Metamorphosis Imposes Variable Constraints on Genome Expansion through Effects on Development

Genome size varies ∼100,000-fold across eukaryotes and has long been hypothesized to be influenced by meta- morphosis in animals. Transposable element accumulation has been identified as a major driver of increase, but the nature of constraints limiting the size of genomes has remained unclear, even as traits such as cell size and rate of development co-vary strongly with genome size. Salamanders, which possess diverse metamorphic and non-metamorphic life histories, join the lung- fish in having the largest vertebrate genomes—3 to 40 times that of humans—as well as the largest range of variation in genome size. We tested 13 biologically-inspired hypotheses exploring how the form of metamorphosis imposes varying constraints on genome expansion in a broadly representative phylogeny containing 118 species of salamanders. We show that metamorphosis during which animals undergo the most extensive and synchronous remodeling imposes the most severe constraint against genome expansion, with the severity of constraint decreasing with reduced extent and synchronicity of remodeling. More generally, our work demonstrates the potential for broader interpretation of phylogenetic comparative analysis in exploring the balance of multiple evolutionary pressures shaping phenotypic evolution

Butyrylcholinesterase genotype and enzyme activity in relation to Gulf War illness: preliminary evidence of gene-exposure interaction from a case¿control study of 1991 Gulf War veterans

Abstract Background Epidemiologic studies have implicated wartime exposures to acetylcholinesterase (AChE)-inhibiting chemicals as etiologic factors in Gulf War illness (GWI), the multisymptom condition linked to military service in the 1991 Gulf War. It is unclear, however, why some veterans developed GWI while others with similar exposures did not. Genetic variants of the enzyme butyrylcholinesterase (BChE) differ in their capacity for metabolizing AChE-inhibiting chemicals, and may confer differences in biological responses to these compounds. The current study assessed BChE enzyme activity and BChE genotype in 1991 Gulf War veterans to evaluate possible association of this enzyme with GWI. Methods This case–control study evaluated a population-based sample of 304 Gulf War veterans (144 GWI cases, meeting Kansas GWI criteria, and 160 controls). BChE enzyme activity levels and genotype were compared, overall, in GWI cases and controls. Potential differences in risk associated with cholinergic-related exposures in theater were explored using stratified analyses to compare associations between GWI and exposures in BChE genetic and enzyme activity subgroups. Results Overall, GWI cases and controls did not differ by mean BChE enzyme activity level or by BChE genotype. However, for the subgroup of Gulf War veterans with less common, generally less active, BChE genotypes (K/K, U/AK, U/A, A/F, AK/F), the association of wartime use of pyridostigmine bromide (PB) with GWI (OR = 40.00, p = 0.0005) was significantly greater than for veterans with the more common U/U and U/K genotypes (OR = 2.68, p = 0.0001). Conclusions Study results provide preliminary evidence that military personnel with certain BChE genotypes who used PB during the 1991 Gulf War may have been at particularly high risk for developing GWI. Genetic differences in response to wartime exposures are potentially important factors in GWI etiology and should be further evaluated in conjunction with exposure effects.Peer Reviewe

Compounding impact of severe weather events fuels marine heatwave in the coastal ocean

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Dzwonkowski, B., Coogan, J., Fournier, S., Lockridge, G., Park, K., & Lee, T. Compounding impact of severe weather events fuels marine heatwave in the coastal ocean. Nature Communications, 11(1), (2020): 4623, doi:10.1038/s41467-020-18339-2.Exposure to extreme events is a major concern in coastal regions where growing human populations and stressed natural ecosystems are at significant risk to such phenomena. However, the complex sequence of processes that transform an event from notable to extreme can be challenging to identify and hence, limit forecast abilities. Here, we show an extreme heat content event (i.e., a marine heatwave) in coastal waters of the northern Gulf of Mexico resulted from compounding effects of a tropical storm followed by an atmospheric heatwave. This newly identified process of generating extreme ocean temperatures occurred prior to landfall of Hurricane Michael during October of 2018 and, as critical contributor to storm intensity, likely contributed to the subsequent extreme hurricane. This pattern of compounding processes will also exacerbate other environmental problems in temperature-sensitive ecosystems (e.g., coral bleaching, hypoxia) and is expected to have expanding impacts under global warming predictions.This work would not have been possible without the help of the Tech Support Group at the Dauphin Island Sea Lab. A portion of this work was conducted at the Jet Propulsion Laboratory, California Institute of Technology, under contract with NASA. This research was made possible by the NOAA RESTORE Science Program (NA17NOS4510101 and NA19NOS4510194) and NOAA NGI NMFS Regional Collaboration Network (18-NGI3-61)

Declining Sex Ratio in a First Nation Community

Members of the Aamjiwnaang First Nation community near Sarnia, Ontario, Canada, voiced concerns that there appeared to be fewer male children in their community in recent years. In response to these concerns, we assessed the sex ratio (proportion of male births) of the Aamjiwnaang First Nation over the period 1984–2003 as part of a community-based participatory research project. The trend in the proportion of male live births of the Aamjiwnaang First Nation has been declining continuously from the early 1990s to 2003, from an apparently stable sex ratio prior to this time. The proportion of male births (m) showed a statistically significant decline over the most recent 10-year period (1994–2003) (m = 0.412, p = 0.008) with the most pronounced decrease observed during the most recent 5 years (1999–2003) (m = 0.348, p = 0.006). Numerous factors have been associated with a decrease in the proportion of male births in a population, including a number of environmental and occupational chemical exposures. This community is located within the Great Lakes St. Clair River Area of Concern and is situated immediately adjacent to several large petrochemical, polymer, and chemical industrial plants. Although there are several potential factors that could be contributing to the observed decrease in sex ratio of the Aamjiwnaang First Nation, the close proximity of this community to a large aggregation of industries and potential exposures to compounds that may influence sex ratios warrants further assessment into the types of chemical exposures for this population. A community health survey is currently under way to gather more information about the health of the Aamjiwnaang community and to provide additional information about the factors that could be contributing to the observed decrease in the proportion of male births in recent years

Brief of Intellectual Property Law Scholars As Amici Curiae in Support of Neither Party, WesternGeco LLC v. Ion Geophysical Corp., No. 16-1011, US Supreme Court

This amici curiae brief was filed on behalf of Intellectual Property Law Scholars in WesternGeco LLC v. Ion Geophysical Corp. in the U.S. Supreme Court. The question presented is: Whether the U.S. Court of Appeals for the Federal Circuit erred in holding that lost profits arising from prohibited combinations occurring outside of the United States are categorically unavailable in cases in which patent infringement is proven under 35 U.S.C. § 271(f). In RJR Nabisco, Inc. v. European Community, 136 S. Ct. 2090 (2016), the Supreme Court articulated a two-step method for assessing the extraterritorial reach of a US statute: 1. A court should determine whether the presumption against extraterritoriality has been rebutted—that is, whether the statute gives a clear, affirmative indication that it applies extraterritorially. If the presumption is rebutted, the statute may have extraterritorial reach. 2. But even if the presumption has not been rebutted, a court should look at the focus of the statute. If the conduct relevant to the statute\u27s focus occurred in the United States, then the case involves a permissible domestic application even if other conduct occurred abroad; but if the conduct relevant to the focus occurred in a foreign country, then the case involves an impermissible extraterritorial application regardless of any other conduct that occurred in U.S. territory. The brief of amici curiae makes the follow points: 1. The Supreme Court has not squarely answered the question as to whether the presumption against extraterritoriality applies separately to remedial provisions of a statute generally (here whether it applies to § 284). We argue it does. 2. We argue that the territorial reach § 284 necessarily depends the relevant provision of § 271 used to find liability. Here, under § 271(f), the presumption is rebutted (though it would not be generally for a case under § 271(a), with NTP v. Research in Motion may be a counter-example when one looks at the focus at step 2)). 3. We also argue that the Court should offer more guidance as to what happens even if the RJR test is satisfied. RJR Nabisco seems to operate in binary fashion -- either the statute has extraterritorial reach or it doesn\u27t. But Microsoft Corp. v. AT&T Corp., and earlier Supreme Court decision also interpreting 35 U.S.C. § 271(f), suggests that the presumption may still have a role in interpreting a statute. We offer two suggestions on how the presumption should operate in this context. First, courts should seriously and formally consider issues of comity and potential conflicts with foreign law in assessing whether to apply U.S. law extraterritorially. Second, that territoriality should remain relevant in assessments of proximate cause

The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26

Human tissues have two distinct cholinesterase activities: acetylcholinesterase and butyrylcholinesterase. Acetylcholinesterase functions in the transmission of nerve impulses, whereas the physiological function of butyrylcholinesterase remains unknown. An atypical form of butyrylcholinesterase or the absence of its activity leads to prolonged apnea following administration of the muscle relaxant suxamethonium. Inheritance of these butyrylcholinesterase variants is consistent with the enzyme activity being encoded in a single autosomal locus, BCHE (formerly CHE1 and E1), which has been assigned to chromosome 3. Previous in situ hybridization of a BCHE cDNA probe gave evidence of homologous sequences at 3q26 and 16q11-q23, raising the possibility of more than one locus coding for butyrylcholinesterase [20.] Hum. Genet. 77: 325-328]. Using a different cDNA probe hybridized in situ to 46,XX,inv(3)(p25q21) metaphase chromosomes, we report here the localization of BCHE to a single autosomal location: 3q26.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29109/1/0000147.pd

Recognition of Lyso-Phospholipids by Human Natural Killer T Lymphocytes

Natural killer T (NKT) cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC). Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology.</p

Phylogenomics Reveals Ancient Gene Tree Discordance in the Amphibian Tree of Life

Molecular phylogenies have yielded strong support for many parts of the amphibian Tree of Life, but poor support for the resolution of deeper nodes, including relationships among families and orders. To clarify these relationships, we provide a phylogenomic perspective on amphibian relationships by developing a taxon-specific Anchored Hybrid Enrichment protocol targeting hundreds of conserved exons which are effective across the class. After obtaining data from 220 loci for 286 species (representing 94% of the families and 44% of the genera), we estimate a phylogeny for extant amphibians and identify gene tree–species tree conflict across the deepest branches of the amphibian phylogeny. We perform locus-by-locus genealogical interrogation of alternative topological hypotheses for amphibian monophyly, focusing on interordinal relationships. We find that phylogenetic signal deep in the amphibian phylogeny varies greatly across loci in a manner that is consistent with incomplete lineage sorting in the ancestral lineage of extant amphibians. Our results overwhelmingly support amphibian monophyly and a sister relationship between frogs and salamanders, consistent with the Batrachia hypothesis. Species tree analyses converge on a small set of topological hypotheses for the relationships among extant amphibian families. These results clarify several contentious portions of the amphibian Tree of Life, which in conjunction with a set of vetted fossil calibrations, support a surprisingly younger timescale for crown and ordinal amphibian diversification than previously reported. More broadly, our study provides insight into the sources, magnitudes, and heterogeneity of support across loci in phylogenomic data sets

Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine

Butyrylcholinesterase (BChE) is a plasma enzyme that catalyzes the hydrolysis of choline esters, including the muscle-relaxant succinylcholine and mivacurium. Patients who present sustained neuromuscular blockade after using succinylcholine usually carry BChE variants with reduced enzyme activity or an acquired BChE deficiency. We report here the molecular basis of the BCHE gene underlying the slow catabolism of succinylcholine in a patient who underwent endoscopic nasal surgery. We measured the enzyme activity of BChE and extracted genomic DNA in order to study the promoter region and all exons of the BCHE gene of the patient, her parents and siblings. PCR products were sequenced and compared with reference sequences from GenBank. We detected that the patient and one of her brothers have two homozygous mutations: nt1615 GCA > ACA (Ala539Thr), responsible for the K variant, and nt209 GAT > GGT (Asp70Gly), which produces the atypical variant A. Her parents and two of her brothers were found to be heterozygous for the AK allele, and another brother is homozygous for the normal allele. Sequence analysis of exon 1 including 5′UTR showed that the proband and her brother are homozygous for –116GG. The AK/AK genotype is considered the most frequent in hereditary hypocholinesterasemia (44%). This work demonstrates the importance of defining the phenotype and genotype of the BCHE gene in patients who are subjected to neuromuscular block by succinylcholine, because of the risk of prolonged neuromuscular paralysis