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Grid cells in the entorhinal cortex appear to represent spatial location via a triangular coordinate system. Such cells, which have been identified in rats, bats and monkeys, are believed to support a wide range of spatial behaviors. Recording neuronal activity from neurosurgical patients performing a virtual-navigation task, we identified cells exhibiting grid-like spiking patterns in the human brain, suggesting that humans and simpler animals rely on homologous spatial-coding schemes.

Pediatric non-Hodgkin lymphoma includes over 30 histologies (many with subtypes), with approximately 800 cases per year in the US, compared to >60,000 cases of adult NHL annually. Improvements in survival in pediatric and adolescent mature B cell NHL over the past 5 decades align with the overall success of the cooperative trial model with dramatic improvements in outcomes through dose escalation of chemotherapy and, more recently, targeted therapy with rituximab. Pediatric dose-intense strategies carry risks of long-term consequences, but treatment failure is nearly universally fatal. By comparison, adult mature B cell lymphoma is typically less aggressive and treated with less intense chemotherapy. Optimizing therapy for adolescents and young adults remains a major challenge that requires creative solutions, including engineering study groups to combine biologically comparable adult and pediatric populations and developing effective salvage strategies that will ultimately be required for investigations of front-line dose reduction. In this review, we discuss challenges and opportunities for improving outcomes for adolescents and young adults with high-grade mature B cell lymphomas, diffuse large B cell lymphoma, and primary mediastinal B cell lymphoma.

Phospholipid synthesis and fat storage as triglycerides are regulated by lipin phosphatidic acid phosphatases (PAPs), whose enzymatic PAP function requires association with cellular membranes. Using hydrogen deuterium exchange mass spectrometry, we find mouse lipin 1 binds membranes through an N-terminal amphipathic helix, the Ig-like domain and HAD phosphatase catalytic core, and a middle lipin (M-Lip) domain that is conserved in mammalian and mammalian-like lipins. Crystal structures of the M-Lip domain reveal a previously unrecognized protein fold that dimerizes. The isolated M-Lip domain binds membranes both in vitro and in cells through conserved basic and hydrophobic residues. Deletion of the M-Lip domain in lipin 1 reduces PAP activity, membrane association, and oligomerization, alters subcellular localization, diminishes acceleration of adipocyte differentiation, but does not affect transcriptional co-activation. This establishes the M-Lip domain as a dimeric protein fold that binds membranes and is critical for full functionality of mammalian lipins.

DeepMind presented notably accurate predictions at the recent 14th Critical Assessment of Structure Prediction (CASP14) conference. We explored network architectures that incorporate related ideas and obtained the best performance with a three-track network in which information at the one-dimensional (1D) sequence level, the 2D distance map level, and the 3D coordinate level is successively transformed and integrated. The three-track network produces structure predictions with accuracies approaching those of DeepMind in CASP14, enables the rapid solution of challenging x-ray crystallography and cryo-electron microscopy structure modeling problems, and provides insights into the functions of proteins of currently unknown structure. The network also enables rapid generation of accurate protein-protein complex models from sequence information alone, short-circuiting traditional approaches that require modeling of individual subunits followed by docking. We make the method available to the scientific community to speed biological research.

ObjectiveThe use of telemedicine has dramatically increased due to the coronavirus disease 2019 pandemic. Many neurosurgeons are now using telemedicine technologies for preoperative evaluations and routine outpatient visits. Our goal was to standardize the telemedicine motor neurologic examination, summarize the evidence surrounding clinical use of telehealth technologies, and discuss financial and legal considerations.MethodsWe identified a 12-member panel composed of spine surgeons, fellows, and senior residents at a single institution. We created an initial telehealth strength examination protocol based on published data and developed 10 agree/disagree statements summarizing the protocol. A blinded Delphi method was utilized to build consensus for each statement, defined as > 80% agreement and no significant disagreement using a 2-way binomial test (significance threshold of p < 0.05). Any statement that did not meet consensus was edited and iteratively resubmitted to the panel until consensus was achieved. In the final round, the panel was unblinded and the protocol was finalized.ResultsAfter the first round, 4/10 statements failed to meet consensus ( < 80% agreement, and p = 0.031, p = 0.031, p = 0.003, and p = 0.031 statistical disagreement, respectively). The disagreement pertained to grading of strength of the upper (3/10 statements) and lower extremities (1/10 statement). The amended statements clarified strength grading, achieved consensus ( > 80% agreement, p > 0.05 disagreement), and were used to create the final telehealth strength examination protocol.ConclusionThe resulting protocol was used in our clinic to standardize the telehealth strength examination. This protocol, as well as our summary of telehealth clinical practice, should aid neurosurgical clinics in integrating telemedicine modalities into their practice.