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Visual search and dual tasks reveal two distinct attentional resources.

Most theories of visual processing assume that a target will "pop out" from an array of distractors ("parallel" visual search, e.g., color or orientation discrimination) if targets and distractors can be discriminated without attention. When the discrimination requires attention (e.g., rotated L vs. T or red-green vs. green-red bisected disks), "serial" examination is needed in visual search. Attentional requirements are also frequently assessed by measuring interference from a concurrently performed attentionally demanding task. It is commonly believed that attention acts equivalently in dual-task and visual search paradigms, based on the implicit assumption that visual attentional requirements can be defined along a single dimension. Here we show that there is no such equivalence: We report on targets that do not trigger pop-out, even though they can be discriminated from distractors with attention occupied elsewhere (natural scenes, color-orientation conjunctions); conversely, we show that certain targets that pop out among distractors need undivided attention to be effectively discriminated from distractors when presented in isolation (rotated L vs. +, depth-rotated cubes). In other words, visual search and dual-task performance reveal attentional resources along two independent dimensions. We suggest an interpretation of these results in terms of neuronal selectivities and receptive field size effects.

Attention↗

Orientational changes of the absorbing dipole or retinal upon the conversion of rhodopsin to bathorhodopsin, lumirhodopsin, and isorhodopsin.

The orientational change of the absorbing dipole of the retinal chromophore in vertebrate rhodopsin (rhodo) upon photo-excitation to bathorhodopsin (batho), lumirhodopsin (lumi) and isorhodopsin (iso), has been studied by polarized absorption and linear dichroism measurements on magnetically oriented frog rod suspensions that were blocked at liquid nitrogen temperature. Both the azimuthal component delta theta and the polar component delta theta of the total angular change were studied in separate experiments. Delta theta was estimated from polarized absorption measurements on rods oriented transversally with respect to the analyzing beam. The data show unequivocally that upon the rhodo leads to batho transition, the dipole shifts out of the membrane plane by only few degrees; delta theta congruent to -3 degree. This azimuthal shift was nearly exactly reversed upon the batho leads to lumi decay. A very small shift (delta theta less than or equal to 1 degree) toward the membrane plane was observed upon a rhodo leads to iso conversion. The polar component delta theta of the angular shift was estimated by studying the photoreversion of linear dichroism induced by photo-excitation with polarized light in rods oriented parallel to the analyzing beam. Upon the rhodo leads to batho transition, ther was a shift delta theta = 11 +/- 3 degrees. The overall angular shift upon this first photo-exciting step, which corresponded to the isomerisation of retinal, was only delta omega = 11 +/- 3 degrees. This is smaller than what may be expected for a cis-trans isomerization of a retinal molecule with one end fixed, and different from what has been previously estimated by another group. These discrepancies are discussed.

Animals↗

Assessment of composition and anisotropic elastic properties of secondary osteon lamellae.

Measurement of the elastic properties of single osteon lamellae is still one of the most demanding tasks in bone mechanics to be solved. By means of site-matched Raman microspectroscopy, acoustic microscopy and nanoindentation the structure, chemical composition and anisotropic elasticity of individual lamellae in secondary osteons were investigated. Acoustic impedance images (911-MHz) and two-dimensional Raman spectra were acquired in sections of human femoral bone. The samples were prepared with orientations at various observation angles theta relative to the femoral long axis. Nanoindentations provided local estimations of the elastic modulus and landmarks necessary for spatial fusion of the acoustic and spectral Raman images. Phosphate nu(1) (961 cm(-1)) and amide I (1665 cm(-1)) band images representing spatial distributions of mineral and collagen were fused with the acoustic images. Acoustic impedance was correlated with the indentation elastic modulus E(IT) (R(2)=0.61). Both parameters are sensitive to elastic tissue anisotropy. The lowest values were obtained in the direction perpendicular to the femoral long axis. Acoustic images exhibit a characteristic bimodal lamellar pattern of alternating high and low impedance values. Since this undulation was not associated with a variation of the phosphate nu(1)-band intensity in the Raman images, it was attributed to variations of the lamellar orientation. After threshold segmentation and conversion to elastic modulus the orientation and transverse isotropic elastic constants were derived for individual ensembles of apparent thin and thick lamellae. Our results suggest that this model represents the effective anisotropic properties of an asymmetric twisted plywood structure made of transverse isotropic fibrils. This is the first report that proves experimentally the ability of acoustic microscopy to map tissue elasticity in two dimensions with micrometer resolution. The combination with Raman microspectroscopy provides a unique way to study bone and mineral metabolism and the relation with mechanical function at the ultrastructural tissue level.

Anisotropy↗

Influence of a dopamine agonist (lisuride) on sex-specific behavioural patterns in rats. I. Short term effects.

Lisuride induces in juvenile male and especially in female rats a significant increase of the initiating activity in tests on social play-fighting behaviour. In neonatally castrated as well as in prenatally stress exposed males, castrated in adulthood, which exhibit under androgen alone bisexual or even predominantly heterotypical sexual behaviour, additional treatment with lisuride resulted in a temporary normalization of sexual orientation in the homotypical male direction. In castrated androgen treated females, lisuride induces a partial conversion of sexual orientation to heterotypical male direction.

Animals↗

Independent insertion of Alu elements in the human ribosomal spacer and their concerted evolution.

A 2,700-bp segment of human ribosomal DNA (rDNA) spacer upstream of the rRNA promoter contains a set of four Alu elements, two in the direction of rRNA transcription and two in the opposite orientation. We report and compare the sequences of these Alu elements found in three rDNA clones and seek to determine the origin of the cluster, either from a single insertion followed by duplications or from multiple simultaneous or independent insertions. The high (20%-27%) divergence among members of a set and the lack of similarity/complementarity of sequences flanking different members of the set demonstrate the independent insertion of each of the four Alu elements into A-rich sequences on the appropriate strand of the rDNA. We also demonstrate that the Alu sets found in different rDNA repeats are subject to concerted evolution, yielding divergences of only 0.4%-3% between Alu elements in equivalent positions. However, the pairs of adjacent similarly oriented Alu elements do not show reduced divergence, indicating that there is no recombination or gene conversion between similarly oriented but not equivalently positioned Alu elements. Finally, crossing-over must occur in the rDNA junction region between Alu element 3 and the nonribosomal sequences at the telomere end of the acrocentric chromosome, so that the Alu elements of the terminal rDNA repeats and the terminal repeats themselves evolve in concert with the rDNA repeats located internally in the tandem array.

Base Sequence↗

Health-related quality of life in type 1 diabetic patients and influence of peripheral nerve involvement.

We examined the relationships between diabetic peripheral nerve involvement and patients' own perception of quality of life in a multidimensional study based on outcome research recommendations. The study enrolled 50 consecutive outpatients with type 1 diabetes mellitus (23 men, 27 women; mean age, 40.1 years). The patients were evaluated with validated clinical tests (e. g. Semmes-Weinstein, vibration perception threshold, muscle strength), neurophysiological tests (sural, peroneal and ulnar nerves) and patient-oriented (SF-36 and NASS) questionnaires. Patient-oriented physical scores were significantly related with: (1) neurophysiological findings of the lower limbs; (2) conventional measurements of sensitivity. Conversely, patient-oriented mental scores were not related with these findings. The patient-oriented questionnaires provided an important perspective of the severity of the disease, often closely related with the biological parameters. They offered new interpretations to conventional biological measurements. In particular, the peripheral nerve picture was strictly related to the physical aspects of the patients' quality of life, and not with the mental aspects.

Adult↗

Relationships among microstructural properties of bone at the human midshaft femur.

Mineralization density and collagen fibre orientation are two aspects of a bone's microstructural organization that influence its mechanical properties. Previous studies by our group have demonstrated a distinctly non-random, though highly variable, spatial distribution of these two variables in the human femoral cortex. In this study of 37 specimens, these variables are examined relative to one another in order to determine whether regions of bone demonstrating higher or lower mineralization density also demonstrate a prevalence of either transversely or longitudinally oriented collagen fibres. An analysis of rank-transformed collagen fibre orientation (as determined by circularly polarized light) and mineralization density (as determined by backscattered electron microscopy) data sets demonstrated that areas of low mineralization density (predominantly in the anterior-lateral cortex) tended to correspond to regions of higher proportions of longitudinally oriented collagen fibres. Conversely, areas of higher mineralization density (postero-medially) tended to correspond to regions of higher proportions of transversely oriented collagen fibres. High variability in the sample led to generally low correlations between the two data sets, however. A second analysis focused only on the orientation of collagen fibres within poorly mineralized bone (representing bone that was newly formed). This analysis demonstrated a lower proportion of transverse collagen fibres in newly formed bone with age, along with some significant regional differences in the prevalence of collagen fibres of either orientation. Again high variability characterized the sample. These results are discussed relative to the hypothesized forces experienced at the midshaft femur.

Adult↗

Efficient gap repair in Drosophila melanogaster requires a maximum of 31 nucleotides of homologous sequence at the searching ends.

Double-strand breaks (DSB) were generated in the Drosophila melanogaster white gene by excision of the P-w(hd) element. An ectopic P-element vector carrying a modified white gene was used as a template for DSB repair. All template-dependent repair events were examined, and four different classes of events were recovered. The two most common products observed were gene conversions external to the P-w(hd) element and gene conversions (targeted transpositions) internal to the P-w(hd) element. These two events were equally frequent. Similar numbers for both orientations of internal conversion events were recovered. The results suggest that P-element excision occurs by a staggered cut that leaves behind at least 33 nucleotides of single-stranded sequence. Our results further demonstrate that an efficient homology search is conducted by the broken end with less than 31 nucleotides.

Animals↗

Short- and long-term effects of a dopamine agonist (lisuride) on sex-specific behavioural patterns in rats.

Lisuride induces in juvenile male and especially in female rats a significant increase of the male-typical initiating activity in tests on social play-fighting behaviour. In neonatally castrated as well as in prenatally stress exposed males, castrated in adulthood, which exhibit under androgen substitution alone bisexual or even predominantly heterotypical sexual behaviour, additional treatment with lisuride resulted in a temporary normalization of sexual orientation in the homotypical male direction, limited to the duration of treatment. In castrated androgen-treated females, lisuride induces a partial conversion of sexual orientation to the heterotypical male direction. When intact newborn females or neonatally castrated males were treated with lisuride during the early postnatal differentiation period of the brain (day 2-12) or, on the other hand, during the peripuberal maturation period (day 26-40), it was found that early postnatal as well as peripuberal activation of the dopaminergic system in females resulted in permanent partial masculinization of sexual orientation. Comparable trends were observed after peripuberal androgen administration in females. In neonatally castrated males, the demasculinized play-fighting as well as the sexual orientation could be normalized--at least in part--by early postnatal or peripuberal lisuride administration. These findings confirm once more our previous reports that neurotransmitters can act directly as organizers of the brain. This holds true not only for the differentiation period but also for the maturation period of the brain.

Androgens↗

Multiperspective assessment of peripheral nerve involvement in diabetic patients.

To assess the relationship between peripheral nerve involvement and the patient's perception of his own quality of life, we studied 36 consecutive out-patients affected by insulin-dependent diabetes mellitus without other diabetic complications other than neuropathy (20 men, 16 women; mean age 39.1 years). We used clinical (Semmes-Weinstein, vibration perception threshold, muscle strength, osteotendinous reflexes), neurophysiological (sural, peroneal and ulnar nerves), metabolic (glycosylated haemoglobin) and patient-oriented (SF-36 and NASS questionnaires) measurements. Patient-oriented physical scores were significantly related to: (1) neurophysiological findings of the inferior limbs; (2) conventional measurements of sensitivity; (3) metabolic assessment. Conversely, patient-oriented mental scores were significantly related only to metabolic assessment. The patient-oriented measure provided an important perspective of the severity of the disease often closely related with the biological parameters and suggested new ways of interpreting conventional biological measurements. In particular, the peripheral nerve picture appeared strictly related with the physical aspects of the patients' quality of life, while the metabolic picture appeared related with both the mental and physical aspects of the quality of life.

Adult↗

[The importance of the medical discussion for diagnosis in general medicine (author's transl)].

The process of diagnostic decision by the doctor was analyzed in 84 first consultations in 3 general practices. In 78 cases or 92.8%, a diagnosis was already made during the first consultation, in 50 or 64.1% on the basis of the discussion between the doctor and patient alone, in 28 cases or 35.9% of the first consultations additional diagnostic examinations were carried out by the doctor. Half a year after the first consultations to any diagnostic investigations at all. The medical conversation has been shown, therefore, to be the doctor's most important diagnostic instrument. Consequently, lack of attention to it in general medical training seems to be unjustified, the change in the patients in general practice makes a psychosomatic orientation of the conversation necessary.

Diagnosis↗

Long-range electrostatic interactions influence the orientation of Fos-Jun binding at AP-1 sites.

Heterodimeric transcription regulatory proteins that bind palindromic DNA sequences can potentially bind their recognition sites in two opposite orientations. The orientation of transcription factor binding can control transcriptional activity by altering interactions with proteins that bind to adjacent regulatory elements. Fos-Jun heterodimers bind to AP-1 sites with different flanking sequences in opposite orientations. A gel-based fluorescence resonance energy transfer assay, gelFRET, was used to define the mechanism whereby amino acid residues and nucleotide base-pairs outside the Fos-Jun-AP-1 contact interface determine the orientation of heterodimer binding. Exchange of three amino acid residues adjacent to the basic DNA contact regions between Fos and Jun reversed the binding orientation. The effects of these amino acid residues on the orientation of heterodimer binding depended on base-pairs flanking the core AP-1 recognition sequence. Single amino acid and base-pair substitutions had parallel effects on DNA bending by Fos-Jun-AP-1 complexes and on heterodimer orientation. The binding orientation exhibited a close correspondence with both the difference in bending propensities of opposite sides of the AP-1 site as well as the difference in bending potentials of the Fos and Jun subunits of the heterodimer. The influence of flanking DNA sequences on heterodimer orientation was attenuated in the presence of high concentrations of multivalent cations. Base substitutions up to one helical turn from the center of the AP-1 site affected the binding orientation. Modification of flanking base-pairs with positively or negatively charged functional groups had opposite effects on the orientation of heterodimer binding. These changes in DNA charge had converse effects on the orientation preferences of heterodimers in which charged amino acid residues adjacent to the basic regions were exchanged between Fos and Jun. These results indicate that the orientation of heterodimer binding is determined primarily by minimization of the electrostatic free energy of the Fos-Jun-AP-1 complex. Consequently, long-range electrostatic interactions influence the architecture of nucleoprotein complexes.

Amino Acid Sequence↗

Childhood conversion reactions in the emergency department: Part I--Diagnostic and management approaches within a biopsychosocial framework.

The pediatric emergency physician faces several difficulties when he is unable to diagnose an organic etiology that sufficiently explains a child's somatic symptoms. Biomedical or psychological approaches alone often result in unsatisfactory outcomes, such as continued symptomatology, increased family anxiety, and either excessive or suboptimal use of medical resources to search for less obvious diseases. This paper suggests that the best approach toward a child's unexplained somatic symptoms is a biopsychosocial orientation that includes conversion reaction within the differential diagnosis. Comprehensive strategies are described for both diagnosis and management of conversion reactions so that both organic and psychosocial factors can be understood and addressed in the emergency department setting. Prognosis, epidemiology, and questions involving the definition of conversion reaction are also discussed. A follow-up paper will address specific diagnostic issues regarding both the general features and the most common presentations of conversion reactions.

Child↗

Oligonucleotide-directed single-base DNA alterations in mouse embryonic stem cells.

We have investigated the use of single-stranded oligodeoxy-nucleotides (ssODN) to produce specific single-base alterations in episomal and chromosomal DNA in mouse embryonic stem (ES) cells. Two different reporter genes, EGFP and LacZ, each with a single point mutation that inactivates reporter activity, were used. ssODN homologous to the target sequence, except for a single mismatch at the mutant base, were used to correct the mutant reporter genes. When tested in CHO-K1 cells, the ssODN showed correction rates of 0.5-1.0%, consistent with prior reports. ssODN in the antisense orientation provided higher rates of gene conversion than those in the sense orientation for both reporter genes. Nuclear extracts from mouse ES cells exhibited nearly the same correction activity as extracts from CHO-K1 cells. ssODN corrected the mutant bases of both episomal and chromosomal mutant reporter genes in mouse ES cells. Although the efficiency of gene correction observed in ES cells is low, approximately 10(-4), these results demonstrate that ssODN can produce single-base alterations in the genomic DNA of mouse ES cells. As conversion efficiency is improved by the continued development of oligonucleotide structure and DNA delivery methods, ssODN could be used to produce ES cells with specific mutations in any gene in a single step. The targeted ES cells could in turn be used to create accurate mouse models of inherited diseases.

Animals↗

[Depressive symptomatology and sleep apnea syndrome].

The sleep apnea syndrome (SAS), which is defined by more than 5 apneas or hypopneas per hour of sleep (9), is quite a frequent affection which concerns 1.4 to 10% of general population (1.7). The major daytime complaints of the SAS are daytime sleepiness, memory and attention disorders, headaches and asthenia especially in the morning, and sexual impotence (9). The nocturnal manifestations are dominated by sonorous and generally long standing snoring, increased by dorsal decubitus and intake of alcohol, with repeated interruptions by respiratory arrests. These manifestations are always noted but rarely spontaneously reported. The sleep, non refreshing, is agitated and perturbed by numerous awakenings. The findings of the clinical examination are poor: obesity is found in 2/3 of the cases and arterial hypertension in 1/2 of the cases (20). Polygraphic recording during sleep only permits an absolute diagnosis. This frequent affection is a real problem of public health because of its numerous complications (3, 10, 12, 13, 18, 21). Symptoms of depression are often found when a patient with a SAS is examined and conversely, symptoms which evoke a SAS can be found in the clinical examination of depressed patients. We decided so to study the thymic and anxious status of 24 patients investigated for a SAS and submitted to a polygraphic recording during sleep. Four clinical parameters were studied: DSM III-R diagnosis criteria, Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HARS) and thymasthenia rating scale of Lecrubier, Payan and Puech. We also reported Total Sleep Time (TST = 6.5 +/- 1.5), Apnea Hypopnea Index (AHI = 26.7 +/- 21.6), number (2.1 +/- 2.8/h) and duration (174.2 +/- 150.8 s/h) of hypoxic events. Results showed that among 24 patients, 8 were depressed according to DSM III-R diagnosis criteria and had MADRS > 25, 22 were anxious, 11 had a major anxiety (HARS > 15) and 15 presented thymasthenia (SET > 15). Significative correlations existed between anxiety and depression (r = 0.82; p < 0.0001), depression and thymasthenia (r = 0.77; p < 0.0001) and thymasthenia and anxiety (r = 0.75; p < 0.0001). Among the 8 depressed patients a correlation existed between AHI and depression (r = 0.72; p = 0.04), but no correlation was found between depression and hypoxic events. These results were comparable to those of Guilleminault (10), Reynolds (21), Kales (12), Bliwise (3), Klonoff (13) and Millman (18) who studied relations between SAS and depression. The evaluation of thymasthenia gave a more precise typology of the depressive state associated to SAS: the type of the mood disorder is more "blunted" and "anhedonic" than "sorrowful", particularly characterised by asthenia, lack of energy, reduction of interests (leisures, libido, work), loss of initiative, difficulties to organise tasks, fall of performances and reduction of pleasure usually felt in pleasant events (15). The physic symptomatology dominated the psychic one. The sleep disorganization, more than metabolic consequences of apneas, could be involved in this associated depressive state. Other neuropsychiatric troubles can be associated to the SAS. In fact, cognitive troubles (2, 8, 14, 16, 19, 22, 24) and personality disorders (12, 18) have been described. Our data confirm previous observations suggesting a frequent association between SAS, depression, fatigue and anxiety. Clinicians should consequently be aware that a depression with severe complaints of fatigue should deserve an investigation oriented towards SAS. Conversely, when a SAS is diagnosed, it is necessary to look for a possible depression in order to set up the most appropriate treatment. The frequency of SAS, like depression's one, increases with age. Prescription and consummation of sedative psychotropic drugs increase too with age. Since respiratory depressant effects of these drugs have been clearly demonstrated, it is important to evoke SAS when depressive and/or anxious states are diagnosed and not to aggravate it. An efficacious treatment of SAS can also cure the associated depressive state, but this one can persist. It is necessary, in this case, to select a non sedative antidepressant.

Adult↗

Imprinting and evolution of two Kruppel-type zinc-finger genes, ZIM3 and ZNF264, located in the PEG3/USP29 imprinted domain.

We have isolated Kruppel-type (C2H2) zinc-finger genes, ZIM3 (zinc-finger gene 3 from imprinted domain) and ZNF264, located downstream of human and mouse USP29 genes (encoding ubiquitin-specific processing protease 29). In human, both ZIM3 and ZNF264 encode zinc-finger proteins with Kruppel-associated box (KRAB) A and B domains at the amino-terminal regions of the predicted proteins. In contrast, mouse Zim3 and Zfp264 seem to have lost protein-coding capability based on the lack of open reading frames (ORFs) in their cDNA sequences. In particular, the 3' end of the Zim3 transcript overlaps with the coding region of the adjacent gene Usp29 in an antisense orientation, indicating the conversion of mouse Zim3 into an antisense transcript gene for Usp29. The expression patterns of ZIM3 and ZNF264 have been largely conserved between human and mouse, with testis-specific expression of ZIM3 and ubiquitous expression of ZNF264, but high expression levels in adult testes in both species. Our studies also demonstrate that both mouse genes are imprinted with maternal expression of Zim3 in adult testes and paternal expression of Zfp264 in neonatal and adult brain. The reciprocal imprinting of two neighboring mouse genes, Zim3 and Zfp264, is consistent with a pattern observed frequently in other imprinted domains, and suggests that the imprinting of these two genes might be coregulated.

Amino Acid Sequence↗