bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol Consumption among the Elderly Citizens in Hungary and Serbia—Comparative Assessment
Authors: Mihailovic Natasa , Szőllősi Gergő József , Rancic Nemanja , János Sándor , Boruzs Klára , Nagy Attila Csaba , Timofeyev Yuriy , Dragojevic-Simic Viktorija , Antunovic Marko , Reshetnikov Vladimir , Ádány Róza , Jakovljevic Mihajlo
Published: February 2020

Studies in the alcohol consumption area are mostly related to the (ab)use of alcohol in young people. However, today, a growing number of researchers are emphasizing the clinical and public health significance of alcohol consumption in the elderly. In the WHO reports, harmful alcohol consumption is responsible for 5.3% of the global burden of the disease. The aim of this study was to investigate the prevalence of alcohol consumption among men and women aged 55 and over in Serbia and Hungary, leveraging data from the 2013 Serbian National Health Survey and from the 2014 Hungarian National Health Survey. Respondents aged 55 and over were analysed based on logistic multivariate models. The prevalence of alcohol consumption was 41.5% and 62.5% in Serbia and Hungary, respectively. It was higher among men in both countries, but among women, it was significantly higher in Hungary than in Serbia. The statistically significant predictors affecting alcohol consumption in Serbia included age, education, well-being index, long-term disease and overall health status, with marital status being an additional factor among men. In Hungary, education and long-term disease affected alcohol consumption in both sexes, while age and employment were additional factors among women. In both countries for both sexes, younger age, more significantly than primary education and good health, was associated with a higher likelihood of alcohol consumption.
The Impact of Spousal Migration on the Mental Health of Nepali Women: A Cross-Sectional Study
Authors: Aryal Nirmal , Regmi Pramod R. , van Teijlingen Edwin , Trenoweth Steven , Adhikary Pratik , Simkhada Padam
Published: February 2020

Spousal separation, lack of companionship, and increased household responsibilities may trigger mental health problems in left-behind female spouses of migrant workers. This study aimed to examine mental ill-health risk in the left-behind female spouses of international migrant workers in Nepal. A cross-sectional survey was carried out in the Nawalparasi district. Study areas were purposively chosen; however, participants were randomly selected. Nepali versions of the 12-item General Health Questionnaire (GHQ), Beck Depression Inventory (BDI), and Connor–Davidson Resilience Scale (CD-RISC) were used. Mental ill-health risk was prevalent in 3.1% of the participants as determined by GHQ. BDI identified mild or moderate depression in 6.5% of the participants with no one having severe depression. In bivariate analysis, a high frequency of communication with the husband was associated with lower mental ill-health risk and depression, as well as increasing resilience. Reduced return intervals of husbands and a high frequency of remittance were also associated with a low GHQ score. In a multiple regression model, adjusting for potential confounding variables, participants who communicated with their husbands at least once a day had a greater mean CD-RISC score (i.e., high resilience against mental ill-health risk) compared to those who did so at least once a week; a mean difference of 3.6 (95% CI 0.4 to 6.9), P = 0.03. To conclude, a low mental ill-health risk was found in the female spouses of migrants.
Adolescents’ Cyber Victimization: The Influence of Technologies, Gender, and Gender Stereotype Traits
Authors: Wright Michelle F. , Wachs Sebastian
Published: February 2020

The purpose of the present study was to investigate the role of gender and gender stereotype traits (masculinity, femininity) in cyber victimization behaviors (cyber relational victimization, cyber verbal victimization, hacking) through different technologies (mobile phones, gaming consoles, social networking sites). There were 456 8th graders (226 females; M age = 13.66, SD = 0.41) from two midwestern middle schools in the United States included in this study. They completed questionnaires on their endorsement of masculine and feminine traits, and self-reported cyber victimization through different technologies. The findings revealed main effects of types of cyber victimization for boys and of technology for girls. In particular, boys with feminine traits experienced the most victimization by cyber verbal aggression, cyber relational aggression, and hacking when compared to the other groups of boys. Girls with feminine traits experienced the most cyber victimization through social networking sites, gaming consoles, and mobile phones in comparison to the other groups of girls. For girls with feminine traits, they reported more cyber relational victimization and cyber verbal victimization through mobile phones and social networking sites, as well as more hacking via social networking sites. Such findings underscore the importance of considering gender stereotype traits, types of victimization, and technologies when examining cyber victimization.
Cancer Patients and Anxiety: A Gender Perspective
Authors: Parás-Bravo Paula , Paz-Zulueta María , Boixadera-Planas Ester , Fradejas-Sastre Víctor , Palacios-Ceña Domingo , Fernández-de-las-Peñas César , Alonso-Blanco Cristina
Published: February 2020

The complexity of the diagnosis and treatment of cancer means that it is often associated with anxiety symptoms. The aim of our study was to further our understanding of the oncological process and the presence of anxiety symptoms, from a gender perspective. A cross-sectional study was performed, examining 402 medical records obtained by simple random sampling of oncology patients at a hospital in northern Spain from July 2012 to July 2014. Data collection took place between February and May 2015. Psychiatric and sociodemographic variables were gathered, as well as pain variables and information regarding the oncological process. The data analysis included a descriptive univariate analysis and a bivariate analysis, and a logistic regression model was performed. Our results suggest that women with cancer suffer more anxiety symptoms than men with cancer. Women with anxiety symptoms represented 76.5% of all patients with anxiety. The OR of suffering anxiety symptoms between women and men was 2.43 (95% CI 1.05–5.63) (p = 0.04). A greater incidence of anxiety symptoms was found in patients with cancer pain and oncological treatment with biological therapy. Our results suggest that the gender perspective is necessary in the management of mental health in patients with cancer. Nonetheless, further studies are necessary to confirm our findings.
CharXgen-Activated Bamboo Charcoal Encapsulated in Sodium Alginate Microsphere as the Absorbent of Uremic Toxins to Retard Kidney Function Deterioration
Authors: Lin Cheng-Jui , Sun Chiao-Yin , Wu Chih-Jen , Wu Chau-Chung , Wu Vincent , Lin Feng-Huei
Published: February 2020

Indoxyl sulphate (IS) and p-cresyl sulphate (PCS) are two protein bound uraemic toxins accumulated in chronic kidney disease (CKD) and associated with adverse outcomes. The purpose of this study isto evaluate the effect of the new activated charcoal, CharXgen, on renal function protection and lowering serum uraemic toxins in CKD animal model. The physical character of CharXgen was analyzed before and after activation procedure by Scanning Electron Microscope (SEM) and X-ray diffractometer (XRD). The effect of CharXgen on biochemistry and lowering uremic toxins was evaluated by in vitro binding assay and CKD animal model. CharXgen have high interior surface area analyzed by SEM and XRD and have been produced from local bamboo after an activation process. CharXgen was able to effectively absorb IS, p-cresol and phosphate in an in vitro gastrointestinal tract simulation study. The animal study showed that CharXgen did not cause intestine blackening. Serum albuminand liver function did not change after feeding with CharXgen. Moreover, renal function was improved in CKD rats fed with CharXgen as compared to the CKD group, and there were no significant differences in the CKD and the CKD + AST-120 groups. Serum IS and PCS were higher in the CKD group and lower in rats treated with CharXgen and AST-120. In rats treated with CharXgen, Fibroblast growth factor 23 was significantly decreased as compared to the CKD group. This change cannot be found in rats fed with AST-120.It indicates that CharXgen is a new safe and non-toxic activated charcoal having potential in attenuating renal function deterioration and lowering protein-bound uraemic toxins. Whether the introduction of this new charcoal could further have renal protection in CKD patients will need to be investigated further.
Jasmonic Acid: An Essential Plant Hormone
Authors: Gomi Kenji
Published: February 2020

The plant hormone jasmonic acid (JA) and its derivative, an amino acid conjugate of JA (jasmonoyl isoleucine: JA-Ile), are signaling compounds involved in the regulation of cellular defense and development in plants [...]
TLR4 Stimulation Promotes Human AVIC Fibrogenic Activity through Upregulation of Neurotrophin 3 Production
Authors: Yao Qingzhou , The Erlinda , Ao Lihua , Zhai Yufeng , Osterholt Maren K. , Fullerton David A. , Meng Xianzhong
Published: February 2020

Background: Calcific aortic valve disease (CAVD) is a chronic inflammatory disease that manifests as progressive valvular fibrosis and calcification. An inflammatory milieu in valvular tissue promotes fibrosis and calcification. Aortic valve interstitial cell (AVIC) proliferation and the over-production of the extracellular matrix (ECM) proteins contribute to valvular thickening. However, the mechanism underlying elevated AVIC fibrogenic activity remains unclear. Recently, we observed that AVICs from diseased aortic valves express higher levels of neurotrophin 3 (NT3) and that NT3 exerts pro-osteogenic and pro-fibrogenic effects on human AVICs. Hypothesis: Pro-inflammatory stimuli upregulate NT3 production in AVICs to promote fibrogenic activity in human aortic valves. Methods and Results: AVICs were isolated from normal human aortic valves and were treated with lipopolysaccharide (LPS, 0.20 µg/mL). LPS induced TLR4-dependent NT3 production. This effect of LPS was abolished by inhibition of the Akt and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathways. The stimulation of TLR4 in human AVICs with LPS resulted in a greater proliferation rate and an upregulated production of matrix metallopeptidases-9 (MMP-9) and collagen III, as well as augmented collagen deposition. Recombinant NT3 promoted AVIC proliferation in a tropomyosin receptor kinase (Trk)-dependent fashion. The neutralization of NT3 or the inhibition of Trk suppressed LPS-induced AVIC fibrogenic activity. Conclusions: The stimulation of TLR4 in human AVICs upregulates NT3 expression and promotes cell proliferation and collagen deposition. The NT3-Trk cascade plays a critical role in the TLR4-mediated elevation of fibrogenic activity in human AVICs. Upregulated NT3 production by endogenous TLR4 activators may contribute to aortic valve fibrosis associated with CAVD progression.
Sexual Dimorphism in Doxorubicin-induced Systemic Inflammation: Implications for Hepatic Cytochrome P450 Regulation
Authors: Grant Marianne K.O. , Abdelgawad Ibrahim Y. , Lewis Christine A. , Zordoky Beshay N.
Published: February 2020

Doxorubicin (DOX) is an effective chemotherapeutic agent used to treat a wide variety of malignancies. In addition to its multi-organ toxicity, DOX treatment has been shown to induce systemic inflammation in patients and experimental animals. Inflammation alters the expression of hepatic cytochrome P450 (CYP) enzymes, which play important roles in drug metabolism and DOX-induced toxicity. Significant sex differences have been reported in DOX-induced toxicity; however, sex differences in DOX-induced systemic inflammation and the potential effects on hepatic CYP expression have not been determined. In the current work, male and female C57Bl/6 mice were administered DOX (20 mg/kg by intraperitoneal injection), and groups of mice were sacrificed 24 and 72 h after DOX administration. DOX elicited a systemic inflammatory response in both male and female mice, but the inflammatory response was stronger in male mice. DOX altered the expression of hepatic CYP isoforms in a sex-dependent manner. Most notably, inhibition of Cyp2c29 and Cyp2e1 was stronger in male than in female mice, which paralleled the sex differences in systemic inflammation. Therefore, sex differences in DOX-induced systemic inflammation may lead to sexually dimorphic drug interactions, in addition to contributing to the previously reported sexual dimorphism in specific DOX-induced organ toxicity.
Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast Cancer
Authors: Winn Jennifer S. , Hasse Zachary , Slifker Michael , Pei Jianming , Arisi-Fernandez Sebastian M. , Talarchek Jacqueline N. , Obeid Elias , Baldwin Donald A. , Gong Yulan , Ross Eric , Cristofanilli Massimo , Alpaugh R. Katherine , Fernandez Sandra V.
Published: February 2020

We studied genomic alterations in 19 inflammatory breast cancer (IBC) patients with advanced disease using samples of tissue and paired blood serum or plasma (cell-free DNA, cfDNA) by targeted next generation sequencing (NGS). At diagnosis, the disease was triple negative (TN) in eleven patients (57.8%), ER+ Her2- IBC in six patients (31.6%), ER+ Her2+ IBC in one patient (5.3%), and ER- Her2+ IBC in one other patient (5.3%). Pathogenic or likely pathogenic variants were frequently detected in TP53 (47.3%), PMS2 (26.3%), MRE11 (26.3%), RB1 (10.5%), BRCA1 (10.5%), PTEN (10.5%) and AR (10.5%); other affected genes included PMS1, KMT2C, BRCA2, PALB2, MUTYH, MEN1, MSH2, CHEK2, NCOR1, PIK3CA, ESR1 and MAP2K4. In 15 of the 19 patients in which tissue and paired blood were collected at the same time point, 80% of the variants detected in tissue were also detected in the paired cfDNA. Higher concordance between tissue and cfDNA was found for variants with higher allele fraction in tissue (AFtissue ≥ 5%). Furthermore, 86% of the variants detected in cfDNA were also detected in paired tissue. Our study suggests that the genetic profile measured in blood cfDNA is complementary to that of tumor tissue in IBC patients.
Comprehensive Transcriptomic Analysis of Auxin Responses in Submerged Rice Coleoptile Growth
Authors: Wu Yu-Sian , Yang Chin-Ying
Published: February 2020

Cultivating rice in wet or water direct seeding systems is simple and time and labor efficient. Rice (Oryza sativa) seeds are a unique cereal that can germinate not only when submerged, but also in anoxic conditions. Many complicated hormone signals interact in submerged seed germination. Ethylene is involved in rice coleoptile elongation, but little is known regarding the role of auxin signaling under submergence. This study demonstrated that the coleoptile is shorter and curlier when submerged with 2,3,5-triiodobenzoic acid (TIBA). In transcriptomic analysis, 3448 of the 31,860 genes were upregulated, and 4360 genes were downregulated with submergence and TIBA treatment. The Gene Ontology function classification results demonstrated that upregulated differentially expressed genes (DEGs) were mainly involved in redox, stress, and signal transduction, whereas the down-regulated DEGs were mainly involved in RNA transcription, stress, and development. Furthermore, auxin signaling involved in the carbohydrate metabolism pathway was demonstrated while using transcriptomic analysis and confirmed in a quantitative real-time polymerase chain reaction. In addition, the transcript levels of development-related genes and mitochondria-electron- transport-related genes were regulated by auxin signaling under submergence. Auxin signaling was not only involved in regulating rice coleoptile elongation and development, but also regulated secondary metabolism, carbohydrate metabolism, and mitochondria electron transport under submergence. Our results presented that auxin signaling plays an important role during rice coleoptile elongation upon the submergence condition and improving the advance of research of direct rice seeding system.
Characterization of the OFP Gene Family and its Putative Involvement of Tuberous Root Shape in Radish
Authors: Wang Yanping , Wang Qingbiao , Hao Wei , Sun Honghe , Zhang Li
Published: February 2020

The shape of the tuberous root, a very important quality trait, varies dramatically among radish cultivars. Ovate family proteins (OFPs) are plant-specific proteins that regulate multiple aspects of plant growth and development. To investigate the possible role of OFPs in radish tuberous root formation, 35 putative RsOFPs were identified from radish, and their expression patterns were detected during tuberous root development in six different radish cultivars. Phylogenetically, RsOFP2.3 clustered together with AtOFP1 and other members of this family that are known to regulate organ shape. Moreover, RsOFP2.3 expression was negatively correlated with tuberous root elongation after the cortex splitting stage, which made this gene the top candidate for the involvement of tuberous root shape. To further characterize the function of RsOFP2.3, it was ectopically expressed in Arabidopsis. RsOFP2.3 overexpression in Arabidopsis led to multiple phenotypical changes, especially the decreased length and increased width of the hypocotyl. Furthermore, RsOFP2.3 expression was induced by all the five classic plant hormones except ethylene, and it was most sensitive to exogenous gibberellic acid treatment. We also found that RsOFP2.3 was localized in the cytoplasm. Taken together, our results suggested the possible involvement for RsOFP2.3 in suppressing radish tuberous root elongation and that it encodes a functional protein which mainly inhibits the elongation of Arabidopsis aerial organs.
Comparative Analysis of the Effect of Inorganic and Organic Chemicals with Silver Nanoparticles on Soybean under Flooding Stress
Authors: Hashimoto Takuya , Mustafa Ghazala , Nishiuchi Takumi , Komatsu Setsuko
Published: February 2020

Extensive utilization of silver nanoparticles (NPs) in agricultural products results in their interaction with other chemicals in the environment. To study the combined effects of silver NPs with nicotinic acid and potassium nitrate (KNO3), a gel-free/label-free proteomic technique was used. Root length/weight and hypocotyl length/weight of soybean were enhanced by silver NPs mixed with nicotinic acid and KNO3. Out of a total 6340 identified proteins, 351 proteins were significantly changed, out of which 247 and 104 proteins increased and decreased, respectively. Differentially changed proteins were predominantly associated with protein degradation and synthesis according to the functional categorization. Protein-degradation-related proteins mainly consisted of the proteasome degradation pathway. The cell death was significantly higher in the root tips of soybean under the combined treatment compared to flooding stress. Accumulation of calnexin/calreticulin and glycoproteins was significantly increased under flooding with silver NPs, nicotinic acid, and KNO3. Growth of soybean seedlings with silver NPs, nicotinic acid, and KNO3 was improved under flooding stress. These results suggest that the combined mixture of silver NPs, nicotinic acid, and KNO3 causes positive effects on soybean seedling by regulating the protein quality control for the mis-folded proteins in the endoplasmic reticulum. Therefore, it might improve the growth of soybean under flooding stress.
Chemoradiotherapy Increases Intratumor Heterogeneity of HPSE Expression in the Relapsed Glioblastoma Tumors
Authors: Suhovskih Anastasia V. , Kazanskaya Galina M. , Volkov Alexander M. , Tsidulko Alexandra Y. , Aidagulova Svetlana V. , Grigorieva Elvira V.
Published: February 2020

Adjuvant chemoradiotherapy is a standard treatment option for glioblastoma multiforme (GBM). Despite intensive care, recurrent tumors developed during the first year are fatal for the patients. Possibly contributing to this effect, among other causes, is that therapy induces changes of polysaccharide heparan sulfate (HS) chains in the cancer cells and/or tumor microenvironment. The aim of this study was to perform a comparative analysis of heparanase (HPSE) expression and HS content in different normal and GBM brain tissues. Immunohistochemical analysis revealed a significant decrease of HPSE protein content in the tumor (12-15-fold) and paratumorous (2.5-3-fold) GBM tissues compared with normal brain tissue, both in cellular and extracellular compartments. The relapsed GBM tumors demonstrated significantly higher intertumor and/or intratumor heterogeneity of HPSE and HS content and distribution compared with the matched primary ones (from the same patient) (n = 8), although overall expression levels did not show significant differences, suggesting local deterioration of HPSE expression with reference to the control system or by the treatment. Double immunofluorescence staining of various glioblastoma cell lines (U87, U343, LN18, LN71, T406) demonstrated a complex pattern of HPSE expression and HS content with a tendency towards a negative association of these parameters. Taken together, the results demonstrate the increase of intratumor heterogeneity of HPSE protein in relapsed GBM tumors and suggest misbalance of HPSE expression regulation by the adjuvant anti-GBM chemoradiotherapy.
Carboxy-Terminal Cementum Protein 1-Derived Peptide 4 (cemp1-p4) Promotes Mineralization through wnt/β-catenin Signaling in Human Oral Mucosa Stem Cells
Authors: Arroyo Rita , López Sonia , Romo Enrique , Montoya Gonzalo , Hoz Lía , Pedraza Claudia , Garfias Yonathan , Arzate Higinio
Published: February 2020

Human cementum protein 1 (CEMP1) is known to induce cementoblast and osteoblast differentiation and alkaline phosphatase (ALP) activity in human periodontal ligament-derived cells in vitro and promotes bone regeneration in vivo. CEMP1′s secondary structure analysis shows that it has a random-coiled structure and is considered an Intrinsic Disordered Protein (IDP). CEMP1′s short peptide sequences mimic the biological capabilities of CEMP1. However, the role and mechanisms of CEMP1′s C-terminal-derived synthetic peptide (CEMP1-p4) in the canonical Wnt/β-catenin signaling pathway are yet to be described. Here we report that CEMP1-p4 promotes proliferation and differentiation of Human Oral Mucosa Stem Cells (HOMSCs) by activating the Wnt/β-catenin pathway. CEMP1-p4 stimulation upregulated the expression of β-catenin and glycogen synthase kinase 3 beta (GSK-3B) and activated the transcription factors TCF1/7 and Lymphoid Enhancer binding Factor 1 (LEF1) at the mRNA and protein levels. We found translocation of β-catenin to the nucleus in CEMP1-p4-treated cultures. The peptide also penetrates the cell membrane and aggregates around the cell nucleus. Analysis of CEMP1-p4 secondary structure revealed that it has a random-coiled structure. Its biological activities included the induction to nucleate hydroxyapatite crystals. In CEMP1-p4-treated HOMSCs, ALP activity and calcium deposits increased. Expression of Osterix (OSX), Runt-related transcription factor 2 (RUNX2), Integrin binding sialoproptein (IBSP) and osteocalcin (OCN) were upregulated. Altogether, these data show that CEMP1-p4 plays a direct role in the differentiation of HOMSCs to a “mineralizing-like” phenotype by activating the β-catenin signaling cascade.
Intratumor Heterogeneity and Therapy Resistance: Contributions of Dormancy, Apoptosis Reversal (Anastasis) and Cell Fusion to Disease Recurrence
Authors: Mirzayans Razmik , Murray David
Published: February 2020

A major challenge in treating cancer is posed by intratumor heterogeneity, with different sub-populations of cancer cells within the same tumor exhibiting therapy resistance through different biological processes. These include therapy-induced dormancy (durable proliferation arrest through, e.g., polyploidy, multinucleation, or senescence), apoptosis reversal (anastasis), and cell fusion. Unfortunately, such responses are often overlooked or misinterpreted as “death” in commonly used preclinical assays, including the in vitro colony-forming assay and multiwell plate “viability” or “cytotoxicity” assays. Although these assays predominantly determine the ability of a test agent to convert dangerous (proliferating) cancer cells to potentially even more dangerous (dormant) cancer cells, the results are often assumed to reflect loss of cancer cell viability (death). In this article we briefly discuss the dark sides of dormancy, apoptosis, and cell fusion in cancer therapy, and underscore the danger of relying on short-term preclinical assays that generate population-based data averaged over a large number of cells. Unveiling the molecular events that underlie intratumor heterogeneity together with more appropriate experimental design and data interpretation will hopefully lead to clinically relevant strategies for treating recurrent/metastatic disease, which remains a major global health issue despite extensive research over the past half century.
Mechanisms of Action of Cassiae Semen for Weight Management: A Computational Molecular Docking Study of Serotonin Receptor 5-HT2C
Authors: Yuen Heidi , Hung Andrew , Yang Angela Wei Hong , Lenon George Binh
Published: February 2020

Overweight and obesity is a growing global health concern. Current management of obesity includes lifestyle intervention, bariatric surgery and medication. The serotonin receptor, 5-HT2C, is known to mediate satiety, appetite and consumption behaviour. Lorcaserin, an appetite control drug, has demonstrated efficacy in appetite control by targeting 5-HT2C but causes undesirable side effects. This study aimed to explore the potential usage of Cassiae semen (CS), a well-known traditional Chinese medicine used to treat obesity. A computational molecular docking study was performed to determine the binding mechanism of CS compounds to the 5-HT2C receptors in both active, agonist-bound and inactive, antagonist-bound conformations. By comparing binding poses and predicted relative binding affinities towards the active or inactive forms of the receptor, we hypothesise that two of the CS compounds studied may be potent agonists which may mimic the appetite suppression effects of lorcaserin: obtusifoliol and cassiaside B2. Furthermore, two ligands, beta-sitosterol and juglanin, were predicted to bind favourably to 5-HT2C outside of the known agonist binding pocket in the active receptor, suggesting that such ligands may serve as positive allosteric modulators of 5-HT2C receptor function. Overall, this study proposed several CS compounds which may be responsible for exerting anti-obesity effects via appetite suppression by 5-HT2C receptor activation.
Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis
Authors: Roszkowska Katarzyna A. , Gizinski Slawomir , Sady Maria , Gajewski Zdzislaw , Olszewski Maciej B.
Published: February 2020

Forty years of research has proven beyond any doubt that p53 is a key regulator of many aspects of cellular physiology. It is best known for its tumor suppressor function, but it is also a regulator of processes important for maintenance of homeostasis and stress response. Its activity is generally antiproliferative and when the cell is damaged beyond repair or intensely stressed the p53 protein contributes to apoptosis. Given its key role in preventing cancer it is no wonder that it is the most frequently mutated gene in human cancer. Surprisingly, a subset of missense mutations occurring in p53 (gain-of-function) cause it to lose its suppressor activity and acquire new functionalities that turn the tumor suppressor protein into an oncoprotein. A solid body of evidence exists demonstrating increased malignancy of cancers with mutated p53 in all aspects considered “hallmarks of cancer”. In this review, we summarize current findings concerning the cellular processes altered by gain-of-function mutations in p53 and their influence on cancer invasiveness and metastasis. We also present the variety of molecular mechanisms regulating these processes, including microRNA, direct transcriptional regulation, protein–protein interactions, and more.
Structural Changes and Astrocyte Response of the Lateral Geniculate Nucleus in a Ferret Model of Ocular Hypertension
Authors: Fujishiro Takashi , Honjo Megumi , Kawasaki Hiroshi , Asaoka Ryo , Yamagishi Reiko , Aihara Makoto
Published: February 2020

We investigated structural changes and astrocyte responses of the lateral geniculate nucleus (LGN) in a ferret model of ocular hypertension (OH). In 10 ferrets, OH was induced via the injection of cultured conjunctival cells into the anterior chamber of the right eye; six normal ferrets were used as controls. Anterograde axonal tracing with cholera toxin B revealed that atrophic damage was evident in the LGN layers receiving projections from OH eyes. Immunohistochemical analysis with antibodies against NeuN, glial fibrillary acidic protein (GFAP), and Iba-1 was performed to specifically label neurons, astrocytes, and microglia in the LGN. Significantly decreased NeuN immunoreactivity and increased GFAP and Iba-1 immunoreactivities were observed in the LGN layers receiving projections from OH eyes. Interestingly, the changes in the immunoreactivities were significantly different among the LGN layers. The C layers showed more severe damage than the A and A1 layers. Secondary degenerative changes in the LGN were also observed, including neuronal damage and astrocyte reactions in each LGN layer. These results suggest that our ferret model of OH is valuable for investigating damages during the retina–brain transmission of the visual pathway in glaucoma. The vulnerability of the C layers was revealed for the first time.
Cholesterol, Oxysterols and LXRs in Breast Cancer Pathophysiology
Authors: Nazih Hassan , Bard Jean Marie
Published: February 2020

Breast cancer is the most frequent cancer among women. In 2018, it is estimated that 627,000 women died from breast cancer. This is approximately 15% of all cancer deaths among women (WHO 2018). Breast cancer is a multifactorial chronic disease. While important progress has been made to treat patients, many questions regarding aspects of this disease relating to carcinogenesis are still open. During carcinogenesis, cells exhibit cholesterol homeostasis deregulation. This results in an accumulation of intracellular cholesterol, which is required to sustain their high growth rate. Cholesterol efflux and influx are two metabolic pathways that are necessary to prevent cholesterol accumulation in the cells. Liver X receptors (LXRs) are nuclear receptors that, upon activation, induce the expression of ABC transporters, responsible for promoting cholesterol efflux, and the expression of IDOL (inducible degrader of low-density lipoprotein receptor), in charge of reducing cholesterol influx. Oxysterols, oxygenated derivatives of cholesterol formed through different pathways, have been discovered as LXR-specific ligands. Some oxysterols are involved in tumor formation while others are considered anti-tumor agents. In the present review, we discuss the involvement of cholesterol, oxysterols and LXRs in breast cancer pathophysiology, with an emphasis on the biological effects of LXR ligands.
The Impact of MNRI Therapy on the Levels of Neurotransmitters Associated with Inflammatory Processes
Authors: Tatarinova Tatiana V. , Deiss Trina , Franckle Lorri , Beaven Susan , Davis Jeffrey
Published: February 2020

The neurotransmitter levels of representatives from five different diagnosis groups were tested before and after participation in the MNRI®—Masgutova Neurosensorimotor Reflex Intervention. The purpose of this study was to ascertain neurological impact on (1) Developmental disorders, (2) Anxiety disorders/OCD (Obsessive Compulsive Disorder), PTSD (Post-Traumatic Stress disorder), (3) Palsy/Seizure disorders, (4) ADD/ADHD (Attention Deficit Disorder/Attention Deficit Disorder Hyperactive Disorder), and (5) ASD (Autism Spectrum Disorder) disorders. Each participant had a form of neurological dysregulation and typical symptoms respective to their diagnosis. These diagnoses have a severe negative impact on the quality of life, immunity, stress coping, cognitive skills, and social assimilation. This study showed a trend towards optimization and normalization of neurological and immunological functioning, thus supporting the claim that the MNRI method is an effective non-pharmacological neuromodulation treatment of neurological disorders. The effects of MNRI on inflammation have not yet been assessed. The resulting post-MNRI changes in participants’ neurotransmitters show significant adjustments in the regulation of the neurotransmitter resulting in being calmer, a decrease of hypervigilance, an increase in stress resilience, behavioral and emotional regulation improvements, a more positive emotional state, and greater control of cognitive processes. In this paper, we demonstrate that the MNRI approach is an intervention that reduces inflammation. It is also likely to reduce oxidative stress and encourage homeostasis of excitatory neurotransmitters. MNRI may facilitate neurodevelopment, build stress resiliency, neuroplasticity, and optimal learning opportunity. There have been no reported side effects of MNRI treatments.
Marine Omega-3 (N-3) Fatty Acids for Cardiovascular Health: An Update for 2020
Authors: Innes Jacqueline K. , Calder Philip C.
Published: February 2020

The omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found in seafood (especially fatty fish), supplements and concentrated pharmaceutical preparations. Long-term prospective cohort studies consistently demonstrate an association between higher intakes of fish, fatty fish and marine n-3 fatty acids (EPA + DHA) or higher levels of EPA and DHA in the body and lower risk of developing cardiovascular disease (CVD), especially coronary heart disease (CHD) and myocardial infarction (MI), and cardiovascular mortality in the general population. This cardioprotective effect of EPA and DHA is most likely due to the beneficial modulation of a number of known risk factors for CVD, such as blood lipids, blood pressure, heart rate and heart rate variability, platelet aggregation, endothelial function, and inflammation. Evidence for primary prevention of CVD through randomised controlled trials (RCTs) is relatively weak. In high-risk patients, especially in the secondary prevention setting (e.g., post-MI), a number of large RCTs support the use of EPA + DHA (or EPA alone) as confirmed through a recent meta-analysis. This review presents some of the key studies that have investigated EPA and DHA in the primary and secondary prevention of CVD, describes potential mechanisms for their cardioprotective effect, and evaluates the more recently published RCTs in the context of existing scientific literature.
Bioinformatics Approaches to the Understanding of Molecular Mechanisms in Antimicrobial Resistance
Authors: Van Camp Pieter-Jan , Haslam David B. , Porollo Aleksey
Published: February 2020

Antimicrobial resistance (AMR) is a major health concern worldwide. A better understanding of the underlying molecular mechanisms is needed. Advances in whole genome sequencing and other high-throughput unbiased instrumental technologies to study the molecular pathogenicity of infectious diseases enable the accumulation of large amounts of data that are amenable to bioinformatic analysis and the discovery of new signatures of AMR. In this work, we review representative methods published in the past five years to define major approaches developed to-date in the understanding of AMR mechanisms. Advantages and limitations for applications of these methods in clinical laboratory testing and basic research are discussed.
Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status
Authors: Currò Monica , Ferlazzo Nadia , Giunta Maria Laura , Montalto Angela Simona , Russo Tiziana , Arena Salvatore , Impellizzeri Pietro , Caccamo Daniela , Romeo Carmelo , Ientile Riccardo
Published: February 2020

Transglutaminase 2 (TG2) is a multifunctional enzyme and two isoforms, TG2-L and TG2-S, exerting opposite effects in the regulation of cell death and survival, have been revealed in cancer tissues. Notably, in cancer cells a hypoxic environment may stimulate tumor growth, invasion and metastasis. Here we aimed to characterize the role of TG2 isoforms in neuroblastoma cell fate under hypoxic conditions. The mRNA levels of TG2 isoforms, hypoxia-inducible factor (HIF)-1α, p16, cyclin D1 and B1, as well as markers of cell proliferation/death, DNA damage, and cell cycle were examined in SH-SY5Y (non-MYCN-amplified) and IMR-32 (MYCN-amplified) neuroblastoma cells in hypoxia/reoxygenation conditions. The exposure to hypoxia induced the up-regulation of HIF-1α in both cell lines. Hypoxic conditions caused the up-regulation of TG2-S and the reduction of cell viability/proliferation associated with DNA damage in SH-SY5Y cells, while in IMR-32 did not produce DNA damage, and increased the levels of both TG2 isoforms and proliferation markers. Different cell response to hypoxia can be mediated by TG2 isoforms in function of MYCN amplification status. A better understanding of the role of TG2 isoforms in neuroblastoma may open new venues in a diagnostic and therapeutic perspective.
Label-Free Comparative Proteomic Analysis Combined with Laser-Capture Microdissection Suggests Important Roles of Stress Responses in the Black Layer of Maize Kernels
Authors: Chen Quanquan , Huang Ran , Xu Zhenxiang , Zhang Yaxin , Li Li , Fu Junjie , Wang Guoying , Wang Jianhua , Du Xuemei , Gu Riliang
Published: February 2020

The black layer (BL) is traditionally used as an indicator for kernel harvesting in maize, as it turns visibly dark when the kernel reaches physiological maturity. However, the molecular roles of BL in kernel development have not been fully elucidated. In this work, microscopy images showed that BL began to appear at a growth stage earlier than 10 days after pollination (DAP), and its color gradually deepened to become dark as the development period progressed. Scanning electron microscopy observations revealed that BL is a tissue structure composed of several layers of cells that are gradually squeezed and compressed during kernel development. Laser-capture microdissection (LCM) was used to sample BL and its neighboring inner tissue, basal endosperm transfer layer (BETL), and outer tissue, inner epidermis (IEP), from 20 DAP of kernels. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling (MALDI-TOF MS profiling) detected 41, 104, and 120 proteins from LCM-sampled BL, BETL, and IEP, respectively. Gene ontology (GO) analysis indicated that the 41 BL proteins were primarily involved in the response to stress and stimuli. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found that the BL proteins were enriched in several defense pathways, such as the ascorbate and aldarate metabolic pathways. Among the 41 BL proteins, six were BL-specific proteins that were only detected from BL. Annotations of five BL-specific proteins were related to stress responses. During kernel development, transcriptional expression of most BL proteins showed an increase, followed by a decrease, and reached a maximum zero to 20 DAP. These results suggest a role for BL in stress responses for protecting filial tissue against threats from maternal sides, which helps to elucidate the biological functions of BL.
The Urinary Exosomal miRNA Expression Profile is Predictive of Clinical Response in Lupus Nephritis
Authors: Garcia-Vives Eloi , Solé Cristina , Moliné Teresa , Vidal Marta , Agraz Irene , Ordi-Ros Josep , Cortés-Hernández Josefina
Published: February 2020

Data on exosomal-derived urinary miRNAs have identified several miRNAs associated with disease activity and fibrosis formation, but studies on prognosis are lacking. We conducted a qPCR array screening on urinary exosomes from 14 patients with biopsy-proven proliferative lupus glomerulonephritis with a renal outcome of clinical response (n = 7) and non-response (n = 7) following therapy. Validation studies were performed by qRT-PCR in a new lupus nephritis (LN) cohort (responders = 22 and non-responders = 21). Responder patients expressed significantly increased levels of miR-31, miR-107, and miR-135b-5p in urine and renal tissue compared to non-responders. MiR-135b exhibited the best predictive value to discriminate responder patients (area under the curve = 0.783). In vitro studies showed exosome-derived miR-31, miR-107, and miR-135b-5p expression to be mainly produced by tubular renal cells stimulated with inflammatory cytokines (e.g IL1, TNFα, IFNα and IL6). Uptake of urinary exosomes from responders by mesangial cells was superior compared to that from non-responders (90% vs. 50%, p < 0.0001). HIF1A was identified as a potential common target, and low protein levels were found in non-responder renal biopsies. HIF1A inhibition reduced mesangial proliferation and IL-8, CCL2, CCL3, and CXCL1 mesangial cell production and IL-6/VCAM-1 in endothelial cells. Urinary exosomal miR-135b-5p, miR-107, and miR-31 are promising novel markers for clinical outcomes, regulating LN renal recovery by HIF1A inhibition.
Hydrothermal Carbon/Carbon Nanotube Composites as Electrocatalysts for the Oxygen Reduction Reaction
Authors: Morais Rafael G. , Rey-Raap Natalia , Costa Rui S. , Pereira Clara , Guedes Alexandra , Figueiredo José L. , Pereira M. Fernando R.
Published: February 2020

The oxygen reduction reaction is an essential reaction in several energy conversion devices such as fuel cells and batteries. So far, the best performance is obtained by using platinum-based electrocatalysts, which make the devices really expensive, and thus, new and more affordable materials should be designed. Biomass-derived carbons were prepared by hydrothermal carbonization in the presence of carbon nanotubes with different oxygen surface functionalities to evaluate their effect on the final properties. Additionally, nitrogen functional groups were also introduced by ball milling the carbon composite together with melamine. The oxygen groups on the surface of the carbon nanotubes favor their dispersion into the precursor mixture and the formation of a more homogenous carbon structure with higher mechanical strength. This type of structure partially avoids the crushing of the nanotubes and the carbon spheres during the ball milling, resulting in a carbon composite with enhanced electrical conductivity. Undoped and N-doped composites were used as electrocatalysts for the oxygen reduction reaction. The onset potential increases by 20% due to the incorporation of carbon nanotubes (CNTs) and nitrogen, which increases the number of active sites and improves the chemical reactivity, while the limiting current density increases by 47% due to the higher electrical conductivity.
The Contribution of Multispectral Satellite Image to Shallow Water Bathymetry Mapping on the Coast of Misano Adriatico, Italy
Authors: Muzirafuti Anselme , Barreca Giovanni , Crupi Antonio , Faina Giancarlo , Paltrinieri Diego , Lanza Stefania , Randazzo Giovanni
Published: February 2020

The results of absolute satellite-derived bathymetry (SDB) are presented in the current study. A comparative analysis was conducted on empirical methods in order to explore the potential of SDB in shallow water on the coast of Misano, Italy. Operations were carried out by relying on limited in situ water depth data to extract and calibrate bathymetry from a QuickBird satellite image acquired on a highly dynamic coastal environment. The image was processed using the log-band ratio and optimal band ratio analysis (OBRA) methods. Preprocessing steps included the conversion of the raw satellite image into top of atmosphere reflectance, spatial filtering, land and water classification, the determination of the optimal OBRA spectral band pairs, and the estimation of relative SDB. Furthermore, calibration and vertical referencing were performed via in situ bathymetry acquired in November 2007. The relative bathymetry obtained from different band ratios were vertically referenced to the local datum using in situ water depth in order to obtain absolute SDB. The coefficient of determination (R2) and vertical root mean square error (RMSE) were computed for each method. A strong correlation with in situ field bathymetry was observed for both methods, with R2 = 0.8682 and RMSE = 0.518 m for the log-band ratio method and R2 = 0.8927–0.9108 and RMSE = 0.35 m for the OBRA method. This indicated a high degree of confidence of the SDB results obtained for the study area, with a high performance of the OBRA method for SDB mapping in turbid water.
A Broadband Tunable Terahertz Metamaterial Absorber Based on Single-Layer Complementary Gammadion-Shaped Graphene
Authors: Chen Fu , Cheng Yongzhi , Luo Hui
Published: February 2020

We present a simple design of a broadband tunable metamaterial absorber (MMA) in the terahertz (THz) region, which consists of a single layer complementary gammadion-shaped (CGS) graphene sheet and a polydimethylsiloxane (PDMS) dielectric substrate placed on a continuous metal film. The Fermi energy level (Ef) of the graphene can be modulated dynamically by the applied DC bias voltage, which enables us to electrically control the absorption performance of the proposed MMA flexibly. When Ef = 0.8 eV, the relative bandwidth of the proposed MMA, which represents the frequency region of absorption beyond 90%, can reaches its maximal value of 72.1%. Simulated electric field distributions reveal that the broadband absorption mainly originates from the excitation of surface plasmon polaritons (SPPs) on the CGS graphene sheet. Furthermore, the proposed MMA is polarization-insensitive and has wide angles for both transverse-electric (TE) and transverse-magnetic (TM) waves in the broadband frequency range. The broadband absorption capacity of the designed MMA can be effectively adjusted by varying the Fermi energy level of graphene. Lastly, the absorbance of the MMA can be adjusted from 42% to 99.1% by changing the Ef from 0 eV to 0.8 eV, which is in agreement with the theoretical calculation by using the interference 41theory. Due to its simple structure and flexible tunability, the proposed MMA has potential application prospects in tunable filtering, modulators, sensing, and other multispectral devices.
Physical Modeling of Cross Wedge Rolling Limitations
Authors: Wójcik Łukasz , Pater Zbigniew , Bulzak Tomasz , Tomczak Janusz
Published: February 2020

This article presents the results of model tests aiming to verify the possibility of applying commercial plasticine as a model material for modelling the limits to the cross-wedge rolling process. This study presents a comparison of the results of laboratory testing and physical modelling of cross-wedge rolling (CWR) processes. Commercial plasticine was the model material used in the research to model 50HS grade steel formed in 1150 °C. The model material was cooled to 0 °C, 5 °C, 10 °C, 12,5 °C, and 15 °C. Physical modelling of neckings and slippages is only possible when the plasticine is heated to 12.5 °C prior to forming. Commercial plasticine does not enable one to model the cracking process inside the rolled element.