bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of point‐of‐care analysers for blood gas and clinical chemistry in Hermann’s tortoises (Testudo hermanni)
Authors: Di Girolamo N. , Ferlizza E. , Selleri P. , Nardini G. , Isani G.
Published: August 2018

Objective

To assess the agreement between point‐of‐care and laboratory analysers in measuring biochemical and blood gas analytes in venous samples from tortoises and to define preliminary reference intervals for venous blood gas analysis in Hermann's tortoises (Testudo hermanni).

Materials and Methods

Jugular venous blood samples from 47 Hermann's tortoises underwent paired analysis with a portable gas analyser (i‐STAT 1, Abaxis), a portable chemical analyser (VetScan VS2, Abaxis), and with the respective reference analysers. Agarose gel electrophoresis was used to determine albumin concentrations on 12 specimens. Agreement was evaluated with Bland–Altman plots and regression analysis using the Passing–Bablok method.

Results

Point‐of‐care analysers had variable agreement with the reference analysers, presenting constant or proportional bias depending on the analyte. Relevant analytes in reptiles, such as ionised and total calcium, had acceptable agreement. The method for determining albumin concentration currently available in both point‐of‐care and laboratory analysers significantly overestimated albumin concentrations as compared to protein electrophoresis.

Clinical Significance

While the use of POC analysers is extremely advantageous in small animal primary care facilities, agreement between point‐of‐care and laboratory analysers varies depending on the analyte. For certain analytes, interchangeability of results is limited and specific reference intervals for point‐of‐care analysers are required. Veterinarians should be aware of the size and the direction of the bias of each analyte.
Heteropogon contortusBL‐1 (Pilli Grass) and Elevated UV‐B Radiation: The Role of Growth, Physiological, and Biochemical Traits in Determining Forage Productivity and Quality
Authors: Hamid Abdul , Singh Suruchi , Agrawal Madhoolika , Agrawal Shashi Bhushan
Published: August 2018

Exposure to elevated UV‐B (eUV‐B) is well known for its phytotoxicity, although studies made with UV‐B exposure and its impact on grasses are limited especially from tropical countries including India. In this study, responses of a valuable grass species,Heteropogon contortusBL‐1, were assessed under eUV‐B (over ambient UV‐B) at different growth stages. Damage caused by eUV‐B was observed in the form of membrane damage and loss of pigments at early stages of growth, whereas tannin, phenol, and protein contents showed their increments at all the growth stages, to overcome the imposed stress. Reducing sugar showed its decline at all the growth stages, whereas starch and sucrose contents were higher mostly at later ages of plant growth. eUV‐B caused a marked variations in anatomical structures with increase of mesophyll and spongy parenchymatous cells in leaves to reduce severity of irradiation, to maintain the growth and productivity. The study also highlights the significant negative influence of eUV‐B on the growth ofH. contortusBL‐1 and its adaptive strategy to minimize the negative impacts. With the progression of age, plants although adopted to UV‐B stress with maintenance of productivity, but palatability of forage was affected due to increment of tannin content.
DETERMINING THE MAXIMUM SPEED LIMIT IN URBAN ROAD TO INCREASE TRAFFIC SAFETY
Authors: Sugiyanto Gito , Malkhamah Siti
Published: August 2018

Speed is one of the main risk factors in road traffic safety and become a traffic problem in developing countries. Three factors that cause accidents are human factor, vehicle, and environment. Speeding is one of the main cause factors in traffic accident. Traffic speed must be limited adjust with the activities in the street and potential accident. The aim of this research is to determine the maximum speed limit in urban road to increase traffic safety and to analyze the percentage of vehicle exceeding speed limit. The method to determine maximum speed limits using 85th percentile. Based on the analysis result, the proposed maximum speed limit on urban road for arterial road type 4/2-UD residential and 4/2-UD CBD is 60 km/h for motorcycle and passenger car, 55 km/h for pick up and light truck, and 50 km/h for bus and truck. Proposed maximum speed limit for collector road type 2/1-UD office area is 45 km/h for motorcycle and 40 km/h for four-wheeled vehicles or more while for collector road type 2/1-UD CBD is 40 km/h for motorcycle and 35 km/h for four-wheeled vehicles or more. The installation of speed limit sign is less effective to reduce the vehicle speed, the speed only reduce 2.9-55 km/h (5.6-10.1%). More than 46.5% of motorcycle users ride exceeding speed limit followed by the passenger cars users (39.43%), microbus/city bus at 31.63%, bus Trans at 28.75%, pick up and light truck at 24.69%. The maximum speed limit in school safety zone on hours/after school is 30 km/h with the consideration that the pedestrian fatality rate on 30 km/h has probability of death 10%.
SUSPENDED SEDIMENT CONCENTRATION ASSESSMENT AS A PRECURSOR TO RIVER CHANNEL SHIFTING IN THE BENGAWAN SOLO RIVER, INDONESIA
Authors: Maulana Mahendra Andiek , Aryani Soemitro Ria Asih , Mukunoki Toshifumi , Anwar Nadjadji
Published: August 2018

This study attempts to recognize the fundamental issues in river morphology by examining suspended sediment concentration (SSC) and flow velocity at the curved channel in an alluvial river. To capture the entire set of the afore mentioned conditions, a field investigation was conducted at the inner and outer banks of the flow path of a curved channel, which is considered as the critical section in river change development. The field observations were conducted over a 1-year period, from January to December 2014, in which both dry and rainy seasons occurred. Because the curved channel is subject to severe erosion, especially around the outer bank, lateral migration of the channel might regularly occur. The field investigation showed that the outer side of the curved section migrated approximately 0.0625 m/month during the study period. The SSC, which peaked at 25% and 43% of the maximal flow velocity in the upstream and downstream sections, respectively, showed the rapid erosion of the curved section leading to lateral channel shifting. A channel resistance evaluation confirmed the potential capability of the riverbed material at the curved section was 20% lower than that in the upstream and downstream sections. According to the SSC and flow features, a new understanding of changing river morphology with respect to a curved channel of the Bengawan Solo River was developed.
Co-regulatory networks of human serum proteins link genetics to disease
Authors: Emilsson Valur , Ilkov Marjan , Lamb John R. , Finkel Nancy , Gudmundsson Elias F. , Pitts Rebecca , Hoover Heather , Gudmundsdottir Valborg , Horman Shane R. , Aspelund Thor , Shu Le , Trifonov Vladimir , Sigurdsson Sigurdur , Manolescu Andrei , Zhu Jun , Olafsson Örn , Jakobsdottir Johanna , Lesley Scott A. , To Jeremy , Zhang Jia , Harris Tamara B. , Launer Lenore J. , Zhang Bin , Eiriksdottir Gudny , Yang Xia , Orth Anthony P. , Jennings Lori L. , Gudnason Vilmundur
Published: August 2018

The blood proteome in disease

Understanding the function of human blood serum proteins in disease has been limited by difficulties in monitoring their production, accumulation, and distribution. Emilsson
et al.
investigated human serum proteins of more than 5000 Icelanders over the age of 65. The composition of blood serum includes a complex regulatory network of proteins that are globally coordinated across most or all tissues. The authors identified modules and functional groups associated with disease and health outcomes and were able to link genetic variants to complex diseases.

Science
, this issue p.
769
Automated Microscopic Analysis of Metal Sulfide Colonization by Acidophilic Microorganisms
Authors: Bellenberg Sören , Buetti-Dinh Antoine , Galli Vanni , Ilie Olga , Herold Malte , Christel Stephan , Boretska Mariia , Pivkin Igor V. , Wilmes Paul , Sand Wolfgang , Vera Mario , Dopson Mark
Published: August 2018

The presented method for the assessment of mineral colonization allows accurate relative comparisons of the microbial colonization of metal sulfide concentrate particles in a time-resolved manner. Quantitative assessment of the mineral colonization development is important for the compilation of improved mathematical models for metal sulfide dissolution. In addition, deep-learning algorithms proved that axenic or mixed cultures of the three species exhibited characteristic biofilm patterns and predicted the biofilm species composition. The method may be extended to the assessment of microbial colonization on other solid particles and may serve in the optimization of bioleaching processes in laboratory scale experiments with industrially relevant metal sulfide concentrates. Furthermore, the method was used to demonstrate that DSF quorum sensing signals directly influence colonization and dissolution of metal sulfides by mineral-oxidizing bacteria, such as
L. ferriphilum
and
S. thermosulfidooxidans
.
Influencing organisational culture is key to successfully implementing root cause analysis to tackle late cancer diagnosis
Authors: Staveley Imogen C M , Bointon Emma S
Published: August 2018

Introduction

Late diagnosis of cancer increases morbidity and mortality, and the overall cost of care. Camden Clinical Commissioning Group (CCG) improved the percentage of patients diagnosed at stage I and II cancer, from 39% in 2012 to 47% in 2015;there remained a need to identify the issues leading to late diagnosis.

Method

Camden CCG adapted the Royal College of General Practitioners’ cancer significant event analysis (SEA) tool to be used by general practitioner (GP) surgeries to identify the causes of delayed cancer diagnoses and to find ways to increase early diagnosis. The effective collection of findings through an online portal, comprehensive communication of these to GPs and clear display of these to commissioners ensured the necessary information to transform systems to facilitate early diagnosis. GPs were encouraged to complete a SEA through financial incentivisation, clinical leadership and Cancer Research UK (CRUK) Facilitator input.

Results

49 root cause analyses were completed and the findings led to changes in behaviour to improve early diagnosis of cancer.

Conclusion

Results show that for SEA to be successfully used across a borough to change individual clinician’s behaviour and to induce system transformation, multiple approaches are required: involvement of all stakeholders from the start, clinical leadership, support from CRUK Facilitators, education and financial incentivisation.
Towards theoretically robust evidence on health equity: a systematic approach to contextualising equity-relevant randomised controlled trials
Authors: Wester Gry , Bærøe Kristine , Norheim Ole Frithjof
Published: August 2018

Reducing inequalities in health and the determinants of health is a widely acknowledged health policy goal, and methods for measuring inequalities and inequities in health are well developed. Yet, the evidence base is weak for how to achieve these goals. There is a lack of high-quality randomised controlled trials (RCTs) reporting impact on the distribution of health and non-health benefits and lack of methodological rigour in how to design, power, measure, analyse and interpret distributional impact in RCTs. Our overarching aim in this paper is to contribute to the emerging effort to improve transparency and coherence in the theoretical and conceptual basis for RCTs on effective interventions to reduce health inequity. We endeavour to achieve this aim by pursuing two more specific objectives. First, we propose an overview of three broader health equity frameworks and clarify their implications for the measurement of health inequality in RCTs. Second, we seek to clarify the relationship between theory and translational challenges that researchers would need to attend to, in order to ensure that equity-relevant RCTs are coherently grounded in theory.
Mercury trends and cycling in northern Wisconsin related to atmospheric and hydrologic processes
Authors: Watras C.J. , Grande D. , Latzka A.W. , Tate L.S.
Published: August 2018

Atmospheric deposition is the principal source of mercury (Hg) to remote northern landscapes, but its fate depends on multiple factors and internal feedbacks. Here we document long-term trends and cycles of Hg in the air, precipitation, surface water, and fish of northern Wisconsin that span the past three decades, and we investigate relationships to atmospheric processes and other variables, especially the regional water cycle. Consistent with declining emission inventories, there was evidence of declining trends in these time series, but the time series for Hg in some lakes and most fish were dominated by a near-decadal oscillation that tracked the regional oscillation of water levels. Concentrations of important solutes (SO4, dissolved organic carbon) and the acid–base status of lake water also tracked water levels in ways that cannot be attributed to simple dilution or concentration. The explanatory mechanism is analogous to the “reservoir effect” wherein littoral sediments are periodically exposed and reflooded, altering the internal cycles of sulfur, carbon, and mercury. These climatically driven, near-decadal oscillations confound short or sparse time series and complicate relationships among Hg emissions, deposition, and bioaccumulation.
Analysis of s-wave, p-wave and d-wave holographic superconductors in Hořava–Lifshitz gravity
Authors: Lin Kai , Kuang Xiao-Mei , Qian Wei-Liang , Pan Qiyuan , Pavan A. B.
Published: August 2018

In this work, the s-wave, p-wave and d-wave holographic superconductors in the Hořava–Lifshitz gravity are investigated in the probe limit. For this approach, it is shown that the equations of motion for different wave states in Einstein gravity can be written as a unified form, and condensates take place in all three cases. This scheme is then generalized to Hořava–Lifshitz gravity, and a unified equation for multiple holographic states is obtained. Furthermore, the properties of the condensation and the optical conductivity are studied numerically. It is found that, in the case of Hořava–Lifshitz gravity, it is always possible to find some particular parameters in the corresponding Einstein case where the condensation curves are identical. For fixed scalar field mass m, a nonvanishing [Formula: see text] makes the condensation easier than in Einstein gravity for s-wave superconductor. However, the p-wave and d-wave superconductors have T[Formula: see text] greater than the s-wave.
AN ANATOMICALLY-RELEVANT COMPUTATIONAL MODEL FOR PRIMARY BLAST EFFECTS ON THE HUMAN LOWER EXTREMITY
Authors: BERTUCCI ROBBIN , PRABHU RAJ , HORSTEMEYER M. F. , MAO YUXIONG , GILBRECH RYAN , SHENG JAMES , WILLIAMS LAKIESHA N. , LIAO JUN
Published: August 2018

Explosions pose serious threats to US soldiers and civilians, often resulting in disability and death. Due to its direct contact with the ground, the lower extremity is commonly injured, and the blast loading often results in traumatic amputations and soft tissue rupture. The exact overpressure signatures that induce these primary blast injuries are still unknown. A high fidelity FE model of the lower extremity blast condition is thus essential to reveal the underlying injury mechanism. In this study, we created an anatomically-relevant lower extremity model and analyzed several different blast cases using Abaqus/Explicit. Pressures, impulses, stresses, and maximum principal strains were evaluated and compared to previous results in the literature. Our FE model and simulation were able to capture the detailed structural responses to a blast wave in the lower extremity; moreover, we showed that the injury patterns could be correlated to biomechanical metrics that may have incited pathologies such as amputations and compartment syndrome. The lower extremity FE model developed in this project allows for a cost-effective and reproducible analysis of blast events and has the potential to improve injury metrics and personal protective equipment design by accurately evaluating the damage imposed on the lower extremity.
The Cyclical Job Ladder
Authors: Moscarini Giuseppe , Postel-Vinay Fabien
Published: August 2018

Many theories of labor market turnover generate a job ladder. Due to search frictions, workers earn rents from employment. All workers agree on which jobs are, in this sense, more desirable and slowly climb the job ladder through job-to-job quits. Occasionally, negative shocks throw them off the ladder and back into unemployment. We review a recent body of theory and empirical evidence on labor market turnover through the lens of the job ladder. We focus on the critical role that the job ladder plays in transmitting aggregate shocks, through the pace and direction of employment reallocation, to economic activity and wages and in shaping business cycles more generally. The main evidence concerns worker transitions, both through nonemployment and from job to job, between firms of different sizes, ages, productivity levels, and wage premiums, as well as the resulting earnings growth. Poaching by firms up the ladder is the main engine of reallocation, which shuts down in recessions.
Agent-based model illustrates the role of the microenvironment in regeneration in healthy and mdx skeletal muscle
Authors: Virgilio Kelley M. , Martin Kyle S. , Peirce Shayn M. , Blemker Silvia S.
Published: August 2018

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease with no effective treatment. Multiple mechanisms are thought to contribute to muscle wasting, including increased susceptibility to contraction-induced damage, chronic inflammation, fibrosis, altered satellite stem cell (SSC) dynamics, and impaired regenerative capacity. The goals of this project were to 1) develop an agent-based model of skeletal muscle that predicts the dynamic regenerative response of muscle cells, fibroblasts, SSCs, and inflammatory cells as a result of contraction-induced injury, 2) calibrate and validate the model parameters based on comparisons with published experimental measurements, and 3) use the model to investigate how changing isolated and combined factors known to be associated with DMD (e.g., altered fibroblast or SSC behaviors) influence muscle regeneration. Our predictions revealed that the percent of injured muscle that recovered 28 days after injury was dependent on the peak SSC counts following injury. In simulations with near-full cross-sectional area recovery (healthy, 4-wk mdx, 3-mo mdx), the SSC counts correlated with the extent of initial injury; however, in simulations with impaired regeneration (9-mo mdx), the peak SSC counts were suppressed relative to initial injury. The differences in SSC counts between these groups were emergent predictions dependent on altered microenvironment factors known to be associated with DMD. Multiple cell types influenced the peak number of SSCs, but no individual parameter predicted the differences in SSC counts. This finding suggests that interventions to target the microenvironment rather than SSCs directly could be an effective method for improving regeneration in impaired muscle.

NEW & NOTEWORTHY A computational model predicted that satellite stem cell (SSC) counts are correlated with muscle cross-sectional area (CSA) recovery following injury. In simulations with impaired CSA recovery, SSC counts are suppressed relative to healthy muscle. The suppressed SSC counts were an emergent model prediction, because all simulations had equal initial SSC counts. Fibroblast and anti-inflammatory macrophage counts influenced SSC counts, but no single factor was able to predict the pathological differences in SSC counts that lead to impaired regeneration.
Insulin inhibits autophagy signaling independent of counterregulatory hormone levels but does not affect the effects of exercise
Authors: Møller Andreas Buch , Voss Thomas Schmidt , Vendelbo Mikkel Holm , Pedersen Steen Bønløkke , Møller Niels , Jessen Niels
Published: August 2018

Acute exercise increases autophagic signaling through Unc-51 like kinase-1 (ULK1) in human skeletal muscle during both anabolic and catabolic conditions. The aim of the present study was to investigate if changes in ULK1 Ser555 phosphorylation during exercise are reflected by changes in phosphorylation of a newly identified ULK1 substrate (ATG14 Ser29) and to elucidate the involvement of circulatory hormones in the regulation of autophagy in human skeletal muscle. We show that 1 h of cycling exercise increases ATG14 Ser29 phosphorylation during both hyperinsulinemic euglycemic and euinsulinemic euglycemic conditions. This could suggest that counterregulatory hormones stimulate autophagy in skeletal muscle, as circulating concentrations of these hormones are highly elevated during exercise. Furthermore, ATG14 Ser29 correlated positively with ULK1 phosphorylation, suggesting that ULK1 Ser555 (activating site) phosphorylation reflects ULK1 kinase activity. In a separate series of experiments, we show that insulin stimulates ULK1 phosphorylation at Ser757 (inhibitory site) in both hypoglycemic and euglycemic conditions, suggesting that counterregulatory hormones (such as epinephrine, norepinephrine, growth hormone, and glucagon) have limited effects on autophagy signaling in human skeletal muscle. In conclusion, 1 h of cycling exercise increases phosphorylation of ATG14 at Ser29 in a pattern that mirrors ULK1 phosphorylation at Ser555. Moreover, insulin effects on autophagy signaling in human skeletal muscle are independent of hypoglycemic and euglycemic conditions.

NEW & NOTEWORTHY Autophagy signaling is regulated in a hierarchical order by exercise, insulin, and counterregulatory hormones. Exercise-induced autophagy signaling is stimulated by local factors in skeletal muscle rather than circulatory hormones. Unc-51 like kinase-1 (ULK1) phosphorylation at Ser555 reflects ULK1 kinase activity.
The Complexity and Simulation of Revenue Sharing Negotiation Based on Construction Stakeholders
Authors: Meng Qingfeng , Chen Jingxian , Qian Kun
Published: August 2018

This paper focuses on the complexity characteristics of a stakeholder’s revenue sharing for time compression in construction projects, such as adopting a life cycle perspective, the preferences of stakeholders, and the adaptability behaviors in the negotiation process. We build an agent‐based model on revenue sharing negotiation. Considering that the agents who are in a weak position not only care about their own benefits but also compare their benefits to others, we design an experimental scenario where a contractor has fairness preference based on China’s reality. According to different sympathy and envy coefficients, we can divide the inequity aversion preference into three typical types, and we research how a contractor’s different types of inequity aversion preferences impact revenue sharing coefficient of agreements, results of successful negotiations, and efficiency in negotiations. Results are as follows: it is advantageous for a contractor to maintain a modest inequity aversion for their own earnings and the degree of sympathy preference in inequity aversion has an important impact on the time to reach consensus while the degree of jealousy preference has no obvious effect. If contractors’ sympathy preference is maintained within a moderate range, it will achieve a higher success rate of negotiations in the negotiation process; the success rate of negotiation is affected largely by the agents’ sympathy preference, though it is also influenced by the jealousy preference, but it is not very sensitive.
Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis
Authors: Chen Xi , Kong Xiaohong , Zhu Jie , Zhang Tingting , Li Yanwei , Ding Guifeng , Wang Huijuan
Published: August 2018

Objective. Thyroid dyshormonogenesis (DH) is a genetically heterogeneous inherited disorder caused by thyroid hormone synthesis abnormalities. This study aims at comprehensively characterizing the mutation spectrum in Chinese patients with DH. Subjects and Methods. We utilized next-generation sequencing to screen for mutations in seven DH-associated genes (TPO, DUOX2, TG, DUOXA2, SLC26A4, SLC5A5, and IYD) in 21 Chinese Han patients with DH from Xinjiang Province. Results. Twenty-eight rare nonpolymorphic variants were found in 19 patients (90.5%), including 19, 5, 3, and 1 variants in DUOX2, TG, DUOXA2, and SLC26A4, respectively. Thirteen (62%) patients carried monogenic mutations, and six (28.5%) carried oligogenic mutations. Fifteen (71%) patients carried 2 or more DUOX2 (14) or DUOXA2 (1) variants. The genetic basis of DH in nine (43%) patients harboring biallelic or triallelic pathogenic variants was resolved. Seventeen patients (81%) carried DUOX2 mutations, most commonly p.R1110Q or p.K530X. No correlations were found between DUOX2 mutation types or numbers and clinical phenotypes. Conclusions. DUOX2 mutations were the most predominant genetic alterations of DH in the study cohort. Oligogenicity may explain the genetic basis of disease in many DH patients. Functional studies and further clinical studies with larger DH patient cohorts are needed to validate the roles of the mutations identified in this study.
Prediction of Surface Roughness and Optimization of Cutting Parameters of Stainless Steel Turning Based on RSM
Authors: Xiao Maohua , Shen Xiaojie , Ma You , Yang Fei , Gao Nong , Wei Weihua , Wu Dan
Published: August 2018

The turning test of stainless steel was carried out by using the central composite surface design of response surface method (RSM) and Taguchi design method of central combination design. The influence of cutting parameters (cutting speed, feed rate, and cutting depth) on the surface roughness was analyzed. The surface roughness prediction model was established based on the second-order RSM. According to the test results, the regression coefficient was estimated by the least square method, and the regression equation was curve fitted. Meanwhile, the significance analysis was conducted to test the fitting degree and response surface design and analysis, in addition to establishing a response surface map and three-dimensional surface map. The life of the machining tool was analyzed based on the optimized parameters. The results show that the influence of feed rate on the surface roughness is very significant. Cutting depth is the second, and the influence of cutting speed is the least. Therefore, the cutting parameters are optimized and tool life is analyzed to realize the efficient and economical cutting of difficult-to-process materials under the premise of ensuring the processing quality.
A Targeted Quantitative Proteomic Approach Assesses the Reprogramming of Small GTPases during Melanoma Metastasis
Authors: Huang Ming , Qi Tianyu F. , Li Lin , Zhang Gao , Wang Yinsheng
Published: August 2018

Small GTPases of the Ras superfamily are master regulators of intracellular trafficking and constitute essential signaling components in all eukaryotes. Aberrant small GTPase signaling is associated with a wide spectrum of human diseases, including cancer. Here, we developed a high-throughput, multiple reaction monitoring–based workflow, coupled with stable isotope labeling by amino acids in cell culture, for targeted quantification of approximately 100 small GTPases in cultured human cells. Using this method, we investigated the differential expression of small GTPases in three pairs of primary and metastatic melanoma cell lines. Bioinformatic analyses of The Cancer Genome Atlas data and other publicly available data as well as cell-based assays revealed previously unrecognized roles of RAB38 in promoting melanoma metastasis. Diminished promoter methylation and the subsequent augmented binding of transcription factor MITF contributed to elevated expression of RAB38 gene in metastatic versus primary melanoma cells. Moreover, RAB38 promoted invasion of cultured melanoma cells by modulating the expression and activities of matrix metalloproteinases-2 and -9. Together, these data establish a novel targeted proteomic method for interrogating the small GTPase proteome in human cells and identify epigenetic reactivation of RAB38 as a contributing factor to metastatic transformation in melanoma.

Significance: A novel quantitative proteomic method leads to the discovery of RAB38 as a new driver of metastasis in melanoma. Cancer Res; 78(18); 5431–45. ©2018 AACR.
miR-155 Is Downregulated in Familial Adenomatous Polyposis and Modulates WNT Signaling by Targeting AXIN1 and TCF4
Authors: Prossomariti Anna , Piazzi Giulia , D'Angelo Leonarda , Miccoli Sara , Turchetti Daniela , Alquati Chiara , Montagna Claudio , Bazzoli Franco , Ricciardiello Luigi
Published: August 2018

Adenomatous Polyposis Coli (APC) gene mutations are responsible for the onset of familial adenomatous polyposis (FAP) and sporadic colorectal cancer and have been associated with miRNAs dysregulation. The capacity of miR-155, a cancer-related miRNA, to target components of the WNT/β-CATENIN pathway suggests that APC gene mutations, controlling miRNAs expression, may critically regulate WNT/β-CATENIN signaling. To this end, APC gene target sequencing was performed on colonic adenomatous polyps and paired normal mucosa clinical specimens from FAP patients (n = 9) to elucidate the role of miR-155-5p in APC-mutant setting. The expression of selected miRNAs and WNT/β-CATENIN signaling components was characterized in FAP patients and non-FAP control subjects (n = 5). miR-155-5p expression and functional effects on WNT cascade, cell survival, growth, and apoptosis were investigated in different colorectal cancer cell lines. A somatic second hit in the APC gene was found in adenomatous polyps from 6 of 9 FAP patients. Heterozygous APC gene mutations in FAP patients were associated with altered expression of candidate miRNAs and increased levels of AXIN1 and AXIN2 mRNAs. miR-155-5p was downregulated in FAP patients and in the APC and β-CATENIN–mutant colorectal cancer cell lines, and critically regulates WNT/β-CATENIN cascade by targeting both AXIN1 and TCF4. Importantly, miR-155-5p may sustain long-term WNT/β-CATENIN activation in colorectal cancer cells upon WNT3A stimulation.

Implications:

This study supports a key role of miR-155-5p in modulating WNT/β-CATENIN signaling in colorectal cancer and unravels a new mechanism for AXIN1 regulation which represents a potential therapeutic target in specific tumor subtypes.
A Review of the Imaging Techniques for Measuring Kidney and Cyst Volume in Establishing Autosomal Dominant Polycystic Kidney Disease Progression
Authors: Magistroni Riccardo , Corsi Cristiana , Martí Teresa , Torra Roser
Published: August 2018

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited renal disorder; it is defined by progressive renal cyst formation and subsequent renal enlargement that leads to end-stage renal disease. Until recently, only symptomatic treatments for ADPKD existed. However, therapies that address the underlying pathophysiology of ADPKD are now available and accurate identification of the rate of disease progression is essential. Summary: Published data on the different imaging modalities for measuring kidney and cyst volumes in ADPKD are reviewed. The advantages and drawbacks of the different techniques for calculating kidney volume from renal imaging are also examined, including the use of manual planimetry, stereology, and the ellipsoid equation, as well as the prospect of semi- and fully automatic techniques. The translation of these approaches into clinical practice and their role in informing treatment decisions is discussed. Key Messages: These new therapies require the accurate monitoring of disease progression, which along with diagnosis and prognosis, relies on the effective use of renal imaging techniques. There is growing support for the use of total kidney volume as a measure of cyst burden and as a prognostic predictor of renal function in ADPKD, showing promise as a marker of disease progression.
The PMEL Gene and Merle in the Domestic Dog: A Continuum of Insertion Lengths Leads to a Spectrum of Coat Color Variations in Australian Shepherds and Related Breeds
Authors: Ballif Blake C. , Ramirez Christina J. , Carl Casey R. , Sundin Kyle , Krug Melissa , Zahand Adam , Shaffer Lisa G. , Flores-Smith Helen
Published: August 2018

Merle is a distinct coat color and pattern found in numerous species, including the domestic dog, characterized by patches of diluted eumelanin (black pigment) interspersed among areas of normal pigmentation. In dogs, this variegated pattern is caused by an insertion of a SINE element into the canine PMEL gene. Although variation in the length of the SINE insertion - due to a variable-length poly(A) tail - has been observed to be associated with variation in merle coat color and patterning, no systematic evaluation of this correlation has been conducted and published in the scientific literature. We performed high-resolution analysis of the SINE insertion lengths in 175 dogs (99 Australian shepherds, 45 miniature Australian shepherds, and 31 miniature American shepherds) and compared the genotypes with the coat phenotypes (when available). SINE insertion lengths varied from 201 to 277 bp, indicating that merle insertion variants can occur in virtually any size along the entire continuum. Genotype-phenotype correlation of 126 dogs with only a single SINE insertion (m/M) identified at least 4 major phenotypic clusters designated as “cryptic,” “atypical,” “classic,” and “harlequin” merle. However, we found several phenotypic outliers that did not cluster within these major groupings, suggesting that insertion size is not the only factor responsible for merle phenotypic variability. In addition, we detected 25 dogs with 2 SINE insertions (M/M) and 24 dogs with more than 2 PMEL (merle) alleles, indicating mosaicism. Genotype-phenotype correlation of M/M dogs suggests that cryptic merle alleles often act like non-merle (m) alleles when combined with atypical, classic, and harlequin-sized alleles. The finding of mosaicism has important implications for the dog's phenotype and the ability to potentially transmit various alleles to its offspring. Furthermore, we identified examples of the SINE insertion poly(A)-tail expansion and contraction between generations, which also has important implications for breeding practices and determining mating pairs to avoid producing double merle dogs. These data demonstrate that there is a continuum of merle insertion lengths associated with a spectrum of coat color and patterns and that genotype-phenotype exceptions and overlap make it difficult to strictly assign certain insertion sizes with an expected coat color, although some generalizations are possible.
Validation of a Wearable Sensor for Measuring Running Biomechanics
Authors: Koldenhoven Rachel M. , Hertel Jay
Published: August 2018

Background: Running biomechanics have traditionally been analyzed in laboratory settings, but this may not reflect natural running gait. Wearable sensors may offer an alternative. Methods: A concurrent validation study to determine agreement between the RunScribeTM wearable sensor (triaxial accelerometer and gyroscope) and the 3D motion capture system was conducted. Twelve injury-free participants (6 males, 6 females; age = 23.1 ± 5.5 years, weekly mileage = 16.1 ± 9.3) ran 1.5 miles on a treadmill. Ten consecutive strides from each limb were collected, and the mean values were analyzed. Pronation excursion, maximum pronation velocity, contact time, and cycle time were compared between measurement platforms using intraclass correlation coefficients (ICC) and Bland-Altman analyses. Results: Excellent ICC estimates were found for maximum pronation velocity, contact time, and cycle time. Pronation excursion demonstrated fair ICC estimates. The mean differences between platforms were small with limits of agreement clustered around zero, except for contact time measures which were consistently higher with the RunScribe compared to the camera-based system. Conclusion: Our study revealed that the RunScribe wearable device showed good to excellent concurrent validity for maximum pronation velocity, contact time, and cycle time; however, direct comparisons or results between the two platforms should not be used.
C/EBPβ Acts Upstream of NF-κB P65 Subunit in Ox-LDL-Induced IL-1β Production by Macrophages
Authors: Ma Jun , Liu Chuan , Yang Yuanqi , Yu Jie , Yang Jie , Yu Sanjiu , Zhang Jihang , Huang Lan
Published: August 2018

Background/Aims: Interleukin-1β (IL-1β) is one of the critical inflammatory factors during atherogenesis. CCAAT/enhancer binding proteins β (C/EBPβ), a regulator of IL-1β production, recently been evidenced as a key player in the development of atherosclerosis. However, the mechanisms of how C/EBPβ regulates the production of IL-1β are unclear. In this study, we aimed to explore the role of C/EBPβ in regulating IL-1β production in macrophages after oxidized low-density lipoprotein (ox-LDL) exposure and the underlying mechanisms. Methods: RAW264.7 macrophages were treated with 0, 25, 50 or 100 μg/ml ox-LDL for 12, 24 or 48 h. Small interfering RNAs were used to silence related proteins. The gene and protein expression levels were determined by quantitative real-time polymerase chain reaction or western blot (WB). IL-1β secretion was assessed by enzyme-linked immunosorbent assay. The cytoplasmic and nuclear proteins were evaluated by nuclear fractionation followed by WB. Localization of p65 was observed by immunofluorescence. The binding activity of p65 to IL-1β was tested by dual-luciferase reporter assay. Results: Ox-LDL increased IL-1β production, accompanied with increasing C/EBPβ and p65 expression in a dose- and time-dependent manner. Moreover, C/EBPβ deficiency in macrophages blocked ox-LDL-induced increases in IL-1β expression, maturation as well as p65 activation. However, p65 deficiency inhibited the increase in IL-1β production, but not C/EBPβ expression. Dual-luciferase reporter results showed that overexpression of C/EBPβ significantly enhanced binding activity of p65 to IL-1β promoter. In addition, C/EBP 1β deficiency in macrophages abolished the ox-LDL-induced gene transcription increases of IL-1β, IL-6, p65 and caspase-1. Conclusions: Our results demonstrate that C/EBPβ acts upstream of NF-κB p65 subunit in ox-LDL-induced IL-1β production in macrophages and may regulate IL-1β maturation by promoting caspase-1. C/EBPβ may be a promising candidate for the prevention and treatment of atherosclerosis.
Knockdown of Mir-135b Sensitizes Colorectal Cancer Cells to Oxaliplatin-Induced Apoptosis Through Increase of FOXO1
Authors: Qin Yan , Li Longhai , Wang Fang , Zhou Xinyi , Liu Yankui , Yin Yuan , Qi Xiaowei
Published: August 2018

Background/Aims: Aberrant expression of microRNAs (miRNAs) is found to be responsible for tumorigenesis, cancer development and chemoresistance. Although oxaliplatin is an effective chemotherapeutic drug for treatment of colorectal cancer (CRC), CRC cells can develop some mechanisms to evade oxaliplatin-induced cell death. It is urgent to explore the novel strategies to increase the chemosensitivity of CRC cells. Methods: QRT-PCR analysis was performed to detect the expression of miR-135b in CRC patients’ serum and CRC cell lines. MTT assays were used to evaluate the effect of anti-miR-135b on oxaliplatin-induced cell death in CRC cell lines. Western blot, flow cytometry and luciferase reporter assays were performed to evaluate the potential mechanism and pathway of anti-miR-135b-promoted apoptosis in oxaliplatin-treated CRC cells. Results: Significant upregulation of miR-135b was observed in CRC cell lines and CRC patients’ serum. Knockdown of miR-135b was found to sensitize colorectal cancer cells to oxaliplatin-induced cytotoxicity. Mechanically, knockdown of miR-135b increased the expression level of FOXO1 in CRC. As the downstream, the increased FOXO1 induced by anti-miR-135b promoted the expression of Bim and Noxa. Since Bim and Noxa act as key pro-apoptotic proteins in mitochondrial apoptosis, anti-miR-135b was able to enhance the oxaliplatin-induced apoptosis dependent on the anti-miR-135b/FOXO1 axis. Conclusions: Anti-miR-135b enhanced the anti-tumor effect of oxaliplatin on CRC. Combination with miR-135b antisense nucleotides may represent a novel strategy to sensitize CRC to oxaliplatin-based treatment.
Trees and Streets
Authors: Beerden Kim
Published: August 2018

Review of: H.I. Flower,The Dancing Lares and the Serpent in the Garden. Religion at the Roman Street Corner. This excellent book shows how religion and politics interacted during the transition from Republic to Empire. Thelaresare considered to be ‘gods of place’—this category will prove to be useful for future studies of Roman religions.
Public Participation in China’s Water Governance
Authors: SPIJKERS Otto , LI Xian , DAI Liping
Published: August 2018

This article analyses the role of public participation in China’s water governance. First, it provides an overview of the relevant international law provisions applicable to China. This is followed by an analysis of the implementation of these international obligations and their incorporation into China’s domestic water governance. The article demonstrates that the problem is not a lack of rules and regulations calling for public participation, but rather that these rules and regulations are often too vague to be meaningfully applied in practice. It is not always clear what type of public participation is called for, and which public should be invited to participate.
Description of two new genera (Antarctotetilla, Levantiniella) and a new species of Tetillidae
Authors: CARELLA MIRCO , URIZ MARIA J.
Published: August 2018

Tetillidae is a sponge family distributed all over the world but with some genera apparently endemic from the Antarctic and Subantarctic (the “Antarctic clade”). Species identification results tricky due to the similarities of their morphological characters. However, molecular phylogenies have helped to resolve the family taxonomy. The last phylogenetic study on Tetillidae suggested the creation of two new genera: Levantiniella and Antarctotetilla. Lenvantiniella, from Middle East Mediterranean Sea, was previously classified within Cinachyrella, from which it differs in the small rounded surface cavities, distinctive from true porocalices. Antarctotetilla has up to now an Antarctic distribution, and harbors species wrongly classified within Tethya, Craniella, or Tetilla. The main differences of Antarctotetilla to other Tetillidae genera are the presence of pores grouped in small areas, and a poorly-defined cortex (pseudocortex). This study aims to re-describe in detail the species of Tetillidae that belong in the two above mentioned new genera, and to highlight that molecular phylogenies should be combined with morphological analyses to improve taxonomical decisions. We also describe a new Tetillidae species with a hair-like hispidation, which we name Antarctotetilla pilosa nov. sp. Furthermore, the types of Tethya coactifera and T. crassispicula (Lendenfeld, 1907) were reexamined because of some morphological similarities with Antarctotetilla. The minibarcode sequences (a small COI fragment) placed them within the Antarctic clade harboring Antarctotetilla and Cinachyra, but did not resolve their genus position. A morphological revision, however, suggests placing T. coactifera in Antarctotetilla, while T. crassispicula, which owns porocalices and a spicule-reinforced cortex, appeared to belong in Cinachyra.
Using Lomb–Scargle Analysis to Derive Empirical Orthogonal Functions from Gappy Meteorological Data
Authors: Dupuis Christopher , Schumacher Courtney
Published: August 2018

The Lomb–Scargle discrete Fourier transform (LSDFT) is a well-known technique for analyzing time series. In this study, a solution for empirical orthogonal functions (EOFs) based on irregularly sampled data is derived from the LSDFT. It is demonstrated that this particular algorithm has no hard limit on its accuracy and yields results comparable to those of complex Hilbert EOF analysis. Two LSDFT algorithms are compared in terms of their performance in evaluating EOFs for precipitation observations from the Tropical Rainfall Measuring Mission satellite. Both are shown to be able to capture the pattern of the diurnal cycle of rainfall over the complex topography and diverse land cover of South America, and both also show other consistent features in the 0–12-day frequency band.
A two-step homogeneous assay for apolipoprotein E-containing high-density lipoprotein-cholesterol
Authors: Takahashi Yuji , Ito Yasuki , Sakurai Toshihiro , Wada Norio , Nagasaka Atsushi , Fujikawa Masato , Chiba Hitoshi , Hui Shu-Ping
Published: August 2018

Background

Apolipoprotein E-containing high-density lipoprotein shows antiatherogenic properties in vitro. There is a need for a homogeneous assay to determine the concentration of apolipoprotein E-containing high-density lipoprotein for in vivo studies.

Methods

In the proposed homogeneous assay, lipoproteins other than apolipoprotein E-containing high-density lipoprotein were eliminated in the first step. Apolipoprotein E-containing high-density lipoprotein-cholesterol was measured in the second step. The control study used a 13% polyethylene glycol precipitation assay (control assay).

Results

The homogeneous assay showed good performance in validation studies. In subjects with normal liver function ( n = 78), a significant correlation was found between the control assay and the homogeneous assay ( r = 0.824). Serum apolipoprotein E-containing high-density lipoprotein cholesterol concentrations, determined by the control assay and the homogeneous assay, respectively, were 0.05 (0.04–0.10) (median [25th–75th percentile]) mmol/L and 0.10 (0.06–0.13) mmol/L for healthy individuals ( n = 12), and 0.03 (0.01–0.13) mmol/L and 0.02 (0.01–0.02) mmol/L for patients with cholestasis ( n = 6). The results indicate that the homogeneous assay recovers cholesterol contained in physiological apolipoprotein E-containing high-density lipoprotein, but not in pathological apolipoprotein E-containing high-density lipoprotein from cholestatic patients.

Conclusions

The proposed two-step homogeneous assay enables selective measurement of physiological apolipoprotein E-containing high-density lipoprotein cholesterol in common autoanalysers. This assay might uncover a role for apolipoprotein E-containing high-density lipoprotein in physiological conditions.
The limitations of the theory and practice of mobilization in trade union organizing
Authors: Holgate Jane , Simms Melanie , Tapia Maite
Published: August 2018

Since the publication of Rethinking Industrial Relations in 1998, John Kelly’s mobilization theory has been used by many scholars attempting to understand union organizing – often using specific campaigns to unpack and analyse various elements of the theory that help to explain the success or failure of collective mobilization. In this article the authors review this literature and highlight the major areas of interest from the book – injustice, framing and leadership – and the contribution to industrial relations research. They find that the terms mobilizing and organizing are used interchangeably, which, they argue, is problematic and has led to confusion about what is actually happening in unions. Unpacking the difference between the two terms can help to explain limitations in the way mobilization theory has been used by scholars, and, at the same time, deepen our understanding of why unions have not been particularly successful in reversing their decline despite the ‘turn to organizing’ over the last few decades.