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PubMed1992

The structure for a radiation oncology protocol. The Committee of Radiation Oncology Group Chairmen.

Multi-institutional Cooperative Group clinical trials involving radiotherapy require unambiguous therapeutic guidelines, so that patients entered from each of the participating institutions will receive essentially uniform treatment. The technical guidelines for a Radiation Oncology Protocol presented in this report represents a consensus of the Radiotherapy Committees in the major NCI funded Cooperative Groups and is derived from over a decade of experience. Although they have been written for external beam therapy, they are applicable to brachytherapy with appropriate technical considerations. It is anticipated that further evolution will occur with the introduction of new technologies such as 3-D treatment planning and delivery, multi-leaf collimation and small field irradiation.

Clinical Protocols↗
PubMed1998

Universal rules and idiosyncratic features in tRNA identity.

Correct expression of the genetic code at translation is directly correlated with tRNA identity. This survey describes the molecular signals in tRNAs that trigger specific aminoacylations. For most tRNAs, determinants are located at the two distal extremities: the anticodon loop and the amino acid accepting stem. In a few tRNAs, however, major identity signals are found in the core of the molecule. Identity elements have different strengths, often depend more on k cat effects than on K m effects and exhibit additive, cooperative or anti-cooperative interplay. Most determinants are in direct contact with cognate synthetases, and chemical groups on bases or ribose moieties that make functional interactions have been identified in several systems. Major determinants are conserved in evolution; however, the mechanisms by which they are expressed are species dependent. Recent studies show that alternate identity sets can be recognized by a single synthetase, and emphasize the importance of tRNA architecture and anti-determinants preventing false recognition. Identity rules apply to tRNA-like molecules and to minimalist tRNAs. Knowledge of these rules allows the manipulation of identity elements and engineering of tRNAs with switched, altered or multiple specificities.

Amino Acyl-tRNA Synthetases↗
PubMed2006

Pheromone-sensitive glomeruli in the primary olfactory centre of ants.

Tremendous evolutional success and the ecological dominance of social insects, including ants, termites and social bees, are due to their efficient social organizations and their underlying communication systems. Functional division into reproductive and sterile castes, cooperation in defending the nest, rearing the young and gathering food are all regulated by communication by means of various kinds of pheromones. No brain structures specifically involved in the processing of non-sexual pheromone have been physiologically identified in any social insects. By use of intracellular recording and staining techniques, we studied responses of projection neurons of the antennal lobe (primary olfactory centre) of ants to alarm pheromone, which plays predominant roles in colony defence. Among 23 alarm pheromone-sensitive projection neurons recorded and stained in this study, eight were uniglomerular projection neurons with dendrites in one glomerulus, a structural unit of the antennal lobe, and the remaining 15 were multiglomerular projection neurons with dendrites in multiple glomeruli. Notably, all alarm pheromone-sensitive uniglomerular projection neurons had dendrites in one of five 'alarm pheromone-sensitive (AS)' glomeruli that form a cluster in the dorsalmost part of the antennal lobe. All alarm pheromone-sensitive multiglomerular projection neurons had dendrites in some of the AS glomeruli as well as in glomeruli in the anterodorsal area of the antennal lobe. The results suggest that components of alarm pheromone are processed in a specific cluster of glomeruli in the antennal lobe of ants.

Animals↗
PubMed2003

Events at the end of mitosis in the budding and fission yeasts.

The mitotic exit network (MEN) and the septation initiation network (SIN) control events at the end of mitosis in S. cerevisiae and S. pombe, respectively. SIN initiates contraction of the actin ring and synthesis of the division septum, thereby bringing about cytokinesis. The MEN is also required for cytokinesis, but its main role is to control inactivation of mitotic cyclin-dependent kinases (CDKs) at the end of mitosis, and thereby regulate mitotic exit. Each revolves around a Ras-family GTPase and involves several protein kinases, and SIN and MEN proteins are localised to the spindle pole body. In S. cerevisiae, a second network, known as FEAR, cooperates with the MEN to bring about mitotic exit, and a third, AMEN, contributes to switching the MEN off. Some of the central components of the FEAR, SIN and MEN have been conserved through evolution, which suggests that aspects of their function in controlling events at the end of mitosis might be conserved in higher eukaryotes.

Actins↗
PubMed1991

[A case of bilateral kidney tumor combined with staghorn calculi and skin cancer].

A rare case of bilateral renal tumor with benign clinical evolution, associated with staghorn calculosis and skin cancer, is reported. Delayed operative treatment was due to difficulties in establishing the diagnosis, controversial results of the sonographic and X-ray examination and lack of cooperation by the patients. The right kidney and regional lymph nodes were removed; metastases were verified on histologic examination of the lymph nodes. After the operation the patient received complex radio-, chemo- and hormonal therapy. Basocellular skin cancer which later developed was cured by contact radiotherapy.

Adenocarcinoma↗
PubMed1995

[Interaction between anti-infective agents and phagocytes].

Metchnikoff was one of the first to suggest the need for cooperation between phagocytes and therapeutic agents for the benefit of health. After the hopes raised by the discovery and the tremendous development of antimicrobials, there is now a creeping pessimism faced with the parallel evolution of resistance strategies in the microbial world. Interest has now turned to the use of immunomodulatory drugs, alone or combined with anti-infectious agents. Another tendency is based on the possibility that antimicrobials directly interfere with the host-microbe interplay. This review is aimed at summarizing our knowledge of the interactions between antimicrobial agents and the phagocyte, still a cornerstone in the natural defence system. Despite the problems inherent in the analysis and clinical relevance of effects observed in the test tube this developing area of research could provide new therapeutic solutions beyond the year 2000.

Anti-Infective Agents↗
PubMed2003

Parasite infection, host resistance and mate choice: battle of the genders in a simultaneous hermaphrodite.

Parasites have been proposed to be fundamental in the evolution of mate choice because differential mating on the basis of heritable disease resistance is expected to lead to progeny with a better genome-environment match than random mating. However, direct empirical data in support of this hypothesis are often lacking, and the relative influences of current and potential infection status (i.e. resistance genotype), and of mate choice versus mate conflict, remain largely unknown. We demonstrate experimentally, using simultaneous hermaphroditic snails (Biomphalaria glabrata) artificially selected for resistance or susceptibility to Schistosoma mansoni infection, that mate choice is influenced by a combination of current and potential parasitic infection status. As predicted by game-theory models, we also found a picture of conflict and cooperation: resistant and susceptible genotypes copulated in either gender and reciprocated (i.e. switched gender) equally when faced with an uninfected partner, but, by contrast, resistant snails actively refused to copulate as females with an infected partner. Such recognition and discrimination has implications for the maintenance of sex and the evolution of recognition systems.

Animals↗
PubMed1989

Evolution of CuZn superoxide dismutase and the Greek key beta-barrel structural motif.

Detailed analysis of the CuZn superoxide dismutase (SOD) structure provides new results concerning the significance and molecular basis for sequence conservation, intron-exon boundary locations, gene duplication, and Greek key beta-barrel evolution. Using 15 aligned sequences, including a new mouse sequence, specific roles have been assigned to all 23 invariant residues and additional residues exhibiting functional equivalence. Sequence invariance is dominated by 15 residues that form the active site stereochemistry, supporting a primary biological function of superoxide dismutation. The beta-strands have no sequence insertions and deletions, whereas insertions occur within the loops connecting the beta-strands and at both termini. Thus, the beta-barrel with only four invariant residues is apparently over-determined, but dependent on multiple cooperative side chain interactions. The regions encoded by exon I, a proposed nucleation site for protein folding, and exon III, the Zn loop involved in stability and catalysis, are the major structural subdomains not included in the internal twofold axis of symmetry passing near the catalytic Cu ion. This provides strong confirmatory evidence for gene evolution by duplication and fusion followed by the addition of these two exons. The proposed evolutionary pathway explains the structural versatility of the Greek key beta-barrel through functional specialization and subdomain insertions in new loop connections, and provides a rationale for the size of the present day enzyme.

Amino Acid Sequence↗
PubMed2006

Identification of large-scale human-specific copy number differences by inter-species array comparative genomic hybridization.

Copy number differences (CNDs), and the concomitant differences in gene number, have contributed significantly to the genomic divergence between humans and other primates. To assess its relative importance, the genomes of human, common chimpanzee, bonobo, gorilla, orangutan and macaque were compared by comparative genomic hybridization using a high-resolution human BAC array (aCGH). In an attempt to avoid potential interference from frequent intra-species polymorphism, pooled DNA samples were used from each species. A total of 322 sites of large-scale inter-species CND were identified. Most CNDs were lineage-specific but frequencies differed considerably between the lineages; the highest CND frequency among hominoids was observed in gorilla. The conserved nature of the orangutan genome has already been noted by karyotypic studies and our findings suggest that this degree of conservation may extend to the sub-microscopic level. Of the 322 CND sites identified, 14 human lineage-specific gains were observed. Most of these human-specific copy number gains span regions previously identified as segmental duplications (SDs) and our study demonstrates that SDs are major sites of CND between the genomes of humans and other primates. Four of the human-specific CNDs detected by aCGH map close to the breakpoints of human-specific karyotypic changes [e.g., the human-specific inversion of chromosome 1 and the polymorphic inversion inv(2)(p11.2q13)], suggesting that human-specific duplications may have predisposed to chromosomal rearrangement. The association of human-specific copy number gains with chromosomal breakpoints emphasizes their potential importance in mediating karyotypic evolution as well as in promoting human genomic diversity.

Animals↗
PubMed2005

Rationale--Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) have a high burden of mortality and cardiovascular morbidity. Additional strategies to modulate cardiovascular risk in this population are needed. Data suggest that anemia is a potent and potentially modifiable risk factor for cardiovascular disease in patients with CKD, but these data remain unsubstantiated by any randomized controlled trial (RCT). Furthermore, the clinical practice guidelines for anemia management in patients with CKD are based on limited data. The need for new RCTs to address critical knowledge deficits, particularly with regard to the impact of anemia therapy on cardiovascular disease and survival, is recognized within the guidelines and independent comprehensive reviews of the existing published trial data. STUDY DESIGN: The Trial to Reduce Cardiovascular Events with Aranesp (Amgen Inc, Thousand Oaks, Calif) (darbepoetin alfa) Therapy (TREAT) is a 4000-patient, multicenter, double-blind RCT, designed to determine the impact of anemia therapy with darbepoetin alfa on mortality and nonfatal cardiovascular events in patients with CKD and type 2 diabetes mellitus. Subjects will be randomized in a 1:1 manner to either darbepoetin alfa therapy to a target hemoglobin (Hb) of 13 g/dL or control, consisting of placebo for Hb > or =9 g/dL or darbepoetin alfa for Hb <9 g/dL until Hb is again Hb > or =9 g/dL. TREAT is event-driven and has a composite primary end point comprising time to mortality and nonfatal cardiovascular events, including myocardial infarction, myocardial ischemia, stroke, and heart failure. TREAT will provide data that are critical to evolution of the management of cardiovascular risk in this high-risk population.

Anemia↗
PubMed1999

Towards sustainable pesticides.

In the light of increasing concern over the environmental impact of pesticides, we look at the evolution of national and international policies for sustainable pesticide use, and the associated data requirements.

Agriculture↗
PubMed2003

Soay rams target reproductive activity towards promiscuous females' optimal insemination period.

Female promiscuity is thought to have resulted in the evolution of male behaviours that confer advantages in the sperm competition that ensues. In mammalian species, males can gain a post-copulatory advantage in this sperm 'raffle' by inseminating females at the optimal time relative to ovulation, leading to the prediction that males should preferentially associate and copulate with females at these times. To the best of our knowledge, we provide the first high-resolution test of this prediction using feral Soay sheep, which have a mating system characterized by male competition for access to highly promiscuous females. We find that competitive males time their mate guarding (and hence copulations) to occur close to the optimal insemination period (OIP), when females are also increasingly likely to 'cooperate' with copulation attempts. Subordinate males practice an alternative mating tactic, where they break the integrity of the consort pair and force copulations on females. The timing of these forced copulations is also targeted towards the OIP. We thus provide quantitative evidence that female promiscuity has resulted in the evolution of reproductive strategies in which males 'load' the sperm raffle by targeting their mating activity towards female OIPs, when the probability of sperm-competition success is at its greatest.

Animals↗
PubMed2000

Molecular phylogeny of the large carpenter bees, genus Xylocopa (Hymenoptera: apidae), based on mitochondrial DNA sequences.

Carpenter bees, genus Xylocopa Latreille, a group of bees found on all continents, are of particular interest to behavioral ecologists because of their utility for studies of the evolution of mating strategies and sociality. This paper presents phylogenetic analyses based on sequences of two mitochondrial genes cytochrome oxidase 1 and cytochrome b for 22 subgenera of Xylocopa. Maximum-parsimony and maximum-likelihood methods were used to infer phylogenetic relationships. The analyses resulted in three resolved clades of subgenera: a South American group (including the subgenera Stenoxylocopa, Megaxylocopa, and Neoxylocopa), a group including the subgenera Xylocopa s.s. and Ctenoxylocopa, and an Ethiopean group (including the subgenera Afroxylocopa, Mesotrichia, Alloxylocopa, Platynopoda, Hoploxylocopa, and Koptortosoma). The relationships between the 11 other subgenera and the resolved clades are unclear. Within the Ethiopian group we found a clear separation of the African and the Oriental taxa and apparent polyphyly of the subgenus Koptortosoma. Using an evolutionary rate for ants, we investigated whether Gondwana vicariance or more recent dispersal events could best explain the present-day distribution of subgenera. Although some taxa show divergences that approach Gondwanan breakup times, most divergences between geographic groups are too recent to support a vicariance hypothesis.

Animals↗