Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia

Intestinal homeostasis is underpinned by LGR5+ve crypt-base columnar stem cells (CBCs), but following injury, dedifferentiation results in the emergence of LGR5-ve regenerative stem cell populations (RSCs), characterized by fetal transcriptional profiles. Neoplasia hijacks regenerative signaling, so we assessed the distribution of CBCs and RSCs in mouse and human intestinal tumors. Using combined molecular-morphological analysis, we demonstrate variable expression of stem cell markers across a range of lesions. The degree of CBC-RSC admixture was associated with both epithelial mutation and microenvironmental signaling disruption and could be mapped across disease molecular subtypes. The CBC-RSC equilibrium was adaptive, with a dynamic response to acute selective pressure, and adaptability was associated with chemoresistance. We propose a fitness landscape model where individual tumors have equilibrated stem cell population distributions along a CBC-RSC phenotypic axis. Cellular plasticity is represented by position shift along this axis and is influenced by cell-intrinsic, extrinsic, and therapeutic selective pressures. Keywords: cell plasticity; colorectal cancer; colorectal neoplasia; intestinal polyps; intestinal stem cells; molecular phenotyping; stem cells

Implementation of FDTD Method for the simulation of the interation electromagnetic wave with dielectric media 1D

El método de diferencias finitas en el dominio del tiempo (FDTD) ha demostrado ser una herramienta útil para el análisis de los fenómenos electromagnéticos. En este trabajo se presenta una implementación eficiente del método FDTD, en la cual se modelan medios dieléctricos y su interacción con ondas electromagnéticas, se implementa la trasformada Rápida de Fourier para medir reflexiones y trasmisiones de la onda en el medio dieléctrico. Se introducen unas condiciones de frontera que permiten evitar reflexiones indeseadas en los bordes del dominio computacional del problema, siendo este es un problema de evolución temporal con dominios no acotados.The finite difference time-domain (FDTD) has proved a useful tool for the analysis of electromagnetic phenomena. This paper presents a graphical application based on MATLAB GUIDE, in which the implementation of the finite difference algorithm is shown in the time domain, to simulate the phenomenon of refraction is presented. Absorbing boundary conditions (ABC) type of perfectly matched layers (PML) will be introduced, as this is a problem of time evolution with unbounded domains

A simple approach to forest structure classification using airborne laser scanning that can be adopted across bioregions

Reliable assessment of forest structural types (FSTs) aids sustainable forest management. We developed a methodology for the identification of FSTs using airborne laser scanning (ALS), and demonstrate its generality by applying it to forests from Boreal, Mediterranean and Atlantic biogeographical regions. First, hierarchal clustering analysis (HCA) was applied and clusters (FSTs) were determined in coniferous and deciduous forests using four forest structural variables obtained from forest inventory data – quadratic mean diameter (QMD), Gini coefficient (GC), basal area larger than mean (BALM) and density of stems (N) –. Then, classification and regression tree analysis (CART) were used to extract the empirical threshold values for discriminating those clusters. Based on the classification trees, GC and BALM were the most important variables in the identification of FSTs. Lower, medium and high values of GC and BALM characterize single storey FSTs, multi-layered FSTs and exponentially decreasing size distributions (reversed J), respectively. Within each of these main FST groups, we also identified young/mature and sparse/dense subtypes using QMD and N. Then we used similar structural predictors derived from ALS – maximum height (Max), L-coefficient of variation (Lcv), L-skewness (Lskew), and percentage of penetration (cover), – and a nearest neighbour method to predict the FSTs. We obtained a greater overall accuracy in deciduous forest (0.87) as compared to the coniferous forest (0.72). Our methodology proves the usefulness of ALS data for structural heterogeneity assessment of forests across biogeographical regions. Our simple two-tier approach to FST classification paves the way toward transnational assessments of forest structure across bioregions

The 14q32 maternally imprinted locus is a major source of longitudinally stable circulating microRNAs as measured by small RNA sequencing.

Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2-5 years in the course of the screening trial, UKCTOCS. We were able to define a subset of longitudinally stable miRNAs (ICC >0.75) that were individually discriminating of women who had no cancer over the study period. These miRNAs were dominated by those originating from the C14MC cluster that is subject to maternal imprinting. This assessment was not significantly affected by common confounders such as age, BMI or time to centrifugation nor alternative methods to data normalisation. Our analysis provides important benchmark data supporting the development of miRNA biomarkers for the impact of life-course exposure as well as diagnosis and prognostication of chronic disease

ESCargo: a regulatable fluorescent secretory cargo for diverse model organisms

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Casler, J. C., Zajac, A. L., Valbuena, F. M., Sparvoli, D., Jeyifous, O., Turkewitz, A. P., Horne-Badovinac, S., Green, W. N., & Glick, B. S. ESCargo: a regulatable fluorescent secretory cargo for diverse model organisms. Molecular Biology of the Cell, (2020): mbcE20090591, doi:10.1091/mbc.E20-09-0591.Membrane traffic can be studied by imaging a cargo protein as it transits the secretory pathway. The best tools for this purpose initially block export of the secretory cargo from the endoplasmic reticulum (ER), and then release the block to generate a cargo wave. However, previously developed regulatable secretory cargoes are often tricky to use or specific for a single model organism. To overcome these hurdles for budding yeast, we recently optimized an artificial fluorescent secretory protein that exits the ER with the aid of the Erv29 cargo receptor, which is homologous to mammalian Surf4. The fluorescentsecretory protein forms aggregates in the ER lumen and can be rapidly disaggregated by addition of a ligand to generate a nearly synchronized cargo wave. Here we term this regulatable secretory proteinESCargo (Erv29/Surf4-dependent Secretory Cargo) and demonstrate its utility not only in yeast cells, but also in cultured mammalian cells, Drosophila cells, and the ciliate Tetrahymena thermophila. Kinetic studies indicate that rapid export from the ER requires recognition by Erv29/Surf4. By choosing an appropriate ER signal sequence and expression vector, this simple technology can likely be used withmany model organisms.This work was supported by NIH grant R01 GM104010 to BSG, by NIH grant R01 GM105783 to APT, by NIH grant R01 GM136961 and American Cancer Society grant RSG-14-176 to SHB, and by NIH grant R01 DA044760 to WNG. JCC was supported by NIH training grant T32 GM007183. AZ was supported by American Heart Association fellowship 16POST2726018 and American Cancer Society fellowship 132123-PF-18-025-01-CSM. Thanks for assistance with fluorescence microscopy to Vytas Bindokas and Christine Labno at the Integrated Microscopy Core Facility, which is supported by the NIH-funded Cancer Center Support Grant P30 CA014599. The pUASt-ManII-eGFP plasmid was a gift from Bing Ye, and the Ubi-Gal4 plasmid was a gift from Rick Fehon.2020-12-2

Trade-offs of crop residue use in smallholder mixed farming systems in Sub-Saharan Africa and South Asia

One of the three pillars of CA is the use of crop residues (CR) for mulching. However, in smallholder farming systems that combine crop production and livestock husbandry (mixed systems), CR are usually an essential source of feed, restricting their availability for mulching. Additionally in these systems, CR fulfil other functions such as providing fuel and additional income through sale. Smallholder production in mixed systems supports the livelihoods of almost two thirds of the global population, especially in Sub-Saharan Africa and South Asia (Herrero et al., 2010). The integration between crops and animals not only enhances agricultural production, but also improves household food intake and income and provides a buffer against climate risks (Thornton, 2010). The need to cover their own food requirements and household expenses pushes smallholder farmers to favour practices with positive returns in the short term, which may affect the sustainability of the systems in the long term. Farmers‘ decisions are influenced by biophysical and socio-economic drivers including climate, population dynamics, market access and other institutional mechanisms. The focus of this paper is on the trade-offs of CR use in a range of smallholder mixed systems in Sub-Saharan Africa (SSA) and South Asia (SA). The objective of this paper is threefold: (i) to describe the different CR farmer uses in these mixed systems; (ii) to understand what biophysical and socio-economic drivers explain differences in CR allocation; and (iii) to include these findings in the broader discussion on long term sustainability issues in mixed systems and constraints for CA practices adoption

Phosphorus and nitrogen losses from temperate permanent grassland on clay-loam soil after the installation of artificial mole and gravel mole drainage

peer-reviewedMole (M) and gravel-mole (GM) drainage systems improve the permeability of soils with high clay contents. They collect and carry away infiltrating water during episodic rainfall events. Characterisation of nutrient fluxes (concentration and flows) in overland flow (OF) and in mole drain flow (MF) across sequential rainfall events is important for environmental assessment of such drainage systems. The objective of this study is to assess the impact of drainage systems on soil nutrient losses. Three treatments were imposed on grazed permanent grassland on a clay loam soil in Ireland (52°30′N, 08°12′W) slope 1.48%: undrained control (C), mole drainage (M) and gravel mole drainage (GM). Plots (100 m × 15 m) were arranged in a randomized complete block design with four replicated blocks. Nitrogen (N) and phosphorus (P) concentrations in OF, MF and groundwater (GW) were measured from each plot over 15 consecutive rainfall events. The results showed that M and GM (P < 0.05) deepened the watertable depth and decreased OF. M and GM increased losses of nitrate-N (22%) and ammonium-N (14%) in GW. Nitrate-N concentrations from all the flow pathways (mean and standard error (s.e.): 0.99 s.e. 0.10 mg L−1) were well below the 11.3 mg L−1 threshold for drinking water. Ammonium-N concentrations from all the flow pathways (mean: 0.64 s.e. 0.14 mg L−1) exceeded drinking water quality standards. On the other hand M and GM lowered total P losses (mean annual losses from C, M and GM: 918, 755 and 853 s.e. 14.1 g ha−1 year−1) by enhancing soil P sorption. Hence M and GM can be implemented on farms under similar management to that described in the present study with a minor impact on N (increased concentration on averaged 18% to GW) and P (reduced by on avenged 114 g ha−1 year−1)

Prevalencia de bacteriuria asintomática en embarazadas de 12 a 16 semana de gestación

ResumenAntecedentes: La bacteriuria asistom&aacute;tica (BA) se presenta entre el 4-7% del total de embarazos; se puede tener como concecuencia el desarrollo de pielonefritis, que puede conducir a parto pret&eacute;rmino y bajo peso al nacer.[Maldonado HF, Antolinez LY, Solano MNC, Tejeiro ML, Valbuena AR. Prevalencia de bacteriuria asintom&aacute;tica en embarazadas de 12 a 16 semana de gestaci&oacute;n. MedUNAB 2005;8:78-81].Palabras clave: Bacteriuria asistom&aacute;tica, Urocultivo, Pielonefritis, Edad gestacional, Embarzo, Control prenata

The association of circulating amylin with β-amyloid in familial Alzheimer's disease.

INTRODUCTION: This study assessed the hypothesis that circulating human amylin (amyloid-forming) cross-seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD). METHODS: Evidence of amylin-AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non-APP/PS1 rats. RESULTS: Amylin-Aβ cross-seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected APP/PS1 rats against AD-associated effects. In contrast, hypersecretion or intravenous injection of human amylin in APP/PS1 rats exacerbated AD-like pathology through disruption of CSF-brain Aβ exchange and amylin-Aβ cross-seeding. DISCUSSION: These findings strengthened the hypothesis of circulating amylin-AD interaction and suggest that modulation of blood amylin levels may alter Aβ-related pathology/symptoms

Mechanical Design Aspects of The LHC Beam screen

Forty-four kilometers of the LHC beam vacuum system [1,2] will be equipped with a perforated co-axial liner, the so-called beam screen. Operating between 5 K and 20 K, the beam screen reduces heat loads to the 1.9 K helium bath of the superconducting magnets and minimises dynamic vacuum effects. Constructed from low magnetic permeability stainless steel with a 50 mm inner layer of high purity copper, the beam screen must provide a maximum aperture for the beam whilst resisting the induced forces due to eddy currents at magnet quench. The mechanical engineering challenges are numerous, and include stringent requirements on geometry, material selection, manufacturing techniques and cleanliness. The industrial fabrication of these 16 metre long UHV components is now in its prototyping phase. A description of the beam screen is given, together with details of the experimental programme aimed at validating the design choices, and results of the first industrial prototypes