Metastatic triple negative breast cancer adapts its metabolism to destination tissues while retaining key metabolic signatures

Triple negative breast cancer (TNBC) metastases are assumed to exhibit similar functions in different organs as in the original primary tumor. However, studies of metastasis are often limited to a comparison of metastatic tumors with primary tumors of their origin, and little is known about the adaptation to the local environment of the metastatic sites. We therefore used transcriptomic data and metabolic network analyses to investigate whether metastatic tumors adapt their metabolism to the metastatic site and found that metastatic tumors adopt a metabolic signature with some similarity to primary tumors of their destinations. The extent of adaptation, however, varies across different organs, and metastatic tumors retain metabolic signatures associated with TNBC. Our findings suggest that a combination of anti-metastatic approaches and metabolic inhibitors selected specifically for different metastatic sites, rather than solely targeting TNBC primary tumors, may constitute a more effective treatment approach

A Semantic Cross-Species Derived Data Management Application

Managing dynamic information in large multi-site, multi-species, and multi-discipline consortia is a challenging task for data management applications. Often in academic research studies the goals for informatics teams are to build applications that provide extract-transform-load (ETL) functionality to archive and catalog source data that has been collected by the research teams. In consortia that cross species and methodological or scientific domains, building interfaces that supply data in a usable fashion and make intuitive sense to scientists from dramatically different backgrounds increases the complexity for developers. Further, reusing source data from outside one's scientific domain is fraught with ambiguities in understanding the data types, analysis methodologies, and how to combine the data with those from other research teams. We report on the design, implementation, and performance of a semantic data management application to support the NIMH funded Conte Center at the University of California, Irvine. The Center is testing a theory of the consequences of "fragmented" (unpredictable, high entropy) early-life experiences on adolescent cognitive and emotional outcomes in both humans and rodents. It employs cross-species neuroimaging, epigenomic, molecular, and neuroanatomical approaches in humans and rodents to assess the potential consequences of fragmented unpredictable experience on brain structure and circuitry. To address this multi-technology, multi-species approach, the system uses semantic web techniques based on the Neuroimaging Data Model (NIDM) to facilitate data ETL functionality. We find this approach enables a low-cost, easy to maintain, and semantically meaningful information management system, enabling the diverse research teams to access and use the data

Sex Hormones and Gender Effects following Trauma-Hemorrhage

Trauma is the leading cause of death in the industrialized world between the ages of one and 40. A number of risk factors including age and gender have been implicated in this regard. It is therefore not surprising that the majority of trauma victims are young males. Their mortality rate following trauma is not only higher compared to females, but they are also more prone to subsequent sepsis. Age and gender are therefore important factors in the prevalence of traumatic injury as well as in susceptibility to subsequent septic complications

Generation and analysis of context-specific genome-scale metabolic models derived from single-cell RNA-Seq data

Single-cell RNA sequencing combined with genome-scale metabolic models (GEMs) has the potential to unravel the differences in metabolism across both cell types and cell states but requires new computational methods. Here, we present a method for generating cell-type-specific genome-scale models from clusters of single-cell RNA-Seq profiles. Specifically, we developed a method to estimate the minimum number of cells required to pool to obtain stable models, a bootstrapping strategy for estimating statistical inference, and a faster version of the task-driven integrative network inference for tissues\ua0algorithm for generating context-specific GEMs. In addition, we evaluated the effect of different RNA-Seq normalization methods on model topology and differences in models generated from single-cell and bulk RNA-Seq data. We applied our methods on data from mouse cortex neurons and cells from the tumor microenvironment of lung cancer and in both cases found that almost every cell subtype had a unique metabolic profile. In addition, our approach was able to detect cancer-associated metabolic differences between cancer cells and healthy cells, showcasing its utility. We also contextualized models from 202 single-cell clusters across 19 human organs using data from Human Protein Atlas and made these available in the web portal Metabolic Atlas, thereby providing a valuable resource to the scientific community. With the ever-increasing availability of single-cell RNA-Seq datasets and continuously improved GEMs, their combination holds promise to become an important approach in the study of human metabolism

Infrared vision for artwork and cultural heritage NDE studies: principles and case studies

This text briefly presents the basis of 'infrared vision' in the context of cultural heritage studies. Infrared vision here encompasses near-infrared as well as thermal infrared schemes of inspection. The theory is briefly presented and attention is then focused on several non-destructive evaluation (NDE) case studies in cultural heritage: painting artwork, under-painting lettering retrieval and the investigation of Egyptian pyramids through the ScanPyramids Mission, led by the Faculty of Engineering of Cairo University and the HIP (Heritage Innovation Preservation) Institute

The effect of fructose feeding on intestinal triacylglycerol production and de novo fatty acid synthesis in humans

A high fructose intake exacerbates postprandial plasma triacylglycerol (TAG) concentration, an independent risk factor for cardiovascular disease, although it is unclear whether this is due to increased production or impaired clearance of triacylglycerol (TAG)-rich lipoproteins. We determined the in vivo acute effect of fructose on postprandial intestinal and hepatic lipoprotein TAG kinetics and de novo lipogenesis (DNL). Five overweight men were studied twice, 4 weeks apart. They consumed hourly mixed-nutrient drinks that were high-fructose (30% energy) or low-fructose (<2% energy) for 11 hours. Oral 2H2O was administered to measure fasting and postprandial DNL. Postprandial chylomicron (CM)-TAG and very low-density lipoprotein (VLDL)-TAG kinetics were measured with an intravenous bolus of [2H5]-glycerol. CM and VLDL were separated by their apolipoprotein B content using antibodies. Plasma TAG (P<0.005) and VLDL-TAG (P=0.003) were greater, and CM-TAG production rate (PR, P=0.046) and CM-TAG fractional catabolic rate (FCR, P=0.073) lower when high-fructose was consumed, with no differences in VLDL-TAG kinetics. Insulin was lower (P=0.005) and apoB48 (P=0.039), apoB100 (P=0.013) and NEFA (P=0.013) were higher after high-fructose. Postprandial hepatic fractional DNL was higher than intestinal fractional DNL with high-fructose (P=0.043) and low-fructose (P=0.043). Fructose consumption had no effect on the rate of intestinal or hepatic DNL. We provide the first measurement of the rate of intestinal DNL in humans. Lower CM-TAG PR and CM-TAG FCR with high-fructose consumption suggests lower clearance of CM, rather than elevated production, may contribute to elevated plasma TAG, possibly due to lower insulin-mediated stimulation of lipoprotein lipase

Ginsenoside Rg3 Reduces the Toxicity of Graphene Oxide Used for pH-Responsive Delivery of Doxorubicin to Liver and Breast Cancer Cells

Doxorubicin (DOX) is extensively used in chemotherapy, but it has serious side effects and is inefficient against some cancers, e.g., hepatocarcinoma. To ameliorate the delivery of DOX and reduce its side effects, we designed a pH-responsive delivery system based on graphene oxide (GO) that is capable of a targeted drug release in the acidic tumor microenvironment. GO itself disrupted glutathione biosynthesis and induced reactive oxygen species (ROS) accumulation in human cells. It induced IL17-directed JAK-STAT signaling and VEGF gene expression, leading to increased cell proliferation as an unwanted effect. To counter this, GO was conjugated with the antioxidant, ginsenoside Rg3, prior to loading with DOX. The conjugation of Rg3 to GO significantly reduced the toxicity of the GO carrier by abolishing ROS production. Furthermore, treatment of cells with GO–Rg3 did not induce IL17-directed JAK-STAT signaling and VEGF gene expression—nor cell proliferation—suggesting GO–Rg3 as a promising drug carrier. The anticancer activity of GO–Rg3–DOX conjugates was investigated against Huh7 hepatocarcinoma and MDA-MB-231 breast cancer cells. GO–Rg3–DOX conjugates significantly reduced cancer cell viability, primarily via downregulation of transcription regulatory genes and upregulation of apoptosis genes. GO–Rg3 is an effective, biocompatible, and pH responsive DOX carrier with potential to improve chemotherapy—at least against liver and breast cancers

E-Mobility -- Advancements and Challenges

Mobile platforms cover a broad range of applications from small portable electric devices, drones, and robots to electric transportation, which influence the quality of modern life. The end-to-end energy systems of these platforms are moving toward more electrification. Despite their wide range of power ratings and diverse applications, the electrification of these systems shares several technical requirements. Electrified mobile energy systems have minimal or no access to the power grid, and thus, to achieve long operating time, ultrafast charging or charging during motion as well as advanced battery technologies are needed. Mobile platforms are space-, shape-, and weight-constrained, and therefore, their onboard energy technologies such as the power electronic converters and magnetic components must be compact and lightweight. These systems should also demonstrate improved efficiency and cost-effectiveness compared to traditional designs. This paper discusses some technical challenges that the industry currently faces moving toward more electrification of energy conversion systems in mobile platforms, herein referred to as E-Mobility, and reviews the recent advancements reported in literature

Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells

The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-γ–, interleukin (IL)-4–, and IL-10–producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1–like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4–secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-β as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy