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Regeneration studies on a crayfish neuromuscular system. I. Connectivity changes after intersegmental nerve transplants.

The superficial flexor muscles of the crayfish are a neuromuscular system of a few muscle cells innervated by six neurons in a precise position-dependent pattern. The neurons are capable of regenerating their normal connectivity patterns within a short span of time when conditions are favorable. The superficial flexor muscles of the second and third segments, despite their similarities in neuronal and muscle cell size and number, have distinctive connectivity patterns; some homologous neurons form similar patterns but other homologous neurons form patterns that are reversed between segments. We transplanted each segment's nerve into each other's muscle in order to observe regeneration of the nerves into a target area that differed in connectivity patterns from their original muscle. During the first weeks of regeneration all neurons formed a connectivity pattern with more connections medially and declining connections laterally, a pattern determined by the medial location of the nerve transplant. This pattern is maintained for most of the neurons, but for some there is an eventual reduction in medial connections as maximum synapse formation shifts to the lateral muscle fibers. Three of the eight neurons studied were able to regenerate connectivity patterns that corresponded to their segment of origin and not to their host muscle. This suggests that intersegmental muscle differences are not influencing the formation of these connectivity patterns, so the neurons will follow their inherent synaptogenesis program.

Animals↗

Multifocal transitional cell carcinoma of the bladder and upper urinary tract: molecular screening of clonal origin by characterizing CD44 alternative splicing patterns.

PURPOSE: CD44 is a widely expressed cell surface adhesion molecule in which various isoforms arise from alternative RNA splicing mechanism during cancer initiation. We assessed whether multifocal transitional cell carcinoma of the urothelium is due to field change and/or intraluminal seeding and implantation. MATERIALS AND METHODS: In a series of 24 patients with synchronous and/or metachronous multiple urothelial cancers we performed reverse transcription-polymerase chain reaction analysis using a set of primers capable of amplifying all CD44 splice variant isoforms. After polymerase chain reaction products were electrophoresed band intensities with areas corresponding to the major isoforms (that is CD44s, CD44v10 and CD44v8-10) were quantified, and CD44v10-to-CD44s and CD44v8-10-to-CD44s ratios were calculated. Moreover, p53 gene mutations in exons 4 to 11 were screened by direct DNA sequencing. RESULTS: Of these 24 cases 18 showed similar CD44v10-to-CD44s and CD44v8-10-to-CD44s ratios in among multiple urothelial cancers in each case. However, in the remaining 6 cases these ratios were quite different among multiple cancer lesions. Furthermore, different types of p53 mutation were detected among multiple cancer lesions in only 2 of 24 cases, which also indicated different patterns of CD44 alternative splicing. CONCLUSIONS: These findings suggest that at least some multiple transitional cell carcinomas of the urothelium seem to be of independent origin based on the analysis of alternative RNA splicing of CD44. Moreover, this hypothesis was further supported by the evaluation of p53 gene mutation.

Alternative Splicing↗

A high-resolution multistrain haplotype analysis of laboratory mouse genome reveals three distinctive genetic variation patterns.

Understanding of the structure and the origin of genetic variation patterns in the laboratory inbred mouse provides insight into the utility of the mouse model for studying human complex diseases and strategies for disease gene mapping. In order to address this issue, we have constructed a multistrain, high-resolution haplotype map for the 99-Mb mouse Chromosome 16 using approximately 70,000 single nucleotide polymorphism (SNP) markers derived from whole-genome shotgun sequencing of five laboratory inbred strains. We discovered that large polymorphic blocks (i.e., regions where only two haplotypes, thus one SNP conformation, are found in the five strains), large monomorphic blocks (i.e., regions where the five strains share the same haplotype), and fragmented blocks (i.e., regions of greater complexity not resembling at all the first two categories) span 50%, 18%, and 32% of the chromosome, respectively. The haplotype map has 98% accuracy in predicting mouse genotypes in two other studies. Its predictions are also confirmed by experimental results obtained from resequencing of 40-kb genomic sequences at 21 distinct genomic loci in 13 laboratory inbred strains and 12 wild-derived strains. We demonstrate that historic recombination, intra-subspecies variations and inter-subspecies variations have all contributed to the formation of the three distinctive genetic signatures. The results suggest that the controlled complexity of the laboratory inbred strains may provide a means for uncovering the biological factors that have shaped genetic variation patterns.

Alleles↗

Genesis of a spatial pattern in the cellular slime mold Polysphondylium pallidum.

The branches in Polysphondylium pallidum whorls are arranged in a radial pattern. We have used a pattern-specific monoclonal antibody to study branch formation and characterize the origin of this pattern. A quantitative spatial analysis of antibody staining reveals that the branching pattern arises from a random distribution. This distribution passes through a series of intermediate stages to yield a radial prepattern. The origins and evolution of this prepattern are satisfactorily accounted for by models that produce spatial patterns by short-range autocatalytic and longer-range inhibitory forces.

Antibodies, Fungal↗

Microfabrication using elastomeric stamp deformation.

Elastomeric stamp deformation has been utilized for the contact printing (CP) of self-assembled monolayers (SAMs) and, more recently, polymers and proteins. Here, we take advantage of this well-studied phenomenon to fabricate a series of new metal thin-film patterns not present on the original stamp. The rounded patterns are of nanoscale thickness, long-range order, and are created from elastomeric stamps with only straight-edged features. The metal was printed onto the surface of an alpha,omega-alkanedithiol self-assembled monolayer (SAM). The new shapes are controlled by a combination of stamp geometry design and the application of external pressure. Previously published rules on stamp deformation for contact printing of SAMs are invalid because the coating is instead a thin-metal film. This method represents a new pathway to micropatterning metal thin films, leading to shapes with higher complexity than the original lithographic masters.

Journal Article↗

Spatial patterns in ant colonies.

The origins of large-scale spatial patterns in biology have been an important source of theoretical speculation since the pioneering work by Turing (1952) on the chemical basis of morphogenesis. Knowing how these patterns emerge and their functional role is important to our understanding of the evolution of biocomplexity and the role played by self organization. However, so far, conclusive evidence for local activation-long-range inhibition mechanisms in real biological systems has been elusive. Here a well-defined experimental and theoretical analysis of the pattern formation dynamics exhibited by clustering behavior in ant colonies is presented. These experiments and a simple mathematical model show that these colonies do indeed use this type of mechanism. All microscopic variables have been measured and provide the first evidence, to our knowledge, for this type of self-organized behavior in complex biological systems, supporting early conjectures about its role in the organization of insect societies.

Animals↗

[Evaluation of serum enzyme levels considering biological half lives of enzymes--alteration of lactate dehydrogenase isoenzyme pattern due to computer simulation].

The rapid clearance of certain releasing enzymes from blood stream may modify their usefulness as markers of disease. Serum LD isoenzyme patterns are often quite different from those in the affected tissues. Such differences result from differences in the biological half lives of the individual isoenzyme. In order to reveal such phenomena, we applied the one-compartment model to simulate the time dependent changes in the serum LD isoenzyme patterns as a most simple model. When we simulated leukemic cells as an affected origin, LD isoenzyme patterns obtained at a stage of clinical deterioration or active stage, were characterized by a high proportion of LD-2, LD-3 and LD-4, and resembled those of the original leukemic cells. In general, strong similarities in alterations of LD isoenzyme patterns were obtained between the clinical observed time course and simulated time course. These changes in LD isoenzyme patterns are practically observed in the cases of leukemia, lymphoma, and so on. If the original organs are identical, then it is change of disease stage that is responsible for modification of variable LD isoenzyme patterns. Such phenomena must therefore be noted--in doing so, we shall be able to estimate the origin of enzyme release, disease stage, and prognosis.

Computer Simulation↗

[Left ventricular blood flow dynamics caused by ventricular premature contraction: pulsed Doppler echocardiographic study].

Cardiac function at the time of ventricular premature contractions (VPC) is influenced by the coupling interval or the site of those origin. Clinical and experimental studies of the effects of VPC on intracardiac pressure dynamics have been performed; however, little is known about left ventricular blood flow dynamics. This study was attempted to determine the characteristics of blood flow dynamics in respect to the site of origin of VPC using pulsed Doppler echocardiography. The subjects consisted of 18 cases with VPC but without apparent organic heart disease. Seven cases had VPCs with a left bundle branch block pattern suggesting possible origin in the right ventricle. The other 11 cases had VPCs with a right bundle branch block pattern indicating the left ventricular origin. With the probe in the apical position, the blood flow patterns of the left ventricular outflow, central and inflow tracts were examined. The results were as follows; 1. Except for one case with shortened coupling interval, all six cases with VPCs originated from the right ventricle showed preservation of left ventricular ejection flow. 2. In two of the three cases with VPC which originated from the left ventricle and with left axis deviation, systolic flow in the left ventricular central area showed "back flow" to the apex. Ejection flow at the outflow tract was markedly diminished or disappeared in all three cases. 3. In all eight cases with VPC which originated from the left ventricle and with right axis deviation, ejection flow was slightly disturbed both in the left ventricular outflow and in the central area. 4. Ejection flow volume assessed by velocity integral indicated similar dynamics as did the ejection flow velocity. 5. In left ventriculography, asynchrony due to dyskinetic motion of the anteroapical wall was observed at the times of VPCs with left axis deviation. In conclusion, the patterns of left ventricular ejection flow dynamics depend on the site of origin of VPCs. This disturbed flow is more apparent in VPCs originating from the left ventricle compared to the right ventricle. This is especially true in cases with left axis deviation, in which VPCs arise from the posterior site of the left ventricle.

Adolescent↗

Mitochondrial DNA variation in Koryaks and Itel'men: population replacement in the Okhotsk Sea-Bering Sea region during the Neolithic.

In this study, we analyzed the mitochondrial DNA (mtDNA) variation in 202 individuals representing one Itel'men and three Koryak populations from different parts of the Kamchatka peninsula. All mtDNAs were subjected to high resolution restriction (RFLP) analysis and control region (CR) sequencing, and the resulting data were combined with those available for other Siberian and east Asian populations and subjected to statistical and phylogenetic analysis. Together, the Koryaks and Itel'men were found to have mtDNAs belonging to three (A, C, and D) of the four major haplotype groups (haplogroups) observed in Siberian and Native American populations (A-D). In addition, they exhibited mtDNAs belonging to haplogroups G, Y, and Z, which were formerly called "Other" mtDNAs. While Kamchatka harbored the highest frequencies of haplogroup G mtDNAs, which were widely distributed in eastern Siberian and adjacent east Asian populations, the distribution of haplogroup Y was restricted within a relatively small area and pointed to the lower Amur River-Sakhalin Island region as its place of origin. In contrast, the pattern of distribution and the origin of haplogroup Z mtDNAs remained unclear. Furthermore, phylogenetic and statistical analyses showed that Koryaks and Itel'men had stronger genetic affinities with eastern Siberian/east Asian populations than to those of the north Pacific Rim. These results were consistent with colonization events associated with the relatively recent immigration to Kamchatka of new tribes from the Siberian mainland region, although remnants of ancient Beringian populations were still evident in the Koryak and Itel'men gene pools.

Alaska↗

Epithelial ovarian carcinoma and European birthplace of grandparents.

OBJECTIVE: The aim of this study was to determine whether the risk of ovarian carcinoma was related to latitude or to genetically based patterns of European geographic origin. PATIENTS AND METHODS: We studied the countries of origin of European-born grandparents of 168 newly diagnosed patients in two hospitals in New York City, compared with 159 controls from similar neighborhoods. We measured the risk of this cancer associated with having one or more white, non-Jewish grandparents born in North Europe versus none or in South Europe versus none. We also classified geographic origins in other ways to reflect the two main trends in genetic variations between Europeans mapped by Cavalli-Sforza et al. (The History and Geography of Human Genes, Princeton University Press, Princeton, 1994). Unconditional logistic regression was used to control for age, parity, years of use of oral contraception, age at menarche, education, Catholic religion, and area of residence and for numbers of Jewish grandparents, siblings, and first-degree relatives with breast or ovarian cancer. RESULTS: Approximately half of the subjects had least one white, non-Jewish grandparent born in Europe. There was no significant effect of ancestral latitude: among women born in the United States the odds ratio (OR) and 95% confidence limits associated with North European ancestry were 0.87 (0.47--1.63) compared with a reference group of women with no such ancestry. The corresponding OR for South Europe was 0.73 (0.39--1.74). Using the genetically based classifications of countries of origin, however, we found significant differences between cases and controls; ancestries from North West Europe and those from countries concentrically near Spain showed lower risks of ovarian carcinoma. CONCLUSIONS: The results support the hypothesis that the previously observed effects of latitude must act through environmental effects or through gene-environment interactions. Other variations in risk related to geographic origins are consistent with known patterns of genetic differences, but require confirmation in larger, population-based studies.

Adult↗

Putative measure of peripheral and brainstem frequency-following in humans.

The human brainstem frequency-following response (FFR) registers phase-locked neural activity to periodic auditory stimuli. FFR waveforms were extracted from the electroencephalogram by averaging responses to repeated auditory stimulation. Two channels of data were simultaneously recorded from horizontally (electrodes placed in ear canals) and vertically (vertex scalp referenced to midline) oriented electrode configurations. Eight participants each received a total of 2000 tone repetitions for each of ten stimulus frequencies ranging from 133 to 950 Hz. FFRs were quantified by fast-Fourier spectral analysis. The largest spectral intensities at the stimulus frequency were recorded in the horizontal FFR, which also followed higher frequencies and showed better signal-to-noise ratios then did the vertical FFR. The horizontal FFR pattern suggests an acoustic nerve origin, while the vertical FFR pattern suggests a central brainstem origin.

Acoustic Stimulation↗

Typing of Legionella pneumophila strains by polymerase chain reaction-mediated DNA fingerprinting.

Well-defined Legionella pneumophila strains were analyzed by amplification of variable genomic regions with arbitrary and repeat sequence primers. Clinical and environmental outbreak-related isolates showed closely related amplicon patterns. Eleven strains of unrelated origins displayed 10 distinct patterns. Fingerprinting of L. pneumophila by polymerase chain reaction appeared to have the potential of being as epidemiologically useful as other genotypic methods.

Bacterial Typing Techniques↗

Mining, compressing and classifying with extensible motifs.

BACKGROUND: Motif patterns of maximal saturation emerged originally in contexts of pattern discovery in biomolecular sequences and have recently proven a valuable notion also in the design of data compression schemes. Informally, a motif is a string of intermittently solid and wild characters that recurs more or less frequently in an input sequence or family of sequences. Motif discovery techniques and tools tend to be computationally imposing, however, special classes of "rigid" motifs have been identified of which the discovery is affordable in low polynomial time. RESULTS: In the present work, "extensible" motifs are considered such that each sequence of gaps comes endowed with some elasticity, whereby the same pattern may be stretched to fit segments of the source that match all the solid characters but are otherwise of different lengths. A few applications of this notion are then described. In applications of data compression by textual substitution, extensible motifs are seen to bring savings on the size of the codebook, and hence to improve compression. In germane contexts, in which compressibility is used in its dual role as a basis for structural inference and classification, extensible motifs are seen to support unsupervised classification and phylogeny reconstruction. CONCLUSION: Off-line compression based on extensible motifs can be used advantageously to compress and classify biological sequences.

Journal Article↗

Oocyte and embryo quality: effect of origin, culture conditions and gene expression patterns.

In general, the majority of immature bovine oocytes fail to develop to the blastocyst stage following maturation, fertilization and culture in vitro. The evidence suggests that while culture conditions during in vitro embryo production can impact on the developmental potential of the early embryo, the intrinsic quality of the oocyte is the key factor determining the proportion of oocytes developing to the blastocyst stage. In addition, evidence suggests that the period of post-fertilization embryo culture is the most critical in determining blastocyst quality. This paper reviews the current literature, with emphasis on the bovine model, demonstrating evidence for an effect of oocyte origin and/or in vitro maturation conditions on the developmental capacity and gene expression patterns in the oocyte. Furthermore, the well-documented effects of post-fertilization culture environment on embryo gene expression and quality are highlighted.

Animals↗

A case of female adnexal tumor of probable Wolffian origin: histologically, tumor cells showed three different patterns.

We report a 63-year-old woman with a female adnexal tumor of probable Wolffian origin, which arose within the leaves of the broad ligament, connected to the left ovary and the fallopian tube. She remains alive without evidence of disease 2 years after left salpingo-oophorectomy without subsequent adjuvant therapy. Microscopically, tumor cells were arranged in three different patterns; closely packed tubules, solid, and sieve-like. Cells had uniform round or oval nuclei and mitoses were rare. Although the majority of these tumors are benign, a few cases have shown malignant potential. Therefore, such tumors should receive careful follow-up for possible recurrence and/or metastasis.

Broad Ligament↗

Classification of soil samples according to geographic origin using gamma-ray spectrometry and pattern recognition methods.

Multivariate data analysis methods were used to recognize and classify soils of unknown geographic origin. A total of 103 soil samples were differentiated into classes, according to regions in Serbia and Montenegro from which they were collected. Their radionuclide (226Ra, 238U, 235U, 40K, 134Cs, 137Cs, 232Th and 7Be) activities detected by gamma-ray spectrometry were then used as the inputs in different pattern recognition methods. For the classification of soil samples using eight selected radionuclides, the prediction ability of linear discriminant analysis (LDA), k-nearest neighbours (kNN), soft independent modelling of class analogy (SIMCA) and artificial neural network (ANN) were 82.8%, 88.6%, 60.0% and 92.1%, respectively.

Radioisotopes↗

MMP and TIMP expression pattern in pleural effusions of different origins.

The matrix metalloproteinases (MMP) are proteolytic enzymes that are essentially involved in the turnover of the extracellular matrix (ECM). Their activity is counterbalanced by specific antagonists, the tissue inhibitors of metalloproteinases (TIMP). In this study, we sought to analyze the expression of MMP and TIMP isoforms in pleural effusions from 88 patients. We compared MMP and TIMP isoform expression in transudates (n = 21) and exudates (n = 67), the latter divided into exudates of paraneoplastic (n = 46) or parainfectious (n = 21) origin. Zymographic and Western blot analyses revealed constant expression of interstitial collagenase (MMP-1), gelatinase-A (MMP-2), and TIMP-1 in all 88 samples. In contrast, analyses of gelatinase-B (MMP-9) demonstrated a specific expression pattern, with high expression in exudates and lack of expression in transudates. Neutrophil collagenase (MMP-8) was detected in trace amounts, and correlated with the number of neutrophils in the effusion. Low levels of TIMP-2 were detected only in exudates and not in transudates. Quantitative analysis of the expression ratio of gelatinase-B to gelatinase-A revealed statistically significant differences between effusions of different origin. The ratio was highest in exudates of paraneoplastic origin and lowest in transudates. Our data thus suggest that interstitial collagenase, gelatinase-A, and TIMP-1 play a role in homeostasis of the pleural space in vivo as constitutively expressed proteins, whereas gelatinase-B and TIMP-2 expression are induced in specific disease states. These observations contribute to the understanding of the pathophysiology of pleural effusions, and may help to characterize and possibly distinguish effusions of different origin.

Adult↗

Metastatic potential of metastases, tumor cell heterogeneity, and therapeutic implications.

The metastasizing capacity of spontaneous metastases of several murine tumors of different histology, origin, and disseminative pattern was investigated to test the hypothesis that metastases originate from various subpopulations within the primary tumor. Overall, tumor cells from individual metastases did not show greater metastasizing capacity than the cells of the original tumor, although a degree of heterogeneity was seen. Differences in the immunologic profile among metastases of the same tumor were also observed. The possible therapeutic implications of these findings are discussed.

Animals↗