Tracking Inflation on a Daily Basis

Using online data for prices and real-time debit card transaction data on changes in expenditures for Switzerland allows us to track inflation on a daily basis. While the daily price index fluctuates around the official price index in normal times, it drops immediately after the lockdown related to the COVID19 pandemic. Official statistics reflect this drop only with a lag, specifically because data collection takes time and is impeded by lockdown conditions. Such daily real-time information can be useful to gauge the relative importance of demand and supply shocks and thus inform policymakers who need to determine appropriate policy measures

A simple method for sphingolipid analysis of tissues embedded in optimal cutting temperature compound

MS-assisted lipidomic tissue analysis is a valuable tool to assess sphingolipid metabolism dysfunction in disease. These analyses can reveal potential pharmacological targets or direct mechanistic studies to better understand the molecular underpinnings and influence of sphingolipid metabolism alterations on disease etiology. But procuring sufficient human tissues for adequately powered studies can be challenging. Therefore, biorepositories, which hold large collections of cryopreserved human tissues, are an ideal retrospective source of specimens. However, this resource has been vastly underutilized by lipid biologists, as the components of OCT compound used in cryopreservation are incompatible with MS analyses. Here, we report results indicating that OCT compound also interferes with protein quantification assays, and that the presence of OCT compound impacts the quantification of extracted sphingolipids by LC-ESI-MS/MS. We developed and validated a simple and inexpensive method that removes OCT compound from OCT compound-embedded tissues. Our results indicate that removal of OCT compound from cryopreserved tissues does not significantly affect the accuracy of sphingolipid measurements with LC-ESI-MS/MS. We used the validated method to analyze sphingolipid alterations in tumors compared with normal adjacent uninvolved lung tissues from individuals with lung cancer and to determine the long-term stability of sphingolipids in OCT compound-cryopreserved normal lung tissues. We show that lung cancer tumors have significantly altered sphingolipid profiles and that sphingolipids are stable for up to 16 years in OCT compound-cryopreserved normal lung tissues. This validated sphingolipidomic OCT compound-removal protocol should be a valuable addition to the lipid biologist\u27s toolbox. Keywords: biorepository; cancer, ceramide; lipidomics; lung adenocarcinoma; lung squamous cell carcinoma; mass spectrometry; non-small cell lung cancer. Copyright © 2020 Rohrbach et al

Inhibition of ethylene involved in resistance to E. turcicum in an exotic-derived double haploid maize population

Northern corn leaf blight (NCLB) is an economically important disease of maize. While the genetic architecture of NCLB has been well characterized, the pathogen is known to overcome currently deployed resistance genes, and the role of hormones in resistance to NCLB is an area of active research. The objectives of the study were (i) to identify significant markers associated with resistance to NCLB, (ii) to identify metabolic pathways associated with NCLB resistance, and (iii) to examine role of ethylene in resistance to NCLB. We screened 252 lines from the exotic-derived double haploid BGEM maize population for resistance to NCLB in both field and greenhouse environments. We used a genome wide association study (GWAS) and stepwise regression to identify four markers associated with resistance, followed by a pathway association study tool (PAST) to identify important metabolic pathways associated with disease severity and incubation period. The ethylene synthesis pathway was significant for disease severity and incubation period. We conducted a greenhouse assay in which we inhibited ethylene to examine the role of ethylene in resistance to NCLB. We observed a significant increase in incubation period and a significant decrease in disease severity between plants treated with the ethylene inhibitor and mock-treated plants. Our study confirms the potential of the BGEM population as a source of novel alleles for resistance. We also confirm the role of ethylene in resistance to NCLB and contribute to the growing body of literature on ethylene and disease resistance in monocots

Targeting defective sphingosine kinase 1 in Niemann–Pick type C disease with an activator mitigates cholesterol accumulation

Niemann–Pick type C (NPC) disease is a lysosomal storage disorder arising from mutations in the cholesterol-trafficking protein NPC1 (95%) or NPC2 (5%). These mutations result in accumulation of low-density lipoprotein-derived cholesterol in late endosomes/lysosomes, disruption of endocytic trafficking, and stalled autophagic flux. Additionally, NPC disease results in sphingolipid accumulation, yet it is unique among the sphingolipidoses because of the absence of mutations in the enzymes responsible for sphingolipid degradation. In this work, we examined the cause for sphingosine and sphingolipid accumulation in multiple cellular models of NPC disease and observed that the activity of sphingosine kinase 1 (SphK1), one of the two isoenzymes that phosphorylate sphingoid bases, was markedly reduced in both NPC1 mutant and NPC1 knockout cells. Conversely, SphK1 inhibition with the isotype-specific inhibitor SK1-I in WT cells induced accumulation of cholesterol and reduced cholesterol esterification. Of note, a novel SphK1 activator (SK1-A) that we have characterized decreased sphingoid base and complex sphingolipid accumulation and ameliorated autophagic defects in both NPC1 mutant and NPC1 knockout cells. Remarkably, in these cells, SK1-A also reduced cholesterol accumulation and increased cholesterol ester formation. Our results indicate that a SphK1 activator rescues aberrant cholesterol and sphingolipid storage and trafficking in NPC1 mutant cells. These observations highlight a previously unknown link between SphK1 activity, NPC1, and cholesterol trafficking and metabolism.Fil: Newton, Jason. Virginia Commonwealth University School of Medicine; Estados UnidosFil: Palladino, Elisa N.D.. Virginia Commonwealth University School of Medicine; Estados UnidosFil: Weigel, Cynthia. Virginia Commonwealth University School of Medicine; Estados UnidosFil: Maceyka, Michael. Virginia Commonwealth University School of Medicine; Estados UnidosFil: Gräler, Markus H.. Universitätsklinikum Jena; AlemaniaFil: Senkal, Can E.. Virginia Commonwealth University School of Medicine; Estados UnidosFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Marvanova, Pavlina. Veterinární univerzita Brno; República ChecaFil: Jampilek, Josef. Univerzita Komenského v Bratislave; EslovaquiaFil: Lima, Santiago. Virginia Commonwealth University; Estados UnidosFil: Milstien, Sheldon. Virginia Commonwealth University School of Medicine; Estados UnidosFil: Spiegel, Sarah. Virginia Commonwealth University School of Medicine; Estados Unido

Development and validation of a Spanish translation of the Yale activity questionnaire

Background: Valid measures of physical activity are critical research tools. The objective of this study was to develop a Spanish translation of the Yale Physical Activity Survey, and to provide preliminary evidence of its validity in a population of Dominican patients with lower extremity arthritis. Methods: A Dominican bilingual health care professional translated the Yale Physical Activity Survey (YPAS) from English to Spanish. Several Dominican adults reviewed the translation to ensure it was linguistically and culturally appropriate. The questionnaire was back-translated to English by a North American researcher who is fluent in Spanish. Discrepancies between the original and back-translated versions were resolved by the translator and back-translator. The Spanish translation was administered to 108 Dominican subjects with advanced hip or knee arthritis prior to (N = 44) or one to four years following (N = 64) total joint replacement. We assessed construct validity by examining the association of YPAS scores and measures of functional status and pain (WOMAC), quality of life (EQ-5D) and the number of painful lower extremity joints. Results: A higher YPAS Part II Activity Dimensions Summary Index score had weak to modest correlations with worse function and quality of life as measured with the WOMAC function scale (r = 0.21, p = 0.03), SF-36 Physical Activity Scale (r = 0.29, p = 0.004) and EQ-5D (r = 0.34, p = 0.0007). Total minutes of vigorous activity and walking had weak to modest correlation with these measures (WOMAC Function Scale (r = 0.15, p = 0.15), SF-36 Physical Activity Scale (r = 0.21, p = 0.04) and EQ-5D utility (r = 0.24, p = 0.02)). Correlations between the YPAS Part I energy expenditure score and these measures were lower (WOMAC Function Scale (r = 0.07, p = 0.49), SF-36 Physical Activity Scale (r = 0.03, p = 0.74) and EQ-5D utility (r = 0.18, p = 0.07)). Conclusions: We have developed a new Spanish translation of the Yale Physical Activity Survey and provided evidence of convergent validity in a sample of Dominican patients prior to or 1–4 years following total joint replacement

Preliminary Evaluation of Biplane Correlation (BCI) Stereographic Imaging for Lung Nodule Detection

A biplane correlation (BCI) imaging system obtains images that can be viewed in stereo, thereby minimizing overlapping structures. This study investigated whether using stereoscopic visualization provides superior lung nodule detection compared to standard postero-anterior (PA) image display. Images were acquired at two oblique views of ±3° as well as at a standard PA position from 60 patients. Images were processed using optimal parameters and displayed on a stereoscopic display. The PA image was viewed in the standard format, while the oblique views were paired to provide a stereoscopic view of the subject. A preliminary observer study was performed with four radiologists who viewed and scored the PA image then viewed and scored the BCI stereoscopic image. The BCI stereoscopic viewing of lung nodules resulted in 71 % sensitivity and 0.31 positive predictive value (PPV) index compared to PA results of 86 % sensitivity and 0.26 PPV index. The sensitivity for lung nodule detection with the BCI stereoscopic system was reduced by 15 %; however, the total number of false positives reported was reduced by 35 % resulting in an improved PPV index of 20 %. The preliminary results indicate observer dependency in terms of relative advantage of either system in the detection of lung nodules, but overall equivalency of the two methods with promising potential for BCI as an adjunct diagnostic technique

Outcomes and risk score for distal pancreatectomy with celiac axis resection (DP-CAR) : an international multicenter analysis

Background: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P=0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P=0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19months (95 CI, 15-25months). Conclusions: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling