269 research outputs found

    Tracking neuronal motility in live murine retinal explants

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    The developing retina undergoes dynamic organizational changes involving significant intra-retinal motility of the encompassing cells. Here, we present a protocol for tracking retinal cell motility in live explanted mouse retinae. Although originally applied to rod and cone photoreceptors, this strategy is applicable to any fluorescently labeled cell in mouse retinae and other similar experimental retinal models. Careful tissue handling is critical for the successful acquisition of high-quality live imaging data. Further instructions for semi-automated in silico data handling are provided. For complete details on the use and execution of this protocol, please refer to Aghaizu et al. (2021)

    Public experiences of mass casualty decontamination

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    In this article, we analyze feedback from simulated casualties who took part in field exercises involving mass decontamination, to gain an understanding of how responder communication can affect people’s experiences of and compliance with decontamination. We analyzed questionnaire data gathered from 402 volunteers using the framework approach, to provide an insight into the public’s experiences of decontamination and how these experiences are shaped by the actions of emergency responders. Factors that affected casualties’ experiences of the econtamination process included the need for greater practical information and better communication from responders, and the need for privacy. Results support previous findings from small-scale incidents that involved decontamination in showing that participants wanted better communication from responders during the process of decontamination, including more practical information, and that the failure of responders to communicate effectively with members of the public led to anxiety about the decontamination process. The similarity between the findings from the exercises described in this article and previous research into real incidents involving decontamination suggests that field exercises provide a useful way to examine the effect of responder communication strategies on the public’s experiences of decontamination. Future exercises should examine in more detail the effect of various communication strategies on the public’s experiences of decontamination. This will facilitate the development of evidence-based communication strategies intended to reduce anxiety about decontamination and increase compliance among members of the public during real-life incidents that involve mass decontamination

    Repeated nuclear translocations underlie photoreceptor positioning and lamination of the outer nuclear layer in the mammalian retina

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    In development, almost all stratified neurons must migrate from their birthplace to the appropriate neural layer. Photoreceptors reside in the most apical layer of the retina, near their place of birth. Whether photoreceptors require migratory events for fine-positioning and/or retention within this layer is not well understood. Here, we show that photoreceptor nuclei of the developing mouse retina cyclically exhibit rapid, dynein-1-dependent translocation toward the apical surface, before moving more slowly in the basal direction, likely due to passive displacement by neighboring retinal nuclei. Attenuating dynein 1 function in rod photoreceptors results in their ectopic basal displacement into the outer plexiform layer and inner nuclear layer. Synapse formation is also compromised in these displaced cells. We propose that repeated, apically directed nuclear translocation events are necessary to ensure retention of post-mitotic photoreceptors within the emerging outer nuclear layer during retinogenesis, which is critical for correct neuronal lamination

    Creation of ultracold molecules from a Fermi gas of atoms

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    Since the realization of Bose-Einstein condensates (BEC) in atomic gases an experimental challenge has been the production of molecular gases in the quantum regime. A promising approach is to create the molecular gas directly from an ultracold atomic gas; for example, atoms in a BEC have been coupled to electronic ground-state molecules through photoassociation as well as through a magnetic-field Feshbach resonance. The availability of atomic Fermi gases provides the exciting prospect of coupling fermionic atoms to bosonic molecules, and thus altering the quantum statistics of the system. This Fermi-Bose coupling is closely related to the pairing mechanism for a novel fermionic superfluid proposed to occur near a Feshbach resonance. Here we report the creation and quantitative characterization of exotic, ultracold 40^{40}K2_2 molecules. Starting with a quantum degenerate Fermi gas of atoms at T < 150 nanoKelvin we scan over a Feshbach resonance to adiabatically create over a quarter million trapped molecules, which we can convert back to atoms by reversing the scan. The small binding energy of the molecules is controlled by detuning from the Feshbach resonance and can be varied over a wide range. We directly detect these weakly bound molecules through rf photodissociation spectra that probe the molecular wavefunction and yield binding energies that are consistent with theory

    Implementation of immunohistochemistry on frozen ear notch tissue samples in diagnosis of bovine viral diarrhea virus in persistently infected cattle

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    <p>Abstract</p> <p>Background</p> <p>Bovine viral diarrhea is a contagious disease of domestic and wild ruminants and one of the most economically important diseases in cattle. Bovine viral diarrhea virus belongs to the genus <it>Pestivirus</it>, within the family <it>Flaviviridae</it>. The identification and elimination of the persistently infected animals from herds is the initial step in the control and eradication programs. It is therefore necessary to have reliable methods for diagnosis of bovine viral diarrhea virus. One of those methods is immunohistochemistry. Immunohistochemistry on formalin fixed, paraffin embedded tissue is a routine technique in diagnosis of persistently infected cattle from ear notch tissue samples. However, such technique is inappropriate due to complicated tissue fixation process and it requires more days for preparation. On the contrary, immunohistochemistry on frozen tissue was usually applied on organs from dead animals. In this paper, for the first time, the imunohistochemistry on frozen ear notch tissue samples was described.</p> <p>Findings</p> <p>Seventeen ear notch tissue samples were obtained during the period 2008-2009 from persistently infected cattle. Samples were fixed in liquid nitrogen and stored on -20°C until testing. Ear notch tissue samples from all persistently infected cattle showed positive results with good section quality and possibility to determinate type of infected cells.</p> <p>Conclusions</p> <p>Although the number of samples was limited, this study indicated that immunohistochemistry on formalin fixed paraffin embedded tissue can be successfully replaced with immunohistochemistry on frozen ear notch tissue samples in diagnosis of persistently infected cattle.</p

    Topiramate in the treatment of compulsive sexual behavior: case report

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    BACKGROUND: Among the multiple mechanisms of action of topiramate, AMPA/kainate antagonism may be particularly interesting for the treatment of disorders characterized by conditioned cognitive and behavioral cue reactivity. CASE PRESENTATION: We report the case of a patient consulting primarily for obesity and cue triggered snacking, who responded well on topiramate at doses up to 50 mg. Coincidentally he reported on an improvement of compulsive nonparaphilic sexual behaviors (consumption of prostitution), which was also strongly triggered by environmental cues. Both addictive behaviors (snacking and consumption of prostitution) reoccurred after discontinuation of topiramate and again responded reintroduction of the drug. CONCLUSION: The present case report of topiramate's effect on comorbid obesity and nonparaphilic addiction could be interpreted as a further indication that topiramate acts on the common pathway underlying conditioned behaviors and seems to be a treatment of behavioral disorders associated with environmental cues

    Shorter spontaneous fixation durations in infants with later emerging autism

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    Little is known about how spontaneous attentional deployment differs on a millisecond-level scale in the early development of autism spectrum disorders (ASD). We measured fine-grained eye movement patterns in 6-to 9-month-old infants at high or low familial risk (HR/LR) of ASD while they viewed static images. We observed shorter fixation durations (i.e. the time interval between saccades) in HR than LR infants. Preliminary analyses indicate that these results were replicated in a second cohort of infants. Fixation durations were shortest in those infants who went on to receive an ASD diagnosis at 36 months. While these findings demonstrate early-developing atypicality in fine-grained measures of attentional deployment early in the etiology of ASD, the specificity of these effects to ASD remains to be determined

    Ensemble Modeling for Aromatic Production in Escherichia coli

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    Ensemble Modeling (EM) is a recently developed method for metabolic modeling, particularly for utilizing the effect of enzyme tuning data on the production of a specific compound to refine the model. This approach is used here to investigate the production of aromatic products in Escherichia coli. Instead of using dynamic metabolite data to fit a model, the EM approach uses phenotypic data (effects of enzyme overexpression or knockouts on the steady state production rate) to screen possible models. These data are routinely generated during strain design. An ensemble of models is constructed that all reach the same steady state and are based on the same mechanistic framework at the elementary reaction level. The behavior of the models spans the kinetics allowable by thermodynamics. Then by using existing data from the literature for the overexpression of genes coding for transketolase (Tkt), transaldolase (Tal), and phosphoenolpyruvate synthase (Pps) to screen the ensemble, we arrive at a set of models that properly describes the known enzyme overexpression phenotypes. This subset of models becomes more predictive as additional data are used to refine the models. The final ensemble of models demonstrates the characteristic of the cell that Tkt is the first rate controlling step, and correctly predicts that only after Tkt is overexpressed does an increase in Pps increase the production rate of aromatics. This work demonstrates that EM is able to capture the result of enzyme overexpression on aromatic producing bacteria by successfully utilizing routinely generated enzyme tuning data to guide model learning

    Association study of promoter polymorphisms at the dopamine transporter gene in Attention Deficit Hyperactivity Disorder

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    <p>Abstract</p> <p>Background</p> <p>Attention deficit hyperactivity disorder (ADHD) is a complex neurobehavioral disorder. The dopamine transporter gene (DAT1/<it>SLC6A3</it>) has been considered a good candidate for ADHD. Most association studies with ADHD have investigated the 40-base-pair variable number of tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1. Only few studies have reported association between promoter polymorphisms of the gene and ADHD.</p> <p>Methods</p> <p>To investigate the association between the polymorphisms -67A/T (rs2975226) and -839C/T (rs2652511) in promoter region of DAT1 in ADHD, two samples of ADHD patients from the UK (n = 197) and Taiwan (n = 212) were genotyped, and analysed using within-family transmission disequilibrium test (TDT).</p> <p>Results</p> <p>A significant association was found between the T allele of promoter polymorphism -67A/T and ADHD in the Taiwanese population (<it>P </it>= 0.001). There was also evidence of preferential transmission of the T allele of -67A/T polymorphism in combined samples from the UK and Taiwan (<it>P </it>= 0.003). No association was detected between the -839C/T polymorphism and ADHD in either of the two populations.</p> <p>Conclusion</p> <p>The finding suggests that genetic variation in the promoter region of DAT1 may be a risk factor in the development of ADHD.</p

    Contributions of phonological and verbal working memory to language development in adolescents with fragile X syndrome

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    Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. Although language delays are frequently observed in FXS, neither the longitudinal course of language development nor its cognitive predictors are well understood. The present study investigated whether phonological and working memory skills are predictive of growth in vocabulary and syntax in individuals with FXS during adolescence. Forty-four individuals with FXS (mean age = 12.61 years) completed assessments of phonological memory (nonword repetition and forward digit recall), verbal working memory (backward digit recall), vocabulary, syntax, and nonverbal cognition. Vocabulary and syntax skills were reassessed at a 2-year follow-up. In a series of analyses that controlled for nonverbal cognitive ability and severity of autism symptoms, the relative contributions of phonological and working memory to language change over time were investigated. These relationships were examined separately for boys and girls. In boys with FXS, phonological memory significantly predicted gains in vocabulary and syntax skills. Further, verbal working memory was uniquely associated with vocabulary gains among boys. In girls with FXS, phonological and working memory skills showed no relationship with language change across the 2-year time period. Our findings indicate that, for adolescent boys with FXS, acquisition of vocabulary and syntax may be constrained by the ability to maintain and manipulate phonological representations online. Implications for the identification and treatment of language disorders in this population are discussed. The present study is the first to identify specific cognitive mechanisms contributing to language growth over time in individuals with FXS
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