Children born very prematurely are deprived of maternal docosahexaenoic acid. This study shows an IQ at 5 years of age that was 3.5 points higher among children who had received neonatal DHA ...supplementation.
Abstract
An ecosystem-based flow analysis model was used to study carbon transfer from primary production (PP) to mesopelagic fish via three groups of copepods: detritivores that access sinking ...particles, vertical migrators, and species that reside in the surface ocean. The model was parameterized for 40°S to 40°N in the world ocean such that results can be compared with recent estimates of mesopelagic fish biomass in this latitudinal range, based on field studies using acoustic technologies, of ∼13 Gt (wet weight). Mesopelagic fish production was predicted to be 0.32% of PP which, assuming fish longevity of 1.5 years, gives rise to predicted mesopelagic fish biomass of 2.4 Gt. Model ensembles were run to analyse the uncertainty of this estimate, with results showing predicted biomass >10 Gt in only 8% of the simulations. The work emphasizes the importance of migrating animals in transferring carbon from the surface ocean to the mesopelagic zone. It also highlights how little is known about the physiological ecology of mesopelagic fish, trophic pathways within the mesopelagic food web, and how these link to PP in the surface ocean. A deeper understanding of these interacting factors is required before the potential for utilizing mesopelagic fish as a harvestable resource can be robustly assessed.
As a key variable in the climate system, soil moisture (SM) plays a central role in the Earth's terrestrial water, energy, and biogeochemical cycles through its coupling with surface latent heat flux ...(LH). Despite the need to accurately represent SM/LH coupling in Earth system models, we currently lack quantitative, observation‐based, and unbiased estimates of its strength. Here we utilize the triple‐collocation (TC) approach introduced in Crow et al. () to SM and LH products obtained from multiple satellite remote sensing platforms and land surface models (LSMs) to obtain unbiased global maps of SM/LH coupling strength. Results demonstrate that relative to coupling strength estimates acquired directly from remote sensing‐based data sets, the application of TC generally enhances estimates of warm‐season SM/LH coupling, especially in the western United States, the Sahel, central Asia, and Australia. However, relative to triple‐collocation estimates, LSMs (still) overpredict SM/LH coupling strength along transitional climate regimes between wet and dry climates, such as the central Great Plains of North America, India, and coastal Australia. Specific climate zones with biased relations in LSMs are identified to geographically focus the reexamination of LSM parameterizations. TC‐based coupling strength estimates are robust to our choice of LSM contributing SM and LH products to the TC analysis. Given their robustness, TC‐based coupling strength estimates can serve as an objective benchmark for investigating model‐predicted SM/LH coupling.
Plain Language Summary
Physical models describing land‐atmosphere coupling have been developed to help better understand the impact of local‐, regional‐, and global‐scale climate on weather and the water cycle. However, verifying the accuracy of these models is challenging over sparsely instrumented areas. Here the strength of land‐atmosphere coupling between soil moisture and terrestrial evapotranspiration is examined by combining multiple global‐scale remote sensing and modeling products into a unified analysis. This analysis is unique in that it can be conducted globally and is unbiased by the presence of random errors in the remote sensing products. As such it provides the first robust estimate of the degree to which soil moisture and evapotranspiration are linked. Results show strong soil moisture/evapotranspiration coupling over the western United States, the African Sahel, central Asia, and Australia. However, they also demonstrate that most existing models are still overpredicting this coupling along transitional regions between wet and dry climates (like the Central Great Plains of North America, India, and coastal Australia). This work will help improve the representation of land‐atmosphere coupling in models used to obtain future climate projections.
Key Points
Multiple sources of remote sensing‐based soil moisture and latent heat flux products are integrated via triple collocation
Global observation‐based estimates of coupling strength between surface soil moisture and latent heat flux are obtained
Land surface models overestimate the strength of this coupling along transitional climate regimes
We apply near-threshold laser photodetachment to characterize the rotational quantum level distribution of OH^{-} ions stored in the cryogenic ion-beam storage ring DESIREE at Stockholm University. ...We find that the stored ions relax to a rotational temperature of 13.4±0.2 K with 94.9±0.3% of the ions in the rotational ground state. This is consistent with the storage ring temperature of 13.5±0.5 K as measured with eight silicon diodes but in contrast to all earlier studies in cryogenic traps and rings where the rotational temperatures were always much higher than those of the storage devices at their lowest temperatures. Furthermore, we actively modify the rotational distribution through selective photodetachment to produce an OH^{-} beam where 99.1±0.1% of approximately one million stored ions are in the J=0 rotational ground state. We measure the intrinsic lifetime of the J=1 rotational level to be 145±28 s.
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer‐related mortality. Despite significant advances made in the treatment of other cancers, current chemotherapies offer ...little survival benefit in this disease. Pancreaticoduodenectomy offers patients the possibility of a cure, but most will die of recurrent or metastatic disease. Hence, preventing metastatic disease in these patients would be of significant benefit. Using principal component analysis (PCA), we identified a LOX/hypoxia signature associated with poor patient survival in resectable patients. We found that LOX expression is upregulated in metastatic tumors from Pdx1‐Cre KrasG12D/+ Trp53R172H/+ (KPC) mice and that inhibition of LOX in these mice suppressed metastasis. Mechanistically, LOX inhibition suppressed both migration and invasion of KPC cells. LOX inhibition also synergized with gemcitabine to kill tumors and significantly prolonged tumor‐free survival in KPC mice with early‐stage tumors. This was associated with stromal alterations, including increased vasculature and decreased fibrillar collagen, and increased infiltration of macrophages and neutrophils into tumors. Therefore, LOX inhibition is able to reverse many of the features that make PDAC inherently refractory to conventional therapies and targeting LOX could improve outcome in surgically resectable disease.
Synopsis
Lysyl oxidase (LOX) is identified as a therapeutic target in pancreatic ductal adenocarcinoma (PDAC). Inhibition of LOX resulted in increased drug efficacy and stromal changes and reduction in metastasis.
A signature of hazardous and protective genes in PDAC was defined. High expression of hypoxia‐associated genes, including LOX, was associated with poor patient prognosis.
Using transgenic mouse models of PDAC, LOX was found to be overexpressed in metastatic disease and its expression was required for PDAC cell invasion.
Inhibition of LOX in transgenic mice inhibited metastasis, while combination therapy with LOX inhibition and gemcitabine induced stromal alterations, immune cell infiltration and tumor necrosis and improved survival.
Lysyl oxidase (LOX) is identified as a therapeutic target in pancreatic ductal adenocarcinoma (PDAC). Inhibition of LOX resulted in increased drug efficacy and stromal changes and reduction in metastasis.
Chordoma is a devastating rare cancer that affects one in a million people. With a mean-survival of just 6 years and no approved medicines, the primary treatments are surgery and radiation. In order ...to speed new medicines to chordoma patients, a drug repurposing strategy represents an attractive approach. Drugs that have already advanced through human clinical safety trials have the potential to be approved more quickly than de novo discovered medicines on new targets. We have taken two strategies to enable this: (1) generated and validated machine learning models of chordoma inhibition and screened compounds of interest in vitro. (2) Tested combinations of approved kinase inhibitors already being individually evaluated for chordoma. Several published studies of compounds screened against chordoma cell lines were used to generate Bayesian Machine learning models which were then used to score compounds selected from the NIH NCATS industry-provided assets. Out of these compounds, the mTOR inhibitor AZD2014, was the most potent against chordoma cell lines (IC
0.35 µM U-CH1 and 0.61 µM U-CH2). Several studies have shown the importance of the mTOR signaling pathway in chordoma and suggest it as a promising avenue for targeted therapy. Additionally, two currently FDA approved drugs, afatinib and palbociclib (EGFR and CDK4/6 inhibitors, respectively) demonstrated synergy in vitro (CI
= 0.43) while AZD2014 and afatanib also showed synergy (CI
= 0.41) against a chordoma cell in vitro. These findings may be of interest clinically, and this in vitro- and in silico approach could also be applied to other rare cancers.
Juvenile dermatomyositis (JDM) is a chronic inflammatory myopathy and vasculopathy driven by genetic and environmental influences. Here, we investigated the genetic underpinnings of an analogous, ...spontaneous disease of dogs also termed dermatomyositis (DMS). As in JDM, we observed a significant association with a haplotype of the major histocompatibility complex (MHC) (DLA-DRB1*002:01/-DQA1*009:01/-DQB1*001:01), particularly in homozygosity (P-val = 0.0001). However, the high incidence of the haplotype among healthy dogs indicated that additional genetic risk factors are likely involved in disease progression. We conducted genome-wide association studies in two modern breeds having common ancestry and detected strong associations with novel loci on canine chromosomes 10 (P-val = 2.3X10-12) and 31 (P-val = 3.95X10-8). Through whole genome resequencing, we identified primary candidate polymorphisms in conserved regions of PAN2 (encoding p.Arg492Cys) and MAP3K7CL (c.383_392ACTCCACAAA>GACT) on chromosomes 10 and 31, respectively. Analyses of these polymorphisms and the MHC haplotypes revealed that nine of 27 genotypic combinations confer high or moderate probability of disease and explain 93% of cases studied. The pattern of disease risk across PAN2 and MAP3K7CL genotypes provided clear evidence for a significant epistatic foundation for this disease, a risk further impacted by MHC haplotypes. We also observed a genotype-phenotype correlation wherein an earlier age of onset is correlated with an increased number of risk alleles at PAN2 and MAP3K7CL. High frequencies of multiple genetic risk factors are unique to affected breeds and likely arose coincident with artificial selection for desirable phenotypes. Described herein is the first three-locus association with a complex canine disease and two novel loci that provide targets for exploration in JDM and related immunological dysfunction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
evolution of self-control MacLean, Evan L; Hare, Brian; Nunn, Charles L ...
Proceedings of the National Academy of Sciences - PNAS,
05/2014, Letnik:
111, Številka:
20
Journal Article
Recenzirano
Odprti dostop
Cognition presents evolutionary research with one of its greatest challenges. Cognitive evolution has been explained at the proximate level by shifts in absolute and relative brain volume and at the ...ultimate level by differences in social and dietary complexity. However, no study has integrated the experimental and phylogenetic approach at the scale required to rigorously test these explanations. Instead, previous research has largely relied on various measures of brain size as proxies for cognitive abilities. We experimentally evaluated these major evolutionary explanations by quantitatively comparing the cognitive performance of 567 individuals representing 36 species on two problem-solving tasks measuring self-control. Phylogenetic analysis revealed that absolute brain volume best predicted performance across species and accounted for considerably more variance than brain volume controlling for body mass. This result corroborates recent advances in evolutionary neurobiology and illustrates the cognitive consequences of cortical reorganization through increases in brain volume. Within primates, dietary breadth but not social group size was a strong predictor of species differences in self-control. Our results implicate robust evolutionary relationships between dietary breadth, absolute brain volume, and self-control. These findings provide a significant first step toward quantifying the primate cognitive phenome and explaining the process of cognitive evolution.
Abstract Respiration of lipids by copepods during diapause (overwintering dormancy) contributes to ocean carbon sequestration via the seasonal lipid pump (SLP). Parameterizing this flux in predictive ...models requires a mechanistic understanding of how life history adaptation in copepods shapes their timing of exit from diapause. We investigate the optimal phenology of Calanus finmarchicus in the Norwegian Sea using an individual-based model in which diapause exit is represented as a trait characterized by phenotypic mean and variance. Without interannual variability, optimal exit correlated with the onset of the spring phytoplankton bloom and phenotypic variance was of no benefit. In contrast, copepods endured reduced fitness and adopted bet-hedging strategies when exposed to interannual variability in bloom timing and predation: later exit from diapause and phenotypic variance maintained adult numbers in anomalous late-bloom years. Exit nevertheless remained well before the peak of the bloom which is a favorable strategy when low predation early in the year enhances survival of eggs and early developmental stages. Our work highlights the complex interactions between C. finmarchicus and its environment and the need for improved understanding of bet-hedging strategies and the cues of diapause exit to progress the representation of the SLP in global biogeochemical models.
Grand challenges in global mental health Collins, Pamela Y; Patel, Vikram; Joestl, Sarah S ...
Nature (London),
07/2011, Letnik:
475, Številka:
7354
Journal Article
Recenzirano
Odprti dostop
... the effort hopes to build a wide-ranging community of research funders - much as the challenge for non-communicable diseases led to the creation of the GACD. ... the challenges underline the fact ...that all care and treatment interventions - psychosocial or pharmacological, simple or complex - should have an evidence base to provide programme planners, clinicians and policy-makers with effective care packages.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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