Hierarchy provides a unifying principle for the macroscale organization of anatomical and functional properties across primate cortex, yet microscale bases of specialization across human cortex are ...poorly understood. Anatomical hierarchy is conventionally informed by invasive tract-tracing measurements, creating a need for a principled proxy measure in humans. Moreover, cortex exhibits marked interareal variation in gene expression, yet organizing principles of cortical transcription remain unclear. We hypothesized that specialization of cortical microcircuitry involves hierarchical gradients of gene expression. We found that a noninvasive neuroimaging measure-MRI-derived T1-weighted/T2-weighted (T1w/T2w) mapping-reliably indexes anatomical hierarchy, and it captures the dominant pattern of transcriptional variation across human cortex. We found hierarchical gradients in expression profiles of genes related to microcircuit function, consistent with monkey microanatomy, and implicated in neuropsychiatric disorders. Our findings identify a hierarchical axis linking cortical transcription and anatomy, along which gradients of microscale properties may contribute to the macroscale specialization of cortical function.
A hallmark of the immune system is the interplay among specialized cell types transitioning between resting and stimulated states. The gene regulatory landscape of this dynamic system has not been ...fully characterized in human cells. Here we collected assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing data under resting and stimulated conditions for up to 32 immune cell populations. Stimulation caused widespread chromatin remodeling, including response elements shared between stimulated B and T cells. Furthermore, several autoimmune traits showed significant heritability in stimulation-responsive elements from distinct cell types, highlighting the importance of these cell states in autoimmunity. Allele-specific read mapping identified variants that alter chromatin accessibility in particular conditions, allowing us to observe evidence of function for a candidate causal variant that is undetected by existing large-scale studies in resting cells. Our results provide a resource of chromatin dynamics and highlight the need to characterize the effects of genetic variation in stimulated cells.
Every night across the world's oceans, numerous marine animals arrive at the surface of the ocean to feed on plankton after an upward migration of hundreds of metres. Just before sunrise, this ...migration is reversed and the animals return to their daytime residence in the dark mesopelagic zone (at a depth of 200-1,000 m). This daily excursion, referred to as diel vertical migration (DVM), is thought of primarily as an adaptation to avoid visual predators in the sunlit surface layer
and was first recorded using ship-net hauls nearly 200 years ago
. Nowadays, DVMs are routinely recorded by ship-mounted acoustic systems (for example, acoustic Doppler current profilers). These data show that night-time arrival and departure times are highly conserved across ocean regions
and that daytime descent depths increase with water clarity
, indicating that animals have faster swimming speeds in clearer waters
. However, after decades of acoustic measurements, vast ocean areas remain unsampled and places for which data are available typically provide information for only a few months, resulting in an incomplete understanding of DVMs. Addressing this issue is important, because DVMs have a crucial role in global ocean biogeochemistry. Night-time feeding at the surface and daytime metabolism of this food at depth provide an efficient pathway for carbon and nutrient export
. Here we use observations from a satellite-mounted light-detection-and-ranging (lidar) instrument to describe global distributions of an optical signal from DVM animals that arrive in the surface ocean at night. Our findings reveal that these animals generally constitute a greater fraction of total plankton abundance in the clear subtropical gyres, consistent with the idea that the avoidance of visual predators is an important life strategy in these regions. Total DVM biomass, on the other hand, is higher in more productive regions in which the availability of food is increased. Furthermore, the 10-year satellite record reveals significant temporal trends in DVM biomass and correlated variations in DVM biomass and surface productivity. These results provide a detailed view of DVM activities globally and a path for refining the quantification of their biogeochemical importance.
We demonstrate that signal spikes in optical backscatter measurements provide information on the diel vertical migration patterns of oceanic zooplankton. During nighttime, we observed high frequency ...spikes in particulate optical backscatter coincident with increased acoustic backscatter from vertically migrating zooplankton. We used our measurements to examine the spatial patterns and daily timing of zooplankton migrations across the eastern Subarctic Pacific Ocean, demonstrating coherence of diel vertical migrations with regional hydrographic features. Vertical zooplankton migration was consistently observed in oligotrophic offshore waters but less apparent in higher productivity waters over the continental shelf, where bottom depth, hydrographic fronts, and plankton abundance influenced apparent zooplankton distributions. Our results suggest that spikes in optical backscatter data, which are normally removed during data processing, can be more fully exploited to examine marine zooplankton dynamics from autonomous measurement systems.
Plain Language Summary
Measurements of light scattering at the ocean's surface provide information about the abundance and species composition of microscopic algae that constitute the base of the marine food web. Here we show that high‐frequency spikes in surface backscatter data, which are normally removed during data processing, can also provide a signal of marine zooplankton, the small animals that consume algae. We observed day/night patterns in backscatter attributable to the daily vertical migration of zooplankton, providing a novel approach to observing this important behavior. Across our study area in the Subarctic Pacific, a clear signature of nighttime migrations was evident in open ocean waters, but not in coastal waters over the continental shelf, where spatial variability in seawater characteristics and phytoplankton abundance influenced apparent zooplankton vertical migrations. Water depth and water clarity were also strong predictors of vertical migration patterns. Building on our results, we propose an approach to facilitate improved analysis of zooplankton abundance from optical backscatter measurements and suggest that reexamination of previous data sets could reveal large‐scale patterns of marine zooplankton vertical migrations.
Key Points
Persistent nighttime spikes in surface ocean particulate backscatter are attributed to the presence of diel migrating zooplankton
Underway surface backscatter data provide information on the spatial patterns and light‐induced timing of diel vertical migration
Optical data reveal physical and biological drivers of zooplankton distribution across contrasting oceanographic regimes
Abstract Objectives Copy number variants (CNVs) are duplications or deletions of genomic regions. Large CNVs are potentially pathogenic and are overrepresented in children with congenital heart ...disease (CHD). We sought to determine the frequency of large CNVs in children with isolated CHD, and to evaluate the relationship of these potentially pathogenic CNVs with transplant-free survival. Methods These cases are derived from a prospective cohort of patients with nonsyndromic CHD (n = 422) identified before first surgery. Healthy pediatric controls (n = 500) were obtained from the electronic Medical Records and Genetic Epidemiology Network, and CNV frequency was contrasted for CHD cases and controls. CNVs were determined algorithmically; subsequently screened for >95% overlap between 2 methods, size (>300 kb), quality score, overlap with a gene, and novelty (absent from databases of known, benign CNVs); and separately validated by quantitative polymerase chain reaction. Survival likelihoods for cases were calculated using Cox proportional hazards modeling to evaluate the joint effect of CNV burden and known confounders on transplant-free survival. Results Children with nonsyndromic CHD had a higher burden of potentially pathogenic CNVs compared with pediatric controls (12.1% vs 5.0%; P = .00016). Presence of a CNV was associated with significantly decreased transplant-free survival after surgery (hazard ratio, 3.42; 95% confidence interval, 1.66-7.09; P = .00090) with confounder adjustment. Conclusions We confirm that children with isolated CHD have a greater burden of rare/large CNVs. We report a novel finding that these CNVs are associated with an adjusted 2.55-fold increased risk of death or transplant. These data suggest that CNV burden is an important modifier of survival after surgery for CHD.
We present optically derived estimates of phytoplankton carbon (Cphyto) and chlorophyll a concentration (Chl) across a wide range of productivity and hydrographic regimes in the Subarctic Pacific ...Ocean. Our high‐frequency measurements capture changes in Cphyto and Chl across regional gradients in macronutrient and micronutrient limitations and submesoscale hydrographic frontal zones. Throughout the majority of our survey region, carbon to chlorophyll ratios (Cphyto:Chl) ranged between 50 and 100. Lower values (10–20) were constrained to the highly productive coastal upwelling system along Vancouver Island, whereas higher estimated values (>200) were found directly off the southern British Columbia continental shelf. Further offshore, Cphyto:Chl was less variable, ranging from 50 to 80 in high nutrient low Chl waters in June and from 80 to 120 in the Gulf of Alaska in July. Much of the variability in Cphyto:Chl throughout the study region could be explained by mixed‐layer light levels (i.e., photoacclimation), with additional variability attributed to nutrient‐controlled changes in phytoplankton growth rates in some regions. Elevated Cphyto:Chl ratios resulting from apparent nutrient stress were found in areas of low macronutrient concentrations. In contrast, iron‐limited waters exhibited Cphyto:Chl ratios lower than predicted from the photoacclimation model. Applying the carbon‐based production model, we derived Cphyto and Chl‐based estimates of net primary productivity, which showed good coherence with independent 14C uptake measurements. Our results highlight the utility of ship‐board optical data to examine phytoplankton physiological ecology and productivity in surface marine waters.
Key Points
Biooptical relationships for both chlorophyll and phytoplankton carbon are robust across a wide range of productivity regimes
Tenfold variability in phytoplankton carbon:chlorophyll ratios is mostly attributed to photoacclimation and nutrient stress
Estimates of net primary productivity derived from optical measurements compare well to independent carbon‐14 uptake measurements
Objective Apolipoprotein E ( APOE ) genotype is a determinant of neurologic recovery after brain ischemia and traumatic brain injury. The APOE ε2 allele has been associated with worse ...neurodevelopmental (ND) outcome after repair of congenital heart defects (CHD) in infancy. Replication of this finding in an independent cohort is essential to validate the observed genotype-phenotype association. Methods The association of APOE genotype with ND outcomes was assessed in a combined cohort of patients with single-ventricle CHD enrolled in the Single Ventricle Reconstruction and Infant Single Ventricle trials. ND outcome was assessed at 14 months using the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. Stepwise multivariable regression was performed to develop predictive models for PDI and MDI scores. Results Complete data were available for 298 of 435 patients. After adjustment for preoperative and postoperative covariates, the APOE ε2 allele was associated with a lower PDI score ( P = .038). Patients with the ε2 allele had a PDI score approximately 6 points lower than those without the risk allele, explaining 1.04% of overall PDI variance, because the ε2 allele was present in only 11% of the patients. There was a marginal effect of the ε2 allele on MDI scores ( P = .058). Conclusions These data validate the association of the APOE ε2 allele with adverse early ND outcomes after cardiac surgery in infants, independent of patient and operative factors. Genetic variants that decrease neuroresilience and impair neuronal repair after brain injury are important risk factors for ND dysfunction after surgery for CHD.
Summer near‐surface seawater sampling in the Canadian Arctic revealed potential for significant errors (nearly 0.1 μmol·(m‐2 s‐1)) in CO2 fluxes calculated from measured air‐sea CO2 gradients. River ...runoff and sea ice melt strongly stratify these waters, often resulting in surface mixed layers only a few meters thick and isolated from waters sampled by shipboard underway systems. Samples collected with the underway system, rosette, and small boats exposed substantial near‐surface gradients in CO2 partial pressure (pCO2) over the top 7 m at many stations. Distributions of temperature, salinity, and fluorescence indicated that the sources of the CO2 system gradients varied between stations, precluding simple corrections to align subsurface data with shallower conditions. Overall, the strong summertime sink of atmospheric CO2 implied by the underway data was not supported by shallower data.
Plain Language Summary
Large quantities of sea ice melt and river runoff in the Arctic Ocean form thin layers of fresh water at the surface that are isolated from deeper water. However, standard methods of sampling surface waters from ships draw water from 2 to 7 m below the surface, which can cause errors in air‐sea CO2 fluxes calculated from measured seawater CO2 concentrations. We have quantified the potential error for waters of the coastal Arctic Ocean by measuring CO2 concentrations in samples collected near the surface using different methods from both large ships and small boats. We found that large errors could result from shipboard sampling at some stations. In particular, measuring the CO2 concentration from automated instruments that draw water from below the ship's hull systematically overestimated atmospheric CO2 absorption by the ocean.
Key Points
In stratified Arctic Ocean waters, sampling depth can introduce large errors into air‐sea CO2 flux estimates at individual stations
Data from an underway system generally overestimated the summer atmospheric CO2 drawdown in the Canadian Arctic Archipelago
Difficulties in advancing effective patient-specific therapies for psychiatric disorders highlight a need to develop a stable neurobiologically grounded mapping between neural and symptom variation. ...This gap is particularly acute for psychosis-spectrum disorders (PSD). Here, in a sample of 436 PSD patients spanning several diagnoses, we derived and replicated a dimensionality-reduced symptom space across hallmark psychopathology symptoms and cognitive deficits. In turn, these symptom axes mapped onto distinct, reproducible brain maps. Critically, we found that multivariate brain-behavior mapping techniques (e.g. canonical correlation analysis) do not produce stable results with current sample sizes. However, we show that a univariate brain-behavioral space (BBS) can resolve stable individualized prediction. Finally, we show a proof-of-principle framework for relating personalized BBS metrics with molecular targets via serotonin and glutamate receptor manipulations and neural gene expression maps derived from the Allen Human Brain Atlas. Collectively, these results highlight a stable and data-driven BBS mapping across PSD, which offers an actionable path that can be iteratively optimized for personalized clinical biomarker endpoints.
Abstract Ocean alkalinity enhancement (OAE) reduces the concentration of dissolved carbon dioxide (CO 2 ) in seawater, leading to atmospheric carbon dioxide removal (CDR). Here we report laboratory ...experiments and a field-trial of alkalinity enhancement through addition of magnesium hydroxide to wastewater and its subsequent discharge to the coastal ocean. In wastewater, a 10% increase of average alkalinity (+0.56 mmol/kg) led to a 74% reduction in aqueous CO 2 (−0.41 mmol/kg) and pH increase of 0.4 units to 7.78 (efficiency 0.73 molCO 2 /mol alkalinity). The alkalinization signal was limited to within a few metres of the ocean discharge, evident as 27.2 μatm reduction in CO 2 partial pressure and 0.017 unit pH increase, and was consistent with rapid dilution of the alkali-treated wastewater. While this proof of concept field trial did not achieve CDR due to its small scale, it demonstrated the potential of magnesium hydroxide addition to wastewater as a CDR solution.
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