Anatomy and Neuroscience - Research Publications

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    Repeated eccentric contractions positively regulate muscle oxidative metabolism and protein synthesis during cancer cachexia in mice
    Hardee, JP ; Fix, DK ; Koh, H-J ; Wang, X ; Goldsmith, EC ; Carson, JA (AMER PHYSIOLOGICAL SOC, 2020-06-01)
    Cancer-induced wasting is accompanied by disruptions to muscle oxidative metabolism and protein turnover that have been associated with systemic inflammation, whereas exercise and stimulated muscle contractions can positively regulate muscle protein synthesis and mitochondrial homeostasis. In preclinical cancer cachexia models, a single bout of eccentric contractions (ECCs) can induce protein synthesis and repeated ECC bouts prevent myofiber atrophy. The cellular mechanisms providing this protection from atrophy have not been resolved. Therefore, the purpose of this study was to determine whether repeated stimulated ECC bouts affect basal muscle oxidative metabolism and protein synthesis during cancer cachexia, and if these changes were associated with plasma IL-6 levels. Male ApcMin/+ (MIN; n = 10) mice initiating cachexia and healthy C57BL/6 (B6; n = 11) control mice performed repeated ECC bouts over 2 wk. MIN mice exhibited body weight loss and elevated plasma IL-6 before and during repeated ECC bouts. Control MIN muscle demonstrated disrupted signaling related to inflammation, oxidative capacity, and protein synthesis regulation, which were all improved by repeated ECC bouts. With cachexia, plasma IL-6 levels were negatively correlated with myofiber cross-sectional area, oxidative capacity, and protein synthesis. Interestingly, ECC improvements in these outcomes were positively correlated with plasma IL-6 levels in MIN mice. There was also a positive relationship between muscle oxidative capacity and protein synthesis after repeated ECC bouts in MIN mice. Collectively, repeated ECC bouts altered the cachectic muscle phenotype independent of systemic wasting, and there was a strong association between muscle oxidative capacity and protein synthesis in this adaptive response.NEW & NOTEWORTHY Cancer-induced muscle wasting is accompanied by disruptions to muscle oxidative metabolism and protein turnover regulation, whereas exercise is a potent stimulator of muscle protein synthesis and mitochondrial homeostasis. In a preclinical model of cancer cachexia, we report that cachectic muscle retains anabolic and metabolic plasticity to repeated eccentric contraction bouts despite an overall systemic wasting environment. The attenuation of muscle atrophy is linked to improved oxidative capacity and protein synthesis during cancer cachexia progression.
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    Dystrophin deficiency disrupts muscle clock expression and mitochondrial quality control in mdx mice
    Hardee, JP ; Caldow, MK ; Chan, ASM ; Plenderleith, SK ; Trieu, J ; Koopman, R ; Lynch, GS (AMER PHYSIOLOGICAL SOC, 2021-08-01)
    Impaired oxidative capacity and mitochondrial function contribute to the dystrophic pathology in muscles of patients with Duchenne muscular dystrophy (DMD) and in relevant mouse models of the disease. Emerging evidence suggests an association between disrupted core clock expression and mitochondrial quality control, but this has not been established in muscles lacking dystrophin. We examined the diurnal regulation of muscle core clock and mitochondrial quality control expression in dystrophin-deficient C57BL/10ScSn-Dmdmdx (mdx) mice, an established model of DMD. Male C57BL/10 (BL/10; n = 18) and mdx mice (n = 18) were examined every 4 h beginning at the dark cycle. Throughout the entire light-dark cycle, extensor digitorum longus (EDL) muscles from mdx mice had decreased core clock mRNA expression (Arntl, Cry1, Cry2, Nr1d2; P < 0.05) and disrupted mitochondrial quality control mRNA expression related to biogenesis (decreased; Ppargc1a, Esrra; P < 0.05), fission (increased; Dnm1l; P < 0.01), fusion (decreased; Opa1, Mfn1; P < 0.05), and autophagy/mitophagy (decreased: Bnip3; P < 0.05; increased: Becn1; P < 0.05). Cosinor analysis revealed a decrease in the rhythmicity parameters mesor and amplitude for Arntl, Cry1, Cry2, Per2, and Nr1d1 (P < 0.001) in mdx mice. Diurnal oscillations in Esrra, Sirt1, Map1lc3b, and Sqstm1 were absent in mdx mice, along with decreased mesor and amplitude of Ppargc1a mRNA expression (P < 0.01). The expression of proteins involved in mitochondrial biogenesis (decreased: PPARGC1A, P < 0.05) and autophagy/mitophagy (increased: MAP1LC3BII, SQSTM1, BNIP3; P < 0.05) were also dysregulated in tibialis anterior muscles of mdx mice. These findings suggest that dystrophin deficiency in mdx mice impairs the regulation of the core clock and mitochondrial quality control, with relevance to DMD and related disorders.
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    Muscular contraction's therapeutic potential for cancer-induced wasting.
    Hardee, JP ; Carson, JA (American Physiological Society, 2022-08-01)
    Skeletal muscle atrophy and dysfunction contribute to morbidity and mortality in patients with cancer. Cachexia pathophysiology is highly complex, given that perturbations to the systemic cancer environment and the interaction with diverse tissues can contribute to wasting processes. Systemic interleukin 6 (IL-6) and glycoprotein 130 (gp130) receptors signaling have established roles in some types of cancer-induced muscle wasting through disruptions to protein turnover and oxidative capacity. Although exercise has documented benefits for cancer prevention and patient survival, there are significant gaps in our understanding of muscle adaptation and plasticity during severe cachexia. Preclinical models have provided valuable insight into the adaptive potential of muscle contraction within the cancer environment. We summarize the current understanding of how resistance-type exercise impacts mechanisms involved in cancer-induced muscle atrophy and dysfunction. Specifically, the role of IL-6 and gp130 receptors in the pathophysiology of muscle wasting and the adaptive response to exercise is explained. The discussion includes current knowledge gaps and future research directions needed to improve preclinical research and accelerate clinical translation in human patients with cancer.
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    Surgical applied anatomy: alive and kicking.
    Farley, E ; Hindmarch, J ; Eizenberg, N ; Midwinter, M (Wiley, 2021-05)
    BACKGROUND: Contention exists amongst anatomists, clinicians and surgeons about how much anatomical knowledge medical students need, although what is taught should be aligned with current surgical practice. The aim of this study was to explore the scope of recent advances in applied anatomy as highlighted in the ANZ Journal of Surgery in each of the surgical specialties. METHODS: The 2018 volume of the ANZ Journal of Surgery was narrowed to 254 articles by applying the search term 'anatomy'. The main topic was extracted from each paper. The content of the paper was assessed for 'novel description' or 'novel application' of anatomical knowledge and classified accordingly. RESULTS: Most papers with an anatomical focus were from general surgery, which focused on surgical techniques, outcomes and management. Vascular surgery had the highest percentage of papers with a novel description and application of anatomy. Although cardiothoracic and paediatric surgery had no papers with a novel description of anatomy, novel applications of anatomy were a focus in each speciality. CONCLUSION: The trend towards novel applications of anatomical knowledge in all surgical specialties should encourage medical schools to shape their anatomy curricula in tandem with such advances as they evolve. The high proportion of novel applications and descriptions of anatomy in general surgery indicates continued growth as a benchmark of anatomical understanding. Vascular surgery's proportion of novel application and description of anatomy may change the way students will learn vascular anatomy to incorporate endovascular, radiologically based approaches.
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    Impact of COVID-19 Pandemic on Cardiovascular Testing in Asia
    Kudo, T ; Lahey, R ; Hirschfeld, CB ; Williams, MC ; Lu, B ; Alasnag, M ; Bhatia, M ; Henry Bom, H-S ; Dautov, T ; Fazel, R ; Karthikeyan, G ; Keng, FYJ ; Rubinshtein, R ; Better, N ; Cerci, RJ ; Dorbala, S ; Raggi, P ; Shaw, LJ ; Villines, TC ; Vitola, JV ; Choi, AD ; Malkovskiy, E ; Goebel, B ; Cohen, YA ; Randazzo, M ; Pascual, TNB ; Pynda, Y ; Dondi, M ; Paez, D ; Einstein, AJ ; Einstein, AJ ; Paez, D ; Dondi, M ; Better, N ; Cerci, R ; Dorbala, S ; Pascual, TNB ; Raggi, P ; Shaw, LJ ; Villines, TC ; Vitola, JV ; Williams, MC ; Pynda, Y ; Hinterleitner, G ; Lu, Y ; Morozova, O ; Xu, Z ; Hirschfeld, CB ; Cohen, Y ; Goebel, B ; Malkovskiy, E ; Randazzo, M ; Choi, A ; Lopez-Mattei, J ; Parwani, P ; Nasery, MN ; Goda, A ; Shirka, E ; Benlabgaa, R ; Bouyoucef, S ; Medjahedi, A ; Nailli, Q ; Agolti, M ; Aguero, RN ; Alak, MDC ; Alberguina, LG ; Arroñada, G ; Astesiano, A ; Astesiano, A ; Norton, CB ; Benteo, P ; Blanco, J ; Bonelli, JM ; Bustos, JJ ; Cabrejas, R ; Cachero, J ; Campisi, R ; Canderoli, A ; Carames, S ; Carrascosa, P ; Castro, R ; Cendoya, O ; Cognigni, LM ; Collaud, C ; Collaud, C ; Cortes, C ; Courtis, J ; Cragnolino, D ; Daicz, M ; De La Vega, A ; De Maria, ST ; Del Riego, H ; Dettori, F ; Deviggiano, A ; Dragonetti, L ; Embon, M ; Enriquez, RE ; Ensinas, J ; Faccio, F ; Facello, A ; Garofalo, D ; Geronazzo, R ; Gonza, N ; Gutierrez, L ; Guzzo, MA ; Guzzo, MA ; Hasbani, V ; Huerin, M ; Jäger, V ; Lewkowicz, JM ; López De Munaín, MNA ; Lotti, JM ; Marquez, A ; Masoli, O ; Masoli, OH ; Mastrovito, E ; Mayoraz, M ; Melado, GE ; Mele, A ; Merani, MF ; Meretta, AH ; Molteni, S ; Montecinos, M ; Noguera, E ; Novoa, C ; Sueldo, CP ; Ascani, SP ; Pollono, P ; Pujol, MP ; Radzinschi, A ; Raimondi, G ; Redruello, M ; Rodríguez, M ; Rodríguez, M ; Romero, RL ; Acuña, AR ; Rovaletti, F ; San Miguel, L ; Solari, L ; Strada, B ; Traverso, S ; Traverzo, SS ; Espeche, MDHV ; Weihmuller, JS ; Wolcan, J ; Zeffiro, S ; Sakanyan, M ; Beuzeville, S ; Boktor, R ; Butler, P ; Calcott, J ; Carr, L ; Chan, V ; Chao, C ; Chong, W ; Dobson, M ; Downie, D ; Dwivedi, G ; Elison, B ; Engela, J ; Francis, R ; Gaikwad, A ; Basavaraj, AG ; Goodwin, B ; Greenough, R ; Hamilton-Craig, C ; Hsieh, V ; Joshi, S ; Lederer, K ; Lee, K ; Lee, J ; Magnussen, J ; Mai, N ; Mander, G ; Murton, F ; Nandurkar, D ; Neill, J ; O'Rourke, E ; O'Sullivan, P ; Pandos, G ; Pathmaraj, K ; Pitman, A ; Poulter, R ; Premaratne, M ; Prior, D ; Ridley, L ; Rutherford, N ; Salehi, H ; Saunders, C ; Scarlett, L ; Seneviratne, S ; Shetty, D ; Shrestha, G ; Shulman, J ; Solanki, V ; Stanton, T ; Stuart, M ; Stubbs, M ; Swainson, I ; Taubman, K ; Taylor, A ; Thomas, P ; Unger, S ; Upton, A ; Vamadevan, S ; Van Gaal, W ; Verjans, J ; Voutnis, D ; Wayne, V ; Wilson, P ; Wong, D ; Wong, K ; Younger, J ; Feuchtner, G ; Mirzaei, S ; Weiss, K ; Maroz-Vadalazhskaya, N ; Gheysens, O ; Homans, F ; Moreno-Reyes, R ; Pasquet, A ; Roelants, V ; Van De Heyning, CM ; Ríos, RA ; Soldat-Stankovic, V ; Stankovic, S ; Albernaz Siqueira, MH ; Almeida, A ; Alves Togni, PH ; Andrade, JH ; Andrade, L ; Anselmi, C ; Araújo, R ; Azevedo, G ; Bezerra, S ; Biancardi, R ; Grossman, GB ; Brandão, S ; Pianta, DB ; Carreira, L ; Castro, B ; Chang, T ; Cunali, F ; Cury, R ; Dantas, R ; de Amorim Fernandes, F ; De Lorenzo, A ; De Macedo Filho, R ; Erthal, F ; Fernandes, F ; Fernandes, J ; Fernandes, F ; De Souza, TF ; Alves, WF ; Ghini, B ; Goncalves, L ; Gottlieb, I ; Hadlich, M ; Kameoka, V ; Lima, R ; Lima, A ; Lopes, RW ; Machado e Silva, R ; Magalhães, T ; Silva, FM ; Mastrocola, LE ; Medeiros, F ; Meneghetti, JC ; Naue, V ; Naves, D ; Nolasco, R ; Nomura, C ; Oliveira, JB ; Paixao, E ; De Carvalho, FP ; Pinto, I ; Possetti, P ; Quinta, M ; Nogueira Ramos, RR ; Rocha, R ; Rodrigues, A ; Rodrigues, C ; Romantini, L ; Sanches, A ; Santana, S ; Sara da Silva, L ; Schvartzman, P ; Matushita, CS ; Senra, T ; Shiozaki, A ; Menezes de Siqueira, ME ; Siqueira, C ; Smanio, P ; Soares, CE ; Junior, JS ; Bittencourt, MS ; Spiro, B ; Mesquita, CT ; Torreao, J ; Torres, R ; Uellendahl, M ; Monte, GU ; Veríssimo, O ; Cabeda, EV ; Pedras, FV ; Waltrick, R ; Zapparoli, M ; Naseer, H ; Garcheva-Tsacheva, M ; Kostadinova, I ; Theng, Y ; Abikhzer, G ; Barette, R ; Chow, B ; Dabreo, D ; Friedrich, M ; Garg, R ; Hafez, MN ; Johnson, C ; Kiess, M ; Leipsic, J ; Leung, E ; Miller, R ; Oikonomou, A ; Probst, S ; Roifman, I ; Small, G ; Tandon, V ; Trivedi, A ; White, J ; Zukotynski, K ; Canessa, J ; Muñoz, GC ; Concha, C ; Hidalgo, P ; Lovera, C ; Massardo, T ; Vargas, LS ; Abad, P ; Arturo, H ; Ayala, S ; Benitez, L ; Cadena, A ; Caicedo, C ; Moncayo, AC ; Moncayo, AC ; Gomez, S ; Gutierrez Villamil, CT ; Jaimes, C ; Londoño, J ; Londoño Blair, JL ; Pabon, L ; Pineda, M ; Rojas, JC ; Ruiz, D ; Escobar, MV ; Vasquez, A ; Vergel, D ; Zuluaga, A ; Gamboa, IB ; Castro, G ; González, U ; Baric, A ; Batinic, T ; Franceschi, M ; Paar, MH ; Jukic, M ; Medakovic, P ; Persic, V ; Prpic, M ; Punda, A ; Batista, JF ; Gómez Lauchy, JM ; Gutierrez, YM ; Gutierrez, YM ; Menéndez, R ; Peix, A ; Rochela, L ; Panagidis, C ; Petrou, I ; Engelmann, V ; Kaminek, M ; Kincl, V ; Lang, O ; Simanek, M ; Abdulla, J ; Bøttcher, M ; Christensen, M ; Gormsen, LC ; Hasbak, P ; Hess, S ; Holdgaard, P ; Johansen, A ; Kyhl, K ; Norgaard, BL ; Øvrehus, KA ; Rønnow Sand, NP ; Steffensen, R ; Thomassen, A ; Zerahn, B ; Perez, A ; Escorza Velez, GA ; Velez, MS ; Abdel Aziz, IS ; Abougabal, M ; Ahmed, T ; Allam, A ; Asfour, A ; Hassan, M ; Hassan, A ; Ibrahim, A ; Kaffas, S ; Kandeel, A ; Ali, MM ; Mansy, A ; Maurice, H ; Nabil, S ; Shaaban, M ; Flores, AC ; Poksi, A ; Knuuti, J ; Kokkonen, V ; Larikka, M ; Uusitalo, V ; Bailly, M ; Burg, S ; Deux, J-F ; Habouzit, V ; Hyafil, F ; Lairez, O ; Proffit, F ; Regaieg, H ; Sarda-Mantel, L ; Tacher, V ; Schneider, RP ; Ayetey, H ; Angelidis, G ; Archontaki, A ; Chatziioannou, S ; Datseris, I ; Fragkaki, C ; Georgoulias, P ; Koukouraki, S ; Koutelou, M ; Kyrozi, E ; Repasos, E ; Stavrou, P ; Valsamaki, P ; Gonzalez, C ; Gutierrez, G ; Maldonado, A ; Buga, K ; Garai, I ; Maurovich-Horvat, P ; Schmidt, E ; Szilveszter, B ; Várady, E ; Banthia, N ; Bhagat, JK ; Bhargava, R ; Bhat, V ; Bhatia, M ; Choudhury, P ; Chowdekar, VS ; Irodi, A ; Jain, S ; Joseph, E ; Kumar, S ; Girijanandan Mahapatra, PD ; Mitra, D ; Mittal, BR ; Ozair, A ; Patel, C ; Patel, T ; Patel, R ; Patel, S ; Saxena, S ; Sengupta, S ; Singh, S ; Singh, B ; Sood, A ; Verma, A ; Affandi, E ; Alam, PS ; Edison, E ; Gunawan, G ; Hapkido, H ; Hidayat, B ; Huda, A ; Mukti, AP ; Prawiro, D ; Soeriadi, EA ; Syawaluddin, H ; Albadr, A ; Assadi, M ; Emami, F ; Houshmand, G ; Maleki, M ; Rostami, MT ; Zakavi, SR ; Zaid, EA ; Agranovich, S ; Arnson, Y ; Bar-Shalom, R ; Frenkel, A ; Knafo, G ; Lugassi, R ; Maor Moalem, IS ; Mor, M ; Muskal, N ; Ranser, S ; Shalev, A ; Albano, D ; Alongi, P ; Arnone, G ; Bagatin, E ; Baldari, S ; Bauckneht, M ; Bertelli, P ; Bianco, F ; Bonfiglioli, R ; Boni, R ; Bruno, A ; Bruno, I ; Busnardo, E ; Califaretti, E ; Camoni, L ; Carnevale, A ; Casoni, R ; Cavallo, AU ; Cavenaghi, G ; Chierichetti, F ; Chiocchi, M ; Cittanti, C ; Colletta, M ; Conti, U ; Cossu, A ; Cuocolo, A ; Cuzzocrea, M ; De Rimini, ML ; De Vincentis, G ; Del Giudice, E ; Del Torto, A ; Della Tommasina, V ; Durmo, R ; Erba, PA ; Evangelista, L ; Faletti, R ; Faragasso, E ; Farsad, M ; Ferro, P ; Florimonte, L ; Frantellizzi, V ; Fringuelli, FM ; Gatti, M ; Gaudiano, A ; Gimelli, A ; Giubbini, R ; Giuffrida, F ; Ialuna, S ; Laudicella, R ; Leccisotti, L ; Leva, L ; Liga, R ; Liguori, C ; Longo, G ; Maffione, M ; Mancini, ME ; Marcassa, C ; Milan, E ; Nardi, B ; Pacella, S ; Pepe, G ; Pontone, G ; Pulizzi, S ; Quartuccio, N ; Rampin, L ; Ricci, F ; Rossini, P ; Rubini, G ; Russo, V ; Sacchetti, GM ; Sambuceti, G ; Scarano, M ; Sciagrà, R ; Sperandio, M ; Stefanelli, A ; Ventroni, G ; Zoboli, S ; Baugh, D ; Chambers, D ; Madu, E ; Nunura, F ; Asano, H ; Chimura, CM ; Fujimoto, S ; Fujisue, K ; Fukunaga, T ; Fukushima, Y ; Fukuyama, K ; Hashimoto, J ; Ichikawa, Y ; Iguchi, N ; Imai, M ; Inaki, A ; Ishimura, H ; Isobe, S ; Kadokami, T ; Kato, T ; Kudo, T ; Kumita, S ; Maruno, H ; Mataki, H ; Miyagawa, M ; Morimoto, R ; Moroi, M ; Nagamachi, S ; Nakajima, K ; Nakata, T ; Nakazato, R ; Nanasato, M ; Naya, M ; Norikane, T ; Ohta, Y ; Okayama, S ; Okizaki, A ; Otomi, Y ; Otsuka, H ; Saito, M ; Sakata, SY ; Sarai, M ; Sato, D ; Shiraishi, S ; Suwa, Y ; Takanami, K ; Takehana, K ; Taki, J ; Tamaki, N ; Taniguchi, Y ; Teragawa, H ; Tomizawa, N ; Tsujita, K ; Umeji, K ; Wakabayashi, Y ; Yamada, S ; Yamazaki, S ; Yoneyama, T ; Rawashdeh, M ; Batyrkhanov, D ; Dautov, T ; Makhdomi, K ; Ombati, K ; Alkandari, F ; Garashi, M ; Coie, TL ; Rajvong, S ; Kalinin, A ; Kalnina, M ; Haidar, M ; Komiagiene, R ; Kviecinskiene, G ; Mataciunas, M ; Vajauskas, D ; Picard, C ; Karim, NKA ; Reichmuth, L ; Samuel, A ; Allarakha, MA ; Naojee, AS ; Alexanderson-Rosas, E ; Barragan, E ; González-Montecinos, AB ; Cabada, M ; Rodriguez, DC ; Carvajal-Juarez, I ; Cortés, V ; Cortés, F ; De La Peña, E ; Gama-Moreno, M ; González, L ; Ramírez, NG ; Jiménez-Santos, M ; Matos, L ; Monroy, E ; Morelos, M ; Ornelas, M ; Ortga Ramirez, JA ; Preciado-Anaya, A ; Preciado-Gutiérrez, ÓU ; Barragan, AP ; Rosales Uvera, SG ; Sandoval, S ; Tomas, MS ; Sierra-Galan, LM ; Sierra-Galan, LM ; Siu, S ; Vallejo, E ; Valles, M ; Faraggi, M ; Sereegotov, E ; Ilic, S ; Ben-Rais, N ; Alaoui, NI ; Taleb, S ; Pa Myo, KP ; Thu, PS ; Ghimire, RK ; Rajbanshi, B ; Barneveld, P ; Glaudemans, A ; Habets, J ; Koopmans, KP ; Manders, J ; Pool, S ; Scholte, A ; Scholtens, A ; Slart, R ; Thimister, P ; Van Asperen, E-J ; Veltman, N ; Verschure, D ; Wagenaar, N ; Edmond, J ; Ellis, C ; Johnson, K ; Keenan, R ; Kueh, SHA ; Occleshaw, C ; Sasse, A ; To, A ; Van Pelt, N ; Young, C ; Cuadra, T ; Roque Vanegas, HB ; Soli, IA ; Issoufou, DM ; Ayodele, T ; Madu, C ; Onimode, Y ; Efros-Monsen, E ; Forsdahl, SH ; Hildre Dimmen, J-M ; Jørgensen, A ; Krohn, I ; Løvhaugen, P ; Bråten, AT ; Al Dhuhli, H ; Al Kindi, F ; Al-Bulushi, N ; Jawa, Z ; Tag, N ; Afzal, MS ; Fatima, S ; Younis, MN ; Riaz, M ; Saadullah, M ; Herrera, Y ; Lenturut-Katal, D ; Vázquez, MC ; Ortellado, J ; Akhter, A ; Cao, D ; Cheung, S ; Dai, X ; Gong, L ; Han, D ; Hou, Y ; Li, C ; Li, T ; Li, D ; Li, S ; Liu, J ; Liu, H ; Lu, B ; Ng, MY ; Sun, K ; Tang, G ; Wang, J ; Wang, X ; Wang, Z-Q ; Wang, Y ; Wang, Y ; Wu, J ; Wu, Z ; Xia, L ; Xiao, J ; Xu, L ; Yang, Y ; Yin, W ; Yu, J ; Yuan, L ; Zhang, T ; Zhang, L ; Zhang, Y-G ; Zhang, X ; Zhu, L ; Alfaro, A ; Abrihan, P ; Barroso, A ; Cruz, E ; Gomez, MR ; Magboo, VP ; Medina, JM ; Obaldo, J ; Pastrana, D ; Pawhay, CM ; Quinon, A ; Tang, JM ; Tecson, B ; Uson, KJ ; Uy, M ; Kostkiewicz, M ; Kunikowska, J ; Bettencourt, N ; Cantinho, G ; Ferreira, A ; Syed, G ; Arnous, S ; Atyani, S ; Byrne, A ; Gleeson, T ; Kerins, D ; Meehan, C ; Murphy, D ; Murphy, M ; Murray, J ; O'Brien, J ; Bang, J-I ; Bom, H ; Cho, S-G ; Hong, CM ; Jang, SJ ; Jeong, YH ; Kang, WJ ; Kim, J-Y ; Lee, J ; Namgung, CK ; So, Y ; Won, KS ; Majstorov, V ; Vavlukis, M ; Salobir, BG ; Štalc, M ; Benedek, T ; Benedek, I ; Mititelu, R ; Stan, CA ; Ansheles, A ; Dariy, O ; Drozdova, O ; Gagarina, N ; Gulyaev, VM ; Itskovich, I ; Karalkin, A ; Kokov, A ; Migunova, E ; Pospelov, V ; Ryzhkova, D ; Saifullina, G ; Sazonova, S ; Sergienko, V ; Shurupova, I ; Trifonova, T ; Ussov, WY ; Vakhromeeva, M ; Valiullina, N ; Zavadovsky, K ; Zhuravlev, K ; Alasnag, M ; Okarvi, S ; Saranovic, DS ; Keng, F ; Jason See, JH ; Sekar, R ; Yew, MS ; Vondrak, A ; Bejai, S ; Bennie, G ; Bester, R ; Engelbrecht, G ; Evbuomwan, O ; Gongxeka, H ; Vuuren, MJ ; Kaplan, M ; Khushica, P ; Lakhi, H ; Louw, L ; Malan, N ; Milos, K ; Modiselle, M ; More, S ; Naidoo, M ; Scholtz, L ; Vangu, M ; Aguadé-Bruix, S ; Blanco, I ; Cabrera, A ; Camarero, A ; Casáns-Tormo, I ; Cuellar-Calabria, H ; Flotats, A ; Fuentes Cañamero, ME ; García, ME ; Jimenez-Heffernan, A ; Leta, R ; Diaz, JL ; Lumbreras, L ; Marquez-Cabeza, JJ ; Martin, F ; Martinez de Alegria, A ; Medina, F ; Canal, MP ; Peiro, V ; Pubul-Nuñez, V ; Rayo Madrid, JI ; Rey, CR ; Perez, RR ; Ruiz, J ; Hernández, GS ; Sevilla, A ; Zeidán, N ; Nanayakkara, D ; Udugama, C ; Simonsson, M ; Alkadhi, H ; Buechel, RR ; Burger, P ; Ceriani, L ; De Boeck, B ; Gräni, C ; Juillet de Saint Lager Lucas, A ; Kamani, CH ; Kawel-Boehm, N ; Manka, R ; Prior, JO ; Rominger, A ; Vallée, J-P ; Khiewvan, B ; Premprabha, T ; Thientunyakit, T ; Sellem, A ; Kir, KM ; Sayman, H ; Sebikali, MJ ; Muyinda, Z ; Kmetyuk, Y ; Korol, P ; Mykhalchenko, O ; Pliatsek, V ; Satyr, M ; Albalooshi, B ; Ahmed Hassan, MI ; Anderson, J ; Bedi, P ; Biggans, T ; Bularga, A ; Bull, R ; Burgul, R ; Carpenter, J-P ; Coles, D ; Cusack, D ; Deshpande, A ; Dougan, J ; Fairbairn, T ; Farrugia, A ; Gopalan, D ; Gummow, A ; Ramkumar, PG ; Hamilton, M ; Harbinson, M ; Hartley, T ; Hudson, B ; Joshi, N ; Kay, M ; Kelion, A ; Khokhar, A ; Kitt, J ; Lee, K ; Low, C ; Mak, SM ; Marousa, N ; Martin, J ; Mcalindon, E ; Menezes, L ; Morgan-Hughes, G ; Moss, A ; Murray, A ; Nicol, E ; Patel, D ; Peebles, C ; Pugliese, F ; Luis Rodrigues, JC ; Rofe, C ; Sabharwal, N ; Schofield, R ; Semple, T ; Sharma, N ; Strouhal, P ; Subedi, D ; Topping, W ; Tweed, K ; Weir-Mccall, J ; Abbara, S ; Abbasi, T ; Abbott, B ; Abohashem, S ; Abramson, S ; Al-Abboud, T ; Al-Mallah, M ; Almousalli, O ; Ananthasubramaniam, K ; Kumar, MA ; Askew, J ; Attanasio, L ; Balmer-Swain, M ; Bayer, RR ; Bernheim, A ; Bhatti, S ; Bieging, E ; Blankstein, R ; Bloom, S ; Blue, S ; Bluemke, D ; Borges, A ; Branch, K ; Bravo, P ; Brothers, J ; Budoff, M ; Bullock-Palmer, R ; Burandt, A ; Burke, FW ; Bush, K ; Candela, C ; Capasso, E ; Cavalcante, J ; Chang, D ; Chatterjee, S ; Chatzizisis, Y ; Cheezum, M ; Chen, T ; Chen, J ; Chen, M ; Choi, A ; Clarcq, J ; Cordero, A ; Crim, M ; Danciu, S ; Decter, B ; Dhruva, N ; Doherty, N ; Doukky, R ; Dunbar, A ; Duvall, W ; Edwards, R ; Esquitin, K ; Farah, H ; Fentanes, E ; Ferencik, M ; Fisher, D ; Fitzpatrick, D ; Foster, C ; Fuisz, T ; Gannon, M ; Gastner, L ; Gerson, M ; Ghoshhajra, B ; Goldberg, A ; Goldner, B ; Gonzalez, J ; Gore, R ; Gracia-López, S ; Hage, F ; Haider, A ; Haider, S ; Hamirani, Y ; Hassen, K ; Hatfield, M ; Hawkins, C ; Hawthorne, K ; Heath, N ; Hendel, R ; Hernandez, P ; Hill, G ; Horgan, S ; Huffman, J ; Hurwitz, L ; Iskandrian, A ; Janardhanan, R ; Jellis, C ; Jerome, S ; Kalra, D ; Kaviratne, S ; Kay, F ; Kelly, F ; Khalique, O ; Kinkhabwala, M ; Iii, GK ; Kircher, J ; Kirkbride, R ; Kontos, M ; Kottam, A ; Krepp, J ; Layer, J ; Lee, SH ; Leppo, J ; Lesser, J ; Leung, S ; Lewin, H ; Litmanovich, D ; Liu, Y ; Lopez-Mattei, J ; Magurany, K ; Markowitz, J ; Marn, A ; Matis, SE ; Mckenna, M ; Mcrae, T ; Mendoza, F ; Merhige, M ; Min, D ; Moffitt, C ; Moncher, K ; Moore, W ; Morayati, S ; Morris, M ; Mossa-Basha, M ; Mrsic, Z ; Murthy, V ; Nagpal, P ; Napier, K ; Nelson, K ; Nijjar, P ; Osman, M ; Parwani, P ; Passen, E ; Patel, A ; Patil, P ; Paul, R ; Phillips, L ; Polsani, V ; Poludasu, R ; Pomerantz, B ; Porter, T ; Prentice, R ; Pursnani, A ; Rabbat, M ; Ramamurti, S ; Rich, F ; Luna, HR ; Robinson, A ; Robles, K ; Rodríguez, C ; Rorie, M ; Rumberger, J ; Russell, R ; Sabra, P ; Sadler, D ; Schemmer, M ; Schoepf, UJ ; Shah, S ; Shah, N ; Shanbhag, S ; Sharma, G ; Shayani, S ; Shirani, J ; Shivaram, P ; Sigman, S ; Simon, M ; Slim, A ; Smith, D ; Smith, A ; Soman, P ; Sood, A ; Srichai-Parsia, MB ; Streeter, J ; T, A ; Tawakol, A ; Thomas, D ; Thompson, R ; Torbet, T ; Trinidad, D ; Ullery, S ; Unzek, S ; Uretsky, S ; Vallurupalli, S ; Verma, V ; Waller, A ; Wang, E ; Ward, P ; Weissman, G ; Wesbey, G ; White, K ; Winchester, D ; Wolinsky, D ; Yost, S ; Zgaljardic, M ; Alonso, O ; Beretta, M ; Ferrando, R ; Kapitan, M ; Mut, F ; Djuraev, O ; Rozikhodjaeva, G ; Le Ngoc, H ; Mai, SH ; Nguyen, XC (Elsevier BV, 2021-09)
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    MicroRNA governs bistable cell differentiation and lineage segregation via a noncanonical feedback
    Li, C-J ; Liau, ES ; Lee, Y-H ; Huang, Y-Z ; Liu, Z ; Willems, A ; Garside, V ; McGlinn, E ; Chen, J-A ; Hong, T (WILEY, 2021-04-01)
    Positive feedback driven by transcriptional regulation has long been considered a key mechanism underlying cell lineage segregation during embryogenesis. Using the developing spinal cord as a paradigm, we found that canonical, transcription-driven feedback cannot explain robust lineage segregation of motor neuron subtypes marked by two cardinal factors, Hoxa5 and Hoxc8. We propose a feedback mechanism involving elementary microRNA-mRNA reaction circuits that differ from known feedback loop-like structures. Strikingly, we show that a wide range of biologically plausible post-transcriptional regulatory parameters are sufficient to generate bistable switches, a hallmark of positive feedback. Through mathematical analysis, we explain intuitively the hidden source of this feedback. Using embryonic stem cell differentiation and mouse genetics, we corroborate that microRNA-mRNA circuits govern tissue boundaries and hysteresis upon motor neuron differentiation with respect to transient morphogen signals. Our findings reveal a previously underappreciated feedback mechanism that may have widespread functions in cell fate decisions and tissue patterning.
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    Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection.
    Gibson, JF ; Bojarczuk, A ; Evans, RJ ; Kamuyango, AA ; Hotham, R ; Lagendijk, AK ; Hogan, BM ; Ingham, PW ; Renshaw, SA ; Johnston, SA ; Lin, X (Public Library of Science (PLoS), 2022-04)
    Meningitis caused by infectious pathogens is associated with vessel damage and infarct formation, however the physiological cause is often unknown. Cryptococcus neoformans is a human fungal pathogen and causative agent of cryptococcal meningitis, where vascular events are observed in up to 30% of patients, predominantly in severe infection. Therefore, we aimed to investigate how infection may lead to vessel damage and associated pathogen dissemination using a zebrafish model that permitted noninvasive in vivo imaging. We find that cryptococcal cells become trapped within the vasculature (dependent on their size) and proliferate there resulting in vasodilation. Localised cryptococcal growth, originating from a small number of cryptococcal cells in the vasculature was associated with sites of dissemination and simultaneously with loss of blood vessel integrity. Using a cell-cell junction tension reporter we identified dissemination from intact blood vessels and where vessel rupture occurred. Finally, we manipulated blood vessel tension via cell junctions and found increased tension resulted in increased dissemination. Our data suggest that global vascular vasodilation occurs following infection, resulting in increased vessel tension which subsequently increases dissemination events, representing a positive feedback loop. Thus, we identify a mechanism for blood vessel damage during cryptococcal infection that may represent a cause of vascular damage and cortical infarction during cryptococcal meningitis.
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    Within subject rise in serum TNFα to IL-10 ratio is associated with poorer attention, decision-making and working memory in jockeys.
    Piantella, S ; O'Brien, WT ; Hale, MW ; Maruff, P ; McDonald, SJ ; Wright, BJ (Elsevier BV, 2022-05)
    Jockeys work in high-risk environments that rely heavily on attention- and decision-making to perform well and safely. Workplace stress literature has often overlooked the impact of stress on cognition, and designs that include physiological measures are rare. This study assessed the prospective concurrent relationships between workplace stress, depression symptoms and low-grade inflammation with cognitive performance among professional jockeys. Professional jockeys (N = 35, Mage = 32.29) provided information on workplace stress and depression symptoms, with serum levels of inflammatory cytokines (IL-6, IL-10, TNFα) and cytokine balance (IL-6: IL-10, TNFα: IL-10) quantified with SIMOA, and cognitive performance with CogSport computer-based testing battery. These measures were repeated after a twelve-month interval. Increased workplace stress between testing intervals was associated to an increased cytokine imbalance (β = 0.447, p = .015) after controlling for age and gender. Increases in cytokine imbalance occurred in unison with decreases in attention (β = 0.516, p = .002), decision-making (β = 0.452, p = .009) and working memory (β = 0.492, p = .004). These preliminary findings suggest the underlying mechanisms linking workplace stress and reduced cognitive performance may be influenced by measures of low-grade inflammation and specifically a cytokine imbalance. Our findings suggest a measure of cytokine balance may explain the heterogenous findings in previous studies that have focussed solely on the association of workplace stress with pro-inflammatory cytokines. Future work is needed however, to provide a broader evidence-base for our claims to better inform designs to intervene in the higher workplace stress-poorer cognition relationship.
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    Sustaining the Australian respiratory workforce through the COVID-19 pandemic: a scoping literature review.
    Stone, E ; Irving, LB ; Tonga, KO ; Thompson, B (Wiley, 2022-07)
    The outbreak of the COVID-19 pandemic in late 2019 and in 2020 presented challenges to healthcare workers (HCW) around the world that were unexpected and dramatic. The relentless progress of infection, starting in China and rapidly spreading to Europe, North America and elsewhere gave more remote countries, like Australia, time to prepare but also time for unease. HCW everywhere had to readjust and change their work practices to cope. Further waves of infection and transmission with newer variants pose challenges to HCW and health systems, even after mass vaccination. Respiratory medicine HCW found themselves at the frontline, developing critical care services to support intensive care units and grappling with unanticipated concerns about safety, risk and the need to retrain. Several studies have addressed the need for rapid changes in the healthcare workforce for COVID-19 and the impact of this preparation on HCW themselves. In this paper, we present a scoping review of the literature on preparing HCW for the pandemic, explore the Australian experience of building the respiratory workforce and propose evidence-based recommendations to sustain this workforce in an unprecedented high-risk environment.
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    Lymphangiogenesis: A new player in the heart's adaptive response to exercise.
    Dozic, S ; Janssens, JV ; Weeks, KL (Elsevier BV, 2022-07)