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Anterior-posterior (A-P) elongation of the palate is a critical aspect of integrated midfacial morphogenesis. Reciprocal epithelial-mesenchymal interactions drive secondary palate elongation that is coupled to the periodic formation of signaling centers within the rugae growth zone (RGZ). However, the relationship between RGZ driven morphogenetic processes, the differentiative dynamics of underlying palatal bone mesenchymal precursors, and the segmental organization of the upper jaw has remained enigmatic. A detailed ontogenetic study of these relationships is important, because palatal segment growth is a critical aspect of normal midfacial growth, can be modified to produce dysmorphology, and is a likely basis for evolutionary differences in upper jaw morphology. Variation in palatal-segment specific growth may also underlie known differences in palatal segment proportions between inbred mouse strains. We completed a combined whole mount gene expression and morphometric analysis of normal murine palatal growth dynamics and their association with palatal segment elongation and resulting upper jaw morphology. Our results demonstrated that the first formed palatal ruga (ruga 1), found just posterior to the RGZ, maintained an association with important nasal, neurovascular and palatal structures throughout early midfacial development; suggesting that these features are positioned at a proximal source of embryonic midfacial directional growth. Our detailed characterization of midfacial morphogenesis revealed a one-to-one relationship between palatal segments and upper jaw bones during the earliest stages of palatal elongation. Growth of the maxillary anlage within the anterior secondary palate is uniquely coupled to RGZ-driven morphogenesis that more than doubles the length of this palatal segment prior to palatal shelf fusion. Our results also demonstrate that the future maxillary-palatine suture, approximated by the position ruga 1 and consistently associated with the palatine anlage, forms predominantly via the posterior differentiation of the maxilla within the expanding anterior secondary palate. Our complementary ontogenetic comparison of three inbred mouse strains identified small but significant strain-specific differences in early embryonic palatal segment contributions to the upper jaw. Although early palatal segment specific growth is not primarily responsible for adult differences in upper jaw morphology between these strains, our ontogenetic series of measurements provide a useful foundation for understanding the impact of background genetic effects on facial shape and elongation. In combination, our results provide a novel and particularly detailed picture of the earliest spatiotemporal dynamics of intramembranous midfacial skeletal specification and differentiation within the context of the surrounding palatal segment A-P elongation and associated rugae formation.

Criegee intermediates play an important role in the oxidizing capacity of the Earth's troposphere. Although extensive studies have been conducted on Criegee intermediates in the past decade, their kinetics with radical species remain underexplored. We investigated the kinetics of the simplest Criegee intermediate, CH 2 OO, with the methyl peroxy radical, CH 3 O 2 , as a model system to explore the reactivities of Criegee intermediates with peroxy radicals. Using a multipass UV-Vis spectrometer coupled to a pulsed-laser photolysis flow reactor, CH 2 OO and CH 3 O 2 were generated simultaneously from the photolysis of CH 2 I 2 /CH 3 I/O 2 /N 2 mixtures with CH 2 OO measured directly near 340 nm. We determined a reaction rate coefficient k CH 2 OO+CH 3 O 2 = (1.7 ± 0.5) × 10 -11 cm 3 s -1 at 294 K and 10 Torr, where the influence of iodine adducts is reduced. This rate coefficient is faster than previous theoretical predictions, highlighting the challenges in accurately describing the interaction between zwitterionic and biradical characteristics of Criegee intermediates.

The genetic architecture of trait variance has long been of interest in genetics and evolution. One of the earliest attempts to understand this architecture was presented in Lerner's Genetic Homeostasis (1954). Lerner proposed that heterozygotes should be better able to tolerate environmental perturbations because of functional differences between the alleles at a given locus, with each allele optimal for slightly different environments. This greater robustness to environmental variance, he argued, would result in smaller trait variance for heterozygotes. The evidence for Lerner's hypothesis has been inconclusive. To address this question using modern genomic methods, we mapped loci associated with differences in trait variance (vQTL) on 1,101 individuals from the F34 of an advanced intercross between LG/J and SM/J mice. We also mapped epistatic interactions for these vQTL in order to understand the influence of epistasis for the architecture of trait variance. We did not find evidence supporting Lerner's hypothesis, that heterozygotes tend to have smaller trait variances than homozygotes. We further show that the effects of most mapped loci on trait variance are produced by epistasis affecting trait means and that those epistatic effects account for about a half of the differences in genotypic-specific trait variances. Finally, we propose a model where the different interactions between the additive and dominance effects of the vQTL and their epistatic partners can explain Lerner's original observations but can also be extended to include other conditions where heterozygotes are not the least variable genotype., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Methyl-ethyl-substituted Criegee intermediate (MECI) is a four-carbon carbonyl oxide that is formed in the ozonolysis of some asymmetric alkenes. MECI is structurally similar to the isoprene-derived methyl vinyl ketone oxide (MVK-oxide) but lacks resonance stabilization, making it a promising candidate to help us unravel the effects of size, structure, and resonance stabilization that influence the reactivity of atmospherically important, highly functionalized Criegee intermediates. We present experimental and theoretical results from the first bimolecular study of MECI in its reaction with SO 2 , a reaction that shows significant sensitivity to the Criegee intermediate structure. Using multiplexed photoionization mass spectrometry, we obtain a rate coefficient of (1.3 ± 0.3) × 10 -10 cm 3 s -1 (95% confidence limits, 298 K, 10 Torr) and demonstrate the formation of SO 3 under our experimental conditions. Through high-level theory, we explore the effect of Criegee intermediate structure on the minimum energy pathways for their reactions with SO 2 and obtain modified Arrhenius fits to our predictions for the reaction of both syn and anti conformers of MECI with SO 2 ( k syn = 4.42 × 10 11 T -7.80 exp(-1401/T) cm 3 s -1 and k anti = 1.26 × 10 11 T -7.55 exp(-1397/T) cm 3 s -1 ). Our experimental and theoretical rate coefficients (which are in reasonable agreement at 298 K) show that the reaction of MECI with SO 2 is significantly faster than MVK-oxide + SO 2 , demonstrating the substantial effect of resonance stabilization on Criegee intermediate reactivity.

UV-vis spectroscopy is widely used for kinetic studies in physical chemistry, as species' absolute cross-sections are usually less sensitive to experimental conditions (i.e., temperature and pressure). Here, we present the design and characterization of a multipass UV-vis absorption spectroscopy white cell coupled to a pulsed-laser photolysis flow reactor. The glass reactor was designed to facilitate studies of gas phase chemical reactions over a range of conditions (239-293 K and 10-550 Torr). Purged windows mitigate contamination from chemical precursors and photolysis products. We report the measured impact of this purging on temperature uniformity and the absorption length and present some supporting flow calculations. The combined optical setup is unique and enables the photolysis laser to be coaligned with a well-defined absorption pathlength probe beam. This alignment leverages the use of one long-pass filter to increase the spectrum flatness and increase the light intensity vs other systems that use two dichroic mirrors. The probe beam is analyzed with a dual exit spectrograph, customized to split the light between an intensified CCD and photomultiplier tube, enabling simultaneous spectrum and single wavelength detection. This multipass system yields a pathlength of ∼450 cm and minimum observable concentrations of ∼3.7 × 1011 molecule cm-3 (assuming cross-sections ∼1.2 × 10-17 cm2). The temperature profile across the reaction region is ±2 K, defined by the worst-case temperature of 239 K, validated by measurements of the N2O4 equilibrium constant. Finally, the system is implemented to study the simplest Criegee intermediate, demonstrating the instrument performance and advantages of simultaneous spectrum and temporal profile measurements., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Sulfur oxide species (RSO x ) play a critical role in many fields, ranging from biology to atmospheric chemistry. Chlorine-containing sulfur oxides may play a key role in sulfate aerosol formation in Venus' cloud layer by catalyzing the oxidation of SO to SO 2 via sulfinyl radicals (RSO). We present results from the gas-phase UV-vis transient absorption spectroscopy study of the simplest sulfinyl radical, ClSO, generated from the pulsed-laser photolysis of thionyl chloride at 248 nm (at 40 Torr of N 2 and 292 K). A weak absorption spectrum from 350 to 480 nm with a peak at 385 nm was observed, with partially resolved vibronic bands (spacing = 226 cm -1 ), and a peak cross section σ(385 nm) = (7.6 ± 1.9) × 10 -20 cm 2 . From ab initio calculations at the EOMEE-CCSD/ano-pVQZ level, we assigned this band to 1 2 A' ← X 2 A″ and 2 2 A' ← X 2 A″ transitions. The spectrum was modeled as a sum of a bound-to-free transition to the 1 2 A' state and a bound-to-bound transition to the 2 2 A' state with similar oscillator strengths; the prediction agreed well with the observed spectrum. We attributed the vibronic structure to a progression in the bending vibration of the 2 2 A' state. Further calculations at the XDW-CASPT2 level predicted a conical intersection between the excited 1 2 A' and 2 2 A' potential energy surfaces near the Franck-Condon region. The geometry of the minimum-energy conical intersection was similar to that of the ground-state geometry. The lack of structure at shorter wavelengths could be evidence of a short excited-state lifetime arising from strong vibronic coupling. From simplified molecular orbital analysis, we attributed the ClSO spectrum to transitions involving the out-of-plane π/π * orbitals along the S-O bond and the in-plane orbital possessing a σ/σ * character along the S-Cl bond. We hypothesize that these orbitals are common to other sulfinyl radicals, RSO, which would share a combination of a strong and a weak transition in the UV (near 300 nm) and visible (400-600 nm) regions.

The temperature-dependent kinetic parameters, branching fractions, and chaperone effects of the self- and cross-reactions between acetonyl peroxy (CH 3 C(O)CH 2 O 2 ) and hydro peroxy (HO 2 ) have been studied using pulsed laser photolysis coupled with infrared (IR) wavelength-modulation spectroscopy and ultraviolet absorption (UVA) spectroscopy. Two IR lasers simultaneously monitored HO 2 and hydroxyl (OH), while UVA measurements monitored CH 3 C(O)CH 2 O 2 . For the CH 3 C(O)CH 2 O 2 self-reaction ( T = 270-330 K), the rate parameters were determined to be A = (1.5 -0.3 +0.4 ) × 10 -13 and E a / R = -996 ± 334 K and the branching fraction to the alkoxy channel, k 2b / k 2 , showed an inverse temperature dependence following the expression, k 2b / k 2 = (2.27 ± 0.62) - [(6.35 ± 2.06) × 10 -3 ] T (K). For the reaction between CH 3 C(O)CH 2 O 2 and HO 2 ( T = 270-330 K), the rate parameters were determined to be A = (3.4 -1.5 +2.5 ) × 10 -13 and E a / R = -547 ± 415 K for the hydroperoxide product channel and A = (6.23 -4.4 +15.3 ) × 10 -17 and E a / R = -3100 ± 870 K for the OH product channel. The branching fraction for the OH channel, k 1b / k 1 , follows the temperature-dependent expression, k 1b / k 1 = (3.27 ± 0.51) - [(9.6 ± 1.7) × 10 -3 ] T (K). Determination of these parameters required an extensive reaction kinetics model which included a re-evaluation of the temperature dependence of the HO 2 self-reaction chaperone enhancement parameters due to the methanol-hydroperoxy complex. The second-law thermodynamic parameters for K P,M for the formation of the complex were found to be Δ r H 250K ° = -38.6 ± 3.3 kJ mol -1 and Δ r S 250K ° = -110.5 ± 13.2 J mol -1 K -1 , with the third-law analysis yielding Δ r H 250K ° = -37.5 ± 0.25 kJ mol -1 . The HO 2 self-reaction rate coefficient was determined to be k 4 = (3.34 -0.80 +1.04 ) × 10 -13 exp [(507 ± 76)/ T ]cm 3 molecule -1 s -1 with the enhancement term k 4,M ″ = (2.7 -1.7 +4.7 ) × 10 -36 exp [(4700 ± 255)/ T ]cm 6 molecule -2 s -1 , proportional to [CH 3 OH], over T = 220-280 K. The equivalent chaperone enhancement parameter for the acetone-hydroperoxy complex was also required and determined to be k 4,A ″ = (5.0 × 10 -38 - 1.4 × 10 -41 ) exp[(7396 ± 1172)/ T ] cm 6 molecule -2 s -1 , proportional to [CH 3 C(O)CH 3 ], over T = 270-296 K. From these parameters, the rate coefficients for the reactions between HO 2 and the respective complexes over the given temperature ranges can be estimated: for HO 2 ·CH 3 OH, k 12 = [(1.72 ± 0.050) × 10 -11 ] exp [(314 ± 7.2)/T] cm 3 molecule -1 s -1 and for HO 2 ·CH 3 C(O)CH 3 , k 15 = [(7.9 ± 0.72) × 10 -17 ] exp [(3881 ± 25)/ T ] cm 3 molecule -1 s -1 . Lastly, an estimate of the rate coefficient for the HO 2 ·CH 3 OH self-reaction was also determined to be k 13 = (1.3 ± 0.45) × 10 -10 cm 3 molecule -1 s -1 .

Alkene ozonolysis generates short-lived Criegee intermediates that are a significant source of hydroxyl (OH) radicals. This study demonstrates that roaming of the separating OH radicals can yield alternate hydroxycarbonyl products, thereby reducing the OH yield. Specifically, hydroxybutanone has been detected as a stable product arising from roaming in the unimolecular decay of the methyl-ethyl-substituted Criegee intermediate (MECI) under thermal flow cell conditions. The dynamical features of this novel multistage dissociation plus a roaming unimolecular decay process have also been examined with ab initio kinetics calculations. Experimentally, hydroxybutanone isomers are distinguished from the isomeric MECI by their higher ionization threshold and distinctive photoionization spectra. Moreover, the exponential rise of the hydroxybutanone kinetic time profile matches that for the unimolecular decay of MECI. A weaker methyl vinyl ketone (MVK) photoionization signal is also attributed to OH roaming. Complementary multireference electronic structure calculations have been utilized to map the unimolecular decay pathways for MECI, starting with 1,4 H atom transfer from a methyl or methylene group to the terminal oxygen, followed by roaming of the separating OH and butanonyl radicals in the long-range region of the potential. Roaming via reorientation and the addition of OH to the vinyl group of butanonyl is shown to yield hydroxybutanone, and subsequent C-O elongation and H-transfer can lead to MVK. A comprehensive theoretical kinetic analysis has been conducted to evaluate rate constants and branching yields (ca. 10-11%) for thermal unimolecular decay of MECI to conventional and roaming products under laboratory and atmospheric conditions, consistent with the estimated experimental yield (ca. 7%).

Reduced nitrogen (N) is central to global biogeochemistry, yet there are large uncertainties surrounding its sources and rate of cycling. Here, we present observations of gas-phase urea (CO(NH 2 ) 2 ) in the atmosphere from airborne high-resolution mass spectrometer measurements over the North Atlantic Ocean. We show that urea is ubiquitous in the lower troposphere in the summer, autumn, and winter but was not detected in the spring. The observations suggest that the ocean is the primary emission source, but further studies are required to understand the responsible mechanisms. Urea is also observed aloft due to long-range transport of biomass-burning plumes. These observations alongside global model simulations point to urea being an important, and currently unaccounted for, component of reduced-N to the remote marine atmosphere. Airborne transfer of urea between nutrient-rich and -poor parts of the ocean can occur readily and could impact ecosystems and oceanic uptake of carbon dioxide, with potentially important climate implications.

The concentration of formic acid in Earth's troposphere is underestimated by detailed chemical models compared to field observations. Phototautomerization of acetaldehyde to its less stable tautomer vinyl alcohol, followed by the OH-initiated oxidation of vinyl alcohol, has been proposed as a missing source of formic acid that improves the agreement between models and field measurements. Theoretical investigations of the OH + vinyl alcohol reaction in excess O 2 conclude that OH addition to the α carbon of vinyl alcohol produces formaldehyde + formic acid + OH, whereas OH addition to the β site leads to glycoaldehyde + HO 2 . Furthermore, these studies predict that the conformeric structure of vinyl alcohol controls the reaction pathway, with the anti -conformer of vinyl alcohol promoting α OH addition, whereas the syn -conformer promotes β addition. However, the two theoretical studies reach different conclusions regarding which set of products dominate. We studied this reaction using time-resolved multiplexed photoionization mass spectrometry to quantify the product branching fractions. Our results, supported by a detailed kinetic model, conclude that the glycoaldehyde product channel (arising mostly from syn -vinyl alcohol) dominates over formic acid production with a 3.6:1.0 branching ratio. This result supports the conclusion of Lei et al. that conformer-dependent hydrogen bonding at the transition state for OH-addition controls the reaction outcome. As a result, tropospheric oxidation of vinyl alcohol creates less formic acid than recently thought, increasing again the discrepancy between models and field observations of Earth's formic acid budget.

Thionyl chloride (Cl 2 SO) serves as a common Cl atom source in widespread applications of chlorine chemistry though little is known about the reactivity and spectroscopy of the ClSO radical after a Cl-S bond cleavage. We performed a Pulsed Laser Photolysis experiment to detect ClSO from Cl 2 SO photolysis at 248 nm in a gas-flow reactor by time-resolved UV-vis transient absorption spectroscopy. A few chemical tests, using I 2 and NO 2 , suggested the structured absorption band between 260 and 320 nm belonged to ClSO radical and that the termolecular ClSO + Cl + M → Cl 2 SO association reaction occurred. From EOMIP-CCSD/ano-pVQZ calculations, the ClSO band was assigned to the 1 2 A″ ← X 2 A″ transition involving the π* ← π transition of the SO bond and the vibrational progression to the SO stretching mode of the 1 2 A″ state, with a maximum cross-section = (2.0 ± 0.5) × 10 -18 cm 2 near 286 nm (1σ uncertainty) and an average spacing of vibrational structure of 658 cm -1 . The rapid decay of the ClSO signal monitored near 303 nm could be fit to a second-order kinetic model over 10-90 Torr, which yields an effective bimolecular rate coefficient k Cl+ClSO = (1.48 ± 0.42) × 10 -11 cm 3 molecule -1 s -1 at 292 K and 90 Torr (1σ uncertainty). This fast recombination reaction suggests that Cl-containing SO x species might act as significant Cl atom reservoirs in sulfur oxide-rich environments such as Venus' atmosphere. Moreover, the reported UV spectrum provides a new means for monitoring the ClSO radicals.

Brain and skull tissues interact through molecular signalling and mechanical forces during head development, leading to a strong correlation between the neurocranium and the external brain surface. Therefore, when brain tissue is unavailable, neurocranial endocasts are often used to approximate brain size and shape. Evolutionary changes in brain morphology may have resulted in secondary changes to neurocranial morphology, but the developmental and genetic processes underlying this relationship are not well understood. Using automated phenotyping methods, we quantified the genetic basis of endocast variation across large genetically varied populations of laboratory mice in two ways: (1) to determine the contributions of various genetic factors to neurocranial form and (2) to help clarify whether a neurocranial variation is based on genetic variation that primarily impacts bone development or on genetic variation that primarily impacts brain development, leading to secondary changes in bone morphology. Our results indicate that endocast size is highly heritable and is primarily determined by additive genetic factors. In addition, a non-additive inbreeding effect led to founder strains with lower neurocranial size, but relatively large brains compared to skull size; suggesting stronger canalization of brain size and/or a general allometric effect. Within an outbred sample of mice, we identified a locus on mouse chromosome 1 that is significantly associated with variation in several positively correlated endocast size measures. Because the protein-coding genes at this locus have been previously associated with brain development and not with bone development, we propose that genetic variation at this locus leads primarily to variation in brain volume that secondarily leads to changes in neurocranial globularity. We identify a strain-specific missense mutation within Akt3 that is a strong causal candidate for this genetic effect. Whilst it is not appropriate to generalize our hypothesis for this single locus to all other loci that also contribute to the complex trait of neurocranial skull morphology, our results further reveal the genetic basis of neurocranial variation and highlight the importance of the mechanical influence of brain growth in determining skull morphology., (© 2022 Anatomical Society.)

Background: Variation in facial shape may arise from the combinatorial or overlapping actions of paralogous genes. Given its many members, and overlapping expression and functions, the EPH receptor family is a compelling candidate source of craniofacial morphological variation. We performed a detailed morphometric analysis of an allelic series of E14.5 Ephb1-3 receptor mutants to determine the effect of each paralogous receptor gene on craniofacial morphology., Results: We found that Ephb1, Ephb2, and Ephb3 genotypes significantly influenced facial shape, but Ephb1 effects were weaker than Ephb2 and Ephb3 effects. Ephb2 -/- and Ephb3 -/- mutations affected similar aspects of facial morphology, but Ephb3 -/- mutants had additional facial shape effects. Craniofacial differences across the allelic series were largely consistent with predicted additive genetic effects. However, we identified a potentially important nonadditive effect where Ephb1 mutants displayed different morphologies depending on the combination of other Ephb paralogs present, where Ephb1 +/- , Ephb1 -/- , and Ephb1 -/- ; Ephb3 -/- mutants exhibited a consistent deviation from their predicted facial shapes., Conclusions: This study provides a detailed assessment of the effects of Ephb receptor gene paralogs on E14.5 mouse facial morphology and demonstrates how the loss of specific receptors contributes to facial dysmorphology., (© 2022 American Association for Anatomy.)

Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses. To enable meta-analyses of morphological variation, particularly in the craniofacial complex and brain, we created MusMorph, a database of standardized mouse morphology data spanning numerous genotypes and developmental stages, including E10.5, E11.5, E14.5, E15.5, E18.5, and adulthood. To standardize data collection, we implemented an atlas-based phenotyping pipeline that combines techniques from image registration, deep learning, and morphometrics. Alongside stage-specific atlases, we provide aligned micro-computed tomography images, dense anatomical landmarks, and segmentations (if available) for each specimen (N = 10,056). Our workflow is open-source to encourage transparency and reproducible data collection. The MusMorph data and scripts are available on FaceBase ( www.facebase.org , https://doi.org/10.25550/3-HXMC ) and GitHub ( https://github.com/jaydevine/MusMorph )., (© 2022. The Author(s).)

Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. The O-fucose is added in the endoplasmic reticulum to folded TSRs by the enzyme Protein O-fucosyltransferase-2 (POFUT2) and is proposed to promote efficient trafficking of substrates. The importance of this modification for function of TSR-proteins is underscored by the early embryonic lethality of mouse embryos lacking Pofut2. To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. Consistent with these changes we saw a decrease in the size of the hypertrophic zone with lower levels of Collagen-X. Unexpectedly, we observed minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone. In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. These combined results suggest that the impact of the Pofut2 mutation is cell-type specific. In addition, these observations raise the possibility that the O-fucose modification on TSRs extends beyond promoting efficient trafficking of POFUT2 substrates and has the potential to influence their function in the extracellular environment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The reactivity of carbonyl oxides has previously been shown to exhibit strong conformer and substituent dependencies. Through a combination of synchrotron-multiplexed photoionization mass spectrometry experiments (298 K and 4 Torr) and high-level theory [CCSD(T)-F12/cc-pVTZ-F12//B2PLYP-D3/cc-pVTZ with an added CCSDT(Q) correction], we explore the conformer dependence of the reaction of acetaldehyde oxide (CH 3 CHOO) with dimethylamine (DMA). The experimental data support the theoretically predicted 1,2-insertion mechanism and the formation of an amine-functionalized hydroperoxide reaction product. Tunable-vacuum ultraviolet photoionization probing of anti - or anti - + syn -CH 3 CHOO reveals a strong conformer dependence of the title reaction. The rate coefficient of DMA with anti -CH 3 CHOO is predicted to exceed that for the reaction with syn -CH 3 CHOO by a factor of ∼34,000, which is attributed to submerged barrier ( syn ) versus barrierless ( anti ) mechanisms for energetically downhill reactions.

We report methane isotopologue data from aircraft and ground measurements in Africa and South America. Aircraft campaigns sampled strong methane fluxes over tropical papyrus wetlands in the Nile, Congo and Zambezi basins, herbaceous wetlands in Bolivian southern Amazonia, and over fires in African woodland, cropland and savannah grassland. Measured methane δ 13 C CH 4 isotopic signatures were in the range -55 to -49‰ for emissions from equatorial Nile wetlands and agricultural areas, but widely -60 ± 1‰ from Upper Congo and Zambezi wetlands. Very similar δ 13 C CH 4 signatures were measured over the Amazonian wetlands of NE Bolivia (around -59‰) and the overall δ 13 C CH 4 signature from outer tropical wetlands in the southern Upper Congo and Upper Amazon drainage plotted together was -59 ± 2‰. These results were more negative than expected. For African cattle, δ 13 C CH 4 values were around -60 to -50‰. Isotopic ratios in methane emitted by tropical fires depended on the C3 : C4 ratio of the biomass fuel. In smoke from tropical C3 dry forest fires in Senegal, δ 13 C CH 4 values were around -28‰. By contrast, African C4 tropical grass fire δ 13 C CH 4 values were -16 to -12‰. Methane from urban landfills in Zambia and Zimbabwe, which have frequent waste fires, had δ 13 C CH 4 around -37 to -36‰. These new isotopic values help improve isotopic constraints on global methane budget models because atmospheric δ 13 C CH 4 values predicted by global atmospheric models are highly sensitive to the δ 13 C CH 4 isotopic signatures applied to tropical wetland emissions. Field and aircraft campaigns also observed widespread regional smoke pollution over Africa, in both the wet and dry seasons, and large urban pollution plumes. The work highlights the need to understand tropical greenhouse gas emissions in order to meet the goals of the UNFCCC Paris Agreement, and to help reduce air pollution over wide regions of Africa. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'.

Methacrolein oxide (MACR-oxide) is a four-carbon, resonance-stabilized Criegee intermediate produced from isoprene ozonolysis, yet its reactivity is not well understood. This study identifies the functionalized hydroperoxide species, 1-hydroperoxy-2-methylallyl formate (HPMAF), generated from the reaction of MACR-oxide with formic acid using multiplexed photoionization mass spectrometry (MPIMS, 298 K = 25 °C, 10 torr = 13.3 hPa). Electronic structure calculations indicate the reaction proceeds via an energetically favorable 1,4-addition mechanism. The formation of HPMAF is observed by the rapid appearance of a fragment ion at m / z 99, consistent with the proposed mechanism and characteristic loss of HO 2 upon photoionization of functional hydroperoxides. The identification of HPMAF is confirmed by comparison of the appearance energy of the fragment ion with theoretical predictions of its photoionization threshold. The results are compared to analogous studies on the reaction of formic acid with methyl vinyl ketone oxide (MVK-oxide), the other four-carbon Criegee intermediate in isoprene ozonolysis.

The contribution of NO x emissions and background O 3 to the sources and partitioning of the oxidants [OX (= O 3 + NO 2 )] at the Marylebone Road site in London during the 2000s and 2010s has been investigated to see the impact of the control measures or technology changes inline with the London Mayor's Air Quality Strategy. The abatement of the pollution emissions has an impact on the trends of local and background oxidants, [OX] L and [OX] B , decreasing by 1.4% per year and 0.4% per year, respectively from 2000 to 2019. We also extend our study to three roadside sites (Din Daeng, Thonburi and Chokchai) in another megacity, Bangkok, to compare [OX] L and [OX] B and their behavioural changes with respect to the Marylebone Road site. [OX] L and [OX] B at the Marylebone Road site (0.21[NO x ] and 32 ppbv) are comparable with the roadside sites of Thailand (0.12[NO x ] to 0.26[NO x ] and 29 to 32 ppbv). The seasonal variation of [OX] B levels displays a spring maximum for London, which is due to the higher northern hemispheric ozone baseline, but a maximum during the dry season is found for Bangkok which is likely due to regional-scale long-range transport from the Asian continent. The diurnal variations of [OX] L for both London and Bangkok roadside sites confirm the dominance of the oxidants from road transport emissions, which are found to be higher throughout the daytime. WRF-Chem-CRI model simulations of the distribution of [OX] showed that the model performed well for London background sites when predicting [OX] levels compared with the measured [OX] levels suggesting that the model is treating the chemistry of the oxidants correctly. However, there are large discrepancies for the model-measurement [OX] levels at the traffic site because of the difficulties in the modelling of [OX] at large road networks in megacities for the complex sub grid-scale dynamics that are taking place, both in terms of atmospheric processes and time-varying sources, such as traffic volumes. For roadside sites in Bangkok, the trend in changes of [OX] is predicted by the model correctly but overestimated in absolute magnitude. We suggest that this large deviation is likely to be due to discrepancies in the EDGAR emission inventory (emission overestimates) beyond the resolution of the model.

The OH + NO 2 reaction is a critically important process for radical chain termination in the atmosphere with a major impact on the ozone budgets of the troposphere and stratosphere. Rate constants for the reaction of OH + NO 2 + M → products have been measured under conditions relevant to the upper troposphere/lower stratosphere with a laser photolysis-laser-induced fluorescence (LP-LIF) technique augmented by in situ optical spectroscopy for quantification of [NO 2 ]. The experiments are carried out over the temperature range of 230-293 K and the pressure range 50-750 Torr of N 2 and air and as a function of [O 2 ]. The observed rate coefficients in N 2 agree with the newest experimental literature data sets and are within experimental uncertainty of current recommended literature values at 293 K but are systematically higher by up to 22% at 700 Torr and 230 K. The efficacy of different falloff parametrizations has been examined and compared to those in literature sources. The collisional quenching efficiency of O 2 was found to be in excellent agreement with current literature sources, and rate coefficients determined in air at 293 and 245 K were observed to be within uncertainty of the rate coefficients measured in N 2 bath gas. This work has improved confidence in the literature rate coefficients under conditions of the lower troposphere (∼760 Torr, 280-310 K) toward the stratosphere (10-100 Torr, 220-250 K).

Isoprene is the most abundant non-methane hydrocarbon emitted into the Earth's atmosphere. Ozonolysis is an important atmospheric sink for isoprene, which generates reactive carbonyl oxide species (R1R2C[double bond, length as m-dash]O+O-) known as Criegee intermediates. This study focuses on characterizing the catalyzed isomerization and adduct formation pathways for the reaction between formic acid and methyl vinyl ketone oxide (MVK-oxide), a four-carbon unsaturated Criegee intermediate generated from isoprene ozonolysis. syn-MVK-oxide undergoes intramolecular 1,4 H-atom transfer to form a substituted vinyl hydroperoxide intermediate, 2-hydroperoxybuta-1,3-diene (HPBD), which subsequently decomposes to hydroxyl and vinoxylic radical products. Here, we report direct observation of HPBD generated by formic acid catalyzed isomerization of MVK-oxide under thermal conditions (298 K, 10 torr) using multiplexed photoionization mass spectrometry. The acid catalyzed isomerization of MVK-oxide proceeds by a double hydrogen-bonded interaction followed by a concerted H-atom transfer via submerged barriers to produce HPBD and regenerate formic acid. The analogous isomerization pathway catalyzed with deuterated formic acid (D2-formic acid) enables migration of a D atom to yield partially deuterated HPBD (DPBD), which is identified by its distinct mass (m/z 87) and photoionization threshold. In addition, bimolecular reaction of MVK-oxide with D2-formic acid forms a functionalized hydroperoxide adduct, which is the dominant product channel, and is compared to a previous bimolecular reaction study with normal formic acid. Complementary high-level theoretical calculations are performed to further investigate the reaction pathways and kinetics.

Pulsed laser photolysis coupled with infrared (IR) wavelength modulation spectroscopy and ultraviolet (UV) absorption spectroscopy was used to study the kinetics and branching fractions for the acetonyl peroxy (CH 3 C(O)CH 2 O 2 ) self-reaction and its reaction with hydro peroxy (HO 2 ) at a temperature of 298 K and pressure of 100 Torr. Near-IR and mid-IR lasers simultaneously monitored HO 2 and hydroxyl, OH, respectively, while UV absorption measurements monitored the CH 3 C(O)CH 2 O 2 concentrations. The overall rate constant for the reaction between CH 3 C(O)CH 2 O 2 and HO 2 was found to be (5.5 ± 0.5) × 10 -12 cm 3 molecule -1 s -1 , and the branching fraction for OH yield from this reaction was directly measured as 0.30 ± 0.04. The CH 3 C(O)CH 2 O 2 self-reaction rate constant was measured to be (4.8 ± 0.8) × 10 -12 cm 3 molecule -1 s -1 , and the branching fraction for alkoxy formation was inferred from secondary chemistry as 0.33 ± 0.13. An increase in the rate of the HO 2 self-reaction was also observed as a function of acetone (CH 3 C(O)CH 3 ) concentration which is interpreted as a chaperone effect, resulting from hydrogen-bond complexation between HO 2 and CH 3 C(O)CH 3 . The chaperone enhancement coefficient for CH 3 C(O)CH 3 was determined to be k A ″ = (4.0 ± 0.2) × 10 -29 cm 6 molecule -2 s -1 , and the equilibrium constant for HO 2 ·CH 3 C(O)CH 3 complex formation was found to be K c (R14) = (2.0 ± 0.89) × 10 -18 cm 3 molecule -1 ; from these values, the rate constant for the HO 2 + HO 2 ·CH 3 C(O)CH 3 reaction was estimated to be (2 ± 1) × 10 -11 cm 3 molecule -1 s -1 . Results from UV absorption cross-section measurements of CH 3 C(O)CH 2 O 2 and prompt OH radical yields arising from possible oxidation of the CH 3 C(O)CH 3 -derived alkyl radical are also discussed. Using theoretical methods, no likely pathways for the observed prompt OH radical formation have been found and the prompt OH radical yields thus remain unexplained.

Geometric morphometrics is the statistical analysis of landmark-based shape variation and its covariation with other variables. Over the past two decades, the gold standard of landmark data acquisition has been manual detection by a single observer. This approach has proven accurate and reliable in small-scale investigations. However, big data initiatives are increasingly common in biology and morphometrics. This requires fast, automated, and standardized data collection. We combine techniques from image registration, geometric morphometrics, and deep learning to automate and optimize anatomical landmark detection. We test our method on high-resolution, micro-computed tomography images of adult mouse skulls. To ensure generalizability, we use a morphologically diverse sample and implement fundamentally different deformable registration algorithms. Compared to landmarks derived from conventional image registration workflows, our optimized landmark data show up to a 39.1% reduction in average coordinate error and a 36.7% reduction in total distribution error. In addition, our landmark optimization produces estimates of the sample mean shape and variance-covariance structure that are statistically indistinguishable from expert manual estimates. For biological imaging datasets and morphometric research questions, our approach can eliminate the time and subjectivity of manual landmark detection whilst retaining the biological integrity of these expert annotations., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare.

The biology of how faces are built and come to differ from one another is complex. Discovering normal variants that contribute to differences in facial morphology is one key to untangling this complexity, with important implications for medicine and evolutionary biology. This study maps quantitative trait loci (QTL) for skeletal facial shape using Diversity Outbred (DO) mice. The DO is a randomly outcrossed population with high heterozygosity that captures the allelic diversity of eight inbred mouse lines from three subspecies. The study uses a sample of 1147 DO animals (the largest sample yet employed for a shape QTL study in mouse), each characterized by 22 three-dimensional landmarks, 56,885 autosomal and X-chromosome markers, and sex and age classifiers. We identified 37 facial shape QTL across 20 shape principal components (PCs) using a mixed effects regression that accounts for kinship among observations. The QTL include some previously identified intervals as well as new regions that expand the list of potential targets for future experimental study. Three QTL characterized shape associations with size (allometry). Median support interval size was 3.5 Mb. Narrowing additional analysis to QTL for the five largest magnitude shape PCs, we found significant overrepresentation of genes with known roles in growth, skeletal and facial development, and sensory organ development. For most intervals, one or more of these genes lies within 0.25 Mb of the QTL's peak. QTL effect sizes were small, with none explaining more than 0.5% of facial shape variation. Thus, our results are consistent with a model of facial diversity that is influenced by key genes in skeletal and facial development and, simultaneously, is highly polygenic., Competing Interests: The authors have declared that no competing interests exist.

Ozonolysis of isoprene, one of the most abundant volatile organic compounds emitted into the Earth's atmosphere, generates two four-carbon unsaturated Criegee intermediates, methyl vinyl ketone oxide (MVK-oxide) and methacrolein oxide (MACR-oxide). The extended conjugation between the vinyl substituent and carbonyl oxide groups of these Criegee intermediates facilitates rapid electrocyclic ring closures that form five-membered cyclic peroxides, known as dioxoles. This study reports the first experimental evidence of this novel decay pathway, which is predicted to be the dominant atmospheric sink for specific conformational forms of MVK-oxide ( anti ) and MACR-oxide ( syn ) with the vinyl substituent adjacent to the terminal O atom. The resulting dioxoles are predicted to undergo rapid unimolecular decay to oxygenated hydrocarbon radical products, including acetyl, vinoxy, formyl, and 2-methylvinoxy radicals. In the presence of O 2 , these radicals rapidly react to form peroxy radicals (ROO), which quickly decay via carbon-centered radical intermediates (QOOH) to stable carbonyl products that were identified in this work. The carbonyl products were detected under thermal conditions (298 K, 10 Torr He) using multiplexed photoionization mass spectrometry (MPIMS). The main products (and associated relative abundances) originating from unimolecular decay of anti -MVK-oxide and subsequent reaction with O 2 are formaldehyde (88 ± 5%), ketene (9 ± 1%), and glyoxal (3 ± 1%). Those identified from the unimolecular decay of syn -MACR-oxide and subsequent reaction with O 2 are acetaldehyde (37 ± 7%), vinyl alcohol (9 ± 1%), methylketene (2 ± 1%), and acrolein (52 ± 5%). In addition to the stable carbonyl products, the secondary peroxy chemistry also generates OH or HO 2 radical coproducts.

Isoprene has the highest emission into Earth's atmosphere of any nonmethane hydrocarbon. Atmospheric processing of alkenes, including isoprene, via ozonolysis leads to the formation of zwitterionic reactive intermediates, known as Criegee intermediates (CIs). Direct studies have revealed that reactions involving simple CIs can significantly impact the tropospheric oxidizing capacity, enhance particulate formation, and degrade local air quality. Methyl vinyl ketone oxide (MVK-oxide) is a four-carbon, asymmetric, resonance-stabilized CI, produced with 21 to 23% yield from isoprene ozonolysis, yet its reactivity has not been directly studied. We present direct kinetic measurements of MVK-oxide reactions with key atmospheric species using absorption spectroscopy. Direct UV-Vis absorption spectra from two independent flow cell experiments overlap with the molecular beam UV-Vis-depletion spectra reported recently [M. F. Vansco, B. Marchetti, M. I. Lester, J. Chem. Phys. 149, 44309 (2018)] but suggest different conformer distributions under jet-cooled and thermal conditions. Comparison of the experimental lifetime herein with theory indicates only the syn -conformers are observed; anti -conformers are calculated to be removed much more rapidly via unimolecular decay. We observe experimentally and predict theoretically fast reaction of syn -MVK-oxide with SO 2 and formic acid, similar to smaller alkyl-substituted CIs, and by contrast, slow removal in the presence of water. We determine products through complementary multiplexed photoionization mass spectrometry, observing SO 3 and identifying organic hydroperoxide formation from reaction with SO 2 and formic acid, respectively. The tropospheric implications of these reactions are evaluated using a global chemistry and transport model., Competing Interests: Competing interest statement: R.L.C., C.A.T., and A. R. Ravishankara are amongst numerous coauthors in the General Discussion associated with the 2017 Faraday Discussion of Atmospheric Chemistry in the Anthropocene [Faraday Discuss. 200, 353–378 (2017)].

Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder characterized by craniofacial, skeletal, and neurological anomalies and is caused by mutations in EFNB1. Heterozygous females are more severely affected by CFNS than hemizygous males, a phenomenon called cellular interference that results from EPHRIN-B1 mosaicism. In Efnb1 heterozygous mice, mosaicism for EPHRIN-B1 results in cell sorting and more severe phenotypes than Efnb1 hemizygous males, but how craniofacial dysmorphology arises from cell segregation is unknown and CFNS etiology therefore remains poorly understood. Here, we couple geometric morphometric techniques with temporal and spatial interrogation of embryonic cell segregation in mouse mutant models to elucidate mechanisms underlying CFNS pathogenesis. By generating EPHRIN-B1 mosaicism at different developmental timepoints and in specific cell populations, we find that EPHRIN-B1 regulates cell segregation independently in early neural development and later in craniofacial development, correlating with the emergence of quantitative differences in face shape. Whereas specific craniofacial shape changes are qualitatively similar in Efnb1 heterozygous and hemizygous mutant embryos, heterozygous embryos are quantitatively more severely affected, indicating that Efnb1 mosaicism exacerbates loss of function phenotypes rather than having a neomorphic effect. Notably, neural tissue-specific disruption of Efnb1 does not appear to contribute to CFNS craniofacial dysmorphology, but its disruption within neural crest cell-derived mesenchyme results in phenotypes very similar to widespread loss. EPHRIN-B1 can bind and signal with EPHB1, EPHB2, and EPHB3 receptor tyrosine kinases, but the signaling partner(s) relevant to CFNS are unknown. Geometric morphometric analysis of an allelic series of Ephb1; Ephb2; Ephb3 mutant embryos indicates that EPHB2 and EPHB3 are key receptors mediating Efnb1 hemizygous-like phenotypes, but the complete loss of EPHB1-3 does not fully recapitulate the severity of CFNS-like Efnb1 heterozygosity. Finally, by generating Efnb1+/Δ; Ephb1; Ephb2; Ephb3 quadruple knockout mice, we determine how modulating cumulative receptor activity influences cell segregation in craniofacial development and find that while EPHB2 and EPHB3 play an important role in craniofacial cell segregation, EPHB1 is more important for cell segregation in the brain; surprisingly, complete loss of EPHB1-EPHB3 does not completely abrogate cell segregation. Together, these data advance our understanding of the etiology and signaling interactions underlying CFNS dysmorphology., Competing Interests: The authors have declared that no competing interests exist.

Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene. Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs). Forty-nine proteins are predicted to be modified by POFUT2, and nearly half are members of the ADAMTS superfamily. Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets. To test this hypothesis and gain insight into the origin of PTRPLS developmental defects, we developed and characterized two mouse B3glct knockout alleles. Using these models, we tested the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development. The mouse B3glct mutants developed craniofacial and skeletal abnormalities comparable to PTRPLS. In addition, we observed highly penetrant hydrocephalus, white spotting and soft tissue syndactyly. We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function. Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Ammonia and amines are emitted into the troposphere by various natural and anthropogenic sources, where they have a significant role in aerosol formation. Here, we explore the significance of their removal by reaction with Criegee intermediates, which are produced in the troposphere by ozonolysis of alkenes. Rate coefficients for the reactions of two representative Criegee intermediates, formaldehyde oxide (CH2OO) and acetone oxide ((CH3)2COO) with NH3 and CH3NH2 were measured using cavity ring-down spectroscopy. Temperature-dependent rate coefficients, k(CH2OO + NH3) = (3.1 ± 0.5) × 10-20T2 exp(1011 ± 48/T) cm3 s-1 and k(CH2OO + CH3NH2) = (5 ± 2) × 10-19T2 exp(1384 ± 96/T) cm3 s-1 were obtained in the 240 to 320 K range. Both the reactions of CH2OO were found to be independent of pressure in the 10 to 100 Torr (N2) range, and average rate coefficients k(CH2OO + NH3) = (8.4 ± 1.2) × 10-14 cm3 s-1 and k(CH2OO + CH3NH2) = (5.6 ± 0.4) × 10-12 cm3 s-1 were deduced at 293 K. An upper limit of ≤2.7 × 10-15 cm3 s-1 was estimated for the rate coefficient of the (CH3)2COO + NH3 reaction. Complementary measurements were performed with mass spectrometry using synchrotron radiation photoionization giving k(CH2OO + CH3NH2) = (4.3 ± 0.5) × 10-12 cm3 s-1 at 298 K and 4 Torr (He). Photoionization mass spectra indicated production of NH2CH2OOH and CH3N(H)CH2OOH functionalized organic hydroperoxide adducts from CH2OO + NH3 and CH2OO + CH3NH2 reactions, respectively. Ab initio calculations performed at the CCSD(T)(F12*)/cc-pVQZ-F12//CCSD(T)(F12*)/cc-pVDZ-F12 level of theory predicted pre-reactive complex formation, consistent with previous studies. Master equation simulations of the experimental data using the ab initio computed structures identified submerged barrier heights of -2.1 ± 0.1 kJ mol-1 and -22.4 ± 0.2 kJ mol-1 for the CH2OO + NH3 and CH2OO + CH3NH2 reactions, respectively. The reactions of NH3 and CH3NH2 with CH2OO are not expected to compete with its removal by reaction with (H2O)2 in the troposphere. Similarly, losses of NH3 and CH3NH2 by reaction with Criegee intermediates will be insignificant compared with reactions with OH radicals.

During the late Pleistocene, isolated lineages of hominins exchanged genes thus influencing genomic variation in humans in both the past and present. However, the dynamics of this genetic exchange and associated phenotypic consequences through time remain poorly understood. Gene exchange across divergent lineages can result in myriad outcomes arising from these dynamics and the environmental conditions under which it occurs. Here we draw from our collective research across various organisms, illustrating some of the ways in which gene exchange can structure genomic/phenotypic diversity within/among species. We present a range of examples relevant to questions about the evolution of hominins. These examples are not meant to be exhaustive, but rather illustrative of the diverse evolutionary causes/consequences of hybridization, highlighting potential drivers of human evolution in the context of hybridization including: influences on adaptive evolution, climate change, developmental systems, sex-differences in behavior, Haldane's rule and the large X-effect, and transgressive phenotypic variation., (© 2019 Wiley Periodicals, Inc.)

Morphometric analysis of anatomical landmarks allows researchers to identify specific morphological differences between natural populations or experimental groups, but manually identifying landmarks is time-consuming. We compare manually and automatically generated adult mouse skull landmarks and subsequent morphometric analyses to elucidate how switching from manual to automated landmarking will impact morphometric analysis results for large mouse (Mus musculus) samples (n = 1205) that represent a wide range of 'normal' phenotypic variation (62 genotypes). Other studies have suggested that the use of automated landmarking methods is feasible, but this study is the first to compare the utility of current automated approaches to manual landmarking for a large dataset that allows the quantification of intra- and inter-strain variation. With this unique sample, we investigated how switching to a non-linear image registration-based automated landmarking method impacts estimated differences in genotype mean shape and shape variance-covariance structure. In addition, we tested whether an initial registration of specimen images to genotype-specific averages improves automatic landmark identification accuracy. Our results indicated that automated landmark placement was significantly different than manual landmark placement but that estimated skull shape covariation was correlated across methods. The addition of a preliminary genotype-specific registration step as part of a two-level procedure did not substantially improve on the accuracy of one-level automatic landmark placement. The landmarks with the lowest automatic landmark accuracy are found in locations with poor image registration alignment. The most serious outliers within morphometric analysis of automated landmarks displayed instances of stochastic image registration error that are likely representative of errors common when applying image registration methods to micro-computed tomography datasets that were initially collected with manual landmarking in mind. Additional efforts during specimen preparation and image acquisition can help reduce the number of registration errors and improve registration results. A reduction in skull shape variance estimates were noted for automated landmarking methods compared with manual landmarking. This partially reflects an underestimation of more extreme genotype shapes and loss of biological signal, but largely represents the fact that automated methods do not suffer from intra-observer landmarking error. For appropriate samples and research questions, our image registration-based automated landmarking method can eliminate the time required for manual landmarking and have a similar power to identify shape differences between inbred mouse genotypes., (© 2019 Anatomical Society.)

This paper describes the development of a new sampling and measurement method to infer methane flux using proxy measurements of CO 2 concentration and wind data recorded by Unmanned Aerial Systems (UAS). The flux method described and trialed here is appropriate to the spatial scale of landfill sites and analogous greenhouse gas emission hotspots, making it an important new method for low-cost and rapid case study quantification of fluxes from currently uncertain (but highly important) greenhouse gas sources. We present a case study using these UAS-based measurements to derive instantaneous methane fluxes from a test landfill site in the north of England using a mass balance model tailored for UAS sampling and co-emitted CO 2 concentration as a methane-emission proxy. Methane flux (and flux uncertainty) during two trials on 27 November 2014 and 5 March 2015, were found to be 0.140 kg s -1 (±61% at 1σ), and 0.050 kg s -1 (±54% at 1σ), respectively. Uncertainty contributing to the flux was dominated by ambient variability in the background (inflow) concentration (>40%) and wind speed (>10%); with instrumental error contributing only ∼1-2%. The approach described represents an important advance concerning the challenging problem of greenhouse gas hotspot flux calculation, and offers transferability to a wide range of analogous environments. This new measurement solution could add to a toolkit of approaches to better validate source-specific greenhouse emissions inventories - an important new requirement of the UNFCCC COP21 (Paris) climate change agreement., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The reaction of perfluorooctanoic acid with the smallest carbonyl oxide Criegee intermediate, CH 2 OO, has been measured and is very rapid, with a rate coefficient of (4.9 ± 0.8) × 10 -10 cm 3 s -1 , similar to that for reactions of Criegee intermediates with other organic acids. Evidence is shown for the formation of hydroperoxymethyl perfluorooctanoate as a product. With such a large rate coefficient, reaction with Criegee intermediates can be a substantial contributor to atmospheric removal of perfluorocarboxylic acids. However, the atmospheric fates of the ester product largely regenerate the initial acid reactant. Wet deposition regenerates the perfluorocarboxylic acid via condensed-phase hydrolysis. Gas-phase reaction with OH is expected principally to result in formation of the acid anhydride, which also hydrolyzes to regenerate the acid, although a minor channel could lead to destruction of the perfluorinated backbone.

Methanol is a benchmark for understanding tropospheric oxidation, but is underpredicted by up to 100% in atmospheric models. Recent work has suggested this discrepancy can be reconciled by the rapid reaction of hydroxyl and methylperoxy radicals with a methanol branching fraction of 30%. However, for fractions below 15%, methanol underprediction is exacerbated. Theoretical investigations of this reaction are challenging because of intersystem crossing between singlet and triplet surfaces - ∼45% of reaction products are obtained via intersystem crossing of a pre-product complex - which demands experimental determinations of product branching. Here we report direct measurements of methanol from this reaction. A branching fraction below 15% is established, consequently highlighting a large gap in the understanding of global methanol sources. These results support the recent high-level theoretical work and substantially reduce its uncertainties.

The OH initiated oxidation of HNO3 in the UT/LS plays an important role in controlling the O3 budget, removing HOx radicals whilst driving NOx/y partitioning chemistry by yielding NO3 radicals: OH + HNO3 → H2O + NO3. In this paper, k1(T, P) was measured using OH (A ← X) Laser Induced Fluorescence (LIF) and the data was modelled over the 223-298 K temperature and 25-750 Torr pressure ranges, using the modified Lindemann-Hinshelwood expression , where k0 = 5.2 × 10-14 exp(200/T) cm3 s-1, k2 = 8.4 × 10-17 exp(1900/T) cm3 s-1 and k3 = 1.6 × 10-34 exp(1745/T) cm3 s-1. A significant source of experimental uncertainty derives from accurate determination of HNO3 concentration, which is impacted by heterogeneous uptake of the low volatility HNO3 onto cold surfaces of the reactors. Our results represent the determination of k1(T, P) using two different in situ [HNO3] measurements: VUV absorption and a new two photon Photolysis Induced Fluoresence (PIF). Experimental results are discussed along with a computational master equation calculation (MESMER), which highlight the need for further theoretical study into the OH + HNO3 mechanism and potential energy surface. The atmospheric impact of these new rate constants were modelled using the STOCHEM-CRI chemistry transport global model, which have shown a small reduction in global budgets of key atmospheric species, with more significant changes in the NOx/HNO3 ratio, peaking in the tropical upper troposphere regions.

Methyl vinyl ketone (MVK) and methacrolein (MACR) are important intermediate products in atmospheric degradation of volatile organic compounds, especially of isoprene. This work investigates the reactions of the smallest Criegee intermediate, CH2OO, with its co-products from isoprene ozonolysis, MVK and MACR, using multiplexed photoionization mass spectrometry (MPIMS), with either tunable synchrotron radiation from the Advanced Light Source or Lyman-α (10.2 eV) radiation for photoionization. CH2OO was produced via pulsed laser photolysis of CH2I2 in the presence of excess O2. Time-resolved measurements of reactant disappearance and of product formation were performed to monitor reaction progress; first order rate coefficients were obtained from exponential fits to the CH2OO decays. The bimolecular reaction rate coefficients at 300 K and 4 Torr are k(CH2OO + MVK) = (5.0 ± 0.4) × 10-13 cm3 s-1 and k(CH2OO + MACR) = (4.4 ± 1.0) × 10-13 cm3 s-1, where the stated ±2σ uncertainties are statistical uncertainties. Adduct formation is observed for both reactions and is attributed to the formation of a secondary ozonides (1,2,4-trioxolanes), supported by master equation calculations of the kinetics and the agreement between measured and calculated adiabatic ionization energies. Kinetics measurements were also performed for a possible bimolecular CH2OO + CO reaction and for the reaction of CH2OO with CF3CHCH2 at 300 K and 4 Torr. For CH2OO + CO, no reaction is observed and an upper limit is determined: k(CH2OO + CO) < 2 × 10-16 cm3 s-1. For CH2OO + CF3CHCH2, an upper limit of k(CH2OO + CF3CHCH2) < 2 × 10-14 cm3 s-1 is obtained.

Criegee intermediates (CIs), carbonyl oxides formed in ozonolysis of alkenes, play key roles in the troposphere. The decomposition of CIs can be a significant source of OH to the tropospheric oxidation cycle especially during nighttime and winter months. A variety of model-measurement studies have estimated surface-level stabilized Criegee intermediate (sCI) concentrations on the order of 1 × 10 4 cm -3 to 1 × 10 5 cm -3 , which makes a non-negligible contribution to the oxidising capacity in the terrestrial boundary layer. The reactions of sCI with the water monomer and the water dimer have been found to be the most important bimolecular reactions to the tropospheric sCI loss rate, at least for the smallest carbonyl oxides; the products from these reactions (e.g. hydroxymethyl hydroperoxide, HMHP) are also of importance to the atmospheric oxidation cycle. The sCI can oxidise SO 2 to form SO 3 , which can go on to form a significant amount of H 2 SO 4 which is a key atmospheric nucleation species and therefore vital to the formation of clouds. The sCI can also react with carboxylic acids, carbonyl compounds, alcohols, peroxy radicals and hydroperoxides, and the products of these reactions are likely to be highly oxygenated species, with low vapour pressures, that can lead to nucleation and SOA formation over terrestrial regions.

Hybridization occurs in a number of mammalian lineages, including among primate taxa. Analyses of ancient genomes have shown that hybridization between our lineage and other archaic hominins in Eurasia occurred numerous times in the past. However, we still have limited empirical data on what a hybrid skeleton looks like, or how to spot patterns of hybridization among fossils for which there are no genetic data. Here we use experimental mouse models to supplement previous studies of primates. We characterize size and shape variation in the cranium and mandible of three wild-derived inbred mouse strains and their first generation (F 1 ) hybrids. The three parent taxa in our analysis represent lineages that diverged over approximately the same period as the human/Neanderthal/Denisovan lineages and their hybrids are variably successful in the wild. Comparisons of body size, as quantified by long bone measurements, are also presented to determine whether the identified phenotypic effects of hybridization are localized to the cranium or represent overall body size changes. The results indicate that hybrid cranial and mandibular sizes, as well as limb length, exceed that of the parent taxa in all cases. All three F 1 hybrid crosses display similar patterns of size and form variation. These results are generally consistent with earlier studies on primates and other mammals, suggesting that the effects of hybridization may be similar across very different scenarios of hybridization, including different levels of hybrid fitness. This paper serves to supplement previous studies aimed at identifying F 1 hybrids in the fossil record and to introduce further research that will explore hybrid morphologies using mice as a proxy for better understanding hybridization in the hominin fossil record., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Morphological integration, or the tendency for covariation, is commonly seen in complex traits such as the human face. The effects of growth on shape, or allometry, represent a ubiquitous but poorly understood axis of integration. We address the question of to what extent age and measures of size converge on a single pattern of allometry for human facial shape., Methods: Our study is based on two large cross-sectional cohorts of children, one from Tanzania and the other from the United States (N = 7,173). We employ 3D facial imaging and geometric morphometrics to relate facial shape to age and anthropometric measures., Results: The two populations differ significantly in facial shape, but the magnitude of this difference is small relative to the variation within each group. Allometric variation for facial shape is similar in both populations, representing a small but significant proportion of total variation in facial shape. Different measures of size are associated with overlapping but statistically distinct aspects of shape variation. Only half of the size-related variation in facial shape can be explained by the first principal component of four size measures and age while the remainder associates distinctly with individual measures., Conclusions: Allometric variation in the human face is complex and should not be regarded as a singular effect. This finding has important implications for how size is treated in studies of human facial shape and for the developmental basis for allometric variation more generally., (© 2017 Wiley Periodicals, Inc.)

Background: Previous analysis suggested that the relative contribution of individual bones to regional skull lengths differ between inbred mouse strains. If the negative correlation of adjacent bone lengths is associated with genetic variation in a heterogeneous population, it would be an example of negative pleiotropy, which occurs when a genetic factor leads to opposite effects in two phenotypes. Confirming negative pleiotropy and determining its basis may reveal important information about the maintenance of overall skull integration and developmental constraint on skull morphology., Results: We identified negative correlations between the lengths of the frontal and parietal bones in the midline cranial vault as well as the zygomatic bone and zygomatic process of the maxilla, which contribute to the zygomatic arch. Through gene association mapping of a large heterogeneous population of Diversity Outbred (DO) mice, we identified a quantitative trait locus on chromosome 17 driving the antagonistic contribution of these two zygomatic arch bones to total zygomatic arch length. Candidate genes in this region were identified and real-time PCR of the maxillary processes of DO founder strain embryos indicated differences in the RNA expression levels for two of the candidate genes, Camkmt and Six2 ., Conclusions: A genomic region underlying negative pleiotropy of two zygomatic arch bones was identified, which provides a mechanism for antagonism in component bone lengths while constraining overall zygomatic arch length. This type of mechanism may have led to variation in the contribution of individual bones to the zygomatic arch noted across mammals. Given that similar genetic and developmental mechanisms may underlie negative correlations in other parts of the skull, these results provide an important step toward understanding the developmental basis of evolutionary variation and constraint in skull morphology.

Lithium ion attachment mass spectrometry provides a non-specific, non-fragmenting, sensitive and robust method for the detection of volatile species in the gas phase. The design, manufacture and results of lithium based ion attachment ionisation sources for two different mass spectrometry systems are presented. In this study trace gas analysis is investigated using a modified Chemical Ionization Mass Spectrometer (CIMS) and vapour pressure measurements are made using a modified Knudsen Effusion Mass Spectrometer (KEMS). In the Li + CIMS, where the Li + ionization acts a soft and unselective ionization source, limits of detection of 0.2 ppt for formic acid, 15 ppt for nitric acid and 120 ppt for ammonia were achieved, allowing for ambient measurements of such species at atmospherically relevant concentrations. In the first application of Lithium ion attachment in ultra-high vacuum (UHV), vapor pressures of various atmospherically relevant species were measured with the adapted KEMS, giving measured values equivalent to previous results from electron impact KEMS. In the Li + KEMS vapour pressures <10 -3 mbar can be measured without any fragmentation, as is seen with the initial electron impact (EI) set up, allowing the vapor pressure of individual components within mixtures to be determined.

The reactions of Criegee intermediates with NO 2 have been proposed as a potentially significant source of the important nighttime oxidant NO 3 , particularly in urban environments where concentrations of ozone, alkenes and NO x are high. However, previous efforts to characterize the yield of NO 3 from these reactions have been inconclusive, with many studies failing to detect NO 3 . In the present work, the reactions of formaldehyde oxide (CH 2 OO) and acetaldehyde oxide (CH 3 CHOO) with NO 2 are revisited to further explore the product formation over a pressure range of 4-40 Torr. NO 3 is not observed; however, temporally resolved and [NO 2 ]-dependent signal is observed at the mass of the Criegee-NO 2 adduct for both formaldehyde- and acetaldehyde-oxide systems, and the structure of this adduct is explored through ab initio calculations. The atmospheric implications of the title reaction are investigated through global modelling.

The rapid reaction of the smallest Criegee intermediate, CH 2 OO, with water dimers is the dominant removal mechanism for CH 2 OO in the Earth's atmosphere, but its products are not well understood. This reaction was recently suggested as a significant source of the most abundant tropospheric organic acid, formic acid (HCOOH), which is consistently underpredicted by atmospheric models. However, using time-resolved measurements of reaction kinetics by UV absorption and product analysis by photoionization mass spectrometry, we show that the primary products of this reaction are formaldehyde and hydroxymethyl hydroperoxide (HMHP), with direct HCOOH yields of less than 10%. Incorporating our results into a global chemistry-transport model further reduces HCOOH levels by 10-90%, relative to previous modeling assumptions, which indicates that the reaction CH 2 OO + water dimer by itself cannot resolve the discrepancy between the measured and predicted HCOOH levels.