bluuebunny/crossref_metadata_2025 huggingface dataset:
NG-STAR genotypes are associated with MDR in Neisseria gonorrhoeae isolates collected in 2017 in Shanghai
Authors: Yang Yijing , Yang Yang , Martin Irene , Dong Yuan , Diao Nannan , Wang Ying , Demczuk Walter , Gu Weiming
Published: November 2019

Objectives

To determine the association of Neisseria gonorrhoeae antimicrobial resistance and genotypes using N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR).

Methods

We characterized 124 N. gonorrhoeae isolates for their antimicrobial susceptibility profiles and NG-STAR ST characteristics using the guidelines of CLSI and EUCAST. The NG-STAR STs of seven loci were analysed. N. gonorrhoeae multiantigen sequence typing (NG-MAST) and MLST analysis was conducted in isolates with specific NG-STAR STs.

Results

NG-STAR differentiated 124 N. gonorrhoeae isolates into 84 STs, of which 66 STs were novel to the NG-STAR database. NG-STAR ST-199, ST-348, ST-428, ST-497 and ST-1138 were the predominant STs. Three N. gonorrhoeae isolates with ceftriaxone and cefixime MICs ≥1.0 mg/L were grouped as NG-STAR ST-233. NG-STAR ST-202 isolates (n=4) were associated with high azithromycin MICs and had an identical NG-MAST ST. The NG-STAR ST-348 group (n=5) comprised more isolates with reduced susceptibility to cefixime (n=4) than cefixime-susceptible isolates (n=1).

Conclusions

NG-STAR analysis differentiated N. gonorrhoeae isolates in settings with a high prevalence of antimicrobial resistance. Specific NG-STAR STs are associated with reduced susceptibility to ceftriaxone or cefixime and resistance to azithromycin in N. gonorrhoeae.
Effect of redox imbalance on protein modifications in lymphocytes of psoriatic patients
Authors: Wójcik Piotr , Gęgotek Agnieszka , Wroński Adam , Jastrząb Anna , Żebrowska Agnieszka , Skrzydlewska Elżbieta
Published: November 2019

Lymphocytes are one of the most important cells involved in the pathophysiology of psoriasis; therefore, the aim of this study was to assess the redox imbalance and protein modifications in the lymphocytes of patients with psoriasis vulgaris (PsV) or psoriatic arthritis (PsA). The results show a stronger shift in redox status to pro-oxidative conditions (observed as an increased reactive oxygen species level, a decrease in catalase activity and lower levels of glutathione peroxidase and vitamin E compared with healthy controls) in the lymphocytes of PsA than PsV patients. It is also favoured by the enhanced level of activators of the Nrf2 transcription factor in lymphocytes of PsV compared with decreased of these proteins level in PsA. Moreover, the differential modifications of proteins by lipid peroxidation products 4-oxononenal (mainly binding proteins) and malondialdehyde (mainly catalytic proteins with redox activity), promoted a pro-apoptotic pathway in lymphocytes of PsV, which was manifested by enhanced expression of pro-apoptotic caspases, particularly caspase 3. Taken together, differences in Nrf2 pathway activation may be responsible for the differential level of redox imbalance in lymphocytes of patients with PsV and PsA. This finding may enable identification of a targeted therapy to modify the metabolic pathways disturbed in psoriasis.
Radiation pattern analyses for seismic multi-parameter inversion of HTI anisotropic media
Authors: Gao Fengxia , Wang Yanghua
Published: November 2019

In seismic waveform inversion, selecting an optimal multi-parameter group is a key step to derive an accurate subsurface model for characterising hydrocarbon reservoirs. There are three parameterizations for the horizontal transverse isotropic (HTI) media, and each parameterization consists of five parameters. The first parameterization (P-I) consists of two velocities and three anisotropy parameters, the second (P-II) consists of five elastic coefficients and the third (P-III) consists of five velocity parameters. The radiation patterns of these three parameterizations indicate a strong interference among five parameters. An effective inversion strategy is a two-stage scheme that first inverts for the velocities or velocity-related parameters and then inverts for all five parameters simultaneously. The inversion results clearly demonstrate that P-I is the best parameterization for seismic waveform inversion in HTI anisotropic media.
An Examination of Sex Differences in a Disease-Specific Model of Disordered Eating Behaviors in Type 1 Diabetes
Authors: Smith Laura B , Foster Nicole , Bollepalli Sureka , Fitterman-Harris Hannah F , Rancourt Diana
Published: November 2019

Objective

Preliminary evidence supports the integration of type 1 diabetes (T1D) disease-specific factors into eating disorder risk models. The current study explored whether cross-sectional associations among constructs included in the modified dual pathway model of eating disorder risk for individuals with T1D are similar across sex among adolescents and young adults with T1D.

Methods

Original study participants were recruited from the T1D Exchange Clinic Network, a U.S. registry of individuals with T1D. Online surveys included measures of general eating disorder risk factors, hypothesized T1D-specific risk factors, and a T1D-specific eating disorder questionnaire. The current study is a secondary analysis with the adolescents (13–17 years; n = 307; 46.9% female) and young adults (18–25 years; n = 313; 62.6% female) from the original sample. In the absence of strong measurement invariance for all measures of interest, sex-specific path models were estimated among the adolescent and young adult cohorts.

Results

Only two paths emerged as significant in the female, but not male, adolescent model. In the young adult cohort, all significant paths were the same across sex.

Conclusions

Both general and T1D-specific risk factors are associated with disordered eating behaviors in the T1D population. Patterns of associations were similar across male and female youth with T1D, suggesting that sex-specific prevention approaches to disordered eating behaviors among T1D youth may not be warranted.
A statistical method to detect non-stationarities of gamma-ray burst jets
Authors: Budai A , Raffai P , Borgulya B , Dawes B A , Szeifert G , Varga V
Published: November 2019

We propose a method to detect possible non-stationarities of gamma-ray burst jets. Assuming that the dominant source of variability in the prompt gamma light curve is the non-stationarity of the jet, we show that there should be a connection between the variability measure and the characteristic angle of the jet derived from the jet break time of the afterglow. We carried out Monte Carlo simulations of long gamma-ray burst observations assuming three radial luminosity density profiles for jets and randomizing all burst parameters, and created samples of gamma light curves by simulating jets undergoing Brownian motions with linear restoring forces. We were able to demonstrate that the connection between the variability and the characteristic angle is an anti-correlation in case of uniform and power-law jet profiles, and a correlation in case of a Gaussian profile. We have found that as low as 50 (144) gamma-ray burst observations with jet angle measurements can be sufficient for a 3σ (5σ) detection of the connection. The number of observations required for the detection depends on the underlying jet beam profile, ranging from 50 (144) to 237 (659) for the four specific profile models we tested.
Diet and Adaptive Evolution of Alanine-Glyoxylate Aminotransferase Mitochondrial Targeting in Birds
Authors: Wang Bing-Jun , Xia Jing-Ming , Wang Qian , Yu Jiang-Long , Song Zhiyin , Zhao Huabin
Published: November 2019

Adaptations to different diets represent a hallmark of animal diversity. The diets of birds are highly variable, making them an excellent model system for studying adaptive evolution driven by dietary changes. To test whether molecular adaptations to diet have occurred during the evolution of birds, we examined a dietary enzyme alanine-glyoxylate aminotransferase (AGT), which tends to target mitochondria in carnivorous mammals, peroxisomes in herbivorous mammals, and both mitochondria and peroxisomes in omnivorous mammals. A total of 31 bird species were examined in this study, which included representatives of most major avian lineages. Of these, 29 have an intact mitochondrial targeting sequence (MTS) of AGT. This finding is in stark contrast to mammals, which showed a number of independent losses of the MTS. Our cell-based functional assays revealed that the efficiency of AGT mitochondrial targeting was greatly reduced in unrelated lineages of granivorous birds, yet it tended to be high in insectivorous and carnivorous lineages. Furthermore, we found that proportions of animal tissue in avian diets were positively correlated with mitochondrial targeting efficiencies that were experimentally determined, but not with those that were computationally predicted. Adaptive evolution of AGT mitochondrial targeting in birds was further supported by the detection of positive selection on MTS regions. Our study contributes to the understanding of how diet drives molecular adaptations in animals, and suggests that caution must be taken when computationally predicting protein subcellular targeting.
A pre-catalytic non-covalent step governs DNA polymerase β fidelity
Authors: Alnajjar Khadijeh S , Krylov Ivan S , Negahbani Amirsoheil , Haratipour Pouya , Kashemirov Boris A , Huang Ji , Mahmoud Mariam , McKenna Charles E , Goodman Myron F , Sweasy Joann B
Published: November 2019

DNA polymerase β (pol β) selects the correct deoxyribonucleoside triphosphate for incorporation into the DNA polymer. Mistakes made by pol β lead to mutations, some of which occur within specific sequence contexts to generate mutation hotspots. The adenomatous polyposis coli (APC) gene is mutated within specific sequence contexts in colorectal carcinomas but the underlying mechanism is not fully understood. In previous work, we demonstrated that a somatic colon cancer variant of pol β, K289M, misincorporates deoxynucleotides at significantly increased frequencies over wild-type pol β within a mutation hotspot that is present several times within the APC gene. Kinetic studies provide evidence that the rate-determining step of pol β catalysis is phosphodiester bond formation and suggest that substrate selection is governed at this step. Remarkably, we show that, unlike WT, a pre-catalytic step in the K289M pol β kinetic pathway becomes slower than phosphodiester bond formation with the APC DNA sequence but not with a different DNA substrate. Based on our studies, we propose that pre-catalytic conformational changes are of critical importance for DNA polymerase fidelity within specific DNA sequence contexts.
Global volatility accounting and structural transformation
Authors: Harchaoui Tarek M
Published: November 2019

This paper examines whether the modern phase of globalization that started in the mid-1980s altered the canonical result which emphasizes that macroeconomic volatility declines with development. The application of a framework that gives due consideration to comovements and structural transformation to a near-universe sample of economies at different stages of economic development suggests the following set of results. First, with an explicit account for the roles of structural transformation and comovements, macroeconomic volatility declines during the modern phase of globalization for the Centre while it increases for the Periphery. Second, macroeconomic volatility of the Periphery declines with development only where structural transformation is ruled out—an unrealistic situation. Third, comovements are found to be quantitatively important, albeit without altering the fact that structural transformation constitutes the primary vehicle of transmissions of volatility from the Centre to the Periphery, where China emerges as the epicentre.
The Effect of Botulinum Toxin Injection into the Common Extensor Tendon in Patients with Chronic Lateral Epicondylitis: A Randomized Trial
Authors: Lee Sang Hoon , Choi Hyun Hee , Chang Min Cheol
Published: November 2019

Background

Botulinum toxin (BTX) is widely used for pain control in various musculoskeletal disorders.

Objectives

We evaluated the analgesic effect of botulinum toxin type A (BTX-A) in chronic lateral epicondylitis and compared the effect between 10 and 50 IU of BTX-A.

Methods

Sixty subjects with chronic lateral epicondylitis were included and underwent a BTX-A injection in the common extensor tendon. The subjects were randomly allocated into two groups: the small-dose group (SD group; 30 subjects, 10 IU) and large-dose group (LD group; 30 subjects, 50 IU). Treatment outcomes were evaluated by measuring the pain level using the numeric rating scale (NRS) and measuring grip strength before and one, two, three, four, five, and six months after treatment.

Results

Subjects in both groups showed a significant decrease in NRS scores at all evaluation time points after treatment. The reduction in NRS scores was significantly greater in the LD group at one, two, three, and four months after treatment. Six months after treatment, 19 subjects (63.3%) in the SD group and 21 (70%) in the LD group reported successful pain relief (pain relief ≥50%). The rate of successful pain relief was not significantly different between the two groups. Grip strength was more increased in the LD group at one, two, three, four, and six months after treatment.

Conclusions

BTX-A injection into the common extensor tendon can be a good treatment option for chronic lateral epicondylitis. The 50-IU BTX-A injection achieved a better outcome than the 10-IU injection.
Testing for Multiple-Horizon Predictability: Direct Regression Based versus Implication Based
Authors: Xu Ke-Li
Published: November 2019

Research in finance and macroeconomics has routinely employed multiple horizons to test asset return predictability. In a simple predictive regression model, we find the popular scaled test can have zero power when the predictor is not sufficiently persistent. A new test based on implication of the short-run model is suggested and is shown to be uniformly more powerful than the scaled test. The new test can accommodate multiple predictors. Compared with various other widely used tests, simulation experiments demonstrate remarkable finite-sample performance. We reexamine the predictive ability of various popular predictors for aggregate equity premium.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Active Solidarity: Intersectional Solidarity in Action
Authors: Einwohner Rachel L. , Kelly-Thompson Kaitlin , Sinclair-Chapman Valeria , Tormos-Aponte Fernando , Weldon S. Laurel , Wright Jared M. , Wu Charles
Published: November 2019

While solidarity lies at the heart of collective action, it is not easily achieved. Social movements are characterized not only by difference within activist ranks but also by power asymmetries that reflect broader domination and distrust. The concept of intersectional solidarity is central to contemporary social justice movements’ efforts to negotiate these divisions, but how can it be achieved? To answer this question, we offer some guidelines for enacting intersectional solidarity, drawing on a theoretically grounded examination of three contemporary social movements in the United States and abroad (Occupy, Gezi Park, and the Women’s March).
Why Is Japan’s Housing Vacancy Rate So High? A History of Postwar Housing Policy
Authors: ZHANG Beibei
Published: November 2019

This article provides an explanation for Japan’s current vacant housing crisis. While existing explanations usually ascribe the crisis to demographic factors or individual governmental policies, this article seeks to transcend those explanations by situating the vacant housing phenomenon within a broader social, economic, and historical context. Drawing on historical materials, the empirical analysis deciphers how the state has subordinated housing development to the overarching objective of economic growth through the manipulation of housing finance policies and land use planning regulations during the postwar period. The article argues that today’s vacant housing crisis is the result of the state’s pro-growth housing policies throughout the postwar period.
Lso-HPE1, an Effector of ‘Candidatus Liberibacter solanacearum’, Can Repress Plant Immune Response
Authors: Levy Julien G. , Gross Rachel , Mendoza-Herrera Azucena , Tang Xiaotian , Babilonia Kevin , Shan Libo , Kuhl Joseph C. , Dibble Margaret S. , Xiao Fangming , Tamborindeguy Cecilia
Published: November 2019

‘Candidatus Liberibacter solanacearum’ is a plant pathogen affecting the families Solanaceae and Apiaceae in different parts of the world. ‘Ca. L. solanacearum’ is a Gram-negative, fastidious α-proteobacterium that is vectored by different psyllid species. Plant-pathogenic bacteria are known for interfering with the host physiology or defense mechanisms, often by secreting bacterial effectors. Effector proteins are critical for virulence; therefore, the identification of effectors could help with disease management. In this study, we characterized the Sec-translocon-dependent ‘Ca. L. solanacearum’–hypothetical protein effector 1 (Lso-HPE1). We compared this protein sequence in the different ‘Ca. L. solanacearum’ haplotypes. We predicted the signal peptide and validated its function using Escherichia coli’s alkaline phosphatase fusion assay. Agrobacterium tumefaciens-mediated transient expression in Nicotiana benthamiana demonstrated that Lso-HPE1 from ‘Ca. L. solanacearum’ haplotypes A and B were able to inhibit the induction of cell death in plants. We also compared gene expression of the Lso-HPE1- transcripts in ‘Ca. L. solanacearum’ haplotypes A and B in tomato and in the vector Bactericera cockerelli. This work validates the identification of a Sec-translocon-dependent ‘Ca. L. solanacearum’ protein possibly involved in suppression of plant cell death.
Streptomyces roseicoloratus sp. nov., isolated from cotton soil
Authors: Zhang Qiao-Yan , Liu Chao-feng , Wang Yang , Xia Zhan-Feng , Huang Yao-Jie , Luo Xiao-Xia
Published: November 2019

A novel bacterium, designated TRM 44457T, belonging to the genus

Streptomyces

, was isolated from soil sampled in cotton fields in Xinjiang, PR China. Comparative 16S rRNA gene sequence analysis indicated that strain TRM 44457T was phylogenetically most closely related to

Streptomyces laurentii

LMG 19959T (99.38 % sequence similarity); however, strain TRM 44457T had a relatively low DNA–DNA relatedness value with

S. laurentii

LMG 19959T as determined by calculating the average nucleotide identity value (84.42 %). Strain TRM 44457T possessed ll-diaminopimelic acid as the diagnostic cell-wall diamino acid, MK-9 (H6) and MK-9 (H10) as the major menaquinone. The polar lipids included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphotidylinositol, phosphatidylinositol mannosides and an unidentified phospholipid. The major fatty acids were anteiso-C15:0, iso-C16:0, anteiso-C17:0, iso-C15:0, C16:0, iso-C17:0, cyclo-C17:0 and anteiso-C17:1ω9c. The genomic DNA G+C content was 72.6 mol%. Based on the evidence from this polyphasic study, strain TRM 44457T represents a novel species of the

Streptomyces

, for which the name Streptomyces roseicoloratus is proposed. The type strain is TRM 44457T (=KCTC 39904T=CCTCC AA 2016040T).
Chlamydia trachomatis: when the virulence-associated genome backbone imports a prevalence-associated major antigen signature
Authors: Borges Vítor , Cordeiro Dora , Salas Ana Isabel , Lodhia Zohra , Correia Cristina , Isidro Joana , Fernandes Cândida , Rodrigues Ana Maria , Azevedo Jacinta , Alves João , Roxo João , Rocha Miguel , Côrte-Real Rita , Vieira Luís , Borrego Maria José , Gomes João Paulo
Published: November 2019

Chlamydia trachomatis

is the most prevalent sexually transmitted bacterium worldwide and the causative agent of trachoma. Its strains are classified according to their ompA genotypes, which are strongly linked to differential tissue tropism and disease outcomes [ocular disease, urogenital disease and lymphogranuloma venereum (LGV)]. While the genome-based species phylogenetic tree presents four main clades correlating with tropism/prevalence, namely ocular, LGV, urogenital T1 (more prevalent genotypes) and urogenital T2 (less prevalent genotypes), inter-clade exchange of ompA is considered a rare phenomenon probably mediating marked tropism alterations. An LGV epidemic, associated with the clonal expansion of the L2b genotype, has emerged in the last few decades, raising concerns particularly due to its atypical clinical presentation (ulcerative proctitis) and circulation among men who have sex with men (MSM). Here, we report an LGV outbreak, mostly affecting human immunodeficiency virus-positive MSM engaging in high-risk sexual practices, caused by an L2b strain with a rather unique non-LGV ompA signature that precluded the laboratory notification of this outbreak as LGV.

C. trachomatis

whole-genome capture and sequencing directly from clinical samples was applied to deeply characterize the genomic backbone of this novel LGV outbreak-causing clone. It revealed a chimeric genome structure due to the genetic transfer of ompA and four neighbouring genes from a serovar D/Da strain, likely possessing the genomic backbone associated with the more prevalent urogenital genotypes (T1 clade), to an LGV (L2b) strain. The hybrid L2b/D-Da strain presents the adhesin and immunodominant antigen MOMP (major outer membrane protein) (encoded by ompA) with an epitope repertoire typical of non-invasive genital strains, while keeping the genome-dispersed virulence fingerprint of a classical LGV strain. As previously reported for inter-clade ompA exchange among non-LGV clades, this novel

C. trachomatis

genomic mosaic involving a contemporary epidemiologically and clinically relevant LGV strain may have implications on its transmission, tissue tropism and pathogenic capabilities. The emergence of variants with epidemic and pathogenic potential highlights the need for more focused surveillance strategies to capture

C. trachomatis

evolution in action.
TP63, SOX2 and KLF5 Establish Core Regulatory Circuitry and Construct Cancer Specific Epigenome in Esophageal Squamous Cell Carcinoma
Authors: Jiang Yan-Yi , Jiang Yuan , Li Chun-Quan , Zhang Ying , Dakle Pushkar , Kaur Harvinder , Deng Jian-Wen , Lin Ruby Yu-Tong , Han Lin , Xie Jian-Jun , Mayakonda Anand , Hazawa Masaharu , Xu Liang , Li YanYu , Aswad Luay , Jeitany Maya , Kanojia Deepika , Guan Xin-Yuan , Fullwood Melissa J. , Lin De-Chen , Koeffler H. Phillip
Published: November 2019

Transcriptional network is controlled by master transcription factors (TFs) andcis-regulatory elements through interacting with target sequences and recruiting epigenetic regulators. By integration of enhancer profiling and chromatin accessibility, we establish super-enhancer (SE) mediated core regulatory circuitry (CRC) for esophageal squamous cell carcinoma (ESCC) and identify tumor cells-dependent CRC TFs-TP63, SOX2 and KLF5. They preferentially co-occupy SE loci and form a positive interconnected auto-regulatory loop through SEs to orchestrate chromatin and transcriptional programming. SE-associated oncogene-ALDH3A1is identified as a novel CRC target contributing to ESCC viability. Using circular chromosome conformation capture sequencing (4C-seq) and CRISPR/Cas9 genome editing, the direct interaction betweenTP63promoter and functional enhancers which is mediated by CRC TFs is identified. Deletion of each enhancer decreases expression of CRC TFs and impairs cell viability, phenocopying the knockdown of each CRC TF. Targeting epigenetic regulation by inhibition of either the BET bromodomain or HDAC disrupts the CRC program and its dependent global epigenetic modification, consequently suppressing ESCC tumor growth. Importantly, combination of both compounds result in synergistic anti-tumor effect.

Graphical Abstract

HIGHLIGHTS

Super-enhancers mediated transcriptional regulatory circuitry is established for ESCC

TP63, SOX2 and KLF5 as CRC TFs co-localize super-enhancer loci to orchestrate chromatin accessibility and transcriptional dysregulation

Complex interaction between functional enhancers andTP63promoter is mediated by CRC TFs

ALDH3A1is a key downstream target of ESCC CRC and is essential for ESCC cell survival

BET degrader-ARV-771 and HDAC inhibitor-Romidepsin synergistically inhibit ESCC tumor growth
The Academic Career Readiness Assessment: Clarifying training expectations for future life sciences faculty
Authors: Clement Laurence , Dorman Jennie B. , McGee Richard
Published: November 2019

We describe here the development and validation of the Academic Career Readiness Assessment (ACRA) rubric, an instrument that was designed to provide more equity in mentoring, transparency in hiring, and accountability in training of aspiring faculty in the life sciences. We report here the results of interviews with faculty at 20 U.S. institutions which resulted in the identification of 14 qualifications and levels of achievement required for obtaining a faculty position at three groups of institutions: research-intensive (R), teaching-only (T), and research and teaching-focused (RT). T institutions hire candidates on teaching experience and pedagogical practices, and on their ability to serve diverse student populations. RT institutions hire faculty on both research and teaching-related qualifications, as well as on the ability to support students in the laboratory. R institutions hire candidates mainly on their research achievements and potential, which may limit the diversification of the life science academic pathway.
Tandem electrospinning for heterogeneous nanofiber patterns
Authors: Wieringa Paul , Truckenmuller Roman , Micera Silvestro , van Wezel Richard , Moroni Lorenzo
Published: November 2019

Smart nanofibrillar constructs can be a promising technological solution for many emerging and established fields, facilitating the potential impact of nano-scale strategies to address relevant technological challenges. As a fabrication technique, electrospinning (ESP) is relatively well-known, accessible, economic, and fast, though until now has shown limitation over control and design of the fibrillar constructs which can be produced. Here, we introduce “Tandem Electrospinning” (T-ESP), a novel technique able to create increasingly complex patterns of fibrous polymeric constructs on a micro and nano-scale. Modifying a standard ESP configuration results in a focusing electric field that is able to spatially define the deposition pattern of multiple polymer jets simultaneously. Additional spatially defined heterogeneity is achieved by tuning polymer solution properties to obtain a gradient of fiber alignment. Heterogeneous fibrous meshes are created with either random, aligned, or a divergent fiber patterns. This approach holds potential for many fields, with application examples shown for Tissue Engineering and Separation Technologies. The technique outlined here provides a rapid, versatile, and accessible method for polymeric nanofabrication of patterned heterogeneous fibrous constructs. Polymer properties are also shown to dictate fiber alignment, providing further insight into the mechanisms involved in the electrospinning fabrication process.
The natural compound Notopterol targets JAK2/3 to ameliorate macrophage-induced inflammation and arthritis
Authors: Wang Qiong , Zhou Xin , Yang Long , Zhao Yongjian , Xiao Jun , Shi Qi , Liang Qianqian , Wang Yongjun , Wang Hongyan
Published: November 2019

Notopterol (NOT) is one of the main constituents of the traditional Chinese medicinal herbNotopterygium incisum Ting ex H.T. Changhas anti-rheumatism activity, but the target of NOT remains unknown. Here we have demonstrated that orally or intraperitoneal administration of NOT exhibits significant therapeutic effects on the collagen-induced arthritis (CIA) model in both DBA/1J and C57/BL6 mice. NOT treatmentin vivoandin vitroreduces production of inflammatory cytokines and chemokines in TNFα- or LPS/IFNγ-stimulated macrophages via blocking the JAK2/3-STAT3/5 activation. Mechanistically, NOT directly binds JAK2 to inhibit its activity via Arg980, Asn981, and Leu932 in the JH1 domain. Importantly, expression of the L938A/R980A/N981A mutant in zebrafish significantly inhibited thein vivoinflammatory response after LPS injection, which showed no further inhibitory effect upon NOT treatment. Combination of NOT and an anti-TNFα antibodies could achieve a better therapeutic effect than anti-TNFα alone in the CIA model. We therefore suggest that as a specific JAK2/3 inhibitor, the natural compound NOT ameliorates pathology of RA, which might be useful to treat other JAK2/3-related diseases.
Spatial modulation of visual signals arises in cortex with active navigation
Authors: Diamanti E. Mika , Reddy Charu Bai , Schröder Sylvia , Muzzu Tomaso , Harris Kenneth D. , Saleem Aman B. , Carandini Matteo
Published: November 2019

During navigation, the visual responses of neurons in primary visual cortex (V1) are modulated by the animal’s spatial position. Here we show that this spatial modulation is similarly present across multiple higher visual areas but largely absent in the main thalamic pathway into V1. Similar to hippocampus, spatial modulation in visual cortex strengthens with experience and requires engagement in active behavior. Active navigation in a familiar environment, therefore, determines spatial modulation of visual signals starting in the cortex.
PCK1 and DHODH drive colorectal cancer liver metastatic colonization and nucleotide biosynthesis under hypoxia
Authors: Yamaguchi Norihiro , Weinberg Ethan M , Nguyen Alexander , Liberti Maria V , Goodarzi Hani , Janjigian Yelena Y , Paty Philip B , Saltz Leonard B , Kingham T Peter , Loo Jia Min , de Stanchina Elisa , Tavazoie Sohail F
Published: November 2019

Colorectal cancer (CRC) is a major cause of human death. Mortality is primarily due to metastatic organ colonization, with liver being the primary organ affected. We modeled metastatic CRC (mCRC) liver colonization using patient-derived primary and metastatic tumor xenografts (PDX). Such PDX modeling predicted patient survival outcomes.In vivoselection of multiple PDXs for enhanced metastatic capacity upregulated the gluconeogenic enzyme PCK1, which enhanced metastatic hypoxic survival by driving anabolic pyrimidine nucleotide biosynthesis. Consistently, highly metastatic tumors upregulated multiple pyrimidine biosynthesis intermediary metabolites. Therapeutic inhibition of the pyrimidine biosynthetic enzyme DHODH with oral leflunomide substantially impaired CRC liver metastatic colonization and hypoxic survival. Our findings provide a potential mechanistic basis for the epidemiologic association of anti-gluconeogenic drugs with improved CRC metastasis outcomes, reveal the exploitation of a gluconeogenesis enzyme for pyrimidine biosynthesis during hypoxia, and implicate DHODH and PCK1 as metabolic therapeutic targets in colorectal cancer metastasis.
Changes in spinal cord hemodynamic reflect modulation of spinal network with different parameters of epidural stimulation
Authors: Tang Shanshan , Cuellar Carlos A. , Song Pengfei , Islam Riazul , Huang Chengwu , Wen Hai , Knudsen Bruce E. , Gong Ping , Lok U-Wai , Chen Shigao , Lavrov Igor A.
Published: November 2019

In this study functional ultrasound (fUS) imaging has been implemented to explore the local hemodynamic response induced by electrical epidural stimulation and to study real-time in vivo functional changes of the spinal cord, taking advantage of the superior spatiotemporal resolution provided by fUS. By quantifying the hemodynamic and electromyographic response features, we tested the hypothesis that the transient hemodynamic response of the spinal cord to electrical epidural stimulation could reflect modulation of the spinal circuitry and accordingly respond to the changes in parameters of electrical stimulation. The results of this study for the first time demonstrate that the hemodynamic response to electrical stimulation could reflect functional organization of the spinal cord. Response in the dorsal areas to epidural stimulation was significantly higher and faster compared to the response in ventral spinal cord. Positive relation between the hemodynamic and the EMG responses was observed at the lower frequencies of epidural stimulation (20 and 40 Hz), which according to our previous findings can facilitate spinal circuitry after spinal cord injury, compared to higher frequencies (200 and 500 Hz). These findings suggest that different mechanisms could be involved in spinal cord hemodynamic changes during different parameters of electrical stimulation and for the first time provide the evidence that functional organization of the spinal cord circuitry could be related to specific organization of spinal cord vasculature and hemodynamic.

Significance Statement

Electrical epidural stimulation (EES) has been successfully applied to control chronic refractory pain and was evolved to alleviate motor impairment after spinal cord injury, in Parkinson’s disease, and other neurological conditions. The mechanisms underlying the EES remain unclear, and current methods for monitoring EES are limited in sensitivity and spatiotemporal resolutions to evaluate functional changes in response to EES. We tested the hypothesis that the transient hemodynamic response of the spinal cord to EES could reflect modulation of the spinal cord circuitry and accordingly respond to the changes in parameters of EES. The proposed methodology opens a new direction for quantitative evaluation of the spinal cord hemodynamic in understanding the mechanisms of spinal cord functional organization and effect of neuromodulation.
Her9/Hes4 is required for retinal photoreceptor development, maintenance, and survival
Authors: Coomer Cagney E. , Wilson Stephen G. , Titialii-Torres Kayla F. , Bills Jessica D. , Krueger Laura A. , Petersen Rebecca A. , Turnbaugh Evelyn M. , Janesch Eden L. , Morris Ann C.
Published: November 2019

The intrinsic and extrinsic factors that regulate vertebrate photoreceptor specification and differentiation are complex, and our understanding of all the players is far from complete. Her9, the zebrafish ortholog of human HES4, is a basic helix-loop-helix-orange (bHLH-O) transcriptional repressor that regulates neurogenesis in several developmental contexts. We have previously shown thather9is upregulated during chronic rod photoreceptor degeneration and regeneration in adult zebrafish, but little is known about the role ofher9during retinal development. To better understand the function of Her9 in the retina, we generated zebrafishher9CRISPR mutants.Her9homozygous mutants displayed striking retinal phenotypes, including decreased numbers of rods and red/green cones, whereas blue and UV cones were relatively unaffected. The reduction in rods and red/green cones correlated with defects in photoreceptor subtype lineage specification. The remaining rods and double cones displayed abnormally truncated outer segments, and elevated levels of apoptosis. In addition to the photoreceptor defects,her9mutants also possessed a reduced proliferative ciliary marginal zone, and decreased and disorganized Müller glia. Mutation ofher9was larval lethal, with no mutants surviving past 13 days post fertilization. Our results reveal a previously undescribed role for Her9/Hes4 in photoreceptor differentiation, maintenance, and survival.
Maize Stem Buckling Failure is Dominated by Morphological Factors
Authors: Stubbs Christopher J , Larson Ryan , Cook Douglas D
Published: November 2019

The maize (Zea mays) stem is a biological structure that must both balance biotic and structural load bearing duties. These competing requirements are particularly relevant in the design of new bioenergy crops. With the right balance between structural and biological activities, it may be possible to design crops that are high-yielding and have digestible biomass. But increased stem digestibility is typically associated with a lower structural strength and higher propensity for lodging. This study investigates the hypothesis that geometric factors are much more influential in determining structural strength than tissue properties. To study these influences, both physical and in silico experiments were used. First, maize stems were tested in three-point bending. Specimen-specific finite element models were created based on x-ray computed tomography scans. Models were validated by comparison with in vitro data. As hypothesized, geometry was found to have a much stronger influence on structural stability than material properties. This information reinforces the notion that deficiencies in tissue strength could be offset by manipulation of stalk morphology, thus allowing the creation of stalks with are both resilient and digestible.

Highlight

This study utilized physical and in silico experiments to confirm that geometric parameters are far more influential in determining stalk strength than mechanical tissue stiffnesses.
Nonrigid point set registration based on Laplace mixture model with local constraints
Authors: Xu Chao , Yang Xianqiang , Liu Xiaofeng
Published: November 2019

Purpose

This paper aims to investigate a probabilistic mixture model for the nonrigid point set registration problem in the computer vision tasks. The equations to estimate the mixture model parameters and the constraint items are derived simultaneously in the proposed strategy.

Design/methodology/approach

The problem of point set registration is expressed as Laplace mixture model (LMM) instead of Gaussian mixture model. Three constraint items, namely, distance, the transformation and the correspondence, are introduced to improve the accuracy. The expectation-maximization (EM) algorithm is used to optimize the objection function and the transformation matrix and correspondence matrix are given concurrently.

Findings

Although amounts of the researchers study the nonrigid registration problem, the LMM is not considered for most of them. The nonrigid registration problem is considered in the LMM with the constraint items in this paper. Three experiments are performed to verify the effectiveness and robustness and demonstrate the validity.

Originality/value

The novel method to solve the nonrigid point set registration problem in the presence of the constraint items with EM algorithm is put forward in this work.
Accounting as a tool of state ideology to control captive workers from a House of Correction
Authors: Silva Adriana Rodrigues , Rodrigues Lúcia Lima , Sangster Alan
Published: November 2019

Purpose

The purpose of this paper is to interpret the use of accounting information relating to the House of Correction, a public safety institution established in Rio de Janeiro for the control of workers under a tutelage system (1831–1864). The aim of the House of Correction was to develop a disciplined workforce of former slaves and other “Free Africans”. Various control and information procedures were put in place to monitor its achievement of this goal.

Design/methodology/approach

This study is based on historical archival research, mainly conducted at the National Archive of Rio de Janeiro and at the Brazilian National Library. The study uses Althusser’s ideology concept and the Marxist concept of reproduction of labour to show how accounting information enabled the administrator of the House of Correction to exercise control over the “Free Africans” consistent with the ideologies of the period and place.

Findings

The authors find that the House of Correction pursued a policy of ensuring “Free Africans” were docile, obedient and familiar with State ideology.

Research limitations/implications

The research is based on a single case study and it shows the need for both comparative and interdisciplinary analysis in order to increase an understanding of the use of accounting information in ancient prison contexts, as well as in contemporary situations.

Originality/value

This paper extends our knowledge of the use of accounting for the control of workers, who were either captive or repressed due to their ethnical differences; and it shows how ideology can be imposed through the use of accounting information. The authors extend theory by applying the Marxist and Althusserian concept of reproduction of labour to the case of “Free Africans”.
Bringing religion back in
Authors: Du Xingqiang , Zeng Quan
Published: November 2019

Purpose

The purpose of this paper is to investigate the influence of religious entrepreneurs on bank loans and further examine the moderating effect of entrepreneurial gender.

Design/methodology/approach

In 2010, the Chinese national survey reported the different religious beliefs of private entrepreneurs. Using this set of survey data, the authors obtain a sample of 4,330 Chinese family firms and employ the Tobit regression approach to examine the relationship between the amount of bank loans and the religious background of entrepreneurs. In addition, the authors use the propensity score matching approach to address the endogeneity issue.

Findings

Based on the data from the 2010 national survey, the authors document that the amount of bank loans is significantly higher for Chinese family firms with religious entrepreneurs than for their counterparts. This finding suggests that religious individuals are inclined to be more ethical and honest and Chinese family firms with religious entrepreneurs transfer soft information to banks, and eventually lenders favor religious entrepreneurs with more bank loans. Moreover, the authors reveal that the amount of bank loans is significantly larger for firms with female entrepreneurs than for those without female entrepreneurs. In addition, entrepreneurial gender attenuates the positive relationship between religious entrepreneurs and bank loans.

Originality/value

This study is one of few studies to examine the influence of an entrepreneur’s religious belief on bank credit decisions and adds to previous studies about religious influence on corporate behavior by revealing a positive association between religious entrepreneurs and bank loans. Moreover, this study validates that female entrepreneurs exert positive effects on the amount of bank loans and attenuate the positive influence of religious entrepreneurs on bank loans.
Trust factors for organic foods: consumer buying behavior
Authors: Lee Tsung Hung , Fu Chung-Jen , Chen Yin Yuan
Published: November 2019

Purpose

The purpose of this paper is to assess the relationship between trust factors and buying behavior among consumers in the organic food market in Taiwan.

Design/methodology/approach

The researchers developed a questionnaire using latent variables including the trust factors, utilitarian attitudes, hedonic attitudes, buying behavior and demographic information of consumers of organic foods. Confirmatory factor analysis and the structural equation modeling were conducted using LISREL 8.80 for Windows.

Findings

The empirical results indicated that health content, locally produced products, organic food labels and price premiums positively and significantly affected utilitarian and hedonic attitudes. Both utilitarian attitudes and hedonic attitudes positively and significantly affected respondents’ buying behavior. A series of theoretical implications were identified.

Practical implications

The researchers concluded that providing consumers with practical information related to organic food, establishing local production facilities, developing content, standardizing labeling procedures and promoting a new organic certification system for small-scale producers will encourage more consumers to purchase organic food.

Originality/value

This study first examines the food trust buying behavior of organic foods and related consumption behavior theory questions. It mainly takes the stimulus–organism–response model as the foundation of its approach. Simultaneously, it also conforms to utilitarian behavior theory, and the process by which consumers become better aware of organic foods’ quality.
Low phenylalanine breads as an alternative for patients with phenylketonuria
Authors: Scortegagna Mariana Lima , Oliveira Viviani Ruffo de , Pasini Isadora , Silva Medelin , Rios Alessandro de Oliveira , Doneda Divair
Published: November 2019

Purpose

Patients with phenylketonuria (PKU) require a phenylalanine (Phe)-restricted diet due to its toxic effects on such subjects. Considering the low availability of specific foods for these patients, the purpose of this paper is to make breads with low Phe content while also conducting physicochemical and sensory analysis of the samples.

Design/methodology/approach

Five bread formulations with a common base were prepared, in which manioc –Manihot esculenta(T1); Baroa potato –Arracacia xanthorrhiza(T2); sweet potatoes –Ipomoea batatas(T3); potatoes –Solanum tuberosum(T4); and, finally, yacon potato –Smallanthus sonchifolius(T5) were added.

Findings

The physical analysis showed that the samples had similar weight, height and size values, indicating that the use of different types of vegetables does not compromise the final result of the preparation. The chemical analysis showed that the loaves were low in protein and Phe and, therefore, are considered safe preparations for patients with PKU. In the sensory analysis, all the preparations presented satisfactory characteristics for consumption, specially the one with the addition of potato.

Research limitations/implications

The preparation of breads with low Phe content is a challenging task as it is necessary to exclude formulations with flours that present better technological performance. However, the results in this study showed that it is possible to get around the difficulties and obtain a viable product with easily purchased ingredients. It is known that sensory analysis with PKU patients as judges could have changed these results because their perception can differ from that of general population. The workgroup is continuing this study and we intend to take sensory analysis with PKU patients to future, as they have a pathology, the study needs special care and respectful ethical aspects.

Originality/value

PKU has a direct influence on the daily diet of the patient, interfering with life decisions that go form eating at their home to where and what to eat in environments out of their control. Therefore, creating specific preparations for such patients is a challenge that assists in adherence to dietary therapy.