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PubMed1991

Interspecific perspective on mechanical and nonmechanical models of primate circumorbital morphology.

Linear dimensions and angular orientations of the browridge, postorbital bar, and postorbital septum were obtained from a representative series of primates and compared with variables associated with several nonmechanical and biomechanical/mechanical models put forward to explain the form and function of the circumorbital region. Analyses of the results indicate that face size is the primary determinant of variation in primate circumorbital morphology. Anteroposterior browridge thickness is correlated with neural-orbital disjunction among anthropoid primates, but not among prosimians. This difference appears related to differences in the construction of the upper face and anterior cranial fossa between prosimians and anthropoids. Little support is demonstrated for the anterior dental loading model of browridge development. Mediolateral postorbital bar width and (to a lesser degree) browridge height are correlated with neurofacial torsion during mastication and variation in masticatory muscle size. These analyses further suggest that since circumorbital structures (especially the browridges) are located the farthest away from the chewing apparatus, they are least affected by masticatory stresses.

Animals↗

PubMed1995

Subfossil Indri indri from the Ankarana Massif of northern Madagascar.

Subfossil specimens of Indri indri have been recovered recently from the Ankarana Massif cave system in the far north of Madagascar. Taken together with material from the central highland site of Ampasambazimba, the range of this species appears to have once included much of the northern half of the island and to have extended north and west beyond the eastern rainforest (not unlike Hapalemur simus). It is probable that forest corridors connected the subfossil localities to the current range at some time in the past. Climatic desiccation (fluctuating or long-term) and/or human degradation of the environment may have created the disjunct distributions of living and subfossil I. indri. It is also possible that I. indri once included populations or subspecies that were better adapted to dry forest, woodland, or mosaic environments, habitats very different from those occupied by their living conspecifics. Such adaptive diversity would have been similar to that of Propithecus diadema which today has subspecies in the montane forests and one (P.d. perrieri) in the dry forests of the northeast. These discoveries add new information on range extensions to the distributional database for the primates of Madagascar, and illustrate the piecemeal process of their extinctions.

Animals↗

PubMed1986

Oculomasticatory myorhythmia: a unique movement disorder occurring in Whipple's disease.

We describe two patients and a previously reported patient who acquired unique pendular vergence oscillations of the eyes and concurrent contractions of the masticatory muscles, i.e., oculomasticatory myorhythmia (OMM). The smooth disjunctive eye movements cycled with a frequency of 0.8 to 1.2 Hz. An analysis of peak velocities (15 to 200 degrees/sec) with respect to peak amplitudes (5 to 25 degrees) revealed dynamics characteristic of normal vergence movements. The pathological alterations resulting in pendular vergence oscillations implicate a separately functioning, physiologically normal vergence system within the brainstem. In addition to paralysis of vertical gaze, each patient also experienced progressive somnolence and intellectual deterioration. An intestinal biopsy in 1 patient established a diagnosis of Whipple's disease, which led to appropriate treatment and amelioration of the OMM. A pathological diagnosis of Whipple's disease of the central nervous system was made in the other 2 patients; results of an intestinal biopsy in one of these patients were normal. No patient had palatal myoclonus, and olivary pseudohypertrophy was not found in two autopsy examinations. Thus, OMM is a distinct movement disorder and has been recognized only in Whipple's disease. We conclude that patients with OMM should be treated presumptively for Whipple's disease of the central nervous system, even if a jejunal biopsy is normal.

Eye Movements↗

PubMed1992

Reproduction in a South American mouse, Abrothrix longipilis.

Approximately 700 Abrothrix longipilis were trapped in Argentina, and their reproductive organs were studied. Some were kept briefly in captivity. Males have the same body length as females but are 8% heavier. Sexually immature males are shorter and lighter than breeding males of the same age. Few individuals in the wild live as long as two years. All overwintering males come into breeding condition in the spring and become infertile in the autumn. All overwintering females have open vaginas in the spring, and most undergo several infertile ovulatory cycles, probably without copulating, before they become pregnant. Corpora lutea of the sterile cycles accumulate; there may be as many as 28 in a pair of ovaries. The average number of ova shed per cycle is 4.66; average litter size is 3.85. Ovulation is spontaneous. There is postpartum ovulation and fertilization without intervening sterile cycles but with maintenance of old corpora lutea. Unusual architecture of the penis and vagina may result from unusual timing of hormone production during development, and the disjunction of ovulation and fertilization may similarly result from hormonal heterochrony at the beginning of the breeding season. The apparently nonadaptive wastage of ova in sterile cycles may be a novel example of kin selection.

Animals↗

PubMed1982

The corticopontine system in the rat. II. The projection pattern.

The projection from various cortical areas to the pontine nuclei (PN) of rats was investigated with anterograde tracing methods. As a general topological rule, a medial to lateral succession of the PN projection fields from the motor, somatosensory, and visual cortices was observed. Apart from the main "private" projections, each cortical area was found to send fibers also to disjunctive "extra-projection" territories which receive convergent inputs from two or more cortical areas. The sensorimotor and visual cortices provide the bulk of corticofugal fibers, but contributions from the following association areas were noted: frontal cortex, (dependent of the thalamic mediodorsal nucleus), rhinal sulcus region, and cingulate cortex.

Animals↗

PubMed1986

Optic tectum of the eastern garter snake, Thamnophis sirtalis. V. Morphology of brainstem afferents and general discussion.

Brainstem neurons that project to the optic tectum of the eastern garter snake were identified by retrograde transport of horseradish peroxidase. The distribution and morphology of tectal afferent axons from the thalamus, pretectum, nucleus isthmi, and midbrain reticular formation were then studied by anterograde transport of horseradish peroxidase. Diencephalic projections to the tectum arise from the ventral lateral geniculate complex ipsilaterally and the ventrolateral nucleus, suprapeduncular nucleus, and nucleus of the ventral supraoptic decussation bilaterally. Three pretectal groups (the lentiform thalamic nucleus, the lentiform mesencephalic-pretectal complex and the geniculate pretectal nucleus) give rise to heavy, bilateral tectal projections. Small neurons in nucleus isthmi and large reticular neurons in nucleus lateralis profundus mesencephali also give rise to bilateral projections. Caudal to the tectum, projections arise bilaterally from the pontine and medullary tegmentum, nuclei of the lateral lemniscus, the posterior colliculus, and the sensory trigeminal nucleus. A small contralateral projection arises from the medial vestibular complex. Tectal afferents from the thalamus, pretectum, nucleus isthmi, and midbrain reticular formation had characteristic morphologies and laminar distributions within the tectum. However, these afferents fall into two groups based on their spatial organization. Afferents from the thalamus and nucleus isthmi arise from small neurons with spatially restricted, highly branched dendritic trees. Their axons terminate in single, highly branched and bouton-rich arbors about 100 micron in diameter. By contrast, afferents from the midbrain reticular formation and the pretectum arise from large neurons with long, radiate, and sparsely branched dendritic trees. Their axons course parallel to the tectal surface and emit numerous collateral branches that are distributed widely through the mediolateral and rostrocaudal extent of either the central or superficial gray layers. Each collateral bears several small, spatially disjunct clusters of boutons.

Animals↗

PubMed1990

Transient patterns of GAP-43 expression during the formation of barrels in the rat somatosensory cortex.

The development of the rat barrel field cortex was investigated with an antibody to the axonal membrane-specific phosphoprotein GAP-43 in order to examine the developmental pattern of afferent projections, and with cytochrome oxidase histochemistry and Nissl stains to reveal the morphogenesis of cortical barrels. On the first two days after birth, GAP-43 immunostaining in the cortical plate was light and diffuse, then became intense in the presumptive layer IV of the parietal cortex on PND3 (day of birth = PND0). Immunoreactive densities were visible as small, focal patches within the centers of prospective barrels. These densities increased in size and intensity over the next few days and then diminished abruptly. On PND7, the distribution of GAP-43 was coextensive with barrels, as defined by cytochrome oxidase histochemistry and Nissl staining. GAP-43 virtually disappeared from the barrels after PND7. From the second postnatal week, GAP-43 immunostaining was evident in the septa between barrels and in the dysgranular regions of SI cortex. This pattern of GAP-43 distribution was complementary to the pattern of cytochrome oxidase activity, and persisted into maturity. In an attempt to identify possible source(s) of GAP-43 positive afferents in the developing barrels, we examined the effects of altering the sensory periphery on the distribution of GAP-43 immunostaining in the cortex. Rat pups had row C whiskers cauterized on PND0 and were sacrificed on PND3 or PND5. Whereas immunopositive densities corresponding to intact whiskers developed in a normal, punctate pattern, cortical representation of the lesioned whiskers formed a continuous band of labeling that was evident as early as PND3. We argue that the disjunctive expression of GAP-43 in the barrel field reflects the pattern of distribution of afferents (most likely from the ventro-basal thalamic nucleus) to the barrel field cortex, and that this pattern may be instructive in the formation of barrels as cytoarchitectonic units. The rapid alteration in patterns of immunostaining following whisker lesions lends further support to the conclusion that the "barrel template" is conveyed to the neocortex by incoming afferents. The possible significance of the transient expression of GAP-43 in the maturing barrel field is discussed.

Aging↗

PubMed1991

Calibration of fluorescence intensities to quantify antibody binding surface determinants of cell subpopulations by flow cytometry.

Quantitative indirect immunofluorescence analysis by flow cytometry was used to determine the mean number of antibody binding sites per cell in a small subpopulation of rat brain cells expressing low levels of a cell surface differentiation antigen recognized by monoclonal antibody (Mab) RB13-6 (Kindler-Röhrborn et al.: Differentiation 30:53-60, 1985). For these non-disjunct distributions of fluorescence intensities, the cut-off border between antigen-positive and antigen-negative cells was defined by a statistical test. To eliminate the influence of accidental disturbances leading to incorrect statistical decisions, the curves for antigen-negative cells were fitted according to cell number and shape. The flow cytometer was calibrated with the use of a clonal cell line for which the average number of Mab RB13-6 binding sites per cell had previously been determined by radioimmunoassay and Scatchard-plot analysis. Using this analytical procedure, both the proportion of Mab binding brain cells and the mean number of Mab binding sites per Mab binding cell could be determined as a function of developmental stage.

Animals↗

PubMed1994

Improved flow-cytometric detection of low P-glycoprotein expression in leukaemic blasts by histogram subtraction analysis.

Expression of the drug efflux pump P-glycoprotein (PGP) was determined by flow cytometry in human lung cancer cell lines and in leukaemic blasts derived from 60 patients with acute myeloid leukaemia (AML). Cells from the PGP-negative parent cell line H69/P and the multidrug resistant (MDR)-variant H69/LX4 could be clearly distinguished by immunostaining with the anti-PGP monoclonal antibody MRK16. In leukaemic blasts, the differences in fluorescence intensities between samples incubated with the idiotypic nonspecific (control sample) and specific antibody (test sample) were small, resulting in nondisjunct distributions. Only in a few leukaemia specimens were PGP-expressing cells detectable by simple subtraction of histograms using a threshold. Therefore, an improved histogram subtraction analysis, based on curve fitting and a statistical test, was applied to distinguish antigen-positive from antigen-negative cells. Moreover, a multiparametric staining procedure employing propidium iodide (PI) and Hoechst 33342 was used to reduce staining artefacts. By this approach, leukaemic cells with low expression of PGP were detected in 39 out of 60 cases. Subpopulations with strong PGP expression, resulting in disjunct fluorescence distributions, were not observed. Only in 5 out of 60 specimens were PGP expressing cells detected by a conventional subtraction of histograms using a threshold. Comparison of data obtained with or without the multiparametric gating procedure indicated that the increase in sensitivity was mainly due to the application of the data analysis. However, exclusion of cell debris using PI and Hoechst staining properties reduced the deviation of data from mean values. No relation between PGP expression and cell cycle position was observed in either cell lines or in leukaemic blasts.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

There are two mechanisms of achiasmate segregation in Drosophila females, one of which requires heterochromatic homology.

There are numerous examples of the regular segregation of achiasmate chromosomes at meiosis I in Drosophila melanogaster females. Classically, the choice of achiasmate segregational partners has been thought to be independent of homology, but rather made on the basis of availability or similarities in size and shape. To the contrary, we show here that heterochromatic homology plays a primary role in ensuring the proper segregation of achiasmate homologs. We observe that the heterochromatin of chromosome 4 functions as, or contains, a meiotic pairing site. We show that free duplications carrying the 4th chromosome pericentric heterochromatin induce high frequencies of 4th chromosome nondisjunction regardless of their size. Moreover, a duplication from which some of the 4th chromosome heterochromatin has been removed is unable to induce 4th chromosome nondisjunction. Similarly, in the absence of either euchromatic homology or a size similarity, duplications bearing the X chromosome heterochromatin also disrupt the segregation of two achiasmate X chromosome centromeres. Although heterochromatic regions are sufficient to conjoin nonexchange homologues, we confirm that the segregation of heterologous chromosomes is determined by size, shape, and availability. The meiotic mutation Axs differentiates between these two processes of achiasmate centromere coorientation by disrupting only the homology-dependent mechanism. Thus there are two different mechanisms by which achiasmate segregational partners are chosen. We propose that the absence of diplotene-diakinesis during female meiosis allows heterochromatic pairings to persist until prometaphase and thus to co-orient homologous centromeres. We also propose that heterologous disjunctions result from a separate and homology-independent process that likely occurs during prometaphase. The latter process, which may not require the physical association of segregational partners, is similar to those observed in many insects, in Saccharomyces cerevisiae and in C. elegans males. We also suggest that the physical basis of this process may reflect known properties of the Drosophila meiotic spindle.

Animals↗

PubMed1989

Characterization of Schizosaccharomyces pombe minichromosome deletion derivatives and a functional allocation of their centromere.

A 530 kb long Schizosaccharomyces pombe linear minichromosome, Ch16, containing a centric region of chromosome III, has previously been made. In the present study, we constructed a number of deletions in the right and/or left arms of Ch16, and compared their structure and behaviour with Ch16. The functional centromere, cen3, is allocated within a 120 kb long region which is covered by the shortest derivative, Ch10, and is comprised mostly of centromeric repeating sequences. The shortest minichromosome is stable in mitosis and the copy number control is apparently precise. In monosomic meiosis it segregates normally. In disomic meioses, however, the frequency of non-disjunction is very high, suggesting that it may not form a pair. The mitotic loss rate of one of the left-arm deletions, ChR32, which lacks a part of the centromeric repeating sequence, is the highest of all the deletions. This deletion also exhibits the highest precocious sister chromatid separation in meiosis I, suggesting that sister chromatid association might become weakened in ChR32. Our results indicate that the proper meiotic segregation of S.pombe minichromosomes is dependent upon the formation of a bivalent. S.pombe may not have the 'distributive segregation' found with Saccharomyces cerevisiae minichromosomes.

Blotting, Southern↗

PubMed1989

The claret locus in Drosophila encodes products required for eyecolor and for meiotic chromosome segregation.

The claret (ca) locus in Drosophila encodes products that are needed both for wild-type eyecolor and for correct meiotic chromosome segregation. Mutants described previously provide evidence that two mutationally independent coding regions are present at ca. We have recovered six new P element-induced and one spontaneous ca mutant. Four of these new mutants affect both eyecolor and chromosome segregation. The high frequency of co-mutation of these two functions suggests that the corresponding genes are closely adjacent to one another. We recovered genomic DNA sequences corresponding to the ca locus by chromosome walking, and showed using revertant analysis that the cloned region encodes ca+. Transformation experiments demonstrate that the mutant effect resulting in meiotic chromosome non-disjunction (nd) and loss is fully rescued by DNA from the cloned region. Two RNAs of 7.4 and 2.2 kb have been identified by Northern blot analysis as the putative eyecolor and segregational products. Expression of the RNAs with respect to males and females, and their presence or absence in ca and nd mutants indicate that the 7.4 kb RNA corresponds to the product needed for wild-type eyecolor and the 2.2 kb RNA is the product required for normal chromosome segregation. These RNAs are transcribed in opposite directions to one another. Alleles that affect both eyecolor and chromosome segregation are deletion mutants that affect both transcripts. Thus, the putative eyecolor and segregational products are encoded by separate genes. Mutants that affect both eyecolor and chromosome segregation apparently do so because they delete essential regions of both genes.

Alleles↗

PubMed1990

The CHL 1 (CTF 1) gene product of Saccharomyces cerevisiae is important for chromosome transmission and normal cell cycle progression in G2/M.

We have analyzed the CTF1 gene, identified in a screen for mutants with decreased chromosome transmission fidelity and shown to correspond to the previously identified chl1 mutation. Chl1 null mutants exhibited a 200-fold increase in the rate of chromosome III missegregation per cell division, and near wild-type rates of marker homozygosis on this chromosome by mitotic recombination. Analysis of the segregation of a marker chromosome indicated that sister chromatid loss (1:0 segregation) and sister chromatid non-disjunction (2:0 segregation) contributed equally to chromosome missegregation. A genomic clone of CHL1 was isolated and used to map its physical position on chromosome XVI. Nucleotide sequence analysis of CHL1 revealed a 2.6 kb open reading frame with a 99 kd predicted protein sequence that contained two PEST sequences and was 23% identical to the coding region of a nucleotide excision repair gene, RAD3. Domains of homology between these two predicted protein sequences included a helix-turn-helix motif and an ATP binding site containing a helicase consensus. Mutants lacking the CHL1 gene product are viable and display two striking, and perhaps interrelated, phenotypes: extreme chromosome instability and a delay in cell cycle progression in G2/M. This delay is independent of the cell cycle checkpoint that requires the function of the RAD9 gene.

Alleles↗

PubMed1992

Complementation of the cs dis2-11 cell cycle mutant of Schizosaccharomyces pombe by a protein phosphatase from Arabidopsis thaliana.

The activities of type I protein phosphatases play a central role in eukaryotic cell cycle control. Here, we report the cloning and characterization from the flowering plant Arabidopsis thaliana of a cDNA clone named PP1-At which is highly homologous to protein phosphatase 1. The deduced amino acid sequence of PP1-At shows that the PP1-At protein is 318 amino acid residues long and has a molecular weight of 35,298 Da. The PP1-At protein has strong similarity to all other known protein phosphatase type 1 catalytic subunits. Approximately 62% of the amino acids are identical to type 1 protein phosphatases of rabbit, mouse, Saccharomyces cerevisiae and Schizosaccharomyces pombe. RNA blot analysis revealed a single mRNA species of approximately the same size as the cDNA isolated. The PP1-At-encoded mRNA of 1.3 kb is abundant in most vegetative Arabidopsis tissues, with the lowest level of expression in leaves. When transferred to the fission yeast S.pombe, the PP1-At-encoded protein can rescue a semidominant mutant, cold sensitive (cs) dis2-11, which under nonpermissive conditions is unable to complete chromosome disjunction.

Amino Acid Sequence↗

PubMed1994

Origins of reversed directionality in the ncd molecular motor.

The head or motor domain of the ncd (non-claret disjunctional) molecular motor is 41% identical to that of kinesin, yet moves along microtubules in the opposite direction to kinesin. We show here that despite the reversed directionality of ncd, its kinetics in solution are homologous in key respects to those of kinesin. The rate limiting step, ADP release, occurs at 0.0033 s-1 at 100 mM NaCl and is accelerated approximately 1000-fold when the motor binds to microtubules. Other reaction steps are all very fast (> 0.1 s-1) compared with ADP release, and the motor is consequently paused in the ncd.ADP state until microtubule binding occurs (Kd = 2 microM), at which point ADP release is triggered and the motor locks onto the microtubule in a rigor-like state. These data identify close functional homology between the strong binding states of kinesin and ncd, and in view of this we discuss a possible mechanism for directional reversal, in which the strong binding states of ncd and kinesin are functionally identical, but the weak binding states are biased in opposite directions.

Adenosine Diphosphate↗

PubMed1999

Reversing the negative cycle: interpreting the mutual influence of adaptive, self-protective measures in the couple.

The author discusses factors that shape the subjective meanings each member of the couple gives to marital interactions and the intersubjective disjunctions between the partners that can result. These include adaptive, self-protective mechanisms, the wish for mastery, guilt, and defense against grieving. Through illuminating these factors, psychoanalytic couple therapy can enhance empathic awareness of how each partner's attitudes, actions, and once adaptive defenses can actualize the other's transference expectations and evoke his or her painful and traumatic childhood relationships and experiences.

Adaptation, Psychological↗

PubMed2007

Bond order and valence indices: a personal account.

The paper accounts for the author's activity in developing bond order and valence indices since the early 80s. These indices represent an important conceptual link between the physical description of molecules as systems of electrons and nuclei and the chemical picture of molecules consisting of atoms kept together by bonds. They are also useful for a systematization and interpretation of the results obtained in the quantum chemical calculations, by permitting to extract from the wave function different pieces of information that may be assigned chemical significance. In some cases they can have some predictive power, too. Historically, the prototypes of such indices were introduced in the semiempirical quantum chemistry; the most important developments were Coulson's charge-bond order matrix in the simple Hückel theory and the Wiberg index in the CNDO framework. (Valence indices were also introduced in the semiempirical theory.) The definition of the ab initio bond order index emerged from the asymptotic term of the exchange energy component of the partitioning performed in the framework of the author's so-called "chemical Hamiltonian approach" using a "mixed" second quantization formalism for overlapping basis sets. They can also be introduced by studying the exchange part of the two-particle density (or of the second-order density matrix). Some properties of the bond order indices are discussed and the author's (until now unpublished) proof is also presented, showing the sufficient conditions under which the bond order index of a homonuclear diatomics is equal to the "chemist's bond order," i.e., the half of the difference between the number of electrons occupying bonding and antibonding orbitals. The ab initio valence indices are also introduced and discussed, and it is stressed that for correlated wave function the same "exchange only" definition of the bond order and valence indices should be used, which was introduced for the SCF case. The recent concept of the "atomic decomposition of identity" is also discussed and it is utilized for introducing bond orders and valences in the framework of the "3D analysis," when atoms are defined not by their basis orbitals but as regions of the three-dimensional (3D) physical space. Two versions of the 3D analysis are considered--the AIM (atoms in molecules)-type decomposing the space into disjunct atomic domains and the "fuzzy atoms" scheme in which there are no sharp boundaries between the atoms but they exhibit a continuous transition from one to another.

Journal Article↗

PubMed2004

Analysis of nerve fibers and their distribution in histologic sections of the human brain.

The field of quantitative analysis and subsequent mapping of the cerebral cortex has developed rapidly. New powerful tools have been applied to investigate large regions of complex folded gyrencephalic cortices in order to detect structural transition regions that might partition different cortical fields of disjunct neuronal functions. We have developed a new mapping approach based on axoarchitectonics, a method of cortical visualization that previously has been used only indirectly with regard to myeloarchitectonics. Myeloarchitectonic visualization has the disadvantage of producing strong agglomerative effects of closely neighbored nerve fibers. Therefore, single and neurofunctional-relevant parameters such as axonal branchings, axon areas, and axon numbers have not been determinable with satisfying precision. As a result, different staining techniques had to be explored in order to achieve a suitable histologic staining for axon visualization. The best results were obtained after modifying the Naoumenko-Feigin staining for axons. From these contrast-rich stained histologic sections, videomicroscopic digital image tiles were generated and analyzed using a new fiber analysis framework. Finally, the analysis of histologic images provided topologic ordered parameters of axons that were transferred into parameter maps. The axon parameter maps were analyzed further via a recently developed traverse generating algorithm that calculated test lines oriented perpendicular to the cortical surface and white matter border. The gray value coded parameters of the parameter maps were then transferred into profile arrays. These profile arrays were statistically analyzed by a reliable excess mass approach we recently developed. We found that specific axonal parameters are preferentially distributed throughout granular and agranular types of cortex. Furthermore, our new procedure detected transition regions originally defined by changes of cytoarchitectonic layering. Statistically significant inhomogeneities of the distribution of certain axon quantities were shown to indicate a subparcellation of areas 4 and 6. The quantification techniques established here for the analysis of spatial axon distributions within larger regions of the cerebral cortex are suitable to detect inhomogeneities of laminar axon patterns. Hence, these techniques can be recommended for systematic and observer-supported cortical area mapping and parcellation studies.

Aged↗