bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic expression of long noncoding RNAs reveals their potential roles in spermatogenesis and fertility†
Authors: Wichman Lauren , Somasundaram Saigopal , Breindel Christine , Valerio Dana M. , McCarrey John R. , Hodges Craig A. , Khalil Ahmad M. 
Published: July 2017

Abstract
Mammalian reproduction requires that males and females produce functional haploid germ cells through complex cellular differentiation processes known as spermatogenesis and oogenesis, respectively. While numerous studies have functionally characterized protein-coding genes and small noncoding RNAs (microRNAs and piRNAs) that are essential for gametogenesis, the roles of regulatory long noncoding RNAs (lncRNAs) are yet to be fully characterized. Previously, we and others have demonstrated that intergenic regions of the mammalian genome encode thousands of long noncoding RNAs, and many studies have now demonstrated their critical roles in key biological processes. Thus, we postulated that some lncRNAs may also impact mammalian spermatogenesis and fertility. In this study, we identified a dynamic expression pattern of lncRNAs during murine spermatogenesis. Importantly, we identified a subset of lncRNAs and very few mRNAs that appear to escape meiotic sex chromosome inactivation, an epigenetic process that leads to the silencing of the X- and Y-chromosomes at the pachytene stage of meiosis. Further, some of these lncRNAs and mRNAs show a strong testis expression pattern suggesting that they may play key roles in spermatogenesis. Lastly, we generated a mouse knockout of one X-linked lncRNA, Tslrn1 (testis-specific long noncoding RNA 1), and found that males carrying a Tslrn1 deletion displayed normal fertility but a significant reduction in spermatozoa. Our findings demonstrate that dysregulation of specific mammalian lncRNAs is a novel mechanism of low sperm count or infertility, thus potentially providing new biomarkers and therapeutic strategies.
Metagenomic Sequencing of an Echovirus 30 Genome From Cerebrospinal Fluid of a Patient With Aseptic Meningitis and Orchitis
Authors: Piantadosi Anne , Mukerji Shibani S , Chitneni Pooja , Cho Tracey A , Cosimi Lisa A , Hung Deborah T , Goldberg Marcia B , Sabeti Pardis C , Kuritzkes Daniel R , Grad Yonatan H 
Published: July 2017

Abstract
Enteroviruses cause a wide spectrum of clinical disease. In this study, we describe the case of a young man with orchitis and aseptic meningitis who was diagnosed with enterovirus infection. Using unbiased “metagenomic” massively parallel sequencing, we assembled a near-complete viral genome, the first use of this method for full-genome viral sequencing from cerebrospinal fluid. We found that the genome belonged to the subgroup echovirus 30, which is a common cause of aseptic meningitis but has not been previously reported to cause orchitis.
Techniques of Neutralization and Identity Work Among Accused Genocide Perpetrators
Authors: Bryant Emily , Schimke Emily Brooke , Nyseth Brehm Hollie , Uggen Christopher 
Published: July 2017

Abstract
Following the 1994 Rwandan genocide, many defendants on trial at the International Criminal Tribunal for Rwanda (ICTR) testified on their own behalf. This article analyzes transcripts of their testimonies to learn (1) how defendants discuss the grave crimes of which they are accused, and (2) how their explanatory styles allow them to rationalize their actions and negotiate their tarnished identities. We find that defendants employ Gresham Sykes and David Matza’s (1957) classic techniques of neutralization as a means of rationalization, impression management, and identity negotiation. Nevertheless, these techniques, along with those developed in the decades since, do not capture all aspects of defendants’ accounts. We thus identify additional techniques of neutralization to provide a more comprehensive understanding of how defendants account for their actions. By extending this classic literature, we call attention to the situational context of international trials, the nature of the crime of genocide, the relatively high social status many defendants once occupied, and existing narratives surrounding the legitimacy of the ICTR. In doing so, our analysis contributes to understandings of narratives of violence and accused genocide perpetrators.
Rule Activation and Ventromedial Prefrontal Engagement Support Accurate Stopping in Self-Paced Learning
Authors: O’Bryan Sean R. , Walden Eric , Serra Michael J. , Davis Tyler 
Published: July 2017

ABSTRACTWhen weighing evidence for a decision, individuals are continually faced with the choice of whether to gather more information or act on what has already been learned. The present experiment employed a self-paced category learning task and fMRI to examine the neural mechanisms underlying stopping of information search and how they contribute to choice accuracy. Participants learned to classify triads of face, object, and scene cues into one of two categories using a rule based on one of the stimulus dimensions. After each trial, participants were given the option to explicitly solve the rule or continue learning. Representational similarity analysis (RSA) was used to examine activation of rule-relevant information on trials leading up to a decision to solve the rule. We found that activation of rule-relevant information increased leading up to participants’ stopping decisions. Stopping was associated with widespread activation that included medial prefrontal cortex and visual association areas. Engagement of ventromedial prefrontal cortex (vmPFC) was associated with accurate stopping, and activation in this region was functionally coupled with signal in dorsolateral prefrontal cortex (dlPFC). Results suggest that activating rule information when deciding whether to stop an information search increases choice accuracy, and that the response profile of vmPFC during such decisions may provide an index of effective learning.
Decline of auditory-motor speech processing in older adults with hearing loss
Authors: Panouillères Muriel TN , Möttönen Riikka 
Published: July 2017

AbstractOlder adults often experience difficulties in understanding speech, partly because of age-related hearing loss. In young adults, activity of the left articulatory motor cortex is enhanced and it interacts with the auditory cortex via the left-hemispheric dorsal stream during speech processing. Little is known about the effect of ageing and age-related hearing loss on this auditory-motor interaction and speech processing in the articulatory motor cortex. It has been proposed that up-regulation of the motor system during speech processing could compensate for hearing loss and auditory processing deficits in older adults. Alternatively, age-related auditory deficits could reduce and distort the input from the auditory cortex to the articulatory motor cortex, suppressing recruitment of the motor system during listening to speech. The aim of the present study was to investigate the effects of ageing and age-related hearing loss on the excitability of the tongue motor cortex during listening to spoken sentences using transcranial magnetic stimulation and electromyography. Our results show that the excitability of the tongue motor cortex was facilitated during listening to speech in young and older adults with normal hearing. This facilitation was significantly reduced in older adults with hearing loss. These findings suggest a decline of auditory-motor processing of speech in adults with age-related hearing loss.
Discrete confidence levels revealed by sequential decisions
Authors: Lisi Matteo , Mongillo Gianluigi , Gorea Andrei 
Published: July 2017

AbstractWhether humans are optimal decision makers is still a debated issue in the realm of perceptual decisions. Taking advantage of the direct link between an optimal decision-making and the confidence in that decision, we offer a new dual-decisions method of inferring such confidence without asking for its explicit valuation. Our method circumvents the well-known miscalibration issue with explicit confidence reports as well as the specification of the cost-function required by ‘opt-out’ or post-decision wagering methods. We show that observers’ inferred confidence in their first decision and its use in a subsequent decision (conditioned upon the correctness of the first) fall short of both the ideal Bayesian strategy, as well as of an under-sampling approximation or a modified Bayesian strategy augmented with an additional bias term to accommodate global miscalibration of confidence. The observed data are instead significantly better fitted by a model positing that observers use only few confidence levels or states, at odds with the continuous confidence function of stimulus level prescribed by a normative behavior. These findings question the validity of normative-Bayesian accounts of subjective confidence and metaperceptual judgments.
Convis: A Toolbox To Fit and Simulate Filter-based Models of Early Visual Processing
Authors: Huth Jacob , Masquelier Timothée , Arleo Angelo 
Published: July 2017

1AbstractWe developed Convis, a Python simulation toolbox for large scale neural populations which offers arbitrary receptive fields by 3D convolutions executed on a graphics card. The resulting software proves to be flexible and easily extensible in Python, while building on the PyTorch library [32], which was previously used successfully in deep learning applications, for just-in-time optimization and compilation of the model onto CPU or GPU architectures. An alternative implementation based on Theano [33] is also available, although not fully supported.Through automatic differentiation, any parameter of a specified model can be optimized to approach a desired output which is a significant improvement over e.g. Monte Carlo or particle optimizations without gradients. We show that a number of models including even complex non-linearities such as contrast gain control and spiking mechanisms can be implemented easily.We show in this paper that we can in particular recreate the simulation results of a popular retina simulation software VirtualRetina [35], with the added benefit of providing (1) arbitrary linear filters instead of the product of Gaussian and exponential filters and (2) optimization routines utilizing the gradients of the model. We demonstrate the utility of 3d convolution filters with a simple direction selective filter. Also we show that it is possible to optimize the input for a certain goal, rather than the parameters, which can aid the design of experiments as well as closed-loop online stimulus generation. Yet, Convis is more than a retina simulator. For instance it can also predict the response of V1 orientation selective cells.Convis is open source under the GPL-3.0 license and available from https://github.com/jahuth/convis/ with documentation at https://jahuth.github.io/convis/.
Translational regulation by bacterial small RNAs via an unusual Hfq-dependent mechanism
Authors: Azam Muhammad S. , Vanderpool Carin K. 
Published: July 2017

ABSTRACTIn bacteria, the canonical mechanism of translational repression by small RNAs (sRNAs) involves sRNA-mRNA base pairing that occludes the ribosome binding site (RBS), directly preventing translation. In this mechanism, the sRNA is the direct regulator, while the RNA chaperone Hfq plays a supporting role by stabilizing the sRNA. There are a few examples where the sRNA does not directly interfere with ribosome binding, yet translation of the target mRNA is still inhibited. Mechanistically, this non-canonical regulation by sRNAs is poorly understood. Our previous work demonstrated repression of the mannose transportermanXmRNA by the sRNA SgrS, but the regulatory mechanism was unknown. Here, we report thatmanXtranslation is controlled by a molecular role-reversal mechanism where Hfq, not the sRNA, is the direct repressor. Hfq binding adjacent to themanXRBS is required for sRNA-mediated translational repression. Translation ofmanXis also regulated by another sRNA, DicF, via the same non-canonical Hfq-dependent mechanism. Our results suggest that the sRNAs recruit Hfq to its binding site or stabilize the mRNA-Hfq complex. This work adds to the growing number of examples of diverse mechanisms of translational regulation by sRNAs in bacteria.
Divergent gene expression levels between diploid and autotetraploidTolmiea(Saxifragaceae) relative to the total transcriptome, the cell, and biomass
Authors: Visger Clayton J. , Wong Gane K-S. , Zhang Yong , Soltis Pamela S. , Soltis Douglas E. 
Published: July 2017

SummaryStudies of gene expression and polyploidy are typically restricted to characterizing differences in transcript concentration. Integrating multiple methods of transcript analysis, we document a difference in transcriptome size, and make multiple comparisons of transcript abundance in diploid and autotetraploidTolmiea.We use RNA spike-in standards to identify and correct for differences in transcriptome size, and compare levels of gene expression across multiple scales: per transcriptome, per cell, and per biomass.In total, ~17% of all loci were identified as differentially expressed (DEGs) between the diploid and autopolyploid species. A shift in total transcriptome size resulted in only ~58% of the total DEGs being identified as differentially expressed following a per transcriptome normalization. When transcript abundance was normalized per cell, ~82% of the total DEGs were recovered. The discrepancy between per-transcriptome and per-cell recovery of DEGs occurs because per-transcriptome normalizations are concentration-based and therefore blind to differences in transcriptome size.While each normalization enables valid comparisons at biologically relevant scales, a holistic comparison of multiple normalizations provides additional explanatory power not available from any single approach. Notably, autotetraploid loci tend to conserve diploid-like transcript abundance per biomass through increased gene expression per cell, and these loci are enriched for photosynthesis-related functions.
Evolving Bacterial Fitness with an Expanded Genetic Code
Authors: Tack Drew S. , Cole Austin C. , Shroff R. , Morrow B.R. , Ellington Andrew D. 
Published: July 2017

AbstractEvolution has for the most part used the canonical 20 amino acids of the natural genetic code to construct proteins. While several theories regarding the evolution of the genetic code have been proposed, experimental exploration of these theories has largely been restricted to phylogenetic and computational modeling. The development of orthogonal translation systems has allowed noncanonical amino acids to be inserted at will into proteins. We have taken advantage of these advances to evolve bacteria to accommodate a 21 amino acid genetic code in which the amber codon ambiguously encodes either 3-nitro-L-tyrosine or stop. Such an ambiguous encoding strategy recapitulates numerous models for genetic code expansion, and we find that evolved lineages first accommodate the unnatural amino acid, and then begin to evolve on a neutral landscape where stop codons begin to appear within genes. The resultant lines represent transitional intermediates on the way to the fixation of a functional 21 amino acid code.
Endogenous synthesis of pyrethrins by cannabis
Authors: Devitt-Lee Adrian , Smith Douglas R. , Chen David , McKernan Kevin , Groves Simone , McCarthy Ciaran 
Published: July 2017

AbstractPyrethrins are a class of natural terpenoid pesticides produced byTanacetum cinerariifolium, commonly known as chrysanthemum. Here we present evidence that cannabis may be able to produce pyrethrins endogenously. Flower from a cannabis plant grown in a closed hydroponic environment contained 2.48 parts per million pyrethrin I by weight. A comparison of the genetics ofT. cinerariifoliumandCannabisdemonstrates Cannabis homologues of the genes that contribute to pyrethrins production inT. cinerariifolium. This provides a plausible pathway for the biosynthesis of pyrethrins in cannabis. Although preliminary, these data indicate a potentially significant confounding variable in both cannabis research and regulations on allowable pyrethrins residues in cannabis products.
Experience-dependent translational state defined by cell type-specific ribosome profiling
Authors: Eacker Stephen M. , Crawford Khadijah , Brichta Lars , Riessland Markus , Ingolia Nicholas T. , Greengard Paul , Dawson Ted M. , Dawson Valina L. 
Published: July 2017

AbstractExperience-dependent neuronal activity regulates the translation of mRNA, supporting memory formation. We have developed a new method termedtranslating ribosome affinity purification andribosomeprofiling (TRiP) which allows us to determine cell type-specific ribosome occupancy of mRNA with nucleotide resolution. Using TRiP we show that a memory-inducing experience creates a distinct translational state in mouse CA1 pyramidal cells. The experience-dependent translation state is characterized by enhanced translation of protein-coding open reading frames (ORFs) including numerous components of the actin cytoskeleton and calcium/calmodulin binding proteins, and by decreased translation of a defined subset of genes containing upstream ORFs (uORFs). Using animals heterozygous for an unphosphorylatable allele of the eukaryotic translation initiation factor 2α (eIF2α), we show that dephosphorylation of eIF2α contributes significantly to the experience-dependent translation state. These observations demonstrate that TRiP is a valuable methodology for studying physiologically relevant changes in translational state in genetically defined cell types.
Mammalian Orthoreovirus Factories Modulate Stress Granule Protein Localization by Interaction with G3BP1
Authors: Choudhury Promisree , Bussiere Luke , Miller Cathy L. 
Published: July 2017

ABSTRACTMammalian orthoreovirus (MRV) infection induces phosphorylation of translation initiation factor eIF2α which promotes formation of discrete cytoplasmic inclusions, termed stress granules (SGs). SGs are emerging as a component of the innate immune response to virus infection, and modulation of SG assembly is a common mechanism employed by viruses to counter this antiviral response. We previously showed that MRV infection induces SGs early, then interferes with SG formation as infection proceeds. In this work, we found that SG associated proteins localized to the periphery of virus-encoded cytoplasmic structures, termed virus factories (VFs), where viral transcription, translation, and replication occur. The localization of SG proteins to VFs was dependent on polysome dissociation and occurred via association of SG effector protein, G3BP1, with MRV non-structural protein σNS, which localizes to VFs via association with VF nucleating protein, μNS. Deletion analysis of the σNS RNA binding domain and G3BP1 RNA (RRM) and ribosomal (RGG) binding domains showed that the association and VF localization of G3BP1 is not occurring solely through RNA or ribosomal binding, but requires both RNA and ribosomal binding domains of G3BP1 for maximal VFL localization and σNS association. Co-expression of σNS and μNS resulted in disruption of normal SG puncta, and in cells lacking G3BP1, MRV replication was enhanced in a manner correlating with strain-dependent induction of host translation shutoff. These results suggest that σNS association with and relocalization of G3BP1 to the VF periphery plays a role in SG disruption to facilitate MRV replication in the host translational shutoff environment.IMPORTANCESGs and SG effector proteins have emerged as important, yet poorly understood, players in the host’s innate immune response to virus infection. MRV infection induces SGs early during infection that are dispersed and/or prevented from forming during late stages of infection despite continued activation of the eIF2α signaling pathway. Cellular and viral components involved in disruption of SGs during late stages of MRV infection remain to be elucidated. This work provides evidence that MRV disruption of SGs may be facilitated by association of MRV non-structural protein σNS with major SG effector protein G3BP1 and subsequent localization of G3BP1 and other SG associated proteins around the periphery of virus encoded factories, interrupting the normal formation of SGs. Our findings also reveal the importance of G3BP1 as an inhibitor of MRV replication during infection for the first time.
Rapid and scalable characterization of CRISPR technologies using an E. coli cell-free transcription-translation system
Authors: Marshall Ryan , Maxwell Colin S. , Collins Scott P. , Luo Michelle L. , Jacobsen Thomas , Beisel Chase L. , Noireaux Vincent 
Published: July 2017

ABSTRACTCRISPR-Cas systems have offered versatile technologies for genome engineering, yet their implementation has been outpaced by the ongoing discovery of new Cas nucleases and anti-CRISPR proteins. Here, we present the use of E. coli cell-free transcription-translation systems (TXTL) to vastly improve the speed and scalability of CRISPR characterization and validation. Unlike prior approaches that require protein purification or live cells, TXTL can express active CRISPR machinery from added plasmids and linear DNA, and TXTL can output quantitative dynamics of DNA cleavage and gene repression. To demonstrate the applicability of TXTL, we rapidly measure guide RNA-dependent DNA cleavage and gene repression for single- and multi-effector CRISPR-Cas systems, accurately predict the strength of gene repression in E. coli, quantify the inhibitory activity of anti-CRISPR proteins, and develop a fast and scalable high-throughput screen for protospacer-adjacent motifs. These examples underscore the potential of TXTL to facilitate the characterization and application of CRISPR technologies across their many uses.
Budding yeast Wpl1p regulates cohesin functions in cohesion, condensation and DNA repair by a common mechanism
Authors: Bloom Michelle S. , Guacci Vincent , Koshland Douglas 
Published: July 2017

AbstractCohesin tethers DNA to mediate sister chromatid cohesion, chromosome condensation, and DNA repair. How the cell regulates cohesin to perform these distinct functions remains to be elucidated. One cohesin regulator, Wpl1p, was characterized in the budding yeast,Saccharomyces cerevisiae, as a promoter of cohesion and as an inhibitor of condensation. Here we provide evidence that Wpl1p has an additional function in promoting the timely repair of DNA damage induced during S-phase. In addition to these biological functions, Wpl1p has been implicated as an inhibitor of cohesin’s ability to stably bind DNA by modulating the interface between two subunits (Mcd1p and Smc3p) of the core cohesin complex. We show that Wpl1p likely modulates this interface to regulate all cohesin’s biological functions. Furthermore, we show that Wpl1p regulates cohesion and condensation through the formation of a functional complex with another cohesin-associated factor, Pds5p. In contrast, Wpl1p regulates DNA repair independently of its interaction with Pds5p. Together these results suggest that Wpl1p regulates distinct biological functions of cohesin by Pds5p-dependent and – independent modulation of the Smc3p-Mcd1p interface.