bluuebunny/crossref_metadata_2025 huggingface dataset:
A molecular phylogeny of Schizothoracinae (Teleostei: Cypriniformes: Cyprinidae) based on 12 protein-coding mitochondrial genes and RAG1 gene analysis
Authors: Du Yurong , Wang Ting , Qi Delin , Qi Desheng , Li Weilin , Zhong Jiangbin , Chen Juan , Guo Songchang , Ma Jianbin
Published: January 2019

The ever-increasing interest in the investigation of origin and speciation of schizothoracine fishes can be dated to 20th century. However, molecular phylogeny of Schizothoracinae and their phylogenetic relationships, as well as the divergence times still remain controversial. In this study, two DNA sets consisting of 12 protein-coding mitochondrial genes from 254 individuals and RAG1 gene from 106 individuals were used to reconstruct the phylogenetic relationships and calculate the divergence times among the subfamily schizothoracinae. Our results indicated that both of the data sets supported a non-monophyletic relationship due to involving of species of Barbinae. However, the phylogenetic relationships based on mtDNA genes were more reliable than that inferred from RAG1 gene. The highly specialized grade formed a monophyletic group, together with Ptychobarbus as a sister group of Diptychus and Gymnodiptychus, which was belonging to specialized grade, indicating that Ptychobarbus may be transition species to involve to highly specialized schizothoracianae. In addition, the primitive grade clustered with Percocypris pingi, a species of Barbinae. Based on mtDNA gene, the speciation time of Schizothoracinae was 66 Ma, and the divergence time of the primitive grade and Percocypris pingi was 64 Ma. The speciation times of the three grades Schizothoracinae were 57 Ma, 51 Ma and 43 Ma, respectively; and the divergence time of specialized and highly specialized grade was 46 Ma. The divergence times of three grades were not consistent with the three stages of uplift of Qinghai-Tibet Plateau, which is older than the times.
Genetically distinct behavioral modules underlie natural variation in thermal performance curves
Authors: Stegeman Gregory W. , Baird Scott E. , Ryu William S. , Cutter Asher D.
Published: January 2019

Thermal reaction norms pervade organismal traits as stereotyped responses to temperature, a fundamental environmental input into sensory and physiological systems. Locomotory behavior represents an especially plastic read-out of animal response, with its dynamic dependence on environmental stimuli presenting a challenge for analysis and for understanding the genomic architecture of heritable variation. Here we characterize behavioral reaction norms as thermal performance curves for the nematodeCaenorhabditis briggsae, using a collection of 23 wild isolate genotypes and 153 recombinant inbred lines to quantify the extent of genetic and plastic variation in locomotory behavior to temperature changes. By reducing the dimensionality of the multivariate phenotypic response with a function-valued trait framework, we identified genetically distinct behavioral modules that contribute to the heritable variation in the emergent overall behavioral thermal performance curve. Quantitative trait locus mapping isolated regions on Chromosome II associated with locomotory activity at benign temperatures and Chromosome V loci related to distinct aspects of sensitivity to high temperatures, with each quantitative trait locus explaining up to 28% of trait variation. These findings highlight how behavioral responses to environmental inputs as thermal reaction norms can evolve through independent changes to genetically distinct modular components of such complex phenotypes.

Article Summary

Plastic responses to environmental inputs, reaction norm phenotypes that can be summarized with parameters of fits to a mathematical function, are pervasive across diverse organismal traits and crucial to organismal fitness. We quantified the nematodeCaenorhabditis briggsae’s behavioral thermal performance curves as function-valued traits for 23 wild isolate genotypes and 153 recombinant inbred lines. We identified quantitative trait loci on multiple chromosomes that define genetically distinct behavioral modules contributing to the emergent overall behavioral thermal performance curve. These findings highlight how dynamic behavioral responses to environmental inputs can evolve through independent changes to genetically distinct modular components of such complex phenotypes.
The symmetrical pattern of base-pair substitutions rates across the chromosome inEscherichia colihas multiple causes
Authors: Niccum Brittany A. , Lee Heewook , MohammedIsmail Wazim , Tang Haixu , Foster Patricia L.
Published: January 2019

Mutation accumulation experiments followed by whole-genome sequencing have revealed that for several bacterial species the rate of base-pair substitutions is not constant across the chromosome but varies in a wave-like pattern symmetrical about the origin of replication. The experiments reported here demonstrate that inEscherichia coliseveral interacting factors determine the wave. Perturbing replication timing, progression, or the structure of the terminus disrupts the pattern. Biases in error-correction by proofreading and mismatch repair are major factors. The activities of the nucleoid binding proteins, HU and Fis, are important, suggesting that mutation rates increase when highly structured DNA is replicated. These factors should apply to most bacterial, and possibly eukaryotic, genomes, and imply that different areas of the genome evolve at different rates.
Eco-Evolutionary Feedbacks Between Predator’s Linkage Disequilibrium and Prey Densities Maintain Diversity
Authors: Patel Swati , Bürger Reinhard
Published: January 2019

Diversity occurs at multiple scales. Within a single population, there is diversity in genotypes and phenotypes. At a larger scale, within ecological communities, there is diversity in species. There have been a number of studies to investigate how diversity at these two scales influence each other through what has been termed eco-evolutionary feedbacks. Here we study a three-species ecological module called apparent competition, in which the predator is evolving in a trait that determines its interaction with two prey species. Unlike previous studies on apparent competition, which employed evolutionary frameworks with greatly simplified genetics, we study a multilocus eco-evolutionary model in which the predator’s evolving trait is determined by two diallelic loci. We ask how eco-evolutionary feedbacks with these two loci affect the coexistence of the prey species and the maintenance of polymorphisms within the predator species. In doing so, we uncover a novel eco-evolutionary feedback between the prey species and the linkage disequilibrium of the two loci of the predator. Through a stability analysis, we demonstrate how these feedbacks affect polymorphisms at both loci and, among others, may generate stable cycling.
Replicating Arabidopsis Model Leaf Surfaces for Phyllosphere Microbiology
Authors: Soffe Rebecca , Bernach Michal , Remus-Emsermann Mitja , Nock Volker
Published: January 2019

Artificial surfaces are commonly used in place of leaves in phyllosphere microbiology to study microbial behaviour on plant leaf surfaces. Studies looking into individual environmental factors influencing microorganisms are routinely carried out using artificial surfaces. Commonly used artificial surfaces include nutrient agar, isolated leaf cuticles, and reconstituted leaf waxes. However, interest is growing in using microstructured surfaces mimicking the complex topography of leaf surfaces for phyllosphere microbiology. As such replica leaf surfaces, produced by microfabrication, are appearing in literature. Replica leaf surfaces have been produced in agar, epoxy, polystyrene, and polydimethylsiloxane (PDMS). However, these protocols are not suitable for replicating fragile leaves such as of the model plant Arabidopsis thaliana. This is of importance as A. thaliana is a model system for molecular plant genetics, molecular plant biology, and microbial ecology. Here we present a versatile replication protocol for replicating fragile leaf surfaces into PDMS. We display the capacity of our replication process using optical microscopy, atomic force microscopy (AFM), and contact angle measurements to compare living and PDMS replica A. thaliana leaf surfaces. To highlight the use of our replica leaf surfaces for phyllosphere microbiology, we visualised bacteria on the replica leaf surfaces in comparison to living leaf surfaces.
SWI/SNF component BAF250a coordinates OCT4 and WNT signaling pathway to control cardiac lineage differentiation
Authors: Lei Ienglam , Tian Shuo , Chen Victor , Zhao Yong , Wang Zhong
Published: January 2019

Dissecting epigenetic mechanisms controlling early cardiac differentiation will provide insights into heart regeneration and heart disease treatment. SWI/SNF complexes remodel nucleosomes to regulate gene expression and play a key role in organogenesis. Here we reported a unique function of BAF250a in regulating the physical interaction of OCT4 and β-CATENIN during cardiac lineage differentiation from human ESCs. BAF250a deletion greatly reduced the physical interaction between OCT4 and β-CATENIN but did not alter the expression of β-CATENIN and OCT4 in the mesodermal progenitor cells. BAF250a ablation led to decreased recruitment of OCT4 and β-CATENIN at promoters of key mesodermal lineage genes, such as MESP1 and EOMES. Subsequently, the expression of lineage specific genes was down-regulated whereas the expression of pluripotent genes was up-regulated. In parallel, BAF250a ablation also altered recruitments of OCT4 and β-CATENIN to the promoter of CCND2 and CCND3, two key genes for S phase entry during cell cycle. Consequently, BAF250a deletion led to prolonged S phase in Mesp1+ cardiac progenitor cells, which in turn inhibited efficient differentiation of Mesp1+ to Isl1+ cells. Furthermore, BAF250a deletion abolished the interaction of OCT4 and BRG1 in mesoderm, suggesting that BAF250a is the key component in SWI/SNF complex that determines the interaction of Oct4/β-catenin in mesoderm. In contrast, we found that BAF250a did not regulate the OCT4/β-CATENIN interaction during neuroectoderm differentiation. Altogether, our results suggest that BAF250a specifically controls proper cardiac mesoderm differentiation by reorganizing the binding of OCT4/β-CATENIN and regulates both key lineage differentiation genes and cell cycle genes coincided in response to WNT/β-CATENIN signal.

Highlights

BAF250a is required for hESC cardiac differentiation

BAF250a is required for the assembly of Brg1/OCT4/β-CATENIN complex and the recruitment of OCT4/β-CATENIN to cardiac genes

BAF250a is dispensable for the interaction of OCT4/β-CATENIN interaction in neuroectoderm differentiation

BAF250a interacts with OCT4/β-CATENIN to promote cardiac differentiation by regulating cell cycle.
MicroRNA-222 regulates fluid shear stress-induced human nucleus pulposus cells degeneration through affecting c-Fos expression
Authors: Miao Haixiong , Yao Yicun , Ye Baoqing , Dai Libing , Liang Weiguo
Published: January 2019

Intervertebral disc degeneration (IVDD) is a chronic disease that correlates with the deterioration of the nucleus pulposus (NP) cells. However, the molecular mechanism of IVDD remains unclear. In this study, we investigated the function of microRNA-222 in IVDD and the potential molecular mechanism. NP cells treated with fluid shear stress (FSS) were used to simulate a model of IVDD in vitro. MicroRNA-222 was significantly downregulated in NP cells stimulated with FSS compared with that in unstimulated NP cells. Human NP cells were also treated with FSS to induce their degeneration. The mRNA and protein levels of C-FOS, MEK, phosphorylated MEK5 (pMEK5), ERK5, and pERK5 were evaluated with RT-PCR and western blotting, respectively. Enzyme-linked immunosorbent assays were used to investigate type II collagen and Aggrecan expression. NP cell proliferation was determined with the Cell Counting Kit-8. MicroRNA-222 was significantly downregulated in NP cells treated with FSS. The production of c-Fos and MEK5 were markedly reduced or increased in NP cells transfected with the has-microRNA-222 mimic or inhibitor, respectively, whether or not they were stimulated with FSS. The overexpression or inhibition of microRNA-222 markedly accelerated or suppressed the apoptosis of FSS-stimulated NP cells, respectively. In the NP cells, the overexpression or inhibition of microRNA-222 massively inhibited or strengthened Aggrecan and type II collagen expression. Together, our data indicated that c-Fos was a target of microRNA-222, and was negatively regulated by microRNA-222 in NP cells. Our findings also suggested that microRNA-222 is a possible therapeutic target for IVDD because it regulates c-Fos.
Protein features for assembly of the RNA editing helicase 2 subcomplex (REH2C) in Trypanosome holo-editosomes
Authors: Kumar Vikas , Doharey Pawan K. , Gulati Shelly , Meehan Joshua , Martinez Mary G. , Hughes Karrisa , Mooers Blaine H.M. , Cruz-Reyes Jorge
Published: January 2019

Uridylate insertion/deletion RNA editing inTrypanosoma bruceiis a complex system that is not found in humans, so there is interest in targeting this system for drug development. This system uses hundreds of small non-coding guide RNAs (gRNAs) to modify the mitochondrial mRNA transcriptome. This process occurs in holo-editosomes that assemble several macromoleculartransfactors around mRNA including the RNA-free RNA editing core complex (RECC) and auxiliary ribonucleoprotein (RNP) complexes. Yet, the regulatory mechanisms of editing remain obscure. The enzymatic accessory RNP complex, termed the REH2C, includes mRNA substrates and products, the multi-domain 240 kDa RNA Editing Helicase 2 (REH2) and an intriguing 8-zinc finger protein termed REH2-Associated Factor 1 (H2F1). Both of these proteins are essential in editing. REH2 is a member of the DExH/RHA subfamily of RNA helicases with a conserved C-terminus that includes a regulatory OB-fold domain. In trypanosomes,H2F1 recruits REH2 to the editing apparatus, andH2F1 downregulation causes REH2 fragmentation. Our systematic mutagenesis dissected determinants in REH2 andH2F1 for the assembly of REH2C, the stability of REH2, and the RNA-mediated association of REH2C with other editingtransfactors. We identified functional OB-fold amino acids in eukaryotic DExH/RHA helicases that are conserved in REH2 and that impact the assembly and interactions of REH2C.H2F1 upregulation stabilized REH2in vivo. Mutation of the core cysteines or basic amino acids in individual zinc fingers affected the stabilizing property ofH2F1 but not its interactions with other examined editing components. This result suggests that most, if not all, fingers may contribute to REH2 stabilization. Finally, a recombinant REH2 (240 kDa) established that the full-length protein is abona fideRNA helicase with ATP-dependent unwinding activity. REH2 is the only DExH/RHA-type helicase in kinetoplastid holo-editosomes.
Sodium rubidium hydrogen citrate, NaRbHC6H5O7, and sodium caesium hydrogen citrate, NaCsHC6H5O7: crystal structures and DFT comparisons
Authors: Cigler Andrew J. , Kaduk James A.
Published: January 2019

The crystal structure of sodium rubidium hydrogen citrate, NaRbHC6H5O7 or [NaRb(C6H6O7)]
n
, has been solved and refined using laboratory powder X-ray diffraction data, and optimized using density functional techniques. This compound is isostructural to NaKHC6H5O7. The Na atom is six-coordinate, with a bond-valence sum of 1.16. The Rb atom is eight-coordinate, with a bond-valence sum of 1.17. The distorted [NaO6] octahedra share edges to form chains along the a-axis direction. The irregular [RbO8] coordination polyhedra share edges with the [NaO6] octahedra on either side of the chain, and share corners with other Rb atoms, resulting in triple chains along the a-axis direction. The most prominent feature of the structure is the chain along [111] of very short, very strong hydrogen bonds; the O...O distances are 2.426 and 2.398 Å. The Mulliken overlap populations in these hydrogen bonds are 0.140 and 0.143 electrons, which correspond to hydrogen-bond energies of about 20.3 kcal mol−1. The crystal structure of sodium caesium hydrogen citrate, NaCsHC6H5O7 or [NaCs(C6H6O7)]
n
, has also been solved and refined using laboratory powder X-ray diffraction data, and optimized using density functional techniques. The Na atom is six-coordinate, with a bond-valence sum of 1.15. The Cs atom is eight-coordinate, with a bond-valence sum of 0.97. The distorted trigonal–prismatic [NaO6] coordination polyhedra share edges to form zigzag chains along the b-axis direction. The irregular [CsO8] coordination polyhedra share edges with the [NaO6] polyhedra to form layers parallel to the (101) plane, unlike the isolated chains in NaKHC6H5O7 and NaRbHC6H5O7. A prominent feature of the structure is the chain along [100] of very short, very strong O—H...O hydrogen bonds; the refined O...O distances are 2.398 and 2.159 Å, and the optimized distances are 2.398 and 2.347 Å. The Mulliken overlap populations in these hydrogen bonds are 0.143 and 0.133 electrons, which correspond to hydrogen-bond energies about 20.3 kcal mol−1.
Joints realized by sintering of pressureless Ag paste
Authors: Pietrikova Alena , Girasek Tomas , Livovsky Lubomir , Durisin Juraj , Saksl Karel
Published: January 2019

Purpose

The purpose of this paper was to investigate an influence of a low temperature pressureless sintering process of silver paste on the quality of sintered joints.

Design/methodology/approach

The authors analyzed various curing conditions of the paste during its sintering process: 175°C/90 min, 200°C/60 min, 250°C/30 min, 250°C/60 min, 350°C/30 min and 350°C/60 min. They analyzed an influence of the surface plating applied on a ceramic substrate/layer (Cu, Ag, AgPt and Au thick film) on the joints quality. The authors analyzed microstructure and electrical resistance of the joints. They evaluated these properties from the point of view of thermal aging process and changing resistance, after a constant current loading of the sintered joints.

Findings

The nanoscale pressureless silver paste can be applied for replacing a pressure-assisted micro-sized silver paste. It was found that the quality of the metal plating applied on the ceramic substrate/layer has a significant impact on the quality of the sintered joints. Copper and AgPt plating have better impact on quality of sintered joints in compare with Ag plating.

Originality/value

This investigation of the quality of the pressureless sintered joints at the silver-silver interface reveals an evident cracking immediately after the silver paste curing. Rapid sintering process typical for silver-based films on the substrate is because of the inter-diffusion between the micro and nanoparticles of silver at interfacial interface.
Optimal stable gait for nonlinear uncertain humanoid robot using central force optimization algorithm
Authors: Huan Tran Thien , Anh Ho Pham Huy
Published: January 2019

Purpose

The purpose of this paper is to design a novel optimized biped robot gait generator which plays an important role in helping the robot to move forward stably. Based on a mathematical point of view, the gait design problem is investigated as a constrained optimum problem. Then the task to be solved is closely related to the evolutionary calculation technique.

Design/methodology/approach

Based on this fact, this paper proposes a new way to optimize the biped gait design for humanoid robots that allows stable stepping with preset foot-lifting magnitude. The newly proposed central force optimization (CFO) algorithm is used to optimize the biped gait parameters to help a nonlinear uncertain humanoid robot walk robustly and steadily. The efficiency of the proposed method is compared with the genetic algorithm, particle swarm optimization and improved differential evolution algorithm (modified differential evolution).

Findings

The simulated and experimental results carried out on the small-sized nonlinear uncertain humanoid robot clearly demonstrate that the novel algorithm offers an efficient and stable gait for humanoid robots with respect to accurate preset foot-lifting magnitude.

Originality/value

This paper proposes a new algorithm based on four key gait parameters that enable dynamic equilibrium in stable walking for nonlinear uncertain humanoid robots of which gait parameters are initiatively optimized with CFO algorithm.
A literature survey of community participation in the natural gas sector in developing countries
Authors: Bishoge Obadia Kyetuza , Zhang Lingling , Mushi Witness Gerald , Matomela Nametso
Published: January 2019

Purpose

This paper aims to analyze the context of community opinions and participation in the natural gas sector in developing countries, a case study of Tanzania. To achieve this purpose, the study pointed out six facts, namely, information on the natural gas sector; awareness of the natural gas-related policies; laws and regulations and the creation of employment opportunities; local experts in the natural gas sector; the use of natural gas revenues; and natural gas for poverty reduction and improvement of social well-being.

Design/methodology/approach

The study is a systematic review of the literature on community participation based on the relevant studies published between 2010 and 2018. A comprehensive literature review was carried out following the seven-step model whereby relevant themes from different potential bibliographic databases such as Google Scholar were systematically selected, compiled and analyzed using descriptive methods.

Findings

The study revealed that despite the various efforts made by the governments and other stakeholders to promote community participation, there is an inadequate level of community participation in the natural gas sector in developing countries. There are limited local experts for natural gas operations and low transparency on natural gas contracts, agreements and revenues. Therefore, there is the need to raise awareness for a highly informed society with a clear sense of ownership of the natural gas wealth among the local communities. Moreover, transparency and accountability are recommended for the sustainable natural gas sector development.

Originality/value

This paper offers new and current cross-sectoral inclusion, opinions, hopes and concerns of the community on the natural gas sector management in developing countries.
Social learning with differentiated products
Authors: Campbell Arthur
Published: January 2019

Learning from friends is a key process by which consumers acquire information about available products. This article embeds social learning in a model of firms producing differentiated products. I consider how the structure of social relationships between consumers influences pricing and welfare. In particular, how a variety of characteristics of social networks ‐ distribution of friendships, homophily, clustering, and correlations between an individual's preferences and number of friends ‐ influence these outcomes. I also find conditions under which consumer awareness and the sensitivity of demand to prices are useful measures of the informational efficiency of markets.
FentAnyl or placebo with KeTamine for emergency department rapid sequence intubation: The FAKT study protocol
Authors: Ferguson Ian , Milligan James , Buttfield Alex , Shepherd Shamus , Burns Brian , Reid Cliff , Aneman Anders , Harris Ian
Published: January 2019

Background

Some critically ill patients require rapid sequence intubation in the emergency department, and ketamine is one sedative agent employed, due to its relative haemodynamic stability. Tachycardia and hypertension are frequent side effects, and in less stable patients, shock can be unmasked or exacerbated. The use of fentanyl as a co‐induction agent may lead to a smoother haemodynamic profile post‐induction, which may lead to reduced mortality in this critically ill cohort. This randomised controlled trial aims to compare the effect of administering fentanyl vs placebo in a standardised induction regimen with ketamine and rocuronium on (a) the percentage of patients in each group with a systolic blood pressure outside the range of 100‐150 mm Hg within 10 minutes of induction, (b) the laryngoscopic view, and (c) 30‐day mortality.

Methods/design

Three hundred patients requiring rapid sequence intubation in participating emergency departments will be randomised to receive either fentanyl or placebo (0.9% saline) in addition to ketamine and rocuronium according to a standardised, weight‐based induction regimen. The primary outcome measure is the percentage of patients in each group with a systolic blood pressure outside the range of 100‐150 mm Hg within 10 minutes of induction. Secondary outcome measures include the laryngoscopic view, percentage of first pass success, 30‐day mortality and number of ventilator‐free days at 30 days.

Discussion

The effect of adding fentanyl to an induction regimen of ketamine and rocuronium will be evaluated, both in terms of post‐intubation physiology, the effect on intubating conditions, and 30‐day mortality.
Short‐ and long‐term mortality in major non‐cardiac surgical patients admitted to the intensive care unit
Authors: Ekeloef Sarah , Thygesen Lau C. , Gögenur Ismail
Published: January 2019

Background

The aim of this register‐based cohort study was to characterize patients admitted to the intensive care unit (ICU) following non‐cardiac surgery and identify risk factors associated with 30‐days, 90‐days and 1‐year mortality after ICU admission.

Methods

Patients aged 18+ years admitted to the intensive care unit within 30‐days of non‐cardiac surgery at four Capital Region hospitals in Denmark between January 2005 and December 2014 were included. Patients were identified through the Danish National Patient Register. The outcomes were 30‐days, 90‐days and 1‐year mortality after ICU admission. Unadjusted and multivariate logistic regression analyses were performed to identify independent risk factors of mortality.

Results

The study included 3311 ICU patients. Gastrointestinal surgery accounted for 71.3%, orthopaedic surgery for 18.4% and urologic surgery for 10.2% of the population. For the total population, the median length of stay in hospital was 18 days (9‐36, 25th‐75th percentile) and 2 days (1‐4, 25th‐75th percentile) in the ICU. Thirty‐days, 90‐days and 1‐year mortality were 37.8%, 44.5% and 51.2% respectively. Mortality within the ICU was 22.3% while the post‐ICU in‐hospital mortality was 19.4%. Higher age, comorbidity, delayed ICU admission, acute surgery, and gastrointestinal and orthopaedic surgery increased 30‐days, 90‐days and 1‐year mortality.

Conclusions

Short‐ and long‐term mortality in non‐cardiac surgical patients admitted to the ICU is very high, especially among the elderly comorbid patients undergoing acute surgery. Future research should focus on targeting clinically modifiable risk factors and performing tailored treatment for these high‐risk patients.
Use of medicines that may precipitate delirium prior to hospitalisation in older Australians with delirium: An observational study
Authors: Kassie Gizat M. , Kalisch Ellett Lisa M. , Nguyen Tuan A. , Roughead Elizabeth E.
Published: January 2019

Objective

To assess the use of medicines associated with delirium prior to hospital admission in older Australian patients with a recorded diagnosis of delirium.

Methods

A retrospective observational study was conducted using de‐identified data from the Australian Government Department of Veterans’ Affairs Health Care Claims Database. The prevalence of use of medicines associated with delirium was determined in people 65 years or older with a delirium diagnosis.

Results

Three‐quarters of the total 22 923 older patients included were taking at least one medicine associated with delirium, the median number of medications per patient was two (interquartile range, 1‐3). The most frequently used medicines known to be associated with delirium were psycholeptics, opioids and tricyclic antidepressants.

Conclusion

A substantial proportion of older hospitalised patients with a delirium diagnosis were taking medicines known or suspected to precipitate delirium prior to admission. There may be an opportunity to decrease medication‐associated delirium by reducing use of risky medication.
Study of Human Leukocyte Antigen (HLA) in 13 cases of familial frontal fibrosing alopecia: CYP21A2 gene p.V281L mutation from congenital adrenal hyperplasia linked to HLA class I haplotype HLA‐A*33:01; B*14:02; C*08:02 as a genetic marker
Authors: Porriño‐Bustamante María Librada , López‐Nevot Miguel Ángel , Aneiros‐Fernández José , Casado‐Ruiz Jorge , García‐Linares Susana , Pedrinacci‐Rodríguez Susana , García‐Lora Elena , Martín‐Casares María Antonia , Fernández‐Pugnaire María Antonia , Arias‐Santiago Salvador
Published: January 2019

Background/Objectives

The aetiology of frontal fibrosing alopecia is unknown, and its genetic aspect remains uncharacterised. The aim of this report is to elucidate if major histocompatibility complex is associated with familial frontal fibrosing alopecia.

Methods

A case–control study was performed of 13 patients with frontal fibrosing alopecia belonging to six families. Their human leukocyte antigen profiles were compared to the data of 636 healthy controls without frontal fibrosing alopecia. Patients underwent high‐resolution genomic typing for human leukocyte antigen class I and II loci by PCR‐SSO for Luminex. In addition, CYP21A2 gene (major histocompatibility complex class III) mutations were detected by PCR‐SSO on strips.

Results

61.5% of patients shared CYP21A2 gene p.V281L linked to the F16A human leukocyte antigen class I haplotype (HLA‐A*33:01; B*14:02; C*08:02; Pc < 0.000001). The patients F16A‐negative shared other human leukocyte antigen class I haplotypes: Y16A (3/13) and S26 (2/13).

Conclusion

CYP21A2 gene p.V281L mutation can be used as a genetic marker for susceptibility to familial frontal fibrosing alopecia. Both the linkage of the mutation to F16A and the fact that F16A‐negative patients share other human leukocyte antigen class I haplotype, point to an antigen‐driven mechanism in susceptible patients with these haplotypes.
A trial comparing emergency front of neck airway performance in a novel obese‐synthetic neck, meat‐modified obese neck and conventional slim manikin
Authors: Le Fevre P. J. , Gough C. , Hearne B. J. , Corbett L. , Seller C. , Cook T. M. , Kelly F. E.
Published: January 2019

Conventional emergency front of neck airway training manikins mimic slim patients and are associated with unrealistic procedural ease. We have described previously a pork belly‐modified manikin that more realistically simulated an obese patient's neck. In this study, we compared a novel obese‐synthetic manikin (obese‐synthetic manikin) with a pork belly‐modified manikin (obese‐meat manikin) and a conventional slim manikin (slim manikin). Thirty‐three experienced anaesthetists undertook simulated emergency front of neck airway procedures on each manikin (total 99 procedures). Time to ventilation was longer on both obese manikins compared with the slim manikin (median (IQR [range]) time to intubation 159 (126–243 [73–647]) s in the obese‐synthetic, 105 (72–138 [43–279]) s in the obese‐meat and 58 (47–74 [30–370]) s in the slim manikin; p < 0.001 between each manikin). Cricothyroidotomy success rate was similar in the both obese manikins but lower when compared with the slim manikin (15/33 obese‐synthetic vs. 14/33 obese‐meat vs. 27/33 slim manikin). Participant feedback indicated performance difficulty was similar between both obese manikins, which were both more difficult than the slim manikin. The tissues of the obese‐meat manikin were judged more realistic than those of either other manikin. Overall, the obese‐synthetic manikin performed broadly similarly to the obese‐meat manikin and was technically more difficult than the conventional slim manikin. The novel obese‐synthetic manikin maybe useful for training and research in front of neck airway procedures.
Skeletal development in blue‐breasted quail embryos
Authors: Nakamura Yoshiaki , Nakane Yoshifumi , Tsudzuki Masaoki
Published: January 2019

The blue‐breasted quail (Coturnix chinensis), the smallest species of quail with short generation interval and excellent reproductive performance, is a potential avian research model. A normal series of skeletal development of avian embryos could be served as a reference standard in the fields of developmental biology and teratological testing as well as in the investigation of mutation with skeletal abnormalities and in the study of the molecular mechanisms of skeletal development through genome manipulation. Furthermore, ossification sequence shows a species‐specific pattern and has potential utility in phylogeny. However, data on the skeletal development of blue‐breasted quail embryos are scarce. Here, we established a series of normal stages for the skeletal development of blue‐breasted quail embryos. Cartilage and ossified bones of blue‐breasted quail embryos were stained blue and red with Alcian blue 8GX and Alizarin red S, respectively. The time and order of chondrification and calcification of their skeletons were documented every 24 hr from 3 to 17 days of incubation, and a 15‐stage series of skeletal development was created. Moreover, a comparative study with the Japanese quail (Coturnix japonica) demonstrated that ossification sequence differed significantly between these two species.
Rumen fluid, feces, milk, water, feed, airborne dust, and bedding microbiota in dairy farms managed by automatic milking systems
Authors: Wu Haoming , Nguyen Qui D. , Tran Tu T. M. , Tang Minh T. , Tsuruta Takeshi , Nishino Naoki
Published: January 2019

Microbiota of the gut, milk, and cowshed environment were examined at two dairy farms managed by automatic milking systems (AMS). Feed, rumen fluid, feces, milk, bedding, water, and airborne dust were collected and the microbiota on each was assessed by Illumina MiSeq sequencing. The most abundant taxa in feed, rumen fluid, feces, bedding, and water were Lactobacillaceae, Prevotellaceae, Ruminococcaceae, Ruminococcaceae, and Lactobacillaceae, respectively, at both farms. Aerococcaceae was the most abundant taxon in milk and airborne dust microbiota at farm 1, and Staphylococcaceae and Lactobacillaceae were the most abundant taxa in milk and airborne dust microbiota at farm 2. The three most prevalent taxa (Aerococcaceae, Staphylococcaceae, and Ruminococcaceae at farm 1 and Staphylococcaceae, Lactobacillaceae, and Ruminococcaceae at farm 2) were shared between milk and airborne dust microbiota. Indeed, SourceTracker indicated that milk microbiota was related with airborne dust microbiota. Meanwhile, hierarchical clustering and canonical analysis of principal coordinates demonstrated that the milk microbiota was associated with the bedding microbiota but clearly separated from feed, rumen fluid, feces, and water microbiota. Although our findings were derived from only two case studies, the importance of cowshed management for milk quality control and mastitis prevention was emphasized at farms managed by AMS.
Methodological aspects of health‐related quality of life measurement and analysis in patients with multiple myeloma
Authors: Nielsen Lene Kongsgaard , Abildgaard Niels , Jarden Mary , Klausen Tobias Wirenfeld
Published: January 2019

Multiple myeloma (MM) is an incurable but treatment‐sensitive cancer. For most patients, this means treatment with multiple lines of anti‐myeloma therapy and a life with disease‐ and treatment‐related symptoms and complications. Health‐related quality of life (HRQoL) issues play an important role in treatment decision‐making. Methodological challenges in longitudinal HRQoL measurements and analyses have been identified, including non‐responses (NR) to scheduled questionnaires. Publications were identified for inclusion in a systematic review of longitudinal HRQoL studies in MM, focussing on methodological aspects of HRQoL measurement and analysis. Diversity in timing of HRQoL data collection and applied statistical methods were noted. We observed a high rate of NR, but the impact of NR was investigated in only 8/23 studies. Thus, evidence‐based knowledge of HRQoL in patients with MM is compromised. To improve quality of HRQoL results and their implementation in daily practice, future studies should follow established guidelines.
Childhood adversity and mechanistic links to hypertension risk in adulthood
Authors: Obi Ijeoma E. , McPherson Kasi C. , Pollock Jennifer S.
Published: January 2019

Adverse childhood experiences (ACEs), defined as traumatic events in childhood that range from various forms of abuse to household challenges and dysfunction, have devastating consequences on adult health. Epidemiological studies in humans and animal models of early life stress (ELS) have revealed a strong association and insight into the mechanistic link between ACEs and increased risk of cardiovascular disease (CVD). This review focuses on the mechanistic links of ACEs in humans and ELS in mice and rats to vasoactive factors and immune mediators associated with CVD and hypertension risk, as well as sex differences in these phenomena. Major topics of discussion in this review are as follows: (a) epidemiological associations between ACEs and CVD risk focusing on hypertension, (b) evidence for association of ACE exposures to immune‐mediated and/or vasoactive pathways, (c) rodent models of ELS‐induced hypertension risk, (d) proinflammatory mediators and vasoactive factors as mechanisms of ELS‐induced hypertension risk. We also provide some overall conclusions and directions of further research.

Linked Articles

This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Roles of EphA1/A2 and ephrin‐A1 in cancer
Authors: Ieguchi Katsuaki , Maru Yoshiro
Published: January 2019

The biological functions of the Eph/ephrin system have been intensively investigated and well documented so far since its discovery in 1987. Although the Eph/ephrin system has been implicated in pathological settings such as Alzheimer's disease and cancer, the molecular mechanism of the Eph/ephrin system in those diseases is not well understood. Especially in cancer, recent studies have demonstrated that most of Eph and ephrin are up‐ or down‐regulated in various types of cancer, and have been implicated in tumor progression, tumor malignancy, and prognosis. However, they lack consistency and are in controversy. The localization patterns of EphA1 and EphA2 in mouse lungs are very similar, and both knockout mice showed similar phenotypes in the lungs. Ephrin‐A1 that is a membrane‐anchored ligand for EphAs was co‐localized with EphA1 and EphA2 in lung vascular endothelial cells. We recently uncovered the molecular mechanism of ephrin‐A1‐induced lung metastasis by understanding the physiological function of ephrin‐A1 in lungs. This review focuses on the function of EphA1, EphA2, and ephrin‐A1 in tumors and an establishment of pre‐metastatic microenvironment in the lungs.
Design, synthesis, and evaluation of a series of novel phenylpropanoic acid derivatives agonists for the FFA1
Authors: Yang Jiaju , Gu Enke , Yan Ting , Shen Daoming , Feng Bainian , Tang Chunlei
Published: January 2019

Free fatty acid 1 (FFA1/GPR40) has attracted extensive attention as a novel target for the treatment of type 2 diabetes for its role in the enhancement of insulin secretion with glucose dependency. Aiming to develop novel potent FFA1 agonists, a new series of phenylpropionic acid derivatives were designed and synthesized on the basis of the modification of chemical cement of TAK‐875, AMG‐837, and LY2881835. Among them, most promising compounds 7, 14, and 15 were obtained with EC50 values of 82, 79, and 88 nM, exhibiting a powerful agonistic activity compared to TAK‐875 (95.1 nM). During Oral glucose tolerance test in normal mice, compound 7, 14, and 15 had significant glucose‐lowering effect at the dose of 50 mg/kg. Furthermore, compound 15 (50 mg/kg) also significantly improved in glucose tolerance in type 2 diabetic mice. Herein, we reported the discovery and optimization of a series of potent FFA1 agonists. The discovery supported further exploration surrounding this scaffold.
The influence of orthodontic treatment on dental caries: An Australian cohort study
Authors: Doğramacı Esma J. , Brennan David S.
Published: January 2019

Objective

To assess the influence of orthodontic treatment on long‐term caries experience in 30‐year‐old South Australians. The research hypothesis that was tested was that those with previous orthodontic treatment would have lower caries experience.

Methods

In 2005‐2006, a sample of 1859 30‐year‐olds from Adelaide, South Australia, who comprised 47% of participants who had previously taken part in an oral epidemiology study in 1988‐1989, were traced from the Australian electoral roll and invited to participate in a cross‐sectional study investigating long‐term dental health outcomes. Participants completed a questionnaire that collected information on socio‐demographic characteristics, dental health behaviours and receipt of orthodontic treatment. This was followed by clinical examination. The outcome variables were the summed decayed, missing and filled teeth (DMFT) score, and its individual components. Data were analysed using negative binomial regression.

Results

The response rate for the questionnaire was 34% (n = 632). There were no systematic differences between those who were followed up and those who were not followed up. Clinical data for 448 participants were available for analyses, representing 24% of the originally contacted individuals. By the age of 30, over a third of participants had received orthodontic treatment. Regardless of initial malocclusion classification, orthodontically treated participants had a lower DMFT score at age 30 but this did not reach statistical significance. Adjusted models controlling for socio‐demographic, dental health behaviour and malocclusion status showed no associations between orthodontic treatment and decayed (Exp B: 1.00, 95% CI: 0.72‐1.40), missing (Exp B: 1.00, 95% CI: 0.59‐1.69), or filled teeth (Exp B: 1.18, 95% CI: 0.93‐1.51) or overall DMFT (Exp B: 1.12, 95% CI: 0.88‐1.41).

Conclusion

There was no difference in the long‐term caries experience of South Australians aged 30 years based on past orthodontic treatment. Our study does not support the contention that those treated orthodontically have better dental health later in life.
Extracorporeal membrane oxygenation for grade 3 primary graft dysfunction after lung transplantation: Long‐term outcomes
Authors: Bellier Jocelyn , Lhommet Pierre , Bonnette Pierre , Puyo Philippe , Le Guen Morgan , Roux Antoine , Parquin François , Chapelier Alain , Sage Edouard ,   the Foch Lung Transplantation Group
Published: January 2019

Introduction

Extracorporeal membrane oxygenation (ECMO) is an efficient and innovative therapeutic tool for primary graft dysfunction (PGD). However, its effect on survival and long‐term lung function is not well known. This study evaluated those parameters in patients with PGD requiring ECMO.

Method

This single‐center, retrospective study included patients who underwent LTx at our institute between January 2007 and December 2013. Patients and disease characteristics, survival, and pulmonary function tests were recorded.

Results

A total of 309 patients underwent LTx during the study period and 211 were included. The patients were predominantly male (53.5%), the median age was 39 years, and the primary pathology was suppurative disease (53.1%). ECMO for PGD was mandatory in 24 (11.7%) cases. Mortality at 3 months in the ECMO group was 50% (N = 12). However, long‐term survival after PGD did not correlate with ECMO. Forced expiratory volume and vital capacity were significantly reduced in patients with PGD requiring ECMO, especially those with idiopathic pulmonary fibrosis.

Conclusion

Veno‐arterial ECMO appears to be suitable for management of PGD after LTx. Patients with PGD requiring ECMO show increased initial mortality; however, long‐term survival was comparable with that of other patients in the study. Lung function does not appear to be related to PGD requiring ECMO.
Bacterial biofilm is associated with higher levels of regulatory T cells in unaffected hidradenitis suppurativa skin
Authors: Kjærsgaard Andersen Rune , Ring Hans Christian , Kallenbach Klaus , Eriksen Jens O. , Jemec Gregor B. E.
Published: January 2019

Background

The role of bacterial biofilm in hidradenitis suppurativa (HS) is highly debated. Less biofilm is found in clinically unaffected axillary perilesional skin of HS patients compared with healthy controls.

Objective

To study the correlation between biofilm and the phenotypical characterization of the preclinical inflammatory infiltrate.

Materials and Methods

An exploratory comparative study of punch biopsies from unaffected axillary HS skin compared to similarly biopsies from healthy controls underwent standard staining procedures for CD4, CD8, CD25, FoxP3 and IL17. Standard‐sized inflammatory histological hotspots were identified manually. Slides were scanned into Leica Biosystems’ Digital Image Hub. Number of stained cells per slide and hotspot was found using an algorithm.

Results

12.5% of HS had biofilm compared to 85% of controls. For full slides, HS patients had more CD4+ cells than controls; HS patients with biofilm had higher CD4+ cell number than controls with or without biofilm and HS patients without biofilm. For hotspots, HS patients with biofilm had higher number of CD4+FoxP3+ cells than HS patients without biofilm and controls with biofilm.

Conclusion

The association between biofilm and the number of regulatory T cells in HS patients supports the concept of dysbiosis as a factor in the preclinical HS lesions.
Diminished membrane recruitment of Akt is instrumental in alcohol‐associated osteopenia via the PTEN/Akt/GSK‐3β/β‐catenin axis
Authors: Chen Yi‐Xuan , Zhu Dao‐Yu , Gao Junjie , Xu Zheng‐Liang , Tao Shi‐Cong , Yin Wen‐Jing , Zhang Yue‐Lei , Gao You‐Shui , Zhang Chang‐Qing
Published: January 2019

Alcohol is considered a leading risk factor for osteopenia. Our previous research indicated that the Akt/GSK‐3β/β‐catenin pathway plays a critical role in the ethanol‐induced antiosteogenic effect in bone mesenchymal stem cells (BMSCs). PI3K/Akt is negatively regulated by the phosphatase and tensin homolog (PTEN) phosphatase. In this study, we found that ethanol increased PTEN expression in the BMSCs and bone tissue of ethanol‐treated Sprague–Dawley rats. PTEN upregulation impaired Akt recruitment to the plasma membrane and suppressed Akt phosphorylation at Ser473, thereby inhibiting Akt/GSK3β/β‐catenin signaling and the expression of COL1 and OCN in BMSCs in vitro and in vivo. The results of in vivo assays indicated that PTEN inhibition protected bone tissue against ethanol. Interestingly, our data revealed that following ethanol stimulation, PTEN and PTEN pseudogene 1 (PTENP1) mRNA expression was increased in a time‐dependent manner, resulting in an increased PTEN protein level. In addition, ethanol upregulated PTEN expression and decreased PTEN phosphorylation (p‐PTEN), indicating an increase in functional PTEN levels. In summary, the ethanol‐mediated transcriptional and post‐transcriptional regulation of PTEN impaired downstream Akt/GSK3β/β‐catenin signaling and BMSC osteogenic differentiation. Therefore, we propose that Akt/GSK3β/β‐catenin activation via PTEN inhibition may be a potential therapeutic approach for preventing the development of alcohol‐induced osteopenia.