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Molecular heterochrony in the early development of Drosophila.

Heterochrony, the relative change of developmental timing, is one of the major modes of macroevolutionary change; it identifies temporally disassociated units of developmental evolution. Here, we report the results of a fine-scale temporal study for the expression of the developmental gene hairy and morphological development in three species of Drosophila, D. melanogaster, D. simulans, and D. pseudoobscura. The results suggest that between and among closely related species, temporal displacement of ontogenetic trajectory is detected even at the earliest stage of development. Overall, D. simulans shows the earliest expression, followed by D. melanogaster, and then by D. pseudoobscura. Setting D. melanogaster as the standard, we find the approximate time to full expression is accelerated by 13 min, 48 s in D. simulans and retarded by 24 min in D. pseudoobscura. Morphologically, again with D. melanogaster setting the standard, initiation of cellularization is faster in D. simulans by 15 min, 42 s; and initiation of morphogenesis is faster in D. simulans by 18 min, 7 s. These results seem to be consistent with the finding that the approximate time to full expression of hairy is accelerated by 13 min, 48 s in D. simulans. On the other hand, the same morphological events are delayed by 5 min, 32 s, and by 11 min, 32 s, respectively, in D. pseudoobscura. These delays are small, compared with the 24-min delay in full expression. The timing changes, in total, seem consistent with continuous phyletic evolution of temporal trajectories. Finally, we speculate that epigenetic interactions of hairy expression timing and cell-cycle timing may have led to morphological differences in the terminal system of the larvae.

Animals↗

Comprehensive analysis of two Alu Yd subfamilies.

Alu elements have inserted in the human genome throughout primate evolution. A small number of Alu insertions have occurred after the divergence of humans from nonhuman primates and therefore should not be present in nonhuman primate genomes. Most of these recently integrated Alu elements are contained with a series of discrete Alu subfamilies that are related to each other based upon diagnostic nucleotide substitutions. We have extracted members of the Alu Yd subfamily that are derivatives of the Alu Y subfamily that share a common 12-bp deletion that defines the Yd lineage from the draft sequence of the human genome. Analysis of the Yd Alu elements resulted in the recovery of two new Alu subfamilies, Yd3 and Yd6, which contain a total of 295 members (198 Yd3 and 97 Yd6). DNA sequence analysis of each of the Alu Yd subfamilies yielded age estimates of 8.02 and 1.20 million years old for the Alu Yd3 and Yd6 subfamilies, respectively. Two hundred Alu Yd3 and Yd6 loci were screened using polymerase chain reaction (PCR) assays to determine their phylogenetic origin and associated levels of human genomic diversity. The Alu Yd3 subfamily appears to have started amplifying relatively early in primate evolution and continued propagating albeit at a low level as many of its members are found in a variety of hominoid (humans, greater and lesser ape) genomes. Only two of the elements are polymorphic in the human genome and absent from the genomes of nonhuman primates. By contrast all of the members of the Alu Yd6 subfamily are restricted to the human genome, with 12% of the elements representing insertion polymorphisms in human populations. A single Alu Yd6 locus contained an independent parallel forward insertion of a paralogous Alu Sq sequence in the owl monkey. These Alu subfamilies are a source of genomic fossil relics for the study of primate phylogenetics and human population genetics.

Alu Elements↗

Distribution and frequency of a polymorphic Alu insertion at the plasminogen activator locus in humans.

We have investigated the frequency distribution, across a broad range of geographically dispersed populations, of alleles of the polymorphic Alu insertion that occurs within the 8th intron of the tissue plasminogen, activator gene (PLAT). This Alu is a member of a recently derived subfamily of Alu elements that has been expanding during human evolution and continues to be transpositionally active. We used a "population tube" approach to screen 10 chromosomes from each of 19 human populations for presence or absence of this Alu in the PLAT locus and found that all tested populations are dimorphic for presence/absence of this insertion. We show that the previously published EcoRI, HincII, PstI, TaqI, and XmnI polymorphisms at the PLAT locus all result from insertion of this Alu and we use both restriction fragment length polymorphism and polymerase chain reaction analysis to examine the frequency of Alu(+) and Alu(-) alleles in a sample of 1003 individuals from 27 human populations and in 38 nonhuman primates. Nonhuman primates are monomorphic for the Alu(-) allele. Human populations differ substantially in allele frequency, and in several populations both alleles are common. Our results date the insertion event prior to the spread and diversification of modern humans.

Base Sequence↗

Co-sleeping, an ancient practice: issues of the past and present, and possibilities for the future.

Co-sleeping-infants sharing the mother's sleep space-has prevailed throughout human evolution, and continued over the centuries of western civilization despite controversy and blame of co-sleeping mothers for the deaths of their infants. By the past century, "crib death" was recognized, later identified as Sudden Infant Death Syndrome (SIDS), and generally found to occur more frequently during bed sharing. Pediatricians warned parents of the dangers of SIDS and other risks of bed sharing, and the frequency of bed sharing decreased markedly over the years. However, during recent decades, bed sharing began to increase, though major issues were raised, including: whether bed sharing actually exacerbates or is protective against the occurrence of SIDS, whether the practice facilitates breast feeding, whether bed sharing is beneficial for an infant's development, and other concerns. Dissention may soon be diminished by use of a crib which opens at the mother's bed-side and is becoming a popular approach to mother-and-infant closeness through the night.

Adult↗

The nature of living systems.

Living systems theory (LST) is concerned with eight levels of living systems, each of which is composed of 20 critical subsystems that carry out essential life processes. As a result of a continuous biosocial evolution involving progressive fray-out of components, the more recently developed levels in this hierarchy have become very complex. A brief summary of LST is presented in this article. Following this is a detailed analysis of current knowledge about the timer, which we have recently included in our list of subsystems.

Animals↗

Depth-dependent mechanical properties of enamel by nanoindentation.

Nanoindentation has recently emerged to be the primary method to study the mechanical behavior and reliability of human enamel. Its hardness and elastic modulus were generally reported as average values with standard deviations that were calculated from the results of multiple nanoindentation testing. In such an approach, it is assumed that the mechanical properties of human enamel are constant, independent of testing parameters, like indent depth and loading rate. However, little is known if they affect the measurements. In this study, we investigated the dependence of the hardness and elastic modulus of human enamel on the indent depth. We found that in a depth range from 100 to 2000 nm the elastic moduli continuously decreased from approximately 104 to 70 GPa, and the hardnesses decreased from approximately 5.7 to 3.6 GPa. We then considered human enamel as a fiber-reinforced composite, and used the celebrated rule of mixture theory to quantify the upper and lower bounds of the elastic moduli, which were shown to cover the values measured in the current study and previous studies. Accordingly, we attributed the depth dependence of the hardness and modulus to the continuous microstructure evolution induced by the nanoindenter tip.

Compressive Strength↗

A unified model of immune response. II: Continuum approach.

In an earlier paper in this journal (1990, J. theor. Biol. 145, 207-215) we developed a unified model for normal immune response, autoimmune response and AIDS, where the concentration of each type of cell involved in the immune response is represented by a discrete automaton and the population dynamics of the relevant cells are formulated in terms of dynamical maps in discrete time. In this paper we study the continuum version of this unified model where the cell concentrations are represented by real variables whose evolution with continuous time is described by differential equations. We discuss possible ways to extend this model incorporating new experimental results and to generalize it along the new emerging trends in network theories of immune response. Our work also illustrates some of the relative advantages and disadvantages of the discrete and continuum formulations of the models of immune response.

Autoimmunity↗

Nef and LTR sequence variation from sequentially derived human immunodeficiency virus type 1 isolates.

Variation in HIV-1 nef and LTR DNA sequences was assessed longitudinally during disease progression in four HIV-1-infected subjects. Point mutations were found among quasispecies obtained at a single time point in each individual, with increasing diversity with disease progression in two of three patients for whom sufficient data were available for analysis. Deletions and rearrangements were more common in late than early stages of disease. Continued sequence evolution in HIV-1 quasispecies with nef deletions along with coexistence of nef-bearing quasispecies suggest that nef-deleted quasispecies are capable of replication in vivo, possibly complemented by quasispecies lacking such deletions and/or by adaptation to a specialized niche within the patients.

Amino Acid Sequence↗

Settlement formation. Part I: a dynamic theory.

"The dynamic process of settlement formation is a fundamental issue in regional science. Our proposed model integrates the economic and migratory sectors in terms of endogenous variables in order to describe the evolution of continuous population distributions as a self-organising process.... The purpose...is to show that under strongly idealised conditions, a population consisting of different subpopulations with different economic activities will evolve into a differentiated population pattern. Each member of the subpopulations has the possibility to migrate between locations stimulated by rational economic reasons. This idea, which seems almost self-evident on the level of qualitative argumentation, [will] be cast into a mathematically self-contained quantitative dynamic model."

Behavior↗

Multiple drug resistance genotype causing failure of antiretroviral treatment in an HIV-infected patient heavily exposed to nucleoside analogues.

A 37-year-old homosexual man began antiretroviral combination therapy with didanosine (ddI), lamivudine (3TC) and indinavir (IDV) after being exposed previously to zidovudine (ZDV), ddI and 3TC in different sequential regimens. The patient's viral load did not fall below a detectable level despite his adherence to drug therapy, which was considered optimal. Stavudine (d4T) was prescribed in the third month of treatment instead of ddI without any evident improvement in the treatment response. A point mutation nested PCR assay showed that the patient carried a virus with a codon Q151M mutation, which confers multiple drug resistance to nucleoside analogues. Genetic sequence analysis showed that, despite none of the classically associated mutations to Q151M being present at the beginning of treatment, continuous genetic evolution under selective drug pressure allowed the virus to accumulate mutations at codons 62, 74 and 116 over time. As expected, the CD4+ cell count declined during the study period, and the viral load remained detectable.

Adult↗

Characterization of a new chromosomal marker for acute lymphoblastic leukemia from a long-term cell line.

A bone marrow aspirate from a child with acute lymphoblastic leukemia (ALL) at first relapse was used to establish cell line # 697. The cultured line and marrow aspirates taken at initial diagnosis and first relapse were examined and compared. Similarities in all patterns evaluated confirmed the leukemic origin of the line. Morphologically, the cells were typically lymphoblastic. Cytochemically, they were slightly acid phosphatase-positive and negative for peroxidase, ASD chloroacetate esterase, and nonspecific esterase. Immunologically, they were found positive for common-ALL antigen (CALLA), Ia-associated antigen, terminal deoxynucleotidyl transferase (TdT), and cytoplasmic IgM (cIgM) and slightly positive for surface IgM (sIgM). Testing for Epstein-Barr virus (EBV) capsid antigen was also positive. Cytogenetic evaluations performed on initial, relapse, and cell line specimens each revealed the presence of a pseudodiploid cell line characterized by a consistent marker chromosome. GTG-, QFQ-, and RF-banding identified the marker as being derived from a translocation involving chromosomes #7 and #19: t(7;19) (q11;q13). Iso 7q, -5, -9, and +2 were also found in significant association with the marker and were viewed as demonstrating continued karyotypic evolution within the cell line. From these data, cell line #697 has been classified as a leukemic line of B-cell lineage in a transitional stage between pre-B and mature B cells.

B-Lymphocytes↗

Multidisciplinary considerations in cancer treatment: origin and scope.

The Tumor Board constitutes the control area where multidisciplinary protocols are created and where each patient's circumstance is thoroughly reviewed from the perspective of all pertinent clinical disciplines. Such input is an essential component of quality control at all levels of management of the cancer patient. This pertains whether in a community hospital or in a specialized cancer center. Cooperative groups and other research organizations have recognized the essential nature of this input, especially for the integration of new measures with those therapeutic modalities that are already established. Thus treatment may show a logical evolution by continuously updating standard approaches through clinical trials posing the most relevant question from the point of view of all modalities, while maintaining stringent quality control. Examples of questions being posed by therapeutic advances in testicular and ovarian cancer are described. The key element in accomplishing these advances is multidisciplinary participation.

Combined Modality Therapy↗

Benign sinonasal neoplasms: a focus on inverting papilloma.

Benign sinonasal neoplasms are a pathologic and clinically varied group of tumors. Inverting papilloma is a notable member of this group, and it is renowned for its high rate of recurrence, its ability to cause local destruction, and its association with malignancy. This article aimed to familiarize the clinician with all the practical aspects of inverting papilloma and its management. The treatment algorithm for this tumor has undergone a complex evolution that continues today.

Bone Neoplasms↗

First results of Liguria-Trento transplant network project: a model for a macroregional network and real-time registry in Italy.

In Italy, health-care telematic is funded and supported at the level of national government or regional institutions. In 1999, the Italian Ministry of Health started to fund the Liguria-Trento Transplant Network (LTTN) project, a health research project with the aim to build an informative system for donor management and transplantation activity in a macroregional area. At the time of LTTN project proposal, no published Transplant Network Informative System fulfilled Italian rules on telematic management of electronic documentation concerning transplantation activity. Partnership of LTTN project were two Regional Transplant Coordinating Centres, Nord Italia Transplant Interregional Coordinating Centre and the Italian Institute of Health/National Transplant Coordinating Centre. Project Total Quality Management methods were adopted. Technological and case analysis followed ANSI-HL7, CEN-TC251, and Object-Oriented Software Engineering standards. A low-tech prototype powered by a web access relational database is running on a transplant network including web-based clients located in 17 intensive care units, in Nord Italia Transplant Interregional Coordinating Centre, and at the Italian Institute of Health/National Transplant Coordinating Centre. LTTN registry includes pretransplant, surgical, and posttransplant phases regarding liver, kidney, pancreas, and kidney-pancreas transplantation in adult and pediatric recipients. Clinical specifications were prioritized in agreement with the RAND/UCLA appropriateness method. Further implementation will include formal rules for data access and output release, fault tolerance, and a continuous registry evolution plan.

Humans↗

Technologies that make administration of vaccines safer.

There is an ever-expanding technology that is aimed at making the administration of vaccines safer. Conventional ways of administering vaccines are being upgraded, modified or replaced by a wide variety of innovations. The paradigm of liquid vaccines, needles and syringes is slow to change, but already developments are occurring that will change for ever the way vaccines are administered and will improve the safety record of immunization. The oral route of vaccine administration has generally been thought of as safe, but until now only the polio vaccine has been widely used in this way. The conventional method of vaccine administration is by injection. Many ingenious devices have become available that now make injecting safer. Inventors are now looking imaginatively to alternative routes and technologies for delivering vaccines. Vaccines are generally manufactured to extremely high standards and rarely are shown to be the cause of safety issues. People remain the weakest safety link is vaccine administration. Technologies that bypasses the ability of man to make bad decisions or to behave incorrectly are of tremendous value. The vaccine world is in the middle of a radical re-think about how vaccines might best be administered. The presentation of the vaccine can be altered to fit new technologies such as powder jet guns, or skin patches. Even the conventional needle and syringe have evolved to much safer versions, and are set to continue this evolution. All this means even safer vaccines and their delivery.

Drug Compounding↗

Apparent elimination of EIAV ancestral species in a long-term inapparent carrier.

Equine infectious anemia virus (EIAV) envelope variation produces newly dominant quasispecies with each sequential disease cycle; new populations arise, and previous plasma quasispecies, including the original inoculum, become undetectable. The question remains whether these ancestral variants exist in tissue reservoirs or if the immune system eliminates quasispecies from persistent infections. To examine this, an EIAV long-term inapparent carrier was immune suppressed with dexamethasone. Immune suppression resulted in increased plasma viral loads by approximately 10(4) fold. Characterization of pre- and post-immune suppression populations demonstrated continual envelope evolution and revealed novel quasispecies distinct from defined populations from previous disease stages. Analysis of the tissue and plasma populations post-immune suppression indicated the original infectious inoculum and early populations were undetectable. Therefore, the host immune system apparently eliminated a diverse array of antigenic variants, but viral persistence was maintained by relentless evolution of new envelope populations from tissue reservoirs in response to ongoing immune pressures.

Animals↗

Why are the genomes of endosymbiotic bacteria so stable?

The comparative analysis of three strains of the endosymbiotic bacterium Buchnera aphidicola has revealed high genome stability associated with an almost complete absence of chromosomal rearrangements and horizontal gene transfer events during the past 150 million years. The loss of genes involved in DNA uptake and recombination in the initial stages of endosymbiosis probably underlies this stability. Gene loss, which was extensive during the initial steps of Buchnera evolution, has continued in the different Buchnera lineages since their divergence.

Buchnera↗

Carpal tunnel syndrome: a historical perspective.

Historical reports about carpal tunnel syndrome (CTS) exist from its first description in 1854 to current developments. Although now a well-recognized entity, it took nearly 100 years from its initial description before accurate pathophysiology was determined and agreed upon by the medical community. Along the way, many individuals have contributed to our present understanding of CTS. Stumbling blocks have included a delay of many years for accurate anatomical localization, as well as incorrect initial surgical treatment selection without scientific basis. By the middle of the 20th century, the standard of care for CTS had reached the standard of our modern era, based on scientific study and documentation. By the latter half of the 20th century, pathophysiology had been established, diagnostic signs and testing had been well evolved, and surgical techniques had become refined. Emerging frontiers being explored from the late 20th century into the new millennium include and incorporate advances in diagnostic and surgical technology and equipment. Patient demographics have also shown evolution. Controversies continue and more research is needed to establish more definitive criteria as to causation of CTS by various factors, including repetitive stress.

Carpal Tunnel Syndrome↗