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PubMed2006

Phylogeography of the Calonectris shearwaters using molecular and morphometric data.

We investigated phylogenetic relationships and the biogeographic history of the Calonectris species complex, using both molecular and biometric data from one population of the Cape Verde shearwater Calonectris edwardsii (Cape Verde Islands), one from the streaked shearwater C. leucomelas (western Pacific Ocean) and 26 from Cory's shearwater populations distributed across the Atlantic (C. d. borealis) and the Mediterranean (C. d. diomedea). The streaked shearwater appeared as the most basal and distant clades, whereas the genetic divergences among the three main clades within the Palearctic were similar. Clock calibrations match the first speciation event within Calonectris to the Panama Isthmus formation, suggesting a vicariant scenario for the divergence of the Pacific and the Palearctic clades. The separation between the Atlantic and Mediterranean clades would have occurred in allopatry by range contraction followed by local adaptation during the major biogeographic events of the Pleistocene. The endemic form from Cape Verde probably evolved as a result of ecological divergence from the Mediterranean subspecies. Finally, one Mediterranean population (Almeria) was unexpectedly grouped into the Atlantic subspecies clade, both by genetic and by morphometric analyses, pointing out the Almeria-Oran oceanographic front (AOOF) as the actual divide between the two Cory's shearwater subspecies. Our results highlight the importance of oceanographic boundaries as potentially effective barriers shaping population and species phylogeographical structure in pelagic seabirds.

Animals↗
PubMed1990

Special needs of the newborn infant in fluid therapy.

The preterm baby, although less able to tolerate high fluid and solute loads, has a remarkable ability to adapt to a rather broad range of environmental challenges, and thus renal function in the preterm infant should no longer be considered impaired. Lower rather than higher fluid administration is the current trend in neonatal care because it is safer and more physiologic. Although changes in body weight over time provide a good indicator of water balance, determination of plasma and urine electrolytes and tonicity are also essential in the monitoring of fluid therapy in preterm infants.

Body Water↗
PubMed2002

Pressure effects on in vivo microbial processes.

Pressures between 10 and 100 MPa can exert powerful effects on the growth and viability of organisms. Here I describe the effects of elevated pressure in this range on mesophilic (atmospheric pressure adapted) and piezophilic (high-pressure adapted) microorganisms. Examination of pressure effects on mesophiles makes use of this unique physical parameter to aid in the characterization of fundamental cellular processes, while in the case of piezophiles it provides information on the essence of the adaptation of life to high-pressure environments, which comprise the bulk of our biosphere. Research is presented on the isolation of pressure-resistant mutants, high-pressure regulation of gene expression, the role of membrane lipids and proteins in determining growth ability at high pressure, pressure effects on DNA replication and topology as well as on cell division, and the role of extrinsic factors in modulating enzyme activity at high pressure.

Archaea↗
PubMed2001

Intraspecific competition in populations of Helix aspersa with different histories of exposure to lead.

A range of invertebrates have become adapted to certain toxic metals, such that, in the presence of the contaminant, some measure of their performance, typically growth or reproduction, is superior to that of an unexposed population. Under such a toxic stress, a population with a history of exposure might outperform a naïve population in competition for limited resources. This study compared the shell growth of laboratory-bred juveniles from six populations of Helix aspersa with different histories of exposure to Pb. In 10 trials using various combinations of two populations, the snails competed for a limited supply of food that contained either no Pb or 500 micrograms/g-1 Pb, for 98 days. Each trial consisted of 10 juveniles, five from each population and was replicated four times. Nearly all of the food provided was consumed quickly after presentation. The total amount of shell growth within each replicate (the sum of the mean growth of the two populations) was highly consistent between trials so that the total amount of shell built was limited by food availability. The presence of Pb in the diet caused no measurable depression of shell growth and exposure history did not appear to confer any competitive advantage or disadvantage in any of the trials. One population consistently grew faster than its competitors in every trial of which it was a part. Shell growth tended to be greater in smaller juveniles. Snail activity is known to be inhibited at high densities and this may have contributed to the lower incremental growth in individuals kept at the higher densities. The competitive advantage enjoyed by one population may be primarily determined by their activity or perhaps their Ca metabolism.

Adaptation, Physiological↗
PubMed1997

Examiner differences in the mini-CEX.

OBJECTIVE: The objective of this study was to analyze whether faculty ratings of residents, using the mini-CEX oral exam format, differed in stringency or were influenced by the clinical setting. It also sought to learn whether the examiners were satisfied with the format. METHOD: A mini-CEX encounter consisted of a single faculty member observing a resident conduct a focused history and physical examination in an inpatient, outpatient, or emergency room setting. After asking the resident for a diagnosis and treatment plan, the faculty member rated the resident and provided educational feedback. The encounters were intended to be short and occur as a routine part of the training, so each resident would be evaluated on many occasions by different faculty. SAMPLE: Sixty-four attending physicians evaluated residents from five internal medicine training programs; data were analyzed for 355 mini-CEX encounters involving 88 residents. RESULTS: There were not large differences among the examiners in their ratings. Moreover, there were not great differences among the ratings in terms of the training program with which the examiner was associated, the setting of the mini-CEX, or the nature of the patient. The examiners were generally satisfied with the format and their level of satisfaction was correlated with the residents' perceptions of the format. CONCLUSION: The mini-CEX adapts itself to a broad range of clinical situations, and these results show that it should produce roughly comparable scores over examiners and settings. This makes it a worthwhile device for evaluation at the local level.

Journal Article↗
PubMed1993

Protein kinase C is required for light adaptation in Drosophila photoreceptors.

Protein kinase C (PKC) is a key enzyme for many cellular processes but its physiological roles are poorly understood. An excellent opportunity to investigate the function of PKC has been provided by the identification of an eye-specific PKC in Drosophila and a null PKC mutant, inaCP209 (refs 5,6). Bright conditioning lights delivered to inaC photoreceptors lead to an abnormal loss of sensitivity in whole cell recordings from dissociated ommatidia; this has been interpreted as 'hyper-adaptation' and PKC's role has been suggested to be distinct from light adaptation. A presumably related finding is that during intense light, the response of inaC declines to baseline. Invertebrate photoreceptors use the phosphoinositide signalling cascade, responding to single photons with so-called quantum bumps which sum to form the macroscopic response to light. Light adaptation allows photoreceptors to adjust their sensitivity over the enormous range of ambient intensities. Although the molecular mechanism of light adaptation remains obscure, it is a negative-feedback process mediated by a rise in cytosolic calcium and a decrease in bump size. We now show that under physiological conditions light adaptation is severely reduced in inaC, suggesting that eye-specific PKC, itself activated by a rise in cytosolic calcium and diacylglycerol, is required for adaptation. Furthermore, we show that in the absence of PKC individual bumps fail to terminate normally, an effect that can account for the pleiotropic manifestations of the inaC phenotype.

Adaptation, Ocular↗
PubMed2005

Linguistic perception: neural processing of a whistled language.

Silbo Gomero is a whistled language that is a rare and endangered surrogate of Spanish, used by shepherds on the island of La Gomera in the Canary Islands for communication over long distances on difficult terrain. Here we show that areas of the brain normally associated with spoken-language function are also activated in proficient whistlers, but not in controls, when they are listening to Silbo Gomero. Our findings demonstrate that the language-processing regions of the human brain can adapt to a surprisingly wide range of signalling forms.

Acoustic Stimulation↗
PubMed1978

Phenotypic diversity in experimental hepatomas: the concept of partially blocked ontogeny. The 10th Walter Hubert Lecture.

Cancer cells should be seen not as exclusively a problem in cell proliferation, but rather as a problem combining the processes of proliferation and differentiation, hence the phrase introduced in 1968: "oncogeny is blocked ontogeny". Cancer tissues resemble foetal tissues in many ways but they differ from foetal tissue in being unable to "recapitulate the total programme leading to an orchestrated collection of organism-serving cells" that are programmed "to make the organ as adaptive as possible to the range of environmental variations in which it evolved". Citing the "Osgood Principle" from the 1950's, recent supporting evidence was described, in which the most mature differentiated cells exert positive and negative feedback upon the proliferation of their progenitor stem cells. Advanced examples in the haemopoietic series were drawn from the work of Sachs, Metcalf, Till and McCulloch, and Kurland and Moore. The blocked ontogeny hypothesis was further elaborated in the concept of "partially-blocked ontogeny", which is intended to describe a situation in which highly differentiated slowly growing tumours contain some cells which have left the proliferating pool to differentiate along the normal pathway, but are blocked somewhere short of the final organism-serving state, in harmony with earlier suggestions by Osgood, by Pierce, and by Sachs.

Amino Acids↗
PubMed2006

Primer: mechanisms of immunologic tolerance.

Successful adaptive immunity against a broad range of pathogens depends on the diversity of randomly generated T-lymphocyte and B-lymphocyte receptors. A subset of these receptors will be self-reactive and must be regulated to prevent autoimmunity. The process of immunologic tolerance addresses this problem by either purging autoreactive receptors from the system or tuning down their reactivity sufficiently to prevent disease. Immature lymphocytes generate a novel receptor during development in the thymus or bone marrow. Engagement of self antigens by these nascent receptors leads to their purging, either by the apoptotic death of the lymphocyte or by the initiation of receptor editing, a process in which the autoreactive receptor is replaced. If the lymphocytes mature further, the activation threshold of autoreactive cells can be tuned by the co-expression of inhibitory receptors or negative signaling molecules, allowing the persistence of the receptor without an increased risk of autoimmunity. T-cell and B-cell receptors that escape these checkpoints can still be regulated in the peripheral immune system by both purging and tuning mechanisms. A separate set of mechanisms, mediated by various regulatory cells, also operates to tune peripheral receptors in a cell-extrinsic fashion. The combined action of these processes ensures that the organism does not suffer autoimmune pathology, even if autoreactive receptors are generated and maintained in the immune system.

Autoimmune Diseases↗
PubMed1996

Pain perception of intravenous heroin users on maintenance therapy with levomethadone.

Methadone is a very potent analgesic drug. Accordingly, maintenance therapy of heroin addicts with methadone may conceal pain producing processes. Here we report on the pain perception of 42 patients on a levomethadone maintenance treatment for intravenous heroin users. Pain perception was measured by single-blind, non-invasive pressure stimulation of the nociceptors located in the dorsal extension aponeurosis and the underlying periosteum of the middle phalanx of a digit before and respectively 1,2, and 4 hours after oral routine drug administration. Measures were related to the individual levomethadone plasma levels. Under steady-state conditions, the pain perception of the patients did not differ from a drug-free placebo control group and was not related to individual levomethadone plasma levels, although an analgesic effect in the reabsorption phase was observed. It is concluded that the individual pain perception of maintained patients is adapted to a normal response range and that even prolonged opioid consumption does not diminish dynamic analgesic responsiveness to levomethadone.

Adult↗
PubMed2006

In vitro efficacy, resistance selection, and structural modeling studies implicate the malarial parasite apicoplast as the target of azithromycin.

Azithromycin (AZ), a broad-spectrum antibacterial macrolide that inhibits protein synthesis, also manifests reasonable efficacy as an antimalarial. Its mode of action against malarial parasites, however, has remained undefined. Our in vitro investigations with the human malarial parasite Plasmodium falciparum document a remarkable increase in AZ potency when exposure is prolonged from one to two generations of intraerythrocytic growth, with AZ producing 50% inhibition of parasite growth at concentrations in the mid to low nanomolar range. In our culture-adapted lines, AZ displayed no synergy with chloroquine (CQ), amodiaquine, or artesunate. AZ activity was also unaffected by mutations in the pfcrt (P. falciparum chloroquine resistance transporter) or pfmdr1 (P. falciparum multidrug resistance-1) drug resistance loci, as determined using transgenic lines. We have selected mutant, AZ-resistant 7G8 and Dd2 parasite lines. In the AZ-resistant 7G8 line, the bacterial-like apicoplast large subunit ribosomal RNA harbored a U438C mutation in domain I. Both AZ-resistant lines revealed a G76V mutation in a conserved region of the apicoplast-encoded P. falciparum ribosomal protein L4 (PfRpl4). This protein is predicted to associate with the nuclear genome-encoded P. falciparum ribosomal protein L22 (PfRpl22) and the large subunit rRNA to form the 50 S ribosome polypeptide exit tunnel that can be occupied by AZ. The PfRpl22 sequence remained unchanged. Molecular modeling of mutant PfRpl4 with AZ suggests an altered orientation of the L75 side chain that could preclude AZ binding. These data imply that AZ acts on the apicoplast bacterial-like translation machinery and identify Pfrpl4 as a potential marker of resistance.

Amodiaquine↗
PubMed2001

Thermal resistance of chicken (Gallus domesticus) plumage: a comparison between broiler and free-range birds.

1. We compared Ross chickens reared under broiler and free-range conditions to see whether there was a difference in thermal resistance of the plumage. 2. There was no difference in resistance to heat loss attributable to rearing environment for plumage from the back and leg but there was a significant difference in the pectoral region. 3. Free-range birds had a thicker plumage and a higher total resistance to heat transfer in the pectoral region, despite showing a lower resistance per unit depth than broiler birds. The pectoral plumage was more heavily soiled in broiler birds, which is the most likely explanation for the higher resistance per unit depth. 4. We suggest that behavioural selection of microclimate is likely to be a more important determinant of heat balance in free-range birds than intrinsic plumage adaptations.

Adaptation, Physiological↗
PubMed1982

Visceral receptors and their afferents in the caudal mesenteric nerve of the duck.

1. The behaviour and reactivities of visceral receptors to different mechanical and chemical stimuli in simple unit preparations from the caudal mesenteric nerve of adult ducks were studied to examine the physiological roles of such receptors. 2. In total, 83 single unit activities were recorded from the caudal mesenteric nerve. 3. Receptors were grouped according to their locations in different layers of the rectum as (i) over the branching points of the blood vessel or in the serosal layer, (ii) in the muscle layer or (iii) in the mucous membrane of the rectum. 4. All the receptors, both spontaneous and non-spontaneous, responded to mechanical probing. Receptors of the muscle layer responded to distension also and showed a slowly-adapting nature. Most of the receptors of the other two groups were of the rapidly-adapting type. 5. Conduction velocity ranged from 0.76 to 34.6 m/s. 6. Sympathetic afferent fibres from the hind gut ascend along the intestinal nerve and join the caudal mesenteric nerve via the colonic ganglion.

Animals↗
PubMed1991

Two light-dependent conductances in Lima rhabdomeric photoreceptors.

Light-dependent membrane currents were recorded from solitary Lima photoreceptors with the whole-cell clamp technique. Light stimulation from a holding voltage near the cell's resting potential evokes a transient inward current graded with light intensity, accompanied by an increase in membrane conductance. While the photocurrent elicited by dim flashes decays smoothly, at higher stimulus intensities two kinetically distinct components become visible. Superfusion with TEA or intracellular perfusion with Cs do not eliminate this phenomenon, indicating that it is not due to the activation of the Ca-sensitive K channels that are present in these cells. The relative amplitude of the late component vs. the early peak of the light response is significantly more pronounced at -60 mV than at -40 mV. At low light intensities the reversal potential of the photocurrent is around 0 mV, but with brighter lights no single reversal potential is found; rather, a biphasic response with an inward and an outward component can be seen within a certain range of membrane voltages. Light adaptation through repetitive stimulation with bright flashes diminishes the amplitude of the early but not the late phase of the photocurrent. These observations can be accounted for by postulating two separate light-dependent conductances with different ionic selectivity, kinetics, and light sensitivity. The light response is also shown to interact with some of the voltage-sensitive conductances: activation of the Ca current by a brief conditioning prepulse is capable of attenuating the photocurrent evoked by a subsequent test flash. Thus, Ca channels in these cells may not only shape the photoresponse, but also participate in the process of light adaptation.

Adaptation, Ocular↗
PubMed2004

Recombination factors for the cylindrical FC65-G ionization chamber in pulsed photon beams and the plane-parallel Roos ionization chamber in pulsed electron beams.

The use of ionization chambers in linac radiotherapy dosimetry requires various corrections to the measured charges, one of these being the recombination correction. The recombination correction factor (k(s)) is generally estimated from the two-voltage analysis (TVA) for each beam quality. However, it is possible that the ionization chamber above some threshold polarizing voltage does not follow the accepted Boag theory very well. Secondly the TVA is time-consuming as the chamber needs to stabilize after each polarizing voltage change and since it must be performed for each beam quality. Another approach consists in using the fact that k(s) is predicted to depend linearly on dose per pulse by Boag theory: determining this relationship once and for all using a multi-voltage analysis (MVA), one also checks the range validity of the Boag theory for the chamber considered. This work presents a thorough analysis of k(s) dependence on dose per pulse of FC65-G (cylindrical) and Roos (plane-parallel) ionization chambers in pulsed photon and electron beams, respectively. Within the uncertainties, the recombination factors are found to be independent of beam quality, and no deviation from the Boag theory is observed within the tested range of polarizing voltages. Before adapting the equations given using the MVA other users should check that their ionization chambers show the same dose per pulse dependence using the TVA for a few beam qualities.

Algorithms↗
PubMed2002

Memory cytotoxic T cell responses to viral tegument and regulatory proteins encoded by open reading frames 4, 10, 29, and 62 of varicella-zoster virus.

Cytotoxic T cell recognition of tegument and regulatory proteins encoded by open reading frames (ORFs) 4, 10, 29, and 62 of varicella-zoster virus (VZV) was evaluated using limiting dilution conditions to estimate the precursor frequencies of memory T cells specific for these proteins in immune subjects. Responder cell frequencies for ORFs 4, 10, and 62 gene products, which are virion tegument components and function as immediate early viral transactivating proteins, were equivalent. CTLp recognition of VZV proteins made in latently infected cells, which include ORF4 and ORF62 proteins, was not maintained preferentially when compared to ORF10 protein, which has not been shown to be expressed during latency. T cell recognition of ORF29 protein, the major DNA binding protein, which is expressed during replication but not incorporated into the virion tegument, was less common than responses to ORFs 4, 10, and 62 gene products. Older individuals had diminished numbers of memory CTLp that lysed autologous targets expressing IE62 protein; these responses were increased after immunization with live attenuated varicella vaccine to the range observed in younger adults. Adaptive immunity to VZV is characterized by a broad repertoire of memory CTL responses to proteins that comprise the virion tegument and regulate viral gene expression in infected cells.

Adult↗
PubMed2005

Economy, speed and size matter: evolutionary forces driving nuclear genome miniaturization and expansion.

BACKGROUND: Nuclear genome size varies 300 000-fold, whereas transcriptome size varies merely 17-fold. In the largest genomes nearly all DNA is non-genic secondary DNA, mostly intergenic but also within introns. There is now compelling evidence that secondary DNA is functional, i.e. positively selected by organismal selection, not the purely neutral or 'selfish' outcome of mutation pressure. The skeletal DNA theory argued that nuclear volumes are genetically determined primarily by nuclear DNA amounts, modulated somewhat by genes affecting the degree of DNA packing or unfolding; the huge spread of nuclear genome sizes is the necessary consequence of the origin of the nuclear envelope and the nucleation of its assembly by DNA, plus the adaptively significant 300 000-fold range of cell volumes and selection for balanced growth by optimizing karyoplasmic volume ratios (essentially invariant with cell volume in growing/multiplying cells). This simple explanation of the C-value paradox is refined here in the light of new insights into the nature of heterochromatin and the nuclear lamina, the genetic control of cell volume, and large-scale eukaryote phylogeny, placing special emphasis on protist test cases of the basic principles of nuclear genome size evolution. GENOME MINIATURIZATION: and Expansion Intracellular parasites (e.g. Plasmodium, microsporidia) dwarfed their genomes by gene loss and eliminating virtually all secondary DNA. The primary driving forces for genome reduction are metabolic and spatial economy and cell multiplication speed. Most extreme nuclear shrinkage yielded genomes as tiny as 0.38 Mb (making the nuclear genome size range effectively 1.8 million-fold!) in some minute enslaved nuclei (nucleomorphs) of cryptomonads and chlorarachneans, chimaeric cells that also retain a separate normal large nucleus. The latter shows typical correlation between genome size and cell volume, but nucleomorphs do not despite co-existing in the same cell for >500 My. Thus mutation pressure does not inexorably increase genome size; selection can eliminate essentially all non-coding DNA if need be. Nucleomorphs and microsporidia even reduced gene size. Expansion of secondary DNA in the main nucleus, and in large-celled eukaryotes generally, must be positively selected for function. Ciliate nuclear dimorphism provides a key test that refutes the selfish DNA and strongly supports the skeletal DNA/karyoplasmic ratio interpretation of genome size evolution. GENETIC CONTROL OF CELL VOLUME IS MULTIGENIC: The quantitatively proportional correlation between genome size and cell size cannot be explained by purely mutational theories, as eukaryote cell volumes are causally determined by cell cycle control genes, not by DNA amounts.

Animals↗
PubMed1988

Modeling the outdoor environment--new perspectives and challenges.

Assessing risk from manmade and naturally occurring radionuclides in the environment has long been of primary interest in radiation protection. Early investigations and decisions relied on direct measurements of radiation in environmental media; however, these techniques were inadequate for determining exposure to humans and biota from very low levels of radiation and in predicting exposures from future releases. The Plowshare Program in 1957 investigated the use of nuclear explosives for peaceful purposes and created an immediate need for predicting the dispersion and ultimate fate of radionuclides that might be vented to the atmosphere or enter groundwater and expose man. As a result, modeling the behavior of radionuclides in the outdoor environment became a field of vigorous interest, merging disciplines of mathematics, biology and physics, among others. Environmental models and, more specifically, models predicting radiation dose from radionuclides in the environment have evolved rapidly and have increased significantly in sophistication, complexity and scope. Application of these models is commonly known as radiological assessment. This presentation examines the current status, future direction and weaknesses of radiological assessment models used in making decisions about radiation. The trend in recent years has been toward more complex models, which has not necessarily improved the accuracy of dose estimates and, in certain cases, has had the opposite effect. The presentation also discusses the future of model development, with particular emphasis on simple techniques and the expanded use of microcomputers, which will make radiological assessment models widely available for risk assessment and for practical applications such as the design of efficient monitoring programs and engineering calculations on the clean-up of contaminated soils. The screening models developed by the National Council on Radiation Protection and Measurements are offered as an example of a powerful yet simple method for demonstrating compliance with standards. Finally, the paper reviews two major areas of challenge for the future--defining uncertainty associated with radiological assessment models and the potential for converting radiological assessment models for use with nonradioactive environmental pollutants such as chemicals. Modeling radionuclides in the environment is adopting a new perspective. Future models will be less complex than their predecessors and will be adaptable to a much broader range of users. Key challenges remain in applying the techniques used for radionuclides to nonradioactive pollutants.

Air Pollutants, Radioactive↗