bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell in situ transcriptomic map of astrocyte cortical layer diversity
Authors: Bayraktar Omer Ali , Bartels Theresa , Polioudakis Damon , Holmqvist Staffan , Haim Lucile Ben , Young Adam M.H. , Prakash Kirti , Brown Alexander , Paredes Mercedes F. , Kawaguchi Riki , Stockley John , Sabeur Khalida , Chang Sandra M. , Huang Eric , Hutchinson Peter , Ullian Erik M. , Geschwind Daniel H. , Coppola Giovanni , Rowitch David H.
Published: October 2018

During organogenesis, patterns and gradients of gene expression underlie organization and diversified cell specification to generate complex tissue architecture. While the cerebral cortex is organized into six excitatory neuronal layers, it is unclear whether glial cells are diversified to mimic neuronal laminae or show distinct layering. To determine the molecular architecture of the mammalian cortex, we developed a high content pipeline that can quantify single-cell gene expression in situ. The Large-area Spatial Transcriptomic (LaST) map confirmed expected cortical neuron layer organization and also revealed a novel neuronal identity signature. Screening 46 candidate genes for astrocyte diversity across the cortex, we identified grey matter superficial, mid and deep astrocyte identities in gradient layer patterns that were distinct from neurons. Astrocyte layers formed in early postnatal cortex and mostly persisted in adult mouse and human cortex. Mutations that shifted neuronal post-mitotic identity or organization were sufficient to alter glial layering, indicating an instructive role for neuronal cues. In normal mouse cortex, astrocyte layer patterns showed area diversity between functionally distinct cortical regions. These findings indicate that excitatory neurons and astrocytes cells are organized into distinct lineage-associated laminae, which give rise to higher order neuroglial complexity of cortical architecture.
Structure of the large extracellular loop of FtsX and its interaction with the essential peptidoglycan hydrolase PcsB inStreptococcus pneumoniae
Authors: Rued Britta E. , Alcorlo Martín , Edmonds Katherine A. , Martínez-Caballero Siseth , Straume Daniel , Fu Yue , Bruce Kevin E. , Wu Hongwei , Håvarstein Leiv Sigve , Hermoso Juan A. , Winkler Malcolm E. , Giedroc David P.
Published: October 2018

Streptococcus pneumoniaeis a leading killer of infants and immunocompromised adults and has become increasingly resistant to major antibiotics. Therefore, the development of new antibiotic strategies is desperately needed. Targeting bacterial cell division is one such strategy, specifically targeting essential proteins for the synthesis and breakdown of peptidoglycan. One complex important to this process is FtsEX. FtsEX comprises an integral membrane protein (FtsX) and cytoplasmic ATPase (FtsE) that resembles an ATP-binding cassette (ABC) transporter. Here, we present NMR solution structural and crystallographic models of the large extracellular domain of FtsX, denoted ECL1. The structure of ECL1 reveals an upper extended β-hairpin and a lower α-helical lobe, each extending from a mixed α-β core. The helical lobe mediates a physical interaction with the peptidoglycan hydrolase PcsB, via the coiled-coil domain of PcsB (PcsB-CC). Characterization ofS. pneumoniaeD39 derived strains harboring mutations in the α-helical lobe shows that this subdomain is essential for cell viability and required for proper cell division ofS. pneumoniae.

IMPORTANCE

FtsX is a ubiquitous bacterial integral membrane protein involved in cell division that regulates the activity of peptidoglycan (PG) hydrolases. FtsX is representative of a large group of ABC3 superfamily proteins that function as “mechanotransmitters,” proteins that relay signals from inside to the outside of the cell. Here we present a structural characterization of the large extracellular loop (ECL1) of FtsX from the human opportunistic pathogenStreptococcus pneumoniae. We show a direct interaction between the peptidoglycan hydrolase PcsB and FtsX, and demonstrate that this interaction is essential for cell viability. As such, FtsX represents an attractive, conserved target for the development of new classes of antibiotics.
Male and female bees show large differences in floral preference
Authors: Roswell Michael , Dushoff Jonathan , Winfree Rachael
Published: October 2018

Intraspecific variation in foraging niche can drive food web dynamics and ecosystem processes. Field studies and theoretical analysis of plant-pollinator interaction networks typically focus on the partitioning of the floral community between pollinator species, with little attention paid to intraspecific variation among plants or foraging bees. In other systems, male and female animals exhibit different, cascading, impacts on interaction partners. Although the foraging ecology of male bees is little known, we expect foraging preferences to differ between male and female bees, which could strongly impact plant-pollinator interaction outcomes.

We designed an observational study to evaluate the strength and prevalence of sexually dimorphic foraging preferences in bees.

We observed bees visiting flowers in semi-natural meadows in New Jersey, USA. To detect differences in flower use against a shared background resource availability, we maximized the number of interactions observed within narrow spatio-temporal windows. To distinguish observed differences in bee use of flower species, which can reflect abundance patterns and sampling effects, from underlying differences in bee preferences, we analyzed our data with both a permutation-based null model and random effects models.

We found that the diets of male and female bees of the same species were often as dissimilar as the diets of bees of different species. Furthermore, we demonstrate differences in preference between male and female bees, and identify plant species that are particularly attractive to each sex. We show that intraspecific differences in preference can be robustly identified within interactions between hundreds of species, without precisely quantifying resource availability, and despite high phenological turnover.

Given the large differences in flower use and preference between male and female bees, ecological sex differences should be integrated into studies of bee demography, plant pollination, and coevolutionary relationships between flowers and insects.
High-level correction of the sickle mutation amplified in vivo during erythroid differentiation
Authors: Magis Wendy , DeWitt Mark A. , Wyman Stacia K. , Vu Jonathan T. , Heo Seok-Jin , Shao Shirley J , Hennig Fiona , Romero Zulema G. , Campo-Fernandez Beatriz , McNeill Matthew , Rettig Garrett R. , Sun Yongming , Lau Patrick J. , Wang Yu , Behlke Mark A. , Kohn Donald B. , Boffelli Dario , Walters Mark C. , Corn Jacob E. , Martin David I.K.
Published: October 2018

Sickle Cell Disease (SCD), one of the world’s most common genetic disorders, causes anemia and progressive multiorgan damage that typically shortens lifespan by decades; currently there is no broadly applicable curative therapy. Here we show that Cas9 RNP-mediated gene editing with an ssDNA oligonucleotide donor yields markerless correction of the sickle mutation in more than 30% of long-term engrafting human hematopoietic stem cells (HSCs), using a selection-free protocol that is directly applicable to a clinical setting. We further find that in vivo erythroid differentiation markedly enriches for corrected ß-globin alleles. Adoption of a high-fidelity Cas9 variant demonstrates that this approach can yield efficient editing with almost no off-target events. These findings indicate that the sickle mutation can be corrected in human HSCs at curative levels with a streamlined protocol that is ready to be translated into a therapy.

ONE SENTENCE SUMMARY

Cas9-mediated correction of the sickle mutation in human hematopoietic stem cells can be accomplished at curative levels.
The nuclear interactome of DYRK1A reveals a functional role in DNA damage repair
Authors: Guard Steven E. , Poss Zachary C. , Ebmeier Christopher C. , Pagratis Maria , Taatjes Dylan J. , Old William M.
Published: October 2018

Loss of function mutations in the protein kinase DYRK1A lead to a syndromic form of autism spectrum disorder and intellectual disability. Conversely, increased DYRK1A dosage is implicated in atypical brain development and neurocognitive deficits in trisomy 21. DYRK1A regulates a diverse array of cellular processes through kinase dependent and independent interactions with substrates and binding partners. Recent evidence implicates DYRK1A in direct regulation of the transcriptional machinery, but many of the molecular details are not yet known. Furthermore, the landscape of DYRK1A interactions in the nucleus is incomplete, impeding progress toward understanding its function in transcription. Here, we used immunoaffinity purification and mass spectrometry to identify nuclear interaction partners of endogenous DYRK1A. These were enriched in DNA damage repair factors, transcriptional elongation factors and E3 ubiquitin ligases. We validated an interaction with RNF169, a factor that promotes homology directed repair upon DNA damage. We further show that knockout of DYRK1A or treatment with DYRK1A inhibitors in HeLa cells impaired efficient recruitment of 53BP1 to DNA double strand breaks induced by ionizing radiation. This nuclear interactome thus reveals a new role for DYRK1A in DNA damage repair and provides a resource for exploring new functions of DYRK1A in the nucleus.
Herbarium records reveal early flowering in response to warming in the southern hemisphere
Authors: Daru Barnabas H. , Kling Matthew M. , Meineke Emily K. , van Wyk Abraham E.
Published: October 2018

Premise of the Study

Herbarium specimens are increasingly used as records of plant flowering phenology, which has advanced for many species in response to climate change. However, most herbarium-based studies on plant phenology focus on taxa from temperate parts of the northern hemisphere. Here, we explore flowering phenologic responses to climate in a temperate/subtropical plant genus Protea (Proteaceae), an iconic group of woody plants with year-round flowering phenology and endemic to sub-Saharan Africa. Protea is widely used in horticulture and is a flagship genus for the flora of the hyperdiverse Cape Floristic Region.

Methods

We used a database of 2154 herbarium records of 25 Protea species to explore patterns in flowering spanning the past 100 years. We used a circular sliding window analysis to characterize phenological patterns in these aseasonal species, plus a novel linear mixed effects model formulation to test how both site-to-site and year-to-year variation in temperature and precipitation affect flowering date across species.

Results

Both warmer sites and warmer years were associated with earlier flowering of 3–5 days/°C. In general, the timing of peak flowering was influenced more strongly by temperature than precipitation. Although species vary widely in when they flower during the year, their phenological responses to temperature are phylogenetically conserved, with closely related species tending to shift flowering time similarly with increasing temperature.

Discussion

Together, our results point to climate-responsive phenology for this important plant genus. Our results indicate that the subtropical, aseasonally-flowering genus Protea has temperature-driven flowering phenologic responses that are remarkably similar in magnitude to those of better-studied northern temperate plant species, suggesting a generality across biomes that has not been described elsewhere.
USP15 participates in HCV propagation through the regulation of viral RNA translation and lipid droplet formation
Authors: Kusakabe Shinji , Suzuki Tatsuya , Sugiyama Yukari , Haga Saori , Horike Kanako , Tokunaga Makoto , Hirano Junki , He Zhang , Chen David Virya , Ishiga Hanako , Komoda Yasumasa , Ono Chikako , Fukuhara Takasuke , Yamamoto Masahiro , Ikawa Masahito , Satoh Takashi , Akira Shizuo , Tanaka Tomohisa , Moriishi Kohji , Fukai Moto , Taketomi Akinobu , Yoshio Sachiyo , Kanto Tatsuya , Suzuki Tetsuro , Okamoto Toru , Matsuura Yoshiharu
Published: October 2018

Hepatitis C virus (HCV) utilizes cellular factors for an efficient propagation. Ubiquitin is covalently conjugated to the substrate to alter its stability or to modulate signal transduction. In this study, we examined the importance of ubiquitination for HCV propagation. We found that inhibition of de-ubiquitinating enzymes (DUBs) or overexpression of non-specific DUBs impaired HCV replication, suggesting that ubiquitination regulates HCV replication. To identify specific DUBs involved in HCV propagation, we set up an RNAi screening against DUBs and successfully identified ubiquitin-specific protease 15 (USP15) as a novel host factor for HCV propagation. Our studies showed that USP15 is involved in translation of HCV RNA and production of infectious HCV particles. In addition, deficiency of USP15 in human hepatic cell lines (Huh7 and Hep3B/miR122 cells) but not in a non-hepatic cell line (293T cells) impaired HCV propagation, suggesting that USP15 participates in HCV propagation through the regulation of hepatocyte-specific functions. Moreover, we showed that loss of USP15 had no effect on innate immune responsesin vitroandin vivo. We also found that USP15-deficient Huh7 cells showed reductions in the sizes and numbers of lipid droplets (LDs), and addition of palmitic acids restored the production of infectious HCV particles. Taken together, these data suggest that USP15 participates in HCV propagation by regulating the translation of HCV RNA and formation of LDs.
Synaptic mechanisms underlying the network state-dependent recruitment of VIP-expressing interneuron-specific interneurons in the CA1 hippocampus
Authors: Luo Xiao , Guet-McCreight Alexandre , Villette Vincent , Francavilla Ruggiero , Marino Beatrice , Chamberland Simon , Skinner Frances K , Topolnik Lisa
Published: October 2018

In the hippocampus, a highly specialized population of vasoactive intestinal peptide (VIP)-expressing interneuron-specific (IS) inhibitory cells provides local circuit disinhibition via preferential innervation of different types of GABAergic interneurons. While disinhibition can be critical in modulating network activity and different forms of hippocampal learning, the synaptic and integrative properties of IS cells and their recruitment during network oscillations remain unknown. Using a combination of patch-clamp recordings, photostimulation, computational modelling as well as recordings of network oscillations simultaneously with two-photon Ca2+-imaging in awake mice in vivo, we identified synaptic mechanisms that can control the firing of IS cells, and explored their impact on the cell recruitment during theta oscillations and sharp-wave-associated ripples. We found that IS cells fire spikes in response to both the Schaffer collateral and the temporoammonic pathway activation. Moreover, integrating their intrinsic and synaptic properties into computational models predicted recruitment of these cells during the rising to peak phases of theta oscillations and during ripples depending on inhibitory contributions. In vivo Ca2+-imaging in awake mice confirmed in part the theoretical predictions, revealing a significant speed modulation of IS cells and their preferential albeit delayed recruitment during theta-run epochs, with firing at the rising phase to peak of the theta cycle. However, it also uncovered that IS cells are not activated during ripples. Thus, given the preferential theta-modulated firing of IS cells in awake hippocampus, we postulate that these cells may be important for information gating during spatial navigation and memory encoding.
GWAS-driven Pathway Analyses and Functional Validation Suggest GLIS1 as a Susceptibility Gene for Mitral Valve Prolapse
Authors: Yu Mengyao , Georges Adrien , Tucker Nathan R. , Kyryachenko Sergiy , Toomer Katelyn , Schott Jean-Jacques , Delling Francesca N. , Ellinor Patrick T. , Levine Robert A. , Slaugenhaupt Susan A. , Hagège Albert A. , Dina Christian , Jeunemaitre Xavier , Milan David J. , Norris Russell A. , Bouatia-Naji Nabila
Published: October 2018

Nonsyndromic Mitral valve prolapse (MVP) is a common degenerative valvular heart disease with severe health consequences, including arrhythmia, heart failure and sudden death. MVP is characterized by excess extracellular matrix secretion and cellular disorganization which leads to bulky valves that are unable to co-apt properly during ventricular systole. However, the triggering mechanisms of this process are mostly unknown. Using pathway enrichment tools applied to GWAS we show that genes at risk loci are involved in biological functions relevant to cell adhesion and migration during cardiac development and in response to shear stress. Through genetic, in silico and in vivo experiments we demonstrates the presence of several genes involved in gene regulation, including GLIS1, a transcription factor that regulates Hedgehog signaling. Our findings define genetic, molecular and cellular mechanisms underlying non-syndromic MVP and implicate disrupted endothelial to mesenchymal transition and cell migration as a potential common cause to this disease.
A post-decisional neural marker of confidence predicts information-seeking in decision-making
Authors: Desender Kobe , Murphy Peter , Boldt Annika , Verguts Tom , Yeung Nick
Published: October 2018

Theoretical work predicts that decisions made with low confidence should lead to increased information-seeking. This is an adaptive strategy because it can increase the quality of a decision, and previous behavioral work has shown that decision-makers engage in such confidence-driven information seeking. The present study aimed to characterize the neural markers that mediate the relationship between confidence and information-seeking. A paradigm was used in which human participants made an initial perceptual decision, and then decided whether or not they wanted to sample more evidence before committing to a final decision and confidence judgment. Pre-decisional and post-decisional ERP components were similarly modulated by the level of confidence and by information-seeking choices. Time-resolved multivariate decoding of scalp EEG signals first revealed that information-seeking choices could be decoded from the time of the initial decision to the time of the subsequent information-seeking choice (within-condition decoding). No above-chance decoding was visible in the pre-response time window. Crucially, a classifier trained to decode high versus low confidence predicted information-seeking choices after the initial perceptual decision (across-condition decoding). This time window corresponds to that of a post-decisional neural marker of confidence. Collectively, our findings demonstrate for the first time that neural indices of confidence are functionally involved in information-seeking decisions.
Right-sided brain lesions predominate among patients with lesional mania: evidence from a systematic review and pooled lesion analysis
Authors: Barahona-Corrêa J. Bernardo , Cotovio Gonçalo , Costa Rui M. , Ribeiro Ricardo , Velosa Ana , Silva Vera Cruz e , Sperber Christoph , Karnath Hans-Otto , Senova Suhan , Oliveira-Maia Albino J.
Published: October 2018

Background

Despite claims that lesional mania is associated with right-hemisphere lesions, supporting evidence is scarce, and association with specific brain areas has not been demonstrated.

Aims

To test whether focal brain lesions in lesional mania are more often right-than left-sided, and if lesions converge on areas relevant to mood regulation.

Methods

We performed a systematic literature search (PROSPERO registration CRD42016053675) on PubMed and Web-Of-Science, using terms that reflected diagnoses and structures of interest, and lesional mechanisms. Two researchers reviewed the articles separately according to PRISMA Guidelines, to select reports of adult-onset hypomania, mania or mixed state following a focal brain lesion. When available, eligible lesion images were manually traced onto the corresponding slices of MNI space, and lesion topography analyzed using standard brain atlases. Pooled-analyses of individual patient data were performed.

Results

Data from 207 lesional mania patients was extracted from 110 reports. Among patients with focal lesions (N=197) more patients had lesions involving the right (84.3%) than the left (34.5%) hemisphere. Among 54 lesion images that were available, right-sided predominance of lesions was confirmed, and found to be was conserved across multiple brain regions, including the temporal lobe, fusiform gyrus and thalamus. These, in addition to several frontal lobe areas, were also identified as preferential lesion sites in comparisons with control lesions.

Conclusions

Pooled-analyses, based on the most comprehensive dataset of lesional mania available to date, confirm a preferential association with right-hemisphere lesions, while suggesting that several brain areas/circuits, relevant to mood regulation, are most frequently affected.
Identifying novel subtypes of irritability using a developmental genetic approach
Authors: Riglin Lucy , Eyre Olga , Thapar Ajay K , Stringaris Argyris , Leibenluft Ellen , Pine Daniel , Tilling Kate , Smith George Davey , O’Donovan Michael C , Thapar Anita
Published: October 2018

Objective

Irritability is a common reason for referral to services, strongly associated with impairment and negative outcomes, but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. This study used a developmental approach to test the hypothesis that there are several forms of irritability, including a ‘neurodevelopmental/ADHD-like’ subtype with onset in childhood and a ‘depression/mood’ subtype with onset in adolescence.

Method

Data were analyzed in the Avon Longitudinal Study of Parents and Children, a prospective UK population-based cohort. Irritability trajectory-classes were estimated for 7924 individuals with data at multiple time-points across childhood and adolescence (4 possible time-points from approximately ages 7 to 15 years). Psychiatric diagnoses were assessed at approximately ages 7 and 15 years. Psychiatric genetic risk was indexed by polygenic risk scores (PRS) for attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) derived using large genome-wide association study results.

Results

Five irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), late-childhood limited (5.2%) and high-persistent (2.4%). The early-onset, high-persistent trajectory was associated with male preponderance, childhood ADHD (OR=108.64 (57.45–204.41), p<0.001) and ADHD PRS (OR=1.31 (1.09–1.58), p=0.005); the adolescent-onset, increasing trajectory was associated with female preponderance, adolescent MDD (OR=5.14 (2.47–10.73), p<0.001) and MDD PRS (OR=1.20, (1.05–1.38), p=0.009). Both trajectory classes were associated with MDD diagnosis and ADHD genetic risk.

Conclusions

The developmental context of irritability may be important in its conceptualization: early-onset persistent irritability maybe more ‘neurodevelopmental/ADHD-like’ and later-onset irritability more ‘depression/mood-like’. This has implications for treatment as well as nosology.
RNA polymerase I transcription fidelity, speed and processivity depend on the interplay of its lobe binding subunits
Authors: Merkl Philipp E. , Pilsl Michael , Fremter Tobias , Längst Gernot , Milkereit Philipp , Griesenbeck Joachim , Tschochner Herbert
Published: October 2018

Eukaryotic RNA polymerases I and III (Pol I and III) consist of core subunits, which are conserved in RNA polymerase II (Pol II). Additionally, Pol I and III have specific subunits, associating with the so-called ‘lobe’ structure first described within Pol II. In Pol I of the yeastS. cerevisiae, these are Rpa34.5, and the N-terminal domains of Rpa49 and Rpa12.2, here referred to as the lobe-binding module (lb-module). We analyzed functions of the lb-module in a definedin vitrotranscription system. Cooperation between lb-module components influenced transcription fidelity, elongation speed, and release of stalled Pol I complexes to continue elongation. Interestingly, lb-module containing Pol I and III, but not Pol II, were able to transcribe nucleosomal templates. Our data suggest, how the Pol I specific subunits may contribute to accurate and processive transcription of ribosomal RNA genes.
Mathematical modelling of serine integrase - mediated gene assembly
Authors: Pokhilko Alexandra , Kane Steven , Stark W. Marshall , Colloms Sean D.
Published: October 2018

Site-specific recombination promoted by serine integrases can be used for ordered assembly of DNA fragments into larger arrays. When a plasmid vector is included in the assembly, the circular product DNA molecules can transformE. colicells. A convenient “one-pot” method using a single integrase involves recombination between pairs of matched orthogonal attachment sites, allowing assembly of up to six DNA fragments. However, the efficiency of assembly decreases as the number of fragments increases, due to accumulation of incorrect products in which recombination has occurred between mismatched sites. Here we use mathematical modelling to analyse published experimental data for the assembly reactions and suggest potential ways to improve assembly efficiency. We assume that unproductive synaptic complexes between pairs of mismatched sites become predominant as the number and diversity of sites increase. Our modelling predicts that the proportion of correct products can be improved by raising fragment DNA concentrations and lowering plasmid vector concentration. The assembly kinetics is affected by the inactivation of integrasein vitro. The model also predicts that the precision might be improved by redesigning the location of attachment sites on fragments to reduce the formation of the wrong circular products. Our preliminary experimental explorations of assembly with ϕC31 integrase confirmed that assembly efficiency might be improved. However, optimization of efficiency would require more experimental work on the mechanisms of wrong product formation. The use of a more efficient integrase (such as Bxb1) might be a more promising approach to assembly optimization. The model might be easily extended for different integrases or/and different assembly strategies, such as those using multiple integrases or multiple substrate structures.
Discrete stepping and nonlinear ramping dynamics underlie spiking responses of LIP neurons during decision-making
Authors: Zoltowski David M. , Latimer Kenneth W. , Yates Jacob L. , Huk Alexander C. , Pillow Jonathan W.
Published: October 2018

Neurons in macaque area LIP exhibit gradual ramping in their trial-averaged spike responses during sensory decision-making. However, recent work has sparked debate over whether single-trial LIP spike trains are better described by discrete “stepping” or continuous drift-diffusion (“ramping”) dynamics. Here we address this controversy using powerful model-based analyses of LIP spike responses. We extended latent dynamical models of LIP spike trains to incorporate non-Poisson spiking, baseline firing rates, and various nonlinear relationships between the latent variable and firing rate. Moreover, we used advanced model-comparison methods, including cross-validation and a fully Bayesian information criterion, to evaluate and compare models. These analyses revealed that when non-Poisson spiking was incorporated into existing stepping and ramping models, a majority of neurons remained better described by stepping dynamics, even when conditioning on evidence level or choice. However, an extended ramping model with a non-zero baseline and a compressive output nonlinearity accounted for roughly as many neurons as the stepping model. The latent dynamics inferred under this model exhibited high diffusion variance for many neurons, making them qualitatively different than slowly-evolving continuous dynamics. These findings generalized to alternative tasks, suggesting that a robust fraction of LIP neurons are better described by each model class.
Strengthening of the efferent olivocochlear system leads to synaptic dysfunction and tonotopy disruption of a central auditory nucleus
Authors: Di Guilmi Mariano N. , Boero Luis E. , Castagna Valeria C. , Rodríguez-Contreras Adrián , Wedemeyer Carolina , Gómez-Casati María Eugenia , Elgoyhen Ana Belén
Published: October 2018

The auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner ear plays a critical role in guiding this process. This is shaped by an efferent pathway that descends from the brainstem and makes transient direct synaptic contacts with inner hair cells (IHCs). In this work, we used an α9 cholinergic receptor knock-in mouse model (of either sex) with enhanced medial efferent activity (Chrna9L9’T, L9’T) to understand the role of the olivocochlear system in the correct establishment of auditory circuits. Wave III of auditory brainstem responses (which represents synchronized activity of synapses within the superior olivary complex) were smaller in L9’T mice, suggesting a central dysfunction. The mechanism underlying this functional alteration was analysed in brain slices containing the medial nucleus of the trapezoid body (MNTB), where neurons are topographically organized along a medio-lateral axis. The topographic organization of MNTB physiological properties observed in WT mice was abolished in the L9’T mice. Additionally, electrophysiological recordings in slices evidenced MNTB synaptic alterations, which were further supported by morphological alterations. The present results suggest that the transient cochlear efferent innervation to IHCs during the critical period before the onset of hearing is involved in the refinement of topographic maps as well as in setting the correct synaptic transmission at central auditory nuclei.

Significance Statement

Cochlear inner hair cells of altricial mammals display spontaneous electrical activity before hearing onset. The pattern and firing rate of these cells is crucial for the correct maturation of the central auditory pathway. A descending efferent innervation from the central nervous system contacts hair cells during this developmental window. The function of this transient efferent innervation remains an open question. The present work shows that the genetic enhancement of efferent function disrupts the orderly topographic distribution at the medial nucleus of the trapezoid body level and causes severe synaptic dysfunction. Thus, the transient efferent innervation to the cochlea is necessary for the correct establishment of the central auditory circuitry.
Pervasiveness of exoribonuclease-resistant RNAs in plant viruses suggests new roles for these conserved RNA structures
Authors: Steckelberg Anna-Lena , Vicens Quentin , Kieft Jeffrey S.
Published: October 2018

Exoribonuclease-resistant RNAs (xrRNAs) are discrete folded RNA elements that block the processive degradation of RNA by exoribonucleases. xrRNAs found in the 3′ untranslated regions (UTRs) of animal-infecting flaviviruses and in all three members of the plant-infecting Dianthovirus adopt a complex ring-like fold that blocks the exoribonuclease; this ability gives rise to viral non-coding subgenomic RNAs. The degree to which these folded RNA elements exist in other viruses and in diverse contexts has been unclear. Using computational tools and biochemical assays, we discovered that xrRNA elements are widely found in viruses belonging to the Tombusviridae and Luteoviridae families of plant-infecting RNA viruses, demonstrating their importance and widespread utility. Unexpectedly, many xrRNAs are located in intergenic regions rather than in the 3’UTR and some are associated with the 5′ ends of subgenomic RNAs with protein-coding potential, suggesting that xrRNAs with similar scaffolds are involved in the maturation or maintenance of diverse subgenomic RNAs, not just the ones generated from the 3′UTR.
Factors Affecting Electroconvulsive Therapy Ictal Outcomes: Duration and Postictal Suppression
Authors: Ingram Wendy Marie , Weston Cody , Lu Wei Dar , Hodge Caleb , Poler S. Mark , Nahi Fatin , Larson Sharon
Published: October 2018

Electroconvulsive therapy (ECT) is an effective and rapid treatment for severe depression, however predictors of therapeutic outcomes remain insufficiently understood. Ictal duration and postictal suppression are two outcomes that may be correlated with patient response, yet patient and treatment variables which may influence these outcomes have not been thoroughly explored. We collected ECT stimulus metrics, EEG parameters, patient demographics, primary diagnosis, and anesthesia type for retrospective ECTs. Univariate and multivariate mixed-effects linear regression models were used to identify variables associated with ictal duration and postictal suppression index. For both outcomes, multivariate models which included all variables resulted in the best fit, reflecting the complex influences of a variety of factors on the ictal response. These results are an important step forward in elucidating patterns in retrospective ECT clinical data which may lead to new clinical knowledge of modifiable factors to optimize ECT treatment outcomes.
How green are residential areas? An analysis of community greening emerging multi-source geo-data
Authors: Chen Yiyong
Published: October 2018

Urban residential greening provides opportunities for social integration and physical exercise. These activities are beneficial to promoting citizens’ mental health, relieving stress and reducing obesity and violent crimes. However, how to measure the distribution and spatial difference of green resources in urban residential areas have been controversial. This study takes the greening of urban residential units in Shenzhen City as its research object, measures the various greening index values of each residential unit, and analyses the spatial distribution characteristics of residential greening, regional differences and influencing factors. Large sample of street view pictures, urban land use and high-resolution remote sensing image data are employed to establish an urban residential greening database containing 14,196 residential units. This study proposes three greening indicators, namely, green coverage index, green view index, and accessible public green land index, for measuring the green coverage of residential units, the visible greening of surrounding street space and the public green land around, respectively. Results show that (1) the greening level of residential units in Shenzhen City is generally high, with the three indicators averaging 32.7%, 30.5% and 15.1%, respectively; (2) the types of residential greening differ per area; and (3) the level of residential greening is affected by development intensity, location, elevation and residential type. Such findings can serve as a reference for improving the greening level of residential units. This study proposes an accessible public green land index as a measure for the spatial relationship between residential units and surrounding green spaces. It suggest that future green space planning should pay more attention to the spatial distribution of public green land, and introduce quantitative indicators to ensure sufficient public green lands around the walking range of residential areas.
Analysis of contributory gut microbiota and lauric acid against necrotic enteritis in Clostridium perfringens and Eimeria side-by-side challenge model
Authors: Yang Wen-Yuan , Lee Yuejia , Lu Hsinyi , Chou Chung-Hsi , Wang Chinling
Published: October 2018

Gut microbiota has been demonstrated to be involved in intestinal nutrition, defense, and immunity, as well as participating in disease progression. This study was to investigate gut microbiota changes in chickens challenged with netB-positive Clostridium perfringens strain 1 (CP1) and/or the predisposing Eimeria species (Eimeria). In addition, the effects of lauric acid, a medium-chain fatty acid (MCFA), on NE reduction and modulation of microbiota were evaluated. The results demonstrated that microbial communities in the jejunum were distinct from those in the cecum, and the microbial community change was more significant in jejunum. Challenge of CP1 in conjunction with Eimeria significantly reduced species diversity in jejunal microbiota, but cecal microbiota remained stable. In the jejunum, CP1 challenge increased the abundance of the genera of Clostridium sensu stricto 1, Escherichia Shigella, and Weissella, but significantly decreased the population of Lactobacillus. Eimeria infection on its own was unable to promote NE, demonstrating decrements of Clostridium sensu stricto 1 and Lactobacillus. Co-infection with CP1 and Eimeria reproduced the majority of NE lesions with significant increment of Clostridium sensu stricto 1 and reduction in Lactobacillus. The changes of these two taxa increased the severity of NE lesions. Further analyses of metagenomeSeq, STAMP, and LEfSe showed significant overgrowth of Clostridium sensu stricto 1 was associated with NE and Eimeria infection than C. perfringens challenge alone. The supplementation of lauric acid did not reduce NE incidence and severity but decreased the relative abundance of Escherichia Shigella. In conclusion, significant overgrowth of Clostridium sensu stricto 1 in the jejunm is the major microbiota contributory to NE. Controlling proliferation of this taxon in the jejunum should be the niche for developing effective strategies against NE.
Risk Factors Associated with Dengue Virus Infection in Guangdong Province: a Community-based Case-control Study
Authors: Liu Jundi , Tian Xiaolu , Deng Yu , Du Zhicheng , Liang Tianzhu , Hao Yuantao , Zhang Dingmei
Published: October 2018

Background

Dengue fever is a mosquito-borne infectious disease, and it is now still epidemic in China, especially in Guangdong Province. Owing to the absence of dengue vaccination, effective preventive measure is critical for controlling of dengue fever. This study aimed to explore the individual risk factors of dengue virus infection in Guangdong Province, as well as to provide a scientific basis for prevention and supervision of dengue fever in future.

Methods

A case-control study including 237 cases and 237 controls was performed. The data was collected from the epidemiological questionnaires. Univariate analysis was used for preliminary screening of 28 variables potentially related to dengue virus infection, and an unconditioned logistic regression analysis was used for multivariate analysis to analysis those statistically significant variables.

Results

Multivariate analysis of the result showed three independent risk factors: activities in the park (odd ratio [OR]= 1.70, 95%CI 1.03 to 2.83), outdoor sports (OR= 1.67, 95%CI 1.07 to 2.62), and poor indoor daylight quality (OR= 2.27, 95%CI 1.00 to 5.15); and two protective factors: two persons per room (OR=0.43, 95%CI 0.28 to 0.67), three persons and above per room (OR=0.43, 95%CI 0.22 to 0.86), using air-condition (OR=0.43, 95%CI 0.20 to 0.93).

Conclusion

These results are conducive to learn the risk factors for dengue virus infection in Guangdong Province. It is crucial to provide effective and efficient strategy to improve environmental protection and anti-mosquito measures. In addition, more systematic studies are needed to explore the other potential risk factors for dengue fever infection.

Author summary

Dengue fever, one of the mosquito-borne infectious diseases, is mainly transmitted by Aedes aegypti in Asia and Southeast Asia countries. Since 1978, the incidence of dengue fever has markedly increased in China especially in Guangdong province. In order to formulate the effective prevention and control measures, we explored the risk factors of dengue virus infection in Guangdong Province by conducting a case-control study. In this study, 237 patients with dengue virus infection and 237 participants without dengue virus infection were included. Then through these questionnaires and data analysis, we found that activities in the park, outdoor sports, and poor indoor daylight quality significantly contributed to the residents’ risk of dengue virus infection. On the other hand, we observed that using air-condition and using anti-mosquito measures were effective personal prevention interventions.
Corrosion inhibition of aluminium alloy by rhamnolipid biosurfactant derived frompseudomonassp. PS-17
Authors: Zin Ivan M. , Pokhmurskii Vasyl I. , Korniy Sergiy A. , Karpenko Olena V. , Lyon Stuart B. , Khlopyk Olha P. , Tymus Mariana B.
Published: October 2018

Purpose

The purpose of this paper is to study the influence of rhamnolipid biosurfactant complex on the corrosion and the repassivation of a freshly cut Al-Cu-Mg aluminium alloy surface.

Design/methodology/approach

The electrochemical methods, supported by quantum-chemical calculations and scanning electron microscopy data, were used.

Findings

It was established that the rhamnolipid biosurfactant effectively inhibits corrosion of the alloy in synthetic acid rainwater. The efficiency of inhibition becomes stronger with the increase of biosurfactant concentration; however, above the critical micelle concentration, the further improvement in inhibition is minor. It is believed that the mechanism of corrosion inhibition is related to the adsorption of the biosurfactant molecule on the aluminium alloy surface and the formation of a barrier film; however, the formation of a complex compound (salt film) between aluminium ions and rhamnolipid on anodic sites of the alloy is not ruled out. In case of surface mechanical activation of the alloy, the biosurfactant molecule effectively prevents corrosion. Furthermore, addition of the biosurfactant to the corrosion environment increases the repassivation kinetics of the alloy by two to four times as compared with an uninhibited environment.

Practical implications

The commercial impact of the study consists in the possibility of obtaining of environmentally safe corrosion inhibitors of aluminium alloys by biosynthesis from renewable agricultural raw materials.

Originality/value

The originality of this paper is to study the effectiveness of “green” corrosion inhibitor based on biogenic product on freshly generated surface of aluminium alloy.
Research on the effect of the pH value on corrosion and protection of copper in desalted water
Authors: Xuejun Xie , Zhang Yuanlin , Wang Rui , Zhang Yu , Ruan Mianzhao
Published: October 2018

Purpose

The hollow copper wires of the generator are seriously corroded in cooling water. This paper aims to explore the mechanism of copper corrosion by thermodynamic calculation and kinetic experiments and to find out the precise pH range for preventing corrosion of copper in stator internal water and dual internal water cooled generators.

Design/methodology/approach

Thermodynamic and kinetic studies were carried out for the purpose of preventing the corrosion of hollow conducting copper wires in the internal cooling water. Thermodynamic calculation results demonstrate hollow copper wires electrochemically corroded by oxygen rather than acids (H+) and find out a precise anti-corrosion pH range. Kinetic experiments research on the effect of the pH value and oxygen concentration on corrosion and protection methods of copper in desalted water.

Findings

Research results demonstrate that, in the internal cooling water, hollow copper wires are electrochemically corroded by oxygen, rather than acids (H+). The method of preventing copper from corrosion in the desalted water is to control the pH value of the stator cooling water and the dual water inner cooling water between 7.86-8.86 and 7.86-9.26, respectively.

Originality/value

The thermodynamic calculation and potentiometric-pH diagram are used to obtain the accurate pH range of the inner cooling water and inner cooling water in the inner cooling water system. The kinetic experiments provide data support for the effect of temperature, pH value and oxygen concentration.
Interdisciplinary design checklists for mechanical, electrical and plumbing coordination in building projects
Authors: Hassanain Mohammad A. , Aljuhani Mohammad , Sanni-Anibire Muizz O. , Abdallah Abdullatif
Published: October 2018

Purpose

The purpose of this paper is to develop and assess interdisciplinary design checklists for mechanical, electrical and plumbing (MEP) systems’ coordination, for building projects, in Saudi Arabia.

Design/methodology/approach

Relevant documents were acquired including: heating, ventilation and air conditioning schedules; ductwork and chilled water pipes layout; and technical queries, among others, from residential and school projects. Next, factors influencing MEP systems’ coordination were extracted, and verified to ensure clarity and validity. They were formulated into design checklist items for MEP systems. Finally, the checklist items were assessed through a questionnaire based on a five-point Likert scale of importance. Respondents were comprised of mechanical, architectural, construction, electrical engineers, design coordinators and quality assurance managers. Data were then analyzed using the relative importance index.

Findings

This study presents 63 design checklist items. The items for each discipline were grouped under four categories, highlighting specific considerations. The findings revealed that careful consideration and communication between the mechanical, structural and architectural design teams was paramount in achieving proper mechanical coordination. Furthermore, it was found that constant communication between the electrical and the other design teams was necessary, to avoid electrical design conflicts. Finally, fire safety consideration was found to be most important in plumbing systems’ coordination.

Originality/value

The checklists for facilitating the MEP coordination process in building projects aim at minimizing waste in resources and enhancing the overall quality and productivity. In the absence of existing checklists, this paper provides a practical benefit to design professionals to alert them to devote more effort to the dominant category of checklist items.