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PubMed2003

Evolution of subterranean diving beetles (Coleoptera: Dytiscidae: Hydroporini, Bidessini) in the arid zone of Australia.

Calcrete aquifers in arid inland Australia have recently been found to contain the world's most diverse assemblage of subterranean diving beetles (Coleoptera: Dytiscidae). In this study we test whether the adaptive shift hypothesis (ASH) or the climatic relict hypothesis (CRH) is the most likely mode of evolution for the Australian subterranean diving beetles by using a phylogeny based on two sequenced fragments of mitochondrial genes (CO1 and 16S-tRNA-ND1) and linearized using a relaxed molecular clock method. Most individual calcrete aquifers contain an assemblage of diving beetle species of distantly related lineages and/or a single pair of sister species that significantly differ in size and morphology. Evolutionary transitions from surface to subterranean life took place in a relatively small time frame between nine and four million years ago. Most of the variation in divergence times of the sympatric sister species is explained by the variation in latitude of the localities, which correlates with the onset of aridity from the north to the south and with an aridity maximum in the Early Pliocene (five mya). We conclude that individual calcrete aquifers were colonized by several distantly related diving beetle lineages. Several lines of evidence from molecular clock analyses support the CRH, indicating that all evolutionary transitions took place during the Late Miocene and Early Pliocene as a result of aridification.

Adaptation, Biological↗

PubMed1984

Multidisciplinary considerations in cancer treatment: origin and scope.

The Tumor Board constitutes the control area where multidisciplinary protocols are created and where each patient's circumstance is thoroughly reviewed from the perspective of all pertinent clinical disciplines. Such input is an essential component of quality control at all levels of management of the cancer patient. This pertains whether in a community hospital or in a specialized cancer center. Cooperative groups and other research organizations have recognized the essential nature of this input, especially for the integration of new measures with those therapeutic modalities that are already established. Thus treatment may show a logical evolution by continuously updating standard approaches through clinical trials posing the most relevant question from the point of view of all modalities, while maintaining stringent quality control. Examples of questions being posed by therapeutic advances in testicular and ovarian cancer are described. The key element in accomplishing these advances is multidisciplinary participation.

Combined Modality Therapy↗

PubMed2000

Formation of a tight 1:1 complex of Clostridium pasteurianum Fe protein-Azotobacter vinelandii MoFe protein: evidence for long-range interactions between the Fe protein binding sites during catalytic hydrogen evolution.

It has been well documented that the combination of the MoFe protein of Azotobacter vinelandii nitrogenase (Av1) with the Fe protein (Cp2) from Clostridium pasteurianum nitrogenase produces an inactive, stable complex. However, we report that this heterologous nitrogenase has a low level of activity for H(2) evolution, with a specific activity of 12 nmol min(-)(1) mg(-)(1) of Av1. This activity does not arise from contaminating hydrogenase since it required the presence of both Cp2 and Av1 and showed saturation kinetics when increasing amounts of Cp2 were added to the assay. Incubation of the two proteins at a 4:1 Cp2:Av1 ratio in the absence of MgATP followed by analytical gel filtration showed, surprisingly, that the stoichiometry of the isolated complex was Av1.Cp2 instead of Av1.(Cp2)(2) as determined previously. The presence of MgATP in the elution buffer did not change the elution profile of the complex. The hydrodynamic radius of the isolated complex determined by dynamic light scattering was 5.93 +/- 0.14 nm, intermediate between Av1 and a stable 2:1 nitrogenase complex, consistent with a 1:1 assignment for the Av1.Cp2 complex. When assayed with Av2, the isolated Av1.Cp2 complex showed full half-site reactivity with a specific activity of 750 nmol of C(2)H(2) reduced min(-)(1) mg(-)(1) of Av1. The EPR spectrum of the isolated complex showed the Cp2 to be oxidized and the Av1 to retain the S = (3)/(2) signal characteristic of FeMoco. In the presence of MgATP, under turnover conditions at a 2:1 ratio of Cp2:Av1, the [4Fe-4S] center of Cp2 was protected from the chelator 2,2'-bipyridyl. This is consistent with the formation of a tight 2:1 complex of Av1.(Cp2)(2) which is more stable than the homologous Cp nitrogenase. Assuming that the Lowe-Thorneley model for nitrogenase applies and that a rate-limiting dissociation of the complex is required for H(2) evolution, then with a rate of 0.032 s(-)(1) the 1:1 complex is too stable to be involved in catalysis. The differences in the stability of the 2:1 and 1:1 complexes indicate cooperativity between the Fe protein binding sites of Av1, which structural data show to be separated by 105 A. On the basis of these observations, we propose a model for nitrogenase catalysis in which the stable 1:1 complex formed between oxidized Fe protein and the one-electron-reduced MoFe protein plays an essential role. In this scheme, the two Fe protein binding sites of the MoFe protein alternately bind and release Fe protein in a shuttle mechanism associated with long-range conformational changes in the MoFe protein.

Adenosine Triphosphate↗

PubMed2006

Rapid transitions between defect configurations in a block copolymer melt.

With in situ scanning force microscopy, we image the ordering of cylindrical microdomains in a thin film of a diblock copolymer melt. Tracking the evolution of individual defects reveals elementary steps of defect motion via interfacial undulations and repetitive transitions between distinct defect configurations on a time scale of tens of seconds. The velocity of these transitions suggests a cooperative movement of clusters of chains. The activation energy for the opening/closing of a connection between two cylinders is estimated.

Microscopy, Atomic Force↗

PubMed2001

Molecular ecology of social behaviour: analyses of breeding systems and genetic structure.

Molecular genetic studies of group kin composition and local genetic structure in social organisms are becoming increasingly common. A conceptual and mathematical framework that links attributes of the breeding system to group composition and genetic structure is presented here, and recent empirical studies are reviewed in the context of this framework. Breeding system properties, including the number of breeders in a social group, their genetic relatedness, and skew in their parentage, determine group composition and the distribution of genetic variation within and between social units. This group genetic structure in turn influences the opportunities for conflict and cooperation to evolve within groups and for selection to occur among groups or clusters of groups. Thus, molecular studies of social groups provide the starting point for analyses of the selective forces involved in social evolution, as well as for analyses of other fundamental evolutionary problems related to sex allocation, reproductive skew, life history evolution, and the nature of selection in hierarchically structured populations. The framework presented here provides a standard system for interpreting and integrating genetic and natural history data from social organisms for application to a broad range of evolutionary questions.

Animals↗

PubMed1993

Heme-heme interactions in a homodimeric cooperative hemoglobin. Evidence from transient Raman scattering.

The comparison of the resonance Raman spectrum of the deoxy dimeric hemoglobin (HbI) from the Arcid clam, Scapharca inaequivalvis, to its CO photoproduct at 10 ns reveals several significant differences in the low frequency vibrational modes including those involving motions of the peripheral substituents on the heme such as the propionates. This finding reflects the involvement of the propionates in a hydrogen bonding network which connects the two heme groups across the subunit interface and is sensitive to ligand binding. A frequency difference in the iron-histidine stretching mode of 6 cm-1 in this invertebrate hemoglobin is substantially smaller than that detected in tetrameric vertebrate hemoglobins under similar conditions. Time evolution studies of the vibrational modes from the photoproduct demonstrate that the transient form relaxes to the deoxy structure concertedly with a half-life of 1 microseconds, the time scale in which tertiary relaxations of tetrameric hemoglobins occur. These data establish that the tertiary and quaternary structural changes take place on the same time scale and confirm a mechanism of cooperativity involving direct interaction between the two heme groups through the peripheral substituents. This direct structural communication provides a very tight linkage between the heme groups prohibiting modulation of the oxygen affinity by factors in the physiological milieu.

Animals↗

PubMed2005

Searching for signals of evolutionary selection in 168 genes related to immune function.

Pathogens have played a substantial role in human evolution, with past infections shaping genetic variation at loci influencing immune function. We selected 168 genes known to be involved in the immune response, genotyped common single nucleotide polymorphisms across each gene in three population samples (CEPH Europeans from Utah, Han Chinese from Guangxi, and Yoruba Nigerians from Southwest Nigeria) and searched for evidence of selection based on four tests for non-neutral evolution: minor allele frequency (MAF), derived allele frequency (DAF), Fst versus heterozygosity and extended haplotype homozygosity (EHH). Six of the 168 genes show some evidence for non-neutral evolution in this initial screen, with two showing similar signals in independent data from the International HapMap Project. These analyses identify two loci involved in immune function that are candidates for having been subject to evolutionary selection, and highlight a number of analytical challenges in searching for selection in genome-wide polymorphism data.

Algorithms↗

PubMed1999

The evolutionary landscape of functional model proteins.

To study the distinct influences of structure and function on evolution, we propose a minimalist model for proteins with binding pockets, called functional model proteins, based on a shifted-HP model on a two-dimensional square lattice. These model proteins are not maximally compact and contain an empty lattice site surrounded by at least three nearest neighbors, thus providing a binding pocket. Functional model proteins possess a unique native state, cooperative folding and tolerance to mutation. Due to the explicit functionality in these models (by design), we have been able to explore their fitness or evolutionary landscapes, as characterized by the size and distribution of homologous families and by the complexity of the inter-relatedness of the functional model proteins. Mindful that these minimalist models are highly idealized and two-dimensional, functional model proteins should nevertheless provide a useful means for exploring the constraints of maintaining structure and function on the evolution of proteins.

Amino Acid Sequence↗

PubMed2026

Toward real-time quantification of driving risks: a systematic review and research agenda of risk field theory.

In complex traffic systems, driving risk often evolves in a continuous and progressive manner prior to crash occurrence. How to effectively represent and analyze such latent risk states remains a central challenge in traffic safety research. In recent years, risk field-based approaches have introduced spatial and spatiotemporal continuous modeling paradigms, providing new perspectives for characterizing the distribution of traffic risk and its dynamic evolution. Motivated by the rapid growth of this research area and the lack of a systematic synthesis, this paper presents a comprehensive review of studies applying risk field theory to driving safety and traffic risk analysis. Following the PRISMA guidelines, relevant literature was collected through multi-database searches and analyzed using a combination of bibliometric analysis and qualitative review. The review systematically summarizes the theoretical foundations, modeling elements, data sources, analytical methods, and application domains of risk field-related research. Particular attention is given to studies that conceptualize traffic risk as a continuous field, complemented by a broader review of traffic risk factor literature to identify key elements and analytical dimensions involved in risk field modeling. On this basis, the paper synthesizes research progress in major application areas, including traffic safety state representation, driving behavior analysis, traffic conflict assessment, and autonomous driving and human-machine cooperative systems. Differences and commonalities among existing studies are compared in terms of modeling strategies, data support, and application scenarios. Through this systematic review, the paper clarifies the main research themes and methodological trends of risk field-based studies, providing a structured framework for understanding the evolution and application of this approach and offering methodological insights for risk perception modeling and safety-oriented decision support in intelligent transportation systems (ITS).

Humans↗

PubMed1988

Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: report from the European Cooperative Group for bone marrow transplantation (8 cases).

Allogenic bone marrow transplantation (BMT) was performed in 8 patients with B chronic lymphocytic leukemia (CLL): 6 males and 2 females with a median age of 41 years (37 to 46). Seven patients were resistant to previous therapy and were grafted in the evolutive phase. Only 1 patient was grafted without any previous treatment. At the time of BMT 5 patients were classified according to the Rai classification in stage IV, 1 in stage III and 2 in stage 1. The delay between diagnosis and BMT was 47 months (5 to 68). Graft versus host disease (GVHD) prophylaxis was methotrexate (1 patient), cyclosporine (2 patients), methotrexate + cyclosporine (3 patients), cyclosporine + physical removal of T cells (2 patients). The conditioning regimen was standard for 5 patients, reinforced for 3 patients with Chlorambucil (1 patient) and etoposide (2 patients). A successful engraftment was obtained in all cases. The lymphocytosis decreased slowly and disappeared from day 0 to day 28. All patients developed an acute GVHD 5 of which resolved. Three patients died: 2 of acute GVHD and 1 of intracerebral hemorrhage. Five patients are alive in persistent complete remission without clinical symptoms and with normal peripheral blood and normal bone marrow. The median follow-up is 27 months (13-53). This small series suggests that allogeneic BMT should be investigated in selected patients as possible curative treatment of CLL.

Acute Disease↗

PubMed2006

The cytomatrix as a cooperative system of macromolecular and water networks.

Water was called by Szent-Gyorgi "life's mater and matrix, mother and medium." This chapter considers both aspects of his statement. Many astrobiologists argue that some, if not all, of Earth's water arrived during cometary bombardments. Amorphous water ices of comets possibly facilitated organization of complex organic molecules, kick-starting prebiotic evolution. In Gaian theory, Earth retains its water as a consequence of biological activity. The cell cytomatrix is a proteinaceous matrix/lattice incorporating the cytoskeleton, a pervasive, holistic superstructural network that integrates metabolic pathways. Enzymes of metabolic pathways are ordered in supramolecular clusters (metabolons) associated with cytoskeleton and/or membranes. Metabolic intermediates are microchanneled through metabolons without entering a bulk aqueous phase. Rather than being free in solution, even major signaling ions are probably clustered in association with the cytomatrix. Chloroplasts and mitochondria, like bacteria and archaea, also contain a cytoskeletal lattice, metabolons, and channel metabolites. Eukaryotic metabolism is mathematically a scale-free or small-world network. Enzyme clusters of bacterial origin are incorporated at a pathway level that is architecturally archaean. The eucaryotic cell may be a product of serial endosymbiosis, a chimera. Cell cytoplasm is approximately 80% water. Water is indisputably a conserved structural element of proteins, essential to their folding, specificity, ligand binding, and to enzyme catalysis. The vast literature of organized cell water has long argued that the cytomatrix and cell water are an entire system, a continuum, or gestalt. Alternatives are offered to mainstream explanations of cell electric potentials, ion channel, enzyme, and motor protein function, in terms of high-order cooperative systems of ions, water, and macromolecules. This chapter describes some prominent concepts of organized cell water, including vicinal water network theory, the association-induction hypothesis, wave-cluster theory, phase-gel transition theories, and theories of low- and high-density water polymorphs.

Animals↗

PubMed2000

A phylogenetic study of the Anopheles punctulatus group of malaria vectors comparing rDNA sequence alignments derived from the mitochondrial and nuclear small ribosomal subunits.

A phylogenetic study of the members of the Anopheles punctulatus group was performed using structural and similarity-based DNA sequence alignments of the small ribosomal subunit (SSU) from both the nuclear and the mitochondrial genomes. The mitochondrial SSU gene (12S, approximately 650 bp) proved to be highly restricted by its secondary structure and displayed little informative sequence variation. Consequently, it was considered unsuitable for a phylogenetic study of these closely related mosquito species. A structural alignment of the nuclear ribosomal DNA SSU (18S, approximately 2000 bp) proved to be more informative than similarity-based alignments. Analyses showed the A. punctulatus group to be monophyletic with two major clades; a Farauti clade containing members displaying an all-black-scaled proboscis (A. farauti 1-3 and 5-7) and the Punctulatus clade containing members displaying extensive white scaling on the apical half of the proboscis (A. farauti 4, A. punctulatus, and An. sp. near punctulatus). Anopheles koliensis was positioned basal to the Farauti clade.

Animals↗

PubMed2006

Tomorrow's radiologist: what future?

Today's radiology is experiencing two major trends, one negative and one positive. The first is the so-called turf war, in other words, the progressive invasion of the imaging domain by other specialists such as cardiologists, urologists, gastroenterologists, gynaecologists etc. who are taking over various techniques from ultrasonography (US) to computed tomography (CT) to magnetic resonance imaging (MRI). In this process, they are aided by new technologies such as picture archiving and communication systems (PACS) and computed-aided diagnosis CAD and by radiology technologists who collaborate with them, replacing radiologists. The positive aspect is the outstanding technological evolution: the advent of molecular imaging, optical imaging, nanotechnologies, teleradiology and percutaneous gene therapy. While dramatically expanding the diagnostic possibilities down to the subcellular level, these techniques demand new forms of training in radiology and interdisciplinary cooperation. Tomorrow's radiologist will need to acquire appropriate clinical knowledge, restore contact with the patient to take on a prominent role in the diagnostic process, learn the basic sciences, foster a multidisciplinary approach and finally be able to use the Internet for learning and continuing education. Tomorrow's radiologists will survive if they learn to reinvent themselves.

Biomedical Research↗

PubMed1999

Spectral tuning of a circadian photopigment in a subterranean 'blind' mammal (Spalax ehrenbergi).

The atrophied subcutaneous eyes of Spalax ehrenbergi (the blind mole rat) express a long wavelength sensitive (LWS) cone opsin. Our data provide strong evidence that this photopigment is spectrally tuned to enhance photon capture in the red light environment of the eye. Furthermore, novel mechanisms appear partially responsible for this sensory fine-tuning. These data support the hypothesis that the LWS opsin of Spalax acts as a functional photopigment and that it is not a 'residue' of the pre-subterranean visual system. As the eye of Spalax has only one known function, the entrainment of circadian rhythms to environmental light, the LWS photopigment is implicated in this task. These results, together with our recent findings that rod and cone photopigments are not required for murine photoentrainment, suggest that multiple photopigments (classical and novel) mediate the effects of light on the mammalian circadian system.

Amino Acid Sequence↗

PubMed1999

Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.

Sequence variation in human genes is largely confined to single-nucleotide polymorphisms (SNPs) and is valuable in tests of association with common diseases and pharmacogenetic traits. We performed a systematic and comprehensive survey of molecular variation to assess the nature, pattern and frequency of SNPs in 75 candidate human genes for blood-pressure homeostasis and hypertension. We assayed 28 Mb (190 kb in 148 alleles) of genomic sequence, comprising the 5' and 3' untranslated regions (UTRs), introns and coding sequence of these genes, for sequence differences in individuals of African and Northern European descent using high-density variant detection arrays (VDAs). We identified 874 candidate human SNPs, of which 22% were confirmed by DNA sequencing to reveal a discordancy rate of 21% for VDA detection. The SNPs detected have an average minor allele frequency of 11%, and 387 are within the coding sequence (cSNPs). Of all cSNPs, 54% lead to a predicted change in the protein sequence, implying a high level of human protein diversity. These protein-altering SNPs are 38% of the total number of such SNPs expected, are more likely to be population-specific and are rarer in the human population, directly demonstrating the effects of natural selection on human genes. Overall, the degree of nucleotide polymorphism across these human genes, and orthologous great ape sequences, is highly variable and is correlated with the effects of functional conservation on gene sequences.

3' Untranslated Regions↗

PubMed2004

Begging and sibling competition: how should offspring respond to their rivals?

Godfray's influential model of competitive begging predicted that offspring should respond to each other's behavior, displaying more intensely when competing with needier rivals. Empirical tests of this prediction have, however, yielded equivocal results. Here, I develop a series of evolutionarily stable strategy models of begging as a signal of need, which show that this prediction holds only for competitive aspects of display that influence the division of food among the brood. No such response is expected for cooperative begging (which influences the total level of provisioning by the parent), and the models even predict the opposite trend under some circumstances (where the indirect costs of extracting additional resources from the parent are high). These contrasting sets of predictions may help to explain the varying empirical results obtained by studies of sibling interaction. Cooperative (as opposed to competitive) begging is likely to be of greater significance in cases where dominant young can gain direct control of allocation (or enjoy some competitive advantage). Dominants are then predicted to parasitize the efforts of their weaker rivals and reduce their own investment in cooperative signaling while continuing to claim a disproportionately large share of the resources provided by the parent.

Animal Communication↗

PubMed2002

Eusociality in African mole-rats: new insights from patterns of genetic relatedness in the Damaraland mole-rat (Cryptomys damarensis).

After the discovery of eusociality in the naked mole-rat, it was proposed that inbreeding and high colony relatedness in this species were the major underlying factors driving cooperative breeding in African molerats. By contrast, field and laboratory studies of the eusocial Damaraland mole-rat (Cryptomys damarensis) have raised the possibility that this species is an obligate outbreeder, although the build-up of inbreeding over several generations could still occur. Using microsatellite markers, we show that most breeding pairs in wild colonies of the Damaraland mole-rat are indeed unrelated (R = 0.02 +/- 0.04) and that mean colony relatedness (R = 0.46 +/- 0.01), determined across 15 colonies from three separate populations, is little more than half that previously identified in naked mole-rats. This finding demonstrates that normal familial levels of relatedness are sufficient for the occurrence of eusociality in mammals. Variation in the mean colony relatedness among populations provides support both for the central role played by ecological constraints in cooperative breeding and for the suggestion that inbreeding in naked mole-rats is a response to extreme constraints on dispersal. Approaches that determine the relative importance of an array of extrinsic factors in driving social evolution in African mole-rats are now required.

Animals↗

PubMed2014

Molecular heterochrony and the evolution of sociality in bumblebees (Bombus terrestris).

Sibling care is a hallmark of social insects, but its evolution remains challenging to explain at the molecular level. The hypothesis that sibling care evolved from ancestral maternal care in primitively eusocial insects has been elaborated to involve heterochronic changes in gene expression. This elaboration leads to the prediction that workers in these species will show patterns of gene expression more similar to foundress queens, who express maternal care behaviour, than to established queens engaged solely in reproductive behaviour. We tested this idea in bumblebees (Bombus terrestris) using a microarray platform with approximately 4500 genes. Unlike the wasp Polistes metricus, in which support for the above prediction has been obtained, we found that patterns of brain gene expression in foundress and queen bumblebees were more similar to each other than to workers. Comparisons of differentially expressed genes derived from this study and gene lists from microarray studies in Polistes and the honeybee Apis mellifera yielded a shared set of genes involved in the regulation of related social behaviours across independent eusocial lineages. Together, these results suggest that multiple independent evolutions of eusociality in the insects might have involved different evolutionary routes, but nevertheless involved some similarities at the molecular level.

Analysis of Variance↗