Caenorhabditis elegans Aging is Associated with a Decline in Proteostasis
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
Some of the first evidence that an aging proteome impacts the overall protein folding environment and the ability of cells and organisms to maintain proteostasis came from an important C. elegans study [68]. The temperature-sensitive mutations were used to detect age-dependent changes in proteostasis. Even in an otherwise wild-type background, these temperature-sensitive mutant proteins only folded correctly at the permissive temperature in young animals. As animals reached even the earliest stages of adulthood (animals were still within their reproductive prime), the temperature-sensitive proteins started to misfold, leading to their characteristic phenotypes even at what is usually a permissive temperature [68]. This means that something, such as accumulated protein damage, reached a critical point right at the transition to adulthood.
Viral Infections of the Lung
Lourdes R. Laraya-Cuasay, Walter T. Hughes in Interstitial Lung Diseases in Children, 2019
Each year federal health care agencies recommend the manufacture of updated inactivated (killed) vaccines based on epidemiologic studies conducted internationally and predictions from these of what specific strains will hit the U.S. during the coming year.32 Although these vaccines, like all vaccines, are imperfect in terms of efficacy and have a significant, but acceptable, incidence of untoward reactions, it has been clearly determined that certain groups of high-risk individuals should be vaccinated on an annual basis. These high-risk individuals include children with chronic disease, especially cardiorespiratory disease. The second priority in terms of CDC recommendations for influenza vaccine prophylaxis includes children with chronic metabolic disease (e.g., diabetes), renal dysfunction, anemia, immunosuppression, or asthma. Influenza vaccine may be a problem to children who have had anaphylaxis to eggs. Influenza vaccine has been demonstrated to be totally safe even in brittle asthmatics. The influenza vaccines available at this time are inactivated vaccines. At the present time, live attenuated or temperature-sensitive mutant vaccines are not routinely available.
Lipids of Aspergillus
Rajendra Prasad, Mahmoud A. Ghannoum in Lipids of Pathogenic Fungi, 2017
The effect of temperature on the composition of fatty acids has been studied using temperature-sensitive mutants. In A. nidulans, total lipids of mycelia showed an increase in the ratio of unsaturated to saturated fatty acids with an increase in the growth temperature of wild type strain,33 whereas the ratio of short-chain to long-chain fatty acids changed inversely with temperature. When the temperature-sensitive mutant was grown at a restrictive temperature, it physiologically adapted itself by decreasing the ratio of unsaturated to saturated fatty acids.
Factors affecting the preparation of nanocrystals: characterization, surface modifications and toxicity aspects
Published in Expert Opinion on Drug Delivery, 2023
Shirleen Miriam Marques, Lalit Kumar
Small-angle neutron scattering (SANS) is a method that can be employed to determine structural characteristics at the nanoscale and to investigate modifications taking place in a substance due to various handling and processing techniques as well as changes occurring in-situ [163,164]. Any alterations in the surface structure of crystals could be investigated through fractal dimension parameters and/or the specific surface area. Moreover, for crystalline substances, the data acquired through SANS could be utilized to correlate alterations taking place on the atomic scale, as probed through diffraction, with structural modifications on the nanoscale [163]. Costabile and coworkers performed SANS on nanocrystals conjugated with PEG to deliver a filamenting temperature-sensitive mutant Z protein inhibitor to the lungs. The damaging effects of interaction with mucin were perceptible at a larger scale, i.e. on the nanocrystal size. Concerning the release pattern, the SANS results suggested that the nanocrystals underwent partial dissolution when incubated with mucin [165].
Clostridioides difficile: innovations in target discovery and potential for therapeutic success
Published in Expert Opinion on Therapeutic Targets, 2021
Tanya M Monaghan, Anna M Seekatz, Benjamin H Mullish, Claudia C. E. R Moore-Gillon, Lisa F. Dawson, Ammar Ahmed, Dina Kao, Weng C Chan
Berberine (9; Figure 2) is a poorly absorbed isoquinoline alkaloid present in numerous plants of the genera Berberis and Coptis. In China, berberine has been used as a herbal medicine to treat gastrointestinal disorders for millenia [131]. It possesses a range of pharmacological and biological activities, including anti-inflammatory and antimicrobial properties against bacteria, fungi, parasites, worms, and viruses. The significant antimicrobial function of berberine is mediated through its ability to inhibit the assembly of FtsZ (filamenting temperature-sensitive mutant Z) and halt bacterial cell division [132]. Mice gavaged with berberine (100 mg/kg/day) for 5 days following standard vancomycin treatment were prevented from developing a CDI relapse in a mouse model of CDI [133]. Combined therapy prevented weight loss, improved the disease activity and histopathology scores, and effectively decreased mortality. Berberine also restored vancomycin-induced dysbiosis by inhibiting the expansion of members of the family Enterobacteriaceae [133].