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Biology subjects

Yong, Z.

Publications and source records attributed to Yong, Z..

4 recordsLinked to original sources

Taxon-resolved sources of organic carbon preserved in lake sediments using the sedaDNA GenC pipeline

Organic carbon (OC) burial in lakes is an important component of the global carbon cycle, but the source organisms of preserved OC remain poorly resolved. Here we develop the genC pipeline, which combines sedimentary ancient DNA concentrations, read-based taxonomic assignments, and group-specific priors for DNA and cellular carbon content to derive OCDNA-projected, a semi-quantitative proxy for the magnitude and taxonomic composition of preserved sedimentary OC. We apply genC to six high-latitude lake records spanning the last 30,000 years. OCDNA-projected broadly agrees with independent proxies for total organic carbon and aquatic contribution, supporting its reliability. Our results indicate that environmental conditions, especially warming, rather than preservation alone, are the main drivers of preserved OC variation. Terrestrial sources, mainly woody plants, dominate lake sediment OC. Eukaryotic algae as well as aquatic and terrestrial bacteria become more important during the warmer Holocene. These results establish sedaDNA as a taxonomically resolved tool for reconstructing long-term changes in preserved lake-sediment OC.

paleontology↗

Divergent stem cell mechanisms governing the primary body axis and appendage regeneration in the axolotl

Exploring the fundamental mechanisms of organ regeneration is crucial for advancing regenerative medicine. The axolotl tail represents a unique opportunity to study regeneration of the primary axis including segmented muscle, vertebrae and skin. During tail development, muscle stem cells (MuSCs) displayed expected specificity to the muscle lineage. Tail amputation, however, induced expansion of MuSC potential yielding clonal contribution to muscle, connective tissue including cartilage, pericytes, and fibroblasts. This expanded potential was not observed during limb regeneration, and cross-transplantation showed these differences in potential are intrinsic. ScRNA-Seq profiling revealed that tail MuSCs revert to an embryonic mesoderm-like state. Through genetic manipulation involving the over-expression of constitutively active TGF-{beta} receptors or Smad7 (antagonist of TGF-{beta} signaling) in MuSCs, we demonstrated that the levels of TGF-{beta} signal determine the fate outcome of MuSCs to connective tissue lineage or muscle respectively. Our findings illustrate a fundamental difference between regeneration of primary axis versus limb and offers a novel stem cell source for regeneration of axial skeletal tissues.

developmental biology↗

Engineering highly multivalent sperm-binding IgG antibodies for potent non-hormonal female contraception

Many women risk unintended pregnancy due to dissatisfaction with available hormonal contraceptive methods. This led us to pursue topical sperm-binding monoclonal antibodies as a strategy for safe, non-hormonal contraception. Motivated by the greater agglutination potencies of polymeric immunoglobulins such as IgM and the exceptional bioprocessing ease in manufacturing IgG, we engineered IgGs possessing 6-10 Fabs against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) are at least 10- to 16-fold more potent and faster than the parent IgG at agglutinating sperm, while preserving Fc-mediated trapping of individual spermatozoa in mucus. The increased potencies translate to effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using 33 micrograms of the 10 Fab HM-IgG. HM-IgGs produce at comparable yields and possess identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for non-hormonal contraception but also a promising platform for generating potent agglutinating mAb for diverse medical applications.

molecular biology↗

A genetically-encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice

Dopamine (DA) is a central monoamine neurotransmitter involved in many physiological and pathological processes. A longstanding yet largely unmet goal is to measure DA changes reliably and specifically with high spatiotemporal precision, particularly in animals executing complex behaviors. Here we report the development of novel genetically-encoded GPCR-Activation-Based-DA (GRABDA) sensors that enable these measurements. In response to extracellular DA rises, GRABDA sensors exhibit large fluorescence increases ({Delta}F/F0[~]90%) with sub-second kinetics, nanomolar to sub-micromolar affinities, and excellent molecular specificity. Importantly, GRABDA sensors can resolve a single-electrical-stimulus evoked DA release in mouse brain slices, and detect endogenous DA release in the intact brains of flies, fish, and mice. In freely-behaving mice, GRABDA sensors readily report optogenetically-elicited nigrostriatal DA release and depict dynamic mesoaccumbens DA changes during Pavlovian conditioning or during sexual behaviors. Thus, GRABDA sensors enable spatiotemporal precise measurements of DA dynamics in a variety of model organisms while exhibiting complex behaviors.

neuroscience↗