Molecular topography of an entire nervous system.

We have produced gene expression profiles of all 302 neurons of the C. elegans nervous system that match the single-cell resolution of its anatomy and wiring diagram. Our results suggest that individual neuron classes can be solely identified by combinatorial expression of specific gene families. For example, each neuron class expresses distinct codes of ∼23 neuropeptide genes and ∼36 neuropeptide receptors, delineating a complex and expansive "wireless" signaling network. To demonstrate the utility of this comprehensive gene expression catalog, we used computational approaches to (1) identify cis-regulatory elements for neuron-specific gene expression and (2) reveal adhesion proteins with potential roles in process placement and synaptic specificity. Our expression data are available at https://cengen.org and can be interrogated at the web application CengenApp. We expect that this neuron-specific directory of gene expression will spur investigations of underlying mechanisms that define anatomy, connectivity, and function throughout the C. elegans nervous system.

Autoimmune Hypoglycemia With Anti-Insulin Autoantibodies in an Eighty-One-Year-Old Woman Without Apparent Risk Factors.

Background/Objective: Insulin autoimmune syndrome (IAS) is a very rare cause of hypoglycemia presenting with recurrent fasting or postprandial hypoglycemia episodes with elevated serum insulin levels and insulin autoantibodies. The objective of this case is to highlight the importance of considering IAS in patients with hypoglycemia. Case Report: We present a case of an 81-year-old female who presented with symptoms of hypoglycemia. She was found to have hyperinsulinemic hypoglycemic episodes without any apparent risk factors for IAS. She had positive-insulin autoantibodies in her serum leading to the diagnosis of IAS. Acutely, hypoglycemia was managed with D50 pushes, oral glucose, and glucagon injection. Discussion: Patients who present with hypoglycemia due to endogenous hyperinsulinemia should have IAS considered as a possible differential diagnosis. Insulin autoantibodies are measured as the gold standard diagnostic test for IAS. Foods with a low glycemic index are the primary treatment for IAS. Conclusion: This case presentation highlights the importance of considering IAS as a differential diagnosis in patients presenting with hypoglycemia secondary to hyperinsulinemia, even in the absence of apparent risk factors.

Factors impacting COVID-19 vaccination intention among medical students.

Medical students represent a significant part of the health-care community and are active members of the coronavirus disease 2019 (COVID-19) response. This study aimed to evaluate various factors associated with COVID-19 vaccine intention among medical students via an online anonymous survey. A total of 370 students completed the online survey, with 229 (61.89%) not vaccinated for COVID-19. Of students not yet vaccinated, 45 (19.65%) were unsure or did not intend to accept the vaccine, while 184 (80.35%) intend to be vaccinated within 6 months. Overall, female gender, health status, clinical science enrollment, and the practice of COVID-19 preventative behaviors significantly correlated with the intention to be vaccinated within 6 months. Greater perceived risk for contracting COVID-19, lesser beliefs that the COVID-19 vaccination trials were rushed, and greater beliefs that being vaccinated would help complete their medical education were uniquely associated with the intention to be vaccinated within 6 months. Collectively, this study identified several factors that influenced medical students' intention to receive the COVID-19 vaccination. This information may be used in future immunization strategies to increase the vaccination rates among this group of future medical professionals.

In silico analysis of the transcriptional regulatory logic of neuronal identity specification throughout the C. elegans nervous system.

The generation of the enormous diversity of neuronal cell types in a differentiating nervous system entails the activation of neuron type-specific gene batteries. To examine the regulatory logic that controls the expression of neuron type-specific gene batteries, we interrogate single cell expression profiles of all 118 neuron classes of the Caenorhabditis elegans nervous system for the presence of DNA binding motifs of 136 neuronally expressed C. elegans transcription factors. Using a phylogenetic footprinting pipeline, we identify cis-regulatory motif enrichments among neuron class-specific gene batteries and we identify cognate transcription factors for 117 of the 118 neuron classes. In addition to predicting novel regulators of neuronal identities, our nervous system-wide analysis at single cell resolution supports the hypothesis that many transcription factors directly co-regulate the cohort of effector genes that define a neuron type, thereby corroborating the concept of so-called terminal selectors of neuronal identity. Our analysis provides a blueprint for how individual components of an entire nervous system are genetically specified.

Temporal, Spatial, Sexual and Environmental Regulation of the Master Regulator of Sexual Differentiation in C. elegans.

Sexual differentiation is controlled by diverse master regulatory factors across the animal kingdom. The transcription factor TRA-1 is the master regulator of somatic sexual differentiation in the nematode C. elegans, where it was reported to be expressed sex-specifically in the non-gonadal soma of hermaphrodites. Using a gfp-tagged allele of tra-1, we reveal unanticipated dynamics of TRA-1 protein expression in five dimensions: space, time, sex, environment, and subcellular localization. We show temporal regulation of TRA-1 protein accumulation in somatic tissues with different onsets of expression in different tissue types, indicating that sexual identity is not uniformly imposed. In hermaphrodites, neuronal expression is initially highly restricted and then increases variably between individuals during larval development until reaching panneuronal expression in the fourth larval stage. Unexpectedly, TRA-1 also accumulates in a subset of sex-shared neurons in the male. Additionally, a food signal is required to turn on TRA-1 expression in the intestine, and environmental stressors shut off TRA-1 expression in the entire non-gonadal soma, suggesting that somatic sexual differentiation may be affected by external conditions. We show that, in contrast to the protein degradation mechanisms that control TRA-1 accumulation in the adult, the temporal, sexual, and spatial specificities of TRA-1 accumulation during development are regulated transcriptionally. A nuclear hormone receptor, daf-12, previously implicated in developmental timing in C. elegans, contributes to temporal accumulation of TRA-1 in the nervous system. Our studies reveal a mosaic and dynamic nature of sexual identity acquisition and uncover hormonal control mechanisms for sexual differentiation of the brain.