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Agency for Science, Technology and Research

GovernmentSingapore, Singapore
About: Agency for Science, Technology and Research is a government organization based out in Singapore, Singapore. It is known for research contribution in the topics: Population & Catalysis. The organization has 16013 authors who have published 24427 publications receiving 832302 citations. The organization is also known as: A*STAR & A-Star.


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Journal ArticleDOI
TL;DR: It is found that in vitro exposure of karyotypesically stable human colorectal cancer cell lines to environmental stress conditions triggered a wide variety of chromosomal changes and karyotypic heterogeneity and heat-induced tetraploid cells were on the average more resistant to chemotherapeutic agents.
Abstract: Understanding how cells acquire genetic mutations is a fundamental biological question with implications for many different areas of biomedical research, ranging from tumor evolution to drug resistance. While karyotypic heterogeneity is a hallmark of cancer cells, few mutations causing chromosome instability have been identified in cancer genomes, suggesting a nongenetic origin of this phenomenon. We found that in vitro exposure of karyotypically stable human colorectal cancer cell lines to environmental stress conditions triggered a wide variety of chromosomal changes and karyotypic heterogeneity. At the molecular level, hyperthermia induced polyploidization by perturbing centrosome function, preventing chromosome segregation, and attenuating the spindle assembly checkpoint. The combination of these effects resulted in mitotic exit without chromosome segregation. Finally, heat-induced tetraploid cells were on the average more resistant to chemotherapeutic agents. Our studies suggest that environmental perturbations promote karyotypic heterogeneity and could contribute to the emergence of drug resistance.

20 citations

Journal ArticleDOI
TL;DR: De deleting KRE6 or SKN1 caused slow growth, cell separation failure, cell wall abnormalities, diminished hyphal growth, poor biofilm formation and loss of virulence in mice, suggesting Kre6 and Skn1 are worthy targets for developing antifungal agents.
Abstract: β-1,6-glucan is an important component of the fungal cell wall. The β-1,6-glucan synthase gene KRE6 was thought to be essential in the fungal pathogen Candida albicans because it could not be deleted in previous efforts. Also, the role of its homolog SKN1 was unclear because its deletion caused no defects. Here, we report the construction and characterization of kre6Δ/Δ, skn1Δ/Δ and kre6Δ/Δ skn1Δ/Δ mutants in C. albicans. While deleting KRE6 or SKN1 had no obvious phenotypic consequence, deleting both caused slow growth, cell separation failure, cell wall abnormalities, diminished hyphal growth, poor biofilm formation and loss of virulence in mice. Furthermore, the GPI-linked cell surface proteins Hwp1 and the invasin Als3 or Ssa1 were not detected in kre6Δ/Δ skn1Δ/Δ mutant. In GMM medium, RT-qPCR and western blotting revealed a constitutive expression of KRE6 and growth conditions-associated activation of SKN1. Like many hypha-specific genes, SKN1 is repressed by Nrg1, but its activation does not involve the transcription factor Efg1. Dysregulation of SKN1 reduces C. albicans ability to damage epithelial and endothelial cells and attenuates its virulence. Given the vital role of β-1,6-glucan synthesis in C. albicans physiology and virulence, Kre6 and Skn1 are worthy targets for developing antifungal agents.

20 citations

Journal ArticleDOI
TL;DR: New ideas and research works which have been carried out over the last several years in this relatively new area with a main focus on their mechanism in self-assembly and applications are discussed, followed by the proposed design considerations to address the challenges that the authors may face in the future.
Abstract: Understanding the mechanism of molecular self-assembly to form well-organized nanostructures is essential in the field of supramolecular chemistry. Particularly, amphiphilic copolymers incorporated with polyhedral oligomeric silsesquioxanes (POSSs) have been one of the most promising materials in material science, engineering, and biomedical fields. In this review, new ideas and research works which have been carried out over the last several years in this relatively new area with a main focus on their mechanism in self-assembly and applications are discussed. In addition, insights into the unique role of POSSs in synthesis, microphase separation, and confined size were encompassed. Finally, perspectives and challenges related to the further advancement of POSS-based amphiphilics are discussed, followed by the proposed design considerations to address the challenges that we may face in the future.

20 citations

Journal ArticleDOI
TL;DR: In this article, the authors used single-cell RNA-seq to survey the human liver and identified potentially implicated liver cell-type for viral ingress, which indicated that in COVID-19-associated liver dysfunction and cell death, a viral infection of TROP2+ progenitors in the liver might significantly impair liver regeneration in patients with liver cirrhosis.
Abstract: The recent coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 was first reported in China (December 2019) and is now prevalent across the globe. Entry of severe acute respiratory syndrome coronavirus 2 into mammalian cells requires the binding of viral Spike (S) proteins to the angiotensin-converting enzyme 2 receptor. Once entered, the S protein is primed by a specialized serine protease, transmembrane serine protease 2 in the host cell. Importantly, besides the respiratory symptoms that are consistent with other common respiratory virus infections when patients become viremic, a significant number of COVID-19 patients also develop liver comorbidities. We explored whether a specific target cell-type in the mammalian liver could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here, we used single-cell RNA-seq to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We analyzed ~300,000 single cells across five different (i.e., human fetal, healthy, cirrhotic, tumor, and adjacent normal) liver tissue types. This study reports on the co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 in a TROP2+ liver progenitor population. Importantly, we detected enrichment of this cell population in the cirrhotic liver when compared with tumor tissue. These results indicated that in COVID-19-associated liver dysfunction and cell death, a viral infection of TROP2+ progenitors in the liver might significantly impair liver regeneration in patients with liver cirrhosis.

20 citations

Journal ArticleDOI
TL;DR: Polymorphisms in NQO1, IL-10 and PTPN11, in combination with HP status, could be used to identify individuals who are more likely to develop IM and therefore GC.
Abstract: Intestinal metaplasia (IM) is an important precursor lesion in the development of gastric cancer (GC). The aim of this study was to investigate genetic factors previously linked to GC risk for their possible association with IM. A total of 18 polymorphisms in 14 candidate genes were evaluated in a Singapore-Chinese population at high risk of developing GC. Genotype frequencies were compared between individuals presenting with (n = 128) or without (n = 246) IM by both univariate and multivariate analysis. Carriers of the NQO1 609 T allele showed an association with IM in individuals who were seropositive for Helicobacter pylori (HP+; OR = 2.61, 95%CI: 1.18-5.80, P = .018). The IL-10 819 C allele was also associated with IM in HP+ individuals (OR = 2.32, 95%CI: 1.21-4.43, P = 0.011), while the PTPN11 A allele was associated with IM in HP- individuals (OR = 2.51, 95%CI: 1.16-5.40, P = 0.019), but showed an inverse association in HP+ subjects (OR = 0.46, 95%CI: 0.21-0.99, P = 0.048). Polymorphisms in NQO1, IL-10 and PTPN11, in combination with HP status, could be used to identify individuals who are more likely to develop IM and therefore GC.

20 citations


Authors

Showing all 16109 results

NameH-indexPapersCitations
Patrick O. Brown183755200985
Alberto Mantovani1831397163826
Paul G. Richardson1831533155912
Barry Halliwell173662159518
Tien Yin Wong1601880131830
Leroy Hood158853128452
Johan G. Eriksson1561257123325
Nancy A. Jenkins155741101587
Neal G. Copeland154726100130
Rui Zhang1512625107917
Seeram Ramakrishna147155299284
Mark M. Davis14458174358
Bin Liu138218187085
Michael J. Meaney13660481128
Michael R. Hayden13589173619
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202329
2022196
20212,127
20202,011
20191,783
20181,750