bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational analysis of the pro‐peptide of a marine intracellular subtilisin protease supports its role in inhibition
Authors: Bjerga Gro E. K. , Larsen Øivind , Arsın Hasan , Williamson Adele , García‐Moyano Antonio , Leiros Ingar , Puntervoll Pål 
Published: June 2018

AbstractIntracellular subtilisin proteases (ISPs) have important roles in protein processing during the stationary phase in bacteria. Their unregulated protein degrading activity may have adverse effects inside a cell, but little is known about their regulatory mechanism. Until now, ISPs have mostly been described from Bacillus species, with structural data from a single homolog. Here, we study a marine ISP originating from a phylogenetically distinct genus, Planococcus sp. The enzyme was successfully overexpressed in E. coli, and is active in presence of calcium, which is thought to have a role in minor, but essential, structural rearrangements needed for catalytic activity. The ISP operates at alkaline pH and at moderate temperatures, and has a corresponding melting temperature around 60 °C. The high‐resolution 3‐dimensional structure reported here, represents an ISP with an intact catalytic triad albeit in a configuration with an inhibitory pro‐peptide bound. The pro‐peptide is removed in other homologs, but the removal of the pro‐peptide from the Planococcus sp. AW02J18 ISP appears to be different, and possibly involves several steps. A first processing step is described here as the removal of 2 immediate N‐terminal residues. Furthermore, the pro‐peptide contains a conserved LIPY/F‐motif, which was found to be involved in inhibition of the catalytic activity.
A Familial Case of Multicentric Carpotarsal Osteolysis Syndrome and Treatment Outcome
Authors: Gomes Alicia , Weiser Peter , Descartes Maria , Upadia Jariya 
Published: June 2018

AbstractMulticentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder caused by heterozygous mutations in the MAFB gene (v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B). This is an autosomal dominant condition with a high frequency of sporadic cases. MCTO is characterized by osteolysis of the carpal, metacarpal, and tarsal bones beginning in early childhood with musculoskeletal rheumatologic symptoms such as pain and disability. Renal involvement can be seen in more than half of the patients; from ages 16 months to 42 years and manifests from proteinuria to end-stage renal failure requiring renal transplantation. The association of MAFB gene mutations with this genetic condition has aided in understanding the pathophysiology of the disease. We report here a 7-year-old Caucasian boy and his 33-year-old mother diagnosed with MCTO, with the boy having concomitant juvenile idiopathic arthritis. He was initially diagnosed with arthritis at age 5 years based on bilateral wrist synovial swelling, morning stiffness, and weakness with family history of his mother being diagnosed with erosive psoriatic arthritis leading to limb deformities. Initial therapy for the boy included methotrexate and infliximab with moderate response. Later, during the course of his disease, he underwent a genetic evaluation at age 7 years for history of learning disabilities and dysmorphic features. Maternal evaluation and radiographic examination led to a clinical diagnosis of MCTO in the mother, and subsequent testing for MAFB gene in the son revealed a mutation at c.206C > T (p.Ser69Leu), the most commonly reported genetic change in MCTO. Nevertheless, further imaging still confirmed ongoing arthritis, and therapy was adjusted based on its progression including abatacept, tocilizumab, and pamidronate. Our report highlights the possibility of concomitant inflammatory arthropathy in MCTO.
Robotic-Assisted Sleeve Lobectomy Using the Four-Arm Technique in the DaVinci Si® and Xi® Systems
Authors: Egberts Jan-Hendrik , Möller Thorben , Becker Thomas 
Published: June 2018

AbstractSleeve lobectomy (SL) makes it possible to resect centrally located lung carcinoma oncological correct while protecting healthy lung tissue. However, this procedure is often limited with conventional video-assisted thoracoscopic surgery, due to the limited mobility of the rigid and long instruments and the limited visualization. Therefore, these interventions are often still performed in the open conventional technique with the well-known disadvantages. Particularly in the reconstruction of the respiratory tract, precise sewing must be performed in a small space to avoid stenosis of the different diameter of the lumina. Robotic surgery offers several advantages through an enlarged three-dimensional view and flexibility of the robotic instruments, which are particularly evident when sewing. So far, there are only a few reports of robotic SL. Here, we describe our experience of performing robotic SL with four arms on both, the currently available DaVinci Xi® and Si® systems.
Lack of Association of Intraventricular Hemorrhage with Retinopathy of Prematurity
Authors: Hand Ivan , Shrier Eric 
Published: June 2018

Objective Retinopathy of prematurity (ROP) is the primary cause of visual impairment in premature infants. Our objective was to study the relationship between ROP and intraventricular hemorrhage (IVH) in the premature infant.
Methods This study was a retrospective chart review of very low birthweight infants of 1,500 g or less admitted to Kings County Hospital Center's neonatal intensive care unit who were screened for ROP over a 6-year period.
Results Of 335 infants screened for ROP, 85 infants were identified to have ROP. Of these, 50 (56%) infants had stage 1 ROP, 25 (29%) had stage 2 ROP, 7 (8%) had stage 3 ROP, and 3 (4%) had stage 4 ROP. The incidence of IVH in our population was 14%. Multiple logistic regression demonstrated a significant association between ROP and gestational age (p = 0.001). There was no significant association between ROP stage and IVH grade. There was also no significant association between birthweight, ethnicity, or 5-minute Apgar score.
Conclusions Our data demonstrated no association between IVH and severity of ROP. There was a statistically significant association between ROP and gestational age. We speculate that these data may be a reflection of improvement in neonatal care, with a declining incidence of IVH as well as increased ROP screening efforts.
Gaiareveals evidence for merged white dwarfs
Authors: Kilic Mukremin , Hambly N C , Bergeron P , Genest-Beaulieu C , Rowell N 
Published: June 2018

AbstractWe use Gaia Data Release 2 to identify 13 928 white dwarfs (WDs) within 100 pc of the Sun. The exquisite astrometry from Gaia reveals for the first time a bifurcation in the observed WD sequence in both Gaia and the Sloan Digital Sky Survey (SDSS) passbands. The latter is easily explained by a helium atmosphere WD fraction of 36 per cent. However, the bifurcation in the Gaia colour–magnitude diagram depends on both the atmospheric composition and the mass distribution. We simulate theoretical colour–magnitude diagrams for single and binary WDs using a population synthesis approach and demonstrate that there is a significant contribution from relatively massive WDs that likely formed through mergers. These include WD remnants of main-sequence (blue stragglers) and post-main-sequence mergers. The mass distribution of the SDSS subsample, including the spectroscopically confirmed WDs, also shows this massive bump. This is the first direct detection of such a population in a volume-limited sample.
Characterization of nonlinear receptive fields of visual neurons by convolutional neural network
Authors: Ukita Jumpei , Yoshida Takashi , Ohki Kenichi 
Published: June 2018

AbstractA comprehensive understanding of the stimulus-response properties of individual neurons is necessary to crack the neural code of sensory cortices. However, a barrier to achieving this goal is the difficulty of analyzing the nonlinearity of neuronal responses. In computer vision, artificial neural networks, especially convolutional neural networks (CNNs), have demonstrated state-of-the-art performance in image recognition by capturing the higher-order statistics of natural images. Here, we incorporated CNN for encoding models of neurons in the visual cortex to develop a new method of nonlinear response characterization, especially nonlinear estimation of receptive fields (RFs), without assumptions regarding the type of nonlinearity. Briefly, after training CNN to predict the visual responses of neurons to natural images, we synthesized the RF image such that the image would predictively evoke a maximum response (“maximization-of-activation” method). We first demonstrated the proof-of-principle using a dataset of simulated cells with various types of nonlinearity, revealing that CNN could be used to estimate the nonlinear RF of simulated cells. In particular, we could visualize various types of nonlinearity underlying the responses, such as shift-invariant RFs or rotation-invariant RFs. These results suggest that the method may be applicable to neurons with complex nonlinearities, such as rotation-invariant neurons in higher visual areas. Next, we applied the method to a dataset of neurons in the mouse primary visual cortex (V1) whose responses to natural images were recorded via two-photon Ca2+ imaging. We could visualize shift-invariant RFs with Gabor-like shapes for some V1 neurons. By quantifying the degree of shift-invariance, each V1 neuron was classified as either a shift-variant (simple) cell or shift-invariant (complex-like) cell, and these two types of neurons were not clustered in cortical space. These results suggest that the novel CNN encoding model is useful in nonlinear response analyses of visual neurons and potentially of any sensory neurons.
Frequent translation of small open reading frames in evolutionary conserved lncRNA regions
Authors: Ruiz-Orera Jorge , Albà M.Mar 
Published: June 2018

SUMMARYThe mammalian transcriptome includes thousands of transcripts that do not correspond to annotated protein-coding genes. Although many of these transcripts show homology between human and mouse, only a small proportion of them have been functionally characterized. Here we use ribosome profiling data to identify translated open reading frames, as well as non-ribosomal protein-RNA interactions, in evolutionary conserved and non-conserved transcripts. We find that conserved regions are subject to significant evolutionary constraints and are enriched in translated open reading frames, as well as non-ribosomal protein-RNA interaction signatures, when compared to non-conserved regions. Translated ORFs can be divided in two classes, those encoding functional micropeptides and those that show no evidence of protein functionality. This study underscores the importance of combining evolutionary and biochemical measurements to advance in a more complete understanding of the transcriptome.
The effects of drought and nutrient addition on soil organisms vary across taxonomic groups, but are constant across seasons
Authors: Siebert Julia , Sünnemann Marie , Auge Harald , Berger Sigrid , Cesarz Simone , Ciobanu Marcel , Guerrero-Ramírez Nathaly R. , Eisenhauer Nico 
Published: June 2018

AbstractAnthropogenic global change alters the activity and functional composition of soil communities that are responsible for crucial ecosystem functions and services. Two of the most pervasive global change drivers are drought and nutrient enrichment. However, the responses of soil organisms to interacting global change drivers remain widely unknown. We tested the interactive effects of extreme drought and fertilization on soil biota ranging from microbes to invertebrates across seasons. We expected drought to reduce the activity of soil organisms and fertilization to induce positive bottom-up effectsviaincreased plant productivity. Furthermore, we hypothesized fertilization to reinforce drought effects through enhanced plant growth, resulting in even dryer soil conditions. Our results revealed that drought had detrimental effects on soil invertebrate feeding activity and simplified nematode community structure, whereas soil microbial activity and biomass were unaffected. Microbial biomass increased in response to fertilization, whereas invertebrate feeding activity substantially declined. Notably, these effects were consistent across seasons. The dissimilar responses suggest that soil biota differ vastly in their vulnerability to global change drivers. As decomposition and nutrient cycling are driven by the interdependent concurrence of microbial and faunal activity, this may imply far-reaching consequences for crucial ecosystem processes in a changing world.
Regulation of the Unfolded Protein Response by BiP AMPylation protects photoreceptors from light-dependent degeneration
Authors: Moehlman Andrew T. , Casey Amanda K. , Servage Kelly , Orth Kim , Krämer Helmut 
Published: June 2018

AbstractIn response to environmental, developmental, and pathological stressors, cells engage homeostatic pathways to maintain their function. Among these pathways, the Unfolded Protein Response protects cells from the accumulation of misfolded proteins in the ER. Depending on ER stress levels, the ER-resident Fic protein catalyzes AMPylation or de-AMPylation of BiP, the major ER chaperone and regulator of the Unfolded Protein Response. This work elucidates the importance of the reversible AMPylation of BiP in maintaining theDrosophilavisual system in response to stress. After 72 hours of constant light, photoreceptors offic-null and AMPylation-resistantBiPT366Amutants, but not wild-type flies, display loss of synaptic function, disintegration of rhabdomeres, and excessive activation of ER stress reporters. Strikingly, this phenotype is reversible: photoreceptors regain their structure and function within 72 hours once returned to a standard light:dark cycle. These findings show that Fic-mediated AMPylation of BiP is required for neurons to adapt to transient stress demands.
Predicting and Analyzing the Response to Selection on Correlated Characters
Authors: Van Dooren Tom J.M , Allen Cerisse E. , Beldade Patrícia 
Published: June 2018

AbstractThe breeder’s equation generally provides robust predictions for the short-term evolution of single characters. When selection targets two or more characters simultaneously, there are often large discrepancies between predicted and observed responses. We assessed how well this standard model predicts responses to bivariate selection on wing color pattern characteristics in the tropical butterflyBicyclus anynana. In separate laboratory selection experiments, two sets of serially repeated eyespots were subjected to ten generations of concerted and antagonistic selection for either size or color composition. We compared predicted and actual selection responses over successive generations, using the phenotypic data, selection differentials, and estimates of the genetic variance-covariance matrixG. We found differences in the precision of predictions between directions of selection but did not find any evidence of systematic biases in our predictions depending on the direction of selection. Our investigation revealed significant environmental effects on trait evolution across generations. When these were accounted for, predictions using the standard model improved considerably. In the experiment on eyespot size, secondary splitting of selection lines allowed the estimation of changes inGafter nine generations of selection. Changes were not in general agreement with expectations from the breeder’s equation. A contour plot of prediction errors across trait space suggests that directional epistasis in the eyespot genotype-phenotype map might occur but estimates of changes inGare too model-dependent to verify whether they agree with that hypothesis. Altogether, our results underscore the need for quantitative genetics to investigate and estimate potential effects of multivariate non-linear genotype-phenotype maps and of environmental effects onG.
A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes
Authors: Sun Yan , Kim Eun Ji , Felt Sébastien A. , Taylor Louis J. , Agarwal Divyansh , Grant Gregory R. , López Carolina B. 
Published: June 2018

AbstractDefective viral genomes of the copy-back type (cbDVGs) are the primary initiators of the antiviral immune response during infection with respiratory syncytial virus (RSV) bothin vitroandin vivo.However, the mechanism governing cbDVG generation remains unknown, thereby limiting our ability to manipulate cbDVG content in order to modulate the host response to infection. Here we report a specific genomic signal that mediates the generation of RSV cbDVGs. Using a customized bioinformatics tool, we identified regions in the RSV genome frequently used to generate cbDVGs during infection. We then created a minigenome system to validate the function of one of these sequences and to determine if specific nucleotides were essential for cbDVG generation at that position. Further, we created a recombinant virus that selectively produced a specific cbDVG based on variations introduced in this sequence. The identified sequence was also found as a common site for cbDVG generation during natural RSV infections, and common cbDVGs generated at this sequence were found among samples from various infected patients. These data demonstrate that sequences encoded in the viral genome are critical determinants of the location of cbDVG generation and, therefore, this is not a stochastic process. Most importantly, these findings open the possibility of genetically manipulating cbDVG formation to modulate infection outcome.Author summaryCopy-back defective viral genomes (cbDVGs) regulate infection and pathogenesis ofMononegavirales.cbDVG are believed to arise from random errors that occur during virus replication and the predominant hypothesis is that the viral polymerase is the main driver of cbDVG generation. Here we describe a specific genomic sequence in the RSV genome that is necessary for the generation of a large proportion of the cbDVG population present during infection. We identified specific nucleotides that when modified altered cbDVG generation at this position, and we created a recombinant virus that selectively produced cbDVGs based on mutations in this sequence. These data demonstrate that the generation of RSV cbDVGs is regulated by specific viral sequences and that these sequences can be manipulated to alter the content and quality of cbDVG generated during infection.
14-3-3 recruits keratin intermediate filaments to mechanically sensitive cell-cell contacts
Authors: Mariani Richard A. , Paranjpe Shalaka , Dobrowolski Radek , Weber Gregory F. 
Published: June 2018

AbstractIntermediate filament cytoskeletal networks simultaneously support mechanical integrity and influence signal transduction pathways. Marked remodeling of the keratin intermediate filament network accompanies collective cellular morphogenetic movements that occur during early embryonic development in the frogXenopus laevis. While this reorganization of keratin is initiated by force transduction on cell-cell contacts mediated by C-cadherin, the mechanism by which keratin filament reorganization occurs remains poorly understood. In this work we demonstrate that 14-3-3 proteins regulate keratin reorganization dynamics in embryonic mesendoderm cells fromXenopusgastrula. 14-3-3 co-localizes with keratin filaments near cell-cell junctions in migrating mesendoderm. Co-immunoprecipitation, mass spectrometry and bioinformatic analyses indicate Keratin 19 is a target of 14-3-3 in the whole embryo and, more specifically, mesendoderm tissue. Inhibition of 14-3-3 results in both the decreased exchange of keratin subunits into filaments and blocks keratin filament recruitment toward cell-cell contacts. Synthetically coupling 14-3-3 to Keratin 19 through a unique fusion construct conversely induces the localization of this keratin population to the region of cell-cell contacts. Taken together, these findings indicate that 14-3-3 acts on keratin intermediate filaments and is involved in their reorganization to sites of cell adhesion.
Reassociation of an invasive plant with its specialist herbivore provides a test of the shifting defence hypothesis
Authors: Wan Jinlong , Huang Bei , Yu Hua , Peng Shaolin 
Published: June 2018

Abstract

The shifting defence hypothesis (SDH) predicts that after invasive plants are introduced to new ranges, they will evolve reduced resistance to specialist herbivores and increased resistance to generalist herbivores because they can escape from specialists but are still attacked by generalists in their nonnative ranges. For this to be true, the subsequent introduction of native specialist herbivores should reverse the above evolutionary processes, but evidence collected so far is scarce.

Here, we address this research gap by comparing resistance to specialist and generalist herbivores and resistance‐related traits in the invasive plant Ambrosia artemisiifolia from five populations with about a decade history of infestation by the accidentally introduced native specialist leaf beetle Ophraella communa (infested populations), and three populations without such infestation history (uninfested populations).

In common garden experiments, the specialist O. communa performed better on uninfested populations than on infested populations, whereas two generalist insects, Spodoptera litura and Helicoverpa armigera, performed better on infested populations. Chemical analyses showed that plants from infested populations had lower concentrations of chlorogenic acid, an antigeneralist secondary compound that can attract O. communa. Furthermore, across mother plants from all populations studied, chlorogenic acid content was negatively correlated with larval growth of S. litura and positively correlated with that of O. communa. Finally, quantitative defence traits did not differ between infested and uninfested populations.

Although our results are most consistent with rapid evolution caused by enemy reassociation, we cannot exclude the possibility that observed differences in resistance result from multiple introductions or selections from other environmental factors.

Synthesis. These results suggest that reassociation with a specialist herbivore from the native range may result in a rapid evolution of increased resistance to specialist herbivores and reduced resistance to generalist herbivores in the introduced range, which is likely to be mediated by the reduced production of secondary chemicals that can deter generalists while attracting the introduced specialist. This study supports the shifting defence hypothesis (SDH) from a new viewpoint, emphasizing the importance of incorporating the impacts of both specialist and generalist herbivores when evaluating the long‐term control effects of classical biological control programmes.