Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the ...favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels’ mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.
Stimulation of the dorsolateral periaqueductal grey matter (dlPAG) in rats evokes an active defensive behaviour together with a cardiorespiratory response characterised by tachypnoea, tachycardia and ...hypertension. The dlPAG neurons involved in these responses are excitatory, presumably glutamatergic, due to the presence of vesicular glutamate transporter VGLUT2 within their axon terminals. Previously, our group described a functional interaction between dlPAG and the pontine A5 region. Accordingly, in the present work, in order to characterize the role of glutamate within this interaction, experiments were carried out in spontaneously breathing anaesthetized rats (sodium pentobarbitone 60 mg/kg i.p., suplemented with 20 mg/kg i.p.). The cardiorespiratory response evoked by electrical stimulation of the dlPAG (1 ms pulses, 20–50 μA, given at 100 Hz, during 5 s) was analysed before and after the microinjection, within the A5 region, of either kynurenic acid (non-specific glutamate receptor antagonist; 5–10 nmol), DAP-5 (NMDA antagonist; 1 pmol), CNQX (non-NMDA antagonist; 1 pmol) or MCPG (metabotropic antagonist; 0,1 nmol). Kynurenic acid decreased the intensity of both the tachypnoea (
p
< 0,001) and tachycardia (
p
< 0,001) induced by dl-PAG stimulation. Blockade of no-NMDA receptors reduced the increase of respiratory frequency, heart rate and pressor response to dl-PAG stimulation (
p
< 0,01,
p
< 0,001,
p
< 0,05 respectively). Blockade of either NMDA or metabotropic receptors reduced the dlPAG-evoked tachycardia and pressor response (
p
< 0,01;
p
< 0,05 respectively). These results suggest a neuromodulatory role for A5 region via glutamate neurotransmission of the dlPAG-evoked cardiorespiratory response, confirming the role of the ventrolateral pons in the neuronal circuits involved in respiratory and heart rate control.
We present subarcsecond 7.5–13 μm imaging- and spectro-polarimetric observations of NGC 1068 using CanariCam on the 10.4-m Gran Telescopio CANARIAS. At all wavelengths, we find: (1) A 90 × 60 pc ...extended polarized feature in the northern ionization cone, with a uniform ∼44
$^\circ$
polarization angle. Its polarization arises from dust and gas emission in the ionization cone, heated by the active nucleus and jet, and further extinguished by aligned dust grains in the host galaxy. The polarization spectrum of the jet–molecular cloud interaction at ∼24 pc from the core is highly polarized, and does not show a silicate feature, suggesting that the dust grains are different from those in the interstellar medium. (2) A southern polarized feature at ∼9.6 pc from the core. Its polarization arises from a dust emission component extinguished by a large concentration of dust in the galaxy disc. We cannot distinguish between dust emission from magnetically aligned dust grains directly heated by the jet close to the core, and aligned dust grains in the dusty obscuring material surrounding the central engine. Silicate-like grains reproduce the polarized dust emission in this feature, suggesting different dust compositions in both ionization cones. (3) An upper limit of polarization degree of 0.3 per cent in the core. Based on our polarization model, the expected polarization of the obscuring dusty material is ≲0.1 per cent in the 8–13 μm wavelength range. This low polarization may be arising from the passage of radiation through aligned dust grains in the shielded edges of the clumps.
Cardiovascular disease (CVD) is the leading cause of death. The mainly risks factors for CVD are diabetes, hypertension and high levels of homocysteine (Hcys), among others. Paraoxonase 1 (PON1) has ...been proposed as an antiatherogenic target for its ability to hydrolyzing oxi-Low-Density-Lipoproteins (LDL) and Hcys-thiolactone. Thus, the aim of the present study was to evaluate the association of Hcys levels, and the activities and concentration of PON1, as well as vitamin B from the diet with a risk for CVD.
A case-control study was carry out in patients with cardiovascular diseases (CVD), Arterial hypertension, but not CVD (AH), and in healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, intake of vitamin B, Hcys, serum amyloid A (SAA), PON1 concentration, and PON1 activities (Arylesterase activity (ARE), Lactonase activity (LAC), and CMPA activity (CMPA)) were evaluated.
The CVD group had the highest concentration of Hcys and SAA than in the AH and control groups (p < 0.01). ARE, LAC, and CMPA activities and PON1 concentration were lowest in the CVD group. A positive-independent association between Hcys levels and CVD was found (OR = 2.09; 95% CI: 1.69–2.56) and this increase when it was adjusted by age, BMI, ApoA1, vitamin B intake, SAA, and PON1 (OR = 14.41; 95% CI: 1.75–118.71). LAC and CMPA, as well as PON1 concentration, were inversely associated with CVD.
LAC activity, PON1 concentration, and Hcys levels might be good biomarkers for CVD and their association could be modified by the intake of vitamin B.
•Patients with cardiovascular disease (CVD) had higher Hcys and SAA levels than controls.•Activities and concentration of PON1 were low in patients with CVD.•Hcys levels were associated with an increase in the OR of belonging to the CVD group.•LAC activity, PON1 concentration, and Hcys levels might be good biomarkers for CVD.
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•Molecular analyses in Margarella contradict the current taxonomic knowledge in the group.•The Antarctic Polar Front (APF) represents an effective biogeographic barrier.•North of the ...APF Margarella includes a single and broadly distributed species.•South of the APF Margarella includes at least three different lineages.•The presence/absence of buoyant kelps plays a key role in Margarella’s biogeography.
Members of the trochoidean genus Margarella (Calliostomatidae) are broadly distributed across Antarctic and sub-Antarctic ecosystems. Here we used novel mitochondrial and nuclear gene sequences to clarify species boundaries and phylogenetic relationships among seven nominal species distributed on either side of the Antarctic Polar Front (APF). Molecular reconstructions and species-delimitation analyses recognized only four species: M. antarctica (the Antarctic Peninsula), M. achilles (endemic to South Georgia), M. steineni (South Georgia and Crozet Island) and the morphologically variable M. violacea (=M. expansa, M. porcellana and M. pruinosa), with populations in southern South America, the Falkland/Malvinas, Crozet and Kerguelen Islands. Margarella violacea and M. achilles are sister species, closely related to M. steineni, with M. antarctica sister to all these. This taxonomy reflects contrasting biogeographic patterns on either side of the APF in the Southern Ocean. Populations of Margarella north of the APF (M. violacea) showed significant genetic variation but with many shared haplotypes between geographically distant populations. By contrast, populations south of the APF (M. antarctica, M. steineni and M. achilles) exhibited fewer haplotypes and comprised three distinct species, each occurring across a separate geographical range. We hypothesize that the biogeographical differences may be the consequence of the presence north of the APF of buoyant kelps – potential long-distance dispersal vectors for these vetigastropods with benthic-protected development – and their near-absence to the south. Finally, we suggest that the low levels of genetic diversity within higher-latitude Margarella reflect the impact of Quaternary glacial cycles that exterminated local populations during their maxima.
Abstract
Bioimpedance spectroscopy has been used to evaluate and characterize the integrity of different tissues and organs, as well as to detect tissue structural alterations. The tissue electrical ...model alterations as an influence of the anisotropy of the tissue structure and its intrinsic metabolism on the degradation dynamic have not been completely understood. In this work, the dynamic of Cole parameters was estimated as a function of degradation time in
ex vivo
skeletal muscle, skin, and white adipose tissues. The results indicate a non-linear behavior function of the Cole parameters through degradation progress in the three evaluated tissues, and such non-linearities might be associated with different capacities of adaptation to anaerobic metabolism, energy production, and water content under stress conditions.
Introduction
The first definition of PAS, enunciated by Richard Gardner in 1985, refers to a disorder originating in the context of legal conflicts related to child custody. Its main characteristic ...would be a smear campaign by the child towards a parent, in the absence of plausible arguments. In this context, the child would experience an oppositional and dichotomous feeling towards his or her parents. In recent years, the presence of PAS has become increasingly important, both in the legal and health fields, largely due to the controversy and debate surrounding its approval and recognition, and there is currently no consensus on the matter.
Objectives
The main objective of this work is to examine the current state of PAS in depth in the different fields in which it is emerging: the medical-scientific and legal spheres. The current controversies and debate, both scientific and legal, will be developed. Research will be carried out on the origin of the concept and its evolution, its symptomatic presentation, the neuropsychological consequences in minors, the role and legal value of expert reports, as well as the existing evaluation methods for the assessment of PAS.
Methods
An extensive literature review was carried out on the subject in question, extracting information mainly from scientific articles, but also from legislative documents, manuals and books.
Results
There are currently no specific laws regulating PAS in European countries. According to Article 10.2 of the Spanish Constitution, norms related to fundamental rights shall be interpreted according to the Universal Declaration of Human Rights. As a direct consequence of the chronic psychological stresses experienced by children, adaptive disorders may appear, often characterised by symptoms of anxiety and depression. In addition, a multitude of neuropsychological consequences have been observed not only in the affected child, but also in the adult he or she will become.
Conclusions
Currently, there is a fervent debate about the validity and recognition of PAS as a diagnostic entity, spanning different disciplines, ranging from health to social and legal. In Europe, professionals in the scientific field have not reached an agreement regarding the approval of PAS. On the one hand, there are those for whom PAS is a verified phenomenon; on the other hand, there are those who flatly reject the existence of this phenomenon. The latter consider PAS an unscientific construct, referring to it as “court syndrome” or “patriarchal alienation syndrome”.
Disclosure of Interest
None Declared
Paraoxonase 1 (PON1) is a calcium-dependent lactonase synthesized primarily in the liver and secreted into the plasma, where it is associates with high density lipoproteins (HDL). PON1 acts as ...antioxidant preventing low-density lipoprotein (LDL) oxidation, a process considered critical in the initiation and progression of atherosclerosis. Additionally, PON1 hydrolyzes and detoxifies some toxic metabolites of organophosphorus compounds (OPs). Thus, PON1 activity and expression levels are important for determining susceptibility to OPs intoxication and risk of developing diseases related to inflammation and oxidative stress. Increasing evidence has demonstrated the modulation of PON1 expression by many factors is due to interaction with nuclear receptors (NRs). Here, we briefly review the studies in this area and discuss the role of nuclear receptors in the regulation of PON1 expression, as well as how understanding these mechanisms may allow us to manipulate PON1 levels to improve drug efficacy and treat disease.
•Human Paraoxonase 1 is regulated through nuclear receptors.•Nuclear receptors AhR, PXR, GR, PPARs, and Nrf2 may regulate PON1.•PON1 is also regulated by proinflammatory cytokines and epigenetic mechanisms.•Nuclear receptors GR, PPAR, AhR, and PXR regulate PON1 expression.
Prospective identification of patients with chronic lymphocytic leukemia (CLL) destined to progress would greatly facilitate their clinical management. Recently, whole-genome DNA methylation analyses ...identified three clinicobiologic CLL subgroups with an epigenetic signature related to different normal B-cell counterparts. Here, we developed a clinically applicable method to identify these subgroups and to study their clinical relevance. Using a support vector machine approach, we built a prediction model using five epigenetic biomarkers that was able to classify CLL patients accurately into the three subgroups, namely naive B-cell-like, intermediate and memory B-cell-like CLL. DNA methylation was quantified by highly reproducible bisulfite pyrosequencing assays in two independent CLL series. In the initial series (n=211), the three subgroups showed differential levels of IGHV (immunoglobulin heavy-chain locus) mutation (P<0.001) and VH usage (P<0.03), as well as different clinical features and outcome in terms of time to first treatment (TTT) and overall survival (P<0.001). A multivariate Cox model showed that epigenetic classification was the strongest predictor of TTT (P<0.001) along with Binet stage (P<0.001). These findings were corroborated in a validation series (n=97). In this study, we developed a simple and robust method using epigenetic biomarkers to categorize CLLs into three subgroups with different clinicobiologic features and outcome.
A
bstract
The
Neutrino Experiment with a Xenon TPC
(NEXT) searches for the neutrinoless double-beta (0
νββ
) decay of
136
Xe using high-pressure xenon gas TPCs with electroluminescent amplification. ...A scaled-up version of this technology with about 1 tonne of enriched xenon could reach in less than 5 years of operation a sensitivity to the half-life of 0
νββ
decay better than 10
27
years, improving the current limits by at least one order of magnitude. This prediction is based on a well-understood background model dominated by radiogenic sources. The detector concept presented here represents a first step on a compelling path towards sensitivity to the parameter space defined by the inverted ordering of neutrino masses, and beyond.
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