High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: Interaction with IQ motif-containing factors

Triple-negative breast cancer (TNBC) represents an aggressive subtype, for which radiation and chemotherapy are the only options. Here we describe the identification of disulfiram, an FDA-approved drug used to treat alcoholism, as well as the related compound thiram, as the most potent growth inhibitors following high-throughput screens of 3185 compounds against multiple TNBC cell lines. The average IC₅₀ for disulfiram was ~300 nM. Drug affinity responsive target stability (DARTS) analysis identified IQ motif-containing factors IQGAP1 and MYH9 as direct binding targets of disulfiram. Indeed, knockdown of these factors reduced, though did not completely abolish, cell growth. Combination treatment with 4 different drugs commonly used to treat TNBC revealed that disulfiram synergizes most effectively with doxorubicin to inhibit cell growth of TNBC cells. Disulfiram and doxorubicin cooperated to induce cell death as well as cellular senescence, and targeted the ESA⁺/CD24^-/low/CD44⁺ cancer stem cell population. Our results suggest that disulfiram may be repurposed to treat TNBC in combination with doxorubicin.     

Availability of and Ease of Access to Calorie Information on Restaurant Websites

Objective

Offering calories on restaurant websites might be particularly important for consumer meal planning, but the availability of and ease of accessing this information are unknown.

Methods

We assessed websites for the top 100 U.S. chain restaurants to determine the availability of and ease of access to calorie information as well as website design characteristics. We also examined potential predictors of calorie availability and ease of access.

Results

Eighty-two percent of restaurants provided calorie information on their websites; 25% presented calories on a mobile-formatted website. On average, calories could be accessed in 2.35±0.99 clicks. About half of sites (51.2%) linked to calorie information via the homepage. Fewer than half had a separate section identifying healthful options (46.3%), or utilized interactive meal planning tools (35.4%). Quick service/fast casual, larger restaurants, and those with less expensive entrées and lower revenue were more likely to make calorie information available. There were no predictors of ease of access.

Conclusion

Calorie information is both available and largely accessible on the websites of America’s leading restaurants. It is unclear whether consumer behavior is affected by the variability in the presentation of calorie information.     

The decline and rise of the Kransberg Cape Vulture colony over 35 years has implications for composite population indices and survey frequency

Long-term monitoring is key for detecting population declines. Composite indices allow researchers to combine trends from disparate monitoring programmes into a single estimate of population change. Inferences from composite indices, however, are limited to the time periods and areas studied. We show that the number of breeding pairs in a colony of Cape Vultures Gyps coprotheres in South Africa declined between the years 1983 and 2003 but increased in both the number of breeding pairs and fledglings per pair from 2004 to 2017. We performed a retrospective power analysis determining the minimum annual frequency with which the colony could have been monitored without sacrificing inference into population trends. This power analysis revealed the post-2003 population increase would not have been apparent if we skipped more than 2 years between surveys. We incorporated our estimates into a previously published composite index for Cape Vultures that considered only data collected pre-2000 and demonstrate that the inference is unchanged if the trend from the decline period or the entire study is incorporated, yet if only the trend during the period of population increase is used, there is no longer a statistically significant decline across the species’ range. Our results demonstrate the utility of long-term monitoring because if our study had concluded before 2003, there would be little evidence of the current population increase at Kransberg.     

An experimental investigation into the effects of traffic noise on distributions of birds: avoiding the phantom road

Many authors have suggested that the negative effects of roads on animals are largely owing to traffic noise. Although suggestive, most past studies of the effects of road noise on wildlife were conducted in the presence of the other confounding effects of roads, such as visual disturbance, collisions and chemical pollution among others. We present, to our knowledge, the first study to experimentally apply traffic noise to a roadless area at a landscape scale—thus avoiding the other confounding aspects of roads present in past studies. We replicated the sound of a roadway at intervals—alternating 4 days of noise on with 4 days off—during the autumn migratory period using a 0.5 km array of speakers within an established stopover site in southern Idaho. We conducted daily bird surveys along our ‘Phantom Road’ and in a nearby control site. We document over a one-quarter decline in bird abundance and almost complete avoidance by some species between noise-on and noise-off periods along the phantom road and no such effects at control sites—suggesting that traffic noise is a major driver of effects of roads on populations of animals.     

Cryptic diversity in flathead fishes (Scorpaeniformes: Platycephalidae) across the Indo‐West Pacific uncovered by DNA barcoding

Identification of taxonomical units underpins most biological endeavours ranging from accurate biodiversity estimates to the effective management of sustainably harvested, protected or endangered species. Successful species identification is now frequently based on a combination of approaches including morphometrics and DNA markers. Sequencing of the mitochondrial COI gene is an established methodology with an international campaign directed at barcoding all fishes. We employed COI sequencing alongside traditional taxonomic identification methods and uncovered instances of deep intraspecific genetic divergences among flathead species. Sixty‐five operational taxonomic units (OTUs) were observed across the Indo‐West Pacific from just 48 currently recognized species. The most comprehensively sampled taxon, Platycephalus indicus, exhibited the highest levels of genetic diversity with eight lineages separated by up to 16.37% genetic distance. Our results clearly indicate a thorough reappraisal of the current taxonomy of P. indicus (and its three junior synonyms) is warranted in conjunction with detailed taxonomic work on the other additional Platycephalidae OTUs detected by DNA barcoding.     

Maternal Immunization Confers Protection to the Offspring against an Attaching and Effacing Pathogen through Delivery of IgG in Breast Milk

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Engineered blood and lymphatic capillaries in 3-D VEGF-fibrin-collagen matrices with interstitial flow

In vitro endothelial cell organization into capillaries is a long standing challenge of tissue engineering. We recently showed the utility of low level interstitial flow in guiding the organization of endothelial cells through a 3-D fibrin matrix-containing covalently bound vascular endothelial growth factor (VEGF). Here this synergistic phenomenon was extended to explore the effects of matrix composition on in vitro capillary morphogenesis of human blood versus lymphatic endothelial cells (BECs and LECs). Different mixtures of fibrin and collagen were used in conjunction with constant concentrations of matrix-bound VEGF and slow interstitial flow over 10 days. Interestingly, the BECs and LECs each showed a distinct preference in terms of organization for matrix composition: LECs organized the most extensively in a fibrin-only matrix, while BEC organization was optimized in the compliant collagen-containing matrices. Furthermore, the BECs and LECs produced architecturally different structures; while BECs organized in thick, branched networks containing wide lumen, the LECs were elongated into slender, overlapping networks with fine lumen. These data demonstrate the importance of the 3-D matrix composition in facilitating and coordinating BEC and LEC capillary morphogenesis, which is important for in vitro vascularization of engineered tissues.