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Biology subjects

Dewan, A.

Publications and source records attributed to Dewan, A..

5 recordsLinked to original sources

Heat Stable and Intrinsically Sterile Liquid Protein Formulations

Over 80% of biologic drugs, and 90% of vaccines, require temperature-controlled conditions throughout the supply chain to minimize thermal inactivation and contamination. This cold chain is costly, requires stringent oversight, and is impractical in remote environments. Here, we report chemical dispersants that non-covalently solvate proteins within fluorous liquids to alter their thermodynamic equilibrium and reduce conformational flexibility. This generates non-aqueous, fluorine-based liquid protein formulations that biochemically rigidify protein structure to yield thermally stable biologics at extreme temperatures (up to 90{degrees}C). These non-aqueous formulations are impervious to contamination by microorganismal pathogens, degradative enzymes, and environmental impurities, and display comparable pre-clinical serum half-life and safety profiles to standard saline protein samples. As a result, we deliver a fluorochemical formulation paradigm that may limit the need for cold chain logistics of protein reagents and biopharmaceuticals.

biophysics↗

Map-independent representation of an aggression-promoting social cue in the main olfactory pathway

AO_SCPLOWBSTRACTC_SCPLOWWhile the olfactory system is required for proper social behaviors, the molecular basis for how social cues are detected via the main olfactory pathway of mammals is not well-characterized. Trimethylamine is a volatile, sex-specific odor found in adult male mouse urine that selectively activates main olfactory sensory neurons that express trace amine-associated receptor 5 (TAAR5). Here we show that trimethylamine, acting via TAAR5, elicits state-dependent attraction or aversion in male mice and drives inter-male aggression. Genetic knockout of TAAR5 significantly reduces aggression-related behaviors, while adding trimethylamine augments aggressive behavior towards juvenile males. We further show that transgenic expression of TAAR5 specifically in olfactory sensory neurons rescues aggressive behaviors in knockout mice, despite extensive remapping of TAAR5 projections to the olfactory bulb. Our results identify a specific main olfactory input that detects a prominent male-specific odor to induce inter-male aggression in a mammalian species and reveal that apparently innate behavioral responses are independent of patterned glomerular input to the olfactory bulb.

neuroscience↗

Undergraduate student interest in healthcare career in the context of COVID-19 pandemic

ObjectivesThe healthcare profession has been long considered an excellent career choice. Pre-medical experience is documented to be important in shaping future medical landscape. In the wake of the pandemic, there has been intense media spotlight on the healthcare profession and change in academic environment, necessitating analyses of student experience. This project aims to assess change in undergraduate student interest in healthcare career using cross-sectional survey study. MethodsThe project was approved by our Institutional Review Board. Voluntary survey collected data on demographics, socioeconomics, media exposure, academic environment, and change in interest in a healthcare profession. Survey was distributed through the university undergraduate pre-health listserv. Total of 297 responses were obtained. Descriptive statistics including Fishers exact test were applied in the analysis. ResultsMajority of the respondents were Asians (54.9%), second generation immigrants (52.2%), and female (73.4%). Large proportion of the respondents were negatively affected by the pandemic, with losing a job or internship personally (42.1%) or a family member or a friend (62.6%). Students had mixed response to online learning environment, with 27.3% of students noting no change, 40.4% students noting increased difficulty, and 32.3% students noting decreased difficulty of classes. During the pandemic, 47.5% of students noted increased interest in pursuing healthcare career. The change in interest in healthcare career was not associated with xdemographics, economic hardship, or online learning environment. DiscussionDespite the challenges of COVID-19 pandemic, students showed strong interest in pursuing healthcare careers.

scientific communication and education↗

A mouse bio-electronic nose for sensitive and versatile chemical detection

When it comes to simultaneous versatility, speed, and specificity in detecting volatile chemicals, biological olfactory systems far outperform all artificial chemical detection devices. Consequently, the use of trained animals for chemical detection in security, defense, healthcare, agriculture, and other applications has grown astronomically. However, the use of animals in this capacity requires extensive training and behavior-based communication. Here we propose an alternative strategy, a bio-electronic nose, that capitalizes on the superior capability of the mammalian olfactory system, but bypasses behavioral output by reading olfactory information directly from the brain. We engineered a brain-machine interface that captures neuronal signals from an early stage of olfactory processing in awake mice, and used machine learning techniques to form a sensitive and selective chemical detector. We chronically implanted a grid electrode array on the surface of the mouse olfactory bulb and systematically recorded responses to a large battery of odorants and odorant mixtures across a wide range of concentrations. The bio-electronic nose has a comparable sensitivity to the trained animal and can detect odors on a variable background. We also introduce a novel genetic engineering approach designed to improve the sensitivity of our bio-electronic nose for specific chemical targets. Our bio-electronic nose outperforms current detection methods and unlocks a wide spectrum of civil, medical and environmental applications.

bioengineering↗

Single olfactory receptors set odor detection thresholds

In many species, survival depends on olfaction, yet the mechanisms that underlie olfactory sensitivity are not well understood. Here, we examine how a conserved subset of olfactory receptors, the trace amine-associated receptors (TAARs) determine odor detection thresholds of mice to amines. We find that deleting all TAARs, or even single TAARs, results in significant odor detection deficits. This finding is not limited to TAARs, as the deletion of a canonical odorant receptor reduced behavioral sensitivity to its preferred ligand. Remarkably, behavioral threshold is set solely by the most sensitive receptor, with no contribution from other highly sensitive receptors. In addition, increasing the number of sensory neurons (and glomeruli) expressing a threshold-determining TAAR does not improve detection, indicating that sensitivity is not limited by the typical complement of sensory neurons. Our findings demonstrate that olfactory thresholds are set by the single highest affinity receptor, and suggest that TAARs are evolutionarily conserved because they determine the sensitivity to a class of biologically relevant chemicals.

neuroscience↗