Discrepancies in indel software resolution with somatic CRISPR/Cas9 tumorigenesis models.

CRISPR/Cas9 gene editing has evolved from a simple laboratory tool to a powerful method of in vivo genomic engineering. As the applications of CRISPR/Cas9 technology have grown, the need to characterize the breadth and depth of indels generated by editing has expanded. Traditionally, investigators use one of several publicly-available platforms to determine CRISPR/Cas9-induced indels in an edited sample.

Simulations predict differing phase responses to excitation vs. inhibition in theta-resonant pyramidal neurons.

Rhythmic activity is ubiquitous in neural systems, with theta-resonant pyramidal neurons integrating rhythmic inputs in many cortical structures. Impedance analysis has been widely used to examine frequency-dependent responses of neuronal membranes to rhythmic inputs, but it assumes that the neuronal membrane is a linear system, requiring the use of small signals to stay in a near-linear regime. However, postsynaptic potentials are often large and trigger nonlinear mechanisms (voltage-gated ion channels).

Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is an aggressive form of cancer that accounts for half of all pediatric soft tissue sarcomas. Little progress has been made in improving survival outcomes over the past three decades. Mouse models of rhabdomyosarcoma are a critical component of translational research aimed at understanding tumor biology and developing new, improved therapies.

Modernizing the NEURON Simulator for Sustainability, Portability, and Performance.

The need for reproducible, credible, multiscale biological modeling has led to the development of standardized simulation platforms, such as the widely-used NEURON environment for computational neuroscience. Developing and maintaining NEURON over several decades has required attention to the competing needs of backwards compatibility, evolving computer architectures, the addition of new scales and physical processes, accessibility to new users, and efficiency and flexibility for specialists. In order to meet these challenges, we have now substantially modernized NEURON, providing continuous integration, an improved build system and release workflow, and better documentation.

Physiotherapists' Experiences with and Perspectives on Implementing an Evidence-Based, Chronic Pain Self-Management Programme in Primary Health Care: A Qualitative Study.

Evidence suggests that a physiotherapist-led chronic pain self-management programme in primary health care (PHC) improves function for people living with chronic pain; however, implementing a new approach to care can be difficult. In this study, we sought to understand the experiences of physiotherapists who had implemented the ChrOnic pain self-ManageMent support with pain science EducatioN and exerCisE (COMMENCE) programme; its perceived barriers, facilitators, benefits, and drawbacks; and how the physiotherapists tailored the programme to their own clinical contexts. This interpretive description qualitative study used semi-structured interviews with physiotherapists who had implemented the COMMENCE programme in PHC.

Effects of and TASK-like shunting current on dendritic impedance in layer 5 pyramidal-tract neurons.

Pyramidal neurons in neocortex have complex input-output relationships that depend on their morphologies, ion channel distributions, and the nature of their inputs, but which cannot be replicated by simple integrate-and-fire models. The impedance properties of their dendritic arbors, such as resonance and phase shift, shape neuronal responses to synaptic inputs and provide intraneuronal functional maps reflecting their intrinsic dynamics and excitability. Experimental studies of dendritic impedance have shown that neocortical pyramidal tract neurons exhibit distance-dependent changes in resonance and impedance phase with respect to the soma.

Human Neocortical Neurosolver (HNN), a new software tool for interpreting the cellular and network origin of human MEG/EEG data.

Magneto- and electro-encephalography (MEG/EEG) non-invasively record human brain activity with millisecond resolution providing reliable markers of healthy and disease states. Relating these macroscopic signals to underlying cellular- and circuit-level generators is a limitation that constrains using MEG/EEG to reveal novel principles of information processing or to translate findings into new therapies for neuropathology. To address this problem, we built Human Neocortical Neurosolver (HNN, https://hnn.

Neuron Names: A Gene- and Property-Based Name Format, With Special Reference to Cortical Neurons.

Precision in neuron names is increasingly needed. We are entering a new era in which classical anatomical criteria are only the beginning toward defining the identity of a neuron as carried in its name. New criteria include patterns of gene expression, membrane properties of channels and receptors, pharmacology of neurotransmitters and neuropeptides, physiological properties of impulse firing, and state-dependent variations in expression of characteristic genes and proteins.

Early experiences in developing and managing the neuroscience gateway.

The last few decades have seen the emergence of computational neuroscience as a mature field where researchers are interested in modeling complex and large neuronal systems and require access to high performance computing machines and associated cyber infrastructure to manage computational workflow and data. The neuronal simulation tools, used in this research field, are also implemented for parallel computers and suitable for high performance computing machines. But using these tools on complex high performance computing machines remains a challenge because of issues with acquiring computer time on these machines located at national supercomputer centers, dealing with complex user interface of these machines, dealing with data management and retrieval.

Electrical behaviour of dendritic spines as revealed by voltage imaging.

Thousands of dendritic spines on individual neurons process information and mediate plasticity by generating electrical input signals using a sophisticated assembly of transmitter receptors and voltage-sensitive ion channel molecules. Our understanding, however, of the electrical behaviour of spines is limited because it has not been possible to record input signals from these structures with adequate sensitivity and spatiotemporal resolution. Current interpretation of indirect data and speculations based on theoretical considerations are inconclusive.

Effects of low frequency electric fields on synaptic integration in hippocampal CA1 pyramidal neurons: implications for power line emissions.

The possible cognitive effects of low frequency external electric fields (EFs), such as those generated by power lines, are poorly understood. Their functional consequences for mechanisms at the single neuron level are very difficult to study and identify experimentally, especially in vivo. The major open problem is that experimental investigations on humans have given inconsistent or contradictory results, making it difficult to estimate the possible effects of external low frequency electric fields on cognitive functions.

Development and validation of the quality-of-life adolescent cleft questionnaire in patients with cleft lip and palate.

Only a few reports in the literature have described the use of specific instruments for assessing the quality of life in adolescents and young adults with cleft lip and palate (CLP). This condition markedly affects their lifestyle, even after surgical treatment. In the present study, we aimed to develop a quality-of-life assessment tool specifically designed for such patients with CLP.

Compartmentalization of GABAergic inhibition by dendritic spines.

γ-aminobutyric acid-mediated (GABAergic) inhibition plays a critical role in shaping neuronal activity in the neocortex. Numerous experimental investigations have examined perisomatic inhibitory synapses, which control action potential output from pyramidal neurons. However, most inhibitory synapses in the neocortex are formed onto pyramidal cell dendrites, where theoretical studies suggest they may focally regulate cellular activity.

Cortical dendritic spine heads are not electrically isolated by the spine neck from membrane potential signals in parent dendrites.

The evidence for an important hypothesis that cortical spine morphology might participate in modifying synaptic efficacy that underlies plasticity and possibly learning and memory mechanisms is inconclusive. Both theory and experiments suggest that the transfer of excitatory postsynaptic potential signals from spines to parent dendrites depends on the spine neck morphology and resistance. Furthermore, modeling of signal transfer in the opposite direction predicts that synapses on spine heads are not electrically isolated from voltages in the parent dendrite.

Robotic adrenalectomy by an open surgeon: are outcomes different?

Our objective is to demonstrate the feasibility of robotic adrenalectomy by a traditional open surgeon using the da Vinci Robotic Surgical System and to analyze our outcomes. All patients who underwent robotic adrenalectomy by a single surgeon from July 2001 to April 2011 were included in the study. Vascular inflow control was obtained early on to facilitate dissection and handling of the adrenal gland.

Electrical advantages of dendritic spines.

Many neurons receive excitatory glutamatergic input almost exclusively onto dendritic spines. In the absence of spines, the amplitudes and kinetics of excitatory postsynaptic potentials (EPSPs) at the site of synaptic input are highly variable and depend on dendritic location. We hypothesized that dendritic spines standardize the local geometry at the site of synaptic input, thereby reducing location-dependent variability of local EPSP properties.

Abnormal Excitability of Oblique Dendrites Implicated in Early Alzheimer's: A Computational Study.

The integrative properties of cortical pyramidal dendrites are essential to the neural basis of cognitive function, but the impact of amyloid beta protein (abeta) on these properties in early Alzheimer's is poorly understood. In animal models, electrophysiological studies of proximal dendrites have shown that abeta induces hyperexcitability by blocking A-type K+ currents (I(A)), disrupting signal integration. The present study uses a computational approach to analyze the hyperexcitability induced in distal dendrites beyond the experimental recording sites.

[Bacterial biofilm identification in the rhinopharingeal mucosa of children with recurrent infection of the upper respiratory tract and otitis media].

Objective: The objective of the present study was to identify bacterial biofilms in tissue samples obtained from paediatric patients undergoing surgical treatment, for recurrent upper airway infections, frequently associated to effusive otitis media, unresponsive to repeated cycles of selective medical antibiotic and anti-inflammatory therapy and assay the ability of Haemophilus influenzae strains, most frequently identified in our cultural examinations, to grow as biofilm in vitro.

Methods: We examined 18 surgical specimens (18 adenoids) from the upper respiratory tract, obtained from 18 paediatric patients. Tissues were cultured using conventional methods and subjected to scanning electron microscopy for detection of biofilm.

Functional structure of the mitral cell dendritic tuft in the rat olfactory bulb.

The input-output transform performed by mitral cells, the principal projection neurons of the olfactory bulb, is one of the key factors in understanding olfaction. We used combined calcium and voltage imaging from the same neuron and computer modeling to investigate signal processing in the mitral cells, focusing on the glomerular dendritic tuft. The main finding was that the dendritic tuft functions as a single electrical compartment for subthreshold signals within the range of amplitudes detectable by voltage-sensitive dye recording.

Model structure analysis in NEURON : toward interoperability among neural simulators.

One of the more important recent additions to the NEURON simulation environment is a tool called ModelView, which simplifies the task of understanding exactly what biological attributes are represented in a computational model. Here, we illustrate how ModelView contributes to the understanding of models and discuss its utility as a neuroinformatics tool for analyzing models in online databases and as a means for facilitating interoperability among simulators in computational neuroscience.

Translating network models to parallel hardware in NEURON.

The increasing complexity of network models poses a growing computational burden. At the same time, computational neuroscientists are finding it easier to access parallel hardware, such as multiprocessor personal computers, workstation clusters, and massively parallel supercomputers. The practical question is how to move a working network model from a single processor to parallel hardware.

[Biotic and abiotic factors that affect the quality of Schinopsis balansae Engl. and Aspidosperma quebracho-blanco Schltdl. seeds].

Aspidosperma quebracho-blanco (white quebracho) and Schinopsis balansae (red quebracho) are distinctive trees of the South American Park in Argentina. Quebrachos are found in forests that have been exploited very intensively. The object of this work was the identification of biotic and abiotic factors specially fungal pathogen that affect the quality of both species and its relation with germination.

Perioperative outcomes and risk factors in gastric surgery for morbid obesity: a 9-year experience.

Objective: Surgical treatment of severe obesity is the most rapidly growing specialty area of surgery. The rapid expansion of bariatric surgery has raised questions and concerns regarding possible increased surgical mortality and morbidity rates in both academic and community settings. The purpose of this study was to evaluate postoperative outcomes and risk factors for bariatric gastric surgery for severe obesity.

ModelDB: A Database to Support Computational Neuroscience.

Wider dissemination and testing of computational models are crucial to the field of computational neuroscience. Databases are being developed to meet this need. ModelDB is a web-accessible database for convenient entry, retrieval, and running of published models on different platforms.

Litterfall and organic matter decomposition in a seasonal forest of the eastern Chaco (Argentina).

Amazonia and the Gran Chaco are the largest phytogeographic units of the Neotropical Region. The Forest Wedge of the Santa Fe province of Argentina is the southernmost part of the Eastern Chaco, and there are three main types of forest, 1) the mixed dense forests, 2) the Schinopsis balansae "quebrachal" and 3) the Prosopis nigra var. ragonesei forests, distributed along an environmental gradient correlated with topographic elevation.