Search for: All records

Despite progress in automated gene annotation, many deficiencies and knowledge gaps remain, even for well-studied organisms. Of particular concern is the accuracy and detail of annotations for transporters of various organic substrates and products of metabolism and for enzymes that do not share sequence homology with well-characterized strains. Unfortunately, annotation errors present in earlier genome-scale metabolic (GSM) models propagate to newer models with few opportunities for later correction. Here, we introduce a systematic computational procedure that applies theEscherichia coligenome-scale metabolic modeliML1515, extended with transcriptional regulatory rules, to design auxotrophs that can grow on glucose but fail to grow on different carbon substrate(s) unless rescued with the addition of an ORF encoding a complementation metabolic function (transport and enzymatic reactions). Using theE. coliGSM model supplemented with regulatory rules that quantify growth/no growth outcomes on different organic substrates, we identified 258 distinct auxotrophic designs (97 single-gene, 142 double-gene, and 19 triple-gene knockouts) for which specific single functions can uniquely complement them. Experimental validation of 61 single-knockout strains demonstrated 59% confirmed auxotrophy and 28% partial auxotrophy. We envision that this collection of auxotrophic strains can be used to disambiguate the metabolic role of unannotated or poorly annotated genes. 

The interplay between circadian rhythms, time awake, and mood remains poorly understood in the real-world. Individuals in high-stress occupations with irregular schedules or nighttime shifts are particularly vulnerable to depression and other mood disorders. Advances in wearable technology have provided the opportunity to study these interactions outside of a controlled laboratory environment. Here, we examine the effects of circadian rhythms and time awake on mood in first-year physicians using wearables. Continuous heart rate, step count, sleep data, and daily mood scores were collected from 2,602 medical interns across 168,311 days of Fitbit data. Circadian time and time awake were extracted from minute-by-minute wearable heart rate and motion measurements. Linear mixed modeling determined the relationship between mood, circadian rhythm, and time awake. In this cohort, mood was modulated by circadian timekeeping (p<0.001). Furthermore, we show that increasing time awake both deteriorates mood (p<0.001) and amplifies mood’s circadian rhythm nonlinearly. These findings demonstrate the contributions of both circadian rhythms and sleep deprivation to underlying mood and show how these factors can be studied in real-world settings using Fitbits. They underscore the promising opportunity to harness wearables in deploying chronotherapies for psychiatric illness. 

Abstract Organic semiconductors with high-spin ground states are fascinating because they could enable fundamental understanding on the spin-related phenomenon in light element and provide opportunities for organic magnetic and quantum materials. Although high-spin ground states have been observed in some quinoidal type small molecules or doped organic semiconductors, semiconducting polymers with high-spin at their neutral ground state are rarely reported. Here we report three high-mobility semiconducting polymers with different spin ground states. We show that polymer building blocks with small singlet-triplet energy gap (Δ E S-T ) could enable small Δ E S-T gap and increase the diradical character in copolymers. We demonstrate that the electronic structure, spin density, and solid-state interchain interactions in the high-spin polymers are crucial for their ground states. Polymers with a triplet ground state ( S  = 1) could exhibit doublet ( S  = 1/2) behavior due to different spin distributions and solid-state interchain spin-spin interactions. Besides, these polymers showed outstanding charge transport properties with high hole/electron mobilities and can be both n- and p-doped with superior conductivities. Our results demonstrate a rational approach to obtain high-mobility semiconducting polymers with different spin ground states.