Biology subjects

Yang, E.

Publications and source records attributed to Yang, E..

4 recordsLinked to original sources

bioRxiv2018

Multiple loci of small effect confer wide variability in efficiency and resistance rate of CRISPR gene drive

Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. CRISPR homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles by homology-directed repair, increasing the frequency of the drive in a population. However, resistance alleles can form when end-joining repair takes place in lieu of homology-directed repair. Such alleles cannot be converted to drive alleles, which would halt the spread of a drive through a population. To investigate the effects of natural genetic variation on resistance formation, we developed a CRISPR homing gene drive in Drosophila melanogaster and crossed it into the genetically diverse Drosophila Genetic Reference Panel (DGRP) lines, measuring several performance parameters. Most strikingly, resistance allele formation post-fertilization in the early embryo ranged from 7% to 79% among lines and averaged 42{+/-}18%. We performed a Genome-Wide Association Study (GWAS) using our results in the DGRP lines and found that the resistance and conversion rates were polygenic, with several genetic polymorphisms showing relatively weak association. RNAi knockdown of several of these genes confirmed their effect, but their small effect sizes implies that their manipulation will yield only modest improvements to the efficacy of gene drives.

genetics↗

bioRxiv2018

Molecular safeguarding of CRISPR gene drive experiments

CRISPR-based gene drives have sparked both enthusiasm and deep concerns due to their potential for genetically altering entire species. This raises the question about our ability to prevent the unintended spread of such drives from the laboratory into a natural population. Here, we experimentally demonstrate the suitability of synthetic target sites and split drives as flexible safeguarding strategies for gene drive experiments.

genetics↗

bioRxiv2018

Lrfn2-mutant mice display suppressed synaptic plasticity and inhibitory synapse development and abnormal social communication and startle response

SALM1, also known as LRFN2, is a PSD-95-interacting synaptic adhesion molecule implicated in the regulation of NMDA receptor (NMDAR) clustering largely based on in vitro data, although its in vivo functions remain unclear. Here, we found that mice lacking SALM1/LRFN2 (Lrfn2-/- mice) show a normal density of excitatory synapses but altered excitatory synaptic function, including enhanced NMDAR-dependent synaptic transmission but suppressed NMDAR-dependent synaptic plasticity in the hippocampal CA1 region. Unexpectedly, SALM1 expression is detected in both glutamatergic and GABAergic neurons, and Lrfn2-/- CA1 pyramidal neurons show decreases in the density of inhibitory synapses and frequency of spontaneous inhibitory synaptic transmission. Behaviorally, ultrasonic vocalization was suppressed in Lrfn2-/- pups separated from their mothers, and acoustic startle was enhanced, but locomotion, anxiety-like behavior, social interaction, repetitive behaviors, and learning and memory were largely normal in adult Lrfn2-/- mice. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, and social communication and startle behaviors in mice.\n\nSignificance StatementSynaptic adhesion molecules regulate synapse development and function, which govern neural circuit and brain functions. The SALM/LRFN family of synaptic adhesion proteins consists of five known members whose in vivo functions are largely unknown. Here we characterized mice lacking SALM1/LRFN2 (SALM1 knockout) known to associate with NMDA receptors and found that these mice showed altered NMDA receptor-dependent synaptic transmission and plasticity, as expected, but unexpectedly also exhibited suppressed inhibitory synapse development and synaptic transmission. Behaviorally, SALM1 knockout pups showed suppressed ultrasonic vocalization upon separation from their mothers, and SALM1 knockout adults showed enhanced responses to loud acoustic stimuli. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, social communication, and acoustic startle behavior.

neuroscience↗

bioRxiv2017

Long-range infra-sound acoustic signaling inhuman in vivo

Acupuncture is widely deployed today, but its basic physiology with Qi and meridian is not understood. This letter postulates that Qi is an infrasound wave packet and meridian is the muscle waveguide. Using video cameras and signal processing in an IRB approved clinical experiment we performed a comparison between control and electro-activated statistical tests on the long range (50-80cm) unidirectional transmission of Qi (p = 0.025). In the reverse direction, there is no transmission even in a distance of less than 10 cm (p = 0.545). The rectification is a surprise but in full agreement with Huang Di Nei Jing.

physiology↗