bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic Study of Conversion Between 2 Formulations of Once-daily Extended-release Tacrolimus in Stable Lung Transplant Patients
Authors: Sintes Helena , Sáez-Giménez Berta , Berastegui Cristina , López-Meseguer Manuel , Monforte Víctor , Bravo Carlos , Vima Jaume , Gómez-Ollés Susana , Roman Antonio
Published: June 2018

Background

The aim of this study was to compare the pharmacokinetic profile, tolerability, and safety of a novel once-daily extended-release formulation of tacrolimus (LCPT) with that of once-daily prolonged-release tacrolimus (ODT) in stable adult lung transplant (LT) recipients.

Methods

Phase II, open-label, single-arm, single-center, prospective pilot pharmacokinetic study. Study population comprised 20 stable LT recipients receiving ODT, mean age 55.9 years (range, 38-67 years), 13 (65%) men. Patients were switched to LCPT in a 1:0.7 (mg/mg) conversion dose. Follow-up was 6 months, and cystic fibrosis patients were excluded. Two 24-hour pharmacokinetic profiles were obtained for each patient, the first on day −14 and the second on day +14 after switching to LCPT. Pharmacokinetic parameters and safety were compared.

Results

Mean (SD) area under the concentration-time curve from 0 to 24 hours was 253.97 (61.90) ng/mL per hour for ODT and 282.44 (68.2) ng/mL per hour for LCPT. Systemic exposure was similar in both (Schuirmann two 1-sided test). Mean (SD) dose was 5.05 (1.67) mg in ODT and 3.36 (1.03) mg in LCPT (P = 0.0002). Time to maximum concentration was 125 minutes for ODT and 325 minutes for LCPT (P < 0.001). Correlation between area under the concentration-time curve from 0 to 24 hours and C24 was 0.896 (r
2) for ODT and 0.893 (r
2) for LCPT. There were no differences in adverse effects. At 6 months, conversion dose was 1:0.59 (mg/mg) in patients with unchanged minimum plasma concentration target levels.

Conclusions

Switching from ODT to LCPT was safe and well tolerated in stable LT recipients without cystic fibrosis. A significantly lower dose of LCPT allows similar bioavailability. A conversion ratio 1:0.6 could be enough to maintain similar target levels.
Free-running enzymatic oligonucleotide synthesis for data storage applications
Authors: Jensen M.A. , Griffin P.B. , Davis R. W.
Published: June 2018

Here we present preliminary results for a method of oligodeoxynucleotide synthesis using terminal deoxynucleotidyl transferase (TdT) to generate mixed base homopolymer runs of defined sequence. In a process we have termed Free-Running Synthesis (FRS), we allow TdT to freely add multiple bases of a given monomer. With this method, homopolymeric runs can be used for writing DNA in a data storage capacity, where a stretch of A’s, for example, will be read as a single base, and the transitions between successive homopolymer runs encodes information. As a proof-of-concept, we demonstrate homopolymer additions of A, C and T onto the 3’ end of a 22 base initiator strand.
Hydrodynamic trapping measures the interaction between membrane-associated molecules
Authors: Junghans Victoria , Hladilkova Jana , Santos Ana Mafalda , Lund Mikael , Davis Simon J. , Jönsson Peter
Published: June 2018

How membrane proteins distribute and behave on the surface of cells is determined by the molecules’ interaction potential. However, measuring this potential, and how it varies with protein-to-protein distance, has been challenging. We here present how a method we call hydrodynamic trapping can achieve this. Our method uses the focused liquid flow from a micropipette to locally accumulate molecules protruding from a lipid membrane. The interaction potential, as well as information about the dimensions of the studied molecule, are obtained by relating the degree of accumulation to the strength of the trap. We have used this to study four representative proteins, with different height-to-width ratios and protein properties; from the globular streptavidin, to the rod-like immune cell proteins CD2, CD4 and CD45. The obtained data illustrates how protein shape, glycosylation and flexibility influence the behaviour of membrane proteins as well as underline the general applicability of the method.
The impact of behavioral interventions on co-infection dynamics: an exploration of the effects of home isolation
Authors: Hendrickx Diana M , Abrams Steven , Hens Niel
Published: June 2018

Behavioral changes due to the development of symptoms have been studied in mono-infections. However, in reality, multiple infections are circulating within the same time period and behavioral changes resulting from contraction of one of the diseases affect the dynamics of the other.

The present study aims at assessing the effect of home isolation on the joint dynamics of two infectious diseases, including co-infection, assuming that the two diseases do not confer cross-immunity. We use an age- and time- structured co-infection model based on partial differential equations. Social contact matrices, describing different mixing patterns of symptomatic and asymptomatic individuals are incorporated into the calculation of the age- and time-specific marginal forces of infection.

Two scenarios are simulated, assuming that one of the diseases has more severe symptoms than the other. In the first scenario, people stay only at home when having symptoms of the most severe disease. In the second scenario, twice as many people stay at home when having symptoms of the most severe disease than when having symptoms of the other disease.

The results show that the impact of home isolation on the joint dynamics of two infectious diseases depends on the epidemiological parameters and properties of the diseases (e.g., basic reproduction number, symptom severity). In case both diseases have a low to moderate basic reproduction number, and there is no home isolation for the less severe disease, the final size of the less severe disease increases with the proportion of symptomatic cases of the most severe disease staying at home, after an initial decrease. When twice as many people stay at home when having symptoms of the most severe disease than when having symptoms of the other disease, increasing the proportion staying at home always reduces the final size of both diseases, and the number of co-infections.

In conclusion, when providing advise if people should stay at home in the context of two or more co-circulating diseases, one has to take into account epidemiological parameters and symptom severity.
Nucleic acid extraction and sequencing from low-biomass synthetic Mars analog soils for in situ life detection
Authors: Mojarro Angel , Hachey Julie , Bailey Ryan , Brown Mark , Doebler Robert , Ruvkun Gary , Zuber Maria T. , Carr Christopher E.
Published: June 2018

Recent studies regarding the origin of life and Mars-Earth meteorite transfer simulations suggest that biological informational polymers, such as nucleic acids (DNA and RNA), have the potential to provide unambiguous evidence of life on Mars. To this end, we are developing a metagenomics-based life-detection instrument which integrates nucleic acid extraction and nanopore sequencing: The Search for Extra-Terrestrial Genomes (SETG). Our goal is to isolate and sequence nucleic acids from extant or preserved life on Mars in order to determine if a particular genetic sequence (1) is distantly-related to life on Earth indicating a shared-ancestry due to lithological exchange, or (2) is unrelated to life on Earth suggesting a convergent origin of life on Mars. In this study, we validate prior work on nucleic acid extraction from cells deposited in Mars analog soils down to microbial concentrations observed in the driest and coldest regions on Earth. In addition, we report low-input nanopore sequencing results equivalent to 1 ppb life-detection sensitivity achieved by employing carrier sequencing, a method of sequencing sub-nanogram DNA in the background of a genomic carrier.
Computational Luminance Constancy from Naturalistic Images
Authors: Singh Vijay , Cottaris Nicolas P. , Heasly Benjamin S. , Brainard David H. , Burge Johannes
Published: June 2018

The human visual system supports stable percepts of object color even though the light that reflects from object surfaces varies significantly with the scene illumination. To understand the computations that support stable color perception, we study how estimating a target object’s luminous reflectance factor (LRF; a measure of the light reflected from the object under a standard illuminant) depends on variation in key properties of naturalistic scenes. Specifically, we study how variation in target object reflectance, illumination spectra, and the reflectance of back-ground objects in a scene impact estimation of a target object’s LRF. To do this, we applied supervised statistical learning methods to the simulated excitations of human cone photoreceptors, obtained from labeled naturalistic images. The naturalistic images were rendered with computer graphics. The illumination spectra of the light sources and the reflectance spectra of the surfaces in the scene were generated using statistical models of natural spectral variation. Optimally decoding target object LRF from the responses of a small learned set of task-specific linear receptive fields that operate on a contrast representation of the cone excitations yields estimates that are within 13% of the correct LRF. Our work provides a framework for evaluating how different sources of scene variability limit performance on luminance constancy.
Impact of Premorbid Infection on Onset and Disease Activity of Rheumatoid Arthritis
Authors: Zhang Ruijun , Li Jing , Chen Jiali , Chen Xiaomei , Li Xue , Li Chun , Jia Yuan , Zhou Yunshan , Ren Limin , Wu Lijun , He Jing , Li Zhanguo
Published: June 2018

Objective

Infections have been implicated in rheumatoid arthritis (RA) development. However, the impact of premorbid infection on initiation and perpetuation of RA has not been well elucidated. Thus, we sought to conduct a large scale on-site survey to study whether premorbid infection may trigger RA and influence status of the disease.

Methods

Premorbid infectious events were collected in cohort of 902 RA patients from December 2015 to June 2016. Type of infections prior to RA onset and its possible effects on disease status were analyzed.

Result

Three hundred and thirty-four out of 902 patients (37.03%) experienced infections within one month preceding RA onset. The most frequent infections were respiratory (16.08%), intestinal (11.09%) and urinary tract (9.87%) infection, respectively. The infection was associated with increased disease activity. Early onset was found in patients with urinary infection. High disease activity risk was increased in patients who pre-exposure to urinary infection (OR=3.813, 95%CI=1.717-12.418) and upper respiratory infection (OR=2.475, 95%CI= 0.971-6.312).

Conclusion

Pre-exposure infections are associated with development of RA. Severe disease status of RA and persistent of active disease status are related to preceding infections.
Statistical Inference Relief (STIR) feature selection
Authors: Le Trang T. , Urbanowicz Ryan J. , Moore Jason H. , McKinney Brett A.
Published: June 2018

Motivation

Relief is a family of machine learning algorithms that uses nearest-neighbors to select features whose association with an outcome may be due to epistasis or statistical interactions with other features in high-dimensional data. Relief-based estimators are non-parametric in the statistical sense that they do not have a parameterized model with an underlying probability distribution for the estimator, making it difficult to determine the statistical significance of Relief-based attribute estimates. Thus, a statistical inferential formalism is needed to avoid imposing arbitrary thresholds to select the most important features.

Methods

We reconceptualize the Relief-based feature selection algorithm to create a new family of STatistical Inference Relief (STIR) estimators that retains the ability to identify interactions while incorporating sample variance of the nearest neighbor distances into the attribute importance estimation. This variance permits the calculation of statistical significance of features and adjustment for multiple testing of Relief-based scores. Specifically, we develop a pseudo t-test version of Relief-based algorithms for case-control data.

Results

We demonstrate the statistical power and control of type I error of the STIR family of feature selection methods on a panel of simulated data that exhibits properties reflected in real gene expression data, including main effects and network interaction effects. We compare the performance of STIR when the adaptive radius method is used as the nearest neighbor constructor with STIR when thefixed-k nearest neighbor constructor is used. We apply STIR to real RNA-Seq data from a study of major depressive disorder and discuss STIR’s straightforward extension to genome-wide association studies.

Availability

Code and data available at http://insilico.utulsa.edu/software/STIR.

Contact

brett.mckinney@gmail.com
Effector Gene Reshuffling Involves Dispensable Mini-chromosomes in the Wheat Blast Fungus
Authors: Peng Zhao , Garcia Ely Oliveira , Lin Guifang , Hu Ying , Dalby Melinda , Migeon Pierre , Tang Haibao , Farman Mark , Cook David , White Frank F. , Valent Barbara , Liu Sanzhen
Published: June 2018

Newly emerged wheat blast disease is a serious threat to global wheat production. Wheat blast is caused by a distinct, exceptionally diverse lineage of the fungus causing rice blast disease. To understand genetic diversity in wheat-infecting strains, we report a near-finished reference genome of a recent field isolate generated using long read sequencing and a novel scaffolding approach with long-distance paired genomic sequences. The genome assemblage includes seven core chromosomes and sequences from a dispensable mini-chromosome that harbors effector genes normally found on the ends of core chromosomes in other strains. No mini-chromosomes were observed in an early field strain, and two mini-chromosomes from another field isolate each contain different effector homologous genes and core chromosome end sequences. The mini-chromosome is highly repetitive and is enriched in transposons occurring most frequently at core chromosome ends. Additionally, transposons in mini-chromosomes lack the characteristic signature for inactivation by repeat-induced point (RIP) mutation genome defenses. Our results, collectively, indicate that dispensable mini-chromosomes and non-dispensable core chromosomes undergo divergent evolutionary trajectories, and mini-chromosomes and core chromosome ends are coupled as a mobile, fast-evolving effector compartment in the wheat pathogen genome.

Significance statement

The emerging blast disease on wheat is proving even harder to control than the ancient, still-problematic rice blast disease. Potential wheat resistance identified using strains isolated soon after disease emergence are no longer effective in controlling recent aggressive field isolates from wheat in South America and South Asia. We report that recent wheat pathogens can contain one or two highly-variable conditionally-dispensable mini-chromosomes, each with an amalgamation of effector sequences that are duplicated or absent from pathogen core chromosome ends. Well-studied effectors found on different core chromosomes in rice pathogens appear side-by-side in wheat pathogen mini-chromosomes. The rice pathogen often overcomes deployed resistance genes by deleting triggering effector genes. Localization of effectors on mini-chromosomes, which are unstably transmitted during growth, would accelerate pathogen adaptation in the field.
Beyond type 1 regulatory T cells: co-expression of LAG3 and CD49b in IL-10-producing T cell lineages
Authors: Huang Weishan , Solouki Sabrina , Carter Chavez , Zheng Song-Guo , August Avery
Published: June 2018

Type 1 regulatory CD4+T (Tr1) cells express high levels of the immunosuppressive cytokine IL-10 but not the master transcription factor Foxp3, and can suppress inflammation and promote immune tolerance. In order to identify and obtain viable Tr1 cells for research and clinical applications, co-expression of CD49b and LAG3 has been proposed as a unique surface signature for both human and mouse Tr1 cells. However, recent studies have revealed that this pattern of co-expression is dependent on the stimulating conditions and the differentiation stage of the CD4+T cells. Here, using an IL-10GFP/Foxp3RFPdual reporter transgenic murine model, we demonstrate that co-expression of CD49b and LAG3 is not restricted to the Foxp3−Tr1 cells, but is also observed in Foxp3+T regulatory (Treg) cells and CD8+T cells that produce IL-10. Our data indicate that IL-10-producing Tr1 cells, Treg cells and CD8+T cells are all capable of co-expressing LAG3 and CD49bin vitrofollowing differentiation under IL-10-inducing conditions, andin vivofollowing pathogenic insult or infection in the pulmonary mucosa. Our findings urge caution in the use of LAG3/CD49b co-expression to identify Tr1 cells, since it may mark IL-10-producing T cell lineages more broadly, including the Foxp3−Tr1 cells, Foxp3+Treg cells and CD8+T cells.
Optimizing guide RNA selection and CRISPR/Cas9 methodology for efficient generation of deletions in C. elegans
Authors: Au Vinci , Li-Leger Erica , Raymant Greta , Flibotte Stephane , Chen George , Martin Kiana , Fernando Lisa , Doell Claudia , Rosell Federico I. , Wang Su , Edgley Mark L. , Rougvie Ann E. , Hutter Harald , Moerman Donald G.
Published: June 2018

The Caenorhabditis elegans Gene Knockout (KO) Consortium is tasked with obtaining null mutations in each of the more than 20,000 open reading frames (ORFs) of this organism. To date, approximately15,000 ORFs have associated putative null alleles. A directed approach using CRISPR/Cas9 methodology is the most promising technique to complete the task. While there has been substantial success in using CRISPR/Cas9 in C. elegans, there has been little emphasis on optimizing the method for generating large insertions/deletions in this organism. To enhance the efficiency of using CRISPR/Cas9 to generate gene knockouts in C. elegans we have developed an online species-specific guide RNA selection tool (http://genome.sfu.ca/crispr). When coupled with previously developed selection vectors, optimization for homology arm length, and the use of purified Cas9 protein, we demonstrate a robust, efficient and effective protocol for generating deletions. Debate and speculation in the larger scientific community about off- target effects due to non-specific Cas9 cutting has prompted us to investigate through whole genome sequencing the occurrence of single nucleotide variants and indels accompanying targeted deletions. We did not detect any off-site variants above the natural spontaneous mutation rate and therefore conclude this modified protocol does not generate off-target events to any significant degree in C. elegans.
NovelexcGenes Involved in Formation of the Tubular Excretory Canals ofC. elegans
Authors: Al-Hashimi Hikmat , Chiarelli Travis , Lundquist Erik A. , Buechner Matthew
Published: June 2018

Regulation of luminal diameter is critical to the function of small single-celled tubes, of which the seamless tubular excretory canals ofC. elegansprovide a tractable genetic model. Mutations in several sets of genes exhibit the Exc phenotype, in which canal luminal growth is visibly altered. Here, a focused reverse genomic screen of genes highly expressed in the canals found 24 genes that significantly affect luminal outgrowth or diameter. These genes encode novel proteins as well as highly conserved proteins involved in processes including gene expression, cytoskeletal regulation, vesicular movement, and transmembrane transport. In addition, two genes act as suppressors on a pathway of conserved genes whose products mediate vesicle movement from early to recycling endosomes. The results provide new tools for understanding the integration of cytoplasmic structure and physiology in forming and maintaining the narrow diameter of single-cell tubules.
Deconvolution of substrate processing by the 26S proteasome reveals a selective kinetic gateway to degradation
Authors: Bard J.A.M. , Bashore C. , Dong K.C. , Martin A.
Published: June 2018

The 26S proteasome is the principle macromolecular machine responsible for protein degradation in eukaryotes. However, little is known about the detailed kinetics and coordination of the underlying substrate-processing steps of the proteasome, and their correlation with observed conformational states. Here, we used reconstituted 26S proteasomes with unnatural amino acid-attached fluorophores in a series of FRET and anisotropy-based assays to probe substrate-proteasome interactions, the individual steps of the processing pathway, and the conformational state of the proteasome itself. We develop a complete kinetic picture of proteasomal degradation, which reveals that the engagement steps prior to substrate commitment are fast relative to subsequent deubiquitination, translocation and unfolding. Furthermore, we find that non-ideal substrates are rapidly rejected by the proteasome, which thus employs a kinetic proofreading mechanism to ensure degradation fidelity and substrate prioritization.
Human salivary amylase gene copy number impacts oral and gut microbiomes
Authors: Poole Angela C. , Goodrich Julia K. , Youngblut Nicholas D. , Luque Guillermo G. , Ruaud Albane , Sutter Jessica L. , Waters Jillian L. , Shi Qiaojuan , El-Hadidi Mohamed , Johnson Lynn M. , Bar Haim Y. , Huson Daniel H. , Booth James G. , Ley Ruth E.
Published: June 2018

Host genetic variation influences the composition of the human microbiome. While studies have focused on associations between the microbiome and single nucleotide polymorphisms in genes, their copy number (CN) can also vary. Here, in a study of human subjects including a 2-week standard diet, we relate oral and gut microbiome to CN at theAMY1locus, which encodes the gene for salivary amylase, active in starch degradation. We show that although diet standardization drove gut microbiome convergence,AMY1-CN influenced oral and gut microbiome composition and function. The gut microbiomes of low-AMY1-CN subjects had an enhanced capacity for breakdown of complex carbohydrates. Those of high-AMY1subjects were enriched in microbiota linked to resistant starch fermentation, had higher fecal SCFAs, and drove higher adiposity when transferred to germfree mice. Gut microbiota results were validated in a larger separate population. This study establishesAMY1-CN as a genetic factor patterning microbiome composition and function.
Comparative Biochemical and Structural Analysis of Novel Cellulose Binding Proteins (Tāpirins) from Extremely Thermophilic Caldicellulosiruptor Species
Authors: Lee Laura L. , Hart William S. , Lunin Vladimir V. , Alahuhta Markus , Bomble Yannick J. , Himmel Michael E. , Blumer-Schuette Sara E. , Adams Michael W.W. , Kelly Robert M.
Published: June 2018

Genomes of extremely thermophilic Caldicellulosiruptor species encode novel cellulose binding proteins, tāpirins, located proximate to the type IV pilus locus. Previously, the C-terminal domain of a tāpirin (Calkro_0844) from Caldicellulosiruptor kronotskyensis was shown to be structurally unique and have a cellulose binding affinity akin to family 3 carbohydrate binding modules (CBM3). Here, full-length and C-terminal versions of tāpirins from Caldicellulosiruptor bescii (Athe_1870), Caldicellulosiruptor hydrothermalis (Calhy_0908), Caldicellulosiruptor kristjanssonii (Calkr_0826), and Caldicellulosiruptor naganoensis (NA10_0869) were produced recombinantly in Escherichia coli and compared to Calkro_0844. All five tāpirins bound to microcrystalline cellulose, switchgrass, poplar, filter paper, but not to xylan. Densitometry analysis of bound protein fractions visualized by SDS-PAGE revealed that Calhy_0908 and Calkr_0826 (from weakly cellulolytic species) associated with the cellulose substrates to a greater extent than Athe_1870, Calkro_0844 and NA10_0869 (from strongly cellulolytic species), perhaps to associate closely with biomass to capture glucans released from lignocellulose by cellulases produced in Caldicellulosiruptor communities. Three-dimensional structures of the C-terminal binding regions of Calhy_0908 and Calkr_0826 were closely related to Calkro_0844, despite the fact that their amino acid sequence identities compared to Calkro_0844 were only 16% and 36%, respectively. Unlike the parent strain, C. bescii mutants lacking the tāpirin genes did not bind to cellulose following short-term incubation, reinforcing the significance of these proteins in cell association with plant biomass. Given the scarcity of carbohydrates in neutral terrestrial hot springs, tāpirins likely help cells scavenge carbohydrates from lignocellulose to support growth and survival of Caldicellulosiruptor species.

Importance

Mechanisms by which microorganisms attach to and degrade lignocellulose are important to understand if effective approaches for conversion of plant biomass into fuels and chemicals are to be developed. Caldicellulosiruptor species grow on carbohydrates from lignocellulose at elevated temperatures and have biotechnological significance for that reason. Novel cellulose binding proteins, called tāpirins, are involved in the way Caldicellulosiruptor species interact with microcrystalline cellulose and here additional information about the diversity of these proteins across the genus is provided, including three dimensional structural comparisons.
Mutation-driven evolution of Pseudomonas aeruginosa in the presence of either ceftazidime or ceftazidime/avibactam
Authors: Sanz-García Fernando , Hernando-Amado Sara , Martínez José Luis
Published: June 2018

Ceftazidime/avibactam is a combination of beta-lactam/beta-lactamases inhibitor, which use is restricted to some clinical cases including cystic fibrosis patients infected with multidrug resistant Pseudomonas aeruginosa, in which mutation is the main driver of resistance. This study aims to predict the mechanisms of mutation-driven resistance that are selected for when P. aeruginosa is challenged with either ceftazidime or ceftazidime/avibactam. For this purpose, P. aeruginosa PA14 was submitted to experimental evolution in the absence of antibiotics and in the presence of increasing concentrations of ceftazidime or ceftazidime/avibactam for 30 consecutive days. Final populations were analysed by whole-genome sequencing. All evolved populations reached similar levels of ceftazidime resistance. Besides, all of them were more susceptible to amikacin and produced pyomelanin. A first event in the evolution was the selection of large chromosomal deletions containing hmgA (involved in pyomelanin production), galU (involved in β-lactams resistance) and mexXY-oprM (involved in aminoglycoside resistance). Besides mutations in mpl and dacB that regulate β-lactamase expression, mutations related to MexAB-OprM overexpression were prevalent. Ceftazidime/avibactam challenge selected mutants in the putative efflux pump PA14_45890-45910 and in a two-component system (PA14_45870-45880), likely regulating its expression. All populations produce pyomelanin and were more susceptible to aminoglycosides likely due to the selection of large chromosomal deletions. Since pyomelanin-producing mutants, presenting similar deletions are regularly isolated from infections, the potential aminoglycosides hyper-susceptiblity and reduced β-lactams susceptibility of pyomelanin-producing P. aeruginosa should be taken into consideration for treating infections by these isolates.
The transfer function of the rhesus macaque oculomotor system for small-amplitude slow motion trajectories
Authors: Skinner Julianne , Buonocore Antimo , Hafed Ziad M.
Published: June 2018

Two main types of small eye movements occur during gaze fixation: microsaccades and slow ocular drifts. While microsaccade generation has been relatively well-studied, ocular drift control mechanisms are unknown. Here we explored the degree to which monkey smooth eye movements, on the velocity scale of slow ocular drifts, can be generated systematically. Two male rhesus macaque monkeys tracked a spot moving sinusoidally, but slowly, along the horizontal or vertical directions. Maximum target displacement in the motion trajectory was 30 min arc (0.5 deg), and we varied the temporal frequency of target motion from 0.2 to 5 Hz. We obtained an oculomotor “transfer function” by measuring smooth eye velocity gain (relative to target velocity) as a function of frequency, similar to past work with large-amplitude pursuit. Monkey eye velocities as slow as those observed during slow ocular drifts were clearly target-motion driven. Moreover, like with large-amplitude smooth pursuit, eye velocity gain varied with temporal frequency. However, unlike with large-amplitude pursuit, exhibiting low-pass behavior, small-amplitude motion tracking was band-pass with the best ocular movement gain occurring at ~0.8-1 Hz. When oblique directions were tested, we found that the horizontal component of pursuit gain was larger than the vertical component. Our results provide a catalogue of the control abilities of the monkey oculomotor system for slow target motions, and they also support the notion that smooth fixational ocular drifts are controllable. This has implications for neural investigations of drift control and the image-motion consequences of drifts on visual coding in early visual areas.
Associations between plant and pollinator communities under grassland restoration respond mainly to landscape connectivity
Authors: Rotchés‐Ribalta Roser , Winsa Marie , Roberts Stuart P. M. , Öckinger Erik
Published: June 2018

Land‐use change can disrupt associations between different trophic groups, but it is unclear if habitat restoration can recover these associations. In Sweden, restoration efforts have been applied to increase areas of semi‐natural grassland previously remaining as small fragments due to abandonment. We assessed how the associations between plant and pollinator communities can be modified by grassland abandonment and restoration, together with landscape connectivity.

We surveyed plant, hoverfly and bee communities in 10 abandoned, 18 restored and 10 intact grasslands in south‐central Sweden, distributed along a gradient of isolation from other species‐rich grasslands. We assessed the effects of management history and connectivity on the relationships between several measures of the composition of plant and pollinator communities as well as between plant community composition and pollinator guilds.

The composition of the local flowering plant community was an important determinant of both hoverfly and bee communities. However, plant‐pollinator associations were modulated by landscape connectivity and, to some extent, by grassland management history. Abundance, species richness and functional richness of bees and species richness of hoverflies were positively associated with local plant communities in isolated grasslands, but these associations weakened in well‐connected grasslands. In contrast, hoverfly abundance correlated positively with plant communities in well‐connected grasslands.

The response of pollinator feeding guilds was consistent with overall pollinator communities. However, abundance of bees adapted to foraging on particular plants (long‐tongued and short‐tongued) responded positively to specific host plant species abundance.

Synthesis and applications. Our results show how land use and landscape context can significantly affect interactions between different trophic levels. Land use and landscape context should therefore be recognised in grassland restoration guidelines. Enhancement of both functional‐rich and species‐rich plant communities, as well as increasing abundance and species and functional richness of host plants for specialist pollinators will amend pollinator diversity. Restoration actions should consider the spatial configuration of the landscape to improve its outcome. Efforts in more isolated grasslands should focus on promoting local habitat quality while, in more connected grasslands, the priority should be maintaining connectivity to well‐preserved grasslands.
Border Effects in House Prices
Authors: Micheli Martin , Rouwendal Jan , Dekkers Jasper
Published: June 2018

This article estimates the effect of the Dutch–German border on house prices. We argue that the difference between house prices at the border indicates the willingness to pay to stay in a country compared to living across the border. After a change in the tax rules in 2001, migration from the Netherlands to Germany increased substantially and the gradient of Dutch house price towards the German border steepened. Combining a German and Dutch real estate dataset and using different estimation strategies, we find that asking prices of comparable housing drop by about 16% when one crosses the Dutch–German border.
Gene expression‐based drug repurposing to target aging
Authors: Dönertaş Handan Melike , Fuentealba Valenzuela Matías , Partridge Linda , Thornton Janet M.
Published: June 2018

Aging is the largest risk factor for a variety of noncommunicable diseases. Model organism studies have shown that genetic and chemical perturbations can extend both lifespan and healthspan. Aging is a complex process, with parallel and interacting mechanisms contributing to its aetiology, posing a challenge for the discovery of new pharmacological candidates to ameliorate its effects. In this study, instead of a target‐centric approach, we adopt a systems level drug repurposing methodology to discover drugs that could combat aging in human brain. Using multiple gene expression data sets from brain tissue, taken from patients of different ages, we first identified the expression changes that characterize aging. Then, we compared these changes in gene expression with drug‐perturbed expression profiles in the Connectivity Map. We thus identified 24 drugs with significantly associated changes. Some of these drugs may function as antiaging drugs by reversing the detrimental changes that occur during aging, others by mimicking the cellular defence mechanisms. The drugs that we identified included significant number of already identified prolongevity drugs, indicating that the method can discover de novo drugs that meliorate aging. The approach has the advantages that using data from human brain aging data, it focuses on processes relevant in human aging and that it is unbiased, making it possible to discover new targets for aging studies.
Stabilization treatment of remitted psychotic depression: the STOP‐PD study
Authors: Bingham K. S. , Meyers B. S. , Mulsant B. H. , Rothschild A. J. , Whyte E. M. , Banerjee S. , Artis A. S. , Alexopoulos G. S. , Flint A. J. ,   the STOP‐PD Study Group
Published: June 2018

Objective

We conducted a 12‐week double‐blind study of stabilization pharmacotherapy in patients with remitted psychotic depression (PD).

Methods

Seventy‐one persons aged 18 years or older who had achieved remission of PD when randomized to either olanzapine plus sertraline or olanzapine plus placebo were continued on the double‐blind treatment associated with remission. Symptoms of depression and psychosis, and weight, were measured once every 4 weeks. Cholesterol, triglycerides, and glucose were measured at stabilization phase baseline and Week 12/termination.

Results

The effect of treatment did not significantly change with time for depression, weight, or metabolic measures in the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7) experienced a relapse of major depression, psychosis, or both. Treatment groups did not differ in the frequency of relapse. In the entire study group, the adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83, 2.48) and the adjusted estimate for change in total cholesterol was a decrease of 14.8 mg/dL (95% CI: 3.5, 26.1) during the 12‐week stabilization phase; the remaining metabolic measures did not significantly change.

Conclusion

Continuation of acute treatment was associated with stability of remission.
Oil palm plantation is not a suitable environment for most forest specialist species of Odonata in Amazonia
Authors: Carvalho F. G. , de Oliveira Roque F. , Barbosa L. , de Assis Montag L. F. , Juen L.
Published: June 2018

Oil palm monoculture is the most rapidly increasing large‐scale crop in Amazonia due to favourable environmental conditions and incentives from executives and governing authorities. In this study we assessed the effects of oil palm plantations on Odonata assemblages in Amazonia streams. We hypothesized that (1) the expansion of oil palm plantations over the natural landscape affects the habitat structure and physicochemical properties of streams at different scales (50 m, 500 m and 1000 m) and (2) oil palm plantations affect the species composition of Odonata assemblages, leading to the replacement of forest specialist species by non‐forest specialists. A total of 22 streams were sampled which were distributed throughout a landscape comprising areas of oil palm plantations Elaeis guineensis Jacq. to streams located inside large forest remnants. The expansion of oil palm monoculture affected the physicochemical properties of the water and habitat of the streams. A larger amount of woody debris was observed within streams surrounded by a greater amount of forest, whereas streams with a greater area of surrounding oil palm had higher pH values and anthropogenic infrastructures (e.g. roads). As expected, the Odonata community was affected by a replacement of forest specialist species with non‐forest specialist species. To mitigate this impact, we suggest increasing the area of native riparian corridors along streams that flow through oil palm plantations.
An illustration of human sperm morphology and their functional ability among different group of subfertile males
Authors: Sunanda P. , Panda B. , Dash C. , Padhy R. N. , Routray P.
Published: June 2018

Condensed sperm chromatin is a prerequisite for natural fertilization. Some reports suggested the prevalence of chromatin condensation defects in teratozoospermia cases with head anomalies; conversely, earlier studies exemplified its occurrence in morphologically normal spermatozoa too. The aim of this study was to compare the condensation defects in correlation with head anomalies among different groups of subfertile males and its impact on the rate of fertilization in assisted reproduction procedures. Ultrastructure analysis of spermatozoa through scanning electron microscopy and atomic force microscopy could facilitate an in‐depth evaluation of sperm morphology. Nuclear condensation defects (%) in spermatozoa were analyzed in 666 subjects, and its effect on the rate of fertilization was analyzed in 116 IVF and 90 intracytoplasmic sperm injection cases. There was no correlation of condensation defects with head anomalies (%). Student's t‐test showed no significant changes in mean values of condensation defects in abnormal semen samples in comparison with the normal group. Condensation defects were observed in normal spermatozoa too, which was negatively associated with the rate of fertilization in IVF (p < 0.01), but intracytoplasmic sperm injection outcome remained unaffected. Ultrastructure study revealed sperm morphological features in height, amplitude, and three‐dimensional views in atomic force microscopy images presenting surface topography, roughness property of head, and compact arrangement of mitochondria over axoneme with height profile at nanoscale. In pathological forms, surface roughness and nuclear thickness were marked higher than the normal spermatozoa. Thus, percentage of normal spermatozoa with condensation defects could be a predictive factor for the rate of fertilization in IVF. From diverse shapes of nucleus in AFM imaging, it could be predicted that defective nuclear shaping might be impeding the activity of some proteins/ biological motors, those regulate the proper Golgi spreading over peri‐nuclear theca.
Hydronephrosis and risk of later development of hypertension
Authors: Carlström Mattias
Published: June 2018

Aim

Congenital ureteral obstruction is a fairly common condition in infants, and its clinical management has been long debated during the last decade. The long‐term physiological consequences of today's conservative non‐surgical management in many asymptomatic hydronephrotic children are unclear.

Methods

Experimental studies in rats and mice, retrospective studies in children and adults, as well as prospective studies in children are included in this mini review.

Results

Experimental models of hydronephrosis in rats and mice have demonstrated that partial ureteropelvic junction obstruction (UPJO) is casually linked with development of hypertension and renal injuries in later life. The mechanisms are multifactorial and involve increased activity of the renin–angiotensin–aldosterone system and renal sympathetic nerve activity. Furthermore, oxidative stress and nitric oxide deficiency in the affected kidney appear to play important roles in the development and maintenance of hypertension. Clinical case reports in adults and recent prospective studies in children have associated hydronephrosis with elevated blood pressure, which could be reduced by surgical management of the obstruction.

Conclusion

Based on current experimental and clinical knowledge regarding the link between partial UPJO and changes in blood pressure, it is proposed that today's non‐operative management of hydronephrosis should be reconsidered to reduce the risk of developing elevated blood pressure or hypertension in later life.
The Welch Emotional Connection Screen: validation of a brief mother–infant relational health screen
Authors: Hane Amie A. , LaCoursiere Jasmine N. , Mitsuyama Mai , Wieman Sarah , Ludwig Robert J. , Kwon Katie Y. , V. Browne Joy , Austin Judy , M. Myers Michael , Welch Martha G.
Published: June 2018

Aim

The Welch Emotional Connection Screen (WECS), assesses mother–infant Emotional Connection in clinical settings. It includes: Attraction, Vocal Communication, Facial Communication, Sensitivity/Reciprocity and clinical decision of Emotional Connection (yes/no). We tested concurrent and construct validity of the WECS and associations with behavioural and physiological measures in preterm infants.

Methods

Videos from 76 mothers–infants (gestational age 36 weeks) during an in‐NICU caregiving paradigm were coded for maternal caregiving behaviour. Videos of mothers–infants were also obtained at 4 months during 10 minutes of face‐to‐face play (coded with WECS and for maternal positivity and infant social engagement) and the still‐face paradigm (coded for infant behavioural approach towards mother; infant electrocardiogram acquired in vivo).

Results

WECS maternal scores were positively associated with maternal sensitivity and quality of vocal contact at 36 weeks (caregiving) and maternal positivity at 4 months (face‐to‐face). WECS infant scores positively correlated with infant social engagement and maternal positivity during face‐to‐face interactions at 4 months. Infants from emotionally not connected dyads (vs. emotionally connected dyads) displayed autonomic dysregulation and less approach‐seeking behaviour towards mother during interactive/play sessions of the still‐face paradigm.

Conclusion

This preliminary evidence supports the WECS as a valid screen for rating mother–preterm infant emotional connection associated with healthier infant biobehavioural stress responding.
Changes in autonomic regulation due to Kangaroo care remain unaffected by using a swaddling device
Authors: Kommers Deedee R. , Joshi Rohan , van Pul Carola , Feijs Loe , Bambang Oetomo Sidarto , Andriessen Peter
Published: June 2018

Aim

To investigate the effects of a swaddling device known as the Hugsy (Hugsy, Eindhoven, the Netherlands) towards improving autonomic regulation. This device can be used both in the incubator and during Kangaroo care to absorb parental scent and warmth. After Kangaroo care, these stimuli can continue to be experienced by infants, while in the incubator. Additionally, a pre‐recorded heartbeat sound can be played.

Method

Autonomic regulation was compared in preterm infants before, during and after Kangaroo care with and without the use of a swaddling device in a within‐subject study carried out in a level III neonatal intensive care unit. Descriptive statistics and effect sizes were calculated corresponding to changes in heart rate, respiratory rate, oxygen saturation, temperature and heart rate variability on intervention versus control days.

Results

In this study of 20 infants with a median (interquartile range) gestational age of 28.4 (27–29.9) weeks, Kangaroo care was associated with a decrease in heart rate, respiratory rate and heart rate variability on both intervention and control days. There were no differences between intervention and control days.

Conclusion

The use of an alternative swaddling device aimed at facilitating Kangaroo care did not enhance autonomic regulation, as measured by vital signs and heart rate variability.
Nasal high‐flow therapy decreased electrical activity of the diaphragm in preterm infants during the weaning phase
Authors: Oda Arata , Parikka Vilhelmiina , Lehtonen Liisa , Porres Ivan , Soukka Hanna
Published: June 2018

Aim

We evaluated whether nasal high‐flow therapy was better than no respiratory support during the weaning phase in preterm infants.

Methods

The study was conducted in the neonatal intensive care unit of the Turku University Hospital between September 2014 and August 2015. Preterm infants who were alternating between nasal high‐flow therapy and unassisted breathing were enrolled. Electrical activity of the diaphragm (EAdi) was recorded and compared during three‐hour time periods for each option.

Results

We studied eight infants at a median gestational age of 31 weeks. The EAdi peak was lower during nasal high‐flow therapy when compared to no respiratory support (6.1 μV vs 7.1 μV, p = 0.02), but the EAdi minimum was similar with and without respiratory support. Neural respiratory rate (62 vs 68 per minute, p = 0.02) and the frequency of sighs (27.8 vs 37.9 per hour, p = 0.03) were lower during nasal high‐flow therapy than no respiratory support.

Conclusion

Nasal high‐flow therapy reduced diaphragm activation in our cohort when compared to no respiratory support, as indicated by the lower Edi peak. An increase in the respiratory rate and the sigh frequency without respiratory support also suggests that nasal high‐flow therapy provided support during the weaning phase.