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Tetrasomy 8 evolving into a segmental triplication 8q in a case of acute monocytic leukemia.

We report a case of AML-M5 with tetrasomy 8 that evolved within a 7-month period to a segmental triplication 8q. Other numerical abnormalities in the initial diagnosis were not found at the relapse; however, a chromosome 1 structural abnormality was maintained, proving the clonal evolution from tetrasomy 8 to a segmental triplication of the long arm of 8. This strongly suggests that there is a functional and selective advantage for duplications and triplications of 8q in these patients.

Aged↗

Diagnostic potential of PhotoSELEX-evolved ssDNA aptamers.

High sensitivity and specificity of two modified ssDNA aptamers capable of photocross-linking recombinant human basic fibroblast growth factor (bFGF((155))) were demonstrated. The aptamers were identified through a novel, covalent, in vitro selection methodology called photochemical systematic evolution of ligands by exponential enrichment (PhotoSELEX). The aptamers exhibited high sensitivity for bFGF((155)) comparable with commercially available ELISA monoclonal antibodies with an absolute sensitivity of at least 0.058 ppt bFGF((155)) under prevailing test conditions. The aptamers exquisitely distinguished bFGF((155)) from consanguine proteins, vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF). A commercially viable diagnostic system incorporating PhotoSELEX-evolved aptamers capable of simultaneous quantification of a large number of analyte molecules is also described. Such a system benefits from covalent bonding of aptamer to target protein allowing vigorous washing with denaturants to improve signal to noise.

Base Sequence↗

Codon reassignment and the evolving genetic code: problems and pitfalls in post-genome analysis.

The in silico translation of open reading frames, using the 'universal genetic code', must be approached with caution. The uncovering of a number of codon reassignments in nuclear and organellar genomes highlights the importance of experimentally confirming the assignments of all 64 codons for the species whose genome is under investigation. Such alterations to codon meaning also suggest that the genetic code is not 'frozen' and continues to evolve.

Codon↗

The methyl-CpG binding domain and the evolving role of DNA methylation in animals.

DNA methylation occurs in bacteria, fungi, plants and animals, however its role varies widely among different organisms. Even within animal genomes, methylation patterns vary substantially from undetectable in nematodes, to global methylation in vertebrate genomes. The number and variety of proteins containing methyl-CpG binding domains (MBDs) that are encoded in animal genomes also varies, with a general correlation between the extent of genomic methylation and the number of MBD proteins. We describe here the evolution of the MBD proteins and argue that the vertebrate MBD complement evolved to exploit the benefits and protect against the dangers of a globally methylated genome.

Amino Acid Sequence↗

Transcytosis of nanoparticle and dendrimer delivery systems: evolving vistas.

The translocation of particulate matter across the gastrointestinal tract is now a well documented phenomenon offering new potential for the delivery of drugs with poor dissolution profiles and labile chemistries via encapsulation in biodegradable nanoparticles. The last few years have seen an acceleration in the number of publications describing the varying facets of this approach and the multidisciplinary nature of this field. This review delineates data from this rather fragmented area and from cognate fields to provide a physicochemical viewpoint of the importance of surface chemistries of oral drug delivery vehicles and their interactions in and with gut contents prior to uptake. The role of lymphoid and non-lymphoid tissues is examined, and the role of bioadhesion is discussed. The exciting potential of molecular encapsulation of drugs via dendrimers and star branched molecules is discussed in the context of nanotechnological applications for the oral route. Evolving vistas include a better understanding of the plasticity of the intestinal epithelium and M-cell induction as well as the influence of disease states on particulate uptake. In this review we address a number of issues deemed vital to an understanding of the subject including (i) some background knowledge on particulate uptake (the subject of several reviews), (ii) factors affecting uptake such as diameter and surface charge and character, (iii) the dynamic nature of particle interactions in the gut, (iv) the dynamic nature of the processes of capture, adhesion, uptake, transcytosis and translocation, and (v) the influence of surface ligands.

Administration, Oral↗

A slowly evolving brachial plexus injury following a proximal humeral fracture in a child.

The association of fractures and neurological injuries is well recognized, especially with certain upper limb fractures. Typically, the nerve injury occurs at the time of initial fracture displacement. A case is reported of an unusual combination of fracture and nerve injury in a child, with the extremely rare occurrence of a slowly evolving nerve injury. The potential for delayed nerve injury following a fracture needs to be appreciated to prevent delays in diagnosis and treatment.

Brachial Plexus↗

Evolving microbes and re-emerging streptococcal disease.

Microbes will evolve and the epidemics they cause will continue to occur in the future as they have in the past. Microbes emerge from the evolutionary stream as a result of genetic events and selective pressures that favor new over old. It is nature's way. Microbes and vectors swim in the evolutionary stream, and they swim much faster than humans. Bacteria reproduce every 30 minutes and, for them, a millennium is compressed into a fortnight. They are "fleet afoot," and the pace of research must keep up with them or they will overtake. Microbes were here on Earth 2 billion years before humans arrived, learning every trick of the trade for survival, and they are likely to be here 2 billion years after we depart. Current research on the rise and decline of epidemics is broadly based and includes evolutionary and population genetics of host-microbe relationships. Within this context, the 19th century pandemic of scarlet fever has been described. The possibility is raised that the GAS, which currently cause STSS, possess some of the virulence factors that caused pandemic scarlet fever. Furthermore, the GAS isolated during the recent outbreaks of ARF in certain locales in the United States have the virulence properties of the GAS frequently isolated in the first half of the 20th century. Finally, it is suggested that the strategy to confront emerging infectious diseases should be the study of infectious diseases from all points of view. They remain the greatest threats to our society.

Acute Disease↗

DiGIR1 and NaGIR1: naturally occurring group I-like ribozymes with unique core organization and evolved biological role.

The group I-like ribozyme GIR1 is a unique example of a naturally occurring ribozyme with an evolved biological function. GIR1 generates the 5'-end of a nucleolar encoded messenger RNA involved in intron mobility. GIR1 is found as a cis-cleaving ribozyme within two very different rDNA group I introns (twin-ribozyme introns) in distantly related organisms. The Didymium GIR1 (DiGIR1) and Naegleria GIR1 (NaGIR1) share fundamental features in structural organization and reactivity, and display significant differences when compared to the related group I splicing ribozymes. GIR1 lacks the characteristic P1 segment present in all group I splicing ribozymes, it has a novel core organization, and it catalyses two site-specific hydrolytic cleavages rather than splicing. DiGIR1 and NaGIR1 appear to have originated from eubacterial group I introns in order to fulfil a common biological challenge: the expression of a protein encoding gene in a nucleolar context.

Animals↗

Expanded divalent metal-ion tolerance of evolved ligase ribozymes.

Class I ligases are artificial ribozymes that catalyze the joining of two single-stranded RNAs. These ribozymes are between 120 and 160 nucleotides in length, making them intermediate in size for catalytic RNAs. Previous characterization of the b1-207 ribozyme suggests that it behaves similar to larger ribozymes in terms of divalent metal-ion dependence. This molecule displays a strong preference for magnesium for catalysis, and is inactive in any other metal except manganese, which actually inhibits its operation in magnesium. Here, we sought to examine the metal-ion usages of two ligases that were obtained through continuous evolution in vitro from the b1-207 sequence framework. We found an expanded catalytic range for the E(100)(#3) and B(16)(#19) ribozymes, as they are both catalytically active in calcium and strontium, and less inhibited by manganese. Though not selected for activity in these salts, the evolved ribozymes exhibit several adaptations to in vitro catalysis, and their ability to accommodate metals other than magnesium can be viewed as an example of a molecular exaptation.

Base Sequence↗

An example of design optimization for high evolvability: string rewriting grammar.

As an example of the optimization of an evolutionary system design, a string rewriting system is studied. A set of rewriting rules that defines the growth of a string is experimentarily optimized in terms of maximizing the 'replicative capacity', that is the occurrence ratio of self-replicating strings. It is shown that the most optimized rule set allows many strings to self-replicate by using a special character able to copy an original string sequentially. Then, using various different rewriting rule sets, the connectivity between self-replicating strings is studied. A set of 'hyperblobs' covering the self-replicating strings is extracted and their connectivity is studied. The experimental results show that a large replicative capacity assures strong connectivity between self-replicating genotypes, making the system highly evolvable.

Algorithms↗

What does it take to evolve behaviorally complex organisms?

What genotypic features explain the evolvability of organisms that have to accomplish many different tasks? The genotype of behaviorally complex organisms may be more likely to encode modular neural architectures because neural modules dedicated to distinct tasks avoid neural interference, i.e. the arrival of conflicting messages for changing the value of connection weights during learning. However, if the connection weights for the various modules are genetically inherited, this raises the problem of genetic linkage: favorable mutations may fall on one portion of the genotype encoding one neural module and unfavorable mutations on another portion encoding another module. We show that this can prevent the genotype from reaching an adaptive optimum. This effect is different from other linkage effects described in the literature and we argue that it represents a new class of genetic constraints. Using simulations we show that sexual reproduction can alleviate the problem of genetic linkage by recombining separate modules all of which incorporate either favorable or unfavorable mutations. We speculate that this effect may contribute to the taxonomic prevalence of sexual reproduction among higher organisms. In addition to sexual recombination, the problem of genetic linkage for behaviorally complex organisms may be mitigated by entrusting evolution with the task of finding appropriate modular architectures and learning with the task of finding the appropriate connection weights for these architectures.

Adaptation, Physiological↗

From electrical wiring to plastic neurons: evolving approaches to the study of pain.

Clinical and animal experimental evidences accumulated during the past four decades indicate an evolving change, championed by Patrick D. Wall, from the old concept of a specific pain pathway and hard-wired nervous system to a dynamic concept of plastic neural mechanisms underlying nociceptive processing like other sensory neural functions. These include: (1) the reciprocal sharing and interaction of various somatic sensory modalities between the ascending pathways; (2) the activation of spinal gating mechanisms through a dorsal column brainstem spinal loop; (3) the role of plastic changes in the nervous system in the production and maintenance of chronic pain; (4) the evidence showing that processing of nociception involves the activation of a diffuse network of transmitting fiber tracts and brain centers that are not exclusively devoted to pain; and (5) the consideration of chronic pain, at least in part, as a sign or reflection of a dysfunction in neuroimmune-endocrine regulations.

Animals↗

A myoglobin evolved from indoleamine 2,3-dioxygenase, a tryptophan-degrading enzyme.

The distribution, isolation, spectral and oxygen-binding properties, stability of ferrous state (autoxidation), amino acid sequence and gene structure of indoleamine 2,3-dioxygenase (IDO)-like myoglobins are summarized, and their evolution is discussed. Although it has long been thought that all hemoglobins and myoglobins have evolved from a common ancestral gene encoding a 14-16 kDa polypeptide, the discovery of IDO-like myoglobin from several gastropod molluscs clearly indicates that there was an alternative pathway for myoglobin evolution.

Amino Acid Sequence↗

The psychoneuroimmunological system: a recently evolved networking organ system.

The phenomenon of psychological influences on immune activity and general physiology has generated a great deal of interest in the last decade. Several theories have been proposed to understand the evolution and the nature of this bi-directional communication and/or influence. It is shown that the existing theories do not fully explain most phenomena associated with this communication. A theory--the networking organ theory--is also suggested that could resolve the issue. The information obtained from recent studies on evolutionary history and the fossil record have been used as the basis for understanding the phenomenon of psychoneuroimmunology. In essence, we are not looking at the unification of the mind and the body, but at a recently evolved system that lends sophistication to the existing connection between the mind and the body.

Animals↗

Morphostasis: an evolving perspective.

In an earlier article, I proposed a pathway by which morphostasis (tissue homeostasis) may have evolved. It began in single-celled organisms and culminated in the mammalian immune system. This evolutionary path is now traced from its source--the intracellular surveillance within an isolated cell of its own internal health. Morphostasis sequentially incorporates heat shock proteins, apoptosis, cell adhesion molecules, complement components, gap junctions, phagocytes, natural killer cells, cytotoxic T-cells, helper cells and antibodies. I propose that the sequence leading to the insertion of gap junctions is an ancestor of the complement attack sequence. Although contentious, this deduction is intriguing, since numerous, minimal clues support the proposition. The broad hypothesis emphasizes a theme that may prove to be a useful framework on which to hang a better understanding of immunology and embryology. It highlights points where a concentrated research effort may rapidly advance our understanding of both.

Animals↗

Studies of intestinal lymphoid tissue. XIII. Immunopathology of the evolving celiac sprue lesion.

Observations, by computerised image-analysis on the evolution of flat mucosae in two celiac sprue patients, are described. Initial immunopathologic features comprised infiltration of epithelium of normal villi by small, non-mitotic lymphocytes, accompanied by crypt hypertrophy and increased crypt cell mitotic activity. The subsequent development, several years later, of flat mucosae was accompanied by mitotic, "immunoblastoid" EL thus fulfilling the diagnostic criteria for celiac sprue. These sequential phases in the evolving flat celiac mucosa parallel experimental graft-versus-host reactions, suggesting that they are fundamentally cell-mediated in type. In becoming flat, it appears obligatory for the mucosa to pass through the early "proliferative-infiltrative" stage in which crypt hypertrophy is a prominent feature.

Adult↗

MSY2: a slowly evolving minisatellite on the human Y chromosome which provides a useful polymorphic marker in Chinese populations.

We present the second human Y-specific minisatellite, MSY2 (DYS440). It consists of three or four copies of a 99-110bp repeat unit and is located about 1kb upstream of the DBY gene. The most common allele contains four units, but a three-unit allele has arisen on at least four occasions; in chimpanzees and orangutans, MSY2 contains only two units. It is therefore evolving slowly and provides a particularly useful polymorphic marker for Chinese populations.

Alleles↗

Nonsurgical reperfusion in evolving myocardial infarction.

Nonsurgical recanalization of the occluded coronary artery has been performed in patients with evolving myocardial infarction since the late 1970s by intracoronary administration of thrombolytic agents at the ostium of the occluded artery or directly to the site of occlusion. The authors review the basic concepts underlying intracoronary thrombolysis, the method applied at their institution and the clinical results. Reperfusion of totally occluded arteries or termination of the ischemic state in subtotally occluded arteries was achieved in 71 (87.7%) of 81 patients. Reocclusion occurred in four patients, in three of these at a time when anticoagulation became temporarily ineffective, emphasizing the need for uninterrupted anticoagulation with a partial thromboplastin time longer than 80 seconds. Thallium scintigraphic studies before and after reperfusion showed a decrease in defect, indicating myocardial salvage, in the successful cases but not in failures or untreated control subjects. A decrease in thallium-201 defect was followed by improvement of regional wall motion and usually also left ventricular ejection fraction. Three of the patients with an unsuccessful result and one patient with a successful result died. Bypass surgery was performed electively in 18 patients because of multiple vessel involvement. Intracoronary thrombolysis appears to be a relatively safe and promising procedure. A large controlled study will be needed for definitive assessment of its role in the management of acute myocardial infarction.

Adult↗