Gene translation depends on accurate decoding of mRNA, the structural mechanism of which remains poorly understood. Ribosomes decode mRNA codons by selecting cognate aminoacyl-tRNAs delivered by elongation factor Tu (EF-Tu). Here we present high-resolution structural ensembles of ribosomes with cognate or near-cognate aminoacyl-tRNAs delivered by EF-Tu. Both cognate and near-cognate tRNA anticodons explore the aminoacyl-tRNA-binding site (A site) of an open 30S subunit, while inactive EF-Tu is separated from the 50S subunit. A transient conformation of decoding-centre nucleotide G530 stabilizes the cognate codon-anticodon helix, initiating step-wise 'latching' of the decoding centre. The resulting closure of the 30S subunit docks EF-Tu at the sarcin-ricin loop of the 50S subunit, activating EF-Tu for GTP hydrolysis and enabling accommodation of the aminoacyl-tRNA. By contrast, near-cognate complexes fail to induce the G530 latch, thus favouring open 30S pre-accommodation intermediates with inactive EF-Tu. This work reveals long-sought structural differences between the pre-accommodation of cognate and near-cognate tRNAs that elucidate the mechanism of accurate decoding.

Physiological measurements in neuroscience experiments often involve complex stimulus paradigms and multiple data channels. Ephus (http://www.ephus.org) is an open-source software package designed for general-purpose data acquisition and instrument control. Ephus operates as a collection of modular programs, including an ephys program for standard whole-cell recording with single or multiple electrodes in typical electrophysiological experiments, and a mapper program for synaptic circuit mapping experiments involving laser scanning photostimulation based on glutamate uncaging or channelrhodopsin-2 excitation. Custom user functions allow user-extensibility at multiple levels, including on-line analysis and closed-loop experiments, where experimental parameters can be changed based on recently acquired data, such as during in vivo behavioral experiments. Ephus is compatible with a variety of data acquisition and imaging hardware. This paper describes the main features and modules of Ephus and their use in representative experimental applications.

Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence.

We investigate a practical approach to solving one instantiation of a distributed hypothesis testing problem under severe rate constraints that shows up in a wide variety of applications such as camera calibration, biometric authentication and video hashing: given two distributed continuous-valued random sources, determine if they satisfy a certain Euclidean distance criterion. We show a way to convert the problem from continuous-valued to binary-valued using binarized random projections and obtain rate savings by applying a linear syndrome code. In finding visual correspondences, our approach uses just 49% of the rate of scalar quantization to achieve the same level of retrieval performance. To perform video hashing, our approach requires only a hash rate of 0.0142 bpp to identify corresponding groups of pictures correctly.