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Background: Surgical treatment of scoliosis includes long and invasive multi-level instrumentation and correction which may result in high rates of postoperative complications, especially in elderly patients with osteopenia or multiple comorbidities. Minimally invasive surgical options may benefit these patients. Case description: A 73-year-old female patient with a history of degenerative lumbar scoliosis, L4–5 pseudarthrosis, and resulting L5-S1 adjacent segment following prior unsuccessful lateral L4–5 interbody fusion presented to the clinic with severe lower back pain and lower extremity radiculopathy. The decision was made to proceed with surgical correction via a robotic-guided prone transpsoas (PTP) approach, which is a novel approach similar to lateral lumbar interbody fusion (LLIF) with the patient in a prone decubitus position. Excellent spinal alignment was achieved with no complications. On two-month follow-up, imaging revealed pedicle screws at the L3, L4, L5 levels and at the sacrum without change and continued interbody cages position with no signs or symptoms of infection. Discussion: Minimally invasive procedures have demonstrated benefit in spine surgery especially for at risk populations. The LLIF procedure has been well established for use in a wide range of spinal pathologies given its noted benefits in increasing spinal column stability through posterior fixation and indirect decompression. However, only marginal improvements in segmental lordosis are expected and there are reports of neurological complications. The PTP procedure has emerged as an alternative to LLIF for the treatment of spinopelvic pathologies. This approach enables greater improvements to spinal lordosis through single-position surgery while simultaneously reducing intraoperative repositioning and providing the known benefits of lateral interbody surgery. Conclusion: Our experience suggests that the PTP approach is safe and effective because it does not require patient repositioning, easily interfaces with robotic guidance, and achieves increased lordosis gains via the prone positional effect compared to LLIF and comparable approaches.

The role of quasar feedback in galaxy evolution remains poorly understood. Throughout this work, we explore the effects of negative feedback on star formation in quasar host galaxies, analysing two distinct populations of quasars. The first is a sample of high-redshift (z > 2) low-ionisation broad absorption line quasars (LoBALs) - a class of quasars hosting energetic mass outflows, in which we find evidence for prolific star formation (>750Mʘyr–1) exceeding that of non-BAL quasars at the same redshift. The second is a population of 207 low-redshift (z < 0.3) quasars, in which we find an enhancement in the SFRs of quasar hosts compared to the underlying galaxy population, with no quasars residing in quiescent hosts over the last 2Gyr. Overall, we find no evidence for galaxy-wide quenching in either population, rather we suggest that the dominant effect of quasar activity is to enhance star formation in the galaxy.

Understanding the connection between nuclear activity and galaxy environment remains critical in constraining models of galaxy evolution. By exploiting extensive catalogued data from the Galaxy and Mass Assembly (GAMA) survey, we identify a representative sample of 205 quasars at 0.1 < z < 0.35 and establish a comparison sample of galaxies, closely matched to the quasar sample in terms of both stellar mass and redshift. On scales, Comment: 26 pages, 20 figures, accepted to ApJ

PRMT5 is an essential arginine methyltransferase and a therapeutic target in MTAP-null cancers. PRMT5 uses adaptor proteins for substrate recruitment through a previously undefined mechanism. Here, we identify an evolutionarily conserved peptide sequence shared among the three known substrate adaptors (CLNS1A, RIOK1, and COPR5) and show that it is necessary and sufficient for interaction with PRMT5. We demonstrate that PRMT5 uses modular adaptor proteins containing a common binding motif for substrate recruitment, comparable with other enzyme classes such as kinases and E3 ligases. We structurally resolve the interface with PRMT5 and show via genetic perturbation that it is required for methylation of adaptor-recruited substrates including the spliceosome, histones, and ribosomal complexes. Furthermore, disruption of this site affects Sm spliceosome activity, leading to intron retention. Genetic disruption of the PRMT5-substrate adaptor interface impairs growth of MTAP-null tumor cells and is thus a site for development of therapeutic inhibitors of PRMT5.

PRMT5 is an essential arginine methyltransferase and a therapeutic target in MTAP-null cancers. PRMT5 uses adaptor proteins for substrate recruitment through a previously undefined mechanism. Here, we identify an evolutionarily conserved peptide sequence shared among the three known substrate adaptors (CLNS1A, RIOK1, and COPR5) and show that it is necessary and sufficient for interaction with PRMT5. We demonstrate that PRMT5 uses modular adaptor proteins containing a common binding motif for substrate recruitment, comparable with other enzyme classes such as kinases and E3 ligases. We structurally resolve the interface with PRMT5 and show via genetic perturbation that it is required for methylation of adaptor-recruited substrates including the spliceosome, histones, and ribosomal complexes. Furthermore, disruption of this site affects Sm spliceosome activity, leading to intron retention. Genetic disruption of the PRMT5-substrate adaptor interface impairs growth of MTAP-null tumor cells and is thus a site for development of therapeutic inhibitors of PRMT5. Current efforts are focused on understanding whether PRMT5-substrate adaptor disruption synergizes with immune therapies or new classes of PRMT5 inhibitors in CDKN2A/MTAP null cancer. Citation Format: Kathleen M. Mulvaney, Brian McMillan, Christa Blomquist, Nischal Acharya, Matthew Ranaghan, Devishi Kesar, Alessandra Ianari, William Sellers. PRMT5 substrate recruitment as a therapeutic target in CDKN2A/MTAP null cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 94.

PRMT5 is an arginine methyltransferase and a therapeutic target in MTAP null cancers. PRMT5 utilizes adaptor proteins for substrate recruitment through a previously undefined mechanism. Here, we identify an evolutionarily conserved peptide sequence shared among the three known substrate adaptors (pICln/CLNS1A, RIOK1 and COPR5) and show it is necessary and sufficient for interaction with PRMT5. We structurally resolve the interface with PRMT5 and show via genetic perturbation that it is required for methylation of adaptor-recruited substrates including the spliceosome, histones, and ribosome assembly complexes. Genetic disruption of the PRMT5-substrate adaptor interface leads to a hypomorphic decrease in growth of MTAP null tumor cells and is thus a novel site for development of therapeutic inhibitors of PRMT5.

Axon pathfinding is critical for nervous system development, and it is orchestrated by molecular cues that activate receptors on the axonal growth cone. Robo family receptors bind Slit guidance cues to mediate axon repulsion. In mammals, the divergent family member Robo3 does not bind Slits, but instead signals axon repulsion from its own ligand, NELL2. Conversely, canonical Robos do not mediate NELL2 signaling. Here, we present the structures of NELL-Robo3 complexes, identifying a mode of ligand engagement for Robos that is orthogonal to Slit binding. We elucidate the structural basis for differential binding between NELL and Robo family members and show that NELL2 repulsive activity is a function of its Robo3 affinity and is enhanced by ligand trimerization. Our results reveal a mechanism of oligomerization-induced Robo activation for axon guidance and shed light on Robo family member ligand binding specificity, conformational variability, divergent modes of signaling, and evolution., Robo3 is a divergent, multifunctional member of the Robo receptor family that mediates axon guidance by its ligand NELL2 instead of the canonical Slit ligands. Here, the authors present the crystal structures of human Robo3 in complex with NELL1 and NELL2, and they show through biophysical and functional assays how NELL-Robo3 affinity and ligand-induced receptor multimerization control axon guidance activity.

Background: Ependymomas are rare tumors originating from neuroepithelial cells lining the wall of the ventricles or central canal of the spinal cord. While these tumors mainly occur within the central nervous system (CNS), there are occasional reports in children and young adult patients with a primary tumor occurrence outside of the CNS. Ependymomas of the sacrococcygeal region have been infrequently described in the literature with no standard of care established. We present a case report and review of the literature regarding this rare entity. Case Description: A 24-year-old woman presented with right gluteal pain worsened by sitting and a palpable soft tissue mass of the sacrococcygeal region. Magnetic resonance imaging revealed a 3.7 cm cystic mass centered in the right gluteal region. She underwent a biopsy at an outside institution, with histology revealing myxopapillary ependymoma. The patient was referred to our hospital and underwent an interdisciplinary neurosurgical and orthopedic oncology en bloc resection of the ependymoma, which intraoperatively appeared to originate from the coccygeal nerve. Conclusion: In the present report, the authors demonstrate that a myxopapillary ependymoma may present as an isolated gluteal mass attached to the coccygeal nerve, without frank CNS involvement. Furthermore, an interdisciplinary approach to surgical resection of this lesion appears to represent an effective treatment modality.

Planetary exploration requires a balance between preemptive planning and financial feasibility. The risk of mid-mission equipment failure, power shortages, or supply depletion incentivizes precautionary measures, but the financial strain of sending unnecessary mass into space limits this practice.To balance the two, our team explored the advantages of biological solutions, namely the self-sustaining abilities of low-mass organisms, to make planetary exploration more self-sufficient and economical. Prioritizing repair over replacement, we are developing self-healing materials embedded with Bacillus subtilis. For longer-lasting energy, we are designing a “biobactery” using linearly oriented Escherichia coli to generate power. For renewable materials, we are engineering bacteria to synthesize and degrade rubber. Individually, these projects offer sustainable alternatives for repair, power, and materials. But when combined, these consolidated insights can provide us with the power to get to Mars and resources to sustain us while we’re there.