The Bare Essentials of Antibiotic Target Validation.
Ontology highlight
ABSTRACT:
SUBMITTER: Hedstrom L
PROVIDER: S-EPMC5520969 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
Publications
The Bare Essentials of Antibiotic Target Validation.
ACS infectious diseases 20161109 1
The convergence of competitive fitness experiments and phenotypic screening would seem to be an auspicious beginning for validation of an antibacterial target. IMPDH was already identified an essential protein in Mycobacterium tuberculosis when not one, but two, groups discovered inhibitors with promising antitubercular activity. A new target appeared to be born. Surprisingly, the two groups came to completely different conclusions about the vulnerability of IMPDH and its future as a drug target ...[more]
Similar Datasets
Project description:This chapter presents the essential characteristics of the coronavirus disease 2019 (COVID-19) coronavirus in terms of the physical, chemical, and biological attributes of the mutant strains causing the current global pandemic, with symptoms ranging from fever; dry cough; tiredness; loss of taste, smell, and speech; sore throat; and chest pain to difficulty in breathing and constituting a threat to the existence of humanity. Preliminary in silico studies of retrieved sequences for coronavirus isolates from some endemic countries, presented in this chapter, extensively revealed the true characteristics of the coronavirus isolates, ranging from molecular weight, total number of atoms, aliphatic index, instability index, extinction coefficient, theoretic isoelectric point, grand hydropathicity, total number of negatively and positively charged amino acids residues, secondary protein structure characteristics, variations in the tertiary protein 3D structures, and the guanine–cytosine content in the RNA sequence of the isolates. Preliminary in silico determination of genetic and thermal stability potentials of the isolates has also been revealed using the instability index, aliphatic index, guanine–cytosine content, hydropathicity, and half-life of the isolates in human reticulocytes in vitro. The scary characteristics of the coronaviruses were revealed in their ability to mutate at a faster rate producing many mutant copies of the virus that are not exact, thus conferring on it the ability to escape the host immune system. This probably is responsible for the resurgence of the viruses with varied characteristics and antigens that differ from the previous strains, thus giving room for the risk of a pandemic. This calls for a more concerted effort in studying the essentials and mutation rates of the viruses to be able to predict the future mutation rate and possible attributes with a view to finding a suitable therapy and drug design for the pandemic and for the biosecurity of humans against the virus in the future.
| S-EPMC8988929 | biostudies-literature
Project description:Aquaphotomics is a novel scientific discipline involving the study of water and aqueous systems. Using light-water interaction, it aims to extract information about the structure of water, composed of many different water molecular conformations using their absorbance bands. In aquaphotomics analysis, specific water structures (presented as water absorbance patterns) are related to their resulting functions in the aqueous systems studied, thereby building an aquaphotome-a database of water absorbance bands and patterns correlating specific water structures to their specific functions. Light-water interaction spectroscopic methods produce complex multidimensional spectral data, which require data processing and analysis to extract hidden information about the structure of water presented by its absorbance bands. The process of extracting information from water spectra in aquaphotomics requires a field-specific approach. It starts with an appropriate experimental design and execution to ensure high-quality spectral signals, followed by a multitude of spectral analysis, preprocessing and chemometrics methods to remove unwanted influences and extract water absorbance spectral pattern related to the perturbation of interest through the identification of activated water absorbance bands found among the common, consistently repeating and highly influential variables in all analytical models. The objective of this paper is to introduce the field of aquaphotomics and describe aquaphotomics multivariate analysis methodology developed during the last decade. Through a worked-out example of analysis of potassium chloride solutions supported by similar approaches from the existing aquaphotomics literature, the provided instruction should give enough information about aquaphotomics analysis i.e. to design and perform the experiment and data analysis as well as to represent water absorbance spectral pattern using various forms of aquagrams-specifically designed aquaphotomics graphs. The explained methodology is derived from analysis of near infrared spectral data of aqueous systems and will offer a useful and new tool for extracting data from informationally rich water spectra in any region. It is the hope of the authors that with this new tool at the disposal of scientists and chemometricians, pharmaceutical and biomedical spectroscopy will substantially progress beyond its state-of-the-art applications.
| S-EPMC6121091 | biostudies-literature
Project description:Application of infection prevention and control (IP&C) measures is synonymous with safety, quality, resource saving, and the rights of all patients, staff and visitors. An extensive literature review was undertaken to identify key IP&C measures that address pediatric-specific requirements, taking into account age-related factors, diseases that occur most frequently among pediatric populations, and the important role of the caregiver in prevention and disease transmission. IP&C initiatives that target and incorporate both human (intrinsic) and environmental (extrinsic) sources of infection are population specific and guide practices and provide safe caring environments when used appropriately. Categories of care specifically geared to the pediatric age-group (0-14 years) are divided into two categories: within-the-healthcare system and outside-of-the-healthcare setting. By taking into account the child's developmental age; physiological, psycho-social and immunological development; differing impacts on the body's natural defense mechanisms, including procedural, device type and length of utilization; and availability of specific technologies and disciplines, the caregiver IP&C strategies can be developed and tailored to address specific needs. Within-the-healthcare setting strategies focus on surveillance, standard and transmission-based precautions, the immune system, age-related factors, institutional regulations, the family and visitation. Outside the healthcare setting preventative and protective measures are vital for providing maximum and comprehensive care. Care provided within and outside the healthcare setting can either be independent of each other or work together to maximize the health and safety of the child. This review article highlights the importance of IP&C knowledge, need for strict adherence to approved standards, and need for auditing compliance to achieve the ultimate goal of providing safe, quality care as well as an infection-free environment.
| S-EPMC6372437 | biostudies-literature
Project description:BackgroundEssential tremor is regarded to be a disease of the central nervous system. Neuroimaging is a rapidly growing field with potential benefits to both diagnostics and research. The exact role of imaging techniques with respect to essential tremor in research and clinical practice is not clear. A systematic review of the different imaging techniques in essential tremor is lacking in the literature.MethodsWe performed a systematic literature search combining the terms essential tremor and familial tremor with the following keywords: imaging, mri, vbm, dwi, fmri, pet and spect, both in abbreviated form as well as in full form. We summarize and discuss the quality and the external validity of each study and place the results in the context of existing knowledge regarding the pathophysiology of essential tremor.ResultsA total of 48 neuroimaging studies met our search criteria, roughly divided into 19 structural and 29 functional and metabolic studies. The quality of the studies varied, especially concerning inclusion criteria. Functional imaging studies indicated cerebellar hyperactivity during rest and during tremor. The studies also pointed to the involvement of the thalamus, the inferior olive and the red nucleus. Structural studies showed less consistent results.Discussion and conclusionNeuroimaging techniques in essential tremor give insight into the pathophysiology of essential tremor indicating the involvement of the cerebellum as the most consistent finding. GABAergic dysfunction might be a major premise in the pathophysiological hypotheses. Inconsistencies between studies can be partly explained by the inclusion of heterogeneous patient groups. Improvement of scientific research requires more stringent inclusion criteria and application of advanced analysis techniques. Also, the use of multimodal neuroimaging techniques is a promising development in movement disorders research. Currently, the role of imaging techniques in essential tremor in daily clinical practice is limited.
| S-EPMC4110352 | biostudies-literature
Project description:With the rise of multi-drug resistant pathogens and the decline in number of potential new antibiotics in development there is a fervent need to reinvigorate the natural products discovery pipeline. Most antibiotics are derived from secondary metabolites produced by microorganisms and plants. To avoid suicide, an antibiotic producer harbors resistance genes often found within the same biosynthetic gene cluster (BGC) responsible for manufacturing the antibiotic. Existing mining tools are excellent at detecting BGCs or resistant genes in general, but provide little help in prioritizing and identifying gene clusters for compounds active against specific and novel targets. Here we introduce the 'Antibiotic Resistant Target Seeker' (ARTS) available at https://arts.ziemertlab.com. ARTS allows for specific and efficient genome mining for antibiotics with interesting and novel targets. The aim of this web server is to automate the screening of large amounts of sequence data and to focus on the most promising strains that produce antibiotics with new modes of action. ARTS integrates target directed genome mining methods, antibiotic gene cluster predictions and 'essential gene screening' to provide an interactive page for rapid identification of known and putative targets in BGCs.
| S-EPMC5570205 | biostudies-literature
Project description:ISG15 is an interferon-induced ubiquitin-like protein (Ubl) that has antiviral properties. The core E1, E2 and E3 enzymes for conjugation of human ISG15 are Ube1L, UbcH8 and Herc5, all of which are induced at the transcriptional level by Type 1 interferon signaling. Several proteomics studies have, together, identified over 300 cellular proteins as ISG15 targets. These targets include a broad range of constitutively expressed proteins and approximately 15 interferon-induced proteins. This chapter provides an overview of the target identification process and the validation of these targets. We also discuss the limited number of examples where the biochemical effect of ISG15 conjugation on target proteins has been characterized.
| S-EPMC5912676 | biostudies-other
Project description:Effectively delivering pharmaceutical aerosols to the lungs of preterm and term infants represents a considerable technical challenge. Small infants are obligatory nose breathers, they have small airways, low tidal volumes and rapid respiration rates. It is ethically unacceptable to investigate aerosol deposition in vivo in newborns due to ethical concerns about the radiation exposure involved in imaging studies and drug delivery and blood draws in pharmacokinetics studies. The purpose of the work reported in this article was thus to report the use of modeling to develop an understanding of the regional deposition of aerosols in neonates and to build a theoretical basis for choosing an optimum aerosol size to maximize delivery and minimize variability. Recent data on aerosol deposition in the nasal airways of newborn term and preterm infants was coupled to an established, scalable, lung deposition model to investigate the effects of age, aerosol size and ventilation on regional airway deposition. In the term newborn infant lung deposition ranged from 25% to 35% depending on Geometric Standard Deviations (GSDs). Intrasubject variability was minimized for aerosols with larger GSD. However, mean lung deposition is reduced with increasing GSD. A compromise between maximum lung deposition and increased intersubject variability appears to be in the region of GSDs of 1.75. In the 30-week GA preterm infant lung deposition is slightly higher than in the term infant despite smaller airways and lower tidal volumes. This is likely due to the lower inhaled flow rates that are concomitant with lower lung volumes. Finally, when aerosol delivery is directly to the trachea, as it would be if delivered via an endotracheal tube there is a monotonic increase in lung deposition with increasing aerosol size with peripheral deposition peaking at 2 to 3 µm. However, practical limitations of aerosol transport through endotracheal tubes, limiting delivered aerosol size, likely caps lung deposition at around 30% to 30% of the delivered dose.
| S-EPMC8105833 | biostudies-literature
Project description:Target vulnerability correlates the level of drug-target engagement required to generate a pharmacological response. High vulnerability targets are those that require only a relatively small fraction of occupancy to achieve the desired pharmacological outcome, whereas low vulnerability targets require high levels of engagement. Here, we demonstrate that the slope of the correlation between drug-target residence time and the post-antibiotic effect (PAE) can be used to define the vulnerability of bacterial targets. For macrolides, a steep slope is observed between residence time on the E. coli ribosome and the PAE, indicating that the ribosome is a highly vulnerable drug target. The analysis of the residence time-PAE data for erythromycin, azithromycin, spiramycin, and telithromycin using a mechanistic pharmacokinetic-pharmacodynamic model that integrates drug-target kinetics into predictions of drug activity lead to the successful prediction of the cellular PAE for tylosin, which has the longest residence time (7.1 h) and PAE (5.8 h). Although the macrolide data support a connection between residence time, PAE, and bactericidality, many bactericidal β-lactam antibiotics do not give a PAE, illustrating the role of factors such as protein resynthesis in the expression of target vulnerability.
| S-EPMC7150629 | biostudies-literature
Project description:BackgroundIt has been suggested that the benefits of drug-eluting stents compared to bare metal stents (BMS) have been overestimated in part because target lesion/vessel revascularization (TLR/TVR) rates in the BMS control group of these trials were spuriously high.MethodsWe used meta-analytic techniques to systematically compare clinical event rates among patients treated with BMS in trials where BMS were the experimental (BMS(experimental)) rather than the control (BMS(control)) intervention. MEDLINE searches were performed to identify eligible randomized trials comparing either drug-eluting stents with BMS(control) or BMS(experimental) with balloon angioplasty in patients with nonacute coronary artery disease. Trial characteristics and 6- to 12-month rates for death, myocardial infarction, TLR/TVR, and major adverse cardiac events were extracted and assessed.ResultsEligible trials yielded 50 BMS cohorts: 19 in the BMS(control) group (4046 patients) and 31 in the BMS(experimental) group (5068 patients). Summary death and infarction rates did not differ between groups. The summary TLR/TVR rates were 16.2% (95% CI 13.5-19.3) versus 13.8% (95% CI 12.0-15.7) in BMS(control) versus BMS(experimental) groups, respectively (P = .15). Among 39 BMS cohorts with < or = 250 patients, TLR/TVR rates were significantly higher in BMS(control) versus BMS(experimental) groups (18.9% [95% CI 16.0-22.2] vs 13.7% [95% CI 11.5-16.3], P = .01). There were no between-group differences among larger BMS cohorts (P = .98).ConclusionsAlthough overall clinical event rates did not differ in the BMS(control) and the BMS(experimental) groups, a higher rate of TVR/TLR was seen in the BMS(control) group among smaller trials.
| S-EPMC3065934 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-11-13 | GSE135151 | GEO