62 research outputs found
Reading Clay: The Temporal and Transformative Potential of Clay in Contemporary Scientific Practice
Clay has a long history in the global south and has been extensively studied by âWesternâ social scientists particularly anthropologists and archeologists in relation to histories of earlier civilisations and cultural practices. Clay in relation to contemporary âscienceâ has received less attention in social science despite the emergence of the sub-discipline of âclay scienceâ and its increasing focus on clay to transform wide ranging aspects of social life. In this paper we work towards an exploration of clay in science. We begin with the question of âwhat is clay?â from the perspective of a multidisciplinary group of scientists, whilst being alert to culturally located and past knowledges of clay that shape current scientific knowledges and practices. Drawing on interviews with six clay scientists we explore the ontological and epistemological process for scientists in âreadingâ clay to reveal how clay is âclassifiedâ, âworked uponâ and âpartneredâ. Our findings suggest that clay comes into being for scientists by being read as an informational and temporal medium and agentic matter with transformative promise to remedy specific threats to human and environmental health
If I Donât Speak to My Child in My Own Language, Then Who Will? Kanak Women Writing Culture for Children
This essay is the first to emerge from an ongoing international project which looks at storytelling for children by Indigenous women in the interests of promoting Indigenous languages and cultures. Impressed and humbled by the energy and commitment of the women writers, we ask, along with New Caledonia based French academic, Patrice Favaro, âWhat can I bring to people who want to write tales drawn from the oral tradition out of their own culture about which I know nothing?â (11). So we, as a group of non-Indigenous women academics, want to acknowledge our lack of knowledge of Kanak traditions along with the multi-disciplinary collaborative approach we bring to this work. We bring insights drawn from sociology, Indigenous studies, literature and education to bear on our analysis of the ground-breaking work of Kanak women writers in the hope that the commitment to further Indigenous interests will be even more widely shared and understood
Eukaryotic HMGB proteins as replacements for HU in E. coli repression loop formation
DNA looping is important for gene repression and activation in Escherichia coli and is necessary for some kinds of gene regulation and recombination in eukaryotes. We are interested in sequence-nonspecific architectural DNA-binding proteins that alter the apparent flexibility of DNA by producing transient bends or kinks in DNA. The bacterial heat unstable (HU) and eukaryotic high-mobility group B (HMGB) proteins fall into this category. We have exploited a sensitive genetic assay of DNA looping in living E. coli cells to explore the extent to which HMGB proteins and derivatives can complement a DNA looping defect in E. coli lacking HU protein. Here, we show that derivatives of the yeast HMGB protein Nhp6A rescue DNA looping in E. coli lacking HU, in some cases facilitating looping to a greater extent than is observed in E. coli expressing normal levels of HU protein. Nhp6A-induced changes in the DNA length-dependence of repression efficiency suggest that Nhp6A alters DNA twist in vivo. In contrast, human HMGB2-box A derivatives did not rescue looping
Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines
Background: EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and
Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and
in combination with EGF.
Methods: Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was
conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression
and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene
expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40
K array A.
Results: Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this
level of cell cycle distribution after treatment, suggesting a predominantly differentiated state.
Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their
viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important
reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating
microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and
showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane
reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes
upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the
2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment.
In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological
effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes
appeared to be less stimulated than for single drug cases.
Conclusion: This is the first study to have systematically investigated the effect of cetuximab or
gefitinib, alone and in combination with EGF, on human colon cancer cell lines. The EGFR inhibitors
have a weaker effect in the presence of EGF that binds EGFR. Cetuximab treatment showed an
expression pattern that inversely correlates with EGF treatment. We found interesting cytomorphological
features closely relating to gene expression profile. Both drugs have an effect on
differentiation towards cellular death
A Single Nucleotide Resolution Model for Large-Scale Simulations of Double Stranded DNA
The computational modelling of DNA is becoming crucial in light of new
advances in DNA nanotechnology, single-molecule experiments and in vivo DNA
tampering. Here we present a mesoscopic model for double stranded DNA (dsDNA)
at the single nucleotide level which retains the characteristic helical
structure, while being able to simulate large molecules -- up to a million base
pairs -- for time-scales which are relevant to physiological processes. This is
made possible by an efficient and highly-parallelised implementation of the
model which we discuss here. We compare the behaviour of our model with single
molecule experiments where dsDNA is manipulated by external forces or torques.
We also present some results on the kinetics of denaturation of linear DNA
SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to
genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility
and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component.
Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci
(eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene),
including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform
genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer
SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the
diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types
The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases
The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to the surveillance of pathogens circulating in both human and animal populations and assess how frequently they are exchanged. This infrastructure will facilitate systematic investigations of pathogen ecology and evolution, enhance understanding of viral cross-species transmission events, and identify relevant risk factors and drivers of zoonotic disease emergence
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, PÂ =Â 1.65Â ĂÂ 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, PÂ =Â 2.3Â ĂÂ 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, PÂ =Â 3.98Â ĂÂ Â 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, PÂ =Â 4.99Â ĂÂ 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
A search for pair-produced resonances in four-jet final states at root s=13 TeV with the ATLAS detector
A search for massive coloured resonances which are pair-produced and decay into two jets is presented. The analysis uses 36.7 fbâ1
â
1
of â
s
= 13 TeV pp collision data recorded by the ATLAS experiment at the LHC in 2015 and 2016. No significant deviation from the background prediction is observed. Results are interpreted in a SUSY simplified model where the lightest supersymmetric particle is the top squark, Ì
t
~
, which decays promptly into two quarks through R-parity-violating couplings. Top squarks with masses in the range 100 GeV<Ì<410
100
GeV
<
m
t
~
<
410
GeV
GeV
are excluded at 95% confidence level. If the decay is into a b-quark and a light quark, a dedicated selection requiring two b-tags is used to exclude masses in the ranges 100 GeV<Ì<470
100
GeV
<
m
t
~
<
470
GeV
GeV
and 480 GeV<Ì<610
480
GeV
<
m
t
~
<
610
GeV
GeV
. Additional limits are set on the pair-production of massive colour-octet resonances
Measurements of electroweak Wjj production and constraints on anomalous gauge couplings with the ATLAS detector
Measurements of the electroweak production of a W boson in association with two jets at high dijet invariant mass are performed using root s = 7 and 8 TeV proton-proton collision data produced by the Large Hadron Collider, corresponding respectively to 4.7 and 20.2 fb(-1) of integrated luminosity collected by the ATLAS detector. The measurements are sensitive to the production of a W boson via a triple-gauge-boson vertex and include both the fiducial and differential cross sections of the electroweak process
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