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At least 937 records · Page 52Linked to original sources
PubMed1995

RNA editing of the coI mRNA throughout the life cycle of Physarum polycephalum.

Editing of RNA via the insertion, deletion or substitution of genetic information affects gene expression in a variety of systems. Previous characterization of the Physarum polycephalum cytochrome c oxidase subunit I (coI) mRNA revealed that both nucleotide insertions and base substitutions occur during the maturation of this mitochondrial message. Both types of editing are known to be developmentally regulated in other systems, including mammals and trypanosomatids. Here we show that the coI mRNA present in Physarum mitochondria is edited via specific nucleotide insertions and C to U conversions at every stage of the life cycle. Primer extension sequencing of the RNA indicates that this editing is both accurate and efficient. Using a sensitive RT-PCR assay to monitor the extent of editing at individual sites of C insertion, we estimate that greater than 98% of the steady-state amount of coI mRNA is edited throughout the Physarum developmental cycle.

Animals↗
PubMed2002

A novel cyclic GMP-dependent protein kinase is expressed in the ring stage of the Plasmodium falciparum life cycle.

Cyclic GMP-dependent protein kinases (PKGs) are the major mediators of the cGMP signal transduction pathway and regulate a variety of physiological effects. We report here the characterization of an unusual PKG from the human malaria parasite Plasmodium falciparum (designated PfPKG). The 97.5 kDa protein contains some of the structural features of mammalian PKGs but, uniquely, contains a third predicted cGMP binding site and a degenerate fourth. Using both protein kinase activity assays and Western blotting with native P. falciparum proteins, we demonstrate here that PfPKG is expressed predominantly in the ring stage of the life cycle, suggesting a role in the development of asexual blood stage parasites. An Escherichia coli-derived recombinant protein (PfPKG2, Met115-Phe853) was purified and shown to have phosphotransferase activity in terms of both substrate phosphorylation and auto-phosphorylation. This activity was stimulated at least fivefold by 1.0 microM cyclic GMP, but was not stimulated by cAMP or by 8-pCPT-cGMP, which is a potent activator of mammalian PKGs. Several protein kinase inhibitors exhibited a range of inhibitory effects on PfPKG activity. Biochemical analysis therefore shows that PfPKG is distinct from mammalian PKGs with respect to both cyclic nucleotide analogue activation and inhibition profiles.

Amino Acid Sequence↗
PubMed2003

Adequate dosing of micronutrients for different age groups in the life cycle.

Many studies of micronutrient supplementation in developing countries have used single-nutrient supplements with either vitamins or minerals. However, people in these countries often suffer from multiple, rather than single, micronutrient deficiencies. The objective of this paper is to discuss the factors that go into determining the adequate dosing of vitamins and/or minerals for people of different ages. To elaborate on the adequacy of micronutrient doses in supplements, a model described by the US FNB was used, which calculates the difference between the mean observed intake for an individual and the estimated average requirement for a life stage and gender group. This model allows estimating the degree of confidence that a certain nutrient intake (from supplements and diet) is adequate. The US/Canadian DRI values have been used as the basis for these calculations, from which it can be concluded that a daily supplement of one RDA of each micronutrient is adequate to cover the personal requirements of all individuals in each respective age and gender group of the population, provided that 20 to 40% of an RDA is supplied by the diet--likely a realistic value for developing countries. DRI values vary significantly between different age groups, reflecting changing needs over a life cycle. With the objective of a supplement to be adequate and safe, the design of a one-for-all supplement covering all age groups is not realistic. Such a supplement would either underscore or surpass the required intake of some of the age groups. Additionally the dosage of certain micronutrients might exceed the upper level of intake for lower age groups. Therefore, it is suggested that three different supplements following the one RDA concept for all micronutrients be developed for research use in developing countries for the following age groups; 1 to 3 years, 4 to 13 years, and females > 14 years (excluding during pregnancy).

Adolescent↗
PubMed1995

Kinetoplastid membrane protein-11 (KMP-11) is differentially expressed during the life cycle of African trypanosomes and is found in a wide variety of kinetoplastid parasites.

An abundant 11-kDa membrane protein was purified from African trypanosomes by organic solvent extraction and octyl-Sepharose chromatography. This protein cross-reacts with monoclonal antibodies originally generated against the lipophosphoglycan-associated protein of Leishmania donovani. Immunoblot analysis showed that the 11-kDa molecule was present in a variety of species of kinetoplastids. It was found in several species and subspecies of African trypanosomes and was present in low amounts in bloodstream forms and in larger amounts in procyclic, epimastigote and metacyclic life cycle stages. Expression of the 11-kDa molecule rapidly increased during transformation from bloodstream forms to procyclic forms, paralleling expression of the major surface glycoprotein of Trypanosoma congolense, the glutamic acid/alanine-rich protein, an analogue of T. brucei procyclin. The molecule was present in procyclic trypanosome membranes at approximately 2 x 10(5)-1 x 10(6) molecules per cell, suggesting it may have an important role in parasite membrane organization and function. Amino-acid analysis of the trypanosome 11-kDa protein showed it had a different composition than that of its leishmania counterpart. Its wide distribution in kinetoplastids and its membrane disposition suggest a name for this class of molecules: kinetoplastid membrane protein-11 (KMP-11).

Amino Acids↗
PubMed2004

The role of the subterranean rodent Ctenomys talarum (Rodentia: Octodontidae) in the life cycle of Taenia taeniaeformis (Cestoda: Taeniidae) in urban environments.

This work is the first report of subterranean rodent Ctenomys talarum (Rodentia: Octodontidae) as intermediate host of Taenia taeniaeformis in urban areas of Mar de Cobo (Buenos Aires Province, Argentina) and to experimentally reproduce in domestic dogs the adult stage of this parasite. Prevalence, mean abundance and mean intensity of infection with T. taeniaeformis larvae in the liver and peritoneal cavity of C. talarum were 64%, 15.3 and 9.8, respectively. Ten adults of T. taeniaeformis were obtained from experimentally infected dogs. Information about the role of subterranean rodents in the life cycle of this parasite is also given. The above mentioned data indicate that T. taeniaeformis is a frequent parasite of this species of rodents, at least within the study area. Also explanations for the high prevalence of larval forms of this parasite in C. talarum populations are given.

Animals↗
PubMed1999

Life-cycle and biology of Sychnocotyle kholo n.g., n. sp. (Trematoda : Aspidogastrea) in Emydura macquarii (Pleurodira : Chelidae) from southern Queensland, Australia.

Sychnocotyle kholo n. g., n. sp. (Aspidogastrea: Aspidogastridae) is described from the small intestine of the freshwater turtle Emydura macquarii (Pleurodira: Chelidae). The new genus is distinguished from other aspidogastrids by the possession of the following suite of characters: no cirrus-sac; no hermaphroditic duct; four rows of alveoli on the ventral disc but no prominent papillae; Laurer's canal opening to the exterior. Eggs hatched to cotylocidia within 37-41 days at 17-24 degrees C. The life-cycle is obligate two-host, involving a mollusc and a freshwater turtle. Juvenile forms, almost entirely single worm infections, were found in the molluscs Corbiculina sp. (Bivalvia: Corbiculidae) and Thiara balonnensis (Prosobranchia: Thiaridae). Sychnocotyle is most likely to have evolved in Australia after the separation of Gondwanaland from Laurasia 120- 100 mya.

Animals↗
PubMedDate not supplied

A life cycle model of continuous clinical process innovation.

The changing healthcare environment has created a sense of urgency for continuous innovation in clinical care processes. Managers and clinicians are investing unprecedented funds and energy in the development of various clinical process innovations (CPI) such as clinical pathways, electronic workstations, and various forms of information technology. While increasing attention has been paid to the development of such initiatives, our understanding of how best to disseminate and ensure their use is limited. In this first of two articles dealing with the dissemination and use of CPI in integrated delivery systems, we present a "life cycle" model of the dissemination process and suggest opportunities for managing CPI. The management of CPI requires more than just an understanding of the factors that may facilitate or impede its implementation and use. Managers require an understanding of the actual process so that they can assess the specific implementation stage at which the organization is presently operating, and design appropriate interventions that can affect the process. A future article will identify the factors that facilitate and inhibit the process and suggest some intervention strategies.

Critical Pathways↗
PubMed2006

Identification and stage-specific association with the translational apparatus of TbZFP3, a CCCH protein that promotes trypanosome life-cycle development.

The post-transcriptional control of gene expression is becoming increasingly important in the understanding of regulated events in eukaryotic cells. The parasitic kinetoplastids have a unique reliance on such processes, because their genome is organized into polycistronic transcription units in which adjacent genes are not coordinately regulated. Indeed, the number of RNA-binding proteins predicted to be encoded in the genome of kinetoplastids is unusually large, invoking the presence of unique RNA regulators dedicated to gene expression in these evolutionarily ancient organisms. Here, we report that a small CCCH zinc finger protein, TbZFP3, enhances development between life-cycle stages in Trypanosoma brucei. Moreover, we demonstrate that this protein interacts both with the translational machinery and with other small CCCH proteins previously implicated in trypanosome developmental control. Antibodies to this protein also co-immunoprecipitate EP procyclin mRNA and encode the major surface antigen of insect forms of T. brucei. Strikingly, although TbZFP3 is constitutively expressed, it exhibits developmentally regulated association with polyribosomes, and mutational analysis demonstrates that this association is essential for the expression of phenotype. TbZFP3 is therefore a novel regulator of developmental events in kinetoplastids that acts at the level of the post-transcriptional control of gene expression.

Amino Acid Sequence↗
PubMed1997

Clonality and life cycles of intestinal crypts explained by a state dependent stochastic model of epithelial stem cell organization.

The organization and control of stem cells is a key issue in epithelial cell biology. The small intestinal murine crypt is a useful tissue to study such problems since stem cells are known to be located at specific positions at the bottom of the crypt where they are self maintaining. Recent data suggest, that (1) the number of active stem cells in a crypt can fluctuate, (2) the immediate progeny of a single stem cell can replace other stem cells eventually leading to monoclonality and (3) the life cycle of crypts may be linked to stem cell dynamics. It is the objective of this paper to suggest a stochastic state-dependent model of stem cell and crypt growth which can explain and-link these phenomena into one comprehensive framework. Monte Carlo simulations are performed to show consistently with available data. The model explains the size distribution of small intestinal crypts in steady state, the observations of stem cell fluctuations and monoclonality conversion, recovery of the crypt population after moderate damage and the rate of crypt fission and extinction. The key assumption of this model is an autoregulatory control of stem cell growth.

Animals↗
PubMed2026

Insights into the Life Cycle and Therapeutic Agents for Monkeypox Virus Infection.

Since the first confirmed case in 1970, the monkeypox virus (MPXV) has emerged as a significant threat to global public health. The World Health Organization (WHO) has declared it a Public Health Emergency of International Concern (PHEIC) on two occasions. Despite decades of research, only tecovirimat has been approved by the European Medicines Agency (EMA) for the treatment of MPXV infection. The genome and structure are similar between MPXV and other orthopoxviruses (OPXVs), suggesting that the strategies used for other OPXVs may be applicable to MPXV. This review systematically summarizes the genome, structure, and critical stages in the life cycle of OPXVs, especially MPXV. A variety of antiviral agents against MPXV and other OPXVs are discussed according to their distinct mechanisms of action: 1) blocking viral entry and fusion, 2) inhibiting DNA replication and processing, 3) disrupting transcription and mRNA processing, 4) preventing virion assembly, maturation and release, 5) modulating immune responses, and 6) mechanism unknown. Overall, this article provides a systematic review of current research progress on potential therapeutic targets and agent for MPXV, aiming to offer innovative insights and strategies for the development of effective therapeutic agents against mpox.

Animals↗
PubMed1992

Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle.

Using a quantitative polymerase chain reaction (PCR) method, we have previously shown that a molecularly cloned isolate of human immunodeficiency virus type 1 (HIV-1) can efficiently enter quiescent primary lymphocytes; however, the reverse transcription process is not completed in these cells. In this study, we further characterized the reverse transcription of HIV-1 in quiescent cells, and our results indicate that while initiation of reverse transcription occurs simultaneously in both activated and quiescent lymphocytes, it not only ends prematurely but also proceeds more slowly in quiescent cells. We also performed experiments to address the role of partial reverse transcripts as intermediates in the viral life cycle. We used azidothymidine either before or after infection with HIV-1 to prevent formation of and further DNA synthesis by partial reverse transcripts, respectively. Decreases in virus production from these cells following mitogenic stimulation indicated that partial reverse transcripts can contribute significantly to virus rescue from infected quiescent cells stimulated subsequent to infection. Furthermore, we established that mitogenic stimulation of infected quiescent cells induces reinitiation of DNA synthesis from partial reverse transcripts. However, the virus rescue is inefficient relative to the initial multiplicity of infection, and this is explained by inefficient completion of DNA synthesis from the partial reverse transcript. Thus, the arrest of reverse transcription in quiescent cells may play an important role in HIV-1 pathogenesis by contributing to the inefficient infection of potential target cells in the peripheral blood of HIV-1-infected individuals.

Base Sequence↗
PubMed2004

Calculating biological behaviors of epigenetic states in the phage lambda life cycle.

The biology and behavior of bacteriophage lambda regulation have been the focus of classical investigations of molecular control of gene expression. Both qualitative and quantitative aspects of this behavior have been systematically characterized experimentally. Complete understanding of the robustness and stability of the genetic circuitry for the lysis-lysogeny switch remains an unsolved puzzle. It is an excellent test case for our understanding of biological behavior of an integrated network based on its physical, chemical, DNA, protein, and functional properties. We have used a new approach to non-linear dynamics to formulate a new mathematical model, performed a theoretical study on the phage lambda life cycle, and solved the crucial part of this puzzle. We find a good quantitative agreement between the theoretical calculation and published experimental observations in the protein number levels, the lysis frequency in the lysogen culture, and the lysogenization frequency for mutants of O(R). We also predict the desired robustness for the lambda genetic switch. We believe that this is the first successful example in the quantitative calculation of robustness and stability of the phage lambda regulatory network, one of the simplest and most well-studied regulatory systems.

Bacteriophage lambda↗
PubMed1991

Phylogenetic analysis of Alloglossidium Simer, 1929 (Digenea: Plagiorchiiformes: Macroderoididae) with discussion of the origin of truncated life cycle patterns in the genus.

Alloglossidium comprises 9 species of North American plagiorchiiform digeneans using ictalurid catfish, freshwater crustacea, and hirudinid leeches as definitive hosts. Two hypotheses about the evolution of this array of definitive hosts were examined using phylogenetic systematic analysis. Two most parsimonious trees, based on 15 homologous series derived from morphological data, each indicated the 2 species utilizing ictalurid catfish definitive hosts are basal members of the group, whereas the 2 species using freshwater crayfish definitive hosts and the 5 utilizing leech definitive hosts each comprise relatively derived monophyletic sister groups. The results suggest that species using crustaceans as definitive hosts are derived by life cycle truncation, whereas those using leeches as definitive hosts appear to be derived through a switch from crustaceans to leeches.

Animals↗
PubMed1991

A chlamydial plasmid is differentially transcribed during the life cycle of Chlamydia trachomatis.

A 7.5-kb cryptic plasmid is found in all serotypes of the obligate intracellular parasite, Chlamydia trachomatis. Although at least nine open reading frames are apparent from sequence analysis of plasmid DNA, only a small region of approximately 500 bp has been consistently shown to be transcriptionally active by Northern blot analysis. In this study, transcription was analyzed using a host-free system in which RNA synthesized by chlamydiae isolated from host cells was hybridized to different regions of the plasmid. The results suggest that fragments corresponding to all open reading frames are transcribed, but at varied relative levels depending upon the stage of the life cycle. The hybridization patterns also suggested a net chemical degradation of plasmid-specified RNA in a 3' to 5' direction.

Autoradiography↗