The Off-Targets of Clustered Regularly Interspaced Short Palindromic Repeats Gene Editing

Funding: The work of VMB was funded by iNOVA4Health – UIDB/Multi/04462/2020 and UIDP/Multi/04462/2020, a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência through national funds, and the FCT grant PTDC/BEX-BCM/5900/2014.The repurposing of the CRISPR/Cas bacterial defense system against bacteriophages as simple and flexible molecular tools has revolutionized the field of gene editing. These tools are now widely used in basic research and clinical trials involving human somatic cells. However, a global moratorium on all clinical uses of human germline editing has been proposed because the technology still lacks the required efficacy and safety. Here we focus on the approaches developed since 2013 to decrease the frequency of unwanted mutations (the off-targets) during CRISPR-based gene editing.publishersversionpublishe

Substituição do Milho pela Farinha de Varredura (Manihot esculenta, Crantz) na Ração de Bezerros Holandeses.: 1. Desempenho e Parâmetros Sangüíneos Replacement of Corn for Cassava Meal (Manihot esculenta, Crantz) in the Holstein Calves Diets: 1. Performance and Blood Parameters

O objetivo deste trabalho foi avaliar o efeito de diferentes níveis de substituição do milho pela farinha de varredura de mandioca (0, 25, 50, 75 e 100%, base da matéria seca), sobre o consumo e conversão alimentar, ganho médio diário e níveis de hematócrito, glicose e uréia sanguíneos. Utilizaram-se 35 bezerros holandeses puros de origem ou puros por cruzamento, não castrados, com idade aproximada de 80 dias e peso vivo médio de 80 kg, distribuídos em delineamento de blocos casualizados. Os animais foram alimentados à vontade, até atingir o consumo de 4 kg/dia de concentrado. Como volumoso, foi utilizado feno inteiro de capim tifton 85. Os animais terminaram o experimento, com peso médio de 164 kg. A elevação dos níveis de substituição ocasionou uma resposta linear decrescente no consumo de matéria seca. A conversão alimentar não diferiu entre os tratamentos. Os ganhos diários para os dois primeiros períodos de 28 dias reduziram-se linearmente, com a elevação dos níveis de substituição, mas não diferiram no último período de 28 dias, apresentando valores estimados, variando de 0,93 a 0,68, 1,10 a 0,89 e 1,09 kg/dia, respectivamente. Os níveis de hematócrito, glicose e uréia não foram influenciados pelos níveis de substituição do milho pela farinha de varredura.<br>The objective of this project was to evaluate the effects of different replacement levels of corn for cassava meal (0, 25, 50, 75, and 100%, dry matter basis) on the dry matter intake and feed:gain ratio, daily weight gain and levels of blood hematocrit, glucose and urea. Thirty five intact Holstein calves, averaging 80 days old and initial live weight of 80 kg, were allotted to a randomized block design and fed concentrate, ad libitum, to reach the intake of 4 kg/day. Tifton 85 bermudagrass was fed as roughage. The final average weight was of 164 kg. The dry matter intake showed a linear behavior as the replacement levels increased. The feed:gain ratio was not affected by the replacement levels. The daily weight gain for the two first periods of 28 days (period 1 and 2, respectively) reduced as the replacement levels increased, but they were not affected in the last 28 days period (period 3), and the respective values ranged from 0.93 to 0.68, 1.10 to 0.89, and 1.09 kg/day. Levels of hematocrit, glucose and urea were not affected by the replacement of corn for cassava meal

Laser Spectroscopy of Muonic Atoms and Ions

Laser spectroscopy of the Lamb shift (2S-2P energy difference) in light muonic atoms or ions, in which one negative muon μ− is bound to a nucleus, has been performed. The measurements yield significantly improved values of the root-mean-square charge radii of the nuclei, owing to the large muon mass, which results in a vastly increased muon wave function overlap with the nucleus. The values of the proton and deuteron radii are 10 and 3 times more accurate than the respective CODATA values, but 7 standard deviations smaller. Data on muonic helium-3 and -4 ions is being analyzed and will give new insights. In future, the (magnetic) Zemach radii of the proton and the helium-3 nuclei will be determined from laser spectroscopy of the 1S hyperfine splittings, and the Lamb shifts of muonic Li, Be, and B can be used to improve the respective charge radii

Publisher Correction: Measuring the α-particle charge radius with muonic helium-4 ions

This Article was originally published online on 27 January 2021 without Open Access. With the author(s)’ decision to opt for Open Access, the copyright of the Article changed on 17 February 2021 to © The Author(s) 2021, and the Article is now licensed/distributed under the terms of a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/.), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The original Article has been corrected online

The next generation of laser spectroscopy experiments using light muonic atoms

Precision spectroscopy of light muonic atoms provides unique information about the atomic and nuclear structure of these systems and thus represents a way to access fundamental interactions, properties and constants. One application comprises the determination of absolute nuclear charge radii with unprecedented accuracy from measurements of the 2S - 2P Lamb shift. Here, we review recent results of nuclear charge radii extracted from muonic hydrogen and helium spectroscopy and present experiment proposals to access light muonic atoms with Z ≥ 3. In addition, our approaches towards a precise measurement of the Zemach radii in muonic hydrogen (μp) and helium (μ 3He+) are discussed. These results will provide new tests of bound-state quantum-electrodynamics in hydrogen-like systems and can be used as benchmarks for nuclear structure theories.ISSN:1742-6588ISSN:1742-659

A multiobjective metaheuristic for a mean-risk static stochastic knapsack problem

Stochastic knapsack problem, Stochastic combinatorial optimisation, Mean-risk objectives, Multiobjective combinatorial optimisation, Multiobjective metaheuristics,

A horizon scan exercise for aquatic invasive alien species in Iberian inland waters

As the number of introduced species keeps increasing unabatedly, identifying and prioritising current and potential Invasive Alien Species (IAS) has become essential to manage them. Horizon Scanning (HS), defined as an exploration of potential threats, is considered a fundamental component of IAS management. By combining scientific knowledge on taxa with expert opinion, we identified the most relevant aquatic IAS in the Iberian Peninsula, i.e., those with the greatest geographic extent (or probability of introduction), severe ecological, economic and human health impacts, greatest difficulty and acceptability of management. We highlighted the 126 most relevant IAS already present in Iberian inland waters (i.e., Concern list) and 89 with a high probability of being introduced in the near future (i.e., Alert list), of which 24 and 10 IAS, respectively, were considered as a management priority after receiving the highest scores in the expert assessment (i.e., top-ranked IAS). In both lists, aquatic IAS belonging to the four thematic groups (plants, freshwater invertebrates, estuarine invertebrates, and vertebrates) were identified as having been introduced through various pathways from different regions of the world and classified according to their main functional feeding groups. Also, the latest update of the list of IAS of Union concern pursuant to Regulation (EU) No 1143/2014 includes only 12 top-ranked IAS identified for the Iberian Peninsula, while the national lists incorporate the vast majority of them. This fact underlines the great importance of taxa prioritisation exercises at biogeographical scales as a step prior to risk analyses and their inclusion in national lists. This HS provides a robust assessment and a cost-effective strategy for decision-makers and stakeholders to prioritise the use of limited resources for IAS prevention and management. Although applied at a transnational level in a European biodiversity hotspot, this approach is designed for potential application at any geographical or administrative scale, including the continental one

A horizon scan exercise for aquatic invasive alien species in Iberian inland waters

As the number of introduced species keeps increasing unabatedly, identifying and prioritising current and potential Invasive Alien Species (IAS) has become essential to manage them. Horizon Scanning (HS), defined as an exploration of potential threats, is considered a fundamental component of IAS management. By combining scientific knowledge on taxa with expert opinion, we identified the most relevant aquatic IAS in the Iberian Peninsula, i.e., those with the greatest geographic extent (or probability of introduction), severe ecological, economic and human health impacts, greatest difficulty and acceptability of management. We highlighted the 126 most relevant IAS already present in Iberian inland waters (i.e., Concern list) and 89 with a high probability of being introduced in the near future (i.e., Alert list), of which 24 and 10 IAS, respectively, were considered as a management priority after receiving the highest scores in the expert assessment (i.e., top-ranked IAS). In both lists, aquatic IAS belonging to the four thematic groups (plants, freshwater invertebrates, estuarine invertebrates, and vertebrates) were identified as having been introduced through various pathways from different regions of the world and classified according to their main functional feeding groups. Also, the latest update of the list of IAS of Union concern pursuant to Regulation (EU) No 1143/2014 includes only 12 top-ranked IAS identified for the Iberian Peninsula, while the national lists incorporate the vast majority of them. This fact underlines the great importance of taxa prioritisation exercises at biogeographical scales as a step prior to risk analyses and their inclusion in national lists. This HS provides a robust assessment and a cost-effective strategy for decision-makers and stakeholders to prioritise the use of limited resources for IAS prevention and management. Although applied at a transnational level in a European biodiversity hotspot, this approach is designed for potential application at any geographical or administrative scale, including the continental one

Brazilian Flora 2020: Leveraging the power of a collaborative scientific network

International audienceThe shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora