bluuebunny/crossref_metadata_2025 huggingface dataset:
CN133, a Novel Brain-Penetrating Histone Deacetylase Inhibitor, Hampers Tumor Growth in Patient-Derived Pediatric Posterior Fossa Ependymoma Models
Authors: Antonelli Roberta , Jiménez Carlos , Riley Misha , Servidei Tiziana , Riccardi Riccardo , Soriano Aroa , Roma Josep , Martínez-Saez Elena , Martini Maurizio , Ruggiero Antonio , Moreno Lucas , Sánchez de Toledo Josep , Gallego Soledad , Bové Jordi , Hooker Jacob M. , Segura Miguel F.
Published: July 2020

Pediatric ependymoma (EPN) is a highly aggressive tumor of the central nervous system that remains incurable in 40% of cases. In children, the majority of cases develop in the posterior fossa and can be classified into two distinct molecular entities: EPN posterior fossa A (PF-EPN-A) and EPN posterior fossa B (PF-EPN-B). Patients with PF-EPN-A have poor outcome and are in demand of new therapies. In general, PF-EPN-A tumors show a balanced chromosome copy number profile and have no recurrent somatic nucleotide variants. However, these tumors present abundant epigenetic deregulations, thereby suggesting that epigenetic therapies could provide new opportunities for PF-EPN-A patients. In vitro epigenetic drug screening of 11 compounds showed that histone deacetylase inhibitors (HDACi) had the highest anti-proliferative activity in two PF-EPN-A patient-derived cell lines. Further screening of 5 new brain-penetrating HDACi showed that CN133 induced apoptosis in vitro, reduced tumor growth in vivo and significantly extended the survival of mice with orthotopically-implanted EPN tumors by modulation of the unfolded protein response, PI3K/Akt/mTOR signaling, and apoptotic pathways among others. In summary, our results provide solid preclinical evidence for the use of CN133 as a new therapeutic agent against PF-EPN-A tumors.
Metabolites as Prognostic Markers for Metastatic Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Platinum-Doublet Chemotherapy
Authors: Hao Desirée , Sengupta Arjun , Ding Keyue , Ubeydullah ER , Krishnaiah Saikumari , Leighl Natasha B. , Shepherd Frances A. , Seymour Lesley , Weljie Aalim
Published: July 2020

The metabolic requirements of metastatic non-small cell lung (mNSCLC) tumors from patients receiving first-line platinum-doublet chemotherapy are hypothesized to imprint a blood signature suitable for survival prediction. Pre-treatment samples prospectively collected at baseline from a randomized phase III trial were assayed using nuclear magnetic resonance (NMR) spectroscopy (n = 341) and ultra-high performance liquid chromatography – mass spectrometry (UPLC-MS) (n = 297). Distributions of time to event outcomes were estimated by Kaplan-Meier analysis, and baseline characteristics adjusted Cox regression modeling was used to correlate markers’ levels to time to event outcomes. Sixteen polar metabolites were significantly correlated with overall survival (OS) by univariate analysis (p < 0.025). Formate, 2-hydroxybutyrate, glycine and myo-inositol were selected for a multivariate model. The median OS was 6.6 months in the high-risk group compared to 11.4 months in the low risk group HR (Hazard Ratio) = 1.99, 95% C.I. (Confidence Interval) 1.45–2.68; p < 0.0001). Modeling of lipids by class (sphingolipids, acylcarnitines and lysophosphatidylcholines) revealed a median OS = 5.7 months vs. 11. 9 months for the high vs. low risk group. (HR: 2.23, 95% C.I. 1.55–3.20; p < 0.0001). These results demonstrate that metabolic profiles from pre-treatment samples may be useful to stratify clinical outcomes for mNSCLC patients receiving chemotherapy. Genomic and longitudinal measurements pre- and post-treatment may yield addition information to personalize treatment decisions further.
Adenoviral Vectors Armed with PAPILLOMAVIRUs Oncogene Specific CRISPR/Cas9 Kill Human-Papillomavirus-Induced Cervical Cancer Cells
Authors: Ehrke-Schulz Eric , Heinemann Sonja , Schulte Lukas , Schiwon Maren , Ehrhardt Anja
Published: July 2020

Human papillomaviruses (HPV) cause malignant epithelial cancers including cervical carcinoma, non-melanoma skin and head and neck cancer. They drive tumor development through the expression of their oncoproteins E6 and E7. Designer nucleases were shown to be efficient to specifically destroy HPV16 and HPV18 oncogenes to induce cell cycle arrest and apoptosis. Here, we used high-capacity adenoviral vectors (HCAdVs) expressing the complete CRISPR/Cas9 machinery specific for HPV18-E6 or HPV16-E6. Cervical cancer cell lines SiHa and CaSki containing HPV16 and HeLa cells containing HPV18 genomes integrated into the cellular genome, as well as HPV-negative cancer cells were transduced with HPV-type-specific CRISPR-HCAdV. Upon adenoviral delivery, the expression of HPV-type-specific CRISPR/Cas9 resulted in decreased cell viability of HPV-positive cervical cancer cell lines, whereas HPV-negative cells were unaffected. Transduced cervical cancer cells showed increased apoptosis induction and decreased proliferation compared to untreated or HPV negative control cells. This suggests that HCAdV can serve as HPV-specific cancer gene therapeutic agents when armed with HPV-type-specific CRISPR/Cas9. Based on the versatility of the CRISPR/Cas9 system, we anticipate that our approach can contribute to personalized treatment options specific for the respective HPV type present in each individual tumor.
TP5, a Peptide Inhibitor of Aberrant and Hyperactive CDK5/p25: A Novel Therapeutic Approach against Glioblastoma
Authors: Tabouret Emeline , Wang Herui , Amin Niranjana , Jung Jinkyu , Appay Romain , Cui Jing , Song Qi , Cardone Antonio , Park Deric M. , Gilbert Mark R. , Pant Harish , Zhuang Zhengping
Published: July 2020

We examined the efficacy of selective inhibition of cyclin-dependent kinase 5 (CDK5) in glioblastoma by TP5. We analyzed its impact in vitro on CDK5 expression and activity, cell survival, apoptosis and cell cycle. DNA damage was analyzed using the expression of γH2A.X and phosphorylated ATM. Its tolerance and efficacy were assessed on in vivo xenograft mouse models. We showed that TP5 decreased the activity but not the expression of CDK5 and p35. TP5 alone impaired cell viability and colony formation of glioblastoma cell lines and induced apoptosis. TP5 increased DNA damage by inhibiting the phosphorylation of ATM, leading to G1 arrest. Whereas CDK5 activity is increased by DNA-damaging agents such as temozolomide and irradiation, TP5 was synergistic with either temozolomide or irradiation due to an accumulation of DNA damage. Concomitant use of TP5 and either temozolomide or irradiation reduced the phosphorylation of ATM, increased DNA damage, and inhibited the G2/M arrest induced by temozolomide or irradiation. TP5 alone suppressed the tumor growth of orthotopic glioblastoma mouse model. The treatment was well tolerated. Finally, alone or in association with irradiation or temozolomide, TP5 prolonged mouse survival. TP5 alone or in association with temozolomide and radiotherapy is a promising therapeutic option for glioblastoma.
Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model
Authors: Miyake Makito , Hori Shunta , Itami Yoshitaka , Oda Yuki , Owari Takuya , Fujii Tomomi , Ohnishi Sayuri , Morizawa Yosuke , Gotoh Daisuke , Nakai Yasushi , Anai Satoshi , Torimoto Kazumasa , Tanaka Nobumichi , Fujimoto Kiyohide
Published: July 2020

Chemotherapy-induced adverse effects can reduce the relative dose intensity and quality of life. In this study, we investigated the potential benefit of supplementary anamorelin and 5-aminolevulinic acid (5-ALA) as preventive interventions against a gemcitabine and cisplatin (GC) combination chemotherapy-induced adverse effects in a mouse model. Non-cancer-bearing C3H mice were randomly allocated as follows and treated for 2 weeks—(1) non-treated control, (2) oral anamorelin alone, (3) oral 5-ALA alone, (4) gemcitabine and cisplatin (GC) chemotherapy, (5) GC plus anamorelin, and (6) GC plus 5-ALA. GC chemotherapy significantly decreased body weight, food intake, skeletal muscle mass and induced severe gastric mucositis, which resulted in decreased ghrelin production and blood ghrelin level. The supplementation of oral anamorelin to GC chemotherapy successfully mitigated decrease of food intake during the treatment period and body weight loss at day 8. In addition, analysis of the resected muscles and stomach revealed that anamorelin suppressed chemotherapy-induced skeletal muscle atrophy by mediating the downregulation of forkhead box protein O-1 (FOXO1)/atrogin-1 signaling and gastric damage. Our findings suggest the preventive effect of anamorelin against GC combination chemotherapy, which was selected for patients with some types of advanced malignancies in clinical practice.
Pre-Treatment Mutational and Transcriptomic Landscape of Responding Metastatic Melanoma Patients to Anti-PD1 Immunotherapy
Authors: Amato Carol M. , Hintzsche Jennifer D. , Wells Keith , Applegate Allison , Gorden Nicholas T. , Vorwald Victoria M. , Tobin Richard P. , Nassar Kelsey , Shellman Yiqun G. , Kim Jihye , Medina Theresa M. , Rioth Matthew , Lewis Karl D. , McCarter Martin D. , Gonzalez Rene , Tan Aik-Choon , Robinson William A.
Published: July 2020

Immunotherapy, such as anti-PD1, has improved the survival of patients with metastatic melanoma. However, predicting which patients will respond to immunotherapy remains a significant knowledge gap. In this study we analyzed pre-immunotherapy treated tumors from 52 patients with metastatic melanoma and monitored their response based on RECIST 1.1 criteria. The responders group contained 21 patients that had a complete or partial response, while the 31 non-responders had stable or progressive disease. Whole exome sequencing (WES) was used to identify biomarkers of anti-PD1 response from somatic mutations between the two groups. Variants in codons G34 and G41 in NFKBIE, a negative regulator of NFkB, were found exclusively in the responders. Mutations in NKBIE-related genes were also enriched in the responder group compared to the non-responders. Patients that harbored NFKBIE-related gene mutations also had a higher mutational burden, decreased tumor volume with treatment, and increased progression-free survival. RNA sequencing on a subset of tumor samples identified that CD83 was highly expressed in our responder group. Additionally, Gene Set Enrichment Analysis showed that the TNFalpha signaling via NFkB pathway was one of the top pathways with differential expression in responders vs. non-responders. In vitro NFkB activity assays indicated that the G34E variant caused loss-of-function of NFKBIE, and resulted in activation of NFkB signaling. Flow cytometry assays indicated that G34E variant was associated with upregulation of CD83 in human melanoma cell lines. These results suggest that NFkB activation and signaling in tumor cells contributes to a favorable anti-PD1 treatment response, and clinical screening to include aberrations in NFkB-related genes should be considered.
Genetics and Opioids: Towards More Appropriate Prescription in Cancer Pain
Authors: Bugada Dario , Lorini Luca F. , Fumagalli Roberto , Allegri Massimo
Published: July 2020

Opioids are extensively used in patients with cancer pain; despite their efficacy, several patients can experience ineffective analgesia and/or side effects. Pharmacogenetics is a new approach to drug prescription based on the “personalized-medicine” concept, i.e., the ability of tailoring treatments to each individual’s genetic/genomic profile. Pharmacogenetics aims to identify specific genetic variants that influence pharmacokinetics and pharmacodynamics of drugs, better determining their effectiveness/safety profile. Opioid response is a complex scenario, but some gene variants have shown a correlation with pain sensitivity, as well as with opioid metabolism and clinical efficacy/adverse events. Although questions remain unanswered, some of these gene variants may already be used to identify specific patients’ phenotypes that are more prone to experience better clinical response (i.e., better analgesia and/or less adverse events). Once adopted, this approach to opioid prescription may improve a patient’s outcome. This review summarizes the available data on genetic variants and opioid response: we will focus on basic pharmacogenetic and its impact in the clinical scenario discussing how they may lead to more appropriate opioid prescription in cancer patients.
Dual-Agent Photodynamic Therapy with Optical Clearing Eradicates Pigmented Melanoma in Preclinical Tumor Models
Authors: Pires Layla , Demidov Valentin , Wilson Brian C. , Salvio Ana Gabriela , Moriyama Lilian , Bagnato Vanderlei S. , Vitkin I. Alex , Kurachi Cristina
Published: July 2020

Treatment using light-activated photosensitizers (photodynamic therapy, PDT) has shown limited efficacy in pigmented melanoma, mainly due to the poor penetration of light in this tissue. Here, an optical clearing agent (OCA) was applied topically to a cutaneous melanoma model in mice shortly before PDT to increase the effective treatment depth by reducing the light scattering. This was used together with cellular and vascular-PDT, or a combination of both. The effect on tumor growth was measured by longitudinal ultrasound/photoacoustic imaging in vivo and by immunohistology after sacrifice. In a separate dorsal window chamber tumor model, angiographic optical coherence tomography (OCT) generated 3D tissue microvascular images, enabling direct in vivo assessment of treatment response. The optical clearing had minimal therapeutic effect on the in control, non-pigmented cutaneous melanomas but a statistically significant effect (p < 0.05) in pigmented lesions for both single- and dual-photosensitizer treatment regimes. The latter enabled full-depth eradication of tumor tissue, demonstrated by the absence of S100 and Ki67 immunostaining. These studies are the first to demonstrate complete melanoma response to PDT in an immunocompromised model in vivo, with quantitative assessment of tumor volume and thickness, confirmed by (immuno) histological analyses, and with non-pigmented melanomas used as controls to clarify the critical role of melanin in the PDT response. The results indicate the potential of OCA-enhanced PDT for the treatment of pigmented lesions, including melanoma.
Accurate In-Vivo Quantification of CD19 CAR-T Cells after Treatment with Axicabtagene Ciloleucel (Axi-Cel) and Tisagenlecleucel (Tisa-Cel) Using Digital PCR
Authors: Badbaran Anita , Berger Carolina , Riecken Kristoffer , Kruchen Anne , Geffken Maria , Müller Ingo , Kröger Nicolaus , Ayuk Francis A. , Fehse Boris
Published: July 2020

Immunotherapy with CD19-specific chimeric antigen receptor (CAR-) T cells has shown excellent efficacy in relapsed/refractory B-cell cancers. The in vivo expansion and persistence of CAR-T cells after infusion are important response- and toxicity-determining variables, but diagnostic tools are largely missing. We showed previously for axi-cel that digital PCR (dPCR) is excellently suited to monitoring CAR-T cells in vivo. Here, we aimed to develop an analogous dPCR assay for tisa-cel. To do so, we cloned and sequenced the CAR construct from the lentiviral tisa-cel vector and designed primers and Black hole quencher (BHQ) probes complimentary to sequences present in the FMC63 scFv part of axi-cel (assay A), tisa-cel (T), and both constructs (U = “universal”). In conjunction with excellent specificity, all assays have a detection limit of one single CAR copy, corresponding to a sensitivity of approximately 1 in 5000 cells (0.02%) for 100 ng genomic DNA (for one vector copy per transduced cell). The new universal assay was first validated using patient samples previously quantified with the axi-cel-specific dPCR and thereafter applied to quantify and monitor adoptively transferred axi-cel and tisa-cel T cells in post-infusion samples (peripheral blood, bone marrow, liquor, and ascites). Actual CAR-T counts per µl were calculated, taking into account vector copy and peripheral blood mononuclear cell (PBMC) numbers, and showed very good correlation with flow cytometry results. We conclude that our novel dPCR assay is optimally suited to monitoring tisa-cel and axi-cel CAR-T cells in real-time in various body fluids.
Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma Identifies RAS and PIK3CA Mutations as Negative Survival Predictors
Authors: Lai Wei-An , Liu Chih-Yi , Lin Shih-Yao , Chen Chien-Chin , Hang Jen-Fan
Published: July 2020

Anaplastic thyroid carcinoma (ATC) is rare but highly aggressive. We investigated the association of selected driver mutations, including BRAF, RAS, PIK3CA, TERT promoter, TP53, POLE, and mismatch repair deficiency (MMR-D) with the clinicopathological features of ATC to identify prognostic and predictive biomarkers. Thirty-nine retrospective cases from pathology archives were enrolled for clinicopathology analysis and immunohistochemistry, and 27 cases had sufficient specimens for further molecular testing using targeted next-generation sequencing and mass spectrometry. BRAFV600E and RAS mutations were identified in 25.9% and 40.7% of ATC, respectively. BRAFV600E mutation was significantly associated with coexisting papillary thyroid carcinoma (p = 0.009) and RAS mutations with female gender (p = 0.012). In univariant analysis, the non-BRAF/RAS tumors were significantly associated with the presence of a sarcomatoid pattern (p = 0.045). PIK3CA, TERT promoter, and TP53 mutations were identified in 14.8%, 81.5%, and 70.4% of cases, respectively. No MMR-D or POLE mutations were detected. In survival analyses, RAS and PIK3CA mutations were significantly associated with inferior outcomes (p = 0.03 and p = 0.006, respectively). In conclusion, driver mutations in ATC are associated with distinct clinicopathological features. RAS and PIK3CA mutations were negative predictors for patient survival. Emerging therapeutic agents targeting BRAF, RAS, and PI3 kinase may benefit a substantial proportion of ATC patients.
Glucose Loading Enhances the Value of 18F-FDG PET/CT for the Characterization and Delineation of Cerebral Gliomas
Authors: Kim Dongwoo , Ko Hae Young , Lee Sangwon , Lee Yong-ho , Ryu Sujin , Kim Seon Yoo , Chung Jee-in , Lee Misu , Moon Ju Hyung , Chang Jong Hee , Yun Mijin
Published: July 2020

This study aimed to assess how to enhance the value of 18F-Fluorodeoxyglucose (FDG) PET/CTs for glioma grading and better delineation of the tumor boundary by glucose loading. In mouse models of brain tumor using U87MG cells, 18F-FDG-PET images were obtained after fasting and after glucose loading. There was a significant difference in the tumor-to-normal cortex-uptake ratio (TNR) between the fasting and glucose-loading scans. 14C-2-Deoxy-D-glucose (14C-DG) uptake was measured in vitro using U87MG, U373MG and primary neurons cultured with different concentrations of glucose. The tumor-to-neuron ratio of 14C-DG uptake increased with up to 10 mM of glucose. Finally, 10 low-grade and 17 high-grade glioma patients underwent fasting and glucose loading 18F-FDG PET/CT and the TNR was compared between scans. The effect of glucose loading was significant in high-grade but not in low-grade gliomas. The receiver operating characteristic curve analyses with a cut-off TNR of 0.81 showed a higher area under the curve after glucose loading than fasting for differentiating low-grade versus high-grade gliomas. In addition, the glucose loading PET/CT was more useful than the fasting PET/CT for the discrimination of oligodendrogliomas from IDH-wildtype glioblastomas. Glucose loading resulted in a greater reduction in 18F-FDG uptake in the normal cortex than in tumors, which increases the usefulness of 18F-FDG PET/CT for grading.
DCE-MRI of Tumor Hypoxia and Hypoxia-Associated Aggressiveness
Authors: Gaustad Jon-Vidar , Hauge Anette , Wegner Catherine S. , Simonsen Trude G. , Lund Kjersti V. , Hansem Lise Mari K. , Rofstad Einar K.
Published: July 2020

Tumor hypoxia is associated with resistance to treatment, aggressive growth, metastatic dissemination, and poor clinical outcome in many cancer types. The potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess the extent of hypoxia in tumors has been investigated in several studies in our laboratory. Cervical carcinoma, melanoma, and pancreatic ductal adenocarcinoma (PDAC) xenografts have been used as models of human cancer, and the transfer rate constant (Ktrans) and the extravascular extracellular volume fraction (ve) have been derived from DCE-MRI data by using Tofts standard pharmacokinetic model and a population-based arterial input function. Ktrans was found to reflect naturally occurring and treatment-induced hypoxia when hypoxia was caused by low blood perfusion, radiation responsiveness when radiation resistance was due to hypoxia, and metastatic potential when metastasis was hypoxia-induced. Ktrans was also associated with outcome for patients with locally-advanced cervical carcinoma treated with cisplatin-based chemoradiotherapy. Together, the studies imply that DCE-MRI can provide valuable information on the hypoxic status of cervical carcinoma, melanoma, and PDAC. In this communication, we review and discuss the studies and provide some recommendations as to how DCE-MRI data can be analyzed and interpreted to assess tumor hypoxia.
Generation Z: Fitting Project Management Soft Skills Competencies—A Mixed-Method Approach
Authors: Magano José , Silva Cláudia , Figueiredo Cláudia , Vitória Andreia , Nogueira Teresa , Pimenta Dinis Maria Alzira
Published: July 2020

Generation Z is arriving in the workforce. Do these youngsters have the skills and traits to fit project teams? This study reviews the literature concerning project management competencies and the traits that are associated with Generation Z. To deepen the understanding of its members (Gen Zers) traits, we explore the self-awareness of their profile, strengths and weaknesses with an empirical study. We used a mixed-method approach, implementing a survey on a sample of 211 college students about to enter the labor market. Comparing our survey results with the literature, we identified differences that reveal some of the lack of awareness of Gen Zers about their traits. Further analysis also revealed a significant correlation between the most highlighted Generation Z traits and essential project management soft skills, pointing to Generation Z as a promissory asset in the project management field. However, other essential project management (PM) soft skills were not grounded in personality traits. Our findings, namely the lack of awareness and association results, suggest the need for further research on educational approaches and re-thinking and targeting education and training policies that could strengthen Generation Z soft skills. Our results also suggest reflections about whether the Gen Zers traits fit the PM competencies sought by organizations.
Effects of Farm Management Practices and Transport Time on Post-Mortem Changes of Longissimus lumborum Muscle Proteins in Suckling Goat Kids
Authors: Martínez Tomás Francisco , Alcalde María Jesús , Sáez María Isabel , Suárez María Dolores
Published: July 2020

The combined effect of farm management practices, transport time, and ageing time on the electrophoretic changes of sarcoplasmic (SPP) and myofibrillar (MFP) protein fractions of goat kids was studied. A total of 64 suckling goat kids were withdrawn from two farms with “high” (GW) and “low” (DW) welfare-friendly management practices, and they were transported for 2 or 6 h immediately before slaughtering. Longissimus lumborum samples were obtained at 3, 8, and 21 days post-mortem, and muscle proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis SDS-PAGE. Both protein extracts displayed significant changes attributable to meat maturation. Managing conditions of kids in DW farms increased the post-mortem susceptibility of muscle proteins. Some MFP of Longissimus lumborum muscle, such as troponin T, as well as 26–30 and 35–37 kDa fractions were influenced significantly by deficient on-farm management, and therefore, these protein fragments might be considered as indicators of low-welfare on-farm management in goat kids.
A Systematic Review of Risk Assessment Associated with Jellyfish Consumption as a Potential Novel Food
Authors: Bonaccorsi Guglielmo , Garamella Giuseppe , Cavallo Giuseppe , Lorini Chiara
Published: July 2020

FAO (Food and Agriculture Organization of the United Nations) predicted that the world’s population will reach over 9 billion in 2050. This condition will require an increase of the global food production by 60%. Technology and scientific research in the near future will soon be oriented towards optimizing the limited existing resources, reducing waste, and improving the consumption of sustainable new foods. Jellyfish could be a valid alternative among novel food. The purpose of this systematic review was to assess microbiological, chemical, physical, and allergenic risks associated with jellyfish consumption. Four research strings have been used to assess evidences about these risks. PRISMA (Preferred Reporting Item for Systematic Reviews and Meta-analysis) guidelines were applied. Finally, 14 articles were found. Results showed a good level of health safety for jellyfish consumption in terms of its allergenic and microbiological risks. No evidence was found about physical risks. As regards chemical safety, it should be fundamental to carry out a constant monitoring of the water where jellyfish are captured or bred. Periodic checks will be necessary on the finished product, such as the analysis of the aluminum content commonly used during the manufacturing process. The number of publications found was rather small, and further investigation will be necessary to enforce the knowledge on jellyfish consumption by humans.
Meat Composition, Fatty Acid Profile and Sensory Attributes of Meat from Goats Fed Diet Supplemented with Fermented Saccharina japonica and Dendropanax morbifera
Authors: Saturno Jamila Fatima L. , Dilawar Muhammad Ammar , Mun Hong-Seok , Kim Dae Hun , Rathnayake Dhanushka , Yang Chul-Ju
Published: July 2020

A 90-day feeding trial was conducted to evaluate the effects of diets supplemented with three concentrations (control or 0%, 0.5% and 1.0%) of fermented Saccharina japonica and Dendropanax morbifera (FSJ-DM) on the meat composition, growth performance, oxidative stability and fatty acid profile of Korean native black goat (KNBG) meat. The feed conversion ratio and body weight gain (1st to 2nd month) were improved significantly (p < 0.05) in response to feed supplemented with 1.0% FSJ-DM. Moisture content was increased, whereas ether extract and cholesterol contents were decreased in meat obtained from goats supplemented with 1.0% FSJ-DM dietary feeds (p < 0.05). In the same diet group, the total saturated fatty acids (ΣSFA) were lower, whereas the sum of polyunsaturated fatty acids (ΣPUFA) was higher, along with higher PUFA/SFA ratio and lower n-6/n-3 ratio (p < 0.05). On an average, the dietary supplementation of 1.0% FSJ-DM reduced the thiobarbituric acid reactive substance (TBARS) and pH values of goat meat. Overall, the results of this study suggest that diet supplemented with 1.0% FSJ-DM improves the meat composition, growth performance and fatty acid profile and reduces lipid oxidation of goat meat.
Use of Air-Protected Headspace to Prevent Yeast Film Formation on the Brine of Leccino and Taggiasca Black Table Olives Processed in Industrial-Scale Plastic Barrels
Authors: Ciafardini Gino , Zullo Biagi Angelo
Published: July 2020

The formation of yeast film on the brine of black table olives during fermentation in plastic barrels on an industrial-scale could be critical for the quality of the product. In order to prevent the formation of yeast film on the brine surface, a structural modified industrial barrel, which excludes oxygen from the headspace, was tested. Tests carried out during two years indicated that the yeast film contamination reached the maximum values at eight months of fermentation, equal to 19% and 24% respectively, for the Taggiasca and Leccino olives, processed in unmodified industrial plastic barrels. No yeast films formed on brines from the same varieties of olives processed in the modified plastic barrels. The brines of both varieties of olives processed in the industrial barrels displayed three dominant yeast species, while five species were detected in the brines from the modified barrels. Wickerhamomyces anomalus and Pichia manshurica were the main producers of yeast films. However, P. manshurica unlike the other yeasts, has shown also a biotype unable to produce films on the brine of the olives. The brines of Leccino and Taggiasca processed in the modified barrels, compared to the control, showed a higher titratable acidity and a higher concentration of CO2 useful to prevent the yeast film formation.
The Bioactive Potential of Functional Products and Bioavailability of Phenolic Compounds
Authors: Dabulici Cristina Monica , Sârbu Ionela , Vamanu Emanuel
Published: July 2020

The expression of bioactivity depends on the assimilation of different classes of natural substances (e.g., phenolic compounds) in vivo. Six functional extracts (Aspalathus linearis, leaves; Paullinia cupana, seeds; Aristotelia chilensis, berries; Ilex paraguariensis, leaves; Syzygium aromaticum, cloves, and wild berries) were analyzed in vitro and in vivo as an alternative to alleviating pathologies associated with oxidative stress (proliferation of cancer cells). The purpose of this research was to evaluate the in vitro and in vivo antioxidant and cytotoxic potential of hydroalcoholic solutions, in addition to the assimilation capacity of bioactive components in Saccharomyces boulardii cells. In vivo antioxidant capacity (critical point value) was correlated with the assimilation ratio of functional compounds. The results of in vitro antioxidant activities were correlated with the presence of quercetin (4.67 ± 0.27 mg/100 mL) and chlorogenic acid (14.38 ± 0.29 mg/100 mL) in I. paraguariensis. Bioassimilation of the main nutraceutical components depended on the individual sample. Phenolic acid levels revealed the poor assimilation of the main components, which could be associated with cell viability to oxidative stress.
Chemical Characterization and Volatile Profile of Trebbiano di Lugana Wine: A Case Study
Authors: Fracassetti Daniela , Camoni Davide , Montresor Lodovico , Bodon Rebecca , Limbo Sara
Published: July 2020

In this study, the volatile profile of Trebbiano di Lugana wine was determined and its chemical composition was considered to understand its potential longevity. Seven wine samples produced in different years (2005–2017) were collected by the same winery and analyzed up to 13 years after bottling. Color, total and polymeric phenols, glutathione, free volatiles and sensory characteristics were assessed. The color turned from yellow to an increased brownish hue as the aging time increased; nonetheless, it was stable up to five years from the production. Thirty-six aroma compounds were detected including higher alcohols, esters, and norisoprenoids (β-damascenone and β-oxo-ionone). While higher alcohols did not show a dependence on the different years of production, a decrease of esters was found over aging with the exception of wine produced in 2009, the latter showing higher levels of glutathione that could limit esters’ hydrolysis. The perception of floral and fruity notes was dependent on the storage time with little differences up to five years after bottling. Trebbiano di Lugana wine could be suitable for aging and this aptitude might be further improved also through the proper choice of closure and packaging systems to encourage logistic and marketing strategies.
Target-Genes Reveal Species and Genotypic Specificity of Anthocyanin Pigmentation in Citrus and Related Genera
Authors: Catalano Chiara , Ciacciulli Angelo , Salonia Fabrizio , Russo Maria Patrizia , Caruso Paola , Caruso Marco , Russo Giuseppe , Distefano Gaetano , Licciardello Concetta
Published: July 2020

Background: Anthocyanin pigmentation characterizes a number of tissues of Citrus and its relatives. The gain and loss of pigmentation is intriguing and is inherited variously among species. Methods: Citrus germplasm was used to investigate the anthocyanin pigmentation of tissues never before considered, including stamen, style and stigma, and of young leaves, petals, rind and flesh of 28 genotypes belonging to 14 species. Citrus genotypes encompassed citron, lemon, sweet orange, lime, and Citrus relatives included Microcitrus, Murraya, and Severinia. A relative qRT-PCR analysis was carried out on the structural and regulatory genes: phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3′-hydroxylase (F3H), dihydroflavonol 4-reductase (DFR), anthocyanidin synthase (ANS), uridine diphosphate glucose flavonoid glucosyl-transferase (UFGT), glutathione S-transferase (GST), Ruby and Noemi. Image analysis and a genomic approach were employed to evaluate how the red pigmentation is inherited among tissues and species. Results: Pigmentation of young leaves and petals is specific to citron and its hybrids. Ruby controls the pigmentation of petals, but not of leaves. The red color of the rind and flesh is a trait that particularly characterizes a diversity of sweet oranges, citron hybrids and Citrus relatives. Color expression depends on external factors and also on developmental stage. The coloration of stamen and style is citron-specific, while a red stigma is exclusive to Moro orange and its hybrids. Conclusion: It is hypothesized that there is a relationship among Citrus species and genes controlling anthocyanin pigmentation.
Epigenetics as an Evolutionary Tool for Centromere Flexibility
Authors: Leo Laura , Marchetti Marcella , Giunta Simona , Fanti Laura
Published: July 2020

Centromeres are the complex structures responsible for the proper segregation of chromosomes during cell division. Structural or functional alterations of the centromere cause aneuploidies and other chromosomal aberrations that can induce cell death with consequences on health and survival of the organism as a whole. Because of their essential function in the cell, centromeres have evolved high flexibility and mechanisms of tolerance to preserve their function following stress, whether it is originating from within or outside the cell. Here, we review the main epigenetic mechanisms of centromeres’ adaptability to preserve their functional stability, with particular reference to neocentromeres and holocentromeres. The centromere position can shift in response to altered chromosome structures, but how and why neocentromeres appear in a given chromosome region are still open questions. Models of neocentromere formation developed during the last few years will be hereby discussed. Moreover, we will discuss the evolutionary significance of diffuse centromeres (holocentromeres) in organisms such as nematodes. Despite the differences in DNA sequences, protein composition and centromere size, all of these diverse centromere structures promote efficient chromosome segregation, balancing genome stability and adaptability, and ensuring faithful genome inheritance at each cellular generation.
SOMmelier—Intuitive Visualization of the Topology of Grapevine Genome Landscapes Using Artificial Neural Networks
Authors: Nikoghosyan Maria , Schmidt Maria , Margaryan Kristina , Loeffler-Wirth Henry , Arakelyan Arsen , Binder Hans
Published: July 2020

Background: Whole-genome studies of vine cultivars have brought novel knowledge about the diversity, geographical relatedness, historical origin and dissemination, phenotype associations and genetic markers. Method: We applied SOM (self-organizing maps) portrayal, a neural network-based machine learning method, to re-analyze the genome-wide Single Nucleotide Polymorphism (SNP) data of nearly eight hundred grapevine cultivars. The method generates genome-specific data landscapes. Their topology reflects the geographical distribution of cultivars, indicates paths of cultivar dissemination in history and genome-phenotype associations about grape utilization. Results: The landscape of vine genomes resembles the geographic map of the Mediterranean world, reflecting two major dissemination paths from South Caucasus along a northern route via Balkan towards Western Europe and along a southern route via Palestine and Maghreb towards Iberian Peninsula. The Mediterranean and Black Sea, as well as the Pyrenees, constitute barriers for genetic exchange. On the coarsest level of stratification, cultivars divide into three major groups: Western Europe and Italian grapes, Iberian grapes and vine cultivars from Near East and Maghreb regions. Genetic landmarks were associated with agronomic traits, referring to their utilization as table and wine grapes. Pseudotime analysis describes the dissemination of grapevines in an East to West direction in different waves of cultivation. Conclusion: In analogy to the tasks of the wine waiter in gastronomy, the sommelier, our ‘SOMmelier’-approach supports understanding the diversity of grapevine genomes in the context of their geographic and historical background, using SOM portrayal. It offers an option to supplement vine cultivar passports by genome fingerprint portraits.
The Role of BMI1 in Late-Onset Sporadic Alzheimer’s Disease
Authors: Hogan Ryan , Flamier Anthony , Nardini Eleonora , Bernier Gilbert
Published: July 2020

Late-onset sporadic Alzheimer’s disease (LOAD) seems to contain a “hidden” component that cannot be explained by classical Mendelian genetics, with advanced aging being the strongest risk factor. More surprisingly, whole genome sequencing analyses of early-onset sporadic Alzheimer’s disease cohorts also revealed that most patients do not present classical disease-associated variants or mutations. In this short review, we propose that BMI1 is possibly epigenetically silenced in LOAD. Reduced BMI1 expression is unique to LOAD compared to familial early-onset AD (EOAD) and other related neurodegenerative disorders; moreover, reduced expression of this single gene is sufficient to reproduce most LOAD pathologies in cellular and animal models. We also show the apparent amyloid and Tau-independent nature of this epigenetic alteration of BMI1 expression. Lastly, examples of the mechanisms underlying epigenetic dysregulation of other LOAD-related genes are also illustrated.
Erratum: Therapeutic Atmosphere in Psychotherapy Sessions. Int. J. Environ. Res. Public Health 2020, 17, 4105
Authors: Siegel Marte L. , Gullestad Binder Eva M. , J. Dahl Hanne Sofie , Czajkowski Nikolai O. , Critchfield Kenneth L. , Høglend Per A. , Ulberg Randi
Published: July 2020

The authors wish to make the following correction to their paper [...]
Sense of Coherence, Health, Well-Being, and Work Satisfaction before and after Implementing Activity-Based Workplaces
Authors: Wijk Katarina , Bergsten Eva L. , Hallman David M.
Published: July 2020

Activity-based workplaces (ABWs) are implemented with possible implications for health, well-being, and work satisfaction in the workplace. Drawing on the theoretical framework, i.e., sense of coherence (SOC), the aim was to investigate how indicators pf SOC—meaningfulness, manageability and comprehensibility—are associated with, or function as barriers or facilitators for, health, well-being and work satisfaction during relocation to an ABW. We followed the implementation of ABWs at the Swedish Transport Administration (2018–2019). Questionnaires were administered before (n = 536), 3 months (n = 409) and 9 months (n = 373) after relocation. Focus group interviews (15) were conducted before and after. Data were analyzed using repeated measures ANOVA and content analysis. Relocation to an ABW was associated with a reduced work satisfaction (physical p < 0.001; psychosocial p < 0.001), and minor changes in health and occupational well-being during relocation (p > 0.001). The reduction in work satisfaction was smaller among employees with high meaningfulness in the relocation process (p < 0.001). All SOC indicators were positively associated with overall health, well-being and work satisfaction (p < 0.001). Interviews suggested that meaningfulness was facilitated by participation in the presented activities and that communication before relocation was crucial. The results indicate that organizations implementing ABWs should promote perceived meaningfulness in the process to mitigate possible declines in satisfaction with the physical and psychosocial work environment.
Modeling of Open Government Data for Public Sector Organizations Using the Potential Theories and Determinants—A Systematic Review
Authors: Khurshid Muhammad Mahboob , Zakaria Nor Hidayati , Rashid Ammar , Ahmad Mohammad Nazir , Arfeen Muhammad Irfanullah , Faisal Shehzad Hafiz Muhammad
Published: July 2020

Open government data (OGD) has huge potential to increase transparency, accountability, and participation while improving efficiency in operations, data-driven and evidence-based policymaking, and trust in government institutions. Despite its potential benefits, OGD has not been widely and successfully adopted in public sector organizations, particularly in developing countries. Therefore, the purpose of this study is to explore the theories/frameworks and potential determinants that influence the OGD adoption in public sector organizations. To ascertain the various determinants of OGD adoption in public sector organizations, this study involved a systematic review of already established theories and determinants addressed in the public sector open data domain. The review revealed that the TOE (technology, organization, environment) framework was dominantly employed over theories in the earlier studies to understand organizational adoption to OGD followed by institutional theory. The results, concerning potential determinants, revealed that some of the most frequently addressed determinants are an organization’s digitization/digitalization capacity, compliance pressure, financial resources, legislation, policy, regulations, organizational culture, political leadership commitment, top-management support, and data quality. The findings will enrich researchers to empirically investigate the exposed determinants and improve the understanding of decision-makers to leverage OGD adoption by taking relevant measures.
Spatially Resolved Correlation between Stiffness Increase and Actin Aggregation around Nanofibers Internalized in Living Macrophages
Authors: Zhou Guoqiao , Zhang Bokai , Wei Liyu , Zhang Han , Galluzzi Massimiliano , Li Jiangyu
Published: July 2020

Plasticity and functional diversity of macrophages play an important role in resisting pathogens invasion, tumor progression and tissue repair. At present, nanodrug formulations are becoming increasingly important to induce and control the functional diversity of macrophages. In this framework, the internalization process of nanodrugs is co-regulated by a complex interplay of biochemistry, cell physiology and cell mechanics. From a biophysical perspective, little is known about cellular mechanics’ modulation induced by the nanodrug carrier’s internalization. In this study, we used the polylactic-co-glycolic acid (PLGA)–polyethylene glycol (PEG) nanofibers as a model drug carrier, and we investigated their influence on macrophage mechanics. Interestingly, the nanofibers internalized in macrophages induced a local increase of stiffness detected by atomic force microscopy (AFM) nanomechanical investigation. Confocal laser scanning microscopy revealed a thickening of actin filaments around nanofibers during the internalization process. Following geometry and mechanical properties by AFM, indentation experiments are virtualized in a finite element model simulation. It turned out that it is necessary to include an additional actin wrapping layer around nanofiber in order to achieve similar reaction force of AFM experiments, consistent with confocal observation. The quantitative investigation of actin reconfiguration around internalized nanofibers can be exploited to develop novel strategies for drug delivery.
Enhancement of the Start-Up Time for Microliter-Scale Microbial Fuel Cells (µMFCs) via the Surface Modification of Gold Electrodes
Authors: Şen-Doğan Begüm , Okan Meltem , Afşar-Erkal Nilüfer , Özgür Ebru , Zorlu Özge , Külah Haluk
Published: July 2020

Microbial Fuel Cells (MFCs) are biological fuel cells based on the oxidation of fuels by electrogenic bacteria to generate an electric current in electrochemical cells. There are several methods that can be employed to improve their performance. In this study, the effects of gold surface modification with different thiol molecules were investigated for their implementation as anode electrodes in micro-scale MFCs (µMFCs). Several double-chamber µMFCs with 10.4 µL anode and cathode chambers were fabricated using silicon-microelectromechanical systems (MEMS) fabrication technology. µMFC systems assembled with modified gold anodes were operated under anaerobic conditions with the continuous feeding of anolyte and catholyte to compare the effect of different thiol molecules on the biofilm formation of Shewanella oneidensis MR-1. Performances were evaluated using polarization curves, Electrochemical Impedance Spectroscopy (EIS), and Scanning Electron Microcopy (SEM). The results showed that µMFCs modified with thiol self-assembled monolayers (SAMs) (cysteamine and 11-MUA) resulted in more than a 50% reduction in start-up times due to better bacterial attachment on the anode surface. Both 11-MUA and cysteamine modifications resulted in dense biofilms, as observed in SEM images. The power output was found to be similar in cysteamine-modified and bare gold µMFCs. The power and current densities obtained in this study were comparable to those reported in similar studies in the literature.
A Customized Two Photon Fluorescence Imaging Probe Based on 2D scanning MEMS Mirror Including Electrothermal Two-Level-Ladder Dual S-Shaped Actuators
Authors: Mehidine Hussein , Li Min , Lendresse Jean-Francois , Bouvet Francoise , Xie Huikai , Abi Haidar Darine
Published: July 2020

We report the design and characterization of a two-photon fluorescence imaging miniature probe. This customized two-axis scanning probe is dedicated for intraoperative two-photon fluorescence imaging endomicroscopic use and is based on a micro-electro-mechanical system (MEMS) mirror with a high reflectivity plate and two-level-ladder double S-shaped electrothermal bimorph actuators. The fully assembled probe has a total outer diameter of 4 mm including all elements. With a two-lens configuration and a small aperture MEMS mirror, this probe can generate a large optical scan angle of 24° with 4 V drive voltage and can achieve a 450 µm FOV with a 2-fps frame rate. A uniform Pixel Dwell Time and a stable scanning speed along a raster pattern were demonstrated while a 57-fs pulse duration of the excitation beam was measured at the exit of the probe head. This miniature imaging probe will be coupled to a two-photon fluorescence endomicroscope oriented towards clinical use.
Batch and Continuous Lactic Acid Fermentation Based on A Multi-Substrate Approach
Authors: Olszewska-Widdrat Agata , Alexandri Maria , López-Gómez José Pablo , Schneider Roland , Venus Joachim
Published: July 2020

The utilisation of waste materials and industrial residues became a priority within the bioeconomy concept and the production of biobased chemicals. The aim of this study was to evaluate the feasibility to continuously produce L-lactic acid from different renewable substrates, in a multi-substrate strategy mode. Based on batch experiments observations, Bacillus coagulans A534 strain was able to continuously metabolise acid whey, sugar beet molasses, sugar bread, alfalfa press green juice and tapioca starch. Additionally, reference experiments showed its behaviour in standard medium. Continuous fermentations indicated that the highest productivity was achieved when molasses was employed with a value of 10.34 g·L−1·h−1, while the lactic acid to sugar conversion yield was 0.86 g·g−1. This study demonstrated that LA can be efficiently produced in continuous mode regardless the substrate, which is a huge advantage in comparison to other platform chemicals.