Cardiovascular disease is a leading cause of death around the world. Overall diet quality and dietary behaviors are core contributors to metabolic health. While therapeutic targets have traditionally focused on levels of lipoprotein cholesterol when evaluating cardiovascular risk, current perspectives on high-density lipoprotein (HDL) have shifted to evaluating the functionality of this lipoprotein particle. Effects of diet on cardiovascular health are mediated through multiple pathways, but the impact on HDL composition and function deserves greater attention. Potential areas of investigation involve changes in particle characteristics, distribution, microRNA cargo, and other functional changes such as improvements to cholesterol efflux capacity. Various dietary patterns like the Mediterranean diet and Dietary Approaches to Stop Hypertension (DASH) diet have beneficial effects on cardiovascular health and may prevent cardiovascular events. These healthful dietary patterns tend to be rich in plant-based foods, with cardiovascular benefits likely resulting from synergistic effects of the individual dietary components. The purpose of this review is to summarize current perspectives on selected functions of HDL particles and how various dietary patterns affect cardiovascular health biomarkers, with a focus on HDL functionality.

The ribosome translates the genetic code into proteins in all domains of life. Its size and complexity demand long-range interactions that regulate ribosome function. These interactions are largely unknown. Here, we apply a global coevolution method, statistical coupling analysis (SCA), to identify coevolving residue networks (sectors) within the 23S ribosomal RNA (rRNA) of the large ribosomal subunit. As in proteins, SCA reveals a hierarchical organization of evolutionary constraints with near-independent groups of nucleotides forming physically contiguous networks within the three-dimensional structure. Using a quantitative, continuous-culture-with-deep-sequencing assay, we confirm that the top two SCA-predicted sectors contribute to ribosome function. These sectors map to distinct ribosome activities, and their origins trace to phylogenetic divergences across all domains of life. These findings provide a foundation to map ribosome allostery, explore ribosome biogenesis, and engineer ribosomes for new functions. Despite differences in chemical structure, protein and RNA enzymes appear to share a common internal logic of interaction and assembly.

Marine microbial communities mediate many biogeochemical transformations in the ocean. Consequently, processes such as primary production and carbon (C) export are linked to nutrient regeneration and are influenced by the resource demand and elemental composition of marine microbial biomass. Laboratory studies have demonstrated that differential partitioning of element resources to various cellular components can directly influence overall cellular elemental ratios, especially with respect to growth machinery (i.e., ribosomal RNA) and phosphorus (P) allocation. To investigate whether allocation to RNA is related to biomass P content and overall C : P biomass composition in the open ocean, we characterized patterns of P allocation and C : P elemental ratios along an environmental gradient of phosphate supply in the North Atlantic subtropical gyre (NASG) from 35.67° N, 64.17° W to 22.676° N, 65.526° W. Because the NASG is characterized as a P-stressed ecosystem, we hypothesized that biochemical allocation would reflect sensitivity to bioavailable phosphate, such that greater phosphate supply would result in increased allocation toward P-rich RNA for growth. We predicted these changes in allocation would also result in lower C : P ratios with increased phosphate supply. However, bulk C : P ratios were decoupled from allocation to nucleic acids and did not appear to vary systematically across a phosphate supply gradient of 2.2–14.7 μmol m⁻² d⁻¹. Overall, we found that C : P ratios ranged from 188 to 306 along the transect, and RNA represented only 6–12% of total particulate P, whereas DNA represented 11–19%. We did find that allocation to RNA was positively correlated with phosphate supply rate, suggesting a consistent physiological response in biochemical allocation to resource supply within the whole community. These results suggest that community composition and/or nonnucleic acid P pools may influence ecosystem-scale variation in C : P stoichiometry more than nucleic acid allocation or P supply in diverse marine microbial communities.

The purpose of this review is to identify clinical risk factors for prostate cancer and to assess the utility and limitations of our current tools for prostate cancer screening. Prostate-specific antigen is the single most important factor for identifying men at increased risk of prostate cancer but is best assessed in the context of other clinical factors; increasing age, race, and family history are well-established risk factors for the diagnosis of prostate cancer. In addition to clinical risk calculators, novel tools such as multiparametric imaging, serum or urinary biomarkers, and genetic profiling show promise in improving prostate cancer diagnosis and characterization. Optimal use of existing and future tools will help alleviate the problems of overdiagnosis and overtreatment of low-risk prostate cancer without reversing the substantial mortality declines that have been achieved in the screening era.

Epidermal necrolysis, the unifying term for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), is a severe cutaneous drug reaction associated with high morbidity and mortality. Given the rarity of this disease, large-scale prospective research studies are limited. Significant institutional and geographical variations in treatment practices highlight the need for standardization of clinical assessment scores and prioritization of research outcome measures in epidermal necrolysis. At the present, clinical assessment is typically simplified to total body surface area (BSA) involvement, with little focus on morphology. Validated clinical scoring systems are used as mortality prognostication tools, with SCORTEN being the best-validated tool thus far, although the ABCD-10 has also been recently introduced. These tools are imperfect in that they tend to either overestimate or underestimate mortality in certain populations and are not designed to monitor disease progression. Although mortality is often used as a primary endpoint for epidermal necrolysis studies, this outcome fails to capture more nuanced changes in skin disease such as arrest of disease progression while also lacking a validated skin-directed inclusion criterion to stratify patients based on the severity of skin disease at study entry. In addition to mortality, many studies also use BSA stabilization or time to re-epithelialization as endpoints, although these are not clearly defined morphologically, and inter- and intra-rater reliability are unclear. More specific, validated cutaneous assessment scores are necessary in order advance therapeutic options for epidermal necrolysis. In this review, we summarize the strengths and weaknesses of current clinical assessment practices in epidermal necrolysis and highlight the need for standardized research tools to monitor cutaneous involvement throughout the hospitalization.

The elemental ratios of marine phytoplankton emerge from complex interactions between the biotic and abiotic components of the ocean, and reflect the plastic response of individuals to changes in their environment. The stoichiometry of phytoplankton is, thus, dynamic and dependent on the physiological state of the cell. We present a theoretical model for the dynamics of the carbon, nitrogen and phosphorus contents of a phytoplankton population. By representing the regulatory processes controlling nutrient uptake, and focusing on the relation between nutrient content and protein synthesis, our model qualitatively replicates existing experimental observations for nutrient content and ratios. The population described by our model takes up nutrients in proportions that match the input ratios for a broad range of growth conditions. In addition, there are two zones of single-nutrient limitation separated by a wide zone of co-limitation. Within the co-limitation zone, a single point can be identified where nutrients are supplied in an optimal ratio. When different species compete, the existence of a wide co-limitation zone implies a more complex pattern of coexistence and exclusion compared to previous model predictions. However, additional comprehensive laboratory experiments are needed to test our predictions. Our model contributes to the understanding of the global cycles of oceanic nitrogen and phosphorus, as well as the elemental ratios of these nutrients in phytoplankton populations.