bluuebunny/crossref_metadata_2025 huggingface dataset:
The Aristocracy in England and Tuscany, 1000 - 1250
Authors: Coss Peter
Published: November 2019

Part I of this book is an in-depth examination of the characteristics of the Tuscan aristocracy across the first two and a half centuries of the second millennium, as studied by Italian historians and others working within the Italian tradition: their origins, interests, strategies for survival and exercise of power; the structure and the several levels of aristocracy and how these interrelated; the internal dynamics and perceptions that governed aristocratic life; and the relationship to non-aristocratic sectors of society. It will look at how aristocratic society changed across this period and how far changes were internally generated as opposed to responses from external stimuli. The relationship between the aristocracy and public authority will also be examined. Part II of the book deals with England. The aim here is not a comparative study but to bring insights drawn from Tuscan history and Tuscan historiography into play in understanding the evolution of English society from around the year 1000 to around 1250. This part of the book draws on the breadth of English historiography but is also guided by the Italian experience. The book challenges the interpretative framework within which much English history of this period tends to be written—that is to say the grand narrative which revolves around Magna Carta and English exceptionalism—and seeks to avoid dangers of teleology, of idealism, and of essentialism. By offering a study of the aristocracy across a wide time-frame and with themes drawn from Italian historiography, I hope to obviate these tendencies and to appreciate the aristocracy firmly within its own contexts.
Communicatio Idiomatum
Authors: Cross Richard
Published: November 2019

This book offers a radical reinterpretation of the sixteenth-century Christological debates between Lutheran and Reformed theologians on the ascription of divine and human predicates to the person of the incarnate Son of God (the communicatio idiomatum). It does so by close attention to the arguments deployed by the protagonists in the discussion, and to the theologians’ metaphysical and semantic assumptions, explicit and implicit. It traces the central contours of the Christological debates, from the discussion between Luther and Zwingli in the 1520s to the Colloquy of Montbéliard in 1586. The book shows that Luther’s Christology is thoroughly Medieval, and that innovations usually associated with Luther—in particular, that Christ’s human nature comes to share in divine attributes—should be ascribed instead to his younger contemporary Johannes Brenz. The discussion is highly sensitive to the differences between the various Luther groups—followers of Brenz, and the different factions aligned in varying ways with Melanchthon—and to the differences between all of these and the Reformed theologians. And by locating the Christological discussions in their immediate Medieval background, the book also provides a comprehensive account of the continuities and discontinuities between the two eras. In these ways, it is shown that the standard interpretations of the Reformation debates on the matter are almost wholly mistaken.
The Emotional Life of the Great Depression
Authors: Marsh John
Published: November 2019

The Emotional Life of the Great Depression documents how Americans responded emotionally to the crisis of the Great Depression. Unlike most books about the 1930s, which focus almost exclusively on the despair of the American people during the decade, The Emotional Life of the Great Depression explores the 1930s through other, equally essential emotions: righteousness, panic, fear, awe, love, and hope. In expanding the canon of Great Depression emotions, the book draws on an eclectic archive of sources, including the ravings of a would-be presidential assassin, stock market investment handbooks, a Cleveland serial murder case, Jesse Owens’s record-setting long jump at the 1936 Berlin Olympics, King Edward VIII’s abdication from his throne to marry a twice-divorced American woman, and the founding of Alcoholics Anonymous. In concert with these, it offers new readings of the imaginative literature of the period, from obscure Christian apocalyptic novels and H.P. Lovecraft short stories to classics such as John Steinbeck’s The Grapes of Wrath and Richard Wright’s Native Son. The upshot is a new take on the Great Depression, one that emphasizes its major events (the stock market crash, unemployment, the passage of the Social Security Act) but also, and perhaps even more so, its sensibilities, its structures of feeling.
The Evolution of Music through Culture and Science
Authors: Townsend Peter
Published: November 2019

Music is an international key aspect of humanity which impacts life, from love songs to religion, politics, and warfare. Changes in culture and developments in science drove musical progress from printing and distribution to instrumental improvements, innovation, and the acoustics of buildings and concert halls. Every aspect increased public demand and changed compositional styles, plus heightened the need for virtuosic star performers. Conversely, the attempts to record and distribute music inspired the growth of recording systems, microphones, and electronic amplifiers, which has resulted in the electronically dominated world as we now know it. The book maps these continuous changes and how they have influenced musical evolution, and it not only explores the past, but attempts to predict the near future in terms of the potential for new electronic instruments and the ongoing shifts between recording and broadcasting techniques (tapes, vinyl, CDs, streaming, etc.), together with their impact on, and the survival of, the music industry. Examples of changes for keyboard, string, and brass instruments, current understanding of voice production, hearing, and brain processing of music are all discussed. This book is for those interested in all aspects of music, from classical to jazz and pop. It does not require either scientific or musical backgrounds, but it will enhance enjoyment of music, and reveal the probable future of musical trends.
Minimal texture of quark mass matrices and precision CKM measurements
Authors: Kaundal Shivali , Bagai Aakriti , Ahuja Gulsheen , Gupta Manmohan
Published: November 2019

We have carried out an extensive analysis of all possible minimal texture quark mass matrices implying 169 texture-6 zero combinations. One finds that all these combinations are ruled out: a good number of these analytically, the other possibilities being excluded by the present quark mixing data. Interestingly, even if there are future changes in the ranges of the light quark masses, these conclusions remain valid.
A comparison of methodologies for the staining and quantification of intracellular components of arbuscular mycorrhizal fungi in the root cortex of two varieties of winter wheat
Authors: Wilkes Thomas I. , Warner Douglas J. , Edmonds-Brown Veronica , Davies Keith G. , Denholm Ian
Published: November 2019

Arbuscular mycorrhizal (AM) fungi are one of the most common fungal organisms to exist in symbiosis with terrestrial plants, facilitating the growth and maintenance of arable crops. Wheat has been studied extensively for AM fungal symbiosis using the carcinogen trypan blue as the identifying stain for fungal components, namely arbuscles, vesicles and hyphal structures. The present study uses Sheaffer blue ink with a lower risk as an alternative to this carcinogenic stain. Justification for this is determined by stained wheat root sections (n=120), with statistically significant increases in the observed abundance of intracellular root cortical fungal structures stained with Sheaffer blue ink compared to trypan blue for both Zulu (P=0.003) and Siskin (P=0.0003) varieties of winter wheat. This new alternative combines an improved quantification of intracellular fungal components with a lower hazard risk at a lower cost.
In vivo directed evolution of AAV in the primate retina
Authors: Byrne Leah C. , Day Timothy P. , Visel Meike , Fortuny Cecile , Dalkara Deniz , Merigan William H. , Schaffer David V. , Flannery John G.
Published: November 2019

Efficient AAV-mediated gene delivery remains a significant obstacle to effective retinal gene therapies. Here, we apply directed evolution – guided by deep sequencing and followed by direct in vivo secondary selection of high-performing vectors with a GFP-barcoded library – to create AAV viral capsids with new capabilities to deliver genes to the outer retina in primates. A replication incompetent library, produced via providing rep in trans, was created to mitigate risk of AAV propagation. Six rounds of in vivo selection with this library in primates – involving intravitreal library administration, recovery of genomes from outer retina, and extensive next generation sequencing of each round – resulted in vectors with redirected tropism to the outer retina and increased gene delivery efficiency to retinal cells. These new viral vectors expand the toolbox of vectors available for primate retina, and may enable less invasive delivery of therapeutic genes to patients, potentially offering retina-wide infection at a similar dosage to vectors currently in clinical use.
Cold and distant: structural features of the nucleoprotein complex of a cold-adapted influenza A virus strain
Authors: Shvetsov A.V. , Lebedev D.V. , Zabrodskaya Y.A. , Shaldzhyan A.A. , Egorova M.A. , Vinogradova D.S. , Konevega A.L. , Gorshkov A.N. , Ramsay E.S. , Radulescu A. , Sergeeva M.V. , Plotnikova M.A. , Komissarov A.B. , Taraskin A.S. , Lebedev K.I. , Garmay Yu.P. , Kuznetsov V.V. , Isaev-Ivanov V.V. , Vasin A.V. , Tsybalova L.M. , Egorov V.V.
Published: November 2019

Two influenza A nucleoprotein variants (wt: G102R; and mutant: G102R and E292G) were studied with regard to macro-molecular interactions in oligomeric form (24-mers). The E292G mutation has been previously shown to provide cold adaptation. Molecular dynamics simulations of these complexes and trajectory analysis showed that the most significant difference between the obtained models was distance differences between nucleoprotein complex strands. Influenza virus nucleoprotein complexes were isolated from strains bearing the corresponding NP amino acid substitutions. The isolated complexes were characterized by transmission electron microscopy and differential scanning fluorimetry (DSF). Presence of the E292G substitution was shown by DSF to affect nucleoprotein complex melting temperature. In the filament interface peptide model, it was shown that the peptide corresponding in primary structure to the wild-type NP (SGYDFEREGYS, wild type peptide) is prone to temperature-dependent self-association, unlike the peptide carrying the substitution corresponding to E292G (SGYDFGREGYS, mutant peptide). It was also shown that the SGYDFEREGYS peptide (wt) is capable of interacting with a recombinant full-size monomeric nucleoprotein (with primary structure corresponding to wild type); this interaction’s equilibrium dissociation constant is five orders of magnitude lower than for the SGYDFGREGYS peptide. Using small-angle neutron scattering (SANS), the supramolecular structures of isolated complexes of these proteins was studied at temperatures of 15, 32, and 37°C. SANS data show that the structures of the studied complexes (mutant or normal proteins with RNA) at elevated temperature differ from the rod-like particle model and react differently to temperature changes. The data suggest that the mechanism behind cold adaptation with E292G is associated with a weakening of the interaction between strands of the ribonucleoprotein complex and, as a result, the appearance of inter-chain interface flexibility necessary for complex function at low temperature.
Gendered Fitness Interests: A Method Partitioning the Effects of Family Composition on Socio-Political Attitudes and Behaviors
Authors: Brooks Robert C. , Blake Khandis R.
Published: November 2019

Whereas most people are biologically either male or female, their genetic interests are almost never aligned with just their own sex. Drawing on the evolutionary theory of inclusive fitness gained through relatives, we partition the effects of kin on fitness into those that derive from female versus male relatives. We argue that the balance of these female- and male-derived effects, which we call ‘Gendered Fitness Interests’ (GFI), might influence human behavior, especially the adoption of socio-political attitudes that have a gendered dimension. Our proposal builds on observations that individual socio-political views covary with the sex of their children or the numbers of relatives of each sex. Further, it is consistent with the relatively small average differences between women’s and men’s socio-political positions. We outline a method for partitioning GFI, and use simulation models to explore some of its properties. We then show that (1) the GFI component of women’s and men’s socio-political attitudes will converge, on average, with age. (2) The contributions of both descendent and non-descendent kin lead to considerable variation in GFI. (3) When men have longer average reproductive lifespans than women, GFI can show small male-biases. (4) Paternity uncertainty reduces the variation in GFI between individuals, and (5) Large family sizes are associated with more variation among individuals in GFI. Our proposal provides a framework for the study of the effects of kin on traits and attitudes with a gendered dimension. In this respect, it may prove generally useful in resolving the complex origins of gendered behavior.
Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair
Authors: Maggiore Joseph C. , Burrell Justin C. , Browne Kevin D. , Katiyar Kritika S. , Laimo Franco A. , Ali Zarina S. , Kaplan Hilton M. , Rosen Joseph M. , Cullen D. Kacy
Published: November 2019

Peripheral nerve injury (PNI) impacts millions annually, often leaving debilitated patients with minimal repair options to improve functional recovery. Our group has previously developed tissue engineered nerve grafts (TENGs) featuring long, aligned axonal tracts from dorsal root ganglia (DRG) neurons that are fabricated in custom bioreactors using the process of axon “stretch-growth”. We have shown that TENGs effectively serve as “living scaffolds” to promote regeneration across segmental nerve defects by exploiting the newfound mechanism of axon-facilitated axon regeneration, or “AFAR”, by simultaneously providing haptic and neurotrophic support. To extend this work, the current study investigated the efficacy of living versus non-living regenerative scaffolds in preserving host sensory and motor neuronal health following nerve repair. Rats were assigned across five groups: naïve, or repair using autograft, nerve guidance tube (NGT) with collagen, NGT + non-aligned DRG populations in collagen, or TENGs. We found that TENG repairs yielded equivalent regenerative capacity as autograft repairs based on preserved health of host spinal cord motor neurons and acute axonal regeneration, whereas NGT repairs or DRG neurons within an NGT exhibited reduced motor neuron preservation and diminished regenerative capacity. These acute regenerative benefits ultimately resulted in enhanced levels of functional recovery in animals receiving TENGs, at levels matching those attained by autografts. Our findings indicate that TENGs may preserve host spinal cord motor neuron health and regenerative capacity without sacrificing an otherwise uninjured nerve (as in the case of the autograft), and therefore represent a promising alternative strategy for neurosurgical repair following PNI.

HIGHLIGHTS

TENGs preserve host spinal cord motor neuron health and regenerative capacity acutely following repair of segmental nerve defects, matching that of the clinical gold-standard autograft and exceeding commercially-available nerve guidance tubes.

TENGs facilitated regeneration across segmental nerve defects, yielding similar degree of chronically surviving host spinal motor neurons and functional recovery as compared to autografts.

Early surgical intervention for segmental nerve defect with living scaffolds, such as TENGs and autografts, preserves the host regenerative capacity, and likely increases the ceiling for total regeneration and functional recovery at chronic time points compared to (acellular) commercially-available nerve guidance tubes.

TENGs preserve host neuronal health and regenerative capacity without sacrificing an otherwise uninjured nerve, and therefore represent a promising alternative strategy to autografts or nerve guidance tube repairs.
The contribution of lincRNAs at the interface between cell cycle regulation and cell state maintenance
Authors: Biasini Adriano , Thil Smith Adam Alexander , Abdulkarim Baroj , Tan Jennifer Yihong , da Silva Maria Ferreira , Marques Ana Claudia
Published: November 2019

Cell cycle progression requires dynamic and tightly-regulated transitions between well-defined cell cycle stages. These transitions are controlled by the interplay of established cell cycle regulators. Changes in the activity of these regulators are thought to underpin differences in cell cycle kinetics between distinct cell types. Here, we investigate whether cell type-specific long intergenic noncoding RNAs (lincRNAs) contribute to embryonic stem cell adaptations, which have been shown to be essential for the maintenance of embryonic stem cell state.

We used single cell RNA-sequencing data of mouse embryonic stem cells (mESC) staged as G1, S, or G2/M to identify genes differentially expressed between these phases. We found differentially expressed lincRNAs to be enriched amongst cell cycle regulated genes. These cell cycle associated lincRNAs (CC-lincRNAs) are co-expressed with protein-coding genes with established roles in cell cycle progression. Interestingly, 70% of CC-lincRNAs are differentially expressed between G1 and S, suggesting they may contribute to the maintenance of the short G1 phase that characterizes the embryonic stem cell cycle. Consistent with this hypothesis, the promoters of CC-lincRNAs are enriched in pluripotency transcription factor binding sites, and their transcripts are frequently co-regulated with genes involved in the maintenance of pluripotency. We tested the impact of 2 CC-lincRNA candidates and show that modulation of their expression is associated with impaired cell cycle progression, further underlining the contribution of mESC-specific lincRNAs to cell cycle modulation in these cells.
Oncologic therapy shapes the fitness landscape of clonal hematopoiesis
Authors: Bolton Kelly L , Ptashkin Ryan N , Gao Teng , Braunstein Lior , Devlin Sean M , Kelly Daniel , Patel Minal , Berthon Antonin , Syed Aijazuddin , Yabe Mariko , Coombs Catherine C. , Caltabellotta Nicole M. , Walsh Mike , Offit Kenneth , Stadler Zsofia , Mandelker Diana , Schulman Jessica , Patel Akshar , Philip John , Bernard Elsa , Gundem Gunes , Arango Juan E , Levine Max , Medina Juan S , Farnoud Noushin , Glodzik Dominik , Li Sonya , Robson Marc E , Lee Choonsik , Pharoah Paul D P , Stopsack Konrad , Spitzer Barbara , Mantha Simon , Fagin James , Boucai Laura , Gibson Christopher J , Ebert Benjamin L , Young Andrew , Druley Todd , Takahasi Koichi , Gillis Nancy , Ball Markus , Padron Eric , Hyman David M , Baselga Jose , Norton Larry , Gardos Stuart , Klimek Virginia M , Scher Howard , Bajorin Dean , Paraiso Eder , Benayed Ryma , Arcila Maria E , Ladanyi Marc , Solit David B , Berger Michael F , Tallman Martin , Garcia-Closas Montserrat , Chatterjee Nilanjan , Diaz Luis A , Levine Ross L , Morton Lindsay M , Zehir Ahmet , Papaemmanuil Elli
Published: November 2019

Clonal hematopoiesis (CH) is frequent in cancer patients and associated with increased risk of therapy related myeloid neoplasms (tMN). To define the relationship between CH, oncologic therapy, and tMN progression, we studied 24,439 cancer patients. We show that previously treated patients have increased rates of CH, with enrichment of mutations in DNA Damage Response (DDR) genes (TP53, PPM1D, CHEK2). Exposure to radiation, platinum and topoisomerase II inhibitors have the strongest association with CH with evidence of dose-dependence and gene-treatment interactions. We validate these associations in serial sampling from 525 patients and show that exposure to cytotoxic and radiation therapy imparts a selective advantage specifically in hematopoietic cells with DDR mutations. In patients who progressed to tMN, the clone at CH demarcated the dominant clone at tMN diagnosis. CH mutational features predict risk of therapy-related myeloid neoplasm in solid tumor patients with clinical implications for early detection and treatment decisions.
Linking lysosomal enzyme targeting genes and energy metabolism with altered gray matter volume in children with persistent stuttering
Authors: Chow Ho Ming , Garnett Emily O. , Li Hua , Etchell Andrew , Sepulcre Jorge , Drayna Dennis , Chugani Diane C. , Chang Soo-Eun
Published: November 2019

Developmental stuttering is a childhood onset neurodevelopmental disorder with an unclear etiology. Subtle changes in brain structure and function are present in both children and adults who stutter. It is a highly heritable disorder, and up to 12-20% of stuttering cases may carry a mutation in one of four genes involved in mannose-6-phosphate mediated protein intracellular trafficking. To better understand the relationship between genetic factors and brain structural changes, we used gene expression data from the Allen Institute for Brain Science (AIBS) and voxel-based morphometry (VBM) to investigate the spatial correspondence between gene expression patterns and differences in gray matter volume (GMV) between children with persistent stuttering (n=26, 87 scans) and their fluent peers (n=44, 139 scans). We found that expression patterns of two stuttering-related genes (GNPTGandNAGPA) in the brain exhibit a strong positive spatial correlation with the magnitude of GMV differences between groups. Further gene set enrichment analyses revealed that genes whose expression was highly correlated with the GMV differences were enriched for glycolysis and oxidative metabolism in mitochondria. Although the results are correlational and cannot inform us about underlying casual mechanisms, our results suggest a possibility that regions with high expression level of genes associated with stuttering may be particularly vulnerable to the effect of alterations in these genes. This effect may be further exacerbated by the relatively high energy utilization in those brain during the period of a sharp increase in brain energy utilization, which coincides with a period of rapid language development and the onset of stuttering during childhood.
Drought-induced mortality: stem diameter variation reveals a point of no return in lavender species
Authors: Lamacque Lia , Charrier Guillaume , Santos Farnese Fernanda dos , Lemaire Benjamin , Améglio Thierry , Herbette Stéphane
Published: November 2019

In the context of climate changes, water availability is expected to severely decline. Consequently, there is a need to predict mortality of woody species, especially to find a physiological threshold to drought-induced mortality. Lavender species (Lavandula angustifoliaandLavandula x intermedia) which are important crops of the Mediterranean region are affected by a decline, notably caused by successive intense drought events. Lavender response to extreme drought events was monitored using continuous stem diameter measurements. Water potential, stomatal conductance, loss of xylem hydraulic conductivity and electrolyte leakage were also measured during desiccation, and recovery was evaluated after rewatering. Two parameters computed from stem diameter variations were related to stress intensity and resilience to stress: PLD (Percentage Loss of Diameter) and stem PLRC (Percentage Loss of Rehydration Capacity of the stem), respectively. We showed that plants did not recover when the PLD reached its maximal value (PLDmax) which was 21.27 ± 0.57% in both lavender species and whatever the growing conditions. This point of no return was associated with a high level of cell lysis evaluated by electrolyte leakage, and occurred far after the xylem hydraulic failure. We discussed the relevance of PLDmaxas a threshold for drought-induced mortality and its physiological significance, in relation to the mortality mechanisms.

One-sentence summary

Under extreme drought, lavender death occurs when the water storage of the elastic compartment of the stem is exhausted.
Investigation of anLPAKIV-2 nonsense mutation in 11,000 individuals: the importance of linkage disequilibrium structure inLPAgenetics
Authors: Di Maio Silvia , Streiter Gertraud , Grüneis Rebecca , Lamina Claudia , Maglione Manuel , Öfner Dietmar , Thorand Barbara , Peters Annette , Eckardt Kai-Uwe , Köttgen Anna , Kronenberg Florian , Coassin Stefan
Published: November 2019

Objective

Elevated Lp(a) plasma concentrations are determined mainly genetically by theLPAgene locus, but up to 70% of the coding sequence is located in the so-called “kringle IV type 2” (KIV-2) copy number variation. This region is not resolved by common genotyping technologies and large epidemiological studies on this region are therefore missing. The Arg21Ter variant (R21X, variant frequency ≈2%) is a functional variant in this region, but it has never been analyzed in large cohorts and is it unknown whether it is captured by genome-wide association studies.

Approach and Results

We developed a highly sensitive allele-specific qPCR assay and genotyped R21X in 10,910 individuals from three populations (GCKD, KORA F3, KORA F4). R21X carriers showed significantly lower mean Lp(a) concentrations (−11.7 mg/dL [−15.5;−7.82], p=3.39e-32). Of particular note, virtually all R21X carriers also carried the splice mutation rs41272114 (D’=0.957, R2=0.275), as confirmed by pulsed-field gel electrophoresis and long-range haplotyping. This proposes that the R21X mutation arose on the background of the rs41272114 splice variant.

Conclusions

We performed the largest epidemiological study on anLPAKIV-2 variant so far. Interestingly, R21X is located on the same haplotype as the splice mutation rs41272114, creating “double-null”LPAalleles that are inactivated by two independent mutations. The effect of the R21X nonsense mutation can thus not be discerned from the effect of rs41272114 splice site mutation. This emphasizes the importance of assessing the complex LD structure withinLPAeven for functional variants.
Do genetic differences in growth thermal reaction norms maintain genetic variation in timing of diapause induction?
Authors: Fossen Erlend I. F. , Raeymaekers Joost A. M. , Einum Sigurd
Published: November 2019

An optimal timing for diapause induction through the sexual production of dormant propagules is expected in populations of annual organisms. Yet, experimental work typically finds high within-population genetic variation in the sexual production of such propagules. Thus, high genetic variation in timing for diapause induction should be a common feature of annual organisms.

Here, we hypothesize that genetic variation in the propensity to produce diapause propagules, Pd, is maintained by a genotype-by-environment interaction in growth performance, where fast-growing genotypes within an environment should delay diapause relative to slow-growing genotypes. From this, we derive two predictions. First, if there is ecological crossover in growth performance, the genetic correlation of Pd between environments should be negative. Second, the correlation between absolute plasticities of growth and Pd should be negative.

We tested these predictions by quantifying ephippia production in genotypes of a population of the facultative sexual cladoceran Daphnia magna at two temperatures. The population biomass at the onset of ephippia production was used as a measure of Pd, whereas somatic growth rate was used to quantify growth. Plasticity for both measurements was derived from thermal reaction norms.

Our results did not support either prediction, as neither the genetic correlation of Pd between environments, nor the correlation between absolute plasticity of growth and Pd were found to be significant.

Our results suggest that genetic variation in the timing of diapause is not maintained by genetic differences in thermal growth reaction norms. We propose as an alternative hypothesis that if there is across year variation in how stochastically the environment deteriorates, fluctuating selection may favor genotypes with different Pd between years.
Genetic deletion of Autotaxin from CD11b+ cells decreases the severity of experimental autoimmune encephalomyelitis
Authors: Ninou Ioanna , Sevastou Ioanna , Magkrioti Christiana , Kaffe Eleanna , Stamatakis George , Thivaios Spyros , Panayotou George , Aoki Junken , Kollias George , Aidinis Vassilis
Published: November 2019

Autotaxin (ATX) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a growth factor-like signaling lysophospholipid. ATX and LPA signaling have been incriminated in the pathogenesis of different chronic inflammatory diseases and various types of cancer. In this report, deregulated ATX and LPA levels were detected in the spinal cord and plasma of mice during the development of experimental autoimmune encephalomyelitis (EAE). Among the different sources of ATX expression in the inflamed spinal cord, F4/80+CD11b+ cells, mostly activated macrophages and microglia, were found to express ATX, further suggesting an autocrine role for ATX/LPA in their activation, an EAE hallmark. Accordingly, ATX genetic deletion from CD11b+ cells attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in neuroinflammatory disorders.
Mechanisms of high-intensity sound exposure on inhibiting hippocampal long-term potentiation: role of brain-derived neurotrophic factor
Authors: de Deus Júnia L. , Amorim Mateus R. , Ribeiro Aline B. , Barcellos-Filho Procópio C. G. , Ceballos César C. , Branco Luiz Guilherme S. , Cunha Alexandra O.S. , Leão Ricardo M.
Published: November 2019

Exposure to humans and experimental animals to loud noises produce cognitive and emotional disorders and recent studies have shown that hippocampal neuronal function is affected by auditory stimulation or deprivation. We have found previously that in the hippocampus of rats exposed to high-intensity sound (110 dB) for one-minute the Schaffer-CA1 long-term potentiation (LTP) is strongly inhibited. Here we investigated possible mechanisms involved in this effect. We found, using c-fos expression, that exposure to 110 dB sound-activated neurons in the CA1 and CA3 hippocampal region. Using electrophysiological recordings in hippocampal slices, we found that both GABAergic and glutamatergic neurotransmission were unaffected by high-intensity sound stimulation. However, hippocampal brain-derived neurotrophic factor (BDNF), which is involved in promoting hippocampal synaptic plasticity, presented decreased levels in sound-stimulated animals. Perfusion of slices with BDNF revert the inhibition of LTP after a single sound stimulus in comparison to sham-stimulated rats. Furthermore, the perfusion with LM 22A4, a TrkB receptor agonist also rescued LTP from sound-stimulated animals. Our results strongly suggest that the exposure to high-intensity sound inhibits the BDNF production in the hippocampus, which could be a possible mechanism of the inhibition of LTP by high-intensity sound exposure.
Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity
Authors: Kim Jae Jin , Lee Seo Yun , Gong Fade , Battenhouse Anna M. , Boutz Daniel R. , Bashyal Aarti , Refvik Samantha T. , Chiang Cheng-Ming , Xhemalce Blerta , Paull Tanya T. , Brodbelt Jennifer S. , Marcotte Edward M. , Miller Kyle M.
Published: November 2019

Bromodomain proteins (BRD) are key chromatin regulators of genome function and stability as well as therapeutic targets in cancer. Here, we systematically delineate the contribution of human BRD proteins for genome stability and DNA double-strand break (DSB) repair using several cell-based assays and proteomic interaction network analysis. Applying these approaches, we identify 24 of the 42 BRD proteins as promoters of DNA repair and/or genome integrity. We identified a BRD-reader function of PCAF that bound TIP60-mediated histone acetylations at DSBs to recruit a DUB complex to deubiquitylate histone H2BK120, to allowing direct acetylation by PCAF, and repair of DSBs by homologous recombination. We also discovered the bromo-and-extra-terminal (BET) BRD proteins, BRD2 and BRD4, as negative regulators of transcription-associated RNA-DNA hybrids (R-loops) as inhibition of BRD2 or BRD4 increased R-loop formation, which generated DSBs. These breaks were reliant on topoisomerase II, and BRD2 directly bound and activated topoisomerase I, a known restrainer of R-loops. Thus, comprehensive interactome and functional profiling of BRD proteins revealed new homologous recombination and genome stability pathways, providing a framework to understand genome maintenance by BRD proteins and the effects of their pharmacological inhibition.
Identifying gene function and module connections by the integration of multispecies expression compendia
Authors: Li Hao , Rukina Daria , David Fabrice P.A. , Li Terytty Yang , Oh Chang-Myung , Gao Arwen W. , Katsyuba Elena , Bou Sleiman Maroun , Komljenovic Andrea , Huang Qingyao , Williams Robert W. , Robinson-Rechavi Marc , Schoonjans Kristina , Morgenthaler Stephan , Auwerx Johan
Published: November 2019

The functions of many eukaryotic genes are still poorly understood. Here, we developed and validated a new method, termed GeneBridge, which is based on two linked approaches to impute gene function and bridge genes with biological processes. First, Gene-Module Association Determination (G-MAD) allows the annotation of gene function. Second, Module-Module Association Determination (M-MAD) allows predicting connectivity among modules. We applied the GeneBridge tools to large-scale multispecies expression compendia—1700 data sets with over 300,000 samples from human, mouse, rat, fly, worm, and yeast—collected in this study. G-MAD identifies novel functions of genes—for example, DDT in mitochondrial respiration and WDFY4 in T cell activation—and also suggests novel components for modules, such as for cholesterol biosynthesis. By applying G-MAD on data sets from respective tissues, tissue-specific functions of genes were identified—for instance, the roles of EHHADH in liver and kidney, as well as SLC6A1 in brain and liver. Using M-MAD, we identified a list of module-module associations, such as those between mitochondria and proteasome, mitochondria and histone demethylation, as well as ribosomes and lipid biosynthesis. The GeneBridge tools together with the expression compendia are available as an open resource, which will facilitate the identification of connections linking genes, modules, phenotypes, and diseases.
Lab in a DAC – high-pressure crystal chemistry in a diamond-anvil cell
Authors: Katrusiak Andrzej
Published: November 2019

The diamond-anvil cell (DAC) was invented 60 years ago, ushering in a new era for material sciences, extending research into the dimension of pressure. Most structural determinations and chemical research have been conducted at ambient pressure, i.e. the atmospheric pressure on Earth. However, modern experimental techniques are capable of generating pressure and temperature higher than those at the centre of Earth. Such extreme conditions can be used for obtaining unprecedented chemical compounds, but, most importantly, all fundamental phenomena can be viewed and understood from a broader perspective. This knowledge, in turn, is necessary for designing new generations of materials and applications, for example in the pharmaceutical industry or for obtaining super-hard materials. The high-pressure chambers in the DAC are already used for a considerable variety of experiments, such as chemical reactions, crystallizations, measurements of electric, dielectric and magnetic properties, transformations of biological materials as well as experiments on living tissue. Undoubtedly, more applications involving elevated pressure will follow. High-pressure methods become increasingly attractive, because they can reduce the sample volume and compress the intermolecular contacts to values unattainable by other methods, many times stronger than at low temperature. The compressed materials reveal new information about intermolecular interactions and new phases of single- and multi-component compounds can be obtained. At the same time, high-pressure techniques, and particularly those of X-ray diffraction using the DAC, have been considerably improved and many innovative developments implemented. Increasingly more equipment of in-house laboratories, as well as the instrumentation of beamlines at synchrotrons and thermal neutron sources are dedicated to high-pressure research.
Combining photoinduced linkage isomerism and nonlinear optical properties in ruthenium nitrosyl complexes
Authors: Mikhailov Artem , Vuković Vedran , Kijatkin Christian , Wenger Emmanuel , Imlau Mirco , Woike Theo , Kostin Gennadiy , Schaniel Dominik
Published: November 2019

The complex trans-[RuNO(NH3)4F]SiF6 was synthesized in quantitative yield and the structure was characterized by X-ray diffraction and spectroscopic methods. The complex crystallizes in the non-centrosymmetric space group Pn. Hirshfeld surface analysis revealed that the dominant intermolecular interactions are of types H...F and F...O, which are likely to be responsible for the packing of the molecules in a non-centrosymmetric structure. Irradiation with blue light leads to the formation of Ru–ON (metastable state MS1) and Ru–η2-(NO) (metastable state MS2) bond isomers, as shown by IR and UV–Vis spectroscopy. The structural features of the MS1 isomer were elucidated by photocrystallography. The complex exhibits exceptionally good thermal stability of the metastable state MS1, such that it can be populated by light at 290–300 K, which is important for potential applications. The second harmonic (SH) emission can be generated by femtosecond-pulsed irradiation of the complex. The generated SH is rather efficient and stable under long-term exposure. Finally, since both metastable states and harmonic generation can be generated at room temperature, an attempt to drive the SH response by photoisomerization of the nitrosyl ligand was made and is discussed.
Incommensurately modulated crystal structure of flamite – natural analogue of \alpha _{\rm H}^{\prime}-Ca2SiO4
Authors: Rashchenko Sergey V. , Seryotkin Yurii V. , Sokol Ella V. , Kokh Svetlana N.
Published: November 2019

Crystal structures of unquenchable high-temperature polymorphs of Ca2SiO4, important in cement chemistry, have eluded single-crystal X-ray analysis. However, the problem may be addressed by studying chemically stabilized Ca2SiO4polymorphs at ambient temperature. Here an incommensurately modulated crystal structure of flamite [Pnma(0β0)00s,q= 0.2728 (2)b*,a= 6.8588 (2) Å,b= 5.4301 (2) Å,c= 9.4052 (3) Å] is described. It is a mineral analogue of orthorhombic \alpha _{\rm H}^{\prime}-Ca2SiO4(stable between 1160 and 1425°C), naturally stabilized by substitution with phosphorus. The incommensurate modulation results from wave-like displacement of cation sites accompanied by tilting of (Si,P)O4tetrahedra and variation of the Na/(Ca + Na + K) ratio along the modulation period. The studied sample from Hatrurim Basin (Negev Desert, Israel) with composition (Ca1.75K0.12Na0.12)1.99(Si0.74P0.26)1.00O4also demonstrates pseudomerohedral cyclic twinning around theaaxis, which results from pseudohexagonal topology of the crystal structure and complicates the indexing of X-ray diffraction data.
Structural elucidation of triclinic and monoclinic SFCA-III – killing two birds with one stone
Authors: Kahlenberg Volker , Krüger Hannes , Goettgens Valerie Sue
Published: November 2019

A part of the system CaO-SiO2–Al2O3–Fe2O3–MgO which is of relevance to iron-ore sintering has been studied in detail. For a bulk composition corresponding to 10.45 wt% CaO, 5.49 wt% MgO, 69.15 wt% Fe2O3, 13.37 wt% Al2O3and 1.55 wt% SiO2synthesis runs have been performed in air in the range between 1100 and 1300°C. Products have been characterized using reflected-light microscopy, electron microprobe analysis and diffraction techniques. At 1250°C, an almost phase-pure material with composition Ca2.99Mg2.67Fe3+14.58Fe2+0.77Al4.56Si0.43O36has been obtained. The compound corresponds to the first Si-containing representative of theM14+6nO20+8npolysomatic series of so-called SFCA phases (Silico-Ferrites ofCalcium andAluminum) withn= 2 and is denoted as SFCA-III. Single-crystal diffraction investigations using synchrotron radiation at the X06DA beamline of the Swiss Light Source revealed that the chemically homogenous sample contained both a triclinic and monoclinic polytype. Basic crystallographic data are as follows: triclinic form:a= 10.3279 (2) Å,b= 10.4340 (2) Å,c= 14.3794 (2) Å, α = 93.4888 (12)°, β = 107.3209 (14)° and γ = 109.6626 (14)°,V= 1370.49 (5) Å3,Z= 2, space group P{\overline 1}; monoclinic form:a= 10.3277 (2) Å,b= 27.0134 (4) Å,c= 10.4344 (2) Å, β = 109.668 (2)°,V= 2741.22 (9) Å3,Z= 4, space groupP21/n. Structure determination of both modifications was successful using diffraction data from the same allotwinned crystal. A description of the observed polytypism within the framework of OD-theory is presented. Triclinic and monoclinic SFCA-III actually correspond to the two possible maximum degree of order structures based on OD-layers containing three spinel (S) and one pyroxene (P) modules (〈S3P〉). The existence of SFCA-III in industrial iron-ore sinters has yet to be confirmed. Polytypism is likely to occur in other SFCA-members (SFCA, SFCA-I) relevant to sintering as well, but has so far been neglected in the characterization of industrial samples. Our results shed light on this phenomenon and may therefore be also helpful for better interpretation of the powder diffraction patterns that are used for phase analysis of iron-ore sinters.
Arsenic, cadmium, and lead contents of rice imported into Qatar-impact on intake
Authors: Elobeid Tahra , Ganji Vijay , Moustafa Khloud , Mohammed Fatima , El-Ouzi Loujain , Attieh Grace
Published: November 2019

Purpose

The purpose of this paper is to determine arsenic, cadmium and lead contents of rice imports and to estimate their impact on these heavy metal intakes in Qatar.

Design/methodology/approach

In total, 30 rice samples imported from various countries (Vietnam, Thailand, India, Pakistan, the USA, Australia, the UK and Lebanon) were analyzed for arsenic, cadmium and lead contents with plasma optical spectrometer. These heavy metal intakes from rice were estimated for Qatar population based on the per capita consumption of rice as per 2018 rice consumption data.

Findings

In all rice samples, mean concentrations of arsenic, cadmium and lead were 1.11 mg/kg, 19.7 µg/kg and 131.3 µg/kg, respectively. Average arsenic, cadmium and lead contents were the highest in rice imported from Thailand (1.25 mg/kg), Vietnam (30 µg/kg) and India (178.3 µg/kg), respectively. Estimated arsenic, cadmium and lead intakes through rice consumption by Qatari population were 225.7, 4 and 26.7 µg/day, respectively.

Originality/value

In all rice imports, arsenic content is approximately 5.5 times higher than the maximum allowable concentration (MAC), whereas the cadmium and lead levels are within the MAC. Because these heavy metals are linked to health, all Middle Eastern countries that import rice from Thailand, Vietnam and India should monitor the metal contents in their food supply on a regular basis.
Understanding eWOM of Chinese Governments information service: a perceived value-based perspective
Authors: Zhang Zhen , Chen Haihua , Xiao Bo
Published: November 2019

Purpose

In a people-oriented society, it is necessary to understand the electronic word of mouth (eWOM) of information service of the government. Government affair microblogs (GAM), which play an important role in orienting online opinions, listening to public voices, establishing government image, is an ideal channel to achieve this goal. In essence, the application of GAM is to improve the communication efficiency between the government and the public. The purpose of this study is to the influence factors of GAM eWOM which will not only benefits the government in better understanding the information dissemination rules of microblogs but also provides directions for the government to improve the information service over microblogs.

Design/methodology/approach

In this paper, the authors investigate and verify the regulating function, herd effect applied on GAM. The authors conduct an innovative empirical study based on perceived value theory, aiming to explore the factors that influence the eWOM of the Chinese Government.

Findings

Experiments on 502 GAM users show that social identification positively affects perceived value while effort cost negatively affects perceived value, and perceived value positively influences the microblogs’ eWOM. The authors also find that the herd effect positively regulates the relationship between perceived value and GAM’s eWOM. Theoretical and practical implications of these findings are discussed.

Originality/value

In this research, the regulating effect of herd effect on the relationship between perceived value and GAM’s eWOM has been explored. This study also provides inspirations for future government information service research and administrative measurement.
Corruption, money laundering and Nigeria’s crisis of development
Authors: Arewa Adebisi
Published: November 2019

Purpose

The purpose of this paper is to demonstrate the congruence between Nigeria’s unremitting rule of law deficit, corruption pandemic and its crisis of developmentalism. The paper proves that market failures and state failures are mutually reinforcing and are functions of systemic official corruption in the private and public sectors of the Nigerian economy.

Design/methodology/approach

This study is library-based. It relies on secondary data generated by the variegated multilateral agencies, law reports of international and municipal tribunals, relevant books, journals, monographs policy papers and so forth as the basis of analysis.

Findings

Findings suggest that Nigeria’s corruption pandemic is a derivative of its unremitting rule of law deficit and that its crisis of developmentalism is a logical function of the pervasive normlessness, very wide latitude for discretion, arbitrariness, weak institutions and lack of centrality of law and its institutions, which characterise its body politik.

Social implications

Systemic corruption in Nigeria affects the citizens’ perception of social justice and equity and undermines economic efficiency. It has also distorted the work reward causality, which has engendered a rentier social-economic order.

Originality/value

By first demonstrating the congruence between Nigeria’s rule of law deficit, corruption and economic and governance failure; the paper focusses on the total breakdown of norms in the Nigerian private and public sectors and resultant stultification of economic growth, sustainable human development and pervasive impoverishment of the citizenry.