bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Traditional Chinese Medicine Zhike-Houpu Herbal Pair on Depressive Behaviors and Hippocampal Serotonin 1A Receptors in Rats After Chronic Unpredictable Mild Stress
Authors: Xia Zian , Zhang Chunhu , Du Yuanhao , Huang Wei , Xing Zhihua , Cao Hui , Nie Kechao , Wang Yang , Xiong Xingui , Yang Bo
Published: October 2018

Objective

Zhike-Houpu herbal pair (ZKHPHP) is a well-known Chinese medicine to treat gastrointestinal motility dysfunction. Recently, many researchers have found that some of the compounds of ZKHPHP such as meranzin hydrate and magnolol have antidepressant effects. However, little is known about the antidepressant mechanism of ZKHPHP. Therefore, the main aim of the study is to evaluate the antidepressant-like effects of ZKHPHP and its possible mechanism of action on 5-hydroxytryptamine receptor 1A (HTR1A) in the hippocampus CA1 region in rats exposed to chronic unpredictable mild stress.

Methods

Male Sprague Dawley rats were randomly divided into the following six groups: normal, model, ZKHPHP (3 g/kg), ZKHPHP (10 g/kg), ZKHPHP (20 g/kg), and ZKHPHP (30 g/kg);n= 8 per group. We exposed the rats to chronic unpredictable mild stress and then assessed antidepressant-like effects of ZKHPHP by measuring weight change, observing the open-field test, and measuring sucrose water consumption. The antidepressant mechanism was examined by measuring the effect of ZKHPHP on HTR1A protein expression and HTR1A mRNA expression in the hippocampus CA1 region by using immunohistochemistry analysis, Western blotting, and real-time reverse transcription-polymerase chain reaction.

Results

ZKHPHP (10 or 20 g/kg) reduced the incidence of depressive-like behaviors and increased HTR1A protein and HTR1A mRNA expression in the hippocampus CA1 in rats displaying depressive behavior, whereas ZKHPHP (3 or 30 g/kg) had no obvious effect on the measured depression indicators.

Conclusions

These data show that ZKHPHP has antidepressant-like effects based on a chronic unpredictable mild stress-induced depression model in rats. ZKHPHP may be attractive as an antidepressant because of its beneficial effects on depression and the absence of gastrointestinal dysregulation, which is a frequently observed unintended effect of many commonly used antidepressive medications.
Antithrombotic Stewardship: Assessing Use of Computerized Clinical Decision Support Tools to Enhance Safe Prescribing of Direct Oral Anticoagulants in Hospitalized Patients
Authors: Ahuja Tania , Raco Veronica , Papadopoulos John , Green David
Published: October 2018

Prescribing patterns for oral anticoagulants in patients with nonvalvular atrial fibrillation and venous thromboembolism is shifting from vitamin K antagonists, such as warfarin to the direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, and apixaban. Although many hospital systems have implemented clinical decision support or enhanced monitoring for patients prescribed warfarin, there is limited evidence to suggest similar levels of enhanced monitoring for DOACs. The antithrombotic stewardship team at our institution developed guidelines and implemented computerized clinical decision support (CCDS) tools to enhance medication and patient safety related to the DOACs. We sought to assess the safety and effectiveness of these CCDS tools available to clinicians upon DOAC prescription in hospitalized patients. We performed a retrospective review of 121 patients who received at least two doses of a DOAC from January 2013 to July 2014. We assessed dosing of the DOAC according to the CCDS provided upon order entry. Adherence to CCDS was 80% (n = 24), 75% (n = 46), and 87% (n = 27) in the dabigatran, apixaban, and rivaroxaban group, respectively. Our data demonstrate that implementing CCDS for DOACs into the electronic medical record may ensure safe prescribing of high-risk medications.
Social and Behavioral Consequences of Participation in HIV Preventive Vaccine Trials in the ANRS COHVAC Cohort
Authors: Durier Christine , Desaint Corinne , Launay Odile
Published: October 2018

From 1992 to 2007, the ANRS (France Recherche Nord & Sud Sida-HIV Hépatites) set up a network of healthy volunteers at low risk of HIV infection and participating in preventive HIV vaccine phase I and II trials. The objectives of the ANRS COHVAC volunteer cohort include the social consequences of trial participation and their sexual behavior over time. For 488 volunteers who received a vaccine candidate, 462 selection files were collected, and from 2008 to 2016, 355 volunteers participated in the prospective cohort, including self-administered and face-to-face questionnaires administered annually. The volunteer population is relatively old, with social characteristics and engagement in society rather high. Most volunteers and people around them well accepted the trials, and participation in vaccine trials was not followed by increased risk-taking regarding HIV infection years later.
Exceptional Risk: Healthy Volunteers' Perceptions of HIV/AIDS Clinical Trials
Authors: Cottingham Marci D. , Kalbaugh Julianne M. , Swezey Teresa , Fisher Jill A.
Published: October 2018

As with all early-stage testing of investigational drugs, clinical trials targeting HIV/AIDS can pose unknown risks to research subjects. Unlike sick participants seeking a therapeutic benefit, the motivations and barriers for healthy volunteers are more complex and understudied. Drawing on interviews and clinical trial data from 178 healthy volunteers, we examine how they perceive HIV/AIDS studies in the early stages of testing. A subset of healthy volunteers see phase I HIV/AIDS studies as particularly risky for reasons ranging from fear of catching the disease or having long-lasting and uncomfortable side effects to inexplicable fears that they cannot even articulate. Some participants have had past negative experiences in such trials that inform these views, but others cite information from staff and other participants as influential. Healthy volunteers' general fears concerning AIDS also shape their views of participating in phase I HIV/AIDS clinical trials.
Superiority of Multidetector Computed Tomography With 3-Dimensional Volume Rendering Over Plain Radiography in the Assessment of Spinal Surgical Instrumentation Complications in Patients With Cancer
Authors: Debnam James M. , Chi Tzehping L. , Ketonen Leena , Wei Wei , Guha-Thakurta Nandita
Published: October 2018

Objective

The objective of this study was to compare multidetector computed tomography (MDCT) images with volume-rendered translucent display (VRTLD) series to plain radiographs for evaluating spinal surgical instrumentation after resection and reconstruction for spinal malignancies.

Methods

In 44 patients with tumor resection and spinal reconstruction, 17 with complications, 3 neuroradiologists evaluated plain radiographs, MDCT images alone, VRTLD images alone, and MDCT images with VRTLD images for identifying complications in 3 categories: subsidence/migration, construct fracture, and screw loosening. Each category was scored as 1 (complications), 2 (no complications), or 3 (not sure), and the minimum score was used for analyses. Clinical/surgical outcomes were the reference standard.

Results

Sensitivity, specificity, and accuracy (95% confidence interval), respectively, were as follows: MDCT/VRTLD, 100%, 100%, 100% (91.96%–100.00%); MDCT alone, 88.24%, 100%, 95.45% (84.53%–99.44%); VRTLD alone, 82.35%, 96.3%, 90.91% (78.33%–97.47%); plain radiographs, 52.94%, 100%, 81.82% (67.29%–91.81%).

Conclusions

Multidetector computed tomography with VRTLD series seems best for evaluation of spinal instrumentation after tumor resection and reconstruction.
Effect of Statistically Iterative Image Reconstruction on Vertebral Bone Strength Prediction Using Bone Mineral Density and Finite Element Modeling: A Preliminary Study
Authors: Anitha D. , Subburaj Karupppasamy , Kopp Felix K. , Mei Kai , Foehr Peter , Burgkart Rainer , Sollmann Nico , Maegerlein Christian , Kirschke Jan S. , Noel Peter B. , Baum Thomas
Published: October 2018

Statistical iterative reconstruction (SIR) using multidetector computed tomography (MDCT) is a promising alternative to standard filtered back projection (FBP), because of lower noise generation while maintaining image quality. Hence, we investigated the feasibility of SIR in predicting MDCT-based bone mineral density (BMD) and vertebral bone strength from finite element (FE) analysis. The BMD and FE-predicted bone strength derived from MDCT images reconstructed using standard FBP (FFBP) and SIR with (FSIR) and without regularization (FSIRB0) were validated against experimental failure loads (Fexp). Statistical iterative reconstruction produced the best quality images with regard to noise, signal-to-noise ratio, and contrast-to-noise ratio. Fexp significantly correlated with FFBP, FSIR, and FSIRB0. FFBP had a significant correlation with FSIRB0 and FSIR. The BMD derived from FBP, SIRB0, and SIR were significantly correlated. Effects of regularization should be further investigated with FE and BMD analysis to allow for an optimal iterative reconstruction algorithm to be implemented in an in vivo scenario.
Are We Overdiagnosing Pulmonary Embolism? “No”
Authors: Remy-Jardin Martine
Published: October 2018

Diagnosis of acute pulmonary embolism currently relies on computed tomography angiography which is acknowledged as a powerful, noninvasive tool. The concept of overdiagnosis is counterbalanced by a series of unanswered questions regarding the natural history of acute pulmonary embolism and the missing links between acute and chronic thromboembolic disease. For numerous reasons, it is less than certain that this concept will survive.
Autophagy Induction Ameliorates Inflammatory Responses in Intestinal Ischemia–Reperfusion Through Inhibiting NLRP3 Inflammasome Activation
Authors: Wang Zishuo , Li Zhenlu , Feng Dongcheng , Zu Guo , Li Yang , Zhao Yan , Wang Guangzhi , Ning Shili , Zhu Jie , Zhang Feng , Yao Jihong , Tian Xiaofeng
Published: October 2018

Intestinal ischemia/reperfusion (I/R)-induced systemic inflammation leads to multiple organ dysfunction syndrome. Previous studies have indicated that the NOD-like receptor protein (NLRP)3 inflammasome modulates intestinal inflammation; however, the pathophysiological mechanisms remain unclear. Autophagy is a critical metabolic mechanism that promotes cellular survival following ischemic injury. Recently, basal autophagy has been implicated in the alleviation of extensive inflammation. However, the role of autophagy in NLRP3 inflammasome activation in intestinal I/R-induced inflammatory injury remains undefined. In the present study, we examined whether NLRP3 inflammasome activation is induced in mice subjected to intestinal I/R injury, which is measured as increased apoptosis-associated speck-like protein containing a CARD levels, caspase-1 activity, and interleukin-1β (IL-1β) secretion. Importantly, the in-vitro results showed that NLRP3 knockdown decreases proinflammatory cytokine production and increases resistance to hypoxia/reoxygenation (H/R)-triggered inflammation. Subsequently, we demonstrated a critical role for autophagy in suppressing intestinal I/R-induced NLRP3 inflammasome activation in vivo. Furthermore, we showed that the loss of autophagy activates inflammasome-mediated IL-1β secretion, which aggravates H/R injury, and NLRP3 knockdown reverses these effects. Collectively, these results directly implicated the homeostatic process of autophagy and NLRP3 inflammasome in ischemic bowel disease and identified a novel pathway for therapeutic intervention in intestinal I/R.
Sepsis Increases Muscle Proteolysis in Severely Burned Adults, but Does not Impact Whole-Body Lipid or Carbohydrate Kinetics
Authors: Murton Andrew , Bohanon Fredrick J. , Ogunbileje John O. , Capek Karel D. , Tran Ellen A. , Chao Tony , Sidossis Labros S. , Porter Craig , Herndon David N.
Published: October 2018

Sepsis is a common and often fatal consequence of severe burn injury, but its exact effects on whole body and muscle metabolism in the burn patient is unclear. To address this, 13 septic and 11 nonseptic patients (age: 36.9 ± 13.0 years) with burns encompassing >30% of their total body surface area underwent muscle protein kinetic studies under postabsorptive conditions using bolus injections of ring-13C6 and 15N phenylalanine isotopes. In parallel, whole-body lipid and carbohydrate kinetics were assessed using constant infusions of [U-13C6]palmitate, [6,6-2H2]glucose, and [2H5]glycerol, and during a 2-h hyperinsulinemic euglycemic clamp. Muscle mRNA levels of genes implicated in the development of muscle cachexia were assessed by qPCR. Fractional breakdown rates of mixed-muscle proteins were found to be 2.4-fold greater in septic versus nonseptic patients (P < 0.05). No discernable differences in fractional synthetic rate of mixed-muscle proteins or rate of appearance of plasma free fatty acids, glycerol, or glucose could be observed between patient groups, although the latter was significantly associated with burn size (P < 0.05). Hyperinsulinemia stimulated whole-body glucose uptake and suppressed endogenous glucose production and whole-body lipolytic rate to equivalent degrees in both groups. Muscle mRNA levels of genes spanning autophagy, lysosomal, and ubiquitin proteasome-mediated proteolysis were not enhanced in septic versus nonseptic patients. Our results demonstrate that accelerated muscle proteolysis appears to be the principal metabolic consequence of sepsis in severe burn patients and could be a contributing factor to the accelerated loss of muscle mass in these individuals. The exact mechanistic basis for these changes remains unclear.
Blue carbon: past, present and future, with emphasis on macroalgae
Authors: Raven John
Published: October 2018

Blue carbon did not originally include macroalgal ecosystems; however evidence is mounting that macroalgal ecosystems function in marine carbon sequestration. The great majority of present day marine macroalgal net primary productivity (NPP) involves haptophytic algae on eroding shores. For these organisms the long-term storage of particulate organic carbon involves export from the site of production of biomass that has evaded parasites and grazers, and that some of the exported biomass is sedimented and stored rather than being mineralized
en route
by detritivores (microbes and fauna). Export from eroding shores, and subsequent storage, of haptophytic marine macroalgal particulate organic carbon could have started by 1.6 Ga. Storage on depositing shores close to the site of NPP by rhizophytic macroalgae and then by rhizophytic coastal seagrasses, tidal marshes and mangroves began not less than 209 Ma ago. Future increases in surface ocean temperatures may bring tropical marine macroalgae to their upper temperature limit, while temperate marine macroalgae will migrate poleward, in both cases assuming that temperature increases faster than genetic adaptation to higher temperature. Increased CO
2
in the surface ocean will generally favour uncalcified over calcified marine macroalgae. This results in decreased CO
2
release from decreased calcification, as well as decreased ballasting by CaCO
3
of exported particulate organic carbon resulting in decreasing sedimentation. While much more work is needed, the available information suggests that macroalgae play a significant role in marine organic carbon storage.
Is callose required for silicification in plants?
Authors: Guerriero Gea , Stokes Ian , Exley Christopher
Published: October 2018

The cell wall polymer callose catalyses the formation of silica
in vitro
and is heavily implicated in biological silicification in
Equisetum
(horsetail) and
Arabidopsis
(thale cress)
in vivo
. Callose, a β-1,3-glucan, is an ideal partner for silicification, because its amorphous structure and ephemeral nature provide suitable microenvironments to support the condensation of silicic acid into silica. Herein, using scanning electron microscopy, immunohistochemistry and fluorescence, we provide further evidence of the cooperative nature of callose and silica in biological silicification in rice, an important crop plant and known silica accumulator. These new data along with recently published research enable us to propose a model to describe the intracellular events that together determine callose-driven biological silicification.
Phylogenetic non-independence in rates of trait evolution
Authors: Sakamoto Manabu , Venditti Chris
Published: October 2018

Statistical non-independence of species’ biological traits is recognized in most traits under selection. Yet, whether or not the evolutionary rates of such biological traits are statistically non-independent remains to be tested. Here, we test the hypothesis that phenotypic evolutionary rates are non-independent, i.e. contain phylogenetic signal, using empirical rates of evolution in three separate traits: body mass in mammals, beak shape in birds and bite force in amniotes. Specifically, we test if evolutionary rates are phylogenetically interdependent. We find evidence for phylogenetic signal in evolutionary rates in all three case studies. While phylogenetic signal diminishes deeper in time, this is reflective of statistical power owing to small sample and effect sizes. When effect size is large, e.g. owing to the presence of fossil tips, we detect high phylogenetic signals even in deeper time slices. Thus, we recommend that rates be treated as being non-independent throughout the evolutionary history of the group of organisms under study, and any summaries or analyses of rates through time—including associations of rates with traits—need to account for the undesired effects of shared ancestry.
Pathogen evolution in finite populations: slow and steady spreads the best
Authors: Parsons Todd L. , Lambert Amaury , Day Troy , Gandon Sylvain
Published: October 2018

The theory of life-history evolution provides a powerful framework to understand the evolutionary dynamics of pathogens. It assumes, however, that host populations are large and that one can neglect the effects of demographic stochasticity. Here, we expand the theory to account for the effects of finite population size on the evolution of pathogen virulence. We show that demographic stochasticity introduces additional evolutionary forces that can qualitatively affect the dynamics and the evolutionary outcome. We discuss the importance of the shape of the pathogen fitness landscape on the balance between mutation, selection and genetic drift. This analysis reconciles Adaptive Dynamics with population genetics in finite populations and provides a new theoretical toolbox to study life-history evolution in realistic ecological scenarios.
John Wallis's world of ink: from manuscripts to library
Authors: Ferlier Louisiane
Published: October 2018

John Wallis's encyclopaedic endeavours were built on a mountain of ink and paper. To consider Wallis's work in the making, this article will draw his portrait as a reader and book collector. Keeper of the University of Oxford archives, he secured donations for the Bodleian and Savilian libraries and obsessively consulted old and new publications, manuscript and printed texts to build and defend his own work. Revealing interconnections between his contributions to theology, cryptography, linguistics, music and mathematics, this paper will focus on Wallis's methodical construction of his personal ‘inkscape’. His passionate obsession with the preservation and dissemination of his thought in print will be considered alongside the research he only consigned in manuscript form, through correspondence and notes. This reconstruction of John Wallis's libraries will therefore provide us with an overview of the
érudit
's contested achievements, as well as a panorama of contemporary scholarly practices.
Roles of glycosaminoglycans as regulators of ligand/receptor complexes
Authors: Smock Robert G. , Meijers Rob
Published: October 2018

Glycosaminoglycans (GAGs) play a widespread role in embryonic development, as deletion of enzymes that contribute to GAG synthesis lead to deficiencies in cell migration and tissue modelling. Despite the biochemical and structural characterization of individual protein/GAG interactions, there is no concept available that links the molecular mechanisms of GAG/protein engagements to tissue development. Here, we focus on the role of GAG polymers in mediating interactions between cell surface receptors and their ligands. We categorize several switches that lead to ligand activation, inhibition, selection and addition, based on recent structural studies of select receptor/ligand complexes. Based on these principles, we propose that individual GAG polymers may affect several receptor pathways in parallel, orchestrating a cellular response to an environmental cue. We believe that it is worthwhile to study the role of GAGs as molecular switches, as this may lead to novel drug candidates to target processes such as angiogenesis, neuroregeneration and tumour metastasis.
Wnt signalling in the development of axon, dendrites and synapses
Authors: He Chun-Wei , Liao Chien-Po , Pan Chun-Liang
Published: October 2018

Wnts are a highly conserved family of secreted glycoproteins that play essential roles in the morphogenesis and body patterning during the development of metazoan species. In recent years, mounting evidence has revealed important functions of Wnt signalling in diverse aspects of neural development, including neuronal polarization, guidance and branching of the axon and dendrites, as well as synapse formation and its structural remodelling. In contrast to Wnt signalling in cell proliferation and differentiation, which mostly acts through β-catenin-dependent pathways, Wnts engage a diverse array of non-transcriptional cascades in neuronal development, such as the planar cell polarity, cytoskeletal or calcium signalling pathways. In this review, we summarize recent advances in the mechanisms of Wnt signalling in the development of axon, dendrite and synapse formation.
A temporal shift in trophic diversity among a predator assemblage in a warming Arctic
Authors: Yurkowski David J. , Hussey Nigel E. , Ferguson Steven H. , Fisk Aaron T.
Published: October 2018

Climate change is leading to northward shifts in species distributions that is altering interspecific interactions at low- and mid-trophic levels. However, little attention has been focused on the effects of redistributions of species on the trophic ecology of a high trophic-level predator assemblage. Here, during a 22-year period (1990–2012) of increasing sea temperature (1.0°C) and decreasing sea ice extent (12%) in Cumberland Sound, Nunavut, Canada, we examined the trophic structure of a near-apex predator assemblage before (1990–2002) and after (2005–2012) an increase in the availability of capelin—generally an indicator species in colder marine environments for a warming climate. Stable isotopes (δ13C and δ15N) were used in a Bayesian framework to assess shifts in diet, niche size and community-wide metrics for beluga whales (Delphinapterus leucas), ringed seals (Pusa hispida), Greenland halibut (Reinhardtius hippoglossoides) and anadromous Arctic char (Salvelinus alpinus). After 2005, consumption of forage fish increased for all predator species, suggesting diet flexibility with changing abiotic and biotic conditions. An associated temporal shift from a trophically diverse to a trophically redundant predator assemblage occurred where predators now play similar trophic roles by consuming prey primarily from the pelagic energy pathway. Overall, these long-term ecological changes signify that trophic shifts of a high trophic-level predator assemblage associated with climate change have occurred in the Arctic food web.
Fuzzy risk assessment of a deeply buried tunnel under incomplete information
Authors: Xia Yuanpu , Xiong Ziming , Lu Hao , Wen Zhu , Ma Chao
Published: October 2018

Risk assessment has always been an important part of safety risk research in tunnel and underground engineering. Owing to the characteristics of tunnel construction, to achieve an expected risk control effect, it is necessary to carry out accurate risk assessment research according to the risk assessment concept based on the entire tunnel construction process. At present, because of the frequent occurrences of safety accidents, a variety of risk assessment models have been proposed for different tunnel projects such as subways and railway tunnels, which can be roughly classified into two types: probability-based and fuzzy set theories. However, the existing models may be more suitable for the construction stage, and the design stage lacks a reliable and practical fuzzy risk assessment method. Therefore, based on fuzzy set theory and similarity measure theory, a risk assessment model is proposed to adapt to the characteristics that the risk information is difficult to quantify the fuzziness in the design phase. Firstly, new ideas of fuzzy risk analysis are proposed to overcome deficiencies in existing methods; secondly, a new similarity measure is constructed; then fusing multi-source fuzzy information based on evidence theory, the relationship between similarity measure and mass function is established. Finally, the new method is applied to the Yuelongmen tunnel. Results show that the concept of risk control and the risk assessment model are feasible.
Low reversed cyclic loading tests for integrated precast structure of lightweight wall with single-row reinforcement under a lightweight steel frame
Authors: Suizi Jia , Wanlin Cao , Yuchen Zhang
Published: October 2018

Given the development of precast structures for low-rise residential buildings, this study explores a new structure—namely, an integrated precast structure of lightweight recycled concrete wall with single-row reinforcement—under a lightweight steel frame filled with recycled concrete (integrated precast structure for short). The lightweight steel frame and lightweight wall cooperate to bear the forces. The applied concealed bracing, either a rebar bracing or a steel plate bracing, increases the shear resistance of the wall. The lightweight steel frame is designed to bear the vertical loading, whereas the seismic load in the horizontal direction is jointly borne by the frame and wall. This study presents the results of low reversed cyclic loading tests on nine specimens of integrated precast structures. An analysis is then carried out to investigate the mechanical properties of the specimens; based on these results, a formula for the force-bearing performance of the inclined section is developed. The results show satisfactory performance as an integrated piece; the proposed structure has two seismic lines of defence, with the lightweight wall restraint by the side frame being the first line and the steel frame being the second line. Because the failure of the wall can be categorized as shear failure, the restraint of the lightweight steel frame significantly reduces the potential damage of the wall. As the beams and columns of the steel frame tend to bend against failure, the wall filling helps resist sliding. Therefore, the reinforced joints of the connecting beams and columns show no visible signs of damage, indicating that the connection between the beams and columns is reliable. The narrow spacing of rebars and the setting of concealed bracing contribute to the increase in ductility and energy efficiency of the integrated structure and the evident reduction in the failure process. Furthermore, the recycled concrete increases the seismic resistance of the structure.
Tasman-PCR: a genetic diagnostic assay for Tasmanian devil facial tumour diseases
Authors: Kwon Young Mi , Stammnitz Maximilian R. , Wang Jinhong , Swift Kate , Knowles Graeme W. , Pye Ruth J. , Kreiss Alexandre , Peck Sarah , Fox Samantha , Pemberton David , Jones Menna E. , Hamede Rodrigo , Murchison Elizabeth P.
Published: October 2018

Tasmanian devils have spawned two transmissible cancer clones, known as devil facial tumour 1 (DFT1) and devil facial tumour 2 (DFT2). DFT1 and DFT2 are transmitted between animals by the transfer of allogeneic contagious cancer cells by biting, and both cause facial tumours. DFT1 and DFT2 tumours are grossly indistinguishable, but can be differentiated using histopathology, cytogenetics or genotyping of polymorphic markers. However, standard diagnostic methods require specialist skills and equipment and entail long processing times. Here, we describe Tasman-PCR: a simple polymerase chain reaction (PCR)-based diagnostic assay that identifies and distinguishes DFT1 and DFT2 by amplification of DNA spanning tumour-specific interchromosomal translocations. We demonstrate the high sensitivity and specificity of this assay by testing DNA from 546 tumours and 804 normal devils. A temporal–spatial screen confirmed the reported geographic ranges of DFT1 and DFT2 and did not provide evidence of additional DFT clones. DFT2 affects disproportionately more males than females, and devils can be co-infected with DFT1 and DFT2. Overall, we present a PCR-based assay that delivers rapid, accurate and high-throughput diagnosis of DFT1 and DFT2. This tool provides an additional resource for devil disease management and may assist with ongoing conservation efforts.
Topological data analysis for true step detection in periodic piecewise constant signals
Authors: Khasawneh Firas A. , Munch Elizabeth
Published: October 2018

This paper introduces a simple yet powerful approach based on topological data analysis for detecting true steps in a periodic, piecewise constant (PWC) signal. The signal is a two-state square wave with randomly varying in-between-pulse spacing, subject to spurious steps at the rising or falling edges which we call digital ringing. We use persistent homology to derive mathematical guarantees for the resulting change detection which enables accurate identification and counting of the true pulses. The approach is tested using both synthetic and experimental data obtained using an engine lathe instrumented with a laser tachometer. The described algorithm enables accurate and automatic calculations of the spindle speed without any choice of parameters. The results are compared with the frequency and sequency methods of the Fourier and Walsh–Hadamard transforms, respectively. Both our approach and the Fourier analysis yield comparable results for pulses with regular spacing and digital ringing while the latter causes large errors using the Walsh–Hadamard method. Further, the described approach significantly outperforms the frequency/sequency analyses when the spacing between the peaks is varied. We discuss generalizing the approach to higher dimensional PWC signals, although using this extension remains an interesting question for future research.
Biological imaging with scanning electrochemical microscopy
Authors: Conzuelo Felipe , Schulte Albert , Schuhmann Wolfgang
Published: October 2018

Scanning electrochemical microscopy (SECM) is a powerful and versatile technique for visualizing the local electrochemical activity of a surface as an ultramicroelectrode tip is moved towards or over a sample of interest using precise positioning systems. In comparison with other scanning probe techniques, SECM not only enables topographical surface mapping but also gathers chemical information with high spatial resolution. Considerable progress has been made in the analysis of biological samples, including living cells and immobilized biomacromolecules such as enzymes, antibodies and DNA fragments. Moreover, combinations of SECM with comple­mentary analytical tools broadened its applicability and facilitated multi-functional analysis with extended life science capabilities. The aim of this review is to present a brief topical overview on recent applications of biological SECM, with particular emphasis on important technical improvements of this surface imaging technique, recommended applications and future trends.
Comparative demography elucidates the longevity of parasitic and symbiotic relationships
Authors: Hecht Luke B. B. , Thompson Peter C. , Rosenthal Benjamin M.
Published: October 2018

Parasitic and symbiotic relationships govern vast nutrient and energy flows, yet controversy surrounds their longevity. Enduring relationships may engender parallel phylogenies among hosts and parasites, but so may ephemeral relationships when parasites colonize related hosts. An understanding of whether symbiont and host populations have grown and contracted in concert would be useful when considering the temporal durability of these relationships. Here, we devised methods to compare demographic histories derived from genomic data. We compared the historical growth of the agent of severe human malaria,
Plasmodium falciparum
, and its mosquito vector,
Anopheles gambiae
, to human and primate histories, thereby discerning long-term parallels and anthropogenic population explosions. The growth history of
Trichinella spiralis
, a zoonotic parasite disseminated by swine, proved regionally specific, paralleling distinctive growth histories for wild boar in Asia and Europe. Parallel histories were inferred for an anemone and its algal symbiont (
Exaiptasia pallida
and
Symbiodinium minutum
). Concerted growth in potatoes and the agent of potato blight (
Solanum tuberosum
and
Phytophthora infestans
) did not commence until the age of potato domestication. Through these examples, we illustrate the utility of comparative historical demography as a new exploratory tool by which to interrogate the origins and durability of myriad ecological relationships. To facilitate future use of this approach, we introduce a tool called C-PSMC to align and evaluate the similarity of demographic history curves.
Female control over multiple matings increases the opportunity for postcopulatory sexual selection
Authors: Gasparini Clelia , Evans Jonathan P.
Published: October 2018

It is widely acknowledged that in most species sexual selection continues after mating. Although it is generally accepted that females play an important role in generating paternity biases (i.e. cryptic female choice, CFC), we lack a quantitative understanding of the relative importance of female-controlled processes in influencing variance in male reproductive fitness. Here, we address this question experimentally using the guppy
Poecilia reticulata
, a polyandrous fish in which pre- and postcopulatory sexual selection jointly determine male reproductive fitness. We used a paired design to quantify patterns of paternity for pairs of rival males across two mating contexts, one in which the female retained full control over double (natural) matings and one where sperm from the same two males were artificially inseminated into the female. We then compared the relative paternity share for a given pair of males across both contexts, enabling us to test the key prediction that patterns of paternity will depend on the extent to which females retain behavioural control over matings. As predicted, we found stronger paternity biases when females retained full control over mating compared with when artificial insemination (AI) was used. Concomitantly, we show that the opportunity for postcopulatory sexual selection (standardized variance in male reproductive success) was greater when females retained control over double matings compared with when AI was used. Finally, we show that the paternity success of individual males exhibited higher repeatability across successive brood cycles when females retained behavioural control of matings compared with when AI was used. Collectively, these findings underscore the critical role that females play in determining the outcome of sexual selection and to our knowledge provide the first experimental evidence that behaviourally moderated components of CFC increase the opportunity for sexual selection.
A non-coding region near
Follistatin
controls head colour polymorphism in the Gouldian finch
Authors: Toomey Matthew B. , Marques Cristiana I. , Andrade Pedro , Araújo Pedro M. , Sabatino Stephen , Gazda Małgorzata A. , Afonso Sandra , Lopes Ricardo J. , Corbo Joseph C. , Carneiro Miguel
Published: October 2018

Discrete colour morphs coexisting within a single population are common in nature. In a broad range of organisms, sympatric colour morphs often display major differences in other traits, including morphology, physiology or behaviour. Despite the repeated occurrence of this phenomenon, our understanding of the genetics that underlie multi-trait differences and the factors that promote the long-term maintenance of phenotypic variability within a freely interbreeding population are incomplete. Here, we investigated the genetic basis of red and black head colour in the Gouldian finch (
Erythrura gouldiae
), a classic polymorphic system in which naturally occurring colour morphs also display differences in aggressivity and reproductive success. We show that the candidate locus is a small (approx. 70 kb) non-coding region mapping to the Z chromosome near the
Follistatin
(
FST
) gene. Unlike recent findings in other systems where phenotypic morphs are explained by large inversions containing hundreds of genes (so-called supergenes), we did not identify any structural rearrangements between the two haplotypes using linked-read sequencing technology. Nucleotide divergence between the red and black alleles was high when compared to the remainder of the Z chromosome, consistent with their maintenance as balanced polymorphisms over several million years. Our results illustrate how pleiotropic phenotypes can arise from simple genetic variation, probably regulatory in nature.
Adaptive periodicity in the infectivity of malaria gametocytes to mosquitoes
Authors: Schneider Petra , Rund Samuel S. C. , Smith Natasha L. , Prior Kimberley F. , O'Donnell Aidan J. , Reece Sarah E.
Published: October 2018

Daily rhythms in behaviour, physiology and molecular processes are expected to enable organisms to appropriately schedule activities according to consequences of the daily rotation of the Earth. For parasites, this includes capitalizing on periodicity in transmission opportunities and for hosts/vectors, this may select for rhythms in immune defence. We examine rhythms in the density and infectivity of transmission forms (gametocytes) of rodent malaria parasites in the host's blood, parasite development inside mosquito vectors and potential for onwards transmission. Furthermore, we simultaneously test whether mosquitoes exhibit rhythms in susceptibility. We reveal that at night, gametocytes are twice as infective, despite being less numerous in the blood. Enhanced infectiousness at night interacts with mosquito rhythms to increase sporozoite burdens fourfold when mosquitoes feed during their rest phase. Thus, changes in mosquito biting time (owing to bed nets) may render gametocytes less infective, but this is compensated for by the greater mosquito susceptibility.
Multi-objective formulation of MSA for phylogeny estimation
Authors: Nayeem Muhammad Ali , Bayzid Md. Shamsuzzoha , Rahman Atif Hasan , Shahriyar Rifat , Rahman M. Sohel
Published: October 2018

Multiple sequence alignment (MSA) is a basic step in many analyses in computational biology, including predicting the structure and function of proteins, orthology prediction and estimating phylogenies. The objective of MSA is to infer the homology among the sequences of chosen species. Commonly, the MSAs are inferred by optimizing a single function or objective. The alignments estimated under one criterion may be different to the alignments generated by other criteria, inferring discordant homologies and thus leading to different evolutionary histories relating the sequences. In recent past, researchers have advocated for the multi-objective formulation of MSA, to address this issue, where multiple conflicting objective functions are being optimized simultaneously to generate a set of alignments. However, no theoretical or empirical justification with respect to a real-life application has been shown for a particular multi-objective formulation. In this study, we investigate the impact of multi-objective formulation in the context of phylogenetic tree estimation. Employing multi-objective metaheuristics, we demonstrate that trees estimated on the alignments generated by multi-objective formulation are substantially better than the trees estimated by the state-of-the-art MSA tools, including PASTA, MUSCLE, CLUSTAL, MAFFT etc. We also demonstrate that highly accurate alignments with respect to popular measures like sum-of-pair (SP) score and total-column (TC) score do not necessarily lead to highly accurate phylogenetic trees. Thus in essence we ask the question whether a phylogeny-aware metric can guide us in choosing appropriate multi-objective formulations that can result in better phylogeny estimation. And we answer the question affirmatively through carefully designed extensive empirical study. As a by-product we also suggest a methodology for primary selection of a set of objective functions for a multi-objective formulation based on the association with the resulting phylogenetic tree.
Hox genes mediate the escalation of sexually antagonistic traits in water striders
Authors: Johan Crumière Antonin Jean , Khila Abderrahman
Published: October 2018

Sexual conflict occurs when traits favoured in one sex impose fitness costs on the other sex. In the case of sexual conflict over mating rate, the sexes often undergo antagonistic coevolution and escalation of traits that enhance female’s resistance to mating and traits that increase male’s persistence. How this escalation in sexually antagonistic traits is established during ontogeny remains unclear. In the water striderRhagovelia antilleana, male persistence traits consist of sex combs in the forelegs and multiple rows of spines and a thick femur in the rearlegs. Female resistance trait consists of a prominent spike-like projection of the pronotum. RNAi knockdown against the Hox geneSex Combs Reducedresulted in the reduction of both the sex comb in males and the pronotum projection in females. RNAi against the Hox geneUltrabithoraxresulted in the complete loss or reduction of all persistence traits in male rearlegs. These results demonstrate that Hox genes can mediate sex-specific escalation of antagonistic traits along the body axis of both sexes.
rCASC: reproducible Classification Analysis of Single Cell sequencing data
Authors: Alessandrì Luca , Beccuti Marco , Arigoni Maddalena , Olivero Martina , Romano Greta , De Libero Gennaro , Pace Luigia , Cordero Francesca , Calogero Raffaele A
Published: October 2018

Single-cell RNA sequencing has emerged as an essential tool to investigate cellular heterogeneity, and highlighting cell sub-population specific signatures. Nowadays, dedicated and user-friendly bioinformatics workflows are required to exploit the deconvolution of single-cells transcriptome. Furthermore, there is a growing need of bioinformatics workflows granting both functional, i.e. saving information about data and analysis parameters, and computation reproducibility, i.e. storing the real image of the computation environment. Here, we present rCASC a modular RNAseq analysis workflow allowing data analysis from counts generation to cell sub-population signatures identification, granting both functional and computation reproducibility.

Availability and Implementation

rCASC is part of the reproducible bioinfomatics project. rCASC is a docker based application controlled by a R package available at https://github.com/kendomaniac/rCASC.

Supplementary information

Supplementary data are available at rCASC github
Variant pathogenic prediction models VSRFM and VSRFM-s, the importance of splicing and allele frequency
Authors: Cabrera-Alarcon JL , Garcia-Martinez J
Published: October 2018

Currently, there are available several tools to predict the effect of variants, with the aim of classify variants in neutral or pathogenic. In this study, we propose a new model trained over ensemble scores with two particularities, first we consider minor frequency allele from gnomAD and second, we split variants based on their splicing for training each specific model. Variants Stacked Random Forest Model (VSRFM) was constructed for variants not involved in splicing and Variants Stacked Random Forest Model for splicing (VSRFM-s) was trained for variants affected by splicing. Comparing these scores with their constituent scores used as features, our models showed the best outcomes. These results were confirmed using an independent data set from Clinvar database, with similar results.
Nutrient acquisition, rather than stress response over diel cycles, drives microbial transcription in a dessicated Namib Desert soil
Authors: León-Sobrino Carlos , Ramond Jean-Baptiste , Maggs-Kölling Gillian , Cowan Don A
Published: October 2018

Hot desert surface soils are characterised by extremely low water activities for large parts of any annual cycle. It is widely assumed that microbial processes in such soils are very limited. Here we present the first metatranscriptomic survey of microbial community function in a low water activity hyperarid desert soil. Sequencing of total mRNA revealed a diverse and active community, dominated byActinobacteria. Metatranscriptomic analysis of samples taken at different times over three days indicated that most functions did not fluctuate on a diel basis, except for a eukaryotic subpopulation which was induced during the cooler night hours. High levels of transcription of chemoautotrophic carbon fixation genes contrasted with limited expression of photosynthetic genes, indicating that chemoautotrophy is an important alternative to photosynthesis for carbon cycling in desiccated desert soils. Analysis of the transcriptional levels of key N-cycling genes provided strong evidence that soil nitrate was the dominant nitrogen input source. Transcriptional network analyses and taxon-resolved functional profiling suggested that nutrient acquisition processes, and not diurnal environmental variation, were the main drivers of community activity in hyperarid Namib Desert soil. While we also observed significant levels of expression of common stress response genes, these genes were not dominant hubs in the co-occurrence network.
Velocity estimation in reinforcement learning
Authors: Velazquez Carlos , Villarreal Manuel , Bouzas Arturo
Published: October 2018

The current work aims to study how people make predictions, under a reinforcement learning framework, in an environment that fluctuates from trial to trial and is corrupted with Gaussian noise. A computer-based experiment was developed where subjects were required to predict the future location of a spaceship that orbited around planet Earth. Its position was sampled from a Gaussian distribution with the mean changing at a variable velocity and four different values of variance that defined our signal-to-noise conditions. Three error-driven algorithms using a Bayesian approach were proposed as candidates to describe our data. The first is the standard delta-rule. The second and third models are delta rules incorporating a velocity component which is updated using prediction errors. The third model additionally assumes a hierarchical structure where individual learning rates for velocity and decision noise come from Gaussian distributions with means following a hyperbolic function. We used leave-one-out cross-validation and the Widely Applicable Information Criterion to compare the predictive accuracy of these models. In general, our results provided evidence in favor of the hierarchical model and highlight two main conclusions. First, when facing an environment that fluctuates from trial to trial, people can learn to estimate its velocity to make predictions. Second, learning rates for velocity and decision noise are influenced by uncertainty constraints represented by the signal-to-noise ratio. This higher order control was modeled using a hierarchical structure, which qualitatively accounts for individual variability and is able to generalize and make predictions about new subjects on each experimental condition.