FKBP5 Modulates Attention Bias for Threat: Associations with Hippocampal Function and Morphology

Context: The FKBP5 gene product regulates glucocorticoid receptor (GR) sensitivity and hypothalamicpituitary‐adrenal axis functioning, and has been associated with a number of stress‐related psychiatric disorders. The study of intermediate phenotypes, such as emotion‐processing biases and their neural substrates, provides a way to clarify the mechanisms by which FKBP5 dysregulation mediates psychopathology risk. Objective: To examine whether allelic variations for a putatively functional SNP associated with FKBP5 gene regulation (rs1360780) would relate differentially to attentional bias for threat; this was measured through behavioral response on a dot probe task and hippocampal activation during task performance. Morphological substrates of differential hippocampal response were also measured. Design: Cross-sectional study examining associations between genotype, behavioral response and neural response (using fMRI) on the dot probe; Voxel-based morphometry (VBM), global and local shape analyses were used to measure structural differences in hippocampi between genotype groups

Mapping Connectivity Damage in the Case of Phineas Gage

White matter (WM) mapping of the human brain using neuroimaging techniques has gained considerable interest in the neuroscience community. Using diffusion weighted (DWI) and magnetic resonance imaging (MRI), WM fiber pathways between brain regions may be systematically assessed to make inferences concerning their role in normal brain function, influence on behavior, as well as concerning the consequences of network-level brain damage. In this paper, we investigate the detailed connectomics in a noted example of severe traumatic brain injury (TBI) which has proved important to and controversial in the history of neuroscience. We model the WM damage in the notable case of Phineas P. Gage, in whom a “tamping iron” was accidentally shot through his skull and brain, resulting in profound behavioral changes. The specific effects of this injury on Mr. Gage's WM connectivity have not previously been considered in detail. Using computed tomography (CT) image data of the Gage skull in conjunction with modern anatomical MRI and diffusion imaging data obtained in contemporary right handed male subjects (aged 25–36), we computationally simulate the passage of the iron through the skull on the basis of reported and observed skull fiducial landmarks and assess the extent of cortical gray matter (GM) and WM damage. Specifically, we find that while considerable damage was, indeed, localized to the left frontal cortex, the impact on measures of network connectedness between directly affected and other brain areas was profound, widespread, and a probable contributor to both the reported acute as well as long-term behavioral changes. Yet, while significantly affecting several likely network hubs, damage to Mr. Gage's WM network may not have been more severe than expected from that of a similarly sized “average” brain lesion. These results provide new insight into the remarkable brain injury experienced by this noteworthy patient

Sex matters during adolescence: Testosterone-related cortical thickness maturation differs between boys and girls

Age-related changes in cortical thickness have been observed during adolescence, including thinning in frontal and parietal cortices, and thickening in the lateral temporal lobes. Studies have shown sex differences in hormone-related brain maturation when boys and girls are age-matched, however, because girls mature 1-2 years earlier than boys, these sex differences could be confounded by pubertal maturation. To address puberty effects directly, this study assessed sex differences in testosterone-related cortical maturation by studying 85 boys and girls in a narrow age range and matched on sexual maturity. We expected that testosterone-by-sex interactions on cortical thickness would be observed in brain regions known from the animal literature to be high in androgen receptors. We found sex differences in associations between circulating testosterone and thickness in left inferior parietal lobule, middle temporal gyrus, calcarine sulcus, and right lingual gyrus, all regions known to be high in androgen receptors. Visual areas increased with testosterone in boys, but decreased in girls. All other regions were more impacted by testosterone levels in girls than boys. The regional pattern of sex-by-testosterone interactions may have implications for understanding sex differences in behavior and adolescent-onset neuropsychiatric disorders. © 2012 Bramen et al

Orthodontics in the era of big data analytics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149344/1/ocr12279_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149344/2/ocr12279.pd

iTools: A Framework for Classification, Categorization and Integration of Computational Biology Resources

The advancement of the computational biology field hinges on progress in three fundamental directions – the development of new computational algorithms, the availability of informatics resource management infrastructures and the capability of tools to interoperate and synergize. There is an explosion in algorithms and tools for computational biology, which makes it difficult for biologists to find, compare and integrate such resources. We describe a new infrastructure, iTools, for managing the query, traversal and comparison of diverse computational biology resources. Specifically, iTools stores information about three types of resources–data, software tools and web-services. The iTools design, implementation and resource meta - data content reflect the broad research, computational, applied and scientific expertise available at the seven National Centers for Biomedical Computing. iTools provides a system for classification, categorization and integration of different computational biology resources across space-and-time scales, biomedical problems, computational infrastructures and mathematical foundations. A large number of resources are already iTools-accessible to the community and this infrastructure is rapidly growing. iTools includes human and machine interfaces to its resource meta-data repository. Investigators or computer programs may utilize these interfaces to search, compare, expand, revise and mine meta-data descriptions of existent computational biology resources. We propose two ways to browse and display the iTools dynamic collection of resources. The first one is based on an ontology of computational biology resources, and the second one is derived from hyperbolic projections of manifolds or complex structures onto planar discs. iTools is an open source project both in terms of the source code development as well as its meta-data content. iTools employs a decentralized, portable, scalable and lightweight framework for long-term resource management. We demonstrate several applications of iTools as a framework for integrated bioinformatics. iTools and the complete details about its specifications, usage and interfaces are available at the iTools web page http://iTools.ccb.ucla.edu

Armadillo 1.1: An Original Workflow Platform for Designing and Conducting Phylogenetic Analysis and Simulations

In this paper we introduce Armadillo v1.1, a novel workflow platform dedicated to designing and conducting phylogenetic studies, including comprehensive simulations. A number of important phylogenetic and general bioinformatics tools have been included in the first software release. As Armadillo is an open-source project, it allows scientists to develop their own modules as well as to integrate existing computer applications. Using our workflow platform, different complex phylogenetic tasks can be modeled and presented in a single workflow without any prior knowledge of programming techniques. The first version of Armadillo was successfully used by professors of bioinformatics at Université du Quebec à Montreal during graduate computational biology courses taught in 2010–11. The program and its source code are freely available at: <http://www.bioinfo.uqam.ca/armadillo>

Arrhythmias in Dilated Cardiomyopathy: Diagnosis and Treatment

In patients with dilated cardiomyopathy (DCM), it is possible to find a broad range of bradyrhythmias and tachyarrhythmias. Bradyrhythmias and supraventricular arrhythmias can frequently occur in some familial forms such as lamin A/C mutations. Nonsustained ventricular arrhythmias (VA) are observed in about 40% of patients with DCM, but their prognostic role is not clear, and conflicting data have been published in the last 30 years. Multiple mechanisms can explain atrial and ventricular tachyarrhythmias in DCM. Reentry is associated with slow conduction across surviving muscle bundles within regions of interstitial fibrosis, but other mechanisms can be involved, as nonuniform anisotropy of impulse propagation, ion channel dysfunction, and reduced gap junction function