Ranchers Diverse in Their Drought Management Strategies

Farm Management, Livestock Production/Industries,

A novel AhR ligand, 2AI, protects the retina from environmental stress.

Various retinal degenerative diseases including dry and neovascular age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy are associated with the degeneration of the retinal pigmented epithelial (RPE) layer of the retina. This consequently results in the death of rod and cone photoreceptors that they support, structurally and functionally leading to legal or complete blindness. Therefore, developing therapeutic strategies to preserve cellular homeostasis in the RPE would be a favorable asset in the clinic. The aryl hydrocarbon receptor (AhR) is a conserved, environmental ligand-dependent, per ARNT-sim (PAS) domain containing bHLH transcription factor that mediates adaptive response to stress via its downstream transcriptional targets. Using in silico, in vitro and in vivo assays, we identified 2,2'-aminophenyl indole (2AI) as a potent synthetic ligand of AhR that protects RPE cells in vitro from lipid peroxidation cytotoxicity mediated by 4-hydroxynonenal (4HNE) as well as the retina in vivo from light-damage. Additionally, metabolic characterization of this molecule by LC-MS suggests that 2AI alters the lipid metabolism of RPE cells, enhancing the intracellular levels of palmitoleic acid. Finally, we show that, as a downstream effector of 2AI-mediated AhR activation, palmitoleic acid protects RPE cells from 4HNE-mediated stress, and light mediated retinal degeneration in mice

Terrestrial ecosystem production: A process model based on global satellite and surface data

This paper presents a modeling approach aimed at seasonal resolution of global climatic and edaphic controls on patterns of terrestrial ecosystem production and soil microbial respiration. We use satellite imagery (Advanced Very High Resolution Radiometer and International Satellite Cloud Climatology Project solar radiation), along with historical climate (monthly temperature and precipitation) and soil attributes (texture, C and N contents) from global (1°) data sets as model inputs. The Carnegie‐Ames‐Stanford approach (CASA) Biosphere model runs on a monthly time interval to simulate seasonal patterns in net plant carbon fixation, biomass and nutrient allocation, litterfall, soil nitrogen mineralization, and microbial CO2 production. The model estimate of global terrestrial net primary production is 48 Pg C yr^(−1) with a maximum light use efficiency of 0.39 g C MJ^(−1) PAR. Over 70% of terrestrial net production takes place between 30°N and 30°S latitude. Steady state pools of standing litter represent global storage of around 174 Pg C (94 and 80 Pg C in nonwoody and woody pools, respectively), whereas the pool of soil C in the top 0.3 m that is turning over on decadal time scales comprises 300 Pg C. Seasonal variations in atmospheric CO_2 concentrations from three stations in the Geophysical Monitoring for Climate Change Flask Sampling Network correlate significantly with estimated net ecosystem production values averaged over 50°–80° N, 10°–30° N, and 0°–10° N

CETN1 is a cancer testis antigen with expression in prostate and pancreatic cancers

Background: The Cancer Testis Antigens (CTAs) are a group of genes that are highly expressed in the normal testis and several types of cancer. Due to their restricted expression in normal adult tissues, CTAs have been attractive targets for immunotherapy and biomarker development. In this work, we discovered that Centrin 1 (CETN1) which is found in the centrosome of all eukaryotes, may be a member of this group and is highly expressed in prostate and pancreatic cancer. Three members of the centrin family of calcium binding proteins (CETN) are localized to the centrosome in all eukaryotes with CDC31 being the sole yeast homolog. CETN1 is a retrogene that probably arose from a retrotransposition of CETN2, an X-linked gene. A previous mouse study shows that CETN1 is expressed solely in the testis, while CETN2 is expressed in all organs. Results: In this work, we show that CETN1 is a new member of the growing group of CTAs. Through the mining of publicly available microarray data, we discovered that human CETN1 expression but not CETN2 or CETN3 is restricted to the testis. In fact, CETN1 is actually down-regulated in testicular malignancies compared to normal testis. Using q-PCR, CETN1 expression is shown to be highly up-regulated in cancer of the prostate and in pancreatic xenografts. Unexpectedly however, CETN1 expression was virtually absent in various cell lines until they were treated with the DNA demethylation agent 5’AZA-2’Deoxycytidine (AZA) but showed no increased expression upon incubation with Histone deacetylase inhibitor Trichostatin-A (TSA) alone. Additionally, like most CTAs, CETN1 appears to be an intrinsically disordered protein which implies that it may occupy a hub position in key protein interaction networks in cancer. Neither CETN1 nor CETN2 could compensate for loss of CDC31 expression in yeast which is analogous to published data for CETN3. Conclusions: This work suggests that CETN1 is a novel CTA with expression in cancer of the prostate and pancreas. In cell lines, the expression is probably regulated by promoter methylation, while the method of regulation in normal adult tissues remains unknown

The Cancer/Testis Antigen Prostate-associated Gene 4 (PAGE4) Is a Highly Intrinsically Disordered Protein

The cancer/testis antigens (CTAs) are an important group of heterogeneous proteins that are predominantly expressed in the testis in the normal human adult but are aberrantly expressed in several types of cancers. Prostate-associated gene 4 (PAGE4) is a member of the CT-X family of CTAs that in addition to testis, is highly expressed in the fetal prostate, and may also play an important role both in benign and malignant prostate diseases. However, the function of this gene remains poorly understood. Here, we show that PAGE4 is a highly (100%) intrinsically disordered protein (IDP). The primary protein sequence conforms to the features of a typical IDP sequence and the secondary structure prediction algorithm metaPrDOS strongly supported this prediction. Furthermore, SDS-gel electrophoresis and analytical size exclusion chromatography of the recombinant protein revealed an anomalous behavior characteristic of IDPs. UV circular dichroism (CD) and NMR spectroscopy confirmed that PAGE4 is indeed a highly disordered protein. In further bioinformatic analysis, the PredictNLS algorithm uncovered a potential nuclear localization signal, whereas the algorithm DBS-Pred returned a 99.1% probability that PAGE4 is a DNA-binding protein. Consistent with this prediction, biochemical experiments showed that PAGE4 preferentially binds a GC-rich sequence. Silencing PAGE4 expression induced cell death via apoptosis and in mice carrying PCa xenografts, siRNA-mediated knockdown of the PAGE4 mRNA attenuated tumor growth in vivo. Furthermore, overexpressing PAGE4 protected cells from stress-induced death. To our knowledge, PAGE4 is the first example of a CTA that is an IDP with an anti-apoptotic function

Meta-analysis of the impact of successful chronic total occlusion percutaneous coronary intervention on left ventricular systolic function and reverse remodeling

We sought to examine the impact of coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on left ventricular (LV) function.We performed a systematic review and meta-analysis of studies published between January 1980 and November 2017 on the impact of successful CTO PCI on LV function.A total of 34 observational studies including 2735 patients were included in the meta-analysis. Over a weighted mean follow-up of 7.9 months, successful CTO PCI was associated with an increase in LV ejection fraction by 3.8% (95%CI 3.0-4.7, P < 0.0001, I2 = 45%). In secondary analysis of 15 studies (1248 patients) that defined CTOs as occlusions of at least 3-month duration and reported follow-up of at least 3-months after the procedure, successful CTO PCI was associated with improvement in LV ejection fraction by 4.3% (95%CI [3.1, 5.6], P < 0.0001). In the 10 studies (502 patients) that reported LV end-systolic volume, successful CTO PCI was associated with a decrease in LV end-systolic volume by 4 mL, (95%CI -6.0 to -2.1, P < 0.0001, I2 = 0%). LV end-diastolic volume was reported in 9 studies with 403 patients and did not significantly change after successful CTO PCI (-2.3 mL, 95%CI -5.7 to 1.2 mL, P = 0.19, I2 = 0%).Successful CTO PCI is associated with a statistically significant improvement in LV ejection fraction and decrease in LV end-systolic volume, that may reflect a beneficial effect of CTO recanalization on LV remodeling. The clinical implications of these findings warrant further investigation

Terrestrial ecosystem production: A process model based on global satellite and surface data

This paper presents a modeling approach aimed at seasonal resolution of global climatic and edaphic controls on patterns of terrestrial ecosystem production and soil microbial respiration. We use satellite imagery (Advanced Very High Resolution Radiometer and International Satellite Cloud Climatology Project solar radiation), along with historical climate (monthly temperature and precipitation) and soil attributes (texture, C and N contents) from global (1°) data sets as model inputs. The Carnegie‐Ames‐Stanford approach (CASA) Biosphere model runs on a monthly time interval to simulate seasonal patterns in net plant carbon fixation, biomass and nutrient allocation, litterfall, soil nitrogen mineralization, and microbial CO2 production. The model estimate of global terrestrial net primary production is 48 Pg C yr^(−1) with a maximum light use efficiency of 0.39 g C MJ^(−1) PAR. Over 70% of terrestrial net production takes place between 30°N and 30°S latitude. Steady state pools of standing litter represent global storage of around 174 Pg C (94 and 80 Pg C in nonwoody and woody pools, respectively), whereas the pool of soil C in the top 0.3 m that is turning over on decadal time scales comprises 300 Pg C. Seasonal variations in atmospheric CO_2 concentrations from three stations in the Geophysical Monitoring for Climate Change Flask Sampling Network correlate significantly with estimated net ecosystem production values averaged over 50°–80° N, 10°–30° N, and 0°–10° N

SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells

Cellular senescence irreversibly arrests cell proliferation, accompanied by a multi-component senescence-associated secretory phenotype (SASP) that participates in several age-related diseases. Using stable isotope labeling with amino acids (SILACs) and cultured cells, we identify 343 SASP proteins that senescent human fibroblasts secrete at 2-fold or higher levels compared with quiescent cell counterparts. Bioinformatic analysis reveals that 44 of these proteins participate in hemostasis, a process not previously linked with cellular senescence. We validated the expression of some of these SASP factors in cultured cells and in vivo. Mice treated with the chemotherapeutic agent doxorubicin, which induces widespread cellular senescence in vivo, show increased blood clotting. Conversely, selective removal of senescent cells using transgenic p16-3MR mice showed that clearing senescent cells attenuates the increased clotting caused by doxorubicin. Our study provides an in-depth, unbiased analysis of the SASP and unveils a function for cellular senescence in hemostasis