Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from ...6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.
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•Malawian mothers with undernourished infants have decreased milk oligosaccharides•Sialylated milk sugars promote growth of animals colonized with infant microbiota•Growth promotion does not occur with provision of inulin or in germ-free mice•Sialylated oligosaccharides impact liver, muscle, and brain metabolism
Two preclinical models for infant undernutrition establish a link between consumption of sialylated milk oligosaccharides, the gut microbiota, and healthy growth.
Presynaptic cannabinoid-1 receptors (CB1-R) bind endogenous and exogenous cannabinoids to modulate neurotransmitter release. CB1-Rs are expressed throughout the basal ganglia, including striatum and ...substantia nigra, where they play a role in learning and control of motivated actions. However, the pattern of CB1-R expression across different striatal compartments, microcircuits and efferent targets, and the contribution of different CB1-R-expressing neurons to this pattern, are unclear. We use a combination of conventional techniques and novel genetic models to evaluate CB1-R expression in striosome (patch) and matrix compartments of the striatum, and in nigral targets of striatal medium spiny projection neurons (MSNs). CB1-R protein and mRNA follow a descending dorsolateral-to-ventromedial intensity gradient in the caudal striatum, with elevated expression in striosomes relative to the surrounding matrix. The lateral predominance of striosome CB1-Rs contrasts with that of the classical striosomal marker, the mu opioid receptor (MOR), which is expressed most prominently in rostromedial striosomes. The dorsolateral-to-ventromedial CB1-R gradient is similar to Drd2 dopamine receptor immunoreactivity and opposite to Substance P. This topology of CB1-R expression is maintained downstream in the globus pallidus and substantia nigra. Dense CB1-R-expressing striatonigral fibers extend dorsally within the substantia nigra pars reticulata, and colocalize with bundles of ventrally extending, striosome-targeted, dendrites of dopamine-containing neurons in the substantia nigra pars compacta (striosome-dendron bouquets). Within striatum, CB1-Rs colocalize with fluorescently labeled MSN collaterals within the striosomes. Cre recombinase-mediated deletion of CB1-Rs from cortical projection neurons or MSNs, and MSN-selective reintroduction of CB1-Rs in knockout mice, demonstrate that the principal source of CB1-Rs in dorsolateral striosomes is local MSN collaterals. These data suggest a role for CB1-Rs in caudal dorsolateral striosome collaterals and striosome-dendron bouquet projections to lateral substantia nigra, where they are anatomically poised to mediate presynaptic disinhibition of both striosomal MSNs and midbrain dopamine neurons in response to endocannabinoids and cannabinomimetics.
The accuracy of microbial community surveys based on marker-gene and metagenomic sequencing (MGS) suffers from the presence of contaminants-DNA sequences not truly present in the sample. Contaminants ...come from various sources, including reagents. Appropriate laboratory practices can reduce contamination, but do not eliminate it. Here we introduce decontam ( https://github.com/benjjneb/decontam ), an open-source R package that implements a statistical classification procedure that identifies contaminants in MGS data based on two widely reproduced patterns: contaminants appear at higher frequencies in low-concentration samples and are often found in negative controls.
Decontam classified amplicon sequence variants (ASVs) in a human oral dataset consistently with prior microscopic observations of the microbial taxa inhabiting that environment and previous reports of contaminant taxa. In metagenomics and marker-gene measurements of a dilution series, decontam substantially reduced technical variation arising from different sequencing protocols. The application of decontam to two recently published datasets corroborated and extended their conclusions that little evidence existed for an indigenous placenta microbiome and that some low-frequency taxa seemingly associated with preterm birth were contaminants.
Decontam improves the quality of metagenomic and marker-gene sequencing by identifying and removing contaminant DNA sequences. Decontam integrates easily with existing MGS workflows and allows researchers to generate more accurate profiles of microbial communities at little to no additional cost.
Yield stability is fundamental to global food security in the face of climate change, and better strategies are needed for buffering crop yields against increased weather variability. Regional- scale ...analyses of yield stability can support robust inferences about buffering strategies for widely-grown staple crops, but have not been accomplished. We present a novel analytical approach, synthesizing 2000-2014 data on weather and soil factors to quantify their impact on county-level maize yield stability in four US states that vary widely in these factors (Illinois, Michigan, Minnesota and Pennsylvania). Yield stability is quantified as both 'downside risk' (minimum yield potential, MYP) and 'volatility' (temporal yield variability). We show that excessive heat and drought decreased mean yields and yield stability, while higher precipitation increased stability. Soil water holding capacity strongly affected yield volatility in all four states, either directly (Minnesota and Pennsylvania) or indirectly, via its effects on MYP (Illinois and Michigan). We infer that factors contributing to soil water holding capacity can help buffer maize yields against variable weather. Given that soil water holding capacity responds (within limits) to agronomic management, our analysis highlights broadly relevant management strategies for buffering crop yields against climate variability, and informs region-specific strategies.
Abstract
We present constraints on cosmological parameters from the Pantheon+ analysis of 1701 light curves of 1550 distinct Type Ia supernovae (SNe Ia) ranging in redshift from
z
= 0.001 to 2.26. ...This work features an increased sample size from the addition of multiple cross-calibrated photometric systems of SNe covering an increased redshift span, and improved treatments of systematic uncertainties in comparison to the original Pantheon analysis, which together result in a factor of 2 improvement in cosmological constraining power. For a flat ΛCDM model, we find Ω
M
= 0.334 ± 0.018 from SNe Ia alone. For a flat
w
0
CDM model, we measure
w
0
= −0.90 ± 0.14 from SNe Ia alone,
H
0
= 73.5 ± 1.1 km s
−1
Mpc
−1
when including the Cepheid host distances and covariance (SH0ES), and
w
0
=
−
0.978
−
0.031
+
0.024
when combining the SN likelihood with Planck constraints from the cosmic microwave background (CMB) and baryon acoustic oscillations (BAO); both
w
0
values are consistent with a cosmological constant. We also present the most precise measurements to date on the evolution of dark energy in a flat
w
0
w
a
CDM universe, and measure
w
a
=
−
0.1
−
2.0
+
0.9
from Pantheon+ SNe Ia alone,
H
0
= 73.3 ± 1.1 km s
−1
Mpc
−1
when including SH0ES Cepheid distances, and
w
a
=
−
0.65
−
0.32
+
0.28
when combining Pantheon+ SNe Ia with CMB and BAO data. Finally, we find that systematic uncertainties in the use of SNe Ia along the distance ladder comprise less than one-third of the total uncertainty in the measurement of
H
0
and cannot explain the present “Hubble tension” between local measurements and early universe predictions from the cosmological model.
A complete, 52-protein, 2.5 million dalton, Mediator-RNA polymerase II pre-initiation complex (Med-PIC) was assembled and analyzed by cryo-electron microscopy and by chemical cross-linking and mass ...spectrometry. The resulting complete Med-PIC structure reveals two components of functional significance, absent from previous structures, a protein kinase complex and the Mediator-activator interaction region. It thereby shows how the kinase and its target, the C-terminal domain of the polymerase, control Med-PIC interaction and transcription.
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•Isolation of a 52-protein, 2.5 MDa Mediator-RNA polymerase II initiation complex•Structural elucidation of the complex by cryo-EM and chemical cross-linking•Model for the regulation of CTD phosphorylation during transcription initiation•Mediator Tail module architecture and dynamics
Visualizing a complete Mediator-RNA polymerase II pre-initiation complex suggests a model explaining the basis for control of transcription initiation by the pol II C-terminal domain.
Neurofibrillary tangles (NFT) and β-amyloid plaques are the neurological hallmarks of both Alzheimer's disease and an unusual paralytic illness suffered by Chamorro villagers on the Pacific island of ...Guam. Many Chamorros with the disease suffer dementia, and in some villages one-quarter of the adults perished from the disease. Like Alzheimer's, the causal factors of Guamanian amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) are poorly understood. In replicated experiments, we found that chronic dietary exposure to a cyanobacterial toxin present in the traditional Chamorro diet, β-N-methylamino-l-alanine (BMAA), triggers the formation of both NFT and β-amyloid deposits similar in structure and density to those found in brain tissues of Chamorros who died with ALS/PDC. Vervets (Chlorocebus sabaeus) fed for 140 days with BMAA-dosed fruit developed NFT and sparse β-amyloid deposits in the brain. Co-administration of the dietary amino acid l-serine with l-BMAA significantly reduced the density of NFT. These findings indicate that while chronic exposure to the environmental toxin BMAA can trigger neurodegeneration in vulnerable individuals, increasing the amount of l-serine in the diet can reduce the risk.
We investigate the relation between corporate tax payments and corporate social responsibility. Because existing theory and empirical studies find inconsistent evidence on the relation between these ...constructs, we investigate whether the two activities act as complements or substitutes. We estimate the relation between measures of corporate social responsibility and (1) the amount of corporate taxes paid, and (2) the amount invested in tax lobbying activities using both ordinary least squares and a system of simultaneous equations. We find consistent evidence that corporate social responsibility is negatively related to five-year cash effective tax rates and positively related to tax lobbying expenditures. Our evidence suggests that, on average, corporate social responsibility and tax payments act as substitutes.
The Global Food‐Energy‐Water Nexus D'Odorico, Paolo; Davis, Kyle Frankel; Rosa, Lorenzo ...
Reviews of geophysics,
September 2018, Letnik:
56, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Water availability is a major factor constraining humanity's ability to meet the future food and energy needs of a growing and increasingly affluent human population. Water plays an important role in ...the production of energy, including renewable energy sources and the extraction of unconventional fossil fuels that are expected to become important players in future energy security. The emergent competition for water between the food and energy systems is increasingly recognized in the concept of the “food‐energy‐water nexus.” The nexus between food and water is made even more complex by the globalization of agriculture and rapid growth in food trade, which results in a massive virtual transfer of water among regions and plays an important role in the food and water security of some regions. This review explores multiple components of the food‐energy‐water nexus and highlights possible approaches that could be used to meet food and energy security with the limited renewable water resources of the planet. Despite clear tensions inherent in meeting the growing and changing demand for food and energy in the 21st century, the inherent linkages among food, water, and energy systems can offer an opportunity for synergistic strategies aimed at resilient food, water, and energy security, such as the circular economy.
Key Points
We investigate the trade‐offs of water use for food or energy production and the nexus among water, food, and energy
We investigate the broader issue of feeding the planet with limited resources while ensuring sustainability, resilience, and equity
We analyze a number of approaches to future food and energy security
Background: Failure to translate best evidence into practice often generates inappropriate, unsafe, and costly healthcare. The continuing professional development (CPD) of physicians and other health ...professionals represents a widely underutilized strategy to improve both clinician performance and healthcare quality and safety.
The evidence: Despite the clear evidence of the potential impact of CPD based in learning theory and science, some CPD providers, health systems, and clinicians themselves implement less-than-effective effective learning strategies. This phenomenon is the product of several factors: within health systems, a lack of recognition of the importance of ongoing, system-linked professional education; among CPD providers, an adherence to old but easy-to-deliver "one-and-done" methods CPD; and even among clinicians themselves, choosing less engaging learning activities, uninformed by objective performance data.
Recommendation: Suggestions to improve this lack of translation of best evidence into practice fall into four groups. Academic medical institutions, employers and educators need to embrace principles and practices of self-directed learning; health systems must share responsibility for the physician learning and the performance data and feedback on which such learning is best-based; physician specialty societies and licensing boards must undertake meaningful re-licensure and re-certification processes; and CPD planners must seek out partnerships with health system leadership and quality improvement managers as they create engaging, integrated, and impactful CPD activities.
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