bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Companion Animals on Quality of Life of Gay and Bisexual Men Diagnosed with Prostate Cancer
Authors: Wright Morgan M. , Schreiner Pamela , Rosser B. R. Simon , Polter Elizabeth J. , Mitteldorf Darryl , West William , Ross Michael W.
Published: November 2019

There has been almost no research on associations of companion animals with quality of life in sexual minorities. Because gay and bisexual men have less social support than their heterosexual peers, some have argued that pet companionship could provide emotional support, while others have argued the opposite, that having a pet is another stressor. This analysis examines the association between having dogs, cats, both animals, or no animals and quality of life using the 12-item Short Form (SF-12) mental and physical composite quality of life scores for gay and bisexual prostate cancer survivors, post-treatment. Participants were 189 gay, bisexual, or other men who have sex with men, who completed online surveys in 2015. Linear regression analysis found that participants with cats and participants with dogs had lower mental quality of life scores than participants without pets. After adjustment for covariates, mental health scores remained significantly lower for cat owners, dog owners, and owners of both animals compared to those of participants who did not have pets. No differences were seen for physical quality of life scores after adjustment. We conclude that pet companionship may be a net stressor for gay and bisexual men following prostate cancer treatment. As this is the first study of pet companionship in sexual minorities, further research is needed to confirm the reliability of these findings, generalizability, and temporality of the association.
A Preclinical Evaluation towards the Clinical Application of Oxygen Consumption Measurement by CERMs by a Mouse Chimera Model
Authors: Kuno Takashi , Tachibana Masahito , Fujimine-Sato Ayako , Fue Misaki , Higashi Keiko , Takahashi Aiko , Kurosawa Hiroki , Nishio Keisuke , Shiga Naomi , Watanabe Zen , Yaegashi Nobuo
Published: November 2019

We have developed an automated device for the measurement of oxygen consumption rate (OCR) called Chip-sensing Embryo Respiratory Measurement system (CERMs). To verify the safety and the significance of the OCR measurement by CERMs, we conducted comprehensive tests using a mouse model prior to clinical trials in a human in vitro fertilization (IVF) program. Embryo transfer revealed that the OCR measured by CERMs did not compromise the full-term development of mice or their future fertility, and was positively correlated with adenosine triphosphate (ATP) production and the mitochondrial membrane potential (ΔΨm), thereby indirectly reflecting mitochondrial oxidative phosphorylation (OXPHOS) activity. We demonstrated that the OCR is independent of embryo morphology (the size) and number of mitochondria (mitochondrial DNA copy number). The OCR correlated with the total cell numbers, whereas the inner cell mass (ICM) cell numbers and the fetal developmental rate were not. Thus, the OCR may serve as an indicator of the numbers of trophectoderm (TE) cells, rather than number or quality of ICM cells. However, implantation ability was neither correlated with the OCR, nor the embryo size in this model. This can probably be attributed to the limitation that chimeric embryos contain non-physiological high TE cells counts that are beneficial for implantation. CERMs can be safely employed in clinical IVF owing to it being a safe, highly effective, non-invasive, accurate, and quantitative tool for OCR measurement. Utilization of CERMs for clinical testing of human embryos would provide further insights into the nature of oxidative metabolism and embryonic viability.
Expression Analysis of mRNA Decay of Maternal Genes during Bombyx mori Maternal-to-Zygotic Transition
Authors: Zhang Meirong , Xu Pingzhen , Pang Huilin , Chen Tao , Zhang Guozheng
Published: November 2019

Maternal genes play an important role in the early embryonic development of the silkworm. Early embryonic development without new transcription depends on maternal components stored in the egg during oocyte maturation. The maternal-to-zygotic transition (MZT) is a tightly regulated process that includes maternal mRNAs elimination and zygotic transcription initiation. This process has been extensively studied within model species. Each model organism has a unique pattern of maternal transcriptional clearance classes in MZT. In this study, we identified 66 maternal genes through bioinformatics analysis and expression analysis in the eggs of silkworm virgin moths (Bombyx mori). All 66 maternal genes were expressed in vitellogenesis in day eight female pupae. During MZT, the degradation of maternal gene mRNAs could be divided into three clusters. We found that eight maternal genes of cluster 1 remained stable from 0 to 3.0 h, 17 maternal genes of cluster 2 were significantly decayed from 0.5 to 1.0 h and 41 maternal genes of cluster 3 were significantly decayed after 1.5 h. Therefore, the initial time-point of degradation of cluster 2 was earlier than that of cluster 3. The maternal gene mRNAs decay of clusters 2 and 3 is first initiated by maternal degradation activity. Our study expands upon the identification of silkworm maternal genes and provides a perspective for further research of the embryo development in Bombyx mori.
Correction: Li, Q., et al. Differential and Interactive Effects of Substrate Topography and Chemistry on Human Mesenchymal Stem Cell Gene Expression. Int. J. Mol. Sci. 2018, 19, 2344
Authors: Li Qiongfang , Zhang Bo , Kasoju Naresh , Ma Jinmin , Yang Aidong , Cui Zhanfeng , Wang Hui , Ye Hua
Published: November 2019

The authors wish to make the following correction to this paper [...]
Salvianolic Acid B Slows the Progression of Breast Cancer Cell Growth via Enhancement of Apoptosis and Reduction of Oxidative Stress, Inflammation, and Angiogenesis
Authors: Katary Mohamed A. , Abdelsayed Rafik , Alhashim Abdulmohsin , Abdelhasib Mohamed , Elmarakby Ahmed A.
Published: November 2019

Breast cancer is the current leading cause of cancer death in females worldwide. Although current chemotherapeutic drugs effectively reduce the progression of breast cancer, most of these drugs have many unwanted side effects. Salvianolic acid B (Sal-B) is a bioactive compound isolated from the root of Danshen Radix with potent antioxidant and anti-inflammatory properties. Since free radicals play a key role in the initiation and progression of tumor cells growth and enhance their metastatic potential, the current study was designed to investigate the antitumor activity of Sal-B and compare it with the antitumor activity of the traditional anticancer drug, cisplatin. In vitro, Sal-B decreased the human breast cancer adenocarcinoma (MCF-7) cells proliferation in a concentration and time dependent manner. In vivo and similar to cisplatin treatment, Sal-B significantly reduced tumor volume and increased the median survival when compared to tumor positive control mice group injected with Ehrlich solid carcinoma cell line (ESC). Sal-B decreased plasma level of malondialdehyde as a marker of oxidative stress and increased plasma level of reduced glutathione (GSH) as a marker of antioxidant defense when compared to control ESC injected mice. Either Sal-B or cisplatin treatment decreased tumor tissue levels of tumor necrosis factor (TNF-α), matrix metalloproteinase-8 (MMP-8), and Cyclin D1 in ESC treated mice. Contrary to cisplatin treatment, Sal-B did not decrease tumor tissue Ki-67 protein in ESC injected mice. Immunohistochemical analysis revealed that Sal-B or cisplatin treatment increased the expression of the apoptotic markers caspase-3 and P53. Although Sal-B or cisplatin significantly reduced the expression of the angiogenic factor vascular endothelial growth factor (VEGF) in ESC injected mice, only Sal-B reduced expression level of COX-2 in ESC injected mice. Our data suggest that Sal-B exhibits antitumor features against breast cancer cells possibly via enhancing apoptosis and reducing oxidative stress, inflammation, and angiogenesis.
Enzymatic and Biological Characterization of Novel Sirtuin Modulators against Cancer
Authors: Carafa Vincenzo , Poziello Angelita , Della Torre Laura , Giovannelli Pia , Di Donato Marzia , Safadeh Elham , Yu Zhijun , Baldi Alfonso , Castoria Gabriella , Tomaselli Daniela , Mai Antonello , Rotili Dante , Nebbioso Angela , Altucci Lucia
Published: November 2019

Sirtuins, a family of nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacetylases, are promising targets for anticancer treatment. Recently, we characterized a novel pan-sirtuin (SIRT) inhibitor, MC2494, displaying antiproliferative effects and able to induce death pathways in several human cancer cell lines and decrease tumor growth in vivo. Based on the chemical scaffold of MC2494, and by applying a structure–activity relationship approach, we developed a small library of derivative compounds and extensively analyzed their enzymatic action at cellular level as well as their ability to induce cell death. We also investigated the effect of MC2494 on regulation of cell cycle progression in different cancer cell lines. Our investigations indicated that chemical substitutions applied to MC2494 scaffold did not confer higher efficacy in terms of biological activity and SIRT1 inhibition, but carbethoxy-containing derivatives showed higher SIRT2 specificity. The carbethoxy derivative of MC2494 and its 2-methyl analog displayed the strongest enzymatic activity. Applied chemical modifications improved the enzymatic selectivity of these SIRT inhibitors. Additionally, the observed activity of MC2494 via cell cycle and apoptotic regulation and inhibition of cell migration supports the potential role of SIRTs as targets in tumorigenesis and makes SIRT-targeting molecules good candidates for novel pharmacological approaches in personalized medicine.
Recent Advances in ROS-Responsive Cell Sheet Techniques for Tissue Engineering
Authors: Koo Min-Ah , Lee Mi Hee , Park Jong-Chul
Published: November 2019

Cell sheet engineering has evolved rapidly in recent years as a new approach for cell-based therapy. Cell sheet harvest technology is important for producing viable, transplantable cell sheets and applying them to tissue engineering. To date, most cell sheet studies use thermo-responsive systems to detach cell sheets. However, other approaches have been reported. This review provides the progress in cell sheet detachment techniques, particularly reactive oxygen species (ROS)-responsive strategies. Therefore, we present a comprehensive introduction to ROS, their application in regenerative medicine, and considerations on how to use ROS in cell detachment. The review also discusses current limitations and challenges for clarifying the mechanism of the ROS-responsive cell sheet detachment.
Defect of Interferon γ Leads to Impaired Wound Healing through Prolonged Neutrophilic Inflammatory Response and Enhanced MMP-2 Activation
Authors: Kanno Emi , Tanno Hiromasa , Masaki Airi , Sasaki Ayako , Sato Noriko , Goto Maiko , Shisai Mayu , Yamaguchi Kenji , Takagi Naoyuki , Shoji Miki , Kitai Yuki , Sato Ko , Kasamatsu Jun , Ishii Keiko , Miyasaka Tomomitsu , Kawakami Kaori , Imai Yoshimichi , Iwakura Yoichiro , Maruyama Ryoko , Tachi Masahiro , Kawakami Kazuyoshi
Published: November 2019

Interferon (IFN)-γ is mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. Although IFN-γ is well known regarding its inhibitory effects on collagen synthesis by fibroblasts in vitro, information is limited regarding its role in wound healing in vivo. In the present study, we analyzed how the defect of IFN-γ affects wound healing. Full-thickness wounds were created on the backs of wild type (WT) C57BL/6 and IFN-γ-deficient (KO) mice. We analyzed the percent wound closure, wound breaking strength, accumulation of leukocytes, and expression levels of COL1A1, COL3A1, and matrix metalloproteinases (MMPs). IFN-γKO mice exhibited significant attenuation in wound closure on Day 10 and wound breaking strength on Day 14 after wound creation, characteristics that are associated with prolonged neutrophil accumulation. Expression levels of COL1A1 and COL3A1 mRNA were lower in IFN-γKO than in WT mice, whereas expression levels of MMP-2 (gelatinase) mRNA were significantly greater in IFN-γKO than in WT mice. Moreover, under neutropenic conditions created with anti-Gr-1 monoclonal antibodies, wound closure in IFN-γKO mice was recovered through low MMP-2 expression levels. These results suggest that IFN-γ may be involved in the proliferation and maturation stages of wound healing through the regulation of neutrophilic inflammatory responses.
Trends in Atopic Dermatitis—From Standard Pharmacotherapy to Novel Drug Delivery Systems
Authors: Souto Eliana B. , Dias-Ferreira João , Oliveira Jéssica , Sanchez-Lopez Elena , Lopez-Machado Ana , Espina Marta , Garcia Maria L. , Souto Selma B. , Martins-Gomes Carlos , Silva Amélia M.
Published: November 2019

Atopic dermatitis (AD) is a predominant and deteriorating chronic inflammation of the skin, categorized by robust burning and eczematous lacerations in diverse portions of the body. AD affects about 20% of both offspring and adults worldwide. The pathophysiology of AD combines environmental, hereditary, and immunological aspects, together with skin barrier dysfunction. The procedures used to prevent the disease are the everyday usage of creams to support the restoration of the epidermal barrier. The classical treatments include the use of topical corticosteroids as a first-line therapy, but also calcineurin inhibitors, antihistamines, antibiotics, phototherapy, and also immunosuppressant drugs in severe cases of AD. Topical drug delivery to deeper skin layers is a difficult task due to the skin anatomic barrier, which limits deeper penetration of drugs. Groundbreaking drug delivery systems, based on nanoparticles (NPs), have received much attention due to their ability to improve solubility, bioavailability, diffusion, targeting to specific types of cells, and limiting the secondary effects of the drugs employed in the treatment of AD. Even so, additional studies are still required to recognize the toxicological characteristics and long-term safety of NPs. This review discusses the current classical pharmacotherapy of AD against new nanoparticle skin delivery systems and their toxicologic risks.
A Meta-Analysis of Comparative Transcriptomic Data Reveals a Set of Key Genes Involved in the Tolerance to Abiotic Stresses in Rice
Authors: Buti Matteo , Baldoni Elena , Formentin Elide , Milc Justyna , Frugis Giovanna , Lo Schiavo Fiorella , Genga Annamaria , Francia Enrico
Published: November 2019

Several environmental factors, such as drought, salinity, and extreme temperatures, negatively affect plant growth and development, which leads to yield losses. The tolerance or sensitivity to abiotic stressors are the expression of a complex machinery involving molecular, biochemical, and physiological mechanisms. Here, a meta-analysis on previously published RNA-Seq data was performed to identify the genes conferring tolerance to chilling, osmotic, and salt stresses, by comparing the transcriptomic changes between tolerant and susceptible rice genotypes. Several genes encoding transcription factors (TFs) were identified, suggesting that abiotic stress tolerance involves upstream regulatory pathways. A gene co-expression network defined the metabolic and signalling pathways with a prominent role in the differentiation between tolerance and susceptibility: (i) the regulation of endogenous abscisic acid (ABA) levels, through the modulation of genes that are related to its biosynthesis/catabolism, (ii) the signalling pathways mediated by ABA and jasmonic acid, (iii) the activity of the “Drought and Salt Tolerance” TF, involved in the negative regulation of stomatal closure, and (iv) the regulation of flavonoid biosynthesis by specific MYB TFs. The identified genes represent putative key players for conferring tolerance to a broad range of abiotic stresses in rice; a fine-tuning of their expression seems to be crucial for rice plants to cope with environmental cues.
Correction: Abdulle, A.E., et al. Hydrogen Sulfide: A Therapeutic Option in Systemic Sclerosis. Int. J. Mol. Sci. 2018, 19, 4121
Authors: Abdulle Amaal Eman , van Goor Harry , Mulder Douwe J.
Published: November 2019

The authors wish to make the following correction to this paper [...]
Key Factors for a One-Pot Enzyme Cascade Synthesis of High Molecular Weight Hyaluronic Acid
Authors: Gottschalk Johannes , Zaun Henning , Eisele Anna , Kuballa Jürgen , Elling Lothar
Published: November 2019

In the last decades, interest in medical or cosmetic applications of hyaluronic acid (HA) has increased. Size and dispersity are key characteristics of biological function. In contrast to extraction from animal tissue or bacterial fermentation, enzymatic in vitro synthesis is the choice to produce defined HA. Here we present a one-pot enzyme cascade with six enzymes for the synthesis of HA from the cheap monosaccharides glucuronic acid (GlcA) and N-acetylglucosamine (GlcNAc). The combination of two enzyme modules, providing the precursors UDP–GlcA and UDP–GlcNAc, respectively, with hyaluronan synthase from Pasteurella multocida (PmHAS), was optimized to meet the kinetic requirements of PmHAS for high HA productivity and molecular weight. The Mg2+ concentration and the pH value were found as key factors. The HA product can be tailored by different conditions: 25 mM Mg2+ and 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES)-NaOH pH 8 result into an HA product with high Mw HA (1.55 MDa) and low dispersity (1.05). Whereas with 15 mM Mg2+ and HEPES–NaOH pH 8.5, we reached the highest HA concentration (2.7 g/L) with a yield of 86.3%. Our comprehensive data set lays the basis for larger scale enzymatic HA synthesis.
Rhododenol Activates Melanocytes and Induces Morphological Alteration at Sub-Cytotoxic Levels
Authors: Kim Minjeong , Lee Chang-Seok , Lim Kyung-Min
Published: November 2019

Rhododenol (RD), a whitening cosmetic ingredient, was withdrawn from the market due to RD-induced leukoderma (RIL). While many attempts have been made to clarify the mechanism underlying RIL, RIL has not been fully understood yet. Indeed, affected subjects showed uneven skin pigmentation, but the features are different from vitiligo, a skin hypopigmentary disorder, alluding to events more complex than simple melanocyte cytotoxicity. Here, we discovered that rhododenol treatment reduced the number of melanocytes in a pigmented 3D human skin model, Melanoderm™, confirming the melanocyte toxicity of RD. Of note, melanocytes that survived in the RD treated tissues exhibited altered morphology, such as extended dendrites and increased cell sizes. Consistently with this, sub-cytotoxic level of RD increased cell size and elongated dendrites in B16 melanoma cells. Morphological changes of B16 cells were further confirmed in the immunocytochemistry of treated cells for actin and tubulin. Even more provoking, RD up-regulated the expression of tyrosinase and TRP1 in the survived B16 cells. Evaluation of mRNA expression of cytoskeletal proteins suggests that RD altered the cytoskeletal dynamic favoring cell size expansion and melanosome maturation. Collectively, these results suggest that RD not only induces cytotoxicity in melanocytes but also can lead to a profound perturbation of melanocyte integrity even at sub-cytotoxic levels.
Genome-Wide Analysis of the DYW Subgroup PPR Gene Family and Identification of GmPPR4 Responses to Drought Stress
Authors: Su Hong-Gang , Li Bo , Song Xin-Yuan , Ma Jian , Chen Jun , Zhou Yong-Bin , Chen Ming , Min Dong-Hong , Xu Zhao-Shi , Ma You-Zhi
Published: November 2019

Pentatricopeptide-repeat (PPR) proteins were identified as a type of nucleus coding protein that is composed of multiple tandem repeats. It has been reported that PPR genes play an important role in RNA editing, plant growth and development, and abiotic stresses in plants. However, the functions of PPR proteins remain largely unknown in soybean. In this study, 179 DYW subgroup PPR genes were identified in soybean genome (Glycine max Wm82.a2.v1). Chromosomal location analysis indicated that DYW subgroup PPR genes were mapped to all 20 chromosomes. Phylogenetic relationship analysis revealed that DYW subgroup PPR genes were categorized into three distinct Clusters (I to III). Gene structure analysis showed that most PPR genes were featured by a lack of intron. Gene duplication analysis demonstrated 30 PPR genes (15 pairs; ~35.7%) were segmentally duplicated among Cluster I PPR genes. Furthermore, we validated the mRNA expression of three genes that were highly up-regulated in soybean drought- and salt-induced transcriptome database and found that the expression levels of GmPPR4 were induced under salt and drought stresses. Under drought stress condition, GmPPR4-overexpressing (GmPPR4-OE) plants showed delayed leaf rolling; higher content of proline (Pro); and lower contents of H2O2, O2− and malondialdehyde (MDA) compared with the empty vector (EV)-control plants. GmPPR4-OE plants exhibited increased transcripts of several drought-inducible genes compared with EV-control plants. Our results provided a comprehensive analysis of the DYW subgroup PPR genes and an insight for improving the drought tolerance in soybean.
Candidate Domestication-Related Genes Revealed by Expression Quantitative Trait Loci Mapping of Narrow-Leafed Lupin (Lupinus angustifolius L.)
Authors: Plewiński Piotr , Książkiewicz Michał , Rychel-Bielska Sandra , Rudy Elżbieta , Wolko Bogdan
Published: November 2019

The last century has witnessed rapid domestication of the narrow-leafed lupin (Lupinus angustifolius L.) as a grain legume crop, exploiting discovered alleles conferring low-alkaloid content (iucundus), vernalization independence (Ku and Julius), and reduced pod shattering (lentus and tardus). In this study, a L. angustifolius mapping population was subjected to massive analysis of cDNA ends (MACE). The MACE yielded 4185 single nucleotide polymorphism (SNP) markers for linkage map improvement and 30,595 transcriptomic profiles for expression quantitative trait loci (eQTL) mapping. The eQTL highlighted a high number of cis- and trans-regulated alkaloid biosynthesis genes with gene expression orchestrated by a regulatory agent localized at iucundus locus, supporting the concept that ETHYLENE RESPONSIVE TRANSCRIPTION FACTOR RAP2-7 may control low-alkaloid phenotype. The analysis of Ku shed light on the vernalization response via FLOWERING LOCUS T and FD regulon in L. angustifolius, providing transcriptomic evidence for the contribution of several genes acting in C-repeat binding factor (CBF) cold responsiveness and in UDP-glycosyltransferases pathways. Research on lentus selected a DUF1218 domain protein as a candidate gene controlling the orientation of the sclerified endocarp and a homolog of DETOXIFICATION14 for purplish hue of young pods. An ABCG transporter was identified as a hypothetical contributor to sclerenchyma fortification underlying tardus phenotype.
Excitatory Amino Acid Transporters in Physiology and Disorders of the Central Nervous System
Authors: Malik Anna R. , Willnow Thomas E.
Published: November 2019

Excitatory amino acid transporters (EAATs) encompass a class of five transporters with distinct expression in neurons and glia of the central nervous system (CNS). EAATs are mainly recognized for their role in uptake of the amino acid glutamate, the major excitatory neurotransmitter. EAATs-mediated clearance of glutamate released by neurons is vital to maintain proper glutamatergic signalling and to prevent toxic accumulation of this amino acid in the extracellular space. In addition, some EAATs also act as chloride channels or mediate the uptake of cysteine, required to produce the reactive oxygen speciesscavenger glutathione. Given their central role in glutamate homeostasis in the brain, as well as their additional activities, it comes as no surprise that EAAT dysfunctions have been implicated in numerous acute or chronic diseases of the CNS, including ischemic stroke and epilepsy, cerebellar ataxias, amyotrophic lateral sclerosis, Alzheimer’s disease and Huntington’s disease. Here we review the studies in cellular and animal models, as well as in humans that highlight the roles of EAATs in the pathogenesis of these devastating disorders. We also discuss the mechanisms regulating EAATs expression and intracellular trafficking and new exciting possibilities to modulate EAATs and to provide neuroprotection in course of pathologies affecting the CNS.
The Anti-Tumorigenic Activity of Sema3C in the Chick Embryo Chorioallantoic Membrane Model
Authors: Valiulytė Indrė , Curkūnavičiūtė Rūta , Ribokaitė Laura , Kazlauskas Arunas , Vaitkevičiūtė Monika , Skauminas Kęstutis , Valančiūtė Angelija
Published: November 2019

Sema3C protein, a member of the class 3 family of secreted semaphorins, play an important role in tumor development by regulating cell proliferation, migration, invasion, and angiogenesis processes. Depending on the type and malignancy grade of the tumor, Sema3C function remains controversial. In this study, we constructed a stably overexpressing Sema3C glioblastoma cell line U87 MG and tested it on the chicken embryo chorioallantoic membrane (CAM) model with the aim to reveal Sema3C protein function on angiogenesis process in ovo. Our experiments showed that Sema3C not only affects angiogenesis of CAM by inhibiting neovascularization but also acts as an anti-tumorigenic molecule by hampering U87 MG cell invasion into mesenchyme. The effects of Sema3C on CAM were similar to the effects of anti-epileptic drug sodium valproate (NaVP). Both, anti-angiogenic and anti-tumorigenic activities of Sema3C were enhanced by the treatment of NaVP and, importantly, were not attributed to the cytotoxic effects. Our studies suggest that Sema3C could be a promising target for glioblastoma treatment.
DGKα in Neutrophil Biology and Its Implications for Respiratory Diseases
Authors: Baldanzi Gianluca , Malerba Mario
Published: November 2019

Diacylglycerol kinases (DGKs) play a key role in phosphoinositide signaling by removing diacylglycerol and generating phosphatidic acid. Besides the well-documented role of DGKα and DGKζ as negative regulators of lymphocyte responses, a robust body of literature points to those enzymes, and specifically DGKα, as crucial regulators of leukocyte function. Upon neutrophil stimulation, DGKα activation is necessary for migration and a productive response. The role of DGKα in neutrophils is evidenced by its aberrant behavior in juvenile periodontitis patients, which express an inactive DGKα transcript. Together with in vitro experiments, this suggests that DGKs may represent potential therapeutic targets for disorders where inflammation, and neutrophils in particular, plays a major role. In this paper we focus on obstructive respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD), but also rare genetic diseases such as alpha-1-antitrypsin deficiency. Indeed, the biological role of DGKα is understudied outside the T lymphocyte field. The recent wave of research aiming to develop novel and specific inhibitors as well as KO mice will allow a better understanding of DGK’s role in neutrophilic inflammation. Better knowledge and pharmacologic tools may also allow DGK to move from the laboratory bench to clinical trials.
Excitatory Amino Acid Transporters (EAATs): Glutamate Transport and Beyond
Authors: Magi Simona , Piccirillo Silvia , Amoroso Salvatore , Lariccia Vincenzo
Published: November 2019

Na+-dependent excitatory amino acid transporters (EAATs) are the major transport mechanisms for extracellular glutamate removal in the central nervous system (CNS). The primary function assigned to EAATs is the maintenance of low extracellular glutamate levels, thus allowing glutamate to be used as a signaling molecule in the brain and to avoid excitotoxicity. However, glutamate has other recognized functions. For instance, it is a key anaplerotic substrate for the tricarboxylic acid (TCA) cycle, as it can be converted to α-ketoglutarate by transaminases or glutamate dehydrogenase. Furthermore, glutamate is a precursor of the main antioxidant glutathione, which plays a pivotal role in preventing oxidative cell death. Therefore, glutamate signaling/use is at the crossroad of multiple metabolic pathways and accordingly, it can influence a plethora of cell functions, both in health and disease. Here, we provide an overview of the main functions of glutamate and its transport systems, analyzing its role as a neurotransmitter and at the same time, the possible metabolic fates it can undergo in the intracellular milieu. Specifically, the metabolic role of glutamate and the molecular machinery proposed to metabolically support its transport will be further analyzed.
Genome-Wide Characterization, Expression Profile Analysis of WRKY Family Genes in Santalum album and Functional Identification of Their Role in Abiotic Stress
Authors: Yan Haifeng , Li Mingzhi , Xiong Yuping , Wu Jianming , Teixeira da Silva Jaime , Ma Guohua
Published: November 2019

WRKY proteins are a large superfamily of transcription factors that are involved in diverse biological processes including development, as well as biotic and abiotic stress responses in plants. WRKY family proteins have been extensively characterized and analyzed in many plant species, including Arabidopsis, rice, and poplar. However, knowledge on WRKY transcription factors in Santalum album is scarce. Based on S. album genome and transcriptome data, 64 SaWRKY genes were identified in this study. A phylogenetic analysis based on the structures of WRKY protein sequences divided these genes into three major groups (I, II, III) together with WRKY protein sequences from Arabidopsis. Tissue-specific expression patterns showed that 37 SaWRKY genes were expressed in at least one of five tissues (leaves, roots, heartwood, sapwood, or the transition zone), while the remaining four genes weakly expressed in all of these tissues. Analysis of the expression profiles of the 42 SaWRKY genes after callus was initiated by salicylic acid (SA) and methyl jasmonate (MeJA) revealed that 25 and 24 SaWRKY genes, respectively, were significantly induced. The function of SaWRKY1, which was significantly up-regulated by SA and MeJA, was analyzed. SaWRKY1 was localized in the nucleus and its overexpression improved salt tolerance in transgenic Arabidopsis. Our study provides important information to further identify the functions of SaWRKY genes and to understand the roles of SaWRKY family genes involved in the development and in SA- and MeJA-mediated stress responses.
Development and Characterization of a Genetic Mouse Model of KRAS Mutated Colorectal Cancer
Authors: Maitra Radhashree , Thavornwatanayong Thongthai , Venkatesh Madhu Kumar , Chandy Carol , Vachss Dov , Augustine Titto , Guzik Hillary , Koba Wade , Liu Qiang , Goel Sanjay
Published: November 2019

Patients with KRAS mutated colorectal cancer (CRC) represent a cohort with unmet medical needs, with limited options of FDA-approved therapies. Representing 40–45% of all CRC patients, they are considered ineligible to receive anti-EGFR monoclonal antibodies that have added a significant therapeutic benefit for KRAS wild type CRC patients. Although several mouse models of CRC have been developed during the past decade, one genetically resembling the KRAS mutated CRC is yet to be established. In this study C57 BL/6 mice with truncated adenomatous polyposis coli (APC) floxed allele was crossed with heterozygous KRAS floxed outbred mice to generate an APCf/f KRAS+/f mouse colony. In another set of breeding, APC floxed mice were crossed with CDX2-Cre-ERT2 mice and selected for APCf/f CDX2-Cre-ERT2 after the second round of inbreeding. The final model of the disease was generated by the cross of the two parental colonies and viable APC f/f KRAS +/f CDX2-Cre-ERT2 (KPC: APC) were genotyped and characterized. The model animals were tamoxifen (TAM) induced to generate tumors. Micro-positron emission tomography (PET) scan was used to detect and measure tumor volume and standard uptake value (SUV). Hematoxylin and eosin (H&E) staining was performed to establish neoplasm and immunohistochemistry (IHC) was performed to determine histological similarities with human FFPE biopsies. The MSI/microsatellite stable (MSS) status was determined. Finally, the tumors were extensively characterized at the molecular level to establish similarities with human CRC tumors. The model KPC: APC animals are conditional mutants that developed colonic tumors upon induction with tamoxifen in a dose-dependent manner. The tumors were confirmed to be malignant within four weeks of induction by H&E staining and higher radioactive [18F] fluoro-2-deoxyglucose (FDG) uptake (SUV) in micro-PET scan. Furthermore, the tumors histologically and molecularly resembled human colorectal carcinoma. Post tumor generation, the KPC: APC animals died of cachexia and rectal bleeding. Implications: This model is an excellent preclinical platform to molecularly characterize the KRAS mutated colorectal tumors and discern appropriate therapeutic strategies to improve disease management and overall survival.
Goals and Challenges in Bacterial Phosphoproteomics
Authors: Yagüe Paula , Gonzalez-Quiñonez Nathaly , Fernández-García Gemma , Alonso-Fernández Sergio , Manteca Angel
Published: November 2019

Reversible protein phosphorylation at serine, threonine and tyrosine is a well-known dynamic post-translational modification with stunning regulatory and signalling functions in eukaryotes. Shotgun phosphoproteomic analyses revealed that this post-translational modification is dramatically lower in bacteria than in eukaryotes. However, Ser/Thr/Tyr phosphorylation is present in all analysed bacteria (24 eubacteria and 1 archaea). It affects central processes, such as primary and secondary metabolism development, sporulation, pathogenicity, virulence or antibiotic resistance. Twenty-nine phosphoprotein orthologues were systematically identified in bacteria: ribosomal proteins, enzymes from glycolysis and gluconeogenesis, elongation factors, cell division proteins, RNA polymerases, ATP synthases and enzymes from the citrate cycle. While Ser/Thr/Tyr phosphorylation exists in bacteria, there is a consensus that histidine phosphorylation is the most abundant protein phosphorylation in prokaryotes. Unfortunately, histidine shotgun phosphorproteomics is not possible due to the reduced phosphohistidine half-life under the acidic pH conditions used in standard LC-MS/MS analysis. However, considering the fast and continuous advances in LC-MS/MS-based phosphoproteomic methodologies, it is expected that further innovations will allow for the study of His phosphoproteomes and a better coverage of bacterial phosphoproteomes. The characterisation of the biological role of bacterial Ser/Thr/Tyr and His phosphorylations might revolutionise our understanding of prokaryotic physiology.
Epigenetic Mechanisms and Posttranslational Modifications in Systemic Lupus Erythematosus
Authors: Navarro Quiroz Elkin , Chavez-Estrada Valeria , Macias-Ochoa Karime , Ayala-Navarro María Fernanda , Flores-Aguilar Aniyensy Sarai , Morales-Navarrete Francisco , de la Cruz Lopez Fernando , Gomez Escorcia Lorena , Musso Carlos G. , Aroca Martinez Gustavo , Gonzales Torres Henry , Diaz Perez Anderson , Cadena Bonfanti Andres , Sarmiento Gutierrez Joany , Meza Jainy , Diaz Arroyo Esperanza , Bello Lemus Yesit , Ahmad Mostapha , Navarro Quiroz Roberto
Published: November 2019

The complex physiology of eukaryotic cells is regulated through numerous mechanisms, including epigenetic changes and posttranslational modifications. The wide-ranging diversity of these mechanisms constitutes a way of dynamic regulation of the functionality of proteins, their activity, and their subcellular localization as well as modulation of the differential expression of genes in response to external and internal stimuli that allow an organism to respond or adapt to accordingly. However, alterations in these mechanisms have been evidenced in several autoimmune diseases, including systemic lupus erythematosus (SLE). The present review aims to provide an approach to the current knowledge of the implications of these mechanisms in SLE pathophysiology.
The Importance of HLA Assessment in “Off-the-Shelf” Allogeneic Mesenchymal Stem Cells Based-Therapies
Authors: Kot Marta , Baj-Krzyworzeka Monika , Szatanek Rafał , Musiał-Wysocka Aleksandra , Suda-Szczurek Magdalena , Majka Marcin
Published: November 2019

The need for more effective therapies of chronic and acute diseases has led to the attempts of developing more adequate and less invasive treatment methods. Regenerative medicine relies mainly on the therapeutic potential of stem cells. Mesenchymal stem cells (MSCs), due to their immunosuppressive properties and tissue repair abilities, seem to be an ideal tool for cell-based therapies. Taking into account all available sources of MSCs, perinatal tissues become an attractive source of allogeneic MSCs. The allogeneic MSCs provide “off-the-shelf” cellular therapy, however, their allogenicity may be viewed as a limitation for their use. Moreover, some evidence suggests that MSCs are not as immune-privileged as it was previously reported. Therefore, understanding their interactions with the recipient’s immune system is crucial for their successful clinical application. In this review, we discuss both autologous and allogeneic application of MSCs, focusing on current approaches to allogeneic MSCs therapies, with a particular interest in the role of human leukocyte antigens (HLA) and HLA-matching in allogeneic MSCs transplantation. Importantly, the evidence from the currently completed and ongoing clinical trials demonstrates that allogeneic MSCs transplantation is safe and seems to cause no major side-effects to the patient. These findings strongly support the case for MSCs efficacy in treatment of a variety of diseases and their use as an “off-the-shelf” medical product.
Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα) Pemafibrate
Authors: Sasaki Yusuke , Raza-Iqbal Sana , Tanaka Toshiya , Murakami Kentaro , Anai Motonobu , Osawa Tsuyoshi , Matsumura Yoshihiro , Sakai Juro , Kodama Tatsuhiko
Published: November 2019

Pemafibrate is the first clinically-available selective peroxisome proliferator-activated receptor α modulator (SPPARMα) that has been shown to effectively improve hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. Global gene expression analysis reveals that the activation of PPARα by pemafibrate induces fatty acid (FA) uptake, binding, and mitochondrial or peroxisomal oxidation as well as ketogenesis in mouse liver. Pemafibrate most profoundly induces HMGCS2 and PDK4, which regulate the rate-limiting step of ketogenesis and glucose oxidation, respectively, compared to other fatty acid metabolic genes in human hepatocytes. This suggests that PPARα plays a crucial role in nutrient flux in the human liver. Additionally, pemafibrate induces clinically favorable genes, such as ABCA1, FGF21, and VLDLR. Furthermore, pemafibrate shows anti-inflammatory effects in vascular endothelial cells. Pemafibrate is predicted to exhibit beneficial effects in patients with atherogenic dyslipidemia and diabetic microvascular complications.
The Alteration of CTNNBIP1 in Lung Cancer
Authors: Chang Jia-Ming , Tsai Alexander Charng-Dar , Huang Way-Ren , Tseng Ruo-Chia
Published: November 2019

β-catenin is a major component of the Wnt/β-catenin signaling pathway, and is known to play a role in lung tumorigenesis. β-catenin-interacting protein 1 (CTNNBIP1) is a known repressor of β-catenin transactivation. However, little is known about the role of CTNNBIP1 in lung cancer. The aim of this study was to carry out a molecular analysis of CTNNBIP1 and its effect on β-catenin signaling, using samples from lung cancer patients and various lung cancer cell lines. Our results indicate a significant inverse correlation between the CTNNBIP1 mRNA expression levels and the CTNNBIP1 promoter hypermethylation, which suggests that the promoter hypermethylation is responsible for the low levels of CTNNBIP1 present in many lung cancer patient samples. The ectopic expression of CTNNBIP1 is able to reduce the β-catenin transactivation; this then brings about a decrease in the expression of β-catenin-targeted genes, such as matrix metalloproteinase 7 (MMP7). Conversely, CTNNBIP1 knockdown is able to increase β-catenin transactivation and the expression of MMP7. In agreement with these findings, a low level of CTNNBIP1 was found to be correlated with a high level of MMP7 when a publicly available microarray dataset for lung cancer was analyzed. Also, in agreement with the above, the ectopic expression of CTNNBIP1 inhibits the migration of lung cancer cells, whereas the CTNNBIP1 knockdown increases cancer cell migration. Our findings suggest that CTNNBIP1 is a suppressor of cancer migration, thus making it a potential prognostic predictor for lung cancer.
High-Pressure Synthesis, Crystal Structure, and Photoluminescence Properties of β-Y2B4O9:Eu3+
Authors: Fuchs Birgit , Schröder Franziska , Heymann Gunter , Jüstel Thomas , Huppertz Hubert
Published: November 2019

A high-pressure/high-temperature experiment at 7.5 GPa and 1673 K led to the formation of the new compound β-Y2B4O9. In contrast to the already known polymorph α-Y2B4O9, which crystallizes in the space group C2/c, the reported structure could be solved via single-crystal X-ray diffraction in the triclinic space group P 1 ¯ (no. 2) and is isotypic to the already known lanthanide borates β-Dy2B4O9 and β-Gd2B4O9. Furthermore, the photoluminescence of an europium doped sample of β-Y2B4O9:Eu3+ (8%) was investigated.
Descriptive Bacterial and Fungal Characterization of Propolis Using Ultra-High-Throughput Marker Gene Sequencing
Authors: Garcia-Mazcorro Jose F. , Kawas Jorge R. , Marroquin-Cardona Alicia G.
Published: November 2019

Bees harbor microorganisms that are important for host health, physiology, and survival. Propolis helps modulate the immune system and health of the colony, but little information is available about its microbial constituents. Total genomic DNA from samples of natural propolis from Apis mellifera production hives from four locations in Mexico were used to amplify a region of the 16S rRNA gene (bacteria) and the internal transcriber spacer (fungi), using PCR. The Illumina MiSeq platform was used to sequence PCR amplicons. Extensive variation in microbial composition was observed between the propolis samples. The most abundant bacterial group was Rhodopila spp. (median: 14%; range: 0.1%–27%), a group with one of the highest redox potential in the microbial world. Other high abundant groups include Corynebacterium spp. (median: 8.4%; 1.6%–19.5%) and Sphingomonas spp. (median: 5.9%; 0.03%–14.3%), a group that has been used for numerous biotechnological applications because of its biodegradative capabilities. Bacillus and Prevotella spp. alone comprised as much as 88% (53% and 35%, respectively) of all bacterial microbiota in one sample. Candida (2%–43%), Acremonium (0.03%–25.2%), and Aspergillus (0.1%–43%) were among the most abundant fungi. The results contribute to a better understanding of the factors associated with the health of Apis mellifera production hives.
Molybdenum Oxides Coatings for High Demanding Accelerator Components
Authors: Scifo Jessica , Marcelli Augusto , Spataro Bruno , Hampai Dariush , Dabagov Sultan , Sarti Stefano , Di Trolio Antonio , Moscatelli Riccardo , Macis Salvatore , Faillace Luigi
Published: November 2019

Large electric gradients are required for a variety of new applications, notably including the extreme high brightness electron sources for X-ray free electron lasers (FELs), radio-frequency (RF) photo-injectors, industrial and medical accelerators, and linear accelerators for particle physics colliders. In the framework of the INFN-LNF, SLAC (USA), KEK (Japan), UCLA (Los Angeles) collaboration, the Frascati National Laboratories (LNF) are involved in the modelling, development, and testing of RF structures devoted to particles acceleration by high gradient electric fields of particles through metal devices. In order to improve the maximum sustainable gradients in normal-conducting RF-accelerating structures, both the RF breakdown and dark current should be minimized. To this purpose, studying new materials as well as manufacturing techniques are mandatory to identify better solutions to such extremely requested applications. In this contribution, we discuss the possibility of using a dedicated coating on a solid copper sample (and other metals) with a relatively thick film to improve and optimize breakdown performances and to minimize the dark current. We present here the first characterization of MoO3 films deposited on copper by pulsed-laser deposition (PLD).
Vulnerability to Psychosis, Ideas of Reference and Evaluation with an Implicit Test
Authors: Bendala-Rodríguez Pedro , Senín-Calderón Cristina , Peluso-Crespi Leonardo , Rodríguez-Testal Juan
Published: November 2019

Background: Ideas of reference (IRs) are observed in the general population on the continuum of the psychotic phenotype (as a type of psychotic-like experiences, PLE). The instruments usually used to evaluate IRs show some problems: They depend on the cooperation of the participant, comprehension of items, social desirability, etc. Aims: The Testal emotional counting Stroop (TECS) was developed for the purpose of improving evaluation of individuals vulnerable to psychosis and its relationship with ideas of reference. The TECS (two versions) was applied as an implicit evaluation instrument for IRs and related processes for early identification of persons vulnerable to psychosis and to test the possible influence of emotional symptomatology. Method: A total of 160 participants (67.5% women) from the general population were selected (Mean (M) = 24.12 years, standard deviation (SD) = 5.28), 48 vulnerable and 112 non-vulnerable. Results: Vulnerability to psychosis was related to greater latency in response to referential stimuli. Version 4 of the TECS showed a slight advantage in identifying more latency in response to referential stimuli among participants with vulnerability to psychosis (Cohen’s d = 1.08). Emotional symptomatology (especially stress), and IQ (premorbid) mediated the relationship between vulnerability and IR response latency. Conclusions: The application of the implicit Testal emotional counting Stroop test (TECS) is useful for evaluating processes related to vulnerability to psychosis, as demonstrated by the increased latency of response to referential stimuli.
Recent Advances in Liquid Biopsy Based on Circulating Tumor DNA
Authors: Sakuma Yu , Fujii Keita , Han Jiayan , Takahashi Ryou-u
Published: November 2019

Many types of cells secrete DNA, RNA, and proteins through microvesicles, such as exosomes and apoptotic bodies, for the purpose of extracellular communication [...]