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PubMed1988

Genomic organization of major sperm protein genes and pseudogenes in the nematode Caenorhabditis elegans.

The major sperm proteins (MSPs) are a family of closely related, small, basic proteins comprising 15% of the protein in Caenorhabditis elegans sperm. They are encoded by a multigene family of more than 50 genes, including many pseudogenes. MSP gene transcription occurs only in late primary spermatocytes. In order to study the genomic organization of transcribed MSP genes, probes specific for the 3' untranslated regions of sequenced cDNA clones were used to isolate transcribed genes from genomic libraries. These and other clones of MSP genes were located in overlapping cosmid clones by DNA fingerprinting. These cosmids were aligned with the genetic map by overlap with known genes or in-situ hybridization to chromosomes. Of 40 MSP genes identified, 37, including all those known to be transcribed, are organized into six clusters composed of 3 to 13 genes each. Within each cluster, MSP genes are not in tandem but are separated by at least several thousand bases of DNA. Pseudogenes are interspersed among functional genes. Genes with similar 3' untranslated sequences are in the same cluster. The six MSP clusters are confined to only three chromosomal loci; one on the left arm of chromosome II and two near the middle of chromosome IV. Additional sperm-specific genes are located in one cluster of MSP genes on chromosome IV. The multiplicity of MSP genes appears to be a mechanism for enhancing MSP synthesis in spermatocytes, and the loose clustering of genes could be a result of the mechanism of gene duplication or could play a role in regulation.

Animals↗
PubMed1997

Two-dimensional electrophoretic analysis of the protein family at 90 kDa of abortifacient Chlamydia psittaci.

Four major clusters, designated A, B, C and D, were distinguished in Western Blots by a monoclonal antibody specific for the "antigen family at 90 kDa" after two-dimensional electrophoretic analysis on immobilized pH gradient of chlamydial elementary bodies of abortifacient C. psittaci. Clusters B, C, and D were closely related with molecular mass (kDa) pI values of 91.5/5.2-5.4, 90/5.0-5.2 and 90.5/5.6-5.8, respectively. Cluster A was larger, with molecular mass/pI of 104.7/5.1-5.3. Evidence for the antigenic relationship between cluster A and clusters B, C and D was further supported by immunological cross-reaction with affinity-purified antibodies from serum of ewes with chlamydial-induced abortion. The experimental values obtained for size and pI of the four clusters correlated well with the calculated values from known sequences coded by multiple chlamydial genes. Direct evidence for the correspondence between the immunoreactive clusters B, C and D and the retrieved genes was provided by antibody binding experiments to recombinant polypeptides representing fragments of the deduced proteins. The 4-member antigen family at 90/104 kDa is the first example of proteins coded by multiple genes within the genus Chlamydia.

Abortion, Veterinary↗
PubMed2006

Anion substitution in zinc chalcogenides.

Anion substitution effects on the structure and energy of zinc chalcogenides were studied with the semiempirical molecular orbital method MSINDO. Cyclic clusters of different sizes were chosen as model systems. The convergence of the bulk properties of the perfect clusters with increasing cluster size was tested. Single and multiple substitution of oxygen atoms in zinc oxide by sulfur and of sulfur atoms in zinc sulfide by oxygen served to determine the energetics of substitution for these two cases. It was found that the substitution of oxygen by sulfur in ZnO is easier than the substitution of sulfur by oxygen in ZnS in agreement with experimental results. The interaction between two oxygen atoms vs. two selenium atoms in zinc sulfide was investigated. Oscillations of the cluster energy in dependence of the distance between the two doping atoms were observed. These are explained by the relative sites of the doping atoms in the crystal lattice. The magnitude of the oscillations is smaller in ZnS:Se than in ZnS:O, because the difference between the anion radii of S2- and Se2- is smaller than between S2- and O2-. This is also reflected in the band gap.

Journal Article↗
PubMed1994

Anterior chamber angle vascularization in Sturge-Weber syndrome. Report of a case.

The case of a 20-year-old woman with a left-sided facial hemangioma and a homolateral glaucoma is reported, complete with the histology of a trabeculectomy specimen. Her left eye had an episcleral hemangioma and goniodysgenetic features in the anterior chamber angle, while the intraocular pressure was measured to be 45 mmHg. The left optic disc showed a large cupping and the left visual field was constricted. The right eye had no glaucomatous changes. Histological examination of the trabeculectomy specimen by both light and electron microscopy showed multiple congenital anomalies. There was a cluster of blood vessels in the trabecular meshwork. Abnormal accumulations of fine granular extracellular matrixes were observed in both the juxtacanalicular connective tissue and around the vascular structures. The lumen of Schlemm's canal was subdivided into three or four parts with few giant vacuole structures. The endothelial cells lining the inner wall of Schlemm's canal contained a well-formed basal lamina with many villi projecting into the lumen. These findings suggest that the multiple anomalies observed in the trabecular tissue may contribute to the manifestation of glaucoma in Sturge-Weber syndrome.

Adult↗
PubMed2005

Early cellular events in multiple sclerosis. Intimations of an extrinsic myelinolytic antigen.

In a previous immunohistological study of tissues from unusually early cases of MS cluster analysis revealed a progression of demyelination through five distinct stages [Gay F, Drye T, Dick G, et al. The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion. Brain 1997;120:1461-83]. Tissues from six of the earliest cases in this series contained regions of normal appearing white and grey matter in which well developed inflammatory events, concentrated in perivascular spaces, were found to extend locally into the perivascular parenchyma to envelop ostensibly intact myelin sheaths. The beginnings of myelin sheath lysis and phagocytosis were subsequently detected within these lesions and similar foci were found in subpial and in subependymal tissues. They were characterised by a spreading HLA Class II antigen expression on microglia, and by the presence of co-locating C3 complement-IgG complexes on capillary basement membranes, on microglial cell membranes and within the cytoplasm of large bodied activated astrocytes. Parenchymal lesions contained significantly few CD4+ T cells and showed no evidence of capillary leakage of plasma proteins. Despite the presence of complexed immunoglobulin and complement, opsonization of the myelin sheath could not be demonstrated. These observations point to the presence in early MS of a diffusing, complement-fixing, myelinolytic antigen, processed mainly within the Virchow-Robin spaces and distributed in the cerebrospinal and extracellular fluid compartments of the central nervous system.

Adult↗
PubMed2005

[Association of cardiovascular risk factors and small arterial elasticity].

OBJECTIVE: To investigate the major cardiovascular risk factors affecting small arterial elasticity and the effect of combined multiple risk factors on it. METHODS: Arterial elasticity indexes (C(1)-large artery and C(2)-small artery) were measured with CVProfilor DO-2020. The status of insulin resistance was evaluated with HOMA (homeostasis model assessment). Subjects were categorized into abnormal C(2) group and control group according to the level of C(2). The former group was further divided into four subgroups (0 to 3) based on the number of risk factors. RESULTS: (1) The levels of age, total cholesterol (TC), low density lipoprotein- cholesterol (LDL-C), fasting blood glucose (FBG), systolic blood pressure (SBP) and diastolic blood pressure (DBP) in abnormal C(2) group were higher than those in control group, whereas C(2) itself was lower than that in control group (P all < 0.05). Age, TC, LDL-C, FBG, SBP and DBP were significantly inversely correlated with C(2). (2) With the clusters of risk factors increasing, C(2) was decreasing (6.5 +/- 2.6 vs 5.4 +/- 2.3 vs 4.7 +/- 2.7 vs 3.1 +/- 1.6, P < 0.001). C(2) decreased significantly in subjects with multiple risk factors (subgroup 3). (3) Fasting plasma insulin and HOMA-IR (insulin resistance index) were significantly higher in subgroup 3 than in the other subgroups (P < 0.05, P < 0.001 respectively). CONCLUSIONS: The elevations of age, TC, LDL-C, FBG, SBP and DBP were the major cardiovascular risk factors on the reduction of C(2), and the effects on it were continuously. With their concurrent effects, multiple risk factors could decrease small arterial elasticity much more significantly. Insulin resistance seems to be closely related to the clusters of multiple risk factors.

Adult↗
PubMed1997

A gene in human chromosome band Xq28 (GABRE) defines a putative new subunit class of the GABAA neurotransmitter receptor.

We have isolated and sequenced a novel human gene (GABRE) of the GABAA neurotransmitter receptor family. A cDNA sequence of the gene coding for a 506 amino acid protein was identified, representing a member of a putative new class (epsilon) of the GABAA receptor. The gene is transcribed at least at low level in several different tissues, with the highest levels being detected in adult heart and placenta. Alternative splicing of GABRE transcripts isolated from different tissues was observed at multiple positions of the gene, yielding an unusually complex variety of cDNA variants. The structure of the 5' region of most cDNAs is compatible with expression of protein sequence epsilon only in adult brain, whereas in other tissues, the majority of transcripts code for truncated protein sequences. The GABRE gene extends over 14 kb and is clustered together with the alpha 3 and the putative beta 4 GABAA receptor subunit genes in an approximately 0.8-Mb interval in chromosome band Xq28, located in the candidate regions of two different neurologic diseases. Based on features of conservation of protein sequences, gene structure, and genomic organization of GABAA receptor gene clusters, we propose that the epsilon and gamma subunit genes have a common ancestor and that GABAA receptor gene clusters in the human genome have diverged by multiple duplication events of an ancestral gene cluster containing one each alpha, beta, and gamma/epsilon precursor gene.

Adult↗
PubMed2001

Deciphering the design of the tropomyosin molecule.

The crystal structure at 2.0-A resolution of an 81-residue N-terminal fragment of muscle alpha-tropomyosin reveals a parallel two-stranded alpha-helical coiled-coil structure with a remarkable core. The high alanine content of the molecule is clustered into short regions where the local 2-fold symmetry is broken by a small (approximately 1.2-A) axial staggering of the helices. The joining of these regions with neighboring segments, where the helices are in axial register, gives rise to specific bends in the molecular axis. We observe such bends to be widely distributed in two-stranded alpha-helical coiled-coil proteins. This asymmetric design in a dimer of identical (or highly similar) sequences allows the tropomyosin molecule to adopt multiple bent conformations. The seven alanine clusters in the core of the complete molecule (which spans seven monomers of the actin helix) promote the semiflexible winding of the tropomyosin filament necessary for its regulatory role in muscle contraction.

Alanine↗
PubMed2000

Geographic clustering of an outer surface protein A mutant of Borrelia burgdorferi. Possible implications of multiple variants for Lyme disease persistence.

DNA sequences encoding full-length outer surface protein (Osp) A were amplified from four joint fluid samples over 4.5 months from a patient with chronic Lyme arthritis, with a variant from wild type only found in sample 3. Rather than a mutation in vivo, these findings suggested a mixed infection in which BORRELIA: containing the wild-type and mutant ospA were waxing and waning in the patient's joint. If so, we reasoned that the mutant should be present in the community. We therefore took the novel epitope resulting from the mutation, expressed as a fusion protein in Escherichia coli, and performed Western blots on 80 high-titred stored sera; however, all except that of our index patient were negative. We then collected 36 stored sera from patients with Lyme disease residing within 10 miles of where the index patient had lived. An additional two sera from this circumscribed area were positive (P = 0.038). These findings show that results from single samples can be misleading, and suggest that the OspAs expressed in force late in Lyme arthritis are the same ones introduced initially into the host. Moreover, they allow a speculative mechanism for disease persistence not previously considered, in which antigenically distinct B. burgdorferi variant proteins present themselves serially to the immune system.

Antigens, Surface↗
PubMed2006

The molecular classification of multiple myeloma.

To better define the molecular basis of multiple myeloma (MM), we performed unsupervised hierarchic clustering of mRNA expression profiles in CD138-enriched plasma cells from 414 newly diagnosed patients who went on to receive high-dose therapy and tandem stem cell transplants. Seven disease subtypes were validated that were strongly influenced by known genetic lesions, such as c-MAF- and MAFB-, CCND1- and CCND3-, and MMSET-activating translocations and hyperdiploidy. Indicative of the deregulation of common pathways by gene orthologs, common gene signatures were observed in cases with c-MAF and MAFB activation and CCND1 and CCND3 activation, the latter consisting of 2 subgroups, one characterized by expression of the early B-cell markers CD20 and PAX5. A low incidence of focal bone disease distinguished one and increased expression of proliferation-associated genes of another novel subgroup. Comprising varying fractions of each of the other 6 subgroups, the proliferation subgroup dominated at relapse, suggesting that this signature is linked to disease progression. Proliferation and MMSET-spike groups were characterized by significant overexpression of genes mapping to chromosome 1q, and both exhibited a poor prognosis relative to the other groups. A subset of cases with a predominating myeloid gene expression signature, excluded from the profiling analyses, had more favorable baseline characteristics and superior prognosis to those lacking this signature.

Chromosome Mapping↗
PubMed2006

Isomorphous substitution in bimetallic oxide clusters.

The geometric and electronic structure of bimetallic oxide clusters is studied as a function of their composition with gas phase vibrational spectroscopy. Infrared multiple photon dissociation spectra of titanium-vanadium oxide cluster anions are measured in the 500 to 1200 wave number range and assigned on the basis of harmonic frequencies calculated using density functional theory. Singly substituted (V(2)O(5))(n-1)(VTiO(5))(-) (n=2-4) cluster anions are shown to form polyhedral caged structures similar to those predicted for their isoelectronic counterparts, the neutral (V(2)O(5))(n) clusters. Upon systematic exchange of V by Ti atoms in V(4-n)Ti(n)O(-)(10) (n=1-4), the structure does not change. The stress induced by the isomorphous substitution results in an increased number of unpaired electrons (n-1) for the Ti-rich systems, leading to a quartet ground state for Ti(4)O(-)(10).

Journal Article↗
PubMed1990

Longitudinal substance use and adult adjustment.

Relationships among long-term use patterns of tobacco, alcohol, marijuana, and other substances from late childhood to young adulthood and adjustment in young adulthood were examined. The sample consisted of 133 participants from the New York Longitudinal Study. Cluster analysis revealed four groups of individuals for each of the substance categories, as well as for use of multiple substances, over the five points of measurement. Cluster membership was related to adjustment differences in young adulthood. Results from a series of ANOVAs indicated that individuals consistently using the highest amounts of alcohol and other drugs exhibited the highest levels of psychiatric symptoms. Follow-up analyses indicated that negative emotional-behavioral states in middle childhood precede problematic patterns of substance use. Implications for intervention in childhood are discussed.

Adaptation, Psychological↗
PubMed1980

Growth, development and pairing of Leucochloridiomorpha constantiae (Trematoda) metacercariae on the chorio-allantois of chick embryos cultivated in vitro.

A simple in vitro technique was devised to culture chick embryos in Petri dishes from the 4th to the 21st day of incubation. Leucochloridiomorpha constantiae (Trematoda) metacercariae were placed either singly or multiply (5/embryo) on the chorio-allantois of in vitro grown embryos on day 7 and were removed on day 14. Growth and development studies were also made on worms grown singly or multiply (5/chick) in the bursa of Fabricius of the domestic chick. Worms grown singly or multiply in embryos were sexually mature, although eggs from these worms were abnormal when compared with eggs from worms recovered from chicks. The mean body area of worms from chicks was 2-3 times greater than that of worms from embryos. The mean body area of single worms from embryos was significantly larger than that of worms grown multiply in this site. However, the mean body area of multiple worms from the chick was significantly larger than that of single worms from this site. Worm pairs or clusters were seen in all embryos with the multiple infections.

Allantois↗
PubMed2006

Heterogeneity of T-cell clones infiltrating primary malignant melanomas.

It is established that primary malignant melanomas (pMM) can be infiltrated by T-cell populations with predominantly one T-cell clone. As pMM generally express multiple tumor-associated antigens (TAA), here we used laser-capture microdissection (LCM) to isolate different tumor-infiltrating lymphocyte (TIL) clusters in order to determine whether pMM are infiltrated only by one single clone or whether the TAA may attract various T-cell populations. As T-cell receptor (TCR) clonality is a useful tool for the demonstration of specific T-cell clones, we analyzed 56 pMM, three cutaneous melanoma metastases, and 15 pairs of pMM with a sentinel lymph node (SLN) for clonal rearrangements of the (TCR) gamma chain gene. We detected the clonality of TCR gamma chain gene in 25 of 56 pMM, and in 10 of 17 SLN studied. In four of the 15 pairs of primary tumor and SLN, we found clonal TCR gamma in both the melanoma and the SLN, with two pairs harboring the identical clone. As we detected different clones in pMM and the corresponding SLN, we subsequently performed LCM in 21 malignant melanomas with multiple lymphocytic clusters for the presence of focal clonal T cells in different regions of the melanoma. In seven melanomas, both clusters of TILs showed the same rearranged TCR gamma chain gene and in five of the seven biopsies the clonal rearrangement occurred in different variable (V) regions of the TCR gamma chain gene. These tumors showed infiltration by more than one clone. In 10 biopsies TCR clonality was restricted to one cluster, while the second microdissected sample of the infiltrate was polyclonal. In conclusion, within one primary malignant melanoma several T-cell clones with different rearrangements may occur. The balance between these clones may decide on the progress of melanoma.

Clone Cells↗
PubMed2005

Eye movements during multiple readings of the same text.

People often read the same text more than once. Studying eye movements during multiple readings of the same texts provides a unique opportunity to observe the consistency of saccadic landing positions. Eye movements were recorded while 5 people read the same 4 texts more than 40 times, no more than 4 times/day, and never on consecutive trials. Other texts, read only once, were interspersed. Comprehension questions and a change-detection task helped maintain attention in the face of the repetition. There were two main findings: (1) repeated reading produced significant, but modest, changes in global saccadic patterns. The only change found in all readers was a reduction in the proportion of regressions. (2) Saccadic landing positions fell into clusters located at a variety of places with respect to word boundaries, and often across word boundaries. A mixed-strategy model of saccadic guidance (look to the center of words, while trying to maintain fairly uniform saccade lengths), could account for the overall strength of clustering, but not for the variability among cluster locations, suggesting that saccadic landing sites are selected in part on the basis of local text characteristics. The reliable clustering of saccadic landing positions found during multiple readings of the same text opens the way for cluster patterns to be used to study eye movement strategies during reading and overcome at least some of the variability associated with traditional global single-text measures.

Adult↗
PubMed1996

Multisolutional clustering and quantization algorithm (MCQ).

We have developed a novel clustering and quantization algorithm that allows the user to create multiple one-to-one correspondences between the actual data and its transformed (clustered and quantized) values, based on the user's hypothesis regarding the nature of the classification task. The types of problems for which the algorithm can be beneficial are discussed. We report experiments employing simulated and real data that suggest the proposed algorithm may be useful in neural network analysis of various phenomena in medicine and biology.

Algorithms↗