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Functional comparison of the nematode Hox gene lin-39 in C. elegans and P. pacificus reveals evolutionary conservation of protein function despite divergence of primary sequences.

Hox transcription factors have been implicated in playing a central role in the evolution of animal morphology. Many studies indicate the evolutionary importance of regulatory changes in Hox genes, but little is known about the role of functional changes in Hox proteins. In the nematodes Pristionchus pacificus and Caenorhabditis elegans, developmental processes can be compared at the cellular, genetic, and molecular levels and differences in gene function can be identified. The Hox gene lin-39 is involved in the regulation of nematode vulva development. Comparison of known lin-39 mutations in P. pacificus and C. elegans revealed both conservation and changes of gene function. Here, we study evolutionary changes of lin-39 function using hybrid transgenes and site-directed mutagenesis in an in vivo assay using C. elegans lin-39 mutants. Our data show that despite the functional differences of LIN-39 between the two species, Ppa-LIN-39, when driven by Cel-lin-39 regulatory elements, can functionally replace Cel-lin-39. Furthermore, we show that the MAPK docking and phosphorylation motifs unique for Cel-LIN-39 are dispensable for Cel-lin-39 function. Therefore, the evolution of lin-39 function is driven by changes in regulatory elements rather than changes in the protein itself.

Amino Acid Sequence↗

Density functional theory of solvation in a polar solvent: extracting the functional from homogeneous solvent simulations.

In the density functional theory formulation of molecular solvents, the solvation free energy of a solute can be obtained directly by minimization of a functional, instead of the thermodynamic integration scheme necessary when using atomistic simulations. In the homogeneous reference fluid approximation, the expression of the free-energy functional relies on the direct correlation function of the pure solvent. To obtain that function as exactly as possible for a given atomistic solvent model, we propose the following approach: first to perform molecular simulations of the homogeneous solvent and compute the position and angle-dependent two-body distribution functions, and then to invert the Ornstein-Zernike relation using a finite rotational invariant basis set to get the corresponding direct correlation function. This rather natural scheme is proved, for the first time to our knowledge, to be valuable for a dipolar solvent involving long range interactions. The resulting solvent free-energy functional can then be minimized on a three-dimensional grid around a solute to get the solvent particle and polarization density profiles and solvation free energies. The viability of this approach is proven in a comparison with "exact" molecular dynamics calculations for the simple test case of spherical ions in a dipolar solvent.

Journal Article↗

Determination of a wave function functional.

We propose expanding the space of variations in traditional variational calculations for the energy by considering the wave function psi to be a functional of a set of functions chi:psi=psi[chi], rather than a function. A constrained search in a subspace over all functions chi such that the functional psi[chi] satisfies a sum rule or leads to a physical observable is then performed. An upper bound to the energy is subsequently obtained by variational minimization. The rigorous construction of such a constrained-search-variational wave function functional is demonstrated.

Quantum Theory↗

Functional Assessment in Migraine (FAIM) questionnaire: development of an instrument based upon the WHO's International Classification of Functioning, Disability, and Health.

OBJECTIVE: The goal of this project was to develop a migraine functional measurement instrument, derived from the World Health Organization International Classification of Impairments, Disabilities, and Handicaps version 2 classification system, which focuses on functional outcomes, and is both reliable and valid. METHODS: The Functional Assessment in Migraine (FAIM) questionnaire was developed using a multistep approach to ensure the brevity, relevance, reliability, and validity of items. A test set of 71 Mental Functioning and 50 Activity and Participation items was generated and administered to migraineurs in the United States and Germany. A subset of 22 Mental Functioning and 28 Activity and Participation items that rated highly on frequency-weighted importance and showed strong psychometric properties was piloted to determine a final item set and to test reliability and validity. RESULTS: The final version of the FAIM included nine Mental Functioning items measuring the dimensions of Attention/Thought (5 items) and Perception (4 items), and a list of 28 Activity and Participation items from which respondents chose the five items most relevant to their lifestyle. Construct validity analysis of FAIM dimensions found significant positive correlations with self-reported symptom severity, moderately significant positive correlations with dimensions of the Migraine-Specific Quality of Life questionnaire and no significant correlation with Short Form Health Survey (SF-12) component scores. CONCLUSION: The FAIM offers physicians a brief and valid method of measuring the impact of migraine on mental functioning and activity and participation as defined by the WHO International Classification of Functioning, Disability, and Health. Additional testing is underway to assess its responsiveness to change.

Adult↗

How does low back pain impact physical function in independent, well-functioning older adults? Evidence from the Health ABC Cohort and implications for the future.

OBJECTIVE: To determine the relationships between low back pain (LBP) frequency and intensity and self-reported and performance-based physical function in a large cohort of well-functioning older adults. DESIGN: Cross-sectional survey and examination. SETTING: Community-based cohort of the Health, Aging, and Body Composition (Health ABC) study. PARTICIPANTS: Participants were 2,766 community-dwelling adults, aged 70-79; 42% were African American, 52% were men. OUTCOME MEASURES: 1) Back pain-location, frequency, intensity; 2) Hip and/or knee pain; 3) Body mass index (BMI); 4) Self-reported difficulty doing functional tasks; 5) Lower extremity function, using the battery from the Established Populations for Epidemiologic Studies in the Elderly (EPESE); 6) Self-rated health; 7) Comorbidity; 8) Depressive symptoms, using the Center for Epidemiological Studies-Depression (CES-D) scale. RESULTS: LBP was common (36%), and its frequency/intensity was significantly associated with other pain and comorbidities. In gender-specific models, LBP frequency/intensity was not significantly associated with EPESE performance score after adjusting for age, race, BMI, CES-D score, knee pain, hip pain, and other comorbidities. LBP frequency/intensity, however, was significantly associated with self-reported difficulty with most functional tasks after adjusting for important confounders. CONCLUSIONS: Among well-functioning community-dwelling older adults, LBP frequency/intensity was associated with perceived difficulty in performing important functional tasks, but not with observed physical performance. The demonstrated dose-response relationship between pain frequency/intensity and self-reported task performance difficulty underscores the importance of clinical efforts to treat pain without necessarily eradicating it. Additional work is needed to determine whether back pain is associated with a risk for progressive functional decline and loss of independence in older adults and whether therapeutic interventions can ameliorate decline and, therefore, preserve independence.

Activities of Daily Living↗

Age and functional correlations of markers of coagulation and inflammation in the elderly: functional implications of elevated crosslinked fibrin degradation products (D-dimers).

OBJECTIVE: To measure markers of inflammation in a cohort of young and old subjects and relate these findings to the functional level of the individuals. DESIGN: For the pilot study, blood samples were obtained from 18 young (age 20-35 years) and 18 old (age 68-83 years) subjects. The main study population included community-dwelling subjects between the ages of 70 and 79. The group consisted of 282 subjects with minimal physical limitations, 17 subjects from the middle third, and 16 from the lower third of physical function rankings. METHODS: Plasma markers were measured by ELISA techniques, and certain biochemical values were obtained through routine clinical tests performed by a commercial laboratory. RESULTS: D-Dimers were higher for physically impaired subjects in all groups, but most prominently among black females, who also had significantly higher D-Dimer levels in every functional group. To inquire whether higher D-Dimers were associated with markers of inflammation, we also examined the macrophage metabolite, neopterin, the neutrophil product, elastase complexed to antitrypsin (E/a), and the albumin globulin ratio (A/G ratio). No differences were found in neopterin or E/a levels on the basis of gender, race, or functional status. The A/G ratio was significantly lower in functionally impaired subjects. CONCLUSION: These preliminary findings demonstrate racial/ethnic and gender differences in D-Dimers in a population of community-dwelling elderly, and suggest that factors influencing hemostasis may be particularly relevant to physical functional status in black women. A sample containing more subjects with lower physical function will be needed to establish the relationship between inflammation, altered hemostasis, and physical function decline.

Adult↗

Functional 3.0-T MR assessment of higher cognitive function: are there advantages over 1.5-T imaging?

PURPOSE: To compare cortical activation patterns associated with manual motor decision tasks at 1.5- and 3.0-T functional magnetic resonance (MR) imaging. MATERIALS AND METHODS: The local ethics committee approved this study, and informed written consent was obtained. Ten right-handed healthy volunteers (eight men and two women; mean age, 35 years +/- 7 [standard deviation]) underwent functional MR imaging twice, once at 1.5 T and once at 3.0 T, while performing cognitive tasks that demanded manual motor decisions (letter-finger matching and lexical and semantic decisions). While stimulus presentation was blocked, an event-related model was employed to analyze subjects' individual responses. A group analysis of functional data was performed with a t test of 1.5- and 3.0-T results in the 10 subjects. RESULTS: Manual motor decisions activated a widespread network of motor- (primary motor, posterior parietal) and decision-related areas (superior frontal cortex or anterior cingulate) at both field strengths (P <.05, corrected). Moreover, additional functional activation was detected in medial (supplementary motor area) and dorsal premotor regions (P <.05, corrected) at 3.0-T functional MR imaging, which was not detectable with corresponding 1.5-T imaging. The mean t value for peak voxels in activated areas detectable with both systems was 1.3 times larger at 3.0 T than that at 1.5 T. CONCLUSION: Functional 3.0-T MR imaging allows detection of additional activation in cortical areas involved in higher executive motor functions compared with functional 1.5-T MR imaging.

Adult↗

Targeting the abnormalities of gastroduodenal functions in functional dyspepsia.

The current definition of functional dyspepsia changes the previous concept of absence of organic disease to the presence of a functional alteration of the upper gastrointestinal tract. From a theoretical point of view, the alteration of any major gastrointestinal function may induce dyspeptic symptoms. However, both asymptomatic subjects with some gastrointestinal functional alteration and dyspeptic patients without a demonstrable dysfunction are not unusual. This may be explained at least in part by the more recent concept of visceral sensitivity. The potential role of acid secretion in the pathogenesis of functional dyspepsia as well as the positive effect of antisecretory drugs in a proportion of patients may be based on an increased gastric acid secretion and duodenal acid overload, a hypersensitivity to acid and/or the development of acid-mediated gastrointestinal motor abnormalities. Helicobacter pylori infection may play a role in this context. Both interdigestive and postprandial gastrointestinal motility, mainly a delayed gastric emptying and an altered intragastric distribution of nutrients, have been described to be disturbed in up to half of the patients with functional dyspepsia. This may also be an explanation for the high frequency of intestinal bacterial overgrowth in these patients. Most probably, visceral hypersensitivity should be present for motor alterations to induce symptoms. This is the basis for future development of new drugs in the management of this functional syndrome. The role of H. pylori in the pathogenesis of functional dyspepsia is a matter of discussion, but a proportion of patients benefit from eradication therapy and, therefore this therapeutic approach should be taken into account.

Duodenum↗

Impaired left ventricular function in chronic aortic valve disease: survival and function after replacement by Björk-Shiley prosthesis.

Postoperative survival and left ventricular function were studied in 128 patients who underwent isolated aortic valve replacement by the Björk-Shiley valve between 1973 and 1977. The average follow-up was 2.1 years. Patients with associated coronary artery disease or mitral valve disease were excluded. Preoperative ejection fraction ranged from 15-84%. Forty-two patients were restudied by cardiac catheterization 9.1 +/- 1.1 months (mean +/- SEM) after valve replacement. The hospital mortality was 11%. Preoperative type of valve lesion, functional class, cardiothoracic ratio, and ejection fraction (EF) had no significant effect on postoperative survival up to 4 years. After operation, left ventricular mass (LVMI) and peak systolic wall stress (PSWS) fell significantly, while EF and mean normalized systolic ejection rate (MNSER) increased in aortic stenosis and in aortic insufficiency. Neither in aortic stenosis nor in aortic insufficiency was there a significant relation between preoperative ejection fraction and postoperative LVMI, EF, MNSER and PSWS. We attributed this to a marked improvement of left ventricular function in patients with preoperative impaired ventricular function. Six patients with paravalvular leak to restudy has a significantly lower EF and MNSER, and a higher PSWS than patients without leak. Patients without leak had normal EF, MNSER and PSWS when compared with 10 normal persons, but LVMI remained moderately elevated. Postoperative transprosthetic gradient was 11.9 mm Hg (range 0-64 mm Hg). We conclude that impaired cardiac function is completely restored after aortic valve replacement by Björk-Shiley valve, if valve function is good. Patients with impaired cardiac function preoperatively did not have a poorer prognosis after operation than patients with normal function.

Adolescent↗

Selective functional properties of dual atrioventricular nodal inputs. Role in nodal conduction, refractoriness, summation, and rate-dependent function in rabbit heart.

BACKGROUND: The atrioventricular node receives its activation signal from the low crista terminalis and low interatrial septum, the summation of which is believed to favor conduction. A functional asymmetry between the inputs is also believed to be involved in nodal reentrant rhythms. We studied the selective functional characteristics of nodal inputs and determined their role in nodal conduction, refractoriness, summation, and rate-dependent function. METHODS AND RESULTS: The nodal properties of recovery, facilitation, and fatigue were characterized with stimulation protocols applied with varying phases between the two inputs in isolated rabbit heart preparations. The effects of the input phase, nodal functional state, and input reference on the nodal conduction time, recovery time, and refractory periods were assessed with multifactorial ANOVAs. It was found that the phase of stimulation significantly affected nodal conduction time but not the refractory periods or the time constant of the recovery. Each input could show longer and shorter conduction time than the other depending on the stimulation phase, input reference, and coupling interval. These effects were similar for different nodal functional states. However, pacing and recording from the low crista resulted in similar conduction and refractory values than did pacing and recording from the low septum. Input summation did not increase the otherwise equal efficacy of individual input in activating the node. Nodal surface recordings confirmed this functional symmetry and equivalent efficacy of the inputs and showed that input effects were confined to the proximal node. CONCLUSIONS: The two nodal inputs have equivalent functional properties and are equally effective in activating the rate-dependent portion of the node. Input interaction affects perinodal activation but not the rate-dependent nodal function.

Analysis of Variance↗

Heterogeneity of immunologic function among subfractions of normal rat alveolar macrophages. II. Activation as a determinant of functional activity.

Previous studies have demonstrated differences in immunologic function among density-fractionated alveolar macrophages. The present study was undertaken to correlate these functional differences among alveolar macrophage density fractions with parameters of macrophage activation. Alveolar macrophages were lavaged from normal rats and separated into 5 density fractions by density gradient centrifugation. Cells from each density fraction were analyzed for parameters of macrophage activation: in vitro cytotoxic function directed against cultured neoplastic cells, ectoenzyme activities, and surface expression of Ia-like determinants. Lavaged alveolar macrophages with in vitro cytotoxic function were concentrated among cells from higher density fractions, and cytotoxic function among the density fractions correlated inversely with ectoenzyme activities. Although the percentage of Ia-positive cells varied among the density fractions, surface expression of Ia-like determinants did not correlate positively with in vitro cytotoxic function. The results show that there is a variable distribution of cytotoxic function among alveolar macrophage density fractions that correlates with enzymatic markers of activation. Thus, we conclude that differential macrophage activation is a potential determinant of the functional heterogeneity observed in rat alveolar macrophages.

5'-Nucleotidase↗

Agreement of function across methods used in school-based functional assessment with preadolescent and adolescent students.

As we begin to apply functional assessment procedures in mainstream educational settings, there is a need to explore options for identifying behavior function that are not only effective but efficient and practical for school personnel to employ. Attempts to simplify the functional assessment process are evidenced by the development of informant assessment measures (e.g., interviews, rating scales). In this study, the agreement (i.e., on relative rankings and primary function) across sources of information regarding behavior function was examined for 19 students in a middle school setting. These measures included teacher ratings, student ratings, student interviews, observer ratings, and conditional probabilities. In addition, for 1 student, whether information obtained through these sources was consistent with that obtained through a brief analog analysis of function was examined. Results indicated low agreement regarding rank order of behavior function and on primary function across all sources of information.

Adolescent↗

Post-stroke depression and functional outcome: a cohort study investigating the influence of depression on functional recovery from stroke.

OBJECTIVE: To investigate the influence of depression on functional recovery after stroke. DESIGN: Multicentre cohort study of 85 patients admitted for clinical rehabilitation. A two-stage case-finding procedure was used to identify patients with depression. For the control group, consecutive nondepressed stroke patients were enrolled. Patients were interviewed at 3-6 weeks and six months after stroke onset. SETTING: Three rehabilitation centres in the vicinity of Amsterdam. MAIN OUTCOME MEASURES: Functional outcome was determined by the Functional Independence Measure (FIM) and the Rehabilitation Activities Profile (RAP). RESULTS: The prevalence of depression (35%) was comparable with the findings of earlier studies in other settings. Patients classified as depressed according to DSM III R criteria (American Psychiatric Association Diagnostic and statistical manual of mental disorders) had a significantly lower functional score, both at onset and after follow-up (FIM and RAP). There was, however, no significant difference in functional improvement between the depressed and the nondepressed group. Mean functional improvement in the six patients treated with antidepressants was 30% better than in the untreated (depressed) patients; numbers were too small for the results to attain statistical significance. Subset analysis showed a significantly higher outcome for nondepressed patients for the FIM subitems personal care and transfers. However, functional improvement was not significantly different for any of the subitems in depressed versus nondepressed patients. CONCLUSION: Stroke patients with depression have significantly lower functional scores both at onset and after six months. Our results suggest under-recognition of post-stroke depression and a possible beneficial effect of antidepressant medication in depressed stroke patients. Further studies are required to determine the effect of antidepressants.

Activities of Daily Living↗

[Relationships of swallowing function to changes in motor functions in stroke patients with motor dysphagia].

AIM: To clarify the clinical features of physical therapy for motor dysphagia by identifying changes in indices when swallowing function changes. METHOD: Subjects comprised 59 stroke patients with motor dysphagia. They were subdivided into 3 groups according to changes in swallowing function (Group A: improved, Group B: deteriorated. Group C: unchanged). Measured indices for swallowing movement consisted of 4 items; distance from the genion to the thyroid cartilage (GT), distance from the thyroid cartilage to the sternum (TS), relative thyroid position (GT/(GT + TS)), and strength of the suprahyoid muscles (GS grade). Measured indices for neck-trunk function consisted of the passive neck range of motion in 4 directions (flexion, extension, lateral flexion, and rotation), and neck-trunk-pelvis stage (NTP stage) as described by Yoshio. Measured indices for swallowing function were the repetitive saliva swallowing test, the modified water swallowing test, the food test, and Saitoh's classification of dysphagia. RESULTS: Group A consisted of 30 patients (mean age, 68.1 years), Group B consisted of 6 patients (mean age, 78.7 years), Group C consisted of 23 patients (mean age, 73.0 years). Group A exhibited significant improvements in GS grade, NTP stage, neck extension and rotation. In Group B, only relative thyroid position was affected. In Group C, no changes were evident. CONCLUSION: To obtain improved swallowing function, approaches aimed at both local function of swallowing muscles and neck-trunk function should be used. Preventing deterioration of swallowing function requires attention to thyroid position affected by inappropriate posture.

Aged↗

Dissociated expressive and receptive language functions on magnetoencephalography, functional magnetic resonance imaging, and amobarbital studies. Case report and review of the literature.

Dissociated language functions are largely invalidated by standard techniques such as the amobarbital test and cortical stimulation. Language studies in which magnetoencephalography (MEG) and functional magnetic resonance (fMR) imaging are used to record data while the patient performs lexicosemantic tasks have enabled researchers to perform independent brain mapping for temporal and frontal language functions (MEG is used for temporal and fMR imaging for frontal functions). In this case report, the authors describe a right-handed patient in whom a right-sided insular glioma was diagnosed. The patient had a right-lateralized receptive language area, but expressive language function was identified in the left hemisphere on fMR imaging- and MEG-based mapping. Examinations were performed in 20 right-handed patients with low-grade gliomas (control group) for careful comparison with and interpretation of this patient's results. In these tests, all patients were asked to generate verbs related to acoustically presented nouns (verb generation) for fMR imaging, and to categorize as abstract or concrete a set of visually presented words consisting of three Japanese letters for fMR imaging and MEG. The most prominent display of fMR imaging activation by the verb-generation task was observed in the left inferior and middle frontal gyri in all participants, including the patient presented here. Estimated dipoles identified with the abstract/concrete categorization task were concentrated in the superior temporal and supramarginal gyri in the left hemisphere in all control patients. In this patient, however, the right superior temporal region demonstrated significantly stronger activations on MEG and fMR imaging with the abstract/concrete categorization task. Suspected dissociation of the language functions was successfully mapped with these two imaging modalities and was validated by the modified amobarbital test and the postoperative neurological status. The authors describe detailed functional profiles obtained in this patient and review the cases of four previously described patients in whom dissociated language functions were found.

Adult↗

The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency.

BACKGROUND: In individuals with moderate to severe renal insufficiency, low protein intake may slow renal function decline. However, the long-term impact of protein intake on renal function in persons with normal renal function or mild renal insufficiency is unknown. OBJECTIVE: To determine whether protein intake influences the rate of renal function change in women over an 11-year period. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. PARTICIPANTS: 1624 women enrolled in the Nurses' Health Study who were 42 to 68 years of age in 1989 and gave blood samples in 1989 and 2000. Ninety-eight percent of women were white, and 1% were African American. MEASUREMENTS: Protein intake was measured in 1990 and 1994 by using a semi-quantitative food-frequency questionnaire. Creatinine concentration was used to estimate glomerular filtration rate (GFR) and creatinine clearance. RESULTS: In multivariate linear regression analyses, high protein intake was not significantly associated with change in estimated GFR in women with normal renal function (defined as an estimated GFR > or = 80 mL/min per 1.73 m2). Change in estimated GFR in this subgroup over the 11-year period was 0.25 mL/min per 1.73 m2 (95% CI, -0.78 to 1.28 mL/min per 1.73 m2) per 10-g increase in protein intake; the change in estimated GFR was 1.14 mL/min per 1.73 m2 (CI, -3.63 to 5.92 mL/min per 1.73 m2) after measurement-error adjustment for protein intake. In women with mild renal insufficiency (defined as an estimated GFR > 55 mL/min per 1.73 m2 but <80 mL/min per 1.73 m2), protein intake was significantly associated with a change in estimated GFR of -1.69 mL/min per 1.73 m2 (CI, -2.93 to -0.45 mL/min per 1.73 m2) per 10-g increase in protein intake. After measurement-error adjustment, the change in estimated GFR was -7.72 mL/min per 1.73 m2 (CI, -15.52 to 0.08 mL/min per 1.73 m2) per 10-g increase in protein intake, an association of borderline statistical significance. High intake of nondairy animal protein in women with mild renal insufficiency was associated with a significantly greater change in estimated GFR (-1.21 mL/min per 1.73 m2 [CI, -2.34 to -0.33 mL/min per 1.73 m2] per 10-g increase in nondairy animal protein intake). CONCLUSIONS: High protein intake was not associated with renal function decline in women with normal renal function. However, high total protein intake, particularly high intake of nondairy animal protein, may accelerate renal function decline in women with mild renal insufficiency.

Adult↗

Morphology and barrier function of the corneal epithelium after penetrating keratoplasty: association with original diseases, tear function, and suture removal.

PURPOSE: To study changes in structure and barrier function of the corneal epithelium after penetrating keratoplasty. METHODS: Sixty-nine eyes of 56 patients undergoing penetrating keratoplasty were studied. Fifty-six age-matched normal eyes served as controls. Corneal epithelial structure was studied by using specular microscopy. Barrier function of the corneal epithelium was examined by slit-lamp fluorophotometry. Vital staining, tear function, and corneal sensitivity also were examined. RESULTS: Fluorescein and rose bengal staining scores, incidence of elongated cells, the mean epithelial area, and mean fluorescein uptake were significantly increased in postkeratoplasty eyes compared with controls. Original disease influenced the results of barrier function, where keratoconus revealed better function than bullous keratopathy or corneal scar. However, no such differences were noted in epithelial structure. Six eyes with absence of palisades of Vogt had revealed significantly increased epithelial area and fluorescein uptake. Removal of the running suture caused a decrease in elongated cells and epithelial cell area without significant changes in barrier function. CONCLUSION: Corneal epithelial structure was significantly impaired in postkeratoplasty eyes. Epithelial barrier function of postkeratoplasty eyes was influenced by original diseases. Removal of sutures improves epithelial structure but not barrier function.

Adolescent↗

Malformation of the functional organization of somatosensory cortex in adult ephrin-A5 knock-out mice revealed by in vivo functional imaging.

The molecular mechanisms that coordinate the functional organization of the mammalian neocortex are largely unknown. We tested the involvement of a putative guidance label, ephrin-A5, in the functional organization of the somatosensory cortex by quantifying the functional representations of individual whiskers in vivo in adult ephrin-A5 knock-out mice, using intrinsic signal optical imaging. In wild-type mice ephrin-A5 is expressed in a gradient in the somatosensory cortex during development. In adult ephrin-A5 knock-out mice, we found a spatial gradient of change in the amount of cortical territory shared by individual whisker functional representations across the somatosensory cortex, as well as a gradient of change in the distance between the functional representations. Both gradients of change were in correspondence with the developmental expression gradient of ephrin-A5 in wild-type mice. These changes involved malformations of the cortical spacing of the thalamocortical components, without concurrent malformations of the intracortical components of individual whisker functional representations. Overall, these results suggest that a developmental guidance label, such as ephrin-A5, is involved in establishing certain spatial relationships of the functional organization of the adult neocortex, and they underscore the advantage of investigating gene manipulation using in vivo functional imaging.

Age Factors↗