Biology subjects

Chan, C. S.

Publications and source records attributed to Chan, C. S..

23 records · Page 2Linked to original sources

bioRxiv2019

Npas1+-Nkx2.1+ Neurons Form A Unique Pallidal Neuron Subclass

Within the basal ganglia circuit, the external globus pallidus (GPe) is critically involved in motor control. Aside from Foxp2+ neurons and ChAT+ neurons that have been established as unique neuron types, there is little consensus on the classification of GPe neurons. Properties of the remaining neuron types are poorly-defined. In this study, we leverage new mouse lines, viral tools, and molecular markers to better define GPe neuron subtypes. We found that Sox6 represents a novel, defining marker for GPe neuron subtypes. Lhx6+ neurons that lack the expression of Sox6 were devoid of both parvalbumin and Npas1. This result confirms previous assertions of the existence of a unique Lhx6+ population. Neurons that arise from the Dbx1+ lineage were similarly abundant in the GPe and displayed a heterogeneous makeup. Importantly, tracing experiments revealed that Npas1+-Nkx2.1+ neurons represent the principal non-cholinergic, cortically-projecting neurons. In other words, they form the pallido-cortical arm of the cortico-pallido-cortical loop. Our data further described that pyramidal-tract neurons in the cortex collateralized within the GPe, forming a closed-loop system between the two brain structures. Overall, our findings reconcile some of the discrepancies that arose from differences in techniques or the reliance on pre-existing tools. While spatial distribution and electrophysiological properties of GPe neurons reaffirm the diversification of GPe subtypes, statistical analyses strongly support the notion that these neuron subtypes can be categorized under the two principal neuron classes--i.e., PV+ neurons and Npas1+ neurons.\n\nSignificance statementThe poor understanding of the neuronal composition in the GPe undermines our ability to interrogate its precise behavioral and disease involvements. In this study, twelve different genetic crosses were used, hundreds of neurons were electrophysiologically-characterized, and over 100,000 neurons were histologically- and/or anatomically-profiled. Our current study further establishes the segregation of GPe neuron classes and illustrates the complexity of GPe neurons in adult mice. Our results support the idea that Npas1+-Nkx2.1+ neurons are a distinct GPe neuron subclass. By providing a detailed analysis of the organization of the cortico-pallidal-cortical projection, our findings establish the cellular and circuit substrates that can be important for motor function and dysfunction.

neuroscience↗

bioRxiv2019

Function and clinical relevance of RHAMM isoforms in pancreatic tumor progression

The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers. We previously screened genes upregulated in human hepatocellular carcinomas for their metastatic function in a mouse model of pancreatic neuroendocrine tumor (PNET) and identified that human RHAMMB promoted liver metastasis. It was unknown whether RHAMMB is upregulated in pancreatic cancer or contributes to its progression. In this study, we found that RHAMM protein was frequently upregulated in human PNETs. We investigated alternative splicing isoforms, RHAMMA and RHAMMB, by RNA-Seq analysis of primary PNETs and liver metastases. RHAMMB, but not RHAMMA, was significantly upregulated in liver metastases. RHAMMB was crucial for in vivo metastatic capacity of mouse and human PNETs. RHAMMA, carrying an extra 15-amino acid-stretch, did not promote metastasis in spontaneous and experimental metastasis mouse models. Moreover, RHAMMB was substantially higher than RHAMMA in pancreatic ductal adenocarcinoma (PDAC). RHAMMB, but not RHAMMA, correlated with both higher EGFR expression and poorer survival of PDAC patients. Knockdown of EGFR abolished RHAMMB-driven PNET metastasis. Altogether, our findings suggest a clinically relevant function of RHAMMB, but not RHAMMA, in promoting PNET metastasis in part through EGFR signaling. RHAMMB can thus serve as a prognostic factor for pancreatic cancer.

cancer biology↗

bioRxiv2018

Marine Fe-oxidizing Zetaproteobacteria: Historical, ecological, and genomic perspectives

The Zetaproteobacteria are a class of bacteria typically associated with marine Fe oxidizing environments. First discovered in the hydrothermal vents at Loihi Seamount, Hawaii, they have become model organisms for marine microbial Fe oxidation. In addition to deep sea and shallow hydrothermal vents, Zetaproteobacteria are found in coastal sediments, other marine subsurface environments, steel corrosion biofilms, as well as saline terrestrial aquifers and springs. Isolates from a range of environments all grow by Fe oxidation. Their success lies partly in their microaerophily, which enables them to compete with abiotic Fe oxidation at the low O2 concentrations common to Fe(II)-rich oxic/anoxic transition zones. Also, Zetaproteobacteria make a variety of biomineral morphologies as a repository for Fe(III) waste, and as attachment structures. To determine the known diversity of the Zetaproteobacteria, we have used 16S rRNA gene sequences to define 59 operational taxonomic units (OTUs), at 97% similarity. While some Zetaproteobacteria taxa appear to be cosmopolitan, various habitats enrich for different sets of Zetaproteobacteria. OTU networks show that certain Zetaproteobacteria co-exist, sharing compatible niches. These niches may correspond with adaptations to O2, H2, and nitrate availability, based on genomic analyses. Also, a putative Fe oxidation gene has been found in diverse Zetaproteobacteria taxa, suggesting that the Zetaproteobacteria evolved as specialists in Fe oxidation. In all, culture, genomic, and environmental studies suggest that Zetaproteobacteria are widespread, and therefore have a broad influence on marine and saline terrestrial Fe cycling.

microbiology↗

bioRxiv2018

ZetaHunter: a reproducible taxonomic classification tool for tracking the ecology of the Zetaproteobacteria and other poorly-resolved taxa

Like many taxa, the Zetaproteobacteria lack well-defined taxonomic divisions, 32 making it difficult to compare between studies. We designed ZetaHunter to reproducibly 33 assign 16S rRNA gene sequences to previously-described OTUs based on a curated 34 database. While ZetaHunter can use any given database, we include a curated 35 classification of publically-available Zetaproteobacteria.

bioinformatics↗

bioRxiv2017

A biological source of marine sedimentary iron oxides

The biogeochemical cycle of iron is intricately linked to numerous element cycles. Although reductive biological processes that bridge the iron cycle to other element cycles are established, little is known about microbial oxidative processes on iron cycling in sedimentary environments--resulting in the formation of iron oxides. Here, we show that a major source of sedimentary iron oxides originates from the metabolic activity of iron-oxidizing bacteria from the class Zetaproteobacteria, stimulated by burrowing animals in coastal sediments. Zetaproteobacteria were estimated to be a global total of 1026 cells in coastal, bioturbated sediments and would equate to an annual production of approximately 7.9 x 1015 grams of sedimentary iron oxides--twenty-five times larger than the annual flux of iron oxides by rivers. These data suggest that iron-oxidizing Zetaproteobacteria are keystone organisms in marine sedimentary environments given their low numerical abundance; yet exert a profound impact via the production of iron oxides.

microbiology↗