The molecular phylogeny of placental mammals and its application to uncovering signatures of molecular adaptation.

Considerable conflict remains in the literature as to the position of the root of placental mammals, and the placement of several intra-ordinal groups. Debate continues over the use of DNA or amino acids datasets and over the use of Supertree or Supermatrix approaches. Known phenomena exist within mammal data that complicate the reconstruction of phylogeny. These include (but are not limited to), variation in longevity, body size, metabolic rates, and germ-line generation time that result in variation in mutation rates and composition biases. Previous attempts to resolve the placental mammal phylogeny have used homogeneous evolutionary models that cannot capture and adequately describe these features across the species sampled. In this thesis I explore the properties of different datasets and data types and their suitability to the resolution of the mammal phylogeny at different depths: (i) the position of the root of the placental mammals, and (ii), the intraordinal placements within the Laurasiatheria. The datasets tested were (i) mitochondrial and nuclear data types, (ii) previously published datasets for mammals, and (iii), datasets I assembled specifically for analyses at different phylogenetic depths. I propose and apply the use of heterogeneous models to resolve the position of the root of the placental mammal phylogeny to these datasets. Reconstruction of a robust mammal phylogeny provides us with an essential framework for understanding the molecular underpinnings of adaptation to environment. The placental mammals display a huge variations in life traits such longevity, body size and DNA repair efficiency, since they emerged ~100 million years ago. With this robust phylogeny, I set out to determine the level of adaptive and non-adaptive processes acting on a set of mammal genes that are linked with longevity and cancer. The results of these analyses yield important insights into data and model suitability, and provide strong evidence for a single hypothesis for the rooting of placental mammals. These results also show that Laurasiatheria intra-ordinal placements are not fully resolved and additional sampling from this diverse clade is required. Using this resolved phylogeny, specific molecular adaptations and non-adaptive mechanisms were identified in the mammalia for a set of telomere-associated genes

Molecular Evolution of Mammalian Genes with Epistatic Interactions in Fertilization

Background Genes that encode proteins associated with sperm competition, fertilization, and sexual conflicts of interest are often among the most rapidly evolving parts of animal genomes. One family of sperm-expressed genes (Zp3r, C4bpa) in the mammalian gene cluster called the regulator of complement activation (RCA) encodes proteins that bind eggs and mediate reproductive success, and are therefore expected to show high relative rates of nonsynonymous nucleotide substitution in response to sexual selection in comparison to other genes not involved in gamete binding at fertilization. We tested that working hypothesis by using phylogenetic models of codon evolution to identify episodes of diversifying positive selection. We used a comparative approach to quantify the evidence for episodic diversifying selection acting on RCA genes with known functions in fertilization (and sensitivity to sexual selection), and contrast them with other RCA genes in the same gene family that function in innate immunity (and are not sensitive to sexual selection). Results We expected but did not find evidence for more episodes of positive selection on Zp3r in Glires (the rodents and lagomorphs) or on C4BPA in Primates, in comparison to other paralogous RCA genes in the same taxon, or in comparison to the same orthologous RCA gene in the other taxon. That result was not unique to RCA genes: we also found little evidence for more episodes of diversifying selection on genes that encode selective sperm-binding molecules in the egg coat or zona pellucida (Zp2, Zp3) in comparison to members of the same gene family that encode structural elements of the egg coat (Zp1, Zp4). Similarly, we found little evidence for episodic diversifying selection acting on two other recently discovered genes (Juno, Izumo1) that encode essential molecules for sperm–egg fusion. Conclusions These negative results help to illustrate the importance of a comparative context for this type of codon model analysis. The results may also point to other phylogenetic contexts in which the effects of selection acting on these fertilization proteins might be more readily discovered and documented in mammals and other taxa

Positive selection neighboring functionally essential sites and disease-implicated regions of mammalian reproductive proteins

<p>Abstract</p> <p>Background</p> <p>Reproductive proteins are central to the continuation of all mammalian species. The evolution of these proteins has been greatly influenced by environmental pressures induced by pathogens, rival sperm, sexual selection and sexual conflict. Positive selection has been demonstrated in many of these proteins with particular focus on primate lineages. However, the <it>mammalia </it>are a diverse group in terms of mating habits, population sizes and germ line generation times. We have examined the selective pressures at work on a number of novel reproductive proteins across a wide variety of <it>mammalia</it>.</p> <p>Results</p> <p>We show that selective pressures on reproductive proteins are highly varied. Of the 10 genes analyzed in detail, all contain signatures of positive selection either across specific sites or in specific lineages or a combination of both. Our analysis of SP56 and Col1a1 are entirely novel and the results show positively selected sites present in each gene. Our findings for the Col1a1 gene are suggestive of a link between positive selection and severe disease type. We find evidence in our dataset to suggest that interacting proteins are evolving in symphony: most likely to maintain interacting functionality.</p> <p>Conclusion</p> <p>Our <it>in silico </it>analyses show positively selected sites are occurring near catalytically important regions suggesting selective pressure to maximize efficient fertilization. In those cases where a mechanism of protein function is not fully understood, the sites presented here represent ideal candidates for mutational study. This work has highlighted the widespread rate heterogeneity in mutational rates across the <it>mammalia </it>and specifically has shown that the evolution of reproductive proteins is highly varied depending on the species and interacting partners. We have shown that positive selection and disease are closely linked in the Col1a1 gene.</p

Health stigma on Twitter:investigating the prevalence and type of stigma communication in tweets about different conditions and disorders

Background: Health-related stigma can act as a barrier to seeking treatment and can negatively impact wellbeing. Comparing stigma communication across different conditions may generate insights previously lacking from condition-specific approaches and help to broaden our understanding of health stigma as a whole.Method: A sequential explanatory mixed-methods approach was used to investigate the prevalence and type of health-related stigma on Twitter by extracting 1.8 million tweets referring to five potentially stigmatized health conditions and disorders (PSHCDs): Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS), Diabetes, Eating Disorders, Alcoholism, and Substance Use Disorders (SUD). Firstly, 1,500 tweets were manually coded by stigma communication type, followed by a larger sentiment analysis (n = 250,000). Finally, the most prevalent category of tweets, “Anti-Stigma and Advice” (n = 273), was thematically analyzed to contextualize and explain its prevalence.Results: We found differences in stigma communication between PSHCDs. Tweets referring to substance use disorders were frequently accompanied by messages of societal peril. Whereas, HIV/AIDS related tweets were most associated with potential labels of stigma communication. We found consistencies between automatic tools for sentiment analysis and manual coding of stigma communication. Finally, the themes identified by our thematic analysis of anti-stigma and advice were Social Understanding, Need for Change, Encouragement and Support, and Information and Advice.Conclusions: Despite one third of health-related tweets being manually coded as potentially stigmatizing, the notable presence of anti-stigma suggests that efforts are being made by users to counter online health stigma. The negative sentiment and societal peril associated with substance use disorders reflects recent suggestions that, though attitudes have improved toward physical diseases in recent years, stigma around addiction has seen little decline. Finally, consistencies between our manual coding and automatic tools for identifying language features of harmful content, suggest that machine learning approaches may be a reasonable next step for identifying general health-related stigma online

Knee joint neuromuscular activation performance during muscle damage and superimposed fatigue

This study examined the concurrent effects of exercise-induced muscle damage and superimposed acute fatigue on the neuromuscular activation performance of the knee flexors of nine males (age: 26.7 ± 6.1yrs; height 1.81 ± 0.05m; body mass 81.2 ± 11.7kg [mean ± SD]). Measures were obtained during three experimental conditions: (i) FAT-EEVID, involving acute fatiguing exercise performed on each assessment occasion plus a single episode of eccentric exercise performed on the first occasion and after the fatigue trial; (ii) FAT, involving the fatiguing exercise only and; (iii) CON consisting of no exercise. Assessments were performed prior to (pre) and at lh, 24h, 48h, 72h, and 168h relative to the eccentric exercise. Repeated-measures ANOVAs showed that muscle damage within the FAT-EEVID condition elicited reductions of up to 38%, 24%) and 65%> in volitional peak force, electromechanical delay and rate of force development compared to baseline and controls, respectively (F[io, 80] = 2.3 to 4.6; p to 30.7%>) following acute fatigue (Fp; i6] = 4.3 to 9.1; p ; Fp, iq = 3.9; p <0.05). The safeguarding of evoked muscle activation capability despite compromised volitional performance might reveal aspects of capabilities for emergency and protective responses during episodes of fatigue and antecedent muscle damaging exercise

Heterogeneous models place the root of the placental mammal phylogeny

Heterogeneity among life traits in mammals has resulted in considerable phylogenetic conflict, particularly concerning the position of the placental root. Layered upon this are gene- and lineage-specific variation in amino acid substitution rates and compositional biases. Life trait variations that may impact upon mutational rates are longevity, metabolic rate, body size, and germ line generation time. Over the past 12 years, three main conflicting hypotheses have emerged for the placement of the placental root. These hypotheses place the Atlantogenata (common ancestor of Xenarthra plus Afrotheria), the Afrotheria, or the Xenarthra as the sister group to all other placental mammals. Model adequacy is critical for accurate tree reconstruction and by failing to account for these compositional and character exchange heterogeneities across the tree and data set, previous studies have not provided a strongly supported hypothesis for the placental root. For the first time, models that accommodate both tree and data set heterogeneity have been applied to mammal data. Here, we show the impact of accurate model assignment and the importance of data sets in accommodating model parameters while maintaining the power to reject competing hypotheses. Through these sophisticated methods, we demonstrate the importance of model adequacy, data set power and provide strong support for the Atlantogenata over other competing hypotheses for the position of the placental root

Geological and thermal control of the hydrothermal system in northern Yellowstone Lake: inferences from high-resolution magnetic surveys

Author Posting. © American Geophysical Union, 2020. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Solid Earth 125(9), (2020): e2020JB019743, doi:10.1029/2020JB019743.A multiscale magnetic survey of the northern basin of Yellowstone Lake was undertaken in 2016 as part of the Hydrothermal Dynamics of Yellowstone Lake Project (HD‐YLAKE)—a broad research effort to characterize the cause‐and‐effect relationships between geologic and environmental processes and hydrothermal activity on the lake floor. The magnetic survey includes lake surface, regional aeromagnetic, and near‐bottom autonomous underwater vehicle (AUV) data. The study reveals a strong contrast between the northeastern lake basin, characterized by a regional magnetic low punctuated by stronger local magnetic lows, many of which host hydrothermal vent activity, and the northwestern lake basin with higher‐amplitude magnetic anomalies and no obvious hydrothermal activity or punctuated magnetic lows. The boundary between these two regions is marked by a steep gradient in heat flow and magnetic values, likely reflecting a significant structure within the currently active ~20‐km‐long Eagle Bay‐Lake Hotel fault zone that may be related to the ~2.08‐Ma Huckleberry Ridge caldera rim. Modeling suggests that the broad northeastern magnetic low reflects both a shallower Curie isotherm and widespread hydrothermal activity that has demagnetized the rock. Along the western lake shoreline are sinuous‐shaped, high‐amplitude magnetic anomaly highs, interpreted as lava flow fronts of upper units of the West Thumb rhyolite. The AUV magnetic survey shows decreased magnetization at the periphery of the active Deep Hole hydrothermal vent. We postulate that lower magnetization in the outer zone results from enhanced hydrothermal alteration of rhyolite by hydrothermal condensates while the vapor‐dominated center of the vent is less altered.The lake surface and AUV magnetic data were acquired under National Park Service research permit YELL‐2016‐SCI‐7018 and the 2016 aeromagnetic data under research permit YELL‐2016‐SCI‐7056. We thank Sarah Haas, Stacey Gunther, Erik Oberg, Annie Carlson, and Patricia Bigelow at the Yellowstone Center for Resources for assistance with permitting and logistics, Ranger Jackie Sene for assistance with logistics and safety at Bridge Bay, Bob Gresswell for providing us with the U.S. Geological Survey (USGS) boat Alamar, the boat pilot Nick Heredia, and Robert Harris and Shaul Hurwitz for fruitful discussions. We are very thankful to Ocean Floor Geophysics (Brian Claus and Steve Bloomer) who provided the magnetometer for the AUV survey and preprocessed the data, and to the REMUS 600 team (Greg Packard and Greg Kurras) for operating and optimizing the AUV during lake operations. Data from the Newport and Boulder observatories were used to process the survey data. We thank the USGS Geomagnetism Program for supporting their operation and INTERMAGNET for promoting high standards of magnetic observatory practice (www.intermagnet.org). This research was funded by the National Science Foundation's Integrated Earth Systems program EAR‐1516361 (HD‐YLAKE project), USGS Mineral Resource and Volcano Hazard Programs, and benefited from major in‐kind support from the USGS Yellowstone Volcano Observatory. Maurice Tivey was supported under National Science Foundation Grant OCE‐1557455. During the course of this study, Claire Bouligand was a visiting scientist at the USGS in Menlo Park, California, USA, benefited from a delegation to Centre National de la Recherche Scientifique (CNRS), and received funding from CNRS‐INSU program SYSTER. ISTerre is part of Labex OSUG@2020 (ANR10 LABX56). Any use of trade, firm, or product names is for descriptive purposes and does not imply endorsement by the U.S. Government.2021-01-2

Airborne measurements of trace gases and aerosols over the London metropolitan region

The Emissions around the M25 motorway (EM25) campaign took place over the megacity of London in the United Kingdom in June 2009 with the aim of characterising trace gas and aerosol composition and properties entering and emitted from the urban region. It featured two mobile platforms, the UK BAe-146 Facility for Airborne Atmospheric Measurements (FAAM) research aircraft and a ground-based mobile lidar van, both travelling in circuits around London, roughly following the path of the M25 motorway circling the city. We present an overview of findings from the project, which took place during typical UK summertime pollution conditions. Emission ratios of volatile organic compounds (VOCs) to acetylene and carbon monoxide emitted from the London region were consistent with measurements in and downwind of other large urban areas and indicated traffic and associated fuel evaporation were major sources. Sub-micron aerosol composition was dominated by secondary species including sulphate (24% of sub-micron mass in the London plume and 29% in the non-plume regional aerosol), nitrate (24% plume; 20% regional) and organic aerosol (29% plume; 31% regional). The primary sub-micron aerosol emissions from London were minor compared to the larger regional background, with only limited increases in aerosol mass in the urban plume compared to the background (~12% mass increase on average). Black carbon mass was the major exception and more than doubled in the urban plume, leading to a decrease in the single scattering albedo from 0.91 in the regional aerosol to 0.86 in the London plume, on average. Our observations indicated that regional aerosol plays a major role on aerosol concentrations around London, at least during typical summertime conditions, meaning future efforts to reduce PM levels in London must account for regional as well as local aerosol sources

Timing of daily calorie loading affects appetite and hunger responses without changes in energy metabolism in healthy subjects with obesity

Acknowledgments The authors gratefully acknowledge Sylvia Stephen, Jean Bryce, Nina Lamza, Karen Taylor, Melanie Hudson, Kat Niblock, Ewa Wojtaczka, Aimee Sutherland, David Bremner, Claire Kidd, and Alicia Bryce at the Human Nutrition Unit of the Rowett Institute for their support in meal preparation and participant assessment. The authors acknowledge the contribution of NIHR Core Biochemistry Assay Laboratory, Cambridge Biomedical Research Centre (gut hormone analysis), and Loek Wouters at Maastricht University, Netherlands (DLW analysis). The authors also gratefully acknowledge Claus-Dieter Mayer for statistical analysis and modeling of the gastric emptying data. The authors gratefully acknowledge funding from the Medical Research Council (grant MR/P012205/1, The Big Breakfast study). A.M.J., P.J.M., G.W.H., and J.A.N.F. also acknowledge funding support from the Scottish Government, Rural and Environment Science and Analytical Services Division. Author contributions Conceptualization, design, and funding acquisition, A.M.J., P.J.M., and J.D.J.; investigation, L.C.R.-C. and C.L.F.; DLW analysis and modeling, K.R.W.; statistical analysis, G.W.H. and J.A.N.F.; writing – original draft, L.C.R.-C. and A.M.J.; writing – review & editing, all authors.Peer reviewedPublisher PD