bluuebunny/crossref_metadata_2025 huggingface dataset:
NetSurfP-2.0: improved prediction of protein structural features by integrated deep learning
Authors: Klausen Michael Schantz , Jespersen Martin Closter , Nielsen Henrik , Kjærgaard Jensen Kamilla , Jurtz Vanessa Isabell , Sønderby Casper Kaae , Sommer Morten Otto Alexander , Winther Ole , Nielsen Morten , Petersen Bent , Marcatili Paolo
Published: April 2018

The ability to predict local structural features of a protein from the primary sequence is of paramount importance for unravelling its function in absence of experimental structural information. Two main factors affect the utility of potential prediction tools: their accuracy must enable extraction of reliable structural information on the proteins of interest, and their runtime must be low to keep pace with sequencing data being generated at a constantly increasing speed.

Here, we present an updated and extended version of the NetSurfP tool (http://www.cbs.dtu.dk/services/NetSurfP-2.0/), that can predict the most important local structural features with unprecedented accuracy and runtime. NetSurfP-2.0 is sequence-based and uses an architecture composed of convolutional and long short-term memory neural networks trained on solved protein structures. Using a single integrated model, NetSurfP-2.0 predicts solvent accessibility, secondary structure, structural disorder, and backbone dihedral angles for each residue of the input sequences.

We assessed the accuracy of NetSurfP-2.0 on several independent test datasets and found it to consistently produce state-of-the-art predictions for each of its output features. We observe a correlation of 80% between predictions and experimental data for solvent accessibility, and a precision of 85% on secondary structure 3-class predictions. In addition to improved accuracy, the processing time has been optimized to allow predicting more than 1,000 proteins in less than 2 hours, and complete proteomes in less than 1 day.
Home ground advantage: selection against dispersers promotes local adaptation in wild Atlantic salmon
Authors: Mobley Kenyon B. , Granroth-Wilding Hanna , Ellmen Mikko , Vähä Juha-Pekka , Aykanat Tutku , Johnston Susan E. , Orell Panu , Erkinaro Jaakko , Primmer Craig R.
Published: April 2018

A long-held, but poorly tested, assumption in natural populations is that individuals that disperse into new areas for reproduction are at a disadvantage compared to individuals that reproduce in their natal habitat, underpinning the eco-evolutionary processes of local adaptation and ecological speciation. Here, we capitalize on fine-scale population structure and natural dispersal events to compare the reproductive success of local and dispersing individuals captured on the same spawning ground in four consecutive parent-offspring cohorts of wild Atlantic salmon (Salmo salar). Parentage analysis conducted on adults and juvenile fish showed that local females and males had 9.6 and 2.9 times higher reproductive success than dispersers, respectively. Our results reveal how dispersal disadvantage in reproductive success may act in natural populations to drive population divergence and local adaptation over microgeographic spatial scales without clear morphological differences or physical barriers to gene flow.
Beyond the traditional simulation design for evaluating type 1 error rate: from ‘theoretical’ to ‘empirical’ null
Authors: Zhang Ting , Sun Lei
Published: April 2018

When evaluating a newly developed statistical test, the first step is to check its type 1 error (TIE) control using simulations. This is often achieved by the standard simulation design S0 under the so-called ‘theoretical’ null of no association. In practice, whole-genome association analyses scan through a large number of genetic markers (Gs) for the ones associated with an outcome of interest (Y), where Y comes from an unknown alternative while the majority of Gs are not associated with Y, that is under the ‘empirical’ null. This reality can be better represented by two other simulation designs, where design S1.1 simulates Y from an alternative model based on G then evaluates its association with independently generated Gnew, while design S1.2 evaluates the association between permutated Yperm and G. More than a decade ago, Efron (2004) has noted the important distinction between the ‘theoretical’ and ‘empirical’ null in false discovery rate control. Using scale tests for variance heterogeneity and location tests of interaction effect as two examples, here we show that not all null simulation designs are equal. In examining the accuracy of a likelihood ratio test, while simulation design S0 shows the method has the correct T1E control, designs S1.1 and S1.2 suggest otherwise with empirical T1E values of 0.07 for the 0.05 nominal level. And the inflation becomes more severe at the tail and does not diminish as sample size increases. This is an important observation that calls for new practices for methods evaluation and interpretation of T1E control.
ADAM22 and ADAM23 modulate the targeting of the Kv1 channel-associated protein LGI1 to the axon initial segment
Authors: Hivert Bruno , Marien Laurène , Agbam Komlan Nassirou , Faivre-Sarrailh Catherine
Published: April 2018

The distribution of voltage-gated potassium channels Kv1 at the axon initial segment (AIS), along the axon and at presynaptic terminals influences intrinsic excitability and transmitter release. Kv1.1/1.2 subunits are associated with cell adhesion molecules (CAMs), including Caspr2 and LGI1 that are implicated in autoimmune and genetic neurological diseases with seizures. In particular, mutations in the LGI1 gene cause autosomal dominant lateral temporal lobe epilepsy (ADTLE). In the present study, we used rat hippocampal neurons in culture to assess whether interplay between distinct Kv1-associated CAMs contributes to targeting at the AIS. Strikingly, LGI1 was highly restricted to the AIS surface when transfected alone, whereas the missense mutant LGI1S473L associated with ADLTE was not. Next, we showed that ADAM22 and ADAM23 acted as chaperones to promote axonal vesicular transport of LGI1 reducing its density at the AIS. Moreover, live-cell imaging of fluorescently labelled CAMs indicated that LGI1 was co-transported in axonal vesicles with ADAM22 or ADAM23. Finally, we showed that ADAM22 and ADAM23 also associate with Caspr2 and TAG-1 to be selectively targeted within different axonal sub-regions. The combinatorial expression of Kv1-associated CAMs may be critical to tune intrinsic excitability in a physiological or an epileptogenic context.
The lost world of Cuatro Cienegas Basin, a relictual bacterial niche in a desert oasis
Authors: Souza V. , Moreno-Letelier A. , Travisano M. , Alcaraz L. D. , Olmedo-Alvarez G. , Eguiarte L. E.
Published: April 2018

Barriers to immigration can lead to localized adaptive radiations and increased endemism. We propose that extreme oligotrophy can be a strong barrier to immigration over geological timescales, and facilitate the evolution of diverse and coevolved microbial communities. We show here that the endangered oasis of Cuatro Ciénegas Basin can be a model for a lost world, where the ancient niche of extreme oligotrophy favoured survival of ancestral microorganisms that persisted due to environmental stability and low extinction rates, generating a diverse and unique bacteria diversity. Diversification/extinction rates in Bacillus showed several CCB endemic clades that diverged from the rest of Bacillus spp. in different times of the Paleozoic and Mesozoic, in contrast to more recent Bacillus, Clostridium and Bacteroidetes lineages. CCB conservation is vital to the understanding of early evolutionary and ecological processes.
Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes
Authors: Alshahrani Mona , Hoehndorf Robert
Published: April 2018

Motivation

In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease’s (or patient’s) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse.

Results

We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

Availability

https://github.com/bio-ontology-research-group/SmuDGE

Contact

robert.hoehndorf@kaust.edu.sa
Polygenic selection drives the evolution of convergent transcriptomic landscapes across continents within a Nearctic sister-species complex
Authors: Rougeux Clément , Gagnaire Pierre-Alexandre , Praebel Kim , Seehausen Ole , Bernatchez Louis
Published: April 2018

In contrast to the plethora of studies focusing on the genomic basis of adaptive phenotypic divergence, the role of gene expression during speciation has been much less investigated and consequently, less understood. Yet, the convergence of differential gene expression patterns between closely related species-pairs might reflect the role of natural selection during the process of ecological speciation. Here, we test for intercontinental convergence in differential transcriptional signatures between limnetic and benthic sympatric species-pairs of Lake Whitefish (Coregonus clupeaformis) and its sister-lineage, the European Whitefish (C. lavaretus), using six replicated sympatric species-pairs (two in North America, two in Norway and two in Switzerland). We characterized both sequence variation in transcribed regions and differential gene expression between sympatric limnetic and benthic species across regions and continents. Our first finding was that differentially expressed genes (DEG) between limnetic and benthic whitefish tend to be enriched in shared polymorphism among sister-lineages. We then used both genotypes and co-variation in expression in order to infer polygenic selection at the gene level. We identified parallel outliers and DEG involving genes primarily over-expressed in limnetic species relative to the benthic species. Our analysis finally revealed the existence of shared genomic bases underlying parallel differential expression across replicated species pairs from both continents, such as a cis-eQTL affecting the pyruvate kinase expression level involved in glycolysis. Our results are consistent with a longstanding role of natural selection in maintaining transcontinental diversity at phenotypic traits involved in ecological speciation between limnetic and benthic whitefishes.
MIN1PIPE: A Miniscope 1-photon-based Calcium Imaging Signal Extraction Pipeline
Authors: Lu Jinghao , Li Chunyuan , Singh-Alvarado Jonnathan , Zhou Zhe Charles , Fröhlich Flavio , Mooney Richard , Wang Fan
Published: April 2018

In vivo calcium imaging using 1-photon based miniscope and microendoscopic lens enables studies of neural activities in freely behaving animals. However, the high and fluctuating background, the inevitable movements and distortions of imaging field, and the extensive spatial overlaps of fluorescent signals emitted from imaged neurons inherent in this 1-photon imaging method present major challenges for extracting neuronal signals reliably and automatically from the raw imaging data. Here we develop a unifying algorithm called MINiscope 1-photon imaging PIPEline (MIN1PIPE) that contains several standalone modules and can handle a wide range of imaging conditions and qualities with minimal parameter tuning, and automatically and accurately isolate spatially localized neural signals. We quantitatively compare MIN1PIPE with other existing partial methods using both synthetic and real datasets obtained from different animal models, and show that MIN1PIPE has a superior performance both in terms of efficiency and precision in analyzing noisy miniscope calcium imaging data.
Decision-making increases episodic memory via post-encoding consolidation
Authors: Murty Vishnu P. , DuBrow Sarah , Davachi Lila
Published: April 2018

The ability for individuals to actively make decisions engages regions within the mesolimbic system and enhances memory for chosen items. In other behavioral contexts, mesolimbic engagement has been shown to enhance episodic memory by supporting consolidation. However, research has yet to investigate how consolidation may support interactions between decision-making and episodic memory. Across two studies, participants encoded items that were occluded by cover screens and could either actively decide which of two items to uncover or were pre-selected by the experimenter. In Study 1, we show that active decision-making reduces forgetting rates across an immediate and 24-hour memory test, a behavioral marker of consolidation. In Study 2, we use functional neuroimaging to characterize putative neural markers of memory consolidation by measuring post-encoding interactions between the hippocampus and perirhinal cortex (PRC). We show that choice-related striatal engagement is associated with increased post-encoding hippocampal-PRC interactions. Finally, we show that a previous reported relationship between choice-related striatal engagement and long-term memory is accounted for by post-encoding hippocampal-PRC interactions. Together these findings support a model by which actively deciding to encode information enhances subsequent consolidation mechanisms to preserve episodic memory for outcomes.
Calcium-Calmodulin Gating of Connexin43 Gap Junctions in the Absence of the pH Gating Domain
Authors: Wei Siyu , Cassara Christian , Lin Xianming , Veenstra Richard D
Published: April 2018

Intracellular protons and calcium ions are two major chemical factors that regulate connexin43 (Cx43) gap junction channels and the synergism or antagonism between pH and Ca2+ has been questioned for decades. In this study, we assessed whether the calcium gating mechanism occurs independently of the pH gating mechanism by utilizing the Cx43-M257 (Cx43K258stop) mutant, a carboxyl-terminal (CT) truncated version of Cx43 lacking the pH gating domain. Dual whole cell patch clamp experiments were performed on Neuroblastoma-2a (N2a) cells or neonatal mouse ventricular myocytes (NMVMs) expressing either full length Cx43 or Cx43-M257 proteins. Addition of 1 μM ionomycin to normal calcium saline reduced Cx43 or Cx43-M257 macroscopic gap junction conductance (gj) to zero within 15 min of perfusion, while this response was prevented by omitting 1.8 mM CaCl2 from the external solution or adding 100 nM calmodulin (CaM) inhibitory peptide to the internal pipette solution. The ability of connexin calmodulin binding domain (Cx CaMBD) mimetic peptides and the Gap19 peptide to inhibit the Ca2+/CaM gating response of Cx43 gap junctions was also examined. Internal addition of a Cx50 cytoplasmic loop CaMBD peptide (200 nM) prevented the Ca2+/ionomycin-induced decrease in Cx43 gj, while 100 μM Gap19 peptide had no effect. Lastly, the transjunctional voltage (Vj) gating properties of NMVM Cx43-M257 gap junctions were investigated. We confirmed that the fast kinetic inactivation component was absent in Cx43-M257 gap junctions, but also observed that the previously reported facilitated recovery of gj from inactivating potentials was abolished by CT truncation of Cx43. We conclude that CT pH gating domain of Cx43 contributes to the Vj-dependent fast inactivation and facilitated recovery of Cx43 gap junctions, but the Ca2+/CaM-dependent gating mechanism remains intact. Sequence-specific Cx CaMBD mimetic peptides act by binding Ca2+/CaM non-specifically and the Cx43 mimetic Gap19 peptide has no effect on this chemical gating mechanism.
Interneuronal gap junctions increase synchrony and robustness of hippocampal ripple oscillations
Authors: Holzbecher André , Kempter Richard
Published: April 2018

1

Sharp wave-ripple (SWRs) are important for memory consolidation. Their signature in the hippocampal extracellular field potential (EFP) can be decomposed into a ≈ 100 ms long sharp wave superimposed by ≈ 200 Hz ripple oscillations. How ripple oscillations are generated is currently not well understood. A promising model for the genesis of ripple oscillations is based on recurrent interneuronal networks (INT-INT). According to this hypothesis, the INT-INT network in CA1 receives a burst of excitation from CA3 that generates the sharp wave, and recurrent inhibition leads to an ultrafast synchronization of the CA1 network causing the ripple oscillations; fast-spiking parvalbumin-positive basket cells (PV+BCs) may constitute the ripple-generating interneuronal network. PV+BCs are also coupled by gap junctions (GJs) but the function of GJs for ripple oscillations has not been quantified. Using simulations of CA1 hippocampal networks of PV+BCs, we show that GJs promote synchrony and increase the neuronal firing rate of the interneuronal ensemble, while the ripple frequency is only affected mildly. The promoting effect of GJs on ripple oscillations depends on fast GJ transmission (≲ 0.5 ms), which requires proximal gap junction coupling (≲ 100 μm from soma).
The impact of board characteristics on the financial performance of Tanzanian firms
Authors: Assenga Modest Paul , Aly Doaa , Hussainey Khaled
Published: April 2018

Purpose

This paper aims to investigate the impact of board characteristics on the financial performance of listed firms in Tanzania. Board characteristics, including outside directors, board size, CEO/Chair duality, gender diversity, board skill and foreign directors are addressed in the Tanzanian context by applying two corporate governance theories, namely, agency theory and resource dependence theory.

Design/methodology/approach

The paper uses balanced panel data regression analysis on 80 firm-years observations (2006-2013) from annual reports, and semi-structured interviews were conducted with 12 key stakeholders. The study uses also a mixed methods approach and applies a convergent parallel design (Creswell and Plano Clark, 2011) to integrate quantitative and qualitative data.

Findings

It was found that in terms of agency theory, while the findings support the separation of CEO/Chairperson roles, they do not support outside directors-financial performance linkage. With regard to resource dependence theory, the findings suggest that gender diversity has a positive impact on financial performance. Furthermore, the findings do not support an association between financial performance and board size, PhD qualification and foreign directors.

Practical implications

The study contributes to the understanding of board-performance link and provides academic evidence to policy makers in Tanzania for current and future governance reforms.

Originality/value

The findings contribute to the literature by providing new and original insights that, within a developing setting, extend current understanding of the association between corporate governance and financial performance. This is predicated, also, on the use of uncommon mixed methods approach.
Developing cultural intelligence: learning together with reciprocal mentoring
Authors: Desai Sheetal , Rao Srinivasa A. , Jabeen Shazi Shah
Published: April 2018

Purpose

This paper aims to focus on how reciprocal mentoring can be used to make employees culturally intelligent.

Design/methodology/approach

The authors conceptualize and present this framework based on their own experience in the industry and research experience in cross-cultural competence.

Findings

Workplaces today are characterized by high levels of multiculturalism. In such environments, being able to navigate this cultural diversity can be a challenge to many employees. Investing in cross-cultural training can be costly and time consuming. In such a situation, what better way to learn and appreciate cultural diversity than by bringing together two individuals from different cultural backgrounds. Reciprocal mentoring for developing cultural intelligence can be an effective practice that organizations can follow to develop intercultural competence amongst its employees.

Practical implications

The concept presented in the paper can help organizations use their own existing resources to develop cultural intelligence company-wide, rather than choosing third-party interventions/training.

Originality/value

This paper provides executives with a quick glimpse into the concept of cultural intelligence and its development through reciprocal mentoring.
HR tech startups in India
Authors: Madhvapaty Havish , Rajesh Anupama
Published: April 2018

Purpose

This article aims to establish the need for professionals and industry to get together on a common platform to engage in discussions, identify innovations and set standards. The movement of employees from unorganized to organized segment is accelerating and subsequently the cost of managing employees is also going to increase manifold for Indian organizations. The HR Tech landscape is pegged at $400m annually and expected to grow significantly.

Design/methodology/approach

The paper looks at the HR Tech landscape and posits how HR technologies can help companies save significant costs, and also bring in advanced techniques such as automation and analytics which will improve work efficiency.

Findings

While big enterprises are also working in the area of HR technology, startups are showing rapid progress, owing to the fact that they do not have to cope with legacy data/technology/operations. Challenges still remain such as failure to lay groundwork for adoption by employees.

Practical implications

While there are diverse products and technologies in the market, the core challenge is to find the right product-market fit. HR buyers have to ensure that the solutions are future proof.

Social implications

Automation is going to affect a lot of jobs, certain profiles more so than others. At a larger scale, integrating automation in work processes will have a substantial adverse impact on employees in these job profiles.

Originality/value

The HR Tech landscape is inundated with technology-first startups. There is a dearth of academic literature. There is also a cogent need for professionals and industry to get together on a common platform to engage in discussions, identify innovations, and set standards.
Investigation of oil uptake modeling and moisture content in fried nuggets using different maize starches
Authors: Yosefzadeh Sani Sepideh , Mortazavi Sayed Ali , Sheikholeslami Zahra , Karimi Mehdi , Elhamirad Amir Hossein
Published: April 2018

Purpose

In the past decades, the desire to use natural source foods has increased because of environmental compatibility, safety and appropriate costs. Sonication is used in food industry owing to its short duration of process and saving energy. The purpose of this study is to investigate the effect of various maize starches in the batter on the oil absorption and quality assessment (moisture content) of chicken nuggets by using five mathematical models.

Design/methodology/approach

To determine the effects of different maize starches on oil absorption parameters, 5 per cent starches native, sonicated starch were substituted in batter instead of wheat flour. Suspensions contained native starch were treated with sonication (70 kHz, 5 min) using an ultrasound probe set. Samples were fried in a fryer at 150, 170 and 190°C for 1, 3and 5 min, respectively. Models were compared with R2 and Arrhenius equation for estimating model prediction sufficiency.

Findings

Obtained results represented that between different formulated samples, maize starch with high temperature had main significant effect (p < 0.05) on moisture content of nuggets. During frying, the amount of oil loses significantly (p < 0.05) depended on temperature and time and sonication treatment.

Originality/value

Incorporation of sonication with maize starch at higher temperature on quality assessment has not been found.
Sardine proteins (Sardina pilchardus) combined with green lemon zest (Citrus latifolia) improve blood pressure, lipid profile and redox status in diabetic hypertensive rats
Authors: Khelladi HadjMostefa , Krouf Djamil , Taleb-Dida Nawal
Published: April 2018

Purpose

This paper aims to study the effect of green lemon zest combined with sardine proteins in diabetic hypertensive rats (DHRs).

Design/methodology/approach

Male Wistar rats (n= 30) weighing 250 ± 10 g were divided into five groups. The first group consumed a diet containing 20 per cent casein (C). The other four groups are rendered diabetic by intraperitoneal injection of streptozotocin (40 mg/kg body weight), then hypertensive by subcutaneous implantation controlled time-release pellet containing ouabain (0.25 mg/pellet). One untreated group (DHR) consumed 20 per cent casein and the three other groups consumed the same diet supplemented with 2 per cent green lemon zest (DHR-lz), or with 20 per cent of sardine protein (group DHR-sp) or with the combination of both sardine proteins and green lemon zest (group DHR-sp + lz).

Findings

DHRs feeding on the combination of both sardine protein (sp) and lemon zest (lz) induced a significant decrease of diastolic blood pressure and heart rates values compared with DHR (p< 0.05). The HDLC values were increased by +55 per cent in DHR-sp + lz compared with DHR group. Moreover, plasma non-HDLC concentrations were decreased significantly compared to DHR, DHR-lz, DHR-sp and C groups. In DHR-sp + lzvs DHR group, TBARS values were decreased by −25 per cent in the liver. Moreover, kidney TBARS were significantly reduced by −66, −51, −65 and −67 per cent compared with C, DHR, DHR-lz and DHR-sp, respectively.

Originality/value

These results suggest that consumption of green lemon zest combined with sardine proteins can reduce blood pressure and tissue oxidative damage and, therefore, help to prevent cardiovascular complications in hypertensive diabetic patients.
Navy expeditionary logistics
Authors: Yoho Keenan , Apte Uday
Published: April 2018

Synopsis

Continuous process improvement has been widely taught in business schools and has yielded real results and success in both for-profit and non-profit sectors. Though there have been many cases developed for use in business schools, few, if any, situate the topic in a military context. Further, expeditionary logistics presents managers with special problems of being removed from their supporting enterprise systems that process, track, and/or control of such logistical elements as purchase orders, inventory, distribution, receivables, and fulfillment. The authors present a case in a military setting that exposes students to the challenges of expeditionary logistics and takes them through the fundamentals of process analysis and process improvement.

Research methodology

The authors used a research methodology of a case study. Data were collected during field visits over the course of multiple interviews. Interviews were conducted with subject matter experts and active professionals serving in US Navy expeditionary logistics roles regarding processes and process performance.

Relevant courses and levels

This case can be applied to senior undergraduate or graduate-level courses in operations management, supply chain management, or logistics.

Theoretical bases

The theoretical bases adopted in this paper are supply chain management, information technology, operations management, and process improvement methodologies such as Six Sigma and Lean.
Opportunistic Behaviour and Trust: Experimental Results from Broccoli Farmers in Ecuador
Authors: Romero Granja Cristina , Wollni Meike
Published: April 2018

Linking smallholder farmers to high‐value markets through contract farming has become an important strategy to increase farm incomes in developing countries. However, various forms of opportunistic behaviour have been reported, threatening the sustainability of inclusive supply chains. When formal institutions are weak, informal codes of conduct like trust can be important complements to facilitate market transactions. We explore the effect of opportunistic behaviour on farmers’ trust, using a field‐framed trust experiment with prior signaling with small‐scale farmers in Ecuador. These farmers are linked to different types of markets, including high‐value export chains, and have been exposed to varying levels of opportunistic behaviour in the past. Our unique dataset allows us to control for self‐selection of game participants. We find that a positive signal triggers a positive response increasing trust, while a negative signal has no effect – possibly reflecting very low overall trust levels. In settings where market linkages have failed previously, ex‐ante credible positive signals could help to build trust and encourage small farmers’ participation in sustainable value chains.
Ten Challenges in Democracy Support – and How to Overcome them
Authors: Dodsworth Susan , Cheeseman Nic
Published: April 2018

Democracy supporters face tough times. Authoritarian reversals across North and sub‐Saharan Africa, combined with a lack of progress in the Middle East and Central Asia, have dampened funders’ enthusiasm for the endeavour. To better understand these setbacks, we identify ten challenges in democracy support. These are the challenges of: (i) difficult cases; (ii) authoritarian backlash; (iii) adapting to context; (iv) confronting politics; (v) managing uncertainty; (vi) unintended side‐effects; (vii) a tight funding environment; (viii) defining and demonstrating success; (ix) competing priorities; and – exacerbating all the rest, (x) a limited evidence base. While much has been written about the need for more coordinated and politically intelligent engagement to meet these challenges, far less has been said about the need to improve our evidence‐base and the way in which policy‐oriented research is produced. We identify several strategies that policy makers and practitioners can use to advance the field. All require better bridges between research, policy and practice, so we offer concrete suggestions about how such bridges can be built.
How do MAR(1) models cope with hidden nonlinearities in ecological dynamics?
Authors: Certain Grégoire , Barraquand Frédéric , Gårdmark Anna
Published: April 2018

Multivariate autoregressive (MAR) models are an increasingly popular technique to infer interaction strengths between species in a community and to predict the community response to environmental change. The most commonly employed MAR(1) models, with one time lag, can be viewed either as multispecies competition models with Gompertz density dependence or, more generally, as a linear approximation of more complex, nonlinear dynamics around stable equilibria. This latter interpretation allows for broader applicability, but may come at a cost in terms of interpretation of estimates and reliability of both short‐ and long‐term predictions.

We investigate what these costs might be by fitting MAR(1) models to simulated 2‐species competition, consumer‐resource and host–parasitoid systems, as well as a larger food web influenced by the environment. We review how MAR(1) coefficients can be interpreted and evaluate how reliable are estimates of interaction strength, rank, or sign; accuracy of short‐term forecasts; as well as the ability of MAR(1) models to predict the long‐term responses of communities submitted to environmental change such as PRESS perturbations.

The net effects of species j on species i are usually (90%‐95%) well recovered in terms of sign or rank, with the notable exception of overcompensatory dynamics. In actual values, net effects of species j on species i are not well recovered when the underlying dynamics are nonlinear. MAR(1) models are better at making short‐term qualitative forecasts (next point going up or down) than at predicting long‐term responses to environmental perturbations, which can be severely over‐ as well as underestimated.

We conclude that when applying MAR(1) models to ecological data, inferences on net effects among species should be limited to signs, or the Gompertz assumption should be tested and discussed. This particular assumption on density‐dependence (log‐linearity) is also required for unbiased long‐term predictions. Overall, we think that MAR(1) models are highly useful tools to resolve and characterize community dynamics, but we recommend to use them in conjunction with alternative, nonlinear models resembling the ecological context in order to improve their interpretation in specific applications.
A comparison of effectiveness among frequent treatments of recurrent spontaneous abortion: A Bayesian network meta‐analysis
Authors: Lv Sha , Yu Jing , Xu Xiaoxiao
Published: April 2018

Objective

A comprehensive network meta‐analysis was designed to clarify contradictions and offer valuable clinical guidance in the treatment of recurrent spontaneous abortion (RSA).

Method

The included clinical trials were selected from the relevant medical journal databases and screened. Treatments were ranked by the surface under the cumulative ranking curve. Heat plots were constructed to analyze the inconsistency between direct data and network results, and adjusted funnel plots were constructed to assess publication bias.

Results

Forty‐nine randomized controlled trials involving a total of 8496 RSA patients were selected. With placebo as control, corticosteroid plus low dose aspirin (LDA) plus unfractionated heparin (UFH), granulocyte colony‐stimulating factor (G‐CSF) alone, and LDA plus low molecular weight heparin (LMWH) all demonstrated effectiveness in increasing successful live birth rates and reducing the incidences of miscarriage. However, no treatment was demonstrably superior to placebo in terms of pregnancy success. For all 3 endpoints (live birth, abortion and success pregnancy), the adjusted funnel plots were symmetric to zero and indicated no publication bias. In terms of live birth and abortion rates, no treatment outperformed placebo in patients with antiphospholipid syndrome.

Conclusion

In consideration of live birth and abortion rates, corticosteroid plus LDA plus UFH appeared to be the optimum treatment strategy; G‐CSF was second, followed by LDA with LMWH, LDA plus LMWH plus intravenous immunoglobulin, corticosteroid with LDA and others. Subgroup analysis demonstrated no benefit of antithrombotic therapy in patients with antiphospholipid syndrome.
Magnesium sulfate differentially modulates fetal membrane inflammation in a time‐dependent manner
Authors: Cross Sarah N. , Nelson Rachel A. , Potter Julie A. , Norwitz Errol R. , Abrahams Vikki M.
Published: April 2018

Problem

Chorioamnionitis and infection‐associated inflammation are major causes of preterm birth. Magnesium sulfate (MgSO4) is widely used in obstetrics as a tocolytic; however, its mechanism of action is unclear. This study sought to investigate how MgSO4 modulates infection‐associated inflammation in fetal membranes (FMs), and whether the response was time dependent.

Method of Study

Human FM explants were treated with or without bacterial lipopolysaccharide (LPS); with or without MgSO4 added either: 1 hour before LPS; at the same time as LPS; 1 hour post‐LPS; or 2 hours post‐LPS. Explants were also treated with or without viral dsRNA and LPS, alone or in combination; and MgSO4 added 1 hour post‐LPS After 24 hours, supernatants were measured for cytokines/chemokines; and tissue lysates measured for caspase‐1 activity.

Results

Lipopolysaccharide‐induced FM inflammation by upregulating the secretion of a number of inflammatory cytokines/chemokines. Magnesium sulfate administered 1‐hour post‐LPS inhibited FM secretion of IL‐1β, IL‐6, G‐CSF, RANTES, and TNFα. Magnesium sulfate administered 2 hours post‐LPS augmented FM secretion of these factors as well as IL‐8, IFNγ, VEGF, GROα and IP‐10. Magnesium sulfate delivered 1‐ hour post‐LPS inhibited LPS‐induced caspase‐1 activity, and inhibited the augmented IL‐1β response triggered by combination viral dsRNA and LPS.

Conclusion

Magnesium sulfate differentially modulates LPS‐induced FM inflammation in a time‐dependent manner, in part through its modulation of caspase‐1 activity. Thus, the timing of MgSO4 administration may be critical in optimizing its anti‐inflammatory effects in the clinical setting. MgSO4 might also be useful at preventing FM inflammation triggered by a polymicrobial viral‐bacterial infection.
National Parliaments’ Use of the Political Dialogue: Institutional Lobbyists, Traditionalists or Communicators?
Authors: Rasmussen Mette Buskjær , Dionigi Maja Kluger
Published: April 2018

In this article, we examine the reasons behind national parliamentary engagement in the political dialogue with the Commission. We do so through a qualitative content analysis of over 200 national parliamentary opinions submitted to the Commission in recent years and interviews with national parliamentary representatives and Commission officials. We demonstrate that national parliaments’ engagement with the Commission is not simply a story about venue shopping in which parliaments seek to compensate for their domestic weaknesses. Their activity is driven by a rich repertoire of institutional actions, where parliaments simultaneously act as institutional lobbyists, traditionalists and communicators. They follow three main strategies, including attempts to control their government, influencing EU legislation directly, and engaging in parliamentary branding. Direct parliamentary lobbying of the Commission does not, however, render parliaments’ traditional role of controlling their government redundant as it improves domestic scrutiny methods.
Latent Profiles of Discrimination and Socialization Predicting Ethnic Identity and Well‐Being Among Asian American Adolescents
Authors: Kiang Lisa , Supple Andrew J. , Stein Gabriela L.
Published: April 2018

Ethnic identity is rooted in sociocultural processes, but little is known about how social interactions predict its longitudinal changes. Using data from 154 Asian American adolescents, latent profile analysis derived four typologies based on unfair treatment (i.e., discrimination, model minority stereotyping) and ethnic socialization (i.e., cultural socialization, preparation for bias, promotion of mistrust): Low Cultural Salience, High Cultural Salience with Marginalization, Culturally Prepared with Low Mistrust, and High Mistrust/Discrimination. Few gender or generational differences in profile membership were found. Positive outcomes were linked to adolescents attuned to both positive and negative experiences, Culturally Prepared with Low Mistrust, who reported increases in ethnic belonging and decreases in negative emotions. The implications for identity formation and adjustment are discussed.
Systemic inflammation and immune cell phenotypes are associated with neuro‐psychiatric symptoms in patients with chronic inflammatory liver diseases
Authors: Aregay Amare , Dirks Meike , Schlaphoff Verena , Owusu Sekyere Solomon , Haag Kim , Falk Christine Susanne , Hengst Julia , Bremer Birgit , Schuppner Ramona , Manns Michael P. , Pflugrad Henning , Cornberg Markus , Wedemeyer Heiner , Weissenborn Karin
Published: April 2018

Background & Aims

Chronic inflammatory liver diseases are frequently associated with neuropsychiatric and cognitive dysfunctions. We hypothesized that symptomatic patients may show altered levels of soluble inflammatory mediators (SIMs) as well as changes in immune cell phenotypes.

Methods

A comprehensive immune‐phenotyping including investigation of 50 SIMs as well as ex‐vivo phenotypes of NK‐cells, CD3+, CD4+, CD8+ and regulatory T cells in 40 patients with viral and autoimmune chronic liver diseases was performed. The patients’ cognitive functions were assessed using an extensive battery of neuropsychological testing.

Results and Conclusion

Overall, our data indicate that while SIMs are significantly up‐regulated, NK‐ and T‐cells are less‐activated in patients with neuropsychiatric symptoms accompanying chronic inflammatory liver diseases compared to patients without these symptoms. Moreover, HCV patients showed a unique pattern of immune alterations as compared to patients with HBV, autoimmune hepatitis and primary biliary cirrhosis. These findings hint towards potential mechanisms explaining these symptoms in patients with chronic liver diseases.
Placental expression of asialoglycoprotein receptor associated with Hepatitis B virus transmission from mother to child
Authors: Vyas Ashish Kumar , Ramakrishna Usha , Sen Bijoya , Islam Mojahidul , Ramakrishna Gayatri , Patra Sharda , Rastogi Archana , Sarin Shiv Kumar , Trehanpati Nirupma
Published: April 2018

Background

Asialoglycoprotein receptor expression on hepatocytes has been associated with endocytosis, binding and uptake of hepatitis B virus. The role of asialoglycoprotein receptor in hepatitis B virus vertical transmission and its expression on placenta has not yet been studied.

Patients and Methods

Thirty‐four HBsAg+ve and 13 healthy pregnant mothers along with their newborns were enrolled. The former were categorized into transmitting and non‐transmitting mothers based on their newborns being hepatitis B surface antigen and hepatitis B virus DNA positive. Expression of asialoglycoprotein receptor and hepatitis B surface antigen in placenta and isoform of asialoglycoprotein receptor on dendritic cell in peripheral and cord blood dendritic cells were analysed using flowcytometry, immune histochemistry, immune florescence and qRT‐PCR.

Results

Twelve HBsAg+ve mothers transmitted hepatitis B virus to their newborns whereas the rest (n = 22) did not. Hepatitis B virus‐transmitting mothers showed increased expression of asialoglycoprotein receptor in trophoblasts of placenta. Immunofluorescence microscopy revealed colocalization of hepatitis B surface antigen and asialoglycoprotein receptor in placenta as well as in DCs of transmitting mothers. There was no significant difference in the expression of asialoglycoprotein receptor on peripheral blood mononuclear cells or chord blood mononuclear cells between the 2 groups. However, hepatitis B virus‐transmitting mothers and their HBsAg+ve newborns showed increased mRNA levels of isoform of asialoglycoprotein receptor on dendritic cell in peripheral blood mononuclear cells. Hepatitis B virus‐transmitting mothers and their HBsAg+ve newborns showed an increased expression of isoform of asialoglycoprotein receptor on dendritic cell on circulating dendritic cells compared to hepatitis B virus non‐transmitting mothers and their negative newborns.

Conclusions

This study revealed that increased expression of asialoglycoprotein receptor in placenta and colocalization with hepatitis B surface antigen strongly indicates its role in intrauterine transmission of hepatitis B virus. Asialoglycoprotein receptor‐blocking strategy can be used for therapeutic intervention of vertical transmission.
Stop the war on DXA!
Authors: Lewiecki E. Michael , Binkley Neil , Bilezikian John P.
Published: April 2018

Dual‐energy X‐ray absorptiometry (DXA) is a versatile technology that is widely used in clinical practice in the management of osteoporosis and other skeletal diseases. It is a safe and inexpensive procedure that measures bone mineral density (BMD) to diagnose osteoporosis, assess fracture risk, and monitor osteoporosis treatment. However, DXA has been subjected to recurring claims that it is overutilized, too expensive, and not helpful in patient management. In recent years, there has been a decline in the number of office‐based DXA facilities, a reduction in BMD tests performed, and fewer women being diagnosed and treated for osteoporosis, despite aging of the population with more people at risk for fractures. Here, we identify some of the challenges to DXA, which in the aggregate amount to a disturbing war on DXA and, as a result, a threat to good patient care. We suggest potential strategies to restore DXA to its proper role in osteoporosis management.
The inoperability extended multisectoral model and the Role of Income Distribution: A U.K. Case Study
Authors: El Meligi Andrea Karim , Ciaschini Maurizio , Ali Khan Yousaf , Pretaroli Rosita , Severini Francesca , Socci Claudio
Published: April 2018

In this paper, an effort is made to enrich the current input–output (I–O) methodologies employed for studying disruptive events, by extending the I–O framework and including all the phases of the circular flow of income into the overall disaster impact. In this respect, the Inoperability Extended Multisectoral Model is created and implemented in order to estimate the higher‐order effects in terms of value added and disposable income. The social accounting matrix, referred to the United Kingdom, is constructed and proposed as a starting point for assessing the effects of a system perturbation related to the eruption of the Volcano Eyjafjallajökull, in mid‐April 2010, which affected air transport services due to the full closure of the U.K.'s airspace for several days. Finally, the ranking of those commodities and institutional sectors which are badly affected can provide guidance to policymakers in order to minimize the overall impact on the economy.
ESRD‐induced dyslipidemia—Should management of lipid disorders differ in dialysis patients?
Authors: Moradi Hamid , Streja Elani , Vaziri Nosratola D.
Published: April 2018

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Although numerous modifiable risk factors in the pathogenesis of CVD and its associated mortality have been identified, dyslipidemia remains to be a key focus for therapy. In this regard, significant progress has been made in reducing cardiovascular mortality via the use of lipid‐lowering agents such as HMG CoA reductase inhibitors (statins). Yet, despite the disproportionate risk of CVD and mortality in patients with advanced chronic and end stage renal disease (ESRD), treatment of dyslipidemia in this patient population has not been associated with a notable improvement in outcomes. Furthermore, observational studies have not consistently found an association between dyslipidemia and poor outcomes in patients with ESRD. However, it is imperative that examination of dyslipidemia and its association with outcomes take place in the context of the many factors that are unique to kidney disease and may contribute to the abnormalities in lipid metabolism in patients with ESRD. Understanding these intricacies and distinct features will be vital not only to the interpretation of the available clinical data in regards to outcomes, but also to the individualization of lipid therapy in ESRD. In this review, we will examine the nature and underlying mechanisms responsible for dyslipidemia, the association of serum lipids and lipoprotein concentrations with outcomes and the results of major trials targeting cholesterol (mainly statins) in patients with ESRD.
Characterization of a novel HLA‐C allele, HLA‐C*04:288, in an Italian patient
Authors: Biagini C. , Fornaciari S. , Mariotti M. L. , Scatena F. , Curcio M.
Published: April 2018

The novel HLA‐C*04:288 differs from HLA‐C*04:01:01:06 by a single nucleotide substitution in exon 2.