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On page 245 showing 4881 ~ 4900 papers out of 2,794,544 papers

Nuclear Receptors Are Differentially Expressed and Activated in KAIMRC1 Compared to MCF7 and MDA-MB231 Breast Cancer Cells.

  • Atef Nehdi‎ et al.
  • Molecules (Basel, Switzerland)‎
  • 2019‎

We recently established a KAIMRC1 cell line that has unique features compared to the known breast cancer cell lines, MCF7 and MDA-MB231. To characterize it further, we investigated the expression profile of nuclear receptors and their respective co-factors in these cell lines. We confirm that in contrast to the triple negative cell line MDA-MB231, the MCF7 and KAIMRC1 are estrogen receptor alpha (ERa) and progesterone receptor alpha (PRa) positive, with significant lower expression of these receptors in KAIMRC1. KAIMRC1 cell is a vitamin D receptor (VDR) negative and V-ErbA-Related Protein 2 (EAR2) positive in contrast to MCF7 and MDA-MB231. Remarkably, the histone deacetylases (HDACs) are highly expressed in KAIRMC1 with HDAC6 and HDAC 7 are exclusively expressed in KAIMRC1 while thyroid hormone receptor-associated protein 80 (TRAP80), telomeric DNA binding protein 1 (TBP1) and TGF-beta receptor interacting protein (TRIP1) are absent in KAIMRC1 but present in MCF7 and MDA-MB231. In a luciferase reporter assay, the ERa coexpression is needed for estrogen receptor element (ERE)-luciferase activation by estradiol in KAIMRC1 but not in MCF7. The co-expression of exogenous Liver X receptor alpha (LXRa)/retinoid X receptor alpha (RXRa) are necessary for LXR responsive element (LXRE) activation by the GW3696 in the three cell lines. However, the activity of peroxisome proliferator-activated receptor response element (PPARE)-tk-luciferase reporter increased when peroxisome proliferator-activated receptors alpha (PPARa)/RXRa were coexpressed but the addition of PPARa agonist (GW7647) did not stimulate further the reporter. The signal of the PPARE reporter increased in a dose-dependent manner with rosiglitazone (PPARg agonist) in KAIMRC1, MCF7, and MDA-MB231 when the proliferator-activated receptors gamma (PPARg)/RXRa receptors were cotransfected. Retinoic acid-induced activation of retinoic acid receptor response element (RARE)-tk-luciferase is dependent on exogenous expression of retinoic acid receptor alpha (RARa)/RXRa heterodimer in MDA-MB 231 but not in MCF7 and KAIMRC1 cell lines. In the three cell lines, Bexarotene-induced retinoid X receptor response element (RXRE)-luciferase reporter activation was induced only if the RXRa/LXRa heterodimer were co-expressed. The vitamin D receptor response element (VDRE)-luciferase reporter activity showed another distinct feature of KAIMRC1, where only co-expression of exogenous vitamin D receptor (VDR)/RXRa heterodimer was sufficient to reach the maximum rate of activation of VDRE reporter. In the proliferation assay, nuclear receptors ligands showed a distinct effect on KAIMRC1 compared to MCF7 and MDA-MB231. Growth inhibition effects of used ligands suggest that KAIMRC1 correlate more closely to MDA-MB231 than MCF7. Vitamin D3, rosiglitazone, novel RXR compound (RXRc) and PPARa compound (GW6471) have the most profound effects. In conclusion, we showed that nuclear receptors are differentially expressed, activated and also their ligand produced distinct effects in KAIMRC1 compared to MCF7 and MDA-MB231. This finding gives us confidence that KAIMRC1 has a unique biological phenotype.


Improving Post-Filtering of Artificial Speech Using Pre-Trained LSTM Neural Networks.

  • Marvin Coto-Jiménez‎
  • Biomimetics (Basel, Switzerland)‎
  • 2019‎

Several researchers have contemplated deep learning-based post-filters to increase the quality of statistical parametric speech synthesis, which perform a mapping of the synthetic speech to the natural speech, considering the different parameters separately and trying to reduce the gap between them. The Long Short-term Memory (LSTM) Neural Networks have been applied successfully in this purpose, but there are still many aspects to improve in the results and in the process itself. In this paper, we introduce a new pre-training approach for the LSTM, with the objective of enhancing the quality of the synthesized speech, particularly in the spectrum, in a more efficient manner. Our approach begins with an auto-associative training of one LSTM network, which is used as an initialization for the post-filters. We show the advantages of this initialization for the enhancing of the Mel-Frequency Cepstral parameters of synthetic speech. Results show that the initialization succeeds in achieving better results in enhancing the statistical parametric speech spectrum in most cases when compared to the common random initialization approach of the networks.


Analysis of Genetic Alterations in Tunisian Patients with Lung Adenocarcinoma.

  • Dhoha Dhieb‎ et al.
  • Cells‎
  • 2019‎

The identification of the mutations that drive lung cancer have furnished new targets for the treatment of non-small cell lung cancer (NSCLC) and led to the development of targeted therapies such as tyrosine kinase inhibitors that are used to combat the molecular changes promoting cancer progression. Furthermore, biomarkers identified from gene analysis can be used to detect early lung cancer, determine patient prognosis, and monitor response to therapy. In the present study we analyzed the molecular profile of seventy-three Tunisian patients with lung adenocarcinoma (LAD). Mutational analyses for EGFR and KRAS were performed using direct sequencing, immunohistochemistry or MassARRAY. Anaplastic lymphoma kinase (ALK) rearrangement was evaluated by immunohistochemistry using the D5F3 clone, and p53 expression was also assessed. The median age of patients at diagnosis was 61 years (range 23-82 years). Using different methodologies, EGFR mutations were found in 5.47% of patients and only exon 19 deletions "E746-A750 del" were detected. KRAS mutations were present in 9.58% of cases, while only one patient was ALK-positive. Moreover, abnormal immunostaining of p53 was detected in 56.16% of patients. In conclusion, the detected rates of EGFR and KRAS mutation and ALK rearrangement were lower than those found in European and Asian countries, whereas, abnormal p53 expression was slightly more frequent. Furthermore, given the small sample size of this study, a more comprehensive analysis of this patient set is warranted.


Molecular Insights into FaEG1, a Strawberry Endoglucanase Enzyme Expressed during Strawberry Fruit Ripening.

  • Karla Jara‎ et al.
  • Plants (Basel, Switzerland)‎
  • 2019‎

The endo-β-1,4-glucanases (EGs) that belong to the glycosyl hydrolase family 9 (GH9) have roles in cell wall synthesis, remodeling and degradation. Previous studies have suggested that EGs may play a key role in the ripening of different fruits including strawberries. In this study, we used reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assays to determine the transcript accumulation of an endo-β-1,4-glucanase (FaEG1) during fruit development in two different strawberry 'Camarosa' and 'Monterey' with contrasting softening ratios. Phylogenetic analyses suggest that FaEG1 belongs to the α group of the GH9 family with other proteins previously described with roles in elongation, abscission and ripening. Comparative modeling was used to obtain the FaEG1 structure. The model displays a α-barrel-type structure that is typical of the GH9 enzyme family, and comprises 12 α-helices, 2 310 helices and 6 β-sheets. The catalytic residues were oriented to the solvent in the middle of an open groove. Protein-ligand interactions were explored with cellulose and two xyloglucans as ligands; the results suggest that the FaEG1-cellulose and FaEG1-XXXGXXXG (the most abundant xyloglucan in strawberries) complexes were more stable complexes than XXFGXXFG. The cell wall degradation was observed by scanning electron microscopy (SEM). The data are congruent with the probable role of the FaEG1 protein in the dissembly of the cellulose-hemicellulose fraction during the ripening of strawberry fruit.


Encapsulation of Thermo-Sensitive Lauric Acid in Silica Shell: A Green Derivate for Chemo-Thermal Therapy in Breast Cancer Cell.

  • Valeria De Matteis‎ et al.
  • Molecules (Basel, Switzerland)‎
  • 2019‎

Lauric acid is a green derivate that is abundant in some seeds such as coconut oil where it represents the most relevant fatty acid. Some studies have emphasized its anticancer effect due to apoptosis induction. In addition, the lauric acid is a Phase Change Material having a melting temperature of about 43.2 °C: this property makes it a powerful tool in cancer treatment by hyperthermal stress, generally induced at 43 °C. However, the direct use of lauric acid can have some controversial effects, and it can undergo degradation phenomena in the extracellular environment. For this reason, we have encapsulated lauric acid in a silica shell with a one-step and reproducible synthetic route in order to obtain a monodispersed SiO2@LA NPs with a good encapsulation efficiency. We have used these NPs to expose breast cancer cell lines (MCF-7) at different concentrations in combination with hyperthermal treatment. Uptake, viability, oxidative stress induction, caspases levels, and morphometric parameters were analyzed. These nanovectors showed double action in anticancer treatments thanks to the synergic effect of temperature and lauric acid activity.


A Storage-Dependent Platinum Functionalization with a Commercial Pre-Polymer Useful for Hydrogen Peroxide and Ascorbic Acid Detection.

  • Patrizia Monti‎ et al.
  • Sensors (Basel, Switzerland)‎
  • 2019‎

A preliminary assessment of properties of the commercial product Chemiplus 2DS HB (BI-QEM Specialties SpA) is proposed. Cyclic voltammetry of this oligomer containing sulfate/sulfone groups shows a single oxidative peak at +0.866 V vs. Ag/AgCl, and its passivating process on Pt electrode suggests the formation of a non-conductive layer. Electrode modification was achieved by exploiting the constant potential amperometry setting potential at +0.900 V vs. Ag/AgCl. A substantial change in the oxidative currents from electroactive species H2O2 and ascorbic acid (AA) were observed on Pt/Chemiplus 2DS HB sensors compared to unmodified Pt. Furthermore, the influence of different storage conditions on modified sensors was examined. A storage solution containing AA concentration from 0.1 until 10 mM maintained effective AA rejection of Pt/Chemiplus 2DS HB after 7 days from construction; H2O2 oxidation capability was also retained. Sulfone and sulfonate groups of Chemiplus 2DS HB are likely responsible for the dimensionality of the film and the electrostatic interaction leading to a self-blocking/self-rejection of AA. The way Pt/Chemiplus can reveal the AA presence depends on the maintaining of AA rejection, and this peculiarity can distinguish it from other sensors or biosensors.


Changes in Anxiety and Depression Traits Induced by Energy Restriction: Predictive Value of the Baseline Status.

  • Claudia Rodriguez-Lozada‎ et al.
  • Nutrients‎
  • 2019‎

Current evidence proposes diet quality as a modifiable risk factor for mental or emotional impairments. However, additional studies are required to investigate the effect of dietary patterns and weight loss on improving psychological symptoms. The aim of this investigation was to evaluate the effect of energy-restriction, prescribed to overweight and obese participants, on anxiety and depression symptoms, as well as the potential predictive value of some baseline psychological features on weight loss. Overweight and obese participants (n = 305) were randomly assigned for 16 weeks to two hypocaloric diets with different macronutrient distribution: a moderately high-protein (MHP) diet and a low-fat (LF) diet. Anthropometrical, clinical, psychological, and lifestyle characteristics were assessed at baseline and at the end of the intervention. The nutritional intervention evidenced that weight loss has a beneficial effect on trait anxiety score in women (β = 0.24, p = 0.03), depression score in all population (β = 0.15, p = 0.02), particularly in women (β = 0.22, p = 0.03) and in subjects who followed the LF diet (β = 0.22, p = 0.04). Moreover, weight loss could be predicted by anxiety status at baseline, mainly in women and in those who were prescribed a LF diet. This trial suggests that weight loss triggers an improvement in psychological traits, and that anxiety symptoms could predict those volunteers that benefit most from a balanced calorie-restricted intervention, which will contribute to individualized precision nutrition.


Hiseq Base Molecular Characterization of Soil Microbial Community, Diversity Structure, and Predictive Functional Profiling in Continuous Cucumber Planted Soil Affected by Diverse Cropping Systems in an Intensive Greenhouse Region of Northern China.

  • Ahmad Ali‎ et al.
  • International journal of molecular sciences‎
  • 2019‎

Cover crops are key determinants of the ecological stability and sustainability of continuous cropping soils. However, their agro-ecological role in differentially reshaping the microbiome structure and functioning under a degraded agroecosystem remains poorly investigated. Therefore, structural and metabolic changes in soil bacterial community composition in response to diverse plant species were assessed. Winter catch leafy vegetables crops were introduced as cover plants in a cucumber-fallow period. The results indicate that cover crop diversification promoted beneficial changes in soil chemical and biological attributes, which increased crop yields in a cucumber double-cropping system. Illumina high-throughput sequencing of 16S rRNA genes indicated that the bacterial community composition and diversity changed through changes in the soil properties. Principal component analysis (PCA) coupled with non-metric multidimensional scaling (NMDS) analysis reveals that the cover planting shaped the soil microbiome more than the fallow planting (FC). Among different cropping systems, spinach-cucumber (SC) and non-heading Chinese cabbage-cucumber (NCCC) planting systems greatly induced higher soil nutrient function, biological activity, and bacterial diversity, thus resulting in higher cucumber yield. Quantitative analysis of linear discriminant analysis effect size (LEfSe) indicated that Proteobacteria, Actinobacteria, Bacteroidetes, and Acidobacteria were the potentially functional and active soil microbial taxa. Rhizospheres of NCCC, leaf lettuce-cucumber (LLC), coriander-cucumber (CC), and SC planting systems created hotspots for metabolic capabilities of abundant functional genes, compared to FC. In addition, the predictive metabolic characteristics (metabolism and detoxification) associated with host-plant symbiosis could be an important ecological signal that provides direct evidence of mediation of soil structure stability. Interestingly, the plant density of non-heading Chinese cabbage and spinach species was capable of reducing the adverse effect of arsenic (As) accumulation by increasing the function of the arsenate reductase pathway. Redundancy analysis (RDA) indicated that the relative abundance of the core microbiome can be directly and indirectly influenced by certain environmental determinants. These short-term findings stress the importance of studying cover cropping systems as an efficient biological tool to protect the ecological environment. Therefore, we can speculate that leafy crop diversification is socially acceptable, economically justifiable, and ecologically adaptable to meet the urgent demand for intensive cropping systems to promote positive feedback between crop-soil sustainable intensification.


Effectiveness of Following Mediterranean Diet Recommendations in the Real World in the Incidence of Gestational Diabetes Mellitus (GDM) and Adverse Maternal-Foetal Outcomes: A Prospective, Universal, Interventional Study with a Single Group. The St Carlos Study.

  • Nuria García de la Torre‎ et al.
  • Nutrients‎
  • 2019‎

We reported that a Mediterranean Diet (MedDiet), supplemented with extra-virgin olive oil (EVOO) and pistachios, reduces GDM incidence and several other adverse outcomes. In order to assess its translational effects in the real world we evaluated the effect of MedDiet from 1st gestational visit in GDM rate compared with control (CG) and intervention (IG) groups from the previously referred trial. As secondary objective we also compared adverse perinatal outcomes between normoglycemic and diabetic women. This trial is a prospective, clinic-based, interventional study with a single group. 1066 eligible normoglycaemic women before 12 gestational weeks were assessed. 932 women (32.4 ± 5.2 years old, pre-gestational BMI 22.5 ± 3.5 kg/m2) received a motivational lifestyle interview with emphasis on daily consumption of EVOO and nuts, were followed-up and analysed. Binary regression analyses were used to examine the risk for each pregnancy outcome, pregnancy-induced hypertension, preeclampsia, gestational weight gain (GWG), caesarean-section, perineal trauma, preterm delivery, small (SGA) and large for gestational age (LGA), and Neonatal Intensive Care Unit admissions. GDM was diagnosed in 13.9%. This rate was significantly lower than the CG: RR 0.81 (0.73-0.93), p < 0.001 and no different from the IG: RR 0.96 (0.85-1.07), p = 0.468. GWG was lower in diabetic women (10.88 ± 6.46 vs. 12.30 ± 5.42 Kg; p = 0.013). Excessive weight gain (EWG) was also lower in GDM [RR 0.91 (0.86-0.96); p < 0.001] without a significant increase of insufficient weight gain. LGA were also lower (1 (0.8%) vs. 31 (3.9%); p < 0.05)), and SGA were similar (5 (3.8%) vs. 30 (3.7%)). LGA were associated to EWG (RR 1.61 (1.35-1.91), p < 0.001). Differences in other maternal-foetal outcomes were not found. In conclusions an early MedDiet nutritional intervention reduces GDM incidence and maternal-foetal adverse outcomes and should be universally applied as 1st line therapy. GDM might not be consider as a high risk pregnancy any longer.


Bacterial Outer Membrane Vesicles (OMVs)-based Dual Vaccine for Influenza A H1N1 Virus and MERS-CoV.

  • Mahmoud M Shehata‎ et al.
  • Vaccines‎
  • 2019‎

Vaccination is the most functional medical intervention to prophylactically control severe diseases caused by human-to-human or animal-to-human transmissible viral pathogens. Annually, seasonal influenza epidemics attack human populations leading to 290-650 thousand deaths/year worldwide. Recently, a novel Middle East Respiratory Syndrome Coronavirus emerged. Together, those two viruses present a significant public health burden in areas where they circulate. Herein, we generated a bacterial outer membrane vesicles (OMVs)-based vaccine presenting the antigenic stable chimeric fusion protein of the H1-type haemagglutinin (HA) of the pandemic influenza A virus (H1N1) strain from 2009 (H1N1pdm09) and the receptor binding domain (RBD) of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (OMVs-H1/RBD). Our results showed that the chimeric antigen could induce specific neutralizing antibodies against both strains leading to protection of immunized mice against H1N1pdm09 and efficient neutralization of MERS-CoV. This study demonstrate that OMVs-based vaccines presenting viral antigens provide a safe and reliable approach to protect against two different viral infections.


Transcriptome Changes of Skeletal Muscle RNA-Seq Speculates the Mechanism of Postprandial Hyperglycemia in Diabetic Goto-Kakizaki Rats During the Early Stage of T2D.

  • Wenlu Zhang‎ et al.
  • Genes‎
  • 2019‎

To address how skeletal muscle contributes to postprandial hyperglycemia, we performed skeletal muscle transcriptome analysis of diabetic Goto-Kakizaki (GK) and control Wistar rats by RNA sequencing (RNA-Seq). We obtained 600 and 1785 differentially expressed genes in GK rats compared to those Wistar rats at three and four weeks of age, respectively. Specifically, Tbc1d4, involved in glucose uptake, was significantly downregulated in the skeletal muscle of GK aged both three and four weeks compared to those of age-matched Wistar rats. Pdk4, related to glucose uptake and oxidation, was significantly upregulated in the skeletal muscle of GK aged both three and four weeks compared to that of age-matched Wistar rats. Genes (Acadl, Acsl1 and Fabp4) implicated in fatty acid oxidation were significantly upregulated in the skeletal muscle of GK aged four weeks compared to those of age-matched Wistar rats. The overexpression or knockout of Tbc1d4, Pdk4, Acadl, Acsl1 and Fabp4 has been reported to change glucose uptake and fatty acid oxidation directly in rodents. By taking the results of previous studies into consideration, we speculated that dysregulation of key dysregulated genes (Tbc1d4, Pdk4, Acadl, Acsl1 and Fabp4) may lead to a decrease in glucose uptake and oxidation, and an increase in fatty acid oxidation in GK skeletal muscle at three and four weeks, which may, in turn, contribute to postprandial hyperglycemia. Our research revealed transcriptome changes in GK skeletal muscle at three and four weeks. Tbc1d4, Acadl, Acsl1 and Fabp4 were found to be associated with early diabetes in GK rats for the first time, which may provide a new scope for pathogenesis of postprandial hyperglycemia.


Estrogen Receptor Status Oppositely Modifies Breast Cancer Prognosis in BRCA1/BRCA2 Mutation Carriers Versus Non-Carriers.

  • Michal Vocka‎ et al.
  • Cancers‎
  • 2019‎

Breast cancer (BC) prognosis in BRCA1 and BRCA2 mutation carriers has been reported contradictorily, and the significance of variables influencing prognosis in sporadic BC is not established in BC patients with hereditary BRCA1/BRCA2 mutations. In this retrospective cohort study, we analyzed the effect of clinicopathological characteristics on BC prognosis (disease-free survival [DFS] and disease-specific survival [DSS]) in hereditary BRCA1/BRCA2 mutation carriers. We enrolled 234 BRCA1/BRCA2 mutation carriers and 899 non-carriers, of whom 191 carriers and 680 non-carriers, with complete data, were available for survival analyses. We found that patients with ER-positive tumors developed disease recurrence 2.3-times more likely when they carried a BRCA1/BRCA2 mutation (23/60; 38.3% ER-positive carriers vs. 74/445; 16.6% ER-positive non-carriers; p < 0.001). ER-positive mutation carriers also had a 3.4-times higher risk of death due to BC compared with ER-positive non-carriers (13/60; 21.7% vs. 28/445; 6.3%; p < 0.001). Moreover, prognosis in ER-negative BRCA1/BRCA2 mutation carriers was comparable with that in ER-positive non-carriers. Our study demonstrates that ER-positivity worsens BC prognosis in BRCA1/BRCA2 mutation carriers, while prognosis for carriers with ER-negative tumors (including early-onset) is significantly better and comparable with that in ER-positive, older BC non-carriers. These observations indicate that BRCA1/BRCA2 mutation carriers with ER-positive BC represent high-risk patients.


Differential Plasma Expression Profiles of Long Non-Coding RNAs Reveal Potential Biomarkers for Systemic Lupus Erythematosus.

  • Guo-Cui Wu‎ et al.
  • Biomolecules‎
  • 2019‎

Identify long non-coding RNAs (lncRNAs) that might serve as biomarkers for systemic lupus erythematosus (SLE) and explore the biological functions of the identified lncRNAs. In the screening phase, we examined the lncRNA expression profile of plasma samples from 24 patients with SLE and 12 healthy controls (HCs) using lncRNA microarray with pooled samples. The candidate lncRNAs were verified in individual samples by quantitative real-time (qRT)-PCR. In the independent validation stage, the identified lncRNAs were evaluated in 240 patients with SLE and 120 HCs. The identified lncRNAs were assessed further in an external validation stage including patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). In addition, we constructed correlated expression networks including coding-non-coding co-expression and competing endogenous RNAs (ceRNAs). Plasma levels of linc0597, lnc0640, and lnc5150 were elevated in SLE patients compared with those of HCs, whereas levels of GAS5 and lnc7074 were decreased. Five lncRNAs were identified as potential SLE biomarkers with an area under the receiver operating characteristic curve (AUC) ranging from 0.604 to 0.833 in the independent validation phase. This panel of five lncRNAs had high diagnostic accuracy for SLE (AUC = 0.966) and distinguished SLE from RA and pSS (AUC = 0.683 and 0.910, respectively). Co-expression analysis showed that GAS5, lnc0640, and lnc5150 may participate in the SLE pathogenesis through the MAPK pathway. The ceRNA network indicated that GAS5, lnc0640, lnc3643, lnc6655, and lnc7074 bind competitively with microRNAs regulating the expression of target genes. Aberrant expression and related pathways suggest the important role of lncRNAs in SLE pathogenesis. In addition, the panel of five lncRNAs (GAS5, lnc7074, linc0597, lnc0640, and lnc5150) in plasma could be used as SLE biomarkers.


Phase-Specific Changes in Rate of Force Development and Muscle Morphology Throughout a Block Periodized Training Cycle in Weightlifters.

  • Dylan G Suarez‎ et al.
  • Sports (Basel, Switzerland)‎
  • 2019‎

The purpose of this study was to investigate the kinetic and morphological adaptations that occur during distinct phases of a block periodized training cycle in weightlifters. Athlete monitoring data from nine experienced collegiate weightlifters was used. Isometric mid-thigh pull (IMTP) and ultrasonography (US) results were compared to examine the effects of three specific phases of a training cycle leading up to a competition. During the high volume strength-endurance phase (SE) small depressions in rate of force development (RFD) but statistically significant (p ≤ 0.05) increases in vastus lateralis cross-sectional area (CSA), and body mass (BM) were observed. The lower volume higher intensity strength-power phase (SP) caused RFD to rebound above pre-training cycle values despite statistically significant reductions in CSA. Small to moderate increases only in the earlier RFD time bands (<150 ms) occurred during the peak/taper phase (PT) while CSA and BM were maintained. Changes in IMTP RFD and CSA from US reflected the expected adaptations of block periodized training phases. Changes in early (<100 ms) and late (≥150 ms) RFD time bands may not occur proportionally throughout different training phases. Small increases in RFD and CSA can be expected in well-trained weightlifters throughout a single block periodized training cycle.


Enhanced Homing of Mesenchymal Stem Cells Overexpressing Fibroblast Growth Factor 21 to Injury Site in a Mouse Model of Traumatic Brain Injury.

  • Rami Ahmad Shahror‎ et al.
  • International journal of molecular sciences‎
  • 2019‎

Mesenchymal stem cells (MSCs) are emerging as a potential therapeutic intervention for brain injury due to their neuroprotective effects and safe profile. However, the homing ability of MSCs to injury sites still needs to be improved. Fibroblast Growth Factor 21 (FGF21) was recently reported to enhance cells migration in different cells type. In this study, we investigated whether MSCs that overexpressing FGF21 (MSC-FGF21) could exhibit enhanced homing efficacy in brain injury. We used novel Molday IONEverGreen™ (MIEG) as cell labeling probe that enables a non-invasive, high-sensitive and real-time MRI tracking. Using a mouse model of traumatic brain injury (TBI), MIEG labeled MSCs were transplanted into the contralateral lateral ventricle followed by real-time MRI tracking. FGF21 retained MSC abilities of proliferation and morphology. MSC-FGF21 showed significantly greater migration in transwell assay compared to control MSC. MIEG labeling showed no effects on MSCs' viability, proliferation and differentiation. Magnetic resonance imaging (MRI) revealed that FGF21 significantly enhances the homing of MSC toward injury site. Histological analysis further confirmed the MRI findings. Taken together, these results show that FGF21 overexpression and MIEG labeling of MSC enhances their homing abilities and enables non-invasive real time tracking of the transplanted cells, provides a promising approach for MSC based therapy and tracking in TBI.


Exploring Ecological Alternatives for Crop Protection Using Coriandrum sativum Essential Oil.

  • Renata Maria Sumalan‎ et al.
  • Molecules (Basel, Switzerland)‎
  • 2019‎

Essential oils (EOs) are a natural source of active compounds with antifungal, antimycotoxigenic, and herbicidal potential, and have been successfully used in organic agriculture, instead of chemical compounds obtained by synthesis, due to their high bioactivity and the absence of toxicity. The aim of this study was to highlight the importance of Coriandrum sativum essential oil (CEO) as a potential source of bioactive constituents and its applications as an antifungal and bioherbicidal agent. The CEO was obtained by steam distillation of coriander seeds and GC-MS technique was used to determine the chemical composition. Furthermore, in vitro tests were used to determine the antifungal potential of CEO on Fusarium graminearum mycelia growth through poisoned food technique, resulting in the minimum fungistatic (MCFs) and fungicidal concentrations (MCFg). The antifungal and antimycotoxigenic effect of CEO was studied on artificially contaminated wheat seeds with F. graminearum spores. Additionally, the herbicidal potential of CEO was studied by fumigating monocotyledonous and dicotyledonous weed seeds, which are problematic in agricultural field crops in Romania. The in vitro studies showed the antifungal potential of CEO, with a minimum concentration for a fungistatic effect of 0.4% and the minimum fungicidal concentration of 0.6%, respectively. An increase in the antifungal effects was observed in the in vivo experiment with F. graminearum, where a mixture of CEO with Satureja hortensis essential oil (SEO) was used. This increase is attributed to the synergistic effect of both EOs. Moreover, the synthesis of deoxynivalenol (DON)-type mycotoxins was found to be less inhibited. Hence, CEO has shown an herbicidal potential on weed seeds by affecting inhibition of germination.


Susceptibility Profiles of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) to Deltamethrin Reveal a Contrast between the Northern and the Southern Benin.

  • Eric Tossou‎ et al.
  • International journal of environmental research and public health‎
  • 2019‎

Helicoverpa armigera is an indigenous species in Africa and has been reported in the destruction of several crops in Benin. Management of H. armigera pest is mainly focused on the use of synthetic pyrethroids, which may contribute to resistance selection. This study aimed to screen the susceptibility pattern of field populations of H. armigera to deltamethrin in Benin. Relevant information on the type of pesticides used by farmers were gathered through surveys. Collected samples of Helicoverpa (F0) were reared to F1. F0 were subjected to morphological speciation followed by a confirmation using restriction fragment length polymorphism coupled with a polymerase chain reaction (RFLP-PCR). F1 (larvae) were used for insecticide susceptibility with deltamethrin alone and in the presence of the P450 inhibitor Piperonyl Butoxide (PBO). Deltamethrin and lambda-cyhalothrin were the most used pyrethroids in tomato and cotton farms respectively. All field-sampled Helicoverpa were found to be H. armigera. Susceptibility assays of H. armigera to deltamethrin revealed a high resistance pattern in cowpea (resistance factor (RF) = 2340), cotton (RF varying from 12 to 516) and tomato (RF=85) farms which is a concern for the control of this major polyphagous agricultural pest. There was a significant increase of mortality when deltamethrin insecticide was combined with piperonyl butoxide (PBO), suggesting the possible involvement of detoxification enzymes such as oxidase. This study highlights the presence of P450 induced metabolic resistance in H. armigera populations from diverse cropping systems in Benin. The recorded high levels of deltamethrin resistance in H. armigera is a concern for the control of this major agricultural pest in Benin as the country is currently embarking into economical expansion of cotton, vegetables and grain-legumes cropping systems.


The Impact of Environmental Transmission and Epidemiological Features on the Geographical Translocation of Highly Pathogenic Avian Influenza Virus.

  • Xueying Li‎ et al.
  • International journal of environmental research and public health‎
  • 2019‎

The factors affecting the transmission and geographic translocation of avian influenza viruses (AIVs) within wild migratory bird populations remain inadequately understood. In a previous study, we found that environmental transmission had little impact on AIV translocation in a model of a single migratory bird population. In order to simulate virus transmission and translocation more realistically, here we expanded this model system to include two migratory bird flocks. We simulated AIV transmission and translocation while varying four core properties: 1) Contact transmission rate; 2) infection recovery rate; 3) infection-induced mortality rate; and 4) migration recovery rate; and three environmental transmission properties: 1) Virion persistence; 2) exposure rate; and 3) re-scaled environmental infectiousness; as well as the time lag in the migration schedule of the two flocks. We found that environmental exposure rate had a significant impact on virus translocation in the two-flock model. Further, certain epidemiological features (i.e., low infection recovery rate, low mortality rate, and high migration transmission rate) in both flocks strongly affected the likelihood of virus translocation. Our results further identified the pathobiological features supporting AIV intercontinental dissemination risk.


Cellular Changes in Injured Rat Spinal Cord Following Electrical Brainstem Stimulation.

  • Walter J Jermakowicz‎ et al.
  • Brain sciences‎
  • 2019‎

Spinal cord injury (SCI) is a major cause of disability and pain, but little progress has been made in its clinical management. Low-frequency electrical stimulation (LFS) of various anti-nociceptive targets improves outcomes after SCI, including motor recovery and mechanical allodynia. However, the mechanisms of these beneficial effects are incompletely delineated and probably multiple. Our aim was to explore near-term effects of LFS in the hindbrain's nucleus raphe magnus (NRM) on cellular proliferation in a rat SCI model. Starting 24 h after incomplete contusional SCI at C5, intermittent LFS at 8 Hz was delivered wirelessly to NRM. Controls were given inactive stimulators. At 48 h, 5-bromodeoxyuridine (BrdU) was administered and, at 72 h, spinal cords were extracted and immunostained for various immune and neuroglial progenitor markers and BrdU at the level of the lesion and proximally and distally. LFS altered cell marker counts predominantly at the dorsal injury site. BrdU cell counts were decreased. Individually and in combination with BrdU, there were reductions in CD68 (monocytes) and Sox2 (immature neural precursors) and increases in Blbp (radial glia) expression. CD68-positive cells showed increased co-staining with iNOS. No differences in the expression of GFAP (glia) and NG2 (oligodendrocytes) or in GFAP cell morphology were found. In conclusion, our work shows that LFS of NRM in subacute SCI influences the proliferation of cell types implicated in inflammation and repair, thus providing mechanistic insight into deep brain stimulation as a neuromodulatory treatment for this devastating pathology.


The Biochemical Activities of the Saccharomyces cerevisiae Pif1 Helicase Are Regulated by Its N-Terminal Domain.

  • David G Nickens‎ et al.
  • Genes‎
  • 2019‎

: Pif1 family helicases represent a highly conserved class of enzymes involved in multiple aspects of genome maintenance. Many Pif1 helicases are multi-domain proteins, but the functions of their non-helicase domains are poorly understood. Here, we characterized how the N-terminal domain (NTD) of the Saccharomyces cerevisiae Pif1 helicase affects its functions both in vivo and in vitro. Removal of the Pif1 NTD alleviated the toxicity associated with Pif1 overexpression in yeast. Biochemically, the N-terminally truncated Pif1 (Pif1ΔN) retained in vitro DNA binding, DNA unwinding, and telomerase regulation activities, but these activities differed markedly from those displayed by full-length recombinant Pif1. However, Pif1ΔN was still able to synergize with the Hrq1 helicase to inhibit telomerase activity in vitro, similar to full-length Pif1. These data impact our understanding of Pif1 helicase evolution and the roles of these enzymes in the maintenance of genome integrity.


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