Whether dietary fiber protects against colorectal cancer is controversial because of conflicting results from human epidemiologic studies. However, these studies and mouse models of colorectal cancer ...have not controlled the composition of gut microbiota, which ferment fiber into short-chain fatty acids such as butyrate. Butyrate is noteworthy because it has energetic and epigenetic functions in colonocytes and tumor-suppressive properties in colorectal cancer cell lines. We used gnotobiotic mouse models colonized with wild-type or mutant strains of a butyrate-producing bacterium to demonstrate that fiber does have a potent tumor-suppressive effect but in a microbiota- and butyrate-dependent manner. Furthermore, due to the Warburg effect, butyrate was metabolized less in tumors where it accumulated and functioned as a histone deacetylase (HDAC) inhibitor to stimulate histone acetylation and affect apoptosis and cell proliferation. To support the relevance of this mechanism in human cancer, we demonstrate that butyrate and histone-acetylation levels are elevated in colorectal adenocarcinomas compared with normal colonic tissues.
These results, which link diet and microbiota to a tumor-suppressive metabolite, provide insight into conflicting epidemiologic findings and suggest that probiotic/prebiotic strategies can modulate an endogenous HDAC inhibitor for anticancer chemoprevention without the adverse effects associated with synthetic HDAC inhibitors used in chemotherapy.
Intermediate-depth earthquakes (30-300 km) have been extensively documented within subducting oceanic slabs, but their mechanics remains enigmatic. Here we decipher the mechanism of these earthquakes ...by performing deformation experiments on dehydrating serpentinized peridotites (synthetic antigorite-olivine aggregates, minerals representative of subduction zones lithologies) at upper mantle conditions. At a pressure of 1.1 gigapascals, dehydration of deforming samples containing only 5 vol% of antigorite suffices to trigger acoustic emissions, a laboratory-scale analogue of earthquakes. At 3.5 gigapascals, acoustic emissions are recorded from samples with up to 50 vol% of antigorite. Experimentally produced faults, observed post-mortem, are sealed by fluid-bearing micro-pseudotachylytes. Microstructural observations demonstrate that antigorite dehydration triggered dynamic shear failure of the olivine load-bearing network. These laboratory analogues of intermediate-depth earthquakes demonstrate that little dehydration is required to trigger embrittlement. We propose an alternative model to dehydration-embrittlement in which dehydration-driven stress transfer, rather than fluid overpressure, causes embrittlement.
Herpes simplex virus 1 (HSV1) is best known for causing oral lesions and mild clinical symptoms, but it can produce a significant range of disease severities and rates of reactivation. To better ...understand this phenotypic variation, we characterized 11 HSV1 strains that were isolated from individuals with diverse infection outcomes. We provide new data on genomic and
plaque phenotype analysis for these isolates and compare these data to previously reported quantitation of the disease phenotype of each strain in a murine animal model. We show that integration of these three types of data permitted clustering of these HSV1 strains into four groups that were not distinguishable by any single dataset alone, highlighting the benefits of combinatorial multi-parameter phenotyping. Two strains (group 1) produced a partially or largely syncytial plaque phenotype and attenuated disease phenotypes in mice. Three strains of intermediate plaque size, causing severe disease in mice, were genetically clustered to a second group (group 2). Six strains with the smallest average plaque sizes were separated into two subgroups (groups 3 and 4) based on their different genetic clustering and disease severity in mice. Comparative genomics and network graph analysis suggested a separation of HSV1 isolates with attenuated vs. virulent phenotypes. These observations imply that virulence phenotypes of these strains may be traceable to genetic variation within the HSV1 population.
Sampling seabirds
The vastness of the worlds' oceans makes them difficult to monitor. Seabirds that forage and breed across oceans globally have been recognized as sentinels of ocean health. Sydeman
...et al.
looked across seabird species of both the Northern and Southern Hemispheres and found varying patterns. Northern Hemisphere species exhibited greater signs of stress and reduced breeding success, indicative of low fish resources. Southern Hemisphere species showed less impact on reproductive output, suggesting that the fish populations there have thus far been less disturbed. The differences across hemispheres indicate different strategies for conservation, with active recovery needed in the north and enhanced protection in the south.
Science
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The breeding success of seabirds is tracking hemispheric differences in ocean warming and human impacts.
Climate change and other human activities are causing profound effects on marine ecosystem productivity. We show that the breeding success of seabirds is tracking hemispheric differences in ocean warming and human impacts, with the strongest effects on fish-eating, surface-foraging species in the north. Hemispheric asymmetry suggests the need for ocean management at hemispheric scales. For the north, tactical, climate-based recovery plans for forage fish resources are needed to recover seabird breeding productivity. In the south, lower-magnitude change in seabird productivity presents opportunities for strategic management approaches such as large marine protected areas to sustain food webs and maintain predator productivity. Global monitoring of seabird productivity enables the detection of ecosystem change in remote regions and contributes to our understanding of marine climate impacts on ecosystems.
Surface curvature both emerges from, and influences the behavior of, living objects at length scales ranging from cell membranes to single cells to tissues and organs. The relevance of surface ...curvature in biology is supported by numerous experimental and theoretical investigations in recent years. In this review, first, a brief introduction to the key ideas of surface curvature in the context of biological systems is given and the challenges that arise when measuring surface curvature are discussed. Giving an overview of the emergence of curvature in biological systems, its significance at different length scales becomes apparent. On the other hand, summarizing current findings also shows that both single cells and entire cell sheets, tissues or organisms respond to curvature by modulating their shape and their migration behavior. Finally, the interplay between the distribution of morphogens or micro‐organisms and the emergence of curvature across length scales is addressed with examples demonstrating these key mechanistic principles of morphogenesis. Overall, this review highlights that curved interfaces are not merely a passive by‐product of the chemical, biological, and mechanical processes but that curvature acts also as a signal that co‐determines these processes.
Curvature as a local descriptor for shape has been revealed to play a fundamental role in the development of biological systems. Advanced 3D characterization methods allow its quantification across time and length scales indicating that cells and tissue growth can cause emergence of curved surfaces but in turn curvature also acts as a trigger for specific biological processes.
Lower physical activity levels and greater fatigability contribute independently to slower gait speed in older adults. To fully understand the bidirectional relations between physical activity and ...fatigability, and to inform potential intervention strategies, we examined whether physical activity or fatigability explains more of the other factor's association on slower gait speed.
Two generations (probands and offspring) of older adults (N = 2079, mean age 73.0 ± 10.0 years, 54.2% women, 99.7% White) enrolled in the Long Life Family Study were assessed at Visit 2 (2014-2017). Self-reported physical activity was measured with the Framingham Physical Activity Index and perceived physical fatigability using the Pittsburgh Fatigability Scale. Statistical mediation analyses were conducted separately by generation with linear mixed-effect models accounting for family relatedness and adjusted for demographics, health conditions, and field center.
Greater perceived physical fatigability explained the association of lower physical activity on slower gait speed via a 22.5% attenuation of the direct association (95% confidence interval CI: 15.0%-35.2%) for the probands and 39.5% (95% CI: 22.8%-62.6%) for the offspring. Whereas lower physical activity explained the association of greater perceived fatigability on slower gait speed via a 22.5% attenuation of the direct association (95% CI: 13.4%-32.8%) for the probands and 6.7% (95% CI: 3.8%-15.4%) for the offspring.
Our findings suggest that the impact of greater perceived physical fatigability on the association between lower physical activity and slower gait speed differs between younger-old and middle-to-oldest-old adults, indicating perceived physical fatigability as a potential mediator in the disablement pathway.
Shyama Kuruvilla and colleagues present findings across 12 country case studies of multisectoral collaboration, showing how diverse sectors intentionally shape new ways of collaborating and learning, ...using “business not as usual” strategies to transform situations and achieve shared goals
Objective: Obstructive sleep apnea (OSA) is a risk factor for motor vehicle crashes (MVC), and patients with diagnosed OSA have a higher likelihood of being involved in a traffic accident. OSA, ...however, is often underdiagnosed in the general population. The purpose of this study was to assess the risk of undiagnosed OSA among hospitalized patients involved in MVCs.
Methods: This is a prospective, observational pilot study of adult trauma patients admitted to a Level 1 trauma center after being the driver in a MVC. Patients were administered the STOP-Bang to assess risk of OSA and were asked questions about the circumstances of the MVC. Patients with a STOP-Bang score 5-8 were considered to be at high risk for OSA. Differences between variables were assessed using independent t-tests and chi-square.
Results: Eighty patients participated in the study, and 26% (n = 21) were considered to be at high risk for OSA based on the STOP-Bang score. Compared to patients at low and intermediate risk, patients at high risk for OSA were significantly older (p < .001), had longer hospitalization (p = .06), and were less likely to discharge home from the hospital (p = .01). Patients at moderate and high risk had higher rates of hospital readmission within 1 year of discharge, when compared to the low risk group. Eighty-four percent of all crashes involved a single occupant (driver) in the vehicle, 58% involved only a single vehicle, and 40% occurred on a rural road. There were no significant differences between risk groups for number of vehicles involved in the accident, location of the accident, or number of vehicle occupants.
Conclusions: Results of this pilot study suggest that more than one-quarter of drivers hospitalized after motor vehicle crashes were at high risk for OSA. Diagnosed or undiagnosed OSA is a significant public health concern and an established risk factor for motor vehicle accidents. Standardized screening for risk of sleep apnea should be considered by primary care physicians when guiding patients on health and behavior decisions, particularly in regards to driving and road safety.
A challenge for screening new anticancer drugs is that efficacy in cell culture models is not always predictive of efficacy in patients. One limitation of standard cell culture is a reliance on ...non-physiological nutrient levels, which can influence cell metabolism and drug sensitivity. A general assessment of how physiological nutrients affect cancer cell response to small molecule therapies is lacking. To address this, we developed a serum-derived culture medium that supports the proliferation of diverse cancer cell lines and is amenable to high-throughput screening. We screened several small molecule libraries and found that compounds targeting metabolic enzymes were differentially effective in standard compared to serum-derived medium. We exploited the differences in nutrient levels between each medium to understand why medium conditions affected the response of cells to some compounds, illustrating how this approach can be used to screen potential therapeutics and understand how their efficacy is modified by available nutrients.
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•Describing a serum-derived culture medium amenable to high-throughput screening•Metabolic drugs as a class show differential efficacy in different media•Differential compound efficacy is explained by different media nutrient levels
Drug response often differs between in vitro and in vivo conditions. Abbott et al. examine how nutrient availability affects drug efficacy by screening compounds in standard versus serum-derived medium. Compounds targeting metabolism were enriched, underscoring the importance of nutrient availability on response to these drugs.
Ecological restoration is a crucial tool for mitigating climate change and addressing the global biodiversity crisis. The extensive knowledge of Black, Indigenous and People of Colour (BIPOC) will ...play a key role in accelerating the advancement of restoration efforts but has historically been excluded. BIPOC traditions and practices of protecting and restoring ecological communities include intricate socio‐ecological systems whose holistic practices preserve cultural knowledge while simultaneously addressing environmental issues.
If we are to have a seat at the table for everyone and meet the lofty goals of the U.N. Decade on Ecosystem Restoration to contribute to reversing the biodiversity and climate crises, the field of restoration ecology can no longer afford to exclude BIPOC communities and their irreplaceable social, cultural, and ecological knowledge.
Solution: We offer opportunities to engage BIPOC communities and their contributions to restoration, and to introduce a restoration community to connect and center BIPOC through the Black Earth Restoration Collective. This is a call to action to those with power and access in restoration ecology to make vital shifts needed to accomplish a more equitable and just approach to restoration.
Ecological restoration is a crucial tool for mitigating climate change and the global biodiversity crisis, but the extensive knowledge of Black, Indigenous and People of Colour (BIPOC) is often excluded though will play a key role in accelerating the advancement of restoration efforts. We argue for the inclusion of BIPOC into restoration, their ideas and introduce The Black Earth Restoration Collective to propel this need and work.
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