Identifying rate-limiting nodes in large-scale cortical networks for visuospatial processing: an illustration using fMRI

With the advent of functional neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), we have gained greater insight into the neural correlates of visuospatial function. However, it may not always be easy to identify the cerebral regions most specifically associated with performance on a given task. One approach is to examine the quantitative relationships between regional activation and behavioral performance measures. In the present study, we investigated the functional neuroanatomy of two different visuospatial processing tasks, judgement of line orientation and mental rotation. Twenty-four normal participants were scanned with fMRI using blocked periodic designs for experimental task presentation. Accuracy and reaction time (RT) to each trial of both activation and baseline conditions in each experiment was recorded. Both experiments activated dorsal and ventral visual cortical areas as well as dorsolateral prefrontal cortex. More regionally specific associations with task performance were identified by estimating the association between (sinusoidal) power of functional response and mean RT to the activation condition; a permutation test based on spatial statistics was used for inference. There was significant behavioral-physiological association in right ventral extrastriate cortex for the line orientation task and in bilateral (predominantly right) superior parietal lobule for the mental rotation task. Comparable associations were not found between power of response and RT to the baseline conditions of the tasks. These data suggest that one region in a neurocognitive network may be most strongly associated with behavioral performance and this may be regarded as the computationally least efficient or rate-limiting node of the network.

Estimating HIV incidence rates from age prevalence data in epidemic situations

We present a method of estimating HIV incidence rates in epidemic situations from data on age-specific prevalence and changes in the overall prevalence over time. The method is applied to women attending antenatal clinics in Hlabisa, a rural district of KwaZulu/Natal, South Africa, where transmission of HIV is overwhelmingly through heterosexual contact. A model which gives age-specific prevalence rates in the presence of a progressing epidemic is fitted to prevalence data for 1998 using maximum likelihood methods and used to derive the age-specific incidence. Error estimates are obtained using a Monte Carlo procedure. Although the method is quite general some simplifying assumptions are made concerning the form of the risk function and sensitivity analyses are performed to explore the importance of these assumptions. The analysis shows that in 1998 the annual incidence of infection per susceptible woman increased from 5.4 per cent (3.3-8.5 per cent; here and elsewhere ranges give 95 per cent confidence limits) at age 15 years to 24.5 per cent (20.6-29.1 per cent) at age 22 years and declined to 1.3 per cent (0.5-2.9 per cent) at age 50 years; standardized to a uniform age distribution, the overall incidence per susceptible woman aged 15 to 59 was 11.4 per cent (10.0-13.1 per cent); per women in the population it was 8.4 per cent (7.3-9.5 per cent). Standardized to the age distribution of the female population the average incidence per woman was 9.6 per cent (8.4-11.0 per cent); standardized to the age distribution of women attending antenatal clinics, it was 11.3 per cent (9.8-13.3 per cent). The estimated incidence depends on the values used for the epidemic growth rate and the AIDS related mortality. To ensure that, for this population, errors in these two parameters change the age specific estimates of the annual incidence by less than the standard deviation of the estimates of the age specific incidence, the AIDS related mortality should be known to within +/-50 per cent and the epidemic growth rate to within +/-25 per cent, both of which conditions are met. In the absence of cohort studies to measure the incidence of HIV infection directly, useful estimates of the age-specific incidence can be obtained from cross-sectional, age-specific prevalence data and repeat cross-sectional data on the overall prevalence of HIV infection. Several assumptions were made because of the lack of data but sensitivity analyses show that they are unlikely to affect the overall estimates significantly. These estimates are important in assessing the magnitude of the public health problem, for designing vaccine trials and for evaluating the impact of interventions. Copyright (C) 2001 John Wiley & Sons, Ltd.

Change in the rate of shell deposition and shell microstructure in response to shell borers in the abalone Haliotis rubra

Gastropod shells consist of two crystal types of calcium carbonate, an outer, prismatic calcite layer and an inner nacreous layer made of aragonite. In cross-section, the nacre of the nacreous layer appears to have a regular brick-like microstructure composed of thin laminae of aragonite crystals, separated by very thin sheets of protein (Lutz and Rhoads, 1980; Nakahara, 1983). In abalone (Genus, Haliotis) and other gastropods, thin layers of non-lamellar pigmented material occur within the nacre and have been termed alternatively, fine lines, growth rings or growth lines (Shepherd et al., 1995). It has been suggested that these pigmented layers are small, prismatic, calcite layers (Shepherd and Avalos-Borja, 1997; Zaremba et al., 1996) but investigations using a Raman laser in Haliotis rubra show that they contain aragonite rather than calcite (Hawkes et al, 1996). Day and Fleming (1992) suggest that the occurrence of pigmented layers is correlated with regular exogenous cues such as reproduction or temperature changes and indeed in some species, pigmented layers in the shell can be used to age abalone (review: Shepherd and Triantafillos, 1997). However, McShane and Smith (1992) suggest that pigmented layers can occur irregularly and therefore may be unreliable indicators of age.

Altered kinetics and benzodiazepine sensitivity of a GABA(A) receptor subunit mutation [gamma(2)(R43Q)] found in human epilepsy

The gamma-aminobutyric acid type A (GABA(A)) receptor mediates fast inhibitory synaptic transmission in the CNS. Dysfunction of the GABA(A) receptor would be expected to cause neuronal hyperexcitability, a phenomenon linked with epileptogenesis. We have investigated the functional consequences of an arginine-to-glutamine mutation at position 43 within the GABA(A) gamma(2)-subunit found in a family with childhood absence epilepsy and febrile seizures. Rapid-application experiments performed on receptors expressed in HEK-293 cells demonstrated that the mutation slows GABA(A) receptor deactivation and increases the rate of desensitization, resulting in an accumulation of desensitized receptors during repeated, short applications. In Xenopus laevis oocytes, two-electrode voltage-clamp analysis of steady-state currents obtained from alpha(1)beta(2)gamma(2) or alpha(1)beta(2)gamma(2)(R43Q) receptors did not reveal any differences in GABA sensitivity. However, differences in the benzodiazepine pharmacology of mutant receptors were apparent. Mutant receptors expressed in oocytes displayed reduced sensitivity to diazepam and flunitrazepam but not the imiclazopyricline zolpidem. These results provide evidence of impaired GABA(A) receptor function that could decrease the efficacy of transmission at inhibitory synapses, possibly generating a hyperexcitable neuronal state in thalamocortical networks of epileptic patients possessing the mutant subunit.

The role of dogs in transmission of gastrointestinal parasites in a remote tea-growing community in northeastern India

The prevalence and risk factors associated with canine gastrointestinal parasitic zoonoses and the role of dogs in the mechanical transmission of human Ascaris infection was examined in three tea estates in Assam, India. Nearly all (99%) dogs harbored one or more zoonotic species of gastrointestinal parasites, with hookworm infection being most common (94%). Parasitic stages presumed to be host-specific for humans such as Ascaris spp. (31%), Trichuris trichiura (25%), and Isospora belli (2%) were also recovered from dog feces. A polymerase chain reaction-linked restriction fragment length polymorphism technique was used to differentiate the species of Ascaris eggs in dog feces. The results of this study demonstrate the role of the dog as a significant disseminator and environmental contaminator of Ascaris lumbricoides in communities where promiscuous defecation by humans occurs.

Excitatory synaptic transmission in the lateral and central amygdala

The amygdala plays a major role in the acquisition and expression of fear conditioning. NMDA receptor-dependent synaptic plasticity within the basolateral amygdala has been proposed to underlie the acquisition and possible storage of fear memories. Here the properties of fast glutamatergic transmission in the lateral and central nuclei of the amygdala are presented. In the lateral amygdala, two types of neurons, interneurons and projection neurons, could be distinguished by their different firing properties. Glutamatergic inputs to interneurons activated AMPA receptors with inwardly rectifying current-voltage relations (I-Vs), whereas inputs to projection neurons activated receptors that had linear I-Vs, indicating that receptors on interneurons lack GluR2 subunits. Inputs to projection neurons formed dual component synapses with both AMPA and NMDA components, whereas at inputs to interneurons, the contribution of NMDA receptors was very small. Neurons in the central amygdala received dual component glutamatergic inputs that activated AMPA receptors with linear I-Vs. NMDA receptor-mediated EPSCs had slow decay time constants in the central nucleus. Application of NR2B selective blockers ifenprodil or CP-101,606 blocked NMDA EPSCs by 70% in the central nucleus, but only by 30% in the lateral nucleus. These data show that the distribution of glutamatergic receptors on amygdalar neurons is not uniform. In the lateral amygdala, interneurons and pyramidal neurons express AMPA receptors with different subunit compositions. Synapses in the central nucleus activate NMDA receptors that contain NR1 and NR2B subunits, whereas synapses in the lateral nucleus contain receptors with both NR2A and NR2B subunits.

Altered inhibitory synaptic transmission in superficial dorsal horn neurones in spastic and oscillator mice

The spastic (spa) and oscillator (ot) mouse have naturally occurring mutations in the inhibitory glycine receptor (GlyR) and exhibit severe motor disturbances when exposed to unexpected sensory stimuli. We examined the effects of the spa and ot mutations on GlyR- and GABA(A)R-mediated synaptic transmission in the superficial dorsal horn (SFDH), a spinal cord region where inhibition is important for nociceptive processing. Spontaneous mIPSCs were recorded from visually identified neurones in parasagittal spinal cord slices. Neurones received exclusively GABA(A)R-mediated mIPSCs, exclusively GlyR-mediated mIPSCs or both types of mIPSCs. In control mice (wild-type and spa/+) over 40 % of neurones received both types of mIPSCs, over 30 % received solely GABA(A)R-mediated mIPSCs and the remainder received solely GlyR-mediated mIPSCs. In spa/spa animals, 97 % of the neurones received exclusively GABA(A)ergic or both types of mIPSCs. In ot/ot animals, over 80 % of the neurones received exclusively GABA(A)R-mediated mIPSCs. GlyR-mediated mIPSC amplitude and charge were reduced in spa/spa and ot/ot animals. GABA,Rmediated mIPSC amplitude and charge were elevated in spa/spa but unaltered in ot/ot animals. GlyR- and GABA(A)R-mediated mIPSC decay times were similar for all genotypes, consistent with the mutations altering receptor numbers but not kinetics. These findings suggest the spastic and oscillator mutations, traditionally considered motor disturbances, also disrupt inhibition in a sensory region associated with nociceptive transmission. Furthermore, the spastic mutation results in a compensatory increase in GABA(A)ergic transmission in SFDH neurones, a form of inhibitory synaptic plasticity absent in the oscillator mouse.

Measuring the decoherence rate in a semiconductor charge qubit

We describe a method by which the decoherence time of a solid-state qubit may be measured. The qubit is coded in the orbital degree of freedom of a single electron bound to a pair of donor impurities in a semiconductor host. The qubit is manipulated by adiabatically varying an external electric field. We show that by measuring the total probability of a successful qubit rotation as a function of the control field parameters, the decoherence rate may be determined. We estimate various system parameters, including the decoherence rates due to electromagnetic fluctuations and acoustic phonons. We find that, for reasonable physical parameters, the experiment is possible with existing technology. In particular, the use of adiabatic control fields implies that the experiment can be performed with control electronics with a time resolution of tens of nanoseconds.

Epidemiological and molecular evidence supports the zoonotic transmission of Glardia among humans and dogs living in the same community

Giardia duodenalis isolates recovered from humans and clogs living in the same locality in a remote tea-growing community of northeast India were characterized at 3 different loci; the SSU-rDNA, elongation factor 1-alpha (ef1-alpha) and triose phosphate isomerase (tpi) gene. Phylogenetic analysis of the SSU-rDNA and ef1-alpha genes provided poor genetic resolution of the isolates within various assemblages, stressing the importance of using multiple loci when inferring genotypes to Giardia. Analysis of the tpi gene provided better genetic resolution and placed canine Giardia isolates within the genetic groupings of human isolates (Assemblages A and B). Further evidence for zoonotic transmission was supported by epidemiological data showing a highly significant association between the prevalence of Giardia in humans and presence of it Giardia-positive dog in the same household (odds ratio 3.01, 95%) CI, 1.11, 8.39, P = 0.0000).

High speed versus conventional grinding in high removal rate machining of alumina and alumina-titania

High removal rate (up to 16.6 mm(3)/s per mm) grinding of alumina and alumina-titania was investigated with respect to material removal and basic grinding parameters using a resin-bond 160 mu m grit diamond wheel at the speeds of 40 and 160 m/s, respectively. The results show that the material removal for the single-phase polycrystalline alumina and the two-phase alumina-titania composite revealed identical mechanisms of microfracture and grain dislodgement under the grinding conditioned selected. There were no distinct differences in surface roughness and morphology for both materials ground at either conventional or high speed. An increase in material removal rate did not necessarily worsen the surface toughness for the two materials at both speeds. Also the grinding forces for the two ceramics demonstrated similar characteristics at any grinding speeds and specific removal rates. Both normal and tangential grinding forces and their force ratios at the high speed were lower than those at the conventional speed, regardless of removal rates. An increase in specific removal rate caused more rapid increases in normal and tangential forces obtained at the conventional grinding speed than those at the high speed. Furthermore, it is found that the high speed grinding at all the removal rates exerted a great amount of coolant-induced normal forces in grinding zone, which were 4-6 times higher than the pure normal grinding forces. (c) 2004 Elsevier Ltd. All rights reserved.

Association between dopamine transporter (DATI) genotype, left-sided inattention, and an enhanced response to methylphenidate in attention-deficit hyperactivity disorder

A polymorphism of the dopamine transporter gene (DAT1, 10-repeat) is associated with attention-deficit hyperactivity disorder (ADHD) and has been linked to an enhanced response to methylphenidate (MPH). One aspect of the attention deficit in ADHD includes a subtle inattention to left space, resembling that seen after right cerebral hemisphere damage. Since left-sided inattention in ADHD may resolve when treated with MPH, we asked whether left-sided inattention in ADHD was related to DAT1 genotype and the therapeutic efficacy of MPH. A total of 43 ADHD children and their parents were genotyped for the DAT1 30 variable number of tandem repeats polymorphism. The children performed the Landmark Test, a well-validated measure yielding a spatial attentional asymmetry index ( leftward to rightward attentional bias). Parents rated their child's response to MPH retrospectively using a three-point scale ( no, mediocre or very good response). Additionally, parents used a symptom checklist to rate behavior while on and off medication. A within-family control design determined whether asymmetry indices predicted biased transmission of 10-repeat parental DAT1 alleles and/or response to MPH. It was found that left-sided inattention predicted transmission of the 10-repeat allele from parents to probands and was associated with the severity of ADHD symptomatology. Children rated as achieving a very good response to MPH displayed left-sided inattention, while those rated as achieving a poorer response did not. Our results suggest a subgroup of children with ADHD for whom the 10-repeat DAT1 allele is associated with left-sided inattention. MPH may be most efficacious in this group because it ameliorates a DAT1-mediated hypodopaminergic state.

Sheep rumen digestion and transmission of weedy Malva parviflora seeds

The effect of sheep digestion and mastication on Malva parviflora L. seed transmission, viability and germination was investigated. Mature M. parviflora seeds were subjected to 2 seed treatments: 'scarified', where the hard seed coat was manually cut to allow inhibition, and 'unscarified', where the hard seed coat was not cut. Seeds were placed directly into the rumen of fistulated sheep and removed at 0, 12, 24, 36 and 48 h of rumen digestion. After 12 h of in sacco exposure to digestion in the rumen, the germination of seeds that were initially scarified dropped from 99.2 to 1.4% and longer exposure periods produced no germinable seeds. In contrast, seeds that were unscarified when placed in the rumen produced over 92% germination regardless of in sacco digestion time, although manual scarification after retrieval was essential to elicit germination. In a second experiment, unscarified seeds (29000) were fed in a single meal to fistulated sheep and feces were collected at regular intervals between 6 and 120 h after feeding. Fecal subsamples were taken to determine number of seeds excreted, seed germination on agar and seed germination from feces. Major seed excretion in the feces commenced after 12 h and continued until 144 h, with peaks between 36 and 72 h after consumption. Although mastication and gut passage killed the majority of unscarified seeds, about 20% were recovered intact and over 90% of these recovered seeds were viable and could, thus, potentially form an extensive seed bank. A few excreted seeds (1%) were able to germinate directly from feces, which increased to a maximum of 10% after subsequent dry summer storage (3 months). Through information gained in this study, there is a potential to utilise livestock in an integrated weed management program for the control of M. parviflora, provided additional measures of weed control are in place such as holding periods (> 7 days) for movement of livestock from weed infested areas.

Structural and electron self-exchange rate variations in isomeric (hexaamine)cobalt(III/II) complexes

The syntheses and characterisation of the new macrocyclic hexaamine trans-(5(S),7(S),12(R),14(R)-tetramethyl)-1,4,8,11-tetraazacyclotetradecane-6,13-diamine (L-6) and its Co-III complex are reported. The X-ray crystal structural analyses of [CoL6]Cl-2(ClO4) [monoclinic, space group C2/c, a = 16.468(3) Angstrom, b = 9.7156(7) Angstrom, c = 15.070(3) Angstrom, beta = 119.431(8)degrees, Z = 4] and the closely related cis-diamino-substituted macrocyclic complex [CoL2](ClO4)(3) . 2H(2)O (L-2 = cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine) [orthorhombic, space group Pna2(1), a = 16.8220(8) Angstrom, b = 10.416(2) Angstrom, c = 14.219(3) Angstrom, Z = 4] reveal significant variations in the observed Co-N bond lengths and coordination geometries, which may be attributed to the trans or cis disposition of the pendent primary amines. The Co-III/II self-exchange electron transfer rate constants for these and other closely related hexaamines have been determined, and variations of some 2 orders of magnitude are found between pairs of trans and cis isomeric Co-III complexes.