SOX10 protein is a key transcription factor during neural crest development. Mutations in
SOX10
are associated with several neurocristopathies such as Waardenburg syndrome type IV (WS4), a congenital ...disorder characterized by the association of hearing loss, pigmentary abnormalities, and absence of ganglion cells in the myenteric and submucosal plexus of the gastrointestinal tract, also known as aganglionic megacolon or Hirschsprung disease (HSCR). Several mutations at this
locus
are known to cause a high percentage of WS4 cases, but no
SOX10
mutations had been ever reported associated to isolated HSCR patient. Therefore, nonsyndromic HSCR was initially thought not to be associated to mutations at this particular
locus
. In the present study, we describe the evaluation of the
SOX10
gene in a series of 196 isolated HSCR cases, the largest patient series evaluated so far, and report a truncating c.153–155del mutation. This is the first time that a
SOX10
mutation is detected in an isolated HSCR patient, which completely changes the scenario for the implications of
SOX10
mutations in human disease, giving us a new tool for genetic counseling.
HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 ...associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain.
All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008.
A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic.
The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy.
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•Novel push–pull 3-arylindolizines bearing pH-responsive amino groups were prepared.•Protonation of the amino group leads to hypsochromically shifted emission bands.•White ...photoluminescence is obtained by precise control of the amount of acid added.•The molecular structure and photophysical properties have been rationalized by DFT.
There is a continuous interest in the development of advanced materials with tunable photophysical properties, among which white light emission represents a major challenge. Indolizines are a kind of azaheterocycles that have gained a great deal of attention in the recent past due to their intriguing photophysical behavior. We report herein on the synthesis of new push–pull indolizines bearing amino and electron-withdrawing groups at positions 1 and 7, respectively, and on their optical response in acidic medium. Exclusive protonation on the amino group has led to a hypsochromic shift in the emission spectra. Interestingly, white photoluminescence can be attained by adjusting the amount of acid as a result of color complementarity between neutral and charged species. Moreover, Density Functional Theory (DFT) calculations on the molecular structure and photophysical properties of these compounds are in agreement with the experimental results, providing very useful information about the main electronic transitions and the influence of protonation on the optical transitions.
cases of hepatitis B virus (HBV) reactivation have been reported in patients with hepatitis C virus (HCV) treated with direct antiviral agents (DAA).
the main objectives of the present study are: a) ...to determine the prevalence of HBV/HCV coinfection in HCV patients treated with DAAs in the Autonomous Community of Madrid (CM) and also to determine the incidence and clinical relevance of HBV reactivation; and b) to determine the HBV screening rates in HCV patients in our region. For that purpose, 1,337 HCV patients were consecutively treated with DAAs in two hospitals located in South CM between January 2015 and June 2017.
nine of the 1,337 (0.67%) participants were HBsAg positive and 356 (26.6%) had previous HBV infection markers. Two of the four (50%) HBsAg positive patients with untreated HBV developed a virological reactivation, but not a biochemical reaction. Of the 356 patients with previous HBV infection markers, all had normal transaminases at the end of treatment and during follow-up. The HBV screening rate amounted to 92.9% of the cohort.
the prevalence of HBV (HBsAg positive) infection in patients with chronic hepatitis C in the southern area of the CM is low. HBV reactivation in HBsAg positive patients treated with DAAs is common, although without clinical relevance. In our region, there is a high rate of HBV screening in patients with HCV that are likely treated with DAAs.
The oxidation and etching of reduced graphene oxide (RGO) by thermal oxidation in air, microwave oxygen plasma, ultraviolet-generated ozone, and scanning tunneling microscopy (STM) lithography have ...been investigated. This type of graphene exhibited a higher reactivity toward oxidation than that of pristine graphite (taken as a reference carbon material), which could be related to its intrinsically defective structure. Etching of RGO as a result of thermal oxidation in air was started at as low a temperature as 400 °C, as compared to ∼500 °C for graphite, indicating that the defects present on the former are different in nature from those found on the surface of pristine graphite. The morphological evolution of individual RGO sheets upon oxidative attack was consistent with the sheets being essentially a patchwork of minute domains (a few to several nanometers large) with two distinct reactivities, higher (lower) reactivity associated with defective (defect-free) domains. The introduction of oxygen functional groups on the basal plane of RGO was revealed directly by X-ray photoelectron spectroscopy and indirectly through STM. STM lithography enabled discrimination between oxidation proper (introduction of oxygen groups) and etching (desorption of the groups as CO or CO2) of the RGO sheets through control of the applied bias voltage. The former was visualized in the STM images as locally depressed features of electronic origin, whereas etching led to the generation of actual trenches on the sheets. Taken together, the present results provide insight into the reactivity of RGO and suggest potential practical applications involving controlled oxidation of this type of graphene.
Nowadays, Ni@C nanostructured materials are attracting a great deal of attention due to their multiple catalytic or magnetic functionalities. In this article we report on the investigation of the ...correlation between the microstructure and magnetic properties of Ni nanoparticles embedded in a carbon matrix. The samples were obtained following a two-step procedure that ensures protection against nanoparticle oxidation, and was carried out in the following way: (i) the synthesis of a nickel-imidazole-based metal-organic framework (MOF) by a simple method in an aqueous medium at moderate temperature (95 °C); and (ii) carbonization of the MOF at different temperatures between 400 and 600 °C to obtain a carbon-supported hybrid material, containing Ni nanoparticles with an "artichoke-like" morphology, where a Ni-FCC core is surrounded by "bracts" of Ni-HCP and Ni
3
C. The average size of the nanoparticle slightly changes from 7 to 10 nm as the carbonization temperature is increased, but the Ni-FCC core diameter ranges from 3 to around 6 nm. We show how the information obtained on the evolution of the magnetic behaviour with carbonization temperature, using X-ray diffraction and electron microscopy, complements each other by providing consistent structural and magnetic characteristics of the investigated Ni@C nanoparticles. In fact, this joint analysis allows us to explain the formation and transformation of different Ni-based crystalline phases along the synthesis process, including Ni
3
C and Ni with both hexagonal and cubic crystalline structures. The amount of conventional Ni-FCC is below 10 wt% for the sample treated at 400 °C and it can reach up to 50 wt% for that treated at 600 °C. Finally, based on our current findings we propose an explanation for understanding the magnetic properties of Ni@C, in which the Ni-FCC core spins mainly govern the magnetic coupling of the whole system.
A novel two-step procedure based on the carbonization of Ni-based MOF allows the formation of Ni@C nanoparticles protected against oxidation. Different crystalline structures are formed, but only Ni-FCC is ferromagnetic.
Background
At the earliest stages of brain development, the neuroepithelium works as an interdependent functional entity together with cerebrospinal fluid, which plays a key regulatory role in ...neuroepithelial cell survival, replication and neurogenesis; however, the underlying mechanism remains unknown in mammals.
Results
We show the presence of fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF), in 13.5‐day rat embryo cerebrospinal fluid (eCSF). Immunohistochemical detection of FGF2 expression localized this factor inside neuroepithelial precursors close to the neuroepithelial‐CSF interface, suggesting that FGF2 from eCSF could originate in the neuroepithelium by apical secretion. The colocalization of FGFR1 and FGF2 in some neuroepithelial cells close to the ventricular surface suggests they are target cells for eCSF FGF2. Brain neuroepithelium EGF expression was negative. By using a neuroepithelial organotypic culture, we demonstrate that FGF2 and EGF from eCSF plays a specific role in triggering the self‐renewal and are involved in neurogenetic induction of mesencephalic neuroepithelial precursor cells during rat development.
Conclusions
We propose eCSF as an intercommunication medium for neuroepithelial precursor behavior control during early rat brain development, and the neuroepithelial regulation of FGF2 and EGF presence in eCSF, as a regulative mechanism controlling precursor proliferation and neurogenesis.
Key Findings
We show the presence of Fibroblast Growth Factor (FGF2 and EGF) in 13.5‐day rat embryos cerebro‐spinal fluid (eCSF).
FGF2 expression localized this factor at the apical end of the neuroepithelial precursors in contact with eCSF.
We demonstrate that FGF2/EGF from eCSF plays a specific role in triggering replication and in neurogenesis induction of neuropeithelial cells.
We propose eCSF as a common phylogenetical factor in neuroepithelial precursor behavior during rat brain development.
Abstract
Objectives
To study the in vitro activity of imipenem/relebactam and comparators and the imipenem/relebactam resistance mechanisms in a Pseudomonas aeruginosa collection from Portugal (STEP, ...2017–18) and Spain (SUPERIOR, 2016–17) surveillance studies.
Methods
P. aeruginosa isolates (n = 474) were prospectively recovered from complicated urinary tract (cUTI), complicated intra-abdominal (cIAI) and lower respiratory tract (LRTI) infections in 11 Portuguese and 8 Spanish ICUs. MICs were determined (ISO broth microdilution). All imipenem/relebactam-resistant P. aeruginosa isolates (n = 30) and a subset of imipenem/relebactam-susceptible strains (n = 32) were characterized by WGS.
Results
Imipenem/relebactam (93.7% susceptible), ceftazidime/avibactam (93.5% susceptible) and ceftolozane/tazobactam (93.2% susceptible) displayed comparable activity. The imipenem/relebactam resistance rate was 6.3% (Portugal 5.8%; Spain 8.9%). Relebactam restored imipenem susceptibility to 76.9% (103/134) of imipenem-resistant isolates, including MDR (82.1%; 32/39), XDR (68.8%; 53/77) and difficult-to-treat (DTR) isolates (67.2%; 45/67). Among sequenced strains, differences in population structure were detected depending on the country: clonal complex (CC)175 and CC309 in Spain and CC235, CC244, CC348 and CC253 in Portugal. Different carbapenemase gene distributions were also found: VIM-20 (n = 3), VIM-1 (n = 2), VIM-2 (n = 1) and VIM-36 (n = 1) in Spain and GES-13 (n = 13), VIM-2 (n = 3) and KPC-3 (n = 2) in Portugal. GES-13-CC235 (n = 13) and VIM type-CC175 (n = 5) associations were predominant in Portugal and Spain, respectively. Imipenem/relebactam showed activity against KPC-3 strains (2/2), but was inactive against all GES-13 producers and most of the VIM producers (8/10). Mutations in genes affecting porin inactivation, efflux pump overexpression and LPS modification might also be involved in imipenem/relebactam resistance.
Conclusions
Microbiological results reinforce imipenem/relebactam as a potential option to treat cUTI, cIAI and LRTI caused by MDR/XDR P. aeruginosa isolates, except for GES-13 and VIM producers.
Abstract
The extragalactic background light (EBL) contains all the radiation emitted by nuclear and accretion processes in stars and compact objects since the epoch of recombination. Measuring the ...EBL density directly is challenging, especially in the near-to-far-infrared wave band, mainly due to the zodiacal light foreground. Instead, gamma-ray astronomy offers the possibility to indirectly set limits on the EBL by studying the effects of gamma-ray absorption in the very high energy (VHE: >100 GeV) spectra of distant blazars. The High Altitude Water Cherenkov Gamma Ray Observatory (HAWC) is one of the few instruments sensitive to gamma rays with energies above 10 TeV. This offers the opportunity to probe the EBL in the near/mid-IR region:
λ
= 1–100
μ
m. In this study, we fit physically motivated emission models to Fermi-LAT gigaelectronvolt data to extrapolate the intrinsic teraelectronvolt spectra of blazars. We then simulate a large number of absorbed spectra for different randomly generated EBL model shapes and calculate Bayesian credible bands in the EBL intensity space by comparing and testing the agreement between the absorbed spectra and HAWC extragalactic observations of two blazars. The resulting bands are in agreement with current EBL lower and upper limits, showing a downward trend toward higher wavelength values
λ
> 10
μ
m also observed in previous measurements.
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