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604 results on '"M. O'Donovan"'

1. Genetic covariance components for measures of nitrogen utilization in grazing dairy cows

Author

E. Tavernier, I.C. Gormley, L. Delaby, M. O'Donovan, and D.P. Berry

Subjects
milk urea nitrogen, heritability, correlation, nitrogen balance, Dairy processing. Dairy products, SF250.5-275, Dairying, SF221-250
Abstract

ABSTRACT: Improved nitrogen utilization of dairy production systems should improve not only the economic output of the systems but also the environmental metrics. One strategy to improve efficiency is through breeding programs. Improving a trait through breeding is conditional on the presence of exploitable genetic variability. Using a database of 1,291 deeply phenotyped grazing dairy cows, the genetic variability for 2 definitions of nitrogen utilization was studied: nitrogen use efficiency (i.e., nitrogen output in milk and meat divided by nitrogen available) and nitrogen balance (i.e., nitrogen available less nitrogen output in milk and meat). Variance components for both variables were estimated using animal repeatability linear mixed models. Genetic variability was detected for both nitrogen utilization metrics, even though their heritability estimates were low (

Published
2024
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2. Cow-level factors associated with nitrogen utilization in grazing dairy cows using a cross-sectional analysis of a large database

Author

E. Tavernier, I.C. Gormley, L. Delaby, S. McParland, M. O'Donovan, and D.P. Berry

Subjects
nitrogen use efficiency, nitrogen balance, milk urea nitrogen, Dairy processing. Dairy products, SF250.5-275, Dairying, SF221-250
Abstract

ABSTRACT: Reducing nitrogen pollution while maintaining milk production is a major challenge of dairy production. One of the keys to delivering on this challenge is to improve the efficiency of how dairy cows use nitrogen. Thus, estimating the nitrogen utilization of lactating grazing dairy cows and exploring the association between animal factors and productivity with nitrogen utilization are the first steps to understanding the nitrogen utilization complex in dairy cows. Nitrogen utilization metrics were derived from milk and body weight records from 1,291 grazing dairy cows of multiple breeds and crossbreeds; all cows had sporadic information on nitrogen intake concurrent with information on nitrogen sinks (and other nitrogen sources, such as body tissue mobilization). Several nitrogen utilization metrics were investigated, including nitrogen use efficiency (nitrogen output as products such as milk and meat divided by nitrogen intake) and nitrogen excreted (nitrogen intake less the nitrogen output as products such as milk and meat). In the present study, a primiparous Holstein-Friesian used, on average, 20.6% of the nitrogen it ate, excreting the surplus as feces and urine, representing 402 g of nitrogen per day. Intercow variability existed, with a between-cow standard deviation of 0.0094 for nitrogen use efficiency and 24 g of nitrogen per day for nitrogen excretion. As lactation progressed, nitrogen use efficiency declined and nitrogen excretion increased. Nevertheless, nitrogen use efficiency improved (i.e., decreased) from first to second parity, even though it did not improve from second to third parity or greater. Furthermore, nitrogen excretion continued to increase from first to third parity or greater. Nitrogen use efficiency and nitrogen excretion were negatively correlated (−0.56 to −0.40), signifying that dairy cows who partition more of the ingested nitrogen into products such as milk and meat, on average, also excrete less nitrogen. Milk urea nitrogen was, at best, weakly correlated with nitrogen use efficiency and nitrogen excretion; the correlations were between −0.01 and 0.06. In conclusion, several cow-level factors such as parity, stage of lactation, and breed were associated with the range of different nitrogen efficiency metrics investigated; moreover, even after accounting for such effects, 4.8% to 6.3% of the remaining variation in the nitrogen use efficiency and nitrogen balance metrics were attributable to intercow differences.

Published
2023
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3. Utilising commercial farm grass growth data to evaluate long-term dry matter production of perennial ryegrass varieties

Author

C. Hearn, M. Egan, M.B. Lynch, T. Tubritt, M. O’Leary, A. Geoghegan, and M. O’Donovan

Subjects
ground score, pasturebase ireland, permanent pasture, persistency, Agriculture (General), S1-972, Nutrition. Foods and food supply, TX341-641
Abstract

Little data are currently available on either the dry matter (DM) production of perennial ryegrass (PRG) swards as they age beyond 5 yr (i.e. permanent pasture) or the performance of PRG varieties on commercial grassland farms. Previous work has generally assumed a connection between DM production and ground score (GS) and this link has been used as a proxy for variety persistence. The evolution of technology in the form of PastureBase Ireland has led to agronomic data of individual paddocks being made available for analysis over multiple years which has allowed the long-term assessment of varieties sown as monocultures on commercial farms. This technology allowed for the inclusion of eight PRG varieties sown in 649 paddocks across 101 farms in Ireland in the current analysis. The results show little association between GS and variety DM production as varieties age to 7 yr. Dry matter production of 1- to 4-yr-old swards appeared to provide a strong indication of variety DM production in years 5–7 post-sowing (r = 0.72, P < 0.05). The interaction of variety and sward age was not associated with DM production. Generally, varieties which produced the most DM in younger swards also produced the most DM in permanent pasture swards. Over longer-term periods these variety differences can manifest into large differences in DM produced and consumed on farm. The current analysis suggests that the long-term production benefits of utilising improved PRG varieties in pasture reseeding may be underestimated.

Published
2023
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4. Multi-omic cross-sectional cohort study of pre-malignant Barrett’s esophagus reveals early structural variation and retrotransposon activity

Author

A. C. Katz-Summercorn, S. Jammula, A. Frangou, I. Peneva, M. O’Donovan, M. Tripathi, S. Malhotra, M. di Pietro, S. Abbas, G. Devonshire, W. Januszewicz, A. Blasko, K. Nowicki-Osuch, S. MacRae, A. Northrop, A. M. Redmond, D. C. Wedge, and R. C. Fitzgerald

Subjects
Science
Abstract

The alterations associated with progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma are not fully characterised. Here, the authors perform a multi-omics analysis of a longitudinally-sampled BE patient cohort, identifying the impact of structural variants, including mobile elements, and the timing of molecular events during progression.

Published
2022
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5. Irish Grassland Research — main achievements and advancements in the past 60 yrs and where to progress to next

Author

M. O’Donovan, P. Dillon, P. Conaghan, and D. Hennessy

Subjects
animal production, grass breeding, grassland, grassland management, grazing, Agriculture (General), S1-972, Nutrition. Foods and food supply, TX341-641
Abstract

In the last 60 yr Irish grassland production has increased substantially in no small part due to high-quality fundamental grassland research. Increased production from grassland has arisen from improved understanding (research and practice) of soil and plant nutrition, plant physiology and variety improvement, while improved understanding of feed evaluation, ruminant nutrition, grazing management and silage technology has contributed to increased utilisation of grassland. Annual grass DM production varies from 12.7 to 15.0 t DM/ha based on Department of Agriculture, Food and the Marine grass variety trials. More recent data from PastureBase Ireland indicate that average annual grass production (2020) on efficient dairy and dry stock farms is 13.5 and 10.0 t DM/ha, respectively. Ireland is now one of the world leaders in grassland research, particularly in the area of grazing utilisation, the development and use of grassland databases, decision support systems and grass selection indices for grass varieties. Future pasture-based systems must extend beyond food production to deliver additional benefits to farmers, to consumers and the wider society. Future systems will require more robust grazing animals with healthier functional traits, more diverse swards supporting improved animal performance and require fewer fertiliser and chemical inputs, and will support more biodiversity and enhanced carbon storage.

Published
2022
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6. Towards sustainable European grassland farming with Inno4Grass: an infrastructure for innovation and knowledge sharing

Author

A. Krause, T. Becker, P.H. Feindt, C. Huyghe, A. Van den Pol-van Dasselaar, and M. O’Donovan

Subjects
collaboration, european innovation partnership (eip), inno4grass, innovation, knowledge sharing, knowledge transfer, Agriculture (General), S1-972, Nutrition. Foods and food supply, TX341-641
Abstract

European agriculture is facing tremendous challenges related to the rapid decrease in farm populations, competitiveness on open markets and the preservation of natural resources. Grasslands, which are highly significant for nature conservation often face land-use competition with arable cropping, urbanisation and other uses. Farmers need dedicated innovations to improve the economic performance of grasslands and their effective implementation in practice. This requires co-creation of knowledge between researchers and farmland practitioners, as was broadly pointed out by the European Commission. This paper describes a novel approach for creating a collaborative space for grassland innovations contributing to profitability of European grassland farms while preserving environmental benefits. Innovative modes of collaboration between practice and science are enabled by an international thematic network across eight European member states. A methodology that serves to collect farmers’ innovative ideas and to stimulate collaboration among various stakeholders (farmers’ groups, extension services, education and research) including cross-border collaborations, where grassland-related knowledge is made available for local conditions. This interactive innovation model fosters knowledge exchange and establishes a farmland-specific information management system. The aim is to stimulate a renewed, collaborative innovation culture for European Union (EU) grasslands. The methods are conceptualised and put into practice by the thematic network project Inno4Grass funded under Horizon 2020.

Published
2021
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8. Clinical Indicators of Symptom Dimensions and Cognitive Ability in Schizophrenia

Author

L. Farakish, S. Legge, M. Owen, M. O’Donovan, J. Walters, and A. Cardno

Subjects
Clinical indicators, Phenotype dimensions, Aetiology, schizophrénia, Psychiatry, RC435-571
Abstract

Introduction Schizophrenia is a heterogeneous disorder and it is unknown what causes individual variability in symptoms and cognitive ability. Objectives To examine the association between nine clinical predictors measurable at the onset of schizophrenia and five phenotype dimensions: positive, negative (diminished expressivity), negative (motivation and pleasure), disorganised symptoms and cognitive ability. Methods 852 participants (mean age 49 years old) with a diagnosis of schizophrenia or schizoaffective depression were included from the CardiffCOGS cross-sectional sample. Phenotype dimensions were created using confirmatory factor analysis and a 5-factor model. Associations were tested using linear regression, adjusting for age and sex. A Bonferroni correction was applied for (p

Published
2022
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9. Ruminant grassland production systems in Ireland

Author

M. O’Donovan, D. Hennessy, and P. Creighton

Subjects
grassland, grazing, ruminant production, sustainability, Agriculture (General), S1-972, Nutrition. Foods and food supply, TX341-641
Abstract

In Ireland grazing systems provide the basis of sustainable livestock production, as grazed grass is the cheapest feed source of nutrients for ruminants. The main future objective for these systems is to achieve high grass utilisation, ensure system sustainability and maintain extremely high animal health and welfare. There is no reason why all three cannot be combined. Ireland’s national farm policy targets growth in exports to €19 billion per annum by 2025. This figure represents an 85% increase from the current 3 yr average. There are major improvements required in the areas of grassland management and its conversion into milk and meat to fulfil such a target. While every farm situation is unique due to varying soil types, climatic conditions, stocking rates and management capabilities, herbage production and utilisation is below optimum on most farms. Irish farms, especially dairy farms, are expanding and will continue to do so over the next number of years. Increasing stocking rates and more compact calving and lambing has resulted in increased spring feed demand. Extra grass needs be grown and utilised in this period to minimise the use of supplementary feed. This paper outlines the importance of grassland on Irish farms, and where farms can improve grassland management, to increase output, lower farm costs and improve further farm system sustainability.

Published
2021
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10. Restricting dairy cow access time to pasture in autumn: The effects on milk production, grazing behaviour and DM intake of late lactation dairy cows

Author

B. Garry, E. Ganche, D. Hennessy, M. O'Donovan, J.P. Murphy, and E. Kennedy

Subjects
Dairy cows, Grazing, Grazing behavior, Pasture access, Wet weather, Animal culture, SF1-1100
Abstract

Extending the grazing season in pasture based systems of dairy production can increase farm profitability; poor weather and soil conditions can reduce the number of grazing days. The study objectives were to (i) examine the effect of restricted access to pasture in the autumn on the milk production, grazing behaviour and DM intake (DMI) of late lactation spring-calving dairy cows and (ii) establish the effect of alternating restricted and continuous access to pasture on dairy cow production, DMI and grazing behaviour. Cows were randomly assigned to one of four grazing treatments: (i) 22 h (full-time) access to pasture (22H; control); (ii) Two 5-h periods of access to pasture (2×5H); (iii) Two 3-h periods of access to pasture (2×3H); and (iv) alternating between full-time and 3-h access to pasture with no more than three continuous days on any one regime, e.g. Monday – full-time access, Tuesday − 2x3H access, Wednesday − 2x3H access; Thursday – full-time access, etc. (2×3HV). Restricted access to pasture was offered after a.m. and p.m. milking. Swards of similar quality and pregrazing herbage mass were offered. Treatment had no effect on milk yield (13.2 kg/day), milk fat (48.2 g/kg), protein (39.0 g/kg) or lactose content (42.6 g/kg) and milk solid yield (1.15 kg/day). Similarly, there was no effect of treatment on final BW (483 kg) or final BCS (2.66). There was no significant difference in DMI (15.1 kg DM/cow/day) between treatments. There was an effect on daily grazing time, 22H cows (565 min/cow/day) grazed for longest time, however, when the 2x3HV treatment had full-time access to pasture, they had a similar grazing time (543 min/cow/day) to the 22H cows and were similar to the 2x3H treatment on days with restricted access to pasture (357 min/cow/day). The 22H and 2x5H animals had similar grass DMI/min (29.2 g/min), the 2x3HV were higher (33.9 g/min) but were similar to the comparable treatment when offered 2x3H access time (41.6 g/min) and when offered 22H access time (27.7 g/min). The results from this study show how when offered a grass only diet of autumn pasture grazing behaviour can be modified by restricting pasture access time without reducing dairy cow production in late lactation at low production levels. There was also no effect of alternating access time between 22H and 2x3H on milk production and DMI in the 2x3HV treatment. Restricted access time to pasture in autumn may be a strategy which farmers can use to extend the grazing season.

Published
2021
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11. Comparison of sheep and dairy cows for in vivo digestibility of perennial ryegrass

Author

B. Garry, F.M. McGovern, E. Kennedy, R. Baumont, T.M. Boland, M.M. Wright, M. O'Donovan, and E. Lewis

Subjects
Feed intake, Grass, Herbage mass, Digestion, Ruminants, Animal culture, SF1-1100
Abstract

Sheep are often used as a proxy for dairy cows when measuring the digestibility of a feed. In recent years grassland management guidelines for ruminant animals have been re-evaluated in accordance with the progression in animal genetics and the acknowledgement that genetic potential has an influence on both feed intake and digestibility. Recommended pre-grazing herbage mass (HM) targets are now much lower with improved perennial ryegrass varieties available for grazing swards. The objective of this study was to compare the in vivo digestibility of perennial ryegrass in wether sheep and lactating dairy cows. The experimental design was selected to measure the effect of animal species (cows, sheep), sward HM measured cutting herbage at 4 cm above ground level (low: 1 700 kg DM/ha and high: 4 000 kg DM/ha) and season (Spring: Apr–May, Summer: Jul–Aug) on the digestibility of perennial ryegrass. Each HM treatment was offered to each animal within species and season for 12 d using a 2 HM × 2 period changeover Latin square design. There were eight cows and eight sheep, so there were four 2 × 2 Latin squares for each animal species (two) at each season (two), giving 64 observations. During each 12 d experimental period, the first 6 d were used for adaptation (adaptation phase) and the final 6 d were used for measurement (measurement phase). In vivo organic matter digestibility (OMD) in spring did not differ between animal species but in summer sheep had higher in vivo OMD than cows. The results described herein highlight the suitability of wether sheep as an alternative to dairy cows for determining the digestibility of perennial ryegrass in spring but not in summer. Stage of growth of the plant, which is intrinsically linked to season, should be considered as results show that digestibility in the ruminant was affected by season but not differentially affected by changing sward HM.

Published
2021
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12. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry

Author

Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. Kitazawa, H. Kitazumi, T. Kito, T. Kobayashi, T. Koeda, J. Kojima, H. Komatsu, I. Komatsu, Y. Koshibu, T. Kotani, T. Kozuka, Y. Kumai, T. Kumazaki, I. Maeda, K. Maeda, Y. Maruyama, S. Matsui, K. Matsushita, Y. Matsuura, K. Mineoi, H. Mitsuhashi, N. Miura, S. Miyaguchi, S. Miyajima, H. Miyamoto, A. Miyashita, S. Miyata, I. Mizuguchi, A. Mizuno, T. Mori, O. Moriai, K. Morishita, O. Murai, Sho Nagai, Shunichi Nagai, E. Nagata, H. Nagata, A. Nakagomi, S. Nakahara, M. Nakamura, R. Nakamura, N. Nakanishi, T. Nakayama, R. Nakazato, T. Nanke, J. Nariyama, Y. Niijima, H. Niinuma, Y. Nishida, Y. Nishihata, K. Nishino, H. Nishioka, K. Nishizawa, I. Niwa, K. Nomura, S. Nomura, M. Nozoe, T. Ogawa, N. Ohara, M. Okada, K. Okamoto, H. Okita, M. Okuyama, H. Ono, T. Ono, Y. Onuki Pearce, S. Oriso, A. Ota, E. Otaki, Y. Saito, H. Sakai, N. Sakamoto, Y. Sakamoto, Y. Samejima, Y. Sasagawa, H. Sasaguri, A. Sasaki, T. Sasaki, Kazuki Sato, Kiyoharu Sato, M. Sawano, S. Seki, Y. Sekine, Y. Seta, K. Sezaki, N. Shibata, Y. Shiina, H. Shimono, Y. Shimoyama, T. Shindo, H. Shinohara, R. Shinohe, T. Shinozuka, T. Shirai, T. Shiraiwa, Y. Shozawa, T. Suga, C. Sugimoto, Kazuo Suzuki, Keita Suzuki, Shu Suzuki, Shunji Suzuki, Susumu Suzuki, Y. Suzuki, M. Tada, A. Taguchi, T. Takagi, Y. Takagi, K. Takahashi, S. Takahashi, H. Takai, C. Takanaka, S. Take, H. Takeda, K. Takei, K. Takenaka, T. Tana, G. Tanabe, K. Taya, H. Teragawa, S. Tohyo, S. Toru, Y. Tsuchiya, T. Tsuji, K. Tsuzaki, H. Uchiyama, O. Ueda, Y. Ueyama, N. Wakaki, T. Wakiyama, T. Washizuka, M. Watanabe, T. Yamada, T. Yamagishi, H. Yamaguchi, Kenichi Yamamoto, Kentaro Yamamoto, Kunihiko Yamamoto, T. Yamamoto, M. Yamaura, M. Yamazoe, K. Yasui, Y. Yokoyama, K. Yoshida, T.W. Lim, C.K. Ching, C.G. Foo, J.H. Chow, D.D. Chen, F.R. Jaufeerally, Y.M. Lee, G. Lim, W.T. Lim, S. Thng, S.Y. Yap, C. Yeo, S. Oh, H.N. Pak, J.-B. Kim, J.H. Kim, S.-W. Jang, D.H. Kim, D.R. Ryu, S.W. Park, D.-K. Kim, D.J. Choi, Y.S. Oh, M.-C. Cho, S.-H. Kim, H.-K. Jeon, D.-G. 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Vorster, A. Waldman, L. Wallis, E. Wilford, K. Wong, S.J. Connolly, A. Spyropoulos, J. Eikelboom, R. Luton, M. Gupta, A.S. Pandey, S. Cheung, R. Leader, P. Beaudry, F. Ayala-Paredes, J. Berlingieri, J. Heath, G. Poirier, M. Du Preez, R. Nadeau, G. Dresser, R. Dhillon, T. Hruczkowski, B. Schweitzer, B. Coutu, P. Angaran, P. MacDonald, S. Vizel, S. Fikry, R. Parkash, A. Lavoie, J. Cha, B. Ramjattan, J. Bonet, K. Ahmad, L. Aro, T. Aves, K. Beaudry, C. Bergeron, J. Bigcanoe, N. Bignell, L. Breakwell, E. Burke, L. Carroll, B. Clarke, T. Cleveland, S. Daheb, P. Dehghani, I. Denis, Z. Djaidani, P. Dorian, S. Douglass, J. Dunnigan, A. Ewert, D. Farquhar, A. Fearon, L. Ferleyko, D. Fournier, B. Fox, M.-C. Grenier, W. Gulliver, K. Haveman, C. Hines, K. Hines, A.M. Jackson, C. Jean, G. Jethoo, R. Kahlon, S. Kelly, R. Kim, V. Korley, J. Kornder, L. Kwan, J. Largy, C. Lewis, S. Lewis, I. Mangat, R. Moor, J. Navratil, I. Neas, J. Otis, R. Otis, M. Pandey, F. Petrie, A. Pinter, M. Raines, P. Roberts, M. Robinson, G. Sas, S. Schulman, L. Snell, S. Spearson, J. Stevenson, T. Trahey, S. Wong, D. Wright, H. Ragy, A. Abd El-Aziz, S.K. Abou Seif, M.G. El Din, S. El Etriby, A. Elbahry, A. El-Etreby, M. Elkhadem, A. Katta, T. Khairy, A. Mowafy, M. Nawar, A. Ohanissian, A. Reda, M. Reda, H. Salem, N. Sami, S. Samir, M. Setiha, M. Sobhy, A. Soliman, N. Taha, M. Tawfik, E. Zaatout, D. Kettles, J. Bayat, H. Siebert, A. Horak, Y. Kelfkens, R. Garda, T. Pillay, M. Guerra, L. van Zyl, H. Theron, A. Murray, R. Louw, D. Greyling, P. Mntla, V. Ueckermann, R. Loghdey, S. Ismail, F. Ahmed, J. Engelbrecht, A. Ramdass, S. Maharajh, W. Oosthuysen, G. Angel, C. Bester, M. Booysen, C. Boshoff, C. Cannon, S. Cassimjee, C. Chami, G. Conway, A. Davids, L. de Meyer, G. Du Plessis, T. Ellis, L. Henley, M. Karsten, E. Loyd, J. Marks, L. Mavhusa, M. Mostert, A. Page, L. Rikhotso, M. Salie, J. Sasto, F. Shaik, A. Skein, L. Smith, G. Tarr, T. Tau, F. van Zyl, W. Al Mahmeed, G. Yousef, A. Agrawal, M. Nathani, M. Ibrahim, E.M. Esheiba, R. Singh, A. Naguib, M. Abu-Mahfouz, M. Al Omairi, A. Al Naeemi, R. Maruthanayagam, N. Bazargani, A. Wassef, R. Gupta, M. Khan, B. Subbaraman, A. Abdul, A. Al Mulla, S. El Bardisy, P. Haridas, S. Jadhav, K. Magdaluyo, M. Makdad, I. Maqsood, R. Mohamed, N. Sharma, R. Sharma, M. Thanzeel, S.Z. Goldhaber, R. Canosa, P. Rama, E. Blumberg, J. Garcia, P. Mullen, V. Wilson, A. Quick, K. Ferrick, W.M. Kutayli, M. Cox, M. Franco, S. Falkowski, R. Mendelson, M. Williams, S. Miller, S. Beach, A. Alfieri, T. Gutowski, I. Haque, R. Reddy, W. Ahmed, P. Delafontaine, D. Diercks, D. Theodoro, K. Remmel, M. Alberts, R. Ison, H. Noveck, P. Duffy, S. Pitta, D. Nishijima, C. Treasure, N. Asafu-Adjaye, K. Ball, M. Bartlett, M. Bentley, S. Bowers, A. Brown, A. Browne, J. Cameron-Watts, M. Canova, D. Cassidy, K. Cervellione, S. Congal, J. DePauw, A. Dickerson, M. Eley, L. Evans, S. Felpel, K. Ferdinand, D. Fielder, P. Gentry, A. Haideri, F. Hakimi, T. Harbour, E. Hartranft, B. Hawkins, M. Headlee, L. Henson, C. Herrick, T. Hicks, S. Jasinski, A. Jones, L. Jones, P. Jones, S. Karl, M. Keeling, J. Kerr, P. Knowles, J. Langdon, M. Lay, J.A. Lee, T. Lincoln, E. Malone, A. Merliss, D. Merritt, J. Minardo, B. Mooso, C. Orosco, V. Palumbo, M. Parker, T. Parrott, S. Paserchia, G. Pearl, J. Peterson, N. Pickelsimer, T. Purcell, J. Raynor, S. Raziano, C. Richard, T. Richardson, C. Robertson, A. Sage, T. Sanghera, P. Shaw, J. Shoemaker, K. Smith, B. Stephanie, A. Thatcher, H. Theobald, N. Thompson, L. Treasure, T. Tripti, C. Verdi, and V. Worthy

Subjects
Surgery, RD1-811, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Published
2018
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13. An examination of two concentrate allocation strategies which are based on the early lactation milk yield of autumn calving Holstein Friesian cows

Author

D. Lawrence, M. O’Donovan, T.M. Boland, E. Lewis, and E. Kennedy

Subjects
feeding method, indoor feeding, mixed ration, concentrate, winter milk, Animal culture, SF1-1100
Abstract

The objective of this experiment was to compare the effects of two concentrate feeding strategies offered with a grass silage and maize silage diet on the dry matter (DM) intake, milk production (MP) and estimated energy balance of autumn calved dairy cows. Over a 2-year period, 180 autumn calving Holstein Friesian cows were examined. Within year, cows were blocked into three MP sub-groups (n=9) (high (HMP), medium (MMP) and low (LMP)) based on the average MP data from weeks 3 and 4 of lactation. Within a block cows were randomly assigned to one of two treatments (n=54), flat rate (FR) concentrate feeding or feed to yield (FY) based on MP sub-group. Cows on the FR treatment were offered a fixed rate of concentrate (5.5 kg DM/cow per day) irrespective of MP sub-group. In the FY treatment HMP, MMP and LMP cows were allocated 7.3, 5.5 and 3.7 kg DM of concentrate, respectively. The mean concentrate offered to the FR and FY treatments was the same. On the FR treatment there was no significant difference in total dry matter intake (TDMI, 17.3 kg) between MP sub-groups. In the FY treatment, however, the TDMI of HMP-FY was 2.2 kg greater than MMP-FY, and 4.5 kg greater than LMP-FY (15.2 kg DM). The milk yield of LMP-FR was 3.5 kg less than the mean of the HMP-FR and MMP-FR treatments (24.5 kg). The milk yield of the HMP-FY treatment was 3.6 and 7.9 kg greater than the MMP-FY and LMP-FY treatments, respectively. The difference in MP between the HMP sub-groups was 2.6 kg, which translates to a response of 1.4 kg of milk per additional 1 kg of concentrate offered. There was no significant difference in MP between the two LMP sub-groups; however, MP increased 0.8 kg per additional 1 kg of concentrate offered between cows on the LMP-FR and LMP-FY treatments. The estimated energy balance was positive for cows on the LMP-FR treatment, but negative for cows on the other treatments. The experiment highlights the variation within a herd in MP response to concentrate, as cows with a lower MP potential are less responsive to additional energy input than cows with a greater MP potential. Cows with a greater MP capacity did not substitute additional concentrate for the basal forage, which indicates an additional demand for energy based on ability of individual cows to produce milk.

Published
2016
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14. Using post-grazing sward height to impose dietary restrictions of varying duration in early lactation: its effects on spring-calving dairy cow production

Author

M. Crosse, M. O’Donovan, T.M. Boland, L. Delaby, E. Ganche, and E. Kennedy

Subjects
dairy cow, post-grazing sward height, feeding regime, early lactation, carryover effect, Animal culture, SF1-1100
Abstract

The objective of this study was to investigate the immediate and carryover effects of imposing two post-grazing sward heights (PGSH) for varying duration during early lactation on sward characteristics and dairy cow production. The experiment was a randomised block design with a 2×2 factorial arrangement of treatments. A total of 80 spring-calving (mean calving date – 6 February) dairy cows were randomly assigned, pre-calving, to one of the two (n=40) PGSH treatments – S (2.7 cm) and M (3.5 cm) – from 13 February to 18 March, 2012 (P1). For the subsequent 5-week period (P2: 19 March to 22 April, 2012), half the animals from each P1 treatment remained on their treatment, whereas the other half of the animals switched to the opposing treatment. Following P2, all cows were managed similarly for the remainder of the lactation (P3: 23 April to 4 November, 2012) to measure the carryover effect. Milk production, BW and body condition score were measured weekly, and grass dry matter intake (GDMI) was measured on four occasions – approximately weeks 5, 10, 15 and 20 of lactation. Sward utilisation (above 2.7 cm; P1 and P2) was significantly improved by reducing the PGSH from 3.5 (0.83) to 2.7 cm (0.96). There was no effect of PGSH on cumulative annual grass dry matter (DM) production (15.3 t DM/ha). Grazing to 2.7 cm reduced GDMI by 1.7 and 0.8 kg DM/cow in P1 and P2, respectively, when compared with 3.5 cm (13.3 and 14.0 kg/cow per day, respectively). Cows grazing to 2.7 cm for both P1 and P2 (SS) tended to have reduced cumulative 10-week milk yield (−105 kg) and milk solids yield (−9 kg) when compared with cows grazing to 3.5 cm for both periods (MM; 1608 and 128 kg/cow, respectively). Treatments that alternated PGSH at the end of P1, SM and MS had intermediate results. There was no interaction between P1 and P2 treatments. There was also no carryover effect of early lactation grazing regime on milk and milk solids production in P3, given the reduction in early lactation milk yield. The results indicate that the diet of dairy cows should not be restricted by imposing a severe PGSH for all of the first 10 weeks of lactation, cows should graze to 3.5 cm for at least 5 of these weeks.

Published
2015
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15. Effect of pre-grazing herbage mass on dairy cow performance, grass dry matter production and output from perennial ryegrass (Lolium perenne L.) pastures

Author

C.M. Wims, L. Delaby, T.M. Boland, and M. O’Donovan

Subjects
grazing management, dairy cow, pasture intake, milk yield, perennial ryegrass, Animal culture, SF1-1100
Abstract

A grazing study was undertaken to examine the effect of maintaining three levels of pre-grazing herbage mass (HM) on dairy cow performance, grass dry matter (DM) production and output from perennial ryegrass (Lolium perenne L.) pastures. Cows were randomly assigned to one of three pre-grazing HM treatments: 1150 – Low HM (L), 1400 – Medium HM (M) or 2000 kg DM/ha – High HM (H). Herbage accumulation under grazing was lowest (P

Published
2014
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16. Adaptation and evaluation of the GrazeIn model of grass dry matter intake and milk yield prediction for grazing dairy cows

Author

B.F. O’Neill, E. Ruelle, M. O’Donovan, L. Shalloo, F.J. Mulligan, T.M. Boland, L. Delaby, R. Delagarde, and E. Lewis

Subjects
dairy cow, grass dry matter intake, milk yield, model, adaptation, Animal culture, SF1-1100
Abstract

The prediction of grass dry matter intake (GDMI) and milk yield (MY) are important to aid sward and grazing management decision making. Previous evaluations of the GrazeIn model identified weaknesses in the prediction of GDMI and MY for grazing dairy cows. To increase the accuracy of GDMI and MY prediction, GrazeIn was adapted, and then re-evaluated, using a data set of 3960 individual cow measurements. The adaptation process was completed in four additive steps with different components of the model reparameterised or altered. These components were: (1) intake capacity (IC) that was increased by 5% to reduce a general GDMI underprediction. This resulted in a correction of the GDMI mean and a lower relative prediction error (RPE) for the total data set, and at all stages of lactation, compared with the original model; (2) body fat reserve (BFR) deposition from 84 days in milk to next calving that was included in the model. This partitioned some energy to BFR deposition after body condition score nadir had been reached. This reduced total energy available for milk production, reducing the overprediction of MY and reducing RPE for MY in mid and late lactation, compared with the previous step. There was no effect on predicted GDMI; (3) The potential milk curve was reparameterised by optimising the rate of decrease in the theoretical hormone related to secretory cell differentiation and the basal rate of secretory cell death to achieve the lowest possible mean prediction error (MPE) for MY. This resulted in a reduction in the RPE for MY and an increase in the RPE for GDMI in all stages of lactation compared with the previous step; and (4) finally, IC was optimised, for GDMI, to achieve the lowest possible MPE. This resulted in an IC correction coefficient of 1.11. This increased the RPE for MY but decreased the RPE for GDMI compared with the previous step. Compared with the original model, modifying this combination of four model components improved the prediction accuracy of MY, particularly in late lactation with a decrease in RPE from 27.8% in the original model to 22.1% in the adapted model. However, testing of the adapted model using an independent data set would be beneficial and necessary to make definitive conclusions on improved predictions.

Published
2014
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17. Effect of perennial ryegrass (Lolium perenne L.) cultivars on the milk yield of grazing dairy cows

Author

C.M. Wims, M. McEvoy, L. Delaby, T.M. Boland, and M. O'Donovan

Subjects
perennial ryegrass, cultivar, sward structure, dairy cow, grazing, Animal culture, SF1-1100
Abstract

The objective of this experiment was to investigate the effect of four perennial ryegrass cultivars: Bealey, Astonenergy, Spelga and AberMagic on the milk yield and milk composition of grazing dairy cows. Two 4 × 4 latin square experiments were completed, one during the reproductive and the other during the vegetative growth phase of the cultivars. Thirty-two Holstein–Friesian dairy cows were divided into four groups, with each group assigned 17 days on each cultivar during both experiments. Within each observation period, milk yield and milk composition, sward morphology and pasture chemical composition were measured. During the reproductive growth phase, organic matter digestibility (OMD) was greater for Bealey and Astonenergy (P < 0.001; +1.6%). AberMagic contained a higher stem proportion (P < 0.01; +0.06) and a longer sheath height (P < 0.001; +1.9 cm). Consequently, cows grazing AberMagic recorded a lower milk yield (P < 0.001; −1.5 kg/day) and a lower milk solids yield (P < 0.001; −0.13 kg/day). During the vegetative growth phase, OMD was greater (P < 0.001; +1.1%) for Bealey, whereas the differences between the cultivars in terms of sward structure were smaller and did not appear to influence animal performance. As a result, cows grazing Bealey recorded a higher milk yield (P < 0.001; +0.9 kg/day) and a higher milk solids yield (P < 0.01; +0.08 kg/day). It was concluded that grass cultivar did influence milk yield due to variations in sward structure and chemical composition.

Published
2013
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18. Predicting grass dry matter intake, milk yield and milk fat and protein yield of spring calving grazing dairy cows during the grazing season

Author

B.F. O'Neill, E. Lewis, M. O'Donovan, L. Shalloo, N. Galvin, F.J. Mulligan, T.M. Boland, and R. Delagarde

Subjects
dairy cow, multiple regression equation, grass dry matter intake, milk yield, milk solids yield, Animal culture, SF1-1100
Abstract

Predicting the grass dry matter intake (GDMI), milk yield (MY) or milk fat and protein yield (milk solids yield (MSY)) of the grazing dairy herd is difficult. Decisions with regard to grazing management are based on guesstimates of the GDMI of the herd, yet GDMI is a critical factor influencing MY and MSY. A data set containing animal, sward, grazing management and concentrate supplementation variables recorded during weeks of GDMI measurement was used to develop multiple regression equations to predict GDMI, MY and MSY. The data set contained data from 245 grazing herds from 10 published studies conducted at Teagasc, Moorepark. A forward stepwise multiple regression technique was used to develop the multiple regression equations for each of the dependent variables (GDMI, MY, MSY) for three periods during the grazing season: spring (SP; 5 March to 30 April), summer (SU; 1 May to 31 July) and autumn (AU; 1 August to 31 October). The equations generated highlighted the importance of different variables associated with GDMI, MY and MSY during the grazing season. Peak MY was associated with an increase in GDMI, MY and MSY during the grazing season with the exception of GDMI in SU when BW accounted for more of the variation. A higher body condition score (BCS) at calving was associated with a lower GDMI in SP and SU and a lower MY and MSY in all periods. A higher BCS was associated with a higher GDMI in SP and SU, a higher MY in SU and AU and a higher MSY in all periods. The pre-grazing herbage mass of the sward (PGHM) above 4 cm was associated with a quadratic effect on GDMI in SP, on MY in SP and SU and on MSY in SU. An increase in daily herbage allowance (DHA) above 4 cm was associated with an increase in GDMI in AU, an increase in MY in SU and AU and MSY in AU. Supplementing grazing dairy cows with concentrate reduced GDMI and increased MY and MSY in all periods. The equations generated can be used by the Irish dairy industry during the grazing season to predict the GDMI, MY and MSY of grazing dairy herds.

Published
2013
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19. Direct and carryover effect of post-grazing sward height on total lactation dairy cow performance

Author

E. Ganche, L. Delaby, M. O'Donovan, T.M. Boland, and E. Kennedy

Subjects
post-grazing height, dairy cow, early lactation, carryover, Animal culture, SF1-1100
Abstract

Grazing pastures to low post-grazing sward heights (PGSH) is a strategy to maximise the quantity of grazed grass in the diet of dairy cows within temperate grass-based systems. Within Irish spring-calving systems, it was hypothesised that grazing swards to very low PGSH would increase herbage availability during early lactation but would reduce dairy cow performance, the effect of which would persist in subsequent lactation performance when compared with cows grazing to a higher PGSH. Seventy-two Holstein–Friesian dairy cows (mean calving date, 12 February) were randomly assigned post-calving across two PGSH treatments (n = 36): 2.7 cm (severe; S1) and 3.5 cm (moderate; M1), which were applied from 10 February to 18 April (period 1; P1). This was followed by a carryover period (period 2; P2) during which cows were randomly reassigned within their P1 treatment across two further PGSH (n = 18): 3.5 cm (severe, SS and MS) and 4.5 cm (moderate, SM and MM) until 30 October. Decreasing PGSH from 3.5 to 2.7 cm significantly decreased milk (−2.3 kg/cow per day), protein (−95 g/day), fat (−143 g/day) and lactose (−109 g/day) yields, milk protein (−1.2 g/kg) and fat (−2.2 g/kg) concentrations and grass dry matter intake (GDMI; −1.7 kg dry matter/cow per day). The severe PGSH was associated with a lower bodyweight (BW) at the end of P1. There was no carryover effect of P1 PGSH on subsequent milk or milk solids yields in P2, but PGSH had a significant carryover effect on milk fat and lactose concentrations. Animals severely restricted at pasture in early spring had a higher BW and slightly higher body condition score in later lactation when compared with M1 animals. During P2, increasing PGSH from 3.5 to 4.5 cm increased milk and milk solids yield as a result of greater GDMI and resulted in higher mean BW and end BW. This study indicates that following a 10-week period of feed restriction, subsequent dairy cow cumulative milk production is unaffected. However, the substantial loss in milk solid yield that occurred during the period of restriction is not recovered.

Published
2013
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20. Restricting dairy cow access time to pasture in early lactation: the effects on milk production, grazing behaviour and dry matter intake

Author

E. Kennedy, J. Curran, B. Mayes, M. McEvoy, J.P. Murphy, and M. O'Donovan

Subjects
restricted access, pasture, grazing behaviour, milk production, silage supplementation, Animal culture, SF1-1100
Abstract

One of the main aims of pasture-based systems of dairy production is to increase the proportion of grazed grass in the diet. This is most easily achieved by increasing the number of grazing days. However, periods of inclement weather conditions can reduce the number of days at pasture. The two objectives of this experiment were: (i) to investigate the effect of restricting pasture access time on animal production, grazing behaviour and dry matter intake (DMI) of spring calving dairy cows in early lactation; and (ii) to establish whether silage supplementation is required when cows return indoors after short grazing periods. In all, 52 Holstein–Friesian spring calving dairy cows were assigned to a four-treatment study from 25 February to 26 March 2008. The four treatments were: full-time access to pasture (22H; control); 4.5-h- pasture access after both milkings (2 × 4.5H); 3-h pasture access after both milkings (2 × 3H); 3-h pasture access after both milkings with silage supplementation by night (2 × 3SH). All treatments were offered 14.4 kg DM/cow per day herbage from swards, with a mean pre-grazing yield of 1739 kg DM/ha above 4 cm, – and were supplemented with 3 kg DM/cow per day of concentrate. The 2 × 3SH treatment was offered an additional 4 kg DM/cow of grass silage by night. Restricting pasture access time (2 × 3H, 2 × 3SH and 2 × 4.5H) had no effect on milk (28.3 kg/cow per day) and solids-corrected milk (27.2 kg/cow per day) yield when compared with the treatment grazing full time. Supplementing animals with grass silage did not increase milk production when compared with all other treatments. Milk protein concentration tended to be lower (P = 0.08; 32.2 g/kg) for the 2 × 3SH animals when compared with the 22H animals (33.7 g/kg). The grass DMI of the 2 × 3SH treatment was significantly lower (−2.3 kg DM/cow per day) than all other treatments (11.9 kg DM/cow per day), yet the total DMI of these animals was highest (16.6 kg DM/cow per day). The 22H cows grazed for 481 min/cow per day, which is significantly longer than all other treatments. The 2 × 3H animals grazed for 98% of the time, whereas the 2 × 3SH grazed for 79% of their time at pasture. Restricting pasture access time did not affect end body weight or body condition score. The results of this study indicate that restricting pasture access time of dairy cows in early lactation does not affect milk production performance. Furthermore, supplementing cows with grass silage does not increase milk production but reduces grazing efficiency.

Published
2011
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21. Les modèles de prévision de l’ingestion journalière d’herbe et de la production laitière des vaches au pâturage

Author

R. DELAGARDE and M. O’DONOVAN

Subjects
Animal culture, SF1-1100, Aquaculture. Fisheries. Angling, SH1-691
Abstract

La diversité des pratiques de gestion des prairies et de complémentation des vaches laitières au pâturage rend très difficile l’estimation de l’ingestion d’herbe par les animaux en fermes. Cet article a pour objectif principal de faire le point sur les modèles simples ou complexes de prévision de l’ingestion des vaches laitières au pâturage. Les modèles les plus complets prennent en compte à la fois les caractéristiques du troupeau, de la prairie pâturée, des conditions de pâturage et des compléments alimentaires apportés au troupeau. Les modèles récents, intégrés dans des outils d’aide à la gestion du pâturage (Pâtur’IN, Sepatou, Grazemore) ou dans des outils d’aide à l’alimentation des vaches au pâturage (GrazFeed, Diet-Check, INRAtion prochainement), sont ici décrits dans leurs principes. Des simulations réalisées à partir des modèles ou des logiciels disponibles permettent également de décrire et de comparer les principales lois de réponse de l’ingestion des vaches aux variations des conditions de pâturage et de complémentation. La précision des différents modèles existants est estimée par une approche statistique globale en comparant l’ingestion observée expérimentalement et celle prévue indépendamment par les modèles à l’échelle troupeau-parcelle (n = 304). L’erreur moyenne de prévision varie de 10 à 25 % selon les modèles, soit de 1,5 à 3,8 kg MS d’herbe ingérée par vache et par jour. Les écarts de précision entre modèles proviennent essentiellement de la façon dont les conditions de pâturage sont prises en compte, notamment pour les situations extrêmes de chargement. Par ailleurs, très peu de modèles permettent de prévoir les performances animales (lait produit, variation de poids) à partir de l’ingestion d’herbe.

Published
2005
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22. Altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder

Author

Jake Valeri, Sinead M. O’Donovan, Wei Wang, David Sinclair, Ratna Bollavarapu, Barbara Gisabella, Donna Platt, Craig Stockmeier, and Harry Pantazopoulos

Subjects
substance use disorder, somatostatin, hippocampus, sleep, circadian, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Substance use disorders are a debilitating group of psychiatric disorders with a high degree of comorbidity with major depressive disorder. Sleep and circadian rhythm disturbances are commonly reported in people with substance use disorder and major depression and associated with increased risk of relapse. Hippocampal somatostatin signaling is involved in encoding and consolidation of contextual memories which contribute to relapse in substance use disorder. Somatostatin and clock genes also have been implicated in depression, suggesting that these molecules may represent key converging pathways involved in contextual memory processing in substance use and major depression. We used hippocampal tissue from a cohort of subjects with substance use disorder (n = 20), subjects with major depression (n = 20), subjects with comorbid substance use disorder and major depression (n = 24) and psychiatrically normal control subjects (n = 20) to test the hypothesis that expression of genes involved in somatostatin signaling and clock genes is altered in subjects with substance use disorder. We identified decreased expression of somatostatin in subjects with substance use disorder and in subjects with major depression. We also observed increased somatostatin receptor 2 expression in subjects with substance use disorder with alcohol in the blood at death and decreased expression in subjects with major depression. Expression of the clock genes Arntl, Nr1d1, Per2 and Cry2 was increased in subjects with substance use disorder. Arntl and Nr1d1 expression in comparison was decreased in subjects with major depression. We observed decreased expression of Gsk3β in subjects with substance use disorder. Subjects with comorbid substance use disorder and major depression displayed minimal changes across all outcome measures. Furthermore, we observed a significant increase in history of sleep disturbances in subjects with substance use disorder. Our findings represent the first evidence for altered somatostatin and clock gene expression in the hippocampus of subjects with substance use disorder and subjects with major depression. Altered expression of these molecules may impact memory consolidation and contribute to relapse risk.

Published
2022
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23. Microorganisms present in artisanal fermented food from South America

Author

Maria Eugenia Jimenez, Ciara M. O’Donovan, Miguel Fernandez de Ullivarri, and Paul D. Cotter

Subjects
fermented food and beverages, South American food, lactic acid bacteria, fungus, microbial diversity, artisanal food, Microbiology, QR1-502
Abstract

Artisanal fermented products (foods and beverages) are produced in an artisanal way in many countries around the world. The main purpose of fermentation is to preserve the food, improve its safety, increase the nutritional and health-promoting value and add specific flavours. In South America, there is a great variety of fermented food produced in an artisanal way. Different raw materials are used such as potatoes, sweet potato, cassava, maize, rice, milk (cow, ewe, goat) and meat (beef, goat, lamb, llama and guanaco). Some of these fermented foods are typical of the region and are part of the culture of native communities, e.g. tocosh, masa agria, puba flour, charqui, chicha, champu and cauim among others (indigenous foods). However, other fermented foods produced in South America introduced by mainly European immigration, such as cheeses and dry sausages, and they are also produced in many different parts of the world. In this work, the microbial composition of the different artisanal fermented products produced in South America is reviewed, taking into consideration the associated raw materials, fermentation conditions and methodologies used for their production.

Published
2022
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24. A bioinformatic inquiry of the EAAT2 interactome in postmortem and neuropsychiatric datasets

Author

Sophie Asah, Sinead M. O’Donovan, Robert E. McCullumsmith, and Khaled Alganem

Subjects
Frontal cortex, Computational biology, Biology, Gyrus Cinguli, Interactome, Article, Biological pathway, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Glutamate reuptake, Amyotrophic lateral sclerosis, Biological Psychiatry, Anterior cingulate cortex, Amyotrophic Lateral Sclerosis, Computational Biology, medicine.disease, 030227 psychiatry, Dorsolateral prefrontal cortex, Psychiatry and Mental health, medicine.anatomical_structure, Excitatory Amino Acid Transporter 2, Schizophrenia, 030217 neurology & neurosurgery
Abstract

Altered expression and localization of the glutamate transporter EAAT2 is found in schizophrenia and other neuropsychiatric (major depression, MDD) and neurological disorders (amyotrophic lateral sclerosis, ALS). However, the EAAT2 interactome, the network of proteins that physically or functionally interact with EAAT2 to support its activity, has yet to be characterized in severe mental illness. We compiled a list of "core" EAAT2 interacting proteins. Using Kaleidoscope, an R-shiny application, we data mined publically available postmortem transcriptome datasets to determine whether components of the EAAT2 interactome are differentially expressed in schizophrenia and, using Reactome, identify which interactome-associated biological pathways are altered. Overall, these "look up" studies highlight region-specific, primarily frontal cortex (dorsolateral prefrontal cortex and anterior cingulate cortex), changes in the EAAT2 interactome and implicate altered metabolism pathways in schizophrenia. Pathway analyses also suggest that perturbation of components of the EAAT2 interactome in animal models of antipsychotic administration impact metabolism. Similar changes in metabolism pathways are seen in ALS, in addition to altered expression of many components of the EAAT2 interactome. However, although EAAT2 expression is altered in a postmortem MDD dataset, few other components of the EAAT2 interactome are changed. Thus, "look up" studies suggest region- and disease-relevant biological pathways related to the EAAT2 interactome that implicate glutamate reuptake perturbations in schizophrenia, while providing a useful tool to exploit "omics" datasets.

Published
2022

25. Modelling the effects of stocking rate, soil type, agroclimate location and nitrogen input on the grass DM yield and forage self-sufficiency of Irish grass-based dairy production systems

Author

E. Ruelle, L. Delaby, L. Shalloo, M. O'Donovan, D. Hennessy, M. Egan, B. Horan, and P. Dillon

Subjects
Genetics, Animal Science and Zoology, Agronomy and Crop Science
Abstract

In pasture-based dairy production systems, identifying the appropriate stocking rate (SR; cows/ha) based on the farm grass growth is a key strategic decision for driving the overall farm business. This paper investigates a number of scenarios examining the effects of SR (2–3 cows/ha (0.25 unit changes)), annual nitrogen (N) fertilizer application rates (0–300 kg N/ha (50 kg/ha unit changes)), soil type (heavy and a free-draining soil) and agroclimate location ((south and northeast of Ireland) across 16 years) on pasture growth and forage self-sufficiency using the pasture-based herd dynamic milk model merged with the Moorepark St Gilles grass growth model. The modelled outputs were grass growth, grass dry matter intake, silage harvested and offered, overall farm forage self-sufficiency and N surplus. The model outputs calculated that annual grass yield increased from 9436 kg DM/ha/year when 0 kg N/ha/year was applied to 14 996 kg DM/ha/year when 300 kg N/ha/year were applied, with an average N response of 18.4 kg DM/kg N applied (range of 9.9–27.7 kg DM/kg N applied). Systems stocked at 2.5 cows/ha and applying 250–300 kg N fertilizer/ha/year were self-sufficient for forage. As N input was reduced from 250 kg N/ha/year, farm forage self-sufficiency declined, as did farm N surplus. The results showed that a reduction in N fertilizer application of 50 kg/ha/year will require a reduction in an SR of 0.18 cows/ha to maintain self-sufficiency (R2 = 0.90).

Published
2022

26. Modulation of the gut microbiome with nisin

Author

Catherine O’Reilly, Ghjuvan M. Grimaud, Mairéad Coakley, Paula M. O’Connor, Harsh Mathur, Veronica L. Peterson, Ciara M. O’Donovan, Peadar G. Lawlor, Paul D. Cotter, Catherine Stanton, Mary C. Rea, Colin Hill, and R. Paul Ross

Subjects
Multidisciplinary
Abstract

Nisin is a broad spectrum bacteriocin used extensively as a food preservative that was identified in Lactococcus lactis nearly a century ago. We show that orally-ingested nisin survives transit through the porcine gastrointestinal tract intact (as evidenced by activity and molecular weight determination) where it impacts both the composition and functioning of the microbiota. Specifically, nisin treatment caused a reversible decrease in Gram positive bacteria, resulting in a reshaping of the Firmicutes and a corresponding relative increase in Gram negative Proteobacteria. These changes were mirrored by the modification in relative abundance of pathways involved in acetate, butyrate (decreased) and propionate (increased) synthesis which correlated with overall reductions in short chain fatty acid levels in stool. These reversible changes that occur as a result of nisin ingestion demonstrate the potential of bacteriocins like nisin to shape mammalian microbiomes and impact on the functionality of the community.

Published
2023

27. Assessing the effects of antipsychotic medications on schizophrenia functional analysis: a postmortem proteome study

Author

Rawan S. Alnafisah, James Reigle, Mahmoud Ali Eladawi, Sinead M. O’Donovan, Adam J. Funk, Jaroslaw Meller, Robert E. Mccullumsmith, and Rammohan Shukla

Subjects
Proteomics, Pharmacology, Psychiatry and Mental health, Proteome, Dopamine, Schizophrenia, Brain, Humans, Prefrontal Cortex, Antipsychotic Agents
Abstract

Antipsychotic drugs (APDs) are effective in treating positive symptoms of schizophrenia (SCZ). However, they have a substantial impact on postmortem studies. As most cohorts lack samples from drug-naive patients, many studies, rather than understanding SCZ pathophysiology, are analyzing the drug effects. We hypothesized that comparing SCZ-altered and APD-influenced signatures derived from the same cohort can provide better insight into SCZ pathophysiology. For this, we performed LCMS-based proteomics on dorsolateral prefrontal cortex (DLPFC) samples from control and SCZ subjects and used statistical approaches to identify SCZ-altered and APD-influenced proteomes, validated experimentally using independent cohorts and published datasets. Functional analysis of both proteomes was contrasted at the biological-pathway, cell-type, subcellular-synaptic, and drug-target levels. In silico validation revealed that the SCZ-altered proteome was conserved across several studies from the DLPFC and other brain areas. At the pathway level, SCZ influenced changes in homeostasis, signal-transduction, cytoskeleton, and dendrites, whereas APD influenced changes in synaptic-signaling, neurotransmitter-regulation, and immune-system processes. At the cell-type level, the SCZ-altered and APD-influenced proteomes were associated with two distinct striatum-projecting layer-5 pyramidal neurons regulating dopaminergic-secretion. At the subcellular synaptic level, compensatory pre- and postsynaptic events were observed. At the drug-target level, dopaminergic processes influenced the SCZ-altered upregulated-proteome, whereas nondopaminergic and a diverse array of non-neuromodulatory mechanisms influenced the downregulated-proteome. Previous findings were not independent of the APD effect and thus require re-evaluation. We identified a hyperdopaminergic cortex and drugs targeting the cognitive SCZ-symptoms and discussed their influence on SCZ pathology in the context of the cortico-striatal pathway.

Published
2022

28. Schizophrenia: a disorder of broken brain bioenergetics

Author

Nicholas D. Henkel, Xiajoun Wu, Sinead M. O’Donovan, Emily A. Devine, Jessica M. Jiron, Laura M. Rowland, Zoltan Sarnyai, Amy J. Ramsey, Zhexing Wen, Margaret K. Hahn, and Robert E. McCullumsmith

Subjects
Cellular and Molecular Neuroscience, Psychiatry and Mental health, Molecular Biology
Published
2022

30. Alpha-synuclein alters the faecal viromes of rats in a gut-initiated model of Parkinson’s disease

Author

Orla O'Sullivan, Lorraine A. Draper, Sarah M. O’Donovan, Wiley Barton, Aideen M. Sullivan, Laura A. Volpicelli-Daley, Colin Hill, Stephen R. Stockdale, and Catherine A. O'Neill

Subjects
Male, medicine.medical_specialty, Parkinson's disease, QH301-705.5, animal diseases, Medicine (miscellaneous), Disease, Neurological disorder, Biology, General Biochemistry, Genetics and Molecular Biology, Article, Rats, Sprague-Dawley, chemistry.chemical_compound, Feces, Internal medicine, medicine, Animals, Human virome, Bacteriophages, Microbiome, Biology (General), skin and connective tissue diseases, Alpha-synuclein, Lewy body, Virome, Neurodegeneration, Parkinson Disease, medicine.disease, Vagus nerve, Computational biology and bioinformatics, Rats, nervous system diseases, Endocrinology, chemistry, nervous system, Immunology, alpha-Synuclein, Enteric nervous system, sense organs, General Agricultural and Biological Sciences
Abstract

Parkinson’s disease (PD) is a chronic neurological disorder associated with the misfolding of alpha-synuclein (α-syn) into aggregates within nerve cells that contribute to their neurodegeneration. Recent evidence suggests α-syn aggregation may begin in the gut and travel to the brain along the vagus nerve, with microbes potentially a trigger initiating α-syn misfolding. However, the effects α-syn alterations on the gut virome have not been investigated. In this study, we show longitudinal faecal virome changes in rats administered either monomeric or preformed fibrils (PFF) of α-syn directly into their enteric nervous system. Differential changes in rat viromes were observed when comparing monomeric and PFF α-syn, with alterations compounded by the addition of LPS. Changes in rat faecal viromes were observed after one month and did not resolve within the study’s five-month observational period. These results suggest that virome alterations may be reactive to host α-syn changes that are associated with PD development., Stockdale et al. assess longitudinal faecal virome changes in a rat model of Parkinson’s Disease (PD) in which either monomeric or preformed fibrils (PFF) of α-synuclein were administered directly into their enteric nervous system. They demonstrate that virome alterations are potentially reactive to host α-synuclein changes that are associated with PD development.

Published
2021

31. Agronomic performance of ten perennial ryegrass varieties on commercial grassland farms

Author

C. Hearn, M. Egan, D.P. Berry, A. Geoghegan, M. O'Leary, M.B. Lynch, and M. O'Donovan

Subjects
Genetics, Animal Science and Zoology, Agronomy and Crop Science
Abstract

Little information is available on the phenotypic performance of perennial ryegrass varieties when exposed to grazing conditions on commercial grassland farms. Grass varieties are classically evaluated in mechanically defoliated plot systems which, although designed to mimic grazing conditions, do not fully capture the range of stresses or interactions that a sward is subjected to under commercial settings or over any period longer than 4 years. The evolution of technology in the form of PastureBase Ireland has led to agronomic data of individual paddocks being made available for analysis over multiple years. Data used in the current study consisted of dry matter (DM) production and ground score data across a 7-year period from ten perennial ryegrass varieties grown as monocultures in 559 paddocks on 98 commercial farms. The results demonstrated how perennial ryegrass variety is associated with a range of agronomic performance traits on commercial farms; including total and seasonal DM production, grazing DM production and number of grazing events. Varieties with the highest total DM production also had the highest spring and mid-season DM production; autumn DM production was associated with the interaction between variety and year. The highest producing variety in the study, AberGain, produced 1342 kg DM/ha/year more than the mean of all other varieties. Variety differences manifested themselves as swards aged, with some varieties increasing in total DM production while others reduced in total DM production. The current work provides a basis for the consideration of on-farm variety assessment in the composition of future variety evaluation protocols.

Published
2021

32. Altered purinergic receptor expression in the frontal cortex in schizophrenia

Author

Rawan Alnafisah, Anna Lundh, Sophie M. Asah, Julie Hoeflinger, Alyssa Wolfinger, Abdul-rizaq Hamoud, Robert E. McCullumsmith, and Sinead M. O’Donovan

Abstract

ATP functions as a neurotransmitter, acting on the ubiquitously expressed family of purinergic P2 receptors. In schizophrenia (SCZ), the pathways that modulate extracellular ATP and its catabolism to adenosine are dysregulated. However, the effects of altered ATP availability on P2 receptor expression in the brain in SCZ have not been assessed. We assayed P2 receptor mRNA and protein expression in the DLPFC and ACC in subjects diagnosed with SCZ and matched, non-psychiatrically ill controls (n = 20–22/group). P2RX7, P2RX4 and male P2RX5 mRNA expression were significantly increased (p p

Published
2022

33. 280 PERCEIVED NEED FOR A CLINICAL ETHICS SUPPORT SERVICE AT AN IRISH UNIVERSITY HOSPITAL

Author

M O'Donovan, P Crowley, E Flanagan, C McManus, E Moloney, C Favier, M McKiernan, N Cornally, L Campbell, K O’Connor, and R O’Caoimh

Subjects
Aging, General Medicine, Geriatrics and Gerontology
Abstract

Background Ethics are the set of moral principles that guide a person’s behaviour. Ethical issues are a key component of healthcare and frequently arise in the management of hospitalized older patients. To improve decision-making and reduce burden on individual hospital staff, Clinical Ethics Support Services (CESS) have been widely-integrated into care pathways internationally. However, the need for CESS has received little attention in Irish hospitals. Methods A cross-sectional analysis of the ethical situation and CESS readiness at a tertiary hospital in Ireland was collected from July-October 2021 and in February 2022 via hard copies and online collection (SurveyMonkey). Both clinical (medicine, nursing other patient care role) and non-clinical (administrative, clerical, ICT, HR, general support staff and management) staff participated. Descriptive statistics were assessed taking the valid percentages, mean 5-item Likert scores and Friedman Test mean rank for ten ranked statements. Results In total, 199 people (13% response rate) completed the survey. Staff were largely (76%) clinical and the majority were qualified >10 years (57%). In all, 78% reported that ethical issues arise in the role (83% clinical staff, 59% non-clinical staff). Most (63%) were unsure who to contact about ethical concerns, instead seeking informal advice from colleagues (>90%). The majority of participants were interested in additional ethical training, especially on decision-making capacity (mean interest 4.18 out of 5), strategies for working with challenging patient/family situations (4.07 out of 5) and end-of-life care (4.06 out of 5). Out of ten options assessed, participants preferenced the development of a formal clinical ethics committee over education and training or the provision of educational materials. Conclusion Ethical issues commonly arise when caring for older hospitalized patients. This study found a perceived need and widespread interest in additional education as well as formal approaches to develop a hospital-based CESS, centred around a formal committee structure.

Published
2022

34. Gene Enrichment Analysis of Astrocyte Subtypes in Psychiatric Disorders and Psychotropic Medication Datasets

Author

Xiaolu Zhang, Alyssa Wolfinger, Xiaojun Wu, Rawan Alnafisah, Ali Imami, Abdul-rizaq Hamoud, Anna Lundh, Vladimir Parpura, Robert E. McCullumsmith, Rammohan Shukla, and Sinead M. O’Donovan

Subjects
Psychotropic Drugs, Astrocytes, Mental Disorders, Humans, General Medicine, astrocyte subtype, psychotropic medication, schizophrenia, major depression, kinase, Antidepressive Agents, Antipsychotic Agents
Abstract

Astrocytes have many important functions in the brain, but their roles in psychiatric disorders and their responses to psychotropic medications are still being elucidated. Here, we used gene enrichment analysis to assess the relationships between different astrocyte subtypes, psychiatric diseases, and psychotropic medications (antipsychotics, antidepressants and mood stabilizers). We also carried out qPCR analyses and “look-up” studies to assess the chronic effects of these drugs on astrocyte marker gene expression. Our bioinformatic analysis identified gene enrichment of different astrocyte subtypes in psychiatric disorders. The highest level of enrichment was found in schizophrenia, supporting a role for astrocytes in this disorder. We also found differential enrichment of astrocyte subtypes associated with specific biological processes, highlighting the complex responses of astrocytes under pathological conditions. Enrichment of protein phosphorylation in astrocytes and disease was confirmed by biochemical analysis. Analysis of LINCS chemical perturbagen gene signatures also found that kinase inhibitors were highly discordant with astrocyte-SCZ associated gene signatures. However, we found that common gene enrichment of different psychotropic medications and astrocyte subtypes was limited. These results were confirmed by “look-up” studies and qPCR analysis, which also reported little effect of psychotropic medications on common astrocyte marker gene expression, suggesting that astrocytes are not a primary target of these medications. Conversely, antipsychotic medication does affect astrocyte gene marker expression in postmortem schizophrenia brain tissue, supporting specific astrocyte responses in different pathological conditions. Overall, this study provides a unique view of astrocyte subtypes and the effect of medications on astrocytes in disease, which will contribute to our understanding of their role in psychiatric disorders and offers insights into targeting astrocytes therapeutically.

Published
2022

36. More than a gut feeling: What is the role of the gastrointestinal tract in female athlete health?

Author

Katherine M. Lydon, Jamie N. Pugh, Ciara M. O’Donovan, Sharon M. Madigan, and Orla O'Sullivan

Subjects
Male, Future studies, Gastrointestinal Diseases, media_common.quotation_subject, Physiology, 030209 endocrinology & metabolism, Physical Therapy, Sports Therapy and Rehabilitation, Bone health, RC1200, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Orthopedics and Sports Medicine, Microbiome, Exercise, media_common, Gastrointestinal tract, biology, business.industry, Athletes, 030229 sport sciences, General Medicine, biology.organism_classification, During menstruation, Gastrointestinal Microbiome, Structure and function, Gastrointestinal Tract, Feeling, Female, business
Abstract

As with much of science, the female athlete is under researched, particularly in the area of gastrointestinal (GI) physiology. Gut function is of pivotal importance to athletes in that it supports digestion and absorption of nutrients, as well as providing a barrier between the external environment and the circulation. While sex-derived differences in GI structure and function have been well characterised at rest, there remains a paucity of data examining this during exercise. The wider impact of the GI system has begun to be realised and it is now widely acknowledged to play a role in more systemic bodily systems. In the current review, we discuss localised issues including the GI structure, function, and microbiome of male and females. We also discuss GI-related symptoms experienced by athletes, highlight the differences in incidence between males and females, and discuss contributing factors. We then move beyond the gut to discuss wider biological processes that have been shown to have both sex-related differences and that are impacted by the GI system. Some of these areas include immune function and risk of illness, sleep, hormones, bone health and the gut-brain-axis. The magnitude of such effects and relationships is currently unknown but there is enough mechanistic data for future studies to consider a more central role that the gastrointestinal tract may play in overall female athlete health. HighlightsThere are both clear similarities and differences in male-female gastrointestinal structure and function.Females typically reported a greater prevalence of gastrointestinal symptoms at rest, in particular during menstruation, but not during exercise.The links between female microbiome, oestrogen, and systemic physiological and biological processes are yet to be fully elucidated.Many of the male-female differences seen (e.g. in immune function) may be, at least in part, influenced by such GI related differences.

Published
2021

37. Activation of acid‐sensing ion channels by carbon dioxide regulates amygdala synaptic protein degradation in memory reconsolidation

Author

Boren Lin, Ye Chun Ruan, Tyler C. Ortyl, Sinead M. O’Donovan, Olivia A. Miller, Farzaneh Sadat Naghavi, Zhen Jin, Jianyang Du, Khaled Alganem, and Robert E. McCullumsmith

Subjects
Male, Proteasome Endopeptidase Complex, AMPA receptor, Protein degradation, Aversive conditioning, Amygdala, Models, Biological, Cellular and Molecular Neuroscience, Ubiquitin, Administration, Inhalation, medicine, Animals, Receptors, AMPA, AMPA receptors, RC346-429, Molecular Biology, Acid-sensing ion channel, Ion channel, Memory Consolidation, biology, Proteasome, Chemistry, Research, Ubiquitination, Excitatory Postsynaptic Potentials, Reconsolidation, Cell biology, Acid Sensing Ion Channels, Mice, Inbred C57BL, medicine.anatomical_structure, Carbon dioxide, Memory retrieval, Proteolysis, Synapses, biology.protein, Memory consolidation, Female, Acid‐sensing ion channels, Neurology. Diseases of the nervous system, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Ion Channel Gating
Abstract

Reconsolidation has been considered a process in which a consolidated memory is turned into a labile stage. Within the reconsolidation window, the labile memory can be either erased or strengthened. Manipulating acid-sensing ion channels (ASICs) in the amygdala via carbon dioxide (CO2) inhalation enhances memory retrieval and its lability within the reconsolidation window. Moreover, pairing CO2 inhalation with retrieval bears the reactivation of the memory trace and enhances the synaptic exchange of the calcium-impermeable AMPA receptors to calcium-permeable AMPA receptors. Our patch-clamp data suggest that the exchange of the AMPA receptors depends on the ubiquitin-proteasome system (UPS), via protein degradation. Ziram (50 µM), a ubiquitination inhibitor, reduces the turnover of the AMPA receptors. CO2 inhalation with retrieval boosts the ubiquitination without altering the proteasome activity. Several calcium-dependent kinases potentially involved in the CO2-inhalation regulated memory liability were identified using the Kinome assay. These results suggest that the UPS plays a key role in regulating the turnover of AMPA receptors during CO2 inhalation.

Published
2021

38. Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach

Author

Hunter M. Eby, Rawan Alnafisah, James Reigle, Alexander William Thorman, Behrouz Shamsaei, Nicholas D. Henkel, Xiaolu Zhang, Xiaojun Wu, Sophie Asah, Justin F. Creeden, Jarek Meller, Ali S Imami, R. Travis Taylor, Sinead M. O’Donovan, and Robert E. McCullumsmith

Subjects
0301 basic medicine, Drug, Coronavirus disease 2019 (COVID-19), Databases, Factual, media_common.quotation_subject, Science, Computational biology, Disease, Virtual drug screening, Antiviral Agents, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Medicine, Humans, Pandemics, media_common, Multidisciplinary, business.industry, Drug discovery, SARS-CoV-2, MEK inhibitor, Drug Repositioning, COVID-19, Computational Biology, COVID-19 Drug Treatment, 030104 developmental biology, Pharmaceutical Preparations, 030220 oncology & carcinogenesis, Selumetinib, Identification (biology), business
Abstract

The COVID-19 pandemic caused by the novel SARS-CoV-2 is more contagious than other coronaviruses and has higher rates of mortality than influenza. Identification of effective therapeutics is a crucial tool to treat those infected with SARS-CoV-2 and limit the spread of this novel disease globally. We deployed a bioinformatics workflow to identify candidate drugs for the treatment of COVID-19. Using an “omics” repository, the Library of Integrated Network-Based Cellular Signatures (LINCS), we simultaneously probed transcriptomic signatures of putative COVID-19 drugs and publicly available SARS-CoV-2 infected cell lines to identify novel therapeutics. We identified a shortlist of 20 candidate drugs: 8 are already under trial for the treatment of COVID-19, the remaining 12 have antiviral properties and 6 have antiviral efficacy against coronaviruses specifically, in vitro. All candidate drugs are either FDA approved or are under investigation. Our candidate drug findings are discordant with (i.e., reverse) SARS-CoV-2 transcriptome signatures generated in vitro, and a subset are also identified in transcriptome signatures generated from COVID-19 patient samples, like the MEK inhibitor selumetinib. Overall, our findings provide additional support for drugs that are already being explored as therapeutic agents for the treatment of COVID-19 and identify promising novel targets that are worthy of further investigation.

Published
2021

39. Role of Astrocytes in Major Neuropsychiatric Disorders

Author

Rawan Alnafisah, Zhexing Wen, Sinead M. O’Donovan, Robert E. McCullumsmith, Abdul-Rizaq Hamoud, Rammohan Shukla, and Xiaolu Zhang

Subjects
0301 basic medicine, medicine.medical_specialty, Postmortem studies, Neurology, business.industry, Central nervous system, General Medicine, medicine.disease, Biochemistry, 03 medical and health sciences, Cellular and Molecular Neuroscience, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Schizophrenia, mental disorders, medicine, Major depressive disorder, Neurochemistry, Bipolar disorder, business, Neuroscience, 030217 neurology & neurosurgery, Astrocyte
Abstract

Astrocytes are the primary homeostatic cells of the central nervous system, essential for normal neuronal development and function, metabolism and response to injury and inflammation. Here, we review postmortem studies examining changes in astrocytes in subjects diagnosed with the neuropsychiatric disorders schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BPD). We discuss the astrocyte-related changes described in the brain in these disorders and the potential effects of psychotropic medication on these findings. Finally, we describe emerging tools that can be used to study the role of astrocytes in neuropsychiatric illness.

Published
2021

40. Endoscopic tumour morphology impacts survival in adenocarcinoma of the oesophagus

Author

Simon L. Parsons, Monika Tripathi, Vijayendran Sujendran, E. Fidziukiewicz, Jim Davies, Ula Mahadeva, Annalise Katz-Summercorn, Neil A. Shepherd, A. Northrop, Simon Tavaré, James A. Gossage, Richard Berrisford, S Lishman, Michael F. Scott, Shaun R. Preston, W. Fickling, Andrew Hindmarsh, Jesper Lagergren, Juliane Perner, Peter Safranek, Hugh Barr, Grant Sanders, Francesca D. Ciccarelli, Xiaodun Li, D. Khoo, Paw Edwards, Helen G. Coleman, Timothy J. Underwood, Christopher J. Peters, D. Loureda, Ayesha Noorani, Laszlo Igali, Maria Secrier, Bhaskar Kumar, Ahmad Miremadi, Irshad Soomro, Wais Habib, Andrew Davies, George B. Hanna, Izhar Bagwan, Matthew D. Eldridge, Andy G. Lynch, S Suortamo, Rehan Haidry, Fuju Chang, Ginny Devonshire, John H. Saunders, Nick Carroll, Michael P. Lewis, Sonia Puig, Stephen J. Hayes, Charles Crichton, Olga Tucker, Sharmila Sothi, Christopher C.W. Hughes, Andrew D Beggs, R. de la Rue, J Zylstra, J. R. O'Neill, Vicki Save, Yeng Ang, Robert C. Walker, E Cheong, Krishna Moorthy, Laurence Lovat, Vicky Goh, Richard J E Skipworth, Richard C. Turkington, S Oakes, Gianmarco Contino, Sriganesh Jammula, R Bott, M O'Donovan, O Old, B Grace, Ricardo McEwen, C Harden, Barbara Nutzinger, Philippe Taniere, Rebecca C. Fitzgerald, Ben E. Byrne, Shalini Malhotra, Nicola Grehan, Damian T. McManus, Anna M. Grabowska, Andrew D. Sharrocks, Sujath Abbas, William R. C. Knight, Shona MacRae, Philip Kaye, and Ted R. Hupp

Subjects
medicine.medical_specialty, Esophageal Neoplasms, medicine.medical_treatment, Constriction, Pathologic, Kaplan-Meier Estimate, Adenocarcinoma, 030230 surgery, 03 medical and health sciences, Polyps, 0302 clinical medicine, medicine, Humans, Neoplasm Invasiveness, Endoscopy, Digestive System, Pathological, Ulcer, Neoadjuvant therapy, Survival analysis, Neoplasm Staging, Proportional Hazards Models, business.industry, Proportional hazards model, Hazard ratio, Margins of Excision, Cancer, General Medicine, Prognosis, medicine.disease, Neoadjuvant Therapy, Confidence interval, Tumor Burden, Esophagectomy, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Multivariate Analysis, Surgery, Esophagogastric Junction, Lymph Nodes, Radiology, Neoplasm Grading, business
Abstract

Prognostication in oesophageal cancer on the basis of preoperative variables is challenging. Many of the accepted predictors of survival are only derived after surgical treatment and may be influenced by neoadjuvant therapy. This study aims to explore the relationship between pre-treatment endoscopic tumour morphology and postoperative survival.Patients with endoscopic descriptions of tumours were identified from the prospectively managed databases including the OCCAMS database. Tumours were classified as exophytic, ulcerating or stenosing. Kaplan Meier survival analysis and multivariable Cox regression analyses were performed to determine hazard ratios (HR) with 95% confidence intervals.262 patients with oesophageal adenocarcinoma undergoing potentially curative resection were pooled from St Thomas' Hospital (161) and the OCCAMS database (101). There were 70 ulcerating, 114 exophytic and 78 stenosing oesophageal adenocarcinomas. Initial tumour staging was similar across all groups (T3/4 tumours 71.4%, 70.2%, 74.4%). Median survival was 55 months, 51 months and 36 months respectively (p 0.001). Rates of lymphovascular invasion (P = 0.0176), pathological nodal status (P = 0.0195) and pathological T stage (P = 0.0007) increased from ulcerating to exophytic to stenosing lesions. Resection margin positivity was 21.4% in ulcerating tumours compared to 54% in stenosing tumours (p 0.001). When compared to stenosing lesions, exophytic and ulcerating lesions demonstrated a significant survival advantage on multivariable analysis (HR 0.56 95% CI 0.31-0.93, HR 0.42 95% CI 0.21-0.82).This study demonstrates that endoscopic morphology may be an important pre-treatment prognostic factor in oesophageal cancer. Ulcerating, exophytic and stenosing tumours may represent different pathological processes and tumour biology.

Published
2020

41. Corticostriatal dysfunction and social interaction deficits in mice lacking the cystine/glutamate antiporter

Author

Pauline Janssen, Laurence Ris, Ann Massie, Charles K. Meshul, Olaya Lara, Lutgarde Arckens, Emmanuel Hermans, Robert E. McCullumsmith, Lise Verbruggen, Madeline J Churchill, Hideyo Sato, Noemi Declerck, Adam J. Funk, Cynthia Moore, Sinead M. O’Donovan, Eduard Bentea, Laura De Pauw, Agnès Villers, Erica A K DePasquale, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Pharmaceutical and Pharmacological Sciences, Faculty of Medicine and Pharmacy, Supporting clinical sciences, and Neuro-Aging & Viro-Immunotherapy

Subjects
Proteomics, 0301 basic medicine, Biochemistry & Molecular Biology, Dendritic spine, Autism Spectrum Disorder, XCT, TIME-DEPENDENT CHANGES, Social Interaction, Glutamic Acid, PREFRONTAL CORTEX, Striatum, BEHAVIORS, Neurotransmission, Medium spiny neuron, Antiporters, Article, Mice, GLUTAMATE, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Postsynaptic potential, Animals, OXIDATIVE STRESS, AUTISM, SYSTEM X(C)(-), Molecular Biology, Psychiatry, Science & Technology, IDENTIFICATION, Chemistry, Neurosciences, Glutamate receptor, MOUSE MODEL, Cell biology, Psychiatry and Mental health, Electrophysiology, 030104 developmental biology, Excitatory postsynaptic potential, Cystine, Neurosciences & Neurology, Life Sciences & Biomedicine, 030217 neurology & neurosurgery
Abstract

The astrocytic cystine/glutamate antiporter system xc− represents an important source of extracellular glutamate in the central nervous system, with potential impact on excitatory neurotransmission. Yet, its function and importance in brain physiology remain incompletely understood. Employing slice electrophysiology and mice with a genetic deletion of the specific subunit of system xc−, xCT (xCT−/− mice), we uncovered decreased neurotransmission at corticostriatal synapses. This effect was partly mitigated by replenishing extracellular glutamate levels, indicating a defect linked with decreased extracellular glutamate availability. We observed no changes in the morphology of striatal medium spiny neurons, the density of dendritic spines, or the density or ultrastructure of corticostriatal synapses, indicating that the observed functional defects are not due to morphological or structural abnormalities. By combining electron microscopy with glutamate immunogold labeling, we identified decreased intracellular glutamate density in presynaptic terminals, presynaptic mitochondria, and in dendritic spines of xCT−/− mice. A proteomic and kinomic screen of the striatum of xCT−/− mice revealed decreased expression of presynaptic proteins and abnormal kinase network signaling, that may contribute to the observed changes in postsynaptic responses. Finally, these corticostriatal deregulations resulted in a behavioral phenotype suggestive of autism spectrum disorder in the xCT−/− mice; in tests sensitive to corticostriatal functioning we recorded increased repetitive digging behavior and decreased sociability. To conclude, our findings show that system xc− plays a previously unrecognized role in regulating corticostriatal neurotransmission and influences social preference and repetitive behavior.

Published
2020

42. Role of TFF3 as an adjunct in the diagnosis of Barrett's esophagus using a minimally invasive esophageal sampling device—The Cytosponge TM

Author

Rebecca C. Fitzgerald, Marcel Gehrung, M O'Donovan, and Anna L. Paterson

Subjects
medicine.medical_specialty, Histology, Population, 030209 endocrinology & metabolism, Article, Pathology and Forensic Medicine, Barrett Esophagus, 03 medical and health sciences, Esophagus, 0302 clinical medicine, medicine, Carcinoma, Humans, Sampling (medicine), Endoscopy, Digestive System, Risk factor, education, Metaplasia, education.field_of_study, medicine.diagnostic_test, business.industry, Intestinal metaplasia, General Medicine, medicine.disease, Immunohistochemistry, Endoscopy, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Barrett's esophagus, Goblet Cells, Radiology, business
Abstract

The incidence of esophageal carcinoma continues to increase whilst its prognosis remains poor. The most dramatic reduction in mortality is likely to follow early diagnosis of the preinvasive precursor lesion, Barrett’s esophagus (BE), coupled with treatment of dysplastic lesions. The major risk factor for BE is gastro-esophageal reflux disease, however this is highly prevalent and only a small proportion of individuals have BE, therefore an endoscopy-based screening strategy to detect BE is unfeasible. Minimally invasive esophageal sampling devices offer an alternative, cost-effective strategy which can be deployed within an at-risk population in a primary care setting to identify individuals with probable BE who can then be referred for endoscopic confirmation. The device that has currently progressed furthest in clinical trials is the Cytosponge™ which collects cells from the gastric cardia, gastro-esophageal junction and along the whole esophageal length. The cell sample is processed into a formalin-fixed paraffin-embedded block and sections assessed for the presence of intestinal metaplasia. TFF3 immunohistochemistry has consistently been shown to be a valuable adjunct that increases the accuracy of the Cytosponge™ test by highlighting early goblet cells which may be missed on morphological assessment and by allowing pseudogoblet cells to be differentiated from true goblet cells.

Published
2019

43. Astrocytes in Neuropsychiatric Disorders: A Review of Postmortem Evidence

Author

Xiaolu, Zhang, Rawan S, Alnafisah, Abdul-Rizaq A, Hamoud, Rammohan, Shukla, Robert E, McCullumsmith, and Sinead M, O'Donovan

Subjects
Depressive Disorder, Major, Bipolar Disorder, Astrocytes, Brain, Humans, Microglia
Abstract

Glial cell types in the central nervous system (CNS) include microglia, oligodendrocytes and the most diverse type, astrocytes. Clinical and experimental evidence suggest critical roles for astrocytes in the pathogenesis of CNS disease. Here, we summarize the extensive morphological heterogeneity and physiological properties of different astrocyte subtypes. We review postmortem studies, discussing astrocyte-related changes found in the brain in subjects diagnosed with the neuropsychiatric disorders schizophrenia, major depressive disorder and bipolar disorder. Finally, we discuss the potential effects of psychotropic medication on these findings. In summary, postmortem studies highlight that the morphology of astrocytes and the expression of functionally important astrocyte markers are altered in the brain in neuropsychiatric disorders and may play a role in the pathophysiology of these serious mental illnesses.

Published
2021

44. Genetic risk for schizophrenia is associated with altered visually-induced gamma band activity: evidence from a population sample stratified polygenic risk

Author

Derek K. Jones, Stavros I. Dimitriadis, David Edmund Johannes Linden, Gavin Perry, Sonya Foley, M O'Donovan, Krish D. Singh, Stan Zammit, Peter Holmans, Jane Hall, Katherine E. Tansey, M. J. Owen, RS: MHeNs - R2 - Mental Health, and RS: MHeNs - R3 - Neuroscience

Subjects
INTERNEURONS, medicine.medical_specialty, CORTEX, media_common.quotation_subject, Population, MAGNETOENCEPHALOGRAPHY, Neurosciences. Biological psychiatry. Neuropsychiatry, Audiology, Predictive markers, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Risk Factors, medicine, Gamma Rhythm, Humans, Contrast (vision), Clinical genetics, Genetic risk, MODULATION, education, HIGH-FREQUENCY OSCILLATIONS, Biological Psychiatry, INDIVIDUAL VARIABILITY, 030304 developmental biology, Balance (ability), media_common, 0303 health sciences, education.field_of_study, PEAK FREQUENCY, medicine.diagnostic_test, business.industry, Magnetoencephalography, medicine.disease, GABA CONCENTRATION, DYSFUNCTION, Psychiatry and Mental health, Schizophrenia, Biomarker (medicine), Birth Cohort, business, OSCILLATORY NEURONAL SYNCHRONIZATION, Gamma band, 030217 neurology & neurosurgery, RC321-571
Abstract

Gamma oscillations (30–90 Hz) have been proposed as a signature of cortical visual information processing, particularly the balance between excitation and inhibition, and as a biomarker of neuropsychiatric diseases. Magnetoencephalography (MEG) provides highly reliable visual-induced gamma oscillation estimates, both at sensor and source level. Recent studies have reported a deficit of visual gamma activity in schizophrenia patients, in medication naive subjects, and high-risk clinical participants, but the genetic contribution to such a deficit has remained unresolved. Here, for the first time, we use a genetic risk score approach to assess the relationship between genetic risk for schizophrenia and visual gamma activity in a population-based sample drawn from a birth cohort. We compared visual gamma activity in a group (N = 104) with a high genetic risk profile score for schizophrenia (SCZ-PRS) to a group with low SCZ-PRS (N = 99). Source-reconstructed V1 activity was extracted using beamformer analysis applied to MEG recordings using individual MRI scans. No group differences were found in the induced gamma peak amplitude or peak frequency. However, a non-parametric statistical contrast of the response spectrum revealed more robust group differences in the amplitude of high-beta/gamma power across the frequency range, suggesting that overall spectral shape carries important biological information beyond the individual frequency peak. Our findings show that changes in gamma band activity correlate with liability to schizophrenia and suggest that the index changes to synaptic function and neuronal firing patterns that are of pathophysiological relevance rather than consequences of the disorder.

Published
2021

45. Strategies to identify candidate repurposable drugs: COVID-19 treatment as a case example

Author

Robert E. McCullumsmith, Sinead M. O’Donovan, and Ali S Imami

Subjects
Financial costs, Drug, Pharmacology, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Computer science, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), media_common.quotation_subject, Neurosciences. Biological psychiatry. Neuropsychiatry, Computational biology, Review Article, Molecular neuroscience, COVID-19 Drug Treatment, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Drug repositioning, ComputingMethodologies_PATTERNRECOGNITION, Drug development, Pharmaceutical Preparations, Humans, Pandemics, Biological Psychiatry, RC321-571, media_common
Abstract

Drug repurposing is an invaluable strategy to identify new uses for existing drug therapies that overcome many of the time and financial costs associated with novel drug development. The COVID-19 pandemic has driven an unprecedented surge in the development and use of bioinformatic tools to identify candidate repurposable drugs. Using COVID-19 as a case study, we discuss examples of machine-learning and signature-based approaches that have been adapted to rapidly identify candidate drugs. The Library of Integrated Network-based Signatures (LINCS) and Connectivity Map (CMap) are commonly used repositories and have the advantage of being amenable to use by scientists with limited bioinformatic training. Next, we discuss how these recent advances in bioinformatic drug repurposing approaches might be adapted to identify repurposable drugs for CNS disorders. As the development of novel therapies that successfully target the cause of neuropsychiatric and neurological disorders has stalled, there is a pressing need for innovative strategies to treat these complex brain disorders. Bioinformatic approaches to identify repurposable drugs provide an exciting avenue of research that offer promise for improved treatments for CNS disorders.

Published
2021

46. Pharmacological impacts on schizophrenia functional analysis: a postmortem proteome study

Author

Adam J. Funk, Rammohan Shukla, Jaroslaw Meller, Robert E. McCullumsmith, Rawan Alnafisah, Sinead M. O’Donovan, and James Reigle

Subjects
Dorsolateral prefrontal cortex, medicine.anatomical_structure, Schizophrenia, Proteome, Dopaminergic, medicine, Context (language use), Striatum, Grey matter, Biology, Proteomics, medicine.disease, Neuroscience
Abstract

Schizophrenia (SCZ) is a severe and debilitating mental illness. Antipsychotic drugs (APDs) are used to treat both positive and negative SCZ symptoms, by influencing the cellular, subcellular-synaptic, and molecular processes. We posit that these effects influence our understanding of SCZ. To address this, we analyzed postmortem dorsolateral prefrontal cortex grey matter samples from control and SCZ subjects (n=10/group) using liquid-chromatography mass-spectrometry-based proteomics. We retrieved SCZ-altered and APD-influenced proteome-sets using linear and mixed linear models, respectively, and validated them experimentally using independent cohorts and insilico using published datasets. Functional analysis of proteome-sets was contrasted at the biological pathway, cell-type, subcellular-synaptic, and drug-target levels. The SCZ-altered proteome was conserved across several studies from DLPFC and other brain areas and was dependent on drug effect. At the pathway level, we observed an aberrant extracellular event and, except for homeostasis, signal-transduction, cytoskeleton, and dendrites associated downregulated changes, the APDs compensated for the majority of the SCZ-altered pathways. At the cell-type level, the up-and down-regulated SCZ-altered events were associated with two different subsets of striatum projecting layer-5 pyramidal-neurons regulating dopaminergic secretion. At the subcellular synaptic level, compensatory pre- and post-synaptic events were observed. At the drug target level, dopaminergic processes influence the SCZ-altered up-regulated proteome, whereas non-dopaminergic and a diverse array of non-neuromodulatory mechanisms influence the SCZ-altered down-regulated proteome. While these findings are dependent on pharmacological effects, they are also consistent with previous SCZ studies, implying the need to re-evaluate previous results. We discuss our findings in the context of cortico-striatal influence in SCZ-pathology.

Published
2021

47. Proteoglycan Clusters as a Site of Coordinated, Multi-Dendritic Plasticity

Author

Luigi Balasco, Sabina Berretta, Anne Boyer-Boiteau, Yuri Bozzi, Peter Durning, Torsten Klengel, Cristina Berciu, Gabriele Chelini, Robert E. McCullumsmith, Kerry J. Ressler, and Sinead M. O’Donovan

Subjects
Extracellular matrix, Proteoglycan, biology, Chemistry, Synaptic plasticity, biology.protein, Sensory system, Stimulus (physiology), Matrix (biology), Plasticity, Neuroscience, Function (biology)
Abstract

Experience-dependent learning depends on synaptic plasticity. While plasticity in individual synapses has been extensively investigated, the mechanisms underlying coordinated changes across sets of synapses on multiple dendrites, likely needed to encode effective adaptations to a salient stimulus, are not well understood. The extracellular matrix is uniquely well suited to fulfill this function, as rapid glia-driven remodeling of its local composition powerfully impact synaptic plasticity. We show that extracellular matrix microenvironments, named CS6 clusters, dynamically form around several dendrites in response to sensory stimuli in coincidence to stimulus-driven synaptic plasticity. CS6 clusters, formed by glia-dependent secretion of extracellular matrix components surrounding sets of adjacent dendrites, may represent a novel structure supporting coordinated synaptic plasticity.One Sentence SummaryExtracellular matrix clusters form microenvironments for coordinated multi-dendrite synaptic plasticity.

Published
2021

48. Assessing the relationships between neurological and psychiatric diseases with astrocyte subtypes and psychotropic medications

Author

Sinead M. O’Donovan, Rammohan Shukla, Mackenzie E Abel, Alyssa Wolfinger, Anna Lundh, Xiaojun Wu, Robert E. McCullumsmith, and Xiaolu Zhang

Subjects
medicine.medical_specialty, medicine.anatomical_structure, business.industry, Gene Enrichment, Medicine, Disease, business, Psychiatry, Marker gene, Depression (differential diagnoses), Astrocyte
Abstract

Astrocytes have many important functions in the brain, but their roles in CNS disorders and their responses to psychotropic medications are still being elucidated. In this study, we used gene enrichment analysis to assess the relationships between different astrocyte subtypes, neurological and psychiatric diseases, and psychotropic medications. We also carried out qPCR analyses and “look-up” studies to further assess the chronic effects of these drugs on astrocyte marker gene expression. Our bioinformatic analysis identified differential gene enrichment of different astrocyte subtypes in CNS disorders. The “common” astrocyte subtype was the most frequently enriched across disorders, but the highest level of enrichment was found in depression, supporting a role for astrocytes in this disorder. We also identified common enrichment of metabolic and signal transduction-related biological processes in astrocyte subtypes and CNS disorders. However, enrichment of different psychotropic medications, including antipsychotics, antidepressants, and mood stabilizers, was limited in astrocyte subtypes. These results were confirmed by “look-up” studies and qPCR analysis, which also reported little effect of common psychotropic medications on astrocyte marker gene expression, suggesting that astrocytes are not a primary target of these medications. Overall, this study provides a unique view of astrocyte subtypes and the effect of medications on astrocytes in disease, which will contribute to our understanding of their role in CNS disorders and offers insights into targeting astrocytes therapeutically.

Published
2021

49. Schizophrenia: a disorder of broken brain bioenergetics

Author

Nicholas D, Henkel, Xiajoun, Wu, Sinead M, O'Donovan, Emily A, Devine, Jessica M, Jiron, Laura M, Rowland, Zoltan, Sarnyai, Amy J, Ramsey, Zhexing, Wen, Margaret K, Hahn, and Robert E, McCullumsmith

Subjects
Psychotic Disorders, Schizophrenia, Brain, Humans, Energy Metabolism, Antipsychotic Agents
Abstract

A substantial and diverse body of literature suggests that the pathophysiology of schizophrenia is related to deficits of bioenergetic function. While antipsychotics are an effective therapy for the management of positive psychotic symptoms, they are not efficacious for the complete schizophrenia symptom profile, such as the negative and cognitive symptoms. In this review, we discuss the relationship between dysfunction of various metabolic pathways across different brain regions in relation to schizophrenia. We contend that several bioenergetic subprocesses are affected across the brain and such deficits are a core feature of the illness. We provide an overview of central perturbations of insulin signaling, glycolysis, pentose-phosphate pathway, tricarboxylic acid cycle, and oxidative phosphorylation in schizophrenia. Importantly, we discuss pharmacologic and nonpharmacologic interventions that target these pathways and how such interventions may be exploited to improve the symptoms of schizophrenia.

Published
2021

50. Adenosine, Schizophrenia and Cancer: Does the Purinergic System Offer a Pathway to Treatment?

Author

Abdul-Rizaq Hamoud, Karen Bach, Ojal Kakrecha, Nicholas Henkel, Xiaojun Wu, Robert E. McCullumsmith, and Sinead M. O’Donovan

Subjects
Adenosine, Incidence, Organic Chemistry, General Medicine, Catalysis, Computer Science Applications, Inorganic Chemistry, Neoplasms, Schizophrenia, Tumor Microenvironment, Humans, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy
Abstract

For over a century, a complex relationship between schizophrenia diagnosis and development of many cancers has been observed. Findings from epidemiological studies are mixed, with reports of increased, reduced, or no difference in cancer incidence in schizophrenia patients. However, as risk factors for cancer, including elevated smoking rates and substance abuse, are commonly associated with this patient population, it is surprising that cancer incidence is not higher. Various factors may account for the proposed reduction in cancer incidence rates including pathophysiological changes associated with disease. Perturbations of the adenosine system are hypothesized to contribute to the neurobiology of schizophrenia. Conversely, hyperfunction of the adenosine system is found in the tumor microenvironment in cancer and targeting the adenosine system therapeutically is a promising area of research in this disease. We outline the current biochemical and pharmacological evidence for hypofunction of the adenosine system in schizophrenia, and the role of increased adenosine metabolism in the tumor microenvironment. In the context of the relatively limited literature on this patient population, we discuss whether hypofunction of this system in schizophrenia, may counteract the immunosuppressive role of adenosine in the tumor microenvironment. We also highlight the importance of studies examining the adenosine system in this subset of patients for the potential insight they may offer into these complex disorders.

Published
2022

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