Editorial: Neuronal calcium sensors in health and disease

[no abstract available

Reduced Mid1 Expression and Delayed Neuromotor Development in daDREAM Transgenic Mice

Downstream regulatory element antagonist modulator (DREAM) is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. Previous work has shown a role for DREAM in cerebellar function regulating the expression of the sodium/calcium exchanger 3 (NCX3) in cerebellar granular neurons to control Ca2+ homeostasis and survival of these neurons. To achieve a global view of the genes regulated by DREAM in the cerebellum, we performed a genome-wide analysis in transgenic cerebellum expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Here we show that DREAM regulates the expression of the midline 1 (Mid1) gene early after birth. As a consequence, daDREAM mice exhibit a significant shortening of the rostro-caudal axis of the cerebellum and a delay in neuromotor development early after birth. Our results indicate a role for DREAM in cerebellar function

Biomechanical behavior of the dentoalveolar unit (UDA) of a central incisor under an orthodontic treatment, using wires of NiTi and NiTiCu: 3D simulation using finite elements

Durante el tratamiento de ortodoncia se pueden encontrar diferentes patologías tanto a nivel periodontal como radicular, las cuales se pueden intensificar si no se utiliza la biomecánica adecuada. Los dispositivos ortodónticos pueden producir cargas de gran magnitud dentro de la UDA originando una oclusión vascular y un corte en el suministro de sangre al ligamento periodontal (LPD). En los tratamientos ortodónticos es común el uso de arcos manufacturados en Nitinol (NiTi) y NitiCopper (NiTiCu) como fuente de generación del estímulo mecánico para producir los movimientos ortodónticos. En esta investigación se determinó que tipo de material para el arco (NiTi o NiTiCu) proporciona una mejor relación entre el estímulo mecánico y la respuesta biológica de la UDA. Para esto, se desarrolló una experimentación in-silico mediante el uso de elementos finitos, modelando los arcos ortodónticos como un material con memoria de forma (SMA). El dominio de trabajo fue obtenido mediante tomografía computacional diferenciando cada uno de los tejidos presentes en la UDA; hueso trabecular y cortical, diente y LPD. Como resultado se obtuvo el comportamiento biomecánico de la UDA y el campo de esfuerzos producidos en el ligamento periodontal y el hueso alveolar, determinando que tipo de material para el arco de ortodoncia disminuye el riesgo de patologías o movimientos ortodónticos no deseados. Palabras clave: Biomecánica, Elementos finitos, ortodoncia

DREAM (Downstream Regulatory Element Antagonist Modulator) contributes to synaptic depression and contextual fear memory

The downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, binds specifically to DNA and several nucleoproteins regulating gene expression and with proteins outside the nucleus to regulate membrane excitability or calcium homeostasis. DREAM is highly expressed in the central nervous system including the hippocampus and cortex; however, the roles of DREAM in hippocampal synaptic transmission and plasticity have not been investigated. Taking advantage of transgenic mice overexpressing a Ca2+-insensitive DREAM mutant (TgDREAM), we used integrative methods including electrophysiology, biochemistry, immunostaining, and behavior tests to study the function of DREAM in synaptic transmission, long-term plasticity and fear memory in hippocampal CA1 region. We found that NMDA receptor but not AMPA receptor-mediated current was decreased in TgDREAM mice. Moreover, synaptic plasticity, such as long-term depression (LTD) but not long-term potentiation (LTP), was impaired in TgDREAM mice. Biochemical experiments found that DREAM interacts with PSD-95 and may inhibit NMDA receptor function through this interaction. Contextual fear memory was significantly impaired in TgDREAM mice. By contrast, sensory responses to noxious stimuli were not affected. Our results demonstrate that DREAM plays a novel role in postsynaptic modulation of the NMDA receptor, and contributes to synaptic plasticity and behavioral memory

Using coding and non-coding rare variants to target candidate genes in patients with severe tinnitus

Tinnitus is the phantom percept of an internal non-verbal set of noises and tones. It is reported by 15% of the population and it is usually associated with hearing and/or brain disorders. The role of structural variants (SVs) in coding and non-coding regions has not been investigated in patients with severe tinnitus. In this study, we performed whole-genome sequencing in 97 unrelated Swedish individuals with chronic tinnitus (TIGER cohort). Rare single nucleotide variants (SNV), large structural variants (LSV), and copy number variations (CNV) were retrieved to perform a gene enrichment analysis in TIGER and in a subgroup of patients with severe tinnitus (SEVTIN, n = 34), according to the tinnitus handicap inventory (THI) scores. An independent exome sequencing dataset of 147 Swedish tinnitus patients was used as a replication cohort (JAGUAR cohort) and population-specific datasets from Sweden (SweGen) and Non-Finish Europeans (NFE) from gnomAD were used as control groups. SEVTIN patients showed a higher prevalence of hyperacusis, hearing loss, and anxiety when they were compared to individuals in the TIGER cohort. We found an enrichment of rare missense variants in 6 and 8 high-constraint genes in SEVTIN and TIGER cohorts, respectively. Of note, an enrichment of missense variants was found in the CACNA1E gene in both SEVTIN and TIGER. We replicated the burden of missense variants in 9 high-constrained genes in the JAGUAR cohort, including the gene NAV2, when data were compared with NFE. Moreover, LSVs in constrained regions overlapping CACNA1E, NAV2, and TMEM132D genes were observed in TIGER and SEVTIN.publishedVersio

UBVRI Light Curves of 44 Type Ia Supernovae

We present UBVRI photometry of 44 type-Ia supernovae (SN Ia) observed from 1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The data set comprises 2190 observations and is the largest homogeneously observed and reduced sample of SN Ia to date, nearly doubling the number of well-observed, nearby SN Ia with published multicolor CCD light curves. The large sample of U-band photometry is a unique addition, with important connections to SN Ia observed at high redshift. The decline rate of SN Ia U-band light curves correlates well with the decline rate in other bands, as does the U-B color at maximum light. However, the U-band peak magnitudes show an increased dispersion relative to other bands even after accounting for extinction and decline rate, amounting to an additional ~40% intrinsic scatter compared to B-band.Comment: 84 authors, 71 pages, 51 tables, 10 figures. Accepted for publication in the Astronomical Journal. Version with high-res figures and electronic data at http://astron.berkeley.edu/~saurabh/cfa2snIa

Distribution pattern of psoriasis, anxiety and depression as possible causes of sexual dysfunction in patients with moderate to severe psoriasis

BACKGROUND: Psoriasis may significantly impair sexual function. Depression and organic factors appear to play a key role in this relation. However, beyond genital psoriasis, the importance of the disease's distribution patterns has not been considered. OBJECTIVES: To research sexual function in psoriasis patients and investigate the roles of anxiety, depression and psoriasis' distribution patterns in sexual dysfunction. METHODS: A comparative study matched for sex and age was performed. Eighty patients with moderate to severe psoriasis and 80 healthy controls were included. The participants completed the Massachusetts General Hospital-Sexual Functioning Questionnaire, the Hospital Anxiety and Depression Scale, and the Self-Administered Psoriasis Area and Severity Index. RESULTS: Psoriasis was associated with sexual dysfunction, odds ratio=5.5 (CI 95% 2.6-11.3; p<0.001). Certain distribution patterns of psoriasis, involving specific body regions, were associated with an increase in sexual dysfunction in the group presenting the disease, odds ratio 7.9 (CI 95% 2.3-33.4; p<0.001). Multivariate logistic regression analysis identified anxiety and depression, and the involvement of these specific areas, as possible independent risk factors for sexual dysfunction in patients with moderate to severe psoriasis. CONCLUSION: This study identifies body areas potentially related to sexual dysfunction, independently of anxiety and depression, in psoriasis patients. The results suggest that the assessment of sexual dysfunction and the involvement of these body areas should be considered as disease severity criteria when choosing the treatment for psoriasis patients

A hybrid method for accurate iris segmentation on at-a-distance visible-wavelength images

[EN] This work describes a new hybrid method for accurate iris segmentation from full-face images independently of the ethnicity of the subject. It is based on a combination of three methods: facial key-point detection, integro-differential operator (IDO) and mathematical morphology. First, facial landmarks are extracted by means of the Chehra algorithm in order to obtain the eye location. Then, the IDO is applied to the extracted sub-image containing only the eye in order to locate the iris. Once the iris is located, a series of mathematical morphological operations is performed in order to accurately segment it. Results are obtained and compared among four different ethnicities (Asian, Black, Latino and White) as well as with two other iris segmentation algorithms. In addition, robustness against rotation, blurring and noise is also assessed. Our method obtains state-of-the-art performance and shows itself robust with small amounts of blur, noise and/or rotation. 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Human identification from at-a-distance images by simultaneously exploiting iris and periocular features (Tsukuba, 2012). p. 553–556. http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=6460194&isnumber=6460043 .C. -W. Tan, A. Kumar, Towards online iris and periocular recognition under relaxed imaging constraints. IEEE Trans. Image Proc.22(10), 3751–3765 (2013).K. Y. Shin, Y. G. Kim, K. R. Park, Enhanced iris recognition method based on multi-unit iris images. Opt. Eng.52(4), 047201–047201 (2013).CASIA iris databases. http://biometrics.idealtest.org/ . Accessed 06 Sept 2017.WVU iris databases. hhttp://biic.wvu.edu/data-sets/synthetic-iris-dataset . Accessed 06 Sept 2017.UBIRIS iris database. http://iris.di.ubi.pt . Accessed 06 Sept 2017.MICHE iris database. http://biplab.unisa.it/MICHE/ . Accessed 06 Sept 2017.P. J. Phillips, et al, in 2005 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR’05), 1. 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Constrained local neural fields for robust facial landmark detection in the wild (Sydney, 2013). p. 354–361. http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=6755919&isnumber=6755862 .X. Zhu, D. Ramanan, in Computer Vision and Pattern Recognition (CVPR), 2012 IEEE Conference On. Face detection, pose estimation, and landmark localization in the wild (IEEEBerlin Heidelberg, 2012), pp. 2879–2886.G. Tzimiropoulos, in 2015 IEEE Conference on Computer Vision and Pattern Recognition (CVPR). Project-out cascaded regression with an application to face alignment (Boston, 2015). p. 3659–3667. http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=7298989&isnumber=7298593 .H. Hofbauer, F. Alonso-Fernandez, P. Wild, J. Bigun, A. Uhl, in 2014 22nd International Conference on Pattern Recognition. A ground truth for iris segmentation (Stockholm, 2014). p. 527–532. http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=6976811&isnumber=6976709 .H. Proença, L. A. Alexandre, in 2007 First IEEE International Conference on Biometrics: Theory, Applications, and Systems. The NICE.I: Noisy Iris Challenge Evaluation - Part I (Crystal City, 2007). p. 1–4. http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=4401910&isnumber=4401902 .J. Daugman, in European Convention on Security and Detection. High confidence recognition of persons by rapid video analysis of iris texture, (1995). p. 244–251. http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=491729&isnumber=10615 .Code of Matlab implementation of Daugman’s integro-differential operator (IDO). https://es.mathworks.com/matlabcentral/fileexchange/15652-iris-segmentation-using-daugman-s-integrodifferential-operator/ . Accessed 06 Sept 2017.Code of Matlab implementation of Zhao and Kumar’s iris segmentation framework under relaxed imaging constraints using total variation model. http://www4.comp.polyu.edu.hk/~csajaykr/tvmiris.htm/ . 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CNNs for automatic glaucoma assessment using fundus images: an extensive validation

Background Most current algorithms for automatic glaucoma assessment using fundus images rely on handcrafted features based on segmentation, which are affected by the performance of the chosen segmentation method and the extracted features. Among other characteristics, convolutional neural networks (CNNs) are known because of their ability to learn highly discriminative features from raw pixel intensities. Methods In this paper, we employed five different ImageNet-trained models (VGG16, VGG19, InceptionV3, ResNet50 and Xception) for automatic glaucoma assessment using fundus images. Results from an extensive validation using cross-validation and cross-testing strategies were compared with previous works in the literature. Results Using five public databases (1707 images), an average AUC of 0.9605 with a 95% confidence interval of 95.92–97.07%, an average specificity of 0.8580 and an average sensitivity of 0.9346 were obtained after using the Xception architecture, significantly improving the performance of other state-of-the-art works. Moreover, a new clinical database, ACRIMA, has been made publicly available, containing 705 labelled images. It is composed of 396 glaucomatous images and 309 normal images, which means, the largest public database for glaucoma diagnosis. The high specificity and sensitivity obtained from the proposed approach are supported by an extensive validation using not only the cross-validation strategy but also the cross-testing validation on, to the best of the authors’ knowledge, all publicly available glaucoma-labelled databases. Conclusions These results suggest that using ImageNet-trained models is a robust alternative for automatic glaucoma screening system. All images, CNN weights and software used to fine-tune and test the five CNNs are publicly available, which could be used as a testbed for further comparisons

Non-capsulated and capsulated Haemophilus influenzae in children with acute otitis media in Venezuela: a prospective epidemiological study

<p>Abstract</p> <p>Background</p> <p>Non-typeable <it>Haemophilus influenzae </it>(NTHi) and <it>Streptococcus pneumoniae </it>are major causes of bacterial acute otitis media (AOM). Data regarding AOM are limited in Latin America. This is the first active surveillance in a private setting in Venezuela to characterize the bacterial etiology of AOM in children < 5 years of age.</p> <p>Methods</p> <p>Between December 2008 and December 2009, 91 AOM episodes (including sporadic, recurrent and treatment failures) were studied in 87 children enrolled into a medical center in Caracas, Venezuela. Middle ear fluid samples were collected either by tympanocentesis or spontaneous otorrhea swab sampling method. Standard laboratory and microbiological techniques were used to identify bacteria and test for antimicrobial resistance. The results were interpreted according to Clinical Laboratory Standards Institute (CLSI) 2009 for non-meningitis isolates. All statistical analyses were performed using SAS 9.1 and Microsoft Excel (for graphical purposes).</p> <p>Results</p> <p>Overall, bacteria were cultured from 69.2% (63 of the 91 episodes); at least one pathogen (<it>S. pneumoniae, H. influenzae, S. pyogenes </it>or <it>M. catarrhalis</it>) was cultured from 65.9% (60/91) of episodes. <it>H. influenzae </it>(55.5%; 35/63 episodes) and <it>S. pneumoniae </it>(34.9%; 22/63 episodes) were the most frequently reported bacteria. Among <it>H. influenzae </it>isolates, 62.9% (22/35 episodes) were non-capsulated (NTHi) and 31.4% (11/35 episodes) were capsulated including types d, a, c and f, across all age groups. Low antibiotic resistance for <it>H. influenzae </it>was observed to amoxicillin/ampicillin (5.7%; 2/35 samples). NTHi was isolated in four of the six <it>H. influenzae </it>positive samples (66.7%) from recurrent episodes.</p> <p>Conclusions</p> <p>We found <it>H. influenzae </it>and <it>S. pneumoniae </it>to be the main pathogens causing AOM in Venezuela. Pneumococcal conjugate vaccines with efficacy against these bacterial pathogens may have the potential to maximize protection against AOM.</p