bluuebunny/crossref_metadata_2025 huggingface dataset:
Empowerment as a Predictor of HIV Testing Among Married Women in Nepal
Authors: Thapa Roshna , Yang Youngran , Kang Jeong Hee , Nho Ju-Hee
Published: January 2019

We examined the association of women empowerment and HIV testing in Nepalese women. Data from the 2012 Nepal Demographic and Health Survey provided a sample of 6,579 females ages 15–49 years. Women empowerment subcategories included participation in decision making, attitudes about safer sex negotiation, and sexual autonomy. Only 454 participants (6.9%) had been tested for HIV. Of note, 41.3% had high participation in decision making, 84.5% showed positive attitudes about safer sex negotiation, and 71.8% scored high in sexual autonomy. After adjusting potential confounders, the odds of being tested were higher for women with positive attitudes about safer sex negotiation (adjusted odds ratio = 1.444, 95% confidence interval: 1.006–2.072, p = .046) and high sexual autonomy (adjusted odds ratio = 3.138, 95% confidence interval: 1.375–7.164, p = .007). Age, education, and wealth were independent factors determining the women's HIV testing approach. Our study can be a guide for interventions and policies to empower women and encourage HIV testing in Nepal.
Novel tyrosine kinase inhibitors for patients with inadequate response in chronic myeloid leukemia
Authors: Mauro Michael J.
Published: January 2019

Purpose of review

The purpose of this review is to summarize treatment expectations and response milestones, to conceptualize the approach to defining inadequate response to therapy and critically appraise current available strategies, as well to highlight novel agents under development to address unmet needs in chronic myeloid leukemia (CML) therapy.

Recent findings

Given excess risk with currently available highly potent ABL1 (Abelson murine leukemia viral oncogene homolog 1) inhibitors, a number of alternate, highly potent compounds have entered the clinic to address select resistance such as the T315I mutation with the promise of greater selectivity and better adverse event profile. In addition, alternate approaches to ABL1 inhibition, targeting the myristoyl pocket of ABL1, are showing promising early results and are moving into later phase trials.

CML is a highly treatable form of leukemia with multiple orally available small molecule inhibitors of the activated BCR-ABL1 (breakpoint cluster region-ABL1) kinase. Despite such an array of therapy options, inadequate response to therapy remains a challenge with a substantial minority of patients facing tyrosine kinase inhibitor (TKI) resistance, intolerance, or both. Unmet needs in Ph+ leukemia include highly selective resistant disease, multi-TKI resistant CML, and advanced phase disease.
Atypical Mandibular Angle Fracture
Authors: Junior Wanderley da Silva Félix , Fanderuff Marina , Reis Thiago Vinicius Rodrigues , Rebellato Nelson Luis Barbosa , Scariot Rafaela , Klüppel Leandro Eduardo
Published: January 2019

The mandibular fracture takes the second position among facial bones fractures, with significant increase of cases in the last years. The aim of this paper is to report a clinical case of a patient with facial trauma due to an automotive accident, resulting in an atypical fracture in a unilateral mandibular angle. In the image examinations an atypical favorable fracture in the right mandibular angle region involving the apex of the erupted 48 tooth was found. The fracture line started in the posterior region of mandibular ramus, below mandibular condyle, and spread out until inferior border of the mandible in premolar region. Despite the atypical design of the mandibular angle fracture described in this paper, the treatment showed satisfactory results, without any aesthetic or functional changes for the patient.
A Novel Application of Virtual Surgical Planning to Facial Feminization Surgery
Authors: Mandelbaum Max , Lakhiani Chrisovalantis , Chao Jerry W.
Published: January 2019

Feminization of the frontonasal-orbital complex is a critical aspect in surgical management of gender dysphoria. Here, we describe our utilization of a prefabricated cutting guide to facilitate frontal sinus setback.
Three Simultaneous Free Flaps to Reconstruct a Complex Frozen Neck and a Large Hypopharyngeal Fistula
Authors: Fodor Lucian , Chirila Magdalena , Sobec Raluca , Sita Laura , Fodor Marius
Published: January 2019

Frozen neck and hypopharyngeal fistula are sometimes present after tumor ablation of the larynx, multiple local surgeries with scar tissue, and radiotherapy and chemotherapy. This multiorgan involvement requires 1 or even 2 flaps. We present a 63-year-old heavy smoker with frozen neck tissue and simultaneous large hypopharyngeal fistula and neck defect. After careful preoperative planning, he was successfully treated with 3 simultaneous free flaps: 2 anterolateral thigh flap (ALT) and 1 lateral arm flap (LAF). One ALT was used as a patch to restore the hypopharynx continuity. A second ALT was used to cover the anterior neck defect and the LAF flap was used to reconstruct the submandibular area. The flaps survived and the patient had a 5 mm proximal fistula which was sutured, and he was able to eat per mouth. By combining multiple free flaps, we were able to restore the function of the hypopharynx and to cover the esthetic units of the neck by avoiding the “turkey neck” appearance.
Secondary Reconstruction of Calvarial Defects by Using Free Flap: Report of Consecutive Cases and Analysis of Strategy
Authors: Heron Antoine , Michot Audrey , Menez Tiphaine , Jecko Vincent , Penchet Guillaume , Casoli Vincent
Published: January 2019

Introduction:

Multiplication of incisions and/or radiotherapy on the scalp, lead to skin necrosis and chronic osteitis. In this situation, reconstructive surgery can be useful to cover complex lack of tissue.

Materials and Methods:

The 5 patients were treated with the neurosurgery department of our hospital. The procedure included debridement of the infected calvarian bone and tissues and coverage by free antebrachial flap. A 2 stages skin graft, using a dermal regeneration template, or direct closure was used for the donor site. Evaluation of flap quality and donor site morbidity was done during hospitalization and 3 months after the procedure.

Results:

The procedure was achieved on 5 patients. All the patients were healed 3 months after surgery. For 1 patient, a second procedure was done in emergency for anastomosis revision. There was non-complication concerning the donor site. All the patients healed with a good coverage.

Conclusion:

Treatment of calvarian bone necrosis needs a very good and reliable coverage, such as free flap can provide. In our opinion, the antebrachial free flap is an interesting option, despite the fact that it is still underused for scalp coverage.
Preferred Experience of Modifications to Emergency Surgical Treatment for Total Scalp Avulsion With Halo-Vest Head Ring and Quick Hair Removing
Authors: Lin Jian , Zhou Feng , Wu Li-Zhi , Li Yu-fei , Li Qing-feng , Zhang Ying-fan , Liu Cai-yue
Published: January 2019

Background:

Total scalp avulsion is a fairly rear but severe soft tissue injury. Even with microsurgical replantation, the survival rate is still low. In this study, the authors incorporated 2 main modifications (Halo-Vest head ring and quick hair removing) and assessed the surgical outcomes versus those of traditional replantation.

Methods: :

Eighteen patients were included in the study who suffered from total scalp avulsion. After consideration of the outcomes from the first 7 patients, the authors modified our surgical procedures and introduced the use of Halo-Vest head ring and quick hair removing in the treatments for the rest 11 patients. The surgical outcomes with both approaches were observed and compared, including the operation time and incidence of scalp necrosis.

Results: :

The mean debridement time was 3.5 hours in traditional treatment versus 1.68 hours in modified treatment. The mean operative time was 11.14 hours in traditional treatment versus 8.05 hours in modified treatment. After the replantation, in those 7 patients without modifications, there was 1 total scalp necrosis and 6 partial scalp necrosis. In those 11 patients with modifications, there was 1 total scalp necrosis and 1 suffered a partial scalp necrosis, while the scalp survived well in other 9 patients. Classical cases with modified or traditional methods were reported respectively.

Conclusion:

The application of Halo-Vest head ring and quick hair removing provides a reliable method to treat total scalp avulsion. It is safe, technically easy and worth being widely used in the clinical application.
A Different Stabilization Technique of Autogenous Cartilage Grafts in Saddle Nose Deformity: Prevention Warping and Resorption
Authors: Gundeslioglu A. Ozlem , Yildirim Mehmet Emin Cem , Yarar Serhat , Uyar Ilker , Ismayilzade Majid
Published: January 2019

Background:

Saddle nose deformity (SND) is a collapse of the cartilage and bone structures forming the dorsal projection of the nose. After the use of autologous cartilage in the treatment of SND, resorption and warping continue to be a problem.

Methods:

This study presents results from 11 patients with SND types III and IV from 2005 to 2017 treated with autologous cartilage fixed with microplates and microscrews. The patients were monitored for at least 1 year. Resorption and warping were measured using postoperative photographs of the patients in the 3rd and 12th months after treatment.

Results:

No signs of resorption or warping were noted in the patients.

Conclusions:

Our findings indicate autologous cartilage use with microplates and microscrews is a viable, long-term treatment option for patients with SND types III and IV.
Outcomes of the Learning Curve in Our First 100 Consecutive Laparoscopic Gastrectomies
Authors: Priego Pablo , Cuadrado Marta , Ballestero Araceli , Galindo Julio , Carda Pedro , Lobo Eduardo
Published: January 2019

Introduction:

Laparoscopic surgery has been increasingly used for treatment of gastric cancer. However, standardization of this minimally invasive approach has not been reached yet because of its technical difficulties and the concern about oncological safety. The aim of the study was to analyze the outcomes of our learning curve in this complex surgical technique.

Material and Methods:

The first consecutive 100 cases of laparoscopic gastrectomy performed at our Hospital from November 2008 to February 2018 were enrolled. Patients were divided into 2 groups on the basis of the period during which they were operated upon. The training phase was considered between 2008 and 2014 (46 cases) and the more developed phase (MDP) between 2015 and 2018 (54 cases). Conversion, lymphadenectomy and retrieved lymph nodes, hospital length of stay, mean operative time, complications, reintervention, and mortality rates were compared between the 2 phases of learning curve.

Results:

The number of retrieved lymph nodes was higher in the MDP (17±8.6 vs. 23.3±10.4; P=0.004). Furthermore, we have also found less complications (47.8% vs. 27.8%; P=0.038), a decreased reintervention rate (15.2% vs. 1.85%; P=0.023), and overall mortality (8.7% vs. 0%; P=0.003) in the MDP. There were no significant differences in conversion rate, mean operative time, and hospital length of stay between phases.

Conclusions:

Although we consider that our learning curve is not yet completed, as the average of monitored parameters have not reached a steady state, the improvement on surgical parameters and postoperative course in the last 2 years have showed that our results are close to the best results published in the literature.
Single Biaxillary Tunneling for Working Space Creation in Bilateral Axillo-Breast Approach (BABA) Thyroidectomy
Authors: Tsai Chung-Yu , Liu Shiuh-Inn , Chen I-Shu , Liang Tsung-Jung
Published: January 2019

Background:

Endoscopic thyroidectomy using the bilateral axillo-breast approach (BABA) achieves excellent cosmetic results. However, concerns have been raised about the extensive dissection and violation of the breast during working space preparation.

Materials and Methods:

We developed a “single biaxillary tunneling” technique for working space creation in BABA thyroidectomy; this technique was applied in 30 cases.

Results:

Skin bruise was hardly visible, and only minor and small bruises were observed. The whole process of working space creation typically finished within 20 to 30 minutes.

Conclusions:

Limited blunt dissection by a single stroke of biaxillary tunneling is a simple method, which significantly reduces ecchymosis formation and is time-efficient. This method can be used in routine practice and is feasible for beginner surgeons.
Overview: biotic signalling for smart pest management
Authors: Kang Le
Published: January 2019

Biotic signalling refers to species or phylogenetic-clade-specific signals that elicit adaptive and acceptable responses within and among organisms. It is not only the molecular basis of the ecological relationships among different species, such as parasitism, symbiosis and predation, but also serves as ideal targets that can be used to manipulate these ecological relationships. This concept was proposed by a group of scientists from the Chinese Academy of Sciences (CAS) and actively pursued in a five-year research project in 2014 funded by the CAS ($40 million), entitled ‘Decoding biotic interactions and mechanism for target management of agricultural pests'. The multi-disciplinary project aimed at a systematic investigation of the intra-species and inter-species and interactions via biotic signalling, with the ultimate goal being the development of novel methods to manage the pest insects and diseases. We hereby propose a topic ‘Biotic signalling sheds light on smart pest control’ as a theme issue for the
Philosophical Transactions of the Royal Society B
. It contains a total of 18 reviews and research articles under the topic of signalling manipulation for pest management. Unravelling these complex interactions among plants, microbial pathogens and insects holds promise for developing novel strategies to protect crop plants without compromising agricultural productivity and environmental health.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
The roles of histidine kinases in sensing host plant and cell–cell communication signal in a phytopathogenic bacterium
Authors: Wang Fang-Fang , Qian Wei
Published: January 2019

It has long been known that phytopathogenic bacteria react to plant-specific stimuli or environmental factors. However, how bacterial cells sense these environmental cues remains incompletely studied. Recently, three kinds of histidine kinases (HKs) were identified as receptors to perceive plant-associated or quorum-sensing signals. Among these kinases, HK VgrS detects iron depletion by binding to ferric iron via an ExxE motif, RpfC binds diffusible signal factor (DSF) by its N-terminal peptide and activates its autokinase activity through relaxation of autoinhibition, and PcrK specifically senses plant hormone–cytokinin and elicits bacterial responses to oxidative stress. These HKs are critical sensors that regulate the virulence of a Gram-negative bacterium,Xanthomonas campestrispv.campestris. Research progress on the signal perception of phytopathogenic bacterial HKs suggests that inter-kingdom signalling between host plants and pathogens controls pathogenesis and can be used as a potential molecular target to protect plants from bacterial diseases.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
Female adult puncture-induced plant volatiles promote mating success of the pea leafminer via enhancing vibrational signals
Authors: Ge Jin , Li Na , Yang Junnan , Wei Jianing , Kang Le
Published: January 2019

Herbivore-induced plant volatiles (HIPVs) synergize with the sex pheromones of herbivorous insects to facilitate mate location. However, the synergism of HIPVs and acoustic signals for sexual communication remains unknown. Here, we investigated the synergy between HIPVs and vibrational duets for sexual communication and mating in the pea leafminer (
Liriomyza huidobrensis
). Our results indicated that adult leafminers do not produce species-specific pheromone, and female-puncture-induced plant volatiles facilitate the attraction of both sexes to host plant leaves and sexual encounters. Insect-derived cues do not participate in mate locations. Both sexes do not produce qualitatively different cuticular hydrocarbons (CHCs), and CHCs from females cannot elicit the antennal and behavioural responses of males. By contrast, induced green leaf volatiles, terpenoids and oximes elicit dramatic antennal responses in both sexes. Electrophysiological and behavioural tests consistently showed that the volatiles (Z)-3-hexenol and (Z)-3-hexenyl-acetate elicited the most intense gas chromatographic-electroantennographic responses, and attracted males and females. Remarkably, these volatiles significantly promoted the occurrence of vibrational duets between the sexes, thereby increasing the mating success of leafminers. Therefore, the synergism of HIPVs and vibrational signals largely promoted the mating success of leafminers, suggesting an alternative control strategy through precision trapping for non-pheromone-producing insects.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
The generation of a comprehensive spectral library for the analysis of the guinea pig proteome by SWATH-MS
Authors: Palmowski Pawel , Watson Rachael , Nicholas Europe-Finner G. , Karolczak-Bayatti Magdalena , Porter Andrew , Treumann Achim , Taggart Michael J
Published: January 2019

Advances in liquid chromatography-mass spectrometry have facilitated the incorporation of proteomic studies to many biology experimental workflows. In particular, the introduction of Data-Independent Acquisition platforms, such as SWATH, offers several advantages for label-free quantitative assessment of complex proteomes over Data-Dependent Acquisition (DDA) approaches. However, SWATH data interpretation requires spectral libraries as a reference resource. This is often not available for many species of experimental models. The guinea pig (cavia porcellus) is an excellent experimental model for translation to many aspects of human physiology and disease yet there is limited experimental information regarding its proteome. In an effort to overcome this knowledge gap, we generated a comprehensive spectral library of the guinea pig proteome. Homogenates and tryptic peptide digests were prepared from 16 tissues and subjected to >200 DDA runs. Analysis of >250,000 peptide-spectrum matches resulted in the construction of a library of 73594 peptides corresponding to 7667 proteins. This spectral library furnishes the research community with the first comprehensive guinea pig proteomic resource that will facilitate future molecular-phenotypic studies using (re-engaging) the guinea pig as an experimental model of relevance to human biology. The guinea pig spectral library and MS data are freely accessible in the MassIVE repository (MSV000083199).
ScaR - A tool for sensitive detection of known fusion transcripts: Establishing prevalence of fusions in testicular germ cell tumors
Authors: Zhao Sen , Hoff Andreas M. , Skotheim Rolf I.
Published: January 2019

Bioinformatics tools for fusion transcript detection from RNA-sequencing data are in general developed for identification of novel fusions, which demands a high number of supporting reads and strict filters to avoid false discoveries. As our knowledge of bona-fide fusion genes becomes more saturated, there is a need to establish their prevalence with high sensitivity. We present ScaR, a tool that uses a scaffold realignment approach for sensitive fusion detection in RNA-seq data. ScaR detects a set of 50 synthetic fusion transcripts from simulated data at a higher sensitivity compared to established fusion finders. Applied to fusion transcripts potentially involved in testicular germ cell tumors (TGCTs), ScaR detects the fusions RCC1-ABHD12B and CLEC6A-CLEC4D in 9% and 28% of 150 TGCTs, respectively. The fusions were not detected in any of 198 normal testis tissues. Thus, we demonstrate high prevalence of RCC1-ABHD12B and CLEC6A-CLEC4D in TGCTs, and their cancer specific features. Further, we find that RCC1-ABHD12B and CLEC6A-CLEC4D are predominantly expressed in the seminoma and embryonal carcinoma histological subtypes of TGCTs, respectively. In conclusion, ScaR is useful for establishing the frequency of known fusion transcripts in larger data sets and detecting clinically relevant fusion transcripts with high sensitivity.

Availability

https://github.com/senzhaocode/ScaR
Longitudinal Intravital Imaging of Biosensor-labeled In Situ Islet Beta Cells
Authors: Reissaus Christopher A. , Twigg Ashley N. , Orr Kara S. , Conteh Abass M. , Martinez Michelle M. , Kamocka Malgorzata M. , Day Richard N. , Tersey Sarah A. , Dunn Kenneth W. , Mirmira Raghavendra G. , Linnemann Amelia K.
Published: January 2019

Impaired function and apoptosis of insulin-secreting islet β-cells is central to disease progression in both type 1 and type 2 diabetes. Oxidative damage resulting from excess reactive oxygen species (ROS) is a central factor in β-cell dysfunction and death, but the dynamic nature of ROS accumulation and its depletion pose a problem for mechanistic studies in vivo. Biosensors, including the redox-sensitive GFP (roGFPs), coupled with intravital microscopy provide a sensitive and dynamic solution to this problem. Here, we utilize a virally-delivered roGFP2-containing human glutaredoxin-1 (Grx1-roGFP2) to selectively monitor β-cell ROS dynamics in vivo in response to toxic glucose analogs. We paired viral biosensor delivery with implanted abdominal imaging windows over the pancreas, thus allowing longitudinal measurements of β-cell ROS and islet area during and after streptozotocin (STZ) exposure. The studies presented here represent a robust experimental platform that could be readily adapted to various transgenic or physiological mouse models in conjunction with any number of available biosensors, and thus opens a vast realm of potential for discovery in islet biology in vivo.
Genetic dysregulation of gene expression and splicing during a ten-year period of human aging
Authors: Balliu Brunilda , Durrant Matthew , de Goede Olivia , Abell Nathan , Li Xin , Liu Boxiang , Gloudemans Michael J , Cook Naomi L. , Smith Kevin S. , Pala Mauro , Cucca Francesco , Schlessinger David , Jaiswal Siddhartha , Sabatti Chiara , Lind Lars , Ingelsson Erik , Montgomery Stephen B
Published: January 2019

Molecular and cellular changes are intrinsic to aging and age-related diseases. Prior cross-sectional studies have investigated the combined effects of age and genetics on gene expression and alternative splicing; however, there has been no long-term, longitudinal characterization of these molecular changes, especially in older age. We performed RNA sequencing in whole-blood from the same individuals from the PIVUS study at ages 70 and 80 to quantify how gene expression, alternative splicing, and their genetic regulation are altered during this 10-year period of advanced aging. We observe that individuals are more similar to their own expression profiles later in life than profiles of other individuals their own age; 93% of samples cluster with their own measurement at another age, and there is a strong correlation of genetic effects on expression between the two ages (median ρG = 0.96). Despite this, we identify 1,291 and 294 genes differentially expressed and alternatively spliced with age, as well as 529 genes with outlying individual trajectories of aging. Further, 7.8% and 9.6% of tested genes show a reduction in genetic associations with expression and alternative splicing in older age, with impacted genes enriched in DNA repair pathways. Together these findings indicate that, although gene expression and alternative splicing and their genetic regulation are mostly stable late in life, a small subset of genes is dynamic and is characterized by changes in expression and splicing and a reduction in genetic regulation.
Orientation-selective adaptation improves perceptual grouping
Authors: Pinchuk-Yacobi Noga , Sagi Dov
Published: January 2019

The role of visual pattern adaptation, and learning, in spatial integration was investigated. Observers performed a perpetual grouping task in which they reported whether a grid of identical tilted bars (45° counterclockwise from the vertical) is perceived as rows or columns. Performance was measured multiple times during a testing session to determine the effects of repeated exposure to the stimuli. To test for possible effects of learning on the within-session dynamics, observers repeated the experiment on five different days. We found that repeated performance produced rapid within-day improvements, which were largely transient, and were not retained when tested on subsequent days. In addition, exposure to stimuli with equal orientation contributed to the within-session improvement, whereas stimuli having an orientation differing by 45° from the orientation used in the grouping task diminished the improvement previously obtained in the same session. Practice with the task, over days, resulted in faster improvements. The transient nature of these exposure-driven improvements and their susceptibility to interference by stimuli designed to reduce adaptation suggests that adaptation was the main cause for the observed improvements. Finally, to investigate the effects of adaptation on internal noise and on spatial integration, we employed an external noise paradigm, showing that internal noise reduction resulted from adaptation. Internal noise was reduced only when spatial integration was effective, suggesting that adaptation improved perception of global stimulus properties. Overall, our results suggest that the grouping task benefits from an adaptation process that rapidly adjusts the visual system to the statistics of the visual stimuli. We suggest that this effect is achieved through spatial decorrelation of neural responses. With practice, the visual system is able to adjust faster to changes in the statistics of the environment.
Pan-cancer genomic amplifications underlie a Wnt hyperactivation phenotype associated with stem cell-like features leading to poor prognosis
Authors: Chang Wai Hoong , Lai Alvina G.
Published: January 2019

Cancer stem cells pose significant obstacles to curative treatment contributing to tumor relapse and poor prognosis. They share many signaling pathways with normal stem cells that control cell proliferation, self-renewal and cell fate determination. One of these pathways known as Wnt is frequently implicated in carcinogenesis where Wnt hyperactivation is seen in cancer stem cells. Yet, the role of conserved genomic alterations in Wnt genes driving tumor progression across multiple cancer types remains to be elucidated. In an integrated pan-cancer study involving 21 cancers and 18,484 patients, we identified a core Wnt signature of 16 genes that showed high frequency of somatic amplifications linked to increased transcript expression. The signature successfully predicted overall survival rates in six cancer cohorts (n=3,050): bladder (P=0.011), colon (P=0.013), head and neck (P=0.026), pan-kidney (P<0.0001), clear cell renal cell (P<0.0001) and stomach (P=0.032). Receiver operating characteristic analyses revealed that the performance of the 16-Wnt-gene signature was superior to tumor staging benchmarks in all six cohorts and multivariate Cox regression analyses confirmed that the signature was an independent predictor of overall survival. In bladder and renal cancer, high risk patients as predicted by the Wnt signature had more hypoxic tumors and a combined model uniting tumor hypoxia and Wnt hyperactivation resulted in further increased death risks. Patients with hyperactive Wnt signaling had molecular features associated with stemness and epithelial-to-mesenchymal transition. Our study confirmed that genomic amplification underpinning pan-cancer Wnt hyperactivation and transcriptional changes associated with molecular footprints of cancer stem cells lead to increased death risks.

List of Abbreviations

TCGA

The Cancer Genome Atlas

KEGG

Kyoto Encyclopedia of Genes and Genomes

GO

Gene Ontology

ROC

Receiver operating characteristic

AUC

Area under the curve

HR

Hazard ratio

TNM

Tumor, node and metastasis

HIF

Hypoxia inducible factor

TF

Transcription factor

EMT

Epithelial-to-mesenchymal transition
Optical determination of absolute membrane potential
Authors: Lazzari-Dean Julia R. , Gest Anneliese M.M. , Miller Evan W.
Published: January 2019

All cells maintain ionic gradients across their plasma membranes, producing transmembrane potentials (Vmem). Mounting evidence suggests a relationship between resting Vmem and the physiology of non-excitable cells with implications in diverse areas, including cancer, cellular differentiation, and body patterning. A lack of non-invasive methods to record absolute Vmem limits our understanding of this fundamental signal. To address this need, we developed a fluorescence lifetime-based approach (VF-FLIM) to visualize and optically quantify Vmem with single-cell resolution. Using VF-FLIM, we report Vmem distributions over thousands of cells, a 100-fold improvement relative to electrophysiological approaches. In human carcinoma cells, we visualize the voltage response to epidermal growth factor stimulation, stably recording a 10-15 mV hyperpolarization over minutes. Using pharmacological inhibitors, we identify the source of the hyperpolarization as the Ca2+-activated K+channel Kca3.1. The ability to optically quantify absolute Vmem with cellular resolution will allow a re-examination of its roles as a cellular signal.
Genome-wide patterns of population structure and linkage disequilibrium in farmed Nile tilapia (Oreochromis niloticus)
Authors: Yoshida Grazyella M. , Barria Agustín , Correa Katharina , Cáceres Giovanna , Jedlicki Ana , Cadiz María I. , Lhorente Jean P. , Yáñez José M.
Published: January 2019

Nile tilapia (Oreochromis niloticus) is one of the most produced farmed fish in the world and represents an important source of protein for human consumption. Farmed Nile tilapia populations are increasingly based on genetically improved stocks, which have been established from admixed populations. To date, there is scarce information about the population genomics of farmed Nile tilapia, assessed by dense single nucleotide polymorphism (SNP) panels. The patterns of linkage disequilibrium (LD) may affect the success of genome-wide association studies (GWAS) and genomic selection and can also provide key information about demographic history of farmed Nile tilapia populations. The objectives of this study were to provide further knowledge about the population structure and LD patterns, as well as, estimate the effective population size (Ne) for three farmed Nile tilapia populations, one from Brazil (POP A) and two from Costa Rica (POP B and POP C). A total of 55, 56 and 57 individuals from POP A, POP B and POP C, respectively, were genotyped using a 50K SNP panel selected from a whole-genome sequencing (WGS) experiment. Two principal components explained about 20% of the total variation and clearly discriminated between the three populations. Population genetic structure analysis showed evidence of admixture, especially for POP C. The contemporary Ne values calculated based to LD values, ranged from 71 to 141. No differences were observed in the LD decay among populations, with a rapid decrease of r2 when increasing inter-marker distance. Average r2 between adjacent SNP pairs ranged from 0.03 to 0.18, 0.03 to 0.17 and 0.03 to 0.16 for POP A, POP B and POP C, respectively. Based on the number of independent chromosome segments in the Nile tilapia genome, at least 4.2 K SNP are required for the implementation of GWAS and genomic selection in farmed Nile tilapia populations.
O-GlcNAc transferase suppresses necroptosis and liver fibrosis
Authors: Zhang Bichen , Li Min-Dian , Yin Ruonan , Liu Yuyang , Yang Yunfan , Mitchell – Richards Kisha A. , Nam Jin Hyun , Li Rui , Wang Li , Iwakiri Yasuko , Chung Dongjun , Robert Marie E. , Ehrlich Barbara E. , Bennett Anton M. , Yu Jun , Nathanson Michael H. , Yang Xiaoyong
Published: January 2019

Over a billion people suffer from chronic liver diseases worldwide, which often leads to fibrosis and then cirrhosis. Treatments for fibrosis remain experimental, in part because no unifying mechanism has been identified that initiates liver fibrosis. Here we report that O-linked β-N-acetylglucosamine (O-GlcNAc) modification protects against hepatocyte necroptosis and initiation of liver fibrosis. Decreased O-GlcNAc levels were seen in patients with liver cirrhosis and in mice with ethanol-induced liver injury. Liver-specific O-GlcNAc transferase (OGT) knockout (OGT-LKO) mice exhibited ballooning degeneration and elevated circulating alanine aminotransferase (ALT) levels at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age. OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis. Furthermore, glycosylation of RIPK3 by OGT reduced RIPK3 protein stability. Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
The off-target kinase landscape of clinical PARP inhibitors
Authors: Antolin Albert A. , Ameratunga Malaka , Banerji Udai , Clarke Paul , Workman Paul , Al-Lazikani Bissan
Published: January 2019

Four PARP inhibitors have been approved by the FDA as cancer therapeutics, yet there are several clinical settings where no strong rationale exists to inform clinicians on which to choose in terms of clinical effectiveness and toxicity. The four drugs have largely similar PARP family inhibition profiles, but several differences at the molecular and clinical level have been reported that remain poorly understood. We previously hypothesized that PARP inhibitors could have an inherent capacity to inhibit kinases off-target. Here, we characterise the off-target kinase landscape of four FDA-approved PARP drugs. We demonstrate that all four PARP inhibitors have a unique polypharmacological profile across the kinome. Niraparib and rucaparib inhibit DYRK1s, CDK16 and PIM3 at clinically achievable submicromolar concentrations. These represent the most potently inhibited off-targets of PARP inhibitors identified to date and should be investigated further to clarify their potential implications for efficacy and safety in the clinic, including use of PARP inhibitors in combination with other agents, including immunotherapy.
One-time Nitrogen Fertilization Shifts Switchgrass Soil Microbiomes within a Context of Larger Spatial and Temporal Variation
Authors: Chen Huaihai , Yang Zamin K. , Yip Dan , Morris Reese H. , Lebreux Steven J. , Cregger Melissa A. , Klingeman Dawn M. , Hui Dafeng , Hettich Robert L. , Wilhelm Steven W. , Wang Gangsheng , Löffler Frank E. , Schadt Christopher W.
Published: January 2019

Soil microbiome responses to short-term nitrogen (N) inputs within the context of existing spatio-temporal variability remain uncertain. Here, we examined soil bacterial and fungal communities pre/post-N fertilization in an 8 year-old switchgrass field, in which twenty-four plots received N fertilization at three levels (0, 100, and 200 kg N ha-1as NH4NO3) for the first time since planting. Soils were collected at two depths, 0-5 and 5-15 cm, for DNA extraction and amplicon sequencing of 16S rRNA genes and ITS regions, and soil metagenomic analysis. Baseline assessment prior to fertilization revealed no pre-existing differences in either bacterial or fungal communities across plots. The one-time N fertilization increased switchgrass yields and tissue N content, and the added N was nearly completely removed from the soil of fertilized plots by the end of the growing season. Both bacterial/archaeal and fungal communities showed large spatial (by depth) and temporal variation (by season) within each plot, accounting for 17 and 12-22 % of the variation in bacterial/archaeal and fungal community composition, respectively. While N fertilization effects accounted for only ~4% of overall variation, some specific microbial groups, including the bacterial genusPseudonocardiaand the fungal genusArchaeorhizomyces,were notably repressed by fertilization at 200 kg N ha-1. Bacterial groups varied with both depth in the soil profile and time of sampling, while temporal variability shaped the fungal community more significantly than vertical heterogeneity in the soil. Thus, variability within the field might override the changes induced by N addition. Continued analyses of these trends over time with fertilization and management are needed to understand whether these transient effects change over time.
PKC regulates the production of fibroblast growth factor 23 (FGF23)
Authors: Bär Ludmilla , Hase Philipp , Föller Michael
Published: January 2019

Serine/threonine protein kinase C (PKC) is activated by diacylglycerol that is released from membrane lipids by phospholipase C in response to activation of G protein-coupled receptors or receptor tyrosine kinases. PKC isoforms are particularly relevant for proliferation and differentiation of cells including osteoblasts. Osteoblasts/osteocytes produce fibroblast growth factor 23 (FGF23), a hormone regulating renal phosphate and vitamin D handling. PKC activates NFκB, a transcription factor complex controlling FGF23 expression. Here, we analyzed the impact of PKC on FGF23 synthesis. Fgf23 expression was analyzed by qRT-PCR in UMR106 osteoblastlike cells and in IDG-SW3 osteocytes. Phorbol ester 12-O-tetradecanoylphorbol-13-acetate (PMA), a PKC activator, up-regulated Fgf23 expression. In contrast, PKC inhibitors calphostin C, Gö6976, sotrastaurin and ruboxistaurin supressed Fgf23 gene expression. NFκB inhibitor withaferin A abolished the stimulatory effect of PMA on Fgf23. PKC is a powerful regulator of FGF23 synthesis, an effect which is at least partly mediated by NFκB.
RHO-1 and the Rho GEF RHGF-1 interact with UNC-6/Netrin signaling to regulate growth cone protrusion and microtubule organization inC. elegans
Authors: Gujar Mahekta R. , Stricker Aubrie M. , Lundquist Erik A.
Published: January 2019

UNC-6/Netrin is a conserved axon guidance cue that directs growth cone migrations in the dorsal-ventral axis ofC. elegansand in the vertebrate spinal cord. UNC-6/Netrin is expressed in ventral cells, and growth cones migrate ventrally toward or dorsally away from UNC-6/Netrin. Recent studies of growth cone behavior during outgrowthin vivoinC. eleganshave led to a polarity/protrusion model in directed growth cone migration away from UNC-6/Netrin. In this model, UNC-6/Netrin first polarizes the growth cone via the UNC-5 receptor, leading to dorsally biased protrusion and F-actin accumulation. UNC-6/Netrin then regulates protrusion based on this polarity. The receptor UNC-40/DCC drives protrusion dorsally, away from the UNC-6/Netrin source, and the UNC-5 receptor inhibits protrusion ventrally, near the UNC-6/Netrin source, resulting in dorsal migration. UNC-5 inhibits protrusion in part by excluding microtubules from the growth cone, which are pro-protrusive. Here we report that the RHO-1/RhoA GTPase and its activator GEF RHGF-1 inhibit growth cone protrusion and MT accumulation in growth cones, similar to UNC-5. However, growth cone polarity of protrusion and F-actin were unaffected by RHO-1 and RHGF-1. Thus, RHO-1 signaling acts specifically as a negative regulator of protrusion and MT accumulation, and not polarity. Genetic interactions suggest that RHO-1 and RHGF-1 act with UNC-5, as well as with a parallel pathway, to regulate protrusion. The cytoskeletal interacting molecule UNC-33/CRMP was required for RHO-1 activity to inhibit MT accumulation, suggesting that UNC-33/CRMP might act downstream of RHO-1. In sum, these studies describe a new role of RHO-1 and RHGF-1 in regulation of growth cone protrusion by UNC-6/Netrin.

Author Summary

Neural circuits are formed by precise connections between axons. During axon formation, the growth cone leads the axon to its proper target in a process called axon guidance. Growth cone outgrowth involves asymmetric protrusion driven by extracellular cues that stimulate and inhibit protrusion. How guidance cues regulate growth cone protrusion in neural circuit formation is incompletely understood. This work shows that the signaling molecule RHO-1 acts downstream of the UNC-6/Netrin guidance cue to inhibit growth cone protrusion in part by excluding microtubules from the growth cone, which are structural elements that drive protrusion.
A simulation investigation of helicopter ground resonance phenomenon
Authors: Stanislawski Jaroslaw
Published: January 2019

Purpose

The purpose of this paper is to present a simulation method applied for investigation of helicopter ground resonance phenomenon.

Design/methodology/approach

The considered physical model of helicopter standing on ground with rotating rotor consists of fuselage and main transmission gear treated as stiff bodies connected by elastic elements. The fuselage is supported on landing gear modeled by spring-damper units. The main rotor blades are treated as set of elastic axes with lumped masses distributed along blade radius. Due to Galerkin method, parameters of blades motion are assumed as a combination of bending and torsion eigen modes. A Runge–Kutta method is applied to solve equations of motions of rotor blades and helicopter fuselage.

Findings

The presented simulation method may be applied in preliminary stage of helicopter design to avoid ground resonance by proper selection of landing gear units and blade damper characteristics.

Practical implications

Ground resonance may occur in form of violently increasing mutual oscillations of helicopter fuselage and lead-lag motion of rotor blades. According to changes of stiffness and damping characteristics, simulations show stable behavior or arising oscillations of helicopter. The effects of different blade balance or defect of blade damper are predicted.

Originality/value

The simulation method may help to determine the envelope of safe operation of helicopter in phase of take-off or landing. The effects of additional disturbances as results of blades pitch control as swashplate deflection are introduced.
When the mobile app is free, the product is your personal data
Authors: Polykalas Spyros E. , Prezerakos George N.
Published: January 2019

Purpose

Mobile devices (smartphones, tables etc.) have become the de facto means of accessing the internet. While traditional Web browsing is still quite popular, significant interaction takes place via native mobile apps that can be downloaded either freely or at a cost. This has opened the door to a number of issues related to privacy protection since the smartphone stores and processes personal data. The purpose of this paper is to examine the extent of access to personal data, required by the most popular mobile apps available in Google Play store. In addition, it is examined whether the relevant procedure is in accordance with the provisions of the new EU Regulation.

Design/methodology/approach

The paper examines more than a thousand mobile apps, available from the Google Play store, with respect to the extent of the requests for access to personal data. In particular, for each available category in Google Play store, the most popular mobile apps have been examined both for free and paid apps. In addition, the permissions required by free and paid mobile apps are compared. Furthermore, a correlation analysis is carried out aiming to reveal any correlation between the extent of required access to personal data and the popularity and the rating of each mobile app.

Findings

The findings of this paper suggest that the majority of examined mobile apps require access to personal data to a high extent. In addition, it is found that free mobile apps request access to personal data in a higher extent compared to the relevant requests by paid apps, which indicates strongly that the business model of free mobile apps is based on personal data exploitation. The most popular types of access permissions are revealed for both free and paid apps. In addition, important questions are raised in relation to user awareness and behavior, data minimization and purpose limitation for free and paid mobile apps.

Originality/value

In this study, the process and the extent of access to personal data through mobile apps are analyzed. Although several studies analyzed relevant issues in the past, the originality of this research is mainly based on the following facts: first, this work took into account the recent Regulation of the EU in relation to personal data (GDPR); second, the authors analyzed a high number of the most popular mobile apps (more than a thousand); and third, the authors compare and analyze the different approaches followed between free and paid mobile apps.
Citizenship performance: a study using Coleman and Borman’s model and validation of the scale
Authors: Mohan Anita , Sophia Sharon
Published: January 2019

Purpose

The purpose of this paper is to give prominence and further understand the Coleman and Borman (2000) citizenship performance model. This study also aims to determine and validate the scale formed from the behaviour statements defined by Coleman and Borman in the Indian context by using standard validating measures.

Design/methodology/approach

The citizenship performance construct was measured and validated with a sample of 150 employees working in the IT/ITES sector in Chennai, India. Exploratory and confirmatory factor analyses were performed on the 27 behavioural statements proposed by Coleman and Borman (2000), which were converted into a five-point Likert scale.

Findings

This paper proposes that citizenship performance can be reliably measured by the 17 items which are based on the 27 citizenship performance behaviour (CPB) statements provided by Coleman and Borman. In addition, it also confirms that citizenship performance is a second-order multi-dimensional construct.

Research limitations/implications

An acceptable but constrained sample was used in this study. The sample frame was limited to the IT/ITES sector in Chennai, a city in Tamil Nadu, India, to minimise cultural influences on the study.

Originality/value

This paper bridges and backs the conceptualisation of the Coleman and Borman (2000) model and the validation of a questionnaire based on their proposed set of CPB statements in the Indian context. This helps to measure the model with its intended questionnaire rather than borrowing items from other scales measuring other dimensions of the OCB domain.