Charlotte A. Weaver

We reconstructed the synaptic circuits of seven columns in the second neuropil or medulla behind the fly's compound eye. These neurons embody some of the most stereotyped circuits in one of the most miniaturized of animal brains. The reconstructions allow us, for the first time to our knowledge, to study variations between circuits in the medulla's neighboring columns. This variation in the number of synapses and the types of their synaptic partners has previously been little addressed because methods that visualize multiple circuits have not resolved detailed connections, and existing connectomic studies, which can see such connections, have not so far examined multiple reconstructions of the same circuit. Here, we address the omission by comparing the circuits common to all seven columns to assess variation in their connection strengths and the resultant rates of several different and distinct types of connection error. Error rates reveal that, overall, <1% of contacts are not part of a consensus circuit, and we classify those contacts that supplement (E+) or are missing from it (E-). Autapses, in which the same cell is both presynaptic and postsynaptic at the same synapse, are occasionally seen; two cells in particular, Dm9 and Mi1, form ≥ 20-fold more autapses than do other neurons. These results delimit the accuracy of developmental events that establish and normally maintain synaptic circuits with such precision, and thereby address the operation of such circuits. They also establish a precedent for error rates that will be required in the new science of connectomics.

Over the last 5 years, stimulated by the changing healthcare environment and the Health Information Technology for Economic and Clinical Health (HITECH) Meaningful Use (MU) Electronic Health Record (EHR) Incentive program, EHR adoption has increased remarkably, and there is early evidence that such adoption has resulted in healthcare safety and quality benefits.1,2 However, with this broad adoption, many clinicians are voicing concerns that EHR use has had unintended clinical consequences, including reduced time for patient-clinician interaction,3 new and burdensome data entry tasks being transferred to front-line clinicians,4,5 and lengthened clinician workdays.6–8 Additionally, interoperability between different EHR systems has languished despite large efforts towards that goal.9,10 These challenges are contributing to physicians’ decreased satisfaction with their work lives.11–13 In professional journals,14 press reports,15–17 on wards, and in clinics, we have heard of the difficulties that the transition from paper records to EHRs has created.18 As a result, clinicians are seeking help to get through their work days, which often extend into evenings devoted to writing notes. Examples of comments we have received from clinicians and patients include: “Computers always make things faster and cheaper. Not this time,” and “My doctor pays more attention to the computer than to me.” Ultimately the healthcare system's goal is to create a robust, integrated, and interoperable healthcare system that includes patients, physician practices, public health, population management, and support for clinical and basic sciences research. This ecosystem has been referred to as the “learning health system.”19 EHRs are an important part of the learning health system, along with many other clinical systems, but future ways in which information is transformed into knowledge will likely require all parts of the system working together. Potentially every patient encounter could present an …

Abstract Quickly and flexibly exploring high-dimensional datasets, such as scRNAseq data, is underserved but critical for hypothesis generation, dataset annotation, publication, sharing, and community reuse. cellxgene is a highly generalizable, web-based interface for exploring high dimensional datasets along categorical, continuous and spatial dimensions, as well as feature annotation. cellxgene is differentiated by its ability to performantly handle millions of observations, and bridges a critical gap by enabling computational and experimental biologists to iteratively ask questions of private and public datasets. In doing so, cellxgene increases the utility and reusability of datasets across the single-cell ecosystem. The codebase can be accessed at https://github.com/chanzuckerberg/cellxgene . For questions and inquiries, please contact cellxgene@chanzuckerberg.com .

ABSTRACT Grain sorghum has been documented to have low protein digestibility relative to other cereal grains. Low protein digestibility of sorghum is most pronounced in cooked foods and is ranked slightly lower than corn as a feed grain. In this article, sorghum germ plasm is identified that has substantially higher uncooked and cooked flour in vitro protein digestibility than normal cultivars. Sorghum lines were found within a high‐lysine opulation derived from the mutant P721Q that have ≈10–15% higher uncooked and ≈25% higher cooked protein digestibilities using a pepsin assay. Highly digestible sorghum grain showed little reduction in digestibility after cooking, compared to the large reduction that is typical of normal sorghum cultivars. Using the three‐enzyme pH‐stat method, we showed that the highly digestible lines had the same degree of peptide bond hydrolysis in ≈5 min, as was found in 60 min in the normal cultivar, P721N. Differences in protein digestibility were related to enyzme susceptibility of the major storage prolamin, α‐kafirin, that comprises ≈50–60% of the total sorghum grain protein. Using the enzyme‐linked immunosorbent assay (ELISA) technique to track the pepsin digestion of α‐kafirin, the highly digestible lines had ≈90–95% α‐kafirin digested in 60 min compared to 45–60% for two normal cultivars. γ‐Kafirin, a minor structural prolamin found mainly at the periphery of protein bodies, was also somewhat more digestible in the highly digestible sorghums. Highly digestible grain was of a floury kernel type, though recently this trait has been found in a modified background. More digestible protein from sorghum grain, that additionally is high in lysine content and has a fairly hard endosperm, could be of important benefit to populations who lack adequate protein in their diets, and may, pending further studies, prove to increase the value of sorghum as a feed grain.