bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-autonomous induction of epithelial lineage infidelity and hyperplasia by DNA damage
Authors: Seldin Lindsey , Macara Ian G. 
Published: May 2019

ABSTRACTSeveral epithelial tissues contain stem cell reserves to replenish cells lost during normal homeostasis or upon injury. However, how epithelial tissues respond to distinct types of damage, and how stem cell plasticity and proliferation are regulated in these contexts, remain poorly understood. Here, we reveal that genotoxic agents, but not mechanical damage, induce hyperplasia and lineage infidelity in three related epithelial tissues: the mammary gland, interfollicular epidermis and hair follicle. Furthermore, DNA damage also promotes stromal proliferation. In the mammary gland, we find that DNA damage activates multipotency within the myoepithelial population and hyper-proliferation of their luminal progeny, resulting in tissue disorganization. Additionally, in epidermal and hair follicle epithelia, DNA damage induces basal cell hyperplasia with the formation of abnormal, multi-layered K14+/K10+ cells. This behavior does not involve apoptosis or immunity, and is epithelial cell non-autonomous; stromal fibroblasts are both necessary and sufficient to induce the epithelial response. Thus, genotoxic agents that are used chemotherapeutically to promote cancer cell death can have the opposite effect on wild-type epithelial tissue, paradoxically promoting hyperplasia and inducing both stemness and lineage infidelity.
Electrocardiographic characterization of non-selective His bundle pacing. Validation of novel diagnostic criteria
Authors: Jastrzębski Marek , Moskal Paweł , Curila Karol , Fijorek Kamil , Kukla Piotr , Bednarek Agnieszka , Kiełbasa Grzegorz , Bednarski Adam , Baranchuk Adrian , Czarnecka Danuta 
Published: May 2019

AbstractAimsPermanent His bundle (HB) pacing is usually accompanied by simultaneous capture of the adjacent right ventricular (RV) myocardium - this is described as a non-selective (ns)-HB pacing. Our aim was to identify ECG criteria for loss of HB capture during ns-HB pacing.MethodsConsecutive patients with permanent HB pacing were recruited. Surface 12-lead ECGs during ns-HB pacing and loss of HB capture (RV-only capture) were obtained. ECG criteria for loss/presence of HB capture were identified. In the validation phase these criteria and the “HB ECG algorithm” were tested by two blinded observers using a separate, sizable set of ECGs.ResultsA total of 353 ECG (226 ns-HB and 128 RV-only) were obtained from 226 patients with permanent HB pacing devices. QRS notch/slur in left ventricular leads and R-wave peak time in lead V6 were identified as the best features for differentiation. The 2-step HB ECG algorithm based on these features correctly classified 87.1% of cases with sensitivity and specificity of 93.2% and 83.9%, respectively. Moreover, the proposed criteria for definitive diagnosis of ns-HB capture (no QRS slur/notch in leads I, V1, V4-V6andthe R-wave peak time in V6 ≤ 100 ms) presented 100% specificity.ConclusionA novel ECG algorithm for the diagnosis of loss of HB capture and novel criteria for definitive confirmation of HB capture were formulated and validated. Practical application of these criteria during implant and follow-up of patients with HB pacing devices is feasible.Condensed AbstractThe 2-step ECG algorithm for loss of His bundle capture based on surface ECG analysis is proposed and validated. This method correctly classified 87.1% of cases with a sensitivity and specificity of 93.2% and 83.9%, respectively.What’s NewThis is the first study that analyzes QRS characteristics during non-selective His bundle pacing in a sizable cohort of patients.Precise criteria and a novel algorithm for electrocardiographic diagnosis of loss of HB capture during presumed non-selective HB pacing were validated.QRS notch/slur in left ventricular leads was identified as a simple and reproducible feature indicating loss of HB capture or lack/loss of correction of intraventricular conduction disturbances.Assessment of R-wave peak time in lead V6 rather than QRS duration for diagnosis of ns-HB pacing was validated.
An investigation of PS-b-PEO polymersomes for the oral treatment and diagnosis of hyperammonemia
Authors: Matoori Simon , Bao Yinyin , Schmidt Aaron , Fischer Eric J. , Ochoa-Sanchez Rafael , Tremblay Mélanie , Oliveira Mariana , Rose Christopher F. , Leroux Jean-Christophe 
Published: May 2019

AbstractAmmonia-scavenging transmembrane pH-gradient poly(styrene)-b-poly(ethylene oxide) polymersomes were investigated for the oral treatment and diagnosis of hyperammonemia, a condition associated with serious neurologic complications in patients with liver disease as well as in infants with urea cycle disorders. While these polymersomes were highly stable in simulated intestinal fluids at extreme bile salt and osmolality conditions, they unexpectedly did not reduce plasmatic ammonia levels in cirrhotic rats after oral dosing. Incubation in dietary fiber hydrogels mimicking the colonic environment suggested that the vesicles were probably destabilized during the dehydration of the intestinal chyme. Our findings question the relevance of commonly used simulated intestinal fluids for studying vesicular stability. With the encapsulation of a pH-sensitive dye in the polymersome core, the local pH increase upon ammonia influx could be exploited to assess the ammonia concentration in the plasma of healthy and cirrhotic rats as well as in other fluids. Due to its high sensitivity and selectivity, this novel polymersome-based assay could prove useful in the monitoring of hyperammonemic patients and in other applications such as drug screening tests.Graphical abstract
Membrane-type 1 matrix metalloproteinase (MMP-14) modulates tissue homeostasis by a non-proteolytic mechanism
Authors: Attur Mukundan , Lu Cuijie , Zhang Xiaodong , Han Tianzhen , Alexandre Cassidy , Valacca Cristina , Zheng Shuai , Meikle Sarina , Dabovic Branka Brukner , Tassone Evelyne , Yang Qing , Kolupaeva Victoria , Yakar Shoshana , Abramson Steven , Mignatti Paolo 
Published: May 2019

SUMMARYMembrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14), a transmembrane proteinase with a short cytoplasmic tail, is a major effector of extracellular matrix (ECM) remodeling. Genetic silencing of MT1-MMP in mouse (Mmp14−/−) and man causes dwarfism, osteopenia, arthritis and lipodystrophy, abnormalities ascribed to defective collagen turnover. We have previously shown non-proteolytic functions of MT1-MMP mediated by its cytoplasmic tail, where the unique tyrosine (Y573) controls intracellular signaling. The Y573D mutation blocks TIMP2/MT1-MMP-induced Erk1/2 and Akt signaling without affecting proteolytic activity. Here we report that a mouse with the MT1-MMP Y573D mutation (Mmp14Y573D/Y573D) shows abnormalities similar to, but also different from those ofMmp14−/−mice. Skeletal stem cells (SSC) ofMmp14Y573D/Y573Dmice show defective differentiation consistent with the mouse phenotype, which is rescued by wild-type SSC transplant. These results provide the firstin vivodemonstration that MT1-MMP modulates bone, cartilage and fat homeostasis by controlling SSC differentiation through a mechanism independent of proteolysis.
Tropomyosin 1 genetically constrains in vitro hematopoiesis
Authors: Thom CS , Jobaliya CD , Lorenz K , Maguire JA , Gagne A , Gadue P , French DL , Voight BF 
Published: May 2019

AbstractIdentifying causal variants and genes from human genetics studies of hematopoietic traits are important to enumerate basic regulatory mechanisms underlying these traits, and could ultimately augment translational efforts to generate platelets and/or red blood cells in vitro. To identify putative causal genes from these data, we performed computational modelling using available genome-wide association data sets for platelet traits. Our model identified a joint collection of genomic features enriched at established platelet trait associations and plausible candidate variants. Additional studies associating variation at these loci with change in gene expression highlighted the Tropomyosin 1 (TPM1) among our top-ranked candidate genes. CRISPR/Cas9-mediated TPM1 knockout in human induced pluripotent stem cells (iPSCs) enhanced hematopoietic progenitor development, increasing total megakaryocyte as well as erythroid cell yields. Our findings may help explain human genetics associations and identify a novel genetic strategy to enhance in vitro hematopoiesis.
Zinc finger RNA binding protein Zn72D regulates ADAR-mediated RNA editing in neurons
Authors: Sapiro Anne L. , Freund Emily C. , Restrepo Lucas , Qiao Huan-Huan , Bhate Amruta , Li Qin , Ni Jian-Quan , Mosca Timothy J. , Li Jin Billy 
Published: May 2019

AbstractAdenosine-to-inosine RNA editing, catalyzed by ADAR enzymes, alters RNA sequences from those encoded by DNA. These editing events are dynamically regulated, but few trans regulators of ADARs are known in vivo. Here, we screen RNA binding proteins for roles in editing regulation using in vivo knockdown experiments in the Drosophila brain. We identify Zinc-Finger Protein at 72D (Zn72D) as a regulator of editing levels at a majority of editing sites in the brain. Zn72D both regulates ADAR protein levels and interacts with ADAR in an RNA-dependent fashion, and similar to ADAR, Zn72D is necessary to maintain proper neuromuscular junction architecture and motility in the fly. Furthermore, the mammalian homolog of Zn72D, Zfr, regulates editing in mouse primary neurons, demonstrating the conservation of this regulatory role. The broad and conserved regulation of ADAR editing by Zn72D in neurons represents a novel mechanism by which critically important editing events are sustained.
Understanding the basis of CYP26 mediated regulation of lens regeneration usingex vivoeye cultures and 4-oxo-RA
Authors: Thomas Alvin G , Adil Mohd Tayyab , Henry Jonathan J 
Published: May 2019

AbstractPURPOSEXenopushas the remarkable ability to regenerate a lens from the basal cornea epithelial cells in response to signals from the retina. Previous work demonstrated that the Retinoic Acid (RA) metabolizing enzyme CYP26 is expressed in the cornea, and that its activity is required for lens regeneration. Gaps remain in our knowledge as to whether CYP26 is needed only to attenuate RA signaling via RA elimination, or whether it also acts to generate retinoid metabolites, such as 4-oxo-RA, to act as signaling ligands. Other key questions are why CYP26 antagonism, but not exogenous retinoids, can reduce cell division in the cornea, and when during regeneration CYP26 is important.MATERIALS AND METHODSEx vivocultures supplemented with RA, 4-oxo-RA, or the CYP26 inhibitor Liarozole were used to assay the effects of these compounds on lens regeneration. Similarly, corneas were explanted, cultured in the presence of these compounds, and assayed for mitotic changes by counting anti-Histone H3 positive nuclei. qPCRs validated responsiveness to these compounds.RESULTSEx vivocultures showed that when the media was supplemented with the RA metabolite 4-oxo-RA in addition to Liarozole, lens regeneration was still inhibited. 4-oxo-RA also does not rescue the loss of cell division in the cornea that is observed upon CYP26 antagonism. Liarozole inhibited regeneration when added 12 hours after lentectomy, but not when added 48 hours after.CONCLUSIONSThese data show that the necessity of CYP26 is not explained as a generator of 4-oxo-RA for regeneration. Moreover, Liarozole-induced mitotic reduction is not explained by 4-oxo-RA deficiency. These results support a model of RA-independent mitotic regulation by CYP26, though other retinoid metabolites may be active. Finally, CYP26 activity is only needed between 12 and 48 hours post-surgery, showing that its action is required only during the earliest stages of lens regeneration.Financial interestsThe authors declare no competing financial interests.
Risk factors for postoperative meningitis after microsurgery for vestibular schwannoma
Authors: Huang Bowen , Ren Yanming , Wang Chenghong , Lan Zhigang , Hui Xuhui , Liu Wenke , Zhang Yuekang 
Published: May 2019

AbstractOBJECTIVEMeningitis after microsurgery for vestibular schwannoma (VS) is a severe complication and result in high morbidity. But few studies have focused on meningitis after VS surgery alone. The purpose of this study was to identify the risk factors for meningitis after VS surgery.METHODSWe undertook a retrospective analysis of all VS patients, who underwent microsurgery of VS and at least live for 7 days after surgery, between 1st June 2015 and 30st November 2018 at West China Hospital of Sichuan University. Univariate and multivariate analyses were performed to identify the risk factors for postoperative meningitis (POM).RESULTSWe collected 410 patients, 27 of whom had POM. Through univariate analysis, hydrocephalus (p=0. 018), Koos grade IV (p=0.04), The operative duration (> 3 hours p=0.03) and intraoperative bleeding volume (≥ 400ml p=0. 02) were significantly correlated to POM. Multivariate analysis showed that Koos grade IV (p=0.04; OR=3.19; 95% CI 1.032-3.190), operation duration (> 3 hours p=0.03 OR= 7.927; 95% CI 1.043-60.265), and intraoperative bleeding volume (≥ 400ml p=0.02; OR=2.551; 95% CI 1.112-5.850) are the independent influencing factors of POM.CONCLUSIONSKoos grade IV, the duration of operation, and the amount of bleeding were identified as independent risk factors for POM after microsurgery of VS. POM caused a prolonged hospital stay.
Capillary hemoglobin electrophoresis of healthy and anemic dogs: quantification, validation, and reference intervals of hemoglobin fractions
Authors: Oikonomidis Ioannis L. , Tsouloufi Theodora K. , Mylonakis Mathios E. , Kritsepi-Konstantinou Maria 
Published: May 2019

AbstractDespite the advances in canine medicine and the rapid gaining of attention of canine models in biomedical field and particularly in hemoglobin genes research, the studies on canine hemoglobin composition are sparse with ambiguous findings. Our aim was: i) to investigate the electrophoretic pattern of canine hemoglobin and the possible effect of age, sex, and anemia using a capillary electrophoresis assay, and ii) to validate this assay and calculate reference intervals (RIs) for canine hemoglobin fractions. Blood samples were collected from 53 healthy and 42 dogs with regenerative and non-regenerative anemias. The Sebia Capillarys 2 flex-piercing was used for hemoglobin analysis and it was validated using canine blood samples. R statistical language was employed for the statistical analyses. A major hemoglobin fraction (named HbA0) and a minor one (named HbA2) were identified in 100% and 47.4% of samples, respectively. The within-run and between-run CV was 0.1% for HbA0and 9.1% and 11.2% for HbA2, respectively. The extremely narrow range of HbA0and HbA2values hampered a linearity study using canine blood samples. The RIs for HbA0and HbA2were 98.9-100% and 0-1.1%, respectively. HbA0and HbA2values were not correlated with age (P=0.866). No differences were observed in the median HbA0and HbA2between the two sexes (P=0.823), and healthy and anemic dogs (P=0.805). In conclusion, the capillary electrophoresis revealed a major hemoglobin fraction and an inconsistently present minor fraction. No effect of age, sex, or anemia was detected. The assay used was validated and RIs were generated, so as to be suitable for use in future investigations.
High-throughput 16S rRNA gene sequencing reveals gut microbial changes in 6-hydroxydopamine-induced Parkinson’s disease mice
Authors: Choi Jin Gyu , Huh Eugene , Kim Namkwon , Kim Dong-Hyun , Oh Myung Sook 
Published: May 2019

AbstractRecently, there has been a rapid increase in studies on the relationship between brain diseases and gut microbiota, and clinical evidence on gut microbial changes in Parkinson’s disease (PD) has accumulated. 6-hydroxydopamine (6-OHDA) is a widely used neurotoxin that leads to PD pathogenesis, but whether the alterations of gut microbial community in 6-OHDA-treated mice has not been investigated. Here we performed the 16S rRNA gene sequencing to analyze changes in gut microbial community of mice. We found that there were no significant changes in species richness and its diversity in the 6-OHDA-lesioned mice. The relative abundance ofLactobacillus gasseriandL. reuteriprobiotic species in feces of 6-OHDA-lesioned mice was significantly decreased compared with those of sham-operated mice, while the commensal bacteriumBacteroides acidifaciensin 6-OHDA-treated mice was remarkably higher than sham-operated mice. These results provides a baseline for understanding the microbial communities of 6-OHDA-induced PD model to investigate the role of gut microbiota in the pathogenesis of PD.
The impact of credit on the technical efficiency of maize-producing households in Northern Ghana
Authors: Martey Edward , Wiredu Alexander N. , Etwire Prince M. , Kuwornu John K.M. 
Published: May 2019

Purpose
Production credit is essential for enhancing the technical efficiency (TE) and the welfare of smallholder farmers in Africa. The purpose of this paper is to examine the impact of credit on smallholders’ TE using cross-sectional data from 223 maize-producing households in Northern Ghana.

Design/methodology/approach
Due to the exogenous assignment of credit and assumption of homogeneity in farm technologies, the propensity score matching (PSM) analysis was used to compare the average difference in TE between farmers that had received credit and those that had not.

Findings
The results revealed that production credit impacts positively on smallholder farmers’ TE. Access to production credit is significantly influenced by access to markets and extension services, distance to market, asset index and land fragmentation. The provision of credit enhances the timely purchase and efficient allocation of farming inputs to produce the maximum possible output. Per capita income and land fragmentation also play important roles in reducing smallholders’ TE.

Practical implications
To increase efficiency gains, credit programs for agricultural interventions should target resource-poor smallholder farmers. The efficiency gains can be sustained through stronger partnerships with financial institutions. Policy interventions aimed at increasing smallholder farmers’ access to production credit (e.g. through the creation of a conducive investment environment that lowers the lending rate and collateral requirements) must be vigorously pursued.

Originality/value
To the best of authors’ knowledge, this is one of the only recent studies to examine the impact of credit on the TE of farming households by applying the translog stochastic frontier production function and the PSM approaches.
Six Sigma metrics based on lognormal distribution for life tests
Authors: Joghee Ravichandran 
Published: May 2019

PurposeThe purpose of this paper is to propose an approach for studying the Six Sigma metrics when the underlying distribution is lognormal.Design/methodology/approachThe Six Sigma metrics are commonly available for normal processes that are run in the long run. However, there are situations in reliability studies where non-normal distributions are more appropriate for life tests. In this paper, Six Sigma metrics are obtained for lognormal distribution.FindingsIn this paper, unlike the normal process, for lognormal distribution, there are unequal tail probabilities. Hence, the sigma levels are not the same for left-tail and right-tail defects per million opportunities (DPMO). Also, in life tests, while left-tail probability is related to DPMO, the right tail is considered as extremely good PMO. This aspect is introduced and based on which the sigma levels are determined for different parameter settings and left- and right-tail probability combinations. Examples are given to illustrate the proposed approach.Originality/valueThough Six Sigma metrics have been developed based on a normality assumption, there have been no studies for determining the Six Sigma metrics for non-normal processes, particularly for life test distributions in reliability studies. The Six Sigma metrics developed here for lognormal distribution is new to the practitioners, and this will motivate the researchers to do more work in this field of research.
“An undisturbed afternoon of writing”: a qualitative study of professors’ job satisfaction
Authors: Larsson Gerry , Alvinius Aida 
Published: May 2019

PurposeThe purpose of this paper is to model factors that contribute to job satisfaction among university professors.Design/methodology/approachThe approach was qualitative; 12 in-depth interviews were conducted with Swedish university full professors representing 11 different academic subjects.FindingsFive facets of job satisfaction were identified: distal environment (e.g. impact on society and the scientific community), proximal social environment, self (e.g. receiving external credit and experiencing internal pride), the uplifts of daily life and formal conditions (e.g. pay and opportunities to continue after retirement). A model was inductively developed according to which professors’ job satisfaction is influenced by interacting contextual and individual antecedent conditions.Research limitations/implicationsBecause a qualitative approach was used, with a limited number of informants, there is a lack of representativeness and the concepts generated are of a sensitizing rather than a definitive character.Practical implicationsAttention should be paid to university professors’ need for autonomy, otherwise public management control strivings may become counter-productive.Originality/valueA new model of professors’ job satisfaction with a richness of details was developed.
Global financial economic crisis transmission on the transition economy
Authors: Alymkulova Nargiza , Ganiev Junus 
Published: May 2019

Purpose
The global financial crisis hit the economy of the Kyrgyz Republic by the third wave of its transmission in early 2009. The purpose of this study is to examine the impact of the global financial economic crisis on the transition economy of the Kyrgyz Republic. As there is a low level of the Kyrgyz Republic’s integration into the global financial and economic processes, it is obvious that channels of transmissions are different.

Design/methodology/approach
The empirical model is the vector autoregression approach. The quarterly data from 2005 to 2013 of the remittances from abroad, trade volumes, exchange rates, credits, deposits and liquidity of the banking system, gross domestic product (GDP) and foreign direct investment (FDI) were used in the empirical analysis.

Findings
The authors found a significant positive relation between transmission channels such as remittances flow, banking sector, international trade and GDP within the first six months. Thus, a decline in the aforementioned variables has a significant affirmative effect on the country’s GDP. Notwithstanding, the exchange-rate channel adversely influences GDP. Thereby, the depreciation of the national currency leads to an increase in GDP.

Originality/value
The study findings allow the Kyrgyz policymakers to foresee the global crisis transmission through the primary channels of transmission mechanism. Nevertheless, a decrease of the deposit level by 1 per cent leads to 2.91 per cent decline in FDI inflows. On the contrary, an increase of the exchange rate by 1 per cent leads to 1.54 per cent decrease in imports.