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Life, Volume 10, Issue 5 (May 2020) – 26 articles

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Cover Story (view full-size image) Human articular chondrocytes (HACs) synthetize the extracellular matrix (ECM) that confer cartilage [...] Read more.
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Open AccessArticle
Health-Related Quality of Life and Frailty in Chronic Liver Diseases
Life 2020, 10(5), 76; https://doi.org/10.3390/life10050076 - 24 May 2020
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Abstract
We sought to examine the relationship between frailty and health-related quality of life as evaluated using the 36-item Short-Form Health Survey (SF-36) questionnaire in Japanese chronic liver disease (CLD) patients (n = 341, 122 liver cirrhosis cases, median age = 66 years). [...] Read more.
We sought to examine the relationship between frailty and health-related quality of life as evaluated using the 36-item Short-Form Health Survey (SF-36) questionnaire in Japanese chronic liver disease (CLD) patients (n = 341, 122 liver cirrhosis cases, median age = 66 years). Frailty was defined as a clinical syndrome in which three or more of the following criteria were met (frailty score 3, 4, or 5): unintentional body weight loss, self-reported exhaustion, muscle weakness (grip strength: <26 kg in men and <18 kg in women), slow walking speed (<1.0 m/s), and low physical activity. Robust (frailty score 0), prefrail (frailty score 1 or 2), and frailty were found in 108 (31.7%), 187 (54.8%), and 46 (13.5%) patients, respectively. In all eight scales of the SF-36 (physical functioning, role physical, bodily pain, general health perception, vitality, social functioning, role emotion, and mental health), and the physical component summary score and mental component summary score, each score was well stratified according to the frailty status (all p < 0.0001). In the multivariate analysis, age (p = 0.0126), physical functioning (p = 0.0005), and vitality (p = 0.0246) were independent predictors linked to the presence of frailty. In conclusion, Japanese CLD patients with frailty displayed poorer conditions, both physically and mentally. Full article
(This article belongs to the Section Medical Research)
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Open AccessArticle
Trace Elements in Home-Processed Food Obtained from Unconventional Animals
Life 2020, 10(5), 75; https://doi.org/10.3390/life10050075 - 23 May 2020
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Abstract
Wild animals have been used as food since ancient times and, currently, the consumption of unconventional animals is increasing worldwide. The process of cooking meat using traditional recipes includes a variety of ingredients, which can influence the total metal intake from the diet. [...] Read more.
Wild animals have been used as food since ancient times and, currently, the consumption of unconventional animals is increasing worldwide. The process of cooking meat using traditional recipes includes a variety of ingredients, which can influence the total metal intake from the diet. In this study, the concentrations of eight essential (Fe, Zn, Cu, Mn, Se, Ni, Mo, and Co) and six non-essential (Pb, Cd, Hg, Al, As, and Cr) trace elements were determined in home-processed food obtained from snails and from three common species of game animals (woodcock, pheasant, and hare), seasoned with anchovies, mushrooms, and different vegetables using inductively coupled plasma mass spectrometry (ICP-MS). In general, Fe was the most abundant trace element, ranging from 18 ± 8 µg/g in pheasant to 99 ± 76 µg/g in snail, and Co was the least abundant, ranging from 0.007 ± 0.003 µg/g in hare to 0.093 ± 0.048 µg/g in snail. Regarding the non-essential trace elements, Pb concentrations showed wide variations, reaching a concentration of 17.30 µg/g in hare, while Cd concentrations were higher in snail, ranging from 0.18 to 0.46 µg/g. These alternative food sources can offer an important contribution to the human nutritional requirements of essential trace elements, in particular of Fe. The high concentrations of Pb and Cd present in some samples should be considered as potentially dangerous for the consumers. Full article
(This article belongs to the Section Animal Science)
Open AccessArticle
Exercise Training, Intermittent Fasting and Alkaline Supplementation as an Effective Strategy for Body Weight Loss: A 12-Week Placebo-Controlled Double-Blind Intervention with Overweight Subjects
Life 2020, 10(5), 74; https://doi.org/10.3390/life10050074 - 21 May 2020
Viewed by 339
Abstract
Background: Intermittent fasting (IF) combined with exercise has been suggested to enhance weight loss. However, both procedures might negatively influence acid–base status. The aim of this study was to determine the combined effects of IF, exercise training and alkaline supplementation in overweight subjects [...] Read more.
Background: Intermittent fasting (IF) combined with exercise has been suggested to enhance weight loss. However, both procedures might negatively influence acid–base status. The aim of this study was to determine the combined effects of IF, exercise training and alkaline supplementation in overweight subjects on body composition and running performance. Methods: 80 overweight subjects of age 45.5 ± 7.8 years were assigned to IF or non-intermittent fasting (nIF). Furthermore, subjects were randomly assigned to take either an alkaline supplement (IF-v, nIF-v) or a placebo (IF-p, nIF-p) twice a day. All subjects performed a personalized endurance exercise program (3–4 times/week for 12 weeks). Body weight, body composition, running performance and acid–base parameters were determined before (pre) and after the 12-week program (post). Results: 68 participants completed the study. There was a significant effect on body weight loss, body fat loss, visceral fat loss and running performance enhancement in all groups (p < 0.01) for pre and post measurements. Body weight decreased in all groups (IF-p: −5.80 ± 0.77 kg and nIF-p: −3.40 ± 0.58 kg; IF-v: −8.28 ± 0.75 kg and nIF-v: −5.59 ± 0.87 kg). In both dietary strategies, weight loss was significantly further enhanced by alkaline supplementation. The increase in running velocity was significantly higher in IF combined with alkaline supplementation (IF-v 1.73 ± 0.23 km/h and IF-p 0.97 ± 0.20 km/h). In addition, alkaline supplementation increased plasma HCO3 concentration and urinary pH. Conclusion: Exercise training in combination with IF and alkaline supplementation is an effective strategy to reduce body weight and improve running performance in a 12-week intervention. Full article
(This article belongs to the Section Medical Research)
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Open AccessArticle
Higher Responsiveness to Rosuvastatin in Polygenic versus Monogenic Hypercholesterolemia: A Propensity Score Analysis
Life 2020, 10(5), 73; https://doi.org/10.3390/life10050073 - 20 May 2020
Viewed by 324
Abstract
Background: The monogenic defect in familial hypercholesterolemia (FH) is detected in ∼40% of cases. The majority of mutation-negative patients have a polygenic cause of high LDL-cholesterol (LDL-C). We sought to investigate whether the underlying monogenic or polygenic defect is associated with the response [...] Read more.
Background: The monogenic defect in familial hypercholesterolemia (FH) is detected in ∼40% of cases. The majority of mutation-negative patients have a polygenic cause of high LDL-cholesterol (LDL-C). We sought to investigate whether the underlying monogenic or polygenic defect is associated with the response to rosuvastatin. Methods: FH Individuals were tested for mutations in LDLR and APOB genes. A previously established LDL-C-specific polygenic risk score (PRS) was used to examine the possibility of polygenic hypercholesterolemia in mutation-negative patients. All of the patients received rosuvastatin and they were followed for 8 ± 2 months. A propensity score analysis was performed to evaluate the variables associated with the response to treatment. Results: Monogenic subjects had higher mean (±SD) baseline LDL-C when compared to polygenic (7.6 ± 1.5 mmol/L vs. 6.2 ± 1.2 mmol/L; p < 0.001). Adjusted model showed a lower percentage of change in LDL-C after rosuvastatin treatment in monogenic patients vs. polygenic subjects (45.9% vs. 55.4%, p < 0.001). The probability of achieving LDL-C targets in monogenic FH was lower than in polygenic subjects (0.075 vs. 0.245, p = 0.004). Polygenic patients were more likely to achieve LDL-C goals, as compared to those monogenic (OR 3.28; 95% CI: 1.23–8.72). Conclusion: Our findings indicate an essentially higher responsiveness to rosuvastatin in FH patients with a polygenic cause, as compared to those carrying monogenic mutations. Full article
(This article belongs to the Section Medical Research)
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Open AccessReview
Ubiquitous Electron Transport in Non-Electron Transfer Proteins
Life 2020, 10(5), 72; https://doi.org/10.3390/life10050072 - 20 May 2020
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Abstract
Many proteins that have no known role in electron transfer processes are excellent electronic conductors. This surprising characteristic is not generally evident in bulk aggregates or crystals, or in isolated, solvated peptides, because the outer hydrophilic shell of the protein presents a barrier [...] Read more.
Many proteins that have no known role in electron transfer processes are excellent electronic conductors. This surprising characteristic is not generally evident in bulk aggregates or crystals, or in isolated, solvated peptides, because the outer hydrophilic shell of the protein presents a barrier to charge injection. Ligands that penetrate this barrier make excellent electrical contacts, yielding conductivities on the order of a S/m. The Fermi Energy of metal electrodes is aligned with the energy of internal electronic states of the protein, as evidenced by resonant transmission peaks at about 0.3V on the Normal Hydrogen Electrode scale. This energy is about 0.7 V less than the oxidation potential of aromatic amino acids, indicating a large reduction in electrostatic reorganization energy losses in the interior of the proteins. Consistent with a possible biological role for this conductance, there is a strong dependence on protein conformation. Thus, direct measurement of conductance is a powerful new way to read out protein conformation in real time, opening the way to new types of single molecule sensors and sequencing devices. Full article
(This article belongs to the Special Issue 10th Anniversary of Life—Recent Advances in Biophysics)
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Open AccessReview
Recent Advances in the Photoautotrophic Metabolism of Cyanobacteria: Biotechnological Implications
Life 2020, 10(5), 71; https://doi.org/10.3390/life10050071 - 19 May 2020
Viewed by 475
Abstract
Cyanobacteria constitute the only phylum of oxygen-evolving photosynthetic prokaryotes that shaped the oxygenic atmosphere of our planet. Over time, cyanobacteria have evolved as a widely diverse group of organisms that have colonized most aquatic and soil ecosystems of our planet and constitute a [...] Read more.
Cyanobacteria constitute the only phylum of oxygen-evolving photosynthetic prokaryotes that shaped the oxygenic atmosphere of our planet. Over time, cyanobacteria have evolved as a widely diverse group of organisms that have colonized most aquatic and soil ecosystems of our planet and constitute a large proportion of the biomass that sustains the biosphere. Cyanobacteria synthesize a vast array of biologically active metabolites that are of great interest for human health and industry, and several model cyanobacteria can be genetically manipulated. Hence, cyanobacteria are regarded as promising microbial factories for the production of chemicals from highly abundant natural resources, e.g., solar energy, CO2, minerals, and waters, eventually coupled to wastewater treatment to save costs. In this review, we summarize new important discoveries on the plasticity of the photoautotrophic metabolism of cyanobacteria, emphasizing the coordinated partitioning of carbon and nitrogen towards growth or compound storage, and the importance of these processes for biotechnological perspectives. We also emphasize the importance of redox regulation (including glutathionylation) on these processes, a subject which has often been overlooked. Full article
(This article belongs to the Section Microbiology and Engineering)
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Open AccessArticle
Subtypes of Depression: Latent Class Analysis in Spanish Old People with Depressive Symptoms
Life 2020, 10(5), 70; https://doi.org/10.3390/life10050070 - 18 May 2020
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Abstract
Major depressive disorder (MDD) is one of the most disabling disorders and the one that most contributes to disability. When it occurs in older people, it is an additional burden to their potential physical and cognitive deficiencies, making MDD an important public health [...] Read more.
Major depressive disorder (MDD) is one of the most disabling disorders and the one that most contributes to disability. When it occurs in older people, it is an additional burden to their potential physical and cognitive deficiencies, making MDD an important public health problem that supposes a large investment in health. There is a clear lack of consistency between the subtypes of depression found in the literature, ranging from two to seven classes, with three being the most commonly found non-melancholic, melancholic and psychotic, or putative psychotics. The aim of this research is to add knowledge to the profiles of depressive symptoms in a representative sample of older Spanish people, and to study the possible relationship of these symptom profiles with variables that have traditionally been related to depression. Spanish data from the sixth wave of SHARE were used, with 612 Spanish older adults living in Spain. A routine of several LCAs with a different number of classes was performed to answer this first aim to classify Spanish adults with depression symptoms. The results pointed out the presence of three different classes among the participants in the study: psychosomatic (11.12%), melancholic (14.21%), and anhedonic (74.67%). This work represents a step forward to understand the heterogeneity of major depressive disorder, facilitating the diagnosis, and subsequent treatment of older adults. Full article
(This article belongs to the Special Issue Mental Health Issues and Quality of Life in Older Individuals)
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Open AccessArticle
The Therapeutic Effectiveness of Full Spectrum Hemp Oil Using a Chronic Neuropathic Pain Model
Life 2020, 10(5), 69; https://doi.org/10.3390/life10050069 - 18 May 2020
Viewed by 1978
Abstract
Background: Few models exist that can control for placebo and expectancy effects commonly observed in clinical trials measuring ‘Cannabis’ pharmacodynamics. We used the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model to measure the effect of “full-spectrum” whole plant [...] Read more.
Background: Few models exist that can control for placebo and expectancy effects commonly observed in clinical trials measuring ‘Cannabis’ pharmacodynamics. We used the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model to measure the effect of “full-spectrum” whole plant extracted hemp oil on chronic neuropathic pain sensitivity in mice. Methods: Male BALBc mice were submitted to the FRICT-ION chronic neuropathic pain model with oral insertion through an incision in the buccal/cheek crease of 3 mm of chromic gut suture (4-0). The suture, wedged along the V2 trigeminal nerve branch, creates a continuous irritation that develops into secondary mechanical hypersensitivity on the snout. Von Frey filament stimuli on the mouse whisker pad was used to assess the mechanical pain threshold from 0–6 h following dosing among animals (n = 6) exposed to 5 μL of whole plant extracted hemp oil combined with a peanut butter vehicle (0.138 mg/kg), the vehicle alone (n = 3) 7 weeks post-surgery, or a naïve control condition (n = 3). Results: Mechanical allodynia was alleviated within 1 h (d = 2.50, p < 0.001) with a peak reversal effect at 4 h (d = 7.21, p < 0.001) and remained significant throughout the 6 h observation window. There was no threshold change on contralateral whisker pad after hemp oil administration, demonstrating the localization of anesthetic response to affected areas. Conclusion: Future research should focus on how whole plant extracted hemp oil affects multi-sensory and cognitive-attentional systems that process pain. Full article
(This article belongs to the Section Medical Research)
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Open AccessArticle
Identification of Differentially Expressed Gene Transcripts in Porcine Endometrium during Early Stages of Pregnancy
Life 2020, 10(5), 68; https://doi.org/10.3390/life10050068 - 16 May 2020
Viewed by 397
Abstract
During the early stages of pregnancy, the uterine endometrium undergoes dramatic morphologic and functional changes accompanied with dynamic variation in gene expression. Pregnancy-stage specific differentially expressed gene (DEG)-transcript-probes were investigated and identified by comparing endometrium transcriptome at 9th day (9D), 12th day (12D) [...] Read more.
During the early stages of pregnancy, the uterine endometrium undergoes dramatic morphologic and functional changes accompanied with dynamic variation in gene expression. Pregnancy-stage specific differentially expressed gene (DEG)-transcript-probes were investigated and identified by comparing endometrium transcriptome at 9th day (9D), 12th day (12D) and 16th day (16D) of early pregnancy in Polish large-white (PLW) gilts. Endometrium comparisons between 9D-vs-12D, 9D-vs-16D and 12D-vs-16D of early pregnancy identified 6049, 374 and 6034 highly significant DEG-transcript-probes (p < 0.001; >2 FC). GO term enrichment analysis identified commonly shared upregulated endometrial DEG-transcript-probes (p < 0.001; >2 FC), that were regulating the gene functions of anatomic structure development and transport (TG), DNA-binding and methyltransferase activity (ZBTB2), ion-binding and kinase activity (CKM), cell proliferation and apoptosis activity (IL1B). Downregulated DEG-transcript-probes (p < 0.001; >2 FC) were involved in regulating the gene functions of phosphatase activity (PTPN11), TC616413 gene-transcript and Sus-scrofa LOC100525539. Moreover, blastn comparison of microarray-probes sequences against sus-scrofa11 assembly identified commonly shared upregulated endometrial DEG-transcript-probes (E < 0.06; >2 FC), that were regulating the gene functions of reproduction and growth (SELENOP), cytoskeleton organization and kinase activity (CDC42BPA), phosphatase activity (MINPP1), enzyme-binding and cell-population proliferation (VAV3), cancer-susceptibility candidate gene (CASC4), cytoskeletal protein-binding (COBLL1), ion-binding, enzyme regulator activity (ACAP2) Downregulated endometrial DEG-transcript-probes (E < 0.06; >2FC) were involved in regulating the gene functions of signal-transduction (TMEM33), catabolic and metabolic processes (KLHL15). Microarray validation experiment on selected candidate genes showed complementarity to significant endometrial DEG-transcript-probes responsible for the regulation of immune response (IL1B, S100A11), lipid metabolism (FABP3, PPARG), cell-adhesion (ITGAV), angiogenesis (IL1B), intercellular transmission (NMB), cell-adhesion (OPN) and response to stimuli (RBP4) was confirmed by RT-PCR. This study provides a clue that identified pregnancy-stage specific microarray transcript probes could be considered as candidate genes for recognition and establishment of early pregnancy in the pig. Full article
(This article belongs to the Section Animal Science)
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Open AccessArticle
Crosslinked Hyaluronic Acid Gels for the Prevention of Intrauterine Adhesions after a Hysteroscopic Myomectomy in Women with Submucosal Myomas: A Prospective, Randomized, Controlled Trial
Life 2020, 10(5), 67; https://doi.org/10.3390/life10050067 - 15 May 2020
Viewed by 283
Abstract
Intrauterine adhesion (IUA), fibrosis, and scarring resulting from damage to the endometrium is a rare but serious clinical disease, contributing to a significant impairment of reproductive function. Uterine instrumentation, especially that of a hysteroscopic myomectomy, has become the main cause of IUA. Therefore, [...] Read more.
Intrauterine adhesion (IUA), fibrosis, and scarring resulting from damage to the endometrium is a rare but serious clinical disease, contributing to a significant impairment of reproductive function. Uterine instrumentation, especially that of a hysteroscopic myomectomy, has become the main cause of IUA. Therefore, a prospective randomized controlled study to assess the effectiveness and short-term safety of the use of hyaluronic acid gels in the prevention of IUA after a hysteroscopic myomectomy and an evaluation of the characteristics of IUA observed at follow-up are presented here. A total of 70 patients were analyzed at the end of 16 March 2020. The results show that the incidence of IUA in women who underwent a hysteroscopic myomectomy is 21.4% (15/70), overall. Women treated with hyaluronic acid gels have a statistically significantly lower incidence of IUAs than non-treated women (12.8% vs. 39.1%, p = 0.012). In addition, women in the anti-adhesive gel treatment group had a dramatically reduced severity of IUA than women in the no-treatment group (p = 0.002). Further analysis shows that the International Federation of Gynecology and Obstetrics (FIGO) classification type and the use of anti-adhesive gels are independent factors associated with moderate and severe degrees of IUA formation. The results here highlight the significant therapeutic benefits of the application of hyaluronic acid gels in women undergoing a hysteroscopic myomectomy, especially for those patients with a uterine myoma classified as FIGO type 2. Since the risk of IUA after a hysteroscopic myomectomy is high, especially for patients who have not received prophylactic anti-adhesive gels, the application of hyaluronic acid gels as a prevention strategy is highly recommended. More studies are encouraged to confirm our observation. Full article
(This article belongs to the Special Issue Reproductive Health Concerns for Women)
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Open AccessArticle
Biosignatures Associated with Freshwater Microbialites
Life 2020, 10(5), 66; https://doi.org/10.3390/life10050066 - 15 May 2020
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Abstract
Freshwater microbialites (i.e., lithifying microbial mats) are quite rare in northern latitudes of the North American continent, with two lakes (Pavilion and Kelly Lakes) of southeastern BC containing a morphological variety of such structures. We investigated Kelly Lake microbialites using carbon isotope systematics, [...] Read more.
Freshwater microbialites (i.e., lithifying microbial mats) are quite rare in northern latitudes of the North American continent, with two lakes (Pavilion and Kelly Lakes) of southeastern BC containing a morphological variety of such structures. We investigated Kelly Lake microbialites using carbon isotope systematics, phospholipid fatty acids (PLFAs) and quantitative PCR to obtain biosignatures associated with microbial metabolism. δ13CDIC values (mean δ13CDIC −4.9 ± 1.1‰, n = 8) were not in isotopic equilibrium with the atmosphere; however, they do indicate 13C-depleted inorganic carbon into Kelly Lake. The values of carbonates on microbialite surfaces (δ13C) fell within the range predicted for equilibrium precipitation from ambient lake water δ13CDIC (−2.2 to −5.3‰). Deep microbialites (26 m) had an enriched δ13Ccarb value of −0.3 ± 0.5‰, which is a signature of photoautotrophy. The deeper microbialites (>20 m) had higher biomass estimates (via PLFAs), and a greater relative abundance of cyanobacteria (measured by 16S copies via qPCR). The majority of PLFAs constituted monounsaturated and saturated PLFAs, which is consistent with gram-negative bacteria, including cyanobacteria. The central PLFA δ13C values were highly depleted (−9.3 to −15.7‰) relative to δ13C values of bulk organic matter, suggesting a predominance of photoautotrophy. A heterotrophic signature was also detected via the depleted iso- and anteiso-15:0 lipids (−3.2 to −5.2‰). Based on our carbonate isotopic biosignatures, PLFA, and qPCR measurements, photoautotrophy is enriched in the microbialites of Kelly Lake. This photoautotrophy enrichment is consistent with the microbialites of neighboring Pavilion Lake. This indication of photoautotrophy within Kelly Lake at its deepest depths raises new insights into the limits of measurable carbonate isotopic biosignatures under light and nutrient limitations. Full article
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Open AccessArticle
Identification and Validation of Aerobic Adaptation QTLs in Upland Rice
Life 2020, 10(5), 65; https://doi.org/10.3390/life10050065 - 14 May 2020
Viewed by 331
Abstract
The aerobic adaptation of upland rice is considered as the key genetic difference between upland rice and lowland rice. Genetic dissection of the aerobic adaptation is important as the basis for improving drought tolerance and terrestrial adaptation by using the upland rice. We [...] Read more.
The aerobic adaptation of upland rice is considered as the key genetic difference between upland rice and lowland rice. Genetic dissection of the aerobic adaptation is important as the basis for improving drought tolerance and terrestrial adaptation by using the upland rice. We raised BC1-BC3 introgression lines (ILs) in lowland rice Minghui 63 (MH63) background. The QTLs of yield and yield-related traits were detected based on ILs under the aerobic and lowland environments, and then the yield-related QTLs were identified in a backcrossed inbred population of BC4F5 under aerobic condition. We further verified phenotypes of QTL near-isogenic lines. Finally, three QTLs responsible for increasing yield in aerobic environment were detected by multiple locations and generations, which were designated as qAER1, qAER3, and qAER9 (QTL of aerobic adaptation). The qAER1 and qAER9 were fine-mapped. We found that qAER1 and qAER9 controlled plant height and heading date, respectively; while both of them increased yields simultaneously by suitable plant height and heading date without delay in the aerobic environment. The phenotypic differences between lowland rice and upland rice in the aerobic environment further supported the above results. We pyramided the two QTLs as corresponding molecular modules in the irrigated lowland rice MH63 background, and successfully developed a new upland rice variety named as Zhongkexilu 2. This study will lay the foundation for using aerobic adaptation QTLs in rice breeding programs and for further cloning the key genes involved in aerobic adaptation. Full article
(This article belongs to the Section Plant Science and Engineering)
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Open AccessArticle
Microarray Profile of Long Noncoding RNA and Messenger RNA Expression in a Model of Alzheimer’s Disease
Life 2020, 10(5), 64; https://doi.org/10.3390/life10050064 - 14 May 2020
Viewed by 345
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by a deficiency in cognitive skills. Although long noncoding RNAs (lncRNAs) have been proposed as associated with AD, the aberrant lncRNAs expression and the co-expression of lncRNAs-mRNAs network in AD remains unclear. Therefore, in [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by a deficiency in cognitive skills. Although long noncoding RNAs (lncRNAs) have been proposed as associated with AD, the aberrant lncRNAs expression and the co-expression of lncRNAs-mRNAs network in AD remains unclear. Therefore, in this study, lncRNA microarray was performed on the brain of APP/PS1 mice at different age, widely used as an AD mouse model, and on age-matched wide-type controls. Our results identified a total of 3306 lncRNAs and 2458 mRNAs as aberrantly expressed among AD mice at different age and their age-matched control. Gene Ontology and pathway analysis of the AD-related lncRNAs and mRNAs indicated that neuroinflammation-related and synaptic transmission signaling pathways represented the main enriched pathways. An lncRNA–mRNA–miRNA network between the differentially expressed transcripts was constructed. Moreover, an mRNA–miRNA network between both significantly dysregulated and highly conserved genes was also constructed, and among this network, the IGF1, P2RX7, TSPO, SERPINE1, EGFR, HMOX1, and NFE212 genes were predicted to play a role in the development of AD. In conclusion, this study illustrated the prognostic value of lncRNAs and mRNAs associated to AD pathology by microarray analysis and might provide potential novel biomarkers in the diagnosis and treatment of AD. Full article
(This article belongs to the Section Life Sciences)
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Open AccessArticle
The Main Structural and Functional Characteristics of Photosystem-II-Enriched Membranes Isolated from Wild Type and cia3 Mutant Chlamydomonas reinhardtii
Life 2020, 10(5), 63; https://doi.org/10.3390/life10050063 - 14 May 2020
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Abstract
Photosystem II (PSII)-enriched membranes retain the original PSII architecture in contrast to PSII cores or PSII supercomplexes, which are usually isolated from Chlamydomonas reinhardtii. Here, we present data that fully characterize the structural and functional properties of PSII complexes in isolated PSII-enriched [...] Read more.
Photosystem II (PSII)-enriched membranes retain the original PSII architecture in contrast to PSII cores or PSII supercomplexes, which are usually isolated from Chlamydomonas reinhardtii. Here, we present data that fully characterize the structural and functional properties of PSII complexes in isolated PSII-enriched membranes from C. reinhardtii. The preparations were isolated from wild-type (WT) and CAH3-deficient mutant cia3 as the influence of CAH3 on the PSII function was previously proposed. Based on the equal chlorophyll content, the PSII-enriched membranes from WT and cia3 have the same amount of reaction centers (RCs), cytochrome b559, subunits of the water-oxidizing complex, Mn ions, and carotenes. They differ in the ratio of other carotenoids, the parts of low/intermediate redox forms of cytochrome b559, and the composition of outer light-harvesting complexes. The preparations had 40% more chlorophyll molecules per RC compared to higher plants. Functionally, PSII-enriched membranes from WT and cia3 show the same photosynthetic activity at optimal pH 6.5. However, the preparations from cia3 contained more closed RCs even at pH 6.5 and showed more pronounced suppression of PSII photosynthetic activity at shift pH up to 7.0, established in the lumen of dark-adapted cells. Nevertheless, the PSII photosynthetic capacities remained the same. Full article
(This article belongs to the Section Microbiology and Engineering)
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Open AccessArticle
Anatomy of Parahesperornis: Evolutionary Mosaicism in the Cretaceous Hesperornithiformes (Aves)
Life 2020, 10(5), 62; https://doi.org/10.3390/life10050062 - 14 May 2020
Viewed by 862
Abstract
The Hesperornithiformes constitute the first known avian lineage to secondarily lose flight in exchange for the evolution of a highly derived foot-propelled diving lifestyle, thus representing the first lineage of truly aquatic birds. First unearthed in the 19th century, and today known from [...] Read more.
The Hesperornithiformes constitute the first known avian lineage to secondarily lose flight in exchange for the evolution of a highly derived foot-propelled diving lifestyle, thus representing the first lineage of truly aquatic birds. First unearthed in the 19th century, and today known from numerous Late Cretaceous (Cenomanian-Maastrichtian) sites distributed across the northern hemisphere, these toothed birds have become icons of early avian evolution. Initially erected as a taxon in 1984 by L. D. Martin, Parahesperornis alexi is known from the two most complete hesperornithiform specimens discovered to date and has yet to be fully described. P. alexi thus contributes significantly to our understanding of hesperornithiform birds, despite often being neglected in favor of the iconic Hesperornis. Here, we present a full anatomical description of P. alexi based upon the two nearly complete specimens in the collections of the University of Kansas Natural History Museum, as well as an extensive comparison to other hesperornithiform taxa. This study reveals P. alexi to possess a mosaic of basal and derived traits found among other hesperornithiform taxa, indicating a transitional form in the evolution of these foot-propelled diving birds. This study describes broad evolutionary patterns within the Hesperornithiformes, highlighting the significance of these birds as not only an incredible example of the evolution of ecological specializations, but also for understanding modern bird evolution, as they are the last known divergence of pre-modern bird diversification. Full article
(This article belongs to the Section Paleontology)
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Open AccessArticle
Loss of Concentration May Occur by Blink Inhibition in DED Simulation Models
Life 2020, 10(5), 61; https://doi.org/10.3390/life10050061 - 13 May 2020
Viewed by 331
Abstract
Purpose: Patients with dry eye disease (DED) often suffer productivity loss and distress due to bothersome symptoms. The aim of this study was to objectively quantify and compare productivity-related emotional states obtained from brain waveforms in natural and simulated DED conditions. Method: 25 [...] Read more.
Purpose: Patients with dry eye disease (DED) often suffer productivity loss and distress due to bothersome symptoms. The aim of this study was to objectively quantify and compare productivity-related emotional states obtained from brain waveforms in natural and simulated DED conditions. Method: 25 healthy adults (6 females and 19 males; mean age ± standard deviation, 22.6 ± 8.3 years) were recruited for the study, which included an electroencephalogram (EEG), measurements of interblinking time, and questionnaires. DED was simulated by suppressing blinking, while spontaneous blinking served as a control. Elements of concentration, stress, and alertness were extracted from the raw EEG waveforms and the values were compared during spontaneous and suppressed blinking. The relation with DED-related parameters was then explored. Written informed consent was obtained from all participants. Results: All participants successfully completed the experimental protocol. Concentration significantly decreased during suppressed blinking in 20 participants (80%), when compared with spontaneous blinking, whereas there were no or small differences in stress or alertness between spontaneous and suppressed blinking. The change in concentration was correlated with interblinking time (β = −0.515, p = 0.011). Conclusion: Loss of concentration was successfully captured in an objective manner using the EEG. The present study may enable us to understand how concentration is affected during blink suppression, which may happen in office work, particularly during computer tasks. Further study using detailed ocular evaluation is warranted to explore the effect of different interventions. Full article
(This article belongs to the Section Medical Research)
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Open AccessArticle
Trehalose Effect on The Aggregation of Model Proteins into Amyloid Fibrils
Life 2020, 10(5), 60; https://doi.org/10.3390/life10050060 - 13 May 2020
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Abstract
Protein aggregation into amyloid fibrils is a phenomenon that attracts attention from a wide and composite part of the scientific community. Indeed, the presence of mature fibrils is associated with several neurodegenerative diseases, and in addition these supramolecular aggregates are considered promising self-assembling [...] Read more.
Protein aggregation into amyloid fibrils is a phenomenon that attracts attention from a wide and composite part of the scientific community. Indeed, the presence of mature fibrils is associated with several neurodegenerative diseases, and in addition these supramolecular aggregates are considered promising self-assembling nanomaterials. In this framework, investigation on the effect of cosolutes on protein propensity to aggregate into fibrils is receiving growing interest, and new insights on this aspect might represent valuable steps towards comprehension of highly complex biological processes. In this work we studied the influence exerted by the osmolyte trehalose on fibrillation of two model proteins, that is, lysozyme and insulin, investigated during concomitant variation of the solution ionic strength due to NaCl. In order to monitor both secondary structures and the overall tridimensional conformations, we have performed UV spectroscopy measurements with Congo Red, Circular Dichroism, and synchrotron Small Angle X-ray Scattering. For both proteins we describe the effect of trehalose in changing the fibrillation pattern and, as main result, we observe that ionic strength in solution is a key factor in determining trehalose efficiency in slowing down or blocking protein fibrillation. Ionic strength reveals to be a competitive element with respect to trehalose, being able to counteract its inhibiting effects toward amyloidogenesis. Reported data highlight the importance of combining studies carried out on cosolutes with valuation of other physiological parameters that may affect the aggregation process. Also, the obtained experimental results allow to hypothesize a plausible mechanism adopted by the osmolyte to preserve protein surface and prevent protein fibrillation. Full article
(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)
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Open AccessArticle
DNA Methylation Influences miRNA Expression in Gonadotroph Pituitary Tumors
Life 2020, 10(5), 59; https://doi.org/10.3390/life10050059 - 13 May 2020
Viewed by 268
Abstract
microRNAs are involved in pathogenesis of cancer. DNA methylation plays a role in transcription of miRNA-encoding genes and may contribute to changed miRNA expression in tumors. This issue was not investigated in pituitary neuroendocrine tumors (PitNETs) previously. DNA methylation patterns, assessed with HumanMethylation450K [...] Read more.
microRNAs are involved in pathogenesis of cancer. DNA methylation plays a role in transcription of miRNA-encoding genes and may contribute to changed miRNA expression in tumors. This issue was not investigated in pituitary neuroendocrine tumors (PitNETs) previously. DNA methylation patterns, assessed with HumanMethylation450K arrays in 34 PitNETs and five normal pituitaries, were used to determine differentially methylated CpGs located at miRNA genes. It showed aberrant methylation in regions encoding for 131 miRNAs. DNA methylation data and matched miRNA expression profiles, determined with next-generation sequencing (NGS) of small RNAs, were correlated in 15 PitNETs. This showed relationship between methylation and expression levels for 12 miRNAs. DNA methylation and expression levels of three of them (MIR145, MIR21, and MIR184) were determined in the independent group of 80 tumors with pyrosequencing and qRT-PCR and results confirmed both aberrant methylation in PitNETs and correlation between methylation and expression. Additionally, in silico target prediction was combined with analysis of established miRNA profiles and matched mRNA expression pattern, assessed with amplicon-based NGS to indicate putative target genes of epigenetically deregulated miRNAs. This study reveals aberrant DNA methylation in miRNA-encoding genes in gonadotroph PitNETs. Methylation changes affect expression level of miRNAs that regulate putative target genes with tumorigenesis-relevant functions. Full article
(This article belongs to the Section Medical Research)
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Open AccessArticle
High-Throughput Identification of MiR-145 Targets in Human Articular Chondrocytes
Life 2020, 10(5), 58; https://doi.org/10.3390/life10050058 - 11 May 2020
Viewed by 343
Abstract
MicroRNAs (miRNAs) play key roles in cartilage development and homeostasis and are dysregulated in osteoarthritis. MiR-145 modulation induces profound changes in the human articular chondrocyte (HAC) phenotype, partially through direct repression of SOX9. Since miRNAs can simultaneously silence multiple targets, we aimed [...] Read more.
MicroRNAs (miRNAs) play key roles in cartilage development and homeostasis and are dysregulated in osteoarthritis. MiR-145 modulation induces profound changes in the human articular chondrocyte (HAC) phenotype, partially through direct repression of SOX9. Since miRNAs can simultaneously silence multiple targets, we aimed to identify the whole targetome of miR-145 in HACs, critical if miR-145 is to be considered a target for cartilage repair. We performed RIP-seq (RNA-immunoprecipitation and high-throughput sequencing) of miRISC (miRNA-induced silencing complex) in HACs overexpressing miR-145 to identify miR-145 direct targets and used cWords to assess enrichment of miR-145 seed matches in the identified targets. Further validations were performed by RT-qPCR, Western immunoblot, and luciferase assays. MiR-145 affects the expression of over 350 genes and directly targets more than 50 mRNAs through the 3′UTR or, more commonly, the coding region. MiR-145 targets DUSP6, involved in cartilage organization and development, at the translational level. DUSP6 depletion leads to MMP13 upregulation, suggesting a contribution towards the effect of miR-145 on MMP13 expression. In conclusion, miR-145 directly targets several genes involved in the expression of the extracellular matrix and inflammation in primary chondrocytes. Thus, we propose miR-145 as an important regulator of chondrocyte function and a new target for cartilage repair. Full article
(This article belongs to the Section Genetics and Genomics Research)
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Open AccessReview
Targeting the C-Terminal Domain Small Phosphatase 1
Life 2020, 10(5), 57; https://doi.org/10.3390/life10050057 - 08 May 2020
Viewed by 328
Abstract
The human C-terminal domain small phosphatase 1 (CTDSP1/SCP1) is a protein phosphatase with a conserved catalytic site of DXDXT/V. CTDSP1’s major activity has been identified as dephosphorylation of the 5th Ser residue of the tandem heptad repeat of the RNA polymerase II C-terminal [...] Read more.
The human C-terminal domain small phosphatase 1 (CTDSP1/SCP1) is a protein phosphatase with a conserved catalytic site of DXDXT/V. CTDSP1’s major activity has been identified as dephosphorylation of the 5th Ser residue of the tandem heptad repeat of the RNA polymerase II C-terminal domain (RNAP II CTD). It is also implicated in various pivotal biological activities, such as acting as a driving factor in repressor element 1 (RE-1)-silencing transcription factor (REST) complex, which silences the neuronal genes in non-neuronal cells, G1/S phase transition, and osteoblast differentiation. Recent findings have denoted that negative regulation of CTDSP1 results in suppression of cancer invasion in neuroglioma cells. Several researchers have focused on the development of regulating materials of CTDSP1, due to the significant roles it has in various biological activities. In this review, we focused on this emerging target and explored the biological significance, challenges, and opportunities in targeting CTDSP1 from a drug designing perspective. Full article
(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)
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Open AccessReview
Synthetic Biology Approaches to Engineer Saccharomyces cerevisiae towards the Industrial Production of Valuable Polyphenolic Compounds
Life 2020, 10(5), 56; https://doi.org/10.3390/life10050056 - 02 May 2020
Viewed by 540
Abstract
Polyphenols are plant secondary metabolites with diverse biological and potential therapeutic activities such as antioxidant, anti-inflammatory and anticancer, among others. However, their extraction from the native plants is not enough to satisfy the increasing demand for this type of compounds. The development of [...] Read more.
Polyphenols are plant secondary metabolites with diverse biological and potential therapeutic activities such as antioxidant, anti-inflammatory and anticancer, among others. However, their extraction from the native plants is not enough to satisfy the increasing demand for this type of compounds. The development of microbial cell factories to effectively produce polyphenols may represent the most attractive solution to overcome this limitation and produce high amounts of these bioactive molecules. With the advances in the synthetic biology field, the development of efficient microbial cell factories has become easier, largely due to the development of the molecular biology techniques and by the identification of novel isoenzymes in plants or simpler organisms to construct the heterologous pathways. Furthermore, efforts have been made to make the process more profitable through improvements in the host chassis. In this review, advances in the production of polyphenols by genetically engineered Saccharomyces cerevisiae as well as by synthetic biology and metabolic engineering approaches to improve the production of these compounds at industrial settings are discussed. Full article
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Open AccessArticle
DnaK3 Is Involved in Biogenesis and/or Maintenance of Thylakoid Membrane Protein Complexes in the Cyanobacterium Synechocystis sp. PCC 6803
Life 2020, 10(5), 55; https://doi.org/10.3390/life10050055 - 30 Apr 2020
Viewed by 413
Abstract
DnaK3, a highly conserved cyanobacterial chaperone of the Hsp70 family, binds to cyanobacterial thylakoid membranes, and an involvement of DnaK3 in the biogenesis of thylakoid membranes has been suggested. As shown here, light triggers synthesis of DnaK3 in the cyanobacterium Synechocystis sp. PCC [...] Read more.
DnaK3, a highly conserved cyanobacterial chaperone of the Hsp70 family, binds to cyanobacterial thylakoid membranes, and an involvement of DnaK3 in the biogenesis of thylakoid membranes has been suggested. As shown here, light triggers synthesis of DnaK3 in the cyanobacterium Synechocystis sp. PCC 6803, which links DnaK3 to the biogenesis of thylakoid membranes and to photosynthetic processes. In a DnaK3 depleted strain, the photosystem content is reduced and the photosystem II activity is impaired, whereas photosystem I is regular active. An impact of DnaK3 on the activity of other thylakoid membrane complexes involved in electron transfer is indicated. In conclusion, DnaK3 is a versatile chaperone required for biogenesis and/or maintenance of thylakoid membrane-localized protein complexes involved in electron transfer reactions. As mentioned above, Hsp70 proteins are involved in photoprotection and repair of PS II in chloroplasts. Full article
(This article belongs to the Special Issue Cellular and Molecular Strategies in Cyanobacterial Survival)
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Open AccessArticle
The Nitrogen Stress-Repressed sRNA NsrR1 Regulates Expression of all1871, a Gene Required for Diazotrophic Growth in Nostoc sp. PCC 7120
Life 2020, 10(5), 54; https://doi.org/10.3390/life10050054 - 29 Apr 2020
Viewed by 442
Abstract
Small regulatory RNAs (sRNAs) are post-transcriptional regulators of bacterial gene expression. In cyanobacteria, the responses to nitrogen availability, that are mostly controlled at the transcriptional level by NtcA, involve also at least two small RNAs, namely NsiR4 (nitrogen stress-induced RNA 4) and NsrR1 [...] Read more.
Small regulatory RNAs (sRNAs) are post-transcriptional regulators of bacterial gene expression. In cyanobacteria, the responses to nitrogen availability, that are mostly controlled at the transcriptional level by NtcA, involve also at least two small RNAs, namely NsiR4 (nitrogen stress-induced RNA 4) and NsrR1 (nitrogen stress-repressed RNA 1). Prediction of possible mRNA targets regulated by NsrR1 in Nostoc sp. PCC 7120 allowed, in addition to previously described nblA, the identification of all1871, a nitrogen-regulated gene encoding a protein of unknown function that we describe here as required for growth at the expense of atmospheric nitrogen (N2). We show that transcription of all1871 is induced upon nitrogen step-down independently of NtcA. All1871 accumulation is repressed by NsrR1 and its expression is stronger in heterocysts, specialized cells devoted to N2 fixation. We demonstrate specific interaction between NsrR1 and the 5′ untranslated region (UTR) of the all1871 mRNA, that leads to decreased expression of all1871. Because transcription of NsrR1 is partially repressed by NtcA, post-transcriptional regulation by NsrR1 would constitute an indirect way of NtcA-mediated regulation of all1871. Full article
(This article belongs to the Special Issue Cellular and Molecular Strategies in Cyanobacterial Survival)
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Open AccessCommunication
A New Record for Microbial Perchlorate Tolerance: Fungal Growth in NaClO4 Brines and its Implications for Putative Life on Mars
Life 2020, 10(5), 53; https://doi.org/10.3390/life10050053 - 28 Apr 2020
Viewed by 634
Abstract
The habitability of Mars is strongly dependent on the availability of liquid water, which is essential for life as we know it. One of the few places where liquid water might be found on Mars is in liquid perchlorate brines that could form [...] Read more.
The habitability of Mars is strongly dependent on the availability of liquid water, which is essential for life as we know it. One of the few places where liquid water might be found on Mars is in liquid perchlorate brines that could form via deliquescence. As these concentrated perchlorate salt solutions do not occur on Earth as natural environments, it is necessary to investigate in lab experiments the potential of these brines to serve as a microbial habitat. Here, we report on the sodium perchlorate (NaClO4) tolerances for the halotolerant yeast Debaryomyces hansenii and the filamentous fungus Purpureocillium lilacinum. Microbial growth was determined visually, microscopically and via counting colony forming units (CFU). With the observed growth of D. hansenii in liquid growth medium containing 2.4 M NaClO4, we found by far the highest microbial perchlorate tolerance reported to date, more than twice as high as the record reported prior (for the bacterium Planococcus halocryophilus). It is plausible to assume that putative Martian microbes could adapt to even higher perchlorate concentrations due to their long exposure to these environments occurring naturally on Mars, which also increases the likelihood of microbial life thriving in the Martian brines. Full article
(This article belongs to the Special Issue Life on Mars)
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Open AccessReview
Factoring Origin of Life Hypotheses into the Search for Life in the Solar System and Beyond
Life 2020, 10(5), 52; https://doi.org/10.3390/life10050052 - 27 Apr 2020
Viewed by 611
Abstract
Two widely-cited alternative hypotheses propose geological localities and biochemical mechanisms for life’s origins. The first states that chemical energy available in submarine hydrothermal vents supported the formation of organic compounds and initiated primitive metabolic pathways which became incorporated in the earliest cells; the [...] Read more.
Two widely-cited alternative hypotheses propose geological localities and biochemical mechanisms for life’s origins. The first states that chemical energy available in submarine hydrothermal vents supported the formation of organic compounds and initiated primitive metabolic pathways which became incorporated in the earliest cells; the second proposes that protocells self-assembled from exogenous and geothermally-delivered monomers in freshwater hot springs. These alternative hypotheses are relevant to the fossil record of early life on Earth, and can be factored into the search for life elsewhere in the Solar System. This review summarizes the evidence supporting and challenging these hypotheses, and considers their implications for the search for life on various habitable worlds. It will discuss the relative probability that life could have emerged in environments on early Mars, on the icy moons of Jupiter and Saturn, and also the degree to which prebiotic chemistry could have advanced on Titan. These environments will be compared to ancient and modern terrestrial analogs to assess their habitability and biopreservation potential. Origins of life approaches can guide the biosignature detection strategies of the next generation of planetary science missions, which could in turn advance one or both of the leading alternative abiogenesis hypotheses. Full article
(This article belongs to the Special Issue Themed Issue Commemorating Prof. David Deamer's 80th Birthday)
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Open AccessArticle
Early-Life Stress Induced Epigenetic Changes of Corticotropin-Releasing Factor Gene in Anorexic Low Body Weight–Selected Chicks
Life 2020, 10(5), 51; https://doi.org/10.3390/life10050051 - 27 Apr 2020
Viewed by 385
Abstract
The expression of neuropeptide Y (NPY) in the arcuate nucleus (ARC) and corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN) were increased when low body weight–selected (LWS) line chicks, which are predisposed to anorexia, were subjected to a combination [...] Read more.
The expression of neuropeptide Y (NPY) in the arcuate nucleus (ARC) and corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN) were increased when low body weight–selected (LWS) line chicks, which are predisposed to anorexia, were subjected to a combination of nutritional and thermal stressors at hatch. We hypothesized that such changes resulted from epigenetic modifications. We determined global DNA methylation, DNA methyltransferase (DNMT) activity, and methylation near the promoter regions of NPY and CRF, in the hypothalamus of LWS chicks on day 5 post-hatch. Stress exposure at hatch induced global hypermethylation and increased DNMT activity in the ARC but not PVN. In the PVN of stressed LWS chicks, there was decreased methylation of a CpG site located at the core binding domain of methyl cytosine binding domain protein 2 (MBD2), near the CRF gene promoter. We then demonstrated that this was associated with disrupted binding of MBD2. There was also reduced utilization of yolk reserves and lean and fat masses in chicks that were stress-exposed. These findings provide novel insights on molecular mechanisms through which stressful events induce or intensify anorexia in predisposed individuals and a novel molecular target for further studies. Full article
(This article belongs to the Section Animal Science)
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