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But as it does so antimicrobial wound cream for dogs safe novabritine 375mg, it generates selection pressures on unlinked genes to antibiotic resistance recombinant dna 375mg novabritine otc respond in some way oral antibiotics for acne pros and cons buy novabritine 1000mg without prescription. One response would be to virus 368 discount 375 mg novabritine with amex suppress the neocentromeres and, as we have seen, there is suggestive evidence of this in the appearance of neocentromeric activity in species hybrids. Another possible response would be to suppress the original centromere and establish the neocentromere as the normal one. If, as in maize, the neocentromere is active only in meiosis, and the original centromere is suppressed only in meiosis, the species would have functionally different centromeres at mitosis and meiosis. Something like this is seen in species with "holocentric" chromosomes, in which the centromere is diffuse and the spindle attaches along the whole length of the chromosome. Interestingly, they are only holocentric at mitosis; at meiosis, they show a standard localized centromere. Localized centromeres may be necessary at meiosis so chromosomes can recombine without ending up attached to 2 spindles and being torn apart. In some parasitic nematodes, the meiosis-specific centromeric sequences are actually lost from the somatic cells, as part of their "chromatin diminution" (described further in Chap. Some moths and bugs also have chromosomes that are holocentric in mitosis but have a localized centromere at meiosis (Holm and Rasmussen 1980, John 1990). We speculate that it was the evolution of meiosis-specific selfish centromeres that led to the evolution of distinct mitosis- and meiosis-specific centromeres, which in turn allowed the evolution of holocentric chromosomes. More generally, meiosis and mitosis may differ in how actively the chromosomes participate in the 2 processes (Dawe and Hiatt 2004). Meiotic chromosomes in maize, Drosophila, and mice have all been shown to actively initiate spindle formation, whereas mitotic chromosomes are typically inert. Selfish Centromeres and Meiosis I the neocentromeres of maize are active at the first meiotic division in a way that they show drive at the second meiotic division. Normal centromeres segregate at the first meiotic division, and so if they are to show drive, they must recognize and exploit some asymmetry at this division. We are not aware of any direct evidence of driving centromeres on normal A chromosomes, but the possibility has been raised many times, and it could help explain some otherwise-puzzling observations. The first puzzling observation is that centromeric sequences change rapidly over evolutionary time, even though the basic structure remains the same. The core of a centromere, where the kinetochore forms and the spindle microtubules attach, typically consists of at least 500kb of tandem repeats, in which the repeat unit size is remarkably constant across a wide range of species: 171bp in primates, 168 in rice, 175 in maize, 155 in a fungus gnat, 186 in a fish, and so on (reviewed in Henikoff et al. These sequences show concerted evolution, with the same sequence evolving on different chromosomes (analogous to the same repeat being found in multiple knobs on different maize chromosomes), and the same sequences are also often 312 Female Drive found on B chromosomes (see Chap. The surprising observation is that, although the unit size is conserved, the centromeric repeats are among the fastest-evolving sequences yet found in eukaryotic genomes, differing even between closely related species (Henikoff et al. Moreover, its associated histone, CenH3, is also relatively fast evolving, even though the noncentromeric histone from which it is derived, H3, is among the most conservative proteins known. In Drosophila and Arabidopsis the centromeric histone has recently been under positive selection (Malik and Henikoff 2001, Talbert et al. Why should centromeric sequences and associated proteins continually evolve while apparently not changing in function and while the spindle apparatus to which they attach hardly evolves at all (Henikoff and Malik 2002)? On the assumption that such rapid coevolution indicates an evolutionary struggle-analogous to the rapid evolution associated with parasite-host interactions or sperm-egg protein interactions-Henikoff et al. Drive is imagined to be relatively weak in each generation, and it is weakly opposed by negative side effects, including a possible reduction in male fertility (Daniel 2002). There is as yet no direct evidence for this idea-for example, we lack a demonstration that chromosomal transmission in females depends on the sequence of the centromeric repeats and how they interact with CenH3. The large number of repeats found in centromeres is circumstantial evidence that strength of binding to the spindle is selectively important, and deletion studies point in the same direction. In a Drosophila melanogaster minichromosome, the size of the centromere affects its chance of transmission, especially, as expected, in females (Murphy and Karpen 1995, Sun et al. But once portions of the key core are deleted, transmission is progressively reduced, especially in females. Similarly in maize, misdivisions of a B chromosome centromere generate a range of centromeric sizes from 200kb to 4Mb and, across this range, decreasing size is associated with lower transmission (Kaszas and Birchler 1998). The situation is made even more intriguing by observations that centromeres may be defined epigenetically, rather than by primary sequence (Amor et al. Note that while these processes of centromeric competition may be strong in outbreeding, sexual species, they are expected to be rare or absent in asexual ones.

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Human Genome Editing: Science infection epsom salt novabritine 1000 mg free shipping, Ethics treatment for dogs with food poisoning proven 375mg novabritine, and Governance Appendix E Glossary80 Adult stem cellAn undifferentiated cell found in a differentiated tissue in an adult organism that can renew itself and can differentiate to antibiotic prophylaxis joint replacement order novabritine 375mg line yield specialized cell types of the tissue in which it is found antibiotics for uti can you drink alcohol purchase 1000 mg novabritine with mastercard. Autologous transplantTransplanted tissue derived from the intended recipient of the transplant. BlastocystA preimplantation embryo in placental mammals (about 5 days after fertilization in humans) of 50-150 cells. The blastocyst consists of a sphere made up of an outer layer of cells (the trophectoderm), a fluid-filled cavity (the blastocoel or blastocyst cavity), and a cluster of cells in the interior (the inner cell mass). Cells from the inner cell mass, if grown in culture, can give rise to embryonic stem cell lines. ChimeraAn organism composed of cells derived from at least two genetically different individuals. The chromosomes usually reside in the nucleus of a cell, except during cell division when the nuclear membrane beaks down and the chromosomes become condensed and can be visualized as discrete entities. CleavageThe process of cell division in the very early embryo before it becomes a blastocyst. Clinical trialA supervised and monitored experimental test in patients of a newly developed clinical application to ensure minimization of risk and optimization of efficacy. Cultured cellA cell maintained in a tissue culture allowing expansion of its numbers. It is often linked to a transcription factor, chromatin-modifying enzyme, or fluorescent protein to mediate alterations to gene expression or to mark specific sites. Deontology ethicsA normative theory regarding which choices are morally required, forbidden, or permitted. DifferentiationThe process whereby an unspecialized early embryonic cell acquires the features of a specialized cell, such as a heart, liver, or muscle cell. Divergence (evolutionary)During evolution, variations occur in the sequences of genes; if these variations confer some advantage natural selection increases their prevalence. Different selective pressures select for different variations so that the prevalence of different gene variants diverges in different populations. DominantA pattern of inheritance of a gene or trait in which a single copy of a particular allele (gene variant) confers a function independent of the nature of the second copy of the gene in a diploid cell of an organism. EctopicFound in an unusual location, such as an ectopic pregnancy outside the uterus. EmbryoAn animal in the early stages of growth and differentiation that are characterized by cleavage (cell division of the fertilized egg), differentiation of fundamental cell types and tissues, and the formation of primitive organs and organ systems; the developing human individual from the time of implantation to the end of the eighth week after conception, after which stage it becomes known as a fetus. Embryonic stem cells can be maintained as pluripotent cells in culture and induced to differentiate into many different cell types. EndonucleaseAn enzyme that breaks down a nucleotide chain into two or more shorter chains by cleaving at internal phosphodiester bonds. EnucleationA process whereby the nuclear material of a cell is removed, leaving only the cytoplasm. When applied to an egg, can be applied to the removal of the maternal chromosomes, when they are not surrounded by a nuclear membrane. EnzymeA protein that acts as a biological catalyst, speeding up chemical reactions. EpiblastA specific layer of cells in an early vertebrate embryo that gives rise to the entire embryo other than yolk sac and placenta. Gain of function-A type of mutation that results in an altered gene product that possesses a new molecular function or a new pattern of gene expression. Gametes are haploid (having only half the number of chromosomes found in somatic cells-23 in humans), so that when two gametes unite at fertilization, the resulting one-cell embryo (zygote) has the full number of chromosomes (46 in humans). Gastrulation-The procedure by which an animal embryo at an early stage of development produces the three primary germ layers-ectoderm, mesoderm, and endoderm. Gene drive-A system of biased inheritance in which the ability of a particular genetic sequence to pass from a parent to its offspring through sexual reproduction is enhanced. Gene drive technology actively copies a sequence on one chromosome to its partner chromosome, so that the organism carries two copies of the intentionally modified gene. Thus, the result of a gene drive is the preferential increase of a specific genotype from one generation to the next, and potentially throughout a population. Alterations in gene expression change the functions of cells, tissues, organs, or whole organisms and sometimes result in observable characteristics associated with a particular gene.

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Furthermore antimicrobial 2014 order 1000mg novabritine, Agrobacterium pathogenicity and Rhizobium nodulation characters are plasmid-borne and interchangeable between individual species and between members of the two genera infection blood trusted 625 mg novabritine. This evidence militates against stable nomenclature based on pathogenic characters for the genus antibiotics eczema order novabritine 625mg free shipping, Agrobacterium antibiotic resistance biology cheap novabritine 375mg visa, or for its species. According to modern approaches to classification of the two genera, all Agrobacterium spp. Differences in pathogenicity can be accommodated by nomenclature referring to the 184 John M. In this chapter, the classification and nomenclature of Agrobacterium is chronicled in relation to the evolution of bacterial taxonomy as a discipline intended to inform natural relationships. Classification of the genus Agrobacterium and of its species has been based on its once-puzzling oncogene pathogenicity, which was the defining character of the genus (Kersters and De Ley, 1984). This was paralleled in the genus Rhizobium Frank 1889, originally reserved for bacteria with the capacity to form symbiotic nitrogen-fixing symbioses with legume species. For both genera, their distinctive generic characteristics are now known to be the result of the presence or absence of interchangeable conjugative plasmids that confer specific oncogenic or nodulating capabilities. However, a character that is the result of arbitrary acquisition or loss of a plasmid is obviously unstable and cannot form the basis of formal nomenclature. Pathogenicity was also used as the single defining character of individual Agrobacterium species (Kersters and De Ley, 1984) although, following comprehensive genetic and phenotypic studies, the genus has been revised with the recognition of natural species (Holmes and Roberts, 1981) to accord with current interpretations of bacterial taxonomy. Nomenclature Agrobacterium-Taxonomy of Plant-Pathogenic Rhizobium Species 185 reflecting species epithets based on pathogenicity alone has also continued to be strongly supported. Although the nomenclature of the genus has been in question since its inception (Pribram, 1933; Conn, 1942; Graham, 1964; Allen and Holding, 1974; Kersters and De Ley, 1984), formal nomenclatural revisions (Keane et al. The account presented here of the taxonomy of oncogenic agrobacteria details the history of their classification in relation to the evolution of bacterial systematic, and the implications that this has on their nomenclature. Full citation includes the names of authors together with the date of publication of the proposal of the taxon, although the reference is not usually recorded in literature cited. This is largely uninformative except to indicate valid publication, and it breaks the flow of text. Hereafter, this treatment reports only authorities for names in Agrobacterium and Rhizobium that are validly published (Lapage et al. Classification, the grouping of bacteria in taxa in a hierarchy based on some principle and methodology (Young et al. Refinements of classification have usually improved understanding of bacterial rela- 186 John M. Young tionships and, when expressed in formal nomenclature, names help to conceptualize those relationships. Nomenclature therefore has the capacity to illuminate classification but, if not strictly applied, can mislead. The evolution of bacterial taxonomy can be divided into three periods (Young et al. In the 19th and early 20th centuries (up to 1940), bacterial nomenclature was notable for the proliferation of species names, in a period when the principles and practices of bacterial taxonomy were relatively undeveloped and when bacteria were regularly given names that reflected particular characters regarded as important in areas of human endeavour. In the period 1940-1975, with progressive expansion of phenotypic databases (Stanier et al. Such natural classifications based on phenotypic comparisons were considered to allow predictions about the characteristics of populations; at any taxonomic level, bacteria in the same taxon were expected to have more attributes in common than with bacteria in other taxa at the same level. Such general purpose or natural classifications can be contrasted with special purpose or artificial classifications (Sneath, 2005) often framed around individual characters of significant interest in areas of human endeavour (Lelliott, 1972). Since 1975, molecular methods have been used increasingly to establish classification and to generate nomenclature (Young, 2001; Young Agrobacterium-Taxonomy of Plant-Pathogenic Rhizobium Species 187 et al. For plant pathogens, specific epithets usually referred to host species or to distinct symptoms, it being assumed that pathogenicity represented the expression of a major component of the underlying phenotype. Generic names were proposed and revised, sometimes without explanation, on the basis of limited investigations of what would now be seen as ephemeral or inadequate criteria. Subsequently, taxa established according to these criteria were often amalgamated. However, when these bacteria were investigated in more detail, the extent of their biochemical diversity became apparent, and the heterogeneity of named genera came to be recognized as concealing recognizable taxa based both on morphological and physiological characters. Young physiological reactions considered to represent fundamental metabolic processes; these are now regarded as the classic methods by which genera were differentiated. That approach allowed the redistribution of most pathogenic species according to broad similarity groups, to Corynebacterium, Erwinia, Pseudomonas, and Xanthomonas.

These may include disrupted interpersonal (particularly family) relationships infection resistant legguards order novabritine 1000 mg on line, absenteeism antibiotic 3 times a day buy 1000mg novabritine mastercard, job loss antibiotic eye drops for cats purchase 375mg novabritine fast delivery, criminal behavior antibiotics for sinus infection augmentin discount novabritine 625 mg otc, poor academic or work performance, failure to develop adaptive coping skills, and a general constriction of normal life activities. Peer relationships often focus extensively on obtaining and using illicit substances or alcohol. The risk of accidents, violence, and suicide is significantly greater for these individuals than for the general population (1449, 1450). Nicotine dependence About 33% of adults who smoke make a serious attempt to stop smoking each year (729). Among those who quit by their own efforts, 33% remain abstinent for only 2 days and 3%­5% remain abstinent for 1 year, after which little relapse occurs (746, 1451). Most smokers make several attempts to quit, and 50% of smokers eventually succeed in quitting (729). Smokers with a history of or current anxiety, depression, or schizophrenia are less likely to stop smoking (731, 760, 873, 1452). This could be due to several factors, including increased nicotine withdrawal or nicotine dependence, less social support, or fewer coping skills (760). Smokers who have current alcohol abuse or dependence are unlikely to stop smoking unless their alcohol-related problem resolves (1452). Whether alcohol or other substance abusers in recovery are less likely to stop smoking is unclear (1452). Smokers who have withdrawal-induced depression or severe craving are less likely to be successful in smoking cessation efforts (755, 760). In addition, fear of weight gain appears to be a major deterrent to cessation attempts, especially among women (771). The presence of cues for smoking is thought to be crucial in producing withdrawal; thus, withdrawal during inpatient stays on smoke-free units is often not as severe as expected (757). Other substance use disorders It is common for initial experiences with substance use to occur before puberty. At the earliest stages of use, experimenters or casual users who go on to develop a substance use disorder are generally indistinguishable from their peers with respect to the type and frequency of substance use. However, there is increasing evidence that individuals have differential vulnerability for the progression from use to abuse to addiction. This has led to a disease concept of addiction (4), including a neuronal basis for many of its clinical features (1453), the presence of genetic vulnerability (1454), and a characteristic chronic, relapsing course that resembles that of many medical disorders. However, because substance use disorders are frequently viewed as purely behavioral problems, many adolescents with these disorders are managed by their parents, school authorities, or the judicial system rather than being treated in specialized adolescent substance abuse treatment programs. The problem is further complicated by the lack of substance abuse treatment programs for adolescents, even in the private sector. In adolescents, growing preoccupation with substance use, frequent episodes of intoxication, use of substances with greater dependence liability. Although in most cases the onset of a substance use disorder occurs in the late teens and early 20s, some individuals begin abusing substances in mid- to late adulthood (948, 1455, 1456). Estimated Drug Use and Dependence Among 15- to 45-Year-Olds in the United States Estimated Cumulativea Occurrence of Extra-medical b Drug Use (%) Estimated Cumulative Occurrence of Drug Dependence (%) Estimated Proportion Becoming Dependent, Once Use Has Occurred (%) Tobacco Cocaine Heroin Alcohol Cannabis a 75. Although the use of multiple substances often continues throughout adolescence, some individuals settle on a "drug of choice" early on. A preference for a particular substance is shaped by a variety of factors, including current fashion, availability, peer influences, and individual biological and psychological factors. Although substance abuse and dependence appear to aggregate in families, which would support a genetic influence (1457), some of this effect may be explained by the concurrent familial distribution of antisocial personality disorder, which may predispose individuals to the development of these disorders. On the other hand, genetic factors do affect the risk of developing alcohol dependence, particularly in male alcohol users with male biological relatives who are also alcohol dependent (1458­1459) and, to a lesser extent, in female users with a strong family history of the disorder (1460­1462). Although there is considerable heterogeneity among patients with substance use disorders, the disease course is often chronic, lasting for years. Periods of sustained use are interrupted by periods of partial or complete remission. Although some individuals are able to achieve prolonged periods of abstinence without formal treatment, abstinence or periods of greatly reduced substance use are more likely to be sustained by patients who are able to maintain active participation in formalized treatment and/or self-help groups. During the first several years of treatment, most substance-dependent patients continue to relapse, although with decreasing frequency. Risk of relapse is higher in the first 12 months after the onset of a remission (8). Many patients experience several cycles of remission and relapse before they conclude that a return to "controlled" substance use is not possible for them.

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