bluuebunny/crossref_metadata_2025 huggingface dataset:
A megaplasmid family responsible for dissemination of multidrug resistance inPseudomonas
Authors: Cazares Adrian , Moore Matthew P. , Grimes Macauley , Emond-Rhéault Jean-Guillaume , Wright Laura L. , Pongchaikul Pisut , Santanirand Pitak , Levesque Roger C. , Fothergill Joanne L. , Winstanley Craig
Published: May 2019

Multidrug resistance (MDR) represents a global threat to health. Although plasmids can play an important role in the dissemination of MDR, they have not been commonly linked to the emergence of antimicrobial resistance in the pathogenPseudomonas aeruginosa. We used whole genome sequencing to characterize a collection ofP. aeruginosaclinical isolates from a hospital in Thailand. Using long-read sequence data we obtained complete sequences of two closely related megaplasmids (>420 kb) carrying large arrays of antibiotic resistance genes located in discrete, complex and dynamic resistance regions, and revealing evidence of extensive duplication and recombination events. A comprehensive pangenomic and phylogenomic analysis indicated that 1) these large plasmids comprise a family present in different members of thePseudomonasgenus and associated with multiple sources (geographical, clinical or environmental); 2) the megaplasmids encode diverse niche-adaptive accessory traits, including multidrug resistance; 3) the pangenome of the megaplasmid family is highly flexible and diverse, comprising a substantial core genome (average of 48% of plasmid genes), but with individual members carrying large numbers of unique genes. The history of the megaplasmid family, inferred from our analysis of the available database, suggests that members carrying multiple resistance genes date back to at least the 1970s.

Funding

This work was supported by the International Pseudomonas Genomics Consortium, funded by Cystic Fibrosis Canada [RCL]; and the Secretaría de Educación, Ciencia, Tecnología e Innovación (SECTEI), Mexico [AC].
Single-cell Lineage Tracing by Integrating CRISPR-Cas9 Mutations with Transcriptomic Data
Authors: Zafar Hamim , Lin Chieh , Bar-Joseph Ziv
Published: May 2019

Recent studies combine two novel technologies, single-cell RNA-sequencing and CRISPR-Cas9 barcode editing for elucidating developmental lineages at the whole organism level. While these studies provided several insights, they face several computational challenges. First, lineages are reconstructed based on noisy and often saturated random mutation data. Additionally, due to the randomness of the mutations, lineages from multiple experiments cannot be combined to reconstruct a consensus lineage tree. To address these issues we developed a novel method, LinTIMaT, which reconstructs cell lineages using a maximum-likelihood framework by integrating mutation and expression data. Our analysis shows that expression data helps resolve the ambiguities arising in when lineages are inferred based on mutations alone, while also enabling the integration of different individual lineages for the reconstruction of a consensus lineage tree. LinTIMaT lineages have better cell type coherence, improve the functional significance of gene sets and provide new insights on progenitors and differentiation pathways.
Ab-initiodiscovery of tumoricidal oligonucleotides in a DNA sequencing machine
Authors: Mamet Noam , Rusinek Itai , Harari Gil , Shapira Zvi , Amir Yaniv , Lavi Erez , Zamir Adva , Borovsky Noam , Joseph Noah , Motin Maria , Saban Dekel , Bachelet Ido
Published: May 2019

We describe a technique for the rapidab-initiodiscovery of target-tailored tumoricidal DNA oligonucleotides inside an Illumina sequencing chip. By sequencing oligonucleotide pools we generate a physical microfluidic map of hundreds of millions of potential oligo clusters, in which every cluster is mapped to a specific set of spatial coordinates. Tumor cells, pre-loaded with a fluorogenic reporter of apoptosis, are then injected into the chip and monitored over time. Apoptotic tumor cells are identified and analyzed across the entire map, automatically revealing the coordinates of oligos that induced this effect. We demonstrate this method by identifying, within just a few hours, new oligos capable of directly and selectively inducing apoptosis in primary human tumor cells. Such a major capability could lead to a new paradigm of personalized cancer therapy.
CNOT1 mediates phosphorylation via Protein kinase A on the circadian clock
Authors: Zhang Yunfeng , Qin Haitang , Feng Yongjie , Gao Peng , Zhong Yingbin , Tan Yicheng , Wang Han , Xu Ying , Takahashi Joseph S. , Huang Guocun
Published: May 2019

At the core of the mammalian circadian feedback loop, CLOCK (NPAS2)-BMAL1 is the positive element to activate transcription of downstream genes encoding the negative elements PERs and CRYs. Here we show that CNOT1 associates with both CLOCK and BMAL1, promotes their phosphorylation and increases their protein stability, and in turn inhibits the transcriptional activity of CLOCK-BMAL1. Expression of either CLOCK, BMAL1 or CNOT1 could interact with endogenous Protein Kinase A (PKA) as assessed by co-immunoprecipitation (Co-IP) and kinase assays. PKA could phosphorylate CLOCK and BMAL1 and this was promoted by CNOT1. Genetic deletion of PKA-Cα by CRISPR-Cas9 results in a longer period of the circadian rhythm; while overexpression of PKA-Cα induces a shorter period. Furthermore, we demonstrate that CNOT1 associates with CLOCK and BMAL1 in the mouse liver and promotes their phosphorylation. PER2, but not CRY2, is also a PKA target. Our results suggest that CNOT1 and PKA play a critical role in the mammalian circadian clock, revealing a conserved function in eukaryotic circadian regulations.
Viral infection causes sex-specific changes in fruit fly social aggregation behaviour
Authors: Siva-Jothy Jonathon A. , Vale Pedro F.
Published: May 2019

Host behavioural changes following infection are common and could be important determinants of host behavioural competence to transmit pathogens. Identifying potential sources of variation in sickness behaviours is therefore central to our understanding of disease transmission. Here, we test how group social aggregation and individual locomotor activity vary between different genotypes of male and female fruit flies (Drosophila melanogaster) following septic infection with Drosophila C Virus. We find genetic-based variation in both locomotor activity and social aggregation but we did not detect an effect of DCV infection on fly activity or sleep patterns within the initial days following infection. However, DCV infection caused sex-specific effects on social aggregation, as male flies in most genetic backgrounds increased the distance to their nearest neighbour when infected. We discuss possible causes for these differences in the context of individual variation in immunity and their potential consequences for disease transmission.
Set1/COMPASS repels heterochromatin invasion at euchromatic sites by disrupting Suv39/Clr4 activity and nucleosome stability
Authors: Greenstein R.A. , Barrales Ramon R. , Sanchez Nicholas A. , Bisanz Jordan E. , Braun Sigurd , Al-Sady Bassem
Published: May 2019

Protection of euchromatin from invasion by gene-repressive heterochromatin is critical for cellular health and viability. In addition to constitutive loci such as pericentromeres and subtelomeres, heterochromatin can be found interspersed in gene-rich euchromatin, where it regulates gene expression pertinent to cell fate. While hetero- and euchromatin are globally poised for mutual antagonism, the mechanisms underlying precise spatial encoding of heterochromatin containment within euchromatic sites remain opaque. We investigated ectopic heterochromatin invasion by manipulating the fission yeast mating type locus boundary, using a single-cell spreading reporter system. We found that heterochromatin repulsion is locally encoded by Set1/COMPASS on certain actively transcribed genes and that this protective role is most prominent at heterochromatin islands, small domains interspersed in euchromatin that regulate cell fate specifiers. Interestingly, this effect can be gene orientation dependent. Sensitivity to invasion by heterochromatin, surprisingly, is not dependent on Set1 altering overall gene expression levels. At least two independent pathways direct this Set1 activity–inhibition of catalysis by Suv39/Clr4 and disruption of nucleosome stability. Taken together, these results describe a mechanism for spatial encoding of euchromatic signals that repel heterochromatin invasion.
Host-Microbial Interactions in Systemic Lupus Erythematosus and Periodontitis
Authors: Pessoa L.C. , Aleti G. , Choudhury S. , Nguyen D. , Yaskell T. , Zang Y. , Weizhong L. , Nelson K.E. , Santos Neto L. L. , Sant’Ana A.C.P. , Freire M.
Published: May 2019

Systemic lupus erythematosus (SLE) is a potentially fatal complex autoimmune disease, that is characterized by widespread inflammation manifesting tissue damage and comorbidities across the human body including heart, blood vessels, joints, skin, liver, kidneys, and periodontal tissues. The etiology of SLE is partially attributed to a deregulated inflammatory response to microbial dysbiosis and environmental changes. In the mouth, periodontal environment provides an optimal niche to assay local dynamic microbial ecological changes in health and disease important to systemic inflammation in SLE subjects. Our aim was to evaluate the reciprocal impact of periodontal subgingival microbiota on SLE systemic inflammation. Ninety-one female subjects were recruited, including healthy (n=31), SLE-inactive (n=29), and SLE-active (n=31). Patients were screened for probing depth (PD), bleeding on probing (BOP), clinical attachment level (CAL), and classified with or without periodontal dysbiosis, periodontitis. Serum inflammatory cytokines were measured by human cytokine panel and subgingival biofilm was examined by DNA-DNA checkerboard. The results showed significant upregulation of proinflammatory cytokines in individuals with SLE when compared to controls. Stratification of subject’s into SLE-inactive (I) and SLE-active (A) phenotypes or periodontitis and non-periodontitis groups provided new insights into SLE pathophysiology. While low-grade inflammation was found in SLE-I subjects, a potent anti-inflammatory cytokine, IL-10 was found to control clinical phenotypes. Out of twenty-four significant differential oral microbial abundances found in SLE, fourteen unique subgingival bacteria profiles were found to be elevated in SLE. Pathogens from periodontal disease sites (Treponema denticola and Tannerella forsythia) showed increase abundance in SLE-A subjects when compared to controls. Cytokine-microbial correlations showed that periodontal pathogens dominating the environment increased proinflammatory cytokines systemically. Deeper clinical attachment loss and periodontal pathogens were found in SLE subjects, especially on SLE-I, likely due to long-term chronic and low-grade inflammation. Altogether, local periodontal pathogen enrichment was positively associated with high systemic inflammatory profiles, relevant to the overall health and SLE disease pathogenesis.
Computationally Enhanced Quantitative Phase Microscopy Reveals Autonomous Oscillations in Mammalian Cell Growth
Authors: Liu Xili , Oh Seungeun , Peshkin Leonid , Kirschner Marc W.
Published: May 2019

The fine balance of growth and division is a fundamental property of the physiology of cells and one of the least understood. Its study has been thwarted by difficulties in the accurate measurement of cell size and the even greater challenges of measuring growth of a single-cell over time. We address these limitations by demonstrating a new computationally enhanced methodology for Quantitative Phase Microscopy (ceQPM) for adherent cells, using improved image processing algorithms and automated cell tracking software. Accuracy has been improved more than two-fold and this improvement is sufficient to establish the dynamics of cell growth and adherence to simple growth laws. It is also sufficient to reveal unknown features of cell growth previously unmeasurable. With these methodological and analytical improvements, we document a remarkable oscillation in growth rate in several different cell lines, occurring throughout the cell cycle, coupled to cell division or birth, and yet independent of cell cycle progression. We expect that further exploration with this improved tool will provide a better understanding of growth rate regulation in mammalian cells.

Significance Statement

It has been a long-standing question in cell growth studies that whether the mass of individual cell grows linearly or exponentially. The two models imply fundamentally distinct mechanisms, and the discrimination of the two requires great measurement accuracy. Here, we develop a new method of computationally enhanced Quantitative Phase Microscopy (ceQPM), which greatly improves the accuracy and throughput of single-cell growth measurement in adherent mammalian cells. The measurements of several cell lines indicate that the growth dynamics of individual cells cannot be explained by either of the simple models but rather present an unanticipated and remarkable oscillatory behavior, suggesting more complex regulation and feedbacks.
The evolution of nitroimidazole antibiotic resistance in Mycobacterium tuberculosis
Authors: Lee Brendon M. , Almeida Deepak V. , Afriat-Jurnou Livnat , Aung Htin Lin , Forde Brian M. , Hards Kiel , Pidot Sacha J. , Ahmed F. Hafna , Mohamed A. Elaaf , Taylor Matthew C. , West Nicholas P. , Stinear Timothy P. , Greening Chris , Beatson Scott A. , Cook Gregory M. , Nuermberger Eric L. , Jackson Colin J.
Published: May 2019

Our inability to predict whether certain mutations will confer antibiotic resistance has made it difficult to rapidly detect the emergence of resistance, identify pre-existing resistant populations and manage our use of antibiotics to effective treat patients and prevent or slow the spread of resistance. Here we investigated the potential for resistance against the new antitubercular nitroimidazole prodrugs pretomanid and delamanid to emerge in Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). Deazaflavin-dependent nitroreductase (Ddn) is the only identified enzyme within M. tuberculosis that activates these prodrugs, via an F420H2-dependent reaction. We show that the native menaquinone-reductase activity of Ddn is important in aerobic respiration and essential for emergence from dormancy, which suggests that for resistance to spread and pose a threat to human health, the native activity of Ddn must be at least partially retained. We tested 75 unique mutations, including all known sequence polymorphisms identified among ~15,000 sequenced M. tuberculosis genomes. Several mutations abolished pretomanid activation in vitro, without causing complete loss of the native activity. We confirmed that a transmissible M. tuberculosis isolate from the hypervirulent Beijing family already possesses one such mutation and is resistant to pretomanid, even though it was never exposed to pretomanid. Notably, delamanid was still effective against this strain, which is consistent with structural analysis that indicates delamanid and pretomanid bind to Ddn differently. We suggest that the mutations identified in this work be monitored for informed use of delamanid and pretomanid treatment and to slow the emergence of resistance.
Unbiased identification of trans regulators of ADAR and A-to-I RNA editing
Authors: Freund Emily C. , Sapiro Anne L. , Li Qin , Linder Sandra , Moresco James J. , Yates John R. , Li Jin Billy
Published: May 2019

Adenosine-to-Inosine RNA editing is catalyzed by ADAR enzymes that deaminate adenosine to inosine. While many RNA editing sites are known, few trans regulators have been identified. We perform BioID followed by mass-spectrometry to identify trans regulators of ADAR1 and ADAR2 in HeLa and M17 neuroblastoma cells. We identify known and novel ADAR-interacting proteins. Using ENCODE data we validate and characterize a subset of the novel interactors as global or site-specific RNA editing regulators. Our set of novel trans regulators includes all four members of the DZF-domain-containing family of proteins: ILF3, ILF2, STRBP, and ZFR. We show that these proteins interact with each ADAR and modulate RNA editing levels. We find ILF3 is a global negative regulator of editing. This work demonstrates the broad roles RNA binding proteins play in regulating editing levels and establishes DZF-domain containing proteins as a group of highly influential RNA editing regulators.
Individual difference in serial dependence results from opposite influences of perceptual choices and motor responses
Authors: Zhang Huihui , Alais David
Published: May 2019

Natural image statistics exhibit temporal regularities of slow changes and short-term correlations and visual perception, too, is biased towards recently seen stimuli, i.e., a positive serial dependence. Some studies report strong individual differences in serial dependence in perceptual decision making: some observers show positive serial effects, others repulsive effects, and some show no bias. To understand these contrasting results, this study separates the influences of physical stimuli per se, perceptual choices and motor responses on serial dependence in perceptual decision making. In two experiments, human observers reported which orientation (45° or −45°, at threshold contrast) they perceived. Experiment 1, used a consistent mapping between stimulus and response buttons while in Experiment 2, observers did two tasks: one with a consistent stimulus-response mapping, the other with a random stimulus-response mapping (perceptual choice and motor response unrelated). Results show that the stimulus percept (not the physical stimulus per se) affected subsequent perceptual choices in an attractive way, and that motor responses produced a repulsive serial effect. When the choice-response mapping was consistent (inseparable choice and response, typical of most experiments), individual differences in the overall serial effect was observed: some were positive, some repulsive, and some were bias-free. These individual differences likely reflect different relative weightings in individuals of a positive choice bias and a repulsive motor bias.
BOCS: DNA k-mer content and scoring for rapid genetic biomarker identification at low coverage
Authors: Korshoj Lee E. , Nagpal Prashant
Published: May 2019

A single, inexpensive diagnostic test capable of rapidly identifying a wide range of genetic biomarkers would prove invaluable in precision medicine. Previous work has demonstrated the potential for high-throughput, label-free detection of A-G-C-T content in DNA k-mers, providing an alternative to single-letter sequencing while also having inherent lossy data compression and massively parallel data acquisition. Here, we apply a new bioinformatics algorithm – block optical content scoring (BOCS) – capable of using the high-throughput content k-mers for rapid, broad-spectrum identification of genetic biomarkers. BOCS uses content-based sequence alignment for probabilistic mapping of k-mer contents to gene sequences within a biomarker database, resulting in a probability ranking of genes on a content score. Simulations of the BOCS algorithm reveal high accuracy for identification of single antibiotic resistance genes, even in the presence of significant sequencing errors (100% accuracy for no sequencing errors, and > 90% accuracy for sequencing errors at 20%), and at well below full coverage of the genes. Simulations for detecting multiple resistance genes within a methicillin-resistant Staphylococcus aureus (MRSA) strain showed 100% accuracy at an average gene coverage of merely 0.515, when the k-mer lengths were variable and with 4% sequencing error within the k-mer blocks. Extension of BOCS to cancer and other genetic diseases met or exceeded the results for resistance genes. Combined with a high-throughput content-based sequencing technique, the BOCS algorithm potentiates a test capable of rapid diagnosis and profiling of genetic biomarkers ranging from antibiotic resistance to cancer and other genetic diseases.
Electroporated recombinant proteins as tools forin vivofunctional complementation, imaging, and chemical biology
Authors: Alex Amal , Piano Valentina , Polley Soumitra , Stuiver Marchel , Voss Stephanie , Ciossani Giuseppe , Overlack Katharina , Voss Beate , Wohlgemuth Sabine , Petrovic Arsen , Wu Yao-Wen , Selenko Philipp , Musacchio Andrea , Maffini Stefano
Published: May 2019

Delivery of native or chemically modified recombinant proteins into mammalian cells shows promise for functional investigations and various technological applications, but concerns that sub-cellular localization and functional integrity of delivered proteins may be affected remain high. Here, we surveyed batch electroporation as a delivery tool for single polypeptides and multi-subunit protein assemblies of kinetochores, a spatially confined and well-studied subcellular structures. After electroporation in human cells, recombinant fluorescent Ndc80 and Mis12 multi-subunit complexes displayed native localization, physically interacted with endogenous binding partners, and functionally complemented depleted endogenous counterparts to promote mitotic checkpoint signaling and chromosome segregation. Farnesylation is required for kinetochore localization of the Dynein adaptor Spindly. In cells with chronically inhibited farnesyl transferase activity,in vitrofarnesylation and electroporation reconstituted robust kinetochore localization of Spindly. Thus, electroporation is uniquely versatile for delivering synthetic and, as required, chemically modified functional mimics of endogenous proteins, and is therefore a promising tool for chemical and synthetic biology.
In situabundance and carbon fixation activity of distinct anoxygenic phototrophs in the stratified seawater lake Rogoznica
Authors: Pjevac Petra , Dyksma Stefan , Goldhammer Tobias , Mujakić Izabela , Koblížek Michal , Mussmann Marc , Amann Rudolf , Orlić Sandi
Published: May 2019

Sulfide-driven anoxygenic photosynthesis is an ancient microbial metabolism that contributes significantly to inorganic carbon fixation in stratified, sulfidic water bodies. Methods commonly applied to quantify inorganic carbon fixation by anoxygenic phototrophs, however, cannot resolve the contributions of distinct microbial populations to the overall process. We implemented a straightforward workflow, consisting of radioisotope labeling and flow cytometric cell sorting based on the distinct autofluorescence of bacterial photo pigments, to discriminate and quantify contributions of co-occurring anoxygenic phototrophic populations toin situinorganic carbon fixation in environmental samples. This allowed us to assign 89.3 ±7.6% of daytime inorganic carbon fixation by anoxygenic phototrophs in Lake Rogoznica (Croatia) to an abundant chemocline-dwelling population of green sulfur bacteria (dominated byChlorobium phaeobacteroides), whereas the co-occurring purple sulfur bacteria (Halochromatiumsp.) contributed only 1.8 ±1.4%. Furthermore, we obtained two metagenome assembled genomes of green sulfur bacteria and one of a purple sulfur bacterium which provides the first genomic insights into the genusHalochromatium, confirming its high metabolic flexibility and physiological potential for mixo-and heterotrophic growth.
Cellular precision of orientation and spatial frequency maps in macaque V1
Authors: Ju Nian-Sheng , Guan Shu-Chen , Tang Shi-Ming , Yu Cong
Published: May 2019

Functional organization of neuronal response properties along the surface of the neocortex is a fundamental guiding principle of neural computation in the brain. Despite this importance, the cellular precision of functional maps is still largely unknown. We address the challenge by using two-photon calcium imaging to measure cell-specific orientation and spatial frequency (SF) responses across fields of macaque V1 superficial layers. The cellular orientation maps confirm iso-orientation domains, but rarely show pinwheels. Pinwheels obtained through conventional Gaussian smoothing and vector summation of orientation responses mostly overlap with blood vessel regions, suggesting false singularities. Cellular SF maps clarify existing controversies by showing weak iso-frequency clusters, which also suggests a weak geometric relationship between orientation and SF maps. Most neurons are tuned to medium frequencies, but the tuning functions are often asymmetric with a wider low- or high-frequency branch, which may help encode low or high SF information for later decoding.
Epithelial Modelling Platform: A Tool for Model Discovery and Assembly with the Physiome Model Repository
Authors: Sarwar Dewan M. , Munarko Yuda , Nickerson David P.
Published: May 2019

In this paper we present a web-based platform enabling scientists to construct a novel epithelial transport model to investigate their hypotheses, aided by building on existing models discovered in the Physiome Model Repository (PMR). We have comprehensively annotated a cohort of epithelial transport models deposited in the PMR as a seeding collection of building blocks that are freely available for reuse. On the platform, users are able to semantically display models for visualization, graphical editing, and model assembly. In addition, we leverage web services from the European Bioinformatics Institute (EBI) to help rank similar models based on the suggestions provided by the platform. In addition to potential use in biomedical and clinical research, novice modellers could use our platform as a learning tool. The source code and links to a live demonstration of the platform are available at https://github.com/dewancse/ epithelial-modelling-platform.
D-alanylation of Teichoic Acids in Bacilli impedes the immune sensing of peptidoglycan in Drosophila
Authors: Attieh Zaynoun , Kallassy Awad Mireille , Rejasse Agnès , Courtin Pascal , Gomperts Boneca Ivo , Chapot-Chartier Marie-Pierre , Sanchis Borja Vincent , El Chamy Laure
Published: May 2019

Modification of cell wall components is a prominent mean for pathogens to hinder host immune defenses. Here, using the Drosophila model, we aimed at characterizing the role of D-alanine esterification of teichoic acids (TAs) in the resistance of Bacillus thuringiensis to host defenses in vivo. We show that, by preventing cationic antimicrobial effectors-mediated bacterial lysis, this cell wall modification also limits the release of peptidoglycan immunostimulatory fragments thus impeding their sensing and the subsequent induction of the IMD- NF-κB pathway. Interestingly, we show that this strategy is also adopted by Lactobacillus plantarum, a bona fide commensal, to fine-tune its immunomodulatory potential in the Drosophila gut. Markedly, we show that the D-alanylation of TAs is essential for the resistance of L. plantarum to gut lysozyme. Altogether our data shed light on the mechanism underlying the persistence and the low immunostimulatory potential of L. plantarum in the Drosophila gut.
The Role of the Public Health Service Equalization Program in the Control of Hypertension in China: Results from a Cross-sectional Health Interview Survey
Authors: Qin Jiangmei , Zhang Yanchun , Fridman Masha , Sweeny Kim , Zhang Lifang , Mao Lu , Lin Chunmei
Published: May 2019

Objectives

Non-communicable diseases (NCDs) have become the main cause of mortality in China. In 2009, the Chinese government introduced the Public Health Service Equalization (PHSE) program to restore the primary healthcare system in both essential medical care and public health service provision. This study evaluates the impact of management on hypertension control and evaluate how the program works.

Methods

The China National Health Development Research Centre (CNHDRC) undertook the Cross-sectional Health Service Interview Survey (CHSIS) of 62,097 people from primary healthcare reform pilot areas, across 17 provinces from eastern, central and western parts of China in 2014. This study is based on CHSIS survey responses from 9,607 participants, who had been diagnosed with hypertension. Regression analysis was used to estimate the impact of management provided under PHSE on hypertension control adjusting for the effects of other known determinants of hypertension control.

Findings

Uncontrolled hypertension was markedly lower among respondents, whose hypertension had been managed (22.4% in managed patients versus 31.1% in unmanaged patients, p<0.001). The interaction between PHSE management and the geographical region was highly significant in the model (p<0.001), suggesting that the PHSE program was not equally effective in all regions. Further analysis suggested that approximately 10% of regional variability was attributed to differences in administrative systems, as there was a significant association (P=0.014) between the presence of established regional Information Management Systems (IMS) and increased PHSE effectiveness. Insurance (χ2(5)=4.4, p=0.496) and Hukou (χ2(1)=2.4, p=0.121), which denote social security and urban rural differences, respectively, were not significant predictor of hypertension control.

Conclusion

Active management of hypertension through the PHSE program was effective with 7.31 million more patients receiving hypertension control and equalization of service delivery was reflected to some extent. The link between established IMS and regional variability in the impact of PHSE highlights the importance of effective management of patient referrals and follow-up. Further investigation is needed to explore the factors that influence the effectiveness of PHSE.
Downregulation of hippocampal NR2A/2B subunits related to cognitive impairment in a pristane-induced lupus BALB/c mice
Authors: Luciano-Jaramillo Jonatan , Sandoval-García Flavio , Vázquez-Del Mercado Mónica , Gutiérrez-Mercado Yanet Karina , Navarro-Hernández Rosa Elena , Martínez-García Erika Aurora , Pizano-Martínez Oscar , Corona-Meraz Fernanda Isadora , Bañuelos-Pineda Jacinto , Floresvillar-Mosqueda Jorge , Martín-Márquez Beatriz Teresita
Published: May 2019

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a severe complication associated with the neurotoxic effects of circulating autoantibodies in the central nervous system (CNS) manifested frequently as a learning and memory deficit. Pristane-induced lupus in BALB/c female mice is an experimental model that resembles some clinical and immunological SLE pathogenesis associated with environmental factors. Nevertheless, there is no experimental evidence that relate pristane-induced lupus with cognitive dysfunction associated with autoantibodies production.

Objective

To evaluate cognitive impairment related to memory deficits in a pristane-induced lupus BALB/c female mice related to mRNA expression levels of NR2A/2B hippocampal subunits in short and long-term memory task at 7 and 12 weeks after LPS exposition (7wLPS and 12wLPS) in a behavioral test with the employment of Barnes maze.

Methods

Fifty-four female BALB/c mice of 8-12 weeks old were included in 2 experimental groups: 7 and 12 weeks after lypopolissacharide (LPS) exposure and classified in subgroups (control, pristane and pristane+LPS). To determine cognitive dysfunction, mice were tested in a Barnes maze. Serum anti-Sm antibodies and relative expression of hippocampal NR2A/NR2B subunits were quantified.

Results

Pristane and pristane+LPS mice showed a prolonged escape latency at 7wLPS than at 12wLPS in short-term memory. Downregulation of hippocampal NR2A subunit was more evident than NR2B in pristane and pristane+LPS at 7wLPS and 12wLPS. The anti-Sm autoantibodies levels correlate with the relative expression of NR2A.

Conclusion

Downregulation of hippocampal NR2A/2B subunits in the pristane-model of lupus in BALB/c mice may be related to anti-Sm autoantibodies production with the consequence of cognitive impairment in early stages of autoimmune disease.
Single-cell selectivity and functional architecture of human lateral occipital complex
Authors: Decramer Thomas , Premereur Elsie , Uytterhoeven Mats , Van Paesschen Wim , van Loon Johannes , Janssen Peter , Theys Tom
Published: May 2019

The human lateral occipital complex (LOC) is more strongly activated by images of objects compared to scrambled controls, but detailed information at the neuronal level is currently lacking. We recorded with microelectrode arrays in the LOC of two patients, and obtained highly selective single-unit, multi-unit and high-gamma responses to images of objects. Contrary to predictions derived from functional imaging studies, all neuronal properties indicated that the subsector of LOC we recorded from occupies an unexpectedly high position in the hierarchy of visual areas. Notably, the response latencies of LOC neurons were long, the shape selectivity was spatially clustered, LOC receptive fields were large and bilateral, and a number of LOC neurons exhibited 3D-structure selectivity (a preference for convex or concave stimuli), which are all properties typical of end-stage ventral stream areas. Thus, our results challenge prevailing ideas about the position of the LOC in the hierarchy of visual areas.
Dispersal ofMycobacterium tuberculosisto indigenous populations driven by historical European trade in the South Pacific
Authors: Mulholland Claire V. , Shockey Abigail C. , Aung Htin L. , Cursons Ray T. , O’Toole Ronan F. , Gautam Sanjay S. , Brites Daniela , Gagneux Sebastien , Roberts Sally A. , Karalus Noel , Cook Gregory M. , Pepperell Caitlin S. , Arcus Vickery L.
Published: May 2019

TheMycobacterium tuberculosiscomplex lineage 4 (L4), also known as the “Euro-American” lineage, is the most widely dispersed of the seven human adapted lineages. L4 is comprised of ten sublineages including L4.4, which has a moderate global distribution and is the most common L4 sublineage in New Zealand. We have used a phylodynamics approach and a dataset of 236 globalM. tuberculosisgenomes to trace the origins and dispersal of L4.4 strains in New Zealand that are predominantly found in Māori and Pacific people. We identify an L4.4.1.1 sublineage clade of European origin, likely French, that is prevalent in indigenous populations in both New Zealand and Canada. Molecular dating suggests that expansion of European trade networks in the early 19th century led to dispersal of this clade to the South Pacific. We also identify historical and social factors within the region that have contributed to the local spread and expansion of these strains, including recent Pacific migrations to New Zealand and the rapid urbanization of Māori in the 20th century. Our results offer new insight into the dispersal ofM. tuberculosisin the South Pacific region and provide a striking example of the role of historical European migrations in the dispersal ofM. tuberculosis.

Author Summary

Tuberculosis kills more people worldwide than any other infectious disease and indigenous populations are disproportionately affected by the disease. Here, we have used a large global dataset ofMycobacterium tuberculosisbacterial genomes to trace the historical origins of tuberculosis strains in New Zealand that are most frequently found in Māori and Pacific people. These strains are locally known as the ‘Rangipo’ and ‘Otara’ strains (both Māori place names) and belong to the “Euro-American” lineage ofM. tuberculosis. Via genome analysis, we find that these strains are closely related toM. tuberculosisstrains found in indigenous populations in Canada that have a European origin. We used a molecular dating approach (a molecular clock) to infer the ages of these strains and date divergence events. The timing we infer corresponds to the introduction of these strains to Polynesia via expanding European trade networks in the South Pacific in the early 19th century and suggests that the Otara strain has migrated to New Zealand from the Pacific Islands multiple times. Our results provide insight into human social phenomena underlying the expansion and dispersal ofM. tuberculosisand reassert the important role of European colonial migrations in the global dispersal of theM. tuberculosisEuro-American lineage. This work also highlights the pejorative and stigmatizing mislabelling of the New Zealand strains with indigenous Māori place names, suggesting that these strains should be renamed.
Regeneration Rosetta: An interactive web application to explore regeneration-associated gene expression and chromatin accessibility
Authors: Rau Andrea , Dhara Sumona P. , Udvadia Ava J. , Auer Paul L.
Published: May 2019

Time-course high-throughput assays of gene expression and enhancer usage in zebrafish provide a valuable characterization of the dynamic mechanisms governing gene regulatory programs during CNS axon regeneration. To facilitate the exploration and functional interpretation of a set of fully-processed data on regeneration-associated temporal transcription networks, we have created an interactive web application called Regeneration Rosetta. Using either built-in or user-provided lists of genes in one of dozens of supported organisms, our web application facilitates the (1) visualization of clustered temporal expression trends; (2) identification of proximal and distal regions of accessible chromatin to expedite downstream motif analysis; and (3) description of enriched functional gene ontology categories. By enabling a straightforward interrogation of these rich data without extensive bioinformatic expertise, Regeneration Rosetta is broadly useful for both a deep investigation of time-dependent regulation during regeneration in zebrafish and hypothesis generation in other organisms.
The shortest-path spanning tree of assembly dimension and its application
Authors: Wang Youli , Dai Liming , Zhang Xueliang , Wang Xiaohui
Published: May 2019

Purpose

The purpose of this paper is to obtain the reasonable dimensioning for each part and a full-dimension model of assembly dimensions.

Design/methodology/approach

The relational path graph of assembly dimension, the shortest-path spanning tree of functional dimension and a revised spanning tree are established in this paper.

Findings

The proposed method can obtain reasonable dimensioning of parts and establishment of dimension model in an assembly.

Originality/value

The proposed method can easily realise by computer and be more suitable to automatic dimensioning and establishment of dimension model of parts.
Dynamic response analysis on vibration of ground and track system induced by metro operation
Authors: Ding Zhi , Li Danwei
Published: May 2019

Purpose

This paper aims to evaluate the dynamic response of surrounding foundation and study the vibration characteristics of track system.

Design/methodology/approach

A double-line underground coupling analysis model was established, which included two moving train, track, liner and the ground field.

Findings

Based on the 2.5D (D is diameter) finite element analysis, the influence of the important factors such as the depth of the subway tunnel, the nature of the foundation soil, the relative position relation of the double tunnel, the subway driving speed on the foundation and the orbital vibration are analyzed in this article.

Originality/value

The results in paper may have reference value for the prediction of train induced vibrations and for the research of dynamic response of ground field.
Mission K-54: turning around the US$3bn Indian auto major – Ashok Leyland
Authors: Cr Rajan , T.N. Swaminathan , Ganduri Uma Rao
Published: May 2019

Learning outcomes

Learning outcomes are eliminating usual options for a turnaround, understanding how organizations can respond to adverse industry /market changes through cost and productivity management, managing strategic cost control turnaround deployed across a company, turning a huge threat into an opportunity and the role of leadership in driving strategic cost management and importance of internal communication and buy-in for a successful implementation.

Case overview/synopsis

Ashok Leyland Ltd. is the 2nd largest manufacturer of commercial vehicles in India, the 4th largest manufacturer of buses in the world and the 12th largest manufacturer of trucks globally. Vinod Dasari joined this company in 2005, and since 2011, he has been the MD and CEO of the company. This case is about restaging of this company that commenced in the year 2013 when the company was heading toward a loss for the very first time in its 65 plus years of history. Ashok Leyland was heaving under its own weight, saddled with overheads, grappling with intense competition from old and new players and struggling to become agile and meet the new challenges in the market. A potential loss of up to Rs 750 crores (US$123m) looked inevitable. The challenges were that major structural changes were required and the company needed not only a transformational change but also a surgery. The company had to come up with savings of Rs 750 crores (US$123m) annually to avoid making losses. The projection of 54,000 unit sales volumes be achieved. Internal communication and buying in by all employees. This case outlines the path chosen by Dasari to restage, turn around, overcome the challenges and deal with employee resistance.

Complexity academic level

This study is applicable for MBA programs in business strategy, strategic marketing, international marketing and BBA programs in business strategy, strategic marketing and international marketing.

Supplementary materials

Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 11: Strategy.
Appreciative enquiry peer review improving quality of services
Authors: Burbach Frank R. , Amani Sarah K.
Published: May 2019

Purpose

Mental health service improvement initiatives often involve the setting of targets and monitoring of performance. The purpose of this paper is to describe the application of appreciative enquiry (AE), a radically different but complementary approach to quality assurance and improvement, to specialist mental health services across a health region.

Design/methodology/approach

This case study describes a regional quality improvement (QI) project involving 12 early intervention in psychosis (EIP) services in South West England. In total, 40 people were trained in AE interviewing skills and in non-reciprocal peer review visits 59 interviews were conducted involving 103 interviewees including service users, carers, clinicians, managers and commissioners. Immediate verbal feedback was provided and main themes summarised in individual reports to host teams using the following headings: team values, strengths, dreams and development plans. A thematic analysis was conducted on team reports and a project report produced which summarised the stages and results of this regional initiative.

Findings

All participants rated the experience as positive; it enhanced staff motivation and led to service development and improvement.

Research limitations/implications

The experiences of these 12 EIP teams may not necessarily be generalisable to other services/regions but this positive approach to service improvement could be widely applied.

Practical implications

AE is applicable in large-scale QI initiatives.

Originality/value

To the authors knowledge this is the first time that AE has been applied to large-scale mental health service improvement and innovation.
Experience-based co-design to improve a pulmonary rehabilitation programme
Authors: Williams Sharon , Turner Alice M. , Beadle Helen
Published: May 2019

Purpose

The purpose of this paper is to investigate patient perspectives on attending pulmonary rehabilitation (PR). This qualitative case study identifies the benefits and challenges to attending PR and presents areas of improvements as recommended by patients.

Design/methodology/approach

A qualitative case study of a UK case study based on a PR programme based on undertaking focus groups (n=3) and interviews (n=15) with current and former patients.

Findings

The findings report patient perspectives of the challenges and benefits of attending a PR programme along with recommendations on how the service could be improved.

Research limitations/implications

The authors focussed solely on a UK PR programme, so the findings might not be applicable to other countries if PR is organised and provided in a unique way or setting.

Practical implications

This paper provides valuable insights to patient perspectives offrom patients attending PR programmes, which are useful to those running and designing these services.

Originality/value

The findings identify the benefits and challenges for patients attending PR programmes and suggest areas where improvements can be made.
An exploration of how domains of quality of care relate to overall care experience
Authors: Shepherd Ashley Jill , Cowie Julie , Beattie Michelle
Published: May 2019

Purpose

The purpose of this paper is to determine the relative influence of the different domains of healthcare quality from the Care Experience Feedback Improvement Tool (CEFIT) and identify key predictors of healthcare quality from the patients’ perspective. Measurement is necessary to determine whether the quality of healthcare is improving. The CEFIT was developed as a brief measure of patient experience. It is important to determine the relative influence of the different domains of healthcare quality to further clarify how the CEFIT can be used and identify key predictors of healthcare quality from the patients’ perspective.

Design/methodology/approach

In sum, 802 people with a healthcare experience during the previous 12 months were telephoned to complete the CEFIT questions and an additional 11-point global rating of patient experience. To estimate the influence of different domains of healthcare quality on patient overall ratings of quality of healthcare experience, the authors regressed the overall rating of patient experience with each component of quality (safety, effectiveness, timely, caring, enables system navigation and person-centred).

Findings

The authors found that all of the domains of the CEFIT influenced patient experience ratings of healthcare quality. Specifically, results show the degree of influence, the impact of demographics and how high scores for overall rating of patient experience can be predicted.

Originality/value

The findings suggest that all of the CEFIT domains are important in terms of capturing the wholeness of the patient experience of healthcare quality to direct local quality improvement.
Reworks causes and related costs in construction: case of Parand mass housing project in Iran
Authors: Balouchi Mohammad , Gholhaki Majid , Niousha Ali
Published: May 2019

Purpose

The purpose of this paper is to identify the main reworks and their causes in a case study of the ongoing mass housing project in Iran. Using the real data captured from the project, the most important causes for reworks have been computed and prioritized.

Design/methodology/approach

More than 900 non-conformance forms filled in the construction site have been used to categorize reworks. Then, the frequency and cost of each rework group in the project have been estimated. Finally, using these data, the primary classification and sorting of the main causes of reworks have been specified.

Findings

Results show “Poor site supervision and inspection” with 24 percent of costs had the most impact and “unclear project management process” with about 6 percent of costs had the least impact on the formation of non-conformances. “Cost of each incidence” (COI) ranged from 0.67 for “The need to categorize the complicated operations” to 1.86 for “Unclear project management process.”

Research limitations/implications

The causes of rework which are not in contractor’s hand (like change orders from the client) have not been considered in this study.

Originality/value

Although some works have been done in rework causes, the key elements and causes of reworks in mass housing projects in developing countries have not been yet fully specified through the real data. Knowing the root causes of reworks can help project managers to remove them and reduce reworks costs in future projects. COI which is defined here for the first time and computed in a relative concept could be a good criterion to compare rework causes between two or more similar projects.