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"Jones, Philip"
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Long-term 3D primary epithelioid cultures reveal genes that regulate esophageal cell fitness
Primary cell cultures need to be frequently passaged, which limits the study of long-term biological processes, such as how mutant clones colonize aging epithelia. Esophageal epithelioids self-maintain for months, recapitulating progenitor cell behavior in vivo. Epithelioid CRISPR–Cas9 screens reveal genes encoding molecules that control cell fitness.
Journal Article
Global warming and changes in drought
Recent studies have produced conflicting results about the impacts of climate change on drought. In this Perspective, a commonly used drought index and observational data are examined to identify the cause of these discrepancies. The authors indicate that improvements in the quality and coverage of precipitation data and quantification of natural variability are necessary to provide a better understanding of how drought is changing.
Several recently published studies have produced apparently conflicting results of how drought is changing under climate change. The reason is thought to lie in the formulation of the Palmer Drought Severity Index (PDSI) and the data sets used to determine the evapotranspiration component. Here, we make an assessment of the issues with the PDSI in which several other sources of discrepancy emerge, not least how precipitation has changed and is analysed. As well as an improvement in the precipitation data available, accurate attribution of the causes of drought requires accounting for natural variability, especially El Niño/Southern Oscillation effects, owing to the predilection for wetter land during La Niña events. Increased heating from global warming may not cause droughts but it is expected that when droughts occur they are likely to set in quicker and be more intense.
Journal Article
Notch1 mutations drive clonal expansion in normal esophageal epithelium but impair tumor growth
NOTCH1
mutant clones occupy the majority of normal human esophagus by middle age but are comparatively rare in esophageal cancers, suggesting
NOTCH1
mutations drive clonal expansion but impede carcinogenesis. Here we test this hypothesis. Sequencing
NOTCH1
mutant clones in aging human esophagus reveals frequent biallelic mutations that block
NOTCH1
signaling. In mouse esophagus, heterozygous
Notch1
mutation confers a competitive advantage over wild-type cells, an effect enhanced by loss of the second allele. Widespread
Notch1
loss alters transcription but has minimal effects on the epithelial structure and cell dynamics. In a carcinogenesis model,
Notch1
mutations were less prevalent in tumors than normal epithelium. Deletion of
Notch1
reduced tumor growth, an effect recapitulated by anti-NOTCH1 antibody treatment.
Notch1
null tumors showed reduced proliferation. We conclude that
Notch1
mutations in normal epithelium are beneficial as wild-type
Notch1
favors tumor expansion. NOTCH1 blockade may have therapeutic potential in preventing esophageal squamous cancer.
Notch1
mutations have opposing effects on clonal growth in normal and tumor cells of the mouse esophagus. In a mouse model of squamous esophageal tumorigenesis, Notch1 blockade reduced premalignant tumor growth, suggesting that it might be an effective prevention strategy for the disease.
Journal Article
The greenhouse gas impacts of converting food production in England and Wales to organic methods
Agriculture is a major contributor to global greenhouse gas (GHG) emissions and must feature in efforts to reduce emissions. Organic farming might contribute to this through decreased use of farm inputs and increased soil carbon sequestration, but it might also exacerbate emissions through greater food production elsewhere to make up for lower organic yields. To date there has been no rigorous assessment of this potential at national scales. Here we assess the consequences for net GHG emissions of a 100% shift to organic food production in England and Wales using life-cycle assessment. We predict major shortfalls in production of most agricultural products against a conventional baseline. Direct GHG emissions are reduced with organic farming, but when increased overseas land use to compensate for shortfalls in domestic supply are factored in, net emissions are greater. Enhanced soil carbon sequestration could offset only a small part of the higher overseas emissions.
Journal Article
Lucy Jones : Awkward beauty
British artist Lucy Jones has been described by art critic Jackie Wullschlager as 'the most exciting English colourist of her generation'' With a clear and often brutally frank vision, her paintings connect a journey through exterior landscapes and interior worlds. 0'Awkward Beauty' is the first publication to draw together both her portraits and landscape paintings produced over the past 25 years, tracing the evolution of a distinctively vibrant painterly language, which she has used to describe the world, herself and, most recently, other people.0Illustrated with more than 100 colour plates, the book demonstrates Jones's broad emotional range, from densely chromatic and vigorously wrought vistas painted in the British countryside, to her raw and powerfully expressive presentations of the figure, addressing the vulnerabilities and the strengths of Jones's own disabilities, and society's way of viewing difference in others.
Book
A Large-Scale Study of Anxiety and Depression in People with Multiple Sclerosis: A Survey via the Web Portal of the UK MS Register
Studies have found that people with Multiple Sclerosis experience relatively high rates of anxiety and depression. Although methodologically robust, many of these studies had access to only modest sample sizes (N<200). The aims of this study were to use responses gained via the web portal of the UK MS Register (N>4000) to: describe the depression and anxiety profiles of people with MS; to determine if anxiety and depression are related to age or disease duration; and to assess whether the levels of anxiety and depression differ between genders and types of MS.
From its launch in May 2011 to the end of December 2011, 7786 adults with MS enrolled to take part in the UK MS Register via the web portal. The responses to the Hospital Anxiety and Depression Scale (HADS) were collated with basic demographic and descriptive MS data provided at registration and the resulting dataset was analysed in SPSS (v.16).
The mean HADS score among the 4178 respondents was 15.7 (SE 0.117, SD 7.55) with a median of 15.0 (IQR 11). Anxiety and depression rates were notably high, with over half (54.1%) scoring ≥ 8 for anxiety and 46.9% scoring ≥ 8 for depression. Women with relapsing-remitting MS were more anxious than men with this type (p<0.001), and than women with other types of MS (p = 0.017). Within each gender, men and women with secondary progressive MS were more depressed than men or women with other types of MS (p<0.001, p<0.001).
This largest known study of its kind has shown that anxiety and depression are highly prevalent in people with MS, indicating that their mental health needs could be better addressed. These findings support service planning and further research to provide the best care for people with MS to help alleviate these debilitating conditions.
Journal Article