Miracle-dz/UniFAR-FTUs huggingface dataset:
The contribution of genes to cortical thickness and volume

We analyzed brain MRI data from 372 young adult twins toidentify cortical regions in which gray matter thickness and volume are influenced by genetics. This was achieved using an A/C/E structural equation model that divides the variance of these traits, at each point on the cortex, into additive genetic (A), shared (C), and unique environmental (E) components. A strong genetic influencewas found in frontal and parietal regions. Inaddition, we correlated cortical thickness with full-scale intelligence quotient for comparison with the A/C/E maps, and several regions where cortical structure was correlated with intelligence quotient are under genetic control. These cortical measures may be useful phenotypes to narrow the searchfor quantitative trait lociinfluencing brain structure.
Connexin: a potential novel target for protecting the central nervous system?

Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings regarding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer′s disease, Parkinson′s disease, X-linked Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.
Sensitivity and Bias in Decision-Making under Risk: Evaluating the Perception of Reward, Its Probability and Value

Background There are few clinical tools that assess decision-making under risk. Tests that characterize sensitivity and bias in decisions between prospects varying in magnitude and probability of gain may provide insights in conditions with anomalous reward-related behaviour. Objective We designed a simple test of how subjects integrate information about the magnitude and the probability of reward, which can determine discriminative thresholds and choice bias in decisions under risk. Design/Methods Twenty subjects were required to choose between two explicitly described prospects, one with higher probability but lower magnitude of reward than the other, with the difference in expected value between the two prospects varying from 3 to 23%. Results Subjects showed a mean threshold sensitivity of 43% difference in expected value. Regarding choice bias, there was a ‘risk premium’ of 38%, indicating a tendency to choose higher probability over higher reward. An analysis using prospect theory showed that this risk premium is the predicted outcome of hypothesized non-linearities in the subjective perception of reward value and probability. Conclusions This simple test provides a robust measure of discriminative value thresholds and biases in decisions under risk. Prospect theory can also make predictions about decisions when subjective perception of reward or probability is anomalous, as may occur in populations with dopaminergic or striatal dysfunction, such as Parkinson's disease and schizophrenia.
Sclerostin in Mineralized Matrices and van Buchem Disease

Sclerostin is an inhibitor of bone formation expressed by osteocytes. We hypothesized that sclerostin is expressed by cells of the same origin and also embedded within mineralized matrices. In this study, we analyzed (a) sclerostin expression using immunohistochemistry, (b) whether the genomic defect in individuals with van Buchem disease (VBD) was associated with the absence of sclerostin expression, and (c) whether this was associated with hypercementosis. Sclerostin was expressed by cementocytes in mouse and human teeth and by mineralized hypertrophic chondrocytes in the human growth plate. In individuals with VBD, sclerostin expression was absent or strongly decreased in osteocytes and cementocytes. This was associated with increased bone formation, but no overt changes in cementum thickness. In conclusion, sclerostin is expressed by all 3 terminally differentiated cell types embedded within mineralized matrices: osteocytes, cementocytes, and hypertrophic chondrocytes.
Investigations of lymphatic drainage from the interstitial space

The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is essential to treat several pathological conditions. The main focus of this study is to model the lymphatic drainage from the interstitial space computationally. The model has been developed to consider a 3D lymphatic network, and biological data has been used to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy-Brinkman equation in the interstitium and the Stokes equation in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradients. Also, the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model have been examined. The computational results are in accordance with the available experimental measurements. In addition, the interstitium is a poroelastic medium. The interstitium undergoes deformation due to filtration, and according to the physiological data, the interstitial fluid volume is a function of interstitial pressure. The interstitial permeability depends on the interstitial hydration. Hence, the interstitial permeability can be considered as a pressure-dependent quantity. Using the Carman-Kozency correlation, we have introduced pressure-dependent permeability into the interstitium, and the computational results are presented to portray the influence of poroelastic properties.
Oxford classification of immunoglobulin A nephropathy: an update

Purpose of reviewThis review summarizes the recommendations for reporting immunoglobulin A (IgA) nephropathy biopsies and their evidence base, discusses the limitations of the Oxford Classification study and presents the findings of recent validation studies. Recent findingsThe Oxford Classification identified four histological lesions as independent prognostic factors: mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S) and tubular atrophy/interstitial fibrosis (T). The MEST criteria predicted outcome in some, but not all, of 13 recent validation studies. M is of independent prognostic value in four out of 13 studies, S in four out of 13 and T in 10 out of 13. Apparently contradictory findings reflect differences in patient selection criteria, treatment and outcome measures. The Oxford Classification study provided indirect evidence that endocapillary hypercellularity is responsive to immunosuppressive therapy. This is confirmed in two validation studies. One study, which included patients with rapidly progressive disease, found glomerular crescents to be a significant prognostic marker. Immunohistological findings correlate with proliferative glomerular lesions but are not of independent prognostic value. SummaryThe Oxford Classification is applicable to patients who were excluded from the original cohort, including those with rapidly progressive disease, and the prognostic value of proliferative glomerular lesions is influenced by immunosuppressive therapy. The Oxford schema will be reviewed in the light of recent findings.
Familiarity breeds content: assessing bird species popularity with culturomics

Understanding public perceptions of biodiversity is essential to ensure continued support for conservation efforts. Despite this, insights remain scarce at broader spatial scales, mostly due to a lack of adequate methods for their assessment. The emergence of new technologies with global reach and high levels of participation provide exciting new opportunities to study the public visibility of biodiversity and the factors that drive it. Here, we use a measure of internet saliency to assess the national and international visibility of species within four taxa of Brazilian birds (toucans, hummingbirds, parrots and woodpeckers), and evaluate how much of this visibility can be explained by factors associated with familiarity, aesthetic appeal and conservation interest. Our results strongly indicate that familiarity (human population within the range of a species) is the most important factor driving internet saliency within Brazil, while aesthetic appeal (body size) best explains variation in international saliency. Endemism and conservation status of a species had small, but often negative, effects on either metric of internet saliency. While further studies are needed to evaluate the relationship between internet content and the cultural visibility of different species, our results strongly indicate that internet saliency can be considered as a broad proxy of cultural interest.
Prevalence of and Factors Associated with Hypertension in Young and Old Women with Systemic Lupus Erythematosus

Objective. Hypertension (HT) is more prevalent in patients with systemic lupus erythematosus (SLE) than among the general population and it has been associated with atherosclerotic cardiovascular diseases in these patients. We examined the proportion of HT and factors associated with it in young and old women with SLE. Methods. Participants (112 women with SLE and 223 healthy age-matched women) were categorized as young (age ≤ 40 years) or old (age > 40 years). We compared cardiovascular and specific SLE-related variables and inflammatory markers in hypertensive and normotensive women with SLE for each age range. We also assessed the factors independently associated with HT in the entire cohort and in each age range by means of a multivariate regression analysis. Results. The prevalence of HT was higher in women with SLE than in controls (56% vs 29%; p < 0.001), and was proportionally higher in younger women with SLE (40% vs 11%; p < 0.001) than in older women with SLE (74% vs 47%; p = 0.001). After adjustment for potential confounders, HT was associated with renal involvement and higher nonobesity-related insulin levels in younger women with SLE. In older patients, HT was associated with age, renal involvement, and obesity. Finally, in the entire cohort, HT was associated with age, insulin, renal involvement, and the Systemic Lupus Erythematosus Disease Activity Index score. Conclusion. An association between HT and insulin has been identified in women with SLE, particularly younger ones. Factors associated with HT in women with SLE differed depending on their age. HT was more prevalent in women with SLE than in control subjects, being proportionally higher in young women with SLE.
The Women's Healthy Ageing Project: Fertile ground for investigation of healthy participants ‘at risk’ for dementia

Abstract Alzheimer's disease neuropathology (amyloid, tauopathies) and brain atrophy are present decades prior to manifestation of clinical symptoms. With the failure of treatment trials it is becoming clearer that the window for prevention and therapeutic intervention is before significant neuronal loss and clinical deterioration of cognition has occurred. Early identification of those at risk of disease and optimizing their management to prevent disease in later life are crucial to delaying disease onset and improving people's quality of life. The Women's Healthy Aging Project (WHAP) is a longitudinal study of over 400 Australian-born women, epidemiologically randomly sampled in 1990. The WHAP aims to identify modifiable mid-life risk factors for the development of late-life cognitive decline, improve the understanding of the pathogenesis of dementia, and target early disease identification utilizing clinical, biomarker and health risk profiles. These aims are fortified by the ability to leverage the considerable database on health, lifestyle and socio-demographics collected prospectively from 1990 to date. This is the first study with a comprehensive neuropsychological battery, over a decade of cognitive follow-up, with all participants being offered amyloid imaging from 2012, and prospective longitudinal data including clinical and physical measures and bio-bank samples from over 20 years prior.
Segmenting and Profiling Visitors to the Ulaanbaatar Naadam Festival by Motivation

The analysis of visitor motivation for attending festivals, as a basis for segmentation, is an important prerequisite for targeting markets, planning festival programmes and product positioning. This study identified five motivation dimensions for visitors attending the 2005 Naadam cultural festival in Mongolia, using factor analysis. A cluster analysis on the five factors produced five stable motivation segments: multipurpose seekers; indifferent; culture and sport seekers; togetherness, socialisation and sports seekers; and socialisation and local event seekers. Significant associations between motivation clusters and visitor age and type were identified, although there was no significant interaction between the clusters and visitor type with respect to overall satisfaction. The results are generally consistent with the outcomes of previous research on festival and event motivation in Europe and North America, suggesting universality of core themes. However, unique combinations of motivation dimensions suggests that further research is required to develop understanding of variable interaction.
B-cell subpopulations in children: National reference values

Peripheral B‐lymphocytes undergo a series of changes during the first few years of life. Encounters with foreign antigens lead to maturation and differentiation. Several primary antibody deficiencies (PADs) affecting B‐cell development are associated with abnormalities in the composition and/or differentiation of B‐cell compartments. The most recent international classifications of primary immunodeficiencies (PIDs) and common variable immunodeficiencies (CVID) have highlighted the importance of B‐cell immunophenotyping and age‐specific reference intervals for diagnostic purposes. We established national reference values for memory B‐cell subpopulations, on the basis of CD27 and surface IgD expression in the peripheral blood of 242 healthy children. We report here the absolute counts and percentages of naive, switched and non‐switched memory B‐cells for seven age groups, from neonates to adults. We found that the naive B‐cells percentage declined between the ages of 6 months and 8 years, after which it remained stable at about 70–80%. Memory B‐cells are already present at birth and their numbers increase throughout childhood, stabilizing between the ages of 12 and 18 years. The definition of reference intervals for pediatric B‐cell levels should facilitate the screening and diagnosis of various B‐cell immunodeficiencies. This multicenter study, providing national reference values, should thus facilitate immunological diagnosis in children.
Synchronized activity of organic cation transporter 3 (Oct3/Slc22a3) and multidrug and toxin extrusion 1 (Mate1/Slc47a1) transporter in transplacental passage of MPP+ in rat.

The aim of the present study was to investigate the expression, localization, and function of organic cation transporter 3 (Oct3, Slc22a3) and multidrug and toxin extrusion protein 1 (Mate1, Slc47a1) in the rat placenta. Using qRT-PCR and Western blotting techniques, we demonstrated abundant Oct3 and Mate1 mRNA and protein expression achieving significantly higher levels than those in the maternal kidney (positive control). Immunohistochemical visualization revealed preferential localization of Oct3 on the basolateral, i.e., fetus facing side of the placenta, whereas Mate1 positivity was located in the labyrinth area predominantly on the apical, i.e., maternal side of the placenta. To investigate the role of these transporters in the transplacental pharmacokinetics, the in situ method of dually perfused rat term placenta was employed in open- and closed-circuit arrangements; 1-methyl-4-phenylpyridinium (MPP(+)) was used as a model substrate of both Oct3 and Mate1. We provide evidence that Oct3 and Mate1 cause considerable asymmetry between maternal-to-fetal and fetal-to-maternal transport of MPP(+) in favor of fetomaternal direction. Using closed-circuit experimental setup, we further describe the capacity of Oct3 and Mate1 to transport their substrate from fetus to mother even against a concentration gradient. We conclude that Oct3, in a concentration-dependent manner, takes up MPP(+) from the fetal circulation into the placenta, whereas Mate1, on the other side of the barrier, is responsible for MPP(+) efflux from placenta to the maternal circulation. These two transport proteins, thus, form an efficient transplacental eliminatory pathway and play an important role in fetal protection and detoxication.
Diverse Electron and Ion Acceleration Characteristics Observed Over Jupiter's Main Aurora

Two new Juno‐observed particle features of Jupiter's main aurora demonstrate substantial diversity of processes generating Jupiter's mysterious auroral emissions. It was previously speculated that sometimes‐observed potential‐driven aurora (up to 400 kV) can turn into broadband stochastic acceleration (dominating at Jupiter) by means of instability. Here direct evidence for such a process is revealed with a “mono‐energetic” electron inverted‐V rising in energy to 200 keV, transforming into a region of broadband acceleration with downward energy fluxes tripling to 3,000 mW/m2, and then transforming back into a mono‐energetic structure ramping down from 200 keV. But a second feature of interest observed nearby is unlikely to have operated in the same way. Here a downward accelerated proton inverted‐V, with inferred potentials to 300–400 kV, occurred simultaneously with downward accelerated broadband electrons with downward energy fluxes as high as any observed (~3,000 mW/m2). This latter feature has no known precedent with Earth auroral observations.
Polarization of hippocampal neurons with competitive surface stimuli: contact guidance cues are preferred over chemical ligands

Neuronal behaviour is profoundly influenced by extracellular stimuli in many developmental and regeneration processes. Understanding neuron responses and integration of environmental signals could impact the design of successful therapies for neurodegenerative diseases and nerve injuries. Here, we have investigated the influence of localized extracellular cues on polarization (i.e. axon formation) of hippocampal neurons. Electron-beam lithography, microfabrication techniques and protein immobilization were used to create a unique system that provided simultaneous and independent chemical and physical cues to individual neurons. In particular, we analysed competitive responses between simultaneous stimulation with chemical ligands, including immobilized nerve growth factor and laminin, and contact guidance cues mediated by surface topography (i.e. microchannels). Contact guidance cues were preferred 70% of the time over chemical ligands by neurons extending axons, which suggests a stronger stimulation mechanism triggered by topography. This investigation contributes to the understanding of neuronal behaviour on artificial substrates, which is applicable to the creation of artificial environments for neural engineering applications.
Effects of the Antiestrogen Tamoxifen and the Aromatase Inhibitor Letrozole on Serum Hormones and Bone Characteristics in a Preclinical Tumor Model for Breast Cancer

Purpose: The purpose of this study was to evaluate and compare the effects of the antiestrogen tamoxifen and the aromatase inhibitor letrozole on tumor growth, serum hormones, uterine weight, body composition, and bone characteristics in mice. Experimental Design: Human estrogen-dependent breast cancer cells stably transfected with the aromatase gene (MCF-7CA cells) were inoculated in Matrigel subcutaneously into ovariectomized nude mice. This model represents postmenopausal breast cancer in many respects, including the fact that estrogen is no longer produced by the ovaries and is not under feedback regulation by gonadotropins. Mice that received subcutaneously implanted MCF-7CA cancer cells were then treated with tamoxifen or letrozole for 7 weeks. Results: As reported previously, tumor growth was markedly inhibited by both tamoxifen (100 μg/day) and letrozole (10 μg/day). Tamoxifen treatment led to increased bone mineral density (BMD) and hyperplastic uteri. Mice treated with letrozole had significantly smaller uteri than the controls and tamoxifen-treated mice. Letrozole did not affect BMD. There was no significant difference in systemic leptin and insulin-like growth factor I levels as a result of tamoxifen or letrozole treatment. Conclusions: Tamoxifen treatment inhibited breast cancer cell growth and increased BMD but caused uterine hypertrophy in this preclinical model of postmenopausal breast cancer. Letrozole inhibited tumor growth without inducing uterine hypertrophy. In addition, letrozole had no effect on BMD. These findings provide experimental evidence that letrozole is an effective and safe (in terms of risk of endometrial cancer risk and osteoporosis) alternative or complement to tamoxifen treatment for breast cancer.
Rho Kinase Inhibitor Fasudil Suppresses the Vasculogenic Mimicry of B16 Mouse Melanoma Cells Both In Vitro and In Vivo

The aim of this study was to investigate the biologic role of the Rho kinase inhibitor fasudil in the vasculogenic mimicry (VM) of B16 mouse melanoma cells. It was previously reported that RhoA plays a critical role in angiogenesis by coordinating endothelial cell cytoskeleton remodeling and promoting endothelial cell motility. Although RhoA has been implicated in the regulation of angiogenesis, little has been described regarding its control of these tumor cell–lined channels. In this study, we established an in vitro model of VM using 3-dimensional cell culturing of mouse B16 melanoma cells and studied VM in vivo by transplanting B16 cells into C57/BL mice. Next, we explored the effect of RhoA and Rho-associated, coiled-coil containing protein kinase (ROCK) on VM formation using the Rho kinase inhibitor fasudil. We provide direct evidence that fasudil leads to reduced vascular-like channels in Matrigel. Additional experiments suggested that fasudil prevents both initial cellular architecture changes and cell migration in vitro. Finally, we provide in-depth evidence for the underlying mechanisms of fasudil-induced VM destruction using the Rho-GTPase agonist lysophosphatidic acid. In vivo studies revealed that fasudil reduced B16 melanoma cell xenograft tumor growth without causing significant toxicity in mice. Fasudil-treated tumors also displayed fewer VM channels. These results suggest that fasudil may be an emerging therapeutic option for targeting cancer VM. Mol Cancer Ther; 14(7); 1582–90. ©2015 AACR.