BACKGROUND

Theories and frameworks (hereafter called models) enhance dissemination and implementation (D&I) research by making the spread of evidence-based interventions more likely. This work organizes and synthesizes these models by (1) developing an inventory of models used in D&I research; (2) synthesizing this information; and (3) providing guidance on how to select a model to inform study design and execution.

METHODS

This review began with commonly cited models and model developers and used snowball sampling to collect models developed in any year from journal articles, presentations, and books. All models were analyzed and categorized in 2011 based on three author-defined variables: construct flexibility, focus on dissemination and/or implementation activities (D/I), and the socioecologic framework (SEF) level. Five-point scales were used to rate construct flexibility from broad to operational and D/I activities from dissemination-focused to implementation-focused. All SEF levels (system, community, organization, and individual) applicable to a model were also extracted. Models that addressed policy activities were noted.

RESULTS

Sixty-one models were included in this review. Each of the five categories in the construct flexibility and D/I scales had at least four models. Models were distributed across all levels of the SEF; the fewest models (n=8) addressed policy activities. To assist researchers in selecting and utilizing a model throughout the research process, the authors present and explain examples of how models have been used.

CONCLUSIONS

These findings may enable researchers to better identify and select models to inform their D&I work.

Estimates of hemodynamic response functions (HRF) are often integral parts of event-related fMRI analyses. Although HRFs vary across individuals and brain regions, few studies have investigated how variations affect the results of statistical analyses using the general linear model (GLM). In this study, we empirically estimated HRFs from primary motor and visual cortices and frontal and supplementary eye fields (SEF) in 20 subjects. We observed more variability across subjects than regions and correlated variation of time-to-peak values across several pairs of regions. Simulations examined the effects of observed variability on statistical results and ways different experimental designs and statistical models can limit these effects. Widely spaced and rapid event-related experimental designs with two sampling rates were tested. Statistical models compared an empirically derived HRF to a canonical HRF and included the first derivative of the HRF in the GLM. Small differences between the estimated and true HRFs did not cause false negatives, but larger differences within an observed range of variation, such as a 2.5-s time-to-onset misestimate, led to false negatives. Although small errors minimally affected detection of activity, time-to-onset misestimates as small as 1 s influenced model parameter estimation and therefore random effects analyses across subjects. Experiment and analysis design methods such as decreasing the sampling rate or including the HRF's temporal derivative in the GLM improved results, but did not eliminate errors caused by HRF misestimates. These results highlight the benefits of determining the best possible HRF estimate and potential negative consequences of assuming HRF consistency across subjects or brain regions.

612 (93.8%) of 65 Staphylococcus aureus strains isolated from 65 patients with toxic-shock syndrome (TSS) produced an enterotoxin-like protein, tentatively identified as staphylococcal enterotoxin F (SEF). One of the other strains produced staphylococcal enterotoxin B and another exterotoxin C. In two blind studies all 34 TSS-associated S. aureau strains examined and 3 (11.5%) of 26 control S. aureau strains produced SEF. 2 of the latter strains were isolated from the vaginas of women who had no history of TSS. SEF was purified, and specific antibodies to it were prepared. Only 4 (4.6%) of 87 S. aureau strains from other sources were found to produce SEF. 5 (17.2%) of 29 TSS patients whose acute sera were available had anti-SEF antibody present in titres of greater than or equal to 1:100 as determined by radioimmunoassay, compared with 44 (78.6%) of 56 controls--demonstrating a greater serosusceptibility of TSS patients to SEF. It is suggested that staphylococcal enterotoxin, particularly SEF, may be a cause of the signs and symptoms of TSS.

Fibroblast growth factors (FGF) are secreted molecules which function through the activation of specific tyrosine kinases receptors, the FGF receptors that transduce the signal by activating different pathways including the Ras/MAP kinase and the phospholipase-C gamma pathways. FGFs are involved in the regulation of many developmental processes including patterning, morphogenesis, differentiation, cell proliferation or migration. Such a diverse set of activities requires a tight control of the transduction signal which is achieved through the induction of different feedback inhibitors such as the Sproutys, Sef and MAP kinase phosphatase 3 which are responsible for the attenuation of FGF signals, limiting FGF activities in time and space.

During appendage regeneration in urodeles and teleosts, tissue replacement is precisely regulated such that only the appropriate structures are recovered, a phenomenon referred to as positional memory. It is believed that there exists, or is quickly established after amputation, a dynamic gradient of positional information along the proximodistal (PD) axis of the appendage that assigns region-specific instructions to injured tissue. These instructions specify the amount of tissue to regenerate, as well as the rate at which regenerative growth is to occur. A striking theme among many species is that the rate of regeneration is more rapid in proximally amputated appendages compared with distal amputations. However, the underlying molecular regulation is unclear. Here, we identify position-dependent differences in the rate of growth during zebrafish caudal fin regeneration. These growth rates correlate with position-dependent differences in blastemal length, mitotic index and expression of the Fgf target genes mkp3, sef and spry4. To address whether PD differences in amounts of Fgf signaling are responsible for position-dependent blastemal function, we have generated transgenic fish in which Fgf receptor activity can be experimentally manipulated. We find that the level of Fgf signaling exhibits strict control over target gene expression, blastemal proliferation and regenerative growth rate. Our results demonstrate that Fgf signaling defines position-dependent blastemal properties and growth rates for the regenerating zebrafish appendage.

We have identified a conserved sequence segment in transmembrane receptors (including SEFs, IL17Rs) and soluble factors (including CIKS/ACT1) in eukaryotes and bacteria - the SEFIR domain. This sequence domain is part of the new STIR domain superfamily comprising also the TIR domain known to mediate TIR-TIR homotypic interactions. In TOLL/IL1R-like pathways, the cytoplasmically localized TIR domain of a receptor and the TIR domain of a soluble adaptor interact physically and activate signalling. The similarity between the SEFIR and TIR domains involves the conserved boxes 1 and 2 of the TIR domain that are implicated in homotypic dimerization, but there is no sequence similarity between SEFIR domains and the TIR sequence box 3. By analogy, we suggest that SEFIR-domain proteins function as signalling components of Toll/IL-1R-similar pathways and that their SEFIR domain mediates physical protein-protein interactions between pathway components.

Spatiotemporal control of the Ras/ERK MAP kinase signaling pathway is among the key mechanisms for regulating a wide variety of cellular processes. In this study, we report that human Sef (hSef), a recently identified inhibitor whose action mechanism has not been fully defined, acts as a molecular switch for ERK signaling by specifically blocking ERK nuclear translocation without inhibiting its activity in the cytoplasm. Thus, hSef binds to activated forms of MEK, inhibits the dissociation of the MEK-ERK complex, and blocks nuclear translocation of activated ERK. Consequently, hSef inhibits phosphorylation and activation of the nuclear ERK substrate Elk-1, while it does not affect phosphorylation of the cytoplasmic ERK substrate RSK2. Downregulation of endogenous hSef by hSef siRNA enhances the stimulus-induced ERK nuclear translocation and the activity of Elk-1. These results thus demonstrate that hSef acts as a spatial regulator for ERK signaling by targeting ERK to the cytoplasm.

1. The purpose of this study is to define the cortical regions that subserve voluntary saccadic eye movements and spatial working memory in humans. 2. Regional cerebral blood flow (rCBF) during performance of oculomotor tasks was measured with [15O]-H2O positron emission tomography (PET). Eleven well-trained, healthy young adults performed the following tasks: visual fixation, visually guided saccades, antisaccades (a task in which subjects made saccades away from rather than toward peripheral targets), and either an oculomotor delayed response (ODR, a task requiring memory-guided saccades after a delay period) or a conditional antisaccade task (a task in which the color of the peripheral target determined whether a saccade toward or away from the target was required). An additional six subjects performed a sequential hand movement task to compare localization of hand-related motor cortex and the frontal eye fields (FEFs) and of the hand- and eye-movement-related regions of the supplementary motor area (SMA). 3. Friston's statistical parametric mapping (SPM) method was used to identify significant changes in rCBF associated with task performance. Because SPM does not take advantage of the anatomic information available in magnetic resonance (MR) scans, each subject's PET scan was registered to that individual's MR scan, after which all PET and MR studies were transformed to conform to a standard reference MR image set. Subtraction images were visually inspected while overlayed on the reference MR scan to which PET images had been aligned, in order to confirm anatomic localization of significant rCBF changes. 4. Compared with visual fixation, performing visually guided saccades led to a significant bilateral activation in FEF, cerebellum, striate cortex, and posterior temporal cortex. Right posterior thalamus activation was also observed. 5. The visually guided saccade task served as the comparison task for the ODR, antisaccade, and conditional antisaccade tasks for identification of task-related changes in rCBF beyond those associated with saccade execution. Performance on the ODR task was associated with a bilateral increase of rCBF in FEFs, SMA, dorsolateral prefrontal cortex (DLPFC), and posterior parietal cortex. The cortical regions of increased regional blood flow during the ODR task also showed increased rCBF during the antisaccade task; however, FEF and SMA activations were significant only in the right hemisphere. These findings closely parallel those of single-cell recording studies with behaving monkeys in indicating that FEF, DLPFC, SMA, and posterior parietal cortex perform computational activity for voluntary purposive saccades. 6. Comparison of PET scans obtained during performance of eye movement and hand movement tasks indicated that peak activations in FEF were located approximately 2 cm lateral and 1 cm anterior to those of hand-related motor cortex. The oculomotor area of SMA, the supplementary eye field (SEF), was located approximately 7-8 mm anterior and superior to the hand-related area of SMA. 7. During performance of antisaccade and ODR tasks, rCBF was significantly lower in ventromedial prefrontal cortex (PFC), along the rectus gyrus, and in ventral anterior cingulate cortex than during the visually guided saccade and fixation tasks. During the antisaccade task, the ventral region of lower rCBF involved medial structures including left ventral striatum and bilateral medial temporal-limbic cortex. During the ODR task, the ventral aspect of the region of lower rCBF extended laterally, rather than medially, to include the temporal poles. The lower blood flow observed in ventromedial PFC during both the antisaccade and ODR tasks, relative to the visually guided saccade and fixation tasks, suggests that modulation of output from ventromedial PFC to limbic cortex and the striatum may play a role in the voluntary control of saccadic eye movements, possibly in the suppression of responses that would interrupt

BACKGROUND

In VOICE, a multisite HIV pre-exposure prophylaxis (PrEP) trial, plasma drug levels pointed to widespread product nonuse, despite high adherence estimated by self-reports and clinic product counts. Using a socio-ecological framework (SEF), we explored socio-cultural and contextual factors that influenced participants' experience of daily vaginal gel and oral tablet regimens in VOICE.

METHODS

In Johannesburg, a qualitative ancillary study was concurrently conducted among randomly selected VOICE participants assigned to in-depth interviews (n = 41), serial ethnographic interviews (n = 21), or focus group discussions (n = 40). Audiotaped interviews were transcribed, translated, and coded thematically for analysis.

RESULTS

Of the 102 participants, the mean age was 27 years, and 96% had a primary sex partner with whom 43% cohabitated. Few women reported lasting nonuse, which they typically attributed to missed visits, lack of product replenishments, and family-related travel or work. Women acknowledged occasionally skipping or mistiming doses because they forgot, were busy, felt lazy or bored, feared or experienced side effects. However, nearly all knew or heard of other study participants who did not use products daily. Three overarching themes emerged from further analyses: ambivalence toward research, preserving a healthy status, and managing social relationships. These themes highlighted the profound and complex meanings associated with participating in a blinded HIV PrEP trial and taking antiretroviral-based products. The unknown efficacy of products, their connection with HIV infection, challenges with daily regimen given social risks, lack of support-from partners and significant others-and the relationship tradeoffs entailed by using the products appear to discourage adequate product use.

CONCLUSIONS

Personal acknowledgment of product nonuse was challenging. This qualitative inquiry highlighted key influences at all SEF levels that shaped women's perceptions of trial participation and experiences with investigational products. Whether these impacted women's behaviors and may have contributed to ineffective trial results warrants further investigation.

Within the medial frontal cortex, the supplementary eye field (SEF), supplementary motor area (SMA), and pre-SMA have been implicated in the control of voluntary action, especially during motor sequences or tasks involving rapid choices between competing response plans. However, the precise roles of these areas remain controversial. Here, we study two extremely rare patients with microlesions of the SEF and SMA to demonstrate that these areas are critically involved in unconscious and involuntary motor control. We employed masked-prime stimuli that evoked automatic inhibition in healthy people and control patients with lateral premotor or pre-SMA damage. In contrast, our SEF/SMA patients showed a complete reversal of the normal inhibitory effect--ocular or manual--corresponding to the functional subregion lesioned. These findings imply that the SEF and SMA mediate automatic effector-specific suppression of motor plans. This automatic mechanism may contribute to the participation of these areas in the voluntary control of action.

The afferent and efferent cortical and subcortical connections of the medial posterior parietal cortex (area 7m) were studied in cebus (Cebus apella) and macaque (Macaca fascicularis) monkeys using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique. The principal intraparietal corticocortical connections of area 7m in both cebus and macaque cases were with the ipsilateral medial bank of the intraparietal sulcus (MIP) and adjacent superior parietal lobule (area 5), inferior parietal lobule (area 7a), lateral bank of the IPS (area 7ip), caudal parietal operculum (PGop), dorsal bank of the caudal superior temporal sulcus (visual area MST), and medial prestriate cortex (including visual area PO and caudal medial lobule). Its principal frontal corticocortical connections were with the prefrontal cortex in the shoulder above the principal sulcus and the cortex in the shoulder above the superior ramus of the arcuate sulcus (SAS), the area purported to contain the smooth eye movement-related frontal eye field (FEFsem) in the cebus monkey by other investigators. There were moderate connections with the cortex in the rostral bank of the arcuate sulcus (purported to contain the saccade-related frontal eye field; FEFsac), supplementary eye field (SEF), and rostral dorsal premotor area (PMDr). Area 7m also had major connections with the cingulate cortex (area 23), particularly the ventral bank of the cingulate sulcus. The principal subcortical connections of area 7m were with the dorsal portion of the ventrolateral thalamic (VLc) nucleus, lateral posterior thalamic nucleus, lateral pulvinar, caudal mediodorsal thalamic nucleus and medial pulvinar, central lateral, central superior lateral, and central inferior intralaminar thalamic nuclei, dorsolateral caudate nucleus and putamen, middle region of the claustrum, nucleus of the diagonal band, zona incerta, pregeniculate nucleus, anterior and posterior pretectal nuclei, intermediate layer of the superior colliculus, nucleus of Darkschewitsch and dorsomedial parvicellular red nucleus (macaque cases only), dorsal, dorsolateral and lateral basilar pontine nuclei, nucleus reticularis tegmenti pontis, locus ceruleus, and superior central nucleus. The findings are discussed in terms of the possibility that area 7m contains a "medial parietal eye field" and belongs to a neural network of oculomotor-related structures that plays a role in the control of eye movement.

Controversy surrounds the role of human medial frontal cortex in controlling actions. Although damage to this area leads to severe difficulties in spontaneously initiating actions, the precise mechanisms underlying such "volitional" deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring and the control of voluntary action, suggesting that these key processes are functionally related or share neural substrates. Here, we combine a novel behavioral paradigm with functional imaging of the oculomotor system to reveal, for the first time, a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas that respond exclusively to either volition or conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict.

The fibroblast growth factors (FGFs) represent a large family of ligands that activate signal transduction pathways leading to diverse biological responses, including many involved in various processes during development. Here, we discuss the discovery of a subset of conserved FGF target genes that encode feedback regulators of FGF signaling itself. Members of the Sprouty, Sef, and mitogen-activated protein kinase phosphatase families are negative modulators of FGF signaling, whereas positive factors that promote FGF signaling include the ETS transcription factors ERM and PEA3 and the transmembrane protein XFLRT3. These molecules affect the FGF signaling cascade at different levels to regulate the final output of the pathway. This multilayered regulation suggests that precise adjustment of FGF signaling is critical in development.

In several regions of the macaque brain, neurons fire during delayed response tasks at a rate determined by the value of the reward expected at the end of the trial. The activity of these neurons might be related either to the internal representation of the appetitive value of the expected reward or to motivation-dependent variations in the monkey's level of motor preparation or motor output. According to the first interpretation, reward-related activity should be most prominent in areas affiliated with the limbic system. According to the second interpretation, it should be most prominent in areas affiliated with the motor system. To distinguish between these alternatives, we carried out single-neuron recording while monkeys performed a memory-guided saccade task in which a visual cue presented early in each trial indicated whether the reward would be large or small. Neuronal activity accompanying task performance was monitored in the dorsolateral prefrontal cortex (PFC), the frontal eye field (FEF), a transitional zone caudal to the frontal eye field (FEF/PM), premotor cortex (PM), the supplementary eye field (SEF), and the rostral part of the supplementary motor area (SMAr). The tendency for neuronal activity to increase after cues that predicted a large reward became progressively stronger in progressively more posterior areas both in the lateral sector of the frontal lobe (PFC < FEF < FEF/PM < PM) and in the medial sector (SEF < SMAr). The very strong reward-related activity of premotor neurons was presumably attributable to the monkey's motivation-dependent level of motor preparation or motor output. This finding points to the need to determine whether reward-related activity in other nonlimbic brain areas, including dorsolateral prefrontal cortex and the dorsal striatum, genuinely represents the value of the expected reward or, alternatively, is related to motivational modulation of motor signals.

Fibroblast growth factors (FGFs) are members of a family of some 30 secreted proteins important in the regulation of cellular proliferation, migration, differentiation and survival. Here we report the identification of a novel modulator of FGF signal transduction, sef, isolated from a zebrafish embryo library through an in situ hybridization screen. The sef gene encodes a transmembrane protein, and belongs to the synexpression group that includes some of the fgf genes. Sef expression is positively regulated by FGF, and ectopic expression of sef in zebrafish or Xenopus laevis embryos specifically inhibits FGF signalling. In co-immunoprecipitation assays, the intracellular domain of Sef interacts with FGF receptors, FGFR1 and FGFR2. Injection of antisense sef morpholino oligos mimicked the phenotypes observed by ectopic fgf8 expression, suggesting that Sef is required to limit FGF signalling during development.

Fibroblast growth factors (FGFs) are pleiotrophic growth factors that control cell proliferation, migration, differentiation and embryonic patterning. During early zebrafish embryonic development, FGFs regulate dorsoventral patterning by controlling ventral bone morphogenetic protein (BMP) expression. FGFs function by binding and activating high-affinity tyrosine kinase receptors. FGF activity is negatively regulated by members of the Sprouty family, which antagonize Ras signalling induced by receptor tyrosine kinases. On the basis of similarities in their expression patterns during embryonic development, we have identified five genes that define a synexpression group -- fgf8, fgf3, sprouty2, sprouty4, as well as a novel gene, sef (similar expression to fgf genes). Sef encodes a conserved putative transmembrane protein that shares sequence similarities with the intracellular domain of the interleukin 17 receptor. Here we show that in zebrafish, Sef functions as a feedback-induced antagonist of Ras/Raf/MEK/MAPK-mediated FGF signalling.

The supplementary motor area (SMA) occupies an expanse of frontal agranular cortex rostral to the primary motor cortex (MI), largely in the mesial surface of the hemisphere. It is basically organized topographically, although the topography is not as apparent as in the MI. The traditionally defined SMA is now regarded as including two separate areas. The caudal part (SMA proper or F3) projects directly to the MI and to the spinal cord. The rostral part (pre-SMA or F6) is more remote from MI and receive projections from the prefrontal cortex and the cingulate motor areas. The supplementary eye field (SEF) is a small area separate from either the SMA or pre-SMA. The SEF is connected to cortical and subcortical areas related to oculomotor control. The SMA is active when subjects perform distal as well as proximal limb movement. Although the SMA is active in relation to relatively simple motor tasks, the functional significance of this relation to 'simple' movement is debatable. The SMA activity is subject to functional plasticity. The SMA is more active than the primary motor cortex if motor tasks are demanding in certain respects. Similarities of lesion effects of the SMA and basal ganglia suggests their intimate relation linked anatomically by the cortico-basal ganglia loops. Studies in both human subjects and in subhuman primates indicate the importance of the SMA in motor tasks that demand retrieval of motor memory. The SMA appears also crucial in temporal organization of movements, especially in sequential performance of multiple movements.

Neurophysiological studies in non-human primates have identified saccade-related neuronal activity in cortical regions including frontal (FEF), supplementary (SEF) and parietal eye fields. Lesion and neuroimaging studies suggest a generally homologous mapping of the oculomotor system in humans; however, a detailed mapping of the precise anatomical location of these functional regions has not yet been achieved. We investigated dorsal frontal and parietal cortex during a saccade task vs. central fixation in 10 adult subjects using functional magnetic resonance imaging (fMRI). The FEF were restricted to the precentral sulcus, and did not extend anteriorly into Brodmann area 8, which has traditionally been viewed as their location in humans. The SEF were located in cortex along the interhemispheric fissure and extended minimally onto the dorsal cortical surface. Parietal activation was seen in precuneus and along the intraparietal sulcus, extending into both superior and inferior parietal lobules. These findings localize areas in frontal and parietal cortex involved in saccade generation in humans, and indicate significant differences from the macaque monkey in both frontal and parietal cortex. These differences may have functional implications for the roles these areas play in visuomotor processes.

One of the mechanisms involved in chromatin remodelling is so-called 'histone replacement'. An example of such a mechanism is the substitution of canonical H2A histone by the histone variant H2A.Z. The ATP-dependent chromatin remodelling complex SWR1 is responsible for this action in yeast. We have previously proposed the existence of an SWR1-like complex in Arabidopsis by demonstrating genetic and physical interaction of the components SEF, ARP6 and PIE1, which are homologues of the yeast Swc6 and Arp6 proteins and the core ATPase Swr1, respectively. Here we show that histone variant H2A.Z, but not canonical H2A histone, interacts with PIE1. Plants mutated at loci HTA9 and HTA11 (two of the three Arabidopsis H2A.Z-coding genes) displayed developmental abnormalities similar to those found in pie1, sef and arp6 plants, exemplified by an early-flowering phenotype. Comparison of gene expression profiles revealed that 65% of the genes differentially regulated in hta9 hta11 plants were also mis-regulated in pie1 plants. Detailed examination of the expression data indicated that the majority of mis-regulated genes were related to salicylic acid-dependent immunity. RT-PCR and immunoblotting experiments confirmed constitutive expression of systemic acquired resistance (SAR) marker genes in pie1, hta9 hta11 and sef plants. Variations observed at the molecular level resulted in phenotypic alterations such as spontaneous cell death and enhanced resistance to the phytopathogenic bacteria Pseudomonas syringae pv. tomato. Thus, our results support the existence in Arabidopsis of an SWR1-like chromatin remodelling complex that is functionally related to that described in yeast and human, and attribute to this complex a role in maintaining a repressive state of the SAR response.

It has been suggested on the basis of previous studies involving functional MRI (fMRI) and single-neuron recording that neurons of the supplementary eye field (SEF) and anterior cingulate cortex (ACC) monitor conflict. To test this idea, we carried out microelectrode recording in monkeys performing a color-conditional eye movement task in which red and green cues instructed leftward and rightward saccades, respectively. In a variant inducing conflict by spatial incompatibility, the cue was presented either at the location of the target (no conflict) or opposite the location of the target (conflict). In a variant inducing conflict by reversal, the foveal cue either remained one color (no conflict) or reversed color after 100 ms (conflict), with the monkey required to follow the instruction conveyed by the second color. In both tasks, conflict was evident in behavioral measures (reduced percent correct and slowed reaction time) and in physiological measures (reduced strength of directional activity among direction-selective neurons). In the SEF, there was a tendency for neurons to fire more strongly on trials involving conflict, but this effect took the form of modulation of task-related activity among direction-selective neurons, not of a pure conflict-monitoring signal. In the ACC, there was no conflict-related enhancement. These results are incompatible with the idea that the SEF and ACC contain populations of neurons specialized for monitoring conflict.

Salmonella enterica serotype Typhi differs from nontyphoidal Salmonella serotypes by its strict host adaptation to humans and higher primates. Since fimbriae have been implicated in host adaptation, we investigated whether the serotype Typhi genome contains fimbrial operons which are unique to this pathogen or restricted to typhoidal Salmonella serotypes. This study established for the first time the total number of fimbrial operons present in an individual Salmonella serotype. The serotype Typhi CT18 genome, which has been sequenced by the Typhi Sequencing Group at the Sanger Centre, contained a type IV fimbrial operon, an orthologue of the agf operon, and 12 putative fimbrial operons of the chaperone-usher assembly class. In addition to sef, fim, saf, and tcf, which had been described previously in serotype Typhi, we identified eight new putative chaperone-usher-dependent fimbrial operons, which were termed bcf, sta, stb, ste, std, stc, stg, and sth. Hybridization analysis performed with 16 strains of Salmonella reference collection C and 22 strains of Salmonella reference collection B showed that all eight putative fimbrial operons of serotype Typhi were also present in a number of nontyphoidal Salmonella serotypes. Thus, a simple correlation between host range and the presence of a single fimbrial operon seems at present unlikely. However, the serotype Typhi genome differed from that of all other Salmonella serotypes investigated in that it contained a unique combination of putative fimbrial operons.

To examine the role of three cortical eye fields during internally guided decision-making processes, we recorded neuronal activities in the frontal eye field (FEF), supplementary eye field (SEF), and lateral intraparietal cortex (LIP) using a free-choice delayed saccade task with two synchronized targets. Although the monkeys must perform the task in a time-locked manner, they were free to choose either the receptive field (RF) target or the nonreceptive field (nRF) target to receive reward. In all three areas we found neurons with stronger activation during trials when the monkey was going to make a saccade to the RF target (RF trials) than to the nRF target (nRF trials). Modulation occurred not only during target presentation (visual bias) but also before target presentation (anticipatory bias). The visual bias was evident as an attenuated visual response to the RF stimulus in nRF trials. The anticipatory bias, however, was seen as an enhancement of pretarget activity in the RF trials. We analyzed the activity during the 500 msec before target presentation and found that 22.5% of FEF and 31.3% of LIP neurons and 49.1% of SEF neurons showed higher activity during the RF trials. To more accurately determine when each neuron started to show preferential activity, we used a new inverse interspike interval analysis procedure. Our results suggest that although all three cortical eye fields reflect attentional and intentional aspects of sensorimotor processing, SEF plays an earlier and perhaps more cognitive role in internally guided decision-making processes for saccades.

Our previous data indicate that there are specific features of the corticostriatal pathways from the prefrontal cortex. First, corticostriatal pathways are composed of focal, circumscribed projections and of diffuse, widespread projections. Second, there is some convergence between terminal fields from different functional regions of the prefrontal cortex. Third, anterior cingulate projections from area 24b occupy a large region of the rostral striatum. The goal of this study was to determine whether these features are also common to the corticostriatal projections from area 8A (including the frontal eye field; FEF), the supplementary eye field (SEF), dorsal and rostral premotor cortex (PMdr) and area 24c. Using a new approach of three-dimensional reconstruction of the corticostriatal pathways, along with dual cortical tracer injections, we mapped the corticostriatal terminal fields from areas 9 and 46, 8A-FEF, SEF, PMdr and 24b and c. In addition, we placed injections of retrogradely transported tracers into key striatal regions. The results demonstrated that: (i) a diffuse projection system is a common feature of the corticostriatal projections from different frontal regions; (ii) key striatal regions receive convergent projections from areas 9 and 46 and from areas 8A-FEF, SEF, PMdr and 24c, suggesting a potential pivotal role of these striatal regions in integrating cortical information; (iii) projections from area 24c, like those from area 24b, terminate widely throughout the striatum, interfacing with terminals from several frontal areas. These features of the corticostriatal frontal pathways suggest a potential integrative striatal network for learning.

Identification of a Strain Energy Function (SEF) is used when describing the complex mechanical properties of soft biological tissues such as the arterial wall. Classic SEFs, such as the one proposed by Chuong and Fung (J. Biomech. Eng. 105(3) (1983) 268), have been mostly phenomenological and neglect the particularities of the wall structure. A more structural model was proposed by Holzapfel et al. (J. Elasticity 61 (2000) 1-48.) when they included the characteristic angle at which the collagen fibers are helically wrapped, resulting in an excellent SEF for applications such as finite element modeling. We have expanded upon the idea of structural SEFs by including not only the wavy nature of the collagen but also the fraction of both elastin and collagen contained in the media, which can be determined by histology. The waviness of the collagen is assumed to be distributed log-logistically. In order to evaluate this novel SEF, we have used it to fit experimental data from inflation-extension tests performed on rat carotids. We have compared the results of the fit to the SEFs of Choung and Fung and Holzapfel et al. The novel SEF is found to behave similarly to that of Holzapfel et al., both succeed in describing the typical S-shaped pressure-radius curves with comparable quality of fit. The parameters of the novel SEF obtained from the fitting, bearing the physical meaning of the elastic modulus of collagen, the elastic modulus of elastin, the collagen waviness, and the collagen fiber angle, were compared to experimental data and discussed.