A robust activity marking system for exploring active neuronal ensembles

Understanding how the brain captures transient experience and converts it into long lasting changes in neural circuits requires the identification and investigation of the specific ensembles of neurons that are responsible for the encoding of each experience. We have developed a Robust Activity Marking (RAM) system that allows for the identification and interrogation of ensembles of neurons. The RAM system provides unprecedented high sensitivity and selectivity through the use of an optimized synthetic activity-regulated promoter that is strongly induced by neuronal activity and a modified Tet-Off system that achieves improved temporal control. Due to its compact design, RAM can be packaged into a single adeno-associated virus (AAV), providing great versatility and ease of use, including application to mice, rats, flies, and potentially many other species. Cre-dependent RAM, CRAM, allows for the study of active ensembles of a specific cell type and anatomical connectivity, further expanding the RAM system’s versatility.Swedish Brain Foundation (Research Fellowship)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (Predoctoral Fellowship)National Institutes of Health (U.S.) (Grants MH091220)National Institutes of Health (U.S.) (Grant NS088421)National Institutes of Health (U.S.) (Grant MH106817)MIT Simons Initiatives on Autism and the Brain (Postdoctoral Fellowship)John Merck Fund (Scholars Program

Seeds, Agricultural Systems and Socio-natures: Towards an Actor-Network Theory Informed Political Ecology of Agriculture

Agriculture has recently been the subject of considerable research and policy attention. Events such as the 2008 ‘world food price crisis’ and concerns over the future of global food security have led to calls for a ‘New Green Revolution’, with an emphasis on boosting yields through new transgenic crop varieties. However, critics have raised concerns over the growing role of global agribusiness and transnational capital in agriculture, as well as the potential social and ecological impacts of new technologies. An analysis of emerging agricultural trends thus demands a framework that is able to negotiate the complex multi-scalar interplay between environmental, technological, scientific, political and economic factors. In this paper, we focus on the potential contribution of a synthesis between political ecology and Actor–Network Theory to our understanding of agricultural networks. We review the literature with a view to teasing out key insights and sketching out future research priorities. We focus on questions surrounding power and agency, the political ecology of scale and the role of situated knowledges and practices.Natasha Watts was supported by an Economic and Social Research Council Studentship (Award KFW/301419246). Ivan Scales was supported by an Early Career Fellowship from the Centre for Research on the Arts, Social Sciences and Humanities at the University of Cambridge and a Royal Geographical Society–Institute of British Geographers. Small Research Grant.This is the author accepted manuscript. The final version is available at http://onlinelibrary.wiley.com/doi/10.1111/gec3.12212/abstract

Sublethal RNA Oxidation as a Mechanism for Neurodegenerative Disease

Although cellular RNA is subjected to the same oxidative insults as DNA and other cellular macromolecules, oxidative damage to RNA has not been a major focus in investigations of the biological consequences of free radical damage. In fact, because it is largely single-stranded and its bases lack the protection of hydrogen bonding and binding by specific proteins, RNA may be more susceptible to oxidative insults than is DNA. Oxidative damage to protein-coding RNA or non-coding RNA will, in turn, potentially cause errors in proteins and/or dysregulation of gene expression. While less lethal than mutations in the genome, such sublethal insults to cells might be associated with underlying mechanisms of several chronic diseases, including neurodegenerative disease. Recently, oxidative RNA damage has been described in several neurodegenerative diseases including Alzheimer disease, Parkinson disease, dementia with Lewy bodies, and prion diseases. Of particular interest, oxidative RNA damage can be demonstrated in vulnerable neurons early in disease, suggesting that RNA oxidation may actively contribute to the onset of the disease. An increasing body of evidence suggests that, mechanistically speaking, the detrimental effects of oxidative RNA damage to protein synthesis are attenuated, at least in part, by the existence of protective mechanisms that prevent the incorporation of the damaged ribonucleotides into the translational machinery. Further investigations aimed at understanding the processing mechanisms related to oxidative RNA damage and its consequences may provide significant insights into the pathogenesis of neurodegenerative and other degenerative diseases and lead to better therapeutic strategies

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

PERJANJIAN KERJASAMA OPERASIONAL RUMAH SAKIT UMUM DAERAH (RSUD) DALAM PENGELOLAAN ALAT KESEHATAN

Sampai saat ini belum terdapat ketentuan perundang-undangan yang khusus (Lex Spesialis) mengatur tentang Perjanjian Kerjasama Operasional (KSO) antara instansi Pemerintah dan badan swasta, baik mengenai syarat-syarat, prosedur, maupun materi muatan minimal yang harus tertuang dalam Perjanjian Kerjasama Operasional. Peraturan yang ada hanya bersifat sektoral atau tersebar dalam berbagai bidang. Perjanjian Kerjasama Operasional (KSO) merupakan jenis perjanjian yang banyak digunakan dalam praktek kegiatan komersial, termasuk oleh Pemerintah. Jenis perjanjian ini lahir dan berkembang dalam praktek bisnis. Landasan hukum perjanjian ini terutama berdasarkan pada prinsip kebebasan berkontrak, sehingga belum terdapat keseragaman dalam menggunakan format Perjanjian Kerjasama Operasional. Batasan perjanjian kerjasama ini juga masih belum jelas, sehingga norma hukum yang berlaku terutama adalah berdasarkan kesepakatan bersama antara para pihak. Perjanjian Kerjasama Operasional (KSO) Rumah Sakit Umum Daerah (RSUD) dalam pengelolaan alat kesehatan didefinisikan sebagai kesepakatan antara RSUD dengan pihak swasta, dimana masing-masing pihak memberikan kontribusi baik berupa sumber dana, sumber daya dan fasilitas yang dimilikinya. Perjanjian kerjasama antara RSUD dengan pihak swasta ini menganut prinsip pembagian keuntungan dan pembebanan resiko bersama, secara jujur dan adil serta berdasarkan kesepakatan bersama yang ditetapkan dalam perjanjian

Reporter

Subtitled: "Tuition Hikes