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At least 505 records · Page 28Linked to original sources
PubMed2005

Quantitative magnetization transfer by trains of radio frequency pulses in human brain: extension of a free evolution model to continuous-wave-like conditions.

A theoretical model of free evolution between repeated magnetic transfer (MT) pulses was extended to continuous-wave (CW)-like conditions showing that only the repetitive "direct" saturation of bulk water changes the transient and stationary behavior. The influence of the pulse repetition period (PR) on progressive saturation was studied in cortical gray matter (GM) and central white matter (WM) under conditions of short periods of free evolution and strong macromolecular saturation. Interpulse delays of 3 ms were achieved in vivo on a 1.5-T MR system with bell-shaped MT pulses of 12-ms duration and nominal flip angles of up to 1440 degrees and single-shot readout by a stimulated echo acquisition mode localization sequence. The frequency offset was chosen between 1 and 3 kHz to avoid excessive direct saturation. The stationary MT ratio (MTR) followed an inverse linear PR dependence, showing a consistent partial saturation of about 90% at zero PR for both WM and GM. Comparison to a relaxation-matched liquid indicated the presence of MT, but not necessarily of direct saturation. The transient behavior indicated considerable direct saturation, but this could also be explained by MT. These inconsistencies showed that the intervals of time evolution in our experiments were too long to be modeled by CW-like conditions. Free evolution takes place during the whole PR rather than during the interpulse delay only. Quantification using the rates of free evolution theory yielded the saturations and rate constants necessary to explain the observed behavior. The theory of rapid CW-like pulsing provides an upper limit for the rate of progressive saturation. This limit is approached at PR below an estimated value of 5 ms. The phenomenological PR dependence of the steady-state MTR may indicate that MT exceeded the direct saturation. Unlike to an idealized CW experiment, the extrapolated value at zero PR is subject to direct effects and not a physically meaningful constant.

Adult↗
PubMed2023

Phylogeny and evolution of SARS-CoV-2 during Delta and Omicron variant waves in India.

SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was reported in patients without comorbidity (97%), while Omicron BA.2 was reported in patients with comorbidity (77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2. Higher propensity of Omicron variants to bronchial tissue, probably ensured increased transmission while Omicron BA.2 became the prevalent variant possibly due to evolutionary trade-off. Virus evolution continues to shape the epidemic and its culmination.Communicated by Ramaswamy H. Sarma.

SARS-CoV-2↗
PubMed2006

A molecular time-scale for eukaryote evolution recalibrated with the continuous microfossil record.

Recent attempts to establish a molecular time-scale of eukaryote evolution failed to provide a congruent view on the timing of the origin and early diversification of eukaryotes. The major discrepancies in molecular time estimates are related to questions concerning the calibration of the tree. To limit these uncertainties, we used here as a source of calibration points the rich and continuous microfossil record of dinoflagellates, diatoms and coccolithophorids. We calibrated a small-subunit ribosomal RNA tree of eukaryotes with four maximum and 22 minimum time constraints. Using these multiple calibration points in a Bayesian relaxed molecular clock framework, we inferred that the early radiation of eukaryotes occurred near the Mesoproterozoic-Neoproterozoic boundary, about 1100 million years ago. Our results indicate that most Proterozoic fossils of possible eukaryotic origin cannot be confidently assigned to extant lineages and should therefore not be used as calibration points in molecular dating.

Amoeba↗
PubMed1992

Polymerase evolution and organism evolution.

The continuing exploration of the structure-function relationships of polymerases and the use of polymerases as phylogenetic tools complement each other, as seen in the literature for the past year. DNA-dependent RNA-polymerase gene sequences, in particular, have been used both to define functional domains in the protein encoded and recently to explore fundamental questions in evolution.

Animals↗
PubMed2005

Refactoring bacteriophage T7.

Natural biological systems are selected by evolution to continue to exist and evolve. Evolution likely gives rise to complicated systems that are difficult to understand and manipulate. Here, we redesign the genome of a natural biological system, bacteriophage T7, in order to specify an engineered surrogate that, if viable, would be easier to study and extend. Our initial design goals were to physically separate and enable unique manipulation of primary genetic elements. Implicit in our design are the hypotheses that overlapping genetic elements are, in aggregate, nonessential for T7 viability and that our models for the functions encoded by elements are sufficient. To test our initial design, we replaced the left 11,515 base pairs (bp) of the 39,937 bp wild-type genome with 12,179 bp of engineered DNA. The resulting chimeric genome encodes a viable bacteriophage that appears to maintain key features of the original while being simpler to model and easier to manipulate. The viability of our initial design suggests that the genomes encoding natural biological systems can be systematically redesigned and built anew in service of scientific understanding or human intention.

Algorithms↗
PubMedDate not supplied

Achieving cardiovascular health through continuing interprofessional development.

In order to achieve cardiovascular health for all Canadians, the ACHIC (Achieving Cardiovascular Health in Canada) partnership advocates that health promotion for healthy lifestyles be incorporated into practice, and that the consistent messages and professional skills required to motivate patients and the public be acquired through interprofessional education and development. Professional education specialists are essential members of health care promotion teams with expertise to develop educational interventions that impact behaviours of health professionals and subsequent patient outcomes. Continuing medical education (CME) is in evolution to continuing professional development (CPD), and then to continuing inter-professional development (CID). Providers of health promotion, public health, and health care can work with health educators to complete the cascade of learning, change in practice, and improvement in patient outcomes. The Canadian health care system can empower Canadians to achieve cardiovascular health, the most important health challenge in the 21st century.

Behavior Therapy↗
PubMed1998

Continuous renal replacement therapy: evolution in technology and current nomenclature.

The evolution of technology and biomaterials has permitted a parallel development of renal replacement therapies in the acute, critically ill patient. From the original description of continuous arteriovenous hemofiltration (CAVH), new techniques such as continuous venous venous hemofiltration (CVVH), hemodiafiltration (HDF) and high flux dialysis (HFD) have been developed and clinically utilized. A parallel improvement in efficiency has been achieved with daily clearances of urea as high as 50 liters or more. The use of special highly permeable dialyzers has also permitted increases in the clearances of larger solutes, thus leading to significant removals of chemical substances involved the acute inflammation and sepsis. In this field, recent observations have suggested the use of hemofiltration with high volumes of fluid exchange. The hardware and software of the newer continuous renal replacement therapy (CRRT) systems are certainly the key points in achieving these results and in safely performing such challenging techniques.

Acute Kidney Injury↗
PubMed2003

Technical evolution of laparoscopic radical prostatectomy after 450 cases.

BACKGROUND AND PURPOSE: In 1998, laparoscopic radical prostatectomy with primary access to the seminal vesicles was introduced. In 1999, we developed a laparoscopic technique similar to the classic retropubic radical prostatectomy. We focus here on the continuous technical evolution of our technique. PATIENTS AND METHODS: From March 1999 to May 2002, we performed 450 laparoscopic radical prostatectomies. All important data of the patients; data concerning the performance of the procedure, including technical modifications, conversion, reintervention, and complication rate; as well as follow-up information were documented contemporaneously. The patients were divided into three groups of 150 individuals each in order to analyze the influence of the technical evolution of the procedure. Additionally, we studied the transferability of our technique, comparing the learning curves of the three surgeons involved in the program. RESULTS: The technical modifications included the routine use of a voice-controlled robot (AESOP) for the camera, exposure of the apex with 120 degrees retracting forceps, a free-hand suturing technique instead of the Endostitch device for the dorsal vein complex, 5-mm clipping instead of bipolar coagulation for the nerve-sparing technique, initial 6 o'clock suturing of the urethra before complete division, control of the prostatic pedicles by use of 12-mm Hemo-lok clips instead of the Ultracision or Endo-GIA, the bladder neck-sparing technique in cases of T(1c) and T(2a) tumors, and interrupted instead of continuous sutures for the vesicourethral anastomosis. All these modifications resulted in a significant decrease in operating time and the rates of transfusion, open conversion, and reintervention. The introduction of the nerve-sparing technique increased the number of tumor-positive margins. The mean operating time of the third surgeon was significantly less than that of the first surgeon, but the transfusion, conversion, and reintervention rates did not differ significantly among the surgeons. CONCLUSIONS: Laparoscopic radical prostatectomy has undergone continuous technical evolution resulting in a significant improvement of the operative results. Although we were able to demonstrate the transferability of this difficult procedure, we feel that it should be performed only at centers of expertise.

Adult↗
PubMed2023

Intra-Host Evolution Provides for the Continuous Emergence of SARS-CoV-2 Variants.

Variants of concern (VOC) in SARS-CoV-2 refer to viruses whose viral genomes differ from the ancestor virus by ≥3 single-nucleotide variants (SNVs) and that show the potential for higher transmissibility and/or worse clinical progression. VOC have the potential to disrupt ongoing public health measures and vaccine efforts. Still, too little is known regarding how frequently new viral variants emerge and under what circumstances. We report a study to determine the degree of SARS-CoV-2 sequence evolution in 94 patients and to estimate the frequency at which highly diverse variants emerge. Two cases accumulated ≥9 SNVs over a 2-week period and one case accumulated 23 SNVs over 3 weeks, including three nonsynonymous mutations in the spike protein (D138H, E554D, D614G). The remainder of the infected patients did not show signs of intra-host evolution. We estimate that in as much as 2% of hospitalized COVID-19 cases, variants with multiple mutations in the spike glycoprotein emerge in as little as 1 month of persistent intra-host virus replication. This suggests the continued local emergence of variants with multiple nonsynonymous SNVs, even in patients without overt immune deficiency. Surveillance by sequencing for (i) viremic COVID-19 patients, (ii) patients suspected of reinfection, and (iii) patients with diminished immune function may offer broad public health benefits. IMPORTANCE New SARS-CoV-2 variants can potentially disrupt ongoing public health measures and vaccine efforts. Still, little is known regarding how frequently new viral variants emerge and under what circumstances. Based on this study, we estimate that in hospitalized COVID-19 cases, variants with multiple mutations may emerge locally in as little as 1 month, even in patients without overt immune deficiency. Surveillance by sequencing for continuously shedding patients, patients suspected of reinfection, and patients with diminished immune function may offer broad public health benefits.

Humans↗
PubMed1979

Evolution of multiple genome mutations during long-term persistent infection by vesicular stomatitis virus.

Persistent infection of BHK21 cells was established with cloned vesicular somatitis virus plus purified Dl particles and maintained in vitro for over 5 years. After 1 year of persistence, the infectious virus RNA genome had evolved several oligonucleotide map changes, and numerous changes had accumulated by 3.5 years. Additional evolution occurred by the fourth year and continued until the fifth year. In contrast, repeated passage of virus in acute infections of several cell types in vitro or in vivo did not lead to detectable oligonucleotide map changes. The short Dl particle originally used to co-infect with infectious virus in establishing persistent infection has been displaced by an ever present and constantly changing population of other Dl particles of differing sizes and radically differing oligonucleotide maps. We conclude that the genomes of both infectious VSV and its Dl particles undergo continuous evolutionary change during years of persistence. In the infectious virus, these changes involve hundreds of mutations which are usually expressed as poorly replicating, temperature-sensitive, small plaque mutants. These are stable mutants which do not revert to wild-type when passaged repeatedly in acute infections at 37 or 33 degrees C. It appears that the sequestered intracellular environment of persistently infected cells favors rapid and continuous virus evolution.

Animals↗
PubMed2004

Epigenetic tinkering and evolution: is there any continuity in the role of cytosine methylation from invertebrates to vertebrates?

The function of DNA methylation has been investigated in depth in vertebrate and plant genomes, establishing that it is involved in gene silencing and transposon control. Data regarding insect methylation, even if still scanty, apparently argue against evolutionary conservation of DNA methylation functions. Cytosine methylation, therefore, proves to be an epigenetic tool repeatedly used to accomplish different functions in different taxa according to a sort of epigenetic tinkering occurring during evolution.

Animals↗
PubMed1994

Evolution of antigen drift/switching: continuously evading pathogens.

Following infection to a host, some pathogens repeatedly alter their antigen expression, and thereby escape the immune defense (antigen drift/switching). This paper examines the evolutionarily stable mutation rate of pathogens which maximizes the stationary pathogen density in a host. Assumptions are: (i) most mutations are deleterious but a minor fraction, p, of mutations can contribute to the alternation of antigenic property of the pathogen; and. (ii) potential antigen types can be indexed in a one-dimensional lattice (the stepping-stone model). The model reveals that: (a) if the mutation rate is higher than a threshold mu(c) = R0/(1-p), where R0 is the per capita growth rate of pathogen before the immune system is activated, pathogens cannot maintain themselves because too many progeny are lost by lethal mutations; (b) if the mutation rate lies between zero and mu(c), the system converges to a traveling wave of antigen variants with a constant wave speed; (c) the evolutionarily stable mutation rate microESS is unexpectedly high: more than 0.25 per genome per replication even if most mutations are lethal. Hence more than a fourth of progeny are born defective in the evolutionarily stable state; (d) the microESS is even higher if multiple infections by pathogens are common. The paper also studies the evolutionarily stable mutation rate if every mutant antigen belongs to a different type (the infinite allele model), and the evolution of antigen switching between a finite number of antigen variants stored in the pathogen genome.

Alleles↗
PubMed2002

Evolution of bacteriophage in continuous culture: a model system to test antiviral gene therapies for the emergence of phage escape mutants.

The emergence of viral escape mutants is usually a highly undesirable phenomenon. This phenomenon is frequently observed in antiviral drug applications for the treatment of viral infections and can undermine long-term therapeutic success. Here, we propose a strategy for evaluating a given antiviral approach in terms of its potential to provoke the appearance of resistant virus mutants. By use of Q beta RNA phage as a model system, the effect of an antiviral gene therapy, i.e., a virus-specific repressor protein expressed by a recombinant Escherichia coli host, was studied over the course of more than 100 generations. In 13 experiments carried out in parallel, 12 phage populations became resistant and 1 became extinct. Sequence analysis revealed that only two distinct phage mutants emerged in the 12 surviving phage populations. For both escape mutants, sequence variations located in the repressor binding site of the viral genomic RNA, which decrease affinity for the repressor protein, conferred resistance to translational repression. The results clearly suggest the feasibility of the proposed strategy for the evaluation of antiviral approaches in terms of their potential to allow resistant mutants to appear. In addition, the strategy proved to be a valuable tool for observing virus-specific molecular targets under the impact of antiviral drugs.

Allolevivirus↗
PubMed2006

The antibody repertoire in evolution: chance, selection, and continuity.

All jawed vertebrates contain the genetic elements essential for the function of the adaptive/combinatorial immune response, have diverse sets of natural antibodies resulting from segmental gene recombination, express comparable functional repertoires and can produce specific antibodies following appropriate immunization. Profound variability occurs in the third hypervariable (CDR3) segments of light and heavy chains even within antibodies of the same ostensible specificity. Germline VH and VL elements, as well as the joining (J) segments are highly conserved among the distinct vertebrate species. Conservation is particularly noted among the VH3-like sequences of all jawed vertebrates in the FR2 and FR3 segments, as well as in the FGXGT(R or K)L J-segment characteristic of light chains and TCRs and the WGXGT(uncharged)VT JH segments. Human VH3-53 and Vlambda6 family orthologs may be present over the entire range of vertebrates. Models of the three-dimensional structures of shark VH/VL combining sites indicate similarity in framework structure and comparable CDR usage to those of man. Although carcharhine shark VH regions show greater than 50% identity to the human VH germline prototype, searches of lower deuterostome and invertebrate databases fail to detect molecules with significant relatedness. Overall, antibodies of jawed vertebrates show tremendous individual diversity, but are constructed incorporating design features that arose with the evolutionary emergence of the jawed vertebrates and have been conserved through at least 450 million years of evolutionary time.

Amino Acid Sequence↗
PubMed2001

Evolution of immunosuppression and continued importance of acute rejection in renal transplantation.

As steady improvement in short-term kidney graft survival and long-term outcomes prolongs the lives of transplant patients, responsibility for their care is shifting away from transplant specialists and into the hands of community nephrologists. Therefore, community nephrologists need to have a deeper understanding of immunosuppressive therapies than ever before. Pharmacologic immunosuppression has been continuously evolving over the past two decades. Azathioprine was introduced in the early 1960s. Introduction of cyclosporine (CsA) in 1983 revolutionized short-term outcomes after renal transplantation. The first monoclonal antibody immunosuppressant, OKT3, was introduced in 1986. The 1990s saw the introduction of a number of important new agents, including mycophenolate mofetil (MMF), tacrolimus, and a microemulsion CsA, as well as two new monoclonal antibodies. Combinations of these new agents, along with improving clinical care, have produced 1-year patient survival approaching 100% and graft survival exceeding 90%. The newest class of agents, the first of which is sirolimus, is called target of rapamycin (TOR) inhibitors and is used with CsA for maintenance therapy. Immunosuppressive drug therapy after kidney transplantation continues to evolve. There is a variety of pharmacologic combinations from which to choose, based on immunologic risk and side effect profiles. As new regimens are developed, ongoing communications between the transplant center and community nephrologists will be required to implement therapeutic changes and optimize patient care successfully.

Graft Rejection↗