General intelligence is an important human quantitative trait that accounts for much of the variation in diverse cognitive abilities. Individual differences in intelligence are strongly associated ...with many important life outcomes, including educational and occupational attainments, income, health and lifespan. Data from twin and family studies are consistent with a high heritability of intelligence, but this inference has been controversial. We conducted a genome-wide analysis of 3511 unrelated adults with data on 549,692 single nucleotide polymorphisms (SNPs) and detailed phenotypes on cognitive traits. We estimate that 40% of the variation in crystallized-type intelligence and 51% of the variation in fluid-type intelligence between individuals is accounted for by linkage disequilibrium between genotyped common SNP markers and unknown causal variants. These estimates provide lower bounds for the narrow-sense heritability of the traits. We partitioned genetic variation on individual chromosomes and found that, on average, longer chromosomes explain more variation. Finally, using just SNP data we predicted ∼1% of the variance of crystallized and fluid cognitive phenotypes in an independent sample (P=0.009 and 0.028, respectively). Our results unequivocally confirm that a substantial proportion of individual differences in human intelligence is due to genetic variation, and are consistent with many genes of small effects underlying the additive genetic influences on intelligence.
Cognitive decline is a feared aspect of growing old. It is a major contributor to lower quality of life and loss of independence in old age. We investigated the genetic contribution to individual ...differences in nonpathological cognitive ageing in five cohorts of older adults. We undertook a genome-wide association analysis using 549 692 single-nucleotide polymorphisms (SNPs) in 3511 unrelated adults in the Cognitive Ageing Genetics in England and Scotland (CAGES) project. These individuals have detailed longitudinal cognitive data from which phenotypes measuring each individual's cognitive changes were constructed. One SNP--rs2075650, located in TOMM40 (translocase of the outer mitochondrial membrane 40 homolog)--had a genome-wide significant association with cognitive ageing (P=2.5 × 10(-8)). This result was replicated in a meta-analysis of three independent Swedish cohorts (P=2.41 × 10(-6)). An Apolipoprotein E (APOE) haplotype (adjacent to TOMM40), previously associated with cognitive ageing, had a significant effect on cognitive ageing in the CAGES sample (P=2.18 × 10(-8); females, P=1.66 × 10(-11); males, P=0.01). Fine SNP mapping of the TOMM40/APOE region identified both APOE (rs429358; P=3.66 × 10(-11)) and TOMM40 (rs11556505; P=2.45 × 10(-8)) as loci that were associated with cognitive ageing. Imputation and conditional analyses in the discovery and replication cohorts strongly suggest that this effect is due to APOE (rs429358). Functional genomic analysis indicated that SNPs in the TOMM40/APOE region have a functional, regulatory non-protein-coding effect. The APOE region is significantly associated with nonpathological cognitive ageing. The identity and mechanism of one or multiple causal variants remain unclear.
The old, red stars that constitute the bulges of galaxies, and the massive black holes at their centres, are the relics of a period in cosmic history when galaxies formed stars at remarkable rates ...and active galactic nuclei (AGN) shone brightly as a result of accretion onto black holes. It is widely suspected, but unproved, that the tight correlation between the mass of the black hole and the mass of the stellar bulge results from the AGN quenching the surrounding star formation as it approaches its peak luminosity. X-rays trace emission from AGN unambiguously, whereas powerful star-forming galaxies are usually dust-obscured and are brightest at infrared and submillimetre wavelengths. Here we report submillimetre and X-ray observations that show that rapid star formation was common in the host galaxies of AGN when the Universe was 2-6 billion years old, but that the most vigorous star formation is not observed around black holes above an X-ray luminosity of 10(44) ergs per second. This suppression of star formation in the host galaxy of a powerful AGN is a key prediction of models in which the AGN drives an outflow, expelling the interstellar medium of its host and transforming the galaxy's properties in a brief period of cosmic time.
An in-plane spin-photon interface is essential for the integration of quantum dot spins with optical circuits. The optical dipole of a quantum dot lies in the plane and the spin is optically accessed ...via circularly polarized selection rules. Hence, a single waveguide, which can transport only one in-plane linear polarization component, cannot communicate the spin state between two points on a chip. To overcome this issue, we introduce a spin-photon interface based on two orthogonal waveguides, where the polarization emitted by a quantum dot is mapped to a path-encoded photon. We demonstrate operation by deducing the spin using the interference of in-plane photons. A second device directly maps right and left circular polarizations to antiparallel waveguides, surprising for a nonchiral structure but consistent with an off-center dot.
We present the cross-identification and source photometry techniques used to process Herschel SPIRE imaging taken as part of the Herschel Multi-Tiered Extragalactic Survey (HerMES). ...Cross-identifications are performed in map-space so as to minimize source-blending effects. We make use of a combination of linear inversion and model selection techniques to produce reliable cross-identification catalogues based on Spitzer MIPS 24-μm source positions. Testing on simulations and real Herschel observations shows that this approach gives robust results for even the faintest sources (S250∼ 10 mJy). We apply our new technique to HerMES SPIRE observations taken as part of the science demonstration phase of Herschel. For our real SPIRE observations, we show that, for bright unconfused sources, our flux density estimates are in good agreement with those produced via more traditional point source detection methods (SUSSEXtractor) by Smith et al. When compared to the measured number density of sources in the SPIRE bands, we show that our method allows the recovery of a larger fraction of faint sources than these traditional methods. However, this completeness is heavily dependent on the relative depth of the existing 24-μm catalogues and SPIRE imaging. Using our deepest multiwavelength data set in the GOODS-N, we estimate that the use of shallow 24-μm catalogues in our other fields introduces an incompleteness at faint levels of between 20–40 per cent at 250 μm.
Abstract
STUDY QUESTION
Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized ...processing/freezing for centers that do not have those capabilities?
SUMMARY ANSWER
Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice.
WHAT IS KNOWN ALREADY
Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring.
STUDY DESIGN, SIZE, DURATION
Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient’s tissue was donated to research and 75% was stored for patient’s future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1.
MAIN RESULTS AND THE ROLE OF CHANCE
The average age of fertility preservation patients was 7.9 (SD = 5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD = 837.3) mg and ranged from 14.4 mg—6880.2 mg. Malignancies (n = 118) were the most common indication for testicular tissue freezing, followed by blood disorders (n = 45) and other conditions (n = 26). Thirty nine percent (n = 74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132.
LIMITATIONS, REASONS FOR CAUTION
This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size.
WIDER IMPLICATIONS OF THE FINDINGS
Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested.
STUDY FUNDING/COMPETING INTEREST(S)
Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.
The role of B cells in transplant tolerance remains unclear. Although B‐cell depletion often prolongs graft survival, sometimes it results in more rapid rejection, suggesting that B cells may have ...regulatory activity. We previously demonstrated that tolerance induction by anti‐CD45RB antibody requires recipient B cells. Here, we show that anti‐CD45RB in combination with anti‐TIM‐1 antibody has a synergistic effect, inducing tolerance in all recipients in a mouse islet allograft model. This effect depends on the presence of recipient B cells, requires B‐cell IL‐10 activity, and is antigen‐specific. These data suggest the existence of a regulatory B‐cell population that promotes tolerance via an IL‐10‐dependent pathway.
The authors demonstrate that B cells are necessary for tolerance induction in some transplant models, and also may confer tolerance induction upon adoptive transfer.
Radio occultation measurements of the Saturn ionosphere have shown that persistent but variable electron density layers appear well below the major peaks. We model here the region of hydrocarbon ions ...that is below the main peak and is produced by absorption of solar photons in the wavelength range 842 to 1116 Å, which penetrate to altitudes below the methane homopause in the wings of the H2 absorption lines, and in the gaps between groups of lines. In this wavelength range, H2 absorbs photons in discrete transitions to rovibrational levels of electronically excited states, which then decay to a range of rovibrational levels of the electronic ground state, or to the continuum of the ground state. The cross sections for these discrete absorptions vary by several orders of magnitude from the peaks to the wings of the absorption lines. We find that the adoption of high resolution photoabsorption cross sections for the H2 bands leads to different photoionization profiles for both the hydrocarbons and H atoms, and to peak CH4+photoproduction profiles that are more than an order of magnitude larger than those computed with low resolution cross sections. For the present model, we find that ionization by energetic electrons that accompany the absorption of soft X‐rays appears in the same altitude range. We predict that a broad region of hydrocarbon ions appears well below the main peak, in the altitude range 600 to 1000 km above the 1 bar level (2–0.04 μbar) with a maximum electron density of ∼3×103cm−3 at low solar activity.
Key Points
We have modeled the Saturn ionosphere for high resolution H2 cross sections
The ionization profiles for H+ and CH4+ are very different
A layer of hydrocarbon ions is found near 650‐1000 km
Intrauterine presence of Porphyromonas gingivalis (Pg), a common oral pathobiont, is implicated in preterm birth. Our aim was to determine if the location of Pg within placental and/or umbilical cord ...sections was associated with a specific delivery diagnosis at preterm delivery (histologic chorioamnionitis, chorioamnionitis with funisitis, preeclampsia, and preeclampsia with HELLP-syndrome, small for gestational age). The prevalence and location of Pg within archived placental and umbilical cord specimens from preterm (25 to 32 weeks gestation) and term control cohorts were evaluated by immunofluorescent histology. Detection of Pg was performed blinded to pregnancy characteristics. Multivariate analyses were performed to evaluate independent effects of gestational age, being small for gestational age, specific preterm delivery diagnosis, antenatal steroids, and delivery mode, on the odds of having Pg in the preterm tissue. Within the preterm cohort, 49 of 97 (51%) placentas and 40 of 97 (41%) umbilical cord specimens were positive for Pg. Pg within the placenta was significantly associated with shorter gestation lengths (OR 0.63 (95%CI: 0.48-0.85; p = 0.002) per week) and delivery via caesarean section (OR 4.02 (95%CI: 1.15-14.04; p = 0.03), but not with histological chorioamnionitis or preeclampsia. However, the presence of Pg in the umbilical cord was significantly associated with preeclampsia: OR 6.73 (95%CI: 1.31-36.67; p = 0.02). In the term cohort, 2 of 35 (6%) placentas and no umbilical cord term specimens were positive for Pg. The location of Pg within the placenta was different between preterm and term groups in that Pg within the villous mesenchyme was only detected in the preterm cohort, whereas Pg associated with syncytiotrophoblasts was found in both preterm and term placentas. Taken together, our results suggest that the presence of Pg within the villous stroma or umbilical cord may be an important determinant in Pg-associated adverse pregnancy outcomes.
Abstract
The Herschel Multi-tiered Extragalactic Survey (HerMES) is a legacy programme designed to map a set of nested fields totalling ∼380 deg2. Fields range in size from 0.01 to ∼20 deg2, using ...the Herschel-Spectral and Photometric Imaging Receiver (SPIRE) (at 250, 350 and 500 μm) and the Herschel-Photodetector Array Camera and Spectrometer (PACS) (at 100 and 160 μm), with an additional wider component of 270 deg2 with SPIRE alone. These bands cover the peak of the redshifted thermal spectral energy distribution from interstellar dust and thus capture the reprocessed optical and ultraviolet radiation from star formation that has been absorbed by dust, and are critical for forming a complete multiwavelength understanding of galaxy formation and evolution.
The survey will detect of the order of 100 000 galaxies at 5σ in some of the best-studied fields in the sky. Additionally, HerMES is closely coordinated with the PACS Evolutionary Probe survey. Making maximum use of the full spectrum of ancillary data, from radio to X-ray wavelengths, it is designed to facilitate redshift determination, rapidly identify unusual objects and understand the relationships between thermal emission from dust and other processes. Scientific questions HerMES will be used to answer include the total infrared emission of galaxies, the evolution of the luminosity function, the clustering properties of dusty galaxies and the properties of populations of galaxies which lie below the confusion limit through lensing and statistical techniques.
This paper defines the survey observations and data products, outlines the primary scientific goals of the HerMES team, and reviews some of the early results.
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