408 research outputs found
Designing Software to Locate Differences in the Shrimp Genome
In order to determine where important differences in the genomic sequence of Pacific White Shrimp occur, many copies each of multiple regions of DNA sequence are needed. Then similar sequences can be aligned so that almost all of the bases are identical between the sequences and differences are easy to notice. One of the major issues with predicting single base position differences (SNPs) in this manner is that DNA sequencing techniques are not 100% consistent in most cases. Consequently, it needs to be determined whether a particular base is different because the true genetic sequence is variable at that position or because the sequencing process resulted in the base position being incorrectly called. SNPidentifier is a newly developed computer program that takes into account the unreliability of sequence data and tries to use only the more reliable sequences to predict where true SNPs are located. The goal of locating SNPs in Pacific White Shrimp is to identify base positions that can possibly be used in the future as molecular markers for traits of interest to shrimp breeders
Brief of Scholars of the History and Original Meaning of the Fourth Amendment as Amici Curiae in Support of Petitioner, Carpenter v. United States, No. 16-402 (U.S. Aug. 14, 2017)
Obtaining and examining cell site location records to find a person is a “search” in any normal sense of the word — a search of documents and a search for a person and her personal effects. It is therefore a “search” within the meaning of the Fourth Amendment in that it constitutes “examining,” “exploring,” “looking through,” “inquiring,” “seeking,” or “trying to find.” Nothing about the text of the Fourth Amendment, or the historical backdrop against which it was adopted, suggests that “search” should be construed more narrowly as, for example, intrusions upon subjectively manifested expectations of privacy that society is prepared to recognize as reasonable.Entrusting government agents with unfettered discretion to conduct searches using cell site location information undermines Fourth Amendment rights. The Amendment guarantees “[t]he right of the people to be secure in their persons, houses, papers, and effects, against unreasonable searches.” The Framers chose that language deliberately. It reflected the insecurity they suffered at the hands of “writs of assistance,” a form of general warrant that granted state agents broad discretion to search wherever they pleased. Such arbitrary power was “unreasonable” to the Framers, being “against the reason of the common law,” and it was intolerable because of its oppressive impact on “the people” as a whole. As emphasized in one of the seminal English cases that inspired the Amendment, this kind of general power to search was “totally subversive of the liberty of the subject.” James Otis’s famous speech denouncing a colonial writ of assistance similarly condemned those writs as “the worst instrument of arbitrary power,” placing “the liberty of every man in the hands of every petty officer.” Thus, although those who drafted and ratified the Fourth Amendment could not have anticipated cellphone technology, they would have recognized the dangers inherent in any state claim of unlimited authority to conduct searches for evidence of criminal activity. Cell site location information provides insight into where we go and what we do. Because this information is constantly generated and can be retrieved by the government long after the activities it memorializes have taken place, unfettered government access to cell site location information raises the specter of general searches and undermines the security of “the people.
Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity
Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for stroke severity in experimental stroke animal models and may have translational significance for clinical stroke patients - targeting endothelial mitochondria may be a clinically useful approach for stroke therapy
Recommended from our members
Inverse Regulation of Inflammation and Mitochondrial Function in Adipose Tissue Defines Extreme Insulin Sensitivity in Morbidly Obese Patients
Obesity is associated with insulin resistance, a major risk factor for type 2 diabetes and cardiovascular disease. However, not all obese individuals are insulin resistant, which confounds our understanding of the mechanistic link between these conditions. We conducted transcriptome analyses on 835 obese subjects with mean BMI of 48.8, on which we have previously reported genetic associations of gene expression. Here, we selected ∼320 nondiabetic (HbA1c <7.0) subjects and further stratified the cohort into insulin-resistant versus insulin-sensitive subgroups based on homeostasis model assessment–insulin resistance. An unsupervised informatics analysis revealed that immune response and inflammation-related genes were significantly downregulated in the omental adipose tissue of obese individuals with extreme insulin sensitivity and, to a much lesser extent, in subcutaneous adipose tissue. In contrast, genes related to β-oxidation and the citric acid cycle were relatively overexpressed in adipose of insulin-sensitive patients. These observations were verified by querying an independent cohort of our published dataset of 37 subjects whose subcutaneous adipose tissue was sampled before and after treatment with thiazolidinediones. Whereas the immune response and inflammation pathway genes were downregulated by thiazolidinedione treatment, β-oxidation and citric acid cycle genes were upregulated. This work highlights the critical role that omental adipose inflammatory pathways might play in the pathophysiology of insulin resistance, independent of body weight
Supply of methionine and arginine alters phosphorylation of mechanistic target of rapamycin (mTOR), circadian clock proteins, and alpha-s1-casein abundance in bovine mammary epithelial cells
[EN] Methionine (Met) and arginine (Arg) regulate casein protein abundance through alterations in activity of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. A potential role for the circadian clock network on the regulation of protein synthesis, partly via activity of mTORC1, has been highlighted in non-ruminants. The main objective of the study was to determine in ruminant mammary cells alterations in mRNA, protein abundance and phosphorylation status of mTORC1-related upstream targets, circadian clock proteins, and protein kinase AMP-activated catalytic subunit alpha (AMPK) in relation to alpha-s1-casein protein (CSN1S1) abundance in response to greater supply of Met and Arg alone or in combination. Primary bovine mammary epithelial cells (BMEC) were incubated for 12 h in a 2 x 2 arrangement of treatments with control media (ideal profile of amino acids, IPAA), or media supplemented with increased Met (incMet), Arg (incArg), or both (incMet + incArg). Data were analyzed testing the main effects of Met and Arg and their interaction. Among 7 amino acid (AA) transporters known to be mTORC1 targets, increasing supply of Arg downregulated SLC1A5, SLC3A2, SLC7A1, and SLC7A5, while increasing supply of Met upregulated SLC7A1. mRNA abundance of the cytosolic Arg sensor (CASTOR1) was lower when supply of Arg and Met alone increased. p-TSC2 (TSC complex subunit 2) was greater when the Arg supply was increased, while the phosphoralation ratio of p-AKT (AKT serine/threonine kinase 1):total (t) AKT and p-AMPK:tAMPK were lower. In spite of this, the ratio of p-mTOR:tmTOR nearly doubled with incArg but such response did not prevent a decrease in CSN1S1 abundance. The abundance of period circadian regulator 1 (PER1) protein nearly doubled with all treatments, but only incMet + incArg led to greater clock circadian regulator (CLOCK) protein abundance. Overall, data suggest that a greater supply of Met and Arg could influence CSN1S1 synthesis of BMEC through changes in the mTORC1, circadian clock, and AMPK pathways. Identifying mechanistic relationships between intracellular energy, total AA supply, and these pathways in the context of milk protein synthesis in ruminants merits further research.L. Hu was recipient of a 2017 Yangzhou University International Academic Exchange award and a Postgraduate Research & Practice Innovation Program of Jiangsu Province (CX137) to train at University of Illinois. L. Hu and M. Wang were supported by project from Natural Science Foundation of China (31672446). H. Dai and Y. Liang received scholarships from China Scholarship Council (Beijing, China) to undertake PhD training at University of Illinois.Hu, L.; Chen, Y.; Cortes, IM.; Coleman, DN.; Dai, H.; Liang, Y.; Parys, C.... (2020). Supply of methionine and arginine alters phosphorylation of mechanistic target of rapamycin (mTOR), circadian clock proteins, and alpha-s1-casein abundance in bovine mammary epithelial cells. Food & Function. 11(1):883-894. https://doi.org/10.1039/c9fo02379hS883894111Rius, A. G., Appuhamy, J. A. D. R. N., Cyriac, J., Kirovski, D., Becvar, O., Escobar, J., … Hanigan, M. D. (2010). Regulation of protein synthesis in mammary glands of lactating dairy cows by starch and amino acids. Journal of Dairy Science, 93(7), 3114-3127. doi:10.3168/jds.2009-2743Moshel, Y., Rhoads, R. E., & Barash, I. (2006). Role of amino acids in translational mechanisms governing milk protein synthesis in murine and ruminant mammary epithelial cells. Journal of Cellular Biochemistry, 98(3), 685-700. doi:10.1002/jcb.20825Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., … Murphy, L. O. (2009). Bidirectional Transport of Amino Acids Regulates mTOR and Autophagy. Cell, 136(3), 521-534. doi:10.1016/j.cell.2008.11.044Appuhamy, J. A. D. R. N., Nayananjalie, W. A., England, E. M., Gerrard, D. E., Akers, R. M., & Hanigan, M. D. (2014). Effects of AMP-activated protein kinase (AMPK) signaling and essential amino acids on mammalian target of rapamycin (mTOR) signaling and protein synthesis rates in mammary cells. Journal of Dairy Science, 97(1), 419-429. doi:10.3168/jds.2013-7189HANIGAN, M. D., CROMPTON, L. A., BEQUETTE, B. J., MILLS, J. A. N., & FRANCE, J. (2002). Modelling Mammary Metabolism in the Dairy Cow to Predict Milk Constituent Yield, with Emphasis on Amino Acid Metabolism and Milk Protein Production: Model Evaluation. Journal of Theoretical Biology, 217(3), 311-330. doi:10.1006/jtbi.2002.3037Osorio, J. S., Ji, P., Drackley, J. K., Luchini, D., & Loor, J. J. (2013). Supplemental Smartamine M or MetaSmart during the transition period benefits postpartal cow performance and blood neutrophil function. Journal of Dairy Science, 96(10), 6248-6263. doi:10.3168/jds.2012-5790Weekes, T. L., Luimes, P. H., & Cant, J. P. (2006). Responses to Amino Acid Imbalances and Deficiencies in Lactating Dairy Cows. Journal of Dairy Science, 89(6), 2177-2187. doi:10.3168/jds.s0022-0302(06)72288-3Wu, G., Bazer, F. W., Davis, T. A., Kim, S. W., Li, P., Marc Rhoads, J., … Yin, Y. (2008). Arginine metabolism and nutrition in growth, health and disease. Amino Acids, 37(1), 153-168. doi:10.1007/s00726-008-0210-yMepham, T. B. (1982). Amino Acid Utilization by Lactating Mammary Gland. Journal of Dairy Science, 65(2), 287-298. doi:10.3168/jds.s0022-0302(82)82191-7Haque, M. N., Rulquin, H., Andrade, A., Faverdin, P., Peyraud, J. L., & Lemosquet, S. (2012). Milk protein synthesis in response to the provision of an «ideal» amino acid profile at 2 levels of metabolizable protein supply in dairy cows. Journal of Dairy Science, 95(10), 5876-5887. doi:10.3168/jds.2011-5230H. Rulquin , G.Raggio , H.Lapierre and S.Lemosquet , Energy and Protein Metabolism and Nutrition , Wageningen Academic Publishers , Wageningen , 2007Nan, X., Bu, D., Li, X., Wang, J., Wei, H., Hu, H., … Loor, J. J. (2014). Ratio of lysine to methionine alters expression of genes involved in milk protein transcription and translation and mTOR phosphorylation in bovine mammary cells. Physiological Genomics, 46(7), 268-275. doi:10.1152/physiolgenomics.00119.2013Fraser, D. L., Ørskov, E. R., Whitelaw, F. G., & Franklin, M. F. (1991). Limiting amino acids in dairy cows given casein as the sole source of protein. Livestock Production Science, 28(3), 235-252. doi:10.1016/0301-6226(91)90145-gDoepel, L., Pacheco, D., Kennelly, J. J., Hanigan, M. D., López, I. F., & Lapierre, H. (2004). Milk Protein Synthesis as a Function of Amino Acid Supply. Journal of Dairy Science, 87(5), 1279-1297. doi:10.3168/jds.s0022-0302(04)73278-6Haque, M. N., Rulquin, H., & Lemosquet, S. (2013). Milk protein responses in dairy cows to changes in postruminal supplies of arginine, isoleucine, and valine. Journal of Dairy Science, 96(1), 420-430. doi:10.3168/jds.2012-5610Salama, A. A. K., Duque, M., Wang, L., Shahzad, K., Olivera, M., & Loor, J. J. (2019). Enhanced supply of methionine or arginine alters mechanistic target of rapamycin signaling proteins, messenger RNA, and microRNA abundance in heat-stressed bovine mammary epithelial cells in vitro. Journal of Dairy Science, 102(3), 2469-2480. doi:10.3168/jds.2018-15219Dong, X., Zhou, Z., Saremi, B., Helmbrecht, A., Wang, Z., & Loor, J. J. (2018). Varying the ratio of Lys:Met while maintaining the ratios of Thr:Phe, Lys:Thr, Lys:His, and Lys:Val alters mammary cellular metabolites, mammalian target of rapamycin signaling, and gene transcription. Journal of Dairy Science, 101(2), 1708-1718. doi:10.3168/jds.2017-13351Deng, L., Jiang, C., Chen, L., Jin, J., Wei, J., Zhao, L., … Wang, P. (2015). The Ubiquitination of RagA GTPase by RNF152 Negatively Regulates mTORC1 Activation. Molecular Cell, 58(5), 804-818. doi:10.1016/j.molcel.2015.03.033Carroll, B., Maetzel, D., Maddocks, O. D., Otten, G., Ratcliff, M., Smith, G. R., … Korolchuk, V. I. (2016). Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity. eLife, 5. doi:10.7554/elife.11058Wolfson, R. L., & Sabatini, D. M. (2017). The Dawn of the Age of Amino Acid Sensors for the mTORC1 Pathway. Cell Metabolism, 26(2), 301-309. doi:10.1016/j.cmet.2017.07.001Wang, S., Tsun, Z.-Y., Wolfson, R. L., Shen, K., Wyant, G. A., Plovanich, M. E., … Sabatini, D. M. (2015). Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science, 347(6218), 188-194. doi:10.1126/science.1257132Wolfson, R. L., Chantranupong, L., Saxton, R. A., Shen, K., Scaria, S. M., Cantor, J. R., & Sabatini, D. M. (2016). Sestrin2 is a leucine sensor for the mTORC1 pathway. Science, 351(6268), 43-48. doi:10.1126/science.aab2674Casey, T. M., Crodian, J., Erickson, E., Kuropatwinski, K. K., Gleiberman, A. S., & Antoch, M. P. (2014). Tissue-Specific Changes in Molecular Clocks During the Transition from Pregnancy to Lactation in Mice1. Biology of Reproduction, 90(6). doi:10.1095/biolreprod.113.116137Lamia, K. A., Storch, K.-F., & Weitz, C. J. (2008). Physiological significance of a peripheral tissue circadian clock. Proceedings of the National Academy of Sciences, 105(39), 15172-15177. doi:10.1073/pnas.0806717105Cho, H., Zhao, X., Hatori, M., Yu, R. T., Barish, G. D., Lam, M. T., … Evans, R. M. (2012). Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β. Nature, 485(7396), 123-127. doi:10.1038/nature11048Vollmers, C., Schmitz, R. J., Nathanson, J., Yeo, G., Ecker, J. R., & Panda, S. (2012). Circadian Oscillations of Protein-Coding and Regulatory RNAs in a Highly Dynamic Mammalian Liver Epigenome. Cell Metabolism, 16(6), 833-845. doi:10.1016/j.cmet.2012.11.004Cao, R. (2018). mTOR Signaling, Translational Control, and the Circadian Clock. Frontiers in Genetics, 9. doi:10.3389/fgene.2018.00367Ramanathan, C., Kathale, N. D., Liu, D., Lee, C., Freeman, D. A., Hogenesch, J. B., … Liu, A. C. (2018). mTOR signaling regulates central and peripheral circadian clock function. PLOS Genetics, 14(5), e1007369. doi:10.1371/journal.pgen.1007369Salfer, I. J., Dechow, C. D., & Harvatine, K. J. (2019). Annual rhythms of milk and milk fat and protein production in dairy cattle in the United States. Journal of Dairy Science, 102(1), 742-753. doi:10.3168/jds.2018-15040Li, S., Hosseini, A., Danes, M., Jacometo, C., Liu, J., & Loor, J. J. (2016). Essential amino acid ratios and mTOR affect lipogenic gene networks and miRNA expression in bovine mammary epithelial cells. Journal of Animal Science and Biotechnology, 7(1). doi:10.1186/s40104-016-0104-xVailati-Riboni, M., Xu, T., Qadir, B., Bucktrout, R., Parys, C., & Loor, J. J. (2019). In vitro methionine supplementation during lipopolysaccharide stimulation modulates immunometabolic gene network expression in isolated polymorphonuclear cells from lactating Holstein cows. Journal of Dairy Science, 102(9), 8343-8351. doi:10.3168/jds.2018-15737Kadegowda, A. K. G., Bionaz, M., Piperova, L. S., Erdman, R. A., & Loor, J. J. (2009). Peroxisome proliferator-activated receptor-γ activation and long-chain fatty acids alter lipogenic gene networks in bovine mammary epithelial cells to various extents. Journal of Dairy Science, 92(9), 4276-4289. doi:10.3168/jds.2008-1932Dong, X., Zhou, Z., Wang, L., Saremi, B., Helmbrecht, A., Wang, Z., & Loor, J. J. (2018). Increasing the availability of threonine, isoleucine, valine, and leucine relative to lysine while maintaining an ideal ratio of lysine:methionine alters mammary cellular metabolites, mammalian target of rapamycin signaling, and gene transcription. Journal of Dairy Science, 101(6), 5502-5514. doi:10.3168/jds.2017-13707Bionaz, M., & Loor, J. J. (2011). Gene Networks Driving Bovine Mammary Protein Synthesis during the Lactation cycle. Bioinformatics and Biology Insights, 5, BBI.S7003. doi:10.4137/bbi.s7003Zhou, Z., Vailati-Riboni, M., Trevisi, E., Drackley, J. K., Luchini, D. N., & Loor, J. J. (2016). Better postpartal performance in dairy cows supplemented with rumen-protected methionine compared with choline during the peripartal period. Journal of Dairy Science, 99(11), 8716-8732. doi:10.3168/jds.2015-10525National Research Council , Nutrient Requirements of Dairy Cattle , National Academies Press , Washington , 2001Batistel, F., Arroyo, J. M., Bellingeri, A., Wang, L., Saremi, B., Parys, C., … Loor, J. J. (2017). Ethyl-cellulose rumen-protected methionine enhances performance during the periparturient period and early lactation in Holstein dairy cows. Journal of Dairy Science, 100(9), 7455-7467. doi:10.3168/jds.2017-12689Batistel, F., Arroyo, J. M., Garces, C. I. M., Trevisi, E., Parys, C., Ballou, M. A., … Loor, J. J. (2018). Ethyl-cellulose rumen-protected methionine alleviates inflammation and oxidative stress and improves neutrophil function during the periparturient period and early lactation in Holstein dairy cows. Journal of Dairy Science, 101(1), 480-490. doi:10.3168/jds.2017-13185Zhou, Z., Ferdous, F., Montagner, P., Luchini, D. N., Corrêa, M. N., & Loor, J. J. (2018). Methionine and choline supply during the peripartal period alter polymorphonuclear leukocyte immune response and immunometabolic gene expression in Holstein cows. Journal of Dairy Science, 101(11), 10374-10382. doi:10.3168/jds.2018-14972Vailati-Riboni, M., Zhou, Z., Jacometo, C. B., Minuti, A., Trevisi, E., Luchini, D. N., & Loor, J. J. (2017). Supplementation with rumen-protected methionine or choline during the transition period influences whole-blood immune response in periparturient dairy cows. Journal of Dairy Science, 100(5), 3958-3968. doi:10.3168/jds.2016-11812Ma, Y. F., Batistel, F., Xu, T. L., Han, L. Q., Bucktrout, R., Liang, Y., … Loor, J. J. (2019). Phosphorylation of AKT serine/threonine kinase and abundance of milk protein synthesis gene networks in mammary tissue in response to supply of methionine in periparturient Holstein cows. Journal of Dairy Science, 102(5), 4264-4274. doi:10.3168/jds.2018-15451Reynolds, C. K., Harmon, D. L., & Cecava, M. J. (1994). Absorption and Delivery of Nutrients for Milk Protein Synthesis by Portal-Drained Viscera. Journal of Dairy Science, 77(9), 2787-2808. doi:10.3168/jds.s0022-0302(94)77220-9Bequette, B. J., Backwell, F. R. C., & Crompton, L. A. (1998). Current Concepts of Amino Acid and Protein Metabolism in the Mammary Gland of the Lactating Ruminant. Journal of Dairy Science, 81(9), 2540-2559. doi:10.3168/jds.s0022-0302(98)70147-xTaylor, P. M. (2013). Role of amino acid transporters in amino acid sensing. The American Journal of Clinical Nutrition, 99(1), 223S-230S. doi:10.3945/ajcn.113.070086Dai, H., Coleman, D. N., Hu, L., Martinez-Cortés, I., Wang, M., Parys, C., … Loor, J. J. (2020). Methionine and arginine supplementation alter inflammatory and oxidative stress responses during lipopolysaccharide challenge in bovine mammary epithelial cells in vitro. Journal of Dairy Science, 103(1), 676-689. doi:10.3168/jds.2019-16631Hatzoglou, M., Fernandez, J., Yaman, I., & Closs, E. (2004). REGULATION OF CATIONIC AMINO ACID TRANSPORT: The Story of the CAT-1 Transporter. Annual Review of Nutrition, 24(1), 377-399. doi:10.1146/annurev.nutr.23.011702.073120Fuchs, B. C., & Bode, B. P. (2005). Amino acid transporters ASCT2 and LAT1 in cancer: Partners in crime? Seminars in Cancer Biology, 15(4), 254-266. doi:10.1016/j.semcancer.2005.04.005Zheng, L., Zhang, W., Zhou, Y., Li, F., Wei, H., & Peng, J. (2016). Recent Advances in Understanding Amino Acid Sensing Mechanisms that Regulate mTORC1. International Journal of Molecular Sciences, 17(10), 1636. doi:10.3390/ijms17101636Suryawan, A. (2011). Regulation of protein synthesis by amino acids in muscle of neonates. Frontiers in Bioscience, 16(1), 1445. doi:10.2741/3798Averous, J., Lambert-Langlais, S., Mesclon, F., Carraro, V., Parry, L., Jousse, C., … Fafournoux, P. (2016). GCN2 contributes to mTORC1 inhibition by leucine deprivation through an ATF4 independent mechanism. Scientific Reports, 6(1). doi:10.1038/srep27698Xia, J., Wang, R., Zhang, T., & Ding, J. (2016). Structural insight into the arginine-binding specificity of CASTOR1 in amino acid-dependent mTORC1 signaling. Cell Discovery, 2(1). doi:10.1038/celldisc.2016.35Chantranupong, L., Scaria, S. M., Saxton, R. A., Gygi, M. P., Shen, K., Wyant, G. A., … Sabatini, D. M. (2016). The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. Cell, 165(1), 153-164. doi:10.1016/j.cell.2016.02.035Cai, W., Wei, Y., Jarnik, M., Reich, J., & Lilly, M. A. (2016). The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function. PLOS Genetics, 12(5), e1006036. doi:10.1371/journal.pgen.1006036Shen, K., Huang, R. K., Brignole, E. J., Condon, K. J., Valenstein, M. L., Chantranupong, L., … Sabatini, D. M. (2018). Architecture of the human GATOR1 and GATOR1–Rag GTPases complexes. Nature, 556(7699), 64-69. doi:10.1038/nature26158Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008). The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1. Science, 320(5882), 1496-1501. doi:10.1126/science.1157535Saxton, R. A., Chantranupong, L., Knockenhauer, K. E., Schwartz, T. U., & Sabatini, D. M. (2016). Mechanism of arginine sensing by CASTOR1 upstream of mTORC1. Nature, 536(7615), 229-233. doi:10.1038/nature19079Inoki, K., Ouyang, H., Zhu, T., Lindvall, C., Wang, Y., Zhang, X., … Guan, K.-L. (2006). TSC2 Integrates Wnt and Energy Signals via a Coordinated Phosphorylation by AMPK and GSK3 to Regulate Cell Growth. Cell, 126(5), 955-968. doi:10.1016/j.cell.2006.06.055Huang, J., & Manning, B. D. (2008). The TSC1–TSC2 complex: a molecular switchboard controlling cell growth. Biochemical Journal, 412(2), 179-190. doi:10.1042/bj20080281Menon, S., Dibble, C. C., Talbott, G., Hoxhaj, G., Valvezan, A. J., Takahashi, H., … Manning, B. D. (2014). Spatial Control of the TSC Complex Integrates Insulin and Nutrient Regulation of mTORC1 at the Lysosome. Cell, 156(4), 771-785. doi:10.1016/j.cell.2013.11.049Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J., & Cantley, L. C. (2002). Identification of the Tuberous Sclerosis Complex-2 Tumor Suppressor Gene Product Tuberin as a Target of the Phosphoinositide 3-Kinase/Akt Pathway. Molecular Cell, 10(1), 151-162. doi:10.1016/s1097-2765(02)00568-3Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005). AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism. Cell Metabolism, 1(1), 15-25. doi:10.1016/j.cmet.2004.12.003Inoki, K., Zhu, T., & Guan, K.-L. (2003). TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival. Cell, 115(5), 577-590. doi:10.1016/s0092-8674(03)00929-2Hindupur, S. K., González, A., & Hall, M. N. (2015). The Opposing Actions of Target of Rapamycin and AMP-Activated Protein Kinase in Cell Growth Control. Cold Spring Harbor Perspectives in Biology, 7(8), a019141. doi:10.1101/cshperspect.a019141Ma, L., Chen, Z., Erdjument-Bromage, H., Tempst, P., & Pandolfi, P. P. (2005). Phosphorylation and Functional Inactivation of TSC2 by Erk. Cell, 121(2), 179-193. doi:10.1016/j.cell.2005.02.031ROLFE, M., McLEOD, L. E., PRATT, P. F., & PROUD, C. G. (2005). Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2). Biochemical Journal, 388(3), 973-984. doi:10.1042/bj20041888Yang, J.-X., Wang, C.-H., Xu, Q.-B., Zhao, F.-Q., Liu, J.-X., & Liu, H.-Y. (2015). Methionyl-Methionine Promotes α-s1 Casein Synthesis in Bovine Mammary Gland Explants by Enhancing Intracellular Substrate Availability and Activating JAK2-STAT5 and mTOR-Mediated Signaling Pathways. The Journal of Nutrition, 145(8), 1748-1753. doi:10.3945/jn.114.208330Ko, C. H., & Takahashi, J. S. (2006). Molecular components of the mammalian circadian clock. Human Molecular Genetics, 15(suppl_2), R271-R277. doi:10.1093/hmg/ddl207Yagita, K., Tamanini, F., van der Horst, G. T. J., & Okamura, H. (2001). Molecular Mechanisms of the Biological Clock in Cultured Fibroblasts. Science, 292(5515), 278-281. doi:10.1126/science.1059542Preitner, N., Damiola, F., Luis-Lopez-Molina, Zakany, J., Duboule, D., Albrecht, U., & Schibler, U. (2002). The Orphan Nuclear Receptor REV-ERBα Controls Circadian Transcription within the Positive Limb of the Mammalian Circadian Oscillator. Cell, 110(2), 251-260. doi:10.1016/s0092-8674(02)00825-5Reinke, H., & Asher, G. (2019). Crosstalk between metabolism and circadian clocks. Nature Reviews Molecular Cell Biology, 20(4), 227-241. doi:10.1038/s41580-018-0096-9Balsalobre, A., Brown, S. A., Marcacci, L., Tronche, F., Kellendonk, C., Reichardt, H. M., … Schibler, U. (2000). Resetting of Circadian Time in Peripheral Tissues by Glucocorticoid Signaling. Science, 289(5488), 2344-2347. doi:10.1126/science.289.5488.2344Lamia, K. A., Sachdeva, U. M., DiTacchio, L., Williams, E. C., Alvarez, J. G., Egan, D. F., … Evans, R. M. (2009). AMPK Regulates the Circadian Clock by Cryptochrome Phosphorylation and Degradation. Science, 326(5951), 437-440. doi:10.1126/science.1172156Zheng, X., & Sehgal, A. (2010). AKT and TOR Signaling Set the Pace of the Circadian Pacemaker. Current Biology, 20(13), 1203-1208. doi:10.1016/j.cub.2010.05.027Ye, R., Selby, C. P., Chiou, Y.-Y., Ozkan-Dagliyan, I., Gaddameedhi, S., & Sancar, A. (2014). Dual modes of CLOCK:BMAL1 inhibition mediated by Cryptochrome and Period proteins in the mammalian circadian clock. Genes & Development, 28(18), 1989-1998. doi:10.1101/gad.249417.114Luciano, A. K., Zhou, W., Santana, J. M., Kyriakides, C., Velazquez, H., & Sessa, W. C. (2018). CLOCK phosphorylation by AKT regulates its nuclear accumulation and circadian gene expression in peripheral tissues. Journal of Biological Chemistry, 293(23), 9126-9136. doi:10.1074/jbc.ra117.000773Dang, F., Sun, X., Ma, X., Wu, R., Zhang, D., Chen, Y., … L
Assessment, Usability, and Sociocultural Impacts of DataONE
DataONE, funded from 2009-2019 by the U.S. National Science Foundation, is an early example of a large-scale project that built both a cyberinfrastructure and culture of data discovery, sharing, and reuse. DataONE used a Working Group model, where a diverse group of participants collaborated on targeted research and development activities to achieve broader project goals. This article summarizes the work carried out by two of DataONE’s working groups: Usability & Assessment (2009-2019) and Sociocultural Issues (2009-2014). The activities of these working groups provide a unique longitudinal look at how scientists, librarians, and other key stakeholders engaged in convergence research to identify and analyze practices around research data management through the development of boundary objects, an iterative assessment program, and reflection. Members of the working groups disseminated their findings widely in papers, presentations, and datasets, reaching international audiences through publications in 25 different journals and presentations to over 5,000 people at interdisciplinary venues. The working groups helped inform the DataONE cyberinfrastructure and influenced the evolving data management landscape. By studying working groups over time, the paper also presents lessons learned about the working group model for global large-scale projects that bring together participants from multiple disciplines and communities in convergence research
Near-Infrared Photometric Survey of Proto-Planetary Nebula Candidates
We present JHK' photometric measurements of 78 objects mostly consisting of
proto-planetary nebula candidates. Photometric magnitudes are determined by
means of imaging and aperture photometry. Unlike the observations with a
photometer with a fixed-sized beam, the method of imaging photometry permits
accurate derivation of photometric values because the target sources can be
correctly identified and confusion with neighboring sources can be easily
avoided. Of the 78 sources observed, we report 10 cases in which the source
seems to have been misidentified or confused by nearby bright sources. We also
present nearly two dozen cases in which the source seems to have indicated a
variability which prompts a follow-up monitoring. There are also a few sources
that show previously unreported extendedness. In addition, we present H band
finding charts of the target sources.Comment: 3 tables, 1 figur
Genetic Structures of Copy Number Variants Revealed by Genotyping Single Sperm
Copy number variants (CNVs) occupy a significant portion of the human genome and may have important roles in meiotic recombination, human genome evolution and gene expression. Many genetic diseases may be underlain by CNVs. However, because of the presence of their multiple copies, variability in copy numbers and the diploidy of the human genome, detailed genetic structure of CNVs cannot be readily studied by available techniques.Single sperm samples were used as the primary subjects for the study so that CNV haplotypes in the sperm donors could be studied individually. Forty-eight CNVs characterized in a previous study were analyzed using a microarray-based high-throughput genotyping method after multiplex amplification. Seventeen single nucleotide polymorphisms (SNPs) were also included as controls. Two single-base variants, either allelic or paralogous, could be discriminated for all markers. Microarray data were used to resolve SNP alleles and CNV haplotypes, to quantitatively assess the numbers and compositions of the paralogous segments in each CNV haplotype.This is the first study of the genetic structure of CNVs on a large scale. Resulting information may help understand evolution of the human genome, gain insight into many genetic processes, and discriminate between CNVs and SNPs. The highly sensitive high-throughput experimental system with haploid sperm samples as subjects may be used to facilitate detailed large-scale CNV analysis
Chronic widespread pain after motor vehicle collision typically occurs through immediate development and nonrecovery: results of an emergency department-based cohort study
Motor vehicle collision (MVC) can trigger chronic widespread pain (CWP) development in vulnerable individuals. Whether such CWP typically develops via the evolution of pain from regional to widespread or via the early development of widespread pain with non-recovery is currently unknown. We evaluated the trajectory of CWP development (American College of Rheumatology criteria) among 948 European-American individuals who presented to the emergency department (ED) for care in the early aftermath of MVC. Pain extent was assessed in the ED and 6 weeks, 6 months, and 1 year after MVC on 100%, 91%, 89%, and 91% of participants, respectively. Individuals who reported prior CWP at the time of ED evaluation (n = 53) were excluded. Trajectory modeling identified a two-group solution as optimal, with the Bayes Factor value (138) indicating strong model selection. Linear solution plots supported a non-recovery model. While the number of body regions with pain in the non-CWP group steadily declined, the number of body regions with pain in the CWP trajectory group (192/895, 22%) remained relatively constant over time. These data support the hypothesis that individuals who develop CWP after MVC develop widespread pain in the early aftermath of MVC which does not remit
iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE
The apical inflammatory cytokine TNF regulates numerous important biological processes including inflammation and cell death, and drives inflammatory diseases. TNF secretion requires TACE (also called ADAM17), which cleaves TNF from its transmembrane tether. The trafficking of TACE to the cell surface, and stimulation of its proteolytic activity, depends on membrane proteins, called iRhoms. To delineate how the TNF/TACE/iRhom axis is regulated, we performed an immunoprecipitation/mass spectrometry screen to identify iRhom-binding proteins. This identified a novel protein, that we name iTAP (iRhom Tail-Associated Protein) that binds to iRhoms, enhancing the cell surface stability of iRhoms and TACE, preventing their degradation in lysosomes. Depleting iTAP in primary human macrophages profoundly impaired TNF production and tissues from iTAP KO mice exhibit a pronounced depletion in active TACE levels. Our work identifies iTAP as a physiological regulator of TNF signalling and a novel target for the control of inflammation.info:eu-repo/semantics/publishedVersio
- …