798 research outputs found
Raquitismo hipofosfatêmico ligado ao X: uma nova mutação
Phosphopenic rickets may be caused by mutations in the PHEX gene (phosphate regulating endopeptidase homolog X-linked). Presently, more than 500 mutations in the PHEX gene have been found to cause hypophosphatemic rickets. The authors report a clinical case of a 4-year-old girl with unremarkable family
history, who presented with failure to thrive and bowing of the legs. Laboratory tests showed hypophosphatemia, elevated alkaline phosphatase, normal calcium, mildly elevated PTH and normal
levels of 25(OH)D and 1.25(OH)D. The radiological study showed bone deformities of the radius and femur.
Clinical diagnosis of phosphopenic rickets was made and the genetic study detected a heterozygous likely pathogenic variant of the PHEX gene: c.767_768del (p.Thr256Serfs*7). This variant was not previously described in the literature or databases. Knowledge about new mutations can improve patient’s outcome.
Genetic analysis can help to establish a genotype-phenotype correlation.info:eu-repo/semantics/publishedVersio
The effects of a Variable IMF on the Chemical Evolution of the Galaxy
In this work we explore the effects of adopting an initial mass function
(IMF) variable in time on the chemical evolution of the Galaxy. In order to do
that we adopt a chemical evolution model which assumes two main infall episodes
for the formation of the Galaxy. We study the effects on such a model of
different IMFs. First, we use a theoretical one based on the statistical
description of the density field arising from random motions in the gas. This
IMF is a function of time as it depends on physical conditions of the site of
star formation. We also investigate the behaviour of the model predictions
using other variable IMFs, parameterized as a function of metallicity. Our
results show that the theoretical IMF when applied to our model depends on time
but such time variation is important only in the early phases of the Galactic
evolution, when the IMF is biased towards massive stars. We also show that the
use of an IMF which is a stronger function of time does not lead to a good
agreement with the observational constraints suggesting that if the IMF varied
this variation should have been small. Our main conclusion is that the G-dwarf
metallicity distribution is best explained by infall with a large timescale and
a constant IMF, since it is possible to find variable IMFs of the kind studied
here, reproducing the G-dwarf metallicity but this worsens the agreement with
other observational constraints.Comment: 7 pages, to appear in "The Chemical Evolution of the Milky Way: Stars
vs Clusters", Vulcano, September 1999, F. Giovannelli and F. Matteucci eds.
(Kluwer, Dordrecht) in pres
Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death
\ua9 2024 The AuthorsHepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF6, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133+ and CD44high cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5-/- MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs
Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study
Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).<p></p>
Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.<p></p>
Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.<p></p>
Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.<p></p>
The origin of dust in galaxies revisited: the mechanism determining dust content
The origin of cosmic dust is a fundamental issue in planetary science. This
paper revisits the origin of dust in galaxies, in particular, in the Milky Way,
by using a chemical evolution model of a galaxy composed of stars, interstellar
medium, metals (elements heavier than helium), and dust. We start from a review
of time-evolutionary equations of the four components, and then, we present
simple recipes for the stellar remnant mass and yields of metal and dust based
on models of stellar nucleosynthesis and dust formation. After calibrating some
model parameters with the data from the solar neighborhood, we have confirmed a
shortage of the stellar dust production rate relative to the dust destruction
rate by supernovae if the destruction efficiency suggested by theoretical works
is correct. If the dust mass growth by material accretion in molecular clouds
is active, the observed dust amount in the solar neighborhood is reproduced. We
present a clear analytic explanation of the mechanism for determining dust
content in galaxies after the activation of accretion growth: a balance between
accretion growth and supernova destruction. Thus, the dust content is
independent of the uncertainty of the stellar dust yield after the growth
activation. The timing of the activation is determined by a critical metal mass
fraction which depends on the growth and destruction efficiencies. The solar
system formation seems to have occurred well after the activation and plenty of
dust would have existed in the proto-solar nebula.Comment: 12 pages, 11 figure
Tri-n-butyltin Hydride-Mediated Radical Reactions of ortho- and meta-Iodobenzamides to Synthesize Benzomacrolactams. Surprising Formation of Biphenyl Compounds from meta-Regioisomers
Conselho Nacional de Desenvolvimento CientÃfico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Reactions of methyl 4-O-allyl-2,3-di-O-benzyl-6-deoxy-6-(3-iodobenzoylamino)-alpha-D-galactopyranoside, its gluco epimer, methyl 2,3-di-O-benzyl-6-deoxy-6-(3-iodobenzoylamino)4-O-(1-pentenyl)-alpha-D-glucopyranoside and its ortho-regioisomer with tri-n-butyltin hydride were performed in different conditions. Depending on reaction conditions the three meta-iodo isomers gave a surprising amount of biphenyl compounds. The 2-iodo isomer led only to the undesired but expected hydrogenolysis product. No cyclized products were isolated in all the reactions. The structures of the new biphenyl products were elucidated by (1)H and (13)C NMR spectroscopy, DEPT, COSY, HMQC and HMBC experiments and ESI-MS/MS. Mechanisms for the formation of these new biphenyl derivatives and hypotheses to explain the different outcomes for radical reactions of 3- or 2-iodobenzamides were presented.20815041514Conselho Nacional de Desenvolvimento CientÃfico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento CientÃfico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP
Analysis of the microstructure of Xenodontinae snake scales associated with different habitat occupation strategies
A Fokker-Planck formalism for diffusion with finite increments and absorbing boundaries
Gaussian white noise is frequently used to model fluctuations in physical
systems. In Fokker-Planck theory, this leads to a vanishing probability density
near the absorbing boundary of threshold models. Here we derive the boundary
condition for the stationary density of a first-order stochastic differential
equation for additive finite-grained Poisson noise and show that the response
properties of threshold units are qualitatively altered. Applied to the
integrate-and-fire neuron model, the response turns out to be instantaneous
rather than exhibiting low-pass characteristics, highly non-linear, and
asymmetric for excitation and inhibition. The novel mechanism is exhibited on
the network level and is a generic property of pulse-coupled systems of
threshold units.Comment: Consists of two parts: main article (3 figures) plus supplementary
text (3 extra figures
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