GV

M. Aguilar, D. Aisa, B. Alpat, A. Alvino, G. Ambrosi, K. Andeen, L. Arruda, N. Attig, P. Azzarello, A. Bachlechner, F. Barão, A. Barrau, L. Barrin, A. Bartoloni, L. Basara, M. Battarbee, R. Battiston, J. Bazo, U. Becker, M. Behlmann, B. Beischer, J. Berdugo, B. Bertucci, G. Bigongiari, V. Bindi, S. Bizzaglia, M. Bizzarri, G. Boella, W. de Boer, K. Bollweg, V. Bonnivard, B. Borgia, S. Borsini, M. Boschini, M. Bourquin, J. Burger, F. Cadoux, X. Cai, M. Capell, S. Caroff, J. Casaus, V. Cascioli, G. Castellini, I. Cernuda, D. Cerreta, F. Cervelli, M. Chae, Y. H. Chang, A. Chen, H. Chen, G. Cheng, H. Chen, L. Cheng, H. Chou, E. Choumilov, V. Choutko, C. Chung, C. Clark, R. Clavero, Nicolas Produit, C. Consolandi, A. Contin, C. Corti, E. Cortina Gil, B. Coste, W. Creus, M. Crispoltoni, Z. Cui, Y. Dai, C. Delgado, S. Della Torre, M. Demirköz, L. Derome, S. Di Falco, L. Di Masso, F. Dimiccoli, C. Díaz, P. von Doetinchem, F. Donnini, W. Du, M. Duranti, D. D’Urso, A. Eline, F. J. Eppling, T. Eronen, Y. Y. Fan, L. Farnesini, J. Feng, E. Fiandrini, A. Fiasson, E. Finch, P. Fisher, Y. Galaktionov, G. Gallucci, B. Garcia, R. García-López, C. Gargiulo, H. Gast, I. Gebauer, M. Gervasi, A. Ghelfi, W. Gillard, F. Giovacchini, P. Goglov, J. Gong, C. Goy, V. Grabski, D. Grandi, M. Graziani, C. Guandalini, I. Guerri, K. Guo, D. Haas, M. Habiby, S. Haino, K. Han, Z. H. He, M. Heil, J. Hoffman, T. Hsieh, Z. Huang, C. Huh, M. Incagli, M. Ionica, W. Jang, H. Jinchi, K. Kanishev, G. Kim, K. Kim, T. Kirn, R. Kossakowski, O. Kounina, A. Kounine, V. Koutsenko, Matthew Scott Krafczyk, G. La Vacca, E. Laudi, G. Laurenti, I. Lazzizzera, A. Lebedev, H. T. Lee, S. Lee, C. Leluc, G. Levi, H. L. Li, J. Li, Q. Li, Q. Li, T. X. Li, W. Li, Y. Li, Z. Li, Z. Li, S. Lim, C. H. Lin, P. Lipari, T. Lippert, D. Liu, H. Liu, M. Lolli, T. Lomtadze, M. Lu, S. Lu, Y. Lu, K. Luebelsmeyer, J. Luo, S. Lv, R. Majka, C. Mañá, J. Marin, T. Martin, G. Martinez, N. Masi, D. Maurin, A. Menchaca-Rocha, Q. Meng, D. Mo, L. Morescalchi, P. Mott, M. Müller, J. Ni, N. Nikonov, F. Nozzoli, P. Nunes, A. Obermeier, A. Oliva, M. Orcinha, Federico Palmonari, C. Palomares, M. Paniccia, A. Papi, M. Pauluzzi, E. Pedreschi, S. Pensotti, R. Pereira, N. Picot-Clemente, F. Pilo, A. Piluso, C. Pizzolotto, V. Plyaskin, M. Pohl, V. Poireau, E. Postaci, A. Putze, L. Quadrani, X. Qi, X. Qin, Z. Qu, T. Räihä, P. Rancoita, D. Rapin, J. Ricol, I. Rodríguez, S. Rosier-Lees, A. Rozhkov, D. Rozza, R. Sagdeev, J. Sandweiss, P. Saouter, C. Sbarra, S. Schael, S. M. Schmidt, A. Schulz von Dratzig, G. Schwering, G. Scolieri, E. Seo, B. Shan, Y. Shan, J. Shi, X. Shi, Y. Shi, T. Siedenburg, D. Son, F. Spada, F. Spinella, W. Sun, W. Sun, M. Tacconi, C. P. Tang, X. Tang, Z. Tang, L. Tao, D. Tescaro, S. Ting, S. Ting, N. Tomassetti, J. Torsti, C. Türkoğlu, T. Urban, V. Vagelli, E. Valente, C. Vannini, E. Valtonen, S. Vaurynovich, M. Vecchi, M. Velasco, J. Vialle, V. Vitale, S. Vitillo, L. Wang, N. Wang, Q. Wang, R. Wang, X. Wang, Z. Wang, Z. Weng, K. Whitman, J. Wienkenhöver, H. Wu, X. Wu, X. Xia, M. Xie, S. Xie, R. Xiong, G. Xin, N. Xu, W. Xu, Qi Yan, J. Yang, M. Yang, Q. Ye, H. Yi, Y. Yu, Z. Yu, S. Zeissler, J. Zhang, M. Zhang, X. B. Zhang, Z. Zhang, Z. Zheng, H. Zhuang, V. Zhukov, A. Zichichi, N. Zimmermann, P. Zuccon, C. Zurbach

A precise measurement of the proton flux in primary cosmic rays with rigidity (momentum/charge) from 1 GV to 1.8 TV is presented based on 300 million events. Knowledge of the rigidity dependence of the proton flux is important in understanding the origin, acceleration, and propagation of cosmic rays. We present the detailed variation with rigidity of the flux spectral index for the first time. The spectral index progressively hardens at high rigidities.

M. Aguilar, L. Ali Cavasonza, G. Ambrosi, L. Arruda, N. Attig, S. Aupetit, P. Azzarello, A. Bachlechner, F. Barão, A. Barrau, L. Barrin, A. Bartoloni, L. Basara, S. Başeğmez-du Pree, M. Battarbee, R. Battiston, U. Becker, M. Behlmann, B. Beischer, J. Berdugo, B. Bertucci, K. F. Bindel, V. Bindi, G. Boella, W. de Boer, K. Bollweg, V. Bonnivard, B. Borgia, M. Boschini, M. Bourquin, E. Bueno, J. Burger, F. Cadoux, X. Cai, M. Capell, S. Caroff, J. Casaus, G. Castellini, F. Cervelli, M. Chae, Y. H. Chang, A. Chen, G. Chen, H. Chen, L. Cheng, H. Chou, E. Choumilov, V. Choutko, C. Chung, C. Clark, R. Clavero, Nicolas Produit, C. Consolandi, A. Contin, C. Corti, W. Creus, M. Crispoltoni, Z. Cui, Y. Dai, C. Delgado, S. Della Torre, O. Demakov, M. Demirköz, L. Derome, S. Di Falco, F. Dimiccoli, C. Díaz, P. von Doetinchem, F. Dong, F. Donnini, M. Duranti, D. D’Urso, A. Egorov, A. Eline, T. Eronen, J. Feng, E. Fiandrini, E. Finch, P. Fisher, V. Formato, Y. Galaktionov, G. Gallucci, B. Garcia, R. García-López, C. Gargiulo, H. Gast, I. Gebauer, M. Gervasi, A. Ghelfi, F. Giovacchini, P. Goglov, D. Gómez-Coral, J. Gong, C. Goy, V. Grabski, D. Grandi, M. Graziani, K. Guo, S. Haino, K. Han, Z. H. He, M. Heil, J. Hoffman, T. Hsieh, H. Huang, Z. Huang, C. Huh, M. Incagli, M. Ionica, W. Jang, H. Jinchi, S. Kang, K. Kanishev, G. Kim, K. Kim, T. Kirn, C. Konak, O. Kounina, A. Kounine, V. Koutsenko, Matthew Scott Krafczyk, G. La Vacca, E. Laudi, G. Laurenti, I. Lazzizzera, A. Lebedev, H. T. Lee, S. Lee, C. Leluc, H. S. Li, J. Li, J. Li, Q. Li, T. X. Li, W. Li, Y. Li, Z. Li, Z. Li, S. Lim, C. H. Lin, P. Lipari, T. Lippert, D. Liu, Hu Liu, V. D. Lordello, S. Lu, Y. Lu, K. Luebelsmeyer, F. Luo, J. Luo, S. Lv, F. Machate, R. Majka, C. Mañá, J. Marin, T. Martin, G. Martinez, N. Masi, D. Maurin, A. Menchaca-Rocha, Q. Meng, V. Mikuni, D. Mo, L. Morescalchi, P. Mott, T. Nelson, J. Ni, N. Nikonov, F. Nozzoli, A. Oliva, M. Orcinha, Federico Palmonari, C. Palomares, M. Paniccia, M. Pauluzzi, S. Pensotti, R. Pereira, N. Picot-Clemente, F. Pilo, C. Pizzolotto, V. Plyaskin, M. Pohl, V. Poireau, A. Putze, L. Quadrani, X. Qi, X. Qin, Z. Qu, T. Räihä, P. Rancoita, D. Rapin, J. Ricol, S. Rosier-Lees, A. Rozhkov, D. Rozza, R. Sagdeev, J. Sandweiss, P. Saouter, S. Schael, S. M. Schmidt, A. Schulz von Dratzig, G. Schwering, E. Seo, B. Shan, J. Shi, T. Siedenburg, D. Son, J. Song, W. Sun, M. Tacconi, X. Tang, Z. Tang, L. Tao, D. Tescaro, S. Ting, S. Ting, N. Tomassetti, J. Torsti, C. Türkoğlu, T. Urban, V. Vagelli, E. Valente, C. Vannini, E. Valtonen, M. Vazquez Acosta, M. Vecchi, M. Velasco, J. Vialle, V. Vitale, S. Vitillo, L. Wang, N. Wang, Q. Wang, X. Wang, X. Wang, Z. Wang, C. C. Wei, Z. Weng, K. Whitman, J. Wienkenhöver, H. Wu, X. Wu, X. Xia, R. Xiong, W. Xu, Qi Yan, J. Yang, M. Yang, Y. Yang, H. Yi, Y. Yu, Z. Yu, S. Zeissler, C. Zhang, J. Zhang, J. Zhang, S. Zhang, S. Zhang, Z. Zhang, Z. Zheng, Z. Q. Zhu, H. Zhuang, V. Zhukov, A. Zichichi, N. Zimmermann, P. Zuccon

AMS-02 is wide acceptance high-energy physics experiment installed on the International Space Station in May 2011 and operating continuously since then. AMS-02 is able to precisely separate cosmic rays light nuclei (1≤ Z ≤ 8) with contaminations less than 10−3. The light nuclei cosmic ray Boron to Carbon flux ratio is very well known sensitive observable for the understanding of the propagation of cosmic rays in the Galaxy, being Boron a secondary product of spallation on the interstellar medium of heavier primary elements such as Carbon and Oxygen. A precision measurement based on 10 million events of the Boron to Carbon ratio in the rigidity range from 2 GV to 1.8 TV is presented.

P. Ntostis, D. Iles, G. Kokkali, T. Vaxevanoglou, E. Kanavakis, A. Pantou, J. Huntriss, K. Pantos, H. Picton

Abstract STUDY QUESTION Are there age-related differences in gene expression during the germinal vesicle (GV) to metaphase II (MII) stage transition in euploid human oocytes? SUMMARY ANSWER A decrease in mitochondrial-related transcripts from GV to MII oocytes was observed, with a much greater reduction in MII oocytes with advanced age. WHAT IS KNOWN ALREADY Early embryonic development is dependent on maternal transcripts accumulated and stored within the oocyte during oogenesis. Transcriptional activity of the oocyte, which dictates its ultimate developmental potential, may be influenced by age and explain the reduced competence of advanced maternal age (AMA) oocytes compared with the young maternal age (YMA). Gene expression has been studied in human and animal oocytes; however, RNA sequencing could provide further insights into the transcriptome profiling of GV and in vivo matured MII euploid oocytes of YMA and AMA patients. STUDY DESIGN, SIZE, DURATION Fifteen women treated for infertility in a single IVF unit agreed to participate in this study. Five GV and 5 MII oocytes from 6, 21–26 years old women (YMA cohort) and 5 GV and 6 MII oocytes from 6, 41–44 years old women (AMA cohort) undergoing IVF treatment were donated. The samples were collected within a time frame of 4 months. RNA was isolated and deep sequenced at the single-cell level. All donors provided either GV or MII oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS Cumulus dissection from donated oocytes was performed 38 h after hCG injection, denuded oocytes were inserted into lysis buffer supplemented with RNase inhibitor. The samples were stored at −80°C until further use. Isolated RNA from GV and MII oocytes underwent library preparation using an oligo deoxy-thymidine (dT) priming approach (SMART-Seq v4 Ultra Low Input RNA assay; Takara Bio, Japan) and Nextera XT DNA library preparation assay (Illumina, USA) followed by deep sequencing. Data processing, quality assessment and bioinformatics analysis were performed using source-software, mainly including FastQC, HISAT2, StringTie and edgeR, along with functional annotation analysis, while scploid R package was employed to determine the ploidy status. MAIN RESULTS AND THE ROLE OF CHANCE Following deep sequencing of single GV and MII oocytes in both YMA and AMA cohorts, several hundred transcripts were found to be expressed at significantly different levels. When YMA and AMA MII oocyte transcriptomes were compared, the most significant of these were related to mitochondrial structure and function, including biological processes, mitochondrial respiratory chain complex I assembly and mitochondrial translational termination (false discovery rate (FDR) 6.0E−10 to 1.2E−7). These results indicate a higher energy potential of the YMA MII cohort that is reduced with ageing. Other biological processes that were significantly higher in the YMA MII cohort included transcripts involved in the translation process (FDR 1.9E−2). Lack of these transcripts could lead to inappropriate protein synthesis prior to or upon fertilisation of the AMA MII oocytes. LARGE SCALE DATA The RNA sequencing data were deposited in the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo), under the accession number: GSE164371. LIMITATIONS, REASONS FOR CAUTION The relatively small sample size could be a reason for caution. However, the RNA sequencing results showed homogeneous clustering with low intra-group variation and five to six biological replicates derived from at least three different women per group minimised the potential impact of the sample size. WIDER IMPLICATIONS OF THE FINDINGS Understanding the effects of ageing on the oocyte transcriptome could highlight the mechanisms involved in GV to MII transition and identify biomarkers that characterise good MII oocyte quality. This knowledge has the potential to guide IVF regimes for AMA patients. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Medical Research Council (MRC Grant number MR/K020501/1).

M. Aguilar, L. A. Cavasonza, G. Ambrosi, L. Arruda, N. Attig, F. Barão, L. Barrin, A. Bartoloni, S. Başeğmez-du Pree, R. Battiston, M. Behlmann, B. Beránek, J. Berdugo, B. Bertucci, V. Bindi, K. Bollweg, B. Borgia, M. Boschini, M. Bourquin, E. Bueno, J. Burger, W. Burger, S. Burmeister, X. Cai, M. Capell, J. Casaus, G. Castellini, F. Cervelli, Y. H. Chang, G. M. Chen, G. R. Chen, H. S. Chen, Y. Chen, L. Cheng, H. Chou, S. Chouridou, V. Choutko, C. Chung, C. Clark, Nicolas Produit, C. Consolandi, A. Contin, C. Corti, Z. Cui, K. Dadzie, A. Dass, C. Delgado, S. Della Torre, M. Demirköz, L. Derome, S. Di Falco, V. Di Felice, C. Díaz, F. Dimiccoli, P. von Doetinchem, F. Dong, F. Donnini, M. Duranti, A. Egorov, A. Eline, J. Feng, E. Fiandrini, P. Fisher, V. Formato, C. Freeman, C. Gamez, R. García-López, C. Gargiulo, H. Gast, M. Gervasi, F. Giovacchini, D. Gómez-Coral, J. Gong, C. Goy, V. Grabski, D. Grandi, M. Graziani, S. Haino, K. Han, R. Hashmani, Z. H. He, B. Heber, T. Hsieh, J. Y. Hu, M. Incagli, W. Jang, Yi Jia, H. Jinchi, G. Karagöz, B. Khiali, G. N. Kim, T. Kirn, M. Konyushikhin, O. Kounina, A. Kounine, V. Koutsenko, D. Krasnopevtsev, A. Kuhlman, A. Kulemzin, G. La Vacca, E. Laudi, G. Laurenti, I. Lazzizzera, A. Lebedev, H. T. Lee, S. C. Lee, J. Q. Li, M. Li, Q. Li, S. Li, J. H. Li, Z. H. Li, J. Liang, C. Light, C. H. Lin, T. Lippert, J. H. Liu, Z. Liu, S. Q. Lu, Y. S. Lu, K. Luebelsmeyer, J. Z. Luo, Xi Luo, F. Machate, C. Mañá, J. Marin, J. Marquardt, T. Martin, G. Martinez, N. Masi, D. Maurin, T. Medvedeva, A. Menchaca-Rocha, Q. Meng, V. Mikhailov, M. Molero, P. Mott, L. Mussolin, J. Negrete, N. Nikonov, F. Nozzoli, A. Oliva, M. Orcinha, M. Palermo, F. Palmonari, M. Paniccia, A. Pashnin, M. Pauluzzi, S. Pensotti, H D Phan, V. Plyaskin, M. Pohl, S. Poluianov, X. Qin, Z. Qu, L. Quadrani, P. Rancoita, D. Rapin, A. R. Conde, E. Robyn, S. Rosier-Lees, A. Rozhkov, D. Rozza, R. Sagdeev, S. Schael, A. S. von Dratzig, G. Schwering, E. Seo, Z. Shakfa, B. Shan, T. Siedenburg, C. Solano, J. W. Song, X. J. Song, R. Sonnabend, L. Strigari, T. Su, Q. Sun, Z. T. Sun, M. Tacconi, X. W. Tang, Z. C. Tang, J. Tian, S. Ting, Nicolas Produit, N. Tomassetti, J. Torsti, T. Urban, I. Usoskin, V. Vagelli, R. Vainio, M. Valencia-Otero, E. Valente, E. Valtonen, M. Vazquez Acosta, M. Vecchi, M. Velasco, J. Vialle, C. X. Wang, L. Wang, L. Q. Wang, N. H. Wang, Q. L. Wang, S. Wang, X. Wang, Yu Wang, Z. M. Wang, J. Wei, Z. Weng, H. Wu, R. Xiong, W. Xu, Qi Yan, Y. Yang, I. Yashin, H. Yi, Y. M. Yu, Z. Q. Yu, M. Zannoni, C. Zhang, F. Zhang, F. Z. Zhang, J. H. Zhang, Z. Zhang, F. Zhao, C. Zheng, Z. M. Zheng, H. Zhuang, V. Zhukov, A. Zichichi, P. Zuccon

We present the precision measurement of the daily proton fluxes in cosmic rays from May 20, 2011 to October 29, 2019 (a total of 2824 days or 114 Bartels rotations) in the rigidity interval from 1 to 100 GV based on 5.5×10^{9} protons collected with the Alpha Magnetic Spectrometer aboard the International Space Station. The proton fluxes exhibit variations on multiple timescales. From 2014 to 2018, we observed recurrent flux variations with a period of 27 days. Shorter periods of 9 days and 13.5 days are observed in 2016. The strength of all three periodicities changes with time and rigidity. The rigidity dependence of the 27-day periodicity is different from the rigidity dependences of 9-day and 13.5-day periods. Unexpectedly, the strength of 9-day and 13.5-day periodicities increases with increasing rigidities up to ∼10  GV and ∼20  GV, respectively. Then the strength of the periodicities decreases with increasing rigidity up to 100 GV.

Xi Chen, Xin Chen, Ding Yan, Na Zhang, Wen Fu, Meixuan Wu, Feifei Ge, Jiangtuan Wang, Xiaofen Li, M. Geng, Jinheng Wang, Daolin Tang, Jinbao Liu

Despite recent advances, severe acute pancreatitis (SAP) remains a lethal inflammation with limited treatment options. Here, we provide compelling evidence of GV-971 (sodium oligomannate), an anti-Alzheimer’s medication, as being a protective agent in various male mouse SAP models. Microbiome sequencing, along with intestinal microbiota transplantation and mass cytometry technology, unveil that GV-971 reshapes the gut microbiota, increasing Faecalibacterium populations and modulating both peripheral and intestinal immune systems. A metabolomics analysis of cecal contents from GV-971–treated SAP mice further identifies short-chain fatty acids, including propionate and butyrate, as key metabolites in inhibiting macrophage M1 polarization and subsequent lethal inflammation by blocking the MAPK pathway. These findings suggest GV-971 as a promising therapeutic for SAP by targeting the microbiota metabolic immune axis. Severe acute pancreatitis (SAP) is a profoundly lethal inflammatory condition with limited therapeutic options. Here, the authors present GV-971, an anti-Alzheimer's medication, as a promising candidate for SAP by effectively restoring intestinal microbiota homeostasis and metabolite profiles.