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PubMed1978

Lung function in alpha-1-antitrypsin deficient sisters.

Two sisters were found to homozygous for alpha-1-antitrypsin deficiency. One was disabled by breathlessness and had advanced clinical and radiological emphysema which was confirmed on lung function testing. The other, of similar age and smoking history, was symptom-free with a normal chest radiograph. She had a slightly increased airways resistance, a reduced gas transfer, a bilaterally reduced apex--base perfusion gradient and a small but generalized increase in physiological dead space in all zones. The minor pulmonary and vascular abnormalities present in the younger sibling suggest that we are witnessing early changes in the evolution of the panacinar emphysema characteristic of alpha-1-antitrypsin deficiency. The reason for the different rates of progress of the disease in these two sisters is not understood.

Adult↗
PubMed1981

Complete amino acid sequences of bovine thymopoietins I, II, and III: closely homologous polypeptides.

Complete amino acid sequences were determined for thymopoietins I and II (revision), isolated from bovine thymus, and for thymopoietin III, a newly identified polypeptide isolated from bovine spleen. Thymopoietin III (TP-III) is a 49 amino acid monomeric peptide that shows minor microheterogeneity at residue 34. The three thymopoietins have largely identical sequences yet some distinct differences, suggesting very recent evolution from a common gene. The complete amino acid sequences are (Formula: see text).

Amino Acid Sequence↗
PubMed1994

Luteal versus placental progesterone: the situation in the cow, pig and bitch.

Placenta and corpus luteum (CL) have acquired different functions for progesterone synthesis and maintenance of pregnancy in the course of placentalia evolution. In the cow and pig, progesterone is produced by the same CL during the entire gestation period with minor or no contribution from the placenta. In the case of an infertile cycle, CL survival is terminated by PGF2 alpha produced by the endometrium. PGF2 alpha secretion is inhibited by the trophoblast in order to guarantee continuous progesterone production. Also in the dog, only the CL synthesizes progesterone and the secretion pattern is similar in pseudopregnant and pregnant animals. The dog CL seems to have an internally programmed life span.

Animals↗
PubMed2005

A vital role of tubulin-tyrosine-ligase for neuronal organization.

Tubulin is subject to a special cycle of detyrosination/tyrosination in which the C-terminal tyrosine of alpha-tubulin is cyclically removed by a carboxypeptidase and readded by a tubulin-tyrosine-ligase (TTL). This tyrosination cycle is conserved in evolution, yet its physiological importance is unknown. Here, we find that TTL suppression in mice causes perinatal death. A minor pool of tyrosinated (Tyr-)tubulin persists in TTL null tissues, being present mainly in dividing TTL null cells where it originates from tubulin synthesis, but it is lacking in postmitotic TTL null cells such as neurons, which is apparently deleterious because early death in TTL null mice is, at least in part, accounted for by a disorganization of neuronal networks, including a disruption of the cortico-thalamic loop. Correlatively, cultured TTL null neurons display morphogenetic anomalies including an accelerated and erratic time course of neurite outgrowth and a premature axonal differentiation. These anomalies may involve a mislocalization of CLIP170, which we find lacking in neurite extensions and growth cones of TTL null neurons. Our results demonstrate a vital role of TTL for neuronal organization and suggest a requirement of Tyr-tubulin for proper control of neurite extensions.

Animals↗
PubMed2006

Structural and mutational analysis of human Ad37 and canine adenovirus 2 fiber heads in complex with the D1 domain of coxsackie and adenovirus receptor.

Adenovirus fibers from most serotypes bind the D1 domain of coxsackie and adenovirus receptor (CAR), although the binding residues are not strictly conserved. To understand this further, we determined the crystal structures of canine adenovirus serotype 2 (CAV-2) and the human adenovirus serotype 37 (HAd37) in complex with human CAR D1 at 2.3 and 1.5A resolution, respectively. Structure comparison with the HAd12 fiber head-CAR D1 complex showed that the overall topology of the interaction is conserved but that the interfaces differ in number and identity of interacting residues, shape complementarity, and degree of conformational adaptation. Using surface plasmon resonance, we characterized the binding affinity to CAR D1 of wild type and mutant CAV-2 and HAd37 fiber heads. We found that CAV-2 has the highest affinity but fewest direct interactions, with the reverse being true for HAd37. Moreover, we found that conserved interactions can have a minor contribution, whereas serotype-specific interactions can be essential. These results are discussed in the light of virus evolution and design of adenovirus vectors for gene transfer.

Adenoviridae↗
PubMed1997

Anti-pancreatic autoimmunity and Graves' disease: study of a cohort of 600 Caucasian patients.

The aim of this study was to investigate the frequencies of clinical diabetes and humoral markers of anti-pancreatic autoimmunity in a homogeneous population of 600 Caucasian patients with recently diagnosed Graves' disease (GD), in order to characterize the specific features of this group of endocrine patients among subjects at risk of diabetes. Ten were already diabetic at GD diagnosis. Among the 590 non-diabetic patients, 29 had islet cell antibodies (ICA), including 15 with low titre ICA and only 1 ICA-positive subject with a familial history of diabetes. Twenty-four patients had insulin autoantibodies, including three in association with ICA. Glutamic acid decarboxylase (GAD)/64 kDa antibodies were found in 16 of the 150 tested sera, including 13 of the 29 ICA-positive sera. Four ICA-positive patients displayed 37/40 kDa antibodies, including three in association with GAD/64 kDa antibodies. During follow-up, one of the ICA-positive patients developed insulin-dependent diabetes, 14 years after the GD diagnosis. To summarize, this anti-pancreatic autoimmunity study was focused on a large but specific and homogeneous group of subjects at risk for diabetes: recently diagnosed GD patients. This population was characterized by a high prevalence of GAD/64 kDa antibodies but also by a low frequency of evolution towards diabetes and the slowness of the process which could be due to the fact that only a minority of subjects possessed a sufficient combination of anti-pancreatic markers at the same time.

Adult↗
PubMed1989

The effect of short-wavelength ultraviolet light on antigens, lectin receptors and the ultrastructure of Crithidia fasciculata.

Crithidia fasciculata is an important trypanosomatid parasite commonly affecting insects and is used extensively as a model for the study of the biochemistry, ultrastructure and organization of the kDNA network of trypanosomatids. The present study describes the evolution of UV-induced morphological changes detectable by transmission electron microscopy in Crithidia fasciculata. Although only rare and minor changes in kinetoplast DNA were demonstrable 7 h after UV irradiation, alterations of this organelle were present in almost all flagellates observed 24 h and 48 h after irradiation. Other cell structures were apparently undamaged. Ultrastructural changes in kDNA did not correspond to changes in antigenicity of protein bands in western blotting against serum from Chagas' disease patients or in the presence of 3 different lectin receptors on the surface of the parasite.

Animals↗
PubMed1979

[Postoperative choroidal detachment and chorioretinal surgery].

Clinical study of postoperative choroidal detachment in about 60 patients. The following parameters have been analyzed: frequency, age of the patient, type of detachment, evolution and surgical technique. The prognosis has been discussed. The question is to know whether choroidal detachment is a minor accident or a major complication. The authors try to give an answer, keeping in mind the different parameters analyzed. A research on therapeutic possibilities has been carried out.

Adult↗
PubMed2006

Experimental rugged fitness landscape in protein sequence space.

The fitness landscape in sequence space determines the process of biomolecular evolution. To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12-130 of the initial random polypeptide and selection for infectivity, the selected phage showed a 1.7x10(4)-fold increase in infectivity, defined as the number of infected cells per ml of phage suspension. Fitness was defined as the logarithm of infectivity, and we analyzed (1) the dependence of stationary fitness on library size, which increased gradually, and (2) the time course of changes in fitness in transitional phases, based on an original theory regarding the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the landscape model, single mutations at single sites among n sites affect the contribution of k other sites to fitness. Based on the results of these analyses, k was estimated to be 18-24. According to the estimated parameters, the landscape was plotted as a smooth surface up to a relative fitness of 0.4 of the global peak, whereas the landscape had a highly rugged surface with many local peaks above this relative fitness value. Based on the landscapes of these two different surfaces, it appears possible for adaptive walks with only random substitutions to climb with relative ease up to the middle region of the fitness landscape from any primordial or random sequence, whereas an enormous range of sequence diversity is required to climb further up the rugged surface above the middle region.

Amino Acid Sequence↗
PubMed1993

The vertebrate genome: isochores and evolution.

Vertebrate genomes are mosaics of isochores--namely, of long (> 300 kb), compositionally homogeneous DNA segments that can be subdivided into a small number of families characterized by different GC levels. In the human genome (which is representative of a number of mammalian genomes, and, more broadly, of the genomes of warm-blooded vertebrates), the compositional range of isochores is 30%-60% GC, and five families of isochores have been identified: two GC-poor families, L1 and L2, together representing 62% of the genome, and three GC-rich families, H1, H2, and H3, representing 22%, 9%, and 3%, respectively (the remaining 4% of the genome is formed by satellite and ribosomal DNA). Gene concentration is strikingly nonuniform, being highest in the H3 isochore family, lowest in the L1 + L2 families, and intermediate in the H1 + H2 families. The H3 family corresponds to T(elomeric) bands of metaphase chromosomes, and the L1 + L2 families correspond to G(iemsa) bands, whereas R(everse) bands comprise both GC-poor and GC-rich isochores. The compositional distributions of large genome fragments, of exons (and their codon positions), and of introns are correlated with each other. They represent compositional patterns and are very different between the genomes of cold- and warm-blooded vertebrates, mainly in that the former are much less heterogeneous in base composition and never reach the highest GC levels attained by the latter. Only relatively small compositional differences are found among the genomes of either cold- or warm-blooded vertebrates. Compositional patterns allow one to define two modes in genome evolution: a conservative mode, with no compositional change, and a transitional (or shifting) mode, with compositional changes. The conservative mode can be observed among either cold- or warm-blooded vertebrates. The transitional mode comprises both major and minor compositional changes. In vertebrate genomes, the major changes are associated with the appearance of GC-rich and very GC-rich isochores in mammalian and avian genomes. Mutational biases play a role in both modes of compositional evolution. According to one viewpoint, the fixation of compositionally biased mutations is responsible for the transitional mode of evolution of bacterial genomes; in the conservative mode of evolution of vertebrates, they accomplish their role in conjunction with differences either in chromatin structures that modulate replication errors or in chromatin transcriptional activities that may lead to various extents of repair-DNA synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

Comparative analysis of the Saccharomyces cerevisiae and Caenorhabditis elegans protein interaction networks.

BACKGROUND: Protein interaction networks aim to summarize the complex interplay of proteins in an organism. Early studies suggested that the position of a protein in the network determines its evolutionary rate but there has been considerable disagreement as to what extent other factors, such as protein abundance, modify this reported dependence. RESULTS: We compare the genomes of Saccharomyces cerevisiae and Caenorhabditis elegans with those of closely related species to elucidate the recent evolutionary history of their respective protein interaction networks. Interaction and expression data are studied in the light of a detailed phylogenetic analysis. The underlying network structure is incorporated explicitly into the statistical analysis. The increased phylogenetic resolution, paired with high-quality interaction data, allows us to resolve the way in which protein interaction network structure and abundance of proteins affect the evolutionary rate. We find that expression levels are better predictors of the evolutionary rate than a protein's connectivity. Detailed analysis of the two organisms also shows that the evolutionary rates of interacting proteins are not sufficiently similar to be mutually predictive. CONCLUSION: It appears that meaningful inferences about the evolution of protein interaction networks require comparative analysis of reasonably closely related species. The signature of protein evolution is shaped by a protein's abundance in the organism and its function and the biological process it is involved in. Its position in the interaction networks and its connectivity may modulate this but they appear to have only minor influence on a protein's evolutionary rate.

Animals↗
PubMed2002

Virulence and pathogenesis.

Why do viruses cause disease? As intracellular parasites they grow at the expense of the host, yet many infections are non-virulent. We tend to focus on unusual outcomes of infection that are important to the individual but trivial for host-parasite evolution, for example, paralytic polio or viral cancer. The assumption that the features of disease help onward transmission of the virus is true for, say, rabies, but not for AIDS or neurodegenerative diseases. Moreover, minor host differences can result in major changes in pathogen virulence. Although viral burden relates to disease severity, pathogenesis is not necessarily coupled with transmission dynamics.

Animals↗
PubMed1990

DNA methylation. The effect of minor bases on DNA-protein interactions.

DNA methylation is found almost ubiquitously in nature and the methyltransferases show evidence of a common evolutionary origin. It will be a fascinating study in protein evolution to follow the ways in which the structures of the various enzymes have developed. Although methylation may have a direct effect on DNA structure the evidence for the importance of this in vivo is accumulating only slowly. In contrast, there is now abundant evidence that methylation of DNA affects DNA-protein interactions and so may have a function in all processes in which such interactions occur. The binding of nucleases is affected in the processes of mismatch repair, DNA restriction and possibly demethylation during differentiation in vertebrates. The binding of transcription factors is affected by DNA methylation and the association of DNA with packaging and segregation proteins may play a part in the control of transcription and replication. The interplay of these effects makes DNA methylation a complex but rewarding area for study. Perhaps we should no longer refer to methylcytosine and methyladenine as minor bases, but rather as key bases which help regulate the functions of DNA.

DNA↗
PubMed1998

Cratering rates on the Galilean satellites.

We exploit recent theoretical advances toward the origin and orbital evolution of comets and asteroids to obtain revised estimates for cratering rates in the jovian system. We find that most, probably more than 90%, of the craters on the Galilean satellites are caused by the impact of Jupiter-family comets (JFCs). These are comets with short periods, in generally low-inclination orbits, whose dynamics are dominated by Jupiter. Nearly isotropic comets (long period and Halley-type) contribute at the 1-10% level. Trojan asteroids might also be important at the 1-10% level; if they are important, they would be especially important for smaller craters. Main belt asteroids are currently unimportant, as each 20-km crater made on Ganymede implies the disruption of a 200-km diameter parental asteroid, a destruction rate far beyond the resources of today's asteroid belt. Twenty-kilometer diameter craters are made by kilometer-size impactors; such events occur on a Galilean satellite about once in a million years. The paucity of 20-km craters on Europa indicates that its surface is of order 10 Ma. Lightly cratered surfaces on Ganymede are nominally of order 0.5-1.0 Ga. The uncertainty in these estimates is about a factor of five. Callisto is old, probably more than 4 Ga. It is too heavily cratered to be accounted for by the current flux of JFCs. The lack of pronounced apex-antapex asymmetries on Ganymede may be compatible with crater equilibrium, but it is more easily understood as evidence for nonsynchronous rotation of an icy carapace.

Astronomical Phenomena↗
PubMed2000

Unusual Interfacial Phase Behavior of Two Nonmiscible Liquids in a Cylindrical Test Tube: Equilibrium Shapes and Stability of Axisymmetric Liquid Bridges under Gravity.

In this paper the unusual interfacial phase behavior of two nonmiscible fluids contained in a cylindrical glass test tube is reported. Water, which is the lighter phase, takes up the upper part of the tube, whereas the denser compound (a hydrofluorocarbon) is in the bottom. However, below some critical volume of water, the denser phase emerges at the air surface, by forming an axisymmetric liquid bridge through the aqueous phase. Above the critical condition, the formation of the bridge, the evolution of the shape of this bridge, and its final breakdown can be visually inspected after shaking the tube. The minority liquid (water) is dispersed in the majority phase (HCFC) as an unstable dispersion of droplets. Droplets rise to the air surface under the action of the buoyant force, and coalesce on the glass wall: this leads to the formation of a bridge (made from the dispersion in the middle of a hollow axisymmetric water drop), whose height increases and thickness decreases during the coalescence process, until it breaks down. Using a free energy analysis, we state the exact variational problem via its Euler-Lagrange equation. However, since this nonlinear differential equation cannot be solved analytically, a simplified "mean-field" approach is developed, which provides a comprehensive insight into the physical origin of these capillary bridges and their stability under gravity. Copyright 2000 Academic Press.

Journal Article↗
PubMed2002

Bacillus anthracis evolution and epidemiology.

Bacillus anthracis is a pathogen that is widely distributed around the globe. However, this great distribution is not accompanied by great genetic diversity. Although subtle morphological and biochemical differences exist, the underlying genetic basis for this plasticity is not known. Indeed, very few single nucleotide differences have been detected among isolates and the only documented high variable sequences are associated with variable number tandem repeated (VNTR) sequences. The differences among the VNTRs has been used to suggest phylogenetic relationships among the worldwide isolates. There is one major clonal split in B. anthracis (A and B), with two minor clusters established within the B branch and four or more minor branches within the A group. The A branch is the most common worldwide, though the B branch is locally important in certain areas. The ecology and the evolution of B. anthracis have been greatly influenced by the spore phase of the lifecycle.

Animals↗
PubMed1994

Impact winter and the Cretaceous/Tertiary extinctions: results of a Chicxulub asteroid impact model.

The Chicxulub impact crater in Mexico is the site of the impact purported to have caused mass extinctions at the Cretaceous/Tertiary (K/T) boundary. 2-D hydrocode modeling of the impact, coupled with studies of the impact site geology, indicate that between 0.4 and 7.0 x 10(17) g of sulfur were vaporized by the impact into anhydrite target rocks. A small portion of the sulfur was released as SO3 or SO4, which converted rapidly into H2SO4 aerosol and fell as acid rain. A radiative transfer model, coupled with a model of coagulation indicates that the aerosol prolonged the initial blackout period caused by impact dust only if the aerosol contained impurities. A larger portion of sulfur was released as SO2, which converted to aerosol slowly, due to the rate-limiting oxidation of SO2. Our radiative transfer calculations, combined with rates of acid production, coagulation, and diffusion indicate that solar transmission was reduced to 10-20% of normal for a period of 8-13 yr. This reduction produced a climate forcing (cooling) of -300 Wm-2, which far exceeded the +8 Wm-2 greenhouse warming, caused by the CO2 released through the vaporization of carbonates, and therefore produced a decade of freezing and near-freezing temperatures. Several decades of moderate warming followed the decade of severe cooling due to the long residence time of CO2. The prolonged impact winter may have been a major cause of the K/T extinctions.

Aerosols↗
PubMedDate not supplied

Inquiring into indicators and origin of catastrophic events at stratigraphic boundaries.

Since 1982, numerous indicators of catastrophic events have been observed at the main stratigraphic boundaries in China during the Phanerozoic, i.e. Precambrian-Cambrian, Permian-Triassic, Cretaceous-Tertiary as well as Ordovician-Silurian and Devonian-Carboniferous boundaries. These markers are boundary clay layer, microspherules, high Ir anomaly, mass extinction of organisms and impact of meteorite. We support the hypothesis of the extraterrestrial origin of catastrophic events and suggest that the events at different stratigraphic boundaries might be different in features and processes.

Aluminum Silicates↗