Showing papers by "University of Düsseldorf published in 2006"

Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia

Abstract: BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa ...

Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial.

Abstract: Summary Background 5-aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas—a finding that is under investigation for intraoperative identification and resection of these tumours. We aimed to assess the effect of fluorescence-guided resection with 5-aminolevulinic acid on surgical radicality, progression-free survival, overall survival, and morbidity. Methods 322 patients aged 23–73 years with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were randomly assigned to 20 mg/kg bodyweight 5-aminolevulinic acid for fluorescence-guided resection (n=161) or to conventional microsurgery with white light (n=161). The primary endpoints were the number of patients without contrast-enhancing tumour on early MRI (ie, that obtained within 72 h after surgery) and 6-month progression-free survival as assessed by MRI. Secondary endpoints were volume of residual tumour on postoperative MRI, overall survival, neurological deficit, and toxic effects. We report the results of an interim analysis with 270 patients in the full-analysis population (139 assigned 5-aminolevulinic acid, 131 assigned white light), which excluded patients with ineligible histological and radiological findings as assessed by central reviewers who were masked as to treatment allocation; the interim analysis resulted in termination of the study as defined by the protocol. Primary and secondary endpoints were analysed by intention to treat in the full-analysis population. The study is registered at http://www.clinicaltrials.gov as NCT00241670. Findings Median follow-up was 35·4 months (95% CI 1·0–56·7). Contrast-enhancing tumour was resected completely in 90 (65%) of 139 patients assigned 5-aminolevulinic acid compared with 47 (36%) of 131 assigned white light (difference between groups 29% [95% CI 17–40], p vs 21·1% [14·0–28·2]; difference between groups 19·9% [9·1–30·7], p=0·0003, Z test). Groups did not differ in the frequency of severe adverse events or adverse events in any organ system class reported within 7 days after surgery. Interpretation Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour, leading to improved progression-free survival in patients with malignant glioma.

Insights into social insects from the genome of the honeybee Apis mellifera

Abstract: Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.

The potential risks of nanomaterials: a review carried out for ECETOC

Abstract: During the last few years, research on toxicologically relevant properties of engineered nanoparticles has increased tremendously. A number of international research projects and additional activities are ongoing in the EU and the US, nourishing the expectation that more relevant technical and toxicological data will be published. Their widespread use allows for potential exposure to engineered nanoparticles during the whole lifecycle of a variety of products. When looking at possible exposure routes for manufactured Nanoparticles, inhalation, dermal and oral exposure are the most obvious, depending on the type of product in which Nanoparticles are used. This review shows that (1) Nanoparticles can deposit in the respiratory tract after inhalation. For a number of nanoparticles, oxidative stress-related inflammatory reactions have been observed. Tumour-related effects have only been observed in rats, and might be related to overload conditions. There are also a few reports that indicate uptake of nanoparticles in the brain via the olfactory epithelium. Nanoparticle translocation into the systemic circulation may occur after inhalation but conflicting evidence is present on the extent of translocation. These findings urge the need for additional studies to further elucidate these findings and to characterize the physiological impact. (2) There is currently little evidence from skin penetration studies that dermal applications of metal oxide nanoparticles used in sunscreens lead to systemic exposure. However, the question has been raised whether the usual testing with healthy, intact skin will be sufficient. (3) Uptake of nanoparticles in the gastrointestinal tract after oral uptake is a known phenomenon, of which use is intentionally made in the design of food and pharmacological components. Finally, this review indicates that only few specific nanoparticles have been investigated in a limited number of test systems and extrapolation of this data to other materials is not possible. Air pollution studies have generated indirect evidence for the role of combustion derived nanoparticles (CDNP) in driving adverse health effects in susceptible groups. Experimental studies with some bulk nanoparticles (carbon black, titanium dioxide, iron oxides) that have been used for decades suggest various adverse effects. However, engineered nanomaterials with new chemical and physical properties are being produced constantly and the toxicity of these is unknown. Therefore, despite the existing database on nanoparticles, no blanket statements about human toxicity can be given at this time. In addition, limited ecotoxicological data for nanomaterials precludes a systematic assessment of the impact of Nanoparticles on ecosystems.

Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology

Abstract: Background The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database.

(–)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans

Abstract: Epidemiological and medical anthropological investigations suggest that flavanol-rich foods exert cardiovascular health benefits. Endothelial dysfunction, a prognostically relevant key event in atherosclerosis, is characterized by a decreased bioactivity of nitric oxide (NO) and impaired flow-mediated vasodilation (FMD). We show in healthy male adults that the ingestion of flavanol-rich cocoa was associated with acute elevations in levels of circulating NO species, an enhanced FMD response of conduit arteries, and an augmented microcirculation. In addition, the concentrations and the chemical profiles of circulating flavanol metabolites were determined, and multivariate regression analyses identified (–)-epicatechin and its metabolite, epicatechin-7-O-glucuronide, as independent predictors of the vascular effects after flavanol-rich cocoa ingestion. A mixture of flavanols/metabolites, resembling the profile and concentration of circulating flavanol compounds in plasma after cocoa ingestion, induced a relaxation in preconstricted rabbit aortic rings ex vivo, thus mimicking acetylcholine-induced relaxations. Ex vivo flavanol-induced relaxation, as well as the in vivo increases in FMD, were abolished by inhibition of NO synthase. Oral administration of chemically pure (–)-epicatechin to humans closely emulated acute vascular effects of flavanol-rich cocoa. Finally, the concept that a chronic intake of high-flavanol diets is associated with prolonged, augmented NO synthesis is supported by data that indicate a correlation between the chronic consumption of a cocoa flavanol-rich diet and the augmented urinary excretion of NO metabolites. Collectively, our data demonstrate that the human ingestion of the flavanol (–)-epicatechin is, at least in part, causally linked to the reported vascular effects observed after the consumption of flavanol-rich cocoa.

IL-31: A new link between T cells and pruritus in atopic skin inflammation

Abstract: Background IL-31 is a novel T-cell–derived cytokine that induces severe pruritus and dermatitis in transgenic mice, and signals through a heterodimeric receptor composed of IL-31 receptor A and oncostatin M receptor. Objective To investigate the role of human IL-31 in pruritic and nonpruritic inflammatory skin diseases. Methods The expression of IL-31 was analyzed by quantitative real-time PCR in skin samples of healthy individuals and patients with chronic inflammatory skin diseases. Moreover, IL-31 expression was analyzed in nonlesional skin of atopic dermatitis patients after allergen or superantigen exposure, as well as in stimulated leukocytes. The tissue distribution of the IL-31 receptor heterodimer was investigated by DNA microarray analysis. Results IL-31 was significantly overexpressed in pruritic atopic compared with nonpruritic psoriatic skin inflammation. Highest IL-31 levels were detected in prurigo nodularis, one of the most pruritic forms of chronic skin inflammation. In vivo , staphylococcal superantigen rapidly induced IL-31 expression in atopic individuals. In vitro , staphylococcal enterotoxin B but not viruses or T H 1 and T H 2 cytokines induced IL-31 in leukocytes. In patients with atopic dermatitis, activated leukocytes expressed significantly higher IL-31 levels compared with control subjects. IL-31 receptor A showed most abundant expression in dorsal root ganglia representing the site where the cell bodies of cutaneous sensory neurons reside. Conclusion Our findings provide a new link among staphylococcal colonization, subsequent T-cell recruitment/activation, and pruritus induction in patients with atopic dermatitis. Taken together, these findings show that IL-31 may represent a novel target for antipruritic drug development.

Adverse Effects of Topical Glucocorticosteroids

Abstract: Topical corticosteroids were introduced into medicine about 50 years ago. They represent a significant milestone in dermatologic therapy. Despite encouragement to report observed adverse drug reactions, the clinical practice of reporting is poor and incomplete. Likewise, adverse effects and safety of topical corticosteroids are neglected in the medical literature. The authors provide an updated review of their adverse-effect profile. Children are more prone to the development of systemic reactions to topically applied medication because of their higher ratio of total body surface area to body weight. Cutaneous adverse effects occur regularly with prolonged treatment and are dependent on the chemical nature of the drug, the vehicle, and the location of its application. The most frequent adverse effects include atrophy, striae, rosacea, perioral dermatitis, acne, and purpura. Those that occur with lower frequency include hypertrichosis, pigmentation alterations, delayed wound healing, and exacerbation of skin infections. Of particular interest is the rate of contact sensitization against corticosteroids, which is considerably higher than generally believed. Systemic reactions such as hyperglycemia, glaucoma, and adrenal insufficiency have also been reported to follow topical application. The authors provide an updated review of local and systemic adverse effects upon administration of topical corticosteroids, including the latest FDA report on the safety of such steroids in children. Learning objective At the completion of this learning activity, participants should be familiar with topical corticosteroids and their proper use.

Eukaryotic evolution, changes and challenges

Abstract: The idea that some eukaryotes primitively lacked mitochondria and were true intermediates in the prokaryote-to-eukaryote transition was an exciting prospect. It spawned major advances in understanding anaerobic and parasitic eukaryotes and those with previously overlooked mitochondria. But the evolutionary gap between prokaryotes and eukaryotes is now deeper, and the nature of the host that acquired the mitochondrion more obscure, than ever before.

Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity

Abstract: Fungal infections are increasing worldwide due to the marked rise in immunodeficiencies including AIDS; however, immune responses to fungi are poorly understood. Dectin-1 is the major mammalian pattern recognition receptor for the fungal component zymosan. Dectin-1 represents the prototype of innate non-Toll-like receptors (TLRs) containing immunoreceptor tyrosine-based activation motifs (ITAMs) related to those of adaptive antigen receptors. Here we identify Card9 as a key transducer of Dectin-1 signalling. Although being dispensable for TLR/MyD88-induced responses, Card9 controls Dectin-1-mediated myeloid cell activation, cytokine production and innate anti-fungal immunity. Card9 couples to Bcl10 and regulates Bcl10-Malt1-mediated NF-kappaB activation induced by zymosan. Yet, Card9 is dispensable for antigen receptor signalling that uses Carma1 as a link to Bcl10-Malt1. Thus, our results define a novel innate immune pathway and indicate that evolutionarily distinct ITAM receptors in innate and adaptive immune cells use diverse adaptor proteins to engage selectively the conserved Bcl10-Malt1 module.

Frequency and Spectrum of Cancers in the Peutz-Jeghers Syndrome

Abstract: BACKGROUND: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited. EXPERIMENTAL DESIGN: We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1 mutations. RESULTS: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis were gastrointestinal in origin, gastroesophageal, small bowel, colorectal, and pancreatic, and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference chi2 = 0.62; 1 df; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk. CONCLUSIONS: The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.

Nerve injury, axonal degeneration and neural regeneration: basic insights.

Abstract: Axotomy or crush of a peripheral nerve leads to degeneration of the distal nerve stump referred to as Wallerian degeneration (WD). During WD a microenvironment is created that allows successful regrowth of nerve fibres from the proximal nerve segment. Schwann cells respond to loss of axons by extrusion of their myelin sheaths, downregulation of myelin genes, dedifferentiation and proliferation. They finally aline in tubes (Bungner bands) and express surface molecules that guide regenerating fibres. Hematogenous macrophages are rapidly recruited to the distal stump and remove the vast majority of myelin debris. Molecular changes in the distal stump include upregulation of neurotrophins, neural cell adhesion molecules, cytokines and other soluble factors and their corresponding receptors. Axonal injury not only induces muscle weakness and loss of sensation but also leads to adaptive responses and neuropathic pain. Regrowth of nerve fibres occurs with high specificity with formerly motor fibres preferentially reinnervating muscle. This involves recognition molecules of the L2/HNK-1 family. Nerve regeneration occurs at a rate of 3-4 mm/day after crush and 2-3 mm/day after sectioning a nerve. Nerve regeneration can be fostered pharmacologically. Upon reestablishment of axonal contact Schwann cells remyelinate nerve sprouts and downregulate surface molecules characteristic for precursor/premyelinating or nonmyelinating Schwann cells. At present it is unclear whether axonal regeneration after nerve injury is impeded in neuropathies.

Larvicidal effects of various essential oils against Aedes, Anopheles, and Culex larvae (Diptera, Culicidae).

Abstract: Mosquitoes in the larval stage are attractive targets for pesticides because mosquitoes breed in water, and thus, it is easy to deal with them in this habitat. The use of conventional pesticides in the water sources, however, introduces many risks to people and/or the environment. Natural pesticides, especially those derived from plants, are more promising in this aspect. Aromatic plants and their essential oils are very important sources of many compounds that are used in different respects. In this study, the oils of 41 plants were evaluated for their effects against third-instar larvae of Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus. At first, the oils were surveyed against A. aegypti using a 50-ppm solution. Thirteen oils from 41 plants (camphor, thyme, amyris, lemon, cedarwood, frankincense, dill, myrtle, juniper, black pepper, verbena, helichrysum and sandalwood) induced 100% mortality after 24 h, or even after shorter periods. The best oils were tested against third-instar larvae of the three mosquito species in concentrations of 1, 10, 50, 100 and 500 ppm. The lethal concentration 50 values of these oils ranged between 1 and 101.3 ppm against A. aegypti, between 9.7 and 101.4 ppm for A. stephensi and between 1 and 50.2 ppm for C. quinquefasciatus.

Repellency effect of forty-one essential oils against Aedes , Anopheles , and Culex mosquitoes

Abstract: Since ancient times, plant products were used in various aspects. However, their use against pests decreased when chemical products became developed. Recently, concerns increased with respect to public health and environmental security requiring detection of natural products that may be used against insect pests. In this study, 41 plant extracts and 11 oil mixtures were evaluated against the yellow fever mosquito, Aedes aegypti (Linnaeus), the malaria vector, Anopheles stephensi (Liston), and the filariasis and encephalitis vector, Culex quinquefasciatus (Say) (Diptera: Culicidae) using the skin of human volunteers to find out the protection time and repellency. The five most effective oils were those of Litsea (Litsea cubeba), Cajeput (Melaleuca leucadendron), Niaouli (Melaleuca quinquenervia), Violet (Viola odorata), and Catnip (Nepeta cataria), which induced a protection time of 8 h at the maximum and a 100% repellency against all three species. This effect needs, however, a peculiar formulation to fix them on the human skin.

Histological classification and molecular genetics of meningiomas.

Abstract: Meningiomas account for up to 30% of all primary intracranial tumours. They are histologically classified according to the World Health Organization (WHO) classification of tumours of the nervous system. Most meningiomas are benign lesions of WHO grade I, whereas some meningioma variants correspond with WHO grades II and III and are associated with a higher risk of recurrence and shorter survival times. Mutations in the NF2 gene and loss of chromosome 22q are the most common genetic alterations associated with the initiation of meningiomas. With increase in tumour grade, additional progression-associated molecular aberrations can be found; however, most of the relevant genes are yet to be identified. High-throughput techniques of global genome and transcriptome analyses and new meningioma models provide increasing insight into meningioma biology and will help to identify common pathogenic pathways that may be targeted by new therapeutic approaches.

Oral Treatment With α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy The SYDNEY 2 trial

Abstract: OBJECTIVE — The aim of this trial was to evaluate the effects of -lipoic acid (ALA) on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy (DSP). RESEARCH DESIGN AND METHODS — In this multicenter, randomized, doubleblind, placebo-controlled trial, 181 diabetic patients in Russia and Israel received once-daily oral doses of 600 mg (n 45) (ALA600), 1,200 mg (n 47) (ALA1200), and 1,800 mg (ALA1800) of ALA (n 46) or placebo (n 43) for 5 weeks after a 1-week placebo run-in period. The primary outcome measure was the change from baseline of the Total Symptom Score (TSS), including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet. Secondary end points included individual symptoms of TSS, Neuropathy Symptoms and Change (NSC) score, Neuropathy Impairment Score (NIS), and patients’ global assessment of efficacy. RESULTS — Mean TSS did not differ significantly at baseline among the treatment groups and on average decreased by 4.9 points (51%) in ALA600, 4.5 (48%) in ALA1200, and 4.7 (52%) in ALA1800 compared with 2.9 points (32%) in the placebo group (all P 0.05 vs. placebo). The corresponding response rates (50% reduction in TSS) were 62, 50, 56, and 26%, respectively. Significant improvements favoring all three ALA groups were also noted for stabbing and burning pain, the NSC score, and the patients’ global assessment of efficacy. The NIS was numerically reduced. Safety analysis showed a dose-dependent increase in nausea, vomiting, and vertigo. CONCLUSIONS — Oral treatment with ALA for 5 weeks improved neuropathic symptoms and deficits in patients with DSP. An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio.

Electromagnetic Activation of Shape Memory Polymer Networks Containing Magnetic Nanoparticles

Abstract: Summary: By incorporation of surface-modified superparamagnetic nanoparticles into shape memory polymer matrices, remote actuation of complex shape transitions by electromagnetic fields is possible. The composite thermosets of oligo(e-caprolactone)dimethacrylate/butyl acrylate contain between 2 and 12 wt.-% magnetite nanoparticles serving as nanoantennas for magnetic heating. It is shown that the particles are dispersed homogenously within the matrix and that the basic thermal and mechanical properties of the polymer matrix are maintained. The specific loss power of the particles is determined to be 30 W · g−1 at 300 kHz and 5.0 W. During the shape transition at 43 °C, no further temperature increase is observed.

Introns and the origin of nucleus–cytosol compartmentalization

Abstract: The origin of the eukaryotic nucleus marked a seminal evolutionary transition. We propose that the nuclear envelope's incipient function was to allow mRNA splicing, which is slow, to go to completion so that translation, which is fast, would occur only on mRNA with intact reading frames. The rapid, fortuitous spread of introns following the origin of mitochondria is adduced as the selective pressure that forged nucleus-cytosol compartmentalization.

Cytokines and chemokines orchestrate atopic skin inflammation

Abstract: Atopic dermatitis (AD) is a common pruritic and chronically relapsing inflammatory skin disease. The pathophysiology of AD includes disturbed skin barrier functions, frequent allergic responses against allergens, defects in the antimicrobial immune defense, and a genetic predisposition. In this review we summarize advances in our understanding of the complex interdependent network of members of the rapidly growing protein superfamilies of cytokines and chemokines that lead to the development of AD.

The role of nitric oxide

Abstract: When studying the impact of endothelins (ETs) on physiology and pathophysiology, this needs to be done in the context of nitric oxide (NO) synthesis and action, since these two are closely intertwined in their action. Here, we will review the work demonstrating the crosstalk between endothelin-1 (ET-1) and NO, and the recent developments regarding the role of these two mediators in inflammatory processes. Moreover, we will discuss the role of NO in pro-inflammatory diseases and the potential mechanisms of the anti-inflammatory activity of ET receptor antagonism.

Immune surveillance in multiple sclerosis patients treated with natalizumab

Abstract: Objective Our objective was to test whether natalizumab, an antibody against very late activating antigen (VLA)-4, interferes with central nervous system immune surveillance as assessed by leukocyte cell numbers and cellular phenotypes in cerebrospinal fluid (CSF) and peripheral blood. Methods Cell numbers and cellular phenotypes in CSF and peripheral blood were analyzed in multiple sclerosis (MS) patients treated with natalizumab, untreated MS patients, and patients with other neurological disease (OND). JC virus DNA in the CSF and peripheral blood was quantified by kinetic polymerase chain reaction. Results CSF leukocyte counts, CD4+ and CD8+ T cells, CD19+ B cells, and CD138+ plasma cells were significantly lower in natalizumab-treated MS patients compared with OND patients and untreated MS patients. JC virus DNA was not detected in CSF or peripheral blood from natalizumab-treated patients. Six months after cessation of natalizumab therapy, low lymphocyte counts in the CSF persisted. The patient with the highest total leukocyte and CD4+ and CD8+T-cell counts in the CSF experienced a clinical relapse. Interpretation These data suggest that natalizumab treatment results in a prolonged decrease of lymphocytes in the CSF and are consistent with the hypothesis that natalizumab impairs immune surveillance of the central nervous system. Ann Neurol 2006;59:743–747

Work stress and health risk behavior.

Abstract: This contribution discusses current knowledge of associations between psychosocial stress at work and health risk behavior, in particular cigarette smoking, alcohol consumption and overweight, by reviewing findings from major studies in the field published between 1989 and 2006. Psychosocial stress at work is measured by the demand-control model and the effort-reward imbalance model. Health risk behavior was analyzed in the broader context of a health-related Western lifestyle with socially and economically patterned practices of consumption. Overall, the review, based on 46 studies, only modestly supports the hypothesis of a consistent association between work stress and health risk behavior. The relatively strongest relationships have been found with regard to heavy alcohol consumption among men, overweight, and the co-manifestation of several risks. Suggestions for further research are given, and the need to reduce stressful experience in the framework of worksite health promotion programs is emphasized.

The tree of one percent

Abstract: Two significant evolutionary processes are fundamentally not tree-like in nature - lateral gene transfer among prokaryotes and endosymbiotic gene transfer (from organelles) among eukaryotes. To incorporate such processes into the bigger picture of early evolution, biologists need to depart from the preconceived notion that all genomes are related by a single bifurcating tree.