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Protein structure prediction can be used to determine the three-dimensional shape of a protein from its amino acid sequence.sup.1. This problem is of fundamental importance as the structure of a protein largely determines its function.sup.2; however, protein structures can be difficult to determine experimentally. Considerable progress has recently been made by leveraging genetic information. It is possible to infer which amino acid residues are in contact by analysing covariation in homologous sequences, which aids in the prediction of protein structures.sup.3. Here we show that we can train a neural network to make accurate predictions of the distances between pairs of residues, which convey more information about the structure than contact predictions. Using this information, we construct a potential of mean force.sup.4 that can accurately describe the shape of a protein. We find that the resulting potential can be optimized by a simple gradient descent algorithm to generate structures without complex sampling procedures. The resulting system, named AlphaFold, achieves high accuracy, even for sequences with fewer homologous sequences. In the recent Critical Assessment of Protein Structure Prediction.sup.5 (CASP13)--a blind assessment of the state of the field--AlphaFold created high-accuracy structures (with template modelling (TM) scores.sup.6 of 0.7 or higher) for 24 out of 43 free modelling domains, whereas the next best method, which used sampling and contact information, achieved such accuracy for only 14 out of 43 domains. AlphaFold represents a considerable advance in protein-structure prediction. We expect this increased accuracy to enable insights into the function and malfunction of proteins, especially in cases for which no structures for homologous proteins have been experimentally determined.sup.7. AlphaFold predicts the distances between pairs of residues, is used to construct potentials of mean force that accurately describe the shape of a protein and can be optimized with gradient descent to predict protein structures., Author(s): Andrew W. Senior [sup.1] , Richard Evans [sup.1] , John Jumper [sup.1] , James Kirkpatrick [sup.1] , Laurent Sifre [sup.1] , Tim Green [sup.1] , Chongli Qin [sup.1] , [...]

An important component of cellular biochemistry is the concentration of proteins and nucleic acids in non-membranous compartments.sup.1,2. These biomolecular condensates are formed from processes that include liquid-liquid phase separation. The multivalent interactions necessary for liquid-liquid phase separation have been extensively studied in vitro.sup.1,3. However, the regulation of this process in vivo is poorly understood. Here we identify an in vivo regulator of liquid-liquid phase separation through a genetic screen targeting factors required for Arabidopsis RNA-binding protein FCA function. FCA contains prion-like domains that phase-separate in vitro, and exhibits behaviour in vivo that is consistent with phase separation. The mutant screen identified a functional requirement for FLL2, a coiled-coil protein, in the formation of FCA nuclear bodies. FCA reduces transcriptional read-through by promoting proximal polyadenylation at many sites in the Arabidopsis genome.sup.3,4. FLL2 was required to promote this proximal polyadenylation, but not the binding of FCA to target RNA. Ectopic expression of FLL2 increased the size and number of FCA nuclear bodies. Crosslinking with formaldehyde captured in vivo interactions between FLL2, FCA and the polymerase and nuclease modules of the RNA 3'-end processing machinery. These 3' RNA-processing components colocalized with FCA in the nuclear bodies in vivo, which indicates that FCA nuclear bodies compartmentalize 3'-end processing factors to enhance polyadenylation at specific sites. Our findings show that coiled-coil proteins can promote liquid-liquid phase separation, which expands our understanding of the principles that govern the in vivo dynamics of liquid-like bodies. A genetic screen for factors required by the Arabidopsis RNA-binding protein FCA identifies FLL2 as necessary in the formation of FCA nuclear bodies, and thus a role for FLL2 in liquid-liquid phase separation., Author(s): Xiaofeng Fang [sup.1] , Liang Wang [sup.2] , Ryo Ishikawa [sup.1] [sup.5] , Yaoxi Li [sup.1] , Marc Fiedler [sup.3] , Fuquan Liu [sup.1] [sup.6] , Grant Calder [sup.1] [...]

This study presents the results of an empirical investigation of attitudes toward bribe taking in Egypt. The authors use the Human Beliefs and Values Survey data to examine several demographic variables to determine whether demographics make a difference. The total sample size was over 3000. The study found that some demographic variables do make a difference. Keywords: Bribe, Egypt, demographic variables, gender, age, religion, employment status, marital status, education level, social class, happiness, health, political spectrum, INTRODUCTION Bribery has been around for thousands of years. In some societies it is an accepted way of doing business, and is viewed either as a means of greasing the [...]