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Biology subjects

Chow, B.

Publications and source records attributed to Chow, B..

3 recordsLinked to original sources

Clinical and molecular characterization of an outbreak of leptospirosis in dogs from Los Angeles County, California, USA, 2021

BackgroundIn 2021, the Los Angeles County (LAC) Department of Public Health suspected a leptospirosis outbreak in LAC affecting over 200 client-owned dogs. ObjectiveTo characterize the outbreak and describe microbiologic findings, risk factors, diagnostic test performance, and outcomes in dogs diagnosed with leptospirosis at two specialty practices. MethodsLeptospira culture isolates from four cases were subjected to serotyping and whole genome sequencing (WGS); WGS was also performed on one enriched genome isolate. After the outbreak, data were gathered on 59 cases through record review and compared to the background hospital population (controls, n=15,536). ResultsAll isolates were Leptospira interrogans serovar Canicola, but each was distinct based on WGS. Cases clustered in space and in time. Cases evaluated during the outbreak peak had increased odds of exposure to indoor congregate facilities (ICFs). None of 47 dogs with known leptospirosis vaccination history were completely vaccinated. Leptospira real-time PCR on blood and urine and initial serologic testing using the microscopic agglutination test and point-of-care tests were positive in 15/56 (27%), 49/54 (91%) dogs, 22/29 (76%), and 27/35 (77%) dogs respectively. Fifty-four (92%) of 59 dogs survived to discharge; some remained azotemic. No associated human cases were identified. Conclusions and Clinical ImportanceL. interrogans serovar Canicola was associated with a leptospirosis outbreak in unvaccinated dogs from LAC, which had public health implications given widespread dog ownership rates. Data analysis suggested multiple infection sources, including ICFs. Urine PCR was the most sensitive diagnostic test. Such outbreaks might be prevented through more widespread vaccination.

microbiology↗

Target-specific co-transmission of acetylcholine and GABA from a subset of cortical VIP+ interneurons

The modulation of cortex by acetylcholine (ACh) is typically thought to originate from long-range projections arising in the basal forebrain. However, a subset of VIP interneurons express ChAT, the synthetic enzyme for ACh, and are a potential local source of cortical ACh. Which neurotransmitters these VIP/ChAT interneurons (VCINs) release is unclear, and which post-synaptic cell types these transmitters target is not known. Using quantitative molecular analysis of VCIN pre-synaptic terminals, we show expression of the molecular machinery to release both ACh and GABA, with ACh release restricted to a subset of boutons. A systematic survey of potential post-synaptic cell types shows that VCINs release GABA primarily onto other inhibitory interneuron subtypes, while ACh neurotransmission is notably sparse, with most ACh release onto layer 1 interneurons and other VCINs. Therefore, VCINs are an alternative source of cortical ACh signaling that supplement GABA-mediated disinhibition with highly targeted excitation through ACh.

neuroscience↗

Rational construction of compact de novo-designed biliverdin-binding proteins

AbstractWe report the rational construction of a de novo-designed biliverdin-binding protein by first principles of protein design, informed by energy minimization modeling in Rosetta. The self-assembling tetrahelical bundles bind biliverdin IXa (BV) cofactor auto-catalytically in vitro, similar to photosensory proteins that bind BV (and related bilins, or linear tetrapyrroles) despite lacking sequence and structural homology to the natural counterparts. Upon identifying a suitable site for cofactor ligation to the protein scaffold, stepwise placement of residues stabilized BV within the hydrophobic core. Rosetta modeling was used in the absence of a high-resolution structure to define the structure-function of the binding pocket. Holoprotein formation indeed stabilized BV, resulting in increased far-red BV fluorescence. By removing segments extraneous to cofactor stabilization or bundle stability, the initial 15-kilodalton de novo-designed fluorescence-activating protein (\"dFP\") was truncated without altering its optical properties, down to a miniature 10-kilodalton \"mini,\" in which the protein scaffold extends only a half-heptad repeat beyond the hypothetical position of the bilin D-ring. This work demonstrates how highly compact holoprotein fluorochromes can be rationally constructed using de novo protein design technology and natural cofactors.

biochemistry↗