Lindstrom, R. et al. Exploring the conserved role of MANF in the unfolded protein response in Drosophila melanogaster. PLoS. ONE. 11, e0151550 (2016). Sheedfar, F., Di Biase, S., Koonen, D. & Vinciguerra, M. Liver diseases and aging: friends or foes? Aging Cell. 12, 950–954 (2013).

Rebo, J. et al. A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nat. Commun. 7, 13363 (2016). Kityk, R., Kopp, J. & Mayer, M. P. Molecular mechanism of J-domain-triggered ATP hydrolysis by Hsp70 chaperones. Mol. Cell 69, 227–237 e4 (2018). I think it's the greatest goal Manchester United have ever scored. It's the best ever goal I've seen live.Franceschi, C. et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N.Y. Acad. Sci. 908, 244–254 (2000). Barzilai, N., Huffman, D. M., Muzumdar, R. H. & Bartke, A. The critical role of metabolic pathways in aging. Diabetes 61, 1315–1322 (2012). Wu, T. et al. Circulating mesencephalic astrocyte-derived neurotrophic factor is increased in newly diagnosed prediabetic and diabetic patients, and is associated with insulin resistance. Endocr. J. 64, 403–410 (2017). Preissler, S. et al. Physiological modulation of BiP activity by trans-protomer engagement of the interdomain linker. eLife 4, e08961 (2015). Manchester United are hoping to strengthen in four positions in January, including in defensive midfield, with concerns over 27-year-old Morocco midfielder Sofyan Amrabat's season so far. (Guardian) , external

In the latest episode of BBC Radio Manchester's The Devils' Advocate podcast, co-hosts Gaz Drinkwater and Amber Haque discuss Alejandro Garnacho's unbelievable overhead finish in Manchester United's 3-0 win at Everton. Hoseki, J. et al. Solution structure and dynamics of mouse ARMET. FEBS Lett. 584, 1536–1542 (2010). Hypothetic involvement of MANF in UPR pathway and related diseases. (a) MANF displayed expression variation and protective effects on neurological and metabolic diseases involving neurodegenerative diseases, myocardial ischemia, type I diabetes, and several tumors, which could be a potential prognostic marker or a therapeutic target. The circulating MANF variated in diabetes mellitus and PCOS [ 91, 92]. With bioinformatic analysis, increased expression of MANF was correlated with a poorer prognosis in cholangiocarcinoma and hepatocellular carcinoma [ 85, 86]. Moreover, MANF exhibited varying degrees of protective effects in vitro and in vivo. Overexpression or using recombinant MANF could promote dopaminergic neuron survival and improve behavior in neurodegenerative and stroke models. MANF overexpression ameliorated HepG2 cell steatosis and inhibited lipogenesis. Also, recombinant MANF protected cardiac myocytes from ischemia/reperfusion-mediated cell death. (b) When ER stress happens, ATF6, IRE2, and PERK separately activate, resulting in apoptosis and autophagy. MANF could interact with BiP, the endoplasmic reticulum chaperone, and finally promote cell survival. ATF6 would be transferred to the Golgi complex and be cleaved into two parts. Then, ATF6 acts as a transcription factor, resulting in the expression alteration of MANF, Xbp1, and CHOP. Meanwhile, IRE1 could be activated through phosphorylation and dimerization, resulting in upregulated expression of MANF and chaperones. Also, IRE1 enables JNK phosphorylation and upregulates the expression of NF- κB, then inducing apoptosis and autophagy. The activated PERK effects with eIF2 α leading to the translation of ATF4 and antioxidant response.

Zhang, G. et al. Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature 497, 211–216 (2013).

Can anyone explain what other lists are being searched and how to identify what different numbers mean within the parenthesis? Castellano, J. M. et al. Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature 544, 488–492 (2017). Dutch midfielder Donny van de Beek, 26, says he will make a January move away from Manchester United if he does not start playing more games, revealing that a summer move to Real Sociedad fell through. (Diario AS, via Sky Sports) , external

Experiments were performed at cell densities of 70–90% confluence. Cells were treated with drugs at the following final concentrations: 0.5 µM thapsigargin (Calbiochem) and 2.5 µg/ml tunicamycin (Melford) first diluted in fresh, pre-warmed medium, and then applied to the cells by medium exchange. Plasmid construction Diffraction data were collected at beamlines in the Diamond Synchrotron Light Source (DLS) (Supplementary Table 3) and processed by the XIA2 pipeline 52 implementing Mosflm 53 or XDS 54 for indexing and integration, Pointless 55 for space group determination, and Aimless 55 for scaling and merging. All three structures were solved by molecular replacement using Phaser 56. For solving the NBD–SAP complex structure, the NBD moiety was searched using PDB 3LDN as a template and the SAP moiety was built manually in COOT 57 based on the high-resolution electron density map. Then this NBD–SAP complex and SAPLIP domain from PDB 2W51 were used as search models for solving the structure of NBD–MANF complex. The linker of MANF was built manually according to the electron density in COOT. The structure of BiP V461F (apo) was solved by searching the NBD (PDB 3LDN) and SBD (PDB 5E85) as models, respectively. Further refinement was performed iteratively using COOT, phenix.refine 58, and refmac5 59 (Supplementary Table 3). MolProbity 60 was consulted throughout the refinement process, at the end of which 99.5% of residues from the two complexes and 97.5% from BiP V461F were in the favored Ramachandran region and none were outliers. Molecular graphics were generated using UCSF Chimera 61 and PyMol (The PyMOL Molecular Graphics System, Version 1.3 Schrödinger, LLC). Fluorescence measurement is based on the idea that man is most commonly used as an exclusive, gender-marked noun meaning “male human being.”

Evans, P. R. An introduction to data reduction: space-group determination, scaling and intensity statistics. Acta Crystallogr. D. Biol. Crystallogr. 67, 282–292 (2011).I just think it was a very bold move. I know why Fernandes did it and it was to help Rashford’s confidence as he’s not had a great season in front of goal. Just look at the flip side. If Rashford had missed that and United hadn’t won the game, that would have overtaken the Garnacho goal as the story.