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Biology subjects

Sun, C.-Y.

Publications and source records attributed to Sun, C.-Y..

5 recordsLinked to original sources

Carbon dioxide sequestration into biomineral armor by ants

Over geologic time, Earths climate has been shaped by the capture and conversion of atmospheric carbon dioxide (CO2) into stable carbonate minerals, including dolomite [CaMg(CO3)2]. Accelerating natural carbon mineralization offers significant potential for mitigating anthropogenic climate change. Using stable carbon isotope tracking, nano-scale secondary ion mass spectroscopy, and 13C SSNMR, we show that, paralleling global biosphere-level processes, Sericomyrmex amabilis fungus-farming ants rapidly convert CO2 in their nest chambers into a biomineral layer covering their exoskeletons. We further reveal that biogenic carbon mineralization by these ants produces partially ordered dolomite. This rapid sequestration of CO2 into defensive armor in ants provides a fascinating natural example of mediation of potentially toxic accumulation of atmospheric CO2 that could inform human efforts to mitigate climate change.

ecology↗

Dynamic Regulation of Cholesterol Metabolism Genes in Dopaminergic Neurons following Methamphetamine Treatment as Revealed by Single-Nucleus RNA Sequencing

Methamphetamine profoundly alters the function of midbrain dopaminergic neurons, yet the molecular mechanisms underlying these effects are not fully understood. Using single-nucleus RNA sequencing, we found that acute methamphetamine exposure leads to a marked up-regulation of cholesterol metabolism genes in dopaminergic neurons of the ventral tegmental area and substantia nigra--a response that was much less pronounced in astrocytes and largely absent in other cell types. Further analysis using a ribosome tagging strategy combined with RNA sequencing revealed that amphetamine, a structurally similar psychostimulant, induced similar gene expression changes, whereas methylphenidate, a structurally distinct psychostimulant, did not, highlighting drug-specific transcriptional responses. Notably, repeated methamphetamine exposure resulted in down-regulation of cholesterol metabolism genes in dopaminergic neurons. Interestingly, we also observed that, compared to neighboring cell types, dopaminergic neurons are highly enriched in genes encoding cholesterol biosynthesis enzymes, including the rate-limiting enzyme Hmgcr, and key regulators Srebf2 and Insig1, challenging the prevailing view that neurons rely mainly on astrocyte-derived cholesterol. In summary, our study highlights dynamic changes in cholesterol metabolism in dopaminergic neurons in response to amphetamines and uncovers the potential importance of cholesterol homeostasis for dopaminergic neuron function.

genomics↗

Double Lock of a Potent Human Monoclonal Antibody against SARS-CoV-2

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10-fold of effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19. HighlightsO_LISARS-CoV-2 specific antibody, HB27, blocks viral receptor binding and membrane fusion C_LIO_LIHB27 confers prophylactic and therapeutic protection against SARS-CoV-2 in mice models C_LIO_LIRhesus macaques showed no adverse side effects when administered with HB27 C_LIO_LICryo-EM studies suggest that HB27 sterically occludes SARS-CoV-2 from its receptor C_LI

biophysics↗

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody

The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19. One sentence summaryA potent neutralizing antibody conferred protection against SARS-CoV-2 in an hACE2 humanized mouse model by sterically blocking the interaction of the virus with its receptor.

biophysics↗

Biomineral armor in leaf-cutter ants

Although calcareous anatomical structures have evolved in diverse animal groups, such structures have been unknown in insects. Here, we report the discovery of high-magnesium calcite [CaMg(CO3)2] armor overlaying the exoskeletons of major workers of the leaf-cutter ant Acromyrmex echinatior. Live-rearing and in vitro synthesis experiments indicate that the biomineral layer accumulates rapidly as ant workers mature, that the layer is continuously distributed, covering nearly the entire integument, and that the ant epicuticle catalyzes biomineral nucleation and growth. In situ nanoindentation demonstrates that the biomineral layer significantly hardens the exoskeleton. Increased survival of ant workers with biomineralized exoskeletons during aggressive encounters with other ants and reduced infection by entomopathogenic fungi demonstrate the protective role of the biomineral layer. The discovery of biosynthesized high-magnesium calcite in the relatively well-studied leaf-cutting ants suggests that calcareous biominerals enriched in magnesium may be more common in metazoans than previously recognized.

biophysics↗