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PubMed1986

Transcription termination and processing sites in the bacteriophage lambda pL operon.

S1 nuclease mapping was performed on transcripts from the major leftward operon of the bacteriophage lambda in order to locate the 3' ends of stable RNA species produced in vivo. The analysis was carried out on RNA purified from either an induced lambda prophage or bacteria carrying a plasmid containing a large segment of lambda including the intact PL operon through the bet gene. The S1 nuclease mapping was performed on transcripts produced in the presence and the absence of the N antitermination function, and in the presence and the absence of either the RNase III processing enzyme or the Rho factor. The results of this work indicate that the intercistronic region between the N and ral genes of lambda contains three sites at which transcripts end under N-Rho+ conditions (positions on the lambda sequence: 34,826, 34,558 and 34,393). The distal two correspond to the two sites previously described in this region as tL1 (on both sides of the BamHI site). In the region between ral and Ea10, we mapped the 3' ends of three species of RNA. The 3' end of one species was found to be located 90 nucleotides proximal to tL2a, at 34,000 in the lambda sequence. The terminator at this site may be partially N-resistant. In an RNase III deficient host, an additional RNA species is formed. The 3' end of this RNA species is located at tL2a (33,910 on the lambda sequence). In the presence of the antitermination N gene product, the readthrough transcripts are processed to form a 3' end at position 33,980 on the lambda sequence. These results suggest that elongation of transcription of the lambda PL operon is reduced gradually by clusters of termination located between genes and that the expression of the terminated products is further controlled by processing of the mRNA.

Bacteriophage lambda↗
PubMed1996

Cortical systems for the recognition of emotion in facial expressions.

This study is part of an effort to map neural systems involved in the processing of emotion, and it focuses on the possible cortical components of the process of recognizing facial expressions. We hypothesized that the cortical systems most responsible for the recognition of emotional facial expressions would draw on discrete regions of right higher-order sensory cortices and that the recognition of specific emotions would depend on partially distinct system subsets of such cortical regions. We tested these hypotheses using lesion analysis in 37 subjects with focal brain damage. Subjects were asked to recognize facial expressions of six basic emotions: happiness, surprise, fear, anger, disgust, and sadness. Data were analyzed with a novel technique, based on three-dimensional reconstruction of brain images, in which anatomical description of surface lesions and task performance scores were jointly mapped onto a standard brain-space. We found that all subjects recognized happy expressions normally but that some subjects were impaired in recognizing negative emotions, especially fear and sadness. The cortical surface regions that best correlated with impaired recognition of emotion were in the right inferior parietal cortex and in the right mesial anterior infracalcarine cortex. We did not find impairments in recognizing any emotion in subjects with lesions restricted to the left hemisphere. These data provide evidence for a neural system important to processing facial expressions of some emotions, involving discrete visual and somatosensory cortical sectors in right hemisphere.

Adult↗
PubMed1998

Reproducibility of fMRI results across four institutions using a spatial working memory task.

Four U.S. sites formed a consortium to conduct a multisite study of fMRI methods. The primary purpose of this consortium was to examine the reliability and reproducibility of fMRI results. FMRI data were collected on healthy adults during performance of a spatial working memory task at four different institutions. Two sets of data from each institution were made available. First, data from two subjects were made available from each site and were processed and analyzed as a pooled data set. Second, statistical maps from five to eight subjects per site were made available. These images were aligned in stereotactic space and common regions of activation were examined to address the reproducibility of fMRI results when both image acquisition and analysis vary as a function of site. Our grouped and individual data analyses showed reliable patterns of activation in dorsolateral prefrontal cortex and posterior parietal cortex during performance of the working memory task across all four sites. This multisite study, the first of its kind using fMRI data, demonstrates highly consistent findings across sites.

Adult↗
PubMed2006

Is neocortex essentially multisensory?

Although sensory perception and neurobiology are traditionally investigated one modality at a time, real world behaviour and perception are driven by the integration of information from multiple sensory sources. Mounting evidence suggests that the neural underpinnings of multisensory integration extend into early sensory processing. This article examines the notion that neocortical operations are essentially multisensory. We first review what is known about multisensory processing in higher-order association cortices and then discuss recent anatomical and physiological findings in presumptive unimodal sensory areas. The pervasiveness of multisensory influences on all levels of cortical processing compels us to reconsider thinking about neural processing in unisensory terms. Indeed, the multisensory nature of most, possibly all, of the neocortex forces us to abandon the notion that the senses ever operate independently during real-world cognition.

Animals↗
PubMed1985

Distribution of mass in relaxed frog skeletal muscle and its redistribution upon activation.

Five orders of equatorial reflection were recorded from both relaxed and fully activated intact frog sartorius muscle using synchrotron x-ray radiation. Electron density maps of the myofilament lattice in axial projection were calculated from the integrated intensities by Fourier synthesis, using all possible phase combinations. These maps were evaluated systematically in terms of their compatibility with electron microscopically and biochemically derived properties of the lattice structure and with the minimum wavelength principle. For the relaxed state, one phase combination emerged as most consistent with these constraints: it shows a thick filament with a compact core surrounded by an annular shell of density. The distribution of mass suggests that the S-2 moiety of the myosin molecule is an integral part of the thick-filament backbone and the S-1 moiety makes up the shell and is tilted or slewed around the backbone. For the active state, there are two feasible maps, which differ according to whether or not the activation process is associated with phase inversion in two of the reflections. Both maps represent patterns of redistribution of mass upon activation in which the thick-filament backbone is practically unaffected and there is movement of density from the annular shell towards the thin filaments. In addition to this outward radial flux of density from the thick-filament periphery, the pattern of net mass transfer involves a pronounced azimuthal component in both cases. The total net mass transfer is equivalent to approximately 20% (no phase change) or approximately 40% (with phase change) of the S-1 mass. From the observed systematic increase in peak widths of the higher orders, the size of the crystalline domain in the myofilament lattice in the relaxed sartorius is estimated to be greater than 650 nm and the variations in myofilament lattice spacing among different myofibrils to be about +/- 3%. Furthermore, in the activated state, the equilibrium positions of the myofilaments are no longer well ordered, but are distributed statistically about the lattice points with a standard deviation of approximately 3 nm.

Animals↗
PubMed1998

An efficient method for correcting the edge artifact due to smoothing.

Spatial smoothing is a common pre-processing step in the analysis of functional brain imaging data. It can increase sensitivity to signals of specific shapes and sizes (Rosenfeld and Kak [1982]: Digital Picture Processing, vol. 2. Orlando, Fla.: Academic; Worsley et al. [1996]: Hum Brain Mapping 4:74-90). Also, some amount of spatial smoothness is required if methods from the theory of Gaussian random fields are to be used (Holmes [1994]: Statistical Issues in Functional Brain Mapping. PhD thesis, University of Glasgow). Smoothing is most often implemented as a convolution of the imaging data with a smoothing kernel, and convolution is most efficiently performed using the Convolution Theorem and the Fast Fourier Transform (Cooley and Tukey [1965]: Math Comput 19:297-301; Priestly [1981]: Spectral Analysis and Time Series. San Diego: Academic; Press et al. [1992]: Numerical Recipes in C: The Art of Scientific Computing, 2nd ed. Cambridge: Cambridge University Press). An undesirable side effect of smoothing is an artifact along the edges of the brain, where brain voxels become smoothed with non-brain voxels. This results in a dark rim which might be mistaken for hypoactivity. In this short methodological paper, we present a method for correcting functional brain images for the edge artifact due to smoothing, while retaining the use of the Convolution Theorem and the Fast Fourier Transform for efficient calculation of convolutions.

Artifacts↗
PubMed2000

Corticocortical connections of visual, sensorimotor, and multimodal processing areas in the parietal lobe of the macaque monkey.

We studied the corticocortical connections of architectonically defined areas of parietal and temporoparietal cortex, with emphasis on areas in the intraparietal sulcus (IPS) that are implicated in visual and somatosensory integration. Retrograde tracers were injected into selected areas of the IPS, superior temporal sulcus, and parietal lobule. The distribution of labeled cells was charted in relation to architectonically defined borders throughout the hemisphere and displayed on computer-generated three-dimensional reconstructions and on cortical flat maps. Injections centered in the ventral intraparietal area (VIP) revealed a complex pattern of inputs from numerous visual, somatosensory, motor, and polysensory areas, and from presumed vestibular- and auditory-related areas. Sensorimotor projections were predominantly from the upper body representations of at least six somatotopically organized areas. In contrast, injections centered in the neighboring ventral lateral intraparietal area (LIPv) revealed inputs mainly from extrastriate visual areas, consistent with previous studies. The pattern of inputs to LIPv largely overlapped those to zone MSTdp, a newly described subdivision of the medial superior temporal area. These results, in conjunction with those from injections into other parietal areas (7a, 7b, and anterior intraparietal area), support the fine-grained architectonic partitioning of cortical areas described in the preceding study. They also support and extend previous evidence for multiple distributed networks that are implicated in multimodal integration, especially with regard to area VIP.

Animals↗
PubMed1983

Rapid resetting of aortic baroreceptors in vitro.

Pressure-response characteristics of arterial baroreceptors (BR) were shown recently to be reset following a 15- to 20-min change in mean arterial pressure (MAP); the curves shifted in the direction of the MAP change. To characterize this rapid BR resetting process more precisely than in vitro studies allow, we utilized an in vitro aortic arch-aortic nerve preparation from Wistar-Kyoto rats. Pressure ramps were used to determine the discharge response curves of single BRs following exposure to precisely controlled conditioning pressures. Rapid resetting occurred in all BRs and followed an exponential time course with a 3- to 5-min time constant. The reset curves were stable for 1 h and were completely reversible. The curves were shifted along the pressure axis in a parallel manner, i.e., pressure threshold (Pth) changed but slope and mean asymptotic discharge were unaltered. In experiments lasting as long as 7 h in which more than two MAP steps were possible, in vitro rapid resetting was a very consistent and reproducible process. Quantitatively, the extent of resetting (delta Pth/delta MAP) averaged 0.33 over an MAP range of 40-160 mmHg. In vitro resetting therefore appears very similar to that observed in vivo, suggesting that the conditioning pressure is the primary, perhaps the sole, determinant of resetting. Resetting occurred at subthreshold MAPs, demonstrating action potentials are not a prerequisite. Efferent neural or hormonal influences are also not required.

Acclimatization↗
PubMed2003

ARTMAP neural networks for information fusion and data mining: map production and target recognition methodologies.

The Sensor Exploitation Group of MIT Lincoln Laboratory incorporated an early version of the ARTMAP neural network as the recognition engine of a hierarchical system for fusion and data mining of registered geospatial images. The Lincoln Lab system has been successfully fielded, but is limited to target/non-target identifications and does not produce whole maps. Procedures defined here extend these capabilities by means of a mapping method that learns to identify and distribute arbitrarily many target classes. This new spatial data mining system is designed particularly to cope with the highly skewed class distributions of typical mapping problems. Specification of canonical algorithms and a benchmark testbed has enabled the evaluation of candidate recognition networks as well as pre- and post-processing and feature selection options. The resulting mapping methodology sets a standard for a variety of spatial data mining tasks. In particular, training pixels are drawn from a region that is spatially distinct from the mapped region, which could feature an output class mix that is substantially different from that of the training set. The system recognition component, default ARTMAP, with its fully specified set of canonical parameter values, has become the a priori system of choice among this family of neural networks for a wide variety of applications.

Computer Simulation↗
PubMed1993

Structure and expression analysis of a member of the human glutamate dehydrogenase (GLUD) gene family mapped to chromosome 10p11.2.

Glutamate dehydrogenase (GLUD) is a key metabolic enzyme of the mitochondrion, playing an important role in mammalian neuronal transmission. GLUD deficiency has been associated with certain forms of neurodegeneration in the human cerebellum. Genomic DNA blot hybridization analysis and identification of a large number of GLUD-specific genomic clones have suggested that human GLUD is encoded by a multigene family consisting of at least six members. A functional GLUD gene, GLUD1, has been mapped to chromosome 10q22.3-23 and a full-length "processed" GLUD gene, GLUDP1, to chromosome Xq22-23. In the context of studing the structure, the role, and the chromosomal organization of the other family members, we have analysed in detail, a cosmid clone solely reactive with the 3' region of the GLUD cDNA. Structure and expression analysis of its GLUD-specific region suggests that it represents a truncated "processed" GLUD pseudogene. Fluorescence in situ hybridization using the entire cosmid as a probe, mapped this GLUD gene locus, termed GLUDP5, to chromosome 10p11.2.

Amino Acid Sequence↗
PubMed2004

Cortical processing of complex sound: a way forward?

The organization of the cortical auditory system remains controversial. In particular, the extent to which there is regional specialization in the cortical processing of complex sound is unclear. Here, we ask whether we are currently asking the right questions of auditory cortex, or using the appropriate techniques to do so. A key factor that will promote such understanding in the future will be increasing dialogue between workers using electrophysiological recording methods to assess the response properties of single neurons and those using imaging techniques to map regional organization. In the future, further insights will be obtained by efforts to test hypotheses developed on the basis of one approach by the use of the other. Imaging can tell the neurophysiologists where to look, and work on single neurons can constrain network models based on imaging. There is a crucial need for better understanding of the anatomy of the auditory cortex in different species and for comparative studies that will underpin both approaches.

Acoustic Stimulation↗
PubMed2005

The human hippocampus: cognitive maps or relational memory?

The hippocampus is widely accepted to play a pivotal role in memory. Two influential theories offer competing accounts of its fundamental operating mechanism. The cognitive map theory posits a special role in mapping large-scale space, whereas the relational theory argues it supports amodal relational processing. Here, we pit the two theories against each other using a novel paradigm in which the relational processing involved in navigating in a city was matched with similar navigational and relational processing demands in a nonspatial (social) domain. During functional magnetic resonance imaging, participants determined the optimal route either between friends' homes or between the friends themselves using social connections. Separate brain networks were engaged preferentially during the two tasks, with hippocampal activation driven only by spatial relational processing. We conclude that the human hippocampus appears to have a bias toward the processing of spatial relationships, in accordance with the cognitive map theory. Our results both advance our understanding of the nature of the hippocampal contribution to memory and provide insights into how social networks are instantiated at the neural level.

Adult↗
PubMed2006

Phylogenetic mapping of recombination hotspots in human immunodeficiency virus via spatially smoothed change-point processes.

We present a Bayesian framework for inferring spatial preferences of recombination from multiple putative recombinant nucleotide sequences. Phylogenetic recombination detection has been an active area of research for the last 15 years. However, only recently attempts to summarize information from several instances of recombination have been made. We propose a hierarchical model that allows for simultaneous inference of recombination breakpoint locations and spatial variation in recombination frequency. The dual multiple change-point model for phylogenetic recombination detection resides at the lowest level of our hierarchy under the umbrella of a common prior on breakpoint locations. The hierarchical prior allows for information about spatial preferences of recombination to be shared among individual data sets. To overcome the sparseness of breakpoint data, dictated by the modest number of available recombinant sequences, we a priori impose a biologically relevant correlation structure on recombination location log odds via a Gaussian Markov random field hyperprior. To examine the capabilities of our model to recover spatial variation in recombination frequency, we simulate recombination from a predefined distribution of breakpoint locations. We then proceed with the analysis of 42 human immunodeficiency virus (HIV) intersubtype gag recombinants and identify a putative recombination hotspot.

Animals↗
PubMed1998

Molecular cloning and characterization of a highly conserved human 67-kDa laminin receptor pseudogene mapping to Xq21.3.

A highly conserved laminin receptor processed pseudogene (LAMRL5) that has been isolated from a fetal brain cDNA library is described. The pseudogene is a complete copy (97.9% identical) of the transcribed laminin receptor (LAMR1) with all the introns precisely removed. The sequence has direct repeats of 18 bp at either end. It has an 885 nucleotide open reading frame from the start methionine codon to the stop codon that contains no deletions, additions or premature stop codons relative to the expressed LAMR1 gene and has the coding potential for a protein of 295 amino acids. Although TATA and CAAT boxes exist in the region 5' to the open reading frame and a polyadenylation signal is present in the 3' region, no evidence could be obtained either by reverse transcriptase-polymerase chain reaction (RT-PCR) or in the expressed sequence tag (EST) database that LAMRL5 is expressed in vivo. If not expressed, it is estimated that this LAMRL5 pseudogene was incorporated into the human genome approximately 3.5-5 million years ago.

Amino Acid Sequence↗
PubMed2006

A guide to the genetics of psychiatric disease.

The road to scientific discovery begins with an awareness of what is unknown. Research in science can in some ways be like putting together the pieces of a puzzle without having the benefit of the box-top picture of the completed puzzle. The "picture" in science is an understanding of how nature works in a particular instance, and it takes many separate pieces of the "puzzle" to put this understanding together. These pieces are always of different kinds of data, often obtained using different approaches and techniques. The challenge of the researcher is to picture or hypothesize each of the missing pieces before actually having them in hand, so they can be sought and tested in the laboratory. This "picturing" is actually having a clear idea of what you don't know: having a clear image of the "shape" of the missing piece. This is easy when the puzzle surrounding the missing piece is already in hand, but more difficult with less of it constrained by what is already known. In putting paper puzzles together, the shape of the pieces is not the only limitation that needs to be satisfied. There is also the picture to satisfy, that is, the picture usually has to make sense. In science these constraints can be manifold, and usually the quality of the research is judged by the number of ways a piece of data integrates into and brings together the rest of the puzzle. The multidimensionality of scientific questions makes it virtually essential that as many different pieces of the puzzle as possible be obtained. The more that is not known about the puzzle, the more pieces you need. Thus it is with the genetics of psychiatric diseases. In this guide, we will explore as many of the domains of the genetic puzzle as we are aware of. We will learn a bit of the language of each and how they fit into the puzzle with at least one anecdote to serve as an example. Mapping unknown territory is always a process, but we hope this guide will increase the reader's awareness of what is unknown.

Alzheimer Disease↗
PubMed1993

Physical mapping of stable RNA genes in Bacillus subtilis using polymerase chain reaction amplification from a yeast artificial chromosome library.

A new approach for mapping genes which utilizes yeast artificial chromosome clones carrying parts of the Bacillus subtilis genome and the polymerase chain reaction technique is described. This approach was used to physically map stable RNA genes of B. subtilis. Results from over 400 polymerase chain reactions carried out with the yeast artificial chromosome clone library, using primers specific for the genes of interest and designed from published sequences, were collected. The locations of 10 known rRNA gene regions (rrnO, rrnA, rrnE, rrnD, rrnB, rrnJ-rrnW, and rrnI-rrnH-rrnG) have been determined by this method, and these results correlate with those observed by standard genetic mapping. All rRNA operons, except rrnB, are found between 0 and 90 degrees, while rrnB has been placed in the area of 270 degrees on the chromosome map. Also localized were the tRNA gene clusters associated with the following ribosomal operons: rrnB (21 tRNAs), rrnJ (9 tRNAs), rrnD (16 tRNAs), and rrnO and rrnA (2 internal tRNAs). A previously unmapped four-tRNA gene cluster, trnY, a tRNA gene region that is not associated with a ribosomal operon, was found near the origin of replication. The P-RNA gene, important for processing of tRNAs, was found between map locations 197 and 204 degrees.

Bacillus subtilis↗
PubMed1997

High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice.

Changes in cortical activity during working memory tasks were examined with electroencephalograms (EEGs) sampled from 115 channels and spatially sharpened with magnetic resonance imaging (MRI)-based finite element deblurring. Eight subjects performed tasks requiring comparison of each stimulus to a preceding one on verbal or spatial attributes. A frontal midline theta rhythm increased in magnitude with increased memory load. Dipole models localized this signal to the region of the anterior cingulate cortex. A slow (low-frequency), parietocentral, alpha signal decreased with increased working memory load. These signals were insensitive to the type of stimulus attribute being processed. A faster (higher-frequency), occipitoparietal, alpha signal was relatively attenuated in the spatial version of the task, especially over the posterior right hemisphere. Theta and alpha signals increased, and overt performance improved, after practice on the tasks. Increases in theta with both increased task difficulty and with practice suggests that focusing attention required more effort after an extended test session. Decreased alpha in the difficult tasks indicates that this signal is inversely related to the amount of cortical resources allocated to task performance. Practice-related increases in alpha suggest that fewer cortical resources are required after skill development. These results serve: (i) to dissociate the effects of task difficulty and practice; (ii) to differentiate the involvement of posterior cortex in spatial versus verbal tasks; (iii) to localize frontal midline theta to the anteromedial cortex; and (iv) to demonstrate the feasibility of using anatomical MRIs to remove the blurring effect of the skull and scalp from the ongoing EEG. The results are discussed with respect to those obtained in a prior study of transient evoked potentials during working memory.

Adult↗
PubMed2002

Large-deviation functions for nonlinear functionals of a Gaussian stationary Markov process.

We introduce a general method, based on a mapping onto quantum mechanics, for investigating the large-T limit of the distribution P(r,T) of the nonlinear functional r[V]=(1/T)integral(T)(0)dT' V[X(T')], where V(X) is an arbitrary function of the stationary Gaussian Markov process X(T). For T-->infinity at fixed r we obtain P(r,T) approximately exp[-theta(r)T], where theta(r) is a large-deviation function. We present explicit results for a number of special cases including V(X)=XH(X) [where H(X) is the Heaviside function], which is related to the cooling and the heating degree days relevant to weather derivatives.

Journal Article↗