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1.
Mol Biol Evol ; 40(3)2023 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-36795638

RESUMEN

The reproductive success of flowering plants with generalized pollination systems is influenced by interactions with a diverse pollinator community and abiotic factors. However, knowledge about the adaptative potential of plants to complex ecological networks and the underlying genetic mechanisms is still limited. Based on a pool-sequencing approach of 21 natural populations of Brassica incana in Southern Italy, we combined a genome-environmental association analysis with a genome scan for signals of population genomic differentiation to discover genetic variants associated with the ecological variation. We identified genomic regions putatively involved in the adaptation of B. incana to the identity of local pollinator functional categories and pollinator community composition. Interestingly, we observed several shared candidate genes associated with long-tongue bees, soil texture, and temperature variation. We established a genomic map of potential generalist flowering plant local adaptation to complex biotic interactions, and the importance of considering multiple environmental factors to describe the adaptive landscape of plant populations.


Asunto(s)
Flores , Magnoliopsida , Abejas/genética , Animales , Flores/genética , Plantas , Adaptación Fisiológica/genética , Polinización , Reproducción
2.
Antimicrob Agents Chemother ; 67(11): e0162522, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37882542

RESUMEN

Understanding the resistance mechanisms of antibiotics in the micro-environment of the infection is important to assess their clinical applicability and potentially prevent resistance development. We compared the laboratory resistance evolution of Escherichia coli to delafloxacin (DLX) compared to ciprofloxacin (CIP), the co-resistance evolution, and underlying resistance mechanisms at different pHs. Three clones from each of the eight clinical E. coli isolates were subjected to subinhibitory concentrations of DLX or CIP in parallel at either pH 7.3 or 6.0. Minimum inhibitory concentrations (MICs) were regularly tested (at respective pHs), and the antibiotic concentration was adjusted accordingly. After 30 passages, MICs were determined in the presence of the efflux pump inhibitor phenylalanine-arginine-ß-naphthylamide. Whole genome sequencing of the parental isolates and their resistant derivatives (n = 54) was performed. Complementation assays were carried out for selected mutations. Quantitative PCR and efflux experiments were carried out for selected derivatives. For DLX-challenged strains, resistance to DLX evolved much slower in acidic than in neutral pH, whereas for CIP-challenged strains, the opposite was the case. Mutations in the quinolone resistance-determining region were mainly seen in CIP-challenged E. coli, whereas a multifactorial mechanism including mutations in efflux-related genes played a role in DLX resistance evolution (predominantly at pH 6.0). This work provides novel insights into the resistance mechanisms of E. coli to delafloxacin and highlights the importance of understanding micro-environmental conditions at the infection site that might affect the true clinical efficacy of antibiotics and challenges our current antibiotic susceptibility-testing paradigm.


Asunto(s)
Ciprofloxacina , Escherichia coli , Ciprofloxacina/farmacología , Fluoroquinolonas/farmacología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana/genética
3.
Environ Microbiol ; 25(12): 3116-3138, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37688461

RESUMEN

Glacier retreat is a visible consequence of climate change worldwide. Although taxonomic change of the soil microbiomes in glacier forefields have been widely documented, how microbial genetic potential changes along succession is little known. Here, we used shotgun metagenomics to analyse whether the soil microbial genetic potential differed between four stages of soil development (SSD) sampled along three transects in the Damma glacier forefield (Switzerland). The SSDs were characterized by an increasing vegetation cover, from barren soil, to biological soil crust, to sparsely vegetated soil and finally to vegetated soil. Results suggested that SSD significantly influenced microbial genetic potential, with the lowest functional diversity surprisingly occurring in the vegetated soils. Overall, carbohydrate metabolism and secondary metabolite biosynthesis genes overrepresented in vegetated soils, which could be partly attributed to plant-soil feedbacks. For C degradation, glycoside hydrolase genes enriched in vegetated soils, while auxiliary activity and carbohydrate esterases genes overrepresented in barren soils, suggested high labile C degradation potential in vegetated, and high recalcitrant C degradation potential in barren soils. For N-cycling, organic N degradation and synthesis genes dominated along succession, and gene families involved in nitrification were overrepresented in barren soils. Our study provides new insights into how the microbial genetic potential changes during soil formation along the Damma glacier forefield.


Asunto(s)
Cubierta de Hielo , Suelo , Microbiología del Suelo , Plantas , Nitrificación
4.
Small ; 19(39): e2302097, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37226377

RESUMEN

Na3 V2 (PO4 )2 O2 F (NVPOF) is widely accepted as advanced cathode material for sodium-ion batteries with high application prospects ascribing to its considerable specific capacity and high working voltage. However, challenges in the full realization of its theoretical potential lie in the novel structural design to accelerate its Na+ diffusivity. Herein, considering the important role of polyanion groups in constituting Na+ diffusion tunnels, boron (B) is doped at the P-site to obtain Na3 V2 (P2- x Bx O8 )O2 F (NVP2- x Bx OF). As evidenced by density functional theory modeling, B-doping induces a dramatic decrease in the bandgap. Delocalization of electrons on the O anions in BO4 tetrahedra is observed in NVP2- x Bx OF, which dramatically lowers the electrostatic resistance experienced by Na+ . As a result, the Na+ diffusivity in the NVP2- x Bx OF cathode has accelerated up to 11 times higher, which secures a high rate property (67.2 mAh g-1 at 60 C) and long cycle stability (95.9% capacity retention at 108.6 mAh g-1 at 10 C after 1000 cycles). The assembled NVP1.90 B0.10 OF//Se-C full cell demonstrates exceptional power/energy density (213.3 W kg-1 @ 426.4 Wh kg-1 and 17970 W kg-1 @ 119.8 Wh kg-1 ) and outstanding capability to withstand long cycles (90.1% capacity retention after 1000 cycles at 105.3 mAh g-1 at 10 C).

5.
Int J Mol Sci ; 24(3)2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36769192

RESUMEN

Pleural mesothelioma (PM) is a cancer where epithelioid, biphasic and sarcomatoid histotypes are observed. Sarcomatoid PM is characterized by mesenchymal features. Multi-omics have been used to characterize the epithelial-to-mesenchymal (EMT) phenotype at the molecular level. We contribute to this effort by including the analysis of RNA editing. We extracted samples with the highest vs. lowest Epithelial score from two PM cohorts and observed increased RNA editing in introns and decreased RNA editing in 3'UTR upon EMT. The same was observed in primary PM primary cultures stratified by transcriptomics analysis into two groups, one of them enriched with mesenchymal features. Our data demonstrate that, as has been observed in other cancer types, RNA editing associates to EMT phenotype in PM.


Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Transición Epitelial-Mesenquimal/genética , Edición de ARN/genética , Neoplasias Pulmonares/genética , Biomarcadores de Tumor/genética , Mesotelioma/genética , Neoplasias Pleurales/genética
6.
Small ; 18(15): e2107541, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35254002

RESUMEN

Mo-Ni alloy-based electrocatalysts are regarded as promising candidates for the hydrogen evolution reaction (HER), despite their vulnerable stability in alkaline solution that hampers further application. Herein, Mo2 TiC2 Tx MXene, is employed as a support for MoNi4 alloy nanocrystals (NCs) to fabricate a unique nanoflower-like MoNi4 -MXn electrocatalyst. A remarkably strong built-in electric field is established at the interface of two components, which facilitates the electron transfer from Mo2 TiC2 Tx to MoNi4 . Due to the accumulation of electrons at the MoNi4 sites, the adsorption of the catalytic intermediates and ionic species on MoNi4 is affected consequently. As a result, the MoNi4 -MX10 nanohybrid exhibits the lowest overpotential, even lower than 10% Pt/C catalyst at the current density of 10 mA cm-2 in 1 m KOH solution (122.19 vs 129.07 mV, respectively). Furthermore, a lower Tafel slope of 55.88 mV dec-1 is reported as compared to that of the 10% Pt/C (65.64 mV dec-1 ). Additionally, the MoNi4 -MX10 catalyst also displays extraordinary chemical stability in alkaline solution, with an activity loss of only 0.15% per hour over 300 h of operation. This reflects the great potential of using MXene-based interfacial engineering for the synthesis of a highly efficient and stable electrocatalyst.

7.
Glob Chang Biol ; 27(7): 1365-1386, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33336444

RESUMEN

Climate change is strongly affecting high-mountain soils and warming in particular is associated with pronounced changes in microbe-mediated C and N cycling, affecting plant-soil interactions and greenhouse gas balances and therefore feedbacks to global warming. We used shotgun metagenomics to assess changes in microbial community structures, as well as changes in microbial C- and N-cycling potential and stress response genes and we linked these data with changes in soil C and N pools and temperature-dependent measurements of bacterial growth rates. We did so by incubating high-elevation soil from the Swiss Alps at 4°C, 15°C, 25°C, or 35°C for 1 month. We found no shift with increasing temperature in the C-substrate-degrader community towards taxa more capable of degrading recalcitrant organic matter. Conversely, at 35°C, we found an increase in genes associated with the degradation and modification of microbial cell walls, together with high bacterial growth rates. Together, these findings suggest that the rapidly growing high-temperature community is fueled by necromass from heat-sensitive taxa. This interpretation was further supported by a shift in the microbial N-cycling potential towards N mineralization and assimilation under higher temperatures, along with reduced potential for conversions among inorganic N forms. Microbial stress-response genes reacted inconsistently to increasing temperature, suggesting that the high-temperature community was not severely stressed by these conditions. Rather, soil microbes were able to acclimate by changing the thermal properties of membranes and cell walls as indicated by an increase in genes involved in membrane and cell wall modifications as well as a shift in the optimum temperature for bacterial growth towards the treatment temperature. Overall, our results suggest that high temperatures, as they may occur with heat waves under global warming, promote a highly active microbial community capable of rapid mineralization of microbial necromass, which may transiently amplify warming effects.


Asunto(s)
Microbiología del Suelo , Suelo , Genética Microbiana , Calor , Temperatura
8.
Gynecol Obstet Invest ; 85(1): 26-33, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31466066

RESUMEN

BACKGROUND: The estrogen receptor α (ERα) gene is a potential candidate gene of gestational diabetes mellitus (GDM). OBJECTIVES: The purpose of the study was to investigate the relationship of ERα gene polymorphism (single nucleotide polymorphism [SNP]) and its expression in placental tissues with the development of GDM. METHODS: The SNPs of PvuII and Xba I in the ERα gene of 175 pregnant women with GDM and 240 healthy pregnant women were detected by polymerase chain reaction-restriction fragment length polymorphism. Immunohistochemistry and western blotting were used to analyze the expression of the ERα gene in placental tissues. RESULTS: The results showed that the frequency of the CC + CT genotype and the C allele frequency of PvuII in the GDM group was significantly higher than that of the control group (p < 0.05). There was no significant difference in the genotype distribution and allele frequency of Xba I between the GDM group and control group. The expression of ERα in placental tissues of pregnant women with GDM was higher than that in the control group (p < 0.05). The participants with the PvuII CC + CT genotype had elevated levels of fasting blood glucose, homeostasis model assessment of insulin resistance (IR), and ERα expression in placental tissues compared with those with the TT genotype in the GDM group (p < 0.05). The SNP of Xba I of ERα gene had no correlation with clinical biochemical indicators of GDM and the expression of ERα in placental tissues (p > 0.05). CONCLUSIONS: This study suggested that SNP of the ERα gene and abnormal expression of ERα in placenta tissues were associated with GDM. The C allele of PvuII may be associated with GDM. In addition, SNP of the PvuII site in pregnant women with GDM was related to the degree of IR and to the upregulation of ERα expression in placental tissues, which may play an important role in the pathogenesis of GDM.


Asunto(s)
Diabetes Gestacional/genética , Receptor alfa de Estrógeno/metabolismo , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Resistencia a la Insulina/genética , Placenta/metabolismo , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Embarazo
9.
BMC Biol ; 17(1): 75, 2019 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-31533702

RESUMEN

BACKGROUND: Cassava is an important food crop in tropical and sub-tropical regions worldwide. In Africa, cassava production is widely affected by cassava mosaic disease (CMD), which is caused by the African cassava mosaic geminivirus that is transmitted by whiteflies. Cassava breeders often use a single locus, CMD2, for introducing CMD resistance into susceptible cultivars. The CMD2 locus has been genetically mapped to a 10-Mbp region, but its organization and genes as well as their functions are unknown. RESULTS: We report haplotype-resolved de novo assemblies and annotations of the genomes for the African cassava cultivar TME (tropical Manihot esculenta), which is the origin of CMD2, and the CMD-susceptible cultivar 60444. The assemblies provide phased haplotype information for over 80% of the genomes. Haplotype comparison identified novel features previously hidden in collapsed and fragmented cassava genomes, including thousands of allelic variants, inter-haplotype diversity in coding regions, and patterns of diversification through allele-specific expression. Reconstruction of the CMD2 locus revealed a highly complex region with nearly identical gene sets but limited microsynteny between the two cultivars. CONCLUSIONS: The genome maps of the CMD2 locus in both 60444 and TME3, together with the newly annotated genes, will help the identification of the causal genetic basis of CMD2 resistance to geminiviruses. Our de novo cassava genome assemblies will also facilitate genetic mapping approaches to narrow the large CMD2 region to a few candidate genes for better informed strategies to develop robust geminivirus resistance in susceptible cassava cultivars.


Asunto(s)
Resistencia a la Enfermedad/genética , Haplotipos/genética , Manihot/genética , Enfermedades de las Plantas/genética , Mapeo Cromosómico/métodos , Susceptibilidad a Enfermedades , Geminiviridae , Predisposición Genética a la Enfermedad , Anotación de Secuencia Molecular
10.
Kidney Int ; 95(2): 375-387, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30502050

RESUMEN

Erythropoietin (Epo) is essential for erythropoiesis and is mainly produced by the fetal liver and the adult kidney following hypoxic stimulation. Epo regulation is commonly studied in hepatoma cell lines, but differences in Epo regulation between kidney and liver limit the understanding of Epo dysregulation in polycythaemia and anaemia. To overcome this limitation, we have generated a novel transgenic mouse model expressing Cre recombinase specifically in the active fraction of renal Epo-producing (REP) cells. Crossing with reporter mice confirmed the inducible and highly specific tagging of REP cells, located in the corticomedullary border region where there is a steep drop in oxygen bioavailability. A novel method was developed to selectively grow primary REP cells in culture and to generate immortalized clonal cell lines, called fibroblastoid atypical interstitial kidney (FAIK) cells. FAIK cells show very early hypoxia-inducible factor (HIF)-2α induction, which precedes Epo transcription. Epo induction in FAIK cells reverses rapidly despite ongoing hypoxia, suggesting a cell autonomous feedback mechanism. In contrast, HIF stabilizing drugs resulted in chronic Epo induction in FAIK cells. RNA sequencing of three FAIK cell lines derived from independent kidneys revealed a high degree of overlap and suggests that REP cells represent a unique cell type with properties of pericytes, fibroblasts, and neurons, known as telocytes. These novel cell lines may be helpful to investigate myofibroblast differentiation in chronic kidney disease and to elucidate the molecular mechanisms of HIF stabilizing drugs currently in phase III studies to treat anemia in end-stage kidney disease.


Asunto(s)
Eritropoyetina/metabolismo , Telocitos/patología , Factores de Transcripción/metabolismo , Anemia/etiología , Anemia/patología , Animales , Hipoxia de la Célula , Línea Celular , Eritropoyetina/genética , Retroalimentación Fisiológica , Riñón/citología , Riñón/patología , Ratones , Ratones Transgénicos , Cultivo Primario de Células , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/patología , Telocitos/metabolismo
12.
Phys Chem Chem Phys ; 20(46): 29333-29340, 2018 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-30444241

RESUMEN

This study presents a new van der Waals (vdW) heterostructure composed of monolayer black phosphorus (BP) and monolayer graphitic SiC (g-SiC). Using first-principles calculations, the structural and electronic properties of the BP/SiC heterostructure were investigated. It was found that by stacking BP with SiC, weak type-I band alignment can be achieved with a band gap of 0.705 eV, where the direct band gap as well as linear dichroism features were well preserved. The electrostatic potential drop in the heterojunction was calculated to be 4.044 eV. By applying perpendicular electric field, the band alignment can be altered to either type-I or type-II, and the band gap can be effectively controlled by field intensity, hence making the heterostructure suitable for various applications.

13.
J Nanosci Nanotechnol ; 18(12): 8276-8281, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-30189947

RESUMEN

Marks decahedral nanoparticles have attracted significant attention in recent years. In this work, a method of synthesizing Marks decahedron via etching regular decahedral nanoparticles is proposed and verified by Pd nanoparticles, which shows a high yield of Marks decahedron. The present work suggests that one can tune the concave size of Marks decahedral via controlling the etching time and the amount of Poly(vinyl pyrrolidone) (PVP). The thermal stability of Marks nanoparticles is explained by Bond-Energy model, which predicts the largest groove to be the most stable configuration. Moreover, the present method can be extended to synthesize Marks decahedral nanoparticles of other elements, and is of great significance for further studies and applications of Mark decahedral nanoparticles.

14.
Regul Toxicol Pharmacol ; 95: 190-197, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29580973

RESUMEN

PEGylated recombinant human endostatin (M2ES) exhibited prolonged serum half-life and enhanced antitumor activity when compared with endostatin. A pre-clinical study was performed to evaluate the safety of M2ES in rats. After intravenous (IV) infusions of M2ES at a dose level of 3, 15 and 75 mg/kg in Sprague Dawley (SD) rats, M2ES was well tolerated in animals, with no observable changes in clinical observation, body weight, food consumption, urine analysis, hematology and serum biochemical analysis. The increase of kidney weights, and slight to severe vacuolation and necrosis of proximal tubule epithelial cells in kidney were observed in 15 and 75 mg/kg M2ES groups, but this adverse-effect was reversible. In summary, the major toxicity target organ of M2ES might be kidney, and the no observed adverse effect level (NOAEL) of M2ES in rats was 3 mg/kg in this study. These pre-clinical safety data contribute to the initiation of the ongoing clinical study.


Asunto(s)
Endostatinas/toxicidad , Polietilenglicoles/toxicidad , Animales , Anticuerpos/sangre , Evaluación Preclínica de Medicamentos , Endostatinas/química , Endostatinas/inmunología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Femenino , Humanos , Túbulos Renales Proximales/citología , Masculino , Necrosis/inducido químicamente , Nivel sin Efectos Adversos Observados , Polietilenglicoles/química , Ratas Sprague-Dawley , Proteínas Recombinantes/química , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/toxicidad , Pruebas de Toxicidad Subcrónica
15.
Environ Microbiol ; 19(5): 1899-1913, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28205377

RESUMEN

Several Chlamydiales families are associated with epitheliocystis, a common condition of the fish gill epithelium. These families share common ancestors with the Chlamydiaceae and environmental Chlamydiae. Due to the lack of culture systems, little is known about the biology of these chlamydial fish pathogens. We investigated epitheliocystis in cultured Orange-spotted grouper (Epinephelus coioides) from North Queensland, Australia. Basophilic inclusions were present in the gills of 22/31 fish and the presence of the chlamydial pathogen in the cysts was confirmed by in situ hybridization. Giant grouper (Epinephelus lanceolatus) cultured in the same systems were epitheliocystis free. 16S rRNA gene sequencing revealed a novel member of the Candidatus Parilichlamydiaceae: Ca. Similichlamydia epinephelii. Using metagenomic approaches, we obtained an estimated 68% of the chlamydial genome, revealing that this novel chlamydial pathogen shares a number of key pathogenic hallmarks with the Chlamydiaceae, including an intact Type III Secretion system and several chlamydial virulence factors. This provides additional evidence that these pathogenic mechanisms were acquired early in the evolution of this unique bacterial phylum. The identification and genomic characterization of Ca. S. epinephelii provides new opportunities to study the biology of distantly-related chlamydial pathogens while shining a new light on the evolution of pathogenicity of the Chlamydiaceae.


Asunto(s)
Lubina/microbiología , Infecciones por Chlamydia/microbiología , Chlamydia/clasificación , Chlamydia/genética , Enfermedades de los Peces/microbiología , Branquias/microbiología , Animales , Australia , Composición de Base/genética , Chlamydia/patogenicidad , Infecciones por Chlamydia/patología , ADN Bacteriano/genética , Genoma Bacteriano/genética , Genómica , ARN Ribosómico 16S/genética , Sistemas de Secreción Tipo III/genética , Factores de Virulencia/genética
16.
Acc Chem Res ; 49(9): 1587-95, 2016 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-27355129

RESUMEN

Conventional thermodynamics for bulk substances encounters challenges when one considers materials on the nanometer scale. Quantities such as entropy, enthalpy, free energy, melting temperature, ordering temperature, Debye temperature, and specific heat no longer remain constant but change with the crystal dimension, size, and morphology. Often, one phenomenon is associated with a variety of theories from different perspectives. Still, a model that can reconcile the size and shape dependence of the thermal properties of the nanoscaled substances remains one of the goals of nanoscience and nanotechnology. This Account highlights the nanoscopic thermodynamics for nanoparticles, nanowires, and nanofilms, with particular emphasis on the bond energy model. The central idea is that the atomic cohesive energy determines the thermodynamic performance of a substance and the cohesive energy varies with the atomic coordination environment. It is the cohesive energy difference between the core and the shell that dictates the nanoscopic thermodynamics. This bond energy model rationalizes the following: (i) how the surface dangling bonds depress the melting temperature, entropy, and enthalpy; (ii) how the order-disorder transition of the nanoparticles depends on particle size and how their stability may vary when they are embedded in an appropriate matrix; (iii) predictions of the existence of face-centered cubic structures of Ti, Zr, and Hf at small size; (iv) how two elements that are immiscible in the bulk can form an alloy on the nanoscale, where the critical size can be predicted. The model has enabled us to reproduce the size and shape dependence of a number of physical properties, such as melting temperature, melting entropy, melting enthalpy, ordering temperature, Gibbs free energy, and formation heat, among others, for materials such as Pd, Au, Ag, Cu, Ni, Sn, Pb, In, Bi, Al, Ti, Zr, Hf, In-Al, Ag-Ni, Co-Pt, Cu-Ag, Cu-Ni, Au-Ni, Ag-Pt, and Au-Pt on the nanometer scale. Furthermore, this model predicts the phenomena of the thermal stability of metal particles on graphene, the superheating of embedded nanoparticles, the order-disorder transition of nanoalloys, the size-temperature phase diagram for low-dimensional solids and the alloying ability on the nanoscale. Extensions of this model may lead to the design of new functional nanomaterials.

17.
Mol Cell Biochem ; 432(1-2): 199-208, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28374141

RESUMEN

Insulin-like growth factor II (IGF-II) can stimulate myogenesis and is critically involved in skeletal muscle differentiation. The presence of negative regulators of this process, however, is not well explored. Here, we showed that in myoblast cells, IGF-II negatively regulated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mRNA expression, while constitutive expression of PGC-1α induced myoblast differentiation. These results suggest that the negative regulation of PGC-1α by IGF-II may act as a negative feedback mechanism in IGF-II-induced myogenic differentiation. Reporter assays demonstrated that IGF-II suppresses the basal PGC-1α promoter activity. Blocking the IGF-II signaling pathway increased the endogenous PGC-1α levels. In addition, pharmacological inhibition of PI3 kinase activity prevented the downregulation of PGC-1α but the activation of mTOR was not required for this process. Importantly, further analysis showed that forkhead transcription factor FoxO1 contributes to mediating the effects of IGF-II on PGC-1 promoter activity. These findings indicate that IGF-II reduces PGC-1α expression in skeletal muscle cells through a mechanism involving PI3K-Akt-FoxO1 but not p38 MAPK or Erk1/2 MAPK pathways.


Asunto(s)
Proteína Forkhead Box O1/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Músculo Esquelético/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Animales , Línea Celular , Proteína Forkhead Box O1/genética , Factor II del Crecimiento Similar a la Insulina/genética , Ratones , Músculo Esquelético/citología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética
18.
PLoS Genet ; 10(7): e1004476, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25010342

RESUMEN

Seeds of flowering plants can be formed sexually or asexually through apomixis. Apomixis occurs in about 400 species and is of great interest for agriculture as it produces clonal offspring. It differs from sexual reproduction in three major aspects: (1) While the sexual megaspore mother cell (MMC) undergoes meiosis, the apomictic initial cell (AIC) omits or aborts meiosis (apomeiosis); (2) the unreduced egg cell of apomicts forms an embryo without fertilization (parthenogenesis); and (3) the formation of functional endosperm requires specific developmental adaptations. Currently, our knowledge about the gene regulatory programs underlying apomixis is scarce. We used the apomict Boechera gunnisoniana, a close relative of Arabidopsis thaliana, to investigate the transcriptional basis underlying apomeiosis and parthenogenesis. Here, we present the first comprehensive reference transcriptome for reproductive development in an apomict. To compare sexual and apomictic development at the cellular level, we used laser-assisted microdissection combined with microarray and RNA-Seq analyses. Conservation of enriched gene ontologies between the AIC and the MMC likely reflects functions of importance to germline initiation, illustrating the close developmental relationship of sexuality and apomixis. However, several regulatory pathways differ between sexual and apomictic germlines, including cell cycle control, hormonal pathways, epigenetic and transcriptional regulation. Enrichment of specific signal transduction pathways are a feature of the apomictic germline, as is spermidine metabolism, which is associated with somatic embryogenesis in various plants. Our study provides a comprehensive reference dataset for apomictic development and yields important new insights into the transcriptional basis underlying apomixis in relation to sexual reproduction.


Asunto(s)
Apomixis/genética , Arabidopsis/genética , Desarrollo Sexual/genética , Transcripción Genética , Arabidopsis/crecimiento & desarrollo , Ciclo Celular/genética , Epigénesis Genética , Regulación de la Expresión Génica de las Plantas , Células Germinativas/crecimiento & desarrollo , Meiosis/genética , Reproducción/genética , Semillas/genética , Semillas/crecimiento & desarrollo
19.
BMC Bioinformatics ; 17(1): 228, 2016 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-27255077

RESUMEN

BACKGROUND: Next generation sequencing (NGS) produces massive datasets consisting of billions of reads and up to thousands of samples. Subsequent bioinformatic analysis is typically done with the help of open source tools, where each application performs a single step towards the final result. This situation leaves the bioinformaticians with the tasks to combine the tools, manage the data files and meta-information, document the analysis, and ensure reproducibility. RESULTS: We present SUSHI, an agile data analysis framework that relieves bioinformaticians from the administrative challenges of their data analysis. SUSHI lets users build reproducible data analysis workflows from individual applications and manages the input data, the parameters, meta-information with user-driven semantics, and the job scripts. As distinguishing features, SUSHI provides an expert command line interface as well as a convenient web interface to run bioinformatics tools. SUSHI datasets are self-contained and self-documented on the file system. This makes them fully reproducible and ready to be shared. With the associated meta-information being formatted as plain text tables, the datasets can be readily further analyzed and interpreted outside SUSHI. CONCLUSION: SUSHI provides an exquisite recipe for analysing NGS data. By following the SUSHI recipe, SUSHI makes data analysis straightforward and takes care of documentation and administration tasks. Thus, the user can fully dedicate his time to the analysis itself. SUSHI is suitable for use by bioinformaticians as well as life science researchers. It is targeted for, but by no means constrained to, NGS data analysis. Our SUSHI instance is in productive use and has served as data analysis interface for more than 1000 data analysis projects. SUSHI source code as well as a demo server are freely available.


Asunto(s)
Biología Computacional/métodos , Programas Informáticos , Secuenciación de Nucleótidos de Alto Rendimiento , Reproducibilidad de los Resultados , Estadística como Asunto
20.
Mol Biol Evol ; 32(12): 3114-31, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26330546

RESUMEN

Viviparity (live birth) has evolved more than 150 times in vertebrates, and represents an excellent model system for studying the evolution of complex traits. There are at least 23 independent origins of viviparity in fishes, with syngnathid fishes (seahorses and pipefish) unique in exhibiting male pregnancy. Male seahorses and pipefish have evolved specialized brooding pouches that provide protection, gas exchange, osmoregulation, and limited nutrient provisioning to developing embryos. Pouch structures differ widely across the Syngnathidae, offering an ideal opportunity to study the evolution of reproductive complexity. However, the physiological and genetic changes facilitating male pregnancy are largely unknown. We used transcriptome profiling to examine pouch gene expression at successive gestational stages in a syngnathid with the most complex brood pouch morphology, the seahorse Hippocampus abdominalis. Using a unique time-calibrated RNA-seq data set including brood pouch at key stages of embryonic development, we identified transcriptional changes associated with brood pouch remodeling, nutrient and waste transport, gas exchange, osmoregulation, and immunological protection of developing embryos at conception, development and parturition. Key seahorse transcripts share homology with genes of reproductive function in pregnant mammals, reptiles, and other live-bearing fish, suggesting a common toolkit of genes regulating pregnancy in divergent evolutionary lineages.


Asunto(s)
Reproducción/genética , Smegmamorpha/genética , Viviparidad de Animales no Mamíferos/genética , Animales , Evolución Biológica , Femenino , Fertilización , Perfilación de la Expresión Génica , Masculino , Análisis de Secuencia de ARN , Conducta Sexual Animal
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