Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inventions”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed2005

Site-saturation mutagenesis is more efficient than DNA shuffling for the directed evolution of beta-fucosidase from beta-galactosidase.

Protein engineers use a variety of mutagenic strategies to adapt enzymes to novel substrates. Directed evolution techniques (random mutagenesis and high-throughput screening) offer a systematic approach to the management of protein complexity. This sub-discipline was galvanized by the invention of DNA shuffling, a procedure that randomly recombines point mutations in vitro. In one influential study, Escherichia coli beta-galactosidase (BGAL) variants with enhanced beta-fucosidase activity (tenfold increase in k(cat)/K(M) in reactions with the novel para-nitrophenyl-beta-d-fucopyranoside substrate; 39-fold decrease in reactivity with the "native"para-nitrophenyl-beta-d-galactopyranoside substrate) were evolved in seven rounds of DNA shuffling and screening. Here, we show that a single round of site-saturation mutagenesis and screening enabled the identification of beta-fucosidases that are significantly more active (180-fold increase in k(cat)/K(M) in reactions with the novel substrate) and specific (700,000-fold inversion of specificity) than the best variants in the previous study. Site-saturation mutagenesis thus proved faster, less resource-intensive and more effective than DNA shuffling for this particular evolutionary pathway.

Base Sequence↗
PubMed2006

A new multi-electrode array design for chronic neural recording, with independent and automatic hydraulic positioning.

We report on a new microdrive design, which enables the construction of multi-electrode arrays capable of chronically recording the multi-unit neural activity of waking animals. Our principal motivation for inventing this device was to simplify the task of positioning electrodes, which consumes a considerable amount of time and requires a high level of skill. With the new microdrives, each electrode is independently and automatically driven into place. A hydraulic drive system is adopted to reduce the size, weight, and cost of the structure. The hydraulic fluid is also used as a part of the electrical circuit, and facilitates the wiring of the electrodes. A routing system has been attached to reduce the number of tube connections. The microdrive is cylindrical, has a diameter of 23.5 mm, a height of 37 mm, and a weight of 15 g. It allows for up to 22 electrodes, which are arranged on a 0.35 mm grid. Each electrode can be positioned at any depth up to approximately 4mm. The microdrive was evaluated under acute and chronic recording experiments, and is shown to be capable of automatically positioning each electrode and successfully recording the neural signals of waking rats.

Animals↗
PubMed2006

An intervention program for ADHD in patients with substance use disorders: preliminary results of a field trial.

The comorbidity of attention deficit hyperactivity disorder (ADHD) is frequently not well recognized in substance abuse treatment institutions in The Netherlands. As a consequence, patients with substance use disorder (SUD) and ADHD often receive suboptimal treatment. To prevent every treatment center from having to invent its own diagnostic procedure and intervention for ADHD, a national working group was established. This group developed an intervention program for the screening, diagnosis, and treatment of ADHD in patients with SUD. This article describes the development and content of this intervention program. An important part of this development was testing the intervention program in two addiction treatment centers in The Netherlands. Systematic screening of ADHD was part of the test. A self-report questionnaire was used. Subjects with positive screening results were referred for the diagnostic procedure. Nine hundred twenty-eight screenings were performed: 207 screened positive, 115 came for further diagnostics, and 65 were ultimately diagnosed with ADHD.

Activities of Daily Living↗
PubMed2006

Max Nitze, the cystoscope and urology.

PURPOSE: Maximilian Carl-Friedrich Nitze (1848 to 1906) designed the modern cystoscope, providing a foundation for urology. MATERIALS AND METHODS: The historical literature, including the original writings of Nitze, was reviewed. RESULTS: The invention of the cystoscope by Nitze revolutionized endoscopy but his true genius lay in his lifelong pursuit of better methods to diagnose and treat patients with urological diseases and in teaching others the practical use and value of cystoscopy. He also designed the first operating cystoscope, took the first endoscopic photographs and published the first textbook in urology. CONCLUSIONS: The legacy of discovery of Max Nitze established the specialty of urology and a legitimate claim as the father of urology.

Cystoscopes↗
PubMed2004

The discovery, isolation and identification of aldosterone: reflections on emerging regulation and function.

This paper has a focus on the early history of aldosterone. The Taits take us on a chronological trawl through the history in which they had a first hand role and made a major contribution-their bioassay was in many ways the key. The gifted Swiss chemists made a critical contribution to the scale and isolation of larger amounts. This was international collaboration at its best. Developing technologies were utilised as crucial cutting edge applications in the advancing front, technology transfer before the word was invented. Measurement of aldosterone and angiotensin were crucial advances to the understanding of the regulation of the hormone. In the period 1960-2003, some 30,000 papers mentioned aldosterone as a keyword, even so advances on a larger scale were slow. I have indicated some of my own work with the Howard Florey team using the adrenal autotransplant in the conscious sheep. Recently, the understanding of the role of induced proteins, the flow on from the RALES trial and the development of eplerenone has revitalised the aldosterone field.

Aldosterone↗
PubMed2004

siRNA technology.

RNA interference (RNAi) represents a mechanism invented by nature to protect the genome. In the past few years the field has emerged at a surprisingly high pace. The underlying molecular mechanism of gene silencing provides us with short interfering RNAs (siRNAs) which allows to target any gene with high specificity and efficiency. siRNAs can now be obtained in various ways allowing for numerous in vitro and in vivo applications. Successful knock-downs of disease-related genes indicate that siRNAs open the door for novel therapeutic procedures.

Animals↗
PubMed2005

Origin and evolution of the Trk family of neurotrophic receptors.

Among the numerous tyrosine kinase receptors, those belonging to the Trk family are distinctively involved in the development of complex traits within the vertebrate nervous system. Until recently, the lack of a proper Nt/Trk system in invertebrates has lead to the belief that they were a vertebrate innovation. Recent data, however, have challenged the field, and proved that bona fide Trk receptors do exist in invertebrates. Here, we review and discuss the evolutionary history of the Trk receptor family, and draw a comprehensive scenario that situates the origin of the Nt/Trk signalling prior to the origin of vertebrates. Probably, a ProtoTrk receptor was invented by means of domain and exon shuffling from pieces of ancient genes, generating the unique combination of domains found in extant Trk receptors. It is suggestive to propose that subtle protein mutations, gene duplications, and co-options in particular territories of a primitive Nt/Trk system were instrumental to the development of a complex vertebrate nervous system.

Animals↗
PubMed2006

The prospective preventative HIV vaccine based on modified poliovirus.

In order to control HIV pandemic, many vaccines are invented. Although none first verified its efficacy in clinic, we hypothesize that HIV vaccine based on poliovirus is potential to develop the promising one, because it can elicit the broad immune response including the main mucosal, humoral and cellular reaction. However, the viral neural virulence is one major concern. The attenuated Sabin strain is a better candidate. While partial poliovirus genes are replaced by HIV antigen genes, the defective interfering particle will fail to produce progeny virions, which may further ensure its security. Although the vaccinal immune efficacy was verified in some similar animal experiments based on poliovirus to express the exogenous genes, more animal and clinical immune trials about HIV-poliovirus chimeric minireplicons are to be carried out and the hypotheses are to be validated.

AIDS Vaccines↗
PubMed2004

Cytoskeletal elements in bacteria.

It has become clear recently that bacteria contain all of the cytoskeletal elements that are found in eukaryotic cells, demonstrating that the cytoskeleton has not been a eukaryotic invention, but evolved early in evolution. Several proteins that are involved in cell division, cell structure and DNA partitioning have been found to form highly dynamic ring structures or helical filaments underneath the cell membrane or throughout the length of the cell. These exciting findings indicate that several highly dynamic processes occur within prokaryotic cells, during growth or differentiation, that are vital for a wide range of cellular tasks.

Bacteria↗
PubMed2004

Paul Ehrlich--in search of the magic bullet.

In 2004, we celebrate the 150th anniversary of the birth of Paul Ehrlich, considered the founder of immunology. His life and work can be divided into three creative periods: first, he developed histological staining, then he accomplished his ground-breaking work on immunology, and eventually invented chemotherapy. Paul Ehrlich can be perceived as a man whose success was not the consequence of a will to power, but of his substantial interest in science.

Allergy and Immunology↗
PubMed2004

Development of a versatile cassette for directional genome walking using cassette ligation-mediated PCR and its application in the cloning of complete lipolytic genes from Bacillus species.

Since the invention of the PCR technology, adaptation techniques to clone DNA fragments flanking the known sequence continue to be developed. We describe a perfectly annealed cassette available in almost unlimited quantities with variable sticky-and blunt-end restriction enzyme recognition sites for efficient restriction and ligation with the restricted target genomic DNA. The cassette provides a 200-bp sequence, which is used to design a variety of cassette-specific primers. The dephosphorylation prevents cassette self-ligation and creates a nick at the cassette: target genome DNA ligation site suppressing unspecific PCR amplifications. We introduce the single-strand amplification PCR (SSA-PCR) technique where a lone known locus-specific primer is firstly used to enrich the targeted template DNA strand resulting in significant PCR product specificity during the second round conventional nested PCR. The distance between the known locus-specific primer and the nearest location of the restriction enzyme used determined the length of the obtained PCR product. We used this technique to walk downstream into the isochorismatase and upstream into the hypothetical conserved genes flanking the mature extracellular lipase gene from Bacillus licheniformis. We further demonstrated the potential of the technique as a cost-effective method during PCR-based prospecting for novel genes by designing "universal" degenerate primers that detected homologues of Family VII bacterial lipolytic genes in Bacillus species. The cassette ligation-mediated PCR was used to clone complete nucleotide sequences encoding functional lipolytic genes from B. licheniformis and Bacillus pumilus.

Amino Acid Sequence↗
PubMed2005

Scientific authorship. Part 1. A window into scientific fraud?

The examination of a single scientific manuscript seldom alerts scientists, reviewers, editors, and scientific administrators to the fabrication and falsification of data and information. This review shows that most documented cases of scientific fraud involve falsification (altering truthful information) and fabrication (inventing information where none previously existed). Plagiarism is much less frequent. The review of published accounts also shows that the publication of scientific papers containing recognizable fraudulent material is very low, probably less than 0.02% and extremely difficult to detect. Because most reported cases of fraud have involved research done at prestigious organizations with distinguished co-authors, and that is published in journals with exacting review processes, it becomes evident that some unscrupulous scientists are adept at fabricating and falsifying data. However, "significant" scientific fraud is detected when scientists repeatedly report results that cannot be independently verified, when colleagues report suspicious behavior, or scientific audits are performed. This review documents and compares many of the better-known cases of scientific fraud. Fraudulent behavior has served as the impetus for the scientific community to develop publication procedures and guidelines that help to guard against not only fraudulent behavior but also against other types of unethical or undesirable behaviors. A companion paper reviews the non-fraudulent issues associated with scientific publication.

Authorship↗
PubMed2004

Experimental evaluation of drills for extended frontal sinusotomy.

OBJECTIVE: Endonasal extended frontal sinusotomy is needed in rare cases of therapy-resistant chronic frontal sinusitis. Several types of burs have been invented to ablate strong bone in the frontal sinus access but nevertheless surgical results seem to differ significantly. The benefits and shortcomings of different burs are subjected to a comparative evaluation. STUDY DESIGN: Five cadaver specimens were duplicated by means of dental molding and casting techniques to provide identical microanatomy for comparative studies on frontal sinusotomy. Different burs (conventional straight bur, right-angled bur according to Blokmanis, and curved frontal sinus bur) were applied to create a type IIb frontal sinusotomy according to Draf in microanatomical replicas. The geometry of the frontonasal neoostium was measured and its dimensions were contrasted to the collateral damage. Bone ablation was calculated by repeated weighting and the area of damaged mucosa was quantified using a 3D analyzing system. RESULTS: A frontal sinus neoostium measuring 9 x 10 mm on average was created by type IIb frontal sinusotomy according to Draf. The complementary use of an angled bur showed some specific improvements that applied best to spacious anatomic specimens. Those specimens subjected to an extensive use of the straight drill revealed significant collateral damage forming a contrast to minor enlargement of the neoostium. The curved frontal sinus bur showed considerable technical insufficiencies. CONCLUSIONS: Judicious use of the straight drill is recommended for those rare cases of therapy-resistant frontal sinusitis treated by an extended type of frontal sinusotomy. New technical refinements of the curved frontal sinus burs should be subjected to repeated evaluation.

Cadaver↗
PubMed2005

Ross River virus: molecular and cellular aspects of disease pathogenesis.

Ross River virus (RRV) is a mosquito-borne alphavirus indigenous to Australia and the Western Pacific region and is responsible for several thousand cases of human RRV disease (RRVD) per annum. The disease primarily involves polyarthritis/arthralgia, with many patients also presenting with rash, myalgia, fever, and/or lethargy. The symptoms can be debilitating at onset, but they usually resolve within 3-6 months. Recent insights into the RRV-host relationship, associated pathology, and molecular biology of infection have generated a number of potential avenues for improved treatment. Although vaccine development has been proposed, the small market size and potential for antibody-dependent enhancement (ADE) of disease make this approach unattractive. Recent insights into the molecular basis of RRV-ADE and the virus's ability to manipulate host inflammatory and immune responses create potential new opportunities for therapeutic invention. Such interventions should overcome virus-induced dysregulation of protective host responses to promote viral clearance and/or ameliorate inflammatory immunopathology.

Alphavirus Infections↗
PubMed2006

Polynucleotide phosphorylase: an evolutionary conserved gene with an expanding repertoire of functions.

RNA metabolism plays a seminal role in regulating diverse physiological processes. Polynucleotide phosphorylase (PNPase) is an evolutionary conserved 3',5' exoribonuclease, which plays a central role in RNA processing in bacteria and plants. Human polynucleotide phosphorylase (hPNPase old-35) was cloned using an inventive strategy designed to identify genes regulating the fundamental physiological processes of differentiation and senescence. Although hPNPase old-35 structurally and biochemically resembles PNPase of other species, targeted overexpression and inhibition studies reveal that hPNPase old-35 has evolved to serve more specialized functions in humans. The present review provides a global perspective on the structure and function of PNPase and then focuses on hPNPase old-35 in the contexts of differentiation and senescence.

Cloning, Molecular↗
PubMed2004

Voronoi and Voronoi-related tessellations in studies of protein structure and interaction.

The three-dimensional structure of a protein can be modeled by a set of polyhedra drawn around its atoms or residues. The tessellation invented by Voronoi in 1908, and other tessellations of space derived from it, provide versatile representations of three-dimensional structures. In recent years, they have been used to investigate a series of issues relating to proteins: atom and residue volumes, packing, folding, interactions and binding.

Algorithms↗
PubMed2005

Evolutionary aspects of whole-genome biology.

A decade of access to whole-genome sequences has been increasingly revealing about the informational network relating all living organisms. Although at one point there was concern that extensive horizontal gene transfer might hopelessly muddle phylogenies, it has not proved a severe hindrance. The melding of sequence and structural information is being used to great advantage, and the prospect exists that some of the earliest aspects of life on Earth can be reconstructed, including the invention of biosynthetic and metabolic pathways. Still, some fundamental phylogenetic problems remain, including determining the root--if there is one--of the historical relationship between Archaea, Bacteria and Eukarya.

Biological Evolution↗
PubMed2006

Comparative genomics and structural biology of the molecular innovations of eukaryotes.

Eukaryotes encode numerous proteins that either have no detectable homologs in prokaryotes or have only distant homologs. These molecular innovations of eukaryotes may be classified into three categories: proteins and domains inherited from prokaryotic precursors without drastic changes in biochemical function, but often recruited for novel roles in eukaryotes; new superfamilies or distinct biochemical functions emerging within pre-existing protein folds; and domains with genuinely new folds, apparently 'invented' at the outset of eukaryotic evolution. Most new folds emerging in eukaryotes are either alpha-helical or stabilized by metal chelation. Comparative genomics analyses point to an early phase of rapid evolution, and dramatic changes between the origin of the eukaryotic cell and the advent of the last common ancestor of extant eukaryotes. Extensive duplication of numerous genes, with subsequent functional diversification, is a distinctive feature of this turbulent era. Evolutionary analysis of ancient eukaryotic proteins is generally compatible with a two-symbiont scenario for eukaryotic origin, involving an alpha-proteobacterium (the ancestor of the mitochondria) and an archaeon, as well as key contributions from their selfish elements.

Animals↗