Biology subjects

Zhuang, J.

Publications and source records attributed to Zhuang, J..

5 recordsLinked to original sources

bioRxiv2018

Biological variation in the sizes, shapes and locations of visual cortical areas in the mouse

Visual cortex is organized into discrete sub-regions or areas that are arranged into a hierarchy and serve different functions in the processing of visual information. In our previous work, we noted that retinotopic maps of cortical visual areas differed between mice, but did not quantify these differences or determine the relative contributions of biological variation and measurement noise. Here we quantify the biological variation in the size, shape and locations of 11 visual areas in the mouse. We find that there is substantial biological variation in the sizes of visual areas, with some visual areas varying in size by two-fold across the population of mice.

neuroscience↗

bioRxiv2018

Impact of Microbial Iron Oxide Reduction on the Transport of Diffusible Tracers and Non-diffusible Nanoparticles in Soils

AbstractIn situ bioremediation to achieve immobilization of toxic metals and radionuclides or detoxification of chlorinated solvents relies on electron donor additions. This practice promotes microbial Fe(III)-oxide mineral reduction that could change soil pore structure, release soil colloids, alter matrix surface properties, and cause the formation of secondary (i.e., reduced) Fe-mineral phases. These processes in turn may impact rates of bioremediation, groundwater quality, and ultimately contaminant fate. Continuous flow columns packed with water-stable soil aggregates high in Fe-oxides were infused with artificial groundwater containing acetate as electron donor and operated for 20 or 60 days inside an anoxic chamber. Soluble Fe(II) and soil colloids were detected in the effluent within one week after initiation of the acetate addition, demonstrating Fe(III)-bioreduction and colloid formation. Br-, 2,6-difluorobenzoate (DFBA), and silica-shelled silver nanoparticles (SSSNP) were selected as diffusible tracer, low-diffusible tracer, and non-diffusible nanoparticles, respectively, to perform transport experiments before and after the active 20-day bioreduction phase, with an aim of assessing the changes in soil structure and surface chemical properties resulting from Fe(III)-bioreduction. The transport of diffusible Br- was not influenced by the Fe(III)-bioreduction as evidenced by identical breakthrough curves before and after the introduction of acetate. Low-diffusible DFBA showed earlier breakthrough and less tailing after the bioreduction, suggesting alterations in flow paths and surface chemical properties of the soils. Similarly, non-diffusible SSSNP exhibited early breakthrough and enhanced transport after the bioreduction phase. Unexpectedly, the bioreduction caused complete retention of SSSNP in the soil columns when the acetate injection was extended from 20 days to 60 days, though no changes were observed for Br- and DFBA during the extended bioreduction period. The large change in the transport of SSSNP was attributed to the enhancement of soil aggregate breakdown and soil colloid release causing mechanical straining of SSSNP and the exposure of iron oxide surfaces previously unavailable within aggregate interiors favorable to the attachment of SSSNP. These results demonstrate that microbial activity can affect soil properties and transport behaviors of diffusivity-varying solutes and colloids in a time dependent fashion, a finding with implication for interpreting the data generated from soil column experiments under continuous flow.\n\nHighlightsO_LIFe(III)-bioreduction causes time-dependent aggregate breakdown and colloid release.\nC_LIO_LIShort-term bioreduction alters soil aggregate surface chemistry and tracer transport.\nC_LIO_LIElectron donor amendment enhances transport of nanoparticle tracer.\nC_LI

microbiology↗

bioRxiv2018

A novel GATA-binding protein 4 gene variation associated with familial atrial septal defect

Atrial septal defect (ASD) is the most common congenital heart defect. Part of ASD exhibits familial predisposition, but the genetic mechanism remains largely unknown. In the current study, we use multiple methods to identify and confirm the gene associated with a familial ASD. Chromosomal microarray analyses, whole exome sequencing, Sanger sequencing, multiple bioinformatics programs, in silico protein structure modeling and molecular dynamics simulation were performed to predict the pathogenic of the variant gene. Dual-Luciferase reporter gene assay was performed to evaluate the influence of downstream target gene of the target variation. A novel, heterozygous, missense variant GATA-binding protein 4 (GATA4):c.958C>T, p.R320W was identified. An autosomal dominant inheritance pattern with incomplete penetrance was observed in the family. Multiple prediction indicate the variant in GATA4 to be deleterious. Molecular dynamics simulation further revealed that the variation of p.R320W could prevent the zinc finger of GATA4 from interacting with the DNA. Dual-Luciferase reporter assay demonstrated a significant decrease in transcriptional activity (0.90{+/-}0.099 vs 1.50{+/-}0.079, p = 0.001) of the variant GATA4 compared with the wild type. We believe the novel variation of GATA4 (c.958C>T, p.R320W) with a pattern of incomplete inheritance that may be highly associated with this familial ASD. The finding enriched our knowledge of variations that may associated with ASD.

genetics↗

bioRxiv2017

Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines

Transgenic mouse lines are invaluable tools for neuroscience but as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically-encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, though rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

neuroscience↗

bioRxiv2017

Human PGBD5 DNA transposase promotes site-specific oncogenic mutations in rhabdoid tumors

Genomic rearrangements are a hallmark of childhood solid tumors, but their mutational causes remain poorly understood. Here, we identify the piggyBac transposable element derived 5 (PGBD5) gene as an enzymatically active human DNA transposase expressed in the majority of rhabdoid tumors, a lethal childhood cancer. Using assembly-based whole-genome DNA sequencing, we observed previously unknown somatic genomic rearrangements in primary human rhabdoid tumors. These rearrangements were characterized by deletions and inversions involving PGBD5-specific signal (PSS) sequences at their breakpoints, with some recurrently targeting tumor suppressor genes, leading to their inactivation. PGBD5 was found to be physically associated with human genomic PSS sequences that were also sufficient to mediate PGBD5-induced DNA rearrangements in rhabdoid tumor cells. We found that ectopic expression of PGBD5 in primary immortalized human cells was sufficient to promote penetrant cell transformation in vitro and in immunodeficient mice in vivo. This activity required specific catalytic residues in the PGBD5 transposase domain, as well as end-joining DNA repair, and induced distinct structural rearrangements, involving PSS-associated breakpoints, similar to those found in primary human rhabdoid tumors. This defines PGBD5 as an oncogenic mutator and provides a plausible mechanism for site-specific DNA rearrangements in childhood and adult solid tumors.

cancer biology↗