Introduction: utism spectrum disorder (ASD) is a heterogeneous clinical condition, and its genetic basis is widely confirmed. The chromosomal microarray analysis (CMA) is a first-line diagnostic test that identifies copy number variants (CNVs). Some of these genomic rearrangements are associated with ASD, but the meaning of most of them is still unknown. Materials and methods: We performed a comparative genome hybridization (array-CGH) analysis in 130 children with confirmed ASD. Genetic results were analyzed and compared to clinical phenotype. Results and discussion.: 61/130 children carry CNVs, 44 presenting variants of unknown significance (u-CNVs), and 17 with susceptibility-CNVs (c-CNVs). Clinical evaluation showed no differences in cognitive abilities, language and EEG abnormalities, ASD symptoms among CNVs group and other patients. Finally, we highlight the role of GPHN, IMMP2L and ZMYND11, as ASD susceptibility genes. Conclusions: Our findings underscore the importance of array-CGH in ASD children since new CNVs and emerging genes appear to be associated with different clinical pictures.
Autism Spectrum Disorder , Humans , Child , Autism Spectrum Disorder/genetics , Comparative Genomic Hybridization , Cognition , Language , DNA-Binding Proteins , Cell Cycle Proteins , Co-Repressor Proteins
Tunneling nanotubes (TNTs) are long F-actin-positive plasma membrane bridges connecting distant cells, allowing the intercellular transfer of cellular cargoes, and are found to be involved in glioblastoma (GBM) intercellular crosstalk. Glial fibrillary acid protein (GFAP) is a key intermediate filament protein of glial cells involved in cytoskeleton remodeling and linked to GBM progression. Whether GFAP plays a role in TNT structure and function in GBM is unknown. Here, analyzing F-actin and GFAP localization by laser-scan confocal microscopy followed by 3D reconstruction (3D-LSCM) and mitochondria dynamic by live-cell time-lapse fluorescence microscopy, we show the presence of GFAP in TNTs containing functional mitochondria connecting distant human GBM cells. Taking advantage of super-resolution 3D-LSCM, we show the presence of GFAP-positive TNT-like structures in resected human GBM as well. Using H2O2 or the pro-apoptotic toxin staurosporine (STS), we show that GFAP-positive TNTs strongly increase during oxidative stress and apoptosis in the GBM cell line. Culturing GBM cells with STS-treated GBM cells, we show that STS triggers the formation of GFAP-positive TNTs between them. Finally, we provide evidence that mitochondria co-localize with GFAP at the tip of close-ended GFAP-positive TNTs and inside receiving STS-GBM cells. Summarizing, here we found that GFAP is a structural component of TNTs generated by GBM cells, that GFAP-positive TNTs are upregulated in response to oxidative stress and pro-apoptotic stress, and that GFAP interacts with mitochondria during the intercellular transfer. These findings contribute to elucidate the molecular structure of TNTs generated by GBM cells, highlighting the structural role of GFAP in TNTs and suggesting a functional role of this intermediate filament component in the intercellular mitochondria transfer between GBM cells in response to pro-apoptotic stimuli.
El tronco y la pelvis se afectan como consecuencia de un ictus, lo que predispone a caídas y dependencia. El objetivo de esta revisión fue describir la cinemática lineal y angular de tronco y pelvis durante la marcha en pacientes con secuela de accidente cerebrovascular. Se incluyeron estudios publicados hasta junio de 2018 que hubieran utilizado un sistema de captura de movimiento 2-3D durante la marcha. La búsqueda fue en Cochrane, Medline, PEDRo, Lilacs, Scielo, EBSCO, ClinicalKey y Elsevier. Se seleccionaron 12 artículos. La cinemática lineal muestra mayores desplazamientos laterales y aceleración en todos los ejes. La cinemática angular en fase de balanceo del segmento parético presenta la pelvis en rotación posterior, elevada y con menor velocidad, y tronco en flexión anterior, inclinación lateral y rotación ipsilaterales. Los estudios tienen alta variabilidad, lo que imposibilita establecer una medida de efecto común. Sin embargo, los resultados permiten describir el comportamiento del tronco y de la pelvis (AU)
The trunk and pelvis are affected after stroke, predisposing individuals to falls and dependency. The aim of this review was to describe the lineal and angular kinematics of the trunk and pelvis in patients with post-stroke sequels during walking. We included studies published up to June 2018 using a 2-3 D motion capture system during walking. We searched the Cochrane, Medline, PEDRo, Lilacs, Scielo, EBSCO, ClinicalKey and Elsevier databases. Twelve articles were selected. Linear kinematics showed greater lateral displacement and acceleration in all axes. Angular kinematics in the swing phase of the paretic segment showed the pelvis in posterior rotation, with elevation and lower velocity and the trunk in anterior flexion, with lateral inclination and ipsilateral rotation. The studies showed wide variability, making it impossible to establish of a common effect. However, the results allow description of the movement of the trunk and pelvis (AU)
Humans , Stroke , Biomechanical Phenomena , Walking , Gait , Range of Motion, Articular
The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.
The trunk and pelvis are affected after stroke, predisposing individuals to falls and dependency. The aim of this review was to describe the lineal and angular kinematics of the trunk and pelvis in patients with post-stroke sequels during walking. We included studies published up to June 2018 using a 2-3 D motion capture system during walking. We searched the Cochrane, Medline, PEDRo, Lilacs, Scielo, EBSCO, ClinicalKey and Elsevier databases. Twelve articles were selected. Linear kinematics showed greater lateral displacement and acceleration in all axes. Angular kinematics in the swing phase of the paretic segment showed the pelvis in posterior rotation, with elevation and lower velocity and the trunk in anterior flexion, with lateral inclination and ipsilateral rotation. The studies showed wide variability, making it impossible to establish of a common effect. However, the results allow description of the movement of the trunk and pelvis.
Gait , Walking , Biomechanical Phenomena , Humans , Range of Motion, Articular , Torso
In this study, we identified copy number variants (CNVs) in 19 European autochthonous pig breeds and in two commercial breeds (Italian Large White and Italian Duroc) that represent important genetic resources for this species. The genome of 725 pigs was sequenced using a breed-specific DNA pooling approach (30-35 animals per pool) obtaining an average depth per pool of 42×. This approach maximised CNV discovery as well as the related copy number states characterising, on average, the analysed breeds. By mining more than 17.5 billion reads, we identified a total of 9592 CNVs (~683 CNVs per breed) and 3710 CNV regions (CNVRs; 1.15% of the reference pig genome), with an average of 77 CNVRs per breed that were considered as private. A few CNVRs were analysed in more detail, together with other information derived from sequencing data. For example, the CNVR encompassing the KIT gene was associated with coat colour phenotypes in the analysed breeds, confirming the role of the multiple copies in determining breed-specific coat colours. The CNVR covering the MSRB3 gene was associated with ear size in most breeds. The CNVRs affecting the ELOVL6 and ZNF622 genes were private features observed in the Lithuanian Indigenous Wattle and in the Turopolje pig breeds respectively. Overall, the genome variability unravelled here can explain part of the genetic diversity among breeds and might contribute to explain their origin, history and adaptation to a variety of production systems.
DNA Copy Number Variations , DNA/genetics , Sus scrofa/genetics , Animals , Breeding , Female , Italy , Male , Phenotype , Species Specificity , Whole Genome Sequencing/veterinary
The epithelial lining of the small intestine consists of multiple cell types, including Paneth cells and goblet cells, that work in cohort to maintain gut health. 3D in vitro cultures of human primary epithelial cells, called organoids, have become a key model to study the functions of Paneth cells and goblet cells in normal and diseased conditions. Advances in these models include the ability to skew differentiation to particular lineages, providing a useful tool to study cell type specific function/dysfunction in the context of the epithelium. Here, we use comprehensive profiling of mRNA, microRNA and long non-coding RNA expression to confirm that Paneth cell and goblet cell enrichment of murine small intestinal organoids (enteroids) establishes a physiologically accurate model. We employ network analysis to infer the regulatory landscape altered by skewing differentiation, and using knowledge of cell type specific markers, we predict key regulators of cell type specific functions: Cebpa, Jun, Nr1d1 and Rxra specific to Paneth cells, Gfi1b and Myc specific for goblet cells and Ets1, Nr3c1 and Vdr shared between them. Links identified between these regulators and cellular phenotypes of inflammatory bowel disease (IBD) suggest that global regulatory rewiring during or after differentiation of Paneth cells and goblet cells could contribute to IBD aetiology. Future application of cell type enriched enteroids combined with the presented computational workflow can be used to disentangle multifactorial mechanisms of these cell types and propose regulators whose pharmacological targeting could be advantageous in treating IBD patients with Crohn's disease or ulcerative colitis.
Gene Expression Profiling/methods , Gene Regulatory Networks , Goblet Cells/metabolism , Intestine, Small/metabolism , Organoids/metabolism , Paneth Cells/metabolism , Animals , Cell Differentiation/genetics , Cell Lineage/genetics , Colitis, Ulcerative/genetics , Colitis, Ulcerative/pathology , Crohn Disease/genetics , Crohn Disease/pathology , Female , Humans , Inflammatory Bowel Diseases/genetics , Inflammatory Bowel Diseases/pathology , Intestinal Mucosa/cytology , Intestinal Mucosa/metabolism , Intestine, Small/cytology , Male , Mice, Inbred C57BL , Organoids/cytology
In this study three DNA extraction procedures, two library preparation protocols and two sequencing platforms were applied to analyse six bacterial cultures and their corresponding DNA obtained as part of a proficiency test. The impact of each variable on sequencing results was assessed using the following parameters: reads quality, assembly and alignment statistics; number of single nucleotide polymorphisms (SNPs), detected applying assembly- and alignment-based strategies; antimicrobial resistance genes (ARGs), identified on de novo assemblies of all sequenced genomes. The investigated nucleic acid extraction procedures, library preparation kits and sequencing platforms do not significantly affect de novo assembly statistics and number of SNPs and ARGs. The only exception was observed for two duplicates, which were associated to one PCR-based library preparation kit. Results from this comparative study can support researchers in the choice toward the available pre-sequencing and sequencing options, and might suggest further comparisons to be performed.
La diarrea crónica por malabsorción de ácidos biliares (MAB) es una patología infradiagnosticada. Se dispone de diferentes herramientas diagnósticas, aunque en la actualidad no existe consenso sobre cuál de estas sería la prueba de referencia o gold standard. En esta revisión se valora la posibilidad de utilizar la gammagrafía con 75Se-ácido tauroselcólico (75SeHCAT(R)) como prueba diagnóstica de referencia y su perspectiva de futuro. Se realizó una búsqueda bibliográfica en Pubmed y OVID, obteniéndose un total de 57 trabajos y usándose finalmente 26 de ellos tras ser seleccionados bajo los conceptos de gold standard, exactitud diagnóstica y otros biomarcadores. Valoramos las ventajas e inconvenientes de las diferentes herramientas diagnósticas: 14C-glicocolato, medición de ácidos biliares en heces, C4 en suero, FGF19 en suero, colestiramina y gammagrafía con ácido tauroselcólico. Consideramos que la gammagrafía con 75SeHCAT(R) es la prueba diagnóstica más recomendada en Europa para el diagnóstico de MAB al presentar los índices más elevados de sensibilidad y especificidad. Presenta una gran relación coste-beneficio, por lo que es la prueba con mayor grado de recomendación. Sin embargo, aún no es posible su uso de forma reconocida como gold standard debido a la falta de estudios que proporcionen datos concluyentes que permitan su consenso. Mientras tanto, se podría aconsejar el uso combinado de la prueba con colestiramina en todos los pacientes que queramos evaluar, independientemente del resultado gammagráfico, como uso de patrón de referencia
Chronic diarrhoea due to bile acid malabsorption (BAM) is an underdiagnosed pathology. Different diagnostic tools are available. However, there is currently no consensus on which of these would be the benchmark test or gold standard. This review evaluates the possibility of using 75Se-taurocholic acid (75SeHCAT(R)) scintigraphy as a benchmark diagnostic test and its perspective for the future. A literature review was conducted in Pubmed and OVID obtaining a total of 57 papers, 26 of which were finally used after being selected under the concepts of gold standard, diagnostic accuracy and other biomarkers. We evaluated the advantages and disadvantages of the different diagnostic tools: 14C-glycocholate, measurement of bile acids in faeces, C4 in serum, FGF19 in serum, cholestyramine, and 75Se-tauroselcolic acid scintigraphy. We consider that the 75SeHCAT(R) scan is the most recommended diagnostic test in Europe for diagnosing BAM as it presents the highest values of sensitivity and specificity. It has a significant cost-benefit ratio, making it the test with the highest degree of recommendation. However, it is still not possible to use it in a recognised way as a gold standard due to the lack of studies that provide conclusive data that allow consensus. In the meantime, the combined use of cholestyramine testing in all patients we want to evaluate, regardless of the scintigraphy result, could be encouraged as a benchmark standard
Humans , Bile Acids and Salts/metabolism , Diarrhea/diagnostic imaging , Steatorrhea/diagnostic imaging , Taurocholic Acid/analogs & derivatives , Algorithms , Benchmarking , Radionuclide Imaging
INTRODUCTION: Melatonin has been studied and used for several years as a sleep-wake cycle modulator in patients with sleep disorders. Experimental evidence has demonstrated the multiple neuroprotective benefits of this indoleamine secreted by the pineal gland. Melatonin is also used in neurological investigations, for its ability to induce sleep in children. In fact, it favors falling asleep during electroencephalogram, Magnetic Resonance Imaging (MRI), and during brainstem auditory evoked potentials. Previous studies are focused on infants and children. No investigation have been performed in neonates, before or during instrumental assessments. MATERIAL AND METHODS: One hundred ten newborns (term and preterm) undergoing brain MRI were enrolled in the study. Thirty minutes before the planned time for the examination, we administered a single dose solution of melatonin- tryptophan-vitamin B6. Twenty minutes after the initial administration of 2 mg, a second dose of 1 mg was administered, if the baby was still awake. If after further 15 min the baby was still not sleeping, an additional dose of 1 mg was administered. RESULTS: In 106 patients we obtained adequate sedation without adverse events, allowing us to perform an adequate quality MRI, with a median time of 25 min to reach sleeping. Only in three patients MRI could not be performed. In patients having a large weight, higher doses of melatonin were necessary to reach sleeping. Considering the pro kg dose of melatonin, the average dose that induced sleepiness in neonates was 0,64 ± 0.16 mg/Kg. CONCLUSION: A solution based on Melatonin- tryptophan-vitamin B6 can be a helpful sedative to administer to neonates undergoing brain MRI, avoiding the use of anesthetics and achieving adequate assessments.
Brain/diagnostic imaging , Central Nervous System Depressants/administration & dosage , Magnetic Resonance Imaging , Melatonin/administration & dosage , Tryptophan/administration & dosage , Vitamin B 6/administration & dosage , Antidepressive Agents, Second-Generation/administration & dosage , Conscious Sedation , Female , Humans , Hypnotics and Sedatives , Infant , Infant, Newborn , Male , Retrospective Studies , Vitamin B Complex/administration & dosage
Chronic diarrhoea due to bile acid malabsorption (BAM) is an underdiagnosed pathology. Different diagnostic tools are available. However, there is currently no consensus on which of these would be the benchmark test or gold standard. This review evaluates the possibility of using 75Se-taurocholic acid (75SeHCAT®) scintigraphy as a benchmark diagnostic test and its perspective for the future. A literature review was conducted in Pubmed and OVID obtaining a total of 57 papers, 26 of which were finally used after being selected under the concepts of gold standard, diagnostic accuracy and other biomarkers. We evaluated the advantages and disadvantages of the different diagnostic tools: 14C-glycocholate, measurement of bile acids in faeces, C4 in serum, FGF19 in serum, cholestyramine, and 75Se-tauroselcolic acid scintigraphy. We consider that the 75SeHCAT® scan is the most recommended diagnostic test in Europe for diagnosing BAM as it presents the highest values of sensitivity and specificity. It has a significant cost-benefit ratio, making it the test with the highest degree of recommendation. However, it is still not possible to use it in a recognised way as a gold standard due to the lack of studies that provide conclusive data that allow consensus. In the meantime, the combined use of cholestyramine testing in all patients we want to evaluate, regardless of the scintigraphy result, could be encouraged as a benchmark standard.
Bile Acids and Salts/metabolism , Diarrhea/diagnostic imaging , Steatorrhea/diagnostic imaging , Taurocholic Acid/analogs & derivatives , Algorithms , Benchmarking , Humans , Radionuclide Imaging
OBJECTIVES: This study aimed to investigate the prevalence of vaginal atrophy (VA) in women across the menopausal age. METHODS: A multicenter cross-sectional investigation was performed on 747 females, 40-55 years of age, in 30 outpatient public services across the nation. The VA diagnosis was based on the combination of patient sensation of vaginal dryness, an objective sign of VA, and pH >5. RESULTS: VA was diagnosed in 36.8% of women. Prevalence ranged from 19.2% (40-45 year olds) to 53.8% (52-55 year olds). pH >5 (37.5%) was less prevalent than isolated VA symptoms or signs. Vaginal dryness (64.0%) was the most prevalent symptom followed by dyspareunia (54.5%), itching (38.5%) burning (38.3%), and dysuria (28.9%). Prevalence of vaginal signs declined from vaginal dryness (60.3%) to vaginal thinning (54.5%), vaginal pallor (47.4%), presence of petecchiae (15.7%), and mucosa fragility (15.1%). Most signs and symptoms showed an age-related increase in frequency and intensity. VA was independently associated (R2 = 0.139; p < 0.0001) with age (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.03-1.13), being in postmenopause (OR 3.45; 95% CI 2.29-5.19), and presence of vasomotor symptoms (OR 3.10; 95% CI 2.09-4.60). CONCLUSION: VA and its symptoms are common in women across the menopausal age. VA identification may favor early management and treatment.
Dyspareunia/epidemiology , Vagina/pathology , Vaginal Diseases/epidemiology , Adult , Atrophy , Cross-Sectional Studies , Dyspareunia/etiology , Female , Humans , Italy/epidemiology , Logistic Models , Middle Aged , Perimenopause , Prevalence , Vaginal Diseases/etiology
Individuals with Parkinson's disease (PD) suffer from motor and mental disturbances due to degeneration of dopaminergic and non-dopaminergic neuronal systems. Although they provide temporary symptom relief, current treatments fail to control motor and non-motor alterations or to arrest disease progression. Aiming to explore safety and possible motor and neuropsychological benefits of a novel strategy to improve the PD condition, a case series study was designed for brain grafting of human neural progenitor cells (NPCs) to a group of eight patients with moderate PD. A NPC line, expressing Oct-4 and Sox-2, was manufactured and characterized. Using stereotactic surgery, NPC suspensions were bilaterally injected into patients' dorsal putamina. Cyclosporine A was given for 10 days prior to surgery and continued for 1 month thereafter. Neurological, neuropsychological, and brain imaging evaluations were performed pre-operatively, 1, 2, and 4 years post-surgery. Seven of eight patients have completed 4-year follow-up. The procedure proved to be safe, with no immune responses against the transplant, and no adverse effects. One year after cell grafting, all but one of the seven patients completing the study showed various degrees of motor improvement, and five of them showed better response to medication. PET imaging showed a trend toward enhanced midbrain dopaminergic activity. By their 4-year evaluation, improvements somewhat decreased but remained better than at baseline. Neuropsychological changes were minor, if at all. The intervention appears to be safe. At 4 years post-transplantation we report that undifferentiated NPCs can be delivered safely by stereotaxis to both putamina of patients with PD without causing adverse effects. In 6/7 patients in OFF condition improvement in UPDRS III was observed. PET functional scans suggest enhanced putaminal dopaminergic neurotransmission that could correlate with improved motor function, and better response to L-DOPA. Patients' neuropsychological scores were unaffected by grafting. Trial Registration: Fetal derived stem cells for Parkinson's disease https://doi.org/10.1186/ISRCTN39104513Reg#ISRCTN39104513.
Mesencephalon , Neural Stem Cells , Parkinson Disease , Putamen , Adolescent , Adult , Aged , Allografts , Dopamine/metabolism , Female , Follow-Up Studies , Humans , Male , Mesencephalon/metabolism , Mesencephalon/pathology , Mesencephalon/surgery , Middle Aged , Neural Stem Cells/metabolism , Neural Stem Cells/pathology , Neural Stem Cells/transplantation , Parkinson Disease/metabolism , Parkinson Disease/pathology , Parkinson Disease/surgery , Putamen/metabolism , Putamen/pathology , Putamen/surgery
La Osteoporosis es un síndrome altamente prevalente en la población mayor, tanto la que ha sufrido fracturas como la que no. Aunque con frecuencia se le relaciona con la menopausia, existen varios otros elementos involucrados en su génesis. Estos frecuentemente coexisten en diversa proporción y son, por lo general, oligosintomáticos o generan signosintomatología muy inespecífica. Esto hace que su diagnóstico y tratamiento se retrase u omita, aumentando el riesgo de caídas y fracturas, y dificultando los procesos de consolidación ósea. Aunque su nivel de evidencia es aún diverso, frecuentemente son hallados cuando se implementa su búsqueda en pacientes mayores fracturados. Por lo que, con independencia de si su relación con la osteoporosis es o no significativa, conviene buscarlos y manejarlos por el riesgo que constituyen por sí mismos. En esta revisión nos referiremos a cuatro de estas condiciones: Hipoalbuminemia, hiponatremia, anemia y deficiencia de vitamina K.
Osteoporosis is very prevalent in the aged and is seen in both those who have suffered fractures and those who have not. Frequently related to the menopause, there are other elements involved in its pathogenesis. These frequently co-exist and are, generally, oligo-symptomatic or have non-specific symptomatology. This causes delays or omissions in their diagnosis and treatment, thereby increasing the risk of falls and fractures and interfering with bone consolidation. Although their evidence levels are diverse, these factors are frequently to be found once directly looked for in the aged fracture patient. Therefore, even though their relation to the osteoporosis may not be significant, it is best to test for them and treat them for the risk they present. In this review we look at four of these conditions: hypoalbuminemia, hyponatremia, anemia and vitamin K deficiency
Avenanthramides (AVNs) are natural polyphenols obtained from oat sprouts and can also be chemically synthetized. The aim of the present study was to assess the anticancer, anti-inflammatory and antioxidant effects of individual synthetized AVNs (s-2c, s-2p, s-2f) and a natural AVN mixture (n-MIX) on CaCo-2 and Hep3B cancer cells. In CaCo-2, the AVN s-2c was found to be the most cytotoxic followed by the n-MIX. In Hep3B cells, a marked cytotoxic effect was found but no significant difference was observed between the synthesized AVNs and the n-MIX. In both CaCo-2 and Hep3B cells, natural and synthetic AVNs activated caspases 8 and 3, and the n-MIX and the AVN s-2c were also able to activate caspase 2. Both synthetic and natural AVNs downregulated pro-survival genes hTERT, COX-2 and MDR1, inhibited the activity of pro-inflammatory COX-2 enzyme and reduced prostaglandin E2 levels, showing the potent chemopreventive effects of these oat-derived phytochemicals. Synthetic AVN s-2c was found to have the highest chemical antioxidant capacity, as indicated by ORAC, DPPH and ABTS values, whereas all AVNs and n-MIX were shown to have similar intracellular antioxidant activity, evaluated by means of the DCFH-DA assay. As AVNs have high bioavailability in humans, results of this study suggest that oat-based foods, fortified with AVNs, could be an alternative to produce functional foods with anticancer, anti-inflammatory and antioxidant effects for health benefits.
Caspase 2/metabolism , Caspase 3/metabolism , Caspase 8/metabolism , Cyclooxygenase 2/metabolism , Cysteine Endopeptidases/metabolism , Plant Extracts/pharmacology , Telomerase/metabolism , ortho-Aminobenzoates/pharmacology , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Antioxidants/chemical synthesis , Antioxidants/pharmacology , Avena/chemistry , Caco-2 Cells , Caspase 2/genetics , Caspase 3/genetics , Caspase 8/genetics , Cyclooxygenase 2/genetics , Cysteine Endopeptidases/genetics , Dinoprostone/metabolism , Humans , Plant Extracts/chemical synthesis , Telomerase/genetics , ortho-Aminobenzoates/chemical synthesis
BACKGROUND: Zucchini fruit is susceptible to chilling injury (CI), but the response to low storage temperature is cultivar dependent. Previous reports about the response of zucchini fruit to chilling storage have been focused on the physiology and biochemistry of this process, with little information about the molecular mechanisms underlying it. In this work, we present a comprehensive analysis of transcriptomic changes that take place after cold storage in zucchini fruit of two commercial cultivars with contrasting response to chilling stress. RESULTS: RNA-Seq analysis was conducted in exocarp of fruit at harvest and after 14 days of storage at 4 and 20 °C. Differential expressed genes (DEGs) were obtained comparing fruit stored at 4 °C with their control at 20 °C, and then specific and common up and down-regulated DEGs of each cultivar were identified. Functional analysis of these DEGs identified similarities between the response of zucchini fruit to low temperature and other stresses, with an important number of GO terms related to biotic and abiotic stresses overrepresented in both cultivars. This study also revealed several molecular mechanisms that could be related to chilling tolerance, since they were up-regulated in cv. Natura (CI tolerant) or down-regulated in cv. Sinatra (CI sensitive). These mechanisms were mainly those related to carbohydrate and energy metabolism, transcription, signal transduction, and protein transport and degradation. Among DEGs belonging to these pathways, we selected candidate genes that could regulate or promote chilling tolerance in zucchini fruit including the transcription factors MYB76-like, ZAT10-like, DELLA protein GAIP, and AP2/ERF domain-containing protein. CONCLUSIONS: This study provides a broader understanding of the important mechanisms and processes related to coping with low temperature stress in zucchini fruit and allowed the identification of some candidate genes that may be involved in the acquisition of chilling tolerance in this crop. These genes will be the basis of future studies aimed to identify markers involved in cold tolerance and aid in zucchini breeding programs.
Cold Temperature , Cucurbita/genetics , Fruit/genetics , Preservation, Biological , Transcriptome , Adaptation, Physiological , Computational Biology/methods , Cucurbita/metabolism , Energy Metabolism , Gene Expression Profiling , Gene Expression Regulation, Plant , Gene Ontology , Molecular Sequence Annotation , Preservation, Biological/methods
The gamma-ray sky has been observed with unprecedented accuracy in the last decade by the Fermi -large area telescope (LAT), allowing us to resolve and understand the high-energy Universe. The nature of the remaining unresolved emission [unresolved gamma-ray background (UGRB)] below the LAT source detection threshold can be uncovered by characterizing the amplitude and angular scale of the UGRB fluctuation field. This Letter presents a measurement of the UGRB autocorrelation angular power spectrum based on eight years of Fermi-LAT Pass 8 data products. The analysis is designed to be robust against contamination from resolved sources and noise systematics. The sensitivity to subthreshold sources is greatly enhanced with respect to previous measurements. We find evidence (with â¼3.7σ significance) that the scenario in which two classes of sources contribute to the UGRB signal is favored over a single class. A double power law with exponential cutoff can explain the anisotropy energy spectrum well, with photon indices of the two populations being 2.55±0.23 and 1.86±0.15.
We use joint observations by the Neil Gehrels Swift X-ray Telescope (XRT) and the Fermi Large Area Telescope (LAT) of gamma-ray burst (GRB) afterglows to investigate the nature of the long-lived high-energy emission observed by Fermi LAT. Joint broadband spectral modeling of XRT and LAT data reveal that LAT non-detections of bright X-ray afterglows are consistent with a cooling break in the inferred electron synchrotron spectrum below the LAT and/or XRT energy ranges. Such a break is sufficient to suppress the high-energy emission so as to be below the LAT detection threshold. By contrast, LAT-detected bursts are best fit by a synchrotron spectrum with a cooling break that lies either between or above the XRT and LAT energy ranges. We speculate that the primary difference between GRBs with LAT afterglow detections and the non-detected population may be in the type of circumstellar environment in which these bursts occur, with late-time LAT detections preferentially selecting GRBs that occur in low wind-like circumburst density profiles. Furthermore, we find no evidence of high-energy emission in the LAT-detected population significantly in excess of the flux expected from the electron synchrotron spectrum fit to the observed X-ray emission. The lack of excess emission at high energies could be due to a shocked external medium in which the energy density in the magnetic field is stronger than or comparable to that of the relativistic electrons behind the shock, precluding the production of a dominant synchrotron self-Compton (SSC) component in the LAT energy range. Alternatively, the peak of the SSC emission could be beyond the 0.1-100 GeV energy range considered for this analysis.
