Anti-cancer uses of non-oncology drugs have occasionally been found, but such discoveries have been serendipitous. We sought to create a public resource containing the growth inhibitory activity of ...4,518 drugs tested across 578 human cancer cell lines. We used PRISM, a molecular barcoding method, to screen drugs against cell lines in pools. An unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines in a manner predictable from the cell lines' molecular features. Our findings include compounds that killed by inducing PDE3A-SLFN12 complex formation; vanadium-containing compounds whose killing depended on the sulfate transporter SLC26A2; the alcohol dependence drug disulfiram, which killed cells with low expression of metallothioneins; and the anti-inflammatory drug tepoxalin, which killed via the multi-drug resistance protein ABCB1. The PRISM drug repurposing resource (https://depmap.org/repurposing) is a starting point to develop new oncology therapeutics, and more rarely, for potential direct clinical translation.
A sewer main serving a large municipal wastewater system ruptured, discharging approximately 3,000,000 gallons (11,355,000
L) of raw human sewage into a multi-branched tidal creek estuary along the ...US East Coast. The biochemical oxygen demand caused severe hypoxia in the system, causing a large fish kill. The sewage load led to high fecal coliform bacteria concentrations in the creek (maximum of 270,000
CFU 100
ml
−1), which declined in an approximate logarithmic manner over the first few days. The spill caused elevated sediment fecal coliform bacteria and enterococcus counts that declined much more gradually than water column counts. Persistence of relatively high concentrations of fecal indicator bacteria in sediments for several weeks after the spill suggests that sediment sampling should be included in response to major sewage spills. The high concentration of nutrients in the spilled sewage led to several algal blooms. However, nutrient concentrations in the water column declined rapidly, demonstrating the value of conserving marshes because of their pollutant filtration function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In this book, Author Katharine N. Harrington examines contemporary writers from the French-speaking world who can be classified as literary “nomads.” The concept of nomadism, based on the experience ...of traditionally mobile peoples lacking any fixed home, reflects a postmodern way of thinking that encourages individuals to reconsider rigid definitions of borders, classifications, and identities. Nomadic identities reflect shifting landscapes that defy taking on fully the limits of any one fixed national or cultural identity. In conceiving of identities beyond the boundaries of national or cultural origin, this book opens up the space for nomadic subjects whose identity is based just as much on their geographical displacement and deterritorialization as on a relationship to any one fixed place, community, or culture. This study explores the experience of an existence between borders and its translation into writing that. While nomadism is frequently associated with post-colonial authors, this study considers an eclectic group of contemporary Francophone writers who are not easily defined by the boundaries of one nation, one culture, or one language. Each of the four writers, J.M.G. LeClézio, Nancy Huston, Nina Bouraoui, and Régine Robin maintains a connection to France, but it is one that is complicated by life experiences, backgrounds, and choices that inevitably expand their identities beyond the Hexagon. Harrington examines how these authors’ life experiences are reflected in their writing and how they may inform us on the state of our increasingly global world where borders and identities are blurred.
This research explores the impacts of a broad range of supplemental carbon sources on growth and development of
Arabidopsis thaliana
. Parameters measured include dark-germinated hypocotyl length, ...light-germinated root growth, rosette growth, chlorophyll concentration and anthocyanin content. Treatment sugars include sucrose, maltose,
d
-glucose,
d
-fructose,
l
-arabinose,
l
-fucose,
d
-galactose,
d
-mannose,
l
-rhamnose and
d
-xylose each supplied at 4, 20 or 100 mM. This comparison of the effect of different carbon sources on multiple parameters and under identical conditions showed that every carbon source had unique qualitative and quantitative effects on
Arabidopsis
growth and development. Root growth was particularly sensitive to supplemental carbon source. Growth on 100 mM sucrose, maltose, glucose or xylose stimulated root growth by ~100%. Growth on arabinose, fucose, galactose, mannose or rhamnose inhibited root growth by 50% or more. Several sugars that strongly inhibited root growth had either no effect (galactose and fucose) or a positive effect (arabinose) on hypocotyl elongation and rosette growth. Rhamnose was the only carbon source that inhibited hypocotyl elongation across all concentrations. Sucrose, maltose, glucose, fructose, arabinose or xylose stimulated rosette growth by ~50%. Chlorophyll content was strongly reduced by mannose while sucrose, glucose, galactose and rhamnose caused smaller reductions. Anthocyanin accumulation was strongly induced by both galactose and mannose. Only mannose impacted all parameters across all concentrations. Based on these data it can be concluded that the effect of each carbon source on
Arabidopsis
growth and development is specific in terms of both magnitude and the parameters impacted.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ultraconserved enhancer sequences show perfect conservation between human and rodent genomes, suggesting that their functions are highly sensitive to mutation. However, current models of enhancer ...function do not sufficiently explain this extreme evolutionary constraint. We subjected 23 ultraconserved enhancers to different levels of mutagenesis, collectively introducing 1,547 mutations, and examined their activities in transgenic mouse reporter assays. Overall, we find that the regulatory properties of ultraconserved enhancers are robust to mutation. Upon mutagenesis, nearly all (19/23, 83%) still functioned as enhancers at one developmental stage, as did most of those tested again later in development (5/9, 56%). Replacement of endogenous enhancers with mutated alleles in mice corroborated results of transgenic assays, including the functional resilience of ultraconserved enhancers to mutation. Our findings show that the currently known activities of ultraconserved enhancers do not necessarily require the perfect conservation observed in evolution and suggest that additional regulatory or other functions contribute to their sequence constraint.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
•Interest in intraindividual brain signal variability is growing in basic and clinical studies.•We examined the reproducibility and efficiency of multiscale entropy algorithms.•Most measures ...exhibited acceptable psychometric properties with wide differences in computational efficiency.
There is a broad family of statistical methods for capturing time series regularity, with increasingly widespread adoption by the neuroscientific community. A common feature of these methods is that they permit investigators to quantify the entropy of brain signals – an index of unpredictability/complexity. Despite the proliferation of algorithms for computing entropy from neural time series data there is scant evidence concerning their relative stability and efficiency. Here we evaluated several different algorithmic implementations (sample, fuzzy, dispersion and permutation) of multiscale entropy in terms of their stability across sessions, internal consistency and computational speed, accuracy and precision using a combination of electroencephalogram (EEG) and synthetic 1/ƒ noise signals. Overall, we report fair to excellent internal consistency and longitudinal stability over a one-week period for the majority of entropy estimates, with several caveats. Computational timing estimates suggest distinct advantages for dispersion and permutation entropy over other entropy estimates. Considered alongside the psychometric evidence, we suggest several ways in which researchers can maximize computational resources (without sacrificing reliability), especially when working with high-density M/EEG data or multivoxel BOLD time series signals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Aim
To describe the nature and consequences of the multi-system genetic condition cystic fibrosis with a view to ensuring optimal dental treatment planning for these patients.
Methods
A literature ...search was conducted to identify the key medical and dental manifestations of cystic fibrosis. These findings are discussed and utilised to create recommendations for treatment planning in patients with cystic fibrosis for the practising dental practitioner.
Results
Cystic fibrosis is a complex, lethal, multisystem autosomal recessive disorder resulting from mutations on chromosome 7 which result in dysfunction of an ion channel that sits on epithelial surfaces. Respiratory disease remains the leading cause of mortality. Survival has greatly increased in recent decades secondary to improved treatment and specialist care. Specific dental manifestations of the disease may result from the condition itself or complications of treatment. Modification of patient management may be necessary to provide optimum patient care.
Conclusion
The pathophysiology and clinical manifestations are relevant to practicing dental practitioners and inform recommendations to be utilised to ensure optimal treatment planning for these patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Issue: Research shows that for the quickly growing older adult population, sustaining independence in everyday activities is a prevalent challenge, often as a result of functional limitations. Along ...with preexisting impairments, physical and sensory age-related changes contribute to older adults experiencing difficulties in functional limitations in performing basic, instrumental, and enhanced activities of daily living. Since many older adults elect to compensate for these challenges through the use of assistive technology, there is a need for technological support solutions that facilitate autonomy and independence among older adults, and relieve the burden of formal and informal caregivers. Method: In this paper we extract pertinent information from survey data in studies that examined the challenges faced by older adults in the USA and we provide direction for the use of appropriate technological solutions. We explore the associated existing assistive technology solutions as well as the acceptance of these technologies by older adults including major barriers to their usage. Results: There is very little recent data available to speak to the current needs of older adults with functional limitations. While several technological support solutions exist, there are issues of acceptance and adoption that deem these solutions ineffective, leading to low usage rates. As a result, we discuss the potential of accessible everyday technologies to meet unfulfilled needs. Conclusion: However, our review highlights the need for more recent data on functional limitations of older adults and provides a call to action for more research to understand older adults' support needs.
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