#3 - Inhibition of the Mitochondrial Calcium Uniporter Reduces Oxidative Phosphorylation in SGK1-Knockout VSMC Upon DietInduced Obesity

Obesity is linked to vascular diseases such as atherosclerosis and coronary artery disease which is a major underlying cause of heart attacks. While the mechanism is not fully known, altering mitochondrial respiration which occurs through oxidative phosphorylation (OXPHOS) may influence the development of vascular disease during obesity. Our previous data with diet-induced obese (DIO) mice demonstrated that serum and glucocorticoid-inducible kinase 1 (SGK1), which regulates cell metabolism, was up-regulated in vascular smooth muscle cells (VSMC) from the aorta. Knocking out SGK1 in VSMCs (KOSGK1) was associated with higher OXPHOS and lower vascular disease relative to wildtype VSMCs (WTSGK1) during DIO. The mitochondrial calcium uniporter (MCU) permits calcium uptake into the mitochondrial matrix causing stimulation of OXPHOS thereby contributing to the maintenance of cellular energy homeostasis. We hypothesized that OXPHOS stimulation in KOSGK1 VSMC may be due to enhanced activity of the MCU. To test this hypothesis, an extracellular oxygen consumption (EOC) assay which measures OXPHOS was used to examine the role of MCU-mediated mitochondrial Ca2+ uptake on basal and maximal OXPHOS activity in WTSGK1 and KOSGK1 VSMCs. Thus, WTSGK1 and KOSGK1 VSMCs from DIO mice were treated ± Ru360 (10mM), an MCU inhibitor and ± FCCP (2.5mM) to stimulate maximal OXPHOS. Consistent with previous data, KOSGK1 VSMCs had significantly higher basal and maximal EOC compared to WTSGK1 VSMCs. Remarkably, RU360 significantly decreased both basal and maximal EOC in KOSGK1 VCMCs. Conversely, there was no effect of RU360 on EOC in WTSGK1 VSMCs. These results suggest a disparity in MCU activity in KOSGK1 VSMCs. In conclusion, these findings implicate mitochondrial Ca2+ uptake in the stimulation of OXPHOS in KOSGK1 VSMCs

DAYTIME DOWN-CANYON FLOWS IN THE EASTERN SIERRA NEVADA, CALIFORNIA

Climatological analyses have been conducted to determine the characteristics of frequently occuring daytime down-canyon flows during summer in the lee of the Sierra Nevada. While these flows have been documented in a historical context, very little is known on the mechanisms that drive these flows. Analyses using longterm climatological data from sites in the lee of the Sierra Nevada, suggest that these westerly flows are thermally driven due to regional pressure differences rather than the downward mixing of upper-level momentum

An automatic deep learning-based workflow for glioblastoma survival prediction using pre-operative multimodal MR images

We proposed a fully automatic workflow for glioblastoma (GBM) survival prediction using deep learning (DL) methods. 285 glioma (210 GBM, 75 low-grade glioma) patients were included. 163 of the GBM patients had overall survival (OS) data. Every patient had four pre-operative MR scans and manually drawn tumor contours. For automatic tumor segmentation, a 3D convolutional neural network (CNN) was trained and validated using 122 glioma patients. The trained model was applied to the remaining 163 GBM patients to generate tumor contours. The handcrafted and DL-based radiomic features were extracted from auto-contours using explicitly designed algorithms and a pre-trained CNN respectively. 163 GBM patients were randomly split into training (n=122) and testing (n=41) sets for survival analysis. Cox regression models with regularization techniques were trained to construct the handcrafted and DL-based signatures. The prognostic power of the two signatures was evaluated and compared. The 3D CNN achieved an average Dice coefficient of 0.85 across 163 GBM patients for tumor segmentation. The handcrafted signature achieved a C-index of 0.64 (95% CI: 0.55-0.73), while the DL-based signature achieved a C-index of 0.67 (95% CI: 0.57-0.77). Unlike the handcrafted signature, the DL-based signature successfully stratified testing patients into two prognostically distinct groups (p-value<0.01, HR=2.80, 95% CI: 1.26-6.24). The proposed 3D CNN generated accurate GBM tumor contours from four MR images. The DL-based signature resulted in better GBM survival prediction, in terms of higher C-index and significant patient stratification, than the handcrafted signature. The proposed automatic radiomic workflow demonstrated the potential of improving patient stratification and survival prediction in GBM patients

Analysis of Factors Driving Incident and Ascending Infection and the Role of Serum Antibody in Chlamydia trachomatis Genital Tract Infection

Background. Chlamydia trachomatis genital tract infection is a major cause of female reproductive morbidity. Risk factors for ascending infection are unknown, and the role for antibody in protection is not well established

Identification of Chlamydia trachomatis Antigens Recognized by T Cells From Highly Exposed Women Who Limit or Resist Genital Tract Infection

Background. Natural infection induces partial immunity to Chlamydia trachomatis. Identification of chlamydial antigens that induce interferon γ (IFN-) secretion by T cells from immune women could advance vaccine development

Three-dimensional food printing: Its readiness for a food and nutrition insecure world

Three-dimensional (3D) food printing is a rapidly emerging technology offering unprecedented potential for customised food design and personalised nutrition. Here, we evaluate the technological advances in extrusion-based 3D food printing and its possibilities to promote healthy and sustainable eating. We consider the challenges in implementing the technology in real-world applications. We propose viable applications for 3D food printing in health care, health promotion and food waste upcycling. Finally, we outline future work on 3D food printing in food safety, acceptability and economics, ethics and regulations. .

Lifetime Pesticide Use and Telomere Shortening among Male Pesticide Applicators in the Agricultural Health Study

Background: Telomere length (TL) in surrogate tissues may be influenced by environmental exposures. Objective: We aimed to determine whether lifetime pesticides use is associated with buccal cell TL. Methods: We examined buccal cell TL in relation to lifetime use of 48 pesticides for 1,234 cancer-free white male pesticide applicators in the Agricultural Health Study (AHS), a prospective cohort study of 57,310 licensed pesticide applicators. Participants provided detailed information on lifetime use of 50 pesticides at enrollment (1993–1997). Buccal cells were collected from 1999 to 2006. Relative telomere length (RTL) was measured using quantitative real-time polymerase chain reaction. We used linear regression modeling to evaluate the associations between specific pesticides and the logarithm of RTL, adjusting for age at buccal cell collection, state of residence, applicator license type, chewing tobacco use, and total lifetime days of all pesticide use. Results: The mean RTL for participants decreased significantly in association with increased lifetime days of pesticide use for alachlor (p = 0.002), 2,4-dichlorophenoxyacetic acid (2,4-D; p = 0.004), metolachlor (p = 0.01), trifluralin (p = 0.05), permethrin (for animal application) (p = 0.02), and toxaphene (p = 0.04). A similar pattern of RTL shortening was observed with the metric lifetime intensity-weighted days of pesticide use. For dichlorodiphenyltrichloroethane (DDT), we observed significant RTL shortening for lifetime intensity-weighted days (p = 0.04), but not for lifetime days of DDT use (p = 0.08). No significant RTL lengthening was observed for any pesticide. Conclusion: Seven pesticides previously associated with cancer risk in the epidemiologic literature were inversely associated with RTL in buccal cell DNA among cancer-free pesticide applicators. Replication of these findings is needed because we cannot rule out chance or fully rule out bias

Factors influencing time to case registration for youth with type 1 and type 2 diabetes: SEARCH for Diabetes in Youth Study

The development of a sustainable pediatric diabetes surveillance system for the United States requires a better understanding of issues related to case ascertainment

Can HIV service data be used for surveillance purposes?: a case study in Guangzhou, China

Abstract Background Timely monitoring HIV epidemic among key populations is a formidable challenge. This study aimed to evaluate the agreement between data collected from an enhanced HIV sentinel surveillance (HSS+) and an HIV service, and to discuss whether testing service data can be used for surveillance purposes. Methods The HSS+ data were collected from HIV sentinel surveillance conducted annually among men who have sex with men (MSM) between 2009 and 2013 in Guangzhou, China. The HIV service data were obtained from the China-Bill & Melinda Gates Foundation Cooperation Program on HIV Prevention and Care (China-Gates HIV Program) in Guangzhou during the same period. The China-Gates HIV Program aimed to increase HIV counseling and testing among MSM. We compared demographic characteristics, condom use, HIV testing history, and the HIV status among individuals in these two datasets. The Armitage-trend test was used to evaluate the HIV epidemic and behaviors of the participants in the two datasets over the study period. Results Overall, a total of 2224 and 5311 MSM were included in the surveillance and service datasets, respectively. The majority of participants in the two datasets were between 20 and 29 years old, at least attended college, and had never been married. However, socio-demographic characteristics varied slightly between the two datasets. Similar trends were observed for the HIV epidemic in these two datasets. The surveillance dataset indicated that HIV prevalence increased from 3.9% in 2009 to 11.4% in 2013 (P-value for trend < 0.001), while data from the HIV service dataset indicated that MSM HIV prevalence during this same period increased from 6.2 to 8.9% (P-value for trend = 0.025). The rates of condom use were similar between the two datasets and remained consistent throughout the study period. Conclusion HIV service data can complement existing HIV surveillance systems for MSM in China, though it may underestimate the HIV prevalence (HSS+ data contains people whose status is already know, while service data contains people who were initially negative or people of unknown status). HIV service data can be used for surveillance purposes, when prerequisite variables are collected from a large number people, if the quality assessment is conducted