bluuebunny/crossref_metadata_2025 huggingface dataset:
Research and data-sharing policy in Sweden – neoliberal courses, forces and discourses*
Authors: Slavnic Zoran
Published: July 2018

The discourse of openness has proved to be a very powerful instrument for promoting new research policies and the (neoliberal) reforms of higher education in all so-called ‘advanced economies’. It has triggered positive democracy-, transparency-, and accountability-related associations when used in the context of politics, fair resource distribution when used in the sphere of public service, and free access to information and knowledge when used in the field of science and higher education. At the same time, international research shows that university autonomy is increasingly being attacked, reduced, and marginalized by the same policies. Power instances outside academia impose new criteria, such as ‘accountability,’ ‘performance,’ ‘quality assurance,’ and ‘good practice.’ They also impose ideas about what good research is, which scientific method is to be prioritized, and what good data are. The process of the de-professionalization, polarization, and proletarianization of the academic profession is increasingly affecting academia. However, none of this has much in common with the open-access discourse. The purpose of this paper is to illustrate how this discussion applies to Sweden. Courses, forces, and discourses of the national research infrastructure development policy in general, and qualitative data preservation policy in particular, are described and deliberated.
Actin blobs prefigure dendrite branching sites
Authors: Nithianandam Vanitha , Chien Cheng-Ting
Published: July 2018

The actin cytoskeleton provides structural stability and adaptability to the cell. Neuronal dendrites frequently undergo morphological changes by emanating, elongating, and withdrawing branches. However, the knowledge about actin dynamics in dendrites during these processes is limited. By performing in vivo imaging of F-actin markers, we found that F-actin was highly dynamic and heterogeneously distributed in dendritic shafts with enrichment at terminal dendrites. A dynamic F-actin population that we named actin blobs propagated bidirectionally at an average velocity of 1 µm/min. Interestingly, these actin blobs stalled at sites where new dendrites would branch out in minutes. Overstabilization of F-actin by the G15S mutant abolished actin blobs and dendrite branching. We identified the F-actin–severing protein Tsr/cofilin as a regulator of dynamic actin blobs and branching activity. Hence, actin blob localization at future branching sites represents a dendrite-branching mechanism to account for highly diversified dendritic morphology.
IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria
Authors: Nakajima Akira , Vogelzang Alexis , Maruya Mikako , Miyajima Michio , Murata Megumi , Son Aoi , Kuwahara Tomomi , Tsuruyama Tatsuaki , Yamada Satoshi , Matsuura Minoru , Nakase Hiroshi , Peterson Daniel A. , Fagarasan Sidonia , Suzuki Keiichiro
Published: July 2018

Immunoglobulin A (IgA) promotes health by regulating the composition and function of gut microbiota, but the molecular requirements for such homeostatic IgA function remain unknown. We found that a heavily glycosylated monoclonal IgA recognizing ovalbumin coats Bacteroides thetaiotaomicron (B. theta), a prominent gut symbiont of the phylum Bacteroidetes. In vivo, IgA alters the expression of polysaccharide utilization loci (PUL), including a functionally uncharacterized molecular family provisionally named Mucus-Associated Functional Factor (MAFF). In both mice and humans, MAFF is detected predominantly in mucus-resident bacteria, and its expression requires the presence of complex microbiota. Expression of the MAFF system facilitates symbiosis with other members of the phylum Firmicutes and promotes protection from a chemically induced model of colitis. Our data reveal a novel mechanism by which IgA promotes symbiosis and colonic homeostasis.
Johann Gottlieb Fichte
Authors: Thomas-Fogiel Isabelle
Published: July 2018

Johann Gottlieb Fichte (b. 1762–d. 1814) is the first representative of what has been called “German idealism.” He precedes both Schelling, who was considered his disciple until their final break, and Hegel. Regarded as a disciple of Kant in 1793, Fichte nevertheless reproached him for not having succeeded in founding the content of his philosophy on an absolute principle. His primary purpose is therefore to make philosophy into a rigorous science. Fichte therefore begins to elaborate in 1794 on what he calls the “Science of Knowledge” (Wissenschaftslehre; WL). He tirelessly proposes new versions of this Science of Knowledge, insisting through the repetition of the title, on the permanence of his initial motivation: to find an absolute foundation for knowledge. The versions of Fichte’s Science of Knowledge (a dozen in total, distinguished by their date: 1794, 1801, etc.) reflect the most general and abstract level of philosophical thought. This first level of philosophy, which is the most general and abstract, is called by Fichte “first philosophy.” The second level corresponds to theoretical philosophy (or the philosophy of nature) and practical philosophy (or ethics as developed, for example, in his Systems of Ethics, in 1798). The third level represents the “particular sciences,” which study more specific and concrete fields, including subdisciplines such as biology and physics, or “natural right” (i.e., “theory of right”) and philosophy of religion. Finally, a fourth level is constituted by the so-called popular writings, aimed at a public of nonphilosophers, for example, The Vocation of Man, The Way Towards the Blessed Life, and Addresses to the German Nation. The contrast between the clear and literary language of these popular writings and the arid abstraction of the Sciences of Knowledge has often been emphasized. Fichte’s body of work seems to pose a problem of continuity for many commentators. Are the multiple versions of Science of Knowledge compatible with each other? To this question, the answer is more often than not a negative one. Fichte’s commentators divided these versions into two or, sometimes, three periods. The vast majority of interpretations assert that Fichte’s thought evolved over time. Such a change is more often expressed as the passage from a doctrine of what is finite (the subject, the “Self”) to a philosophy of absolute (God, Being). The problem of this evolution has become one of the most difficult aspect of interpreting Fichte’s thought.
Brazilian Cinema
Authors: Shaw Lisa
Published: July 2018

Studies of Brazilian cinema came to the fore in the 1960s and 1970s with the emergence of the avant-garde, politicized Cinema Novo, which dialogued with New Wave cinemas in Europe, particularly France, and in other parts of Latin America. Several landmark studies by scholars such as Ismail Xavier and Randal Johnson analyzed the movement in depth and remain key works. Since then, scholarship in both Portuguese and English has broadened its scope to embrace commercially oriented Brazilian films dating back to the early sound era, including popular genres (such as in the work of João Luiz Vieira, Stephanie Dennison, and Lisa Shaw), as well as the historical evolution of Brazilian cinema, and the relationship between the film industry and the state throughout the 20th century and into the new millennium. Most recently, various scholars in Brazil and abroad, notably Lúcia Nagib, have analyzed the nation’s cinematic output, particularly since its “rebirth” in the mid-1990s—the so-called retomada—from a thematic perspective, focusing on the reworking of themes from Cinema Novo—such as poverty and violence—in nonpoliticized, box-office hits, such as Central do Brasil (Central Station, 1998, dir. Walter Salles) and Cidade de Deus (City of God, 2002, dirs. Fernando Meirelles and Kátia Lund), or within the wider context of Latin American production. Following in the wake of the seminal work of Robert Stam, issues of race and ethnicity continue to provide a focus for studies of Brazilian cinema, as do questions of sexuality and gender. Scholars are increasingly turning their attentions to questions of the national and the transnational in post-retomada films, and are now looking at Brazilian film history from new perspectives, such as the role and significance of film stars and their marketing, as well as cinema’s relationship with other media and arts.
Katharine Hepburn
Authors: Rybin Steven
Published: July 2018

It is certainly possible to imagine as strong a person as Katharine Hepburn (b. 1907–d. 2003) existing without the classical Hollywood studio system. It is rather difficult to imagine a Hollywood without Hepburn, however, given her omnipresence on American screens for the better part of a century. Emblematic of the independence sought by many women across varying professions in the United States in the years after the ratification of the Nineteenth Amendment to the US Constitution in 1920, Hepburn’s iconic presence onscreen across seven decades of film and television effectively demarcated—and frequently transcended—culturally prevalent ideas regarding what a female performer might achieve in film in the United States. Born in 1907, Hepburn—the daughter of a suffragist mother and a doctor father—eventually chose a career in performance. Her journey began with an uneven career on the stage in the 1920s. Hepburn’s breakthrough in the theater arrived via an appearance in The Warrior’s Husband (1932) and this success led to her screen debut in George Cukor’s adaptation of the Clemence Dane stage play A Bill of Divorcement (1932; play written 1922). Hepburn would occasionally return to the stage—in her early career, and most notoriously, in the Jed Harris play The Lake, in 1933; and later, more successfully, in the stage version of The Philadelphia Story, in 1939; As You Like It, in 1950; The Millionairess, in 1952; Coco, in 1969 and 1971; A Matter of Gravity, in 1976; and The West Side Waltz, in 1981. But Hepburn was most at home in cinema, as her legendary work with many important filmmakers of the classical era—Cukor, Dorothy Arzner, Frank Capra, Howard Hawks, John Huston, David Lean, and George Stevens, among others—attests. Hepburn is that rare Hollywood star whose importance in popular culture matches her pride of place in academic film studies. She is a crucial presence in both, as numerous popular biographies and an extensive body of literature in academic writing in film studies reveals. Except for a brief section providing an overview of a few key Hepburn biographies and memoirs that will be of interest to the scholar, this bibliography focuses on discussions of Hepburn in academic scholarship.
Wearable Eye-tracking for Research: Automated dynamic gaze mapping and accuracy/precision comparisons across devices
Authors: Macinnes Jeff J. , Iqbal Shariq , Pearson John , Johnson Elizabeth N.
Published: July 2018

Wearable eye-trackers offer exciting advantages over screen-based systems, but their use in research settings has been hindered by significant analytic challenges as well as a lack of published performance measures among competing devices on the market. In this article, we address both of these limitations. We describe (and make freely available) an automated analysis pipeline for mapping gaze data from an egocentric coordinate system (i.e. the wearable eye-tracker) to a fixed reference coordinate system (i.e. a target stimulus in the environment). This pipeline allows researchers to study aggregate viewing behavior on a 2D planar target stimulus without restricting the mobility of participants. We also designed a task to directly compare calibration accuracy and precision across 3 popular models of wearable eye-trackers: Pupil Labs 120Hz Binocular glasses, SMI ETG 2 glasses, and the Tobii Pro Glasses 2. Our task encompassed multiple viewing conditions selected to approximate distances and gaze angles typical for short- to mid-range viewing experiments. This work will promote and facilitate the use of wearable eye-trackers for research in naturalistic viewing experiments.
Identification of biomarker and HPV strain for Cervical Cancer from pre-existing RNAseq data
Authors: Guo Suhan , Hao Yuhan , Brown Stuart
Published: July 2018

Human papillomavirus (HPV) increased the risk of afflicting cervical cancer. Among over a hundred strains, HPV-16 and HPV-18 caused 70% of cervical cancers and precancerous cervical lesions (WHO 2018). To reveal the profile of HPV strains, HPViewer is designed by Hao et al. (2018) for metagenomic or human genomic shotgun sequencing data analysis. The application of HPViewer in detecting HPV strains in RNA sequencing data was assessed and results were communicated in the table. The performance of HPViewer in analyzing RNA sequencing data from multiple sources, demonstrated the potential of enlarging the application of HPViewer to RNA sequencing data. Furthermore, we attempted to verify the capability of a potential biomarker p16INK4a in detecting cervical cancer from precancerous lesions. Considering the protein nature of this biomarker, the experiment was designed to detect the differentially expressed gene, associating with this protein function group, in RNA-seq data from two articles. Compare to the findings from Royse et al. (2014), confirmatory result was reproduced that comparisons between both groups yielded insignificant outcome. Since data from single article was insufficient to provide meaningful clue, final dataset was collected from multiple sources. The results were compromised by batch effect, but they supported p16INK4a to be a prospective biomarker for cervical cancer diagnosis.
Sclerostin Deficiency Alters Peripheral B Lymphocyte Responses in Mice
Authors: Chow Arthur , Mason Jourdan , Coney Larrisha , Bajwa Jamila , Carlisle Cameron , Zaslavsky Anna , Pellman Yvette , García-Ojeda Marcos E. , Economides Aris , Loots Gabriela G. , Manilay Jennifer O.
Published: July 2018

Understanding how changes in bone physiology and homeostasis affect immune responses will inform how to retain strong immunity in patients with bone disease and in aged individuals. We previously identified sclerostin (Sost) as a mediator of cell communication between the skeletal and the immune system. Elevated bone mineral density in Sost-knockout (Sost-/-) mice contributes to an altered bone marrow microenvironment and adversely affects B cell development. B cells originate from hematopoietic stem cells within the bone marrow and mature in peripheral lymphoid organs to produce antibodies in response to infection and/or vaccination. In this study, we investigated whether the aberrant B cell development observed in the bone marrow of Sost-/- mice extends to peripheral B cells in the spleen during immune challenge, and if these changes were age-dependent. Concomitant with more severe changes in bone architecture, B cell development in the bone marrow and in the spleen worsened with age in Sost-/- mice. B cell responses to T-independent antigens were enhanced in young Sost-/- mice, whereas responses to T-dependent antigens were impaired. Our results support the hypothesis that the adverse effects of B cell development in the Sost-deficient bone marrow microenvironment extends to the peripheral B cell immune response to protein antigens, and suggest that the B cell response to routine vaccinations should be monitored regularly in patients being treated with sclerostin antibody therapy. In addition, our results open the possibility that Sost regulates the T-independent B cell response, which might be applicable to the improvement of vaccines towards non-protein antigens.
Targeted Reduction of Pathogenic Heteroplasmy Through Binding of G-Quadruplex DNA
Authors: Naeem Mansur M. , Maheshan Rathena , Costford Sheila R. , Kaufman Brett A. , Sondheimer Neal
Published: July 2018

Pathogenic mitochondrial DNA (mtDNA) variants are typically heteroplasmic, with coexistence of variant and wild type genomes. Because heteroplasmy dictates phenotype, the reduction of heteroplasmy is potentially therapeutic. We identified pathogenic variants that increased the potential for formation of non-canonical G-quadruplexes (GQ) within mtDNA. The Leigh Syndrome (LS)-associated mt.10191T>C variant has a high probability of local GQ formation that was enhanced by the variant. Structural studies of mt.10191C-containing oligonucleotides confirmed the formation of GQ, and its interaction with the small molecule GQ-binding agent berberine increased GQ stability. The GQ formed at mt.10191 impeded polymerase processivity, and inhibition was enhanced by the mt.10191C variant. We applied a cyclical treatment of two GQ binding compounds, berberine or RHPS4, to primary fibroblasts from LS patients with heteroplasmic mt.10191T>C mutation. This treatment induced alternating mtDNA depletion and repopulation and was effective in shifting heteroplasmy towards the nonpathogenic allele, leading to an increase in complex I protein levels. This study demonstrates the potential for using small-molecule GQ-binding agents to induce beneficial shifts in mitochondrial heteroplasmy.
Object-based attention prioritizes working memory contents at a theta rhythm
Authors: Peters Benjamin , Kaiser Jochen , Rahm Benjamin , Bledowski Christoph
Published: July 2018

Attention selects relevant information regardless of whether it is physically present or internally stored in working memory. Perceptual research has shown that attentional selection of external information is better conceived as rhythmic prioritization than as stable allocation. Here we tested this principle using information processing of internal representations held in working memory. Participants memorized four spatial positions that formed the endpoints of two objects. One of the positions was cued for a delayed match-non-match test. When uncued positions were probed, participants responded faster to uncued positions located on the same object as the cued position than to those located on the other object, revealing object-based attention in working memory. Manipulating the interval between cue and probe at a high temporal resolution revealed that reaction times oscillated at a theta rhythm of 6 Hz. Moreover, oscillations showed an anti-phase relationship between memorized but uncued positions on the same versus other object as the cued position, suggesting that attentional prioritization fluctuated rhythmically in an object-based manner. Our results demonstrate the highly rhythmic nature of attentional selection in working memory. Moreover, the striking similarity between rhythmic attentional selection of mental representations and perceptual information suggests that attentional oscillations are a general mechanism of information processing in human cognition. These findings have important implications for current, attention-based models of working memory.
Challenges and perspectives of quantitative functional sodium imaging (fNaI)
Authors: Gandini Wheeler-Kingshott Claudia AM , Reimer Frank , Palesi Fulvia , Ricciardi Antonio , Castellazzi Gloria , Golay Xavier , Prados Ferran , Solanky Bhavana , D’Angelo Egidio U
Published: July 2018

Brain function has been investigated via the blood oxygenation level dependent (BOLD) effect using magnetic resonance imaging (MRI) for the past decades. Advances in sodium imaging offer the unique chance to access signal changes directly linked to sodium ions (23Na) flux across the cell membrane, which generates action potentials, hence signal transmission in the brain. During this process 23Na transiently accumulates in the intracellular space. Here we show that quantitative functional sodium imaging (fNaI) at 3T is potentially sensitive to 23Na concentration changes during finger tapping, which can be quantified in grey and white matter regions key to motor function. For the first time, we measured a 23Na concentration change of 0.54 mmol/l in the ipsilateral cerebellum, 0.46 mmol/l in the contralateral primary motor cortex, 0.27 mmol/l in the corpus callosum and −11 mmol/l in the ipsilateral primary motor cortex, suggesting that fNaI is sensitive to distributed functional alterations. Open issues persist on the role of the glymphatic system in maintaining 23Na homeostasis, the role of excitation and inhibition as well as volume distributions during neuronal activity. Hemodynamic and physiological signal recordings coupled to realistic models of tissue function will be critical to understand the mechanisms of such changes and contribute to meeting the overarching challenge of measuring neuronal activity in vivo.
A conserved mechanism for meiotic chromosome organization through self-assembly of a filamentous chromosome axis core
Authors: West Alan M.V. , Rosenberg Scott C. , Ur Sarah N. , Lehmer Madison K. , Ye Qiaozhen , Hagemann Götz , Caballero Iracema , Usón Isabel , Herzog Franz , Corbett Kevin D.
Published: July 2018

The meiotic chromosome axis plays key roles in meiotic chromosome organization and recombination, yet the underlying protein components of this structure are highly diverged. Here, we show that “axis core proteins” from budding yeast (Red1), mammals (SYCP2/SYCP3), and plants (ASY3/ASY4) are evolutionarily related and play equivalent roles in chromosome axis assembly. We first identify motifs in each complex that recruit meiotic HORMADs, the master regulators of meiotic recombination. We next find that axis core complexes form homotetrameric (Red1) or heterotetrameric (SYCP2:SYCP3 and ASY3:ASY4) coiled-coil assemblies that further oligomerize into micron-length filaments. Thus, the meiotic chromosome axis core in fungi, mammals, and plants shares a common molecular architecture and role in axis assembly and recombination control. We propose that the meiotic chromosome axis self-assembles through cooperative interactions between dynamic DNA loop-extruding cohesin complexes and the filamentous axis core, then serves as a platform for chromosome organization, recombination, and synaptonemal complex assembly.
Climate, habitat, and geographic range overlap drive plumage evolution
Authors: Miller Eliot T. , Leighton Gavin M. , Freeman Benjamin G. , Lees Alexander C. , Ligon Russell A.
Published: July 2018

Organismal appearances are shaped by selection from both abiotic and biotic drivers 1–5. For example, Gloger’s rule describes the pervasive pattern that more pigmented populations are found in more humid areas 1,6,7, and substrate matching as a form of camouflage to reduce predation is widespread across the tree of life 8–10. Sexual selection is a potent driver of plumage elaboration 5,11, and species may also converge on nearly identical colours and patterns in sympatry, often to avoid predation by mimicking noxious species 3,4 To date, no study has taken an integrative approach to understand how these factors determine the evolution of colour and pattern across a large clade of organisms. Here we show that both habitat and climate profoundly shape avian plumage. However, we also find a strong signal that many species exhibit remarkable convergence not explained by these factors nor by shared ancestry. Instead, this convergence is associated with geographic overlap between species, suggesting strong, albeit occasional, selection for interspecific mimicry. Consequently, both abiotic and biotic factors, including interspecific interactions, are potent drivers of phenotypic evolution.
High Genetic Potential for Proteolytic Decomposition in Northern Peatland Ecosystems
Authors: Graham Emily B. , Yang Fan , Bell Sheryl , Hofmockel Kirsten S.
Published: July 2018

Nitrogen (N) is a scarce nutrient commonly limiting primary productivity. Microbial decomposition of complex carbon (C) into small organic molecules (e.g., free amino acids) has been suggested to supplement biologically-fixed N in high latitude peatlands. We evaluated the microbial (fungal, bacterial, and archaeal) genetic potential for organic N depolymerization in peatlands at Marcell Experimental Forest (MEF) in northern Minnesota. We used guided gene assembly to examine the abundance and diversity of protease genes; and further compared to those of N-fixing (nifH) genes in shotgun metagenomic data collected across depth at two distinct peatland environments (bogs and fens). Microbial proteases greatly outnumberednifHgenes with the most abundant gene families (archaeal M1 and bacterial Trypsin) each containing more sequences than all sequences attributed tonifH. Bacterial protease gene assemblies were diverse and abundant across depth profiles, indicating a role for bacteria in releasing free amino acids from peptides through depolymerization of older organic material and contrasting the paradigm of fungal dominance in depolymerization in forest soils. Although protease gene assemblies for fungi were much less abundant overall than for bacteria, fungi were prevalent in surface samples and therefore may be vital in degrading large soil polymers from fresh plant inputs during early stage of depolymerization. In total, we demonstrate that depolymerization enzymes from a diverse suite of microorganisms, including understudied bacterial and archaeal lineages, are likely to play a substantial role in C and N cycling within northern peatlands.

Importance

Nitrogen (N) is a common limitation on primary productivity, and its source remains unresolved in northern peatlands that are vulnerable to environmental change. Decompositionof complex organic matter into free amino acids has been proposed as an important N source, but the genetic potential of microorganisms mediating this process has not been examined. Such information can elucidate possible responses of northern peatlands to environmental change. We show high genetic potential for microbial production of free amino acids across a range of microbial guilds. In particular, the abundance and diversity of bacterial genes encoding proteolytic activity suggests a predominant role for bacteria in regulating productivity and contrasts a paradigm of fungal dominance of organic N decomposition. Our results expand our current understanding of coupled carbon and nitrogen cycles in north peatlands and indicate that understudied bacterial and archaeal lineages may be central in this ecosystem’s response to environmental change.
Specific activation of HIV-1 from monocytic reservoir cells by bromodomain inhibitor in humanized mice in vivo
Authors: Li Guangming , Zhang Zheng , Reszka-Blanco Natalia , Li Feng , Chi Liqun , Ma Jianping , Jeffrey Jerry , Cheng Liang , Su Lishan
Published: July 2018

The combination antiretroviral therapy (cART) effectively suppresses HIV-1 infection and enables HIV-infected individuals to live long productive lives. However, the persistence of HIV-1 reservoir cells with latent or low-replicating HIV-1 in patients under cART make HIV-1 infection an incurable disease. Recent studies have focused on the development of strategies such as epigenetic modulators to activate and purge these reservoirs. Bromodomain inhibitors (BETi) are epigenetic modulating compounds able to activate viral transcription in HIV-1 latency cell lines in a positive transcription elongation factor b (P-TEFb)-dependent manner. Little is known about the efficacy of activating HIV-1 reservoir cells under cART by BETi in vivo. In this study, we seek to test the potential of a BETi (I-BET151) in activating HIV-1 reservoir cells under effective cART in humanized mice in vivo. We discover that I-BET151 efficiently activates HIV-1 transcription in monocytic cells, but not in CD4+T cells, during suppressive cART in vivo. We further reveal that HIV-1 proviruses in monocytic cells are more sensitive to I-BET151 treatment than in T cells in vitro. Finally, we demonstrate that I-BET151-activated viral transcription in monocytic cells is dependent on both CDK2 and CDK9, whereas only CDK9 is involved in activation of HIV-1 by I-BET151 in T cells. Our findings indicate a role of myeloid cells in HIV-1 persistence, and highlights the limitation of measuring or targeting T cell reservoirs alone in terms of HIV-1 cure, as well as provides a potential strategy to reactivate monocytic reservoirs during cART.

IMPORTANCE

It has been reported the low level of active P-TEFb critically contributes to the maintenance of HIV-1 latency or low-replication in HIV-1 reservoir cells under cART. Bromodomain inhibitors are used to activate HIV-1 replication in vitro but their effect on activation of the HIV-1 resevoirs with cART in vivo is not clear. We found that BETi (I-BET151) treatment reactivated HIV-1 gene expression in humanized mice during suppressive cART. Interestingly, I-BET151 preferentially reactivated HIV-1 gene expression in monocytic cells, but not in CD4 T cells. Furthermore, I-BET151 significantly increased HIV-1 transcription in monocytic cells, but not in latently infected CD4 T cells, via CDK2-dependent mechanisms. Our findings suggest that BETi can preferentially activate monocytic HIV-1 reservoir cells, and a combination of latency reversal agents targeting different cell types and pathways is needed to achieve reactivation of different HIV-1 reservoir cells during cART.
Examination of AustralianStreptococcus suisIsolates From Clinically Affected Pigs in a Global Context and the Genomic Characterisation of ST1 as a Predictor of Virulence
Authors: O’Dea Mark A , Laird Tanya , Abraham Rebecca , Jordan David , Lugsomya Kittitat , Fitt Laura , Gottschalk Marcello , Truswell Alec , Abraham Sam
Published: July 2018

Streptococcus suisis a major zoonotic pathogen that causes severe disease in both humans and pigs. In this study, we investigatedS. suisfrom 148 cases of clinical disease in pigs from 46 pig herds over a period of seven years. These isolates underwent whole genome sequencing, genome analysis and antimicrobial susceptibility testing. Genome sequence data of Australian isolates was compared at the core genome level to clinical isolates from overseas. Results demonstrated eight predominant multi-locus sequence types and two majorcpsgene types (cps2 and 3). At the core genome level Australian isolates clustered predominantly within one large clade consisting of isolates from the UK, Canada and North America. In particular, serotype 2 MLST25 strains were very closely associated with Canadian and North American strains. A very small proportion of Australian swine isolates (5%) were phylogenetically associated with south-east Asian and UK isolates, many of which were classified as causing systemic disease, and derived from cases of human and swine disease. In addition, we show that ST1 clones carry a constellation of putative virulence genes not present in other Australian STs, and that this is mirrored in overseas ST1 clones. Based on this dataset we provide a comprehensive outline of the currentS. suisclones associated with disease in Australian pigs and their global context, and discuss the implications this has on antimicrobial therapy, potential vaccine candidates and public health.

Importance

In this study, we examine in detail, the genomic characteristics of 148Streptococcus suisisolates from clinically diseased Australian pigs. We report the antimicrobial susceptibility profiles, virulence gene analysis and relationship to isolates from other regions of the world. We also demonstrate that ST1 clones, regardless of serotype, carry a large array of putative virulence genes while maintaining a small total gene content. This compilation of data has major ramifications for vaccine development, and refines the understanding of the distribution of various strains of this potentially-fatal zoonotic agent in the global pig industry
Fungal polysaccharopeptides reduce obesity by richness of specific microbiota and modulation of lipid metabolism
Authors: Li Xiaojun , Chen Peng , Zhang Peng , Chang Yifan , Cui Mingxu , Duan Jinyou
Published: July 2018

The prevalence of obesity and related disorders has vastly increased throughout the world and prevention of such circumstances thus represents a major challenge. Here, we show that protein-bound β-glucan (PBG), one representative of Coriolus versicolor polysaccharopeptides which are broadly used as immune boosters and clinically implicated in treatment of cancers and chronic hepatitis, could be a potent anti-obesity agent. PBG could reduce obesity and metabolic inflammation in mice fed with a high-fat diet (HFD). Gut microbiota analysis revealed that PBG markedly increased the abundance of Akkermansia muciniphila although it didn’t rescue HFD-induced change in the Firmicutes to Bacteroidetes ratio. It appeared that PBG altered host physiology and created an intestinal microenvironment favorable for A. muciniphila colonization. Fecal transplants from PBG-treated animals in part reduced obesity in recipient HFD-fed mice. Further, PBG was shown to promote lipid metabolism in microbiota-depleted mice. Thus, our data highlights that PBG might exert its anti-obesity effects through a mirobiota-dependent (richness of specific microbiota) and -independent (modulation of lipid metabolism) manner. The fact that Coriolus versicolor polysaccharopeptides are approved oral immune boosters in cancers and chronic hepatitis with well-established safety profiles may accelerate the development of PBG as a novel drug for obesity treatment.
A multiscale analysis of DNA phase separation: From atomistic to mesoscale level
Authors: Sun Tiedong , Mirzoev Alexander , Minhas Vishal , Korolev Nikolay , Lyubartsev Alexander P. , Nordenskiöld Lars
Published: July 2018

DNA condensation and phase separation is of utmost importance for DNA packing in vivo with important applications in medicine, biotechnology and polymer physics. The presence of hexagonally ordered DNA is observed in virus capsids, sperm heads and in dinoflagellates. Rigorous modelling of this process in all-atom MD simulations is presently difficult to achieve due to size and time scale limitations. We used a hierarchical approach for systematic multiscale coarse-grained (CG) simulations of DNA phase separation induced by the three-valent cobalt(III)-hexammine (CoHex3+). Solvent-mediated effective potentials for a CG model of DNA were extracted from all-atom MD simulations. Simulations of several hundred 100-bp-long CG DNA oligonucleotides in the presence of explicit CoHex3+ ions demonstrated aggregation to a liquid crystalline hexagonally ordered phase. Following further coarse-graining and extraction of effective potentials, we conducted modelling at mesoscale level. In agreement with electron microscopy observations, simulations of an 10.2-kbp-long DNA molecule showed phase separation to either a toroid or a fibre with distinct hexagonal DNA packing. The mechanism of toroid formation is analysed in detail. The approach used here is based only on the underlying all-atom force field and uses no adjustable parameters and may be generalized to modelling chromatin up to chromosome size.
Rewiring of transcription factor binding in differentiating human embryonic stem cells is constrained by DNA sequence repeat symmetry
Authors: Goldshtein Matan , Lukatsky David B.
Published: July 2018

We analyze design principles of transcription factor (TF) recognition by genomic DNA in differentiating human embryonic stem cells for 36 TFs and five histone modifications in four developmental layers, using the data recently measured by Tsankov et al. This analysis reveals that DNA sequence repeat symmetry plays a central role in defining TF-DNA binding preferences across different developmental layers. In particular, we find that different TFs bind similar symmetry patterns within a given developmental layer. While the TF cluster content undergoes modifications upon transitions between different developmental layers, most TFs possess dominant preferences for similar DNA repeat symmetry types. Histone modifications also exhibit strong preferences for similar DNA repeat symmetry patterns, with the symmetry strength differentiating between different histone modifications. Overall, our findings show that despite the enormous sequence complexity of the TF-DNA binding landscape in differentiating human embryonic stem cells, this landscape can be quantitatively characterized in simple terms, using the notion of DNA sequence repeat symmetry.
RNA-Dependent Amplification of Mammalian mRNA Encoding Extracellular Matrix Components: Identification of Chimeric RNA Intermediates for α1, β1, and γ1 Chains of Laminin
Authors: Volloch Vladimir , Rits Sophia , Olsen Bjorn
Published: July 2018

The aim of the present study was to test for the occurrence of key elements predicted by the previously postulated mammalian RNA-dependent mRNA amplification model in a tissue producing massive amounts of extracellular matrix proteins. At the core of RNA-dependent mRNA amplification, until now only described in one mammalian system, is the self-priming of an antisense strand and extension of its 3’ terminus into a sense-oriented RNA containing the protein-coding information of a conventional mRNA. The resulting product constitutes a new type of biomolecule. It is chimeric in that it contains covalently connected antisense and sense sequences in a hairpin configuration. Cleavage of this chimeric intermediate in the loop region of a hairpin structure releases mRNA which contains an antisense segment in its 5’UTR; depending on the position of self-priming, the chimeric end product may encode the entire protein or its C-terminal fragment. The occurrence of such composite chimeric molecules is unique for this type of mRNA amplification and represents a conclusive “identifier” of this process. We report here the detection, by next generation sequencing, of such chimeric junction sequences for mRNAs molecules encoding αl, β1, and γ1 chains of laminin in cells of the extracellular matrix-generating Engelbreth-Holm-Swarm (EHS) mouse tumor, best known for producing extraordinarily large amounts of “Matrigel”.
TheDrosophilachromodomain protein Kismet activates steroid hormone receptor transcription to govern axon pruning and memoryin vivo
Authors: Latcheva Nina K. , Viveiros Jennifer M. , Marenda Daniel R.
Published: July 2018

Axon pruning is critical for the proper synapse elimination required for sculpting precise neural circuits. Though axon pruning has been described in the literature for decades, relatively little is known about the molecular and cellular mechanisms that govern axon pruningin vivo. Here, we show that the epigenetic reader Kismet (Kis) binds to cisregulatory elements of the steroid hormone receptorEcdysone Receptor(EcR) gene inDrosophilaneurons. Kis is required to activateEcRtranscription at these elements and promote H3K36 di- and tri-methylation and H4K16 acetylation. We show that exogenous EcR can rescue axon pruning and memory defects associated with loss of Kis, and that the histone deacetylase inhibitor SAHA can rescue these phenotypes. EcR protein abundance is a cell-autonomous, rate-limiting step required to initiate axon pruning inDrosophila,and our data suggests that this step is under epigenetic control.

Highlights (bullet points up to 4)

The chromodomain reader Kismet activates transcription of the steroid hormone receptorEcR-B1in theDrosophilato initiate developmental axon pruning.

Kismet promotes H3K36 di- and tri-methylation and H4K16 acetylation at theEcRlocus and upstream cis-regulatory sites.

Axon pruning and memory defects associated with loss of Kismet are significantly rescued by general HDAC inhibition.
Interplay of primary sequence and RNA secondary structure in determining 5′ splice site choice
Authors: Tosto Frances Anne , Shilo Asaf , Rausch Jason W. , Le Grice Stuart F. J. , Misteli Tom
Published: July 2018

Selective use of 5′ splice sites is a common mechanism by which pre-mRNAs are alternatively spliced. Whereas the sequence requirements of 5′ splice site choice have been well characterized, other important determinants remain poorly defined. Here we apply a combination of structural mapping by SHAPE-MaP and targeted mutational analysis in a cell-based system to comprehensively probe the interplay of primary sequence, secondary RNA structure, regulatory elements and linear splice site position to determine mechanisms of splice site choice in vivo. Using the disease-causing alternative 5′ splice site selection in LMNA in the premature aging disorder Hutchinson-Gilford Progeria Syndrome as a model system, we identify RNA secondary structural elements near the alternative 5′ splice sites. We show that splice site choice is significantly influenced by the structural context of the available splice sites. While local structure alone is not sufficient to account for splice site selection, the choice of 5′ splice sites depends on the structural stability of the 5′ splice site region which is conferred by downstream elements. In addition, relative positioning of the competing sites within the primary sequence of the pre-mRNA is a predictor of 5′ splice site usage, with the distal position favored over the proximal, regardless of sequence composition. Together, these results reveal an intricate interplay amongst RNA sequence, secondary structure and splice site position in determining 5′ splice site choice.
Temporal and spatial variation in distribution of fish environmental DNA in England’s largest lake
Authors: Handley Lori Lawson , Read Daniel S. , Winfield Ian J. , Kimbell Helen , Johnson Harriet , Li Jianlong , Hahn Christoph , Blackman Rosetta , Wilcox Rose , Donnelly Rob , Szitenberg Amir , Hänfling Bernd
Published: July 2018

Environmental DNA offers great potential as a biodiversity monitoring tool. Previous work has demonstrated that eDNA metabarcoding provides reliable information for lake fish monitoring, but important questions remain about temporal and spatial repeatability, which is critical for understanding the ecology of eDNA and developing effective sampling strategies. Here, we carried out comprehensive spatial sampling of England’s largest lake, Windermere, during summer and winter to 1) examine repeatability of the method, 2) compare eDNA results with contemporary gill-net survey data, 3) test the hypothesis of greater spatial structure of eDNA in summer compared to winter due to differences in water mixing between seasons, and 4) compare the effectiveness of shore and offshore sampling for species detection. We find broad consistency between results from three sampling events in terms of species detection and abundance, with eDNA detecting more species than established methods and being significantly correlated to rank abundance determined by long-term data. As predicted, spatial structure was much greater in the summer, reflecting less mixing of eDNA than in the winter. For example Arctic charr, a deep-water species, was only detected in deep, mid-lake samples in the summer, while littoral or benthic species such as minnow and stickleback were more frequently detected in shore samples. By contrast in winter, the eDNA of these species was more uniformly distributed. This has important implications for design of sampling campaigns, for example, deep-water species could be missed and littoral/benthic species overrepresented by focusing exclusively on shoreline samples collected in the summer.
Evaluation of the antifibrotic potency by knocking down SPARC, CCR2 and SMAD3
Authors: Ding Weifeng , Pu Weilin , Jiang Shuai , Ma Yanyun , Liu Qingmei , Wu Wenyu , Chu Haiyan , Zou Hejian , Jin Li , Wang Jiucun , Zhou Xiaodong
Published: July 2018

The genes of SPARC, CCR2, and SMAD3 are implicated in orchestrating inflammation and fibrosis in scleroderma and other fibrotic disorders. Aim of the studies was to examine synergistic effect of inhibition of these genes in treating fibrosis. The peptide nanoparticles were used to deliver the siRNAs in bleomycin-induced fibrotic mice. Triple combination of siRNAs targeting on Sparc, Ccr2 and Smad3 achieved favorable anti-inflammatory and anti-fibrotic effects. Inhibition of inflammation was evidenced by reduced inflammatory cells and proinflammatory cytokines in the BALF and/or the tissues. Activation of fibroblasts was suppressed in mouse tissues in which α-Sma and collagens were significantly reduced. Aberrant expression of the genes in fibroblasts, monocytes/macrophage, endothelial and epithelial cells were reinstalled after the treatment. In addition, transcriptome profiles indicated that some bleomycin-induced alterations of multiple biological pathways were recovered to varying degrees by the treatment. The results indicated that the triple combination of siRNAs systemically reinstated multiple biopathways, probably through controlling on different cell types including fibroblasts, monocytes/macrophages, endothelial cells and others. The multi-target-combined therapeutic approach examined herein may represent a novel and effective therapy for fibrosis.
A two-dimensional cadmium(II) coordination polymer constructed from 4-carboxy-1-(4-carboxylatobenzyl)-2-propyl-1H-imidazole-5-carboxylate and 1-(4-carboxylatobenzyl)-2-propyl-1H-imidazole-4-carboxylate ligands
Authors: Li Fenfang , Zhu Miaoli , Lu Liping
Published: July 2018

Crystals of poly[[aqua[μ3-4-carboxy-1-(4-carboxylatobenzyl)-2-propyl-1H-imidazole-5-carboxylato-κ5
O
1
O
1′:N
3,O
4:O
5][μ4-1-(4-carboxylatobenzyl)-2-propyl-1H-imidazole-4-carboxylato-κ7
N
3,O
4:O
4,O
4′:O
1,O
1′:O
1]cadmium(II)] monohydrate], {[Cd2(C15H14N2O4)(C16H14N2O6)(H2O)]·H2O}
n
or {[Cd2(Hcpimda)(cpima)(H2O)]·H2O}
n
, (I), were obtained from 1-(4-carboxybenzyl)-2-propyl-1H-imidazole-4,5-dicarboxylic acid (H3cpimda) and cadmium(II) chloride under hydrothermal conditions. The structure indicates that in-situ decarboxylation of H3cpimda occurred during the synthesis process. The asymmetric unit consists of two Cd2+ centres, one 4-carboxy-1-(4-carboxylatobenzyl)-2-propyl-1H-imidazole-5-carboxylate (Hcpimda2−) anion, one 1-(4-carboxylatobenzyl)-2-propyl-1H-imidazole-4-carboxylate (cpima2−) anion, one coordinated water molecule and one lattice water molecule. One Cd2+ centre, i.e. Cd1, is hexacoordinated and displays a slightly distorted octahedral CdN2O4 geometry. The other Cd centre, i.e. Cd2, is coordinated by seven O atoms originating from one Hcpimda2− ligand and three cpima2− ligands. This Cd2+ centre can be described as having a distorted capped octahedral coordination geometry. Two carboxylate groups of the benzoate moieties of two cpima2− ligands bridge between Cd2 centres to generate [Cd2O2] units, which are further linked by two cpima2− ligands to produce one-dimensional (1D) infinite chains based around large 26-membered rings. Meanwhile, adjacent Cd1 centres are linked by Hcpimda2− ligands to generate 1D zigzag chains. The two types of chains are linked through a μ2-η2 bidentate bridging mode from an O atom of an imidazole carboxylate unit of cpima2− to give a two-dimensional (2D) coordination polymer. The simplified 2D net structure can be described as a 3,6-coordinated net which has a (43)2(46.66.83) topology. Furthermore, the FT–IR spectroscopic properties, photoluminescence properties, powder X-ray diffraction (PXRD) pattern and thermogravimetric behaviour of the polymer have been investigated.