Simulating Potential Impacts of Future Climate Change on Post-Rainy Season Sorghum Yields in India

Given the wide use of the multi-climate model mean (MMM) for impact assessment studies, this work examines the fidelity of Coupled Model Intercomparison Project Phase 5 (CMIP5) in simulating the features of Indian summer monsoons as well as the post-rainy seasons for assessing the possible impacts of climate change on post-rainy season sorghum crop yields across India. The MMM simulations captured the spatial patterns and annual cycles of rainfall and surface air temperatures. However, bias was observed in the precipitation amounts and daily rainfall intensity. The trends in the simulations of MMM for both precipitation and temperatures were less satisfactory than the observed climate means. The Crop Environment Resource Synthesis (CERES)-sorghum model was used to estimate the potential impacts of future climate change on post-rainy season sorghum yield values. On average, post-rainy season sorghum yields are projected to vary betwee

Human pluripotent embryonal carcinoma NTERA2 cl.D1 cells maintain their typical morphology in an angiomyogenic medium

BACKGROUND: Pluripotent embryonal carcinomas are good potential models, to study, "in vitro," the mechanisms that control differentiation during embryogenesis. The NTERA2cl.D1 (NT2/D1) cell line is a well known system of ectodermal differentiation. Retinoic acid (RA) induces a dorsal pattern of differentiation (essentially neurons) and bone morphogenetic protein (BMP) or hexamethylenebisacetamide (HMBA) induces a more ventral (epidermal) pattern of differentiation. However, whether these human cells could give rise to mesoderm derivatives as their counterpart in mouse remained elusive. We analyzed the morphological characteristics and transcriptional activation of genes pertinent in cardiac muscle and endothelium differentiation, during the growth of NT2/D1 cells in an inductive angiomyogenic medium with or without Bone Morphogenetic Protein 2 (BMP2). RESULTS: Our experiments showed that NT2/D1 maintains their typical actin organization in angiomyogenic medium. Although the beta myosin heavy chain gene was never detected, all the other 15 genes analyzed maintained their expression throughout the time course of the experiment. Among them were early and late cardiac, endothelial, neuronal and teratocarcinoma genes. CONCLUSION: Our results suggest that despite the NT2/D1 cells natural tendency to differentiate into neuroectodermal lineages, they can activate genes of mesodermal lineages. Therefore, we believe that these pluripotent cells might still be a good model to study biological development of mesodermal derivatives, provided the right culture conditions are met

Chromosomal instability drives metastasis through a cytosolic DNA response

Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS–STING (cyclic GMP-AMP synthase–stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. By subverting lethal epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs

Ordered and deterministic cancer genome evolution after p53 loss

Although p53 inactivation promotes genomic instability1 and presents a route to malignancy for more than half of all human cancers2,3, the patterns through which heterogenous TP53 (encoding human p53) mutant genomes emerge and influence tumorigenesis remain poorly understood. Here, in a mouse model of pancreatic ductal adenocarcinoma that reports sporadic p53 loss of heterozygosity before cancer onset, we find that malignant properties enabled by p53 inactivation are acquired through a predictable pattern of genome evolution. Single-cell sequencing and in situ genotyping of cells from the point of p53 inactivation through progression to frank cancer reveal that this deterministic behaviour involves four sequential phases-Trp53 (encoding mouse p53) loss of heterozygosity, accumulation of deletions, genome doubling, and the emergence of gains and amplifications-each associated with specific histological stages across the premalignant and malignant spectrum. Despite rampant heterogeneity, the deletion events that follow p53 inactivation target functionally relevant pathways that can shape genomic evolution and remain fixed as homogenous events in diverse malignant populations. Thus, loss of p53-the 'guardian of the genome'-is not merely a gateway to genetic chaos but, rather, can enable deterministic patterns of genome evolution that may point to new strategies for the treatment of TP53-mutant tumours

Decoupling wastewater impacts from hydrogeochemical trends in impacted groundwater resources

In the urban environment, anthropogenic activities provide numerous potential sources of contamination, which can often lead to difficulties in identifying the processes impacting groundwater quality (natural and anthropogenic). This is particularly relevant at Wastewater Treatment Plants (WWTPs) that are often subject to changes in land use and composition of contaminant sources over time and space, as well as multiple potential hydrogeochemical interactions. To help address this issue, we demonstrate how long-term time-series analysis of major ions and key contaminants of concern, which are routinely collected by WWTP operators, can be analysed using hydrogeochemical plotting tools, multivariate statistics and targeted isotopic analysis, to provide a means of better characterising key hydrogeochemical influences and anthropogenic inputs. Application of this approach to a WWTP in south-eastern Australia indicated that anthropogenic impacts were the primary driver influencing the local hydrogeochemical environment and groundwater quality. However, secondary processes, including mineral (particularly calcite) dissolution, ion exchange and possible dedolomitisation, as well as natural degradation/transformation of contaminants were also important. Long-term, time-series analysis of trends in NO3-N, NH4-N, Ca2+, SO42−, HCO3− and K+ in conjunction with the other lines of evidence, allowed for enhanced separation between individual contaminant sources, particularly when paired with a detailed site history and Conceptual Site Model (CSM). This indicated that off-site agricultural impacts post-date most site derived impacts, and to date, have not significantly added to the identified contaminant plume. The outcomes of this work have significant global application in the identification, assessment, and control of environmental and health risks at complex sites and show how significant value (rarely obtained) can be derived from the analysis of routine monitoring datasets, particularly when analysed using a multiple lines of evidence approach

Combining environmental isotopes with Contaminants of Emerging Concern (CECs) to characterise wastewater derived impacts on groundwater quality

The potential for Wastewater Treatment Plants (WWTPs) to cause adverse impacts to groundwater quality is a major global environmental challenge. Robust and sensitive techniques are required to characterise these impacts, particularly in settings with multiple potential contaminant sources (e.g. agricultural vs. site-derived). Stable (δ2HH2O, δ18OH2O, δ15NNO3, δ18ONO3 and δ13CDIC) and radioactive (3H and 14C) isotopes were used in conjunction with three Contaminants of Emerging Concern (CECs) - carbamazepine, simazine and sulfamethoxazole - to discriminate between multiple potential contamination sources at an Australian WWTP. The radioactive isotope tritium provided a sensitive indicator of recent (post-1990s) leakage, with groundwater activities between 0.68 and 1.83 TU, suggesting WWTP infrastructure (activities between 1.65 and 2.41) acted as a recharge ‘window’, inputting treated or partially treated effluent to the underlying groundwater system. This was corroborated by water stable isotopes, which showed clear demarcation between δ18OH2O and δ2HH2O in background groundwater (δ18OH2O and δ2HH2O values of approximately −5 and −28‰, respectively) and those associated with on-site wastewater (median δ18OH2O and δ2HH2O values of −1.2 and −7.6‰, respectively), with groundwater down-gradient of the plant plotting on a mixing line between these values. The CECs, particularly the carbamazepine:simazine ratio, provided a means to further distinguish wastewater impacts from other sources, with groundwater down-gradient of the plant reporting elevated ratios (median of 0.98) compared to those up-gradient (median of 0.11). Distinctive CEC ratios in impacted groundwater close to the WWTP (∼3.0) and further down-gradient (2.7–9.3) are interpreted to represent a change in composition over time (i.e., recent vs. legacy contamination), consistent with the site development timeline and possible changes in effluent composition resulting from infrastructure upgrades over time. The data indicate a complex set of co-mingled plumes, reflecting different inputs (in terms of both quantity and concentration) over time. Our approach provides a means to better characterise the nature and timing of wastewater derived impacts on groundwater systems, with significant global implications for site management, potentially allowing more targeted monitoring, management and remedial actions to be undertaken