Biology subjects

Su, P.

Publications and source records attributed to Su, P..

26 records · Page 2Linked to original sources

bioRxiv2020

Alisertib exerts KRAS allele specific anticancer effects in colorectal cancer

Colorectal cancer (CRC) is a common cancer causing substantial mortality and morbidity worldwide. Oncogene RAS mutations occur notably in [~]45% of CRCs, associated with a poor prognosis. KRAS is subject to multiple tiers of regulation, including kinase. Aurora kinases has been implicated in many types of tumor onsets and progression, making them as a promising therapeutic targets. Alisertib (ALS), selectively inhibits Aurora kinase A (AURKA) and exerts potent anticancer activities in vitro and in vivo studies, but the latent anticancer effect of ALS on CRC remains unclear in the context of different KRAS mutations. This study aimed to assess the effects of ALS on RAS signaling pathway in a panel of CRC lines expressing different KRAS alleles, including Caco-2 (KRAS WT), Colo-678 (KRAS G12D), SK-CO-1 (KRAS G12V), HCT116 (KRAS G13D), CCCL-18 (KRAS A146T), and HT29 (BRAF V600E). The results showed that ALS modulated the active form of KRAS in a RAS allele specific manner across the panel of CRC lines; ALS differentially regulated RAS signal via PI3K/Akt and MAPK pathways; and ALS induced apoptosis and autophagy in a RAS allele specific manner. Of note, in combination of ALS and MEK inhibitor, selumetinib, enhanced ALS regulatory effects in CRC lines in a RAS allele specific manner on apoptosis, autophagy, and cell growth. Taken together, this study suggests that ALS differentially regulates RAS signaling pathway and manipulates cell apoptosis and autophagy in RAS allele specific manner. The combinatorial approach of ALS and MEK inhibitor may represent a new therapeutic strategy for precision therapy of CRC in a RAS allele manner.

cancer biology↗

bioRxiv2020

High-throughput whole-brain mapping of rhesus monkey at micron resolution

Whole-brain mesoscale mapping of primates has been hindered by large brain size and the relatively low throughput of available microscopy methods. Here, we present an integrative approach that combines primate-optimized tissue sectioning and clearing with ultrahigh-speed, large-scale, volumetric fluorescence microscopy, capable of completing whole-brain imaging of a rhesus monkey at 1 {micro}m x 1 {micro}m x 2.5 {micro}m voxel resolution within 100 hours. A progressive strategy is developed for high-efficiency, long-range tracing of individual axonal fibers through the dataset of hundreds of terabytes, establishing a "Serial sectioning and clearing, 3-dimensional Microscopy, with semi-Automated Reconstruction and Tracing" (SMART) pipeline. This system supports effective connectome-scale mapping of large primates that reveals distinct features of thalamocortical projections of the rhesus monkey brain at the level of individual axonal fibers.

neuroscience↗

bioRxiv2019

MACF1 Facilitates SMAD7 Nuclear Translocation to Drive Bone Formation in Mice

MACF1 is a large crosslinker that contributes to cytoskeleton integrity and cell differentiation. Loss of MACF1 impairs multiple cellular functions in neuron development and epidermal migration, and is the molecular basis for many diseases such as heart failure and Parkinsons disease. MACF1 is highly abundant in bones, however, its involvements in osteogenic differentiation and bone formation are still unknown. In this study, by conditional gene targeting to delete the Macf1 gene specifically in MSCs, we observed ossification retardation and bone loss in MACF1 deficient mice in different developmental stages, which we traced to disorganized cytoskeleton and decreased osteogenic differentiation capability in MSCs. Further, we show that MACF1 interacts and facilitates SMAD7 nuclear translocation to initiate downstream transcription. These findings are hopefully to expand the biological scope of MACF1 in bones, and provide experimental basis for targeting MACF1 in degenerative bone diseases such as osteoporosis.

developmental biology↗

bioRxiv2019

Using distant supervision to augment manually annotated data for relation extraction

Significant progress has been made in applying deep learning on natural language processing tasks recently. However, deep learning models typically require a large amount of annotated training data while often only small labeled datasets are available for many natural language processing tasks in biomedical literature. Building large-size datasets for deep learning is expensive since it involves considerable human effort and usually requires domain expertise in specialized fields. In this work, we consider augmenting manually annotated data with large amounts of data using distant supervision. However, data obtained by distant supervision is often noisy, we first apply some heuristics to remove some of the incorrect annotations. Then using methods inspired from transfer learning, we show that the resulting models outperform models trained on the original manually annotated sets.

bioinformatics↗

bioRxiv2019

Characterization of Rhodopseudomonas palustris population dynamics on tobacco phyllosphere and induction of plant resistance to Tobacco mosaic virus i

Although many biocontrol bacteria can be used to improve plant tolerance to stresses and to promote plant growth, the hostile environmental conditions on plant phyllosphere and the limited knowledge on bacterial colonization on plant phyllosphere minimized the beneficial effects produced by the biocontrol bacteria. Rhodopseudomonas palustris strain GJ-22 is known as a phyllosphere biocontrol agent. In this paper we described detailed processes of strain GJ-22 colony establishment at various colonization stages. We have shown that the preferable location sites of bacterial aggregates on leaf phyllosphere are grooves between plant epidermal cells. In this study, we categorized bacterial colonies into four phases. Analyses of expressions of plant defense-related genes showed that, starting from Phase III, bacterial cells in the Type 3 and Type 4 colonies started produce unidentified signals to induce host defense again Tobacco mosaic virus infection. To our knowledge, this is the first report focused on the colonization process of a phyllosphere biocontrol agent.

microbiology↗

bioRxiv2018

Cultural background influences electrical stimulation effects on the social brain

ABSTRACTCultural background influences social cognition, however no study has examined brain stimulation differences attributable to cultural background. 104 young adults [52 South-East Asian Singaporeans (SEA); 52 Caucasian Australians (CA)] received anodal high-definition transcranial direct current stimulation (HD-tDCS) to the dorsomedial prefrontal cortex (dmPFC) or the right temporoparietal junction (rTPJ). Participants completed tasks with varying demands on self-other processing including visual perspective taking and episodic memory with self and other encoding. At baseline, SEA showed greater self-other integration than CA in the level one (line-of-sight) VPT task as indexed by greater interference from the alternate perspective. Anodal HD-tDCS to the dmPFC resulted in the CA performing closer to the SEA during egocentric perspective judgements. Baseline performance on level two (embodied rotation) VPT task and the self-reference effect in memory (SRE) was comparable between the two groups. In the combined sample, HD-tDCS to the rTPJ decreased the interference from the egocentric perspective during level two VPT and dmPFC HD-tDCS removed the SRE in episodic memory. Stimulation effects were comparable when baseline performance was comparable. When baseline performance differed, stimulation differences were identified. Therefore, social cognitive differences due to cultural background are an important consideration in social brain stimulation studies.\n\nHIGHLIGHTSO_LICompared with Caucasians, South-East Asians were influenced by the alternate perspective to a greater extent during level one visual perspective taking\nC_LIO_LIAnodal HD-tDCS to the dmPFC shifted Caucasians closer to the baseline performance of South-East Asians\nC_LIO_LIAnodal HD-tDCS to the dmPFC removed the self-reference effect in episodic memory in both cultural groups\nC_LIO_LIAnodal HD-tDCS to the dmPFC reduced overall memory performance in the South-East Asians but not in the Caucasian group\nC_LIO_LIAnodal HD-tDCS to the rTPJ reduced egocentric interference in a level two visual perspective taking task in both cultural groups\nC_LI

neuroscience↗

bioRxiv2018

Improving cross-cultural \"mind-reading\" with electrical brain stimulation

Background: A cross-cultural disadvantage exists when inferring the mental state of others, which may be detrimental for individuals acting in an increasingly globalized world. The dorsomedial prefrontal cortex (dmPFC) is a key hub of the social brain involved in ToM. Therefore, we explored whether facilitation of dmPFC function by focal high-definition tDCS can improve cross-cultural mind-reading.\n\nMethod: 52 (26 F/M) Singaporeans performed the Caucasian version of the Reading the Mind in the Eyes Test (RMET) and received HD-tDCS to either the dmPFC or a control site (right temporoparietal junction,rTPJ) in sham-controlled, double-blinded, crossover studies. Contact with Caucasians was determined for the Singaporean cohort as a potential mediator of RMET performance and HD-tDCS response. 52 Caucasians completed the RMET during sham-tDCS and served as a comparison group.\n\nResults: A cross-cultural disadvantage on the RMET was confirmed in the Singaporean cohort and this disadvantage was more pronounced in those participants who had less contact with Caucasians. Importantly, HD-tDCS to the dmPFC improved RMET performance in those with less contact. No effect was identified for rTPJ HD-tDCS or for the age/sex control task demonstrating task and site specificity of the stimulation effects.\n\nConclusion: Electrical stimulation of the dmPFC selectively improves the rate of cross-cultural ToM inference from facial cues, effectively removing cross-cultural disadvantage that was found in individuals with lower cross-cultural exposure.

neuroscience↗

bioRxiv2017

Scalable volumetric imaging for ultrahigh-speed brain mapping at synaptic resolution

We describe a new light-sheet microscopy method for fast, large-scale volumetric imaging. Combining synchronized scanning illumination and oblique imaging over cleared, thick tissue sections in smooth motion, our approach achieves high-speed 3D image acquisition of an entire mouse brain within 2 hours, at a resolution capable of resolving synaptic spines. It is compatible with immunofluorescence labeling, enabling flexible cell-type specific brain mapping, and is readily scalable for large biological samples such as primate brain.

neuroscience↗