Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could... Show moreNeurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in C9ORF72. Using integrative computational methods combining all omics datasets, we identified novel and known dysregulated pathways. We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. A different differentiation protocol was used to derive a separate set of C9ORF72 and control motor neurons. Many individual -omics differed by protocol, but some core dysregulated pathways were consistent. This strategy of analyzing patient-specific neurons provides disease-related outcomes with small numbers of heterogeneous lines and reduces variation from single-omics to elucidate network-based signatures. Show less
As said by former United Nations Secretary-General Kofi Annan, "Snakebite is the most important tropical disease you've never heard of." Listed as a priority neglected tropical disease by the World... Show moreAs said by former United Nations Secretary-General Kofi Annan, "Snakebite is the most important tropical disease you've never heard of." Listed as a priority neglected tropical disease by the World Health Organization, snakebite envenoming (SBE) kills in excess of 125,000 people per year. However, due to the complexity and overlap of snake venom compositions, few reliable venom diagnostic methods for genus-/species-specific identification, which is crucial for successful SBE therapy, are available. Here, we develop a strategy to select and prepare genus-specific snake venom antibodies, which allows rapid and efficient clinical diagnosis of snakebite. Multi-omics approaches are used to choose candidate antigens from snake venoms and identify genus-specific antigenic epitope peptide fragments (GSAEPs) with ideal immunogenicity, specificity, and spatial accessibility. Double-antibody sandwich ELISA kit was established by matching a polyclonal antibody against a natural antigen and a monoclonal antibody that was prepared by natural protein as antigen and can specifically target the GSAEPs. The kit shows the ability to accurately identify venoms from similar genera of Trimeresurus and Protobothrops with a detection limit of 6.25 ng/ml on the snake venoms and a little cross-reaction, thus proving high feasibility and applicability. Show less
FOXP3(+) regulatory T cells (Treg cells) are a specialized population of CD4(+) T cells that restrict immune activation and are essential to prevent systemic autoimmunity. In the intestine, the... Show moreFOXP3(+) regulatory T cells (Treg cells) are a specialized population of CD4(+) T cells that restrict immune activation and are essential to prevent systemic autoimmunity. In the intestine, the major function of Treg cells is to regulate inflammation as shown by a wide array of mechanistic studies in mice. While Treg cells originating from the thymus can home to the intestine, the majority of Treg cells residing in the intestine are induced from FOXP3(neg) conventional CD4(+) T cells to elicit tolerogenic responses to microbiota and food antigens. This process largely takes place in the gut draining lymph nodes via interaction with antigen-presenting cells that convert circulating naive T cells into Treg cells. Notably, dysregulation of Treg cells leads to a number of chronic inflammatory disorders, including inflammatory bowel disease. Thus, understanding intestinal Treg cell biology in settings of inflammation and homeostasis has the potential to improve therapeutic options for patients with inflammatory bowel disease. Here, the induction, maintenance, trafficking, and function of intestinal Treg cells is reviewed in the context of intestinal inflammation and inflammatory bowel disease. In this review we propose intestinal Treg cells do not compose fixed Treg cell subsets, but rather (like T helper cells), are plastic and can adopt different programs depending on microenvironmental cues. Show less
Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.Methods: We analyzed data for 121,435 women diagnosed with... Show moreBackground: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (P-adj > 0.30). The strongest associations were between all-cause mortality and BMI >= 30 versus 18.5-25 kg/m(2) [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age >= 30 years versus < 20 years at first pregnancy [0.79 (0.72-0.86)]; >0-< 5 years versus >= 10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking.Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype.Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care. Show less
A continuous growth of international trade, especially between developing countries, has greatly increased carbon dioxide (CO2) emissions associated with energy consumption over the past two... Show moreA continuous growth of international trade, especially between developing countries, has greatly increased carbon dioxide (CO2) emissions associated with energy consumption over the past two decades. Given the more intensified intraregional cooperation and trade within the Belt and Road Initiative (BRI), this study aims to trace the imbalance of CO2 embodied in trade between nations in BRI and the rest of the world, providing new insights into the drivers of emissions growth by contrasting consumption, production and technological differences-based perspectives. Results indicate that the BRI contributed to over 50% of global carbon footprint and 92% of its increase in 1995–2015. The BRI was a net exporter of trade-embodied emissions, whose technological-adjusted carbon footprint remained remarkably large due to comparatively high carbon intensity. Geographically, carbon leakage has gradually moved from China and India to other BRI countries, especially to Southeast Asia, West Asia and Africa. Technological change was the key driver of emissions reduction, followed by the change in industrial structure. The growth in final demand per capita was the most important driver for the growth of CO2 emissions in BRI. Improving carbon efficiency remains a critical step for BRI nations to slow down not only emissions growth but also carbon leakage. The paper managed to provide novel insights into the carbon leakage in BRI by contrasting the consumption, production and technological differences-based perspectives, thus being able to better inform policymakers on region-specific low-carbon transition and global climate governance. Show less
In this article, I explore how we can expand the project of Buddhist feminism by drawing on Chinese Yogācāra philosophy. With a focus on the writings of Xuanzang (c. 602–664) and his disciple Kuiji... Show moreIn this article, I explore how we can expand the project of Buddhist feminism by drawing on Chinese Yogācāra philosophy. With a focus on the writings of Xuanzang (c. 602–664) and his disciple Kuiji (632–682), I investigate how the Yogācāra theory of consciousness can be read as a gendered account of non-duality. The term ‘Yogācāra dialectics’ is thus coined to describe this theory of non-duality that highlights fluidity and transformability. As I will argue, Chinese Yogācārins developed the dialectics of gender by means of which they were able to subtly erode sexism in premodern times. Show less
Lee, W.S., Zhou, K.; Hepting, M.; Li, J.; Nag, A.; Walters, A.C.; Garcia-Fernandez, M.; ... ; Devereaux, T.P. 2021
