PiRaNhA: A server for the computational prediction of RNA-binding residues in protein sequences

The PiRaNhA web server is a publicly available online resource that automatically predicts the location of RNA-binding residues (RBRs) in protein sequences. The goal of functional annotation of sequences in the field of RNA binding is to provide predictions of high accuracy that require only small numbers of targeted mutations for verification. The PiRaNhA server uses a support vector machine (SVM), with position-specific scoring matrices, residue interface propensity, predicted residue accessibility and residue hydrophobicity as features. The server allows the submission of up to 10 protein sequences, and the predictions for each sequence are provided on a web page and via email. The prediction results are provided in sequence format with predicted RBRs highlighted, in text format with the SVM threshold score indicated and as a graph which enables users to quickly identify those residues above any specific SVM threshold. The graph effectively enables the increase or decrease of the false positive rate. When tested on a non-redundant data set of 42 protein sequences not used in training, the PiRaNhA server achieved an accuracy of 85%, specificity of 90% and a Matthews correlation coefficient of 0.41 and outperformed other publicly available servers. The PiRaNhA prediction server is freely available at http://www.bioinformatics.sussex.ac.uk/PIRANHA. © The Author(s) 2010. Published by Oxford University Press

An RNA interference-based screen of transcription factor genes identifies pathways necessary for sensory regeneration in the avian inner ear

Sensory hair cells of the inner ear are the mechano-electric transducers of sound and head motion. In mammals, damage to sensory hair cells leads to hearing or balance deficits. Non-mammalian vertebrates such as birds can regenerate hair cells after injury. In a previous study, we characterized transcription factor gene expression during chicken hair cell regeneration. In those studies, a laser micro-beam or ototoxic antibiotics were used to damage the sensory epithelia (SE). The current study focused on 27 genes that were up-regulated in regenerating SE compared to untreated SE in the previous study. Those genes were knocked down by siRNA, to determine their requirement for supporting cell proliferation and to measure resulting changes in the larger network of gene expression. We identified 11 genes necessary for proliferation and also identified novel interactive relationships between many of them. Defined components of the WNT, PAX and AP1 pathways were shown to be required for supporting cell proliferation. These pathways intersect on WNT4, which is also necessary for proliferation. Among the required genes, the CCAAT enhancer binding protein, CEBPG, acts downstream of Jun Kinase and JUND in the AP1 pathway. The WNT co-receptor LRP5 acts downstream of CEBPG as does the transcription factor BTAF1. Both of these genes are also necessary for supporting cell proliferation. This is the first large scale screen of its type and suggests an important intersection between the AP1 pathway, the PAX pathway and WNT signaling in the regulation of supporting cell proliferation during inner ear hair cell regeneration

Landesque capital as an alternative to food storage in Melanesia: Irrigated taro terraces in New Georgia, Solomon Islands

In the Pacific islands, subsistence diversity made possible continuous production of food while welldeveloped exchange networks redistributed these foodstuffs as well as items within the prestige economy. All these were aspects of the ‘storage structures’ that enabled social and nutritional value to be saved, accumulated and later mobilised. In addition, there were investments in the land, landesque capital, which secured future food surpluses and so provided an alternative to food storage, in a region where the staple foods were mostly perishable, yams excepted, and food preservation was difficult. Landesque capital included such long-term improvements to productivity as terraces, mounds, irrigation channels, drainage ditches, soil structural changes and tree planting. These investments provided an effective alternative to food storage and made possible surplus production for exchange purposes. As an example, in the New Georgia group of the western Solomon Islands irrigated terraces, termed ruta, were constructed for growing the root crop taro (Colocasia esculenta). Surplus taro from ruta enabled inland groups to participate in regional exchange networks and so obtain the shell valuables that were produced by coastal groups. In this paper, we reconstruct how this exchange system worked in New Georgia using ethno-archaeological evidence, we chart its prehistoric rise and post-colonial fall, and we outline the factors that constrained its long-term expansion.Our gratitude for support during earlier fieldwork in the New Georgia group has already been expressed in previous publications. The 2014 project was supported by the Smuts Fund and Foreign Travel Fund, University of Cambridge, and by St John’s College, Cambridge.This is the accepted manuscript. The final version is available from Maney at http://dx.doi.org/10.1179/1749631414Y.000000004

Novel opsin gene variation in large-bodied, diurnal lemurs

Some primate populations include both trichromatic and dichromatic (red-green colour blind) individuals due to allelic variation at the X-linked opsin locus. This polymorphic trichromacy is well described in day-active New World monkeys. Less is known about colour vision in Malagasy lemurs, but, unlike New World monkeys, only some day-active lemurs are polymorphic, while others are dichromatic. The evolutionary pressures underlying these differences in lemurs are unknown, but aspects of species ecology, including variation in activity pattern, are hypothesized to play a role. Limited data on X-linked opsin variation in lemurs make such hypotheses difficult to evaluate. We provide the first detailed examination of X-linked opsin variation across a lemur clade (Indriidae). We sequenced the X-linked opsin in the most strictly diurnal and largest extant lemur, Indri indri, and nine species of smaller, generally diurnal indriids (Propithecus). Although nocturnal Avahi (sister taxon to Propithecus) lacks a polymorphism, at least eight species of diurnal indriids have two or more X-linked opsin alleles. Four rainforest-living taxa-I. indri and the three largest Propithecus species-have alleles not previously documented in lemurs. Moreover, we identified at least three opsin alleles in Indri with peak spectral sensitivities similar to some New World monkeys

Oral Advocacy Before the United States Supreme Court: Does It Affect the Justices\u27 Decisions?

Our empirical investigation focuses on two areas. First, we are interested in the quality of the oral advocacy presented to the Court, especially in terms of its etiology, as well as its effectiveness. We investigate these questions empirically by utilizing notes taken by Blackmun during oral arguments while he sat on the Court. Specifically, we here utilize the grades that Justice Blackmun assigned to each attorney’s oral arguments. This information allows us to answer two related questions: (1) why do some attorneys make better arguments before the Court; and (2) does the quality of oral advocacy influence who wins and loses? Second, we turn our attention to the information the Justices elicit about themselves during oral arguments. We analyze data on how often Justice Blackmun paid attention to the views expressed by his brethren during oral arguments (by examining when and why he recorded the comments of a particular colleague during orals) and the factors that led him to pay attention to some, but not all, of his colleagues. Additionally, we utilize Blackmun’s notes to demonstrate that what transpired during oral arguments provided him with an indication of whether his colleagues would vote to affirm or reverse the lower court decision at issue. We do so through an examination of when Justice Blackmun attempted to predict the votes of his colleagues in his oral argument notes. The Article proceeds as follows. In the next two Parts, we take up our first set of questions, which focuses on whether experienced and resourceful attorneys provide better arguments and whether arguments presented by counsel can affect decisions Justices make. Part IV focuses on whether Justices attempt to learn about their colleagues during oral arguments and whether such information affects the coalition-formation process that follows the arguments. Finally, we analyze whether what transpires during oral arguments can help a Justice make predictions about how a case will ultimately be decided

Hepatic transcriptional responses to copper in the three-spined stickleback are affected by their pollution exposure history

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Some fish populations inhabiting contaminated environments show evidence of increased chemical tolerance, however the mechanisms contributing to this tolerance, and whether this is heritable, are poorly understood. We investigated the responses of two populations of wild three-spined stickleback (Gasterosteus aculeatus) with different histories of contaminant exposure to an oestrogen and copper, two widespread aquatic pollutants. Male stickleback originating from two sites, the River Aire, with a history of complex pollution discharges, and Siblyback Lake, with a history of metal contamination, were depurated and then exposed to copper (46μg/L) and the synthetic oestrogen ethinyloestradiol (22ng/L). The hepatic transcriptomic response was compared between the two populations and to a reference population with no known history of exposure (Houghton Springs, Dorset). Gene responses included those typical for both copper and oestrogen, with no discernable difference in response to oestrogen between populations. There was, however, some difference in the magnitude of response to copper between populations. Siblyback fish showed an elevated baseline transcription of genes encoding metallothioneins and a lower level of metallothionein induction following copper exposure, compared to those from the River Aire. Similarly, a further experiment with an F1 generation of Siblyback fish bred in the laboratory found evidence for elevated transcription of genes encoding metallothioneins in unexposed fish, together with an altered transcriptional response to 125μg/L copper, compared with F1 fish originating from the clean reference population exposed to the same copper concentration. These data suggest that the stickleback from Siblyback Lake have a differential response to copper, which is inherited by the F1 generation in laboratory conditions, and for which the underlying mechanism may include an elevation of baseline transcription of genes encoding metallothioneins. The genetic and/or epigenetic mechanisms contributing to this inherited alteration of metallothionein transcription have yet to be established.This work was funded by the UK NERC postgenomic and proteomic programme grant NE/C507661/1 and by a Fisheries Society of the British Isles research grant to EMS. Birmingham functional genomics facilities were funded by BBSRC grant 6/JIF13209. We thank R.E. Godfrey, S. Jondhale, A. Jones, and L. Klovrza for technical assistance, J.K. Chipman for help and support, and the Environment Agency for provision of water chemistry data

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death