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Life, Volume 10, Issue 9 (September 2020) – 62 articles

Cover Story (view full-size image): The peptidyl transferase center of the modern ribosome has been previously found to encompass an area of twofold pseudosymmetry (SymR). We verify that this structure is highly conserved with respect to both ribosome transition state and phylogenetic diversity. The possible role of six non-standard interactions between the A-region and the P-region is discussed, as is the effect that magnesium may have had in the coordination, stabilization, association, and evolutionary history of the two halves. View this paper
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13 pages, 264 KiB  
Article
Correlation between Expression Profiles of Key Signaling Genes in Colorectal Cancer Samples from Type 2 Diabetic and Non-Diabetic Patients
by Zsuzsanna Elek, Zsolt Rónai, Gergely Keszler, László Harsányi, Endre Kontsek, Zoltán Herold, Magdolna Herold, Anikó Somogyi and Zsófia Bánlaki
Life 2020, 10(9), 216; https://doi.org/10.3390/life10090216 - 22 Sep 2020
Cited by 2 | Viewed by 1923
Abstract
Several lines of epidemiological and biochemical evidence support the association of type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC). T2DM has been shown to impinge on the transcriptome of colon tumor cells, promoting their proliferation and invasion. In order to gain insight [...] Read more.
Several lines of epidemiological and biochemical evidence support the association of type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC). T2DM has been shown to impinge on the transcriptome of colon tumor cells, promoting their proliferation and invasion. In order to gain insight into diabetes-specific modulation of colon cancer signaling, we analyzed gene expression patterns of more than five hundred genes encoding signaling proteins on TaqMan OpenArray panels from colonoscopic colorectal tumor samples of type 2 diabetic and non-diabetic patients. In total, 48 transcripts were found to be differentially expressed in tumors of T2DM patients as compared to healthy colon samples. Enrichment analysis with the g:GOSt (Gene Ontology Statistics) functional profiling tool revealed that the underlying genes can be classified into five signaling pathways (in decreasing order of significance: Wnt (wingless-type)/β-catenin; Hippo; TNF (tumor necrosis factor); PI3K/Akt (phosphoinositide-3 kinase/protein kinase B), and platelet activation), implying that targeted downregulation of these signaling cascades might help combat CRC in diabetic patients. Transcript levels of some of the differentially expressed genes were also measured from surgically removed diabetic and non-diabetic CRC specimens by individual qPCR (quantitative real-time PCR) assays using the adjacent normal tissue mRNA levels as an internal control. The most significantly altered genes in diabetic tumor samples were largely different from those in non-diabetic ones, implying that T2DM profoundly alters the expression of signaling genes and presumably the biological characteristics of CRC. Full article
(This article belongs to the Section Medical Research)
20 pages, 2563 KiB  
Article
Case Report: Identification of a Novel Variant (m.8909T>C) of Human Mitochondrial ATP6 Gene and Its Functional Consequences on Yeast ATP Synthase
by Qiuju Ding, Róża Kucharczyk, Weiwei Zhao, Alain Dautant, Shutian Xu, Katarzyna Niedzwiecka, Xin Su, Marie-France Giraud, Kewin Gombeau, Mingchao Zhang, Honglang Xie, Caihong Zeng, Marine Bouhier, Jean-Paul di Rago, Zhihong Liu, Déborah Tribouillard-Tanvier and Huimei Chen
Life 2020, 10(9), 215; https://doi.org/10.3390/life10090215 - 22 Sep 2020
Cited by 7 | Viewed by 2629
Abstract
With the advent of next generation sequencing, the list of mitochondrial DNA (mtDNA) mutations identified in patients rapidly and continuously expands. They are frequently found in a limited number of cases, sometimes a single individual (as with the case herein reported) and in [...] Read more.
With the advent of next generation sequencing, the list of mitochondrial DNA (mtDNA) mutations identified in patients rapidly and continuously expands. They are frequently found in a limited number of cases, sometimes a single individual (as with the case herein reported) and in heterogeneous genetic backgrounds (heteroplasmy), which makes it difficult to conclude about their pathogenicity and functional consequences. As an organism amenable to mitochondrial DNA manipulation, able to survive by fermentation to loss-of-function mtDNA mutations, and where heteroplasmy is unstable, Saccharomyces cerevisiae is an excellent model for investigating novel human mtDNA variants, in isolation and in a controlled genetic context. We herein report the identification of a novel variant in mitochondrial ATP6 gene, m.8909T>C. It was found in combination with the well-known pathogenic m.3243A>G mutation in mt-tRNALeu. We show that an equivalent of the m.8909T>C mutation compromises yeast adenosine tri-phosphate (ATP) synthase assembly/stability and reduces the rate of mitochondrial ATP synthesis by 20–30% compared to wild type yeast. Other previously reported ATP6 mutations with a well-established pathogenicity (like m.8993T>C and m.9176T>C) were shown to have similar effects on yeast ATP synthase. It can be inferred that alone the m.8909T>C variant has the potential to compromise human health. Full article
(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)
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8 pages, 224 KiB  
Communication
Seroprevalence of Antibodies against SARS-CoV-2 among the Personnel and Students of the National and Kapodistrian University of Athens, Greece: A Preliminary Report
by Ourania E. Tsitsilonis, Dimitrios Paraskevis, Evi Lianidou, Vassilios Pierros, Athanasios Akalestos, Efstathios Kastritis, Paraskevi Moutsatsou, Andreas Scorilas, Thomas Sphicopoulos, Evangelos Terpos, Nikolaos Thomaidis, Athanassios Tsakris, Nikolaos Voulgaris, Christina C. Daskalaki, Zoi Evangelakou, Christina Fouki, Despoina D. Gianniou, Sentiljana Gumeni, Evangelia-Georgia Kostaki, Ioannis V. Kostopoulos, Maria S. Manola, Nikolaos Orologas-Stavrou, Chrysanthi Panteli, Eleni-Dimitra Papanagnou, Pantelis Rousakis, Aimilia D. Sklirou, Stavroula Smilkou, Dimitra Stergiopoulou, Ioannis P. Trougakos, Soritios Tsiodras, Petros P. Sfikakis and Meletios-Athanasios Dimopoulosadd Show full author list remove Hide full author list
Life 2020, 10(9), 214; https://doi.org/10.3390/life10090214 - 21 Sep 2020
Cited by 24 | Viewed by 4592
Abstract
Due to early implementation of public health measures, Greece had low number of SARS-CoV-2 infections and COVID-19 severe incidents in hospitalized patients. The National and Kapodistrian University of Athens (ΝΚUA), especially its health-care/medical personnel, has been actively involved in the first line of [...] Read more.
Due to early implementation of public health measures, Greece had low number of SARS-CoV-2 infections and COVID-19 severe incidents in hospitalized patients. The National and Kapodistrian University of Athens (ΝΚUA), especially its health-care/medical personnel, has been actively involved in the first line of state responses to COVID-19. To estimate the prevalence of antibodies (Igs) against SARS-CoV-2 among NKUA members, we designed a five consecutive monthly serosurvey among randomly selected NKUA consenting volunteers. Here, we present the results from the first 2500 plasma samples collected during June–July 2020. Twenty-five donors were tested positive for anti-SARS-CoV-2 Igs; thus, the overall seroprevalence was 1.00%. The weighted overall seroprevalence was 0.93% (95% CI: 0.27, 2.09) and varied between males [1.05% (95% CI: 0.18, 2.92)] and females [0.84% (95% CI: 0.13, 2.49)], age-groups and different categories (higher in participants from the School of Health Sciences and in scientific affiliates/faculty members/laboratory assistants), but no statistical differences were detected. Although focused on the specific population of NKUA members, our study shows that the prevalence of anti-SARS-CoV-2 Igs for the period June–July 2020 remained low and provides knowledge of public health importance for the NKUA members. Given that approximately one in three infections was asymptomatic, continuous monitoring of the progression of the pandemic by assessing Ig seroprevalence is needed. Full article
(This article belongs to the Special Issue Ecology, Evolution and Epidemiology of Coronaviruses)
14 pages, 413 KiB  
Review
Current Progress and Perspective: Clinical Imaging of Islet Transplantation
by Taylor Marie Richards, Aixia Sun, Hasaan Hayat, Neil Robertson, Zhaoda Zhang, Jinda Fan and Ping Wang
Life 2020, 10(9), 213; https://doi.org/10.3390/life10090213 - 19 Sep 2020
Cited by 5 | Viewed by 2759
Abstract
Islet transplantation has great potential as a cure for type 1 diabetes. At present; the lack of a clinically validated non-invasive imaging method to track islet grafts limits the success of this treatment. Some major clinical imaging modalities and various molecular probes, which [...] Read more.
Islet transplantation has great potential as a cure for type 1 diabetes. At present; the lack of a clinically validated non-invasive imaging method to track islet grafts limits the success of this treatment. Some major clinical imaging modalities and various molecular probes, which have been studied for non-invasive monitoring of transplanted islets, could potentially fulfill the goal of understanding pathophysiology of the functional status and viability of the islet grafts. In this current review, we summarize the recent clinical studies of a variety of imaging modalities and molecular probes for non-invasive imaging of transplanted beta cell mass. This review also includes discussions on in vivo detection of endogenous beta cell mass using clinical imaging modalities and various molecular probes, which will be useful for longitudinally detecting the status of islet transplantation in Type 1 diabetic patients. For the conclusion and perspectives, we highlight the applications of multimodality and novel imaging methods in islet transplantation. Full article
(This article belongs to the Section Radiobiology and Nuclear Medicine)
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11 pages, 977 KiB  
Article
The Impact of a Nanocellulose-Based Wound Dressing in the Management of Thermal Injuries in Children: Results of a Retrospective Evaluation
by Julia Cattelaens, Laura Turco, Luc M. Berclaz, Birgit Huelsse, Wolfgang Hitzl, Tobias Vollkommer and Karl J. Bodenschatz
Life 2020, 10(9), 212; https://doi.org/10.3390/life10090212 - 19 Sep 2020
Cited by 17 | Viewed by 3668
Abstract
The aim of this retrospective study is to evaluate for the first time the impact of a nanocellulose-based wound dressing in the treatment of pediatric patients with both partial- and deep-thickness burns. Usability and effectiveness were defined based on parameters such as frequency [...] Read more.
The aim of this retrospective study is to evaluate for the first time the impact of a nanocellulose-based wound dressing in the treatment of pediatric patients with both partial- and deep-thickness burns. Usability and effectiveness were defined based on parameters such as frequency of dressing changes under narcosis, duration of hospital stay, onset of complications, need for additional treatments, and follow up scar formation assessment. Fifty-six children who sustained burns in the year 2018 and were treated with a nanocellulose-based wound dressing were included in the trial. The mean stay in hospital was 6.7 days. Patients underwent dressing changes under narcosis 2.4 times on average, and none had wound-associated infection. In all, 82% of the patients were treated only with nanocellulose-based wound dressings, and reepithelialization occurred after ten days. The majority of patients had scars with normal pigmentation (98%), vascularization (91%), height (92%), and pliability (92%). In conclusion, using a nanocellulose-based wound dressing for the treatment of both superficial, partial-thickness and deep, full-thickness burns has several advantages. Compared with the results published in literature on other wound dressings, it requires a moderate number of dressing changes under narcosis and results in short hospital stays. Additionally, it has a low associated infection rate and promotes wound healing. Full article
(This article belongs to the Section Medical Research)
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18 pages, 1374 KiB  
Article
The Association between Periodontitis and Human Colorectal Cancer: Genetic and Pathogenic Linkage
by Federica Di Spirito, Paolo Toti, Vincenzo Pilone, Francesco Carinci, Dorina Lauritano and Ludovico Sbordone
Life 2020, 10(9), 211; https://doi.org/10.3390/life10090211 - 18 Sep 2020
Cited by 34 | Viewed by 2493
Abstract
Periodontitis has been associated with an increased risk of and mortality associated with human colorectal cancer (CRC). Current evidence attributes such an association to the direct and indirect effects of virulence factors belonging to periodontal pathogens, to inflammatory mediators and to genetic factors. [...] Read more.
Periodontitis has been associated with an increased risk of and mortality associated with human colorectal cancer (CRC). Current evidence attributes such an association to the direct and indirect effects of virulence factors belonging to periodontal pathogens, to inflammatory mediators and to genetic factors. The aims of the study were to assess the existence of a genetic linkage between periodontitis and human CRC, to identify genes considered predominant in such a linkage, thus named leader genes, and to determine pathogenic mechanisms related to the products of leader genes. Genes linking periodontitis and CRC were identified and classified in order of predominance, through an experimental investigation, performed via computer simulation, employing the leader gene approach. Pathogenic mechanisms relating to leader genes were determined through cross-search databases. Of the 83 genes linking periodontitis and CRC, 12 were classified as leader genes and were pathogenically implicated in cell cycle regulation and in the immune-inflammatory response. The current results, obtained via computer simulation and requiring further validation, support the existence of a genetic linkage between periodontitis and CRC. Cell cycle dysregulation and the alteration of the immuno-inflammatory response constitute the pathogenic mechanisms related to the products of leader genes. Full article
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15 pages, 937 KiB  
Article
Association of Genes Related to Oxidative Stress with the Extent of Coronary Atherosclerosis
by Milena Racis, Anna Stanisławska-Sachadyn, Wojciech Sobiczewski, Marcin Wirtwein, Michał Krzemiński, Natalia Krawczyńska, Janusz Limon, Andrzej Rynkiewicz and Marcin Gruchała
Life 2020, 10(9), 210; https://doi.org/10.3390/life10090210 - 18 Sep 2020
Cited by 3 | Viewed by 2178
Abstract
Oxidative stress is believed to play a critical role in atherosclerosis initiation and progression. In line with this, in a group of 1099 subjects, we determined eight single nucleotide polymorphisms (SNPs) related to oxidative stress (PON1 c.575A>G, MPO c.−463G>A, SOD2 c.47T>C, GCLM [...] Read more.
Oxidative stress is believed to play a critical role in atherosclerosis initiation and progression. In line with this, in a group of 1099 subjects, we determined eight single nucleotide polymorphisms (SNPs) related to oxidative stress (PON1 c.575A>G, MPO c.−463G>A, SOD2 c.47T>C, GCLM c.−590C>T, NOS3 c.894G>T, NOS3 c.−786T>C, CYBA c.214C>T, and CYBA c.−932A>G) and assessed the extent of atherosclerosis in coronary arteries based on Gensini score. An increased risk of having a Gensini score in the higher half of the distribution was observed for the PON1 c.575G allele (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.004–1.617, p = 0.046). Next, the genetic risk score (GRS) for the additive effect of the total number of pro-oxidative alleles was assessed. We noted an increase in the risk of having a Gensini score above the median with the maximum number of risk alleles (OR = 2.47, 95% CI: 1.19–5.23, p = 0.014). A univariate Spearman’s test revealed significant correlation between the total number of pro-oxidant alleles (GRS) and the Gensini score (ρ = 0.068, p = 0.03). In conclusion, the PON1 c.575A>G variant and the high number of risk alleles (GRS) were independent risk factors for a high Gensini score. We suggest, however, that GRS might occur as a more valuable component in adding a predictive value to the genetic background of atherosclerosis. Full article
(This article belongs to the Section Genetics and Genomics)
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9 pages, 1847 KiB  
Article
Comparing Three Different Extraction Techniques on Essential Oil Profiles of Cultivated and Wild Lotus (Nelumbo nucifera) Flower
by Chun-Yun Zhang and Mingquan Guo
Life 2020, 10(9), 209; https://doi.org/10.3390/life10090209 - 16 Sep 2020
Cited by 10 | Viewed by 3083
Abstract
Essential oil components of Nelumbo nucifera flowers from cultivated and wild lotus samples were analyzed and compared using three different extraction techniques, i.e., headspace extraction (HE), steam distillation (SD) and solvent extraction (SE), coupled with GC-MS. Forty-two peaks in the GC-MS analysis were [...] Read more.
Essential oil components of Nelumbo nucifera flowers from cultivated and wild lotus samples were analyzed and compared using three different extraction techniques, i.e., headspace extraction (HE), steam distillation (SD) and solvent extraction (SE), coupled with GC-MS. Forty-two peaks in the GC-MS analysis were identified as essential oil components extracted by the three methods from N. nucifera flower. The major essential oil components extracted by SD method were found to be Z,Z-10,12-hexadecadienal and E-14-hexadecenal with relative contents of 16.3% and 16.7%, respectively, which is different from that of SE method, i.e., n-hexadecanoic acid and Z,Z-9,12-octadecadienoic acid accounting for 25.8% and 26.8%, respectively. HE method demonstrated a possibility to be used as an in situ and simplest method for extracting the essential oil components from raw materials. By adding a small amount of glycerinum onto the surface of the air-dried flower sample as a solvent trap in the HE method, the volatility of the essential oil components was found to increase by two times for the first time, which could be further utilized to improve the extraction efficiency and the recovery of the essential oil components from other materials for more applications. In addition, the comparison of essential oil components between cultivated and wild samples showed that they differed only in the chemical contents but not in chemical components. This will be a comprehensive report on the chemical information of the essential oil components of N. nucifera flower and provide guidance for its further exploration as high value-added products in the food and healthcare industries. Full article
(This article belongs to the Section Plant Science)
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15 pages, 340 KiB  
Review
Treatment of Advanced Melanoma: Past, Present and Future
by Taku Fujimura, Yumi Kambayashi, Kentaro Ohuchi, Yusuke Muto and Setsuya Aiba
Life 2020, 10(9), 208; https://doi.org/10.3390/life10090208 - 16 Sep 2020
Cited by 19 | Viewed by 3103
Abstract
Therapeutic options for treating advanced melanoma are progressing rapidly. Until six years ago, the regimen for treating advanced melanoma mainly comprised cytotoxic agents such as dacarbazine, and type I interferons. Since 2014, anti-programmed cell death 1 (PD1) antibodies have become recognized as anchor [...] Read more.
Therapeutic options for treating advanced melanoma are progressing rapidly. Until six years ago, the regimen for treating advanced melanoma mainly comprised cytotoxic agents such as dacarbazine, and type I interferons. Since 2014, anti-programmed cell death 1 (PD1) antibodies have become recognized as anchor drugs for treating advanced melanoma with or without additional combination drugs such as ipilimumab. In addition, v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) kinase inhibitors in combination with mitogen-activated protein kinase kinase (MEK) inhibitors are among the most promising chemotherapeutic regimens for treating advanced BRAF-mutant melanoma, especially in patients with low tumor burden. Since anti-PD1 antibodies are widely applicable for the treatment of both BRAF wild-type and mutated advanced melanomas, several clinical trials for drugs in combination with anti-PD1 antibodies are ongoing. This review focuses on the development of the anti-melanoma therapies available today, and discusses the clinical trials of novel regimens for the treatment of advanced melanoma. Full article
(This article belongs to the Special Issue Melanoma: Dark Tumor with Little Light for Metastasis Treatment)
18 pages, 2565 KiB  
Review
Osteoclasts and Microgravity
by John Kelly Smith
Life 2020, 10(9), 207; https://doi.org/10.3390/life10090207 - 16 Sep 2020
Cited by 22 | Viewed by 4658
Abstract
Astronauts are at risk of losing 1.0% to 1.5% of their bone mass for every month they spend in space despite their adherence to diets and exercise regimens designed to protect their musculoskeletal systems. This loss is the result of microgravity-related impairment of [...] Read more.
Astronauts are at risk of losing 1.0% to 1.5% of their bone mass for every month they spend in space despite their adherence to diets and exercise regimens designed to protect their musculoskeletal systems. This loss is the result of microgravity-related impairment of osteocyte and osteoblast function and the consequent upregulation of osteoclast-mediated bone resorption. This review describes the ontogeny of osteoclast hematopoietic stem cells and the contributions macrophage colony stimulating factor, receptor activator of the nuclear factor-kappa B ligand, and the calcineurin pathways make in osteoclast differentiation and provides details of bone formation, the osteoclast cytoskeleton, the immune regulation of osteoclasts, and osteoclast mechanotransduction on Earth, in space, and under conditions of simulated microgravity. The article discusses the need to better understand how osteoclasts are able to function in zero gravity and reviews current and prospective therapies that may be used to treat osteoclast-mediated bone disease. Full article
(This article belongs to the Special Issue New Insights in Osteoclasts’ Biology)
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18 pages, 6442 KiB  
Article
Did a Complex Carbon Cycle Operate in the Inner Solar System?
by Joseph A. Nuth, Frank T. Ferguson, Hugh G. M. Hill and Natasha M. Johnson
Life 2020, 10(9), 206; https://doi.org/10.3390/life10090206 - 16 Sep 2020
Cited by 2 | Viewed by 2048
Abstract
Solids in the interstellar medium consist of an intimate mixture of silicate and carbonaceous grains. Because 99% of silicates in meteorites were reprocessed at high temperatures in the inner regions of the Solar Nebula, we propose that similar levels of heating of carbonaceous [...] Read more.
Solids in the interstellar medium consist of an intimate mixture of silicate and carbonaceous grains. Because 99% of silicates in meteorites were reprocessed at high temperatures in the inner regions of the Solar Nebula, we propose that similar levels of heating of carbonaceous materials in the oxygen-rich Solar Nebula would have converted nearly all carbon in dust and grain coatings to CO. We discuss catalytic experiments on a variety of grain surfaces that not only produce gas phase species such as CH4, C2H6, C6H6, C6H5OH, or CH3CN, but also produce carbonaceous solids and fibers that would be much more readily incorporated into growing planetesimals. CH4 and other more volatile products of these surface-mediated reactions were likely transported outwards along with chondrule fragments and small Calcium Aluminum-rich Inclusions (CAIs) to enhance the organic content in the outer regions of the nebula where comets formed. Carbonaceous fibers formed on the surfaces of refractory oxides may have significantly improved the aggregation efficiency of chondrules and CAIs. Carbonaceous fibers incorporated into chondritic parent bodies might have served as the carbon source for the generation of more complex organic species during thermal or hydrous metamorphic processes on the evolving asteroid. Full article
(This article belongs to the Special Issue Chemical Evolution of Organic Molecules in Solar System Small Bodies)
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16 pages, 4016 KiB  
Article
Diacylglycerol Acetyltransferase Gene Isolated from Euonymus europaeus L. Altered Lipid Metabolism in Transgenic Plant towards the Production of Acetylated Triacylglycerols
by Daniel Mihálik, Andrea Lančaričová, Michaela Mrkvová, Šarlota Kaňuková, Jana Moravčíková, Miroslav Glasa, Zdeno Šubr, Lukáš Predajňa, Richard Hančinský, Simona Grešíková, Michaela Havrlentová, Pavol Hauptvogel and Ján Kraic
Life 2020, 10(9), 205; https://doi.org/10.3390/life10090205 - 16 Sep 2020
Cited by 3 | Viewed by 2350
Abstract
Euonymus species from the Celastraceae family are considered as a source of unusual genes modifying the oil content and fatty acid composition of vegetable oils. Due to the possession of genes encoding enzyme diacylglycerol acetyltransferase (DAcT), Euonymus plants can synthesize and accumulate acetylated [...] Read more.
Euonymus species from the Celastraceae family are considered as a source of unusual genes modifying the oil content and fatty acid composition of vegetable oils. Due to the possession of genes encoding enzyme diacylglycerol acetyltransferase (DAcT), Euonymus plants can synthesize and accumulate acetylated triacyglycerols. The gene from Euonymus europaeus (EeDAcT) encoding the DAcT was identified, isolated, characterized, and modified for cloning and genetic transformation of plants. This gene has a unique nucleotide sequence and amino acid composition, different from orthologous genes from other Euonymus species. Nucleotide sequence of original EeDAcT gene was modified, cloned into transformation vector, and introduced into tobacco plants. Overexpression of EeDAcT gene was confirmed, and transgenic host plants produced and accumulated acetylated triacylglycerols (TAGs) in immature seeds. Individual transgenic plants showed difference in amounts of synthesized acetylTAGs and also in fatty acid composition of acetylTAGs. Full article
(This article belongs to the Special Issue Metabolism of Photosynthetic Organisms)
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11 pages, 990 KiB  
Article
Palmitate but Not Oleate Exerts a Negative Effect on Oxygen Utilization in Myoblasts of Patients with the m.3243A>G Mutation: A Pilot Study
by Leila Motlagh Scholle, Helena Schieffers, Samiya Al-Robaiy, Annemarie Thaele, Diana Lehmann Urban and Stephan Zierz
Life 2020, 10(9), 204; https://doi.org/10.3390/life10090204 - 16 Sep 2020
Cited by 1 | Viewed by 2277
Abstract
It is known that exposure to excess saturated fatty acids, especially palmitate, can trigger cellular stress responses interpreted as lipotoxicity. The effect of excessive free fatty acids on oxidative phosphorylation capacity in myoblasts of patients with the m.3243A>G mutation was evaluated with the [...] Read more.
It is known that exposure to excess saturated fatty acids, especially palmitate, can trigger cellular stress responses interpreted as lipotoxicity. The effect of excessive free fatty acids on oxidative phosphorylation capacity in myoblasts of patients with the m.3243A>G mutation was evaluated with the mitochondrial (Mito) stress test using a Seahorse XF96 analyzer. ß-oxidation, measured with the Seahorse XF96 analyzer, was similar in patients and controls, and reduced in both patients and controls at 40 °C compared to 37 °C. Mito stress test in the absence of fatty acids showed lower values in patients compared to controls. The mitochondrial activity and ATP production rates were significantly reduced in presence of palmitate, but not of oleate in patients, showing a negative effect of excessive palmitate on mitochondrial function in patients. Diabetes mellitus is a frequent symptom in patients with m.3243A>G mutation. It can be speculated that the negative effect of palmitate on mitochondrial function might be related to diacylglycerols (DAG) and ceramides (CER) mediated insulin resistance. This might contribute to the elevated risk for diabetes mellitus in m.3243A>G patients. Full article
(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)
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17 pages, 1675 KiB  
Article
A Single Faecal Microbiota Transplantation Altered the Microbiota of Weaned Pigs
by Tanya L. Nowland, Valeria A. Torok, Wai Y. Low, Kate J. Plush, Mary D. Barton and Roy N. Kirkwood
Life 2020, 10(9), 203; https://doi.org/10.3390/life10090203 - 15 Sep 2020
Cited by 5 | Viewed by 2438
Abstract
Weaning is a stressful time for piglets, often leading to weight loss and is associated with increased morbidity and mortality. A leading cause for these post-weaning problems is enteric dysbiosis and methods to improve piglet health at this crucial developmental stage are needed. [...] Read more.
Weaning is a stressful time for piglets, often leading to weight loss and is associated with increased morbidity and mortality. A leading cause for these post-weaning problems is enteric dysbiosis and methods to improve piglet health at this crucial developmental stage are needed. This study aimed to determine whether an enteric dysbiosis caused by weaning could be corrected via a faecal microbiota transplantation (FMT) from healthy piglets from a previous wean. Two or four focal piglets per litter were assigned to one of two treatments; FMT two days post weaning (n = 21; FMT) or a control which received saline two days post weaning (n = 21; CON). FMT consisted of homogenised donor faeces administered orally at 3 mL/kg. Weaning occurred at 18 days of age and weights and faecal samples were collected on days 18, 20, 24 and 35. 16S rRNA amplicon analysis was used to assess the faecal microbiota of piglets. FMT increased Shannon’s diversity post weaning (p < 0.001) and reduced the scratch score observed at 24 days of age (p < 0.001). The bacterial populations significantly differed in composition at each taxonomic level. In FMT pigs, significant increases in potentially pathogenic Escherichia coli were observed. However, increases in beneficial bacteria Lactobacillus mucosae and genera Fibrobacteres and Bacteroidetes were also observed in FMT treated animals. To our knowledge, this is the first study to observe a significant effect on piglet faecal microbiota following a single FMT administered post weaning. Therefore, FMT post weaning can potentially alleviate enteric dysbiosis. Full article
(This article belongs to the Special Issue Microbiome–Animal Interaction)
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8 pages, 563 KiB  
Communication
Evidence of Pepsin-Related Ocular Surface Damage and Dry Eye (PROD Syndrome) in Patients with Laryngopharyngeal Reflux
by Rocco Plateroti, Marta Sacchetti, Giuseppe Magliulo, Andrea Maria Plateroti, Annalisa Pace, Antonietta Moramarco, Alessandro Lambiase and Alice Bruscolini
Life 2020, 10(9), 202; https://doi.org/10.3390/life10090202 - 15 Sep 2020
Cited by 9 | Viewed by 2868
Abstract
Background: patients with laryngopharyngeal reflux (LPR) showed detectable levels of tear pepsin that explain the nasolacrimal obstruction. The purpose of this study was to determine whether patients with LPR show ocular surface changes and to investigate the relationship between lacrimal pepsin concentration and [...] Read more.
Background: patients with laryngopharyngeal reflux (LPR) showed detectable levels of tear pepsin that explain the nasolacrimal obstruction. The purpose of this study was to determine whether patients with LPR show ocular surface changes and to investigate the relationship between lacrimal pepsin concentration and ocular alterations. Methods: Fifty patients with positive endoscopic signs for LPR and an equal or higher score of 13 and 7 for Reflux Symptom Index and Reflux Finding Score were enrolled. Twenty healthy patients with no reflux disease and dry eye were included as the control group. After evaluation of ocular discomfort symptoms, the tear break-up time test, corneal staining, and tear sampling were performed. Tear pepsin levels were measured using Pep-testTM kit. Results: Patients with LPR showed ocular surface changes including epithelial damage (48%) and impairment of lacrimal function (72%). Tear pepsin levels were detectable in 32 out of 50 (64%) patients with LPR (mean ± SD: 55.4 ± 67.5 ng/mL) and in none of the control subjects. Most of the LPR patients complained of ocular discomfort symptoms, including itching (38%), redness (56%), or foreign body sensation (40%). Tear pepsin levels were significantly correlated with the severity of LPR disease and with ocular surface changes. Conclusions: A multidisciplinary approach, including ophthalmological evaluation, should be considered in order to improve the management of patients with LPR. Full article
(This article belongs to the Section Medical Research)
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14 pages, 2789 KiB  
Article
Further Characterization of the Pseudo-Symmetrical Ribosomal Region
by Mario Rivas and George E. Fox
Life 2020, 10(9), 201; https://doi.org/10.3390/life10090201 - 14 Sep 2020
Cited by 8 | Viewed by 2732
Abstract
The peptidyl transferase center of the modern ribosome has been found to encompass an area of twofold pseudosymmetry (SymR). This observation strongly suggests that the very core of the ribosome arose from a dimerization event between two modest-sized RNAs. It was previously shown [...] Read more.
The peptidyl transferase center of the modern ribosome has been found to encompass an area of twofold pseudosymmetry (SymR). This observation strongly suggests that the very core of the ribosome arose from a dimerization event between two modest-sized RNAs. It was previously shown that at least four non-standard interactions exist between the two halves of SymR. Herein, we verify that the structure of the SymR is highly conserved with respect to both ribosome transition state and phylogenetic diversity. These comparisons also reveal two additional sites of interaction between the two halves of SymR and refine our understanding of the previously known interactions. In addition, the possible role that magnesium may have in the coordination, stabilization, association, and evolutionary history of the two halves (A-region and P-region) was examined. Together, the results identify a likely site where structural elements and Mg2+ ions may have facilitated the ligation of two aboriginal RNAs into a single unit. Full article
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13 pages, 3089 KiB  
Article
Exercise Preconditioning Attenuates the Response to Experimental Colitis and Modifies Composition of Gut Microbiota in Wild-Type Mice
by Jinkyung Cho, Donghyun Kim and Hyunsik Kang
Life 2020, 10(9), 200; https://doi.org/10.3390/life10090200 - 14 Sep 2020
Cited by 10 | Viewed by 2493
Abstract
This study investigated the suppressive effect of exercise preconditioning against colitis induced by high-fat diet (HF) plus dextran sulfate sodium (DSS) in wild-type mice. Male mice (C57BL/6) aged 6 weeks were assigned to standard chow (SC, n = 10) or HF (n [...] Read more.
This study investigated the suppressive effect of exercise preconditioning against colitis induced by high-fat diet (HF) plus dextran sulfate sodium (DSS) in wild-type mice. Male mice (C57BL/6) aged 6 weeks were assigned to standard chow (SC, n = 10) or HF (n = 10) or HF followed by DSS (HF+DSS, n = 10) or exercise preconditioning (EX) followed by HF+DSS (EX+HF+DSS, n = 10) for a total of 15 weeks. After 12 weeks of dietary treatments and/or exercise preconditioning, mice in the DSS groups were subjected to administration of 2 cycles of 5-day DSS (2% w/v) with a 7-day interval between cycles. HF resulted in colitis symptoms and histological changes, infiltration of immunity cells, decreased gut barrier proteins, increased pro-inflammatory and chemotactic cytokines and decreased anti-inflammatory cytokine such as adiponectin, which deteriorated after administration of DSS. Exercise preconditioning alleviated HF+DSS-induced colitis and caused significant modifications in gut microbiota: decreased Bacteroides vulgatus (p = 0.050) and increased Akkermansia muciniphila (p = 0.050). The current findings suggest that exercise preconditioning attenuates the severity of HF+DSS-induced colitis in C57BL/6 mice. Full article
(This article belongs to the Section Medical Research)
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12 pages, 2262 KiB  
Article
Discovery of N-glycan Biomarkers for the Canine Osteoarthritis
by Hyunjun Lee, Ahyun Lee, Nari Seo, Jiwon Oh, Oh-Kyeong Kweon, Hyun Joo An and Jaehan Kim
Life 2020, 10(9), 199; https://doi.org/10.3390/life10090199 - 14 Sep 2020
Cited by 4 | Viewed by 2531
Abstract
Protein glycosylation is a post-translational modification that impacts on protein activity, stability, and interactions. It was sensitively altered by the cellular state and, therefore, is now used for a diagnostic or prognostic indicator of various human diseases such as cancer. To evaluate the [...] Read more.
Protein glycosylation is a post-translational modification that impacts on protein activity, stability, and interactions. It was sensitively altered by the cellular state and, therefore, is now used for a diagnostic or prognostic indicator of various human diseases such as cancer. To evaluate the clinical feasibility in the veterinary area, the N-glycan biomarkers were discovered from canine serum for the diagnosis of osteoarthritis (OA), which is one of the most common diseases of dogs. N-glycome was obtained from 20 μL of canine serum by the enzymatic cleavage followed by the purification and enrichment using solid-phase extraction. Independent compositions of 163 and 463 N-glycans were found from healthy control (n = 41) and osteoarthritis patients (n = 92), respectively. Initially, 31 of the potential biomarkers were screened by the p-values below 1.0 × 10−10 from ANOVA. Then, the area under the curve (AUC) and the intensity ratio between OA patient and healthy control (P/C ratio) were calculated. Considering the diagnostic efficacy, the AUC bigger than 0.9 and the P/C ratio larger than 3.0 were used to discover 16 N-glycans as diagnostic biomarkers. Particularly, five of the diagnostic biomarkers were AUC above 0.99 and three of N-glycans had AUC 1.0. The results suggest a clear possibility for N-glycan biomarkers to be used as a clinical tool in the veterinary medical area enabling to provide objective and non-invasive diagnostic information. Full article
(This article belongs to the Special Issue Osteoarthritis Pathology and Treatment)
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16 pages, 891 KiB  
Review
Noninvasive Tests (NITs) for Hepatic Fibrosis in Fatty Liver Syndrome
by Ma Ai Thanda Han
Life 2020, 10(9), 198; https://doi.org/10.3390/life10090198 - 13 Sep 2020
Cited by 10 | Viewed by 7034
Abstract
Fatty liver syndrome is an emerging health problem in the world, due to the high prevalence of obesity and alcohol use disorder. Given the nature of the disease’s advancement to cirrhosis and liver-related complications, it is important to assess the severity of the [...] Read more.
Fatty liver syndrome is an emerging health problem in the world, due to the high prevalence of obesity and alcohol use disorder. Given the nature of the disease’s advancement to cirrhosis and liver-related complications, it is important to assess the severity of the disease, which is typically done via a liver biopsy. Due to the limitations and risks of liver biopsy, the role of noninvasive tests is essential and evolving to stratify the stage of the liver disease, predict the outcomes, and/or monitor the treatment response. This review is focused on noninvasive tests, including the use of serum-based biomarkers, ultrasound-based shear wave elastography, transient elastography, and magnetic resonance elastography in both clinical and research settings. Full article
(This article belongs to the Special Issue Fatty Liver Syndrome)
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10 pages, 2266 KiB  
Review
From Bench to Bedside in Tongue Muscle Cancer Invasion and Back again: Gross Anatomy, Microanatomy, Surgical Treatments and Basic Research
by Luca Calabrese, Maria Eleonora Bizzoca, Roberto Grigolato, Fausto Antonio Maffini, Marta Tagliabue, Rosa Negro, Stefania Leuci, Michele Davide Mignogna and Lorenzo Lo Muzio
Life 2020, 10(9), 197; https://doi.org/10.3390/life10090197 - 12 Sep 2020
Cited by 9 | Viewed by 2958
Abstract
Tongue squamous cell carcinoma is the most common malignancy in the oral cavity. Despite advances in diagnosis and treatment, the prognosis of advanced states has not significantly improved. Depth of invasion, pattern of invasion such as tumor budding grade, lingual lymph node metastasis [...] Read more.
Tongue squamous cell carcinoma is the most common malignancy in the oral cavity. Despite advances in diagnosis and treatment, the prognosis of advanced states has not significantly improved. Depth of invasion, pattern of invasion such as tumor budding grade, lingual lymph node metastasis in early stages, collective cell migration and circulating tumor cells in peripheral blood are some examples of the mechanisms that are currently receiving increasing attention in the evaluation of the prognosis of tongue cancers. Anatomic-based surgery showed that it is possible to improve loco-regional control of tongue cancer. In patients with a “T-N tract involvement”, there is significantly more distant recurrence (40%) in patients undergoing a compartmental tongue surgery. In general, the neoplastic infiltration of the lingual muscles is traced back to the finding of neoplastic tissue along the course of a muscle; however, the muscle fibers, due to their spatial conformation and the organization of the extracellular matrix, could influence the movement of tumor cells through the muscle, leaving its three-dimensional structure unchanged. We need to exclude the possibility that tongue muscle fibers represent a mechanism for the diffusion of cancer cells without muscle invasion. Full article
(This article belongs to the Special Issue Oral Cancer—Diagnosis and Therapeutics 2020)
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12 pages, 2181 KiB  
Article
Integrated RNA-seq Analysis Indicates Asynchrony in Clock Genes between Tissues under Spaceflight
by Shin-ichiro Fujita, Lindsay Rutter, Quang Ong and Masafumi Muratani
Life 2020, 10(9), 196; https://doi.org/10.3390/life10090196 - 11 Sep 2020
Cited by 13 | Viewed by 5549
Abstract
Rodent models have been widely used as analogs for estimating spaceflight-relevant molecular mechanisms in human tissues. NASA GeneLab provides access to numerous spaceflight omics datasets that can potentially generate novel insights and hypotheses about fundamental space biology when analyzed in new and integrated [...] Read more.
Rodent models have been widely used as analogs for estimating spaceflight-relevant molecular mechanisms in human tissues. NASA GeneLab provides access to numerous spaceflight omics datasets that can potentially generate novel insights and hypotheses about fundamental space biology when analyzed in new and integrated fashions. Here, we performed a pilot study to elucidate space biological mechanisms across tissues by reanalyzing mouse RNA-sequencing spaceflight data archived on NASA GeneLab. Our results showed that clock gene expressions in spaceflight mice were altered compared with those in ground control mice. Furthermore, the results suggested that spaceflight promotes asynchrony of clock gene expressions between peripheral tissues. Abnormal circadian rhythms are associated not only with jet lag and sleep disorders but also with cancer, lifestyle-related diseases, and mental disorders. Overall, our findings highlight the importance of elucidating the causes of circadian rhythm disruptions using the unique approach of space biology research to one day potentially develop countermeasures that benefit humans on Earth and in space. Full article
(This article belongs to the Collection Space Life Sciences)
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15 pages, 3583 KiB  
Article
The Effects of Metformin on the Gut Microbiota of Patients with Type 2 Diabetes: A Two-Center, Quasi-Experimental Study
by Hanako Nakajima, Fumie Takewaki, Yoshitaka Hashimoto, Shizuo Kajiyama, Saori Majima, Hiroshi Okada, Takafumi Senmaru, Emi Ushigome, Naoko Nakanishi, Masahide Hamaguchi, Masahiro Yamazaki, Yoshiki Tanaka, Yousuke Oikawa, Shunji Nakajima, Hiroshi Ohno and Michiaki Fukui
Life 2020, 10(9), 195; https://doi.org/10.3390/life10090195 - 11 Sep 2020
Cited by 20 | Viewed by 6660
Abstract
Metformin is reported to affect human gut microbiota; however, the nature of this association in Japanese patients with type 2 diabetes mellitus (T2DM) is unknown. We enrolled 31 patients with T2DM who took metformin for the first time in this study. We compared [...] Read more.
Metformin is reported to affect human gut microbiota; however, the nature of this association in Japanese patients with type 2 diabetes mellitus (T2DM) is unknown. We enrolled 31 patients with T2DM who took metformin for the first time in this study. We compared them before and after four weeks of taking metformin. Fecal samples were collected and 16S rDNA sequences were performed to identify the gut microbiota. Blood samples and Gastrointestinal Symptom Rating Scale (GSRS) questionnaire results, denoting gastro-intestinal symptoms, were also collected. In the whole-group analysis, no significant differences were found at the phylum level. In a subgroup of 21 patients that excluding those using medications affecting gut microbiota, there was a significant decrease of the phylum Firmicutes (p = 0.042) and of the ratio of the Firmicutes and Bacteroidetes abundances (p = 0.04) after taking metformin. Changes in abdominal pain (r = −0.56, p = 0.008) and regurgitation (r = −0.53, p = 0.01) were associated with Parabacteroides. Despite there being no direct association with abdominal symptoms, our study revealed that the composition of gut microbiota in Japanese individuals with T2DM partially changed after starting metformin. Full article
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11 pages, 338 KiB  
Article
Pregnancy Outcomes in Late Onset Pompe Disease
by Ozlem Goker-Alpan, Vellore G. Kasturi, Maninder K. Sohi, Renuka P. Limgala, Stephanie L. Austin, Tabitha Jennelle, Maryam Banikazemi and Priya S. Kishnani
Life 2020, 10(9), 194; https://doi.org/10.3390/life10090194 - 11 Sep 2020
Cited by 4 | Viewed by 2671
Abstract
There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In [...] Read more.
There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2–0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes. Full article
(This article belongs to the Special Issue Reproductive Health Concerns for Women)
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8 pages, 841 KiB  
Article
Effect of Astaxanthin on the Expression and Activity of Aquaporin-3 in Skin in an In-Vitro Study
by Nobutomo Ikarashi, Risako Kon, Chika Nagoya, Airi Ishikura, Yuri Sugiyama, Jiro Takahashi and Kiyoshi Sugiyama
Life 2020, 10(9), 193; https://doi.org/10.3390/life10090193 - 11 Sep 2020
Cited by 11 | Viewed by 4461
Abstract
Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione) is a red lipophilic pigment with strong antioxidant action. Oral or topical administration of astaxanthin has been reported to improve skin function, including increasing skin moisture. In this study, we examined the mechanism by which astaxanthin improves skin function by focusing [...] Read more.
Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione) is a red lipophilic pigment with strong antioxidant action. Oral or topical administration of astaxanthin has been reported to improve skin function, including increasing skin moisture. In this study, we examined the mechanism by which astaxanthin improves skin function by focusing on the water channel aquaporin-3 (AQP3), which plays important roles in maintaining skin moisture and function. When astaxanthin was added to PHK16-0b or HaCaT cells, the mRNA expression level of AQP3 increased significantly in a concentration-dependent manner in both cell lines. The AQP3 protein expression level was also confirmed to increase when astaxanthin was added to HaCaT cells. Similarly, when astaxanthin was added to 3D human epidermis model EpiSkin, AQP3 expression increased. Furthermore, when glycerol and astaxanthin were simultaneously added to EpiSkin, glycerol permeability increased significantly compared with that observed for the addition of glycerol alone. We demonstrated that astaxanthin increases AQP3 expression in the skin and enhances AQP3 activity. This result suggests that the increased AQP3 expression in the skin is associated with the increase in skin moisture by astaxanthin. Thus, we consider astaxanthin useful for treating dry skin caused by decreased AQP3 due to factors such as diabetes mellitus and aging. Full article
(This article belongs to the Special Issue Aquaporins and Human Health)
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10 pages, 5536 KiB  
Communication
Protein-Coding Genes in Euarchontoglires with Pseudogene Homologs in Humans
by Lev I. Rubanov, Oleg A. Zverkov, Gregory A. Shilovsky, Alexandr V. Seliverstov and Vassily A. Lyubetsky
Life 2020, 10(9), 192; https://doi.org/10.3390/life10090192 - 10 Sep 2020
Cited by 1 | Viewed by 2393
Abstract
An original bioinformatics technique is developed to identify the protein-coding genes in rodents, lagomorphs and nonhuman primates that are pseudogenized in humans. The method is based on per-gene verification of local synteny, similarity of exon-intronic structures and orthology in a set of genomes. [...] Read more.
An original bioinformatics technique is developed to identify the protein-coding genes in rodents, lagomorphs and nonhuman primates that are pseudogenized in humans. The method is based on per-gene verification of local synteny, similarity of exon-intronic structures and orthology in a set of genomes. It is applicable to any genome set, even with the number of genomes exceeding 100, and efficiently implemented using fast computer software. Only 50 evolutionary recent human pseudogenes were predicted. Their functional homologs in model species are often associated with the immune system or digestion and mainly express in the testes. According to current evidence, knockout of most of these genes leads to an abnormal phenotype. Some genes were pseudogenized or lost independently in human and nonhuman hominoids. Full article
(This article belongs to the Section Genetics and Genomics)
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13 pages, 1040 KiB  
Article
The Effect of Tobacco Smoking and Smoking Cessation on Urinal miRNAs in a Pilot Study
by Zdenka Navratilova, Stanislav Losse, Pavla Petrova, Katerina Sikorova, Alzbeta Chabronova and Martin Petrek
Life 2020, 10(9), 191; https://doi.org/10.3390/life10090191 - 10 Sep 2020
Cited by 2 | Viewed by 2099
Abstract
The diseases associated with tobacco smoking affect miRNAs and small single-stranded non-coding RNAs. However, there are no data on urinal miRNAs in healthy smokers. We searched for the possible effect of smoking and smoking cessation on miRNA urine expression. For screening, Affymetrix miRNA [...] Read more.
The diseases associated with tobacco smoking affect miRNAs and small single-stranded non-coding RNAs. However, there are no data on urinal miRNAs in healthy smokers. We searched for the possible effect of smoking and smoking cessation on miRNA urine expression. For screening, Affymetrix miRNA 4.0 arrays were used in 33 urine samples obtained from six never smokers and from current smokers in three time-points before smoking cessation (n = 10), after short time abstinence (3–8 weeks), and after long-term abstinence (1 year). For validation, a quantitative (q) polymerase chain reaction (PCR) method was used in 93 urine samples obtained from 18 never smokers and 25 current smokers in three time-points before smoking cessation, after short time abstinence (3–8 weeks), and after long-term abstinence (1 year). In screening analysis, 5 miRNAs (hsa-miR-3620-5p, hsa-miR-3613-5p, hsa-miR-3921, hsa-miR-5094, and hsa-miR-337-3p) were dysregulated in current vs. never smokers after multiple testing corrections. Smoking cessation was accompanied by miRNA dysregulation that did not reach a significant level after a multiple testing correction. In validation analysis, three miRNAs correlated with cotinine, but they were affected neither after smoking cessation nor between current and never smokers. Our whole-genome screening of 2.578 miRNAs and validation suggest that tobacco smoking has no or only a small effect on urinal miRNAs. Full article
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12 pages, 11334 KiB  
Article
Suppression of the Swallowing Reflex during Rhythmic Jaw Movements Induced by Repetitive Electrical Stimulation of the Dorsomedial Part of the Central Amygdaloid Nucleus in Rats
by Yoshihide Satoh and Kojun Tsuji
Life 2020, 10(9), 190; https://doi.org/10.3390/life10090190 - 10 Sep 2020
Cited by 5 | Viewed by 1792
Abstract
A previous study indicated that the swallowing reflex is inhibited during rhythmic jaw movements induced by electrical stimulation of the anterior cortical masticatory area. Rhythmic jaw movements were induced by electrical stimulation of the central amygdaloid nucleus (CeA). The swallowing central pattern generator [...] Read more.
A previous study indicated that the swallowing reflex is inhibited during rhythmic jaw movements induced by electrical stimulation of the anterior cortical masticatory area. Rhythmic jaw movements were induced by electrical stimulation of the central amygdaloid nucleus (CeA). The swallowing central pattern generator is the nucleus of the solitary tract (NTS) and the lateral reticular formation in the medulla. Morphological studies have reported that the CeA projects to the NTS and the lateral reticular formation. It is therefore likely that the CeA is related to the control of the swallowing reflex. The purpose of this study was to determine if rhythmic jaw movements driven by CeA had inhibitory roles in the swallowing reflex induced by electrical stimulation of the superior laryngeal nerve (SLN). Rats were anesthetised with urethane. The SLN was solely stimulated for 10 s, and the swallowing reflex was recorded (SLN stimulation before SLN + CeA stimulation). Next, the SLN and the CeA were electrically stimulated at the same time for 10 s, and the swallowing reflex was recorded during rhythmic jaw movements (SLN + CeA stimulation). Finally, the SLN was solely stimulated (SLN stimulation following SLN + CeA stimulation). The number of swallows was reduced during rhythmic jaw movements. The onset latency of the first swallow was significantly longer in the SLN + CeA stimulation than in the SLN stimulation before SLN + CeA stimulation and SLN stimulation following SLN + CeA stimulation. These results support the idea that the coordination of swallowing reflex with rhythmic jaw movements could be regulated by the CeA. Full article
(This article belongs to the Section Evolutionary Biology)
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11 pages, 4330 KiB  
Article
Helios Expression in Tumor-Infiltrating Lymphocytes Correlates with Overall Survival of Advanced Gastric Cancer Patients
by Wei-Ming Chen, Jing-Lan Liu, Huei-Chieh Chuang, Yong-Lin Chang, Chia-Ming Yeh, Cheng-Shyong Wu and Shu-Fen Wu
Life 2020, 10(9), 189; https://doi.org/10.3390/life10090189 - 10 Sep 2020
Cited by 1 | Viewed by 2433
Abstract
Immunotherapy is a highly promising approach for the treatment of gastric cancer, the third-leading cause of overall cancer death worldwide. In particular, tumor-infiltrating lymphocytes and peripheral blood mononuclear cells are believed to mediate host immune responses, although this activity may vary depending on [...] Read more.
Immunotherapy is a highly promising approach for the treatment of gastric cancer, the third-leading cause of overall cancer death worldwide. In particular, tumor-infiltrating lymphocytes and peripheral blood mononuclear cells are believed to mediate host immune responses, although this activity may vary depending on the activation status and/ or their microenvironments. Here, we examined the expression of a specific zinc finger transcription factor, Helios (IKZF2), in gastric tumor-infiltrating lymphocytes by immunohistochemistry and the correlation with survival. Segregation of gastric cancer patients into high- vs. low-Helios-expressing tumor-infiltrating lymphocytes showed those with high expression to exhibit longer survival in gastric cancer patients, Helicobacter pylori-infected gastric cancer patients and advanced stage (III–IV) gastric cancer patients. In particular, Helios expression was an independent factor for survival in advanced gastric cancer patients. We performed immunofluorescence staining to detect Helios expression in tumor-infiltrating lymphocytes and peripheral blood mononuclear cells. We found that Helios is expressed more in CD4+ T cells and little in CD8+ T cells in infiltrated lymphocytes in gastric cancer. In summary, we believe that the study of specific characteristics of tumor-infiltrating lymphocytes can delineate the interactions of immune and tumor cells to improve upon immunotherapy strategies. Full article
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17 pages, 2812 KiB  
Article
The Molecular Effects of a High Fat Diet on Endometrial Tumour Biology
by Michael Wilkinson, Piriyah Sinclair, Ludmilla Dellatorre-Teixeira, Patrick Swan, Eoin Brennan, Bruce Moran, Dirk Wedekind, Paul Downey, Kieran Sheahan, Emer Conroy, William M. Gallagher, Neil Docherty, Carel le Roux and Donal J. Brennan
Life 2020, 10(9), 188; https://doi.org/10.3390/life10090188 - 10 Sep 2020
Cited by 4 | Viewed by 3010
Abstract
We sought to validate the BDII/Han rat model as a model for diet-induced obesity in endometrial cancer (EC) and determine if transcriptomic changes induced by a high fat diet (HFD) in an EC rat model can be used to identify novel biomarkers in [...] Read more.
We sought to validate the BDII/Han rat model as a model for diet-induced obesity in endometrial cancer (EC) and determine if transcriptomic changes induced by a high fat diet (HFD) in an EC rat model can be used to identify novel biomarkers in human EC. Nineteen BDII/Han rats were included. Group A (n = 7) were given ad lib access to a normal calorie, normal chow diet (NCD) while Group B (n = 12) were given ad lib access to a calorie rich HFD for 15 months. RNAseq was performed on endometrial tumours from both groups. The top-ranking differentially expressed genes (DEGs) were examined in the human EC using The Cancer Genome Atlas (TCGA) to assess if the BDII/Han rat model is an appropriate model for human obesity-induced carcinogenesis. Weight gain in HFD rats was double the weight gain of NCD rats (50 g vs. 25 g). The incidence of cancer was similar in both groups (4/7—57% vs. 4/12—33%; p = 0.37). All tumours were equivalent to a Stage 1A, Grade 2 human endometrioid carcinoma. A total of 368 DEGs were identified between the tumours in the HFD group compared to the NCD group. We identified two upstream regulators of the DEGs, mir-33 and Brd4, and a pathway analysis identified downstream enrichment of the colorectal cancer metastasis and ovarian cancer metastasis pathways. Top-ranking DEGs included Tex14, A2M, Hmgcs2, Adamts5, Pdk4, Crabp2, Capn12, Npw, Idi1 and Gpt. A2M expression was decreased in HFD tumours. Consistent with these findings, we found a significant negative correlation between A2M mRNA expression levels and BMI in the TCGA cohort (Spearman’s Rho = −0.263, p < 0.001). A2M expression was associated with improved overall survival (HR = 0.45, 95% CI 0.23–0.9, p = 0.024). Crabp2 expression was increased in HFD tumours. In human EC, CRABP2 expression was associated with reduced overall survival (HR = 3.554, 95% CI 1.875–6.753, p < 0.001). Diet-induced obesity can alter EC transcriptomic profiles. The BDII/Han rat model is a suitable model of diet-induced obesity in endometrial cancer and can be used to identify clinically relevant biomarkers in human EC. Full article
(This article belongs to the Section Medical Research)
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14 pages, 1653 KiB  
Article
Simultaneous Exposure of Cultured Human Lymphoblastic Cells to Simulated Microgravity and Radiation Increases Chromosome Aberrations
by Sakuya Yamanouchi, Jordan Rhone, Jian-Hua Mao, Keigi Fujiwara, Premkumar B. Saganti, Akihisa Takahashi and Megumi Hada
Life 2020, 10(9), 187; https://doi.org/10.3390/life10090187 - 10 Sep 2020
Cited by 18 | Viewed by 2917
Abstract
During space travel, humans are continuously exposed to two major environmental stresses, microgravity (μG) and space radiation. One of the fundamental questions is whether the two stressors are interactive. For over half a century, many studies were carried out in space, [...] Read more.
During space travel, humans are continuously exposed to two major environmental stresses, microgravity (μG) and space radiation. One of the fundamental questions is whether the two stressors are interactive. For over half a century, many studies were carried out in space, as well as using devices that simulated μG on the ground to investigate gravity effects on cells and organisms, and we have gained insights into how living organisms respond to μG. However, our knowledge on how to assess and manage human health risks in long-term mission to the Moon or Mars is drastically limited. For example, little information is available on how cells respond to simultaneous exposure to space radiation and μG. In this study, we analyzed the frequencies of chromosome aberrations (CA) in cultured human lymphoblastic TK6 cells exposed to X-ray or carbon ion under the simulated μG conditions. A higher frequency of both simple and complex types of CA were observed in cells exposed to radiation and μG simultaneously compared to CA frequency in cells exposed to radiation only. Our study shows that the dose response data on space radiation obtained at the 1G condition could lead to the underestimation of astronauts’ potential risk for health deterioration, including cancer. This study also emphasizes the importance of obtaining data on the molecular and cellular responses to irradiation under μG conditions. Full article
(This article belongs to the Special Issue Radiobiology in Space)
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