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Cortical regions involved in eye movements, shifts of attention, and gaze perception.

Human vision is an active process that involves shifting attention across the visual scene, with or without moving the eyes. Such shifts of attention can be generated at will (endogenously) or be triggered automatically, i.e., generated in response to exogenous stimuli including socially relevant cues such as someone else's gaze. What are the common and distinct brain mechanisms involved in these processes? To address this question, we carried out a quantitative effect-location meta-analysis of 59 brain-imaging experiments whose results were published using standardized coordinates. For each condition of interest, namely voluntary and visually triggered eye movements, voluntary and visually triggered (covert) shifts of attention, and perception of someone else's gaze, we computed activation likelihood estimation (ALE) maps. Those maps represent at each voxel of the brain the probability of reporting a signal change related to the condition of interest. For eye movements, this analysis confirmed the spatial location of the frontal eye fields, supplementary eye fields, and parietal saccade-related regions. The map of covert shifts of attention demonstrated highest similarity with the map of saccadic eye movements. Gaze perception showed common activation likelihood with the other conditions in the right intraparietal sulcus and in the lateral precentral gyrus. It demonstrated more similarity with the reflexive than with the voluntary saccades and shifts of attention. We propose that a core network of frontoparietal and temporal brain regions is recruited when we shift the focus of our attention with or without eye movements in response to the appearance of a visual target, as well as when we see someone else shift his or her gaze.

Attention↗

Epidermal growth factor receptor in adult human dorsal root ganglia.

Transforming growth factor-alpha (TGFalpha) enhances neuronal survival and neurite outgrowth in cultured dorsal root ganglia (DRG) sensory neurons. It binds a membrane protein, denominated epidermal growth factor receptor (EGFr). EGFr has been localized in developing and adult human DRG. However, it remains to be elucidated whether all DRG neurons express EGFr or whether differences exist among neuronal subtypes. This study was undertaken to investigate these topics in adult human DRG using immunoblotting, and combined immunohistochemistry and image analysis techniques. A mouse monoclonal antibody (clone F4) mapping within the intracytoplasmic domain of EGFr was used. Immunoblotting revealed two main proteins with estimated molecular masses of approximately/equal to 65 kDa and 170 kDa, and thus consistent with the full-length EGFr. Additional protein bands were also encountered. Light immunohistochemistry revealed specific immunoreactivity (IR) for EGFr-like proteins in most (86%) primary sensory neurons, the intensity of immunostaining being stronger in the small- and intermediate-sized ones. Furthermore, EGFr-like IR was also observed in the satellite glial cells of the ganglia as well as in the intraganglionic and dorsal root Schwann cells. Taken together, our findings demonstrate that EGFr, and other related proteins containing the epitope labeled with the antibody F4, are responsible for the EGFr IR reported in DRG. Furthermore, we demonstrated heterogeneity in the expression of EGFr-like IR in adult human primary sensory neurons, which suggests different responsiveness to their ligands.

Adult↗

Inhibitory effect of capsaicin evoked trigeminal pain on warmth sensation and warmth evoked potentials.

The aim of the study was to evaluate the effect of tonic pain evoked by topical application of capsaicin on the somatosensory sensation of warmth. The warmth pathways were studied in ten healthy subjects by recording the scalp potentials evoked by non-painful warm laser stimuli delivered on both the right and left perioral region (warmth C-fiber related laser-evoked potentials (C-LEPs)). Tonic pain was induced by topical capsaicin application above the lateral part of the right upper lip. The area of primary and secondary hyperalgesia were mapped. C-LEPs were obtained from 31 scalp electrodes before, during, and after capsaicin application. C-LEPs from the right perioral region were evoked by laser stimuli delivered to the area of secondary hyperalgesia during capsaicin application and on both the areas of primary and secondary hyperalgesia after capsaicin removal. While the lateralized N1/P1 component (around 185 ms of latency) was not affected by the capsaicin, the amplitudes of the later vertex C-LEPs (around 260 and 410 ms of latency for the N2a and P2 potentials, respectively) evoked from the secondary hyperalgesic area on the right side and from a symmetrical non-hyperalgesic area on the left perioral region were significantly decreased during capsaicin application and after capsaicin removal, as compared with the baseline recordings. At the same times, the rating of the laser-evoked warmth sensation was reduced significantly. This inhibitory effect can occur at brainstem level and is possibly due to: 1) trigemino-cortico-trigeminal circuits, similar to those mediating the classical diffuse noxious inhibitory control, or 2) an increased background activity of the capsaicin-insensitive A-fibers, which mediate the secondary hyperalgesia. Probably due to a peripheral inhibitory mechanism, neither reliable C-LEP components nor warmth sensation were evoked by laser pulses delivered to the primary hyperalgesic area. This is the first neurophysiological evidence in humans of an inhibitory effect of pain on warmth sensation.

Adult↗

A simple and accurate method for generating co-dominant markers: an application of conformation-sensitive gel electrophoresis to linkage analysis in the silkworm.

A simple and sensitive method for linkage analysis is described, which is based on conformation-sensitive gel electrophoresis (CSGE). Using urea-containing agarose gels or a commercially available polyacrylamide-derived matrix, 13 polymorphic markers were newly identified for known genes of the silkworm, Bombyx mori, which had been scored as monomorphic by PCR-RFLP analysis. This method for detecting polymorphisms is quite sensitive, and can be performed with inexpensive reagents and apparatus that is available in most molecular biology laboratories.

Animals↗

Functional connections among cortical regions: topography of EEG coherence.

The covariance among EEG signals can be examined with coherence analysis. Evidence that the right hemisphere has a more diffuse receptotopic organization than the left, together with evidence that it may have a higher proportion of white to gray matter, suggests a high degree of functional connectedness among right hemisphere regions. To determine whether this is reflected in greater EEG coherence among right than left hemisphere locations, we constructed a matrix of cross-spectra among all unique pairs of EEG channels in an 8-channel montage, then statistically de-structured this matrix to examine multiple coherences and both inter- and intra-hemispheric partial multiple coherences. Analyses on data from the resting EEGs of 14 right-handed men examined weekly for several months showed higher coherences for right hemisphere locations. For the inter-hemispheric partial multiple coherences the frontal lobe values were also higher on the right, but the occipital inter-hemispheric coherences were higher on the left. These asymmetries have interesting parallels with anatomical asymmetries of the human cortex and may have functional implications.

Adult↗

Structure and developmental expression of a larval cuticle protein gene of the silkworm, Bombyx mori.

Structure and expression of the gene for a larval cuticle protein of the silkworm, Bombyx mori were studied. A major cuticle protein, termed 'LCP30' was purified from the urea extract of integuments of the fifth (final) instar larvae. Immunoblot analysis by use of the anti-LCP30 antibody revealed that LCP30 begins to accumulate in larvae as early as 10 h after hatch and is present throughout the larval stages. The LCP30 epitope is also detectable in the adult abdominal integument but is absent from pupal integument and adult wing. Screening of an epidermal cDNA expression library with the antibody probe yielded a cDNA clone for LCP30. Primary structure deduced from the cDNA sequence showed that LCP30 bears an arginine-glycine-aspartate (RGD) sequence. The region around this domain exhibits striking similarity with the amino acid sequences found in vertebrate collagens. The genomic DNA clone coding for LCP30 was isolated by screening a B. mori gene library with the LCP30 cDNA probe. The gene consists of five exons interspersed by four introns spanning over 2.7 kb region of chromosomal DNA. The LCP30 mRNA is detectable at high levels at larval intermolt stages, gradually declines after the fourth molt and totally disappears at mid-fifth larval instar, indicating that the expression of LCP30 gene is regulated in a stage-specific fashion in the epidermal cells. Topical application of a juvenile hormone analogue (methoprene) to the fifth instar larvae followed by RNA blot and S1 nuclease mapping analyses of the epidermal RNA proved that juvenile hormone activates transcription of the LCP30 gene.

Amino Acid Sequence↗

Patenting genes. J. Craig Venter and the Human Genome Project.

He often begins to answer before you have finished asking your question, but his replies are to the point. He speaks with emotion about the people he hopes to help, particularly children with fatal genetic diseases. 'I prefer to do something: the outcome of doing nothing is perfectly clear', he says. He began sequencing human genes while others were discussing how and when to do so. His methods have been called inelegant, redundant, wasteful, and too 'industrial'. Will his method fail to detect some infrequently transcribed genes? That's all right with him. He is not concerned with finding all the human genes, but rather with the fastest possible route to a useful catalog of most human genes.

Chromosome Mapping↗

The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology.

The human orbitofrontal cortex is an important brain region for the processing of rewards and punishments, which is a prerequisite for the complex and flexible emotional and social behaviour which contributes to the evolutionary success of humans. Yet much remains to be discovered about the functions of this key brain region, and new evidence from functional neuroimaging and clinical neuropsychology is affording new insights into the different functions of the human orbitofrontal cortex. We review the neuroanatomical and neuropsychological literature on the human orbitofrontal cortex, and propose two distinct trends of neural activity based on a meta-analysis of neuroimaging studies. One is a mediolateral distinction, whereby medial orbitofrontal cortex activity is related to monitoring the reward value of many different reinforcers, whereas lateral orbitofrontal cortex activity is related to the evaluation of punishers which may lead to a change in ongoing behaviour. The second is a posterior-anterior distinction with more complex or abstract reinforcers (such as monetary gain and loss) represented more anteriorly in the orbitofrontal cortex than simpler reinforcers such as taste or pain. Finally, we propose new neuroimaging methods for obtaining further evidence on the localisation of function in the human orbitofrontal cortex.

Brain Mapping↗

Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a new member of the S100 gene cluster on chromosome 1q21.

Here, we report the characterization of a human cDNA coding for the recently published amino acid sequence of a calcium-binding S100 protein, S100A12 (CGRP, calgranulin C, CAAF1, p6). The exon/intron structure of the S100A12 gene is similar to most other S100 genes. It is composed of three exons which are divided by two introns of 900 bp and 400 bp. The protein is encoded by sequences in exons 2 and 3, with exon 2 coding for the N-terminal 45 amino acids and exon 3 coding for the C-terminal 46 amino acids. So far, ten S100 genes are known to be located on human chromosome 1q21 in a clustered organization. Hence, we investigated whether S100A11 (S100C, calgizzarin) and S100A12 are also localized in the S100 gene cluster. We found both genes within the cluster, with S100A11 being close to S100A10 and S100A12 between the genes S100A8 and S100A9. Therefore, the S100 gene cluster now is composed of 12 differentially expressed family members.

Amino Acid Sequence↗

Evaluation and management of ventricular outflow tract tachycardias.

Ventricular tachycardia (VT) arising from the right or left ventricular outflow tract (OT) is a recognized arrhythmia in individuals with structurally normal hearts. Treatment options for OTVT include medications, ablation and, rarely, an implantable cardioverter defibrillator (ICD). In the past few years ablation techniques have developed to the point where most OTVTs can be successfully ablated. However, a percentage of cases have remained where ablation is unsuccessful. Some of these cases may represent an epicardial focus of the VT. Several approaches to epicardial VT ablation have been described. We recently described a LVOT-VT variant, which may be epicardial in nature, in a group of patients in whom prior ablation attempts had failed. A trans-aortic ablation approach to outflow tract VT was successful in these patients.

Anti-Arrhythmia Agents↗

Multiple neural spike train data analysis: state-of-the-art and future challenges.

Multiple electrodes are now a standard tool in neuroscience research that make it possible to study the simultaneous activity of several neurons in a given brain region or across different regions. The data from multi-electrode studies present important analysis challenges that must be resolved for optimal use of these neurophysiological measurements to answer questions about how the brain works. Here we review statistical methods for the analysis of multiple neural spike-train data and discuss future challenges for methodology research.

Action Potentials↗

E-neuroscience: challenges and triumphs in integrating distributed data from molecules to brains.

Imaging, from magnetic resonance imaging (MRI) to localization of specific macromolecules by microscopies, has been one of the driving forces behind neuroinformatics efforts of the past decade. Many web-accessible resources have been created, ranging from simple data collections to highly structured databases. Although many challenges remain in adapting neuroscience to the new electronic forum envisioned by neuroinformatics proponents, these efforts have succeeded in formalizing the requirements for effective data sharing and data integration across multiple sources. In this perspective, we discuss the importance of spatial systems and ontologies for proper modeling of neuroscience data and their use in a large-scale data integration effort, the Biomedical Informatics Research Network (BIRN).

Animals↗

The identification of novel potential injury mechanisms and candidate biomarkers in renal allograft rejection by quantitative proteomics.

Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control (HC) (n = 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p < 0.05) with a significant finding that SUMO2 (small ubiquitin-related modifier 2) was identified as a "hub" protein for graft injury irrespective of causation. Sixty-nine urine proteins had differences in abundance (p < 0.01) in AR compared with stable graft, of which 12 proteins were up-regulated in AR with a mean fold increase of 2.8. Nine urine proteins were highly specific for AR because of their significant differences (p < 0.01; fold increase >1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a finding that supports the utility of monitoring these urinary proteins for the specific and sensitive noninvasive diagnosis of acute renal allograft rejection.

Acute Kidney Injury↗