that was recently approved by the FDA, have shown good initial response but pa- tients often relapse due to secondary mutations in the FLT3 TKD, like D835Y and F691 L mutations. Methods: Alkynyl aminoisoquinoline and naphthyridine compounds were synthesized via Sonogashira coupling. The compounds were evaluated for their in vitro and in vivo effects on leukemia growth. Findings: The compounds inhibited FLT3 kinase activity at low nanomolar concentrations. The lead compound, HSN431, also inhibited Src kinase activity. The compounds potently inhibited the viability of MV4–11 and MOLM-14 AML cells with IC50 values b1 nM. Furthermore, the viability of drug-resistant AML cells harboring the D835Y and F691 L mutations were potently inhibited. In vivo efficacy studies in mice demonstrated that the compounds could drastically reduce AML proliferation in mice. Interpretation: Compounds that inhibit FLT3 and downstream targets like Src (for example HSN431) are good leads for development as anti-AML agents

Parents and GPs’ understandings and beliefs about food allergy testing in children with eczema:qualitative interview study within the Trial of Eczema allergy Screening Tests (TEST) feasibility trial

Aim To explore parent and general practitioner (GP) understanding and beliefs about food allergy testing for children with eczema.Design and setting Qualitative interview study in UK primary care within the Trial of Eczema allergy Screening Tests feasibility trial.Participants Semi-structured interviews with parents of children with eczema taking part in the feasibility study and GPs at practices hosting the study.Results 21 parents and 11 GPs were interviewed. Parents discussed a range of potential causes for eczema, including a role for food allergy. They believed allergy testing to be beneficial as it could potentially identify a cure or help reduce symptoms and they found negative tests reassuring, suggesting to them that no dietary changes were needed. GPs reported limited experience and uncertainty regarding food allergy in children with eczema. While some GPs believed referral for allergy testing could be appropriate, most were unclear about its utility. They thought it should be reserved for children with severe eczema or complex problems but wanted more information to advise parents and help guide decision making.Conclusions Parents’ motivations for allergy testing are driven by the desire to improve their child’s condition and exclude food allergy as a possible cause of symptoms. GPs are uncertain about the role of allergy testing and want more information about its usefulness to support parents and help inform decision making.Trial registration number ISRCTN15397185

De novo Assembly of the Burying Beetle Nicrophorus orbicollis (Coleoptera: Silphidae) Transcriptome Across Developmental Stages with Identification of Key Immune Transcripts

Burying beetles (Nicrophorus spp.) are among the relatively few insects that provide parental care while not belonging to the eusocial insects such as ants or bees. This behavior incurs energy costs as evidenced by immune deficits and shorter life-spans in reproducing beetles. In the absence of an assembled transcriptome, relatively little is known concerning the molecular biology of these beetles. This work details the assembly and analysis of the Nicrophorus orbicollis transcriptome at multiple developmental stages. RNA-Seq reads were obtained by next-generation sequencing and the transcriptome was assembled using the Trinity assembler. Validation of the assembly was performed by functional characterization using Gene Ontology (GO), Eukaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Differential expression analysis highlights developmental stage-specific expression patterns, and immunity-related transcripts are discussed. The data presented provides a valuable molecular resource to aid further investigation into immunocompetence throughout this organism’s sexual development

Pennsylvania Folklife Vol. 15, No. 1

• The Year of the Rupjonjim • Pennsylvania Summer-Houses and Summer-Kitchens • Religious and Educational References in Lancaster County Wills • Genealogy and Folk-Culture • Pennsylvania German Folktales: An Annotated Bibliography • Italian Immigrant Life in Northampton County, Pennsylvania, 1890-1915 Part IIhttps://digitalcommons.ursinus.edu/pafolklifemag/1021/thumbnail.jp

Predicting physiological imbalance in Holstein dairy cows by three different sets of milk biomarkers

Blood biomarkers may be used to detect physiological imbalance and potential disease. However, blood sampling is difficult and expensive, and not applicable in commercial settings. Instead, individual milk samples are readily available at low cost, can be sampled easily and analysed instantly. The present observational study sampled blood and milk from 234 Holstein dairy cows from experimental herds in six European countries. The objective was to compare the use of three different sets of milk biomarkers for identification of cows in physiological imbalance and thus at risk of developing metabolic or infectious diseases. Random forests was used to predict body energy balance (EBAL), index for physiological imbalance (PI-index) and three clusters differentiating the metabolic status of cows created on basis of concentrations of plasma glucose, β-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA) and serum IGF-1. These three metabolic clusters were interpreted as cows in balance, physiological imbalance and “intermediate cows” with physiological status in between. The three sets of milk biomarkers used for prediction were: milk Fourier transform mid-IR (FT-MIR) spectra, 19 immunoglobulin G (IgG) N-glycans and 8 milk metabolites and enzymes (MME). Blood biomarkers were sampled twice; around 14 days after calving (days in milk (DIM)) and around 35 DIM. MME and FT-MIR were sampled twice weekly 1−50 DIM whereas IgG N-glycan were measured only four times. Performances of EBAL and PI-index predictions were measured by coefficient of determination (R2cv) and root mean squared error (RMSEcv) from leave-one-cow-out cross-validation (cv). For metabolic clusters, performance was measured by sensitivity, specificity and global accuracy from this cross-validation. Best prediction of PI-index was obtained by MME (R2cv = 0.40 (95 % CI: 0.29−0.50) at 14 DIM and 0.35 (0.23−0.44) at 35 DIM) while FT-MIR showed a better performance than MME for prediction of EBAL (R2cv = 0.28 (0.24−0.33) vs 0.21 (0.18−0.25)). Global accuracies of predicting metabolic clusters from MME and FT-MIR were at the same level ranging from 0.54 (95 % CI: 0.39−0.68) to 0.65 (0.55−0.75) for MME and 0.51 (0.37−0.65) to 0.68 (0.53−0.81) for FT-MIR. R2cv and accuracies were lower for IgG N-glycans. In conclusion, neither EBAL nor PI-index were sufficiently well predicted to be used as a management tool for identification of risk cows. MME and FT-MIR may be used to predict the physiological status of the cows, while the use of IgG N-glycans for prediction still needs development. Nevertheless, accuracies need to be improved and a larger training data set is warranted

Wood traits explain microbial but not termite‐driven decay in Australian tropical rainforest and savanna

1. Variation in decay rates across woody species is a key uncertainty in predicting the fate of carbon stored in deadwood, especially in the tropics. Quantifying the relative contributions of biotic decay agents, particularly microbes and termites, under different climates and across species with diverse wood traits could help explain this variation. 2. To fill this knowledge gap, we deployed woody stems from 16 plant species native to either rainforest (n = 10) or savanna (n = 6) in northeast Australia, with and without termite access. For comparison, we also deployed standardized, non-native pine blocks at both sites. We hypothesized that termites would increase rates of deadwood decay under conditions that limit microbial activity. Specifically, termite contributions to wood decay should be greater under dry conditions and in wood species with traits that constrain microbial decomposers. 3. Termite discovery of stems was surprisingly low with only 17.6% and 22.6% of accessible native stems discovered in the rainforest and savanna respectively. Contrary to our hypothesis, stems discovered by termites decomposed faster only in the rainforest. Termites discovered and decayed pine blocks at higher rates than native stems in both the rainforest and savanna. 4. We found significant variation in termite discovery and microbial decay rates across native wood species within the same site. Although wood traits explained 85% of the variation in microbial decay, they did not explain termite-driven decay. For stems undiscovered by termites, decay rates were greater in species with higher wood nutrient concentrations and syringyl:guiacyl lignin ratios but lower carbon concentrations and wood densities. 5. Synthesis. Ecosystem-scale predictions of deadwood turnover and carbon storage should account for the impact of wood traits on decomposer communities. In tropical Australia, termite-driven decay was lower than expected for native wood on the ground. Even if termites are present, they may not always increase decomposition rates of fallen native wood in tropical forests. Our study shows how the drivers of wood decay differ between Australian tropical rainforest and savanna; further research should test whether such differences apply world-wide

Primary and malignant cholangiocytes undergo CD40 mediated Fas dependent Apoptosis, but are insensitive to direct activation with exogenous fas ligand

Introduction Cholangiocarcinoma is a rare malignancy of the biliary tract, the incidence of which is rising, but the pathogenesis of which remains uncertain. No common genetic defects have been described but it is accepted that chronic inflammation is an important contributing factor. We have shown that primary human cholangiocyte and hepatocyte survival is tightly regulated via co-operative interactions between two tumour necrosis family (TNF) receptor family members; CD40 and Fas (CD95). Functional deficiency of CD154, the ligand for CD40, leads to a failure of clearance of biliary tract infections and a predisposition to cholangiocarcinoma implying a direct link between TNF receptor-mediated apoptosis and the development of cholangiocarcinoma. Aims To determine whether malignant cholangiocytes display defects in CD40 mediated apoptosis. By comparing CD40 and Fas-mediated apoptosis and intracellular signalling in primary human cholangiocytes and three cholangiocyte cell lines. Results Primary cholangiocytes and cholangiocyte cell lines were relatively insensitive to direct Fas-mediated killing with exogenous FasL when compared with Jurkat cells, which readily underwent Fas-mediated apoptosis, but were extremely sensitive to CD154 stimulation. The sensitivity of cells to CD40 activation was similar in magnitude in both primary and malignant cells and was STAT-3 and AP-1 dependent in both. Conclusions 1) Both primary and malignant cholangiocytes are relatively resistant to Fas–mediated killing but show exquisite sensitivity to CD154, suggesting that the CD40 pathway is intact and fully functional in both primary and malignant cholangiocytes 2) The relative insensitivity of cholangiocytes to Fas activation demonstrates the importance of CD40 augmentation of Fas dependent death in these cells. Agonistic therapies which target CD40 and associated intracellular signalling pathways may be effective in promoting apoptosis of malignant cholangiocytes