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At least 217 records · Page 12Linked to original sources
PubMed2006

Consequences of telomere shortening at an active VSG expression site in telomerase-deficient Trypanosoma brucei.

Trypanosoma brucei evades the host immune response by sequential expression of a large family of variant surface glycoproteins (VSG) from one of approximately 20 subtelomeric expression sites (ES). VSG transcription is monoallelic, and little is known about the regulation of antigenic switching. To explore whether telomere length could affect antigenic switching, we created a telomerase-deficient cell line, in which telomeres shortened at a rate of 3 to 6 bp at each cell division. Upon reaching a critical length, short silent ES telomeres were stabilized by a telomerase-independent mechanism. The active ES telomere progressively shortened and frequently broke. Upon reaching a critical length, the short active ES telomere stabilized, but the transcribed VSG was gradually lost from the population and replaced by a new VSG through duplicative gene conversion. We propose a model in which subtelomeric-break-induced replication-mediated repair at a short ES telomere leads to duplicative gene conversion and expression of a new VSG.

Animals↗
PubMed1980

R-plasmic transfer from Serratia liquefaciens to Escherichia coli in vitro and in vivo in the digestive tract of gnotobiotic mice associated with human fecal flora.

It was shown that a strain of Serratia liquefaciens harbors a conjugative R-plasmid responsible for reistance to the following 14 antibiotics: ampicillin, carbenicillin, cephalothin, butirosin, neomycin, paramomycin, kanamycin, lividomycin, gentamicin, tobramycin, streptomycin, tetracycline, sulfonamide, and chloramphenicol, which belong to five families, the beta-lactamines, the aminoglycosides, the tetracyclines, the sulfonamides, and the phenicols. Resistance to th 14 antibiotics was cotransferred by in vitro conjugation between S. liquefaciens and strains of Escherichia coli. Mating between S. liquefaciens and E. coli also occurred in vivo, in the digestive tract of axenic mice and gnotobiotic mice associated with the whole human fecal flora. It was also shown that mating between these two strains occurred even when the donor S. liquefaciens strain was only transient in the digestive tract of the gnotobiotic host animals. A dense population of Bacteroides (10(10) viable cells per g of fresh feces) did not hinder this mating. All the matings occurred in the absence of an antibiotic selection pressure, and the resulting transferred strain of E. coli did not have the same colonizing capacity as the recipient parental strain. However, during antibiotic administration to mice, and even after the end of the drug intake, the transconjugant became established in the dominant population and replaced the parental recipient strain.

Animals↗
PubMed2005

Umbilical cord blood-derived stem cells and brain repair.

Human umbilical cord blood (HUCB) is now considered a valuable source for stem cell-based therapies. HUCB cells are enriched for stem cells that have the potential to initiate and maintain tissue repair. This potential is especially attractive in neural diseases for which no current cure is available. Furthermore, HUCB cells are easily available and less immunogenic compared to other sources for stem cell therapy such as bone marrow. Accordingly, the number of cord blood transplants has doubled in the last year alone, especially in the pediatric population. The therapeutic potential of HUCB cells may be attributed to inherent ability of stem cell populations to replace damaged tissues. Alternatively, various cell types within the graft may promote neural repair by delivering neural protection and secretion of neurotrophic factors. In this review, we evaluate the preclinical studies in which HUCB was applied for treatment of neurodegenerative diseases and for traumatic and ischemic brain damage. We discuss how transplantation of HUCB cells affects these disorders and we present recent clinical studies with promising outcome.

Animals↗
PubMed2003

Demand for sexual health services during the Olympic Games: both sides of the Sherman effect.

To determine the impact of the Olympic Games the Sydney Sexual Health Centre database was accessed for demographic, health care utilization, and morbidity variables for two periods of interest: 15-29 September 2000 (the 'Olympic period'), and 1-30 September 1999 ('1999 comparison period'). Differences were tested by chi-square statistics and by calculation of odds ratios (ORs) using SPSS. During the Olympic period twice as many of the new patients had arrived in Australia that year (35% c.f. 18%: OR 2.46, 95% CI 1.49-4.05, P=0.0002). Per attendance the proportion with symptoms or a known sexually transmitted infection (STI) contact was higher during the Games (29% c.f. 16% OR 1.67, 95% CI 1.1.27-2.21, P=0.0002) and there was a marginally higher yield of bacterial STIs (6% c.f. 3%: OR 1.83, 95% CI 1.06-3.13 P=0.03). The normal clinic population was replaced by an increased proportion of symptomatic patients who were recent arrivals in Australia.

Australia↗
PubMed1997

The therapeutic potential of inducing molecules.

Many fundamental developmental mechanisms that result in the generation and formation of specific cells and organ systems are not limited to embryogenesis. Regenerative processes in the adult serve to help regulate cellular turnover in systems where specific cell numbers or balance is crucial. In addition, these processes can be re-activated to replace cell populations which are lost due to damage or disease. Induction of differentiation of one cell type by another is one mechanism that also acts as a regenerative process in the adult. Molecules which direct these processes are termed inducing molecules and they are prevalent and active in many adult organ systems such as the haematopoietic, osteogenic and reproductive systems. To date, recombinant forms of inducing molecules identified in the haematopoietic system are being used clinically to stimulate production of specific cell types that are depleted during chemotherapy or dialysis treatments. The prospect that other inducing molecules for other organ systems may be as effective clinically has prompted intense research. The ability to harness inducing molecules as effective therapeutic agents to treat cell deficits in congenital or acquired disease states is the goal of several biotechnology companies.

Journal Article↗
PubMed2005

Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in cerebellar granule neurons.

Two-pore domain potassium (K2P) channel expression is believed to underlie the developmental emergence of a potassium leak conductance [IK(SO)] in cerebellar granule neurons (CGNs), suggesting that K2P function is an important determinant of the input conductance and resting membrane potential. To investigate the role that different K2P channels may play in the regulation of CGN excitability, we generated a mouse lacking TASK-1, a K2P channel known to have high expression levels in CGNs. In situ hybridization and real-time PCR studies in wild-type and TASK-1 knock-outs (KOs) demonstrated that the expression of other K2P channels was unaltered in CGNs. TASK-1 knock-out mice were healthy and bred normally but exhibited compromised motor performance consistent with altered cerebellar function. Whole-cell recordings from adult cerebellar slice preparations revealed that the resting excitability of mature CGNs was no different in TASK-1 KO and littermate controls. However, the modulation of IK(SO) by extracellular Zn2+, ruthenium red, and H+ was altered. The IK(SO) recorded from TASK-1 knock-out CGNs was no longer sensitive to alkalization and was blocked by Zn2+ and ruthenium red. These results suggest that a TASK-1-containing channel population has been replaced by a homodimeric TASK-3 population in the TASK-1 knock-out. These data directly demonstrate that TASK-1 channels contribute to the properties of IK(SO) in adult CGNs. However, TASK channel subunit composition does not alter the resting excitability of CGNs but does influence sensitivity to endogenous modulators such as Zn2+ and H+.

Animals↗