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The complete mitochondrial sequence of Tarsius bancanus: evidence for an extensive nucleotide compositional plasticity of primate mitochondrial DNA.

Inconsistencies between phylogenetic interpretations obtained from independent sources of molecular data occasionally hamper the recovery of the true evolutionary history of certain taxa. One prominent example concerns the primate infraordinal relationships. Phylogenetic analyses based on nuclear DNA sequences traditionally represent Tarsius as a sister group to anthropoids. In contrast, mitochondrial DNA (mtDNA) data only marginally support this affiliation or even exclude Tarsius from primates. Two possible scenarios might cause this conflict: a period of adaptive molecular evolution or a shift in the nucleotide composition of higher primate mtDNAs through directional mutation pressure. To test these options, the entire mt genome of Tarsius bancanus was sequenced and compared with mtDNA of representatives of all major primate groups and mammals. Phylogenetic reconstructions at both the amino acid (AA) and DNA level of the protein-coding genes led to faulty tree topologies depending on the algorithms used for reconstruction. We propose that these artifactual affiliations rather reflect the nucleotide compositional similarity than phylogenetic relatedness and favor the directional mutation pressure hypothesis because: (1) the overall nucleotide composition changes dramatically on the lineage leading to higher primates at both silent and nonsilent sites, and (2) a highly significant correlation exists between codon usage and the nucleotide composition at the third, silent codon position. Comparisons of mt genes with mt pseudogenes that presumably transferred to the nucleus before the directional mutation pressure took place indicate that the ancestral DNA composition is retained in the relatively fossilized mtDNA-like sequences, and that the directed acceleration of the substitution rate in higher primates is restricted to mtDNA.

Animals↗

Development and validation of a scale to measure work-related fatigue and recovery: the Occupational Fatigue Exhaustion/Recovery Scale (OFER).

OBJECTIVE: Various empirical studies link persistent failure to recover from acute fatigue to the evolution of chronic fatigue. However, existing fatigue measurement scales do not tend to distinguish between acute and chronic fatigue elements well, and none include a measure of effective recovery from fatigue. METHODS: The 15 item Occupational Fatigue Exhaustion Recovery (OFER) scale has been developed and validated in three study populations specifically to measure work-related fatigue. RESULTS: The OFER scale possesses robust, gender-bias free psychometric characteristics. Its three subscales identify and distinguish between chronic work-related fatigue traits, acute end-of-shift states and effective fatigue recovery between shifts. CONCLUSION: These studies confirm the mediating role of intershift-shift recovery in the evolution of adaptive end-of-shift fatigue states to maladaptive persistent fatigue traits. The OFER scale is suggested as a potentially valuable new tool for use in work-related fatigue research.

Adult↗

Cardiovascular disease in the dialysis population: prognostic significance of arterial disorders.

PURPOSE OF REVIEW: Cardiovascular disease is a major factor in the high mortality of patients with end-stage renal disease, and this population is particularly appropriate to analyse the impact of cardiovascular risk markers on outcome. RECENT FINDINGS: Cardiovascular risk markers in end-stage renal disease include age, left ventricular mass, carotid intima-media thickness, blood pressure and aortic stiffness (pulse wave velocity). Aortic pulse wave velocity has been shown to be an independent predictor of cardiovascular mortality in patients with end-stage renal disease and the general population. Aortic pulse wave velocity has the highest sensitivity and specificity as a predictor of cardiovascular death in end-stage renal disease patients. Pulse wave velocity is an integrated index of vascular function and structure, and is a major determinant of systolic hypertension, thereby increasing left ventricular afterload, left ventricular hypertrophy and left ventricular oxygen consumption. Decreased diastolic blood pressure, another consequence of arterial stiffening, is associated with decreased coronary perfusion contributing to ischaemic heart disease and evolution of adaptive into maladaptive left ventricular hypertrophy. SUMMARY: Aortic stiffness measurements could serve as an important tool in identifying end-stage renal disease patients at higher risk of cardiovascular disease. The ability to identify these patients would lead to better risk stratification and earlier and more cost-effective preventive therapy.

Adult↗

Invasion of an asexual American water flea clone throughout Africa and rapid displacement of a native sibling species.

The huge ecological and economic impact of biological invasions creates an urgent need for knowledge of traits that make invading species successful and factors helping indigenous populations to resist displacement by invading species or genotypes. High genetic diversity is generally considered to be advantageous in both processes. Combined with sex, it allows rapid evolution and adaptation to changing environments. We combined paleogenetic analysis with continent-wide survey of genetic diversity at nuclear and mitochondrial loci to reconstruct the invasion history of a single asexual American water flea clone (hybrid Daphnia pulexxDaphnia pulicaria) in Africa. Within 60 years of the original introduction of this invader, it displaced the genetically diverse, sexual population of native D. pulex in Lake Naivasha (Kenya), despite a formidable numerical advantage of the local population and continuous replenishment from a large dormant egg bank. Currently, the invading clone has spread throughout the range of native African D. pulex, where it appears to be the only occurring genotype. The absence of genetic variation did not hamper either the continent-wide establishment of this exotic lineage or the effective displacement of an indigenous and genetically diverse sibling species.

Africa↗

Frequency-dependent selection in bacterial populations.

There are many situations in which the direction and intensity of natural selection in bacterial populations will depend on the relative frequencies of genotypes. In some cases, this selection will favour rare genotypes and result in the maintenance of genetic variability; this is termed stabilizing frequency-dependent selection. In other cases, selection will only favour genotypes when they are common. Rare types cannot invade and genetic variability will not be maintained; this is known as disruptive frequency-dependent selection. Phage-mediated selection for bacteria with novel restriction-modification systems is frequency-dependent and stabilizing. In mass culture, selection for the production of toxins and allelopathic agents is likely to be frequency-dependent but disruptive. This also occurs in selection favouring genes and transposable elements that cause mutations. Here I review the results of theoretical and experimental studies of stabilizing and disruptive frequency-dependent selection in bacterial populations, and speculate on the importance of this kind of selection in the adaptation and evolution of these organisms and their accessory elements (plasmid, phage and transposons).

Bacteria↗

Genetic mapping of the compatibility between a lily isolate of Cucumber mosaic virus and a satellite RNA.

Five isolates of Cucumber mosaic virus (CMV) from Lilium sp. (lily), which were isolated from specimens in Japan, Korea and Taiwan, were unable to support satellite RNA (satRNA) accumulation. In order to map the CMV sequences that are involved in satRNA support, HL-CMV (Japanese lily isolate), Y-CMV (ordinary strain) and Y-satellite RNA (Y-sat) were used as the source material. The pseudorecombinants between Y-CMV and HL-CMV revealed that RNA1 was essential for satRNA replication in lily. The results of chimeric constructs and various mutations showed that two amino acid residues (at positions 876 and 891) in the 1a protein were the determinants for the inability of HL-CMV to support a satRNA. Specifically, Thr at position 876 had a more pronounced effect than Met at position 891. Specific changes in RNA sequence were also detected in the 3' terminus of Y-sat and these particular alterations allowed it to be supported by HL-CMV. It is believed that, through evolution, the adaptation of CMV to lily resulted in the introduction of amino acid changes in the 1a protein, changes that coincidentally affected the ability of lily CMV to support satRNAs.

Amino Acid Motifs↗

A BAC-based physical map of the Drosophila buzzatii genome.

Large-insert genomic libraries facilitate cloning of large genomic regions, allow the construction of clone-based physical maps, and provide useful resources for sequencing entire genomes. Drosophila buzzatii is a representative species of the repleta group in the Drosophila subgenus, which is being widely used as a model in studies of genome evolution, ecological adaptation, and speciation. We constructed a Bacterial Artificial Chromosome (BAC) genomic library of D. buzzatii using the shuttle vector pTARBAC2.1. The library comprises 18,353 clones with an average insert size of 152 kb and an approximately 18x expected representation of the D. buzzatii euchromatic genome. We screened the entire library with six euchromatic gene probes and estimated the actual genome representation to be approximately 23x. In addition, we fingerprinted by restriction digestion and agarose gel electrophoresis a sample of 9555 clones, and assembled them using FingerPrint Contigs (FPC) software and manual editing into 345 contigs (mean of 26 clones per contig) and 670 singletons. Finally, we anchored 181 large contigs (containing 7788 clones) to the D. buzzatii salivary gland polytene chromosomes by in situ hybridization of 427 representative clones. The BAC library and a database with all the information regarding the high coverage BAC-based physical map described in this paper are available to the research community.

Animals↗

Genetic and epigenetic consequences of recent hybridization and polyploidy in Spartina (Poaceae).

To study the consequences of hybridization and genome duplication on polyploid genome evolution and adaptation, we used independently formed hybrids (Spartina x townsendii and Spartina x neyrautii) that originated from natural crosses between Spartina alterniflora, an American introduced species, and the European native Spartina maritima. The hybrid from England, S. x townsendii, gave rise to the invasive allopolyploid, salt-marsh species, Spartina anglica. Recent studies indicated that allopolyploid speciation may be associated with rapid genetic and epigenetic changes. To assess this in Spartina, we performed AFLP (amplified fragment length polymorphism) and MSAP (methylation sensitive amplification polymorphism) on young hybrids and the allopolyploid. By comparing the subgenomes in the hybrids and the allopolyploid to the parental species, we inferred structural changes that arose repeatedly in the two independently formed hybrids. Surprisingly, 30% of the parental methylation patterns are altered in the hybrids and the allopolyploid. This high level of epigenetic regulation might explain the morphological plasticity of Spartina anglica and its larger ecological amplitude. Hybridization rather than genome doubling seems to have triggered most of the methylation changes observed in Spartina anglica.

DNA Methylation↗

Transfer of plastid DNA from tobacco to the soil bacterium Acinetobacter sp. by natural transformation.

Acquisition of new genetic information by horizontal gene transfer is a major mechanism of genetic adaptation and evolution in prokaryotes. Naturally transformable cells of Acinetobacter sp. were exposed to plant DNA from leaf and root tissue of transplastomic tobacco. With the aadA gene (resistance against spectinomycin and streptomycin) as anchor sequence, the transfer of segments of the tobacco plastid DNA to Acinetobacter by homology-facilitated illegitimate recombination occurred at a frequency of 1.2 x 10(-7) per cell, which was about 0.1% of the frequency of fully homologous transfers. Without anchor sequence, transfer was not detected (</=1.3 x 10(-10)). The integrated plastid DNA segments extended up to 2539 nucleotides and often encompassed tobacco genes (trnL, ycf5). Expression of trnL (leucyl-tRNA) in a transformant was shown by reverse transcription polymerase chain reaction. About 44% of integration events occurred at a single hot-spot and 38% at other multiply used sites. All illegitimate recombination sites were GC-rich microhomologies of 3-6 bp often neighboured by further microhomologies. The sites were located in plant DNA at the ends of distinct larger high-GC regions, which suggests a role for GC-aided association of heterologous sequences in illegitimate DNA end joining. The results show that integration of plant DNA into a bacterial genome by natural transformation is possible and is probably stimulated by hot-spots of illegitimate recombination.

Acinetobacter↗

The pelvis as a passageway. II. The modern human pelvis.

Following on from part I on evolution and adaptations of the pelvis, this paper suggests that variations in the shape and size of both ancient and modern human pelves may be better explained by nutritional factors than by hormonal influences or race.

Body Height↗

Genome sequencing and population genomics provide insights into the demographic history, genetic load, and local adaptation of an endangered Tertiary relict.

Endangered Tertiary relict trees represent an exceptional evolutionary heritage with small and isolated populations, yet little is known about how demographic history, local adaptation, and genetic load have affected their long-term survival and extinction risk. We performed whole-genome sequencing and population genomic analyses on Ulmus elongata L. K. Fu & C. S. Ding, an endangered Tertiary relict tree endemic to East Asia. By integrating genomes from U. elongata and seven other endangered trees from public databases, we identified rate-decelerated genes across endangered trees and genes under positive selection of U. elongata associated with tissue development, detoxification, and immune response, and signal transduction and regulation mechanisms potentially leading to endangered status. Demographic analyses revealed continuous population decline from the late Miocene to present, especially during the last glacial maximum (LGM) and last 10&#x2009;000&#x2009;years. Spearman correlation indicated a strong negative relationship between effective population size and human population density (rpopulation density&#x2009;=&#x2009;-0.90, P&#x2009;<&#x2009;0.001) as well as cropland use (rcropland use&#x2009;=&#x2009;-0.89, P&#x2009;<&#x2009;0.001). Genotype-environment association (GEA) analyses identified a set of candidate genes associated with temperature and precipitation, supporting a polygenic adaptation model in U. elongata. Overall, our findings underscore the severe population bottlenecks that have led to the fixation of strongly deleterious mutations and inbreeding, further compromising the adaptive potential and long-term viability of U. elongata. Furthermore, assessments of genomic vulnerability under future climate scenarios revealed higher genetic offsets in northern region of Fujian and Jiangxi populations, suggesting these regions require prioritized conservation efforts due to reduced adaptive capacity.

Endangered Species↗

Surprisingly frequent chromosomal instability in cultivated peanut.

This study, the third in a three-part series, investigates whether chromosomal instability persists in cultivated peanut. The allotetraploid peanut (Arachis hypogaea; genome type AABB) originated from the hybridization and polyploidization of A. duranensis (AA) and A. ipa&#xeb;nsis (BB). Our first study established that this was an extremely narrow genetic origin, likely from a single hybridization event. This raised a paradox: how did such narrow genetics give rise to the phenotypic diversity seen in cultivated peanut? The second study addressed this, showing that a single neoallotetraploid spontaneously generates striking diversity, and that homoeologous exchanges-abundant in early generations following polyploidy-are a key mechanism in creating this diversity. In contrast to this early-generation instability, cultivated peanut is generally considered to be genetically stable, presumably due to selection. This third study tests whether residual instability still occurs in modern peanut. From a single plant of the highly selfed 'genome stock' of the cultivar 'Tifrunner', we advanced lineages through seven generations in a pollinator-free greenhouse. Among 233 plants, we identified three new large-scale chromosomal instability events: a large deletion on chromosome B01, associated with reduced pod width and seed weight, and two ABBB compositions involving chromosomes A02/B02 and A05/B05. With these observations in hand, we reinterpreted previously published data from two recombinant inbred populations. Together, these results indicate that at least 1% of pure pedigree A. hypogaea plants exhibit spontaneous large-scale chromosomal changes-a surprising frequency of instability that likely contributes to peanut's long-term adaptability and evolution.

Arachis↗

Transposable elements as modulators of homoeologous gene&#xa0;expression in bread wheat: lessons from the pan-transcriptome era.

Bread wheat (Triticum aestivum L.) is an allohexaploid (AABBDD) whose three ancestral subgenomes generate complex patterns of gene regulation. Most genes exist as homoeologous triads, and the relative expression balance among copies, homoeolog expression bias, is central to polyploid evolution and adaptation. Recent high-quality assemblies, long-read transcriptomics, and pan-transcriptome resources have uncovered extensive cultivar-specific transcriptional diversity. Because transposable elements (TEs) compose over 80% of the wheat genome, they are prime candidates for shaping subgenome asymmetry. We synthesize recent pan-genomic and transcriptomic evidence, including genome-wide associations between TE insertions and genome-specific expression, and propose a unifying framework in which TEs modulate homoeolog expression by donating cis-regulatory sequences, altering chromatin states, producing small RNAs, and driving structural variation. We discuss experimental and computational challenges for establishing causality, and outline future functional and translational strategies to leverage TE-associated regulatory diversity in wheat breeding.

Triticum↗

HEMOGLOBIN AND OXYGEN: AFFINITIES IN SEVEN SPECIES OF SCIURIDAE.

Studies of the respiratory function of the bloods of seven species of squirrels suggest that, in the evolution and adaptive radiation of this group, the oxygen affinity of hemoglobin has changed in a manner to better adapt the various species to different ways of life and different habitats. These changes are shown by the relative positions of the oxygen-dissociation curves of bloods of several species having dissimilar habits and environments.

Animals↗

Behavior of captive white-footed mice.

Detailed studies of the behavior of captive white-footed mice have cast a number of old problems in new perspectives. Many responses of small captive mammals cannot be interpreted at face value because of severe distortions of behavior that are caused by depriving the wild animal of natural outlets for activity. Confined animals are likely to seize upon and repeatedly exercise virtually any opportunities to modify (and alter their relationships with) their surroundings. In addition they have a strong tendency to counteract nonvolitional and "unexpected" deviations from the status quo. As a result, their responses do not bear an immutable relationship to the nature of the stimulus or other variable being modified; stimuli and activities that are rewarding in certain circumstances are avoided in others. These aspects of behavior have been illustrated by studies of nest occupancy, running in motordriven wheels, and control of intensity of illumination. The results of the control-of-illumination studies suggest the complex interplay of tendencies to modify features of the environment, to avoid conditions imposed compulsorily, and to select preferred levels of illumination. The importance of split-second timing, coordination, and quick reflex actions in the running of activity wheels is indicated by the fact that experienced white-footed mice prefer running in square "wheels" and wheels with hurdles to running in plain round wheels. The relatively conservative behavior of these mice in selecting between multiple sources of food and water and different types of activity wheels suggests the need for careful experimental design in free-choice studies with inexperienced animals. The tendency of trained animals to give some so-called "incorrect" responses even after long experience can be interpreted most reasonably in terms of the adaptive value of a certain degree of variability of behavior in the wild. White-footed mice readily master complex regimes in which several different levers and shutters must be pressed or rotated in certain sequences within seconds for different rewards. They quickly learn to traverse mazes containing hundreds of blind alleys and do so frequently without extrinsic reward. It is unlikely that these remarkable learning performances even begin to approach the capacities of the animals. When two female mice having markedly different solitary behavior patterns were placed in consort, the behavior of each changed, becoming more like that of the other, and the animals showed a strong tendency to remain in each other's company. The behavior of mice in enclosures of great extent casts doubt upon the postulate that hunger and thirst play leading roles in the motivation of wide-ranging locomotor movements. Accordingly, studies of deprived domestic animals in simple mazes may have but limited significance for understanding the behavior of wild and relatively unconfined animals. The existence of marked individual differences between mice selected at random from wild populations sounds the need for a cautious approach in the interpretation of results obtained with highly inbred domestic animals. The relatively uniform behavior of inbred strains represents only a small fragment of the total response spectrum for the species and probably has minimal significance for adaptation and evolution in the wild. When allowed to control the intensity of illumination by operating a series of switches, white-footed mice establish a roughly 24-hour regime consistent with that experienced in the wild, namely dim light during periods of activity and very dim light during periods of inactivity. Consistent with this finding, when exposed to a dim-dark light cycle, the mice are active during the dim phase, not in darkness. Artificial twilight transitions of both constant and varying color temperature have several marked effects upon the activity of white-footed mice. The existence of a strong orienting influence of dim light on the direction of wheel-running suggests that mice in the wild use the twilight sun and the moon (and possibly other celestial light sources) as navigational references.

Animals↗

Metronidazole activation is mutagenic and causes DNA fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H. pylori RdxA(+) (Nitroreductase) gene.

Much of the normal high sensitivity of wild-type Helicobacter pylori to metronidazole (Mtz) depends on rdxA (HP0954), a gene encoding a novel nitroreductase that catalyzes the conversion of Mtz from a harmless prodrug to a bactericidal agent. Here we report that levels of Mtz that partially inhibit growth stimulate forward mutation to rifampin resistance in rdxA(+) (Mtz(s)) and also in rdxA (Mtz(r)) H. pylori strains, and that expression of rdxA in Escherichia coli results in equivalent Mtz-induced mutation. A reversion test using defined lac tester strains of E. coli carrying rdxA(+) indicated that CG-to-GC transversions and AT-to-GC transitions are induced more frequently than other base substitutions. Alkaline gel electrophoretic tests showed that Mtz concentrations near or higher than the MIC for growth also caused DNA breakage in H. pylori and in E. coli carrying rdxA(+), suggesting that this damage may account for most of the bactericidal action of Mtz. Coculture of Mtz(s) H. pylori with E. coli (highly resistant to Mtz) in the presence of Mtz did not stimulate forward mutation in E. coli, indicating that the mutagenic and bactericidal products of Mtz metabolism do not diffuse significantly to neighboring (bystander) cells. Our results suggest that the widespread use of Mtz against other pathogens in people chronically infected with H. pylori may stimulate mutation and recombination in H. pylori, thereby speeding host-specific adaptation, the evolution of virulence, and the emergence of resistance against Mtz and other clinically useful antimicrobials.

Amino Acid Substitution↗

Staphylococcus aureus Prophage-Encoded Protein Causes Abortive Infection and Provides Population Immunity against Kayviruses.

Both temperate and obligately lytic phages have crucial roles in the biology of staphylococci. While superinfection exclusion among closely related temperate phages is a well-characterized phenomenon, the interactions between temperate and lytic phages in staphylococci are not understood. Here, we present a resistance mechanism toward lytic phages of the genus Kayvirus, mediated by the membrane-anchored protein designated PdpSau encoded by Staphylococcus aureus prophages, mostly of the Sa2 integrase type. The prophage accessory gene pdpSau is strongly linked to the lytic genes for holin and ami2-type amidase and typically replaces genes for the toxin Panton-Valentine leukocidin (PVL). The predicted PdpSau protein structure shows the presence of a membrane-binding &#x3b1;-helix in its N-terminal part and a cytoplasmic positively charged C terminus. We demonstrated that the mechanism of action of PdpSau does not prevent the infecting kayvirus from adsorbing onto the host cell and delivering its genome into the cell, but phage DNA replication is halted. Changes in the cell membrane polarity and permeability were observed from 10&#x2009;min after the infection, which led to prophage-activated cell death. Furthermore, we describe a mechanism of overcoming this resistance in a host-range Kayvirus mutant, which was selected on an S. aureus strain harboring prophage 53 encoding PdpSau, and in which a chimeric gene product emerged via adaptive laboratory evolution. This first case of staphylococcal interfamily phage-phage competition is analogous to some other abortive infection defense systems and to systems based on membrane-destructive proteins. IMPORTANCE Prophages play an important role in virulence, pathogenesis, and host preference, as well as in horizontal gene transfer in staphylococci. In contrast, broad-host-range lytic staphylococcal kayviruses lyse most S. aureus strains, and scientists worldwide have come to believe that the use of such phages will be successful for treating and preventing bacterial diseases. The effectiveness of phage therapy is complicated by bacterial resistance, whose mechanisms related to therapeutic staphylococcal phages are not understood in detail. In this work, we describe a resistance mechanism targeting kayviruses that is encoded by a prophage. We conclude that the defense mechanism belongs to a broader group of abortive infections, which is characterized by suicidal behavior of infected cells that are unable to produce phage progeny, thus ensuring the survival of the host population. Since the majority of staphylococcal strains are lysogenic, our findings are relevant for the advancement of phage therapy.

Humans↗

Molecular biology and pathogenicity of mycoplasmas.

The recent sequencing of the entire genomes of Mycoplasma genitalium and M. pneumoniae has attracted considerable attention to the molecular biology of mycoplasmas, the smallest self-replicating organisms. It appears that we are now much closer to the goal of defining, in molecular terms, the entire machinery of a self-replicating cell. Comparative genomics based on comparison of the genomic makeup of mycoplasmal genomes with those of other bacteria, has opened new ways of looking at the evolutionary history of the mycoplasmas. There is now solid genetic support for the hypothesis that mycoplasmas have evolved as a branch of gram-positive bacteria by a process of reductive evolution. During this process, the mycoplasmas lost considerable portions of their ancestors' chromosomes but retained the genes essential for life. Thus, the mycoplasmal genomes carry a high percentage of conserved genes, greatly facilitating gene annotation. The significant genome compaction that occurred in mycoplasmas was made possible by adopting a parasitic mode of life. The supply of nutrients from their hosts apparently enabled mycoplasmas to lose, during evolution, the genes for many assimilative processes. During their evolution and adaptation to a parasitic mode of life, the mycoplasmas have developed various genetic systems providing a highly plastic set of variable surface proteins to evade the host immune system. The uniqueness of the mycoplasmal systems is manifested by the presence of highly mutable modules combined with an ability to expand the antigenic repertoire by generating structural alternatives, all compressed into limited genomic sequences. In the absence of a cell wall and a periplasmic space, the majority of surface variable antigens in mycoplasmas are lipoproteins. Apart from providing specific antimycoplasmal defense, the host immune system is also involved in the development of pathogenic lesions and exacerbation of mycoplasma induced diseases. Mycoplasmas are able to stimulate as well as suppress lymphocytes in a nonspecific, polyclonal manner, both in vitro and in vivo. As well as to affecting various subsets of lymphocytes, mycoplasmas and mycoplasma-derived cell components modulate the activities of monocytes/macrophages and NK cells and trigger the production of a wide variety of up-regulating and down-regulating cytokines and chemokines. Mycoplasma-mediated secretion of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1 (IL-1), and IL-6, by macrophages and of up-regulating cytokines by mitogenically stimulated lymphocytes plays a major role in mycoplasma-induced immune system modulation and inflammatory responses.

Animals↗