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L M Parsons

Publications and source records attributed to L M Parsons.

At least 37 records · Page 2Linked to original sources

Functional volumes modeling: scaling for group size in averaged images.

Functional volumes modeling (FVM) is a statistical construct for metanalytic modeling of the locations of brain functional areas as spatial probability distributions. FV models have a variety of applications, in particular, to serve as spatially explicit predictions of the Talairach-space locations of functional activations, thereby allowing voxel-based analyses to be hypothesis testing rather than hypothesis generating. As image averaging is often applied in the analysis of functional images, an important feature of FVM is that a model can be scaled to accommodate any degree of intersubject image averaging in the data set to which the model is applied. In this report, the group-size scaling properties of FVM were tested. This was done by: (1) scaling a previously constructed FV model of the mouth representation of primary motor cortex (M1-mouth) to accommodate various degrees of averaging (number of subjects per image = n = 1, 2, 5, 10), and (2) comparing FVM-predicted spatial probability contours to location-distributions observed in averaged images of varying n composed from randomly sampling a 30-subject validation data set.

Brain Mapping↗

Interregional connectivity to primary motor cortex revealed using MRI resting state images.

The topographic organization of cortical neurons is traditionally examined using histological procedures. Functional magnetic resonance imaging (fMRI) offers the potential noninvasively to detect interregional connectivity of human brain. In the brain, there is spontaneous firing of neurons even in the resting state. Such spontaneous firing will increase local blood flow, cause MRI signal fluctuations, and affect remotely located neurons through the efferent output. By calculating covariance of each voxel referenced to the time course of a selected brain region, it is possible to detect the neurons connected to the selected region. Using this covariance method, neural connectivity to primary motor cortex was assessed during a resting state in six healthy right-handed volunteers. This interregional connectivity is similar to connectivity established by other anatomical, histochemical, and physiological techniques. This method may offer in vivo noninvasive measurements of neural projections.

Adult↗

Cerebrally lateralized mental representations of hand shape and movement.

Previous psychophysical and neuroimaging studies suggest that perceiving the handedness of a visually presented hand depends on sensorimotor processes that are specific to the limb of the stimulus and that may be controlled by the cerebral hemisphere contralateral to the limb. Therefore, it was hypothesized that disconnection between cerebral hemispheres would disrupt mental simulation of a hand presented to the ipsilateral, but not the contralateral, hemisphere. This hypothesis was examined by the present study in which two callosotomy patients and eight healthy controls judged the handedness of drawings of left and right hands in various positions, without moving or inspecting their own hands. Stimuli were presented for 150 msec in the right or left visual hemifield. As predicted, for each hemisphere, patients' accuracy was high when the hand was contralateral to the perceiving hemisphere, but it was not above chance when it was ipsilateral to the perceiving hemisphere. Controls' accuracy was high in both conditions. Response time analyses indicate patients, like controls, mentally simulated reaching into stimulus postures. When the stimulus laterality was ipsilateral to the perceiving hemisphere, patients imagined the hand contralateral to the perceiving hemisphere reaching into the stimulus posture but did not detect the mismatch, guessing with a response bias or responding on the basis of shape similarity. We conclude that each hemisphere could represent the shape and movement of the contralateral hand but could not for the ipsilateral hand. Mentally simulating one's action and discriminating body part handedness both depend on lateralized sensorimotor and somatosensory representations.

Adult↗

Beyond the single study: function/location metanalysis in cognitive neuroimaging.

Cognitive neuroimaging maps the brain locations of mental operations. This process is iterative, as no single study can fully characterize a mental operation or its brain location. This iterative discovery process, in combination with the location-reporting standard (i.e. spatial coordinates) of the cognitive neuroimaging community, has engendered a new form of metanalysis. Response locations from multiple studies have been analyzed collectively so as to better describe the spatial distribution of brain activations, with promising results. New hypotheses regarding elementary mental operations and their respective brain locations are being generated and refined via metanalysis. These hypotheses are being tested and confirmed by subsequent, prospective experiments. Function/location metanalysis is an important new tool for hypothesis generation in cognitive neuroimaging. This form of metanalysis is fundamentally different from the effect-size metanalyses prevalent in other literatures, with unique advantages and challenges.

Brain Mapping↗

Conjugal transfer of chromosomal DNA in Mycobacterium smegmatis.

The genus Mycobacterium includes the major human pathogens Mycobacterium tuberculosis and Mycobacterium leprae. The development of rational drug treatments for the diseases caused by these and other mycobacteria requires the establishment of basic molecular techniques to determine the genetic basis of pathogenesis and drug resistance. To date, the ability to manipulate and move DNA between mycobacterial strains has relied on the processes of transformation and transduction. Here, we describe a naturally occurring conjugation system present in Mycobacterium smegmatis, which we anticipate will further facilitate the ability to manipulate the mycobacterial genome. Our data rule out transduction and transformation as possible mechanisms of gene transfer in this system and are most consistent with conjugal transfer. We show that recombinants are not the result of cell fusion and that transfer occurs from a distinct donor to a recipient. One of the donor strains is mc(2)155, a highly transformable derivative that is considered the prototype laboratory strain for mycobacterial genetics; the demonstration that it is conjugative should increase its genetic manipulability dramatically. During conjugation, extensive regions of chromosomal DNA are transferred into the recipient and then integrated into the recipient chromosome by multiple recombination events. We propose that DNA transfer is occurring by a mechanism similar to Hfr conjugation in Escherichia coli.

Conjugation, Genetic↗

Sensory and cognitive functions.

New neuroimaging studies provide striking evidence that the cerebellum is intensely and selectively active during sensory and cognitive tasks, even in the absence of explicit or implicit motor behavior. Focal activity is observed in the lateral cerebellar hemispheres during the processing of auditory, visual, cutaneous, spatial, and tactile information, and in anterior-medial cerebellar regions during somatomotor behavior. Moreover, a double dissociation exists between (a) cerebellar activity and sensory processing and (b) motor behavior and activity in known motor areas in the cerebral cortex. These findings contradict the classical motor coordination theory of cerebellar function but are predicted by, or are at least consistent with, new alternative theories.

Animals↗

Drug resistance in tuberculosis.

Drug-resistant tuberculosis remains a worldwide problem. New laboratory methods have improved our ability to more rapidly identify resistant strains, but the most effective approach is to prevent the appearance of resistance by appropriate choice of antibiotics and directly-observed therapy. Mycobacterium tuberculosis is treated with familiar and unique drugs; consequently, mechanisms of resistance have some unique features. All drug resistance thus far identified develops by mutational events rather than acquisition of resistance genes from other bacteria. An agenda is presented for countering the appearance of further drug resistance in mycobacteria.

Anti-Bacterial Agents↗

Alterations in levels of DnaK and GroEL result in diminished survival and adherence of stressed Haemophilus ducreyi.

Haemophilus ducreyi is a hemin-requiring bacterium causing the genital ulcer disease chancroid. Previously we demonstrated that the heat shock protein GroEL was immunogenic and possibly highly expressed in a mammalian host. The present study was initiated to (i) determine the relative amounts of GroEL expressed by H. ducreyi during in vitro exposure to stresses and (ii) evaluate whether a high level of GroEL is directly or indirectly required for survival and adherence of stressed H. ducreyi. Using scanning densitometry of sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles, we found that H. ducreyi expressed high basal levels of GroEL, averaging fivefold greater than in Escherichia coli. These high GroEL levels increased up to twofold upon exposure of the organism to heat shock or high levels of hydrogen peroxide and during adherence to two human genital cell lines. Furthermore, when the gene for DnaK was present on a multicopy plasmid in H. ducreyi, a 1.8-fold increase in DnaK and a 2.3-fold reduction in GroEL were seen. These results suggest that DnaK serves as a negative modulator of H. ducreyi GroEL. Subsequently we found that H. ducreyi with lower GroEL had diminished ability to survive when challenged by heat and oxidative stresses. In addition, the long, parallel chains characteristic of virulent strains of H. ducreyi were absent when GroEL was lowered, so that fewer bacterial cells adhered to the human cells. These results suggest that the unusually high basal levels of GroEL are involved, either directly or indirectly, in the survival, chaining, and adherence of H. ducreyi in the presence of the combined stresses of the host environment.

Bacterial Adhesion↗

Cerebellum implicated in sensory acquisition and discrimination rather than motor control.

Recent evidence that the cerebellum is involved in perception and cognition challenges the prevailing view that its primary function is fine motor control. A new alternative hypothesis is that the lateral cerebellum is not activated by the control of movement per se, but is strongly engaged during the acquisition and discrimination of sensory information. Magnetic resonance imaging of the lateral cerebellar output (dentate) nucleus during passive and active sensory tasks confirmed this hypothesis. These findings suggest that the lateral cerebellum may be active during motor, perceptual, and cognitive performances specifically because of the requirement to process sensory data.

Adult↗

Mesoderm-specific expression of the divergent homeobox gene Hlx during murine embryogenesis.

We have determined the expression pattern of the divergent homeobox gene Hlx during post-implantation mouse development, utilizing in situ hybridization. Expression was mesoderm-specific and occurred in a complex tissue distribution. Transcripts were first detected at 9.5 days post coitum (p.c.) in splanchnic mesoderm of the midgut and hindgut region, then during organogenesis, prominently in mesenchyme of the developing liver, gall bladder, and intestines, as well as their mesenteric tissues. In the foregut, lung mesenchyme became positive from 10.5 days p.c. Hlx transcripts were also detected in a subset of skeletal myogenic cells: those within branchial arches from 9.5 days p.c. and within limb buds from 12 days p.c. Hlx was not expressed in myogenic cells which are derived from the myotome and populate the trunk. However, from 10 days p.c., expression was seen in a region of the sclerotome immediately adjacent to the myotome and corresponding to precursors of the ribs and vertebral neural arches. In the anterior-posterior aspect of the developing sclerotome, Hlx expression was out of register with original segmental boundaries (intersomitic fissures), a pattern consistent with a classical hypothesis that the developing vertebral column undergoes resegmentation. Hlx expression was also observed in vibrissae, pericardium, snout mesenchyme, and meningeal epithelium. Overall, expression of Hlx in only a subset of individual lineage progenitors and at know sites of inductive tissue interactions, suggests that the gene regulates local patterning or growth through cell:cell signalling at those embryonic sites.

Animals↗

Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5.

The murine homeo box gene Nkx2-5 is expressed in precardiac mesoderm and in the myocardium of embryonic and fetal hearts. Targeted interruption of Nkx2-5 resulted in abnormal heart morphogenesis, growth retardation and embryonic lethality at approximately 9-10 days postcoitum (p.c.). Heart tube formation occurred normally in mutant embryos, but looping morphogenesis, a critical determinant of heart form, was not initiated at the linear heart tube stage (8.25-8.5 days p.c.). Commitment to the cardiac muscle lineage, expression of most myofilament genes and myofibrillogenesis were not compromised. However, the myosin light-chain 2V gene (MLC2V) was not expressed in mutant hearts nor in mutant ES cell-derived cardiocytes. MLC2V expression normally occurs only in ventricular cells and is the earliest known molecular marker of ventricular differentiation. The regional expression in mutant hearts of two other ventricular markers, myosin heavy-chain beta and cyclin D2, indicated that not all ventricle-specific gene expression is dependent on Nkx2-5. The data demonstrate that Nkx2-5 is essential for normal heart morphogenesis, myogenesis, and function. Furthermore, this gene is a component of a genetic pathway required for myogenic specialization of the ventricles.

Animals↗

Use of implicit motor imagery for visual shape discrimination as revealed by PET.

Positron emission tomography (PET) can be used to map brain regions that are active when a visual object (for example, a hand) is discriminated from its mirror form. Chronometric studies suggest that viewers 'solve' this visual shape task by mentally modelling it as a reaching task, implicitly moving their left hand into the orientation of any left-hand stimulus (and conversely for a right-hand stimulus). Here we describe an experiment in which visual and somatic processing are dissociated by presenting right hands to the left visual field and vice versa. Frontal (motor), parietal (somatosensory) and cerebellar (sensorimotor) regions similar to those activated by actual and imagined movement are strongly activated, whereas primary somatosensory and motor cortices are not. We conclude that mental imagery is realized at intermediate-to-high order, modality-specific cortical systems, but does not require primary cortex and is not constrained to the perceptual systems of the presented stimuli.

Adult↗

Laboratory diagnosis of chancroid using species-specific primers from Haemophilus ducreyi groEL and the polymerase chain reaction.

To enhance laboratory identification of Haemophilus ducreyi, the causative agent of the genital ulcer disease chancroid, a polymerase chain reaction (PCR) assay was developed using target DNA sequences from the essential H. ducreyi gene, groEL. Positive reactions were obtained in this PCR assay with 139 isolates of H. ducreyi from patients in worldwide locations from the 1940s to the 1990s. In contrast, 24 other bacterial species were negative. When genital ulcer specimens from 162 African patients with clinically diagnosed chancroid were evaluated, 66 were culture positive. The sensitivity of PCR as compared with culture was 89% (59 of 66), and specificity was 79% (76 of 96). However, representative samples of the 20 culture-negative, PCR-positive specimens were confirmed as positive by a second PCR assay using different H. ducreyi-specific primers. Thus, combined results of culture and PCR detected H. ducreyi in 86 specimens, with resolved sensitivities of 92% (79 of 86) for PCR, and 77% (66 of 86) for culture. These results suggest that PCR assays for H. ducreyi have great potential for augmenting or replacing problematic cultural techniques.

Bacterial Proteins↗

Temporal and kinematic properties of motor behavior reflected in mentally simulated action.

Related perceptual, motor, and cognitive performances were examined to reveal the accuracy of the properties of action spontaneously represented when mentally simulating moving one's hand. The kinematic configuration of the body represented and transformed in mental simulations was not fixed or canonical but corresponded to one's current configuration. Mental simulation time mimicked movement time for natural efficient movement from a posture midway between each of the hand's joint limits into many other postures. Equal time was required for simulated and real movements into more common, comfortable postures; shorter but proportional time was required for simulated movement than real movement into less common postures that involved longer trajectories, coordinated activity at more joints, motion near extremes of joint limits, and uncomfortable kinesthetic sensations. The findings suggest that sensorimotor structures support mental simulations of actions.

Functional Laterality↗

Effect of amitriptyline on neurotransmitter levels in adult mice following infection with the avirulent strain of Semliki Forest virus.

Infection of adult mice with the avirulent strain of Semliki Forest virus (SFV) led to neurochemical abnormalities, notably depressed levels of catecholamines (CATs) such as noradrenaline (NA), adrenaline (A) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (a metabolite of NA) particularly in the hypothalamus and the inferior colliculus but not in the temporal cortex. In addition, depressed levels of NA and A were also found in the cerebrospinal fluid (CSF) and the serum. Administration of a tricyclic antidepressant drug, amitriptyline, kept the levels of NA, A and MHPG similar to those of the saline-treated control mice in the hypothalamus, inferior colliculus and CSF.

Amitriptyline↗

Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants.

We have isolated two murine homeobox genes, Nkx-2.5 and Nkx-2.6, that are new members of a sp sub-family of homeobox genes related to Drosophila NK2, NK3 and NK4/msh-2. In this paper, we focus on the Nkx-2.5 gene and its expression pattern during post-implantation development. Nkx-2.5 transcripts are first detected at early headfold stages in myocardiogenic progenitor cells. Expression preceeds the onset of myogenic differentiation, and continues in cardiomyocytes of embryonic, foetal and adult hearts. Transcripts are also detected in future pharyngeal endoderm, the tissue believed to produce the heart inducer. Expression in endoderm is only found laterally, where it is in direct apposition to promyocardium, suggesting an interaction between the two tissues. After foregut closure, Nkx-2.5 expression in endoderm is limited to the pharyngeal floor, dorsal to the developing heart tube. The thyroid primordium, a derivative of the pharyngeal floor, continues to express Nkx-2.5 after transcript levels diminish in the rest of the pharynx. Nkx-2.5 transcripts are also detected in lingual muscle, spleen and stomach. The expression data implicate Nkx-2.5 in commitment to and/or differentiation of the myocardial lineage. The data further demonstrate that cardiogenic progenitors can be distinguished at a molecular level by late gastrulation. Nkx-2.5 expression will therefore be a valuable marker in the analysis of mesoderm development and an early entry point for dissection of the molecular basis of myogenesis in the heart.

Amino Acid Sequence↗

Identification of functional regions of the positively acting regulatory gene amdR from Aspergillus nidulans.

The amdR (intA) regulatory gene of Aspergillus nidulans encodes a 765-amino-acid polypeptide which determines the omega-amino acid induction of at least five structural genes. The AmdR polypeptide contains a potential Zn(II)2Cys6 DNA-binding motif which has been shown to be present in the N-terminal region of a large number of fungal activator proteins. In vitro mutagenesis of the fourth cysteine of this motif abolishes AmdR function as shown by loss of complementation of an amdR- mutation and by the AmdR- phenotype of a mutant gene replacement strain. Studies using constructs in which the proposed AmdR DNA-binding motif is replaced with that from another activator, FacB, shows that induction is independent of DNA-binding specificity and that sequences in the C-terminal region of AmdR are activation domains. Sequencing of several amdR mutant alleles which affect activation and/or induction, together with studies of deletion constructs indicate that changes in the conformation of the protein determines its activity and that this is modulated by inducers.

Aspergillus nidulans↗