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Age-induced changes in single locus coeruleus brain transplants grown in oculo: an in vivo electrochemical study.

Brain stem tissue from fetal Sprague-Dawley rats containing the nucleus locus coeruleus (LC) was transplanted into the anterior chamber of the eye of young adult host rats and was studied at 4-6 months (young control) or 24-28 months after grafting (old). High-speed in vivo electrochemical measurements were used to characterize the potassium-evoked synaptic overflow of norepinephrine (NE) in both young and aged LC brain grafts. The amplitudes of potassium-evoked NE overflow were attenuated in the aged grafts as compared to the young LC grafts. In addition, the rise times of potassium-evoked responses were longer in the old LC grafts than in the young transplants. In contrast, the NE content of aged LC grafts, as determined by high-performance liquid chromatography coupled with electrochemical detection (HPLC-EC), was only slightly diminished and not significantly different from the NE levels seen in young LC grafts. However, light microscopical evaluation using tyrosine-hydroxylase immunocytochemistry revealed pyknotic cell bodies and fluorescent accumulations in aged locus coeruleus transplants which were indicative of degeneration in these grafts. The present data demonstrate a significant age-related decline in the presynaptic function of NE-containing neurons in intraocular locus coeruleus transplants of Sprague-Dawley rats.

Aging↗

Experiences with single locus DNA probes in casework.

DNA profiling in this laboratory has been employed primarily in cases of sexual assault and the largest category of items examined has been internal vaginal swabs. 79% of these gave a profile which was different from that of the victim. Results have been obtained from swabs taken up to 70 h after intercourse. In cases where DNA results were obtained, one or more suspects were excluded in 29% of the cases.

Blood Stains↗

Resolution of the two loci for autosomal dominant aniridia, AN1 and AN2, to a single locus on chromosome 11p13.

Two distinct loci have been proposed for aniridia; AN1 for autosomal dominant aniridia on chromosome 2p and AN2 for the aniridia in the WAGR contiguous gene syndrome on chromosome 11p13. In this report, the kindred segregating for autosomal dominant aniridia, which suggested linkage to acid phosphatase-1 (ACP1) and led to the assignment of the AN1 locus on chromosome 2p, has been updated and expanded. Linkage analysis between the aniridia phenotype and ACP1 does not support the original linkage results, excluding linkage up to theta = 0.17 with Z = -2. Tests for linkage to other chromosome 2p markers. APOB, D2S71, D2S5, and D2S1, also excluded linkage to aniridia. Markers that have been isolated from the chromosome 11p13 region were then analyzed in this aniridia family. Two RFLPs at the D11S323 locus give significant evidence for linkage. The PvuII polymorphism detected by probe p5S1.6 detects no recombinants, with a maximum lod score of Z = 6.97 at theta = 0.00. The HaeIII polymorphism detected by the probe p5BE1.2 gives a maximum lod score of Z = 2.57 at theta = 0.00. Locus D11S325 gives a lod score of Z = 1.53 at theta = 0.00. These data suggest that a locus for aniridia (AN1) on chromosome 2p has been misassigned and that this autosomal dominant aniridia family is segregating for an aniridia mutation linked to markers in the 11p13 region.

Alkaline Phosphatase↗

Head-to-head comparison on the immunogenicity of two HIV/AIDS vaccine candidates based on the attenuated poxvirus strains MVA and NYVAC co-expressing in a single locus the HIV-1BX08 gp120 and HIV-1(IIIB) Gag-Pol-Nef proteins of clade B.

In this investigation we have generated and defined the immunogenicity of two novel HIV/AIDS vaccine candidates based on the highly attenuated vaccinia virus strains, MVA and NYVAC, efficiently expressing in the same locus (TK) and under the same viral promoter the codon optimized HIV-1 genes encoding gp120 and Gag-Pol-Nef antigens of clade B (referred as MVA-B and NYVAC-B). In infected human HeLa cells, gp120 is released from cells and GPN is produced as a polyprotein; NYVAC-B induces severe apoptosis but not MVA-B. The two poxvirus vectors showed genetic stability of the inserts. In BALB/c and in transgenic HHD mice for human HLA-A2 class I, both vectors are efficient immunogens and induced broad cellular immune responses against peptides represented in the four HIV-1 antigens. Some differences were observed in the magnitude and breadth of the immune response in the mouse models. In DNA prime/poxvirus boost protocols, the strongest immune response, as measured by fresh IFN-gamma and IL-2 ELISPOT, was obtained in BALB/c mice boosted with NYVAC-B, while in HHD mice there were no differences between the poxvirus vectors. When the prime/boost was performed with homologous or with combination of poxvirus vectors, the protocols MVA-B/MVA-B and NYVAC-B/NYVAC-B, or the combination NYVAC-B/MVA-B gave the most consistent broader immune response in both mouse models, although the magnitude of the overall response was higher for the DNA-B/poxvirus-B regime. All of the immunization protocols induced some humoral response against the gp160 protein from HIV-1 clone LAV. Our findings indicate that MVA-B and NYVAC-B meet the criteria to be potentially useful vaccine candidates against HIV/AIDS.

AIDS Vaccines↗

Frequency-dependent viability selection (a single-locus, multi-phenotype model).

Frequency-dependent natural selection models are examined where the viability of an individual in the diploid population is determined by its phenotype and the frequency of other phenotypes present. The equilibria of the multi-phenotypic system are characterized through local mean fitness functions. It is shown that stability can best be analyzed by combining the principles of maximization of population mean fitness with the evolutionary stability conditions that apply when phenotypic fitnesses relative to the genetic constraints are equal.

Animals↗

Selection equilibria in a multiallele single-locus setting.

The aim of the paper is to clarify and unify various well-known results in the setting mentioned in the title, since some of these results are either inaccurate, or incomplete; or refer to different concepts bearing the same name. Emphasis is given to the general case, i.e. we include the situation of singular fitness matrix, a topic which is generally avoided. We proceed by using a specific generalized inverse of the fitness matrix. A full bibliography is given.

Alleles↗

Chromosome aberrations in canine multicentric lymphomas detected with comparative genomic hybridisation and a panel of single locus probes.

Recurrent chromosome aberrations are frequently observed in human neoplastic cells and often correlate with other clinical and histopathological parameters of a given tumour type. The clinical presentation, histology and biology of many canine cancers closely parallels those of human malignancies. Since humans and dogs demonstrate extensive genome homology and share the same environment, it is expected that many canine cancers will also be associated with recurrent chromosome aberrations. To investigate this, we have performed molecular cytogenetic analyses on 25 cases of canine multicentric lymphoma. Comparative genomic hybridisation analysis demonstrated between one and 12 separate regions of chromosomal gain or loss within each case, involving 32 of the 38 canine autosomes. Genomic gains were almost twice as common as losses. Gain of dog chromosome (CFA) 13 was the most common aberration observed (12 of 25 cases), followed by gain of CFA 31 (eight cases) and loss of CFA 14 (five cases). Cytogenetic and histopathological data for each case are presented, and cytogenetic similarities with human non-Hodgkin's lymphoma are discussed. We have also assembled a panel of 41 canine chromosome-specific BAC probes that may be used for accurate and efficient chromosome identification in future studies of this nature.

Animals↗