Biology subjects

Sack, D.

Publications and source records attributed to Sack, D..

3 recordsLinked to original sources

bioRxiv2021

Non-toxigenic Vibrio cholerae challenge strains for evaluating vaccine efficacy and inferring mechanisms of protection

Human challenge studies are instrumental for testing cholera vaccines, but these studies use outdated strains and require inpatient facilities. Here, we created next-generation isogenic Ogawa and Inaba V. cholerae challenge strains (ZChol strains) derived from a contemporary Zambian clinical isolate representative of current dominant pandemic V. cholerae. To minimize the risk of severe diarrhea these strains were rendered non-toxigenic, since antibody responses which limit V. cholerae colonization are the primary mechanism of immune protection. These strains did not cause diarrhea in infant mice and proved to accurately gauge reduction in intestinal colonization mediated by effective vaccination. They are also valuable as targets for measuring vibriocidal antibody responses. Using barcoded ZChol strains, we discovered that vaccination tightens the infection bottleneck without restricting pathogen expansion in vivo. ZChol strains have the potential to enhance the safety, relevance, and scope of future cholera vaccine challenge studies and be valuable reagents for studies of immunity to cholera.

microbiology↗

bioRxiv2021

Complex feline disease mapping using a dense genotyping array

The current feline genotyping array of 63k single nucleotide polymorphisms has proven its utility within breeds, and its use has led to the identification of variants associated with Mendelian traits in purebred cats. However, compared to single gene disorders, association studies of complex diseases, especially with the inclusion of random bred cats with relatively low linkage disequilibrium, require a denser genotyping array and an increased sample size to provide statistically significant associations. Here, we undertook a multi-breed study of 1,122 cats, most of which were admitted and phenotyped for nine common complex feline diseases at the Cornell University Hospital for Animals. Using a proprietary 340k single nucleotide polymorphism mapping array, we identified significant genome-wide associations with hyperthyroidism, diabetes mellitus, and eosinophilic keratoconjunctivitis. These results provide genomic locations for variant discovery and candidate gene screening for these important complex feline diseases, which are relevant not only to feline health, but also to the development of disease models for comparative studies.

genetics↗

bioRxiv2019

Effects of the copper IUD on composition of the vaginal microbiota in the olive baboon

ObjectivesAssess the impact of transcervical insertion, use, and removal of copper intrauterine devices (Cu-IUD) on baboon physiology (e.g. weight, menstruation) and vaginal microbiota.\n\nStudy designVaginal swabs were taken before insertion (pre-IUD), during IUD use (IUD), and after removal (post-IUD) and microbiota assessed by 16S rRNA-encoding gene sequence analysis.\n\nResultsNo animals showed physical changes or discomfort during pre-IUD, IUD, or post-IUD phases. There were no changes to the microbiome associated with insertion or use of Cu-IUD over 16 weeks, although removal resulted in perturbation to community structure.\n\nConclusionsBaboons tolerate Cu-IUD insertion with minimal device-associated changes to their vaginal microbiome throughout use and have no significant changes to their physiology or menstrual cycle during any phase.\n\nImplicationsA baboon model of Cu-IUD may allow investigations into the intersection of Cu-IUDs, reproductive tract disorders and pathogens that would not be possible in human studies.

microbiology↗