bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA Recognition and Immunity—Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms
Authors: Uehata Takuya , Takeuchi Osamu
Published: July 2020

RNA acts as an immunostimulatory molecule in the innate immune system to activate nucleic acid sensors. It functions as an intermediate, conveying genetic information to control inflammatory responses. A key mechanism for RNA sensing is discriminating self from non-self nucleic acids to initiate antiviral responses reliably, including the expression of type I interferon (IFN) and IFN-stimulated genes. Another important aspect of the RNA-mediated inflammatory response is posttranscriptional regulation of gene expression, where RNA-binding proteins (RBPs) have essential roles in various RNA metabolisms, including splicing, nuclear export, modification, and translation and mRNA degradation. Recent evidence suggests that the control of mRNA stability is closely involved in signal transduction and orchestrates immune responses. In this study, we review the current understanding of how RNA is sensed by host RNA sensing machinery and discuss self/non-self-discrimination in innate immunity focusing on mammalian species. Finally, we discuss how posttranscriptional regulation by RBPs shape immune reactions.
CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway
Authors: Cheng Chih-Lun , Yang Shang-Chih , Lai Chien-Ying , Wang Cheng-Kai , Chang Ching-Fang , Lin Chun-Yu , Chen Wei-Ju , Lin Po-Yu , Wu Han-Chung , Ma Nianhan , Lu Frank Leigh , Lu Jean
Published: July 2020

Human embryonic stem cells (hESCs) have important roles in regenerative medicine, but only a few studies have investigated the cytokines secreted by hESCs. We screened and identified chemokine (C-X-C motif) ligand 14 (CXCL14), which plays crucial roles in hESC renewal. CXCL14, a C-X-C motif chemokine, is also named as breast and kidney-expressed chemokine (BRAK), B cell and monocyte-activated chemokine (BMAC), and macrophage inflammatory protein-2γ (MIP-2γ). Knockdown of CXCL14 disrupted the hESC self-renewal, changed cell cycle distribution, and further increased the expression levels of mesoderm and endoderm differentiated markers. Interestingly, we demonstrated that CXCL14 is the ligand for the insulin-like growth factor 1 receptor (IGF-1R), and it can activate IGF-1R signal transduction to support hESC renewal. Currently published literature indicates that all receptors in the CXCL family are G protein-coupled receptors (GPCRs). This report is the first to demonstrate that a CXCL protein can bind to and activate a receptor tyrosine kinase (RTK), and also the first to show that IGF-1R has another ligand in addition to IGFs. These findings broaden our understanding of stem cell biology and signal transduction.
Head and Neck Cancer Stem Cell-Enriched Spheroid Model for Anticancer Compound Screening
Authors: Goričan Larisa , Gole Boris , Potočnik Uroš
Published: July 2020

Cancer stem cells (CSCs), a rare cell population in tumors, are resistant to conventional chemotherapy and thus responsible for tumor recurrence. To screen for active compounds targeting CSCs, a good CSC-enriched model compatible with high-throughput screening (HTS) is needed. Here, we describe a new head and neck cancer stem cell-enriched spheroid model (SCESM) suitable for HTS analyses of anti-CSC compounds. We used FaDu cells, round-bottom ultra-low adherent (ULA) microplates, and stem medium. The formed spheroids displayed increased expression of all stem markers tested (qRT-PCR and protein analysis) in comparison to the FaDu cells grown in a standard adherent culture or in a well-known HTS-compatible multi-cellular tumor spheroid model (MCTS). Consistent with increased stemness of the cells in the spheroid, confocal microscopy detected fast proliferating cells only at the outer rim of the SCESM spheroids, with poorly/non-proliferating cells deeper in. To confirm the sensitivity of our model, we used ATRA treatment, which strongly reduced the expression of selected stem markers. Altogether, we developed a CSC-enriched spheroid model with a simple protocol, a microplate format compatible with multimodal detection systems, and a high detection signal, making it suitable for anti-CSC compounds’ HTS.
Peroxisome Proliferator-Activated Receptors and Caloric Restriction—Common Pathways Affecting Metabolism, Health, and Longevity
Authors: Duszka Kalina , Gregor András , Guillou Hervé , König Jürgen , Wahli Walter
Published: July 2020

Caloric restriction (CR) is a traditional but scientifically verified approach to promoting health and increasing lifespan. CR exerts its effects through multiple molecular pathways that trigger major metabolic adaptations. It influences key nutrient and energy-sensing pathways including mammalian target of rapamycin, Sirtuin 1, AMP-activated protein kinase, and insulin signaling, ultimately resulting in reductions in basic metabolic rate, inflammation, and oxidative stress, as well as increased autophagy and mitochondrial efficiency. CR shares multiple overlapping pathways with peroxisome proliferator-activated receptors (PPARs), particularly in energy metabolism and inflammation. Consequently, several lines of evidence suggest that PPARs might be indispensable for beneficial outcomes related to CR. In this review, we present the available evidence for the interconnection between CR and PPARs, highlighting their shared pathways and analyzing their interaction. We also discuss the possible contributions of PPARs to the effects of CR on whole organism outcomes.
Evaluation of Fat Accumulation and Adipokine Production during the Long-Term Adipogenic Differentiation of Porcine Intramuscular Preadipocytes and Study of the Influence of Immunobiotics
Authors: Tada Asuka , Kober AKM Humayun , Islam Md. Aminul , Igata Manami , Takagi Michihiro , Suzuki Masahiko , Aso Hisashi , Ikeda-Ohtsubo Wakako , Yoda Kazutoyo , Miyazawa Kenji , He Fang , Takahashi Hideki , Villena Julio , Kitazawa Haruki
Published: July 2020

The degree of fat accumulation and adipokine production are two major indicators of obesity that are correlated with increased adipose tissue mass and chronic inflammatory responses. Adipocytes have been considered effector cells for the inflammatory responses due to their capacity to express Toll-like receptors (TLRs). In this study, we evaluated the degree of fat accumulation and adipokine production in porcine intramuscular preadipocyte (PIP) cells maintained for in vitro differentiation over a long period without or with stimulation of either TNF-α or TLR2-, TLR3-, or TLR4-ligands. The cytosolic fat accumulation was measured by liquid chromatography and the expression of adipokines (CCL2, IL-6, IL-8 and IL-10) were quantified by RT-qPCR and ELISA at several time points (0 to 20 days) of PIP cells differentiation. Long-term adipogenic differentiation (LTAD) induced a progressive fat accumulation in the adipocytes over time. Activation of TLR3 and TLR4 resulted in an increased rate of fat accumulation into the adipocytes over the LTAD. The production of CCL2, IL-8 and IL-6 were significantly increased in unstimulated adipocytes during the LTAD, while IL-10 expression remained stable over the studied period. An increasing trend of adiponectin and leptin production was also observed during the LTAD. On the other hand, the stimulation of adipocytes with TLRs agonists or TNF-α resulted in an increasing trend of CCL2, IL-6 and IL-8 production while IL-10 remained stable in all four treatments during the LTAD. We also examined the influences of several immunoregulatory probiotic strains (immunobiotics) on the modulation of the fat accumulation and adipokine production using supernatants of immunobiotic-treated intestinal immune cells and the LTAD of PIP cells. Immunobiotics have shown a strain-specific ability to modulate the fat accumulation and adipokine production, and differentiation of adipocytes. Here, we expanded the utility and potential application of our in vitro PIP cells model by evaluating an LTAD period (20 days) in order to elucidate further insights of chronic inflammatory pathobiology of adipocytes associated with obesity as well as to explore the prospects of immunomodulatory intervention for obesity such as immunobiotics.
The Distribution of Circulating Tumor Cells Is Different in Metastatic Lobular Compared to Ductal Carcinoma of the Breast—Long-Term Prognostic Significance
Authors: Narbe Ulrik , Bendahl Pär-Ola , Aaltonen Kristina , Fernö Mårten , Forsare Carina , Jørgensen Charlotte Levin Tykjær , Larsson Anna-Maria , Rydén Lisa
Published: July 2020

Background: Invasive lobular carcinoma (ILC) has distinguishing features when compared to invasive ductal carcinoma of no special type (NST). In this study, we explored the distributional and prognostic characteristics of circulating tumor cells (CTCs) in metastatic ILC and NST. Materials and methods: Patients were included in an observational trial (ClinicalTrials.gov NCT01322893) with ILC (n = 28) and NST (n = 111). CTC count (number/7.5 mL blood) was evaluated with serial sampling (CellSearch). The primary endpoint was progression-free survival (PFS). Results: The CTC counts were higher in ILC (median 70) than in NST cases (median 2) at baseline (p < 0.001). The evidence for ≥5 CTCs as a prognostic factor for PFS in ILC was weak, but stronger with higher cut-offs (CTC ≥ 20: hazard ratio (HR) 3.0, p = 0.01) (CTC ≥ 80: HR 3.6, p = 0.004). In NST, however, the prognostic effect of CTCs ≥5 was strong. Decline in CTC count from baseline to three months was associated with improved prognosis in ILC and NST. Conclusions: The number of CTCs is higher in ILC than in NST, implying that a higher CTC cut-off could be considered for ILC when applying the CellSearch technique.
Engineering CD4+ T Cells to Enhance Cancer Immunity
Authors: Sillito Francesca , Holler Angelika , Stauss Hans J.
Published: July 2020

This review presents key advances in combining T cell receptor (TCR) gene transfer to redirect T-cell specificity with gene engineering in order to enhance cancer-protective immune function. We discuss how emerging insights might be applied to CD4+ T cells. Although much attention has been paid to the role of CD8+ cytotoxic T cells in tumour protection, we provide convincing evidence that CD4+ helper T cells play a critical role in cancer immune responses in animal models and also in patients. We demonstrate that genetic engineering technologies provide exciting opportunities to extend the specificity range of CD4+ T cells from MHC class-II-presented epitopes to include peptides presented by MHC class I molecules. Functional enhancement of tumour immunity can improve the sensitivity of T cells to cancer antigens, promote survival in a hostile tumour microenvironment, boost cancer-protective effector mechanisms and enable the formation of T-cell memory. Engineered cancer-specific CD4+ T cells may contribute to protective immunity by a direct pathway involving cancer cell killing, and by an indirect pathway that boosts the function, persistence and memory formation of CD8+ T cells.
Characteristics of Extracellular Vesicles Released by the Pathogenic Yeast-Like Fungi Candida glabrata, Candida parapsilosis and Candida tropicalis
Authors: Karkowska-Kuleta Justyna , Kulig Kamila , Karnas Elzbieta , Zuba-Surma Ewa , Woznicka Olga , Pyza Elzbieta , Kuleta Patryk , Osyczka Artur , Rapala-Kozik Maria , Kozik Andrzej
Published: July 2020

Candida spp. yeast-like fungi are opportunistic pathogens in humans and have been recently found to release extracellular vesicles (EVs) that are involved in many vital biological processes in fungal cells. These include communication between microorganisms and host–pathogen interactions during infection. The production of EVs and their content have been significantly characterized in the most common candidal species Candida albicans, including the identification of numerous virulence factors and cytoplasmic proteins in the EV cargo. We have here conducted the isolation and proteomic characterization of EVs produced by the clinically important non-albicans Candida species C. glabrata, C. tropicalis and C. parapsilosis. With the use of ultracentrifugation of the cell-free culture supernatant, the candidal EVs were collected and found to be a heterogeneous population of particles for each species with sizes ranging from 60–280 nm. The proteinaceous contents of these vesicles were analyzed using LC-MS/MS, with particular attention paid to surface-expressed proteins that would come into immediate and direct contact with host cells. We thereby identified 42 extracellular and surface-connected proteins from C. glabrata, 33 from C. parapsilosis, and 34 from C. tropicalis, including membrane-associated transporters, glycoproteins and enzymes involved in the organization of the fungal cell wall, as well as several cytoplasmic proteins, including alcohol dehydrogenase, enolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and pyruvate kinase, for which the vesicular transport is a possible mechanism underlying their non-classical secretion.
High-Dimensional Single-Cell Quantitative Profiling of Skeletal Muscle Cell Population Dynamics during Regeneration
Authors: Petrilli Lucia Lisa , Spada Filomena , Palma Alessandro , Reggio Alessio , Rosina Marco , Gargioli Cesare , Castagnoli Luisa , Fuoco Claudia , Cesareni Gianni
Published: July 2020

The interstitial space surrounding the skeletal muscle fibers is populated by a variety of mononuclear cell types. Upon acute or chronic insult, these cell populations become activated and initiate finely-orchestrated crosstalk that promotes myofiber repair and regeneration. Mass cytometry is a powerful and highly multiplexed technique for profiling single-cells. Herein, it was used to dissect the dynamics of cell populations in the skeletal muscle in physiological and pathological conditions. Here, we characterized an antibody panel that could be used to identify most of the cell populations in the muscle interstitial space. By exploiting the mass cytometry resolution, we provided a comprehensive picture of the dynamics of the major cell populations that sensed and responded to acute damage in wild type mice and in a mouse model of Duchenne muscular dystrophy. In addition, we revealed the intrinsic heterogeneity of many of these cell populations.
Modulation of Determinant Factors to Improve Therapeutic Combinations with Immune Checkpoint Inhibitors
Authors: Dosset Magalie , Joseph Elodie Lauret-Marie , Rivera Vargas Thaiz , Apetoh Lionel
Published: July 2020

Immune checkpoint inhibitors (ICPi) have shown their superiority over conventional therapies to treat some cancers. ICPi are effective against immunogenic tumors. However, patients with tumors poorly infiltrated with immune cells do not respond to ICPi. Combining ICPi with other anticancer therapies such as chemotherapy, radiation, or vaccines, which can stimulate the immune system and recruit antitumor T cells into the tumor bed, may be a relevant strategy to increase the proportion of responding patients. Such an approach still raises the following questions: What are the immunological features modulated by immunogenic therapies that can be critical to ensure not only immediate but also long-lasting tumor protection? How must the combined treatments be administered to the patients to harness their full potential while limiting adverse immunological events? Here, we address these points by reviewing how immunogenic anticancer therapies can provide novel therapeutic opportunities upon combination with ICPi. We discuss their ability to create a permissive tumor microenvironment through the generation of inflamed tumors and stimulation of memory T cells such as resident (TRM) and stem-cell like (TSCM) cells. We eventually underscore the importance of sequence, dose, and duration of the combined anticancer therapies to design optimal and successful cancer immunotherapy strategies.
Ebola Virus Nucleocapsid-Like Structures Utilize Arp2/3 Signaling for Intracellular Long-Distance Transport
Authors: Grikscheit Katharina , Dolnik Olga , Takamatsu Yuki , Pereira Ana Raquel , Becker Stephan
Published: July 2020

The intracellular transport of nucleocapsids of the highly pathogenic Marburg, as well as Ebola virus (MARV, EBOV), represents a critical step during the viral life cycle. Intriguingly, a population of these nucleocapsids is distributed over long distances in a directed and polar fashion. Recently, it has been demonstrated that the intracellular transport of filoviral nucleocapsids depends on actin polymerization. While it was shown that EBOV requires Arp2/3-dependent actin dynamics, the details of how the virus exploits host actin signaling during intracellular transport are largely unknown. Here, we apply a minimalistic transfection system to follow the nucleocapsid-like structures (NCLS) in living cells, which can be used to robustly quantify NCLS transport in live cell imaging experiments. Furthermore, in cells co-expressing LifeAct, a marker for actin dynamics, NCLS transport is accompanied by pulsative actin tails appearing on the rear end of NCLS. These actin tails can also be preserved in fixed cells, and can be visualized via high resolution imaging using STORM in transfected, as well as EBOV infected, cells. The application of inhibitory drugs and siRNA depletion against actin regulators indicated that EBOV NCLS utilize the canonical Arp2/3-Wave1-Rac1 pathway for long-distance transport in cells. These findings highlight the relevance of the regulation of actin polymerization during directed EBOV nucleocapsid transport in human cells.
TRPV4 Inhibition and CRISPR-Cas9 Knockout Reduce Inflammation Induced by Hyperphysiological Stretching in Human Annulus Fibrosus Cells
Authors: Cambria Elena , Arlt Matthias J. E. , Wandel Sandra , Krupkova Olga , Hitzl Wolfgang , Passini Fabian S. , Hausmann Oliver N. , Snedeker Jess G. , Ferguson Stephen J. , Wuertz-Kozak Karin
Published: July 2020

Mechanical loading and inflammation interact to cause degenerative disc disease and low back pain (LBP). However, the underlying mechanosensing and mechanotransductive pathways are poorly understood. This results in untargeted pharmacological treatments that do not take the mechanical aspect of LBP into account. We investigated the role of the mechanosensitive ion channel TRPV4 in stretch-induced inflammation in human annulus fibrosus (AF) cells. The cells were cyclically stretched to 20% hyperphysiological strain. TRPV4 was either inhibited with the selective TRPV4 antagonist GSK2193874 or knocked out (KO) via CRISPR-Cas9 gene editing. The gene expression, inflammatory mediator release and MAPK pathway activation were analyzed. Hyperphysiological cyclic stretching significantly increased the IL6, IL8, and COX2 mRNA, PGE2 release, and activated p38 MAPK. The TRPV4 pharmacological inhibition significantly attenuated these effects. TRPV4 KO further prevented the stretch-induced upregulation of IL8 mRNA and reduced IL6 and IL8 release, thus supporting the inhibition data. We provide novel evidence that TRPV4 transduces hyperphysiological mechanical signals into inflammatory responses in human AF cells, possibly via p38. Additionally, we show for the first time the successful gene editing of human AF cells via CRISPR-Cas9. The pharmacological inhibition or CRISPR-based targeting of TRPV4 may constitute a potential therapeutic strategy to tackle discogenic LBP in patients with AF injury.
Comment on “Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity”
Authors: Bevelacqua Joseph J. , Welsh James , Mortazavi S.M.J.
Published: July 2020

This letter addresses our concerns about a paper by Melnik et al [...]
Impact of Chromosome 9 Numerical Imbalances in Oral Squamous Cell Carcinoma: A Pilot Grid-Based Centromere Analysis
Authors: Kyrodimos Efthymios , Chrysovergis Aristeidis , Mastronikolis Nicholas , Tsiambas Evangelos , Riziotis Christos , Roukas Dimitrios , Fotiades Panagiotis , Stavraka Chara , Ragos Vasileios , Paschopoulos Minas , Papanikolaou Vasileios
Published: July 2020

Oral squamous cell carcinoma (OSCC) is considered an aggressive malignancy, mainly due to its increased propensity to provide local and distant lymph node metastases. Gross chromosome instability (CI; polysomy/aneuploidy/monosomy), combined or not with specific gene alterations, is implicated in the development and progression of solid malignancies, including OSCC. In order to further study the relationship between these genetic alterations and the aggressive biological behavior of OSCCs, we investigated the frequency and impact of chromosome 9 numerical imbalances in these tumors. Fifty (n = 50) formalin-fixed, paraffin-embedded primary OSCC tissue sections were used. Chromogenic in situ hybridization (CISH) was implemented for detecting chromosome 9 (CEN—centromere enumeration) numerical alterations. Concerning the screening process in CISH slides, a novel, real-time reference and calibration grid platform was implemented. Chromosome 9 polysomy was observed in 8/50 (16%) tissue sections, whereas the rest of them demonstrated a normal, diploid pattern (42/50; 84%). Chromosome 9 polysomy was associated with the grade of differentiation of the examined tumors (p = 0.036). Chromosome 9 numerical imbalances (polysomy) were observed in sub-groups of OSCCs correlating with a progressive dedifferentiation of the malignant tissues. Concerning the implementation of the proposed grid-based platform as described above on CISH slides, it provides a novel, fast, and accurate screening mapping mechanism for detecting chromosome numerical imbalances.
Do Locals Have a Say? Community Experiences of Participation in Governing Forest Plantations in Tanzania
Authors: Degnet Mohammed B. , van der Werf Edwin , Ingram Verina , Wesseler Justus H.H.
Published: July 2020

As large-scale forest plantations expand in developing countries, concerns are rising about their relation to and integration with adjacent local communities. In developing countries with weak enforcement of property rights, private plantations are more likely than state-owned plantations to involve villagers in plantation’s activities in order to secure and guarantee their access to land and labor resources. Certification standards of the Forest Stewardship Council (FSC) and adherence to responsible investment guidelines further strengthen this likelihood by requiring plantations to consult and engage local communities. Using household data from Tanzania, we assess households’ experiences with their participation in plantation activities by comparing the experiences of households in villages adjacent to private, FSC-certified plantations with those of households in villages adjacent to a non-certified, state-owned plantation. Our quantitative analyses show that households in the villages adjacent to the private, certified plantations are more likely to report to participate in plantation activities. Our results show that the certified plantations are more likely to respond to community complaints and grievances. We further find that male-headed households and households of plantation employees are more likely than female-headed households and households without plantation employees to participate in plantations’ activities. Our results imply that forest management certification can complement state policy approaches of sustainable forest management to enhance community participation in forest management.
Botanical Origin, Pollen Profile, and Physicochemical Properties of Algerian Honey from Different Bioclimatic Areas
Authors: Homrani Mounia , Escuredo Olga , Rodríguez-Flores María Shantal , Fatiha Dalache , Mohammed Bouzouina , Homrani Abdelkader , Seijo M. Carmen
Published: July 2020

The palynological and physicochemical analysis of 62 honey samples produced in different biogeographical areas of Algeria was conducted. Results showed high variety in the botanical origin of samples and their physicochemical profile. Twenty-six samples were polyfloral honey, 30 were unifloral honey from different botanical sources such as Eucalyptus, Citrus, Apiaceae, Punica, Erica, Rosmarinus, Eriobotrya, or Hedysarum, and 6 were characterized as honeydew honey. Pollen analysis allowed the identification of 104 pollen types belonging to 51 botanical families, whereas the physicochemical profile showed important variations between samples. Multivariate techniques were used to compare the characteristics of samples from different biogeographical areas, showing significant differences between humid-area samples, located in the northeast of the country, and samples taken in semiarid, subhumid, and arid zones. Principal-component analysis (PCA) extracted nine components explaining 72% of data variance, being 30%, the sum of Component 1 and Component 2. The plot of both components showed samples grouped upon botanical and geographical origin. The results of this paper highlighted the great variability in honey production of Algeria, evidencing the importance of honey characterization to guarantee authenticity and to valorize local production.
Understanding the Frying Process of Plant-Based Foods Pretreated with Pulsed Electric Fields Using Frying Models
Authors: Xu Zihan , Leong Sze Ying , Farid Mohammed , Silcock Patrick , Bremer Phil , Oey Indrawati
Published: July 2020

Deep-fried foods (e.g., French fries, potato/veggie crisps) are popular among consumers. Recently, there has been an increased interest in the application of Pulsed Electric Fields (PEF) technology as a pretreatment of plant-based foods prior to deep-frying to improve quality (e.g., lower browning tendency and oil uptake) and reduce production costs (e.g., better water and energy efficiencies). However, the influence of a PEF pretreatment on the frying process and related chemical reactions for food materials is still not fully understood. PEF treatment of plant tissue causes structural modifications, which are likely to influence heat, mass and momentum transfers, as well as altering the rate of chemical reactions, during the frying process. Detailed insights into the frying process in terms of heat, mass (water and oil) and momentum transfers are outlined, in conjunction with the development of Maillard reaction and starch gelatinisation during frying. These changes occur during frying and consequently will impact on oil uptake, moisture content, colour, texture and the amount of contaminants in the fried foods, as well as the fried oil, and hence, the effects of PEF pretreatment on these quality properties of a variety of fried plant-based foods are summarised. Different mathematical models to potentially describe the influence of PEF on the frying process of plant-based foods and to predict the quality parameters of fried foods produced from PEF-treated plant materials are addressed.
Inhibitory Effect of Steamed Soybean Wastewater Against DSS-Induced Intestinal Inflammation in Mice
Authors: Jeong Soojung , Oh Jisun , Lim Ji Sun , Kim Sunghee , Jeong Deokyeol , Kim Soo Rin , Kim Jong-Sang
Published: July 2020

This study was performed to examine the beneficial potential of steamed soybean wastewater (SSW), which is generated during the manufacture of fermented soybean products and usually discarded as a by-product. The SSW was found to contain considerable amounts of isoflavones and had concentration-dependent radical scavenging capabilities. Moreover, oral administration of SSW effectively prevented colonic damage induced by dextran sulfate sodium (DSS), based on improvement of morphological and histological features, reduction of oxidative stress indicators, suppression of proinflammatory cytokine production, downregulation of inflammatory marker expression in the colonic tissue, and inhibition of the inflammatory activation of macrophages. It suggests that SSW could prevent intestinal inflammation in humans, although its efficacy should be verified through careful study design in humans. These findings have implications for enhancement of the value-added of SSW and for reduction of wastewater treatment costs incurred by the food industry.
Sheep and Goat Meat Processed Products Quality: A Review
Authors: Teixeira Alfredo , Silva Severiano , Guedes Cristina , Rodrigues Sandra
Published: July 2020

Even though sheep and goat processed meat products are not as popular as pork, beef or poultry and are generally considered not as important, they have a very important role in meat consumption around the world. A concise review of the origin and type of the most important sheep and goat processed meat products produced in different countries and world regions is made. The manuscript also summarizes the most recent studies on sheep and goat processed meats on the physicochemical characterizations, sensory quality, microbiological quality and safety. Some conclusions and future trends in production, processing and commercial potentiality for sheep and goat processed meat products are discussed. Several possibilities exist to make them more diversified and appealing to the market. Processing meat from culled animals is an interesting way to value animals with low market acceptability. Some as fermented sausages, cured legs and pâtés have great commercial potential as highly acceptable consumer commodities. An interesting field of food research is the rediscovery of a new generation of goat and sheep meat products as functional foods that will respond to the constant innovation required by the meat industry. Everything related to food safety must be considered in the future.
Consumer Food Waste Behavior among Emerging Adults: Evidence from China
Authors: Tsai Wang-Chin , Chen Xuqi , Yang Chun
Published: July 2020

With the aggravation of global climate change, the issue of environmental protection has become the focus of global attention, and countries all over the world have devoted themselves to the sustainable development of resources to reduce the negative impact of the environment on human society. Reducing the resource waste is an important aspect of the sustainable development, among which food waste is a critical part. According to a report of the United Food and Agriculture Organization of the United Nations (FAO), 35% of food is wasted during consumption. Although households are the main contributors to food waste during consumption, the situation in university canteens cannot be ignored. As universities have a high degree of social influence, some policies and activities are piloted in universities, and then, promoted to society after achieving significant results. In future social development, the food waste behavior of consumers at the early stage of adulthood will have a significant impact on society. Therefore, it is necessary to understand the factors that lead to food waste by early adulthood consumers. This study focuses on food waste by end consumers and explores factors in the food waste behavior of the emerging adulthood consumer, which can be used as a reference for improving food waste in schools, governments, and other related industries in the future. The results show that the model of factors influencing the food waste behavior of emerging adulthood consumers established in this study is acceptable. According to the analysis results of the structural equation modeling (SEM), it can be seen that the influences of environmental concerns on the attitude toward behavior, subjective norms, and perceived behavioral control are ranked first, second, and third, respectively. While emerging adulthood consumers have a high degree of independence and self-awareness, schools, governments, media networks, and other related industries also need to establish a more complete system and form of cherishing food, in order to encourage emerging adulthood consumers to change their behavior and attitude spontaneously.
Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae
Authors: Jordá Tania , Puig Sergi
Published: July 2020

Ergosterol is an essential component of fungal cell membranes that determines the fluidity, permeability and activity of membrane-associated proteins. Ergosterol biosynthesis is a complex and highly energy-consuming pathway that involves the participation of many enzymes. Deficiencies in sterol biosynthesis cause pleiotropic defects that limit cellular proliferation and adaptation to stress. Thereby, fungal ergosterol levels are tightly controlled by the bioavailability of particular metabolites (e.g., sterols, oxygen and iron) and environmental conditions. The regulation of ergosterol synthesis is achieved by overlapping mechanisms that include transcriptional expression, feedback inhibition of enzymes and changes in their subcellular localization. In the budding yeast Saccharomyces cerevisiae, the sterol regulatory element (SRE)-binding proteins Upc2 and Ecm22, the heme-binding protein Hap1 and the repressor factors Rox1 and Mot3 coordinate ergosterol biosynthesis (ERG) gene expression. Here, we summarize the sterol biosynthesis, transport and detoxification systems of S. cerevisiae, as well as its adaptive response to sterol depletion, low oxygen, hyperosmotic stress and iron deficiency. Because of the large number of ERG genes and the crosstalk between different environmental signals and pathways, many aspects of ergosterol regulation are still unknown. The study of sterol metabolism and its regulation is highly relevant due to its wide applications in antifungal treatments, as well as in food and pharmaceutical industries.
Genotype–Phenotype Correlation in Children: The Impact of FBN1 Variants on Pediatric Marfan Care
Authors: Stark Veronika C. , Hensen Flemming , Kutsche Kerstin , Kortüm Fanny , Olfe Jakob , Wiegand Peter , von Kodolitsch Yskert , Kozlik-Feldmann Rainer , Müller Götz C. , Mir Thomas S.
Published: July 2020

Currently, no reliable genotype–phenotype correlation is available for pediatric Marfan patients in everyday clinical practice. We investigated correlations of FBN1 variants with the prevalence and age of onset of Marfan manifestations in childhood and differentiated three groups: missense/in-frame, splice, and nonsense/frameshift variants. In addition, we differentiated missense variants destroying or generating a cysteine (cys-missense) and alterations not affecting cysteine. We categorized 105 FBN1-positive pediatric patients. Patients with cys-missense more frequently developed aortic dilatation (p = 0.03) requiring medication (p = 0.003), tricuspid valve prolapse (p = 0.03), and earlier onset of myopia (p = 0.02) than those with other missense variants. Missense variants correlated with a higher prevalence of ectopia lentis (p = 0.002) and earlier onset of pulmonary artery dilatation (p = 0.03) than nonsense/frameshift, and dural ectasia was more common in the latter (p = 0.005). Pectus excavatum (p = 0.007) appeared more often in patients with splice compared with missense/in-frame variants, while hernia (p = 0.04) appeared earlier in the latter. Findings on genotype–phenotype correlations in Marfan-affected children can improve interdisciplinary therapy. In patients with cys-missense variants, early medical treatment of aortic dilatation seems reasonable and early regular ophthalmologic follow-up essential. Patients with nonsense/frameshift and splice variants require early involvement of orthopedic specialists to support the growing child.
Advances in Omic Studies Drive Discoveries in the Biology of Anisakid Nematodes
Authors: D’Amelio Stefano , Lombardo Fabrizio , Pizzarelli Antonella , Bellini Ilaria , Cavallero Serena
Published: July 2020

Advancements in technologies employed in high-throughput next-generation sequencing (NGS) methods are supporting the spread of studies that, combined with advances in computational biology and bioinformatics, have greatly accelerated discoveries within basic and biomedical research for many parasitic diseases. Here, we review the most updated “omic” studies performed on anisakid nematodes, a family of marine parasites that are causative agents of the fish-borne zoonosis known as anisakiasis or anisakidosis. Few deposited data on Anisakis genomes are so far available, and this still hinders the deep and highly accurate characterization of biological aspects of interest, even as several transcriptomic and proteomic studies are becoming available. These have been aimed at discovering and characterizing molecules specific to peculiar developmental parasitic stages or tissues, as well as transcripts with pathogenic potential as toxins and allergens, with a broad relevance for a better understanding of host–pathogen relationships and for the development of reliable diagnostic tools.
Convergence of Prognostic Gene Signatures Suggests Underlying Mechanisms of Human Prostate Cancer Progression
Authors: Luca Bogdan-Alexandru , Moulton Vincent , Ellis Christopher , Connell Shea P. , Brewer Daniel S. , Cooper Colin S.
Published: July 2020

The highly heterogeneous clinical course of human prostate cancer has prompted the development of multiple RNA biomarkers and diagnostic tools to predict outcome for individual patients. Biomarker discovery is often unstable with, for example, small changes in discovery dataset configuration resulting in large alterations in biomarker composition. Our hypothesis, which forms the basis of this current study, is that highly significant overlaps occurring between gene signatures obtained using entirely different approaches indicate genes fundamental for controlling cancer progression. For prostate cancer, we found two sets of signatures that had significant overlaps suggesting important genes (p < 10−34 for paired overlaps, hypergeometrical test). These overlapping signatures defined a core set of genes linking hormone signalling (HES6-AR), cell cycle progression (Prolaris) and a molecular subgroup of patients (PCS1) derived by Non Negative Matrix Factorization (NNMF) of control pathways, together designated as SIG-HES6. The second set (designated SIG-DESNT) consisted of the DESNT diagnostic signature and a second NNMF signature PCS3. Stratifications using SIG-HES6 (HES6, PCS1, Prolaris) and SIG-DESNT (DESNT) classifiers frequently detected the same individual high-risk cancers, indicating that the underlying mechanisms associated with SIG-HES6 and SIG-DESNT may act together to promote aggressive cancer development. We show that the use of combinations of a SIG-HES6 signature together with DESNT substantially increases the ability to predict poor outcome, and we propose a model for prostate cancer development involving co-operation between the SIG-HES6 and SIG-DESNT pathways that has implication for therapeutic design.
Cortical Granule Distribution and Expression Pattern of Genes Regulating Cellular Component Size, Morphogenesis, and Potential to Differentiation are Related to Oocyte Developmental Competence and Maturational Capacity In Vivo and In Vitro
Authors: Kulus Magdalena , Kranc Wiesława , Jeseta Michal , Sujka-Kordowska Patrycja , Konwerska Aneta , Ciesiółka Sylwia , Celichowski Piotr , Moncrieff Lisa , Kocherova Ievgeniia , Józkowiak Małgorzata , Kulus Jakub , Wieczorkiewicz Maria , Piotrowska-Kempisty Hanna , Skowroński Mariusz T. , Bukowska Dorota , Machatkova Marie , Hanulakova Sarka , Mozdziak Paul , Jaśkowski Jędrzej M. , Kempisty Bartosz , Antosik Paweł
Published: July 2020

Polyspermia is an adverse phenomenon during mammalian fertilization when more than one sperm fuses with a single oocyte. The egg cell is prepared to prevent polyspermia by, among other ways, producing cortical granules (CGs), which are specialized intracellular structures containing enzymes that aim to harden the zona pellucida and block the fusion of subsequent sperm. This work focused on exploring the expression profile of genes that may be associated with cortical reactions, and evaluated the distribution of CGs in immature oocytes and the peripheral density of CGs in mature oocytes. Oocytes were isolated and then processed for in vitro maturation (IVM). Transcriptomic analysis of genes belonging to five ontological groups has been conducted. Six genes showed increased expression after IVM (ARHGEF2, MAP1B, CXCL12, FN1, DAB2, and SOX9), while the majority of genes decreased expression after IVM. Using CG distribution analysis in immature oocytes, movement towards the cortical zone of the oocyte during meiotic competence acquisition was observed. CGs peripheral density decreased with the rise in meiotic competence during the IVM process. The current results reveal important new insights into the in vitro maturation of oocytes. Our results may serve as a basis for further studies to investigate the cortical reaction of oocytes.
BCL2L15 Depletion Inhibits Endometrial Receptivity via the STAT1 Signaling Pathway
Authors: Yang Diqi , Liu Ai , Wu Yanqin , Li Bin , Nan Sha , Yin Ruiling , Zhu Hongmei , Chen Jianguo , Ding Yi , Ding Mingxing
Published: July 2020

In domestic ruminants, endometrial receptivity is critical for a successful pregnancy and economic efficiency. Although the endometrium undergoes major cellular changes during peri-implantation, the precise mechanisms regulating goat endometrial receptivity remain unknown. In this study, we investigated the functional roles and signal transduction of the B-cell lymphoma 2 (Bcl-2)-like protein 15 (BCL2L15) in the regulation of endometrial receptivity in vitro. Our results showed that BCL2L15 was up-regulated in goat endometrial epithelial cells (EECs) under progesterone (P4), estradiol (E2), and interferon-tau (IFN-τ) treatments. Our knockdown of BCL2L15 by specific shRNA that significantly hampered endometrial receptivity. In the absence of BCL2L15, the signal transducer and activator of transcription (STAT)1 and STAT3 pathway were activated. Additionally, pretreatment with the STAT1 inhibitor, fludarabine, restored the effect of silencing BCL2L15 on the endometrial receptivity, but not the STAT3 inhibitor Stattic. Overall, these results suggested that BCL2L15 is the key regulator of endometrial receptivity in goats, regulating the endometrial receptivity through the STAT1 pathway. Understanding the function of BCL2L15-STAT1 in endometrial receptivity is important to the exploration of new targets for the diagnosis and treatment of early pregnancy failure, and improving the success rates for artificial reproduction.
A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings
Authors: Shchagina Olga , Bessonova Ludmila , Bychkov Igor , Beskorovainaya Tatiana , Poliakov Aleksander
Published: July 2020

Congenital myasthenic syndrome-22 (CMS22, OMIM 616224) is a very rare recessive hereditary disorder. At the moment, ten CMS22 patients are described, with the disorder caused by nine different Loss-of-Function mutations and 14 gross deletions in the PREPL gene. The materials for our study were DNA samples of five family members: two patients with myasthenia, their healthy sibling and parents. Clinical exome analysis was carried out for one patient, then the whole family was checked for target variants with Sanger sequencing, quantitative multiplex ligation-dependent probe amplification, and chromosome 2 microsatellite markers study. To determine the functional significance of the splicing variant, we applied the minigene assay. The cause of the proband’s disorder is a compound heterozygous state of two previously non-described pathogenic PREPL variants: a c.1528C>T (p.(Arg510Ter)) nonsense mutation and a c.2094G>T pseudo-missense variant, which, simultaneously with a p.(Lys698Asn) amino acid substitution, affects splicing, leading to exon 14 skipping in mRNA. The second patient’s disorder was caused by a homozygous nonsense c.1528C>T (p.(Arg510Ter)) mutation due to maternal uniparental disomy (UPD) of chromosome 2. In this study, we describe a unique case, in which two siblings with a rare disorder have different pathologic genotypes.
CYP4F2 and VKORC1 Polymorphisms Amplify the Risk of Carotid Plaque Formation
Authors: Vesa Stefan Cristian , Vlaicu Sonia Irina , Vacaras Vitalie , Crisan Sorin , Sabin Octavia , Pasca Sergiu , Trifa Adrian Pavel , Rusz-Fogarasi Tamas , Sava Madalina , Buzoianu Anca Dana
Published: July 2020

Introduction: Atherosclerosis represents the process by which fibrous plaques are formed in the arterial wall, increasing its rigidity with a subsequent decrease in blood flow which can lead to several cardiovascular events. Seeing as vitamin K antagonists are involved in the pathogenesis of atherosclerosis, we decided to investigate whether polymorphisms in genes that influence vitamin K metabolism might have an impact in modulating the risk of plaque formation. Patients and Methods: In the current study we included adult patients admitted in the Clinical Municipal Hospital of Cluj-Napoca without any carotid or femoral plaques clinically visible at the initial investigation, and a five year follow-up was subsequently performed. We recorded the following patient characteristics: age at inclusion, gender, area of living, smoking, presence of carotid and/or femoral plaques at five years, ischemic heart disease, arterial hypertension, atrial fibrillation, heart failure, diabetes mellitus, obesity, dyslipidemia, drug (oral anticoagulants, antihypertensives, hypolipidemic, anti-diabetic) use and status for the following gene polymorphisms: VKORC1 1639 G>A, CYP4F2 1347 G>T and GGCX 12970 C>G. Results: We observed that the major predictor of both carotid and femoral plaque formation is represented by ischemic cardiac disease. VKORC1 and CYP4F2 polymorphisms did not predict plaque formation, except for VKORC1 homozygous mutants. Nonetheless, both VKORC1 and CYP4F2 interacted with ischemic cardiac disease, increasing the risk of developing a carotid plaque, while only CYP4F2, but not VKORC1, interacted with ischemic cardiac disease to increase the risk of femoral plaque formation. Conclusions: We documented that CYP4F2 and VKORC1 polymorphisms boost the proinflammatory plaque environment (observed indirectly through the presence of ischemic heart disease), increasing the risk of plaque development.
Major QTLs for Trunk Height and Correlated Agronomic Traits Provide Insights into Multiple Trait Integration in Oil Palm Breeding
Authors: Teh Chee-Keng , Ong Ai-Ling , Mayes Sean , Massawe Festo , Appleton David Ross
Published: July 2020

Superior oil yield is always the top priority of the oil palm industry. Short trunk height (THT) and compactness traits have become increasingly important to improve harvesting efficiency since the industry started to suffer yield losses due to labor shortages. Breeding populations with low THT and short frond length (FL) are actually available, such as Dumpy AVROS pisifera (DAV) and Gunung Melayu dura (GM). However, multiple trait stacking still remains a challenge for oil palm breeding, which usually requires 12–20 years to complete a breeding cycle. In this study, yield and height increment in the GM × GM (GM-3341) and the GM × DAV (GM-DAV-3461) crossing programs were evaluated and palms with good yield and smaller height increment were identified. In the GM-3341 family, non-linear THT growth between THT_2008 (seven years old) and THT_2014 (13 years old) was revealed by a moderate correlation, suggesting that inter-palm competition becomes increasingly important. In total, 19 quantitative trait loci (QTLs) for THT_2008 (8), oil per palm (O/P) (7) and FL (4) were localized on the GM-3341 linkage map, with an average mapping interval of 2.01 cM. Three major QTLs for THT_2008, O/P and FL are co-located on chromosome 11 and reflect the correlation of THT_2008 with O/P and FL. Multiple trait selection for high O/P and low THT (based on the cumulative effects of positive alleles per trait) identified one palm from 100 palms, but with a large starting population of 1000–1500 seedling per cross, this low frequency could be easily compensated for during breeding selection.