Faculty Opinions recommendation of Biological plasticity rescues target activity in CRISPR knock outs.

Author(s):  
Constantinos Demetriades
2019 ◽  
Vol 16 (11) ◽  
pp. 1087-1093 ◽  
Author(s):  
Arne H. Smits ◽  
Frederik Ziebell ◽  
Gerard Joberty ◽  
Nico Zinn ◽  
William F. Mueller ◽  
...  

Author(s):  
Y.V. Mikhaylova ◽  
◽  
M.A. Tyumentseva ◽  
A.A. Shelenkov ◽  
Y.G. Yanushevich ◽  
...  

In this study, we assessed the efficiency and off-target activity of the CRISPR/CAS complex with one of the selected guide RNAs using the CIRCLE-seq technology. The gene encoding the human chemokine receptor CCR5 was used as a target sequence for genome editing. The results of this experiment indicate the correct choice of the guide RNA and efficient work of the CRISPR- CAS ribonucleoprotein complex used. CIRCLE-seq technology has shown high sensitivity compared to bioinformatic methods for predicting off-target activity of CRISPR/CAS complexes. We plan to evaluate the efficiency and off-target activity of CRISPR/CAS ribonucleoprotein complexes with other guide RNAs by slightly adjusting the CIRCLE-seq-technology protocol in order to reduce nonspecific DNA breaks and increase the number of reliable reads.


2015 ◽  
Vol 3 (5) ◽  
Author(s):  
Eva Jablonka ◽  
Ehud Lamm

<p class="p1"><span class="s1"><strong>Abstract </strong></span>| Lamarck has left many legacies for future generations of biologists<span class="s2"><strong>. </strong></span>His best known legacy was an explicit suggestion, developed in the <em>Philosophie zoologique </em>(PZ), that the effects of use and disuse (acquired characters) can be inherited and can drive species transformation.This suggestion was formulated as two laws, which we refer to as the law of biological plasticity and the law of phenotypic continuity<span class="s2"><strong>. </strong></span>We put these laws in their historical context and distinguish between Lamarck’s key insights and later neo-Lamarckian interpretations of his ideas<span class="s2"><strong>.</strong></span>We argue that Lamarck’s emphasis on the role played by the organization of living beings and his physiological model of reproduction are directly relevant to 21st-century concerns, and illustrate this by discussing intergenerational genomic continuity and cultural evolution.</p>


2021 ◽  
pp. 153178
Author(s):  
Elise Bouffard ◽  
Balyn W Zaro ◽  
Melissa M Dix ◽  
Benjamin Cravatt ◽  
Chi-Huey Wong

Author(s):  
Thomas Blaschke ◽  
Jürgen Bajorath

AbstractExploring the origin of multi-target activity of small molecules and designing new multi-target compounds are highly topical issues in pharmaceutical research. We have investigated the ability of a generative neural network to create multi-target compounds. Data sets of experimentally confirmed multi-target, single-target, and consistently inactive compounds were extracted from public screening data considering positive and negative assay results. These data sets were used to fine-tune the REINVENT generative model via transfer learning to systematically recognize multi-target compounds, distinguish them from single-target or inactive compounds, and construct new multi-target compounds. During fine-tuning, the model showed a clear tendency to increasingly generate multi-target compounds and structural analogs. Our findings indicate that generative models can be adopted for de novo multi-target compound design.


RNA ◽  
2010 ◽  
Vol 16 (5) ◽  
pp. 879-884 ◽  
Author(s):  
R. A. Klinghoffer ◽  
J. Magnus ◽  
J. Schelter ◽  
M. Mehaffey ◽  
C. Coleman ◽  
...  
Keyword(s):  

2018 ◽  
Vol 45 (6) ◽  
pp. 528 ◽  
Author(s):  
T. L. Kreplins ◽  
M. S. Kennedy ◽  
P. J. Adams ◽  
P. W. Bateman ◽  
S. D. Dundas ◽  
...  

Context Livestock predation is a worldwide phenomenon, causing financial losses and emotional strain on producers. Wild dogs (Canis familiaris) cause millions of dollars of damage to cattle, sheep and goat production in Australia every year, and despite on-going control (baiting, trapping, shooting, and fencing), they remain a significant problem for livestock producers across many pastoral and agricultural regions of Australia. Aims We aimed to quantify the uptake of dried meat baits by wild dogs and determine whether an olfactory lure (fish oil) could increase uptake. Methods Camera traps and sand pads were used to monitor bait uptake for three baiting events on two pastoral properties in the southern rangelands of Western Australia in 2016 and 2017. Key results Of the 337 monitored baits with a known outcome, young wild dogs (<8 months old) removed only four, three of which were covered in a fish-oil lure. In warmer months, baits were largely consumed by varanids, and in cooler months, when baits were taken it was predominantly by corvids. Varanids and corvids took more baits than expected on the basis of activity indices. Kangaroos, feral cats and wild dogs consumed significantly fewer baits than expected from their activity on camera. Conclusions We have no evidence that adult wild dogs removed baits, despite many opportunities to do so (wild dogs passing cameras), and fewer wild dogs took baits than expected on the basis of activity events seen on camera. Olfactory lures may have the potential to increase bait uptake by naïve individuals (i.e. young dogs), but the sample size was small. Implications Increasing the number of baiting events per year, trialling novel baits, and baiting during low non-target activity are some of the recommended methods that may increase bait persistence and uptake by wild dogs.


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