Complete head cerebral sensitivity mapping for diffuse correlation spectroscopy using subject-specific magnetic resonance imaging models

We characterize cerebral sensitivity across the entire adult human head for diffuse correlation spectroscopy, an optical technique increasingly used for bedside cerebral perfusion monitoring. Sixteen subject-specific magnetic resonance imaging-derived head models were used to identify high sensitivity regions by running Monte Carlo light propagation simulations at over eight hundred uniformly distributed locations on the head. Significant spatial variations in cerebral sensitivity, consistent across subjects, were found. We also identified correlates of such differences suitable for real-time assessment. These variations can be largely attributed to changes in extracerebral thickness and should be taken into account to optimize probe placement in experimental settings

The Seasonal Flux and Fate of Dissolved Organic Carbon Through Bacterioplankton in the Western North Atlantic

The oceans teem with heterotrophic bacterioplankton that play an appreciable role in the uptake of dissolved organic carbon (DOC) derived from phytoplankton net primary production (NPP). As such, bacterioplankton carbon demand (BCD), or gross heterotrophic production, represents a major carbon pathway that influences the seasonal accumulation of DOC in the surface ocean and, subsequently, the potential vertical or horizontal export of seasonally accumulated DOC. Here, we examine the contributions of bacterioplankton and DOM to ecological and biogeochemical carbon flow pathways, including those of the microbial loop and the biological carbon pump, in the Western North Atlantic Ocean (∼39–54°N along ∼40°W) over a composite annual phytoplankton bloom cycle. Combining field observations with data collected from corresponding DOC remineralization experiments, we estimate the efficiency at which bacterioplankton utilize DOC, demonstrate seasonality in the fraction of NPP that supports BCD, and provide evidence for shifts in the bioavailability and persistence of the seasonally accumulated DOC. Our results indicate that while the portion of DOC flux through bacterioplankton relative to NPP increased as seasons transitioned from high to low productivity, there was a fraction of the DOM production that accumulated and persisted. This persistent DOM is potentially an important pool of organic carbon available for export to the deep ocean via convective mixing, thus representing an important export term of the biological carbon pump

The Seasonal Flux and Fate of Dissolved Organic Carbon Through Bacterioplankton in the Western North Atlantic

The oceans teem with heterotrophic bacterioplankton that play an appreciable role in the uptake of dissolved organic carbon (DOC) derived from phytoplankton net primary production (NPP). As such, bacterioplankton carbon demand (BCD), or gross heterotrophic production, represents a major carbon pathway that influences the seasonal accumulation of DOC in the surface ocean and, subsequently, the potential vertical or horizontal export of seasonally accumulated DOC. Here, we examine the contributions of bacterioplankton and DOM to ecological and biogeochemical carbon flow pathways, including those of the microbial loop and the biological carbon pump, in the Western North Atlantic Ocean (∼39–54°N along ∼40°W) over a composite annual phytoplankton bloom cycle. Combining field observations with data collected from corresponding DOC remineralization experiments, we estimate the efficiency at which bacterioplankton utilize DOC, demonstrate seasonality in the fraction of NPP that supports BCD, and provide evidence for shifts in the bioavailability and persistence of the seasonally accumulated DOC. Our results indicate that while the portion of DOC flux through bacterioplankton relative to NPP increased as seasons transitioned from high to low productivity, there was a fraction of the DOM production that accumulated and persisted. This persistent DOM is potentially an important pool of organic carbon available for export to the deep ocean via convective mixing, thus representing an important export term of the biological carbon pump

Neonatal NET-Inhibitory Factor improves survival in the cecal ligation and puncture model of polymicrobial by inhibiting neutrophil extracellular traps

IntroductionNeutrophil extracellular traps (NETs) clear pathogens but may contribute Q8 pathogenically to host inflammatory tissue damage during sepsis. Innovative therapeutic agents targeting NET formation and their potentially harmful collateral effects remain understudied.MethodsWe investigated a novel therapeutic agent, neonatal NET-Inhibitory Factor (nNIF), in a mouse model of experimental sepsis – cecal ligation and puncture (CLP). We administered 2 doses of nNIF (1 mg/ kg) or its scrambled peptide control intravenously 4 and 10 hours after CLP treatment and assessed survival, peritoneal fluid and plasma NET formation using the MPO-DNA ELISA, aerobic bacterial colony forming units (CFU) using serial dilution and culture, peritoneal fluid and stool microbiomes using 16S rRNA gene sequencing, and inflammatory cytokine levels using a multiplexed cytokine array. Meropenem (25 mg/kg) treatment served as a clinically relevant treatment for infection.ResultsWe observed increased 6-day survival rates in nNIF (73%) and meropenem (80%) treated mice compared to controls (0%). nNIF decreased NET formation compared to controls, while meropenem did not impact NET formation. nNIF treatment led to increased peritoneal fluid and plasma bacterial CFUs consistent with loss of NET-mediated extracellular microbial killing, while nNIF treatment alone did not alter the peritoneal fluid and stool microbiomes compared to vehicle-treated CLP mice. nNIF treatment also decreased peritoneal TNF-a inflammatory cytokine levels compared to scrambled peptide control. Furthermore, adjunctive nNIF increased survival in a model of sub-optimal meropenem treatment (90% v 40%) in CLP-treated mice.DiscussionThus, our data demonstrate that nNIF inhibits NET formation in a translationally relevant mouse model of sepsis, improves survival when given as monotherapy or as an adjuvant with antibiotics, and may play an important protective role in sepsis

Dietary patterns and associations with body mass index in low-income, ethnic minority youth in the United States according to baseline data from four randomized controlled trials

Few studies have derived data-driven dietary patterns in youth in the United States (US). This study examined data-driven dietary patterns and their associations with BMI measures in predominantly low-income, racial/ethnic minority US youth. Data were from baseline assessments of the four Childhood Obesity Prevention and Treatment Research (COPTR) Consortium trials: NET-Works (N=534; 2–4-year-olds), GROW (N=610; 3–5-year-olds), GOALS (N=241; 7–11-year-olds), and IMPACT (N=360; 10–13-year-olds). Weight and height were measured. Children/adult proxies completed 3 24-hour dietary recalls. Dietary patterns were derived for each site from 24 food/beverage groups using k-means cluster analysis. Multivariable linear regression models examined associations of dietary patterns with BMI and percentage of the 95th BMI percentile. Healthy (produce and whole grains) and Unhealthy (fried food, savory snacks, and desserts) patterns were found in NET-Works and GROW. GROW additionally had a dairy and sugar-sweetened beverage based pattern. GOALS had a similar Healthy pattern and a pattern resembling a traditional Mexican diet. Associations between dietary patterns and BMI were only observed in IMPACT. In IMPACT, youth in the Sandwich (cold cuts, refined grains, cheese, and miscellaneous [e.g., condiments]) compared to Mixed (whole grains and desserts) cluster had significantly higher BMI [β=0.99 (95% CI: 0.01, 1.97)] and percentage of the 95th BMI percentile [β=4.17 (95% CI: 0.11, 8.24)]. Healthy and Unhealthy patterns were the most common dietary patterns in COPTR youth, but diets may differ according to age, race/ethnicity, or geographic location. Public health messages focused on healthy dietary substitutions may help youth mimic a dietary pattern associated with lower BMI

Improving our fundamental understanding of the role of aerosol−cloud interactions in the climate system

The effect of an increase in atmospheric aerosol concentrations on the distribution and radiative properties of Earth’s clouds is the most uncertain component of the overall global radiative forcing from preindustrial time. General circulation models (GCMs) are the tool for predicting future climate, but the treatment of aerosols, clouds, and aerosol−cloud radiative effects carries large uncertainties that directly affect GCM predictions, such as climate sensitivity. Predictions are hampered by the large range of scales of interaction between various components that need to be captured. Observation systems (remote sensing, in situ) are increasingly being used to constrain predictions, but significant challenges exist, to some extent because of the large range of scales and the fact that the various measuring systems tend to address different scales. Fine-scale models represent clouds, aerosols, and aerosol−cloud interactions with high fidelity but do not include interactions with the larger scale and are therefore limited from a climatic point of view. We suggest strategies for improving estimates of aerosol−cloud relationships in climate models, for new remote sensing and in situ measurements, and for quantifying and reducing model uncertainty

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas