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Metabolic dysfunction-associated steatohepatitis (MASH) represents a global health threat. MASH pathophysiology involves hepatic lipid accumulation and progression to severe conditions like cirrhosis and, eventually, hepatocellular carcinoma. Fibroblast growth factor (FGF)-19 has emerged as a key regulator of metabolism, offering potential therapeutic avenues for MASH and associated disorders. We evaluated the therapeutic potential of non-mitogenic (NM)-FGF19 mRNA formulated in liver-targeted lipid nanoparticles (NM-FGF19-mRNAs-LNPs) in C57BL/6NTac male mice with diet-induced obesity and MASH (DIO-MASH: 40% kcal fat, 20% kcal fructose, 2% cholesterol). After feeding this diet for 21 weeks, NM-FGF19-mRNAs-LNPs or control (C-mRNA-LNPs) were administered (0.5 mg/kg, i.v.) weekly for another six weeks, in which diet feeding continued. NM-FGF19-mRNAs-LNPs treatment in DIO-MASH mice resulted in reduced body weight, adipose tissue depots, and serum transaminases, along with improved insulin sensitivity. Histological analyses confirmed the reversal of MASH features, including steatosis reduction without worsening fibrosis. NM-FGF19-mRNAs-LNPs reduced total hepatic bile acids (BAs) and changed liver BA composition, markedly influencing cholesterol homeostasis and metabolic pathways as observed in transcriptomic analyses. Extrahepatic effects included the down-regulation of metabolic dysfunction-associated genes in adipose tissue. This study highlights the potential of NM-FGF19-mRNA-LNPs therapy for MASH, addressing both hepatic and systemic metabolic dysregulation. NM-FGF19-mRNA demonstrates efficacy in reducing liver steatosis, improving metabolic parameters, and modulating BA levels and composition. Given the central role played by BA in dietary fat absorption, this effect of NM-FGF19-mRNA may be mechanistically relevant. Our study underscores the high translational potential of mRNA-based therapies in addressing the multifaceted landscape of MASH and associated metabolic perturbations. [ABSTRACT FROM AUTHOR]

Background/Objectives: To determine the prevalence of amyloidosis through the analysis of synovial tissue and transverse carpal ligament (TCL) in patients undergoing surgery for carpal tunnel syndrome (CTS), detect predictive factors for the presence of amyloid, and assess cardiac involvement degree. Methods: A prospective study with longitudinal cohort follow-up at a teaching hospital. Patients undergoing CTS surgery from 1 January 2019 to 31 May 2021 were included. Samples from synovial and TCL tissues were examined for amyloid presence. Multivariate analysis was used to detect predictive factors of the presence of amyloid. Patients with amyloid underwent echocardiography, laboratory analyses, and scintigraphy. Results: Two hundred and forty-six patients were included. The prevalence of amyloid was 11.4% in TCL and 12.6% in synovial tissues. Age (p = 0.035; OR 1.123), bilateral CTS symptoms (p = 0.022; OR 3.647), and trigger finger (p < 0.001; OR 3.537) were predictors of the presence of amyloid. Seventeen patients were diagnosed with transthyretin amyloidosis (ATTR) located in the carpus (no scintigraphic cardiac uptake or grade 0), one with light chain amyloidosis, eight with ATTR with cardiac involvement (grades 2–3), and five with ATTR in the carpus and scintigraphic uptake grade 1 (with normal echocardiogram and blood and urine tests). Conclusions: We detected amyloid in 12.6% of unselected consecutive patients who underwent CTS surgery. Biopsy in patients with CTS for amyloid detection, especially in elderly patients with bilateral symptoms and trigger finger, may be useful for the early diagnosis of amyloidosis, primarily due to transthyretin. [ABSTRACT FROM AUTHOR]

Background: Cerebral amyloid angiopathy (CAA) is characterized by amyloid-β (Aβ) deposition in cerebral vessels, leading to lobar cerebral microbleeds (CMB) and intracerebral hemorrhages (ICH). Apolipoprotein J (ApoJ) is a multifunctional chaperone related to Aβ aggregation and clearance. Our study investigated the vascular impact of chronic recombinant human Apolipoprotein J (rhApoJ) treatment in a transgenic mouse model of β-amyloidosis with prominent CAA. Methods: Twenty-month-old APP23 C57BL/6 mice received 25 doses of rhApoJ (1 mg/kg) (n = 9) or saline (n = 8) intraperitoneally for 13 weeks, while Wild-type (WT) mice received saline (n = 13). Postmortem brains underwent T2*-weighted magnetic resonance imaging (MRI) to detect hemorrhagic lesions. Aβ levels and distribution, cerebral fibrinogen leakage, brain smooth muscle actin (sma), and plasma matrix metalloproteinases and inflammatory markers were analyzed after treatments. Additionally, plasma samples from 22 patients with lobar ICH were examined to determine the clinical relevance of the preclinical findings. Results: rhApoJ-treated APP23 presented fewer cortical CMBs (50–300 μm diameter) (p = 0.012) and cortical larger hemorrhages (> 300 μm) (p = 0.002) than saline-treated mice, independently of Aβ brain levels. MRI-detected hemorrhagic lesions correlated with fibrinogen cerebral extravasation (p = 0.011). Additionally, rhApoJ-treated mice presented higher number of sma-positive vessels than saline-treated mice (p = 0.038). In rhApoJ-treated mice, human ApoJ was detected in plasma and in occasional leptomeningeal vessels, but not in the parenchyma, suggesting that its mechanism of action operates through the periphery. The administration of rhApoJ induced an increase in plasma Groα (p = 0.035) and MIP-1α (p = 0.035) levels, while lower MMP-12 (p = 0.046) levels, compared to the saline-treated group. In acute lobar ICH patients, MMP-12 plasma levels correlated with larger hemorrhage volume (p = 0.040) and irregular ICH shape (p = 0.036). Conclusions: Chronic rhApoJ treatment in aged APP23 mice ameliorated CAA-related neurovascular damage by reducing the occurrence of CMB. We propose that rhApoJ may prevent blood-brain barrier (BBB) leakage and CMB appearance partly through circulating MMP-12 modulation. [ABSTRACT FROM AUTHOR]

Introduction: Gender incongruence (GI) is characterized by a marked incongruence between an individual's experienced/expressed gender and the assigned sex at birth. It includes strong displeasure about his or her sexual anatomy and secondary sex characteristics. In some people, this condition produces a strong distress with anxiety and depression named gender dysphoria (GD). This condition appears to be associated with genetic, epigenetics, hormonal as well as social factors. Given that L-glutamate is the major excitatory neurotransmitter in the central nervous system, also associated with male sexual behavior as well as depression, we aimed to determine whether metabotropic glutamate receptors are involved in GD. Methods: We analyzed 74 single nucleotide polymorphisms located at the metabotropic glutamate receptors (mGluR1, mGluR3, mGluR4, mGluR5, mGluR7 and mGluR8) in 94 transgender versus 94 cisgender people. The allele and genotype frequencies were analyzed by c2 test contrasting male and female cisgender and transgender populations. The strength of the associations was measured by binary logistic regression, estimating the odds ratio (OR) for each genotype. Measurement of linkage disequilibrium, and subsequent measurement of haplotype frequencies were also performed considering three levels of significance: P = 0.05, P = 0.005 and P = 0.0005. Furthermore, false positives were controlled with the Bonferroni correction (P = 0.05/74 = 0.00067). Results: After analysis of allele and genotypic frequencies, we found twenty-five polymorphisms with significant differences at level P = 0.05, five at P = 0.005 and two at P = 0.0005. Furthermore, the only two polymorphisms (rs9838094 and rs1818033) that passed the Bonferroni correction were both related to the metabotropic glutamate receptor 7 (mGluR7) and showed significant differences for multiple patterns of inheritance. Moreover, the haplotype T/G [OR=0.34 (0.19-0.62); P<0.0004] had a lower representation in the transgender population than in the cisgender population, with no evidence of sex cross-interaction. Conclusion: We provide genetic evidence that the mGluR7, and therefore glutamatergic neurotransmission, may be involved in GI and GD. [ABSTRACT FROM AUTHOR]

Mathematical modeling of neuronal dynamics has experienced a fast growth in the last decades thanks to the biophysical formalism introduced by Hodgkin and Huxley in the 1950s. Other types of models (for instance, integrate and fire models), although less realistic, have also contributed to understand neuronal dynamics. However, there is still a vast volume of data that have not been associated with a mathematical model, mainly because data are acquired more rapidly than they can be analyzed or because it is difficult to analyze (for instance, if the number of ionic channels involved is huge). Therefore, developing new methodologies to obtain mathematical or computational models associated with data (even without previous knowledge of the source) can be helpful to make future predictions. Here, we explore the capability of a wavelet neural network to identify neuronal (single-cell) dynamics. We present an optimized computational scheme that trains the ANN with biologically plausible input currents. We obtain successful identification for data generated from four different neuron models when using all variables as inputs of the network. We also show that the empiric model obtained is able to generalize and predict the neuronal dynamics generated by variable input currents different from those used to train the artificial network. In the more realistic situation of using only the voltage and the injected current as input data to train the network, we lose predictive ability but, for low-dimensional models, the results are still satisfactory. We understand our contribution as a first step toward obtaining empiric models from experimental voltage traces. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the impact of functional shifts in a time-discrete cross-catalytic system. We use the hypercycle model considering that one of the species shifts from a cooperator to a degrader. At the bifurcation caused by this functional shift, an invariant curve collapses to a point P while, simultaneously, two fixed points collide with P in a transcritical bifurcation. Moreover, all points of a line containing P become fixed points at the bifurcation and only at the bifurcation in a degenerate scenario. We provide a complete analytical description of this degenerate bifurcation. As a result of our study, we prove the existence of the invariant curve arising from the transition to cooperation. [ABSTRACT FROM AUTHOR]

Gender identity refers to the consciousness of being a man, a woman or other condition. Although it is generally congruent with the sex assigned at birth, for some people it is not. If the incongruity is distressing, it is defined as gender dysphoria (GD). Here, we measured whole-genome DNA methylation by the Illumina © Infinium Human Methylation 850k array and reported its correlation with cortical thickness (CTh) in 22 transgender men (TM) experiencing GD versus 25 cisgender men (CM) and 28 cisgender women (CW). With respect to the methylation analysis, TM vs. CW showed significant differences in 35 CpGs, while 2155 CpGs were found when TM vs. CM were compared. With respect to correlation analysis, TM showed differences in methylation of CBLL1 and DLG1 genes that correlated with global and left hemisphere CTh. Both genes were hypomethylated in TM compared to the cisgender groups. Early onset TM showed a positive correlation between CBLL1 and several cortical regions in the frontal (left caudal middle frontal), temporal (right inferior temporal, left fusiform) and parietal cortices (left supramarginal and right paracentral). This is the first study relating CBLL1 methylation with CTh in transgender persons and supports a neurodevelopmental hypothesis of gender identity. [ABSTRACT FROM AUTHOR]

Sarcopenic obesity (SO) is diagnosed when sarcopenia and obesity coexist in patients. The objective of this study was to determine the prevalence of SO under different diagnostic criteria in community-dwelling Spanish adults aged over 65 years residing in Valencia (Spain). The research was conducted as an observational and cross-sectional study with a sample size of 202 subjects. To diagnose sarcopenia, we used the tests proposed by the European Working Group on Sarcopenia in Older People in 2019 (EWGSOP2): SARC-F, grip strength, sit-to-stand, gait speed, Appendicular Skeletal Muscle Mass (ASMM), and Short Physical Performance Battery (SPPB). For obesity diagnosis, we used body mass index (BMI), waist circumference (WC), total body fat percentage (%TBF), and tricipital skinfold (TS). The prevalence of SO was 16.5% in women and 29% in men, according to any of the diagnostic criteria used to determine obesity. A higher proportion of SO was observed as age increased in both groups, although no significant differences were found. Most values obtained in tests related to SO diagnosis were worse in the group affected by the disease; however, there were two exceptions related to the amount of ASMM. In total, 18.8% of the participants presented SO according to any diagnostic criteria related to obesity. Our results suggest significant differences in the number of SO cases depending on diagnostic criteria used to determine the participants' obesity. BMI, WC, and TBF% were shown as principal variables to be included in obesity diagnosis within the SO construct. These findings underscore the need to unify criteria to standardize the diagnosis of SO in the global population. [ABSTRACT FROM AUTHOR]

Background and Purpose: Therapies based on apolipoprotein A‐I (ApoA‐I), classically tested for cardiovascular diseases, were recently proposed for Alzheimer's disease (AD). Based on a drug reprofiling approach, our objective was to explore the use of a natural variant of ApoA‐I form, ApoA‐I‐Milano (M), as a treatment for AD. ApoA‐I‐M contains the R173C mutation, and confers protection against atherosclerosis development, although ApoA‐I‐M carriers exhibit low HDL levels. Experimental Approach: Middle‐aged (12‐month‐old) and aged (21‐month‐old) APP23 mice were intraperitoneally treated for 10 weeks with human recombinant ApoA‐I‐M (hrApoA‐I‐M) protein or saline. Pathology progression through behavioural parameters and biochemical determinations was evaluated. Key Results: In middle‐aged group, hrApoA‐I‐M treatment reduced the anxiety behaviour associated with this AD model. In aged mice, hrApoA‐I‐M reversed T‐Maze performance alterations, a cognitive improvement accompanied by neuronal loss recovery in the dentate gyrus. Aged mice treated with hrApoA‐I‐M showed lower brain Aβ40 soluble levels and elevated Aβ40 levels in cerebrospinal fluid, without modifying insoluble brain Aβ burden. Interestingly, hrApoA‐I‐M sub‐chronic treatment induced a molecular effect on the cerebrovasculature, increasing occludin expression and ICAM‐1 presence, as well as promoting an elevation of plasma soluble RAGE in all hrApoA‐I‐M‐treated mice, drastically decreasing the AGEs/sRAGE ratio, a marker of endothelial damage. Conclusion and Implications: Peripheral hrApoA‐I‐M treatment shows a beneficial impact on working memory, involving mechanisms related with brain Aβ mobilization and modulation of the levels of cerebrovascular markers. Our study shows the potential therapeutic applicability of a safe and non‐invasive treatment based on peripheral administration of hrApoA‐I‐M in AD. [ABSTRACT FROM AUTHOR]

To determine the prevalence of myocardial uptake (MU) and to identify predictors of MU in patients undergoing scintigraphy. Retrospective single-center series of technetium-99 m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scans performed from March 2017 to March 2020. All patients undergoing scintigraphy were included, except those with preexisting amyloidosis. The features of MU, patients' characteristics and comorbidities were documented. Multivariate analysis was used to find items predicting MU. A total of 3,629 99mTc-DPD scans (total 11,444) were performed in patients aged > 70. The overall prevalence of MU was 2.7% (82/3,629); 1.2% in 2017–2018, to 2% in 2018–2019, and to 3.7% in 2019–2020. The prevalence of MU in patients without suspected cardiomyopathy was 1.2%; 1.1% in 2017–2018, 1.5% in 2018–2019 and 1% in 2019–2020. There is an increase in the number of requests due to suspected cardiomyopathy from 0.2% in 2017–2018 to 1.4% in 2018–2019 and to 4.8% in 2019–2020. Age, male sex, hypertension, heart failure, atrial fibrillation, atrioventricular block, aortic stenosis, and carpal tunnel syndrome were found to be predictors of MU. In patients without heart failure, only age, atrial fibrillation, and carpal tunnel syndrome were predicted MU. The prevalence of MU in scintigraphic studies surged over time due to the incremental referrals under the indication of cardiomyopathy workup. Atrial fibrillation and carpal tunnel syndrome were predictors for MU in patients without heart failure. Identifying patients with MU and no heart failure for extended screening for ATTR can lead to an earlier diagnosis and application of novel treatments. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-b (Ab) in brain vessels and is a main cause of lobar intracerebral hemorrhage (ICH) in the elderly. CAA is associated with magnetic resonance imaging (MRI) markers of small vessel disease (SVD). Since Ab is also accumulated in Alzheimer's disease (AD) in the brain parenchyma, we aimed to study if several single nucleotide polymorphisms (SNPs) previously associated with AD were also associated with CAA pathology. Furthermore, we also studied the influence of APOE and CLU genetic variants in apolipoprotein E (ApoE) and clusterin/apolipoprotein J (ApoJ) circulating levels and their distribution among lipoproteins. Methods: The study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA. Results: We observed several SNPs associated with CAA neuroimaging MRI markers [cortical superficial siderosis (cSS), enlarged perivascular spaces in the centrum semiovale (CSO-EPVS), lobar cerebral microbleeds (CMB), white matter hyperintensities (WMH), corticosubcortical atrophy and CAA-SVD burden score]. Concretely, ABCA7 (rs3764650), CLU (rs9331896 and rs933188), EPHA1 (rs11767557), and TREML2 (rs3747742) were significantly associated with a CAASVD burden score. Regarding circulating levels of apolipoproteins, protective AD SNPs of CLU [rs11136000 (T) and rs9331896 (C)] were significantly associated with higher HDL ApoJ content in the lobar ICH cohort. APOE+2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOE+4 carriers presented lower plasma ApoE levels. Additionally, we observed that lower circulating ApoJ and ApoE levels were significantly associated with CAA-related MRI markers. More specifically, lower LDL-associated ApoJ and plasma and HDLassociated ApoE levels were significantly associated with CSO-EPVS, lower ApoJ content in HDL with brain atrophy and lower ApoE content in LDL with the extent of cSS. Discussion: This study reinforces the relevance of lipid metabolism in CAA and cerebrovascular functionality. We propose that ApoJ and ApoE distribution among lipoproteins may be associated with pathological features related to CAA with higher ApoE and ApoJ levels in HDL possibly enhancing atheroprotective, antioxidative, and anti-inflammatory responses in cerebral b-amyloidosis. [ABSTRACT FROM AUTHOR]

We present several results on the determination of the number and distribution of limit cycles or centers for planar systems of differential equations. In most cases, the study of a recurrence is one of the key points of our approach. These results include the counting of the number of configurations of stabilities of nested limit cycles, the study of the number of different configurations of a given number of limit cycles, the proof of some quadratic lower bounds for Hilbert numbers and some questions about the number of centers for planar polynomial vector fields. [ABSTRACT FROM AUTHOR]

In this work, α-Ag2−2xCuxWO4 (0 ≤ x ≤ 0.16) solid solutions with enhanced antibacterial (against methicillin-resistant Staphylococcus aureus) and antifungal (against Candida albicans) activities are reported. A plethora of techniques (X-ray diffraction with Rietveld refinements, inductively coupled plasma atomic emission spectrometry, micro-Raman spectroscopy, attenuated total reflectance–Fourier transform infrared spectroscopy, field emission scanning electron microscopy, ultraviolet–visible spectroscopy, photoluminescence emissions, and X-ray photoelectron spectroscopy) were employed to characterize the as-synthetized samples and determine the local coordination geometry of Cu2+ cations at the orthorhombic lattice. To find a correlation between morphology and biocide activity, the experimental results were sustained by first-principles calculations at the density functional theory level to decipher the cluster coordinations and electronic properties of the exposed surfaces. Based on the analysis of the under-coordinated Ag and Cu clusters at the (010) and (101) exposed surfaces, we propose a mechanism to explain the biocide activity of these solid solutions. [ABSTRACT FROM AUTHOR]

How the brain represents gender identity is largely unknown, but some neural differences have recently been discovered. We used an intrinsic ignition framework to investigate whether there are gender differences in the propagation of neural activity across the whole‐brain and within resting‐state networks. Studying 29 trans men and 17 trans women with gender incongruence, 22 cis women, and 19 cis men, we computed the capability of a given brain area in space to propagate activity to other areas (mean‐ignition), and the variability across time for each brain area (node‐metastability). We found that both measurements differentiated all groups across the whole brain. At the network level, we found that compared to the other groups, cis men showed higher mean‐ignition of the dorsal attention network and node‐metastability of the dorsal and ventral attention, executive control, and temporal parietal networks. We also found higher mean‐ignition values in cis men than in cis women within the executive control network, but higher mean‐ignition in cis women than cis men and trans men for the default mode. Node‐metastability was higher in cis men than cis women in the somatomotor network, while both mean‐ignition and node‐metastability were higher for cis men than trans men in the limbic network. Finally, we computed correlations between these measurements and a body image satisfaction score. Trans men's dissatisfaction as well as cis men's and cis women's satisfaction toward their own body image were distinctively associated with specific networks in each group. Overall, the study of the whole‐brain network dynamical complexity discriminates gender identity groups, functional dynamic approaches could help disentangle the complex nature of the gender dimension in the brain. [ABSTRACT FROM AUTHOR]

A low-cost handheld e-nose unit for assessing composition and quality of food in the field or for automatic discrimination of different foodstuffs would have significant commercial advantages and provide a positive impact on consumer safety and confidence. Whilst many studies have focused on the freshness of specific foodstuffs, the preliminary results presented in this report indicate that a low-cost (circa 30 euro) e-nose, based on MQ series gas sensors, using sinusoidally varying heater voltages, can successfully differentiate between samples of unspoiled lamb, hake, salmon, beef, pork and chicken, even using default, non-optimized control parameters, which could be applied in food adulteration and fraudulent labelling detection or in smart appliances to automatically select cooking parameters. Samples were exposed to the e-nose for five cycles of two minutes each and, by subjecting the response waveforms to Discrete Fourier Transform (DFT) analysis, harmonic component amplitudes were extracted. These data items were then fed into two different Machine Learning supervised classification methods (discriminant analysis and random forest) to determine which foodstuff was present. The relevance of the different DFT harmonic components and MQ sensors in the foodstuffs classification was quantified. Classification accuracies in excess of 95% were demonstrated. [ABSTRACT FROM AUTHOR]

Background Minority stress via discrimination, stigmatization, and exposure to violence can lead to development of mood and anxiety disorders and underlying neurobiochemical changes. To date, the neural and neurochemical correlates of emotion processing in transgender people (and their interaction) are unknown. Methods This study combined functional magnetic resonance imaging and magnetic resonance spectroscopy to uncover the effects of anxiety and perceived stress on the neural and neurochemical substrates, specifically choline, on emotion processing in transgender men. Thirty transgender men (TM), 30 cisgender men, and 35 cisgender women passively viewed angry, neutral, happy, and surprised faces in the functional magnetic resonance imaging scanner, underwent a magnetic resonance spectroscopy scan, and filled out mood- and anxiety-related questionnaires. Results As predicted, choline levels modulated the relationship between anxiety and stress symptoms and the neural response to angry and surprised (but not happy faces) in the amygdala. This was the case only for TM but not cisgender comparisons. More generally, neural responses in the left amygdala, left middle frontal gyrus, and medial frontal gyrus to emotional faces in TM resembled that of cisgender women. Conclusions These results provide first evidence, to our knowledge, of a critical interaction between levels of analysis and that choline may influence neural processing of emotion in individuals prone to minority stress. [ABSTRACT FROM AUTHOR]

The pathological accumulation of parenchymal and vascular amyloid-beta (Aβ) are the main hallmarks of Alzheimer's disease (AD) and Cerebral Amyloid Angiopathy (CAA), respectively. Emerging evidence raises an important contribution of vascular dysfunction in AD pathology that could partially explain the failure of anti-Aβ therapies in this field. Transgenic mice models of cerebral β-amyloidosis are essential to a better understanding of the mechanisms underlying amyloid accumulation in the cerebrovasculature and its interactions with neuritic plaque deposition. Here, our main objective was to evaluate the progression of both parenchymal and vascular deposition in APP23 and 5xFAD transgenic mice in relation to age and sex. We first showed a significant age-dependent accumulation of extracellular Aβ deposits in both transgenic models, with a greater increase in APP23 females. We confirmed that CAA pathology was more prominent in the APP23 mice, demonstrating a higher progression of Aβ-positive vessels with age, but not linked to sex, and detecting a pronounced burden of cerebral microbleeds (cMBs) by magnetic resonance imaging (MRI). In contrast, 5xFAD mice did not present CAA, as shown by the negligible Aβ presence in cerebral vessels and the occurrence of occasional cMBs comparable to WT mice. In conclusion, the APP23 mouse model is an interesting tool to study the overlap between vascular and parenchymal Aβ deposition and to evaluate future disease-modifying therapy before its translation to the clinic. [ABSTRACT FROM AUTHOR]

Genome‐wide association studies have described several genes as genetic susceptibility loci for Alzheimer's disease (AD). Among them, CD2AP encodes CD2‐associated protein, a scaffold protein implicated in dynamic actin remodeling and membrane trafficking during endocytosis and cytokinesis. Although a clear link between CD2AP defects and glomerular pathology has been described, little is known about the function of CD2AP in the brain. The aim of this study was to analyze the distribution of CD2AP in the AD brain and its potential associations with tau aggregation and β‐amyloid (Aβ) deposition. First, we performed immunohistochemical analysis of CD2AP expression in brain tissue from AD patients and controls (N = 60). Our results showed granular CD2AP immunoreactivity in the human brain endothelium in all samples. In AD cases, no CD2AP was found to be associated with Aβ deposits in vessels or parenchymal plaques. CD2AP neuronal inclusions similar to neurofibrillary tangles (NFT) and neuropil thread‐like deposits were found only in AD samples. Moreover, immunofluorescence analysis revealed that CD2AP colocalized with pTau. Regarding CD2AP neuronal distribution, a hierarchical progression from the entorhinal to the temporal and occipital cortex was detected. We found that CD2AP immunodetection in neurons was strongly and positively associated with Braak neurofibrillary stage, independent of age and other pathological hallmarks. To further investigate the association between pTau and CD2AP, we included samples from cases of primary tauopathies (corticobasal degeneration [CBD], progressive supranuclear palsy [PSP], and Pick's disease [PiD]) in our study. Among these cases, CD2AP positivity was only found in PiD samples as neurofibrillary tangle‐like and Pick body‐like deposits, whereas no neuronal CD2AP deposits were detected in PSP or CBD samples, which suggested an association of CD2AP neuronal expression with 3R‐Tau‐diseases. In conclusion, our findings open a new road to investigate the complex cellular mechanism underlying the tangle conformation and tau pathology in the brain. [ABSTRACT FROM AUTHOR]

A planar quasi-endfire surface-wave antenna (SWA) using substrate integrated waveguide (SIW) technology for integration with CubeSats and other small satellites is proposed in this letter. This antenna can be attached to the body of the satellite, resulting in a compact and low-cost design. A quasi-endfire beam pattern is achieved by the radiation of the fundamental TM $_0$ surface wave mode at the edge of a grounded dielectric slab (GDS). This mode is excited by a leaky SIW T-junction creating a uniform wavefront that propagates through a truncated parallel-plate waveguide (PPW). A matching section based on an array of subwavelength patches is also added at the interface between the PPW and the GDS for reduced reflections and improved antenna radiation performance. The measured prototype demonstrated realized gain values of 13.3 dBi at 18.6 GHz for a competitive structure size of 5 $\lambda _0$ × 4.8 $\lambda _0$ and with a simulated total radiation efficiency of 93.4%, providing high data rate capabilities for downlink communications. This antenna could be suitable for CubeSat or other small satellite commercial missions, for example, Earth and planetary observations or intersatellite links. [ABSTRACT FROM AUTHOR]

Large-scale brain network interactions have been described between trans- and cis-gender binary identities. However, a temporal perspective of the brain's spontaneous fluctuations is missing. We investigated the functional connectivity dynamics in transmen with gender incongruence and its relationship with interoceptive awareness. We describe four states in native and meta-state spaces: (i) one state highly prevalent with sparse overall connections; (ii) a second with strong couplings mainly involving components of the salience, default, and executive control networks. Two states with global sparse connectivity but positive couplings (iii) within the sensorimotor network, and (iv) between salience network regions. Transmen had more dynamical fluidity than cismen, while cismen presented less meta-state fluidity and range dynamism than transmen and ciswomen. A positive association between attention regulation and fluidity and meta-state range dynamism was found in transmen. There exist gender differences in the temporal brain dynamism, characterized by distinct interrelations of the salience network as catalyst interacting with other networks. We offer a functional explanation from the neurodevelopmental cortical hypothesis of a gendered-self. [ABSTRACT FROM AUTHOR]

Transgender men and women represent about 0.6 -1.1%% of the general population. Gender affirming hormone therapy (GAHT) helps ameliorate gender dysphoria and promote well-being. However, these treatments' cardiovascular (CV) effects are difficult to evaluate due to the limited number of extensive longitudinal studies focused on CV outcomes in this population. Furthermore, these studies are mainly observational and difficult to interpret due to a variety of hormone regimens and observation periods, together with possible bias by confounding factors (comorbidities, estrogen types, smoking, alcohol abuse, HIV infection). In addition, the introduction of GAHT at increasingly earlier ages, even before the full development of the secondary sexual characteristics, could lead to long-term changes in CV risk compared to current data. This review examines the impact of GAHT in the transgender population on CV outcomes and surrogate markers of CV health. Furthermore, we review available data on changes in DNA methylation or RNA transcription induced by GAHT that may translate into changes in metabolic parameters that could increase CV risk. [ABSTRACT FROM AUTHOR]

Brain accumulation of amyloid-beta (Aβ) is a crucial feature in Alzheimer´s disease (AD) and cerebral amyloid angiopathy (CAA), although the pathophysiological relationship between these diseases remains unclear. Numerous proteins are associated with Aβ deposited in parenchymal plaques and/or cerebral vessels. We hypothesized that the study of these proteins would increase our understanding of the overlap and biological differences between these two pathologies and may yield new diagnostic tools and specific therapeutic targets. We used a laser capture microdissection approach combined with mass spectrometry in the APP23 transgenic mouse model of cerebral-β-amyloidosis to specifically identify vascular Aβ-associated proteins. We focused on one of the main proteins detected in the Aβ-affected cerebrovasculature: MFG-E8 (milk fat globule-EGF factor 8), also known as lactadherin. We first validated the presence of MFG-E8 in mouse and human brains. Immunofluorescence and immunoblotting studies revealed that MFG-E8 brain levels were higher in APP23 mice than in WT mice. Furthermore, MFG-E8 was strongly detected in Aβ-positive vessels in human postmortem CAA brains, whereas MFG-E8 was not present in parenchymal Aβ deposits. Levels of MFG-E8 were additionally analysed in serum and cerebrospinal fluid (CSF) from patients diagnosed with CAA, patients with AD and control subjects. Whereas no differences were found in MFG-E8 serum levels between groups, MFG-E8 concentration was significantly lower in the CSF of CAA patients compared to controls and AD patients. Finally, in human vascular smooth muscle cells MFG-E8 was protective against the toxic effects of the treatment with the Aβ40 peptide containing the Dutch mutation. In summary, our study shows that MFG-E8 is highly associated with CAA pathology and highlights MFG-E8 as a new CSF biomarker that could potentially be used to differentiate cerebrovascular Aβ pathology from parenchymal Aβ deposition. [ABSTRACT FROM AUTHOR]

Introduction: The main objective was to carry out a global DNA methylation analysis in a population with gender incongruence before gender-affirming hormone treatment (GAHT), in comparison to a cisgender population. Methods: A global CpG (cytosine-phosphate-guanine) methylation analysis was performed on blood from 16 transgender people before GAHT vs. 16 cisgender people using the Illumina© Infinium Human Methylation 850k BeadChip, after bisulfite conversion. Changes in the DNA methylome in cisgender vs. transgender populations were analyzed with the Partek® Genomics Suite program by a 2-way ANOVA test comparing populations by group and their sex assigned at birth. Results: The principal components analysis (PCA) showed that both populations (cis and trans) differ in the degree of global CpG methylation prior to GAHT. The 2-way ANOVA test showed 71,515 CpGs that passed the criterion FDR p < 0.05. Subsequently, in male assigned at birth population we found 87 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2) of which 22 were located in islands. The most significant CpGs were related to genes: WDR45B, SLC6A20, NHLH1, PLEKHA5, UBALD1, SLC37A1, ARL6IP1, GRASP , and NCOA6. Regarding the female assigned at birth populations, we found 2 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2), but none were located in islands. One of these CpGs, related to the MPPED2 gene, is shared by both, trans men and trans women. The enrichment analysis showed that these genes are involved in functions such as negative regulation of gene expression (GO:0010629), central nervous system development (GO:0007417), brain development (GO:0007420), ribonucleotide binding (GO:0032553), and RNA binding (GO:0003723), among others. Strengths and Limitations: It is the first time that a global CpG methylation analysis has been carried out in a population with gender incongruence before GAHT. A prospective study before/during GAHT would provide a better understanding of the influence of epigenetics in this process. Conclusion: The main finding of this study is that the cis and trans populations have different global CpG methylation profiles prior to GAHT. Therefore, our results suggest that epigenetics may be involved in the etiology of gender incongruence. [ABSTRACT FROM AUTHOR]

Complex dynamical fluctuations, from intracellular noise, brain dynamics or computer traffic display bursting dynamics consistent with a critical state between order and disorder. Living close to the critical point has adaptive advantages and it has been conjectured that evolution could select these critical states. Is this the case of living cells? A system can poise itself close to the critical point by means of the so-called self-organized criticality (SOC). In this paper we present an engineered gene network displaying SOC behaviour. This is achieved by exploiting the saturation of the proteolytic degradation machinery in E. coli cells by means of a negative feedback loop that reduces congestion. Our critical motif is built from a two-gene circuit, where SOC can be successfully implemented. The potential implications for both cellular dynamics and behaviour are discussed. Biological systems are known to behave in optimal ways when poised close to critical points, right on the edge between order and disorder. Here the authors show how this state can be engineered in living cells. [ABSTRACT FROM AUTHOR]

Tumour cell heterogeneity is a major barrier for efficient design of targeted anti-cancer therapies. A diverse distribution of phenotypically distinct tumour-cell subpopulations prior to drug treatment predisposes to non-uniform responses, leading to the elimination of sensitive cancer cells whilst leaving resistant subpopulations unharmed. Few strategies have been proposed for quantifying the variability associated to individual cancer-cell heterogeneity and minimizing its undesirable impact on clinical outcomes. Here, we report a computational approach that allows the rational design of combinatorial therapies involving epigenetic drugs against chromatin modifiers. We have formulated a stochastic model of a bivalent transcription factor that allows us to characterise three different qualitative behaviours, namely: bistable, high- and low-gene expression. Comparison between analytical results and experimental data determined that the so-called bistable and high-gene expression behaviours can be identified with undifferentiated and differentiated cell types, respectively. Since undifferentiated cells with an aberrant self-renewing potential might exhibit a cancer/metastasis-initiating phenotype, we analysed the efficiency of combining epigenetic drugs against the background of heterogeneity within the bistable sub-ensemble. Whereas single-targeted approaches mostly failed to circumvent the therapeutic problems represented by tumour heterogeneity, combinatorial strategies fared much better. Specifically, the more successful combinations were predicted to involve modulators of the histone H3K4 and H3K27 demethylases KDM5 and KDM6A/UTX. Those strategies involving the H3K4 and H3K27 methyltransferases MLL2 and EZH2, however, were predicted to be less effective. Our theoretical framework provides a coherent basis for the development of an in silico platform capable of identifying the epigenetic drugs combinations best-suited to therapeutically manage non-uniform responses of heterogenous cancer cell populations. Author summary: Heterogeneity in cancer cell populations is one of the main engines of resistance to targeted therapies, as it induces nonuniform responses within the population that clears the sensitive subpopulation, whilst leaving unaffected the non-responsive cells. Although this is a well-known fact, few successful approaches have been proposed aimed at both quantifying the variability associated to cell heterogeneity, and characterising strategies that circumvent its drug-resistance inducing effects. Here we present a computational approach that addresses these issues in the particular context of targeting epigenetic regulators (specifically, chromatin modifiers), which have been proposed as therapeutic targets in several types of cancer and also in ageing-related diseases. Our model predicts that the more successful combinations involve modulators of demethylase activity (specifically, KDM5/6 and UTX). By contrast, strategies involving EZH2 activity are predicted to be less effective. Our results support the use of our framework as a platform for in silico drug trials, as it accounts for non-homogeneous response of cell populations to drugs as well as identifying which subpopulations are more likely to respond to specific strategies. [ABSTRACT FROM AUTHOR]

A multifed radially periodic two-dimensional leaky-wave antenna is proposed for the generation of a directional beam continuously scanning in elevation by changing the frequency, and over a discrete number of directions in azimuth when activating different elements of the feeding system. The structure is planar and constituted by a circular grounded dielectric slab loaded with microstrip rings, properly positioned around the sources to support the propagation of an angularly directional surface wave over a sector determined by the corresponding activated feeder. This produces a perturbation of the surface wave, resulting in the generation of a directional leaky wave over the aperture, whose complex propagation constant is described by a single fast backward spatial harmonic. The antenna radiation features are numerically investigated in conjunction with the dispersion analysis of the structure, validated through a conventional generalized-pencil-of-function approach. Full-wave simulations have been developed to design a practical feeder, which is constituted by a circular arrangement of commercial coaxial connectors. The proposed multiport antenna is validated by means of measurements performed on a microwave manufactured prototype. The design represents an attractive simple and cost-effective solution to achieve a high-gain beam scanning over the three-dimensional space, alternative to more conventional phased-array design based on cumbersome and lossy feeding networks. [ABSTRACT FROM AUTHOR]

Copyright of HiSTOReLo: Revista de Historia Regional y Local is the property of Universidad Nacional de Colombia, Centro Editorial Facultad de Ciencias Humanas y Economicas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study examines the relationship between corporate social responsibility (CSR) and dynamic productivity change of each input employed and investment undertaken in the US food and beverage manufacturing industry. We compute input‐ and investment‐specific dynamic Luenberger indicators and decompose them into the contributions of input‐ and investment‐specific dynamic technical inefficiency changes and dynamic technological changes. We then relate these indicators to an overall CSR measure and aspect‐specific CSR measures (governance, environment, and social). Our results confirm that the association between CSR and productivity change has different signs and effects on specific inputs or investments. We also find that only certain aspects of CSR participate in the association between CSR and dynamic productivity change and its components. [EconLit citations: C61, D24, L66, M14]. [ABSTRACT FROM AUTHOR]

We propose the design and testing of a 2-D Fabry–Perot structure based on a multilayer (ML) slab arrangement fed by a circular array of simple sources. Such a class of planar leaky-wave (LW) antenna can be made of low-loss commercial laminates, and it is bounded on top by a subwavelength partially reflecting surface. The antenna is designed to suppress undesired radiation from the quasi-TEM mode while leaking power by the excitation of a fast TM1 leaky mode, which is a perturbed version of the guided-wave supported by the corresponding parallel-plate waveguide. An accurate dispersive analysis for the ML structure is developed, and an original feeding system is designed and optimized to provide the needed wideband impedance matching. Thanks to translational invariance enabled by the homogenized nature of the partially reflecting screen, the antenna is used as a radiating element in the design of a LW-enhanced phased array, constituted by an arrangement of vertical probes to generate directive pencil beams steerable at a single frequency in azimuth and by changing frequency in elevation. [ABSTRACT FROM AUTHOR]

Copyright of Retos: Nuevas Perspectivas de Educación Física, Deporte y Recreación is the property of Federacion Espanola de Asociaciones de Docentes de Educacion Fisica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Matrix metalloproteinases (MMPs) are proteolytic zinc-endopeptidases regulated by tissue Inhibitors of matrix metalloproteinases (TIMPs). We evaluated the potential of MMPs and TIMPs as clinical tools for Intracranial Haemorrhage (ICH). Spontaneous non‐traumatic ICH patients were recruited from two hospitals: Complejo Hospitalario de Navarra (CHN = 29) and Vall d´Hebron (VdH = 76). Plasmatic levels of MMP-1, −2, −7, −9, −10 and TIMP-1 and their relationship with clinical, radiological and functional variables were evaluated. We further studied the effect of TIMP-1 (0.05–0.2 mg/Kg) in an experimental tail-bleeding model. In CHN, TIMP-1 was associated with admission-hematoma volume and MMP-7 was elevated in patients with deep when compared to lobar hematoma. In VdH, admission-hematoma volume was associated with TIMP-1 and MMP-7. When data from both hospitals were combined, we observed that an increase in 1 ng/ml in TIMP-1 was associated with an increase of 0.14 ml in haemorrhage (combined β = 0.14, 95% CI = 0.08–0.21). Likewise, mice receiving TIMP-1 (0.2 mg/Kg) showed a shorter bleeding time (p < 0.01). Therefore, the association of TIMP-1 with hematoma volume in two independent ICH cohorts suggests its potential as ICH biomarker. Moreover, increased TIMP-1 might not be sufficient to counterbalance MMPs upregulation indicating that TIMP-1 administration might be a beneficial strategy for ICH. [ABSTRACT FROM AUTHOR]

In Neuroscience, mathematical modelling involving multiple spatial and temporal scales can unveil complex oscillatory activity such as excitable responses to an input current, subthreshold oscillations, spiking or bursting. While the number of slow and fast variables and the geometry of the system determine the type of the complex oscillations, canard structures define boundaries between them. In this study, we use geometric singular perturbation theory to identify and characterise boundaries between different dynamical regimes in multiple-timescale firing rate models of the developing spinal cord. These rate models are either three or four dimensional with state variables chosen within an overall group of two slow and two fast variables. The fast subsystem corresponds to a recurrent excitatory network with fast activity-dependent synaptic depression, and the slow variables represent the cell firing threshold and slow activity-dependent synaptic depression, respectively. We start by demonstrating canard-induced bursting and mixed-mode oscillations in two different three-dimensional rate models. Then, in the full four-dimensional model we show that a canard-mediated slow passage creates dynamics that combine these complex oscillations and give rise to mixed-mode bursting oscillations (MMBOs). We unveil complicated isolas along which MMBOs exist in parameter space. The profile of solutions along each isola undergoes canard-mediated transitions between the sub-threshold regime and the bursting regime; these explosive transitions change the number of oscillations in each regime. Finally, we relate the MMBO dynamics to experimental recordings and discuss their effects on the silent phases of bursting patterns as well as their potential role in creating subthreshold fluctuations that are often interpreted as noise. The mathematical framework used in this paper is relevant for modelling multiple timescale dynamics in excitable systems. [ABSTRACT FROM AUTHOR]

This work is motivated by an application for the homogenization of global navigation satellite system (GNSS)-derived integrated water vapour series. Indeed, these series are affected by abrupt changes due to equipment changes or environmental effects. The detection and correction of the series from these changes are a crucial step before any use for climate studies. In addition to these abrupt changes, it has been observed in the series a non-stationary of the variability. We propose in this paper a new segmentation model that is a breakpoint detection in the mean model of a Gaussian process with heterogeneous variance on known time intervals. In this segmentation case, the dynamic programming algorithm used classically to infer the breakpoints cannot be applied anymore. We propose a procedure in two steps: we first estimate robustly the variances and then apply the classical inference by plugging these estimators. The performance of our proposed procedure is assessed through simulation experiments. An application to real GNSS data is presented. [ABSTRACT FROM AUTHOR]

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Copyright of Trabajos y Comunicaciones is the property of Universidad Nacional de La Plata and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Rationale: The Boston criteria are used worldwide for the in vivo diagnosis of cerebral amyloid angiopathy and are the basis for clinical decision-making and research in the field. Given substantial advances in cerebral amyloid angiopathy's clinical aspects and MRI biomarkers, we designed a multicenter study within the International cerebral amyloid angiopathy Association aimed at further validating the diagnostic accuracy of the Boston and potentially improving and updating them. Aim: We aim to derive and validate an updated "version 2.0" of the Boston criteria across the spectrum of cerebral amyloid angiopathy-related presentations and MRI biomarkers. Sample size estimates: Participating centers with suitable available data (see Methods) were identified from existing collaborations and an open invitation to the International Cerebral Amyloid Angiopathy Association emailing list. Our study sample will include: (1) a derivation cohort – Massachusetts General Hospital (MGH), Boston cases from inception to 2012 (∼150 patients); (2) temporal external validation cohort – MGH, Boston cases from 2012 to 2018 (∼100 patients); and (3) geographical external validation cohort – non-Boston cases (∼85 patients). Methods and design: Multicenter collaborative study. We will collect and analyze data from patients' age ≥ 50 with any potential sporadic cerebral amyloid angiopathy-related clinical presentations (spontaneous intracerebral hemorrhage, transient focal neurological episodes and cognitive impairment), available brain MRI ("index test"), and histopathologic assessment for cerebral amyloid angiopathy ("reference standard" for diagnosis). Trained raters will assess MRI for all prespecified hemorrhagic and non-hemorrhagic small vessel disease markers of interest, according to validated criteria and a prespecified protocol, masked to clinical and histopathologic features. Brain tissue samples will be rated for cerebral amyloid angiopathy, defined as Vonsattel grade ≥2 for whole brain autopsies and ≥1 for cortical biopsies or hematoma evacuation. Based on our estimated available sample size, we will undertake pre-specified cohort splitting as above. We will: (a) pre-specify variables and statistical cut-offs; (b) examine univariable and multivariable associations; and (c) then assess classification measures (sensitivity, specificity etc.) for each MRI biomarker individually, in relation to the cerebral amyloid angiopathy diagnosis reference standard on neuropathology in a derivation cohort. The MRI biomarkers strongly associated with cerebral amyloid angiopathy diagnosis will be selected for inclusion in provisional (probable and possible cerebral amyloid angiopathy) Boston criteria v2.0 and validated using appropriate metrics and models. Study outcomes: Boston criteria v2.0 for clinical cerebral amyloid angiopathy diagnosis. Discussion: This work aims to potentially update and improve the diagnostic test accuracy of the Boston criteria for cerebral amyloid angiopathy and to provide wider validation of the criteria in a large sample. We envision that this work will meet the needs of clinicians and investigators and help accelerate progress towards better treatment of cerebral amyloid angiopathy. [ABSTRACT FROM AUTHOR]

The conductance-based refractory density (CBRD) approach is a parsimonious mathematical–computational framework for modelling interacting populations of regular spiking neurons, which, however, has not been yet extended for a population of bursting neurons. The canonical CBRD method allows to describe the firing activity of a statistical ensemble of uncoupled Hodgkin–Huxley-like neurons (differentiated by noise) and has demonstrated its validity against experimental data. The present manuscript generalises the CBRD for a population of bursting neurons; however, in this pilot computational study, we consider the simplest setting in which each individual neuron is governed by a piecewise linear bursting dynamics. The resulting population model makes use of slow–fast analysis, which leads to a novel methodology that combines CBRD with the theory of multiple timescale dynamics. The main prospect is that it opens novel avenues for mathematical explorations, as well as, the derivation of more sophisticated population activity from Hodgkin–Huxley-like bursting neurons, which will allow to capture the activity of synchronised bursting activity in hyper-excitable brain states (e.g. onset of epilepsy). [ABSTRACT FROM AUTHOR]

This letter presents a width-modulated microstrip line leaky-wave antenna (LWA) with substrate-integrated waveguide and microstrip feeding. In particular, the planar antenna system consists of an integrated surface-wave launcher and three identical rows of quasi-periodic width-modulated microstrip lines for TM leaky-wave excitation, which produces a tailored binomial-like aperture distribution on the guiding surface. The behavior of the antenna when changing the width-modulated lines for different aperture distributions is also analyzed and presented. The measured LWA demonstrates a fan beam pattern in the far field with realized gain values greater than 10 dBi and with a beam direction of about $-$ 20 $^\circ$ from broadside at 23 GHz. Also, far-field measurements and near-field data indicate that the half-power beamwidth is below 10 $^\circ$ , and the position of the main beam maximum is relatively stable, i.e., ranging from about $-$ 23 $^\circ$ to $-$ 15 $^\circ$ between 23 and 24 GHz. The measured prototype is also well matched over these frequencies and $|S_{11}| < $ $-$ 20 dB at 23.5 GHz. [ABSTRACT FROM AUTHOR]

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Stroke is a leading cause of death and disability worldwide. However, after years of in-depth research, the pathophysiology of stroke is still not fully understood. Increasing evidence shows that matrix metalloproteinases (MMPs) and "a disintegrin and metalloproteinase" (ADAMs) participate in the neuro-inflammatory cascade that is triggered during stroke but also in recovery phases of the disease. This review covers the involvement of these proteins in brain injury following cerebral ischemia which has been widely studied in recent years, with efforts to modulate this group of proteins in neuroprotective therapies, together with their implication in neurorepair mechanisms. Moreover, the review also discusses the role of these proteins in specific forms of neurovascular disease, such as small vessel diseases and intracerebral hemorrhage. Finally, the potential use of MMPs and ADAMs as guiding biomarkers of brain injury and repair for decision-making in cases of stroke is also discussed. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Animal Science is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cerebral amyloid angiopathy (CAA) is a common cause of lobar intracerebral hemorrhage (ICH) in elderly individuals and it is the result of the cerebrovascular deposition of beta-amyloid (Aβ) protein. CAA is frequently found in patients with Alzheimer's disease (AD), although it has an independent contribution to the cognitive deterioration associated with age. Specific apolipoproteins (Apo) have been associated with Aβ fibrillization and clearance from the brain. In this regard, in the present study, we analyzed the brain levels of ApoE, ApoA-I, and ApoJ/clusterin in autopsy brains from 20 post-mortem cases with CAA type I, CAA type II, with parenchymal Aβ deposits or without Aβ deposits. Our objective was to find a possible differential pattern of apolipoproteins distribution in the brain depending on the CAA pathological presentation. The protein expression levels were adjusted by the APOE genotype of the patients included in the study. We found that ApoE and ApoJ were abundantly present in meningeal, cortical, and capillary vessels of the brains with vascular Aβ accumulation. ApoE and ApoJ also deposited extracellularly in the parenchyma, especially in cases presenting Aβ diffuse and neuritic parenchymal deposits. In contrast, ApoA-I staining was only relevant in capillary walls in CAA type I cases. On the other hand, ICH was the principal cause of death among CAA patients in our cohort. We found that CAA patients with ICH more commonly had APOEε2 compared with CAA patients without ICH. In addition, patients who suffered an ICH presented higher vascular ApoE levels in brain. However, higher ApoE presence in cortical arteries was the only independent predictor of suffering an ICH in our cohort after adjusting by age and APOE genotype. In conclusion, while ApoE and ApoJ appear to be involved in both vascular and parenchymal Aβ pathology, ApoA-I seems to be mainly associated with CAA, especially in CAA type I pathology. We consider that our study helps to molecularly characterize the distribution subtypes of Aβ deposition within the brain. [ABSTRACT FROM AUTHOR]

A smart cable system and its elements for selective communications and sensor-based data collection within corridors, subways, and tunnels are proposed with applications to the aeronautical, transportation, and space sectors. The main hardware components of the cable system are defined by active and programmable radio-frequency (RF) switches that can enable controlled radiation at specific nodes or hotspots. More importantly, our proposed cable concept provides an evolution from the conventional coaxial cable with distributed antennas, as well as the classic leaky feeder cable, which is typically employed for communications within corridors and mines. Moreover, the proposed smart cable moves toward a hybrid wireless node and programmable system for selective coverage. Planar circuits and low-profile RF electronic components are employed for a low-cost implementation. In this communication, our focus is on the assessment of the proposed smart cable system, its radiating nodes (RNs), as well as the estimation of the system performance based on the measurements of the RN prototypes. Wireless networks, RFID sensors, and power transmission systems can be additional applications for the proposed smart cable. System performance estimations for a real corridor satisfy typical RFID sensitivity requirements with received power levels between −39 and −46 dBm in the worst case. [ABSTRACT FROM AUTHOR]

An annular periodic leaky-wave antenna (LWA) fed by a simple azimuth-symmetric source is designed to generate a high-gain omnidirectional conical-beam pattern, which scans with frequency over a wide angular range. The proposed structure is defined by a finite metallic radial strip grating printed on a grounded dielectric slab, which supports an $n=0$ cylindrical leaky wave (CLW). The distinctive features of CLWs supported by such a truncated structure are also highlighted and discussed. The directional far-field pattern generated by the proposed LWA, in conjunction with its nondiffracting and wideband behavior in the near field (as previously reported by the authors), defines an original dual-operational LWA. Possible applications include next-generation wireless power transfer systems that provide functionality in both the near and far field, vehicle roof-mounted antennas for base-station data connectivity as well as future short-range near-field communications, and object tracking by ceiling-mounting devices for indoor localization. [ABSTRACT FROM AUTHOR]

We consider heteroclinic attractor networks motivated by models of competition between neural populations during binocular rivalry. We show that gamma distributions of dominance times observed experimentally in binocular rivalry and other forms of bistable perception, commonly explained by means of noise in the models, can be achieved with quasiperiodic perturbations. For this purpose, we present a methodology based on the separatrix map to model the dynamics close to heteroclinic networks with quasiperiodic perturbations. Our methodology unifies two different approaches, one based on Melnikov integrals and the other one based on variational equations. We apply it to two models: first, to the Duffing equation, which comes from the perturbation of a Hamiltonian system and, second, to a heteroclinic attractor network for binocular rivalry, for which we develop a suitable method based on Melnikov integrals for non-Hamiltonian systems. In both models, the perturbed system shows chaotic behavior, while dominance times achieve good agreement with gamma distributions. Moreover, the separatrix map provides a new (discrete) model for bistable perception which, in addition, replaces the numerical integration of time-continuous models and, consequently, reduces the computational cost and avoids numerical instabilities. [ABSTRACT FROM AUTHOR]