Incremental Mutual Information: A New Method for Characterizing the Strength and Dynamics of Connections in Neuronal Circuits

Understanding the computations performed by neuronal circuits requires characterizing the strength and dynamics of the connections between individual neurons. This characterization is typically achieved by measuring the correlation in the activity of two neurons. We have developed a new measure for studying connectivity in neuronal circuits based on information theory, the incremental mutual information (IMI). By conditioning out the temporal dependencies in the responses of individual neurons before measuring the dependency between them, IMI improves on standard correlation-based measures in several important ways: 1) it has the potential to disambiguate statistical dependencies that reflect the connection between neurons from those caused by other sources (e. g. shared inputs or intrinsic cellular or network mechanisms) provided that the dependencies have appropriate timescales, 2) for the study of early sensory systems, it does not require responses to repeated trials of identical stimulation, and 3) it does not assume that the connection between neurons is linear. We describe the theory and implementation of IMI in detail and demonstrate its utility on experimental recordings from the primate visual system

Transfer RNA-derived small RNAs in the cancer transcriptome

The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing

Microguards and micromessengers of the genome

The regulation of gene expression is of fundamental importance to maintain organismal function and integrity and requires a multifaceted and highly ordered sequence of events. The cyclic nature of gene expression is known as ‘transcription dynamics’. Disruption or perturbation of these dynamics can result in significant fitness costs arising from genome instability, accelerated ageing and disease. We review recent research that supports the idea that an important new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the genome against short-term transcriptional fluctuations, in a process we term ‘microguarding’. An additional emerging role for miRNAs is as ‘micromessengers’—through alteration of gene expression in target cells to which they are trafficked within microvesicles. We describe the scant but emerging evidence that miRNAs can be moved between different cells, individuals and even species, to exert biologically significant responses. With these two new roles, miRNAs have the potential to protect against deleterious gene expression variation from perturbation and to themselves perturb the expression of genes in target cells. These interactions between cells will frequently be subject to conflicts of interest when they occur between unrelated cells that lack a coincidence of fitness interests. Hence, there is the potential for miRNAs to represent both a means to resolve conflicts of interest, as well as instigate them. We conclude by exploring this conflict hypothesis, by describing some of the initial evidence consistent with it and proposing new ideas for future research into this exciting topic

‘Our newsroom in the cloud’: Slack, virtual newsrooms and journalistic practice

Virtual newsrooms have enormous potential: enabling journalists around the world to pool their knowledge, skills and perspectives within joint projects, such as the Panama Papers. These virtual newsrooms are supported by Online Collaborative Software (OCS), the most popular of which is Slack. But although many of the world’s top news organisations now use Slack, there is no empirical research examining its impact on workplace processes or culture. This article presents the results of a year-long ethnographic study of a global digital news outlet, whose remote journalists collaborate, almost exclusively, via Slack. We found that the platform deepened relationships and enabled new creative practices across geographic regions. However, it also contributed to the erasure of the line between private and professional spheres for workers, and introduced new opportunities for management to shape newsroom culture. We argue that the concept of ‘space’ as developed by Harvey can helpfully frame the analysis of these new, important digital platforms

An associative memory of Hodgkin-Huxley neuron networks with Willshaw-type synaptic couplings

An associative memory has been discussed of neural networks consisting of spiking N (=100) Hodgkin-Huxley (HH) neurons with time-delayed couplings, which memorize P patterns in their synaptic weights. In addition to excitatory synapses whose strengths are modified after the Willshaw-type learning rule with the 0/1 code for quiescent/active states, the network includes uniform inhibitory synapses which are introduced to reduce cross-talk noises. Our simulations of the HH neuron network for the noise-free state have shown to yield a fairly good performance with the storage capacity of $\alpha_c = P_{\rm max}/N \sim 0.4 - 2.4$ for the low neuron activity of $f \sim 0.04-0.10$. This storage capacity of our temporal-code network is comparable to that of the rate-code model with the Willshaw-type synapses. Our HH neuron network is realized not to be vulnerable to the distribution of time delays in couplings. The variability of interspace interval (ISI) of output spike trains in the process of retrieving stored patterns is also discussed.Comment: 15 pages, 3 figures, changed Titl

Seasonal changes in patterns of gene expression in avian song control brain regions.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity

Mice produce ultrasonic vocalizations by intra-laryngeal planar impinging jets

Rodent ultrasonic vocalizations (USVs) are a vital tool for linking gene mutations to behavior in mouse models of communication disorders, such as autism [1. However, we currently lack an understanding of how physiological and physical mechanisms combine to generate acoustic features of the vocalizations, and thus cannot meaningfully relate those features to experimental treatments. Here we test and provide evidence against the two leading hypotheses explaining USV production: superficial vocal fold vibrations [2, and a hole-tone whistle [3. Instead, we propose and provide theoretical and experimental evidence for an alternative and novel vocal production mechanism: a glottal jet impinging onto the laryngeal inner planar wall. Our data provide a framework for future research on the neuromuscular control of mouse vocal production and for interpreting mouse vocal behavior phenotypes.National Science Foundation (Grant ID: IOS 1257768), Danish Research Council, Carlsberg Foundatio

Review Article: Medical management of opioid dependence in South Africa

Medical practitioners in South Africa are increasingly confronted with requests to treat patients with opioid use disorders. Many do not possess the required knowledge and skills to deal with these patients effectively. This overview of the medical treatment of opioid dependence was compiled by an elected working group of doctors working in the field of substance dependence. Recommendations are based on current best practice derived from scientific evidence and consensus of the working group, but should never replace individual clinical judgement.South African Medical Journal Vol. 98 (4) 2008: pp. 280-28

A multi-disciplinary perspective on emergent and future innovations in peer review [version 2; referees: 2 approved]

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research. With the advent of web technologies, we are now witnessing a phase of innovation and experimentation in our approaches to peer review. These developments prompted us to examine emerging models of peer review from a range of disciplines and venues, and to ask how they might address some of the issues with our current systems of peer review. We examine the functionality of a range of social Web platforms, and compare these with the traits underlying a viable peer review system: quality control, quantified performance metrics as engagement incentives, and certification and reputation. Ideally, any new systems will demonstrate that they out-perform and reduce the biases of existing models as much as possible. We conclude that there is considerable scope for new peer review initiatives to be developed, each with their own potential issues and advantages. We also propose a novel hybrid platform model that could, at least partially, resolve many of the socio-technical issues associated with peer review, and potentially disrupt the entire scholarly communication system. Success for any such development relies on reaching a critical threshold of research community engagement with both the process and the platform, and therefore cannot be achieved without a significant change of incentives in research environments