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12
result(s) for
"Sheeba, Caroline J."
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Nanoparticles Alter Secondary Metabolism in Plants via ROS Burst
by
Sheeba, Caroline J.
,
Marslin, Gregory
,
Franklin, Gregory
in
antioxidant enzymes
,
Antioxidants
,
Cerium oxides
2017
The particles within the size range of 1 and 100 nm are known as nanoparticles (NPs). NP-containing wastes released from household, industrial and medical products are emerging as a new threat to the environment. Plants, being fixed to the two major environmental sinks where NPs accumulate - namely water and soil, cannot escape the impact of nanopollution. Recent studies have shown that plant growth, development and physiology are significantly affected by NPs. But, the effect of NPs on plant secondary metabolism is still obscure. The induction of reactive oxygen species (ROS) following interactions with NPs has been observed consistently across plant species. Taking into account the existing link between ROS and secondary signaling messengers that lead to transcriptional regulation of secondary metabolism, in this perspective we put forward the argument that ROS induced in plants upon their interaction with NPs will likely interfere with plant secondary metabolism. As plant secondary metabolites play vital roles in plant performance, communication, and adaptation, a comprehensive understanding of plant secondary metabolism in response to NPs is an utmost priority.
Journal Article
Long-term experimental evolution reveals purifying selection on piRNA-mediated control of transposable element expression
by
Belicard, Tony
,
Sarkies, Peter
,
Konrad, Anke
in
Animals
,
Biomedical and Life Sciences
,
C. elegans
2020
Background
Transposable elements (TEs) are an almost universal constituent of eukaryotic genomes. In animals, Piwi-interacting small RNAs (piRNAs) and repressive chromatin often play crucial roles in preventing TE transcription and thus restricting TE activity. Nevertheless, TE content varies widely across eukaryotes and the dynamics of TE activity and TE silencing across evolutionary time is poorly understood.
Results
Here, we used experimentally evolved populations of
C. elegans
to study the dynamics of TE expression over 409 generations. The experimental populations were evolved at population sizes of 1, 10 and 100 individuals to manipulate the efficiency of natural selection versus genetic drift. We demonstrate increased TE expression relative to the ancestral population, with the largest increases occurring in the smallest populations. We show that the transcriptional activation of TEs within active regions of the genome is associated with failure of piRNA-mediated silencing, whilst desilenced TEs in repressed chromatin domains retain small RNAs. Additionally, we find that the sequence context of the surrounding region influences the propensity of TEs to lose silencing through failure of small RNA-mediated silencing.
Conclusions
Our results show that natural selection in
C. elegans
is responsible for maintaining low levels of TE expression, and provide new insights into the epigenomic features responsible.
Journal Article
Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity
by
Marslin, Gregory
,
Franklin, Gregory
,
Revina, Ann Mary
in
Analysis
,
Animals
,
Antineoplastic Agents - chemistry
2015
Clinical effectiveness of imatinib mesylate in cancer treatment is compromised by its off-target cardiotoxicity. In the present study, we have developed physically stable imatinib mesylate-loaded poly(lactide-co-glycolide) nanoparticles (INPs) that could sustainably release the drug, and studied its efficacy by in vitro anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast cancer cells compared to the equivalent concentration of free imatinib mesylate. Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no significant cardiotoxicity or associated changes. Whereas, increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and reduced white blood cell, red blood cell, and hemoglobin content were observed in the animals administered with free drug. While the histological sections from hearts of animals that received INPs did not show any significant cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic vacuolization were observed in the heart sections of animals administered with free imatinib mesylate. Based on these results, we conclude that nano-encapsulation of imatinib mesylate increases its efficacy against cancer cells, with almost no cardiotoxicity.
Journal Article
Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb
by
Sheeba, Caroline J.
,
Andrade, Raquel P.
,
Palmeirim, Isabel
in
AKT protein
,
Cell differentiation
,
Cell proliferation
2012
Embryo development requires precise orchestration of cell proliferation and differentiation in both time and space. A molecular clock operating through gene expression oscillations was first described in the presomitic mesoderm (PSM) underlying periodic somite formation. Cycles of HES gene expression have been further identified in other progenitor cells, including the chick distal limb mesenchyme, embryonic neural progenitors and both mesenchymal and embryonic stem cells. In the limb, hairy2 is expressed in the distal mesenchyme, adjacent to the FGF source (AER) and along the ZPA-derived SHH gradient, the two major regulators of limb development. Here we report that hairy2 expression depends on joint AER/FGF and ZPA/SHH signaling. FGF plays an instructive role on hairy2, mediated by Erk and Akt pathway activation, while SHH acts by creating a permissive state defined by Gli3-A/Gli3-R>1. Moreover, we show that AER/FGF and ZPA/SHH present distinct temporal and spatial signaling properties in the distal limb mesenchyme: SHH acts at a long-term, long-range on hairy2, while FGF has a short-term, short-range action. Our work establishes limb hairy2 expression as an output of integrated FGF and SHH signaling in time and space, providing novel clues for understanding the regulatory mechanisms underlying HES oscillations in multiple systems, including embryonic stem cell pluripotency.
Journal Article
Test Anxiety Levels of Board Exam Going Students in Tamil Nadu, India
by
Marslin, Gregory
,
Franklin, Gregory
,
Sheeba, Caroline J.
in
Academic achievement
,
Academic failure
,
Adolescent
2014
The latest report by the National Crime Records Bureau has positioned Tamil Nadu as the Indian state with highest suicide rate. At least in part, this is happening due to exam pressure among adolescents, emphasizing the imperative need to understand the pattern of anxiety and various factors contributing to it among students. The present study was conducted to analyze the level of state anxiety among board exam attending school students in Tamil Nadu, India. A group of 100 students containing 50 boys and 50 girls from 10th and 12th grades participated in the study and their state anxiety before board exams was measured by Westside Test Anxiety Scale. We found that all board exam going students had increased level of anxiety, which was particularly higher among boys and 12th standard board exam going students. Analysis of various demographic variables showed that students from nuclear families presented higher anxiety levels compared to their desired competitive group. Overall, our results showing the prevalence of state anxiety among board exam going students in Tamil Nadu, India, support the recent attempt taken by Tamil Nadu government to improve student’s academic performance in a healthier manner by appointing psychologists in all government schools.
Journal Article
Signaling pathways influencing tumor microenvironment and their exploitation for targeted drug delivery
by
Marslin, Gregory
,
Franklin, Gregory
,
Sheeba, Caroline J.
in
active targeting
,
Angiogenesis
,
Apoptosis
2014
In the recent years, the “tumor microenvironment” has been receiving growing attention due to its involvement in neoplastic transformation, tumor growth, invasion, and protection of tumor cells from host immune response. All these events are facilitated by chemical signals produced by the tumor as well as the surrounding stromal cells. This review is divided into two main parts in which the first part discusses the receptor tyrosine kinase (RTK)-mediated growth factor signaling, steroid hormone (SH) signaling, ancient signaling pathways, and other molecules that are involved in tumorigenesis and how they interact with each other to create a complex tumor microenvironment. In the second part, we bring together the recent nanocarrier-mediated drug delivery approaches to target the signaling pathways/molecules present in the tumor microenvironment.
Journal Article
Long-term experimental evolution reveals purifying selection on piRNA-mediated control of transposable element expression
by
Belicard, Tony
,
Sarkies, Peter
,
Konrad, Anke
in
Epigenetic inheritance
,
Gene expression
,
Genetic research
2020
Transposable elements (TEs) are an almost universal constituent of eukaryotic genomes. In animals, Piwi-interacting small RNAs (piRNAs) and repressive chromatin often play crucial roles in preventing TE transcription and thus restricting TE activity. Nevertheless, TE content varies widely across eukaryotes and the dynamics of TE activity and TE silencing across evolutionary time is poorly understood. Here, we used experimentally evolved populations of C. elegans to study the dynamics of TE expression over 409 generations. The experimental populations were evolved at population sizes of 1, 10 and 100 individuals to manipulate the efficiency of natural selection versus genetic drift. We demonstrate increased TE expression relative to the ancestral population, with the largest increases occurring in the smallest populations. We show that the transcriptional activation of TEs within active regions of the genome is associated with failure of piRNA-mediated silencing, whilst desilenced TEs in repressed chromatin domains retain small RNAs. Additionally, we find that the sequence context of the surrounding region influences the propensity of TEs to lose silencing through failure of small RNA-mediated silencing. Our results show that natural selection in C. elegans is responsible for maintaining low levels of TE expression, and provide new insights into the epigenomic features responsible.
Journal Article
Auxin pretreatment promotes regeneration of sugarcane (Saccharum spp. hybrids) midrib segment explants
2006
We have developed a new, simple, quick and genotype-independent method for direct regeneration of sugarcane using novel midrib segment explants. Our protocol involves two steps: the pretreatment of starting material on MS (Murashige and Skoog (1962) Physiol Plant 15:473-497) medium containing 3.0 mg/l 2,4-dichlorophenoxyacetic acid (2,4-D) for 8 days under continuous dark and subsequent transfer of the explants to MS medium augmented with 0.1 mg/l benzyladenine (BA) and 0.1 mg/l naphthaleneacetic acid (NAA) under light-dark conditions. On the regeneration medium, numerous globular structures appeared from the explants and subsequently differentiated into shoots. Regenerated shoots attained 2-5 cm height within 30 days of culture initiation and readily rooted on MS basal medium. Hardened plants were successfully established in the greenhouse. The regulation of sugarcane morphogenesis by auxin pretreatment is discussed.
Journal Article
Long-term experimental evolution reveals purifying selection on piRNA-mediated control of transposable element expression
by
Belicard, Tony
,
Sarkies, Peter
,
Konrad, Anke
in
Chromatin
,
Evolution
,
Evolution & development
2020
Transposable elements (TEs) are a key component of eukaryotic genomes. TEs can copy themselves independently of the host genome, thus are often considered to be selfish genomic elements. However, TE dynamics within genomes have contributed to adaptive evolution leading to speculation that natural selection preserves TE expression. Here we used experimental evolution of C. elegans to study the dynamics of TE expression over 400 generations in population sizes maintained at 1, 10 and 100 individuals. We demonstrate increased TE expression relative to the ancestral population, with the largest increases corresponding to smaller population sizes. Using high-throughput small RNA sequencing we show that the transcriptional activation of TEs within active regions of the genome is associated with loss of piRNA-mediated silencing, whilst desilenced TEs in repressed chromatin domains retain small RNAs. Additionally, we find that the sequence context of the surrounding region influences the propensity of TEs to lose silencing through failure of small RNA-mediated silencing. Together, our results show that natural selection in C. elegans is responsible for maintaining low levels of TE expression, and provide new insights into the epigenomic features responsible. Footnotes * Improved presentation of figures. Revised analysis of longitudinal change in TE expression in Figure 1. Text revised to clarify interpretation of Figures 5 and 6.
Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights
by
Godoy, Myrna C. B.
,
Sujit, Sheeba J.
,
Vaporciyan, Ara A.
in
59/78
,
692/4028/67/1612/1350
,
692/4028/67/1857
2024
While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and
18
F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume. Additionally, these subtypes complement ctDNA in predicting disease recurrence. Radiogenomics analysis unveil the molecular underpinnings of these imaging subtypes, highlighting downregulation in interferon alpha and gamma pathways in the high-risk subtype. In summary, our study demonstrates that these habitat imaging subtypes effectively stratify NSCLC patients based on their risk levels for disease recurrence after initial curative surgery or radiotherapy, providing valuable insights for personalized treatment approaches.
Predicting recurrence risk in non small cell lung cancer can help to guide treatment decisions. Here, the authors use CT and PET imaging to develop predictive imaging subtypes, which can be integrated with existing ctDNA methods to predict recurrence.
Journal Article