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"Sun, S."
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CYLD: a tumor suppressor deubiquitinase regulating NF-kappaB activation and diverse biological processes
Protein ubiquitination is a reversible reaction, in which the ubiquitin chains are deconjugated by a family of deubiquitinases (DUBs). The presence of a large number of DUBs suggests that they likely possess certain levels of substrate selectivity and functional specificity. Indeed, recent studies show that a tumor suppressor DUB, cylindromatosis (CYLD), has a predominant role in the regulation of NF-kappaB, a transcription factor that promotes cell survival and oncogenesis. NF-kappaB activation involves attachment of K63-linked ubiquitin chains to its upstream signaling factors, which is thought to facilitate protein-protein interactions in the assembly of signaling complexes. By deconjugating these K63-linked ubiquitin chains, CYLD negatively regulates NF-kappaB activation, which may contribute to its tumor suppressor function. CYLD also regulates diverse physiological processes, ranging from immune response and inflammation to cell cycle progression, spermatogenesis, and osteoclastogenesis. Interestingly, CYLD itself is subject to different mechanisms of regulation.
Journal Article
Biofortification of rice with lysine using endogenous histones
Rice is the most consumed cereal grain in the world, but deficient in the essential amino acid lysine. Therefore, people in developing countries with limited food diversity who rely on rice as their major food source may suffer from malnutrition. Biofortification of stable crops by genetic engineering provides a fast and sustainable method to solve this problem. In this study, two endogenous rice lysine-rich histone proteins, RLRH1 and RLRH2, were over-expressed in rice seeds to achieve lysine biofortification. Their protein sequences passed an allergic sequence-based homology test. Their accumulations in rice seeds were raised to a moderate level by the use of a modified rice glutelin 1 promoter with lowered expression strength to avoid the occurrence of physiological abnormalities like unfolded protein response. The expressed proteins were further targeted to protein storage vacuoles for stable storage using a glutelin 1 signal peptide. The lysine content in the transgenic rice seeds was enhanced by up to 35 %, while other essential amino acids remained balanced, meeting the nutritional standards of the World Health Organization. No obvious unfolded protein response was detected. Different degrees of chalkiness, however, were detected in the transgenic seeds, and were positively correlated with both the levels of accumulated protein and lysine enhancement. This study offered a solution to the lysine deficiency in rice, while at the same time addressing concerns about food safety and physiological abnormalities in biofortified crops.
Journal Article
Kernel methods and machine learning
\"Offering a fundamental basis in kernel-based learning theory, this book covers both statistical and algebraic principles. It provides over 30 major theorems for kernel-based supervised and unsupervised learning models. The first of the theorems establishes a condition, arguably necessary and sufficient, for the kernelization of learning models. In addition, several other theorems are devoted to proving mathematical equivalence between seemingly unrelated models. With over 25 closed-form and iterative algorithms, the book provides a step-by-step guide to algorithmic procedures and analysing which factors to consider in tackling a given problem, enabling readers to improve specifically designed learning algorithms, build models for new applications and develop efficient techniques suitable for green machine learning technologies. Numerous real-world examples and over 200 problems, several of which are Matlab-based simulation exercises, make this an essential resource for graduate students and professionals in computer science, electrical and biomedical engineering. Solutions to problems are provided online for instructors\"-- Provided by publisher.
Book
Drought tolerance as a driver of tropical forest assembly: resolving spatial signatures for multiple processes
Spatial patterns in trait variation reflect underlying community assembly processes, allowing us to test hypotheses about their trait and environmental drivers by identifying the strongest correlates of characteristic spatial patterns. For 43 evergreen tree species (> 1cm dbh) in a 20 ha seasonal tropical rainforest plot in Xishuangbanna, China, we compared the ability of drought tolerance traits, other physiological traits and commonly measured functional traits to predict the spatial patterns expected from the assembly processes of habitat associations, niche overlap-based competition, and hierarchical competition. We distinguished the neighborhood-scale (0- 20m) patterns expected from competition from larger-scale habitat associations with a wavelet method. Species' drought tolerance and habitat variables related to soil water supply were strong drivers of habitat associations, and drought tolerance showed a significant spatial signal for influencing competition. Overall, the traits most strongly associated with habitat, as quantified using multivariate models, were leaf density, leaf turgor loss point (πtlp; also known as the leaf wilting point), and stem hydraulic conductivity (r2 range for the best fit models = 0.27-0.36). At neighborhood scales, species spatial associations were positively correlated with similarity in πtlp, consistent with predictions for hierarchical competition. Although the correlation between πtlp and interspecific spatial associations was weak (r2 < 0.01), this showed a persistent influence of drought tolerance on neighborhood interactions and community assembly. Quantifying the full impact of traits on competitive interactions in forests may require incorporating plasticity among individuals within species, especially among specific life stages, and moving beyond individual traits to integrate the impact of multiple traits on whole-plant performance and resource demand.
Journal Article
Student clashes on campus : a leadership guide to free speech
\"This book unpacks the tension between free speech and the social justice priority to support all students. Drawing on court cases, institutional policies and procedures, and notable campus practices, this book answers the question: How do campus leaders develop interests of social justice and create a campus that is inclusive and inviting of all identities while also respecting students' free speech rights? This useful guide provides insights about the myriad of challenges that campus leaders have faced, along with practical approaches to address these issues on their own campuses. Experts Sun and McClellan interrogate the assumptions, thoughts, events, rules, and actions often at-play when free expression clashes with a college's mission of diversity, inclusion, and social justice. This book helpfully guides campus leaders to consider a series of legal frameworks and promising policies as solutions for balancing social justice and free speech.\" -- Provided by publisher
Book
Analysis of multiple bacterial species and antibiotic classes reveals large variation in the association between seasonal antibiotic use and resistance
Understanding how antibiotic use drives resistance is crucial for guiding effective strategies to limit the spread of resistance, but the use–resistance relationship across pathogens and antibiotics remains unclear. We applied sinusoidal models to evaluate the seasonal use–resistance relationship across 3 species ( Staphylococcus aureus , Escherichia coli , and Klebsiella pneumoniae ) and 5 antibiotic classes (penicillins, macrolides, quinolones, tetracyclines, and nitrofurans) in Boston, Massachusetts. Outpatient use of all 5 classes and resistance in inpatient and outpatient isolates in 9 of 15 species–antibiotic combinations showed statistically significant amplitudes of seasonality (false discovery rate (FDR) < 0.05). While seasonal peaks in use varied by class, resistance in all 9 species–antibiotic combinations peaked in the winter and spring. The correlations between seasonal use and resistance thus varied widely, with resistance to all antibiotic classes being most positively correlated with use of the winter peaking classes (penicillins and macrolides). These findings challenge the simple model of antibiotic use independently selecting for resistance and suggest that stewardship strategies will not be equally effective across all species and antibiotics. Rather, seasonal selection for resistance across multiple antibiotic classes may be dominated by use of the most highly prescribed antibiotic classes, penicillins and macrolides.
Journal Article
Inhibition of mTOR complex 2 induces GSK3/FBXW7-dependent degradation of sterol regulatory element-binding protein 1 (SREBP1) and suppresses lipogenesis in cancer cells
Cancer cells feature increased
de novo
lipogenesis. Sterol regulatory element-binding protein 1 (SREBP1), when presented in its mature form (mSREBP1), enhances lipogenesis by increasing transcription of several of its target genes. Mammalian target of rapamycin (mTOR) complexes, mTORC1 and mTORC2, are master regulators of cellular survival, growth and metabolism. A role for mTORC1 in the regulation of SREBP1 activity has been suggested; however, the connection between mTORC2 and SREBP1 has not been clearly established and hence is the focus of this study. mTOR kinase inhibitors (for example, INK128), which inhibit both mTORC1 and mTORC2, decreased mSREBP1 levels in various cancer cell lines. Knockdown of rictor, but not raptor, also decreased mSREBP1. Consistently, reduced mSREBP1 levels were detected in cells deficient in rictor or Sin1 compared with parent or rictor-deficient cells with re-expression of ectopic rictor. Hence it is mTORC2 inhibition that causes mSREBP1 reduction. As a result, expression of the mSREBP1 target genes acetyl-CoA carboxylase and fatty-acid synthase was suppressed, along with suppressed lipogenesis in cells exposed to INK128. Moreover, mSREBP1 stability was reduced in cells treated with INK128 or rictor knockdown. Inhibition of proteasome, GSK3 or the E3 ubiquitin ligase, FBXW7, prevented mSREBP1 reduction induced by mTORC2 inhibition. Thus mTORC2 inhibition clearly facilitates GSK3-dependent, FBXW7-mediated mSREBP1 degradation, leading to mSREBP1 reduction. Accordingly, we conclude that mTORC2 positively regulates mSREBP1 stability and lipogenesis. Our findings reveal a novel biological function of mTORC2 in the regulation of lipogenesis and warrant further study in this direction.
Journal Article
Chemosensory sensilla of the Drosophila wing express a candidate ionotropic pheromone receptor
The Drosophila wing was proposed to be a taste organ more than 35 years ago, but there has been remarkably little study of its role in chemoreception. We carry out a differential RNA-seq analysis of a row of sensilla on the anterior wing margin and find expression of many genes associated with pheromone and chemical perception. To ask whether these sensilla might receive pheromonal input, we devised a dye-transfer paradigm and found that large, hydrophobic molecules comparable to pheromones can be transferred from one fly to the wing margin of another. One gene, Ionotropic receptor (IR)52a, is coexpressed in neurons of these sensilla with fruitless, a marker of sexual circuitry; IR52a is also expressed in legs. Mutation of IR52a and optogenetic silencing of IR52a+ neurons decrease levels of male sexual behavior. Optogenetic activation of IR52a+ neurons induces males to show courtship toward other males and, remarkably, toward females of another species. Surprisingly, IR52a is also required in females for normal sexual behavior. Optogenetic activation of IR52a+ neurons in mated females induces copulation, which normally occurs at very low levels. Unlike other chemoreceptors that act in males to inhibit male-male interactions and promote male-female interactions, IR52a acts in both males and females, and can promote male-male as well as male-female interactions. Moreover, IR52a+ neurons can override the circuitry that normally suppresses sexual behavior toward unproductive targets. Circuit mapping and Ca2+ imaging using the trans-Tango system reveals second-order projections of IR52a+ neurons in the subesophageal zone (SEZ), some of which are sexually dimorphic. Optogenetic activation of IR52a+ neurons in the wing activates second-order projections in the SEZ. Taken together, this study provides a molecular description of the chemosensory sensilla of a greatly understudied taste organ and defines a gene that regulates the sexual circuitry of the fly.
Journal Article