Effect of methylene blue on the genomic response to reperfusion injury induced by cardiac arrest and cardiopulmonary resuscitation in porcine brain

<p>Abstract</p> <p>Background</p> <p>Cerebral ischemia/reperfusion injury is a common secondary effect of cardiac arrest which is largely responsible for postresuscitative mortality. Therefore development of therapies which restore and protect the brain function after cardiac arrest is essential. Methylene blue (MB) has been experimentally proven neuroprotective in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. However, no comprehensive analyses have been conducted at gene expression level.</p> <p>Methods</p> <p>Pigs underwent either untreated cardiac arrest (CA) or CA with subsequent cardiopulmonary resuscitation (CPR) accompanied with an infusion of saline or an infusion of saline with MB. Genome-wide transcriptional profiling using the Affymetrix porcine microarray was performed to 1) gain understanding of delayed neuronal death initiation in porcine brain during ischemia and after 30, 60 and 180 min following reperfusion, and 2) identify the mechanisms behind the neuroprotective effect of MB after ischemic injury (at 30, 60 and 180 min).</p> <p>Results</p> <p>Our results show that restoration of spontaneous circulation (ROSC) induces major transcriptional changes related to stress response, inflammation, apoptosis and even cytoprotection. In contrast, the untreated ischemic and anoxic insult affected only few genes mainly involved in intra-/extracellular ionic balance. Furthermore, our data show that the neuroprotective role of MB is diverse and fulfilled by regulation of the expression of soluble guanylate cyclase and biological processes accountable for inhibition of apoptosis, modulation of stress response, neurogenesis and neuroprotection.</p> <p>Conclusions</p> <p>Our results support that MB could be a valuable intervention and should be investigated as a therapeutic agent against neural damage associated with I/R injury induced by cardiac arrest.</p

LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same

Since the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson's disease, a considerable amount of work has gone into uncovering its basic cellular function. This effort has led to the implication of LRRK2 in a bewildering range of cell biological processes and pathways, and probable roles in a number of seemingly unrelated medical conditions. In this review we summarise current knowledge of the basic biochemistry and cellular function of LRRK2. Topics covered include the identification of phosphorylation substrates of LRRK2 kinase activity, in particular Rab proteins, and advances in understanding the activation of LRRK2 kinase activity via dimerisation and association with membranes, especially via interaction with Rab29. We also discuss biochemical studies that shed light on the complex LRRK2 GTPase activity, evidence of roles for LRRK2 in a range of cell signalling pathways that are likely cell type specific, and studies linking LRRK2 to the cell biology of organelles. The latter includes the involvement of LRRK2 in autophagy, endocytosis, and processes at the trans-Golgi network, the endoplasmic reticulum and also key microtubule-based cellular structures. We further propose a mechanism linking LRRK2 dimerisation, GTPase function and membrane recruitment with LRRK2 kinase activation by Rab29. Together these data paint a picture of a research field that in many ways is moving forward with great momentum, but in other ways has not changed fundamentally. Many key advances have been made, but very often they seem to lead back to the same places

Predicting attitudinal and behavioral responses to COVID-19 pandemic using machine learning

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multinational data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution-individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar results were found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, and collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-neglible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic.Published versio

Predicting attitudinal and behavioral responses to COVID-19 pandemic using machine learning

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multi-national data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution—individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar was found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-negligible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic

National identity predicts public health support during a global pandemic

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics

A global experiment on motivating social distancing during the COVID-19 pandemic

Significance Communicating in ways that motivate engagement in social distancing remains a critical global public health priority during the COVID-19 pandemic. This study tested motivational qualities of messages about social distancing (those that promoted choice and agency vs. those that were forceful and shaming) in 25,718 people in 89 countries. The autonomy-supportive message decreased feelings of defying social distancing recommendations relative to the controlling message, and the controlling message increased controlled motivation, a less effective form of motivation, relative to no message. Message type did not impact intentions to socially distance, but people’s existing motivations were related to intentions. Findings were generalizable across a geographically diverse sample and may inform public health communication strategies in this and future global health emergencies. Abstract Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Pengaruh Pemberian Pupuk Npk Anorganik Dan Pupuk Kandang Kambing Pada Pertumbuhan Dan Hasiltanaman Brokoli (Brassica Oleracea L.)

Brokoli (Brassica oleracea L. Var. italica) merupakan tanaman hortikultura yang dimanfaatkan bunganya. Produksi tanaman brokoli pada tahun 2012 hingga tahun 2015 mengalami penurunan produksi dari 135.837 menjadi 118.394 ton (BPS, 2016). Oleh karena itu, belum dapat mencukupi kebutuhan pasar lokal, apalagi untuk mencukupi pasar Internasional yang setiap tahun selalu mengalami peningkatan 20-30%. Teknik perbaikan budidaya brokoli dapat dilakukan dengan pemberian pupuk NPK anorganik dan pupuk kandang kambing. Pemberian pupuk kandang kambing bertujuan untuk memperbaiki sifat fisik tanah dan komposisi hara tanah. Tekstur dari kotoran kambing khas, karena berbentuk butiran-butiran yang agak sukar dipecah secara fisik sehingga sangat berpengaruh terhadap dekomposisi dan proses penyediaan haranya. Selain menggunakan pupuk organik, pupuk anorganik juga diperlukan untuk meningkatkan produksi brokoli. Salah satu jenis pupuk anorganik yang sering digunakan adalah pupuk NPK anorganik. Pupuk anorganik juga mampu menambah unsur hara tanah, tetapi penggunaan pupuk anorganik secara berlebihan dapat menimbulkan dampak negatif bagi tanah. Jumlah pupuk yang diberikan ke tanaman akanmempengaruhi hasil produksi yang akan didapat. Tujuan penelitian ini ialah untuk mempelajari dan mendapatkan pengaruh pemberian pupuk NPK anorganik dan pupuk kandang kambing terhadap pertumbuhan dan hasil tanaman brokoli (Brassica olaracea L.).Pemberian pupuk NPK anorganik dan pupuk kandang kambing akan memberikan pengaruh lebih baik bagi pertumbuhan dan hasil tanaman brokoli (Brassica olaracea L.). Penelitian dilaksanakan di Junggo, Kecamatan Bumiaji, Kota Batu, Jawa Timur. pada bulan Maret hingga Juni 2020. Alat yang digunakan pada penelitian ini ialah cangkul, ember, timbangan analitik, oven, amplop coklat, meteran, penggaris, alat tulis, kamera, alat LAM (Leaf Area Meter) dan mika label. Bahan yang digunakan ialah benih brokoli varietas Green Magic, pupuk NPK Phonska, cocopeat, air dan pupuk kandang kambing. Penelitian ini menggunakan Rancangan Acak Kelompok (RAK) yang terdiri dari 9 kombinasi perlakuan dengan 3 kali ulangan P1 = Kontrol, P2 = 800 kg ha-1NPK, P3 = 800 kg ha-1NPK + 8 ton ha-1 Kandang Kambing, P4 = 800 kg ha-1NPK + 10 ton ha-1 kandang kambing, P5 = 600 kg ha-1NPK + 12 ton ha-1 kandang kambing, P6 = 600 kg ha- 1NPK + 8 ton ha-1 kandang kambing, P7 = 400 kg ha-1NPK + 10 ton ha-1 kandang kambing, P8 = 400 kg ha-1NPK + 12 ton ha-1 kandang kambing, P9 = 200 kg ha- 1NPK + 12 ton ha-1 kandang kambing. Parameter pengamatan meliputi pengamatan pertumbuhan dan hasil. Parameter pengamatan pertumbuhan meliputi jumlah daun dan tinggi tanaman. Parameter pengamatan hasil meliputi luas daun, diameter batang, diameter bunga brokoli, berat bunga segar brokoli dan berat bunga kering brokoli. Data yang diperoleh dari hasil pengamatan dianalisis menggunakan ANOVA (Analysis of Variance) dengan uji tabel F dengan taraf ii 5%. Apabila hasilterdapat perbedaan antar perlakuan, maka akan dilanjutkan dengan lanjut Beda Nyata Jujur (BNJ) pada taraf 5%. Hasil penelitian menunjukkan bahwa kombinasi pupuk NPK dan pupuk kandang kambing berpengaruh meningkatkan pada pertumbuhan dan hasil tanaman Brokoli. Perlakuan 800 kg ha-1 NPK + 10 ton ha-1 kandang kambing memberikan hasil yang paling baik dibanding perlakuan lainnya pada seluruh parameter pengamatan. Kombinasi pupuk anorganik dan pupuk organik mampu memberikan hasil bobot basah bunga brokoli sebesar 203 % atau sebesar 6,85 ton dibanding perlakuan kontrol, serta peningkatan hasil sebesar 181 % atau sebesar 6,05 ton dibanding perlakuan pupuk standar. Olah karena itu, dapat disimpulkan bahwa kombinasi pemberian pupuk NPK dan pupuk kandang kambing berpengaruh baik bagi pertumbuhan dan hasil tanaman brokoli