bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex admixture preceded and followed the extinction of wisent in the wild
Authors: Węcek Karolina , Hartmann Stefanie , Paijmans Johanna L. A. , Taron Ulrike , Xenikoudakis Georgios , Cahill James A. , Heintzman Peter D. , Shapiro Beth , Baryshnikov Gennady , Bunevich Aleksei N. , Crees Jennifer J. , Dobosz Roland , Manaserian Ninna , Okarma Henryk , Tokarska Małgorzata , Turvey Samuel T. , Wójcik Jan M. , Żyła Waldemar , Szymura Jacek M. , Hofreiter Michael , Barlow Axel
Published: June 2016

Retracing complex population processes that precede extreme bottlenecks may be impossible using data from living individuals. The wisent (Bison bonasus), Europe’s largest terrestrial mammal, exemplifies such a population history, having gone extinct in the wild but subsequently restored by captive breeding efforts. Using low coverage genomic data from modern and historical individuals, we investigate population processes occurring before and after this extinction. Analysis of aligned genomes supports the division of wisent into two previously recognised subspecies, but almost half of the genomic alignment contradicts this population history as a result of incomplete lineage sorting and admixture. Admixture between subspecies populations occurred prior to extinction and subsequently during the captive breeding program. Admixture with theBoscattle lineage is also widespread but results from ancient events rather than recent hybridisation with domestics. Our study demonstrates the huge potential of historical genomes for both studying evolutionary histories and for guiding conservation strategies.
The genetics of an early Neolithic pastoralist from the Zagros, Iran
Authors: Gallego-Llorente M. , Connell S. , Jones E. R. , Merrett D. C. , Jeon Y. , Eriksson A. , Siska V. , Gamba C. , Meiklejohn C. , Beyer R. , Jeon S. , Cho Y. S. , Hofreiter M. , Bhak J. , Manica A. , Pinhasi R.
Published: June 2016

The agricultural transition profoundly changed human societies. We sequenced and analysed the first genome (1.39×) of an early Neolithic woman from Ganj Dareh, in the Zagros Mountains of Iran, a site with early evidence for an economy based on goat herding,ca. 10,000 BP. We show that Western Iran was inhabited by a population genetically most similar to hunter-gatherers from the Caucasus, but distinct from the Neolithic Anatolian people who later brought food production into Europe. The inhabitants of Ganj Dareh made little direct genetic contribution to modern European populations, suggesting they were somewhat isolated from other populations in the region. Runs of homozygosity are of a similar length to those from Neolithic Anatolians, and shorter than those of Caucasus and Western Hunter-Gatherers, suggesting that the inhabitants of Ganj Dareh did not undergo the large population bottleneck suffered by their northern neighbours. While some degree of cultural diffusion between Anatolia, Western Iran and other neighbouring regions is possible, the genetic dissimilarity of early Anatolian farmers and the inhabitants of Ganj Dareh supports a model in which Neolithic societies in these areas were distinct.
Comparing alternative pipelines for cross-platform microarray gene expression data integration with RNA-seq data in breast cancer
Authors: Frolova Alina , Bondarenko Vladyslav , Obolenska Maria
Published: June 2016

Background

According to major public repositories statistics an overwhelming majority of the existing and newly uploaded data originates from microarray experiments. Unfortunately, the potential of this data to bring new insights is limited by the effects of individual study-specific biases due to small number of biological samples. Increasing sample size by direct microarray data integration increases the statistical power to obtain a more precise estimate of gene expression in a population of individuals resulting in lower false discovery rates. However, despite numerous recommendations for gene expression data integration, there is a lack of a systematic comparison of different processing approaches aimed to asses microarray platforms diversity and ambiguous probesets to genes correspondence, leading to low number of studies applying integration.

Results

Here, we investigated five different approaches of the microarrays data processing in comparison with RNA-seq data on breast cancer samples. We aimed to evaluate different probesets annotations as well as different procedures of choosing between probesets mapped to the same gene. We show that pipelines rankings are mostly preserved across Affymetrix and Illumina platforms. BrainArray approach based on updated annotation and redesigned probesets definition and choosing probeset with the maximum average signal across the samples have best correlation with RNA-seq, while averaging probesets signals as well as scoring the quality of probes sequences mapping to the transcripts of the targeted gene have worse correlation. Finally, randomly selecting probeset among probesets mapped to the same gene significantly decreases the correlation with RNA-seq.

Conclusion

We show that methods, which rely on actual probesets signal intensities, are advantageous to methods considering biological characteristics of the probes sequences only and that cross-platform integration of datasets improves correlation with the RNA-seq data. We consider the results obtained in this paper contributive to the integrative analysis as a worthwhile alternative to the classical meta-analysis of the multiple gene expression datasets.
Decoding brain activity using a large-scale probabilistic functional-anatomical atlas of human cognition
Authors: Rubin Timothy N. , Koyejo Oluwasanmi , Gorgolewski Krzysztof J. , Jones Michael N. , Poldrack Russell A. , Yarkoni Tal
Published: June 2016

A central goal of cognitive neuroscience is to decode human brain activity--i.e., to infer mental processes from observed patterns of whole-brain activation. Previous decoding efforts have focused on classifying brain activity into a small set of discrete cognitive states. To attain maximal utility, a decoding framework must be open-ended, systematic, and context-sensitive--i.e., capable of interpreting numerous brain states, presented in arbitrary combinations, in light of prior information. Here we take steps towards this objective by introducing a Bayesian decoding framework based on a novel topic model---Generalized Correspondence Latent Dirichlet Allocation---that learns latent topics from a database of over 11,000 published fMRI studies. The model produces highly interpretable, spatially-circumscribed topics that enable flexible decoding of whole-brain images. Importantly, the Bayesian nature of the model allows one to “seed” decoder priors with arbitrary images and text--enabling researchers, for the first time, to generative quantitative, context-sensitive interpretations of whole-brain patterns of brain activity.
Protocol: Genome-scale CRISPR-Cas9 Knockout and Transcriptional Activation Screening
Authors: Joung Julia , Konermann Silvana , Gootenberg Jonathan S. , Abudayyeh Omar O. , Platt Randall J. , Brigham Mark D. , Sanjana Neville E. , Zhang Feng
Published: June 2016

Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. Recently, the RNA-guided endonuclease Cas9 from the microbial immune system CRISPR (clustered regularly interspaced short palindromic repeats) has been adapted for genome-scale screening by combining Cas9 with guide RNA libraries. Here we describe a protocol for genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system. Custom-or ready-made guide RNA libraries are constructed and packaged into lentivirus for delivery into cells for screening. As each screen is unique, we provide guidelines for determining screening parameters and maintaining sufficient coverage. To validate candidate genes identified from the screen, we further describe strategies for confirming the screening phenotype as well as genetic perturbation through analysis of indel rate and transcriptional activation. Beginning with library design, a genome-scale screen can be completed in 6-10 weeks followed by 3-4 weeks of validation.
Efficient inference of recent and ancestral recombination within bacterial populations
Authors: Mostowy Rafal , Croucher Nicholas J. , Andam Cheryl P. , Corander Jukka , Hanage William P. , Marttinen Pekka
Published: June 2016

Prokaryotic evolution is affected by horizontal transfer of genetic material through recombination. Inference of an evolutionary tree of bacteria thus relies on accurate identification of the population genetic structure and recombination-derived mosaicism. Rapidly growing databases represent a challenge for computational methods to detect recombinations in bacterial genomes. We introduce a novel algorithm calledfastGEARwhich identifies lineages in diverse microbial alignments, and recombinations between them and from external origins. The algorithm detects both recent recombinations (affecting a few isolates) and ancestral recombinations between detected lineages (affecting entire lineages), thus providing insight into recombinations affecting deep branches of the phylogenetic tree. In sim-ulations,fastGEARhad comparable power to detect recent recombinations and outstanding power to detect the ancestral ones, compared to state-of-the-art methods, often with a fraction of computational cost. We demonstrate the utility of the method by analysing a collection of 616 whole-genomes of a recombinogenic pathogenStreptococcus pneumoniae, for which the method provided a high-resolution view of recombination across the genome. We examined in detail the penicillin-binding genes across theStreptococcusgenus, demonstrating previously undetected genetic exchanges between different species at these three loci. Hence,fastGEARcan be readily applied to investigate mosaicism in bacterial genes across multiple species. Finally,fastGEARcorrectly identified many known recombination hotspots and pointed to potential new ones. Matlab code and Linux/Windows executables are available athttps://users.ics.aalto.fi/~pemartti/fastGEAR/
“Gap hunting” to characterize clustered probe signals in Illumina methylation array data
Authors: Andrews Shan V. , Ladd-Acosta Christine , Feinberg Andrew P. , Hansen Kasper D. , Fallin M. Daniele
Published: June 2016

Background

The Illumina 450K array has been widely used in epigenetic association studies. Current quality-control (QC) pipelines typically remove certain sets of probes, such as those containing a SNP or with multiple mapping locations. An additional set of potentially problematic probes are those with DNA methylation (DNAm) distributions characterized by two or more distinct clusters separated by gaps. Data-driven identification of such probes may offer additional insights for downstream analyses.

Results

We developed a procedure, termed “gap hunting”, to identify probes showing clustered distributions. Among 590 peripheral blood samples from the Study to Explore Early Development, we identified 11,007 “gap probes”. The vast majority (9,199) are likely attributed to an underlying SNP(s) or other variant in the probe, although SNP-affected probes exist that do not produce a gap signals. Specific factors predict which SNPs lead to gap signals, including type of nucleotide change, probe type, DNA strand, and overall methylation state. These expected effects are demonstrated in paired genotype and 450k data on the same samples. Gap probes can also serve as a surrogate for the local genetic sequence on a haplotype scale and can be used to adjust for population stratification.

Conclusions

The characteristics of gap probes reflect potentially informative biology. QC pipelines may benefit from an efficient data-driven approach that “flags” gap probes, rather than filtering such probes, followed by careful interpretation of downstream association analyses. Our results should translate directly to the recently released Illumina 850K EPIC array given the similar chemistry and content design.
The role of single occupancy effects on integrase dynamics in a cell-free system
Authors: Artavanis Georgios , Hsiao Victoria , Hayes Clarmyra A. , Murray Richard M.
Published: June 2016

Phage integrase-based circuits are an alternative approach to relying on transcriptional and translational repression for biomolecular circuits. Previous research has shown that circuits based on integrases can perform a variety of functions, including counters, Boolean logic operators, memory modules and temporal event detectors. It is therefore essential to develop a principled theoretical and experimental framework for the design, implementation and study of such circuits. One of the fundamental questions that such a framework should address concerns the functionality limitations and temporal dynamics of the integrases as regulatory elements. Here, we test the functionality of several large serine integrases from a recently published library in a cell-free transcription-translation (TX-TL) platform. Additionally, we use a combination of experimental data and models to investigate integrase dynamics as a function of enzyme concentration and number of binding sites.

We report that sequestration of integrase molecules, either in the form of monomers or dimers, by the integrase's own binding sites dominates integrase dynamics, and that the delay in the activation of the reporter is negatively correlated with integrase plasmid concentration. We have validated our sequestration hypothesis by building a model with MATLAB’s SimBiology toolbox, and running simulations with various integrase and binding sites concentrations. The simulation results qualitatively match the experimental results, and offer further insights into the system.
Temporal Modulations Reveal Distinct Rhythmic Properties of Speech and Music
Authors: Ding Nai , Patel Aniruddh D. , Chen Lin , Butler Henry , Luo Cheng , Poeppel David
Published: June 2016

Speech and music have structured rhythms, but these rhythms are rarely compared empirically. This study, based on large corpora, quantitatively characterizes and compares a major acoustic correlate of spoken and musical rhythms, the slow (0.25-32 Hz) temporal modulations in sound intensity. We show that the speech modulation spectrum is highly consistent cross 9 languages (including languages with typologically different rhythmic characteristics, such as English, French, and Mandarin Chinese). A different, but similarly consistent modulation spectrum is observed for Western classical music played by 6 different instruments. Western music, including classical music played by single instruments, symphonic, jazz, and rock music, contains more energy than speech in the low modulation frequency range below 4 Hz. The temporal modulations of speech and music show broad but well-separated peaks around 5 and 2 Hz, respectively. These differences in temporal modulations alone, without any spectral details, can discriminate speech and music with high accuracy. Speech and music therefore show distinct and reliable statistical regularities in their temporal modulations that likely facilitate their perceptual analysis and its neural foundations.
Meta population modelling of narwhals in East Canada and West Greenland - 2017
Authors: Witting Lars
Published: June 2016

This paper combines a catch allocation model for narwhals in East Canada and West Greenland with Bayesian population modelling of the eight summer aggregations of narwhals in the region. The catch allocation model allocates the catches in different hunting areas and seasons to the different summer aggregations, and the population models analyse the impact of these catches on the population dynamics of the eight narwhal aggregations.

The population models run from 1970, and the catch allocation model needs population trajectories from 1970 to the present in order to estimate the catches taken from the different summer aggregations during this period. In an initial run it uses linear transitions between the available abundance estimates; but more elaborate population trajectories are estimated by the fit of the population models to the abundance data. The two models are therefore run in an iterative manner until the catch histories that are estimated by the allocation model, and the abundance trajectories that are estimated by the population models, converge between runs.

Given a converged model and potential future catch options for the different hunts, the model estimates the probabilities of fulfilling management options for the eight summer aggregations of narwhals.
ADAR-Independent A-to-I RNA Editing is Generally Adaptive for Sexual Reproduction in Fungi
Authors: Wang Qinhu , Jiang Cong , Liu Huiquan , Xu Jin-Rong
Published: June 2016

ADAR-mediated A-to-I RNA editing is a well-known RNA modification mechanism in metazoans that can cause nonsynonymous changes leading to amino acid substitutions. Despite a few cases that are clearly functionally important, the biological significance of most nonsynonymous editing sites in animals remains largely unknown. Recently, genome-wide A-to-I editing was found to occur mainly in the coding regions and specifically during sexual reproduction in the wheat scab fungusFusarium graminearumthat lacks ADAR orthologs. In this study, we found that both the frequency and editing level of nonsynonymous editing is significantly higher than those of synonymous editing, suggesting that nonsynonymous editing is generally beneficial and under positive selection inF. graminearum. We also showed that nonsynonymous editing favorably targets functionally more important and more conserved genes, but at less-conserved sites, indicating that the RNA editing system is adapted to fine turn protein functions by avoiding potentially deleterious editing events. Furthermore, nonsynonymous editing inF. graminearumwas found to be under codon-specific selection and most types of codon changes tend to cause amino acid substitutions with distinct physical-chemical properties and smaller molecular weights, which likely have more profound impact on protein structures and functions. In addition, we found that the most abundant synonymous editing of leucine codons is adapted to fine turn the protein expression by increasing codon usage bias. These results clearly show that A-to-I RNA editing in fungi is generally adaptive and recoding RNA editing may play an important role in sexual development in filamentous ascomycetes.
The role of evolutionary selection in the dynamics of protein structure evolution
Authors: Gilson Amy I. , Marshall-Christensen Ahmee , Choi Jeong-Mo , Shakhnovich Eugene I.
Published: June 2016

Homology modeling is a powerful tool for predicting a protein’s structure. This approach is successful because proteins whose sequences are only 30% identical still adopt the same structure, while structure similarity rapidly deteriorates beyond the 30% threshold. By studying the divergence of protein structure as sequence evolves in real proteins and in evolutionary simulations, we show that this non-linear sequence-structure relationship emerges as a result of selection for protein folding stability in divergent evolution. Fitness constraints prevent the emergence of unstable protein evolutionary intermediates thereby enforcing evolutionary paths that preserve protein structure despite broad sequence divergence. However on longer time scales, evolution is punctuated by rare events where the fitness barriers obstructing structure evolution are overcome and discovery of new structures occurs. We outline biophysical and evolutionary rationale for broad variation in protein family sizes, prevalence of compact structures among ancient proteins and more rapid structure evolution of proteins with lower packing density.
Firing patterns of serotonin neurons underlying cognitive flexibility
Authors: Matias Sara , Lottem Eran , Dugué Guillaume P. , Mainen Zachary F.
Published: June 2016

Serotonin is implicated in mood and affective disorders1,2but growing evidence suggests that its core endogenous role may be to promote flexible adaptation to changes in the causal structure of the environment3–8. This stems from two functions of endogenous serotonin activation: inhibiting learned responses that are not currently adaptive9,10and driving plasticity to reconfigure them1113. These mirror dual functions of dopamine in invigorating reward-related responses and promoting plasticity that reinforces new ones16,17. However, while dopamine neurons are known to be activated by reward prediction errors18,19, consistent with theories of reinforcement learning, the reported firing patterns of serotonin neurons21–23do not accord with any existing theories1,24,25. Here, we used long-term photometric recordings in mice to study a genetically-defined population of dorsal raphe serotonin neurons whose activity we could link to normal reversal learning. We found that these neurons are activated by both positive and negative prediction errors, thus reporting the kind of surprise signal proposed to promote learning in conditions of uncertainty26,27. Furthermore, by comparing cue responses of serotonin and dopamine neurons we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Together, these findings show how the firing patterns of serotonin neurons support a role in cognitive flexibility and suggest a revised model of dopamine-serotonin opponency with potential clinical implications.
Potential energy landscapes reveal the information-theoretic nature of the epigenome
Authors: Jenkinson Garrett , Pujadas Elisabet , Goutsias John , Feinberg Andrew P.
Published: June 2016

Epigenetics is defined as genomic modifications carrying information independent of DNA sequence heritable through cell division. In 1940, Waddington coined the term “epigenetic landscape” as a metaphor for pluripotency and differentiation, but epigenetic potential energy landscapes have not yet been rigorously defined. Using well-grounded biological assumptions and principles of statistical physics and information theory, we derive potential energy landscapes from whole genome bisulfite sequencing data that allow us to quantify methylation stochasticity genome-wide and discern epigenetic differences using Shannon’s entropy and the Jensen-Shannon distance. We discover a “developmental wheel” of germ cell lineages and an association between entropy and chromatin structure. Viewing methylation maintenance as a communications system, we introduce methylation channels and show that higher-order chromatin organization can be predicted from their informational properties. Our results provide a fundamental understanding of the information-theoretic nature of the epigenome and a powerful methodology for studying its role in disease and aging.
Shedding light on the grey zone of speciation along a continuum of genomic divergence
Authors: Roux Camille , Fraïsse Christelle , Romiguier Jonathan , Anciaux Yoann , Galtier Nicolas , Bierne Nicolas
Published: June 2016

Speciation results from the progressive accumulation of mutations that decrease the probability of mating between parental populations, or reduce the fitness of hybrids - the so-called species barriers. The speciation genomic literature, however, is mainly a collection of case studies, each with its own approach and specificities, such that a global view of the gradual process of evolution from one to two species is currently lacking. Of primary importance is the prevalence of gene flow between diverging entities, which is central in most species concepts, and has been widely discussed in recent years. Here we explore the continuum of speciation thanks to a comparative analysis of genomic data from 61 pairs of populations/species of animals with variable levels of divergence. Gene flow between diverging gene pools is assessed under an Approximate Bayesian Computation (ABC) framework. We show that the intermediate "grey zone" of speciation, in which taxonomy is often controversial, spans from 0.5% to 2% of net synonymous divergence, irrespective of species life-history traits or ecology. Thanks to appropriate modeling of among-loci variation in genetic drift and introgression rate, we clarify the status of the majority of ambiguous cases and uncover a number of cryptic species. Our analysis also reveals the high incidence in animals of semi-isolated species, when some but not all loci are affected by barriers to gene flow, and highlights the intrinsic difficulty, both statistical and conceptual, of delineating species in the grey zone of speciation.
On portfolio optimization
Authors: Berger Theo , Fieberg Christian
Published: June 2016

Purpose

The purpose of this paper is to show how investors can incorporate the multi-scale nature of asset and factor returns into their portfolio decisions and to evaluate the out-of-sample performance of such strategies.

Design/methodology/approach

The authors decompose daily return series of common risk factors and of all stocks listed in the Dow Jones Industrial Index (DJI) from 2000 to 2015 into different time scales to separate short-term noise from long-run trends. Then, the authors apply various (multi-scale) factor models to determine variance-covariance matrices which are used for minimum variance portfolio selection. Finally, the portfolios are evaluated by their out-of-sample performance.

Findings

The authors find that portfolios which are constructed on variance-covariance matrices stemming from multi-scale factor models outperform portfolio allocations which do not take the multi-scale nature of asset and factor returns into account.

Practical implications

The results of this paper provide evidence that accounting for the multi-scale nature of return distributions in portfolio decisions might be a promising approach from a portfolio performance perspective.

Originality/value

The authors demonstrate how investors can incorporate the multi-scale nature of returns into their portfolio decisions by applying wavelet filter techniques.
Commentary: enhancing community inclusion for people with complex needs through partnership working
Authors: Carnaby Steve
Published: June 2016

Purpose

– The purpose of this paper is to serve as a commentary on the work reported by Hilary Johnson and her colleagues, which used partnership working as a lever for developing community inclusion for people with complex communication needs.

Design/methodology/approach

– The commentary uses the wider literature on social inclusion as well as narrative from current policy in England on the development of “Transforming Care Partnerships” to explore some of the issues raised by the research.

Findings

– The conclusion is that physical integration is only the starting point for a vision where people with the most complex needs live the “included life” which evolves by developing partnership working and reciprocal relationships between people with and without disabilities.

Originality/value

– This paper attempts to highlight relevant key research in the area of social integration as a way of reviewing the likely impact of recent policy on the lives of people with intellectual disabilities and the most complex needs.
The effects of physical prehabilitation in elderly patients undergoing colorectal surgery: a systematic review
Authors: Bruns E. R. J. , van den Heuvel B. , Buskens C. J. , van Duijvendijk P. , Festen S. , Wassenaar E. B. , van der Zaag E. S. , Bemelman W. A. , van Munster B. C.
Published: June 2016

Aim

Prehabilitation, defined as enhancement of the preoperative condition of a patient, is a possible strategy for improving postoperative outcome. Lack of muscle strength and poor physical condition, increasingly prevalent in older patients, are risk factors for postoperative complications. Eighty‐five per cent of patients with colorectal cancer are aged over 60 years. Since surgery is the cornerstone of their treatment, this review systemically examined the literature on the effect of physical prehabilitation in older patients undergoing colorectal surgery.

Method

Trials and case–control studies investigating the effect of physical prehabilitation in patients over 60 years undergoing colorectal surgery were retrieved from MEDLINE, EMBASE, CINAHL and the Cochrane library. Patient characteristics, the type of intervention and outcome measurements were recorded. The risk of bias and heterogeneity was assessed.

Results

Five studies including 353 patients were identified. They were small, containing an average of 77 patients and were of moderate methodological quality. Compliance rates of the prehabilitation programme varied from 16 to 97%. None of the studies could identify a significant reduction of postoperative complications or length of hospital stay. Four studies showed physical improvement (walking distance, respiratory endurance) in the prehabilitation group. Clinical heterogeneity precluded a meta‐analysis.

Conclusion

Prehabilitation is a possible means of enhancing the physical condition of patients preoperatively. The quality of studies in older patients undergoing colorectal surgery is poor, despite the increase in elderly people with colorectal cancer. Defining specific patient groups at risk and standardizing the outcome are essential for improving the results of treatment.
Sex Hormones Protect Against Amyloid‐β Induced Oxidative Stress in the Choroid Plexus Cell Line Z310
Authors: Costa A. R. , Marcelino H. , Gonçalves I. , Quintela T. , Tomás J. , Duarte A. C. , Fonseca A. M. , Santos C. R. A.
Published: June 2016

The choroid plexus (CP) epithelium is a unique structure in the brain that forms an interface between the peripheral blood on the basal side and the cerebrospinal fluid (CSF) on the apical side. It is a relevant source of many polypeptides secreted to the CSF with neuroprotective functions and also participates in the elimination and detoxification of brain metabolites, such as β‐amyloid (Aβ) removal from the CSF through transporter‐mediated influx. The CP is also a target tissue for sex hormones (SHs) that have recognised neuroprotective effects against a variety of insults, including Aβ toxicity and oxidative stress in the central nervous system. The present study aimed to understand how SHs modulate Aβ‐induced oxidative stress in a CP cell line (Z310 cell line) by analysing the effects of Aβ1–42 on oxidative stress, mitochondrial function and apoptosis, as well as by assessing how 17β‐oestradiol (E2) and 5α‐dihydrotestosterone (DHT) modulated these effects and the cellular uptake of Aβ1–42 by CP cells. Our findings show that E2 and DHT treatment reduce Aβ1–42‐induced oxidative stress and the internalisation of Aβ1–42 by CP epithelial cells, highlighting the importance of considering the background of SHs and therefore sex‐related differences in Aβ metabolism and clearance by CP cells.
Peripheral and Central Mechanisms Involved in the Hormonal Control of Male and Female Reproduction
Authors: Rudolph L. M. , Bentley G. E. , Calandra R. S. , Paredes A. H. , Tesone M. , Wu T. J. , Micevych P. E.
Published: June 2016

Reproduction involves the integration of hormonal signals acting across multiple systems to generate a synchronised physiological output. A critical component of reproduction is the luteinising hormone (LH) surge, which is mediated by oestradiol (E2) and neuroprogesterone interacting to stimulate kisspeptin release in the rostral periventricular nucleus of the third ventricle in rats. Recent evidence indicates the involvement of both classical and membrane E2 and progesterone signalling in this pathway. A metabolite of gonadotrophin‐releasing hormone (GnRH), GnRH‐(1‐5), has been shown to stimulate GnRH expression and secretion, and has a role in the regulation of lordosis. Additionally, gonadotrophin release‐inhibitory hormone (GnIH) projects to and influences the activity of GnRH neurones in birds. Stress‐induced changes in GnIH have been shown to alter breeding behaviour in birds, demonstrating another mechanism for the molecular control of reproduction. Peripherally, paracrine and autocrine actions within the gonad have been suggested as therapeutic targets for infertility in both males and females. Dysfunction of testicular prostaglandin synthesis is a possible cause of idiopathic male infertility. Indeed, local production of melatonin and corticotrophin‐releasing hormone could influence spermatogenesis via immune pathways in the gonad. In females, vascular endothelial growth factor A has been implicated in an angiogenic process that mediates development of the corpus luteum and thus fertility via the Notch signalling pathway. Age‐induced decreases in fertility involve ovarian kisspeptin and its regulation of ovarian sympathetic innervation. Finally, morphological changes in the arcuate nucleus of the hypothalamus influence female sexual receptivity in rats. The processes mediating these morphological changes have been shown to involve the rapid effects of E2 controlling synaptogenesis in this hypothalamic nucleus. In summary, this review highlights new research in these areas, focusing on recent findings concerning the molecular mechanisms involved in the central and peripheral hormonal control of reproduction.
Accuracy of a Flash Glucose Monitoring System in Diabetic Dogs
Authors: Corradini S. , Pilosio B. , Dondi F. , Linari G. , Testa S. , Brugnoli F. , Gianella P. , Pietra M. , Fracassi F.
Published: June 2016

Background

A novel flash glucose monitoring system (FGMS) (FreeStyle Libre, Abbott, UK) was recently developed for humans. It continuously measures the interstitial glucose (IG) concentrations for 14 days.

Objectives

To assess the clinical and analytical accuracy of the FGMS in diabetic dogs.

Animals

Ten client‐owned diabetic dogs on insulin treatment.

Methods

Prospective and observational study. The FGMS was placed on the neck for up to 14 days. During the 1st–2nd, 6–7th, and 13–14th days from application, the IG measurements were compared with the plasma (EDTA) glucose (PG) concentrations analyzed by a reference hexokinase based method.

Results

The application and the use of the FGMS were apparently painless, easy, and well tolerated by all dogs. Mild erythema at the site of the application was found in 5/10 dogs at the end of the wearing period. A good correlation between IG and PG concentrations (rho = 0.94; P < .001) was found. The FGMS was 93, 99, and 99% accurate at low, normal, and high blood glucose concentrations. Mean ± standard deviation difference from the reference method was 2.3 ± 46.8 mg/dL.

Conclusion and clinical importance

The FGMS is easy to use and is accurate for IG glucose measurement in diabetic dogs.
The importance of family support in pediatrics and its impact on healthcare satisfaction
Authors: Sigurdardottir Anna Olafia , Garwick Ann W. , Svavarsdottir Erla Kolbrun
Published: June 2016

Aims

To evaluate predictors of healthcare satisfaction for parents whose children received hospital‐based healthcare services at the Children's hospital at Landspitali University Hospital.

Methods

In this cross‐sectional study, data on perceived family support, family quality of life, expressive family functioning, coping strategies and healthcare satisfaction were collected from 159 mothers and 60 fathers (N = 177 families) of children and adolescents from 2011 to 2012.

Results

Logistic regression analysis revealed that, for mothers, 38.8% of the variance in satisfaction with healthcare services was predicted by perceived family support and their coping strategies, while for fathers, 59.9% of the variance of their satisfaction with healthcare service was predicted by perceived family support, family quality of life and whether the child had been hospitalised before.

Discussion

Perceived family support was the one factor that was found to predict both the mothers' and the fathers' satisfaction with healthcare services. Knowing which factors predict satisfaction with health care among parents of hospitalised children with different chronic illnesses and health issues can inform the delivery of effective family‐focused interventions and evidence‐based practice to families.
Nine Decades of Fluid Mechanics
Authors: Gad-el-Hak Mohamed
Published: June 2016

As the ASME Division of Fluids Engineering celebrates its 90th Anniversary, I make a broad-brush sweep of progress in the field of fluid mechanics during this period. Selected theoretical, numerical, and experimental advances are described. The inventions of laser and computer have profound effects on humanity, but their influence on fluid mechanics is particularly elucidated in this review.
Blind cave fish may provide insights into human health
Authors: Pennisi Elizabeth
Published: June 2016

Cave adaptations are connected to diabetes, eye problems, and other conditions that afflict people.
Severity of Lower Urinary Tract Symptoms among Middle Aged and Elderly Nigerian Men: Impact on Quality of Life
Authors: Adegun Patrick Temi , Adebayo Philip Babatunde , Areo Peter Olufemi
Published: June 2016

Objectives. To compare the severity of LUTS among middle aged and elderly Nigerian men and determine the influence of LUTS severity on QoL.Methods. This cross-sectional study was conducted among new patients presenting with LUTS attending Urology clinic between 2011 and 2015. Assessment of symptoms was based on IPSS and bother score completed by the eligible subjects on the same day of their clinic visits.Results. Four hundred patients were studied comprising 229 middle aged and 171 elderly men. Interquartile range (IQR) of IPSS scores for men <65 years and those ≥65 years was 14.0 (16.0) and 19 (15.0), respectively (p<0.001). Mild LUTS was significantly associated with best, good, and poor quality of life while moderate LUTS was associated with poor QoL. Severe LUTS was significantly associated with all the categories of QoL (Best-Worst). Among the cohort of subjects with poor QoL, elderly patients had a significantly higher median IPSS score (p<0.05).Conclusions. There is no level of severity of LUTS in which patients’ QoL is not impaired although mild symptomatology may be associated with better QoL and severe symptomatology with poor QoL. Careful attention to QoL may help identify patients who require early and prompt treatment irrespective of the IPSS.
Isolation and Identification of the Antimicrobial Agent Beauvericin from the EndophyticFusarium oxysporum5-19 with NMR and ESI-MS/MS
Authors: Zhang Huawei , Ruan Chuanfen , Bai Xuelian , Zhang Miao , Zhu Shuangshuang , Jiang Yingying
Published: June 2016

Endophytic microbe has been proved to be one of rich sources of bioactive natural products with potential application for new drug and pesticide discovery. One cyclodepsipeptide, beauvericin, was firstly isolated from the fermentation broth ofFusarium oxysporum5-19 endophytic onEdgeworthia chrysanthaLinn. Its chemical structure was unambiguously identified by a combination of spectroscopic methods, such as HRESI-MS and1H and13C NMR. ESI-MS/MS was successfully used to elucidate the splitting decomposition route of the positive molecule ion of beauvericin. Antimicrobial results showed that this cyclodepsipeptide had inhibitory effect on three human pathogenic microbes,Candida albicans,Escherichia coli, andStaphylococcus aureus. In particular, beauvericin exhibited the strongest antimicrobial activity againstS. aureuswith MIC values of 3.91 μM, which had similar effect with that of the positive control amoxicillin.
Service Radius Model and Service Scope Optimization of City Public Parking Garage
Authors: Zeng Chao , Tang Boming , Liu Tangzhi
Published: June 2016

The service radius of public parking garage is related to the supply of parking spots and parking behavior characteristics of drivers. However, the empirical and statistical methods in the optimization of public parking garage have limitations. Based on the theory of value engineering and satisfaction, an optimization model for public parking garage service radius is established, which satisfies the requirements of both drivers and owners. Then, an amended model is proposed by using accessibility theory and the principle of moment balance. This model, in consideration of city resistance and walking impedance, is modified from the circular service scope to an irregular polygon, which is more suitable for the actual situation. Finally, the method is verified by a practical example. The results suggest that the optimization model of the service radius and the optimization method of service scope can not only balance the needs of drivers and public parking garages’ owners, but also improve the operation efficiency of parking garages, so that they are more fit for the actual situation of parking service areas. This paper provides new ideas and methods to determine public parking garage service radius and service scope.
Application of the Multitype Strauss Point Model for Characterizing the Spatial Distribution of Landslides
Authors: Das Iswar , Stein Alfred
Published: June 2016

Landslides are common but complex natural hazards. They occur on the Earth’s surface following a mass movement process. This study applies the multitype Strauss point process model to analyze the spatial distributions of small and large landslides along with geoenvironmental covariates. It addresses landslides as a set of irregularly distributed point-type locations within a spatial region. Their intensity and spatial interactions are analyzed by means of the distance correlation functions, model fitting, and simulation. We use as a dataset the landslide occurrences for 28 years from a landslide prone road corridor in the Indian Himalayas. The landslides are investigated for their spatial character, that is, whether they show inhibition or occur as a regular or a clustered point pattern, and for their interaction with landslides in the neighbourhood. Results show that the covariates lithology, land cover, road buffer, drainage density, and terrain units significantly improved model fitting. A comparison of the output made with logistic regression model output showed a superior prediction performance for the multitype Strauss model. We compared results of this model with the multitype/hard core Strauss point process model that further improved the modeling. Results from the study can be used to generate landslide susceptibility scenarios. The paper concludes that a multitype Strauss point process model enriches the set of statistical tools that can comprehensively analyze landslide data.
High Dose Ilaprazole/Amoxicillin as First-Line Regimen forHelicobacter pyloriInfection in Korea
Authors: Kwack WonGun , Lim YunJeong , Lim ChiYeon , Graham David Y.
Published: June 2016

Objective. The eradication rate ofHelicobacter pylori(H. pylori) following standard triple therapy has declined over the past few decades. This study has determined whether high dose dual therapy (PPI and amoxicillin) is adequate for eradicatingH. pyloriin Korea.Methods. This was an open-labeled study ofH. pyloriinfected treatment-naive patients. Subjects received dual therapy for 14 days: ilaprazole 40 mg tablets given twice a day and amoxicillin 750 mg tablets given 4 times a day. At the end of the therapy, the subjects visited the clinic to confirm compliance and monitor for any side effects. Subjects visited again after 4–6 weeks to confirmH. pyloristatus through a urea breath test.Results.The cure rate ofH. pyloriwas 79.3% (23 of 29) (95% confidence interval: 61.6–90.2) in the intention-to-treat analysis and 82.1% (23 of 28) in the per-protocol analysis. Compliance rates were high (96.6%) and side effects were minimal and tolerable.Conclusion.A high dose of ilaprazole + amoxicillin was ineffective as the first-line therapy for eradicatingH. pyloriin Korea. Future studies should focus on intragastric pH measurements and assess amoxicillin resistance.
Symmetric Lipomatosis Arising in the Tongue Presenting as Macroglossia and Articulatory Disorder
Authors: Kudoh Masanori , Omura Ken , Satsukawa Arata , Matsumoto Koshi , Taguchi Takahide , Harada Hiroyuki , Ishii Yoshimasa
Published: June 2016

Symmetric lipomatosis is definitively characterized by symmetric, tumorous lipomatous proliferation of adipose tissue that often develops in the head and neck, shoulders, and upper trunk. However, in the oral region, symmetric lipomatosis of the tongue (SLT) is an extremely rare condition related to generalized lipidosis that is often caused by chronic alcoholism. It is characterized by multiple symmetric lipomatous nodules and diffuse bilateral swelling located within the tongue. We report an extremely rare case of SLT arising in an 80-year-old man with a long history of alcoholic liver cirrhosis. He exhibited multiple soft nodular protrusions on the bilateral margin of the tongue presenting as macroglossia for years. Although MR imaging showed multiple fatty masses on both sides of the tongue, there was no elevated tumor mass on the bilateral margin. The patient underwent bilateral partial glossectomy under general anesthesia. Histopathologically, the resected tumor exhibited diffuse infiltration with mature adipose tissue lacking a fibrous capsule. Due to the lipidosis and the unusual presentation of multiple lesions, the lesion was ultimately diagnosed as SLT. At present, after surgery, the patient wears a full-denture and is in excellent condition, with no sign of recurrence, improved QOL, and recovery of masticatory, articulatory, and speech intelligibility functions.
Spontaneous Heterotopic Pregnancy: Dual Case Report and Review of Literature
Authors: Chadee Annika , Rezai Shadi , Kirby Catherine , Chadwick Ekaterina , Gottimukkala Sri , Hamaoui Abraham , Stankovich Vasiliy , Hale Theodore , Gilak Hamid , Momtaz Mohammad , Sasken Harvey , Henderson Cassandra E.
Published: June 2016

Introduction.Heterotopic pregnancy is a rare complication usually seen in populations at risk for ectopic pregnancy or those undergoing fertility treatments. It is a potentially dangerous condition occurring in only 1 in 30,000 spontaneous pregnancies. With the advent of Assisted Reproduction Techniques (ART) and ovulation induction, the overall incidence of heterotopic pregnancy has risen to approximately 1 in 3,900 pregnancies. Other risk factors include a history of pelvic inflammatory disease (PID), tubal damage, pelvic surgery, uterine Mullerian abnormalities, and prior tubal surgery. Heterotopic pregnancy is a potentially fatal condition, rarely occurring in natural conception cycles. Most commonly, heterotopic pregnancy is diagnosed at the time of rupture when surgical management is required.Case.This paper represents two cases of heterotopic pregnancies as well as a literature review.Conclusion.Heterotopic pregnancy should be suspected in patients with an adnexal mass, even in the absence of risk factors. Clinicians must be alert to the fact that confirming an intrauterine pregnancy clinically or by ultrasound does not exclude the coexistence of an ectopic pregnancy. A high index of suspicion in women is needed for early and timely diagnosis, and management with laparotomy or laparoscopy can result in a favorable and successful obstetrical outcome.