Biology subjects

Chin, K.

Publications and source records attributed to Chin, K..

22 records · Page 2Linked to original sources

bioRxiv2019

RESTORE: Robust intEnSiTy nORmalization mEthod for Multiplexed Imaging

Recent advances in multiplexed imaging technologies promise to improve the understanding of the functional states of individual cells and the interactions between the cells in tissues. This often requires compilation of results from multiple samples. However, quantitative integration of information between samples is complicated by variations in staining intensity and background fluorescence that obscure biological variations. Failure to remove these unwanted artefacts will complicate downstream analysis and diminish the value of multiplexed imaging for clinical applications. Here, to compensate for unwanted variations, we automatically identify negative control cells for each marker within the same tissue and use their expression levels to infer background signal level. The intensity profile is normalized by the inferred level of the negative control cells to remove between-sample variation. Using a tissue microarray data and a pair of longitudinal biopsies sample, we demonstrated that the proposed approach can remove unwanted variations effectively and shows robust performance.

systems biology↗

bioRxiv2019

HER2 Cancer Protrusion Growth Signaling Regulated by Unhindered, Localized Filopodial Dynamics

Protrusions are plasma membrane extensions that are found in almost every cell in the human body. Cancer cell filopodial and lamellipodial protrusions play key roles in the integral processes of cell motility and signaling underlying tumor invasion and metastasis. HER2 (ErbB-2) is overexpressed in diverse types of tumors and regulates PI3K-pathway-mediated protrusion growth. It is known that HER2 resides at breast cancer cell protrusions, but how protrusion-based HER2 spatiotemporal dynamics shape cancer signaling is unclear. Here, we study how HER2 location and motion regulate protrusion signaling and growth using quantitative spatio-temporal molecular imaging approaches. Our data highlight morphologically-segregated features of filopodial and lamellipodial protrusions, in in vitro 2D breast cancer cells and in vivo intact breast tumor. Functional-segregation parallels morphological-segregation, as HER2 and its activated downstream pAKT-PI3K signaling remain spatially-localized at protrusions, provoking new protrusion growth proximal to sites of HER2 activation. HER2 in SKBR3 breast cancer cell filopodia exhibits fast, linearly-directed motion that is distinct from lamellipodia and non-protrusion subcellular regions ([~]3-4 times greater diffusion constant, rapid speeds of 2-3 um2/s). Surprisingly, filopodial HER2 motion is passive, requiring no active energy sources. Moreover, while HER2 motion in lamellipodia and non-protrusion regions show hindered diffusion typical of membrane proteins, HER2 diffuses freely within filopodia. We conclude that HER2 activation, propagation, and functional protrusion growth is a local process in which filopodia have evolved to exploit Brownian thermal fluctuations within a barrier-free nanostructure to transduce rapid signaling. These results support the importance of developing filopodia and other protrusion-targeted strategies for cancer.

cancer biology↗

bioRxiv2019

Improvements in upper extremity function in children with unilateral spastic cerebral palsy after intensive training correlates with interhemispheric connectivity

AIMSThe corpus callosum (CC) regulates signalling between the two hemispheres and plays an important role in upper limb functions. There is limited evidence on the relationships between the integrity of the CC and upper limb functions in children with USCP. Furthermore, the extent of how much the CC can be used as a biomarker to predict hand functions following intensive interventions remains unknown. We examined 1) the relationship between hand function and tractography of the CC, and 2) the associations between the integrity of the CC and changes in hand function following intensive intervention.\n\nMETHODSForty-four participants received 90 hours of intensive therapy and were randomly allocated in one of two training groups: Hand-arm Bimanual Intensive Therapy (HABIT) or Constraint-Induced Movement Therapy (CIMT). Hand functions were assessed pre-and post-intervention by a blinded clinician using the Jebsen-Taylor of Hand Function (JTTHF), Assisting Hand Assessment (AHA), and Box and Blocks test (BBT). Functional goals and daily functioning were measured using the Canadian Occupational Performance Measure and the Abilhand-Kids. CC tractography was reconstructed using diffusion tensor imaging (DTI). Corpus callosum was segmented into three regions of interest (genu, midbody and splenium). Linear regression and pearson correlations were used to assess the relationships between bimanual outcomes and DTI parameters.\n\nRESULTSBoth groups demonstrated improvement of hand function (p<0.05). JTTHF, AHA and BBT significant correlated with DTI variables for all ROIs (p<0.05). Bimanual and perceived manual ability of children changes following CIMT were negatively correlated with number of streamlines and number of voxel for the whole CC (r=-.442, p=0.05), midbody (r=-.458, p=0.042) and spelnium (r=-.512, p=0.021). No significant correlation was observed for the HABIT group.\n\nINTERPRETATIONTractography of the CC was found to be associated with unimanual and bimanual functions at baseline. Children with reduced integrity of the CC and with greater bimanual impairments improve more from CIMT. On the contrary, all children in the HABIT group had similar improvements independent of the CC integrity.

neuroscience↗

bioRxiv2018

A novel role for Cyclic Nucleotide-Gated Ion Channel 2 (DND1) in auxin signaling

Cyclic Nucleotide Gated Ion Channels (CNGCs) have been firmly established as Ca2+-conducting ion channels that regulate a wide variety of physiological responses in plants. CNGC2 has been implicated in plant immunity and Ca2+ signaling due to the autoimmune phenotypes exhibited by null mutants of CNGC2. However, cngc2 mutants display additional phenotypes that are unique among autoimmune mutants, suggesting that CNGC2 has functions beyond defense and generates distinct Ca2+ signals in response to different triggers. In this study we found that cngc2 mutants showed reduced gravitropism, consistent with a defect in auxin signaling. This was mirrored in the diminished auxin response detected by the auxin reporters DR5::GUS and DII-VENUS and in a strongly impaired auxin-induced Ca2+ response. Moreover, the cngc2 mutant exhibits higher levels of the endogenous auxin indole-3-acetic acid (IAA), indicating that excess auxin in cngc2 causes its pleiotropic phenotypes. These auxin signaling defects and the autoimmunity syndrome of cngc2 could be suppressed by loss-of-function mutations in the auxin biosynthesis gene YUCCA6 (YUC6), as determined by identification of the cngc2 suppressor mutant repressor of cngc2 (rdd1) as an allele of YUC6. A loss-of-function mutation in the upstream auxin biosynthesis gene TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS (TAA1, WEAK ETHYLENE INSENSITIVE8) also suppressed the cngc2 phenotypes, further supporting the tight relationship between CNGC2 and the TAA-YUC-dependent auxin biosynthesis pathway. Taking these results together, we propose that the Ca2+ signal generated by CNGC2 is a part of the negative feedback regulation of auxin homeostasis in which CNGC2 balances cellular auxin perception by influencing auxin biosynthesis.

plant biology↗