bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gemin4is an essential gene in mice, and its overexpression in human cells causes relocalization of the SMN complex to the nucleoplasm
Authors: Meier Ingo D. , Walker Michael P. , Matera A. Gregory 
Published: January 2018

AbstractGemin4 is a member of the Survival Motor Neuron (SMN) protein complex, which is responsible for the assembly and maturation of Sm-class small nuclear ribonucleoproteins (snRNPs). In metazoa, Sm snRNPs are assembled in the cytoplasm and subsequently imported into the nucleus. We previously showed that the SMN complex is required for snRNP importin vitro, although it remains unclear which specific components direct this process. Here, we report that Gemin4 overexpression drives SMN and the other Gemin proteins from the cytoplasm into the nucleus. Moreover, it disrupts the subnuclear localization of the Cajal body marker protein, coilin, in a dose-dependent manner. We identified three putative nuclear localization signal (NLS) motifs within Gemin4, one of which is necessary and sufficient to direct nuclear import. Overexpression of Gemin4 constructs lacking this NLS sequestered Gemin3 and, to a lesser extent Gemin2, in the cytoplasm but had little effect on the nuclear accumulation of SMN. We also investigated the effects of Gemin4 depletion in the laboratory mouse,mus musculus. Gemin4null mice die early in embryonic development, demonstrating that Gemin4 is an essential mammalian protein. When crossed onto a severe SMA mutant background, heterozygous loss ofGemin4failed to modify the early postnatal mortality phenotype of SMA type I (Smn-/-;SMN2+/+) mice. We conclude that Gemin4 plays an essential role in mammalian snRNP biogenesis, and may facilitate import of the SMN complex (or subunits thereof) into the nucleus.
Acute Hyperalgesia and Delayed Dry Eye After Corneal Abrasion Injury
Authors: Hegarty Deborah M. , Hermes Sam M. , Morgan Michael M. , Aicher Sue A. 
Published: January 2018

AbstractCorneal nerves mediate pain from the ocular surface, lacrimation, and blinking, all of which protect corneal surface homeostasis and help preserve vision. Corneal nerve density correlates with neuropathic pain states and is used as an assessment of small fiber neuropathies. Because pain, lacrimation and blinking are rarely assessed at the same time, it is not known if their regulatory mechanisms have similar temporal dynamics after acute corneal injury. We examined changes in corneal nerve density, evoked and spontaneous pain, and ocular homeostasis in Sprague-Dawley male rats after a superficial epithelial injury with heptanol that acutely abolished nerve endings within the central cornea. Despite a profound loss of epithelial nerve endings, pain was transiently enhanced after abrasion injury, while basal tear production was normal. We found no relationship between epithelial nerve density and pain or homeostatic responses. Axotomy following corneal abrasion increased expression of both ATF3 (a nerve injury marker) and CGRP (a nociceptive peptide) in trigeminal ganglia 24 hours after injury. These molecular changes were absent on the contralateral side, despite reductions in corneal epithelial nerve density in the uninjured eye. ATF3 and CGRP levels in trigeminal ganglion were normal at one week post-injury when pain responses were normal. In contrast, CGRP was upregulated in peripheral corneal endings one week after injury, when dry eye symptoms emerged. Our results demonstrate dynamic trafficking of CGRP within trigeminal sensory nerves, with elevations in the ganglion correlated with pain behaviors and elevations in peripheral endings correlated with dry eye symptoms.
Phylogenetic distribution of roseobacticides in the Roseobacter group and their effect on microalgae
Authors: Sonnenschein Eva C. , Phippen Christopher Broughton William , Bentzon-Tilia Mikkel , Rasmussen Silas Anselm , Nielsen Kristian Fog , Gram Lone 
Published: January 2018

SummaryThe Roseobacter-group species Phaeobacter inhibens produces the antibacterial tropodithietic acid (TDA) and the algaecidal roseobacticides with both compound classes sharing part of the same biosynthetic pathway. The purpose of this study was to investigate the production of roseobacticides more broadly in TDA-producing roseobacters and to compare the effect of producers and non-producers on microalgae. Of 33 roseobacters analyzed, roseobacticide production was a unique feature of TDA-producing P. inhibens, P. gallaeciensis and P. piscinae strains. One TDA-producing Phaeobacter strain, 27-4, was unable to produce roseobacticides, possibly due to a transposable element. TDA-producing Ruegeria mobilis and Pseudovibrio did not produce roseobacticides. Addition of roseobacticide-containing bacterial extracts affected the growth of the microalgae Rhodomonas salina, Thalassiosira pseudonana and Emiliania huxleyi, while growth of Tetraselmis suecica was unaffected. During co-cultivation, growth of E. huxleyi was initially stimulated by the roseobacticide producer DSM 17395, while the subsequent decline in algal cell numbers during senescence was enhanced. Strain 27-4 that does not produce roseobacticides had no effect on algal growth. Both bacterial strains, DSM 17395 and 27-4, grew during co-cultivation presumably utilizing algal exudates. Furthermore, TDA-producing roseobacters have potential as probiotics in marine larviculture and it is promising that the live feed Tetraselmis was unaffected by roseobacticides-containing extracts.Originality-significance statementSome Roseobacter-group bacteria produce the antibacterial compound tropodithetic acid (TDA) and have potential as probiotics in marine aquaculture. However, a few of these strains additionally produce algaecidal compounds, the roseobacticides, which would restrict their use in marine larviculture where algae are used as live feed for fish larvae. We herein found that roseobacticides are limited to TDA-producing Phaeobacter strains and were not biosynthesized by TDA-producers outside this genus. Roseobacticides affected several strains of microalgae, but not the chlorophyte that is used as live feed in the aquaculture industry. Thus, the application of Roseobacter strains as probiotics is not hampered. Furthermore, these results demonstrate how Roseobacter-group strains act as gardeners of microalgae and thereby would be involved in environmental processes on a larger scale.
Anterior thalamic excitation and feed-forward inhibition of presubicular neurons projecting to medial entorhinal cortex
Authors: Nassar Mérie , Simonnet Jean , Huang Li-Wen , Mathon Bertrand , Cohen Ivan , Bendels Michael H.K. , Beraneck Mathieu , Miles Richard , Fricker Desdemona 
Published: January 2018

ABSTRACTThe presubiculum contains head direction cells that are crucial for spatial navigation. Here, we examined the connectivity and strengths of thalamic inputs to presubicular layer 3 neurons projecting to the medial entorhinal cortex in the mouse. We recorded pairs of projection neurons and interneurons while optogenetically stimulating afferent fibers from the anterior thalamic nuclei (ATN). Thalamic input differentially affects presubicular neurons: layer 3 pyramidal neurons and fast-spiking parvalbumin expressing (PV) interneurons are directly and monosynaptically activated, with depressing dynamics, while somatostatin (SST) expressing interneurons are indirectly excited, during repetitive ATN activity. This arrangement ensures that the thalamic excitation of layer 3 cells is often followed by disynaptic inhibition. Feed-forward inhibition is largely mediated by PV interneurons which have a high probability of connection to presubicular pyramidal cells. Our data point to a specific role of presubicular microcircuits in shaping thalamic head-direction signals transmitted to medial entorhinal cortex: Short-latency PV cell activation may enforce temporally precise head direction tuning during fast turns. However, depression at ATN-PV synapses during repeated activation tends to facilitate pyramidal cell firing when head direction is maintained. Operations performed in presubicular layer 3 circuits seem well-adapted for spatial fine-tuning of head direction signals sent to the medial entorhinal cortex.SIGNIFICANCE STATEMENTHow microcircuits participate in shaping neural inputs is crucial to understanding information processing in the brain. Here, we show how the presubiculum may process thalamic head directional information before transmitting it to the medial entorhinal cortex. Synaptic inputs from the anterior thalamic nuclei (ATN) excite layer 3 pyramidal cells (PC) and parvalbumin (PV) interneurons, which mediate disynaptic feed-forward inhibition. Somatostatin (SST) interneurons are excited indirectly. Presubicular circuits may switch between two regimes according to the angular velocity of head movements. During immobility, SST-PC interactions support maintained head directional firing with attractor-like dynamics. During rapid head turns, in contrast, PV mediated feed-forward inhibition acts to tune the head direction signal transmitted to medial entorhinal cortex.
Inferring identical by descent sharing of sample ancestors promotes high resolution relative detection
Authors: Ramstetter Monica D. , Shenoy Sushila A. , Dyer Thomas D. , Lehman Donna M. , Curran Joanne E. , Duggirala Ravindranath , Blangero John , Mezey Jason G. , Williams Amy L. 
Published: January 2018

AbstractAs genetic datasets increase in size, the fraction of samples with one or more close relatives grows rapidly, resulting in sets of mutually related individuals. We present DRUID—Deep Relatedness Utilizing Identity by Descent—a method that works by inferring the identical by descent (IBD) sharing profile of an ungenotyped ancestor of a set of close relatives. Using this IBD profile, DRUID infers relatedness between unobserved ancestors and more distant relatives, thereby combining information from multiple samples to remove one or more generations between the deep relationships to be identified. DRUID constructs sets of close relatives by detecting full siblings and also uses a novel approach to identify the aunts/uncles of two or more siblings, recovering 92.2% of real aunts/uncles with zero false positives. In real and simulated data, DRUID correctly infers up to 10.5% more relatives than PADRE when using data from two sets of distantly related siblings, and 10.7–31.3% more relatives given two sets of siblings and their aunts/uncles. DRUID frequently infers relationships either correctly or within one degree of the truth, with PADRE classifying 43.3–58.3% of tenth degree relatives in this way compared to 79.6–96.7% using DRUID.
The Amyloid Clearance Defect in ApoE4 Astrocytes is Corrected by Epigenetic Restoration of NHE6
Authors: Prasad Hari , Rao Rajini 
Published: January 2018

SummaryThe accumulation of amyloid protein Aβ in senile plaques is a key driver and hallmark of Alzheimer disease (AD), a major cause of death and dementia in the elderly. The strongest genetic risk factor in sporadic AD is the ε4 allele of Apolipoprotein E (ApoE4), which potentiates pre-symptomatic endosomal dysfunction and defective clearance of Aβ, although how these two pathways are linked has been unclear. Here, we show that aberrant accumulation of endosomal protons in ApoE4 astrocytes traps the LRP1 receptor in non-productive intracellular compartments, leading to loss of surface expression and Aβ clearance. Hyperacidification of endosomal pH is caused by selective down regulation of the Na+/H+ exchanger NHE6, which functions as a critical proton leak pathway, in ApoE4 brain and astrocytes. In vivo, the NHE6KO mouse model shows elevated Aβ in the brain. Epigenetic restoration of NHE6 expression with histone deacetylase inhibitors normalized ApoE4-specific defects in endosomal pH, LRP1 trafficking and amyloid clearance. Thus, NHE6 is a prominent effector of ApoE4 and emerges as a promising therapeutic target in Alzheimer disease.
Investigating the viral ecology of global bee communities with high-throughput metagenomics
Authors: Galbraith David A. , Fuller Zachary L. , Brockmann Axel , Frazier Maryann , Gikungu Mary W. , Kapheim Karen M. , Kerby Jeffrey T. , Kocher Sarah D. , Losyev Oleksiy , Muli Elliud , Patch Harland M. , Sakamoto Joyce M. , Stanley Scott , Vaudo Anthony D. , Grozinger Christina M. 
Published: January 2018

ABSTRACTBee viral ecology is a fascinating emerging area of research: viruses exert a range of effects on their hosts, exacerbate the impacts of other environmental stressors, and, importantly, are readily shared across multiple bee species in a community. However, our understanding of bee viral communities is limited, as it is primarily derived from studies of North American and European Apis mellifera populations. Here, we examined viruses in populations of A. mellifera and 11 other bee species from 9 countries, across 5 continents and Oceania. We developed a novel pipeline to rapidly, inexpensively, and robustly screen for bee viruses. This pipeline includes purification of encapsulated RNA/DNA viruses, sequence-independent amplification, high throughput sequencing, integrated assembly of contigs, and filtering to identify contigs specifically corresponding to viral sequences. We identified sequences corresponding to (+)ssRNA, (-)ssRNA, dsRNA, and ssDNA viruses. Overall, we found 127 contigs corresponding to novel viruses (i.e. previously not observed in bees), with 29 represented by >0.1 % of the reads in a given sample. These viruses and viral families were distributed across multiple regions and species. This study provides a robust pipeline for metagenomics analysis of viruses, and greatly expands our understanding of the diversity of viruses found in bee communities.
Impact of stimulus size and orientation on individual face decoding in monkey face-selective cortex
Authors: Taubert Jessica , Van Belle Goedele , Vogels Rufin , Rossion Bruno 
Published: January 2018

ABSTRACTFace-selective neurons in the monkey temporal cortex discharge at different rates in response to pictures of different faces. Here we tested whether the population response of neurons in the face-selective area ML (located in the middle Superior Temporal Sulcus) tolerates two affine transformations; one, picture-plane inversion, known to have a deleterious impact on the average response of face-selective neurons and the other, stimulus size, thought to have little or no impact on face-selective neurons. We recorded the response of 57 ML neurons in two monkeys. Face stimuli were presented at two sizes (10 and 5 degrees of visual angle) and two orientations (upright and inverted). The results indicate that different faces elicited distinct patterns of activity across ML neurons that were tolerant of changes in size. However, the results of the orientation manipulation were mixed; despite observing a reduced response to inverted faces, classifier performance was above chance for both upright and inverted faces and the classification score did not differ significantly for inverted and upright faces. We conclude that population responses in area ML to different faces are dependent on stimulus orientation but are more tolerant to changes in stimulus size.
Managing e-books in a business school library: case study of Ebrary Academic Complete
Authors: Anilkumar Hanumappa , Dora Mallikarjun , Desai Asha 
Published: January 2018

Purpose
The purpose of the study is to review the e-books collection, namely, Ebrary Academic Complete, by understanding its features, cost and usage at Vikram Sarabhai Library, Indian Institute of Management Ahmedabad (IIMA). The study attempts to understand the usefulness of Ebrary in terms of its currency of titles, publishers, subjects and cost.

Design/methodology/approach
The paper is based on five-year usage data of Ebrary Academic Complete at Vikram Sarabhai Library, IIMA. The data on usage of Ebrary was downloaded and analyzed on different parameters to find out the overall value or use of Ebrary Academic Complete package from the perspective of a management library.

Findings
The research concluded that there was an increase in usage of Ebrary Academic Complete over time. The subject analysis revealed that titles from “Business and Economics”, “Computers” and “Social Science” were the highest used. The publisher analysis indicated that John Wiley & Sons topped in both the highest number of titles in the package and highest used titles. The annual subscription fee model of Ebrary Academic Complete adopted by Vikram Sarabhai Library was working well with a gradual increase in usage bringing down the per title access costs.

Originality/value
The study helps in understanding the approach to evaluating e-book collections in terms of currency of content, subjects covered, publishers included and costs involved. The detailed analysis would assist libraries in decision-making with regard to e-book collection development.
Transitioning from unemployment to self-employment for over 50s
Authors: Kenny Breda , Rossiter Isabel 
Published: January 2018

PurposeThe purpose of this paper is to identify the entrepreneurial learning and support needs of older unemployed, highlighting the barriers that need to be addressed, and to explore the impact of a tailored entrepreneurship training programme.Design/methodology/approachAn interpretivist philosophical standpoint is adopted with an action research approach to engage key informants to design, implement and evaluate the programme. Focus groups and interviews with 132 older unemployed individuals and 50 stakeholders across six countries were conducted as well as pre- and post-programme evaluations and surveys with 55 programme participants across three countries.FindingsThis research provides a deeper understanding of the entrepreneurial learning and support needs of older unemployed.Research limitations/implicationsThe small sample size of participants measured using a hybrid measure of ESE is a limitation.Practical implicationsFor entrepreneurship educators, the components of designing and delivering an entrepreneurship programme for older unemployed are identified. For enterprise and unemployment support agencies, it provides evidence of the initial and ongoing support needs for starting and running a business in later life.Originality/valueA framework specific to older unemployed individuals turning towards self-employment or entrepreneurship is proposed and tested in this paper. The framework proposes that individual and contextual antecedents influence the decision to become self-employed in later life and that the training, support and entrepreneurial experience helps to overcome barriers and shapes individual and societal outcomes.
Beyond effectuation
Authors: Murdock Karen A. , Varnes Claus J. 
Published: January 2018

PurposeThe purpose of this paper is to show that the entrepreneurial project ongoingly is transformed. Empirically, three defining junctions demonstrate the malleability of the entrepreneurial project in perpetual action, expanding beyond effectuation theory on what constitutes given means, affordable loss, and other key concepts from this theoretical perspective. Drawing upon actor-network theory (ANT), this study demonstrates how different framing and support devices implicate different human and non-human actors in changing interpositions within the entrepreneurial process.Design/methodology/approachThis study uses a longitudinal case study design. The case provides an overview of a new business’s emergence based on three identified translations, each representing critical junctures in the business’s development. An ethnographic approach is selected, which combines observations with qualitative interviews. This design allows the authors to focus on how the project emerges and is continuously supported by allies but is sometimes not supported by various human and non-human actors.FindingsThis study demonstrates that the entrepreneurial project undertaken by the entrepreneurial network changes as new humans or non-humans become part of it. Including a resource in the network means simultaneously changing the network. This interactionism shows that what sparks interest or attracts resources to a business idea is not simply an influx of additional resources but is simultaneously a dynamic definition of the entrepreneurial endeavour.Originality/valueThis paper examines how ideas are transformed into business ventures by using the ANT to expand understanding from effectuation theory. This shows that means, for instance, are not given but are co-created by the process of translation. In addition, which losses are affordable can be determined by the process within which the entrepreneur frames the project and manages to associate allies within and into the network.
Growth expectations through innovative entrepreneurship
Authors: Poblete Carlos 
Published: January 2018

PurposeThe purpose of this paper is to propose a model suggesting that innovation may act as a motivating force that increases entrepreneurs’ growth expectations, in which entrepreneurs’ growth expectations are shaped by their subjective values and entrepreneurial experience moderates this relationship.Design/methodology/approachThis paper conducts statistical analysis on a sample of 11,579 entrepreneurs from 24 countries who participated in the IIIP survey of innovation in 2011 under the Global Entrepreneurship Monitor project.FindingsThe results suggest that entrepreneurs involved in innovative entrepreneurship are more likely to have higher growth expectations, with subjective values playing a direct and indirect role in entrepreneurs’ expectations of firm growth. Additionally, the results indicate that the duration of entrepreneurial experience moderates the relationship between strategic orientation and confidence in innovation. This finding suggests there is feedback between having beliefs about the benefits of innovation and being an innovative entrepreneur, resulting in an over-estimation – at least in comparative terms – regarding firm growth rates. This relationship is stronger for novice entrepreneurs since experienced entrepreneurs tend to be more cautious about their expectations of growing.Originality/valueThis study deepens our understanding of the complex processes through which organizational-level decisions ultimately influence individual-level factors. The present findings contribute to progress in this task by suggesting that strategies aimed at cultivating innovation feed entrepreneurs’ subjective values of innovation as well as expectations of growth. Although the duration of entrepreneurial experience moderates the relationship between acting as an innovative entrepreneur and subjective values of innovation, the results suggest that entrepreneurs’ expectations are primarily driven by their internal perceptions of reality.