Karyotype differentiation of four Cestrum species (Solanaceae) revealed by fluorescent chromosome banding and FISH

The karyotypes of four South American species of Cestrum (C. capsulare,C. corymbosum,C. laevigatum and C. megalophylum) were studied using conventional staining, C-CMA/DAPI chromosome banding and FISH with 45S and 5S rDNA probes. The karyotypes showed a chromosome number of 2n = 2x = 16, with metacentric chromosomes, except for the eighth submeta- to acrocentric pair. Several types of heterochromatin were detected, which varied in size, number, distribution and base composition. The C-CMA+ bands and 45S rDNA were located predominantly in terminal regions. The C-CMA + /DAPI + bands appeared in interstitial and terminal regions, and the C-DAPI + bands were found in all chromosome regions. The 5S rDNA sites were observed on the long arm of pair 8 in all species except C. capsulare, where they were found in the paracentromeric region of the long arm of pair 4. The differences in band patterns among the species studied here, along with data from other nine species reported in the literature, suggest that the bands are dispersed in an equilocal and non-equilocal manner and that structural rearrangements can be responsible for internal karyotype diversification. However, it is important to point out that the structural changes involving repetitive segments did not culminate in substantial changes in the general karyotype structure concerning chromosome size and morphology

Characterization of In Vivo Keratin 19 Phosphorylation on Tyrosine-391

Keratin polypeptide 19 (K19) is a type I intermediate filament protein that is expressed in stratified and simple-type epithelia. Although K19 is known to be phosphorylated on tyrosine residue(s), conclusive site-specific characterization of these residue(s) and identification potential kinases that may be involved has not been reported.In this study, biochemical, molecular and immunological approaches were undertaken in order to identify and characterize K19 tyrosine phosphorylation. Upon treatment with pervanadate, a tyrosine phosphatase inhibitor, human K19 (hK19) was phosphorylated on tyrosine 391, located in the 'tail' domain of the protein. K19 Y391 phosphorylation was confirmed using site-directed mutagenesis and cell transfection coupled with the generation of a K19 phospho (p)-Y391-specific rabbit antibody. The antibody also recognized mouse phospho-K19 (K19 pY394). This tyrosine residue is not phosphorylated under basal conditions, but becomes phosphorylated in the presence of Src kinase in vitro and in cells expressing constitutively-active Src. Pervanadate treatment in vivo resulted in phosphorylation of K19 Y394 and Y391 in colonic epithelial cells of non-transgenic mice and hK19-overexpressing mice, respectively.Human K19 tyrosine 391 is phosphorylated, potentially by Src kinase, and is the first well-defined tyrosine phosphorylation site of any keratin protein. The lack of detection of K19 pY391 in the absence of tyrosine phosphatase inhibition suggests that its phosphorylation is highly dynamic

Plakophilin3 Loss Leads to an Increase in PRL3 Levels Promoting K8 Dephosphorylation, Which Is Required for Transformation and Metastasis

The desmosome anchors keratin filaments in epithelial cells leading to the formation of a tissue wide IF network. Loss of the desmosomal plaque protein plakophilin3 (PKP3) in HCT116 cells, leads to an increase in neoplastic progression and metastasis, which was accompanied by an increase in K8 levels. The increase in levels was due to an increase in the protein levels of the Phosphatase of Regenerating Liver 3 (PRL3), which results in a decrease in phosphorylation on K8. The increase in PRL3 and K8 protein levels could be reversed by introduction of an shRNA resistant PKP3 cDNA. Inhibition of K8 expression in the PKP3 knockdown clone S10, led to a decrease in cell migration and lamellipodia formation. Further, the K8 PKP3 double knockdown clones showed a decrease in colony formation in soft agar and decreased tumorigenesis and metastasis in nude mice. These results suggest that a stabilisation of K8 filaments leading to an increase in migration and transformation may be one mechanism by which PKP3 loss leads to tumor progression and metastasis

Diagnosis and management of Silver–Russell syndrome: first international consensus statement

This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver–Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited. SRS is primarily a clinical diagnosis; however, molecular testing enables confirmation of the clinical diagnosis and defines the subtype. A 'normal' result from a molecular test does not exclude the diagnosis of SRS. The management of children with SRS requires an experienced, multidisciplinary approach. Specific issues include growth failure, severe feeding difficulties, gastrointestinal problems, hypoglycaemia, body asymmetry, scoliosis, motor and speech delay and psychosocial challenges. An early emphasis on adequate nutritional status is important, with awareness that rapid postnatal weight gain might lead to subsequent increased risk of metabolic disorders. The benefits of treating patients with SRS with growth hormone include improved body composition, motor development and appetite, reduced risk of hypoglycaemia and increased height. Clinicians should be aware of possible premature adrenarche, fairly early and rapid central puberty and insulin resistance. Treatment with gonadotropin-releasing hormone analogues can delay progression of central puberty and preserve adult height potential. Long-term follow up is essential to determine the natural history and optimal management in adulthood

New Hard-TeV Extreme Blazars Detected with the MAGIC Telescopes*

Extreme high-frequency-peaked BL Lac objects (EHBLs) are blazars that exhibit extremely energetic synchrotron emission. They also feature nonthermal gamma-ray emission whose peak lies in the very high-energy (VHE, E > 100 GeV) range, and in some sources exceeds 1 TeV: this is the case for hard-TeV EHBLs such as 1ES 0229+200. With the aim of increasing the EHBL population, 10 targets were observed with the MAGIC telescopes from 2010 to 2017, for a total of 265 hr of good-quality data. The data were complemented by coordinated Swift observations. The X-ray data analysis confirms that all but two sources are EHBLs. The sources show only a modest variability and a harder-when-brighter behavior, typical for this class of objects. At VHE gamma-rays, three new sources were detected and a hint of a signal was found for another new source. In each case, the intrinsic spectrum is compatible with the hypothesis of a hard-TeV nature of these EHBLs. The broadband spectral energy distributions (SEDs) of all sources are built and modeled in the framework of a single-zone, purely leptonic model. The VHE gamma-ray-detected sources were also interpreted with a spine-layer model and a proton synchrotron model. The three models provide a good description of the SEDs. However, the resulting parameters differ substantially in the three scenarios, in particular the magnetization parameter. This work presents the first mini catalog of VHE gamma-ray and multiwavelength observations of EHBLs

Constraints on Gamma-Ray and Neutrino Emission from NGC 1068 with the MAGIC Telescopes

Starburst galaxies and star-forming active galactic nuclei are among the candidate sources thought to contribute appreciably to the extragalactic gamma-ray and neutrino backgrounds. NGC 1068 is the brightest of the star-forming galaxies found to emit gamma-rays from 0.1 to 50 GeV. Precise measurements of the high-energy spectrum are crucial to study the particle accelerators and probe the dominant emission mechanisms. We have carried out 125 hr of observations of NGC 1068 with the MAGIC telescopes in order to search for gamma-ray emission in the very-high-energy band. We did not detect significant gamma-ray emission, and set upper limits at the 95% confidence level to the gamma-ray flux above 200 GeV f < 5.1. x. 10(-13) cm(-2) s(-1). This limit improves previous constraints by about an order of magnitude and allows us to put tight constraints on the theoretical models for the gamma-ray emission. By combining the MAGIC observations with the Fermi-LAT spectrum we limit the parameter space (spectral slope, maximum energy) of the cosmic ray protons predicted by hadronuclear models for the gamma-ray emission, while we find that a model postulating leptonic emission from a semi-relativistic jet is fully consistent with the limits. We provide predictions for IceCube detection of the neutrino signal foreseen in the hadronic scenario. We predict a maximal IceCube neutrino event rate of 0.07 yr(-1)

Testing emission models on the extreme blazar 2WHSP J073326.7+515354 detected at very high energies with the MAGIC telescopes

Extreme high-energy-peaked BL Lac objects (EHBLs) are an emerging class of blazars. Their typical two-hump-structured spectral energy distribution (SED) peaks at higher energies with respect to conventional blazars. Multiwavelength (MWL) observations constrain their synchrotron peak in the medium to hard X-ray band. Their gamma-ray SED peaks above the GeV band, and in some objects it extends up to several TeV. Up to now, only a few EHBLs have been detected in the TeV gamma-ray range. In this paper, we report the detection of the EHBL 2WHSP J073320,7+515354, observed and detected during 2018 in TeV gamma rays with the MAGIC telescopes. The broad-band SED is studied within an MWL context, including an analysis of the Fermi-LAT data over 10 yr of observation and with simultaneous Swift-XRT, Swift-UVOT, and KVA data. Our analysis results in a set of spectral parameters that confirms the classification of the source as an EIME. In order to investigate the physical nature of this extreme emission, different theoretical frameworks were tested to model the broadband SED. The hard TeV spectrum of 2WHSP J073326.7+515354 sets the SED far from the energy equipartition regime in the standard one-zone leptonic scenario of blazar emission. Conversely, more complex models of the jet, represented by either a two-zone spine-layer model or a hadronic emission model, better represent the broad-hand SED

Monitoring of the radio galaxy M 87 during a low -emission state from m 2012 to 2015 with MAGIC

M 87 is one of the closest (z = 0.004 36) extragalactic sources emitting at very high energies (VHF, E > 100 GeV). The aim of this work is to locale the region of the VHF gamma-ray emission and to describe the observed broad-band spectral energy distribution (SED) during the low VHF gamma-ray state. The data from M 87 collected between 2012 and 2015 as part of a MAGIC monitoring programme are analysed and combined with multiwavelength data from Fermi-LAT, Chandra, HST, FVN, VLBA, and the Liverpool Telescope. The averaged VHE gamma-ray spectrum can be fitted from 100 GeV to 10 TeV with a simple power law with a photon index of (-2.41 0.07), while the integral flux above 300 GeV is (1.44 0.13) x 10-12 cm 2 s I. During the campaign between 2012 and 2015, M87 is generally found in a low-emission state at all observed wavelengths. The VIIE gamma-ray flux from the present 2012-2015M 87 campaign is consistent with a constant flux with some hint of variability ( 3 a) on a daily time-scale in 2013. The low-state gamma-ray emission likely originates from the same region as the flare-state emission. Given the broad-band SED, both a leptonic synchrotron self-Compton and a hybrid photohadronic model reproduce the available data well, even if the latter is preferred. We note, however, that the energy stored in the magnetic field in the leptonic scenario is very low, suggesting a matter-dominated emission region