Towards care-full co-design with older adults: A feminist posthuman praxis.

Gerontechnology design is often rooted in deficit imaginaries of frail ageing bodies, with little consideration given to the sociomateriality of older adults' everyday lives, as shaped by complex social, political, historical and cultural forces. While co-design approaches have gone some way in supporting the participation of older adults, little attention has been given to how design processes can be responsive to the more-than-human lived materialities of older adults' everyday lives. More generally, there is also a need for deeper ethical engagement with the more-than-human assemblages that shape the politics and practices of co-design.

Targeting Cholesterol Biosynthesis with Statins Synergizes with AKT Inhibitors in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is responsible for a disproportionate number of breast cancer patient deaths due to extensive molecular heterogeneity, high recurrence rates, and lack of targeted therapies. Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT pathway occurs in approximately 50% of TNBC patients. Here, we performed a genome-wide CRISPR/Cas9 screen with PI3Kα and AKT inhibitors to find targetable synthetic lethalities in TNBC.

Beyond landscape's visible realm: Recorded sound, nature, and wellbeing.

This article draws on an AHRC/EPSRC funded project called 'A Sense of Place: Exploring nature and wellbeing through the non-visual senses'. The project used sound and smell technologies, as well as material textures and touch, to ask: what does 'wellbeing' mean for people in relation to the non-visual aspects of nature, and how might technology play a role in promoting it (if at all)? This article takes recorded sound as a case study. It argues that recorded soundscapes should be understood on their own terms rather than as 'less than' or a simulation of natural environments.

MAPK Pathway Suppression Unmasks Latent DNA Repair Defects and Confers a Chemical Synthetic Vulnerability in -, and -Mutant Melanomas.

Although the majority of -mutant melanomas respond to BRAF/MEK inhibitors, these agents are not typically curative. Moreover, they are largely ineffective in - and -mutant tumors. Here we report that genetic and chemical suppression of HDAC3 potently cooperates with MAPK pathway inhibitors in all three RAS pathway-driven tumors.

Melanoma Therapeutic Strategies that Select against Resistance by Exploiting MYC-Driven Evolutionary Convergence.

Diverse pathways drive resistance to BRAF/MEK inhibitors in BRAF-mutant melanoma, suggesting that durable control of resistance will be a challenge. By combining statistical modeling of genomic data from matched pre-treatment and post-relapse patient tumors with functional interrogation of >20 in vitro and in vivo resistance models, we discovered that major pathways of resistance converge to activate the transcription factor, c-MYC (MYC). MYC expression and pathway gene signatures were suppressed following drug treatment, and then rebounded during progression.

The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers.

Genes encoding subunits of SWI/SNF (BAF) chromatin remodelling complexes are collectively altered in over 20% of human malignancies, but the mechanisms by which these complexes alter chromatin to modulate transcription and cell fate are poorly understood. Utilizing mouse embryonic fibroblast and cancer cell line models, here we show via ChIP-seq and biochemical assays that SWI/SNF complexes are preferentially targeted to distal lineage specific enhancers and interact with p300 to modulate histone H3 lysine 27 acetylation. We identify a greater requirement for SWI/SNF at typical enhancers than at most super-enhancers and at enhancers in untranscribed regions than in transcribed regions.

Parasites and hepatic lesions among pink salmon, Oncorhynchus gorbuscha (Walbaum), during early seawater residence.

Juvenile pink salmon, Oncorhynchus gorbuscha (Walbaum), in the Broughton Archipelago region of western Canada were surveyed over 2 years for sea lice (Lepeophtheirus salmonis and Caligus clemensi), gross and microscopic lesions and evidence of infections with viruses and bacteria. The 1071 fish examined had an approximate ocean residence time no longer than 3 months. A high prevalence of degenerative liver lesions, renal myxosporean parasites and a low prevalence of skin lesions and sea lice were observed.