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Acute and Chronic Transforming Retroviruses
Published in Pimentel Enrique, Oncogenes, 2020
The protein product of M-MuSV strain 124 is the protein p31v-mos, which contains the sequences corresponding to the viral oncogene v-mos.56 The variant M-MuSV virus ts 110 is a temperature-sensitive mutant which produces at the permissive temperature (33°C) a 85,000-dalton gag-mos hybrid protein, termed p85gag-mos, but at the restricted temperature (39°C) express a 58,00-dalton gag protein, termed p58gag, which do not contain a viral oncogene product.57,58 This phenomenon is due to a temperature-sensitive RNA splicing event in which the message at the permissive temperature contains gag and mos sequences fused in an open reading frame, whose translation results in the synthesis of p85gag-mos. This protein possesses kinase activity and induces transformation of susceptible cells. Thus, temperature manipulations allows for examination of phenotypic changes associated with the synthesis of phenotypic changes associated with the synthesis of the hybrid protein containing the transforming viral sequences.58
Viral Infections of the Lung
Published in Lourdes R. Laraya-Cuasay, Walter T. Hughes, 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.
Mutagenic Consequences Of Chemical Reaction with DNA
Published in Philip L. Grover, Chemical Carcinogens and DNA, 2019
The most attractive hypothesis is that the fidelity of an existing polymerase (see Section II) is reduced under conditions of Weigle-reactivation and error-prone repair. The most direct evidence suggesting this comes from the work of Bridges and Motters-head,106 who have used a temperature-sensitive mutant to show that DNA polymerase 3 is an essential enzyme for error-prone repair and that the effect on error-prone repair of a mutant DNA polymerase 3 shows greater temperature sensitivity than the effect on normal polymerizing ability.
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].