Genotyping of classical human leukocyte antigen (HLA) alleles is an essential tool in the analysis of diseases and adverse drug reactions with associations mapping to the major histocompatibility ...complex (MHC). However, deriving high-resolution HLA types subsequent to whole-genome single-nucleotide polymorphism (SNP) typing or sequencing is often cost prohibitive for large samples. An alternative approach takes advantage of the extended haplotype structure within the MHC to predict HLA alleles using dense SNP genotypes, such as those available from genome-wide SNP panels. Current methods for HLA imputation are difficult to apply or may require the user to have access to large training data sets with SNP and HLA types. We propose HIBAG, HLA Imputation using attribute BAGging, that makes predictions by averaging HLA-type posterior probabilities over an ensemble of classifiers built on bootstrap samples. We assess the performance of HIBAG using our study data (n=2668 subjects of European ancestry) as a training set and HLA data from the British 1958 birth cohort study (n≈1000 subjects) as independent validation samples. Prediction accuracies for HLA-A, B, C, DRB1 and DQB1 range from 92.2% to 98.1% using a set of SNP markers common to the Illumina 1M Duo, OmniQuad, OmniExpress, 660K and 550K platforms. HIBAG performed well compared with the other two leading methods, HLA*IMP and BEAGLE. This method is implemented in a freely available HIBAG R package that includes pre-fit classifiers for European, Asian, Hispanic and African ancestries, providing a readily available imputation approach without the need to have access to large training data sets.
The study of hot corinos in solar-like protostars has been so far mostly limited to the Class 0 phase, hampering our understanding of their origin and evolution. In addition, recent evidence suggests ...that planet formation starts already during Class I phase, which therefore represents a crucial step in the future planetary system chemical composition. Hence, the study of hot corinos in Class I protostars has become of paramount importance. Here, we report the discovery of a hot corino towards the prototypical Class I protostar L1551 IRS5, obtained within the ALMA (Atacama Large Millimeter/submillimeter Array) Large Program FAUST (Fifty AU STudy of the chemistry in the disc/envelope system of solar-like protostars). We detected several lines from methanol and its isotopologues (13CH3OH and CH2DOH), methyl formate, and ethanol. Lines are bright towards the north component of the IRS5 binary system, and a possible second hot corino may be associated with the south component. The methanol lines' non-LTE analysis constrains the gas temperature (∼100 K), density (≥1.5 × 10^8 per cu.cm), and emitting size (∼10 au in radius). All CH3OH and 13CH3OH lines are optically thick, preventing a reliable measure of the deuteration. The methyl formate and ethanol relative abundances are compatible with those measured in Class 0 hot corinos. Thus, based on this work, little chemical evolution from Class 0 to I hot corinos occurs.
To better characterize murine intestinal microbiota, a large number (187) of Gram-positive-staining, rod- and coccoid-shaped, and facultatively or strictly anaerobic bacteria were isolated from small ...and large intestinal contents from mice. Based on 16S rRNA gene sequencing, a total 115 isolates formed three phylogenetically distinct clusters located within the family
Erysipelotrichaceae
.
Group 1, as represented by strain NYU-BL-A3
T
, was most closely related to
Allobaculum stercoricanis
, with 16S rRNA gene sequence similarity values of 87.7 %. A second group, represented by NYU-BL-A4
T
, was most closely related to
Faecalibaculum rodentium
, with 86.6 % 16S rRNA gene sequence similarity. A third group had a nearly identical 16S rRNA gene sequence (99.9 %) compared with the recently described
Faecalibaculum rodentium
, also recovered from a laboratory mouse; however, this strain had a few differences in biochemical characteristics, which are detailed in an emended description. The predominant (>10 %) cellular fatty acids of strain NYU-BL-A3
T
were C
16 : 0
and C
18 : 0
, and those of strain NYU-BL-A4
T
were C
10 : 0
, C
16 : 0
, C
18 : 0
and C
18 : 1
ω9
c
. The two groups could also be distinguished by multiple biochemical reactions, with the group represented by NYU-BL-A4
T
being considerably more active. Based on phylogenetic, biochemical and chemotaxonomic criteria, two novel genera are proposed,
Ileibacterium valens
gen. nov., sp. nov. with NYU-BL-A3
T
(=ATCC TSD-63
T
=DSM 103668
T
) as the type strain and
Dubosiella newyorkensis
gen. nov., sp. nov. with NYU-BL-A4
T
(=ATCC TSD-64
T
=DSM 103457
T
) as the type strain.
We combine small-angle x-ray scattering (SAXS) and wide-angle x-ray scattering (WAXS) with aerodynamic levitation techniques to study in situ phase transitions in the liquid state under contactless ...conditions. At very high temperatures, yttria-alumina melts show a first-order transition, previously inferred from phase separation in quenched glasses. We show how the transition coincides with a narrow and reversible maximum in SAXS indicative of liquid unmixing on the nanoscale, combined with an abrupt realignment in WAXS features related to reversible shifts in polyhedral packing on the atomic scale. We also observed a rotary action in the suspended supercooled drop driven by repetitive transitions (a polyamorphic rotor) from which the reversible changes in molar volume (1.2 ± 0.2 cubic centimeters) and entropy (19 ± 4 joules mole⁻¹ kelvin⁻¹) can be estimated.
The implementation and evaluation of malaria control programs would be greatly facilitated by new tools for the rapid assessment of malaria transmission intensity. Because acquisition and maintenance ...of antimalarial antibodies depend on exposure to malaria infection, such antibodies might be used as proxy measures of transmission intensity. We have compared the prevalence of IgG antibodies with three Plasmodium falciparum asexual stage antigens in individuals of all ages living at varying altitudes encompassing a range of transmission intensities from hyper- to hypoendemic in northeastern Tanzania, with alternative measures of transmission intensity. The prevalence of antibodies to merozoite surface protein-119was significantly more closely correlated with altitude than either point-prevalence malaria parasitemia or single measures of hemoglobin concentration. Analysis of age-specific seroprevalence rates enabled differentiation of recent (seasonal) changes in transmission intensity from longer-term transmission trends and, using a mathematical model of the annual rate of seroconversion, estimation of the longevity of the antibody response. Thus, serological tools allow us to detect variations in malaria transmission over time. Such tools will be invaluable for monitoring trends in malaria endemicity and the effectiveness of malaria control programs.
A model of the photoelectron collision‐induced component of the Mars dayglow using recent cross sections and solar flux is described. The calculation of the photoelectron source of excitation is ...based on a stochastic solution of the Boltzmann equation using the direct simulation Monte Carlo method. The neutral atmosphere is taken from outputs of a global circulation model, and recent inelastic collision cross sections are adopted. The calculated vertical profiles of the CO Cameron bands and CO2+ doublet emissions integrated along the line of sight compare well with the Spectroscopy for the Investigation of the Characteristics of the Atmosphere of Mars (SPICAM) limb profiles observed with the SPICAM spectrograph on board Mars Express made at Ls = 166° during the summer season at northern midlatitudes. The comparison shows agreement to within the uncertainties of the excitation cross sections. Seasonal changes in the brightness and the altitude of the emission peaks are predicted with intensity variations in the range 15–20%.
Mutations and common polymorphisms in interferon regulatory factor 6 (IRF6) are associated with both syndromic and nonsyndromic forms of cleft lip/palate (CLP). To date, much of the focus on this ...transcription factor has been on identifying its direct targets and the gene regulatory network in which it operates. Notably, however, IRF6 is found predominantly in the cytoplasm, with its import into the nucleus tightly regulated like other members of the IRF family. To provide further insight into the role of IRF6 in the pathogenesis of CLP, we sought to identify direct IRF6 protein interactors using a combination of yeast 2-hybrid screens and co-immunoprecipitation assays. Using this approach, we identified NME1 and NME2, well-known regulators of Rho-type GTPases, E-cadherin endocytosis, and epithelial junctional remodeling, as bona fide IRF6 partner proteins. The NME proteins co-localize with IRF6 in the cytoplasm of primary palatal epithelial cells in vivo, and their interaction with IRF6 is significantly enhanced by phosphorylation of key serine residues in the IRF6 C-terminus. Furthermore, CLP associated IRF6 missense mutations disrupt the ability of IRF6 to bind the NME proteins and result in elevated activation of Rac1 and RhoA, compared to wild-type IRF6, when ectopically expressed in 293T epithelial cells. Significantly, we also report the identification of 2 unique missense mutations in the NME proteins in patients with CLP (NME1 R18Q in an IRF6 and GRHL3 mutation-negative patient with van der Woude syndrome and NME2 G71V in a patient with nonsyndromic CLP). Both variants disrupted the ability of the respective proteins to interact with IRF6. The data presented suggest an important role for cytoplasmic IRF6 in regulating the availability or localization of the NME1/2 complex and thus the dynamic behavior of epithelia during lip/palate development.
With the oceans covering 71% of the Earth, sea spray aerosol (SSA) particles profoundly impact climate through their ability to scatter solar radiation and serve as seeds for cloud formation. The ...climate properties can change when sea salt particles become mixed with insoluble organic material formed in ocean regions with phytoplankton blooms. Currently, the extent to which SSA chemical composition and climate properties are altered by biological processes in the ocean is uncertain. To better understand the factors controlling SSA composition, we carried out a mesocosm study in an isolated ocean-atmosphere facility containing 3,400 gallons of natural seawater. Over the course of the study, two successive phytoplankton blooms resulted in SSA with vastly different composition and properties. During the first bloom, aliphatic-rich organics were enhanced in submicron SSA and tracked the abundance of phytoplankton as indicated by chlorophyll-a concentrations. In contrast, the second bloom showed no enhancement of organic species in submicron particles. A concurrent increase in ice nucleating SSA particles was also observed only during the first bloom. Analysis of the temporal variability in the concentration of aliphatic-rich organic species, using a kinetic model, suggests that the observed enhancement in SSA organic content is set by a delicate balance between the rate of phytoplankton primary production of labile lipids and enzymatic induced degradation. This study establishes a mechanistic framework indicating that biological processes in the ocean and SSA chemical composition are coupled not simply by ocean chlorophyll-a concentrations, but are modulated by microbial degradation processes. This work provides unique insight into the biological, chemical, and physical processes that control SSA chemical composition, that when properly accounted for may explain the observed differences in SSA composition between field studies.
•We construct a map of the NO nightglow on Venus from SPICAV nadir observations.•We analyze the statistical distribution and the great variability of the emission.•We compare our map with those from ...Pioneer-Venus mission and recent O2(a1Δg) nightglow.•Superrotating zonal winds are weak near 95km but important in the lower thermosphere.•We point out possible sources of momentum transfer in the thermosphere.
Nitric oxide δ (190–240nm) and γ (255–270nm) bands have been observed on the Venus nightside with Venus Express SPICAV instrument operated in the nadir mode. These ultraviolet emissions arise from the de-excitation of NO molecules created by radiative recombination of O(3P) and N(4S) atoms. These atoms are produced on the dayside of the planet through photodissociation of CO2 and N2 molecules and are transported to the nightside by the global subsolar to antisolar circulation. We analyze a wide dataset of nadir observations obtained since 2006 to determine the statistical distribution of the NO nightglow and its variability. Individual observations show a great deal of variability and may exhibit multiple maxima along latitudinal cuts. We construct and compare a global NO map with the results obtained during the Pioneer-Venus mission and with the recently observed O2(a1Δg) nightglow distribution. The NO airglow distribution shows a statistical bright region extending from 01:00 to 03:30 local time and 25°S to 10°N, very similar to the Pioneer results obtained 35years earlier during maximum solar activity conditions. The shift from the antisolar point and the difference with the O2 airglow indicate that superrotating zonal winds are statistically weak near 97km, but play an important role near 115km. We compare these results with other evidence for superrotation in the thermosphere and point out possible sources of momentum transfer.
Limb observations with the SPICAM ultraviolet spectrometer on board the Mars Express orbiter revealed ultraviolet nightglow emission in the δ (190–240 nm) and γ (225–270 nm) bands of nitric oxide. ...This emission arises from radiative recombination between O(3P) and N(4S) atoms that are produced on the day side and form excited NO molecules on the night side. In this study, we analyze the night limb observations obtained during the MEX mission. In particular, we describe the variability of the emission brightness and its peak altitude. We examine possible correlations with latitude, local time, magnetic field strength or solar activity. We show that the altitude of maximum emission varies between 55 and 92 km while the brightness is in the range 0.2 to 10.5 kR. The total vertical emission rate ranges from 8 to 237 R with an average value of 36 ± 52 R. The observed topside scale height of the emission profile varies between 3.8 and 11.0 km, with a mean value of 6 ± 1.7 km. We use a chemical‐diffusive atmospheric model where the eddy coefficient, whose value in the Mars thermosphere is uncertain, is a free parameter to match the observed peak altitude of the emission. The model solves the continuity equation for O(3P), N(4S), and NO using a finite volume method on a one‐dimensional grid. We find that the downward flux of N atoms at 100 km varies by two orders of magnitude, ranging from 107 to 109 atoms cm−2 s−1.
PDF
