bluuebunny/crossref_metadata_2025_split huggingface dataset:
ETV4 promotes late development of prostatic intraepithelial neoplasia and cell proliferation through direct and p53-mediated downregulation of p21
Authors: Cosi Irene , Pellecchia Annamaria , De Lorenzo Emanuele , Torre Eugenio , Sica Michela , Nesi Gabriella , Notaro Rosario , De Angioletti Maria 
Published: August 2020

AbstractBackgroundETV4 is one of the ETS proteins overexpressed in prostate cancer (PC) as a result of recurrent chromosomal translocations. In human prostate cell lines, ETV4 promotes migration, invasion, and proliferation; however, its role in PC has been unclear. In this study, we have explored the effects of ETV4 expression in the prostate in a novel transgenic mouse model.MethodsWe have created a mouse model with prostate-specific expression of ETV4 (ETV4 mice). By histochemical and molecular analysis, we have investigated in these engineered mice the expression of p21, p27, and p53. The implications of our in vivo findings have been further investigated in human cells lines by chromatin-immunoprecipitation (ChIP) and luciferase assays.ResultsETV4 mice, from two independent transgenic lines, have increased cell proliferation in their prostate and two-thirds of them, by the age of 10 months, developed mouse prostatic intraepithelial neoplasia (mPIN). In these mice,cdkn1aand its p21 protein product were reduced compared to controls; p27 protein was also reduced. By ChIP assay in human prostate cell lines, we show that ETV4 binds to a specific site (-704/-696 bp upstream of the transcription start) in theCDKN1Apromoter that was proven, by luciferase assay, to be functionally competent. ETV4 further controlsCDKN1Aexpression by downregulating p53 protein: this reduction of p53 was confirmed in vivo in ETV4 mice.ConclusionsETV4 overexpression results in the development of mPIN but not in progression to cancer. ETV4 increases prostate cell proliferation through multiple mechanisms, including downregulation ofCDKN1Aand its p21 protein product: this in turn is mediated through direct binding of ETV4 to theCDKN1Apromoter and through the ETV4-mediated decrease of p53. This multi-faceted role of ETV4 in prostate cancer makes it a potential target for novel therapeutic approaches that could be explored in this ETV4 transgenic model.
Sequence-based prediction of SARS-CoV-2 vaccine targets using a mass spectrometry-based bioinformatics predictor identifies immunogenic T cell epitopes
Authors: Poran Asaf , Harjanto Dewi , Malloy Matthew , Arieta Christina M. , Rothenberg Daniel A. , Lenkala Divya , van Buuren Marit M. , Addona Terri A. , Rooney Michael S. , Srinivasan Lakshmi , Gaynor Richard B. 
Published: August 2020

AbstractBackgroundThe ongoing COVID-19 pandemic has created an urgency to identify novel vaccine targets for protective immunity against SARS-CoV-2. Early reports identify protective roles for both humoral and cell-mediated immunity for SARS-CoV-2.MethodsWe leveraged our bioinformatics binding prediction tools for human leukocyte antigen (HLA)-I and HLA-II alleles that were developed using mass spectrometry-based profiling of individual HLA-I and HLA-II alleles to predict peptide binding to diverse allele sets. We applied these binding predictors to viral genomes from theCoronaviridaefamily and specifically focused on T cell epitopes from SARS-CoV-2 proteins. We assayed a subset of these epitopes in a T cell induction assay for their ability to elicit CD8+T cell responses.ResultsWe first validated HLA-I and HLA-II predictions onCoronaviridaefamily epitopes deposited in the Virus Pathogen Database and Analysis Resource (ViPR) database. We then utilized our HLA-I and HLA-II predictors to identify 11,897 HLA-I and 8046 HLA-II candidate peptides which were highly ranked for binding across 13 open reading frames (ORFs) of SARS-CoV-2. These peptides are predicted to provide over 99% allele coverage for the US, European, and Asian populations. From our SARS-CoV-2-predicted peptide-HLA-I allele pairs, 374 pairs identically matched what was previously reported in the ViPR database, originating from other coronaviruses with identical sequences. Of these pairs, 333 (89%) had a positive HLA binding assay result, reinforcing the validity of our predictions. We then demonstrated that a subset of these highly predicted epitopes were immunogenic based on their recognition by specific CD8+T cells in healthy human donor peripheral blood mononuclear cells (PBMCs). Finally, we characterized the expression of SARS-CoV-2 proteins in virally infected cells to prioritize those which could be potential targets for T cell immunity.ConclusionsUsing our bioinformatics platform, we identify multiple putative epitopes that are potential targets for CD4+and CD8+T cells, whose HLA binding properties cover nearly the entire population. We also confirm that our binding predictors can predict epitopes eliciting CD8+T cell responses from multiple SARS-CoV-2 proteins. Protein expression and population HLA allele coverage, combined with the ability to identify T cell epitopes, should be considered in SARS-CoV-2 vaccine design strategies and immune monitoring.
Proteomic analysis revealed common, unique and systemic signatures in gender-dependent hepatocarcinogenesis
Authors: Li Huiling , Rong Zhuona , Wang Hong , Zhang Nan , Pu Chunwen , Zhao Yi , Zheng Xu , Lei Chuanyi , Liu Yang , Luo Xiaoqin , Chen Jun , Wang Fujin , Wang Aiguo , Wang Jingyu 
Published: August 2020

AbstractHepatocellular carcinoma (HCC) is the most common liver cancer and is highly malignant. Male prevalence and frequent activation of the Ras signaling pathway are distinct characteristics of HCC. However, the underlying mechanisms remain to be elucidated. By exploringHras12Vtransgenic mice showing male-biased hepatocarcinogenesis, we performed a high-throughput comparative proteomic analysis based on tandem-mass-tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the tissue samples obtained from HCC (T) and their paired adjacent precancerous (P) ofHras12Vtransgenic male and female mice (Ras-Tg) and normal liver (W) of wild-type male and female mice (Non-Tg). The further validation and investigation were performed using quantitative real-time PCR and western blot. Totally, 5193 proteins were quantified, originating from 5733 identified proteins. Finally, 1344 differentially expressed proteins (DEPs) (quantified in all examined samples; |ratios| ≥ 1.5,p< 0.05) were selected for further analysis. Comparison within W, P, and T of males and females indicated that the number of DEPs in males was much higher than that in females. Bioinformatics analyses showed the common and unique cluster-enriched items between sexes, indicating the common and gender-disparate pathways towards HCC. Expression change pattern analysis revealed HCC positive/negative-correlated andrasoncogene positive/negative-correlated DEPs and pathways. In addition, it showed that therasoncogene gradually and significantly reduced the responses to sex hormones from hepatocytes to hepatoma cells and therefore shrunk the gender disparity between males and females, which may contribute to the cause of the loss of HCC clinical responses to the therapeutic approaches targeting sex hormone pathways. Additionally, gender disparity in the expression levels of key enzymes involved in retinol metabolism and terpenoid backbone/steroid biosynthesis pathways may contribute to male prevalence in hepatocarcinogenesis. Further, the biomarkers, SAA2, Orm2, and Serpina1e, may be sex differences. In conclusion, common and unique DEPs and pathways toward HCC initiated byrasoncogene from sexually dimorphic hepatocytes provide valuable and novel insights into clinical investigation and practice.
Large-scale production of recombinant miraculin protein in transgenic carrot callus suspension cultures using air-lift bioreactors
Authors: Park Yun-Ji , Han Jong-Eun , Lee Hyoshin , Jung Yu-Jin , Murthy Hosakatte Niranjana , Park So-Young 
Published: August 2020

AbstractMiraculin, derived from the miracle fruit (Synsepalum dulcificum), is a taste-regulating protein that interacts with human sweet-taste receptors and transforms sourness into sweet taste. Since miracle fruit is cultivated in West Africa, mass production of miraculin is limited by regional and seasonal constraints. Here, we investigated mass production of recombinant miraculin in carrot (Daucus carota L.) callus cultures using an air-lift bioreactor. To increase miraculin expression, the oxidative stress-inducible SWPA2 promoter was used to drive the expression of miraculin gene under various stress treatments. An 8 h treatment of hydrogen peroxide (H2O2) and salt (NaCl) increased the expression of miraculin gene by fivefold compared with the untreated control. On the other hand, abscisic acid, salicylic acid, and methyl jasmonate treatments showed no significant impact on miraculin gene expression compared with the control. This shows that since H2O2 and NaCl treatments induce oxidative stress, they activate the SWPA2 promoter and consequently up-regulate miraculin gene expression. Thus, the results of this study provide a foundation for industrial-scale production of recombinant miraculin protein using transgenic carrot cells as a heterologous host.
Immune Landscape of Pituitary Tumors Reveals Association Between Macrophages and Gonadotroph Tumor Invasion
Authors: Principe Moitza , Chanal Marie , Ilie Mirela Diana , Ziverec Audrey , Vasiljevic Alexandre , Jouanneau Emmanuel , Hennino Ana , Raverot Gerald , Bertolino Philippe 
Published: August 2020

Abstract

Purpose
Pituitary neuroendocrine tumors (PitNETs) are frequent intracranial neoplasms that present heterogenic characteristics. Little is known about the immune cell network that exists in PitNETs and its contribution to their aggressive behavior.

Methods
Here we combined flow cytometry, t-SNE analysis, and histological approaches to define the immune landscape of surgically resected PitNETs. Xenografts of rodent pituitary tumor cells and resected PitNETs were performed in Rag2KO mice, in combination with in vitro analysis aimed at dissecting the role of pituitary tumor-cells in monocyte recruitment.

Results
We report that gonadotroph PitNETs present an increased CD68+ macrophage signature compared to somatotroph, lactotroph, and corticotroph PitNETs. Transcriptomic and histological characterizations confirmed gonadotroph infiltrating macrophages expressed CD163, MRC-1, ARG1, and CSF1R M2 macrophage markers. Use of growth hormone (GH)3/GH4 somatotroph and LβT2/αT3.1 gonadotroph cells drove THP1 macrophage migration through respective expression of CCL5 or CSF1. Although both LβT2 and GH3 cells recruited F4/80 macrophages following their engraftment in mice, only LβT2 gonadotroph cells showed a capacity for M2-like polarization. Similar observations were performed on patient-derived xenografts from somatotroph and gonadotroph tumors. Analysis of clinical data further demonstrated a significant correlation between the percentage of CD68+ and CD163+ infiltrating macrophages and the invasive character of gonadotroph tumors.

Conclusions
Gonadotroph tumor drive the recruitment of macrophages and their subsequent polarization to an M2-like phenotype. More importantly, the association between infiltrating CD68+/CD163+ macrophages and the invasiveness of gonadotroph tumors points to macrophage-targeted immunotherapies being a potent strategy to limit the progression of gonadotroph PitNETs.
Cellular Pathophysiology of Mutant Voltage-Dependent Ca2+ Channel CACNA1H in Primary Aldosteronism
Authors: Gürtler Florian , Jordan Katrin , Tegtmeier Ines , Herold Janina , Stindl Julia , Warth Richard , Bandulik Sascha 
Published: August 2020

Abstract
The physiological stimulation of aldosterone production in adrenocortical glomerulosa cells by angiotensin II and high plasma K+ depends on the depolarization of the cell membrane potential and the subsequent Ca2+ influx via voltage-activated Ca2+ channels. Germline mutations of the low-voltage activated T-type Ca2+ channel CACNA1H (Cav3.2) have been found in patients with primary aldosteronism. Here, we investigated the electrophysiology and Ca2+ signaling of adrenal NCI-H295R cells overexpressing CACNA1H wildtype and mutant M1549V in order to understand how mutant CACNA1H alters adrenal cell function. Whole-cell patch-clamp measurements revealed a strong activation of mutant CACNA1H at the resting membrane potential of adrenal cells. Both the expression of wildtype and mutant CACNA1H led to a depolarized membrane potential. In addition, cells expressing mutant CACNA1H developed pronounced action potential–like membrane voltage oscillations. Ca2+ measurements showed an increased basal Ca2+ activity, an altered K+ sensitivity, and abnormal oscillating Ca2+ changes in cells with mutant CACNA1H. In addition, removal of extracellular Na+ reduced CACNA1H current, voltage oscillations, and Ca2+ levels in mutant cells, suggesting a role of the partial Na+ conductance of CACNA1H in cellular pathology. In conclusion, the pathogenesis of stimulus-independent aldosterone production in patients with CACNA1H mutations involves several factors: i) a loss of normal control of the membrane potential, ii) an increased Ca2+ influx at basal conditions, and iii) alterations in sensitivity to extracellular K+ and Na+. Finally, our findings underline the importance of CACNA1H in the control of aldosterone production and support the concept of the glomerulosa cell as an electrical oscillator.
Effects of 8 wk of 16:8 Time-restricted Eating in Male Middle- and Long-Distance Runners
Authors: BRADY AIDAN J. , LANGTON HENRY M. , MULLIGAN MOLLIE , EGAN BRENDAN 
Published: August 2020

ABSTRACT

Purpose
Eight weeks of time-restricted eating (TRE) in concert with habitual exercise training was investigated for effects on body composition, energy and macronutrient intakes, indices of endurance running performance, and markers of metabolic health in endurance athletes.

Methods
Male middle- and long-distance runners (n = 23) were randomly assigned to TRE (n = 12) or habitual dietary intake (CON; n = 11). TRE required participants to consume all of their dietary intake within an 8-h eating window (so-called 16:8 TRE), but dietary patterns, food choices, and energy intake were ad libitum during this window. Participants continued their habitual training during the intervention period. Participants completed an incremental exercise test before (PRE) and after (POST) the 8-wk intervention for the assessment of blood lactate concentrations, running economy, and maximal oxygen uptake. Fasted blood samples were analyzed for glucose, insulin, and triglyceride concentrations. Dietary intake was assessed at PRE, MID (week 4), and POST using a 4-d semiweighed food diary.

Results
Seventeen participants (TRE, n = 10; CON, n = 7) completed the intervention. Training load did not differ between groups for the duration of the intervention period. TRE resulted in a reduction in body mass (mean difference of −1.92 kg, 95% confidence interval = −3.52 to −0.32, P = 0.022). Self-reported daily energy intake was lower in TRE at MID and POST (group–time interaction, P = 0.049). No effect of TRE was observed for oxygen consumption, respiratory exchange ratio, running economy, blood lactate concentrations, or heart rate during exercise, nor were there any effects on glucose, insulin, or triglyceride concentrations observed.

Conclusion
Eight weeks of 16:8 TRE in middle- and long-distance runners resulted in a decrease in body mass commensurate with a reduction in daily energy intake, but it did not alter indices of endurance running performance or metabolic health.
Early childhood caries prevention: non-dental health professionals' viewpoint
Authors: Nancy Javotte , Barsby Terence , Theillaud Marie , Barbey-Massin Christelle , Thébaud Noëlie-B 
Published: August 2020

Background: Dental caries can develop early in life and have harmful consequences. Objective: To examine non-dental practitioners' knowledge of early childhood caries (ECC). Methods: A questionnaire on oral health and caries knowledge was emailed to five types of health professional who work with young children: paediatricians, GPs, midwives, paediatric nurses and paediatric healthcare assistants. Questions concerned: when a child should first visit a dentist; at what age toothbrushing should start; aetiopathogenic factors; early diagnosis; and the effect of breastfeeding. Results: 494 health professionals (79 paediatricians, 59 physicians, 217 midwives, 92 paediatric nurses and 47 paediatric healthcare assistants) participated. Although most (89.86%) discussed oral health with parents, responses on when a child should first see a dentist and when toothbrushing should start varied. Almost half of respondents said they could diagnose caries but not all were confident in this. Aetiological factors in ECC mentioned included oral hygiene, bottle feeding, sugar intake, genetics and a lack of fluoride. Conclusion: Non-dental practitioners lack knowledge about ECC, so cannot help prevent it. Initiatives including interprofessional training would improve their knowledge of oral health in early childhood.
Juggling to find balance: hearing the voices of undergraduate student nurses
Authors: Mills Anne , Ryden Julie , Knight Anneyce 
Published: August 2020

Background: Accounts of stress are common among students on nursing programmes. Prolonged high levels of stress can contribute to poor learning, the development of detrimental health behaviours, attrition and burnout. Aims: To examine the health and wellbeing implications of undertaking a BSc nursing degree in the UK for first-year students. Methods: Qualitative narrative analysis of 100 written student reflections on the influences on their health and wellbeing was undertaken. Findings: Nursing students must juggle multiple competing demands on their physical capabilities, personal resources, income and time. Students are constantly seeking to achieve balance and personal equilibrium through the use of a variety of coping strategies. Conclusion: This work calls upon the profession, the nursing regulator, nursing programmes within higher education institutions and health Trusts to review the framework and content of undergraduate BSc nurse education. Programme requirements should enhance the health and wellbeing of students while simultaneously delivering education and practice opportunities necessary to meet professional requirements.
M-ary DPSK coded binary to gray, BCD to gray, and octal to binary all-optical code converters based on SOA-MZI configuration at 500  Gb/s
Authors: Michael Margarat , Caroline B. Elizabeth , Xavier Susan Christina 
Published: August 2020

Gray codes are broadly used as the cyclic codes to assist error correction in optical communications. In this paper, we have proposed the novel design of three different types of all-optical gray code converters based on the semiconductor optical amplifier (SOA) Mach–Zehnder interferometer (MZI) configuration. The XOR and OR gates are the basic devices used for the proposed design of binary to gray, binary-coded decimal (BCD) to gray, and octal to binary code converters. For the first time, to the best of the authors’ knowledge, a high data rate of 500 Gbps is achieved for the three types of all-optical code converters using the SOA-MZI configuration by exploiting an M-ary differential phase shift keying (DPSK) modulation scheme. The performance factors of the proposed all-optical code converters like extinction ratio, bit error rate, and quality factor are calculated.
Learning complex scattering media for optical encryption
Authors: Zhou Lina , Xiao Yin , Chen Wen 
Published: August 2020

Optical encryption has provided a new insight for securing information;
however, it is always desirable that high security can be achieved to
withstand the attacks. In this Letter, we propose a new method via
learning complex scattering media for optical encryption. After the
recordings through complex scattering media, a designed learning model
is trained. The proposed method uses an optical setup with complex
scattering media to experimentally record the ciphertexts and uses a
learning model to generate security keys. During the decryption, the
trained learning model with its parameters is applied as security
keys. In addition, various parameters, e.g., virtual phase-only masks,
can be flexibly applied to further enlarge key space. It is
experimentally demonstrated that the proposed learning-based
encryption approach possesses high security. The proposed method could
open up a new research perspective for optical encryption.
Journaliste, femme et senior : une double peine ?
Authors: Le Cam Florence , Libert Manon 
Published: August 2020

Ce texte repose sur une question simple, presque dichotomique : l’âge est-il oui ou non un facteur aggravant d’inégalités pour les journalistes femmes ? En repartant sur une partie des résultats qui avaient montré le plus de différences entre hommes et femmes dans le rapport Être femme journaliste en Belgique francophone (Le Cam et al., 2018), le texte reprend l’analyse des données quantitatives de l’enquête Portrait des journalistes belges en 2018 (Van Leuven et al., 2019) pour creuser la situation d’emploi et la sécurité économique des journalistes seniors (hommes et femmes), en tentant de mettre au jour les spécificités des situations des femmes journalistes seniors. Le constat est clair : l’âge renforce la permanence de la logique de genre en accentuant même certaines discriminations.
Exergy analysis of conventional and hydrothermal liquefaction–esterification processes of microalgae for biodiesel production
Authors: Prasakti Laras , Pratama Sangga Hadi , Fauzi Ardian , Pradana Yano Surya ,   Rochmadi, Budiman Arief 
Published: August 2020

AbstractAs fossil fuels were depleting at an alarming rate, the development of renewable energy has become necessary. One of the promising renewable energy to be used is biodiesel. The interest in using third-generation feedstock, which is microalgae, is rapidly growing. The use of third-generation biodiesel feedstock will be more beneficial as it does not compete with food crop use and land utilization. The advantageous characteristic which sets microalgae apart from other biomass sources is that microalgae have high biomass yield. Conventionally, microalgae biodiesel is produced by lipid extraction followed by transesterification. In this study, combination process between hydrothermal liquefaction (HTL) and esterification is explored. The HTL process is one of the biomass thermochemical conversion methods to produce liquid fuel. In this study, the HTL process will be coupled with esterification, which takes fatty acid from HTL as raw material for producing biodiesel. Both the processes will be studied by simulating with Aspen Plus and thermodynamic analysis in terms of energy and exergy. Based on the simulation process, it was reported that both processes demand similar energy consumption. However, exergy analysis shows that total exergy loss of conventional exergy loss is greater than the HTL-esterification process.
Synthesis and characterization of a novel chitosan-grafted-polyorthoethylaniline biocomposite and utilization for dye removal from water
Authors: Ahmad Mirza Nadeem , Hussain Arif , Anjum Muhammad Naveed , Hussain Tajamal , Mujahid Adnan , Hammad Khan Muhammad , Ahmed Toheed 
Published: August 2020

AbstractChitosan was grafted with polyorthoethylaniline through oxidative polymerization using ammonium persulfate as oxidant, resulting in the formation of a biocomposite of chitosan-grafted-polyorthoethylaniline (CH-g-POEA). The synthesized biocomposite (CH-g-POEA) was characterized by FTIR, SEM, and TGA. Adsorption of methyl orange (MO) dye by CH-g-POEA was studied, wherein the Langmuir isotherm model with a R2 of 0.9979 and adsorption capacity of 45.7 mg/g was evaluated.