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A review of 716 consecutive free flaps for oncologic surgical defects: refinement in donor-site selection and technique.

Free-tissue transfer has become an important method for reconstructing complex oncologic surgical defects. This study is a retrospective review of a 10-year experience with 716 consecutive free flaps in 698 patients. Regional applications included the head and neck (69 percent), trunk and breast (14 percent), lower extremity (12 percent), and upper extremity (5 percent). Donor sites included the rectus abdominis (195), fibula (193), forearm (133), latissimus dorsi (69),jejunum (55), gluteus (28), scapula (26), and seven others (17). Microvascular anastomoses were performed to large-caliber recipient vessels using a continuous suture technique; end-to-end anastomoses were preferred (75 percent). Flaps were designed to avoid the need for vein grafts. Conventional postoperative flap monitoring methods were used. These included clinical observation supplemented by Doppler ultrasonography, surface temperature probes, and pin prick testing. Buried flaps were either evaluated with Doppler ultrasonography or not monitored. The overall success rate for free-flap reconstruction of oncologic surgical defects was 98 percent. Fifty-seven flaps (8 percent) were reexplored for either anastomotic or infectious problems. Reexplored flaps were salvaged in 40 cases (70 percent). Surviving flaps resulted in a healed wound and did not delay postoperative radiation or chemotherapy. The incidence of major and minor postoperative complications was 34 percent. The mean duration of hospitalization was 20 days, and the average cost was $40,224. The results of this study support the need for only seven donor sites to solve the majority (98 percent) of oncologic problems requiring microsurgical expertise. The evolution of preferred donor sites for specific regional applications is illustrated in this 10-year experience. Technical refinements have simplified performing the microsurgical anastomoses and essentially eliminated the need for vein grafts. Conventional monitoring has led to the rapid identification of vascular compromise and subsequent flap salvage in the majority of non-buried free flaps.

Adolescent↗

The evolution of beta-adrenergic dysfunction during the induction of canine cobalt cardiomyopathy.

This study was designed to investigate the changes in the beta adrenergic system during the induction of cobalt cardiomyopathy in dogs. Cobalt sulphate, at a dose of 5 mg X kg-1 X day-1 was administered intravenously with a low protein, low thiamine diet to 13 dogs. The percentage change of the left ventricular minor axis with systole by echocardiogram (% delta D) and dP/dtmax were used to monitor left ventricular function. Noradrenaline (NA) was measured in 24 h urine samples. Left ventricular (LV) free wall biopsies were assayed for noradrenaline (LV-NA), cyclic AMP, cyclic GMP and dopamine beta hydroxylase (LV-DBH). Lymphocytes were assayed for beta-receptor density. All dogs were studied at baseline and seven were studied after a midpoint cumulative dose of 60 to 90 mg X kg-1 of cobalt; the remaining six dogs were studied when they were in heart failure and had received more than 110 mg X kg-1. During the induction of heart failure the heart rate rose from 112 +/- 6 (means +/- SE) at baseline to 154 +/- 9 at the midpoint and 153 +/- 9 (both P less than 0.05) at the final measurement while the % delta D fell from 35 +/- 2% to 31 +/- 3% and 23 +/- 2% (P less than 0.05) and dP/dt fell from 333 +/- 40 kPa X s-1 at baseline to 254 +/- 46 kPa X s-1 (P less than 0.05) and 207 +/- 33 kPa X s-1 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Photochemistry of the atmosphere of Titan: comparison between model and observations.

The photochemistry of simple molecules containing carbon, hydrogen, nitrogen, and oxygen atoms in the atmosphere of Titan has been investigated using updated chemical schemes and our own estimates of a number of key rate coefficients. Proper exospheric boundary conditions, vertical transport, and condensation processes at the tropopause have been incorporated into the model. It is argued that he composition, climatology, and evolution of Titan's atmosphere are controlled by five major processes: (a) photolysis and photosensitized dissociation of CH4; (b) conversion of H to H2 and escape of hydrogen; (c) synthesis of higher hydrocarbons; (d) coupling between nitrogen and hydrocarbons; (e) coupling between oxygen and hydrocarbons. Starting with N2, CH4, and H2O, and invoking interactions with ultraviolet sunlight, energetic electrons, and cosmic rays, the model satisfactorily accounts for the concentrations of minor species observed by the Voyager IRIS and UVS instruments. Photochemistry is responsible for converting the simpler atmospheric species into more complex organic compounds, which are subsequently condensed at the tropopause and deposited on the surface. Titan might have lost 5.6 x 10(4), 1.8 x 10(3), and 4.0 g cm-2, or the equivalent of 8, 0.25, and 5 x 10(-4) bars of CH4, N2, and CO, respectively, over geologic time. Implications of abiotic organic synthesis on Titan for the origin of life on Earth are briefly discussed.

Atmosphere↗

KSHV strains: the origins and global spread of the virus.

Nucleotide sequence analysis at five distinct loci across the 140, 000 bp genomes of more than 60 KSHV samples from KS and PEL tumors from North America, Africa, the Middle East, Asia and the Pacific revealed that they cluster into four major subtypes (A, B, C and D) that have close associations with the geographic and ethnic background of the patients. In particular, the ORF-K1 protein subtypes encoded at the extreme LHS of the genome display up to 30% amino acid variability resulting from 85% non-synonymous nucleotide substitution rates. In addition, two alternative highly diverged forms of the complex spliced ORF-K15 gene (P or M) map at the extreme RHS of the genome and are essentially unlinked to the ORF-K1 genotypes. We conclude that: (1) KSHV is an ancient human virus with several major subtypes that reflect the migrationary divergence of modern human populations over the past 35,000-60,000 years; (2) the novel immunoglobulin receptor-like signal transducing protein ORF-K1 is subject to unusually strong biological selective pressures; and (3) a minority of KSHV genomes have undergone recombination events with a related virus producing two different alleles of the ORF-K15 latency membrane protein.

Alleles↗

Genetic algorithm-based maximum-likelihood analysis for molecular phylogeny.

A heuristic approach to search for the maximum-likelihood (ML) phylogenetic tree based on a genetic algorithm (GA) has been developed. It outputs the best tree as well as multiple alternative trees that are not significantly worse than the best one on the basis of the likelihood criterion. These near-optimum trees are subjected to further statistical tests. This approach enables ones to infer phylogenetic trees of over 20 taxa taking account of the rate heterogeneity among sites on practical time scales on a PC cluster. Computer simulations were conducted to compare the efficiency of the present approach with that of several likelihood-based methods and distance-based methods, using amino acid sequence data of relatively large (5-24) taxa. The superiority of the ML method over distance-based methods increases as the condition of simulations becomes more realistic (an incorrect model is assumed or many taxa are involved). This approach was applied to the inference of the universal tree based on the concatenated amino acid sequences of vertically descendent genes that are shared among all genomes whose complete sequences have been reported. The inferred tree strongly supports that Archaea is paraphyletic and Eukarya is specifically related to Crenarchaeota. Apart from the paraphyly of Archaea and some minor disagreements, the universal tree based on these genes is largely consistent with the universal tree based on SSU rRNA.

Algorithms↗

Photosynthetic pathway alters hydraulic structure and function in woody plants.

Xylem structure and function is proposed to reflect an evolutionary balance between demands for efficient movement of water to the leaf canopy and resistance to cavitation during high xylem tension. Water use efficiency (WUE) affects this balance by altering the water cost of photosynthesis. Therefore species of greater WUE, such as C(4) plants, should have altered xylem properties. To evaluate this hypothesis, we assessed the hydraulic and anatomical properties of 19 C(3) and C(4) woody species from arid regions of the American west and central Asia. Specific conductivity of stem xylem ( K(s) ) was 16%-98% lower in the C(4) than C(3) shrubs from the American west. In the Asian species, the C(3) Nitraria schoberi had similar and Halimodendron halodendron higher K(s) values compared with three C(4) species. Leaf specific conductivity ( K(L); hydraulic conductivity per leaf area) was 60%-98% lower in the C(4) than C(3) species, demonstrating that the presence of the C(4) pathway alters the relationship between leaf area and the ability of the xylem to transport water. C(4) species produced similar or smaller vessels than the C(3) shrubs except in Calligonum, and most C(4) shrubs exhibited higher wood densities than the C(3) species. Together, smaller conduit size and higher wood density indicate that in most cases, the C(4) shrubs exploited higher WUE by altering xylem structure to enhance safety from cavitation. In a minority of cases, the C(4) shrubs maintained similar xylem properties but enhanced the canopy area per branch. By establishing a link between C(4) photosynthesis and xylem structure, this study indicates that other phenomena that affect WUE, such as atmospheric CO(2) variation, may also affect the evolution of wood structure and function.

Carbon Dioxide↗

'Glyco-deglyco' processes during the synthesis of N-glycoproteins.

For the past 15 years, it has appeared increasingly evident that the N-glycosylation process was accompanied by the release of oligomannoside type oligosaccharides. This material is constituted of oligosaccharide-phosphates and of neutral oligosaccharides possessing one GlcNAc (OS-Gn1) or two GlcNAc (OS-Gn2) at the reducing end. It has been demonstrated that oligosaccharide-phosphates originated from the cleavage by a specific pyrophosphatase, of non-glycosylated cytosolic faced oligosaccharide-PP-Dol and chiefly the Man5GlcNAc2-PP-Dol. The Man5GlcNAc2-P, as the main product, is recovered in the cytosolic compartment and is further degraded to Man5GlcNAc1 by as for yet not depicted enzymes. In contrast, OS-Gn2 produced from hydrolysis of oligosaccharide-PP-Dol (presumably as a transfer reaction onto water) when the amount of protein acceptor is limiting, are generated into the lumen of rough endoplasmic reticulum (ER). They are further submitted to processing alpha-glucosidases and rough ER mannosidase and are (mainly as Man8GlcNAc2) exported into the cytosolic compartment. This material is further degraded into a single component, the Man5GlcNAc1: Man alpha 1-2Man alpha 1-2Man alpha 1-3 (Man alpha 1-6)Man beta 1-4GlcNAc by the sequential action of a cytosolic neutral chitobiase followed by cytosolic mannosidase. Furthermore, OS-Gn1 could have a dual origin: on the one hand, they originate from OS-Gn2 by the cytosolic degradation pathway indicated above; on the other hand, we will discuss a possible origin from the degradation or remodeling of newly synthesized glycoproteins. Considered first as a minor phenomenon, these observations have lead to the concept of intracellular oligomannoside trafficking, a process which results from more fundamental phenomena such as the control of the dolichol cycle, and the so-called quality-control of glycoprotein. In this review, we would like to describe the evolution of ideas on the origin, intracellular trafficking and putative roles of these oligomannosides released during the N-glycosylation process. We propose that these early stage 'glyco-deglyco' processes represent a way of control of N-glycosylation and of the fate of N-glycoproteins.

Animals↗

The nature of human altruism.

Some of the most fundamental questions concerning our evolutionary origins, our social relations, and the organization of society are centred around issues of altruism and selfishness. Experimental evidence indicates that human altruism is a powerful force and is unique in the animal world. However, there is much individual heterogeneity and the interaction between altruists and selfish individuals is vital to human cooperation. Depending on the environment, a minority of altruists can force a majority of selfish individuals to cooperate or, conversely, a few egoists can induce a large number of altruists to defect. Current gene-based evolutionary theories cannot explain important patterns of human altruism, pointing towards the importance of both theories of cultural evolution as well as gene-culture co-evolution.

Altruism↗

p1B15: a cDNA clone of the rat mRNA encoding cyclophilin.

We present the complete nucleotide sequence of a cDNA encoding rat cyclophilin. The 743-nucleotide sequence contains a 42-nucleotide 5' noncoding region, a 492 nucleotide open reading frame corresponding to a translation product of 164 amino acids with a molecular weight of 17,874, and a 3' noncoding region of 209 nucleotides. Primer extension studies reveal the presence of one minor and two major transcription start sites. Southern blot analyses are consistent with as many as 20 copies of the cyclophilin gene and possible pseudogenes. Cyclophilin mRNA is expressed in virtually all types of tissues of rat and monkey and appears to have been highly conserved during mammalian evolution.

Amino Acid Sequence↗

On the number of ancestors to a DNA sequence.

If homologous sequences in a population are not subject to recombination, they can all be traced back to one ancestral sequence. However, the rest of our genome is subject to recombination and will be spread out on a series of individuals. The distribution of ancestral material to an extant chromosome is here investigated by the coalescent with recombination, and the results are discussed relative to humans. In an ancestral population of actual size 1.3 million a minority of <6.4% will carry material ancestral to any present human. The estimated actual population size can be even higher, 5 million, reducing the percentage to 1.7%.

DNA↗

Establishing LA VIDA: a community-based partnership to prevent intimate violence against Latina women.

LA VIDA--the Southwest Detroit Partnership to Prevent Intimate Violence Against Latina Women--evolved in response to community concern about the problem of intimate partner violence (IPV) and the lack of culturally competent preventive and support services for Latino women and men in southwest Detroit. Since 1997, diverse organizations have mobilized as a community-academic partnership to ensure the availability, accessibility, and utilization of IPV services. This article describes and analyzes the evolution of LA VIDA within a community-based participatory research framework using a case study approach that draws on multiple data sources including group and individual interviews and field notes. The challenges and lessons learned in addressing a complex multifaceted problem such as IPV in an ethnic minority community are highlighted in an examination of the process of mobilizing diverse organizations, conducting community diagnosis and needs assessment activities, establishing goals and objectives within a social ecological framework, and integrating evaluation during the development phase.

Community Health Centers↗

["Glyco-deglyco" processes during the biosynthesis of glycoproteins].

For the past fifteen years, it has appeared increasingly evident that the N-glycosylation process was accompanied by the release of oligomannoside type oligosaccharides. This material is constituted of oligosaccharide-phosphates and of neutral oligosaccharides possessing one GlcNAc (OS-Gn1) or two GlcNAc (OS-Gn2) at the reducing end. It has been demonstrated that oligosaccharide-phosphates originated from the cleavage, by a specific pyrophosphatase, of non-glucosylated cytosolic faced oligosaccharide-PP-Dol and chiefly the Man5GlcNAc2-PP-Dol. The Man5GlcNAc2-P, as the main product, is recovered in the cytosolic compartment and is further degraded to Man5GlcNAc1 by not-yet depicted enzymes. In contrast, OS-Gn2 produced from hydrolysis of oligosaccharide-PP-Dol (presumably as a transfer reaction onto water) when the amount of protein acceptor is limiting, are generated into the lumen of rough endoplasmic reticulum (rough ER). They are further submitted to processing a-glucosidases and rough ER mannosidase and are (mainly as Man8GlcNAc2) exported into the cytosolic compartment. This material is further degraded into a single component, the Man5GlcNAc1, by the sequential action of a cytosolic neutral chitobiase followed by cytosolic mannosidase(s). Furthermore, OS-Gn1 could have a dual origin: in one hand, they originate from OS-Gn2 by the cytosolic degradation pathway indicated above, on the other hand, we will discuss a possible origin from the degradation or remodelling of newly synthesized glycoproteins. Considered first as a minor phenomenon, these observations have lead to the concept of intracellular oligomannoside trafficking, a process which results from more fundamental phenomena such as the control of the dolichol cycle, and the so-called quality-control of glycoprotein. In this review, we would like to describe the evolution of ideas on the origin, intracellular trafficking and putative roles of these oligomannosides released during during the N-glycosylation process. We propose that these early stage "glyco-deglyco" processes represent a way of control of N-glycosylation and of the fate of N-glycoproteins. This review is dedicated to Pr Paul Boulanger who has spent a large part of his career to determine the structure of proteins in order to understand their functions. If it is well established that many biological functions are born by proteins, it appears more and more evident that co- or post translational modifications are of importance in the modulation of these functions. Among them, the glycosylation appears as a major event which intervene in the 3D structure of the protein, which control his biological time-life and which may act in many recognition processes.

Animals↗

Natural history of hips with borderline acetabular index and acetabular dysplasia in infants.

Management of clinically stable hips with an increased age-related acetabular index (AI) remains controversial. The authors' purpose was to document the natural history of such hips. Sixty-eight clinically stable hips with an increased age-related AI were followed up for a mean of 9.5 years. Four patterns of evolution were observed: type 1 (25 hips) had rapid progression to normal range in the first 2 years; type 2 (19 hips) had slow improvement, with AI values reaching the normal range between 4 and 11 years; type 3 (20 hips) had improved hip morphology with persistence of minor deviations from the normal values; and type 4 (4 hips) showed no improvement. Initially, none of the hips with type 1, 2, or 3 pattern showed radiologic signs of displacement; in contrast, all our type 4 hips were radiologically eccentered. Clinically stable and radiologically well-centered hips with an increased age-related AI improved spontaneously without treatment. For these cases, clinical and radiologic follow-up is all that is needed.

Acetabulum↗

Population genetic and phylogenetic evidence for positive selection on regulatory mutations at the factor VII locus in humans.

The abundance of cis-regulatory polymorphisms in humans suggests that many may have been important in human evolution, but evidence for their role is relatively rare. Four common polymorphisms in the 5' promoter region of factor VII (F7), a coagulation factor, have been shown to affect its transcription and protein abundance both in vitro and in vivo. Three of these polymorphisms have low-frequency alleles that decrease expression of F7 and may provide protection against myocardial infarction (heart attacks). The fourth polymorphism has a minor allele that increases the level of transcription. To look for evidence of natural selection on the cis-regulatory variants flanking F7, we genotyped three of the polymorphisms in six Old World populations for which we also have data from a group of putatively neutral SNPs. Our population genetic analysis shows evidence for selection within humans; surprisingly, the strongest evidence is due to a large increase in frequency of the high-expression variant in Singaporean Chinese. Further characterization of a Japanese population shows that at least part of the increase in frequency of the high-expression allele is found in other East Asian populations. In addition, to examine interspecific patterns of selection we sequenced the homologous 5' noncoding region in chimpanzees, bonobos, a gorilla, an orangutan, and a baboon. Analysis of these data reveals an excess of fixed differences within transcription factor binding sites along the human lineage. Our results thus further support the hypothesis that regulatory mutations have been important in human evolution.

Animals↗

Genetic variability and evolution of the Schistosoma genome analysed by using random amplified polymorphic DNA markers.

The usefulness of random amplified polymorphic DNA markers (RAPD) was assayed in an attempt to discriminate among species, strains and individuals within the genus Schistosoma. Depending on the species, 40-50 arbitrary decamer oligonucleotides were used as primers to amplify total DNA by the polymerase chain reaction (PCR). An important polymorphism was observed among 5 species, allowing a phylogenetic tree to be outlined. These differences can be used for rapid and accurate identification. A limited but easily detectable polymorphism was revealed among 3 strains of a single species (Schistosoma mansoni). Minor differences were observed among individuals of a single strain. A RAPD marker allows sexual discrimination between individuals from the terminal spined-egg species group. Although a limited number of strains have been examined, the results already indicate clearly that RAPD markers constitute a powerful tool for the analysis of genetic variability. This new tool will considerably extend the information available from morphology, isozyme and limited restriction fragment length polymorphism data and opens the way to genetic analysis of these species.

Animals↗

An asymmetric underlying rule in the assignment of codons: possible clue to a quick early evolution of the genetic code via successive binary choices.

Aminoacyl-tRNA synthetases (aaRSs) are responsible for creating the pool of correctly charged aminoacyl-tRNAs that are necessary for the translation of genetic information (mRNA) by the ribosome. Each aaRS belongs to either one of only two classes with two different mechanisms of aminoacylation, making use of either the 2'OH (Class I) or the 3'OH (Class II) of the terminal A76 of the tRNA and approaching the tRNA either from the minor groove (2'OH) or the major groove (3'OH). Here, an asymmetric pattern typical of differentiation is uncovered in the partition of the codon repertoire, as defined by the mechanism of aminoacylation of each corresponding tRNA. This pattern can be reproduced in a unique cascade of successive binary decisions that progressively reduces codon ambiguity. The deduced order of differentiation is manifestly driven by the reduction of translation errors. A simple rule can be defined, decoding each codon sequence in its binary class, thereby providing both the code and the key to decode it. Assuming that the partition into two mechanisms of tRNA aminoacylation is a relic that dates back to the invention of the genetic code in the RNA World, a model for the assignment of amino acids in the codon table can be derived. The model implies that the stop codon was always there, as the codon whose tRNA cannot be charged with any amino acid, and makes the prediction of an ultimate differentiation step, which is found to correspond to the codon assignment of the 22nd amino acid pyrrolysine in archaebacteria.

Amino Acyl-tRNA Synthetases↗

Developmental aspects of pediatric fMRI: considerations for image acquisition, analysis, and interpretation.

Functional MRI provides a powerful means to identify and trace the evolution, development, and consolidation of cognitive neural networks through normal childhood. Neural network perturbations due to disease and other adverse factors during development can also be explored. Studies performed to date suggest that normal children older than 5 years show activation maps comparable to adults for similar cognitive paradigms. Minor differences in adult and pediatric activation maps may reflect age dependent strategies or maturation of cognitive networks. However, there are important physiologic and anatomic differences in children, varying with age, that may affect the acquisition, analysis, and interpretation of pediatric fMRI data. Differences between children and adult fMRI comparison studies may reflect technical aspects of data acquisition as much as developmental and brain maturation factors.

Aging↗

Evolutionary change in 5S rRNA secondary structure and a phylogenic tree of 352 5S rRNA species.

The secondary structure models of 5S rRNA have been constructed from the primary structure of 352 5S rRNA species available at present. All the 5S rRNAs examined can take essentially the same secondary structure, however they reveal characteristic differences between eukaryotes, metabacteria (= archaebacteria) and eubacteria. These three types of models can be further subgrouped by minor but characteristic differences. A phylogenic tree of organisms has been constructed using these 5S rRNA sequences by the weighted pairing method (WPG method). The tree reveals that there exist several major groups of eubacteria which seem to have diverged into different directions in the early stages of bacterial evolution. After emergence of eubacteria, metabacteria and eukaryotes separated from each other from their common ancestor. In the eukaryotic evolution, red algae (Rhodophyta) emerged first, and thereafter, thraustocytrids-Proctista, Ascomycota, green plants (green algae and land plants), Basidiomycota, Chromophyta (brown algae, diatoms and golden-yellow algae), slime- and water molds, various protozoans, and animals emerged in this order.

Animals↗