bluuebunny/crossref_metadata_2025 huggingface dataset:
A Tale of Two Positivities and the N400: Distinct neural signatures are evoked by confirmed and violated predictions at different levels of representation
Authors: Kuperberg Gina R. , Brothers Trevor , Wlotko Edward W.
Published: August 2018

It has been proposed that hierarchical prediction is a fundamental computational principle underlying neurocognitive processing. Here we ask whether the brain engages distinct neurocognitive mechanisms in response to inputs that fulfillversusviolate strong predictions at different levels of representation during language comprehension. Participants read three-sentence scenarios in which the third sentence constrained for a broad event structure, e.g. {Agent caution animate-Patient}.High constraintcontexts additionally constrained for a specific event/lexical item, e.g. a two-sentence context about a beach, lifeguards and sharks constrained for the event, {Lifeguards cautioned Swimmers} and the specific lexical item, “swimmers”.Low constraintcontexts did not constrain for any specific event/lexical item. We measured ERPs on critical nouns that fulfilled and/or violated each of these constraints. We found clear, dissociable effects to fulfilled semantic predictions (a reduced N400), to event/lexical prediction violations (an increasedlate frontal positivity), and to event structure/animacy prediction violations (an increasedlate posterior positivity/P600). We argue that thelate frontal positivityreflects a large change in activity associated with successfully updating the comprehender’s current situation model with new unpredicted information. We suggest that thelate posterior positivity/P600is triggered when the comprehender detects a conflict between the input and her model of the communicator and communicative environment. This leads to an initial failure to incorporate new unpredicted input, which may be followed by second-pass attempts to make sense of the discourse through reanalysis, repair, or reinterpretation. Together, these findings provide strong evidence that confirmed and violated predictions at different levels of representation manifest as distinct spatiotemporal neural signatures.
Increased frequency of travel in the presence of cross-immunity may act to decrease the chance of a global pandemic
Authors: Thompson R.N. , Thompson C.P. , Pelerman O. , Gupta S. , Obolski U.
Published: August 2018

The high frequency of modern travel has led to concerns about a devastating pandemic since a lethal pathogen strain could spread worldwide quickly. Many historical pandemics have arisen following pathogen evolution to a more virulent form. However, some pathogen strains invoke immune responses that provide partial cross-immunity against infection with related strains. Here, we consider a mathematical model of successive outbreaks of two strains – a low virulence strain outbreak followed by a high virulence strain outbreak. Under these circumstances, we investigate the impacts of varying travel rates and cross-immunity on the probability that a major epidemic of the high virulence strain occurs, and the size of that outbreak. Frequent travel between subpopulations can lead to widespread immunity to the high virulence strain, driven by exposure to the low virulence strain. As a result, major epidemics of the high virulence strain are less likely, and can potentially be smaller, with more connected subpopulations. Cross-immunity may be a factor contributing to the absence of a global pandemic as severe as the 1918 influenza pandemic in the century since.
Cross-cancer pleiotropic associations with lung cancer risk in African Americans
Authors: Jones Carissa C. , Bradford Yuki , Amos Christopher I. , Blot William J. , Chanock Stephen J. , Harris Curtis C. , Schwartz Ann G. , Spitz Margaret R. , Wiencke John K. , Wrensch Margaret R. , Wu Xifeng , Aldrich Melinda C.
Published: August 2018

Background

Identifying genetic variants with pleiotropic associations across multiple cancers can reveal shared biologic pathways. Prior pleiotropic studies have primarily focused on European descent individuals. Yet population-specific genetic variation can occur and potential pleiotropic associations among diverse racial/ethnic populations could be missed. We examined cross-cancer pleiotropic associations with lung cancer risk in African Americans.

Methods

We conducted a pleiotropic analysis among 1,410 African American lung cancer cases and 2,843 controls. We examined 36,958 variants previously associated (or in linkage disequilibrium) with cancer in prior genome-wide association studies. Logistic regression analyses were conducted, adjusting for age, sex, global ancestry, study site, and smoking status.

Results

We identified three novel genomic regions significantly associated (FDR-corrected p-value < 0.10) with lung cancer risk (rs336958 on 5q14.3, rs7186207 on 16q22.2, and rs11658063 on 17q12). On chromosome16q22.2, rs7186207 was significantly associated with increased risk (OR=1.24, 95% CI: 1.12-1.38) and functional annotation using GTEx showed rs7186207 modifiesDHODHgene expression. The risk allele at rs336958 on 5q14.3 was associated with reduced lung cancer risk (OR=0.68, 95% CI: 0.56-0.82), while the risk allele at rs11658063 on 17q12 was associated with increased risk (OR=1.24, 95% CI: 1.11-1.39).

Conclusion

We identified novel associations on chromosomes 5q14.3, 16q22.2, and 17q12, which containHNF1B, DHODH,andHAPLN1genes, respectively. SNPs within these regions have been previously associated with multiple cancers. This is the first study to examine cross-cancer pleiotropic associations for lung cancer in African Americans.

Impact

Our findings demonstrate novel cross-cancer pleiotropic associations with lung cancer risk in African Americans.
Molecular and evolutionary strategies of meiotic cheating by selfish centromeres
Authors: Akera Takashi , Trimm Emily , Lampson Michael A.
Published: August 2018

Asymmetric division in female meiosis creates selective pressure favoring selfish centromeres that bias their transmission to the egg. This centromere drive can explain the paradoxical rapid evolution of both centromere DNA and centromere-binding proteins despite conserved centromere function. Here, we define a molecular pathway linking expanded centromeres to histone phosphorylation and recrui™ent of microtubule destabilizing factors in an intraspecific hybrid, leading to detachment of selfish centromeres from spindle microtubules that would direct them to the polar body. We also introduce a second hybrid model, exploiting centromere divergence between species, and show that winning centromeres in one hybrid become losers in the other. Our results indicate that increasing destabilizing activity is a general strategy for drive, but centromeres have evolved distinct strategies to increase that activity. Furthermore, we show that drive depends on slowing meiotic progression, suggesting that a weakened meiotic spindle checkpoint evolved as a mechanism to suppress selfish centromeres.
On the role of different age groups during pertussis epidemics in California, 2010 and 2014
Authors: Mahmud Ayesha , Lipsitch Marc , Goldstein Edward
Published: August 2018

Background

There is limited information on the roles of different age groups in propagating pertussis outbreaks, and the temporal changes in those roles since the introduction of acellular pertussis vaccines.

Methods

The relative roles of different age groups in propagating the 2010 and the 2014 pertussis epidemics in California were evaluated using the RR statistic that measures the change in the group’s proportion among all detected cases before-vs.-after the epidemic peak.

Results

For the 2010-11 epidemic, evidence for a predominant transmission age group was weak, with the largest RR estimates being 1.26(95%CI (1.08,1.46)) (aged 11-13y); 1.19(1.01,1.4) (aged 9-10y); 1.17(0.86,1.59) (aged 14-15y); 1.12(0.86,1.46) (aged 16-19y); and 1.1(0.89,1.36) (aged 7-8y). The 2014 epidemic showed a strong signal of the role of older adolescents, with the highest RR estimate being in those aged 14-15y (RR=1.83(1.61,2.07)), followed by adolescents aged 16-19y (RR=1.41(1.24,1.61)) and 11-13y (RR=1.26(1.12,1.41)), with lower RR estimates in other age groups.

Conclusions

As the time following introduction of acellular pertussis vaccines in California progressed, older adolescents played an increasing role in transmission during the major pertussis outbreaks. Booster pertussis vaccination for older adolescents with vaccines effective against pertussis transmission should be considered with the aim of mitigating future pertussis epidemics in the community.
Environmental association identifies candidates for tolerance to low temperature and drought
Authors: Lei Li , Poets Ana M. , Liu Chaochih , Wyant Skylar R. , Hoffman Paul J. , Carter Corey K. , Trantow Richard M. , Shaw Brian G. , Li Xin , Muehlbauer Gary J. , Katagiri Fumiaki , Morrell Peter L.
Published: August 2018

Barley(Hordeum vulgaressp.vulgare)is cultivated from the equator to the Arctic Circle. The wild progenitor species,Hordeum vulgare ssp. spontaneum, occupies a relatively narrow latitudinal range (~30 – 40° N) primarily at low elevation (< 1,500 m). Adaptation to the range of cultivation has occurred over ~8,000 years. The genetic basis of this adaptation is amenable to study through environmental association. Using genotyping from 7,864 SNPs in 803 barley landraces, we performed mixed model association analysis relative to bioclimatic variables and analysis of allele frequency differentiation across multiple partitions of the data. Using resequencing data from a subset of these landraces, we tested for linkage disequilibrium (LD) between SNPs queried in genotyping and SNPs in neighboring loci. Six loci previously reported to contribute to adaptive differences in flowering time and abiotic stress in barley and six loci previously identified in other plant species were identified in our analyses. In many cases, patterns of LD are consistent with the causative variant occurring in the immediate vicinity of the queried SNP. The identification of barley orthologs to well characterized genes may provide new understanding of the nature of adaptive variation and could permit a more targeted use of potentially adaptive variants in barley breeding and germplasm improvement.
Reproductive functions and genetic architecture of the seminal fluid and sperm proteomes of the mosquitoAedes aegypti
Authors: Degner Ethan C. , Ahmed-Braimah Yasir H. , Borziak Kiril , Wolfner Mariana F. , Harrington Laura C. , Dorus Steve
Published: August 2018

The yellow fever mosquito,Aedes aegypti,transmits several viruses, including dengue, Zika, and chikungunya. Some proposed efforts to control this vector involve manipulating reproduction to suppress wild populations or replacing them with disease-resistant mosquitoes. The design of such strategies requires an intimate knowledge of reproductive processes, yet our basic understanding of reproductive genetics in this vector remains largely incomplete. To accelerate future investigations, we have comprehensively catalogued sperm and seminal fluid proteins (SFPs) transferred to females in the ejaculate using tandem mass spectrometry. By excluding female-derived proteins using an isotopic labelling approach, we identified 870 sperm proteins and 280 seminal fluid proteins. Functional composition analysis revealed parallels with known aspects of sperm biology and SFP function in other insects. To corroborate our proteome characterization, we also generated transcriptomes for testes and the male accessory glands—the primary contributors toAe. aegyptisperm and seminal fluid, respectively. Differential gene expression of accessory glands from virgin and mated males suggests that protein translation is upregulated post-mating. Several SFP transcripts were also modulated after mating, but >90% remained unchanged. Finally, a significant enrichment of SFPs was observed on chromosome 1, which harbors the male sex determining locus in this species. Our study provides a comprehensive proteomic and transcriptomic characterization of ejaculate production and composition and thus provides a foundation for future investigations ofAe. aegyptireproductive biology, from functional analysis of individual proteins to broader examination of reproductive processes.
Body mass index trajectories preceding first report of poor self-rated health: a longitudinal case-control analysis of the English Longitudinal Study of Ageing:
Authors: Hulman Adam , Ibsen Daniel B , Laursen Anne Sofie D , Dahm Christina C
Published: August 2018

Background: Studies have consistently found that obesity is associated with poor self-rated health, but how body mass index (BMI) developed in the lead up to poor self-rated health is unknown. Methods: We nested a longitudinal case-control study in the English Longitudinal Study of Ageing (1998-2015) to investigate BMI trajectories in the years preceding a first self-report of poor health. Participants rated their health at each data collection; every other collection included a BMI assessment by a nurse. Case status was defined as a first report of poor health during follow-up. Three age- and sex-matched controls were identified per case using density sampling. BMI trajectories were fitted to time backwards prior to first report of poor health using mixed-effects models. Age and sex were potential modifiers. We conducted subgroup analyses of those not reporting certain chronic diseases or smoking. Results: We identified 732 cases and 2195 controls. Age, but not sex, modified the association between BMI and self-rated health. Participants reporting poor health at age 60 had a 1.5 kg/m2 (95%CI: 0.8 to 2.1) higher BMI at the time of reporting than controls, and their BMI had previously increased sharply. After age 75, cases no longer had higher BMI than controls, and their BMI had decreased sharply prior to reporting poor health. Age was also an effect modifier among those without diabetes, however BMI trajectories were more similar among the middle-aged. Conclusion: Development of BMI was associated with poor self-rated health; however, the nature of the association depended markedly on age.
β-actin mRNA interactome mapping by proximity biotinylation
Authors: Mukherjee Joyita , Hermesh Orit , Eliscovich Carolina , Nalpas Nicolas , Franz-Wachtel Mirita , Maček Boris , Jansen Ralf-Peter
Published: August 2018

The molecular function and fate of mRNAs are controlled by RNA-binding proteins (RBPs). However, identification of the interacting proteome of a specific mRNA in vivo is still very challenging. Based on the widely-used RNA tagging with MS2 aptamers for RNA visualization, we developed a novel RNA proximity biotinylation (RNA-BioID) method by tethering biotin ligase (BirA*) via MS2 coat protein (MCP) at the 3’-UTR of endogenous MS2 tagged β-actin mRNA (MBS) in mouse embryonic fibroblasts (MEFs). We demonstrate the dynamics of the β-actin mRNA interactome by characterizing its changes upon serum-induced localization of the mRNA. Apart from the previously known interactors, we identified over 60 additional β-actin associated RBPs by RNA-BioID. Among them the KH-domain containing protein FUBP3/MARTA2 has shown to be required for β-actin mRNA localization. We found that FUBP3 binds to the 3’-UTR of β-actin mRNA, is essential for β-actin mRNA localization but does not interact with the characterized β-actin zipcode element. RNA-BioID provides a tool to identify new mRNA interactors and to study the dynamic view of the interacting proteome of endogenous mRNAs in space and time.

Significance statement

Transport of specific mRNAs to defined sites in the cytoplasm allows local protein production and contributes to cell polarity, embryogenesis, and neuronal function. These localized mRNAs contain signals (zipcodes) that help directing them to their destination site. Zipcodes are recognized by RNA-binding proteins that, with the help of molecular motor proteins and supplementary factors, mediate mRNA trafficking. To identify all proteins assembling with a localized mRNA we advanced a proximity labeling method (BioID) by tethering a biotin ligase to the 3’ untranslated region of mRNA encoding the conserved beta-actin protein. We demonstrate that this method allows the identification of novel, functionally important proteins that are required for mRNA localization.
Alternative oxidase induction protects Candida albicans from respiratory stress and promotes hyphal growth
Authors: Duvenage Lucian , Walker Louise A. , Bojarczuk Aleksandra , Johnston Simon A. , McCallum Donna M. , Munro Carol A. , Gourlay Campbell W.
Published: August 2018

The human fungal pathogenCandida albicanspossesses two genes expressing a cyanide-insensitive Alternative Oxidase (Aox) enzymes in addition to classical and parallel electron transfer chains (ETC). In this study, we examine the role of Aox inC.albicansunder conditions of respiratory stress, which may be inflicted during its interaction with the human host or co-colonising bacteria. We find that the level of Aox expression is sufficient to modulate resistance to classical ETC inhibition under respiratory stress and are linked to gene expression changes that can promote both survival and pathogenicity. For example we demonstrate that Aox function is important for the regulation of filamentation inC.albicansand observe that cells lacking Aox function lose virulence in a zebrafish infection model. Our investigations also identify that pyocyanin, a phenazine produced by the co-colonising bacteriumPseudomonas aeruginosa, inhibits Aox-based respiration inC.albicans. These results suggest that Aox plays important roles within respiratory stress response pathways whichC.albicansmay utilise both as a commensal organism and as a pathogen.
The evolution of infanticide by females in mammals
Authors: Lukas Dieter , Huchard Elise
Published: August 2018

In most mammalian species, females regularly interact with kin, and it may thus be difficult to understand the evolution of some aggressive and harmful competitive behaviour among females, such as infanticide. Here, we investigate the evolutionary determinants of infanticide by females by combining a quantitative analysis of the taxonomic distribution of infanticide with a qualitative synthesis of the circumstances of infanticidal attacks in published reports. Our results show that female infanticide is widespread across mammals and varies in relation to social organization and life-history, being more frequent where females breed in groups and have intense bouts of high reproductive output. Specifically, female infanticide occurs where the proximity of conspecific offspring directly threatens the killer’s reproductive success by limiting access to critical resources for her dependent progeny, including food, shelters, care or a social position. In contrast, infanticide is not immediately modulated by the degree of kinship among females, and females occasionally sacrifice closely related juveniles. Our findings suggest that the potential direct fitness rewards of gaining access to reproductive resources have a stronger influence on the expression of female aggression than the indirect fitness costs of competing against kin.
Applying optimal control theory to complex epidemiological models to inform real-world disease management
Authors: Bussell E.H. , Dangerfield C.E. , Gilligan C.A. , Cunniffe N.J.
Published: August 2018

Mathematical models provide a rational basis to inform how, where and when to control disease. Assuming an accurate spatially-explicit simulation model can be fitted to spread data, it is straightforward to use it to test the performance of a range of management strategies. However, the typical complexity of simulation models and the vast set of possible controls mean that only a small subset of all possible strategies can ever be tested. An alternative approach – optimal control theory – allows the very best control to be identified unambiguously. However, the complexity of the underpinning mathematics means that disease models used to identify this optimum must be very simple. We highlight two frameworks for bridging the gap between detailed epidemic simulations and optimal control theory: open-loop and model predictive control. Both these frameworks approximate a simulation model with a simpler model more amenable to mathematical analysis. Using an illustrative example model we show the benefits of using feedback control, in which the approximation and control are updated as the epidemic progresses. Our work illustrates a new methodology to allow the insights of optimal control theory to inform practical disease management strategies, with the potential for application to diseases of plants, animals and humans.
Neural basis of Transcranial Magnetic Stimulation at the single-cell Level
Authors: Romero Maria C. , Davare Marco , Armendariz Marcelo , Janssen Peter
Published: August 2018

Transcranial Magnetic Stimulation (TMS) can non-invasively modulate neural activity in humans. Despite three decades of research, the spatial extent of the cortical area activated by TMS is still controversial. Moreover, how TMS interacts with task-related activity during motor behavior is unknown. We applied single-pulse TMS over the macaque parietal cortex while recording single-unit activity at various distances from the center of stimulation during grasping. The spatial extent of the TMS-induced activation was remarkably restricted, affecting single neurons in a volume of cortex measuring less than 2 mm. In task-related neurons, TMS evoked a transient excitation followed by reduced activity, which was paralleled by a significantly longer grasping time. Furthermore, TMS- induced activity and task-related activity did not summate in single neurons. These results furnish crucial experimental evidence for the neural basis of the TMS effect at the single-cell level and uncover, the neural underpinnings of behavioral effects of TMS.
Compressive strengths of PEG gels with glycerol and bioglass particles
Authors: Golshan Ariel , Curtis Jenesis A. , Lianos Vasilios , Rabbany Sina Y. , de Guzman Roche C.
Published: August 2018

Poly(ethylene glycol) (PEG)-based materials can potentially be used as biomechanical matrices for regenerative medicine implants including the replacement of intervertebral (IV) discs. Glycerol and other plasticizers (low-MW PEG, propylene glycol, and sorbitol) were added to the bulk PEG matrix, gelled using chemical and photochemical methods at different temperature and pressure settings, and compression properties acquired and analyzed. Incorporation of surface bioactive glass particles shortened the blood clotting time, while alginate and laponite additives improved the gel’s mechanical properties to 645 kPa compressive modulus, 12% yield strain, and 79 kPa yield strength. This IV disc-modeled system endured the cyclic loading and unloading test indicative of an elastic response; but required improvement of its biomechanical tolerance.
Genotype-Phenotype Relations of the von Hippel-Lindau Tumor Suppressor Inferred from a Large-Scale Analysis of Disease Mutations and Interactors
Authors: Minervini Giovanni , Quaglia Federica , Tabaro Francesco , Tosatto Silvio C.E.
Published: August 2018

Familiar cancers represent a privileged point of view for studying the complex cellular events inducing tumor transformation. Von Hippel-Lindau syndrome, a familiar predisposition to develop cancer is a clear example. Here, we present our efforts to decipher the role of von Hippel-Lindau tumor suppressor protein (pVHL) in cancer insurgence. We collected high quality information about both pVHL mutations and interactors to investigate the association between patient phenotypes, mutated protein surface and impaired interactions. Our data suggest that different phenotypes correlate with localized perturbations of the pVHL structure, with specific cell functions associated to different protein surfaces. We propose five different pVHL interfaces to be selectively involved in modulating proteins regulating gene expression, protein homeostasis as well as to address extracellular matrix (ECM) and ciliogenesis associated functions. These data were used to drive molecular docking of pVHL with its interactors and guide Petri net simulations of the most promising alterations. We predict that disruption of pVHL association with certain interactors can trigger tumor transformation, inducing metabolism imbalance and ECM remodeling. Collectively taken, our findings provide novel insights into VHL-associated tumorigenesis. This highly integrated in silico approach may help elucidate novel treatment paradigms for VHL disease.

Author summary

Cancer is generally caused by a series of mutations accumulating over time in a healthy tissue, which becomes re-programmed to proliferate at the expense of the hosting organism. This process is difficult to follow and understand as events in a multitude of different genes can lead to similar outcomes without apparent cause. The von Hippel-Lindau (VHL) tumor suppressor is one of the few genes harboring a familiar cancer syndrome, i.e. VHL mutations are known to cause a predictable series of events leading cancer in the kidneys and a few selected other tissues. This article describes a large-scale analysis to relate known VHL mutations to specific cancer pathways by looking at the molecular interactions. Different cancer types appear to be caused by mutations changing the surface of specific parts of the VHL protein. By looking at the VHL interactors involved, it is therefore possible to identify other candidate genes for mutations leading to very similar cancer types.
The impact of global transcriptional regulation on bacterial gene order
Authors: Yubero Pablo , Poyatos Juan F.
Published: August 2018

Bacterial gene expression depends on the allocation of limited transcriptional resources provided a particular growth rate and growth condition. Early studies in a few genes suggested this global regulation to generate a unifying hyperbolic expression pattern. Here, we developed a large-scale method that generalizes these experiments to quantify the response to growth of over 700 genes thata priorido not exhibit any specific control. We distinguish a core subset following a promoter-specific hyperbolic response. Within this group, we sort genes with regard to their responsiveness to the global regulatory program to show that those with a particularly sensitive linear response are located near the origin of replication. We then find evidence that this genomic architecture is biologically significant by examining position conservation ofE. coligenes in 100 bacteria. The response to the transcriptional resources of the cell results consequently in an additional feature contributing to bacterial genome organization.
Analysis of a structured intronic region of the LMP2 pre-mRNA from EBV reveals associations with human regulatory proteins
Authors: Kumarasinghe Nuwanthika , Moss Walter N.
Published: August 2018

Objective: The pre-mRNA of the Epstein–Barr virus LMP2 (latent membrane protein 2) has a region of unusual RNA structure that partially spans two consecutive exons and the entire intervening intron; suggesting RNA folding might affect splicing—particularly via interactions with human regulatory proteins. To better understand the roles of protein associations with this structured intronic region, we undertook a combined bioinformatics (motif searching) and experimental analysis (biotin pulldowns and RNA immunoprecipitations) of protein binding. Result: Characterization of the ribonucleoprotein composition of this region revealed several human proteins as interactors: regulatory proteins hnRNP A1 (heterogeneous nuclear ribonucleoprotein A1), hnRNP U, HuR (human antigen R), and PSF (polypyrimidine tract-binding protein-associated splicing factor), as well as, unexpectedly, the cytoskeletal protein actin. Treatment of EBV-infected cells with drugs that alter actin polymerization specifically showed marked effects on splicing in this region. This suggests a potentially novel role for nuclear actin in regulation of viral RNA splicing.
Complex cell-state changes revealed by single cell RNA sequencing of 76,149 microglia throughout the mouse lifespan and in the injured brain
Authors: Hammond Timothy R. , Dufort Connor , Dissing-Olesen Lasse , Giera Stefanie , Young Adam , Wysoker Alec , Walker Alec J. , Segel Michael , Nemesh James , Saunders Arpiar , Macosko Evan , Franklin Robin J. M. , Piao Xianhua , McCarroll Steve , Stevens Beth
Published: August 2018

Microglia, the resident immune cells of the brain, rapidly change states in response to their environment, but we lack molecular and functional signatures of different microglial populations. In this study, we analyzed the RNA expression patterns of more than 76,000 individual microglia during development, old age and after brain injury. Analysis uncovered at least nine transcriptionally distinct microglial states, which expressed unique sets of genes and were localized in the brain using specific markers. The greatest microglial heterogeneity was found at young ages; however, several states - including chemokine-enriched inflammatory microglia - persisted throughout the lifespan or increased in the aged brain. Multiple reactive microglial subtypes were also found following demyelinating injury in mice, at least one of which was also found in human MS lesions. These unique microglia signatures can be used to better understand microglia function and to identify and manipulate specific subpopulations in health and disease.
Crystal structure of the [(1,3-dimesityl-1H-imidazol-3-ium-2-yl)methanolato]copper(II) chloride dimer: insertion of formaldehyde into a copper–carbene bond
Authors: Dodds Christopher A. , Kennedy Alan R.
Published: August 2018

The crystal structure of bis[μ-(1,3-dimesityl-1H-imidazol-3-ium-2-yl)methanolato-κ2
O:O]bis[dichloridocopper(II)], [Cu2Cl4(C22H26N2O)2], is reported. The complex is assumed to have formed via the insertion of formaldehyde into the copper–carbon bond in an N-heterocyclic carbene complex of copper(I) chloride. The structure of the binuclear molecule possesses a crystallographically centrosymmetric Cu2O2 central core with the O atoms bridging between the CuII atoms and thus Z′ = 0.5. The copper centres are further ligated by two chloride ligands, resulting in the CuII atoms residing in a distorted square-planar environment. The Cu—O bond lengths are shorter than those previously reported in structures with the same central Cu2O2 motif. The complex displays C—H...Cl interactions involving the H atoms of the heterocycle backbone and the chloride ligands of a neighbouring molecule.
Crystal structure of tetrakis(μ2-(E)-2,4-dibromo-6-{[2-(pyridin-2-yl)ethyl]iminomethyl}phenolato)trizinc bis(perchlorate) acetonitrile disolvate
Authors: Okeke Ugochukwu , Otchere Raymond , Gultneh Yilma , Butcher Ray J.
Published: August 2018

The title compound, [Zn3(C14H11Br2N2O)4](ClO4)2·2CH3CN, crystallizes as a symmetrical trinuclear cation with all three metal atoms being located on a twofold rotation axis. It contains a tetrahedral ZnII atom that bridges two six-coordinate ZnII atoms. The complex contains N- and O-donor atoms of four tridentate 2,4-dibromo-6-{[2-(pyridin-2-yl)ethyl]iminomethyl}phenolate ligands. The ratio of ZnII atoms to ligands is 3:4. The two terminal ZnII cations adopt distorted octahedral geometries and the central ZnII cation adopts a distorted tetrahedral geometry. In the cation there are π–π interactions between the dibromophenyl rings, as well as halogen-bonding interactions between the dibromophenyl rings in the cation, which stabilize its conformation. In addition, there are C—H...O interactions between the anions and both the cations and solvent molecules as well as C—H...N interactions between the cation and solvent molecules. These interspecies interactions link the cations, anions and solvent molecules into a complex three-dimensional array
Crystal structure of bis(pivaloylhydroxamato-κ2
O,O′)copper(II)
Authors: Goleva Kateryna , Naumova Dina , Pavlishchuk Anna , Addison Anthony W. , Zeller Matthias
Published: August 2018

Reaction of copper(II) nitrate with pivaloylhydroxamic acid yielded the title compound, [Cu(pivHA)2] (where pivHA− is pivaloyl hydroxamate, C5H10NO2). The centrosymmetric mononuclear complex consists of a CuII ion, which is located on a center of inversion, with two coordinated pivaloyl hydroxamate monoanions. The CuII ion has a square-planar coordination environment consisting of four O atoms – two carbonyl O atoms and two hydroxamate O atoms from two hydroxamate pivHA− ligands. The pivHA− anions are coordinated to copper(II) in a trans-mode, forming two five-membered O,O′-chelate rings.
(2S,3S)-2-Azaniumyl-4-[(1S,4aS,4bS,6S,7S,8aS,10aS)-6,7-dihydroxy-2,4b,8,8,10a-pentamethyl-1,4,4a,4b,5,6,7,8,8a,9,10,10a-dodecahydrophenanthren-1-yl]-3-methoxybutanoate–methanol–water (1/1/1)
Authors: Eitel Michael , Schollmeyer Dieter , Gross Harald , Koch Pierre
Published: August 2018

The title compound, which crystallized as a methanol and water solvate, C24H41NO5·CH4O·H2O, was obtained by heterologous expression of the brasilicardin gene cluster in the bacterium Amycolatopsis japonicum. In the crystal, the components are linked by numerous hydrogen bonds, generating a three-dimensional network.
Familial acanthosis nigricans with the FGFR3 mutation: Differences of pigmentation between male and female patients
Authors: Yasuda Masahito , Morimoto Naoko , Shimizu Akira , Toyoshima Takae , Yokoyama Yoko , Ishikawa Osamu
Published: August 2018

Familial acanthosis nigricans caused by the mutation of the fibroblast growth factor receptor 3 (FGFR3) gene is characterized by short stature, hypochondroplasia and acanthosis nigricans. We herein report a Japanese family that showed a missense mutation of c.1948A>C (p.K650Q) in FGFR3. The pigmentation of acanthosis nigricans was more prominent in male patients than in female patients in this family. We immunohistochemically analyzed the distribution of melanocytes. Although pigmentation in the basal layer was denser in the proband, there was no difference in the distribution and number of melanocytes.
How Monetary Policy Affects Your Gross Domestic Product
Authors: Haldane Andrew G
Published: August 2018

During the financial crisis, monetary policy was loosened significantly. Debate continues about the extent to which low interest rates and quantitative easing (QE) may have had adverse distributional impacts, whether by income, wealth, age or region. Using quantified simulations on micro data, I show that looser monetary policy had a significantly positive financial impact on the majority of cohorts of UK society. The impact of monetary policy loosening on income and wealth inequality was small and the overall impact on household welfare significantly positive. These results differ from public perceptions of monetary policy. Personalised information on the impact of monetary policy on household balance sheets could help to correct these misperceptions.
Meadow Restoration Increases Baseflow and Groundwater Storage in the Sierra Nevada Mountains of California
Authors: Hunt Luke J.H. , Fair Julie , Odland Maxwell
Published: August 2018

In mountains of the western United States, channel incision has drawn down the water table across thousands of square kilometers of meadow floodplain. Here climate change is resulting in earlier melt and reduced snowpack and water resource managers are responding by investing in meadow restoration to increase springtime storage and summer flows. The record‐setting California drought (2012–2015) provided an opportunity to evaluate this strategy under the warmer and drier conditions expected to impact mountain water supplies. In 2012, 0.1 km2 of meadow floodplain was reconnected by filling an incised channel through Indian Valley in the central Sierra Nevada Mountains of California. Despite sustained drought conditions after restoration, summer baseflow from the meadow increased 5–12 times. Before restoration, the total summer outflow from the meadow was 5% more than the total summer inflow. After restoration, total summer outflow from the meadow was between 35% and 95% more than total summer inflow. In the worst year of the drought (2015), when inflow to the meadow ceased for at least one month, summer baseflow was at least five times greater than before restoration. Groundwater levels also rose at four out of five sites near the stream channel. Filling the incised channel and reconnecting the meadow floodplain increased water availability and streamflow, despite unprecedented drought conditions.
Early onset neutropenia and thrombocytopenia following rituximab in lupus nephritis
Authors: Shah Sanket , Kavadichanda Chengappa G. , Belani Pooja , Ganesh Rajesh N. , Negi Vir Singh
Published: August 2018

Biologics have emerged as an important modality of treatment in rheumatic diseases and have allowed the rheumatologist to explore varied therapeutic uses of these drugs. Rituximab, a monoclonal antibody against CD20 receptor is an important member of the biologic armamentarium for the treatment of various refractory autoimmune inflammatory rheumatic diseases. The drug is now widely used in systemic lupus erythematosus for several complications which are refractory to conventional therapy. Although relatively safe, the post‐marketing surveillance of rituximab has revealed a few rare but important adverse reactions. Cytopenia including neutropenia following rituximab, has been vastly reported as a late event (>4 weeks), but a few cases of early onset neutropenia (EON) and thrombocytopenia are also found in the literature. We describe a case of a 35‐year‐old woman with refractory lupus nephritis who developed asymptomatic EON and thrombocytopenia following rituximab infusion. The neutropenia responded well to granulocyte colony‐stimulating factor treatment and the platelets spontaneously recovered. This case report is aimed at highlighting the importance of identifying early onset cytopenia following rituximab which may have an important bearing on the final outcome for the patient.
Exploring population responses to environmental change when there is never enough data: a factor analytic approach
Authors: Hindle Bethan J. , Rees Mark , Sheppard Andy W. , Quintana‐Ascencio Pedro F. , Menges Eric S. , Childs Dylan Z.
Published: August 2018

Temporal variability in the environment drives variation in vital rates, with consequences for population dynamics and life‐history evolution. Integral projection models (IPMs) are data‐driven structured population models widely used to study population dynamics and life‐history evolution in temporally variable environments. However, many datasets have insufficient temporal replication for the environmental drivers of vital rates to be identified with confidence, limiting their use for evaluating population level responses to environmental change.

Parameter selection, where the kernel is constructed at each time step by randomly selecting the time‐varying parameters from their joint probability distribution, is one approach to including stochasticity in IPMs. We consider a factor analytic (FA) approach for modelling the covariance matrix of time‐varying parameters, whereby latent variable(s) describe the covariance among vital rate parameters. This decreases the number of parameters to estimate and, where the covariance is positive, the latent variable can be interpreted as a measure of environmental quality. We demonstrate this using simulation studies and two case studies.

The simulation studies suggest the FA approach provides similarly accurate estimates of stochastic population growth rate to estimating an unstructured covariance matrix. We demonstrate how the latent parameter can be perturbed to show how selection on reproductive delays in the monocarp Carduus nutans changes under different environmental conditions. We develop a demographic model of the fire dependent herb Eryngium cuneifolium to show how a putative driver of the variation in environmental quality can be incorporated with the addition of a single parameter. Using perturbation analyses we determine optimal management strategies for this species.

This approach estimates fewer parameters than previous approaches and allows novel eco‐evolutionary insights. Predictions on population dynamics and life‐history evolution under different environmental conditions can be made without necessarily identifying causal factors. Putative environmental drivers can be incorporated with relatively few parameters, allowing for predictions on how populations will respond to changes in the environment.
Population demography and biology of a new species of giant spiny trapdoor spider (Araneae: Idiopidae: Euoplos) from inland Queensland: developing a ‘slow science’ study system to address a conservation crisis
Authors: Rix Michael G , Wilson Jeremy D , Rix Alan G , Wojcieszek Aleena M , Huey Joel A , Harvey Mark S
Published: August 2018

‘Slow science’ approaches to understanding the ecology, natural history and demography of species have declined over recent decades, despite the critical importance of these studies to conservation biology. With the progression of the Anthropocene, populations of invertebrates are under increasing pressure across the globe, yet few long‐term datasets exist to track potential changes or declines. Here, we present a newly developed ‘slow science’ study system, to understand the demography, biology and molecular ecology of a potentially threatened species of giant idiopid trapdoor spider from inland eastern Australia. This previously undescribed species in the tribe Euoplini, here newly described as Euoplos grandis Wilson & Rix sp. nov., has a highly fragmented distribution in the southern Brigalow Belt bioregion of south‐eastern Queensland, in a landscape largely cleared for cropped agriculture. The conservation significance of Idiopidae has long been recognised, and these spiders remain a flagship group for terrestrial invertebrate conservation in Australia. By studying growth rates, life spans, recruitment, natural history, fitness, gene flow, dispersal and other aspects of population and individual health, we aim gradually to uncover the population dynamics of a discrete natural population. In this paper, we summarise longitudinal data for 69 individual trapdoor spiders following an initial 18 months of study, and highlight preliminary demographic trends, biological observations and avenues for future genetic research. Ultimately, the aim of this study is to provide a baseline dataset for the conservation of Australian Idiopidae, and a guiding case study for similar taxa elsewhere in Australia.
Echocardiographic determination of resting haemodynamics and optimal positioning in term pregnant women
Authors: Dennis A. T. , Buckley A. , Mahendrayogam T. , Castro J. M. , Leeton L.
Published: August 2018

Optimal positioning for anaesthesia in pregnant women involves balancing the need for ideal tracheal intubation conditions (achieved by the head elevated ramped position), with the prevention of reduced cardiac output from aortocaval compression (achieved by left lateral pelvic tilt). No studies have examined the effect on cardiac output of left lateral pelvic tilt in the ramped position. We studied non‐labouring, non‐anaesthetised healthy term pregnant women who underwent baseline (left lateral decubitus) cardiac assessment using transthoracic echocardiography. We then compared cardiac output, maternal physiological variables, fetal heart rate and comfort scores in three positions: left lateral decubitus; ramped position with wedge; and ramped position alone. Thirty women completed the study. Mean (SD) age, gestation and body mass index were 33.5 (3.93) years, 38.5 (0.94) weeks and 29.0 (4.0) kg.m−2, respectively. Mean ejection fraction, left ventricular internal diameter and mitral valve E/e’ were 55.2 (6.8) %, 4.70 (0.43) cm and 7.50 (1.82), respectively. There were no differences in cardiac output between the positions (p = 0.503). There were no differences in systolic (p = 0.955) or diastolic (p = 0.987) blood pressure, maternal heart rate (p = 0.133), oxygen saturation, respiratory rate (p = 0.964) or fetal heart rate (p = 0.361) between ramped with wedge and ramped alone positions. Left lateral decubitus was most comfortable (p = 0.001), however, there were no differences in comfort levels between ramped with wedge and ramped alone positions. The ramped position without left lateral tilt is safe and acceptable in non‐labouring, non‐anaesthetised, healthy term pregnant women. Left lateral pelvic tilt may be unnecessary in the head elevated ramped position in term pregnant women.
Impact of residual disease on overall survival in women with Federation of Gynecology and Obstetrics stage IIIB‐IIIC vs stage IV epithelial ovarian cancer after primary surgery
Authors: Sørensen Sarah M. , Schnack Tine H. , Høgdall Claus
Published: August 2018

Introduction

The objective of this study was to determine the impact of intra‐abdominal residual disease size, type (carcinomatosis, tumor mass or both), and location (upper/lower abdominal/both) on overall survival in women with Federation of Gynecology and Obstetrics (FIGO) stage IIIB‐IIIC vs stage IV epithelial ovarian cancer who underwent primary debulking surgery.

Material and methods

Altogether 2092 women diagnosed with advanced epithelial ovarian cancer undergoing primary debulking surgery in Denmark during 2005‐2016 were identified in the Danish Gynecological Cancer Database. The impact of residual disease size, type, and location were evaluated using univariate and multivariate analyses.

Results

Complete cytoreduction (residual disease = 0) was achieved in 47.3% and 38.4% of women with stage IIIB‐IIIC and IV epithelial ovarian cancer, respectively. A benefit in overall survival was observed in women with residual disease = 0 compared with women with residual disease, and among women with residual disease ≤1 cm compared with residual disease >2 cm in both stages IIIB‐IIIC and stage IV in multivariate analyses. Multivariate analyses showed an inferior overall survival for women with both residual carcinomatosis and residual tumor mass compared with those with residual tumor mass or residual carcinomatosis only for stage IIIB‐IIIC and IV, and an inferior overall survival for women with residual disease located in both the upper and lower abdomen compared with residual disease in the upper abdomen only in stages IIIB‐IIIC.

Conclusions

Our results confirm the positive prognostic impact of both complete cytoreduction and residual disease ≤1 cm in stages IIIB‐IIIC as well as stage IV epithelial ovarian cancer. Women with stage IV do benefit from cytoreductive surgery and should be considered for primary debulking surgery, if residual disease = 0 can initially be expected.