bluuebunny/crossref_metadata_2025 huggingface dataset:
Low rate of follow-up colonoscopy after positive results of colorectal cancer screening in a Chinese urban core district
Authors: Guo Yawen , Jiang Qingwu , Tanimoto Tetsuya , Kami Masahiro , Peng Peng , He Yongpin , Yang Xiaoming , Zhang Xin , Gao Wenjun , Wang Yanming , Chu Xiaoting , Wang Yunhui , Kato Shigeaki , Ding Xiaocao
Published: August 2019

Colorectal cancer (CRC) is one of the most common cancers in China. In 2003, a systematic CRC registry that enables the determination of CRC incidence and mortality and a CRC screening project were introduced in the Jing’an district of Shanghai by the municipal government. This study assessed the registry data to determine the status of CRC and CRC screening rates in the core district of an urban area of China. Data were retrieved from the Official registry information systems of Jing’an district Shanghai Cance. The incidence and mortality of CRC, as well as population-based CRC screening rates, were analysed. Individuals who screened positive for CRC based upon results of a high-risk factor questionnaire (HRFQ) and a faecal immunochemical test (FIT) were selected for follow-up colonoscopy (CSPY). From the registry data collected between 2003 and 2013, the standardized incidence rate was 26.44/105, with a significant gender difference. The CRC standardized mortality rate was 10.08/105. In 2013, 17,866 individuals (21.6%) enrolled for CRC screening among the 82,602 candidate residents. The positive screening rate was 16.28% (2909/17866). Among the 2909 positives, 508 (17.5%) underwent follow-up CSPY. In 41.3% of these individuals (210/508), abnormal lesions were detected. Of these, 8 (1.57%) lesions were diagnosed as CRC, and 142 (28.0%) were identified as precancerous lesions. During the assessment period, both the incidence and mortality of CRC in the Jing’an district were determined in the area of high CRC prevalence in Chin. Nevertheless, the rate of participation in CRC screening was low (21.6%), and the rate of participation in follow-up CSPY for individuals who screened positive was only 17.5%. Improved participation in CRC screening and follow-up CSPY is expected to lower the incidence and mortality of CRC significantly in the rural areas of China. (288)
Epicuticular wax lipid composition of endemic European Betula species and its application to chemotaxonomy and paleobotany
Authors: Weber J. , Schwark L.
Published: August 2019

Plants, in particular trees with specific habitat demands are excellent indicators of climate state. Vegetation successions in subrecent and deep geologic time is recorded in fossil macro-remains or pollen accumulating in geological archives like limnic and marine sediments, peat bogs and mires. Birch trees in Europe form a major part in plant successions and constitute the dwarf species Betula nana and Betula humilis representing cold-adapted habitats or climates and two tree birches, Betula pubescens and Betula pendula characteristic for temperate habitats or climates. These birch species exhibit highly similar pollen shape and size, preventing their unambiguous application as paleoclimate/paleovegetation proxies. We here present a chemotaxonomic differentiation of the four European birch species based on their epicuticular wax lipids. The dominating lipid classes in epicuticular birch waxes were found to be n-alkanes (in the range of n-C23 to n-C33), straight-chain primary alcohols and fatty acids (in the range of n-C20 to n-C32), and long-chain wax ester (in the range of n-C38 to n-C46) in variable amounts and distributions. When preserved in geological archives these lipids may serve in paleovegetation/paleoclimate reconstruction. Long-chain wax esters are susceptible to hydrolysis and upon diagenesis the release of ester-bound alcohols and fatty acids may modify the distribution pattern of the corresponding primary free lipids. Quantitative analysis of the hydrolyzable wax ester proportion revealed primary distribution patterns of birch lipids not to change substantially upon release of bound analogues. The specific composition and abundance of epicuticular wax lipids facilitates unambiguous chemotaxonomic separation of the four European birch species. Wax lipid-based discrimination in field application, however, is complicated by mixing of alkyl lipids derived from different birch species and contribution of wax lipids from other plants. In cases, where palynology indicates a high contribution of Betula species to European vegetation associations, wax lipids may serve for differentiation of the species contributing.
Study on thermal insulation of diagonal-braced wood frame wall
Authors: Liu Mingbin , Lu Feng , Yang Xiaolin , Ruyuan Yang
Published: August 2019

This preprint has been removed because it was erroneously supplied by a journal.
Gains through selection for grain yield in a winter wheat breeding program
Authors: Lozada Dennis N. , Carter Arron H.
Published: August 2019

Increased genetic gains for complex traits in plant breeding programs can be achieved through different selection strategies. The objective of this study was to compare potential gains for grain yield in a winter wheat breeding program through estimating response to selectionRvalues across several selection approaches including phenotypic (PS), marker-based (MS), genomic (GS), and a combination of PS and GS. Five populations of Washington State University (WSU) winter wheat breeding lines evaluated from 2015 to 2018 in Lind and Pullman, WA, USA were used in the study. Selection was conducted by selecting the top 20% of lines based on observed yield (PS strategy), genomic estimated breeding values (GS), presence of yield “enhancing” alleles of the most significant single nucleotide polymorphism (SNP) markers identified from genome-wide association mapping (MS), and high observed yield and estimated breeding values (PS+GS). Overall, PS compared to other individual strategies showed the highest response. However, when combined with GS, a 23% improvement inRfor yield was observed, indicating that gains could be improved by complementing traditional PS with GS. Using GS alone as a selection strategy for grain yield should be taken with caution. MS was not that successful in terms ofRrelative to the other selection approaches. Altogether, we demonstrated that gains through increased response to selection for yield could be achieved in the WSU winter wheat breeding program by implementing different selection strategies either exclusively or in combination.
Pollen morphology of Polish species from the genusRubusL. (Rosaceae) and its systematic importance
Authors: Lechowicz Kacper , Wrońska-Pilarek Dorota , Bocianowski Jan , Maliński Tomasz
Published: August 2019

The genusRubusL. (Rosaceae) has as yet not been investigated satisfactorily in terms of palynology. This genus is taxonomically very difficult due to the large number of species and problems with their delimitation, as well as very different distribution areas of particular species. The aim of this study was to investigate pollen morphology and for the first time the ranges of intrageneric and interspecific variability ofRubusspecies, as well as verify the taxonomic usefulness of these traits in distinguishing studied taxa from this genus. They were analysed for 11 quantitative pollen characteristics and the following qualitative ones: exine ornamentation, pollen outline and shape, as well as bridge structure. Analyses were conducted on a total of 1740 pollen grains, which represent 58 blackberry species belonging to a majority of subgenera and all the sections and series found in Poland. The diagnostic characters included exine ornamentation (exine ornamentation type, width and direction of grooves and striae, number and diameter of perforations) and length of the polar axis (P). The arrangement of the examined species on the dendrogram does not corroborate division of the genusRubusinto subgenera, sections and series currently adopted in taxonomy. The lack of dependence may result from apomixis observed inRubus, which could reduce natural variability. Pollen features should be treated in taxonomy as auxiliary, because they fail to differentiate several (10) individual species, while the other ones create groups with similar pollen traits.
MINFLUX nanoscopy delivers multicolor nanometer 3D-resolution in (living) cells
Authors: Gwosch Klaus C. , Pape Jasmin K. , Balzarotti Francisco , Hoess Philipp , Ellenberg Jan , Ries Jonas , Hell Stefan W.
Published: August 2019

The ultimate goal of biological superresolution fluorescence microscopy is to provide three-dimensional resolution at the size scale of a fluorescent marker. Here, we show that, by localizing individual switchable fluorophores with a probing doughnut-shaped excitation beam, MINFLUX nanoscopy provides 1–3 nanometer resolution in fixed and living cells. This progress has been facilitated by approaching each fluorophore iteratively with the probing doughnut minimum, making the resolution essentially uniform and isotropic over scalable fields of view. MINFLUX imaging of nuclear pore complexes of a mammalian cell shows that this true nanometer scale resolution is obtained in three dimensions and in two color channels. Relying on fewer detected photons than popular camera-based localization, MINFLUX nanoscopy is poised to open a new chapter in the imaging of protein complexes and distributions in fixed and living cells.
Engineered Living Materials based on Adhesin-mediated Trapping of Programmable Cells
Authors: Guo Shuaiqi , Dubuc Emilien , Rave Yahav , Verhagen Mick P.A. , Twisk Simone A.E. , van der Hek Tim , Oerlemans Guido J.M. , van den Oetelaar Maxime C.M. , van Hazendonk Laura S. , Brüls Mariska , Eijkens Bruno V. , Joostens Pim L. , Keij Sander R. , Xing Weizhou , Nijs Martijn , Stalpers Jetske , Sharma Manoj , Gerth Marieke , Boonen Roy J.E.A. , Verduin Kees , Merkx Maarten , Voets Ilja K. , de Greef Tom F.A.
Published: August 2019

Engineered living materials have the potential for wide-ranging applications such as biosensing and treatment of diseases. Programmable cells provide the functional basis for living materials, however, their release into the environment raises numerous biosafety concerns. Current designs that limit the release of genetically engineered cells typically involve the fabrication of multi-layer hybrid materials with sub-micron porous matrices. Nevertheless the stringent physical barriers limit the diffusion of macromolecules and therefore the repertoire of molecules available for actuation in response to communication signals between cells and their environment. Here, we engineer a first-of-its-kind living material entitled ‘Platform for Adhesin-mediated Trapping of Cells in Hydrogels’ (PATCH). This technology is based on engineered E. coli that displays an adhesion protein derived from an Antarctic bacterium with high affinity for glucose. The adhesin stably anchors E. coli in dextran-based hydrogels with large pore diameters (10-100 μm) and reduces the leakage of bacteria into the environment by up to 100-fold. As an application of PATCH, we engineered E. coli to secrete lysostaphin via the Type 1 Secretion System and demonstrated that living materials containing this E. coli inhibit the growth of S. aureus, including the strain resistant to methicillin (MRSA). Our tunable platform allows stable integration of programmable cells in dextran-based hydrogels without compromising free diffusion of macromolecules and could have potential applications in biotechnology and biomedicine.
Proof-of-concept for the detection of early osteoarthritis pathology by endomicroscopy
Authors: Tschaikowsky Mathäus , Brander Sofia , Balzer Bizan N. , Rolauffs Bernd , Hugel Thorsten
Published: August 2019

Osteoarthritis (OA) is a degenerative joint disease and the leading cause of global disability. Clinical trials to date have been unable to pinpoint early and potentially reversible disease states with current clinical technology and hence disease-modifying OA drug candidates cannot be tested early in the disease. To overcome this obstacle, we correlate articular cartilage stiffness changes and cellular spatial organization. The former is a well-understood and functionally relevant OA pathology, while the latter allows discriminating between healthy vs early OA, based on distinct cellular spatial patterns. We demonstrated that an extensive loss of atomic force microscopy-detected stiffness can be seen in cartilage tissues with spatial patterns exhibiting the earliest identifiable OA. In addition, the translation of commercially available clinically usable probe-based confocal laser-endomicroscopy allows us to detect these early OA spatial patterns. This study resolves a major clinical trial obstacle by presenting the proof-of-concept that early OA pathology can be detected by already available clinical technology.

One Sentence Summary

We report a correlation between articular cartilage surface nanoscale stiffness and chondrocyte spatial organization; using this correlation enables early pathology detection by currently available clinical optical methods.
Dysfunction of Torr causes a Harlequin-type ichthyosis-like phenotype in Drosophila melanogaster
Authors: Wang Y , Norum M , Oehl K , Yang Y , Zuber R , Yang J , Farine JP , Gehring N , Flötenmeyer M , Ferveur J.-F , Moussian B
Published: August 2019

Prevention of desiccation is a constant challenge for terrestrial organisms. Land insects have an extracellular coat, the cuticle, that plays a major role in protection against exaggerated water loss. Here, we report that the ABC transporter Torr - a human ABCA12 paralog - contributes to the waterproof barrier function of the cuticle in the fruit fly Drosophila melanogaster. We show that the reduction or elimination of Torr function provokes rapid desiccation. Torr is also involved in defining the inward barrier against xenobiotics penetration. Consistently, the amounts of cuticular hydrocarbons that are involved in cuticle impermeability decrease markedly when Torr activity is reduced. GFP-tagged Torr localises to membrane nano-protrusions within the cuticle, likely pore canals. This suggests that Torr is mediating the transport of cuticular hydrocarbons (CHC) through the pore canals to the cuticle surface. The envelope, which is the outermost cuticle layer constituting the main barrier, is unaffected in torr mutant larvae. This contrasts with the function of Snu, another ABC transporter needed for the construction of the cuticular inward and outward barriers, that nevertheless is implicated in CHC deposition. Hence, Torr and Snu have overlapping and independent roles to establish cuticular resistance against transpiration and xenobiotic penetration. The torr deficient phenotype parallels the phenotype of Harlequin ichthyosis caused by mutations in the human abca12 gene. Thus, it seems that the cellular and molecular mechanisms of lipid barrier assembly in the skin are conserved in vertebrates in invertebrates.

Author Summary

As in humans, lipids on the surface of the skin of insects protect the organism against excessive water loss and penetration of potentially harmful substances. During evolution, a greasy surface was indeed an essential trait for adaptation to life outside a watery environment. Here, we show that the membrane-gate transporter Torr is needed for the deposition of barrier lipids on the skin surface in the fruit fly Drosophila melanogaster through extracellular nano-tubes, called pore canals. In principle, the involvement of Torr parallels the scenario in humans, where the membrane-gate transporter ABCA12 is implicated in the construction of the lipid-based stratum corneum of the skin. In both cases, mutations in the genes coding for the respective transporter cause rapid water-loss and are lethal soon after birth. We conclude that the interaction between the organism and the environment obviously implies an analogous mechanism of barrier formation and function in vertebrates and invertebrates.
Fascin regulates protrusions and delamination to mediate invasive, collective cell migrationin vivo
Authors: Lamb Maureen C. , Anliker Kelsey K. , Tootle Tina L.
Published: August 2019

Fascin is an actin bundling protein that is essential for developmental cell migrations and promotes cancer metastasis. In addition to bundling actin, Fascin has several actin-independent roles. Border cell migration duringDrosophilaoogenesis provides an excellent model to study Fascin’s various roles during invasive, collective cell migration. Border cell migration requires Fascin. Fascin functions not only within the migrating border cells, but also within the nurse cells, the substrate for this migration. Loss of Fascin results in increased, shorter and mislocalized protrusions during migration. Data supports the model that Fascin promotes the activity of Enabled, an actin elongating factor, to regulate migration. Additionally, loss of Fascin inhibits border cell delamination. These defects are partially due to altered E-cadherin localization in the border cells; this is predicted to be an actin-independent role of Fascin. Overall, Fascin is essential for multiple aspects of this invasive, collective cell migration, and functions in both actin-dependent and -independent manners. These findings have implications beyondDrosophila, as border cell migration has emerged as a model to study mechanisms mediating cancer metastasis.
DUX4-induced bidirectional HSATII satellite repeat transcripts form intranuclear double stranded RNA foci in human cell models of FSHD
Authors: Shadle Sean C. , Bennett Sean R. , Wong Chao-Jen , Karreman Nancy A. , Campbell Amy E. , van der Maarel Silvère M. , Bass Brenda L. , Tapscott Stephen J.
Published: August 2019

The DUX4 transcription factor is normally expressed in the cleavage stage embryo and regulates genes involved in embryonic genome activation. Mis-expression of DUX4 in skeletal muscle, however, is toxic and causes facioscapulohumeral muscular dystrophy (FSHD). We recently showed DUX4-induced toxicity is due, in part, to the activation of the double-stranded RNA (dsRNA) response pathway and the accumulation of intranuclear dsRNA foci. Here, we determined the composition of DUX4-induced dsRNAs. We found that a subset of DUX4-induced dsRNAs originate from inverted Alu repeats embedded within the introns of DUX4-induced transcripts and from DUX4-induced dsRNA-forming intergenic transcripts enriched for endogenous retroviruses, Alu and LINE-1 elements. However, these repeat classes were also represented in dsRNAs from cells not expressing DUX4. In contrast, pericentric human satellite II (HSATII) repeats formed a class of dsRNA specific to the DUX4 expressing cells. Further investigation revealed that DUX4 can initiate the bidirectional transcription of normally heterochromatin-silenced HSATII repeats. DUX4 induced HSATII RNAs co-localized with DUX4-induced nuclear dsRNA foci and with intranuclear aggregation of EIF4A3 and ADAR1. Finally, gapmer-mediated knockdown of HSATII transcripts depleted DUX4-induced intranuclear ribonucleoprotein aggregates and decreased DUX4-induced cell death, suggesting that HSATII formed dsRNAs contribute to DUX4 toxicity.
Local human movement patterns and land use impact exposure to zoonotic malaria in Malaysian Borneo
Authors: Fornace Kimberly M , Alexander Neal , Abidin Tommy R , Brock Paddy M , Chua Tock H , Vythilingam Indra , Ferguson Heather M. , Manin Benny O. , Wong Meng L. , Ng Sui Hann , Cox Jon , Drakeley Chris J
Published: August 2019

Human movement into insect vector and wildlife reservoir habitats determines zoonotic disease risks; however, few data are available to quantify the impact of land use on pathogen transmission. Here, we utilise GPS tracking devices and novel applications of ecological methods to develop fine-scale models of human space use relative to land cover to assess exposure to the zoonotic malaria Plasmodium knowlesi in Malaysian Borneo. Combining data with spatially explicit models of mosquito biting rates, we demonstrate the role of individual heterogeneities in local space use in disease exposure. At a community level, our data indicate that areas close to both secondary forest and houses have the highest probability of human P. knowlesi exposure, providing quantitative evidence for the importance of ecotones. Despite higher biting rates in forests, incorporating human movement space use into exposure estimates illustrates the importance of intensified interactions between pathogens, insect vectors and people around habitat edges.
The orphan nuclear receptor estrogen-related receptor beta (ERRβ) in triple-negative breast cancer
Authors: Fernandez Aileen I. , Geng Xue , Chaldekas Krysta , Harris Brent , Duttargi Anju , Berry V. Layne , Berry Deborah L. , Mahajan Akanksha , Cavalli Luciane R. , Gyorffy Balázs , Tan Ming , Riggins Rebecca B.
Published: August 2019

Purpose

Triple negative breast cancer (TNBC)/ basal-like breast cancer (BLBC) is a highly aggressive form of breast cancer prevalent in African-American (AA) women. We previously reported that a small molecule agonist ligand for the orphan nuclear receptor estrogen-related receptor beta (ERRβ orESRRB) has growth inhibitory and anti-mitotic activity in TNBC cell lines. In this study, we evaluate the association ofESRRBmRNA, copy number levels, and protein expression with demographic, clinicopathological, and gene expression features in breast tumor clinical specimens.

Methods

ESRRBmRNA level expression and clinical associations were analyzed using RNAseq data. Array-based comparative genomic hybridization determinedESRRBcopy number in AA and Caucasian women. Transcription factor activity was measured using promoter-reporter luciferase assays in TNBC cell lines. Semi-automatic quantification of immunohistochemistry measured ERRβ protein expression on a 150-patient tissue microarray series.

Results

ESRRBmRNA expression is significantly lower in TNBC/BLBC vs. other breast cancer subtypes. There is no evidence ofESRRBcopy number loss.ESRRBmRNA expression is correlated with the expression of genes associated with neuroactive ligand-receptor interaction, metabolic pathways, and deafness. These genes contain G/C-rich transcription factor binding motifs. TheESRRBmessage is alternatively spliced into three isoforms, which we show have different transcription factor activity in basal-like vs. other TNBC cell lines. We further show that the ERRβ2 and ERRβsf isoforms are broadly expressed in breast tumors at the protein level.

Conclusions

DecreasedESRRBmRNA expression, and distinct patterns of ERRβ isoform subcellular localization and transcription factor activity are key features in TNBC/BLBC.
Chromosome 17: neXt-MP50 C-HPP Challenge Completed
Authors: Zhang Hongjiu , Siddiqui Omer , Guan Yuanfang , Omenn Gilbert S.
Published: August 2019

The C-HPP Team for Chromosome 17 has documented meeting the neXt-MP50 Missing Protein Challenge. Protein-level PE1 evidence including MS and protein-protein interaction data from the global proteomics community has reduced the number of PE2,3,4 proteins coded on Chromosome 17 by 50 since the 2016 baseline in neXtProt. As a follow-up to our analysis and prioritization of Chr 17 missing proteins last year, we describe what predictions and guidance were successful in this update and we explain the dynamics of a net reduction of PE2,3,4 Missing Proteins. This analysis can serve as a guide for other C-HPP chromosome teams seeking high-quality evidence for the 2129 remaining missing proteins.
Auxin-induced nanoclustering of membrane signaling complexes underlies cell polarity establishment in Arabidopsis
Authors: Pan Xue , Fang Linjing , Liu Jianfeng , Senay-Aras Betul , Lin Wenwei , Zheng Shuan , Zhang Tong , Manor Uri , Chen Weitao , Yang Zhenbiao
Published: August 2019

Cell polarity is fundamental to the development of both eukaryotic and prokaryotic organisms, yet the mechanism of its establishment remains poorly understood. Here we show that signal-activated nanoclustering of membrane proteins and a cytoskeleton-based feedback loop provide an important mechanism for the establishment of cell polarity. The phytohormone auxin promoted sterol-dependent nanoclustering of cell surface transmembrane receptor-like kinase 1 (TMK1) to initiate cell polarity during the morphogenesis of Arabidopsis puzzle piece-shaped leaf pavement cells (PC). Auxin-triggered nanoclustering of TMK1 stabilized flotillin-associated ordered nanodomains, which were essential for auxin-mediated formation of ROP6 GTPase nanoclusters that act downstream TMK1 to promote cortical microtubule ordering. Mathematical modeling further demonstrated the essential role of this auxin-mediated stabilization of TMK1 and ROP6 nanoclusters, and predicted the additional requirement of ROP6-dependent cortical microtubules for further stabilization of TMK1-sterol nanodomains and the polarization of PC. This prediction was experimentally validated by genetic and biochemical data. Our studies reveal a new paradigm for polarity establishment: A diffusive signal triggers cell polarization by activating cell surface receptor-mediated lateral segregation of signaling components and a cytoskeleton-mediated positive feedback loop of nanodomain stabilization.

Highlights

Sterols are required for cell polarity in Arabidopsis leaf epidermal cells

Auxin promotes lipid ordering and polar distribution of ordered lipid nanodomains at the plasma membrane (PM)

Auxin stabilizes sterol-dependent nanoclustering of transmembrane kinase (TMK1), a PM auxin signal transducer

Auxin-induced TMK1 nanoclustering is required but insufficient for cell polarization

Microtubule-based feedback stabilization of the auxin-induced TMK1 nanodomains can generate cell polarity
Integrating untargeted metabolomics, genetically informed causal inference, and pathway enrichment to define the obesity metabolome
Authors: Hsu Yu-Han H. , Astley Christina M. , Cole Joanne B. , Vedantam Sailaja , Mercader Josep M. , Metspalu Andres , Fischer Krista , Fortney Kristen , Morgen Eric K. , Gonzalez Clicerio , Gonzalez Maria E. , Esko Tonu , Hirschhorn Joel N.
Published: August 2019

Background

Obesity and its associated diseases are major health problems characterized by extensive metabolic disturbances. Understanding the causal connections between these phenotypes and variation in metabolite levels can uncover relevant biology and inform novel intervention strategies. Recent studies have combined metabolite profiling with genetic instrumental variable (IV) analyses to infer the direction of causality between metabolites and obesity, but often omitted a large portion of untargeted profiling data consisting of unknown, unidentified metabolite signals.

Methods

We expanded upon previous research by identifying body mass index (BMI)-associated metabolites in multiple untargeted metabolomics datasets, and then performing bidirectional IV analysis to classify these metabolites based on their inferred causal relationships with BMI. Meta-analysis and pathway analysis of both known and unknown metabolites across datasets were enabled by our recently developed bioinformatics suite, PAIRUP-MS.

Results

We identified 10 known metabolites that are more likely to be the causes (e.g. alpha-hydroxybutyrate) or effects (e.g. valine) of BMI, or may have more complex bidirectional cause-effect relationships with BMI (e.g. glycine). Importantly, we also identified about 5 times more unknown than known metabolites in each of these three categories. Pathway analysis incorporating both known and unknown metabolites prioritized 40 enriched (p < 0.05) metabolite sets for the cause versus effect groups, providing further support that these two metabolite groups are linked to obesity via distinct biological mechanisms.

Conclusions

These findings demonstrate the potential utility of our approach to uncover causal connections with obesity from untargeted metabolomics datasets. Combining genetically informed causal inference with the ability to map unknown metabolites across datasets provides a path to jointly analyze many untargeted datasets with obesity or other phenotypes. This approach, applied to larger datasets with genotype and untargeted metabolite data, should generate sufficient power for robust discovery and replication of causal biological connections between metabolites and various human diseases.
Description of a new member of the family Erysipelotrichaceae: Clostridium fusiformis sp. nov., isolated from healthy human feces
Authors: Ghimire Sudeep , Wongkuna Supapit , Scaria Joy
Published: August 2019

A Gram-positive, non-motile, rod-shaped facultative anaerobic bacterial strain SG502T was isolated from the healthy human fecal samples in Brookings, SD, USA. The comparison of the 16S rRNA gene placed the strain within the Clostridium cluster XVI, where, Clostridium innocuum ATCC 14501T, Longicatena caecimuris strain PG-426-CC-2, Eubacterium dolichum DSM 3991T and Eubacterium tortuosum DSM 3987T were its closest taxa with 95.15%, 94.49%, 93.28%, and 93.20% sequence identities respectively. The optimal growth temperature and pH for the strain SG502T were 37°C and 7.0 respectively. Acetate was the major short-chain fatty acid product of the strain SG502T when grown in BHI-M medium. The major cellular fatty acids produced by the strain SG502T were C18:1 ω9c, C18:0 and C16:0. The DNA G+C content of the strain was 34.34 mol%. The average nucleotide identity of the genome of the strain SG502T and its closest neighbor C. innocuum ATCC 14501T was 63.48%. Based on the polyphasic analysis, the type strain SG502T (=DSM 107282T), represents a novel species of the genus Clostridium for which the name Clostridium fusiformis sp. nov. is proposed.
Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations
Authors: Bengtsen Tone , Holm Viktor L. , Kjølbye Lisbeth Ravnkilde , Midtgaard Søren R. , Johansen Nicolai Tidemand , Tesei Giulio , Bottaro Sandro , Schiøtt Birgit , Arleth Lise , Lindorff-Larsen Kresten
Published: August 2019

Nanodiscs are membrane mimetics that consist of a protein belt surrounding a lipid bilayer, and are broadly used for characterization of membrane proteins. Here, we investigate the structure, dynamics and biophysical properties of two small nanodiscs, MSP1D1ΔH5 and ΔH4H5. We combine our SAXS and SANS experiments with molecular dynamics simulations and previously obtained NMR and EPR data to derive and validate a conformational ensemble that represents the structure and dynamics of the nanodisc. We find that it displays conformational heterogeneity with various elliptical shapes, and with substantial differences in lipid ordering in the centre and rim of the discs. Together, our results reconcile previous apparently con2icting observations about the shape of nanodiscs, and paves the way for future integrative studies of larger complex systems such as membrane proteins embedded in nanodiscs.
Single Cell Analysis Reveals Multiple Requirements for Zinc in the Mammalian Cell Cycle
Authors: Lo Maria N. , Damon Leah J. , Tay Jian Wei , Palmer Amy E.
Published: August 2019

Despite recognition of the fundamental role of zinc (Zn2+) for growth and proliferation, mechanisms of how Zn2+deficiency arrests these processes remain enigmatic. We induced subtle intracellular Zn2+perturbations and tracked asynchronously cycling cells throughout division using fluorescent reporters, high throughput microscopy, and quantitative analysis. We found that Zn2+deficiency induces quiescence and Zn2+resupply stimulates cell-cycle reentry. By monitoring single cells after Zn2+deprivation, we found that depending on where cells were in the cell cycle, they either went quiescent or entered the cell cycle but stalled in S phase. Stalled cells were defective in DNA synthesis and had increased DNA damage levels, suggesting a role for Zn2+in maintaining genome integrity. Finally, we found that Zn2+deficiency-induced quiescence does not require the cell-cycle inhibitor p21. Overall, our study provides new insights into when Zn2+is required during the mammalian cell cycle and the consequences Zn2+deficiency.
Synteny-based analyses indicate that sequence divergence is not the main source of orphan genes
Authors: Vakirlis Nikolaos , Carvunis Anne-Ruxandra , McLysaght Aoife
Published: August 2019

The origin of “orphan” genes, species-specific sequences that lack detectable homologues, has remained mysterious since the dawn of the genomic era. There are two dominant explanations for orphan genes: complete sequence divergence from ancestral genes, such that homologues are not readily detectable; andde novoemergence from ancestral non-genic sequences, such that homologues genuinely do not exist. The relative contribution of the two processes remains unknown. Here, we harness the special circumstance of conserved synteny to estimate the contribution of complete divergence to the pool of orphan genes. By separately comparing yeast, fly and human genes to related taxa using conservative criteria, we find that complete divergence accounts, on average, for at most a third of eukaryotic orphan and taxonomically restricted genes. We observe that complete divergence occurs at a stable rate within a phylum but at different rates between phyla, and is frequently associated with gene shortening akin to pseudogenization. Two cancer-related human genes,DEC1andDIRC1, have likely originated via this route in a primate ancestor.
Talin-vinculin precomplex drives adhesion maturation by accelerated force transmission and vinculin recruitment
Authors: Han Sangyoon J , Azarova Evgenia V , Whitewood Austin J , Bachir Alexia , Guttierrez Edgar , Groisman Alex , Horwitz Alan Rick , Goult Benjamin T , Dean Kevin , Danuser Gaudenz
Published: August 2019

Talin, vinculin, and paxillin are mechanosensitive proteins that are recruited early to integrin-based nascent adhesions (NAs). Using machine learning, traction microscopy, single-particle-tracking, and fluorescence fluctuation analysis, we find that talin, vinculin, and paxillin are recruited in near-synchrony to NAs maturing to focal adhesions. After initial recruitment of all three proteins under minimal load, vinculin accumulates in these NAs at a ~5 fold higher rate than in non-maturing NAs and with faster growth in traction. We identify a domain in talin, R8, which exposes a vinculin-binding-site (VBS) without requiring load. Stabilizing this domain via mutation lowers load-free vinculin binding to talin, impairs maturation of NAs, and reduces the rate of additional vinculin recruitment. Taken together, our data show that talin's concurrent localization with vinculin, before engagement with integrins, is essential for NA maturation, which entails traction-mediated unfolding of talin and exposure of additional VBSs triggering further vinculin binding.
Escherichia coliclonobiome: assessing the strains diversity in feces and urine by deep amplicon sequencing
Authors: Shevchenko Sofiya G. , Radey Matthew , Tchesnokova Veronika , Kisiela Dagmara , Sokurenko Evgeni V.
Published: August 2019

While microbiome studies have focused on diversity on the species or higher level, bacterial species in microbiomes are represented by different, often multiple strains. These strains could be clonally and phenotypically very different, making assessment of strain content vital to a full understanding of microbiome function. This is especially important with respect to antibiotic resistant strains, the clonal spread of which may be dependent on competition between them and susceptible strains from the same species. The pandemic, multi-drug resistant, and highly pathogenicE. colisubclone ST131-H30 (H30) is of special interest, as it has already been found persisting in the gut and bladder of healthy people. In order to rapidly assessE. coliclonal diversity, we developed a novel method based on deep sequencing of two loci used for sequence typing, along with an algorithm for analysis of resulting data. Using this method, we assessed fecal and urinary samples from healthy women carryingH30, and were able to uncover considerable diversity, including strains with frequencies at <1% of theE. colipopulation. We also found that even in the absence of antibiotic use,H30 could complete dominate the gut and, especially, urine of healthy carriers. Our study offers a novel tool for assessing a species’ clonal diversity (clonobiome) within the microbiome, that could be useful in studying population structure and dynamics of multi-drug resistant and/or highly pathogenic strains in their natural environments.

IMPORTANCE

Bacterial species in the microbiome are often represented by multiple genetically and phenotypically different strains, making insight into subspecies diversity critical to a full understanding of the microbiome, especially with respect to opportunistic pathogens. However, methods allowing efficient high-throughput clonal typing are not currently available. This study combines a conventionalE. colityping method with deep amplicon sequencing to allow analysis of many samples concurrently. While our method was developed forE. coli, it may be adapted for other species, allowing for microbiome researchers to assess clonal strain diversity in natural samples. Since assessment of subspecies diversity is particularly important for understanding the spread of antibiotic resistance, we applied our method to study of a pandemic multidrug-resistantE. coliclone. The results we present suggest that this clone could be highly competitive in healthy carriers, and that the mechanisms of colonization by such clones need to be studied.
Superior Colliculus to VTA pathway controls orienting response to conspecific stimuli
Authors: Prévost-Solié Clément , Contestabile Alessandro , Espinosa Pedro , Musardo Stefano , Bariselli Sebastiano , Huber Chieko , Carleton Alan , Bellone Camilla
Published: August 2019

Social behaviours characterize cooperative, mutualistic aggressive or parental interactions that occurs among conspecifics. Although several neuronal substrates of social behaviour have been identified, whether defined circuits are dedicated to specific aspect of conspecific interaction is still an open question. Ventral Tegmental Area (VTA) contributes to the rewarding properties of conspecific interaction. However, how information related to conspecifics are conveyed to the VTA is still largely unknown. In this study, we identified a population of Superior Colliculus (SC) neurons projecting to the VTA which increase their activity before conspecific interaction and control orienting response towards unfamiliar conspecifics. Finally, we show that SC inputs target a subpopulation of Dopamine (DA) neurons within the VTA that in turn project to dorsolateral striatum (DLS). Our work supports the hypothesis that specialized sub-circuits are dedicated to process different aspect of social interaction.
Stress Resistance Screen in a Human Primary Cell Line Identifies Small Molecules that Affect Aging Pathways and ExtendC. elegans’Lifespan
Authors: Zhang Peichuan , Zhai Yuying , Cregg James , Ang Kenny Kean-Hooi , Arkin Michelle , Kenyon Cynthia
Published: August 2019

Increased resistance to environmental stress at the cellular level is correlated with the longevity of long-lived mutants and wild-animal species. Moreover, in experimental organisms, screens for increased stress resistance have yielded mutants that are long-lived. To find entry points for small molecules that might extend healthy longevity in humans, we screened ∼100,000 small molecules in a human primary-fibroblast cell line and identified a set that increased oxidative-stress resistance. Some of the hits fell into structurally-related chemical groups, suggesting that they may act on common targets. Two small molecules increasedC. elegans’stress resistance, and at least 9 extended their lifespan by ∼10-50%. Thus, screening for increased stress resistance in human cells can enrich for compounds with promising pro-longevity effects. Further characterization of these compounds, including a chalcone that promoted stress resistance independently ofNRF2, may elucidate new ways to extend healthy human lifespan.
Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits
Authors: Alcott Callison E. , Yalamanchili Hari Krishna , Ji Ping , van der Heijden Meike E. , Saltzman Alexander B. , Leng Mei , Bhatt Bhoomi , Hao Shuang , Wang Qi , Saliba Afaf , Tang Jianrong , Malovannaya Anna , Wagner Eric J. , Liu Zhandong , Zoghbi Huda Y.
Published: August 2019

We previously showed that NUDT21-spanning copy-number variations (CNVs) are associated with intellectual disability (Gennarino et al., 2015). However, the patients’ CNVs also included other genes. To determine if reduced NUDT21 function alone can cause disease, we generated Nudt21+/- mice to mimic the human state of decreased expression. We found that although these mice have 50% reduced Nudt21 mRNA, they only have 30% less of its cognate protein, CFIm25. Despite this partial protein-level compensation, the Nudt21+/- mice have learning deficits and cortical hyperexcitability. Further, to determine the molecular mechanism driving neural dysfunction, we partially inhibited NUDT21 in human stem cell-derived neurons to reduce CFIm25 by 30%. This reduction in CFIm25 was sufficient to induce misregulated alternative polyadenylation (APA) and protein levels in hundreds of genes, dozens of which cause intellectual disability when mutated. Altogether, these results indicate that disruption of NUDT21-regulated APA events in the brain can cause intellectual disability.
A new algorithm for the reconstruction of protein molecular envelopes from X-ray solution scattering data
Authors: Badger John
Published: August 2019

At sufficiently low resolution, the scattering density within the volume occupied by a well folded protein molecule appears relatively flat. By enforcing this condition, three-dimensional protein molecular envelopes may be reconstructed using information obtained from X-ray solution scattering profiles. A practical approach for solving the low-resolution structures of protein molecules from solution scattering data involves modelling the protein shape using a set of volume-filling points (`beads') and transforming the scattering data to a more convenient target, the pair distance distribution function, P(r). Using algorithms described here, the beads interact via a modified Lennard–Jones potential and their positions are adjusted and confined until they fit the expected protein volume and agreement with P(r) is obtained. This methodology allows the protein volume to be modelled by an arbitrary, user-defined number of beads, enabling the rapid reconstruction of protein structures of widely varying sizes. Tests carried out with a variety of synthetic and experimental data sets show that this approach gives efficient and reliable determinations of protein molecular envelopes.
Niobium isocyanide complexes, Nb(CNAr)6, with Ar = 2,6-dimethylphenyl (Xyl), a diamagnetic dimer containing four reductively coupled isocyanides, and Ar = 2,6-diisopropylphenyl (Dipp), a paramagnetic monomer analogous to the highly unstable hexacarbonylniobium(0)
Authors: Kucera Benjamin E. , Roberts Christopher J. , Young Victor G. , Brennessel William W. , Ellis John E.
Published: August 2019

Treatment of bis(mesitylene)niobium(0) with 6–7 equivalents of 2,6-dimethylphenyl isocyanide (CNXyl) affords two products with the empirical formula Nb(CNXyl)
n
(n = 7 or 6), which have been shown to be the diamagnetic dimers bis[μ-N,N′,N′′,N′′′-tetrakis(2,6-dimethylphenyl)squaramidinato(2−)]bis[pentakis(2,6-dimethylphenyl isocyanide)niobium(I)], [Nb2(C9H9N)10(C36H36N4)] or [Nb(CNXyl)5]2[μ-C4(NXyl)4]·xSolvent, 1, and bis[μ-N,N′,N′′,N′′′-tetrakis(2,6-dimethylphenyl)squaramidinato(2−)]bis[tetrakis(2,6-dimethylphenyl isocyanide)niobium(I)] tetrahydrofuran trisolvate, [Nb2(C9H9N)8(C36H36N4)]·3C4H8O or [Nb(CNXyl)4]2[μ-C4(NXyl)4]·3THF (THF = tetrahydrofuran), 2. Each contains NbI bound to either five or four terminal isocyanides, respectively, and to an unprecedented bridging tetraarylsquaramidinate(2−) unit, coordinated as a bidentate ligand to each niobium center, symmetrically due to the crystallographic inversion center that coincides with the centroid of the central C4 unit. Thus, in the presence of CNXyl, the bis(mesitylene)niobium(0) is oxidized to niobium(I), resulting in the facile loss of both mesitylene groups and the reductive coupling of two CNXyl groups per niobium to provide the first examples of tetraarylsquaramidinate(2−) ligands, [cyclo-C4N4Ar4]2−, coordinated to metals. In contrast, bis(mesitylene)niobium(0) reacts with the more crowded 2,6-diisopropylphenyl isocyanide (CNDipp) to afford the paramagnetic monomer hexakis(2,6-diisopropylphenyl isocyanide)niobium(0), [Nb(C13H17N)6] or Nb(CNDipp)6, 3, the first zero-valent niobium isocyanide analog of the highly unstable Nb(CO)6, which is presently only known to exist in an argon matrix at 4.2 K.
A performance measurement system for change initiatives
Authors: Naslund Dag , Norrman Andreas
Published: August 2019

Purpose

The purpose of this paper is to develop, implement, test and further enhance a framework for measuring organizational change initiatives.

Design/methodology/approach

The conceptual part of the framework is based on the structured analysis of existing literature. The framework was further developed during an action research (AR) study where the authors developed, implemented, evaluated and improved the measurement system for organizational change initiatives.

Findings

The academic literature is rich in conceptual articles providing required characteristics of a “good” measurement system and frameworks for how organizations should measure performance. However, academia provides less empirical evidence of how these performance measurement systems can be implemented, evaluated and improved. In this paper, the authors present a study where the developed measurement system has been implemented, evaluated and improved. The results in terms of how the actual framework worked as well as the response from the case organizations are equally positive.

Research limitations/implications

The framework has been implemented in two different, major change initiatives in one case organization. While the results are truly encouraging, the framework needs to be further tested and refined in more organizations.

Practical implications

There is a gap between academic perception and practical reality regarding how organizations should measure performance in general as well as measuring organizational change initiatives. The presented, and empirically tested, framework measures both the results of the change initiative (effectiveness) the actual change process (efficiency) as well as the perception of the change initiative and process from different key stakeholders.

Originality/value

This is the first developed, implemented and further improved measurement system for organizational change which measures both the efficiency and effectiveness of the change initiative (process).