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PubMed1984

Renal osteodystrophy in CAPD patients.

To assess the influence of continuous ambulatory peritoneal dialysis (CAPD) on the evolution of renal osteodystrophy, we studied 36 adult patients with end-stage renal failure before starting dialysis and after 7-30 months. 17 patients (12 males and 5 females) were treated by CAPD as first treatment and 19 (14 males and 5 females) received maintenance hemodialysis. The two groups were age- and sex-matched and no patient received vitamin D. All patients had adequate clinical and metabolic follow-up with a radiological survey and quantitative bone histology at the start of dialysis and at the end of the study. Serum phosphate concentrations were much easier to control in CAPD than in hemodialysis patients. There was no difference in the evolutive pattern of vascular and periarticular calcifications in the two groups. The 25-hydroxyvitamin D3 levels were frequently lower in CAPD than in hemodialysis patients. In some CAPD patients, there was a significant loss of trabecular bone volume at the end of the study. The radiological and histological appearances of secondary hyperparathyroidism improved or seemed to worsen to a lesser degree in CAPD compared to hemodialysis patients.

Adult↗

PubMed1998

Population dynamics in the evolution of RNA viruses.

RNA virus quasispecies are subjected to processes of positive Darwinian selection, to a very active and continuous negative selection and to random genetic drift. The course of RNA virus evolution is often unpredictable, and recent results suggest that even highly conserved motifs, once regarded as essential for infectivity, may be rendered dispensable by singular evolutionary events. An immediate consequence of the quasispecies genetic organization of RNA viruses is a surprising ability to gain fitness once a minimal replication ability is established in a biological environment. The unique features of RNA genetics should not be underestimated since they are at the basis of the emergence of new viral diseases and of the current difficulties to control many diseases associated variable viruses.

Animals↗

PubMed2002

Observation of structural transformations in metal oxygen.

X-ray diffraction and Raman measurements have been performed on solid oxygen up to, respectively, 115 and 120 GPa. Metallization at 96 GPa is shown to be associated with a continuous displacive structural transformation. At 110 GPa, a new structure is stabilized. The evolution of the vibron mode reflects also the sequence of phase transitions through the continuity of the vibron frequency at 96 GPa, then the broadening of the vibron peak into the background and finally the reappearance of a sharp vibron at 110 GPa with a -2.5% discontinuity in the frequency. The observation of the vibron peak demonstrates that metallic oxygen is molecular up to at least 120 GPa.

Journal Article↗

PubMed2006

HIV-1 entry inhibitors: classes, applications and factors affecting potency.

Antiviral agents targeting human immunodeficiency virus type-1 (HIV-1) attachment, co-receptor engagement and fusion, collectively referred to as entry inhibitors, are emerging as promising therapeutic agents in the treatment of HIV-1 infection. Viral evolution and concomitant emergence of resistant strains will continue to be an important consideration in the development of any new therapeutic against HIV-1. However, unique challenges facing the development of entry inhibitors center around the highly variable and flexible nature of the HIV-1 envelope protein (Env). For example, the evolution of Env during the course of HIV-1 infection increases the efficiency of Env-CCR5 interactions, which consequently increases Env-mediated fusogenicity and decreases sensitivity to entry inhibitors. This points to a relationship between co-receptor interactions and fusogenicity that merits further consideration in the design of HIV-1 entry inhibitors. It also underscores the importance of considering the biological properties of late-emerging HIV-1 variants in the design of new therapeutics. This review examines the various entry inhibitors that are undergoing preclinical or clinical testing or which are in the early stages of clinical use, their applications in a clinical setting and possible factors that may affect potency against HIV-1.

Anti-HIV Agents↗

PubMed1974

The effect of bicarbonate on photosynthetic oxygen evolution in flashing light in chloroplast fragments.

The ability of bicarbonate ion (HCO(3) (-)) to stimulate photosynthetic oxygen evolution in maize chloroplast fragments exposed to continuous light depends on light intensity. Stimulation by HCO(3) (-) is less at low intensities. In HCO(3) (-)-depleted chloroplasts exposed to brief saturating light flashes, period 4 oscillations (in O(2) yield per flash) are damped within three cycles. Readdition of HCO(3) (-) to these preparations restores the oscillatory pattern to higher flash numbers, indicating that HCO(3) (-) reduces the probability of "misses" in the photosystem II reaction center. The rate of the dark relaxation reaction S(n) (') --> S(n+1) (where S refers to the oxidation state of the oxygen-evolving mechanism and n = 0, 1, or 2), after a photoact in the photosystem II reaction center, is retarded in HCO(3) (-)-depleted chloroplasts compared to the rate for this reaction in depleted chloroplasts to which HCO(3) (-) has been resupplied. However, the final oxygen-evolving reaction after the accumulation of four positive charges appears to be independent of HCO(3) (-). Bicarbonate has no effect on the dark deactivation of the higher oxidation states (S(2) and S(3)) of the positive charge-accumulating system. We propose two alternate ways in which the kinetic model of oxygen evolution developed by Kok et al. [(1970) Photochem. Photobiol. 11, 457-475] can be extended to include the action of HCO(3) (-).

Journal Article↗

PubMed2000

Independent contrasts succeed where ancestor reconstruction fails in a known bacteriophage phylogeny.

Methods of ancestor reconstruction are important tools for evolutionary inference that are difficult to test empirically because ancestral states are rarely known with certainty. We evaluated reconstruction methods for continuous phenotypic characters using taxa from an experimentally generated bacteriophage phylogeny. Except for one slowly evolving character, the estimated ancestral states of continuous phenotypic characters were highly inaccurate and biased, even when including a known ancestor at the root. This error was caused by a directional trend in character evolution and by rapid rates of character evolution. Computer simulations confirmed that such factors affect reconstruction of continuous characters in general. We also used phenotypic viral characters to evaluate two methods that attempt to estimate the correlation between characters during evolution. Whereas a nonphylogenetic regression was relatively inaccurate and biased, independent contrasts accurately estimated the correlation between characters with little bias.

Bacteriophage T7↗

PubMed2004

Stability improvement of antibodies for extracellular and intracellular applications: CDR grafting to stable frameworks and structure-based framework engineering.

By combining the knowledge gained from an analysis of the biophysical properties of natural antibody variable domains, the effects of mutations obtained in directed evolution experiments, and the detailed structural comparison of antibodies, it has now become possible to engineer antibodies for higher thermodynamic stability and more efficient folding. This is particularly important when antibodies are to be used under conditions where the disulfide bonds cannot form, i.e., in intracellular applications (as "intrabodies"). We describe in detail two methods for the knowledge-based improvement of antibody stability and folding efficiency. While CDR grafting from a non-human to the most closely related human antibody framework is an established technique to reduce the immunogenicity of a therapeutic antibody, CDR grafting for stabilization implies the use of a more distantly related acceptor framework with superior biophysical characteristics. The use of such dissimilar frameworks requires particular attention to antigen contact residues outside the classical CDR definition and to residues capable of indirectly affecting the conformation of the antigen binding site. As a second alternative, the stability of a suboptimal framework can be improved by the introduction of point mutations designed to optimize key residue interactions. We describe the analysis methods used to identify such point mutations, which can be introduced all at once, while maintaining the framework features necessary for antigen binding. These rational approaches render the continued "rediscovery" of certain mutations by directed evolution unnecessary, but they can also be used in conjunction with such methods to discover even better molecules.

Animals↗

PubMed1995

Theory of mind: evolutionary history of a cognitive specialization.

Traditional analyses of the evolution of intelligence have emphasized commonality and continuity among species. However, recent research suggests that humans might have specialized in a particular kind of intelligence that is related to understanding mental states such as desires, intentions and beliefs. Data indicate that the ability to reflect on one's own mental states, as well as those of others, might be the result of evolutionary changes in the prefrontal cortex. Behavioral studies in children and chimpanzees reveal both similarities and striking differences in the developmental pathways that lead to theory-of-mind capacities. Humans and great apes share many ancient patterns of social behavior, but it is too early to be certain if they interpret them in the same manner. Humans might have evolved a cognitive specialization in theory of mind, forever altering their view of the social universe.

Animals↗

PubMed2002

Evolution of human intelligence: the roles of brain size and mental construction.

Two competing philosophical paradigms characterize approaches to the evolution of the human mind. One postulates continuity between animal and human behavioral capacities. The other assumes that humans and animals are separated by major qualitative behavioral and mental gaps. This paper presents a continuity model that suggests that expanded human mental capacities primarily reflect the increased information processing capacities of the enlarged human brain including the enlarged neocortex, cerebellum, and basal ganglia. These increased information processing capacities enhance human abilities to combine and recombine highly differentiated actions, perceptions, and concepts in order to construct larger, more complex, and highly variable behavioral units in a variety of behavioral domains including language, social intelligence, tool-making, and motor sequences. Environmental input, including self-generated input, interacts with mental constructional capacities to assure that developing humans acquire species-typical and culturally-specific behavioral patterns. This mental constructional model is compatible with our current understanding of differences between human and non-human primate brains, of human brain plasticity, and of the minimal genetic differences between humans and chimpanzees.

Animals↗

PubMed2006

Gavin Rylands de Beer: how embryology foreshadowed the dilemmas of the genome.

Gavin de Beer is remembered, at best, as a shadowy figure among those who gradually built up our current view of evolution and the role of genetics. This view derives from the Modern Synthesis - the recognition that emerged in the 1930s that genetics can adequately explain Darwinian evolution and speciation through natural selection. I argue that de Beer's theories of embryology had a crucial role in the Modern Synthesis, and that his work indirectly continues to influence how we think about the genome, evolution and developmental biology.

Animals↗

PubMed1994

Historical origins of current concepts of carcinogenesis.

The first attempts to understand the causes of cancer were based on generalizations of what might now be termed a "holistic" nature, and hereditary influences were recognized at an early stage; these views survive principally through a supposed positive connection between psychological factors such as stress and diminished ability to combat the progressive development of tumors through some form of immunologically mediated rejection of potentially cancerous cells. While evidence for immunosurveillance is generally accepted, it is now widely regarded as almost wholly confined to instances where tumor viruses are involved as causative agents. The earliest theorists drew an analogy between the processes of carcinogenesis and of evolution; the cancer cells acquired the ability to outstrip their normal counterparts in their capacity for proliferation. This was even before evolution had been interpreted as involving a continuous succession of mutations. Evidence was already to hand before the end of the 18th century that exogenous agents, notably soot, a product of the "industrial revolution," could cause skin cancer. Somewhat over 100 years later, another industrial innovation, the manufacture of synthetic dyestuffs, implicated specific chemical compounds that could act systemically to cause bladder cancer. Meanwhile, the 19th century saw the establishment of the fundamentals of modern medical science; of particular relevance to cancer was the demonstration that it involved abnormalities in the process of cell division. The commencement of the 20th century was marked by a rediscovery of the concept of mutation; and it was proposed that cancer originated through uncontrolled division of somatically mutated cells. At around this time, two further important exogenous causative agents were discovered: X-rays and tumor viruses. In the late 1920s, x-radiation became the first established exogenous cause of mutagenesis. The discoverer of this phenomenon, H. J. Muller, suggested that while mutation in a single cell was the primary causative mechanism in carcinogenesis, its generally observed logarithmic increase in incidence with age reflected a "multihit" process, and that multiple successive mutations were required in the progeny of the original mutants. He also recognized that the rate of proliferation of potentially cancerous cells would markedly influence the probability of their subsequent mutation. These considerations are essentially the foundation of the generally accepted view of carcinogenesis that now seems unlikely to be superseded. However, this acceptance did not come about unopposed. The analogy between carcinogenesis and evolution was disliked by many biologists because it embodied the concept that cancer was an inevitable consequence of our evolutionary origins.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkylation↗

PubMed1993

Natural evolution of coronavirus defective-interfering RNA involves RNA recombination.

Defective-interfering (DI) RNAs of RNA viruses, in general, are generated and continue to evolve in size during serial undiluted passages of viruses. This evolution was thought to occur by independent generation of DI RNAs during virus passages and subsequent selection of new DI RNAs under new cellular conditions. Here we demonstrate that recombination between the old DI RNA and the helper viral RNA can be one of the mechanisms for natural DI RNA evolution. A mouse hepatitis virus (MHV) DI RNA, DIssE RNA, was transcribed in vitro and transfected into a mouse cell line infected with a different MHV strain (A59), which is distinguishable from the original natural helper MHV (JHM). During subsequent serial undiluted passages of the harvested virus, several novel DI RNA species were generated, while the original DIssE RNA disappeared by passage 11. cDNA cloning and sequence analysis of one of these novel DI RNAs, designated DI-2, revealed that it is composed of four discontinuous regions of the genomic sequence and is different from the structure of the original DIssE RNA. Sequence comparison among DI-2, DIssE, and helper MHV-A59 RNAs showed that DI-2 sequence is similar to DIssE in the first and second regions, but similar to the helper A59 virus in the third and last regions. Thus, this DI RNA was generated by RNA recombination between the original DIssE RNA and the helper viral RNA. These results indicate that recombination between DI RNA and helper virus RNA can be involved in the natural evolution of DI RNAs.

Animals↗

PubMed2005

The genesis and evolution of homeobox gene clusters.

Once called the 'Rosetta stone' of developmental biology, the homeobox continues to fascinate both evolutionary and developmental biologists. The birth of the homeotic, or Hox, gene cluster, and its subsequent evolution, has been crucial in mediating the major transitions in metazoan body plan. Comparative genomics studies indicate that the more recently discovered ParaHox and NK clusters were linked to the Hox cluster early in evolution, and that together they constituted a 'megacluster' of homeobox genes that conspicuously contributed to body-plan evolution.

Evolution, Molecular↗

PubMed2000

Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution.

Vertebrate epithelial appendages are elaborate topological transformations of flat epithelia into complex organs that either protrude out of external (integument) and internal (oral cavity, gut) epithelia, or invaginate into the surrounding mesenchyme. Although they have specific structures and diverse functions, most epithelial appendages share similar developmental stages, including induction, morphogenesis, differentiation and cycling. The roles of the SHH pathway are analyzed in exemplary organs including feather, hair, tooth, tongue papilla, lung and foregut. SHH is not essential for induction and differentiation, but is involved heavily in morphogenetic processes including cell proliferation (size regulation), branching morphogenesis, mesenchymal condensation, fate determination (segmentation), polarizing activities and so on. Through differential activation of these processes by SHH in a spatiotemporal-specific fashion, organs of different shape and size are laid down. During evolution, new links of developmental pathways may occur and novel forms of epithelial appendages may emerge, upon which evolutionary selections can act. Sites of major variations have progressed from the body plan to the limb plan to the epithelial appendage plan. With its powerful morphogenetic activities, the SHH pathway would likely continue to play a major role in the evolution of novel epithelial appendages.

Animals↗

PubMed2006

The era of microbiology: a golden phoenix.

The discoveries over the last decade have demonstrated that microbiology is a central scientific discipline with practical applications in agriculture, medicine, bioremediation, biotechnology, engineering, and other fields. It is clear that the roles of microbes in nature are so diverse that the process of mining this genetic variation for new applications will continue long into the future. Moreover, the rapid rate of microbial evolution ensures that there will be no permanent solution to agricultural, medical, or environmental problems caused by microbes. These problems will demand a continual stream of creative new approaches that evolve along with the microbes. Thus, the excitement of this field will continue long into the future. However, these opportunities and imperatives demand a deep understanding of basic microbial physiology, genetics, and ecology. Major challenges that lay ahead are to impart the broad training needed to entice and enable the next generation of microbiologists, and to educate the public and government representatives about the continued and critical importance of this field for health and the economy.

Biological Evolution↗

PubMed2000

Greening of intermittent-light-grown bean plants in continuous light: thylakoid components in relation to photosynthetic performance and capacity for photoprotection.

Phaseolus vulgaris (cvv. Windsor longpod and snap bean) plants, etiolated during germination, were exposed to intermittent light (2 min light every 2 hr) for up to 68 hr and then transferred to continuous white light. On transfer of the plants to continuous light (100 photons mumol m-2 s-1, 24 degrees C), the quantum yield of oxygen evolution increased two-fold in about 30 hr. The chlorophyll content per unit leaf area or unit fresh weight increased dramatically, but the fresh weight per unit leaf area was relatively constant. The changes were expressed on the basis of fresh weight or leaf area. On this basis, the contents of photosystem (PS) I and II increased in continuous light, by a factor of 3 and 8, respectively. While the chlorophyll b content and the contents of apoproteins of light-harvesting chlorophyll-protein complexes (LHCIIb, CP29, CP26 and CP24) increased markedly, neither the total carotenoid content nor the de-epoxidation state of the xanthophylls [ratio of zeaxanthin(Z) + antheraxanthin(A) to (Z + A + violaxanthin) was about 0.4)] responded significantly on transfer to continuous light. The fast rise of the flash-induced electrochromic signal (delta A518) was well correlated with the increases in PS I and PS II reaction centres, and with chlorophyll b and total carotenoid contents. The increase in the quantum yield of oxygen evolution during greening in continuous light is attributed to a more balanced distribution of excitation energy between the two photosystems, facilitated by the increased number of PS II units, the increased antenna size of each unit and the enhancement of grana formation. The chloroplast in intermittent light was found to contain abundant xanthophyll cycle pigments and the psbS gene product, presumably adequate for photoprotection in continuous light as soon as chlorophyll a/b- protein complexes are synthesized. The results suggest that greening in continuous light is accompanied by adjustments that include enhanced quantum efficiency of photosynthesis and development of a capacity for harmless dissipation of excess excitation energy.

Fabaceae↗

PubMed2003

Origin of feathers: Feather beta (beta) keratins are expressed in discrete epidermal cell populations of embryonic scutate scales.

The feathers of birds develop from embryonic epidermal lineages that differentiate during outgrowth of the feather germ. Independent cell populations also form an embryonic epidermis on scutate scales, which consists of peridermal layers, a subperiderm, and an alpha stratum. Using an antiserum (anti-FbetaK) developed to react specifically with the beta (beta) keratins of feathers, we find that the feather-type beta keratins are expressed in the subperiderm cells of embryonic scutate scales, as well as the barb ridge lineages of the feather. However, unlike the subperiderm of scales, which is lost at hatching, the cells of barb ridges, in conjunction with adjacent cell populations, give rise to the structural elements of the feather. The observation that an embryonic epidermis, consisting of peridermal and subperidermal layers, also characterizes alligator scales (Thompson, 2001. J Anat 198:265-282) suggests that the epidermal populations of the scales and feathers of avian embryos are homologous with those forming the embryonic epidermis of alligators. While the embryonic epidermal populations of archosaurian scales are discarded at hatching, those of the feather germ differentiate into the periderm, sheath, barb ridges, axial plates, barbules, and marginal plates of the embryonic feather filament. We propose that the development of the embryonic feather filament provides a model for the evolution of the first protofeather. Furthermore, we hypothesize that invagination of the epidermal lineages of the feather filament, namely the barb ridges, initiated the formation of the follicle, which then allowed continuous renewal of the feather epidermal lineages, and the evolution of diverse feather forms.

Amino Acid Sequence↗

PubMedDate not supplied

Changing face of pain: evolution of pain research in psychosomatic medicine.

OBJECTIVE: This article provides an overview of how psychosomatic research on pain has evolved over the past 60 years as exemplified by studies published in Psychosomatic Medicine. METHODS: Each issue of Psychosomatic Medicine from 1939 to 1999 was reviewed to identify papers that dealt with pain, painful medical conditions, or pain management. A total of 150 papers were identified and grouped into seven categories: 1) case studies; 2) studies of personality traits and other individual differences; 3) psychophysiological studies of pain; 4) studies using pain induction techniques; 5) studies examining the relation of relation of race, ethnicity, and culture to pain; 6) studies of pain unique to women; and 7) studies examining treatments for pain. RESULTS: A substantial number of studies on pain and painful conditions were published in the Journal in the 1940s and 1950s, and that number has almost doubled in the most recent full decade of the Journal. Within the pain area, however, the topics of interest to psychosomatic researchers have been, and continue to be, quite diverse. Although publications on certain methods or topics (eg, psychodynamic case studies, physiological correlates of pain) have decreased over time, publications on other topics (eg, personality traits and individual differences) have remained relatively constant, and publications on still other topics (eg, studies using pain induction techniques; studies of race, ethnicity, and culture; women's pain; and treatment studies) have flourished recently. CONCLUSIONS: Considered overall, the results of our review suggest that the face of pain research published in PM has changed considerably in the past 60 years. Given the ongoing commitment of psychosomatic researchers to this area, we expect this evolution to continue in the years to come.

Female↗