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Misacylation of yeast amber suppressor tRNA(Tyr) by E. coli lysyl-tRNA synthetase and its effective repression by genetic engineering of the tRNA sequence.

Through an exhaustive search for Escherichia coli aminoacyl-tRNA synthetase(s) responsible for the misacylation of yeast suppressor tRNA(Tyr), E. coli lysyl-tRNA synthetase was found to have a weak activity to aminoacylate yeast amber suppressor tRNA(Tyr) (CUA) with L-lysine. Since our protein-synthesizing system for site-specific incorporation of unnatural amino acids into proteins is based on the use of yeast suppressor tRNA(Tyr)/tyrosyl-tRNA synthetase (TyrRS) pair as the "carrier" of unusual amino acid in E. coli translation system, this misacylation must be repressed as low as possible. We have succeeded in effectively repressing the misacylation by changing several nucleotides in this tRNA by genetic engineering. This "optimized" tRNA together with our mutant TyrRS should serve as an efficient and faithful tool for site-specific incorporation of unnatural amino acids into proteins in a protein-synthesizing system in vitro or in vivo.

Amino Acyl-tRNA Synthetases↗

The NLM Gateway: a metasearch engine for disparate resources.

The U.S. National Library of Medicine (NLM) has created a metasearch engine called the NLM Gateway at the URL "gateway.nlm.nih.gov". The Gateway allows the user to issue one search that takes place on multiple NLM retrieval engines. A composite result set is presented in several categories of information: journal citations; books, serials and audiovisuals; consumer health; meeting abstracts; and other collections.

Databases as Topic↗

Novel algorithms for searching conformational space.

The modelling of biological molecules by molecular dynamics is beset by a range of problems. The most important of these is the multiple-minima problem. The deep metastable minima can cause difficulties in proper equilibration of a molecular system and result in the simulated system being trapped in a long-lived metastable state. One way to overcome these problems is to re-engineer the 'Newtonian Rules' in order to more efficiently search conformational space. Re-engineering of the 'Newtonian Rules' implies a redesign of the physical laws arising from them. This is done in various ways by the RUSH, Hybrid Monte Carlo and PEACS algorithms. This paper explores applications of these algorithms, and compares them to a traditional molecular dynamics method.

Alanine↗

Cochlear prostheses. A state-of-the-art review.

Work on cochlear prostheses for the auditory rehabilitation of the profoundly deaf represents a challenging problem. Some early, but perhaps premature, surgical attempts have helped to bring the entire issue into focus. Systemic studies are now under way in many different places. Although the purely engineering problems as well as the surgical ones appear solvable at this time, the remaining unsolved problems lie in two areas: 1) the bioengineering interfacing, i.e., the search for methods needed to connect an engineering (electronic) device to the neural auditory system in an efficient manner; and 2) clinical tests for the assessment of the functional state of the cochlear nerve.

Acoustics↗

Osteoblastic phenotype expression of MC3T3-E1 cells cultured on polymer surfaces.

BACKGROUND: Current efforts in bone tissue engineering have as one focus the search for a scaffold material that will support osteoblast proliferation, matrix mineralization, and, ultimately, bone formation. The goal is to develop a bone substitute that is functionally equivalent to autograft bone. Previously published reports have shown that osteoblasts exhibit varying rates and degrees of proliferation and mineralization when grown on different surfaces. METHODS: This study presents a histologic and biomolecular analysis of MC3T3-E1 murine preosteoblast cells grown on poly(lactide-co-glycolide) (PLGA) versus poly(-caprolactone) (PCL), two commonly studied scaffold polymers. MC3T3-E1 cells were cultured on slides coated with either PLGA or PCL, and on uncoated glass slides as control, with six slides in each group. After 6 weeks in culture, the cells were stained for osteocalcin, alkaline phosphatase activity, and matrix mineralization. In addition, to assess the effects of the surface material on phenotypic expression at the molecular level, MC3T3-E1 cells were cultured on polymer-coated 24-well plates for 4 days, and analyzed by reverse transcription polymerase chain reaction for the expression of osteocalcin and alkaline phosphatase. RESULTS: The results showed that three groups of slides stained positively for osteocalcin at 6 weeks. However, markedly less alkaline phosphatase activity and mineralization were observed on the cells grown on PCL. Real-time polymerase chain reaction assays subsequently revealed decreased expression of both markers by cells cultured on PCL compared with PLGA. CONCLUSIONS: These results suggest that PCL does not support the full expression of an osteoblastic phenotype by MC3T3-E1 cells. PCL, therefore, is less desirable as a scaffold polymer in bone tissue engineering in so far as supporting bone formation is concerned. However, because PCL has favorable handling characteristics and strength, modifications of PCL may prompt further investigation.

3T3 Cells↗

A review and methodologic critique of the literature refuting whiplash syndrome.

The validity of whiplash syndrome has been a source of debate in the medical literature for many years. Some authors have published articles suggesting that whiplash injuries are impossible at certain collision speeds; others have stated that the problem is psychological, or is feigned as a means to obtain secondary financial gain. These articles contradict the majority of the literature, which shows that whiplash injuries and their sequelae are a highly prevalent problem that affects a significant proportion of the population. The authors of the current literature critique reviewed the biomedical and engineering literature relating to whiplash syndrome, searching for articles that refuted the validity of whiplash injuries. Twenty articles containing nine distinct statements refuting the validity of whiplash syndrome were found that fit the inclusion criteria. The methodology described in these articles was evaluated critically to determine if the authors' observations regarding the validity of whiplash syndrome were scientifically sound. The authors of the current critique found that all of the articles contained significant methodologic flaws with regard to their respective authors' statements refuting the validity of whiplash syndrome. The most frequently found flaws were inadequate study size, nonrepresentative study sample, nonrepresentative crash conditions (for crash tests), and inappropriate study design. As a result of the current literature review, it was determined that there is no epidemiologic or scientific basis in the literature for the following statements: whiplash injuries do not lead to chronic pain, rear impact collisions that do not result in vehicle damage are unlikely to cause injury, and whiplash trauma is biomechanically comparable with common movements of daily living.

Accidents, Traffic↗

Sitting biomechanics part I: review of the literature.

OBJECTIVE: To develop a new sitting spinal model and an optimal driver's seat by using review of the literature of seated positions of the head. spine, pelvis, and lower extremities. DATA SELECTION: Searches included MEDLINE for scientific journals, engineering standards, and textbooks. Key terms included sitting ergonomics, sitting posture, spine model, seat design, sitting lordosis, sitting electromyography, seated vibration, and sitting and biomechanics. DATA SYNTHESIS: In part I, papers were selected if (1) they contained a first occurrence of a sitting topic, (2) were reviews of the literature, (3) corrected errors in previous studies, or (4) had improved study designs compared with previous papers. In part II, we separated information pertaining to sitting dynamics and drivers of automobiles from part 1. RESULTS: Sitting causes the pelvis to rotate backward and causes reduction in lumbar lordosis, trunk-thigh angle, and knee angle and an increase in muscle effort and disc pressure. Seated posture is affected by seat-back angle, seat-bottom angle and foam density, height above floor, and presence of armrests. CONCLUSION: The configuration of the spine, postural position, and weight transfer is different in the 3 types of sitting: anterior, middle, and posterior. Lumbar lordosis is affected by the trunk-thigh angle and the knee angle. Subjects in seats with backrest inclinations of 110 to 130 degrees, with concomitant lumbar support, have the lowest disc pressures and lowest electromyography recordings from spinal muscles. A seat-bottom posterior inclination of 5 degrees and armrests can further reduce lumbar disc pressures and electromyography readings while seated. To reduce forward translated head postures, a seat-back inclination of 110 degrees is preferable over higher inclinations. Work objects, such as video monitors, are optimum at eye level. Forward-tilting, seat-bottom inclines can increase lordosis, but subjects give high comfort ratings to adjustable chairs, which allow changes in position.

Biomechanical Phenomena↗

Sensing effectors make sense.

'Housekeepers' of living organisms maintain salt and water balance, monitor blood sugar and schedule their work to the season and the time of day. In order to perform their chores, they rely on information about the status quo. The traditional concept of a sensor that communicates with a central comparator authorizing an effector, which was inspired by engineers, has become blurred in the search for morphological correlates of such regulatory cascades. In many cases, neurones, which are both sensory and neurosecretory, and endocrine cells equipped with smart detectors, reliably regulate autonomous functions by using local rather than central computing. Like the well-trained staff of a smoothly run household, such 'sensing effectors' translate information into action.

Animals↗

Patent coverage by abstracting services. 4. Coverage of microbiological patents.

The paper reports a study on the coverage by seven major abstracting services in the field of microbiology in regard to patents. Only three of the services--Chemical Abstracts, Microbiology Abstracts, Section A, and Food Science and Technology Abstracts--cover patents at all. We assessed the three services in terms of the information they provide about patents and then in terms of their performance in retrieving patents taken from a master list of patents on genetic engineering and Vitamin D, obtained by searches on World Patents Index. Timeliness of the three services was also assessed. We found that none of the standard abstracting services in the field cover patents satisfactorily and they are slow in picking up patents. The research demonstrates that by scanning just Japanese, Soviet, U.S., and British patents, both timely and comprehensive coverage of the microbiological patent literature can be obtained.

Abstracting and Indexing↗

Phage bioinformatics tools: a review of computational approaches for bacteriophage research.

Rising clinical interest in phage therapy and the exponential growth of metagenomic sequence catalogues have driven a rapid expansion of bacteriophage bioinformatics. More than 80 dedicated tools, mostly published since 2020, now span identification, assembly, annotation, taxonomy, lifestyle prediction, defence-system detection, and host prediction. Aimed at experienced practitioners and developers, this review synthesizes the field through the lens of three successive computational paradigms: sequence homology, bounded by database completeness; machine learning, constrained by labelled training data; and foundation models, which now achieve Matthews correlation coefficients above 0.95 in identification tasks and, through structure-informed prediction, raise functional annotation to over half of phage genes. Furthermore, we map the upstream components, namely, gene callers, homology engines, protein language models, and structural search tools, that underpin most downstream pipelines, exposing shared infrastructure and ecosystem-level fragility when dependencies change. To translate this into practice, we propose web-based and command-line reference workflows calibrated to user expertise and sample types. Finally, we set an agenda for the next wave of tool development. Roughly half of phage genes still resist functional annotation despite structural methods; no broadly generalizable strain-level host predictor exists for phage therapy; varying true-positive rates (0%-97%) underscore the absence of standardized community benchmarks analogous to Critical Assessment of Structure Prediction or Critical Assessment of Metagenome Interpretation. As generative genome models begin designing synthetic phages, progress will depend less on producing standalone tools than on rigorous evaluation, interoperable infrastructure, and clinically meaningful prediction targets.

Computational Biology↗

A disulfide-bound HIV-1 V3 loop sequence on the surface of human rhinovirus 14 induces neutralizing responses against HIV-1.

An immunogenic sequence from the V3 loop of the MN isolate of human immunodeficiency virus type 1 (HIV-1), His-Ile-Gly-Pro-Gly-Arg-Ala-Phe, was transplanted onto a surface loop of the VP2 capsid protein of human rhinovirus 14. To optimize for virus viability and immunogenicity of the transplanted sequence, the HIV sequence was flanked by (1) a cysteine residue that could form a disulfide bond and (2) randomized amino acids (in either of two arrangements) to generate numerous presentations of the Cys-Cys loop. The location for engineering in VP2 was chosen by searching the geometries of disulfide-bound loops in known protein structures. A model for the structure of the transplanted V3 loop sequence was developed using molecular dynamics and energy minimization calculations. Proteolytic digestion with and without reducing agent demonstrated the presence of the disulfide bond in the chimeric virus examined. Monoclonal and polyclonal antibodies directed against the V3 region of the HIV-1MN strain potently neutralized two chimeric viruses. Guinea pig antisera against two chimeric viruses were able to neutralize HIV-1MN and HIV-1ALA-1 in cell culture. The ability of chimeric viruses to elicit antibodies capable of neutralizing the source of the transplanted sequence could be favorable for vaccine development.

Animals↗

[Bibliometric analysis on tissue engineering research literatures].

OBJECTIVE: To comprehend the progress of tissue engineering research and speculate its developmental trends. METHODS: MEDLINE search was conducted to retrieve the papers published between 1987 to 1999 under the main headings of tissue engineering. Years, nationalities, languages, journals, authors and heading frequencies of 314 papers were analyzed by bibliometrics. RESULTS: Since 1990, the number of tissue engineering research literatures had doubled, and papers between 1998 and 1999 made up 57.96% of the total papers. All papers came from 15 nations, in 6 languages and 140 journals; 64.97% came from United States and 25.79% from England, Netherlands and Germany; 93.95% was in English; 42.04% was published on 15 journals. Vacanti JP and 19 other authors presented 5 to 24 papers. Heading frequencies were cytology 22.89%, transplantation 13.30%, scaffolds and extracellular matrixes 11.72%, implanting 10.60%, polymers 8.91%, potential applications 8.91%, artificial substitutes 6.88%, tissue culture 6.70% and biogenetics 4.96%. CONCLUSION: Tissue engineering literatures mainly come from United States, England, Netherlands and Germany. English is the major language. J Biomed Mater Res and 14 other journals are important journals about tissue engineering research. Vacanti JP and 19 other authors are prolific authors. Cytology, transplantation, scaffolds and extracellular matrixes and implanting are hot topics and key points on tissue engineering research.

Animals↗

A review and methodologic critique of the literature supporting 'chronic whiplash injury': part I - research articles.

The existence of a 'chronic whiplash injury' has been a source of debate in the medical literature for many years. Some authors have published articles suggesting that chronic whiplash syndrome is the result of chronic pathology (injury), and that this injury may occur at any collision speed; others have stated that any psychological factors are secondary rather than primary (etiologic) to the problem of chronic pain, or that secondary gain is a rare or uncommon phenomenon. These articles contradict scientific measures and efforts which show that for Quebec Task Force Grade 1 and 2 whiplash-associated disorders, the highly prevalent problem of chronic pain may be a culturally and psychosocially determined phenomenon, in which confounding psychosocial variables determine the behaviour and outcome following an otherwise benign acute injury. The authors of the current literature critique reviewed the biomedical and engineering literature relating to whiplash syndrome, searching for articles that supported the construct of 'chronic whiplash injuries'. Thirty seven articles containing fourteen distinct statements supporting the construct of 'chronic whiplash injuries' were found that fit the inclusion criteria. The methodology described in these articles was evaluated critically to determine if the authors' conclusions regarding 'chronic whiplash injuries' were scientifically sound. The authors of the current critique found that all of the articles contained significant methodologic errors relative to their respective authors' statements regarding chronic whiplash. The most frequent concerns reside with sampling, experimental design and interpretation of data.

Accidents, Traffic↗

A review and methodologic critique of the literature supporting 'chronic whiplash injury'. Part II. Reviews, editorials, and letters.

In an earlier publication (part I) we conducted a critique of the literature supporting whiplash as a 'chronic injury', specifically examining original research which contradicts scientific measures and efforts showing that the highly prevalent problem of chronic whiplash is a cultural and psychosocially determined phenomenon. We reviewed the biomedical and engineering literature relating to whiplash syndrome, searching for articles that supported the construct of 'chronic whiplash injuries' and found that all of the articles contained significant methodologic errors relative to their respective authors' statements regarding chronic whiplash. The most frequent concerns reside with sampling, experimental design and interpretation of data. In Part II of this critique we examine other article types (reviews, editorials, letters). The authors of the current critique found that these articles also contained significant errors or biases relative to their respective authors' statements regarding chronic whiplash. The most frequent concerns reside with terminology, citation methods, scientific reasoning, and lack of address of contrary evidence.

Bias↗

A biologically derived approach to tissue modeling.

Our approach to tissue modeling incorporates biologically derived primitives into a computational engine (CellSim) coupled with a genetic search algorithm. By expanding an evolved synthetic genome CellSim is capable of developing a virtual tissue with higher order properties. Using primitives based on cell signaling, gene networks, cell division, growth, and death, we have encoded a 64-cell cube-shaped tissue with emergent capacity to repair itself when up to 60% of its cells are destroyed. Other tissue shapes such as sheets of cells also repair themselves. Capacity for self-repair is an emergent property derived from, but not specified by, the rule sets used to generate these virtual tissues.

Cells↗

[Ecological/hygienic and toxicological evaluation of combustion products of aviation kerosene and liquefied natural gas].

Products of kerosene combustion in the present-day aeroengines contain more than 200 compounds of incomplete combustion, partial oxidation, and thermal decomposition of fuel and oil. Most of these are strong toxicants for humans. Increase of temperature in the turbine engine combustion chamber led to production of very toxic nitrogen oxides. In search for the ecologically safe and less toxic alternative attention of fuel engineers was drawn to liquefied natural gas which compares well and even excels kerosene in ecological, economic and many other respects.

Aircraft↗

Theoretical design of a gene therapy to prevent AIDS but not human immunodeficiency virus type 1 infection.

Recent reports confirm that, due to the presence of long-lived, latently infected cell populations, eradication of human immunodeficiency virus type 1 (HIV-1) from infected patients by using antiretroviral drugs will be exceedingly difficult. An alternative to virus eradication may be to use gene therapy to induce a pseudo-latent state in virus-producing cells, thus transforming HIV-1 into a lifelong, but manageable, virus. Conditionally replicating HIV-1 (crHIV-1) gene therapy vectors provide an avenue for subduing HIV-1 expression in infected cells (by creating a parasite, crHIV-1, of the parasite HIV-1), potentially reducing the HIV-1 set point and delaying AIDS onset. Development of crHIV-1 vectors has proceeded in vitro, but the requirements for a crHIV-1 vector to proliferate and persist in vivo have not been explored. We expand a widely accepted mathematical model of HIV-1 in vivo dynamics to include a crHIV-1 gene therapy virus and derive a simple criterion for designing crHIV-1 viruses that will persist in vivo. The model introduces only two new parameters-HIV-1 inhibition and crHIV-1 production-and both can be experimentally engineered and controlled. Analysis demonstrates that crHIV-1 gene therapy can indefinitely reduce HIV-1 set point to levels comparable to those achieved with highly active antiretroviral therapy, provided crHIV-1 production is more efficient than HIV-1. Paradoxically, highly efficient therapeutic inhibition of HIV-1 was found to be disadvantageous. Thus, the field may benefit by shifting the search for more potent antiviral genes toward engineering optimized therapy viruses that package ultra-efficiently while downregulating viral production moderately.

Acquired Immunodeficiency Syndrome↗

An automated PLS search for biologically relevant QSAR descriptors.

An automated PLS engine, WB-PLS, was applied to 1632 QSAR series with at least 25 compounds per series extracted from WOMBAT (WOrld of Molecular BioAcTivity). WB-PLS extracts a single Y variable per series, as well as pre-computed X variables from a table. The table contained 2D descriptors, the drug-like MDL 320 keys as implemented in the Mesa A&C Fingerprint module, and in-house generated topological-pharmacophore SMARTS counts and fingerprints. Each descriptor type was treated as a block, with or without scaling. Cross-validation, variable importance on projections (VIP) above 0.8 and q2 > or = 0.3 were applied for model significance. Among cross-validation methods, leave-one-in-seven-out (CV7) is a better measure of model significance, compared to leave-one-out (measuring redundancy) and leave-half-out (too restrictive). SMARTS counts overlap with 2D descriptors (having a more quantitative nature), whereas MDL keys overlap with in-house fingerprints (both are more qualitative). The SMARTS counts is the most effective descriptor system, when compared to the other three. At the individual level, size-related descriptors and topological indices (in the 2D property space), and branched SMARTS, aromatic and ring atom types and halogens are found to be most relevant according to the VIP criterion.

Automation↗