Biology subjects

Schwartz, N. B.

Publications and source records attributed to Schwartz, N. B..

4 recordsLinked to original sources

bioRxiv2026

The role of the NLRP3 inflammasome in a CLN2 mouse model of neuroinflammation

Neuronal ceroid lipofuscinoses, or Batten disease, comprises a group of inherited pediatric neurodegenerative disorders, and is characterized by the lysosomal accumulation of the fluorescent storage material lipofuscin. The human classical late-infantile form of the disorder (CLN2) is caused by mutations in the CLN2/Tripeptidyl peptidase 1 (TPP1) gene. Comparable to human CLN2, a knockout of the Tpp1 gene (Tpp1 -/-) in the mouse leads to progressive vision loss, ataxia, motor atrophy, seizures, and premature death. While we previously showed using bulk RNA-seq analysis that reactive gliosis develops between 3 and 4 months in this animal model, the role of the inflammasome in CLN2 remains unexplored. The inflammasome is a multiprotein complex formed through pattern recognition receptor engagement, which culminate in the cleavage and release of interleukin-1 beta. Here we report that while some inflammasome-associated genes are upregulated as early as 1-month in the Tpp1 -/- cerebellum, it is not until 3-months-old that all gene transcripts necessary for inflammasome assembly and function are upregulated, leading to IL1{beta} release. In Tpp1 -/- slice cultures, we demonstrated that MCC950, an inhibitor of inflammasome assembly, downregulates transcriptional expression of genes associated with reactive microglia and inflammasome function. Furthermore, prophylactic administration of MCC950 in drinking water of Tpp1 -/- animals for two months is sufficient to lower the expression of these same genes in the forebrain and cerebellum, suggesting that inflammasome inhibitors are promising therapeutics for CLN2 and neurodegeneration broadly.

cell biology↗

bioRxiv2021

The Effect of COVID-19 on the Postdoctoral Experience: a comparison of pre-pandemic and pandemic surveys.

In the interest of advocating for the postdoctoral community in the United States, we present results from survey data collected before and during the COVID-19 pandemic on the same population of postdocs. In 2019, 5,929 postdocs in the US completed a comprehensive survey, and in 2020, a subset completed a follow-up survey several months into the pandemic. The results show that the pandemic has substantially impacted postdocs mental health and wellness irrespective of gender, race, citizenship, or other identities. Postdocs also reported a significant impact on their career trajectories and progression, reduced confidence in achieving career goals, and negative perceptions of the job market compared to pre-COVID-19. International postdocs also reported experiencing distinct stressors due to the changes in immigration policy. Notably, having access to Postdoctoral Associations and Postdoctoral Offices positively impacted postdocs overall well-being and helped mitigate the personal and professional stresses and career uncertainties caused by the pandemic. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/468693v2_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@174d7e3org.highwire.dtl.DTLVardef@9893dorg.highwire.dtl.DTLVardef@114470org.highwire.dtl.DTLVardef@1a4278f_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract of survey responses to: Why or how has your research been disrupted or not disrupted due to the pandemic? Overall, postdocs responded with feelings of loss of control as the pandemic was acting upon them and taking away their ability to complete their work. C_FIG

scientific communication and education↗

bioRxiv2020

Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth

The umbilical artery lumen occludes rapidly at birth, preventing blood loss, whereas the umbilical vein remains patent, providing the newborn with a placental infusion. Here, we identify differential arterial-venous proteoglycan dynamics as a determinant of these contrasting vascular responses. We show that the umbilical artery, unlike the vein, has an inner layer enriched in the hydrated proteoglycan aggrecan, external to which lie contraction-primed smooth muscle cells (SMC). At birth, SMC contraction drives inner layer buckling and centripetal displacement to occlude the arterial lumen, a mechanism elicited by biomechanical and computational analysis. Vascular dimorphism arises from spatially regulated proteoglycan expression and breakdown in umbilical vessels. Mice lacking aggrecan or the metalloprotease ADAMTS1, which degrades proteoglycans, demonstrated their opposing roles in umbilical cord arterial-venous dimorphism and contrasting effects on SMC differentiation. Umbilical vessel dimorphism is conserved in mammals, suggesting that their differential proteoglycan dynamics were a positive selection step in mammalian evolution.Competing Interest StatementThe authors have declared no competing interest.View Full Text

developmental biology↗

bioRxiv2018

Career Choice, Gender, and Mentor Impact: Results of the U.S. National Postdoc Survey

The postdoctoral community is an essential component of the academic and scientific workforce. As economic and political pressures impacting these enterprises continue to change, the postdoc experience has evolved from short, focused periods of training into often multidisciplinary, extended positions with less clear outcomes. As efforts are underway to amend U.S. federally funded research policies, the paucity of postdoc data has made evaluating the impact of policy recommendations challenging. Here we present comprehensive survey results from over 7,600 postdocs based at 351 academic and non-academic U.S. institutions in 2016. In addition to demographic and salary information, we present multivariate analyses on the factors that influence postdoc career plans and mentorship satisfaction in this population. We further analyze gender dynamics and expose wage disparities and career choice differences. Academic research positions remain the predominant career choice of postdocs in the U.S., although unequally between postdocs based on gender and residency status. Receiving mentorship training during the postdoctoral period has a large, positive effect on postdoc mentorship satisfaction. Strikingly, the quality of and satisfaction with postdoc mentorship appears to also heavily influence career choice. The data presented here are the most comprehensive data on the U.S. postdoc population to date. These results provide an evidence basis for informing government and institutional policies, and establish a critical cornerstone for quantifying the effects of future legislation aimed at the academic and scientific workforce.

scientific communication and education↗