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PubMed2005

An expansion of the dual clip-domain serine proteinase family in Manduca sexta: gene organization, expression, and evolution of prophenoloxidase-activating proteinase-2, hemolymph proteinase 12, and other related proteinases.

Prophenoloxidase-activating proteinases (PAPs) take part in insect defense responses including melanotic encapsulation and wound healing. To understand their gene structure and regulation, we screened a genomic library and isolated overlapping lambda clones for Manduca sexta PAP-2, hemolymph proteinase 12 (HP12), and HP24. Complete nucleotide sequence analysis indicated that all three genes encode polypeptides with two regulatory clip domains at the amino terminus, a linker region, and a catalytic serine proteinase domain at the carboxyl terminus. Each gene contains eight exons, with introns located at equivalent positions. Similar sequences are present in introns as well as exons, indicating that these genes arose from recent gene duplication and sequence divergence. We analyzed their 5' flanking sequences and identified putative immune and hormone responsive elements. Reverse transcription-polymerase chain reactions confirmed that PAP-2 and HP12 mRNA levels in the larval fat body and hemocytes increased after a bacterial challenge. However, HP24 expression was barely detected. PAP-2 transcripts in cultured fat body became less abundant after 20-hydroxyecdysone treatment. Thus, PAP-2, HP12, and HP24 mRNA levels are differentially regulated by immune and developmental signals. Comparison with HP15, HP23, and PAP-3 sequences suggested an evolutionary pathway of the dual clip-domain serine proteinases in M. sexta.

5' Flanking Region↗
PubMed2000

Long-Term Landscape Evolution of the Northparkes Region of the Lachlan Fold Belt, Australia: Constraints from Fission Track and Paleomagnetic Data.

Apatite fission track thermochronology (AFTT) and paleomagnetic (PM) results have been used to constrain the Late Paleozoic to Cenozoic landscape evolution of the Lachlan Fold Belt (LFB) around the Northparkes copper-gold deposit in east-central New South Wales. The present-day landscape of this region of the LFB is relatively flat with little expression of the underlying rock and has previously been interpreted to indicate long-term stability of the region since the end of LFB orogenesis in the Early Carboniferous. This was presumably borne out by PM analyses from thick weathered horizons within open pits at the mine, which suggested that significant periods of weathering, and hence relative landscape stability, prevailed during the Early to middle Carboniferous and at some time during the Cenozoic. Results from AFTT analyses, however, indicate that the region must have experienced significant episodes of cooling/denudation during the mid-Permian to mid-Triassic and during the early Cenozoic, as well as episodes of heating/burial during the Late Carboniferous to mid-Permian and during the late Mesozoic. When combined, the AFTT and PM results are in fact consistent and indicate that since the late Paleozoic the landscape of the LFB around the Northparkes deposit has evolved through multiple episodes of denudation and deposition as well as periods of relative stability during which the thick weathering horizons formed. Together these results establish a complementary chronological framework that constrains the Late Palaeozoic to Cenozoic landscape evolution of the Northparkes region and highlights the importance of using dual data sets in elucidating the long-term landscape evolution of similar "stable" terranes.

Journal Article↗
PubMed1999

Emergence of a dual-catalytic RNA with metal-specific cleavage and ligase activities: the spandrels of RNA evolution.

In vitro selection, or directed molecular evolution, allows the isolation and amplification of rare sequences that satisfy a functional-selection criterion. This technique can be used to isolate novel ribozymes (RNA enzymes) from large pools of random sequences. We used in vitro evolution to select a ribozyme that catalyzes a novel template-directed RNA ligation that requires surprisingly few nucleotides for catalytic activity. With the exception of two nucleotides, most of the ribozyme contributes to a template, suggesting that it is a general prebiotic ligase. More surprisingly, the catalytic core built from randomized sequences actually contains a 7-nt manganese-dependent self-cleavage motif originally discovered in the Tetrahymena group I intron. Further experiments revealed that we have selected a dual-catalytic RNA from random sequences: the RNA promotes both cleavage at one site and ligation at another site, suggesting two conformations surrounding at least one divalent metal ion-binding site. Together, these results imply that similar catalytic RNA motifs can arise under fairly simple conditions and that multiple catalytic structures, including bifunctional ligases, can evolve from very small preexisting parts. By breaking apart and joining different RNA strands, such ribozymes could have led to the production of longer and more complex RNA polymers in prebiotic evolution.

Animals↗
PubMed1995

Evolution of bone densitometry in patients with myeloma treated with conventional or intensive therapy.

BACKGROUND: Demineralization is a common hallmark of multiple myeloma (MM) that can be evaluated by dual-energy X-ray absorptiometry (DEXA). The evolution of lumbar and whole body bone density were investigated by DEXA in patients with MM treated by conventional or intensive therapy supported by autologous blood stem cell transplantation. METHODS: Sixty six patients younger than 66 years with MM were randomly assigned to either conventional (30 patients, Group A) or intensive therapy supported by autologous blood stem cell transplantation (36 patients, Group B). For all patients, lumbar bone mineral density (BMD) was measured by DEXA at diagnosis and 13.2 +/- 4.2 months after the initiation of treatment. Whole body examinations were performed in 45 patients; in addition to whole body BMD, independent BMD values were recorded for various skeletal sites. RESULTS: At diagnosis, mean lumbar Z score (lumbar mean BMD value) was low (-1.24 +/- 1.45) without any significant difference between the 2 groups. Under treatment, lumbar BMD increased 0.7% in Group A and 4.6% in Group B (P = 0.02). This difference was mainly related to nonresponders in group A who featured a lumbar BMD change of -3.9%, whereas patients in remission in both groups displayed a 4.1% increase (P < 0.001). There was a correlation between the variation of lumbar BMD and the decrease of the serum or urinary monoclonal component (r = 0.34, P = 0.006). After intensive therapy, increase of lumbar BMD was higher in men than in women (7.2% vs. 1%, P = 0.005) perhaps because of variations in hormonal status in women. Unexpectedly, whole body BMD decreased in responders (-3%) because of a decrease in appendicular BMD outweighing the increase in axial BMD. This suggests a redistribution from cortical to cancellous bone in patients with MM responsive to chemotherapy. CONCLUSION: Bone densitometry is a marker of treatment response that may be particularly useful in nonsecretory and light chain MM. Moreover, it provides new information on bone remodeling in patients treated for MM, which may have therapeutic consequences.

Absorptiometry, Photon↗
PubMed1995

Of microbes and macrophages: entry, survival and persistence.

The macrophage is capable of fulfilling the roles of both host cell and effector cell in the immune clearance of many microbial infections. This dual capacity has led to the evolution of intriguing mechanisms whereby pathogens ensure the establishment and maintenance of intracellular infections. The strategies developed range from passive avoidance mechanisms to extremely active modulation of cell function. Recent advances have been made in our appreciation of the processes of intramacrophage parasitization from initial ligand-receptor interactions, through establishment of a stable intracellular environment, to the maintenance of a persistent infection.

Animals↗
PubMed2006

Synchronous prosthetic implantation through a transscrotal incision: an outcome analysis.

PURPOSE: The ease of the transscrotal approach for penile prosthesis implantation and the proximity of the urethra has allowed the evolution of a new strategy for dual implantation of an AUS and IPP at a single setting. Concerns regarding increased infection rates and poor outcomes have prevented widespread acceptance of this simultaneous implantation technique. A multi-institutional evaluation of dual prosthesis implantation was performed to determine the overall efficacy, safety and long-term success of this innovative approach. MATERIALS AND METHODS: We performed a multi-institutional, retrospective analysis in patients with 2 urological prostheses (AUS and IPP). Only patients undergoing dual implantation via a single transscrotal technique were included for evaluation. Comorbidities, infection rates, and intraoperative and postoperative complications were recorded. RESULTS: A total of 22 men underwent AUS and IPP device implantation between 2000 and 2003 in a synchronous manner. Mean followup was 17 months. Complications were urethral erosion in 2 patients (9%) and reservoir migration in 2 (9%), of whom 1 underwent revision. Importantly no patient experienced a prosthetic infection postoperatively. The overall revision rate was 14%, due to urethral erosion of the AUS in 2 patients and reservoir migration in 1. All patients reported urinary leakage requiring 1 pad daily or less. CONCLUSIONS: Our initial intermediate followup in patients who underwent synchronous dual prosthetic implantation was favorable. The inherent advantage of a single anesthetic event and a single transscrotal incision should encourage widespread acceptance of this technique.

Aged↗
PubMed1987

Selection by differential molecular survival: a possible mechanism of early chemical evolution.

A model is proposed to account for selective chemical evolution, progressing from a relatively simple initial set of abiotic synthetic phenomena up to the elaborately sophisticated processes that are almost certainly required to produce the complex molecules, such as replicatable RNA-like oligonucleotides, needed for a Darwinian form of selection to start operating. The model makes the following assumptions: (i) that a small number of micromolecular substances were present at high concentration; (ii) that a random assembly mechanism combined these molecules into a variety of multimeric compounds comprising a wide repertoire of rudimentary catalytic activities; and (iii) that a lytic system capable of breaking down the assembled products existed. The model assumes further that catalysts supplied with substrates were significantly protected against breakdown. It is shown that, by granting these assumptions, an increasingly complex network of metabolic pathways would progressively be established. At the same time, the catalysts concerned would accumulate selectively to become choice substrates for elongation and other modifications that could enhance their efficiency, as well as their survival. Chemical evolution would thus proceed by a dual process of metabolic extension and catalytic innovation. Such a process should be largely deterministic and predictable from initial conditions.

Biochemical Phenomena↗
PubMed2004

Dynamics of the two-dimensional gonihedric spin model.

In this paper, we study dynamical aspects of the two-dimensional (2D) gonihedric spin model using both numerical and analytical methods. This spin model has vanishing microscopic surface tension and it actually describes an ensemble of loops living on a 2D surface. The self-avoidance of loops is parametrized by a parameter kappa . The kappa=0 model can be mapped to one of the six-vertex models discussed by Baxter, and it does not have critical behavior. We have found that allowing for kappa not equal 0 does not lead to critical behavior either. Finite-size effects are rather severe, and in order to understand these effects, a finite-volume calculation for non-self-avoiding loops is presented. This model, like his 3D counterpart, exhibits very slow dynamics, but a careful analysis of dynamical observables reveals nonglassy evolution (unlike its 3D counterpart). We find, also in this kappa=0 case, the law that governs the long-time, low-temperature evolution of the system, through a dual description in terms of defects. A power, rather than logarithmic, law for the approach to equilibrium has been found.

Journal Article↗
PubMed2002

The complement of protein phosphatase catalytic subunits encoded in the genome of Arabidopsis.

Reversible protein phosphorylation is critically important in the modulation of a wide variety of cellular functions. Several families of protein phosphatases remove phosphate groups placed on key cellular proteins by protein kinases. The complete genomic sequence of the model plant Arabidopsis permits a comprehensive survey of the phosphatases encoded by this organism. Several errors in the sequencing project gene models were found via analysis of predicted phosphatase coding sequences. Structural sequence probes from aligned and unaligned sequence models, and all-against-all BLAST searches, were used to identify 112 phosphatase catalytic subunit sequences, distributed among the serine (Ser)/threonine (Thr) phosphatases (STs) of the protein phosphatase P (PPP) family, STs of the protein phosphatase M (PPM) family (protein phosphatases 2C [PP2Cs] subfamily), protein tyrosine (Tyr) phosphatases (PTPs), low-M(r) protein Tyr phosphatases, and dual-specificity (Tyr and Ser/Thr) phosphatases (DSPs). The Arabidopsis genome contains an abundance of PP2Cs (69) and a dearth of PTPs (one). Eight sequences were identified as new protein phosphatase candidates: five dual-specificity phosphatases and three PP2Cs. We used phylogenetic analyses to infer clustering patterns reflecting sequence similarity and evolutionary ancestry. These clusters, particularly for the largely unexplored PP2C set, will be a rich source of material for plant biologists, allowing the systematic sampling of protein function by genetic and biochemical means.

Animals↗
PubMed2005

Allergic contact dermatitis from natural rubber latex in atopic dermatitis and the risk of later Type I allergy.

The aims of the study were to assess whether contact dermatitis in children could be due to a delayed hypersensitivity reaction to natural rubber latex (NRL) and to define risk factors for later occurrence of Type I hypersensitivity to this allergen. Among 1800 children investigated for contact dermatitis, 55 were referred on suspicion of rubber allergy and had patch tests to NRL, as well as prick tests and blood tests for specific immunoglobulin E (IgE). A 2-year follow-up was then carried out. Delayed hypersensitivity to NRL was confirmed in 32 children. Patch testing with NRL proved to be positive, and clinical improvement confirmed the diagnosis and relevance of patch tests. 30 of these 32 patients had associated atopic dermatitis (AD). Prick tests and blood tests for specific IgE to latex were negative at the time of diagnosis. A 2-year follow-up showed that 10 of 27 patients presenting initially with a positive patch test without associated Type I sensitization later developed immediate hypersensitivity. Children with AD are at high risk for allergy to NRL protein. Exclusion of this allergen should be strongly advised in atopics because of the dual risk of dermatitis and later evolution into severe Type I hypersensitivity.

Allergens↗
PubMed1987

[The Schilling test in Biermer's disease, problems of false negative reactions. Apropos of a case].

A case of pernicious anemia in a 30 years old men is described. This disease was typical for the hematologic, immunologic and medullary patterns, for his evolution, but the Schilling test, a dual tracer method, did not confirm the diagnosis. The contradictory of this result can be explained wether by the bias of the test itself, or by the intestinal malabsorption due to the vitamin B12 deficiency, or by other factors like bacterial overgrowth state (associated in the pernicious anemia) and a high level of antibodies to intrinsic factor.

Adult↗
PubMed2004

Directed evolution of protein inhibitors of DNA-nucleases by in vitro compartmentalization (IVC) and nano-droplet delivery.

In vitro compartmentalization (IVC) uses water-in-oil emulsions to create artificial cell-like compartments in which genes can be individually transcribed and translated. Here, we present a new application of IVC for the selection of DNA-nuclease inhibitors. We developed a nano-droplets delivery system that allows the transport of various solutes, including metal ions, into the emulsion droplets. This transport mechanism was used to regulate the activity of colicin nucleases that were co-compartmentalized with the genes, so that the nucleases were activated by nickel or cobalt ions only after the potential inhibitor genes have been translated. Thus, genes encoding nuclease inhibitors survived the digestion and were subsequently amplified and isolated. Selection is therefore directly for inhibition, and not for binding of the nuclease. The stringency of selection can be easily modulated to give high enrichments (100-500-fold) and recoveries. We demonstrated its utility by selecting libraries of the gene encoding the cognate inhibitor of colicin E9 (immunity protein 9, or Im9) for inhibition of another colicin (ColE7). The in vitro evolved inhibitors show significant inhibition of ColE7 both in vitro and in vivo. These Im9 variants carry mutations into residues that determine the selectivity of the natural counterpart (Im7) while completely retaining the residues that are conserved throughout the family of immunity protein inhibitors. The in vitro evolution process confirms earlier hypotheses regarding the "dual recognition" binding mechanism and the way in which new colicin-immunity pairs diverged from existing ones.

Colicins↗
PubMed2002

Cloning and genomic characterization of Felis domesticus papillomavirus type 1.

A novel papillomavirus was cloned from hyperkeratotic cutaneous lesions of a Persian domestic cat. The Felis domesticus papillomavirus (FdPV-1) genome counts 8300 bp and has a typical genome structure with an early region (E1, E2, E4, E6, E7), a late region (L1, L2), and a noncoding upstream regulatory region (URR or NCR1) between the end of L1 and the beginning of E6. The FdPV-1 also shows an unusual second noncoding region (NCR2) of 1.3 kb, situated between the end of E2 and the beginning of L2. This NCR2 is uniquely related to a similar region in the canine oral papillomavirus (COPV). Phylogenetic analysis places FdPV-1 together with COPV, the cottontail rabbit papillomavirus, human papillomavirus type 1 (HPV-1), and HPV-63 in the group of the benign cutaneous papillomaviruses. The position of FdPV-1 in the phylogenetic tree allows us to hypothesize that already in an early phase of the papillomavirus molecular evolution, a split occurred into viruses with a dual tropism primarily for cutaneous epithelia but also secondarily for mucosal surfaces, and viruses with a specific monotropism for mucosal surfaces. The close relationship between FdPV-1 and COPV, and between their Canidae and Felidae hosts, supports the hypothesis that papillomaviruses have speciated and coevolved together with their hosts throughout vertebrate evolution. A papillomavirus mutation rate of 0.73 to 0.96 x 10(-8) nucleotide substitutions per base per year was calculated.

Animals↗
PubMed2005

From target to projectile and back again: self-duality of high-energy scattering evolution in QCD.

We prove that the complete kernel for the high-energy evolution in QCD must be self-dual. The relevant duality transformation is formulated in precise mathematical terms and is shown to transform the charge density into the functional derivative with respect to the single-gluon scattering matrix. This transformation interchanges the high and the low density regimes. We demonstrate that the original Jalilian-Marian-Iancu-McLerran-Weigert-Leonidov-Kovner kernel, valid at large density, is indeed dual to the low density limit of the complete kernel derived recently in hep-ph/0501198.

Journal Article↗
PubMed1989

Responsiveness of the Epstein-Barr virus NotI repeat promoter to the Z transactivator is mediated in a cell-type-specific manner by two independent signal regions.

Cells latently infected with Epstein-Barr virus (EBV) can be activated to express lytic-cycle polypeptides by the introduction of the EBV-encoded Z transactivator, indicating that this protein has a pivotal role in virus reactivation. We examined the target specificity of the Z transactivator in short-term contransfection assays and found that the most responsive target to Z transactivation was the divergent NotI repeat promoter, located within the EBV BamHI H fragment. In contrast, target plasmids containing the cat gene linked to heterologous viral promoters were not activated by cotransfection with the Z gene. S1 nuclease analysis of RNA from chemically induced B95-8 cells and from Vero cells cotransfected with NotI repeat promoter-CAT and Z showed that Z transactivation increased the level of correctly initiated, stable RNA transcripts. The NotI repeat gene (ntr) gives rise to a highly abundant mRNA species after chemical induction of lytic virus replication, but no protein product had been previously identified. Using monospecific antiserum raised against a synthetic peptide from the BHLF1 open reading frame, we demonstrated that the ntr gene encodes a protein product that is found in nuclear patches colocalizing with nucleoli. A series of deletions introduced into the upstream sequences of the NotI-repeat-promoter revealed two separate Z-response regions. The minimal promoter region between -7 and -155 of the leftward RNA cap site and an upstream region between -644 and -902 were both independently capable of conferring Z responsiveness. However, the minimal region, which was activated by Z cotransfection in Vero cells, was poorly responsive in lymphocytes, whereas the response of the far-upstream region to Z cotransfection was lymphocyte specific. In its human host, EBV infects both epithelial and lymphocyte populations. This dual lifestyle may have led to the evolution of multiple Z-response signals that enable the Z transactivator to interact with both cell-specific promoter and enhancer factors.

Animals↗
PubMed1987

Tangent simple systems method applied to a precise study of viscoelastic behaviour of human blood.

The tangent simple systems (TSS) method, proposed in (1), is applied in order to study the viscoelastic behaviour of human blood in transient flow for a rectangular low shear rate step. The tangent simple systems which were used are Maxwell liquids. These systems allow one to obtain plots of variations of instantaneous values of viscosity coefficient mu, elasticity modulus G and retardation time tau = mu/G of the studied blood samples, as a function of flow duration. Variations of both parameters mu and G versus time are represented by two exponential functions which involve three couples of parameters (mu o, mu infinity), (Go, G infinity) and (tau mu, tau G). These parameters can be considered as the characteristics of each blood sample. Another representation of the results, called the dual rheogram, is also indicated. The dual rheogram enables one to follow the evolution of the blood structure. Several examples of application of the TSS method to normal blood sample and to suspensions of artificially modified red blood cells (RBC) are given.

Blood Viscosity↗
PubMed1983

Birds, behavior, and anatomical evolution.

Study of more than 200 species suggests that the anatomical differences among birds are as big as those among other vertebrates of comparable taxonomic rank. The result is notable because, for more than 100 years, many biologists have believed that birds are more uniform anatomically than other classes of vertebrates. Furthermore, assessment of biochemical and geological evidence suggests that the time scale for bird evolution could be quite short. Hence, birds may share with placental mammals the distinction of having had a high rate of anatomical evolution, compared to that in lower vertebrates. The rate appears to have been very high in songbirds and higher primates and extremely high in the genus Homo. In an attempt to explain such contrasts in rates of anatomical evolution, we advance the hypothesis that in higher vertebrates, behavior, rather than environmental change, is the major driving force for evolution at the organismal level. This hypothesis predicts accelerated anatomical evolution in species composed of numerous mobile individuals with the dual capacity for behavioral innovation and social propagation of new habits. Consistent with this hypothesis, we demonstrate a correlation between relative brain size and rate of anatomical evolution in land vertebrates.

Animals↗