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a historical perspective on the discovery

Sean G Mack, Randi L Turner, Daniel J Dwyer
The dramatic spread and diversity of antibiotic-resistant pathogens has significantly reduced the efficacy of essentially all antibiotic classes, bringing us ever closer to a postantibiotic era. Exacerbating this issue, our understanding of the multiscale physiological impact of antimicrobial challenge on bacterial pathogens remains incomplete. Concerns over resistance and the need for new antibiotics have motivated the collection of omics measurements to provide systems-level insights into antimicrobial stress responses for nearly 20 years...
March 9, 2018: Trends in Microbiology
Monika Fuxreiter
The proposal that coupled folding to binding is not an obligatory mechanism for intrinsically disordered (ID) proteins was put forward 10years ago. The notion of fuzziness implies that conformational heterogeneity can be maintained upon interactions of ID proteins, which has a functional impact either on regulated assembly or activity of the corresponding complexes. Here I review how the concept has evolved in the past decade, via increasing experimental data providing insights into the mechanisms, pathways and regulatory modes...
February 22, 2018: Journal of Molecular Biology
Rex A Hess, Paul S Cooke
Estrogens have traditionally been considered female hormones. Nevertheless, the presence of estrogenic substances in males has been known for over 90 years. Initial work with estrogen suggested that it was deleterious to male reproduction because exogenous estrogen treatments induced developmental abnormalities. However, demonstrations of estrogen synthesis in the testis and high concentrations of 17β-estradiol (E2) in rete testis fluid suggested that the female hormone might have a function in normal male reproduction...
February 9, 2018: Biology of Reproduction
Samer Gnaim, Ori Green, Doron Shabat
The majority of known chemiluminescent compounds produce light through oxidation-dependent mechanisms. The unique notion of triggering chemiluminescence by a chemical reaction other than oxidation was first introduced by Schaap in 1987 with the development of chemically and enzymatically activated phenoxy-dioxetanes. Such dioxetanes are distinctive among chemiluminescent molecules since the oxidized high-energy species, the dioxetane, is stable for years at room temperature. Light emission is selectively activated by deprotection of the phenol-protecting group...
February 9, 2018: Chemical Communications: Chem Comm
Cristobal G Dos Remedios
In 2017, a Special Issue of Biophysical Reviews was devoted to "Titin and Its Binding Partners. The issue contained a review: "An historical perspective of the discovery of titin filaments" by dos Remedios and Gilmour that was intended to be a history of the discovery of the giant protein titin, previously named connectin. The review took readers back to the earliest discovery of the so-called third filament component of skeletal and cardiac muscle sarcomeres and ended in 1969. Recently, my colleague Shin'ichi Ishiwata gently reminded me of two papers published in 1990 and 1993 that were unwittingly omitted from the original historical perspective...
January 13, 2018: Biophysical Reviews
Charles J Kowalski, Adam J Mrdjenovich
In this essay, we defend the design of the Salk polio vaccine trial and try to put some limits on the role schemata should play in designing clinical research studies. Our presentation is structured as a response to de Freitas and Pietrobon (de Freitas, R. S. and R. Pietrobon. 2007. Whoever could get rid of the context of discovery/context of justification dichotomy? A proposal based on recent developments in clinical research. Journal of Medicine and Philosophy 32:25-42.) who identified the CONSORT statement as a schema that would have, had it existed at the time, ruled out the design of the Salk polio vaccine trial of 1954 in favor of a completely randomized controlled clinical trial (RCT)...
January 12, 2018: Journal of Medicine and Philosophy
Zoe Cournia, Bryce Allen, Woody Sherman
Accurate in silico prediction of protein-ligand binding affinities has been a primary objective of structure-based drug design for decades due to the putative value it would bring to the drug discovery process. However, computational methods have historically failed to deliver value in real-world drug discovery applications due to a variety of scientific, technical, and practical challenges. Recently, a family of approaches commonly referred to as relative binding free energy (RBFE) calculations, which rely on physics-based molecular simulations and statistical mechanics, have shown promise in reliably generating accurate predictions in the context of drug discovery projects...
December 15, 2017: Journal of Chemical Information and Modeling
Mehdi Arbabi-Ghahroudi
Tremendous effort has been expended over the past two and a half decades to understand many aspects of camelid heavy chain antibodies, from their biology, evolution, and immunogenetics to their potential applications in various fields of research and medicine. In this article, I present a historical perspective on the development of camelid single-domain antibodies (sdAbs or VH Hs, also widely known as nanobodies) since their discovery and discuss the advantages and disadvantages of these unique molecules in various areas of research, industry, and medicine...
2017: Frontiers in Immunology
Kirsten E Gardner
Soon after the discovery of insulin in the early 1920s, the popular press celebrated the miraculous discovery. Although insulin had no curative effect on the chronic state of diabetes, it was frequently heralded as a "cure." This paper examines how the discovery of insulin intersected with the rise of diabetic technology and the transfer of medical technology to the home setting. By analyzing diabetic manuals written for patients and physicians, letters exchanged between patient and physician, medical journals, magazines and newspapers, I trace how patients learned about insulin and more significantly how patients adopted measurement technologies designed to allow better home administration of insulin...
November 16, 2017: Journal of Medical Humanities
Elena Rivas-Marín, Damien P Devos
These are exciting times for PVC researchers! The PVC superphylum is composed of the bacterial phyla Planctomycetes, Verrucomicrobia, Chlamydiae (those three founders giving it its name), Lentisphaerae and Kirimatiellaeota as well as some uncultured candidate phyla, such as the Candidatus Omnitrophica (previously known as OP3). Despite early debates, most of the disagreements that surround this group of bacteria have been recently resolved. In this article, we review the history of the study of PVC bacteria, with a particular focus on the misinterpretations that emerged early in the field and their resolution...
October 20, 2017: Antonie Van Leeuwenhoek
Samuel S Hinman, Kristy S McKeating, Quan Cheng
No abstract text is available yet for this article.
November 7, 2017: Analytical Chemistry
Christopher B Geyer
No abstract text is available yet for this article.
October 12, 2017: Biology of Reproduction
Juan Manuel González-Rosa, Caroline E Burns, C Geoffrey Burns
Cardiovascular disease is the leading cause of death worldwide. Compared to other organs such as the liver, the adult human heart lacks the capacity to regenerate on a macroscopic scale after injury. As a result, myocardial infarctions are responsible for approximately half of all cardiovascular related deaths. In contrast, the zebrafish heart regenerates efficiently upon injury through robust myocardial proliferation. Therefore, deciphering the mechanisms that underlie the zebrafish heart's endogenous regenerative capacity represents an exciting avenue to identify novel therapeutic strategies for inducing regeneration of the human heart...
June 2017: Regeneration
Manuel A Garrido-Ramos
Satellite DNA represents one of the most fascinating parts of the repetitive fraction of the eukaryotic genome. Since the discovery of highly repetitive tandem DNA in the 1960s, a lot of literature has extensively covered various topics related to the structure, organization, function, and evolution of such sequences. Today, with the advent of genomic tools, the study of satellite DNA has regained a great interest. Thus, Next-Generation Sequencing (NGS), together with high-throughput in silico analysis of the information contained in NGS reads, has revolutionized the analysis of the repetitive fraction of the eukaryotic genomes...
September 18, 2017: Genes
Hui Peng, Rui Sun
Natural killer (NK) cells represent a heterogeneous population of innate lymphocytes with phenotypically and functionally distinct subsets. In particular, recent studies have identified a unique subset of NK cells residing within the liver that are maintained as tissue-resident cells, confer antigen-specific memory responses and exhibit different phenotypical and developmental characteristics compared with conventional NK (cNK) cells. These findings have encouraged researchers to uncover tissue-resident NK cells at other sites, and detailed analyses have revealed that these tissue-resident NK cells share many similarities with liver-resident NK cells and tissue-resident memory T cells...
September 18, 2017: Cellular & Molecular Immunology
Christopher M McGraw, Christopher S Ward, Rodney C Samaco
Neurobehavioral disorders comprised of neurodegenerative, neurodevelopmental, and psychiatric disorders together represent leading causes of morbidity and mortality. Despite significant academic research and industry efforts to elucidate the disease mechanisms operative in these disorders and to develop mechanism-based therapies, our understanding remains incomplete and our access to tractable therapeutic interventions severely limited. The magnitude of these short-comings can be measured by the growing list of disappointing clinical trials based on initially promising compounds identified in genetic animal models...
September 2017: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
Sam Henry, Bridget T McInnes
OBJECTIVES: This paper provides an introduction and overview of literature based discovery (LBD) in the biomedical domain. It introduces the reader to modern and historical LBD models, key system components, evaluation methodologies, and current trends. After completion, the reader will be familiar with the challenges and methodologies of LBD. The reader will be capable of distinguishing between recent LBD systems and publications, and be capable of designing an LBD system for a specific application...
October 2017: Journal of Biomedical Informatics
Fu-Shuang Li, Jing-Ke Weng
Plants have long been recognized for their therapeutic properties. For centuries, indigenous cultures around the world have used traditional herbal medicine to treat a myriad of maladies. By contrast, the rise of the modern pharmaceutical industry in the past century has been based on exploiting individual active compounds with precise modes of action. This surge has yielded highly effective drugs that are widely used in the clinic, including many plant natural products and analogues derived from these products, but has fallen short of delivering effective cures for complex human diseases with complicated causes, such as cancer, diabetes, autoimmune disorders and degenerative diseases...
July 31, 2017: Nature Plants
Lauren S Jackson, Dojin Ryu
A symposium entitled "Public Health Perspectives of Mycotoxins in Food" was held at the 251st American Chemical Society (ACS) Meeting in March 2016 in San Diego, CA, and was sponsored by the ACS Division of Agricultural and Food Chemistry. The purpose of the symposium was to convene the leading mycotoxin researchers throughout the world to discuss the current state of knowledge as well as research needs with respect to evaluating the toxicological properties of mycotoxins and ways to detect, control, and reduce human and animal exposure to these natural toxins...
August 23, 2017: Journal of Agricultural and Food Chemistry
Josef Flammer, Katarzyna Konieczka
This review describes the clinical and basic research that led to the description of Flammer syndrome. It is narrated from a personal perspective. This research was initiated by the observation of an increased long-term fluctuation of visual fields in a subgroup of glaucoma patients. As these patients had strikingly cold hands, peripheral blood flow was tested with a capillary microscopy, and vasospastic syndrome (VS) was diagnosed. Further studies on these patients revealed frequently weakened autoregulation of ocular blood flow and increased flow resistivity in retroocular vessels...
June 2017: EPMA Journal
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