bluuebunny/crossref_metadata_2025 huggingface dataset:
Atlastins mediate selective autophagy of the endoplasmic reticulum
Authors: Liang Jin Rui , Lingeman Emily , Ahmed Saba , Corn Jacob
Published: March 2018

The selective lysosomal degradation (autophagy) of entire organelles is required for cellular homeostasis, and its dysregulation is involved in degenerative disorders such as Parkinson’s Disease. While autophagy of mitochondria (mitophagy) is becoming better understood, other forms of organelle autophagy are relatively unexplored. Here we develope multiple quantitative assays to measure organelle autophagy using flow cytometry, microscopy, and Western blotting. Focusing on autophagy of the endoplasmic reticulum (ER-phagy), we show that these assays allow facile measurement of ER-phagy, and that ER-phagy is inhibited by knockdown of either core autophagy components or the recently reported FAM134B ER-phagy receptor. Using these assays, we further identify that Atlastins, the ER-resident GTPases involved in ER membrane morphology, are key positive effectors of ER-phagy. Atlastin-depleted cells have decreased ER-phagy under starvation conditions, and Atlastin’s role in ER-phagy requires both a functional GTPase domain and proper ER localization. The three Atlastin family members functionally compensate for one another during ER-phagy and may form heteromeric complexes with one another. We also find that Atlastins act downstream of the FAM134B ER-phagy receptor. We propose that during ER-phagy, Atlastins remodel ER membrane to separate pieces of FAM134B-marked ER for efficient autophagosomal engulfment. Human mutations in Atlastins led to hereditary spastic paraplegia, and our results suggest that this disease may be linked to deficiencies in ER-phagy rather than ER morphology.
Selective maternal seeding and environment shape the human gut microbiome
Authors: Korpela Katri , Costea Paul , Coelho Luis Pedro , Kandels-Lewis Stefanie , Willemsen Gonneke , Boomsma Dorret I. , Segata Nicola , Bork Peer
Published: March 2018

Vertical transmission of bacteria from mother to infant at birth is postulated to initiate a life-long host-microbe symbiosis, playing an important role in early infant development. However, only the tracking of strictly defined unique microbial strains can clarify where the intestinal bacteria come from, how long the initial colonizers persist, and whether colonization by other strains from the environment can replace existing ones. Using rare single nucleotide variants in fecal metagenomes of infants and their family members, we show strong evidence of selective and persistent transmission of maternal strain populations to the vaginally born infant and their occasional replacement by strains from the environment, including those from family members, in later childhood. Only strains from the classes Actinobacteria and Bacteroidia, which are essential components of the infant microbiome, are transmitted from the mother and persist for at least 1 yr. In contrast, maternal strains of Clostridia, a dominant class in the mother's gut microbiome, are not observed in the infant. Caesarean-born infants show a striking lack of maternal transmission at birth. After the first year, strain influx from the family environment occurs and continues even in adulthood. Fathers appear to be more frequently donors of novel strains to other family members than receivers. Thus, the infant gut is seeded by selected maternal bacteria, which expand to form a stable community, with a rare but stable continuing strain influx over time.
ARCIMBOLDOon coiled coils
Authors: Caballero Iracema , Sammito Massimo , Millán Claudia , Lebedev Andrey , Soler Nicolas , Usón Isabel
Published: March 2018

ARCIMBOLDOsolves the phase problem by combining the location of small model fragments usingPhaserwith density modification and autotracing usingSHELXE. Mainly helical structures constitute favourable cases, which can be solved using polyalanine helical fragments as search models. Nevertheless, the solution of coiled-coil structures is often complicated by their anisotropic diffraction and apparent translational noncrystallographic symmetry. Long, straight helices have internal translational symmetry and their alignment in preferential directions gives rise to systematic overlap of Patterson vectors. This situation has to be differentiated from the translational symmetry relating different monomers.ARCIMBOLDO_LITEhas been run on single workstations on a test pool of 150 coiled-coil structures with 15–635 amino acids per asymmetric unit and with diffraction data resolutions of between 0.9 and 3.0 Å. The results have been used to identify and address specific issues when solving this class of structures usingARCIMBOLDO. Features fromPhaserv.2.7 onwards are essential to correct anisotropy and produce translation solutions that will pass the packing filters. As the resolution becomes worse than 2.3 Å, the helix direction may be reversed in the placed fragments. Differentiation between true solutions and pseudo-solutions, in which helix fragments were correctly positioned but in a reverse orientation, was found to be problematic at resolutions worse than 2.3 Å. Therefore, after every new fragment-placement round, complete or sparse combinations of helices in alternative directions are generated and evaluated. The final solution is once again probed by helix reversal, refinement and extension. To conclude, density modification andSHELXEautotracing incorporating helical constraints is also exploited to extend the resolution limit in the case of coiled coils and to enhance the identification of correct solutions. This study resulted in a specialized mode withinARCIMBOLDOfor the solution of coiled-coil structures, which overrides the resolution limit and can be invoked from the command line (keyword coiled_coil) orARCIMBOLDO_LITEtask interface inCCP4i.
Ensembles generated from crystal structures of single distant homologues solve challenging molecular-replacement cases inAMPLE
Authors: Rigden Daniel J. , Thomas Jens M. H. , Simkovic Felix , Simpkin Adam , Winn Martyn D. , Mayans Olga , Keegan Ronan M.
Published: March 2018

Molecular replacement (MR) is the predominant route to solution of the phase problem in macromolecular crystallography. Although routine in many cases, it becomes more effortful and often impossible when the available experimental structures typically used as search models are only distantly homologous to the target. Nevertheless, with current powerful MR software, relatively small core structures shared between the target and known structure, of 20–40% of the overall structure for example, can succeed as search models where they can be isolated. Manual sculpting of such small structural cores is rarely attempted and is dependent on the crystallographer's expertise and understanding of the protein family in question. Automated search-model editing has previously been performed on the basis of sequence alignment, in order to eliminate, for example, side chains or loops that are not present in the target, or on the basis of structural features (e.g.solvent accessibility) or crystallographic parameters (e.g.Bfactors). Here, based on recent work demonstrating a correlation between evolutionary conservation and protein rigidity/packing, novel automated ways to derive edited search models from a given distant homologue over a range of sizes are presented. A variety of structure-based metrics, many readily obtained from online webservers, can be fed to the MR pipelineAMPLEto produce search models that succeed with a set of test cases where expertly manually edited comparators, further processed in diverse ways withMrBUMP, fail. Further significant performance gains result when the structure-based distance geometry methodCONCOORDis used to generate ensembles from the distant homologue. To our knowledge, this is the first such approach whereby a single structure is meaningfully transformed into an ensemble for the purposes of MR. Additional cases further demonstrate the advantages of the approach.CONCOORDis freely available and computationally inexpensive, so these novel methods offer readily available new routes to solve difficult MR cases.
rac-(9R,10R)-3,6,9,10-Tetrabromo-8,8-dimethyl-9,10-dihydro-2H,8H-pyrano[2,3-f]chromen-2-one (tetrabromoseselin): a photobiochemically active pyranocoumarin
Authors: Bauri A. K. , Foro Sabine , Rahman A. F. M. M.
Published: March 2018

The title molecule, C14H10Br4O3, is a tetrabrominated substituted pyranocoumarin synthesized by bromination of seselin (systematic name: 8,8-dimethyl-2H,8H-pyrano[2,3-f]chromene-2-one) isolated from the Indian herbTrachyspermum stictocapum. The pyran ring has a distorted half-chair conformation and its mean plane is inclined to mean plane of the coumarin unit by 3.33 (17)°. In the crystal, molecules are linked by pairs of C—H...O hydrogen bonds, forming inversion dimmers with anR22(16) ring motif. The dimers are linked by pairs of C—H...Br hydrogen bonds, enclosing anR22(16) ring motif, forming chains propagating along the [1-10] direction. Within the chains there are offset π–π interactions involving inversion-related benzene rings with an intercentroid distance of 3.788 (2) Å.
Deriving the transition probability matrix using computational mechanics
Authors: Riveros Guillermo A. , Rosario-Pérez Manuel E.
Published: March 2018

Purpose

The combined effects of several complex phenomena cause the deterioration of elements in steel hydraulic structures (SHSs) within the US lock system: corrosion, cracking and fatigue, impact and overloads. Predicting the future condition state of these structures by the use of current condition state inspection data can be achieved through the probabilistic chain deterioration model. The purpose of this study is to derive the transition probability matrix using final elements modeling of a miter gate.

Design/methodology/approach

If predicted accurately, this information would yield benefits in determining the need for rehabilitation or replacement of SHS. However, because of the complexity and difficulties on obtaining sufficient inspection data, there is a lack of available condition states needed to formulate proper transition probability matrices for each deterioration case.

Findings

This study focuses on using a three-dimensional explicit finite element analysis (FEM) of a miter gate that has been fully validated with experimental data to derive the transition probability matrix when the loss of flexural capacity in a corroded member is simulated.

Practical implications

New methodology using computational mechanics to derive the transition probability matrices of navigation steel structures has been presented.

Originality/value

The difficulty of deriving the transition probability matrix to perform a Markovian analysis increases when limited amount of inspection data is available. The used state of practice FEM to derive the transition probability matrix is not just necessary but also essential when the need for proper maintenance is required but limited amount of the condition of the structural system is unknown.
Frequency domain analysis method of nonstationary random vibration based on evolutionary spectral representation
Authors: Zhao Yan , Si L.T. , Ouyang H.
Published: March 2018

Purpose

A novel frequency domain approach, which combines the pseudo excitation method modified by the authors and multi-domain Fourier transform (PEM-FT), is proposed for analyzing nonstationary random vibration in this paper.

Design/methodology/approach

For a structure subjected to a nonstationary random excitation, the closed-form solution of evolutionary power spectral density of the response is derived in frequency domain.

Findings

The deterministic process and random process in an evolutionary spectrum are separated effectively using this method during the analysis of nonstationary random vibration of a linear damped system, only modulation function of the system needs to be estimated, which brings about a large saving in computational time.

Originality/value

The method is general and highly flexible as it can deal with various damping types and nonstationary random excitations with different modulation functions.
A novel hybrid meshless method for seepage flows in non-homogeneous and anisotropic soils
Authors: Hajiazizi Mohammad , Graili Adel
Published: March 2018

Purpose

The purpose of this paper is to extend the scaled boundary radial point interpolation method (SBRPIM), as a novel semi-analytical scheme, to the analysis of the steady state confined seepage flows.

Design/methodology/approach

This method combines the advantages of the scaled boundary finite element method and the BRPIM. In this method, only boundary nodes are used, no fundamental solution of the problem is required, and as the shape functions constructed based on the RPIM satisfy the Kronecker delta function property, the boundary conditions of problems can be imposed accurately and easily.

Findings

Three numerical examples, including seepage flow through homogeneous and non-homogeneous soils, are analyzed in this paper. Comparing the flow net obtained by SBRPIM and other numerical methods confirms the ability of the proposed method in analyzing seepage flows. In addition, in these examples, the accuracy of the SBRPIM in modeling the velocity singularity at a sharp corner is illustrated. SBRPIM accurately models the singularity point in non-homogeneous and anisotropic soil.

Originality/value

SBRPIM method is a simple effective tool for analyzing various kinds of engineering problems. It is easy to implement for modeling the velocity singularity at a sharp corner. The proposed method accurately models the singularity point in non-homogeneous and anisotropic soil.
Investigating the effects of operators on warranty cost under sales delay conditions
Authors: Dorabati Sepideh Eskandari , Hamadani Ali Zeinal , Fazlollahtabar Hamed
Published: March 2018

Purpose

Due to the fact that the non-standard products, being used by customers, may cause failures in products with sales delays, which naturally affect the warranty policy. Thus, it seems to be necessary to study these two concepts simultaneously. The paper aims to discuss these issues.

Design/methodology/approach

In this paper, a model is developed for estimating the expected warranty costs under sales delay conditions when two operator costs (failing but not reported and non-failing but reported) are included.

Findings

The proposed model is validated using a numerical example for a two types of intermittent and fatal failures occur under a non-renewing warranty policy.

Originality/value

Sales delay is the time interval between the date of production and the date of sale. Most reported literature on warranty claims data analysis related to sales delay have mainly focussed on estimating the probability distribution of the sales delay.
Maintenance and setup planning in manufacturing systems under uncertainties
Authors: Kibouka Guy Richard , Nganga-Kouya Donatien , Kenné Jean-Pierre , Polotski Vladimir , Songmene Victor
Published: March 2018

Purpose

The purpose of this paper is to find the optimal production and setup policies for a manufacturing system that produces two different types of parts. The manufacturing system consists of one machine subject to random failures and repairs. Reconfiguring the machine to switch production from one type of product to another generates a non-production time and a significant cost.

Design/methodology/approach

This paper proposes an approach based on the development of optimal production and setup policies, taking into account the possibilities of undertaking the setup for all modes of the machine, and covering them at the end of setup. New optimality conditions are developed in terms of modified Hamilton-Jacobi-Bellman (HJB) equations and recursive numerical methods are applied to solve such equations.

Findings

The proposed approach led to determine more realistic production rates of both parts and setup sequences for the different modes of the machine that significantly influence the inventory and the system capacity. A numerical example and sensitivity analysis are used to determine the structure of the optimal policies and to show the helpfulness and robustness of the results obtained.

Practical implications

Following the steps of the proposed approach will provide the control policies for industrial manufacturing systems with setup permitted at all modes of the machine, and when the setup does not necessarily restore the machine to its operational mode. The proposed optimal policy takes into account the stochastic nature of the machine mode at the end of setup and we show that ignoring it leads to non-natural policies and underestimates significantly the safety stock thresholds.

Originality/value

Considering the assumptions presented in this paper leads to a new structure of the control laws for the production planning of manufacturing systems with setup.
Doing Well and Good: An Exploration of the Role of Mindfulness in the Entrepreneurial Opportunity Recognition and Evaluation Process
Authors: Kelly Louise , Dorian Marina
Published: March 2018

The purpose of this conceptual paper is to integrate two previously disparate areas of research: mindfulness and the entrepreneurial process. This present study conceptualizes the impact of mindfulness on the choices entrepreneurs face. Specifically, the research theorizes the positive effects of mindfulness on the opportunity recognition process, including evaluation of entrepreneurs. Furthermore, we propose that metacognition mediates this relationship, and emotional self-regulation moderates it. This conceptual research also suggests that mindfulness is positively related to the ethical decision-making and opportunity recognition and evaluation. Finally, compassion is proposed as a factor that mediates the relationship between mindfulness and ethical choices in opportunity recognition.
The composition of precarity: ‘emerging’ composers’ experiences of opportunity culture in contemporary classical music
Authors: Smith Neil Thomas , Thwaites Rachel
Published: March 2018

This paper examines the precarious working lives of ‘emerging’ composers attempting to build a career in the world of new classical music in the UK. This topic is approached by considering the ‘composition opportunity’, success in which is seen as an important element in ‘making it’ in this sphere. We argue that such schemes in fact manifest a crucial tension in the nature of artistic labour, and are, at the very least, problematic in their function as conduits towards full professional identity. They may instead act to maintain the precarious working situation of composers in a neoliberal age. The working lives of artists are all too rarely illuminated, and new music composers are no exception; this survey of 47 emerging composers is the largest study of such individuals in the UK.
Effect of a Data‐driven Intervention on Opioid Prescribing Intensity Among Emergency Department Providers: A Randomized Controlled Trial
Authors: Michael Sean S. , Babu Kavita M. , Androski Christopher , Reznek Martin A.
Published: March 2018

Objective

Little is known about accuracy of provider self‐perception of opioid prescribing. We hypothesized that an intervention asking emergency department (ED) providers to self‐identify their opioid prescribing practices compared to group norms—and subsequently providing them with their actual prescribing data—would alter future prescribing compared to controls.

Methods

This was a prospective, multicenter randomized trial in which all attending physicians, residents, and advanced practice providers at four EDs were randomly assigned either to no intervention or to a brief data‐driven intervention during which providers were: 1) asked to self‐identify and explicitly report to research staff their perceived opioid prescribing in comparison to their peers and 2) then given their actual data with peer group norms for comparison. Our primary outcome was the change in each provider's proportion of patients discharged with an opioid prescription at 6 and 12 months. Secondary outcomes were opioid prescriptions per hundred total prescriptions and normalized morphine milligram equivalents prescribed. Our primary comparison stratified intervention providers by those who underestimated their prescribing and those who did not underestimate their prescribing, both compared to controls.

Results

Among 109 total participants, 51 were randomized to the intervention, 65% of whom underestimated their opioid prescribing. Intervention participants who underestimated their baseline prescribing had larger‐magnitude decreases than controls (Hodges‐Lehmann difference = –2.1 prescriptions per hundred patients at 6 months [95% confidence interval {CI} = –3.9 to –0.5] and –2.2 per hundred at 12 months [95% CI = –4.8 to –0.01]). Intervention participants who did not underestimate their prescribing had similar changes to controls.

Conclusions

Self‐perception of prescribing was frequently inaccurate. Providing clinicians with their actual opioid prescribing data after querying their self‐perception reduced future prescribing among providers who underestimated their baseline prescribing. Our findings suggest that guideline and policy interventions should directly address the potential barrier of inaccurate provider self‐awareness.
Functional responses of an apex predator and a mesopredator to an invading ungulate: Dingoes, red foxes and sambar deer in south‐east Australia
Authors: Forsyth David M. , Caley Peter , Davis Naomi E. , Latham A. David M. , Woolnough Andrew P. , Woodford Luke P. , Stamation Kasey A. , Moloney Paul D. , Pascoe Charlie
Published: March 2018

Biological invasions by large herbivores involve the establishment of novel interactions with the receiving mammalian carnivore community, but understanding these interactions is difficult due to the large spatiotemporal scales at which such dynamics would occur. We quantified the functional responses of a native apex predator (the dingo (Canis familiaris), which includes wild dogs and their hybrids) and a non‐native mesopredator (red fox; Vulpes vulpes) to an invading non‐native ungulate (sambar deer; Cervus unicolor) in Australia. We predicted that the apex predator would exhibit a stronger functional response to increasing sambar deer abundance than the mesopredator. We used a state–space model to link two 30‐year time series: (i) sambar deer abundance (hunter catch‐per‐unit‐effort); and (ii) percentages of sambar deer in dingo (N = 4531) and fox (N = 5002) scats. Sambar deer abundance increased over fourfold during 1984−2013. The percentages of sambar deer in dingo and fox scats increased during this 30‐year period, from nil in both species in 1984 to 8.2% in dingoes and 0.5% in foxes in 2013. Dingoes exhibited a much stronger functional response to increasing sambar deer abundance than foxes. The prediction that invading deer would be utilized more by the apex predator than by the mesopredator was therefore supported. The increasing abundance of sambar deer during the period 1984−2013 provided an increasingly important food source for dingoes. In contrast, the smaller red fox utilized sambar deer much less. Our study demonstrates that prey enrichment can be an important consequence of large herbivore invasions and that the effect varies predictably with the trophic position of the mammalian carnivores in the receiving community.
Size and Structure of Disaster Relief when State Capacity is Limited: China’s 1823 Flood
Authors: Ni Yuping , Uebele Martin
Published: March 2018

This paper presents new archival evidence about the amount and structure of central government disaster relief during China’s devastating flood of 1823. The flood affected 20 per cent of China’s counties, and spending per capita was sizable and distributed between provinces depending on the intensity of flooding. Because of its relative small size and limited state capacity, the Chinese government ultimately spent about half of its annual tax revenues on relief during 1823. Given China’s ensuing secular economic stagnation, this is consistent with models emphasising state capacity for economic growth.
Functional outcome after laparoscopic nerve‐sparing sacrocolpopexy: a prospective cohort study
Authors: Christmann‐Schmid Corina , Koerting Isabell , Ruess Esther , Faehnle Ivo , Krebs Jörg
Published: March 2018

Introduction

To date sacrocolpopexy is regarded as the reference standard treatment for primarily apical compartment prolapse and multicompartment prolapse. Most bladder and bowel dysfunction improves postoperatively after sacrocolpopexy; however, de novo bowel or de novo bladder dysfunction can occur. The inferior hypogastric nerve is commonly known among pelvic surgeons. However, the inferior hypogastric nerve and its fine fibers are difficult to identify; iatrogenic lesion is commonly tolerated although this can lead to bladder, bowel and sexual dysfunction. This study was performed to assess the functional outcome after nerve‐sparing sacrocolpopexy.

Material and methods

From 2014 to 2016 all women undergoing a laparoscopic sacrocolpopexy for apical or multicompartment prolapse stage >2 were included in this prospective study. Laparoscopic sacrocolpopexy was performed using the nerve‐sparing approach. Objective outcome was assessed by preoperative and postoperative POP‐Q changes. De novo bladder and de novo bowel dysfunction were subjectively and objectively evaluated.

Results

In all, 137 women were included. Significant objective improvement for point Aa and C (p < 0.0001) preoperatively to postoperatively was seen. The posterior compartment remained unchanged with point Ba −2. De novo overactive bladder and de novo bladder outlet obstruction with elevated postresidual volume were seen for both in 0.7% (1/137). De novo stress urinary incontinence was seen in 0.7% (5/137). De novo constipation was seen in 5%, bowel incontinence in 0% and resolution of pre‐existing obstipation in 14.5%. De novo laxative use (9%) in the first 12 weeks was the most common postoperative problem.

Conclusion

We could demonstrate that when a nerve‐sparing technique is applied for sacrocolpopexy low de novo bladder (18%) and de novo bowel dysfunction can be seen.
National survey showed that Chinese city children under two years of age had similar feeding patterns to developed countries
Authors: Wu Hua‐hong , Li Hui , Zhang Ya‐qin , Zong Xin‐nan , Zhu Zong‐han , Yu Yang
Published: March 2018

Aim

This 2015 study was a part of the National Growth Survey of Children under seven years of age, which has been carried out in nine Chinese cities every 10 years since 1975. Our aim was to assess children's feeding practices and nutritional supplements.

Methods

This was a cross‐sectional survey of 89 006 healthy children aged one to 24 months. All data were collected by face‐to‐face interviews during child health visits, using a questionnaire.

Results

The exclusive breastfeeding rate was 53% in infants under six months of age, and the continued breastfeeding rate was 51% among infants who were 10–12 months and 5% when they were 21–24 months. Infants were weaned at a mean of 9.3 months in urban areas and 9.4 months in suburban areas. Cereals were provided as complementary food at a mean age of five months, eggs at six months, meat at eight and a half months and bean products at over 12 months. The most common nutritional supplements given to the children were vitamins A and D and calcium.

Conclusion

The feeding practices of Chinese city children were similar to those in developed countries, but strategies are needed to promote more rational consumption of nutritional supplements.
Pharmacokinetics and pharmacodynamics of dexmedetomidine‐induced vasoconstriction in healthy volunteers
Authors: Talke Pekka , Anderson Brian J.
Published: March 2018

Aims

Alpha‐2 agonists are direct peripheral vasoconstrictors, which achieve these effects by activating vascular smooth muscle alpha‐2 adrenoceptors. The impact of this response during dexmedetomidine infusion remains poorly quantified. Our goal was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD, vasoconstriction) effects of a computer‐controlled dexmedetomidine infusion in healthy volunteers.

Methods

After local ethics committee approval, we studied 10 healthy volunteers. To study the peripheral vasoconstrictive effect of dexmedetomidine without concurrent sympatholytic effects, sympathetic fibres were blocked with a brachial plexus block. Volunteers received a dexmedetomidine target‐controlled infusion for 15 min, to a target concentration of 0.3 ng ml–1. Arterial blood samples were collected during and for 60 min after dexmedetomidine infusion for PK analysis. Peripheral vasoconstriction (PD) was assessed using finger photoelectric plethysmography. PK/PD analysis was carried out using nonlinear mixed‐effect models.

Results

We found that the computer‐controlled infusion pump delivered mean concentrations greater than 0.3 ng ml–1 over the 15‐min infusion duration. The peripheral vasoconstrictive effect correlated with dexmedetomidine plasma concentrations during and after the infusion. A three‐compartment model provided a better fit to the data than a two‐compartment model.

Conclusions

We found that dexmedetomidine‐induced vasoconstriction is concentration dependent over time. Dexmedetomidine PK were best estimated by a three‐compartment model with allometric scaling. Our results may contribute to future modelling of dexmedetomidine‐induced haemodynamic effects.
Impairment of K‐Ras signaling networks and increased efficacy of epidermal growth factor receptor inhibitors by a novel synthetic miR‐143
Authors: Akao Yukihiro , Kumazaki Minami , Shinohara Haruka , Sugito Nobuhiko , Kuranaga Yuki , Tsujino Takuya , Yoshikawa Yuki , Kitade Yukio
Published: March 2018

Despite considerable research on K‐Ras inhibitors, none had been established until now. We synthesized nuclease‐resistant synthetic miR‐143 (miR‐143#12), which strongly silenced K‐Ras, its effector signal molecules AKT and ERK, and the K‐Ras activator Sos1. We examined the anti‐proliferative effect of miR‐143#12 and the mechanism in human colon cancer DLD‐1 cell (G13D) and other cell types harboring K‐Ras mutations. Cell growth was markedly suppressed in a concentration‐dependent manner by miR‐143#12 (IC50: 1.32 nmol L−1) with a decrease in the K‐Ras mRNA level. Interestingly, this mRNA level was also downregulated by either a PI3K/AKT or MEK inhibitor, which indicates a positive circuit of K‐Ras mRNA expression. MiR‐143#12 silenced cytoplasmic K‐Ras mRNA expression and impaired the positive circuit by directly targeting AKT and ERK mRNA. Combination treatment with miR‐143#12 and a low‐dose EGFR inhibitor induced a synergistic inhibition of growth with a marked inactivation of both PI3K/AKT and MAPK/ERK signaling pathways. However, silencing K‐Ras by siR‐KRas instead of miR‐143#12 did not induce this synergism through the combined treatment with the EGFR inhibitor. Thus, miR‐143#12 perturbed the K‐Ras expression system and K‐Ras activation by silencing Sos1 and, resultantly, restored the efficacy of the EGFR inhibitors. The in vivo results also supported those of the in vitro experiments. The extremely potent miR‐143#12 enabled us to understand K‐Ras signaling networks and shut them down by combination treatment with this miRNA and EGFR inhibitor in K‐Ras‐driven colon cancer cell lines.
Adapting the bioblitz to meet conservation needs
Authors: Parker Sophie S. , Pauly Gregory B. , Moore James , Fraga Naomi S. , Knapp John J. , Principe Zachary , Brown Brian V. , Randall John M. , Cohen Brian S. , Wake Thomas A.
Published: March 2018

When conservation strategies require new, field‐based information, practitioners must find the best ways to rapidly deliver high‐quality survey data. To address this challenge, several rapid‐assessment approaches have been developed since the early 1990s. These typically involve large areas, take many months to complete, and are not appropriate when conservation‐relevant survey data are urgently needed for a specific locale. In contrast, bioblitzes are designed for quick collection of site‐specific survey data. Although bioblitzes are commonly used to achieve educational or public‐engagement goals, conservation practitioners are increasingly using a modified bioblitz approach to generate conservation‐relevant data while simultaneously enhancing research capacity and building working partnerships focused on conservation concerns. We term these modified eventsexpert bioblitzes. Several expert bioblitzes have taken place on lands of conservation concern in Southern California and have involved collaborative efforts of government agencies, nonprofit organizations, botanic gardens, museums, and universities. The results of expert bioblitzes directly informed on‐the‐ground conservation and decision‐making; increased capacity for rapid deployment of expert bioblitzes in the future; and fostered collaboration and communication among taxonomically and institutionally diverse experts. As research and conservation funding becomes increasingly scarce, expert bioblitzes can play an increasingly important role in biodiversity conservation.
Predictive Movements and Human Reinforcement Learning of Sequential Action
Authors: de Kleijn Roy , Kachergis George , Hommel Bernhard
Published: March 2018

Sequential action makes up the bulk of human daily activity, and yet much remains unknown about how people learn such actions. In one motor learning paradigm, the serial reaction time (SRT) task, people are taught a consistent sequence of button presses by cueing them with the next target response. However, the SRT task only records keypress response times to a cued target, and thus it cannot reveal the full time‐course of motion, including predictive movements. This paper describes a mouse movement trajectory SRT task in which the cursor must be moved to a cued location. We replicated keypress SRT results, but also found that predictive movement—before the next cue appears—increased during the experiment. Moreover, trajectory analyses revealed that people developed a centering strategy under uncertainty. In a second experiment, we made prediction explicit, no longer cueing targets. Thus, participants had to explore the response alternatives and learn via reinforcement, receiving rewards and penalties for correct and incorrect actions, respectively. Participants were not told whether the sequence of stimuli was deterministic, nor if it would repeat, nor how long it was. Given the difficulty of the task, it is unsurprising that some learners performed poorly. However, many learners performed remarkably well, and some acquired the full 10‐item sequence within 10 repetitions. Comparing the high‐ and low‐performers’ detailed results in this reinforcement learning (RL) task with the first experiment's cued trajectory SRT task, we found similarities between the two tasks, suggesting that the effects in Experiment 1 are due to predictive, rather than reactive processes. Finally, we found that two standard model‐free reinforcement learning models fit the high‐performing participants, while the four low‐performing participants provide better fit with a simple negative recency bias model.
Human leukocyte antigen compatibility and lymphocyte cross‐matching play no significant role in the current adult‐to‐adult living donor liver transplantation
Authors: Badawy Amr , Kaido Toshimi , Yoshizawa Atsushi , Yagi Shintaro , Fukumitsu Ken , Okajima Hideaki , Uemoto Shinji
Published: March 2018

Background

The impact of human leukocyte antigen (HLA) compatibility and positive lymphocyte cross‐match (LCM) on organ transplantation is well‐recognized particularly in kidney and heart transplantation; however, it is still debatable in liver transplantation (LT). So, the aim of this study was to evaluate the impact of HLA mismatch and positive LCM on the outcome of LT.

Methods

We retrospectively analyzed the data of all adult recipients who underwent living donor LT at our institute between January 2010 and July 2016. We excluded all ABO blood group incompatible LDLT patients and patients with incomplete data regarding HLA genotyping (n = 134). The type and degree of HLA‐A, HLA‐B, HLA‐C, HLA‐DR, HLA‐DQ mismatch and LCM were assessed in each donor‐recipient pair and their relationship to the occurrence of rejection, CMV infection and graft survival was evaluated.

Results

A higher percentage (>50%) of donor‐recipient pairs had 1 HLA mismatch at each locus in the host‐vs‐graft direction and seventeen recipients (13%) had positive LCM. Human leukocyte antigen mismatch and positive LCM were not correlated with increased incidence of acute rejection (P = .37, P = .6, respectively), CMV infection post‐transplant (P = .52, P = .76, respectively), or graft failure (HR 1.22, P = .68 and HR 1.73, P = .34, respectively).

Conclusion

Positive LCM and HLA mismatches did not affect the overall graft survival after adult‐to‐adult LDLT and should not be considered as contraindications for liver transplantation.
THE PLANTS OF JOHN BRADBY BLAKE
Authors: Huang Hongwen
Published: March 2018

Analysis of the John Bradby Blake plant illustrations in the library of the Oak Spring Garden Foundation identifies a total of 138 species belonging to over 100 genera and 62 families. Especially well‐represented are useful plants of all kinds, including a high proportion of plants that are used in Chinese traditional medicine.
South‐western Atlantic reef fishes: Zoogeographical patterns and ecological drivers reveal a secondary biodiversity centre in the Atlantic Ocean
Authors: Pinheiro Hudson T. , Rocha Luiz A. , Macieira Raphael M. , Carvalho‐Filho Alfredo , Anderson Antônio B. , Bender Mariana G. , Di Dario Fabio , Ferreira Carlos Eduardo L. , Figueiredo‐Filho Jessé , Francini‐Filho Ronaldo , Gasparini João L. , Joyeux Jean‐Christophe , Luiz Osmar J. , Mincarone Michael M. , Moura Rodrigo L. , Nunes José de Anchieta C. C. , Quimbayo Juan P. , Rosa Ricardo S. , Sampaio Cláudio L. S. , Sazima Ivan , Simon Thiony , Vila‐Nova Daniele A. , Floeter Sergio R.
Published: March 2018

Aim

To present an updated database of fish species recorded on south‐western Atlantic reef environments and to explore the ecological drivers of the structure, the latitudinal gradient of biodiversity and the centre of endemism in this peripheral province.

Location

South‐western Atlantic (SWA): Brazilian and Argentinian Provinces.

Methods

A database composed of 733 fish species along 23 locations in the SWA (00°55′ N to 43°00′ S) was compiled based on primary data, literature and museum records. Cluster and beta diversity analyses were carried out to evaluate faunal overlaps among locations and subprovinces. “Target‐area‐distance effect” and “stepping stones dispersal” hypotheses for assemblage composition were tested through Mantel tests. Relationships between the distribution patterns and ecological traits of reef fish species were investigated through generalized linear mixed‐effect models.

Results

Out of the 733 fish species, 405 are SWA resident reef fishes, of which 111 (27%) are endemics and 78 are threatened with extinction. Cluster analysis detected six subprovinces in the SWA structured following the target‐area‐distance model, and with no evidence for a latitudinal gradient in diversity. The greatest overall richness and endemic species richness were found in the east–south‐eastern region. Depth range, habitat use and body size were the main drivers of SWA reef fish assemblage structure.

Main conclusions

The Brazilian and Argentinian coasts constitute different provinces structured by oceanographic barriers and environmental filters. Similarities among oceanic islands indicate connectivity driven by stochastic and ecological factors. Species richness and endemism indicate that peripheral provinces may also bear centres of origin and biodiversity, patterns driven by parapatric/ecological speciation and the overlap between tropical and subtropical reef fish species. Ecological drivers of reef fish distribution, such as habitat specialization and body size, support hypotheses of speciation in the periphery. New approaches for spatial planning, marine protected areas and off‐reserve marine management are essential for the conservation and sustainability of SWA reef fishes.
Different glucagon effects during DPP‐4 inhibition versus SGLT‐2 inhibition in metformin‐treated type 2 diabetes patients
Authors: Alsalim Wathik , Persson Margaretha , Ahrén Bo
Published: March 2018

Aims

Previous studies have shown that dipeptidyl peptidase (DPP)‐4 inhibition lowers glucagon levels whereas sodium‐glucose co‐transporter 2 (SGLT‐2) inhibition increases them. This study evaluated the extent of these opposite effects in a direct comparative head‐to‐head study.

Methods

In a single‐centre, randomized study with a cross‐over design, 28 metformin‐treated patients with type 2 diabetes (T2D) (mean age, 63 years; baseline HbA1c, 6.8%) were treated with vildagliptin (50 mg twice daily) or dapagliflozin (10 mg once daily) for 2 weeks, with a 4‐week wash‐out period between the two separate treatments. After each treatment period, a meal test was undertaken, with measurements of islet and incretin hormones and 4‐hour area under the curve (AUC) levels were estimated.

Results

Fasting glucagon (35.6 ± 2.5 vs 39.4 ± 3.4 pmoL/L; P = .032) and postprandial glucagon (4‐hour AUCglucagon, 32.1 ± 2.3 vs 37.5 ± 2.7 nmoL/L min; P = .001) were ~15% lower after vildagliptin compared to dapagliflozin treatment. This was associated with stronger early (15 minute) C‐peptide response and higher 4‐hour AUCC‐peptide (P < .010), higher 4‐hour AUC of the intact form of glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) (P < .001) and lower 4‐hour AUC of total GIP and GLP‐1 (P < .001).

Conclusion

Treatment with DPP‐4 inhibition with vildagliptin results in 15% lower fasting and postprandial glucagon levels compared to SGLT‐2 inhibition with dapagliflozin. DPP‐4 inhibition also induces more rapid insulin secretion and higher levels of intact incretin hormones, resulting in stronger feedback inhibition of incretin hormone secretion than SGLT‐2 inhibition.
Visual orientation of the black fungus gnat, Bradysia difformis, explored using LEDs
Authors: Stukenberg Niklas , Ahrens Niklas , Poehling Hans‐Michael
Published: March 2018

Fungus gnats occur worldwide with more than 1 700 described species. They can cause serious damages on ornamentals, crop plants, and edible mushrooms, and are considered to be a serious pest in the last years. Bradysia difformisFrey (Diptera: Sciaridae) represents a common species in Europe. Usually, yellow sticky traps are used for monitoring and control in greenhouses and fluorescent tube‐based light traps are additionally applied for control in mushroom cultivation. The importance of such visual trapping measures for efficient monitoring or alternative control increases in biological and integrated plant protection. However, detailed color preferences of fungus gnats are mostly unknown. We studied the visual orientation of B. difformis with light‐emitting diodes (LEDs) in a broad range of peak wavelengths from 371 nm (ultraviolet, UV) to 619 nm (amber). We determined attractive wavelengths in consecutive choice experiments in daylight and darkness. Highest numbers of adult B. difformis were attracted to UV radiation (382 nm) followed by green‐yellow light (532–592 nm). The responses to UV and the green‐yellow range were relatively unspecific and mostly independent from intensity. Combination of UV and yellow LEDs improved trapping efficacy compared to a single UV or yellow LED trap, as well as compared to a common yellow sticky trap. When both wavelengths were compared to a black surface to increase contrasts, the black surface was preferred over yellow, but was less attractive than UV. Thus, B. difformis displays two, probably wavelength‐specific, behaviors to UV radiation and green‐yellow light, with UV being the most attractive stimulus. These behaviors might be directly related to underlying photoreceptors, suggesting dichromatic vision in B. difformis.
Tobacco retail licences and state formation in early modern England and Wales
Authors: Taylor Alexander G.
Published: March 2018

This article addresses one under‐studied aspect of Charles I's finances during his Personal Rule: the licensing of tobacco retailers. While it was ultimately a failed project, the tobacco retail licence project was fiscally successful before the transformative events of the 1640s triggered its demise. The project enabled tobacco retail licensees to establish commercial outlets for the marketing of tobacco throughout England and Wales, and cooperation with pre‐existing officeholders contributed to the apprehension of unlicensed retailers. Ultimately, the geographic breadth of tobacco licences translated into much‐needed royal revenue which, when added to other projects and patents, contributed to the king's financial survival. The evidence presented here suggests that we may want to rethink some of our assumptions for how the process of state formation worked and that earlier seventeenth‐century ‘prototypes’ of taxation were more fiscally successful than previously recognized.
Self‐perceived educational needs of junior assistant professors in Conservative Dentistry and Endodontics in France
Authors: Kérourédan O. , Smirani R. , Oriez D. , Péli J. F. , Seux D. , Quinton A. , Devillard R.
Published: March 2018

Introduction

Academic dental educators play a major role in training future dentists. They help students to develop medical knowledge and behavioural skills that improve the quality and rigor of their future practice. Therefore, their experience and knowledge are critical to ensure effective learning. However, a French national workshop revealed that most junior assistant professors lack educational skills at the beginning of their career. The aim of this study was to assess educational training needs of junior assistant professors in the Department of Conservative Dentistry and Endodontics.

Materials and Methods

An electronic survey was sent to junior assistant professors belonging to Departments of Conservative Dentistry and Endodontics within the 16 French dental schools in 2016. This survey was designed to collect data regarding their motivations, teaching expertise and interest in pedagogy.

Results

Sixty of the 69 junior educators turned in their answers, which represents a response rate of 87%. About 86.7% of respondents cited their attraction to teaching as one of the main reasons behind their application. The major difficulty encountered by junior faculty was related to course preparation. Only 15% had received educational training despite the fact that 98.3% were convinced of the usefulness of such a training for junior teachers.

Conclusion

This study identified the motivations and difficulties encountered by junior assistant professors. This collection of educational needs should be considered when planning a national programme for educational training of dental faculty that will promote the acquisition of teaching skills and improve the education of dental students.