bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive ultrasonic modulation of visual evoked response by GABA delivery through the blood brain barrier
Authors: Constans C. , Ahnine H. , Santin M. D. , Lehericy S. , Tanter M. , Pouget P. , Aubry J-F
Published: June 2018

We demonstrate the feasibility of non-invasively modulating the visual cortex activity of non-human primates by local ultrasound-induced delivery of an inhibitory neurotransmitter (GABA). GABA was injected intravenously after the blood brain barrier (BBB) was transiently disrupted with focused ultrasound (FUS) coupled with ultrasound contrast agents (UCA). Visual evoked potentials exhibited a significant and progressive decrease of the activity. Combined effects of neuromodulation and BBB opening were shown to be 8.7 times less important than GABA-induced inhibition. During the sonication, the UCA harmonic response was monitored to estimate the level of stable cavitation (signature of BBB opening efficiency) and to avoid damages due to inertial cavitation (automatic shutdown of the sonication when detected). As recent developments in beam forming have shown that ultrasound beams can be focused non-invasively in deep-seated human brain locations, our results hold promise to explore and treat the brain with a non-invasive, controllable, repeatable and reversible method.
Chromosome polymorphisms track trans-Atlantic divergence, admixture and adaptive evolution in salmon
Authors: Lehnert Sarah J. , Bentzen Paul , Kess Tony , Lien Sigbjørn , Horne John B. , Clément Marie , Bradbury Ian R.
Published: June 2018

Pleistocene glaciations drove repeated range contractions and expansions shaping contemporary intraspecific diversity. Atlantic salmon (Salmo salar) from the western and eastern Atlantic range diverged >600K YBP, with each clade isolated in independent southern refugia during glacial maxima, driving trans-Atlantic genomic and karyotypic differences. Here, we investigate genomic consequences of glacial isolation and transAtlantic secondary contact using a 220K single nucleotide polymorphism (SNP) array genotyped in 80 North American and European populations. Throughout North America, we identified large inter-individual variation and discrete linkage blocks within and between chromosomes with known rearrangements: Ssa01/Ssa23 translocation and Ssa08/Ssa29 fusion. Spatial genetic analyses suggest independence of rearrangements, with Ssa01/Ssa23 showing high European introgression (>50%) in northern populations indicative of post-glacial trans-Atlantic secondary contact, contrasting low European ancestry genome-wide (3%). Ssa08/Ssa29 showed greater intra-population diversity suggesting a derived chromosome fusion polymorphism within North America. Evidence of selection on both regions suggests adaptive variation associated with karyotypes. Our study highlights how Pleistocene glaciations can drive large-scale intraspecific variation in genomic architecture of northern species.
Genome-scale reconstructions of the mammalian secretory pathway predict metabolic costs and limitations of protein secretion
Authors: Gutierrez Jahir M. , Feizi Amir , Li Shangzhong , Kallehauge Thomas B. , Hefzi Hooman , Grav Lise M. , Ley Daniel , Hizal Deniz Baycin , Betenbaugh Michael J. , Voldborg Bjorn , Kildegaard Helene Faustrup , Lee Gyun Min , Palsson Bernhard O. , Nielsen Jens , Lewis Nathan E.
Published: June 2018

In mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. The pathway complexity, however, obfuscates its impact on the secretion of different proteins. Unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. Here we delineate the core secretory pathway functions and integrate them with genome-scale metabolic reconstructions of human, mouse, and Chinese hamster cells. The resulting reconstructions enable the computation of energetic costs and machinery demands of each secreted protein. By integrating additional omics data, we find that highly secretory cells have adapted to reduce expression and secretion of other expensive host cell proteins. Furthermore, we predict metabolic costs and maximum productivities of biotherapeutic proteins and identify protein features that most significantly impact protein secretion. Finally, the model successfully predicts the increase in secretion of a monoclonal antibody after silencing a highly expressed selection marker. This work represents a knowledgebase of the mammalian secretory pathway that serves as a novel tool for systems biotechnology.
The genome and metabolome of the tobacco tree, Nicotiana glauca: a potential renewable feedstock for the bioeconomy
Authors: Usade Björn , Tohge Takayuki , Scossa Federico , Sierro Nicolas , Schmidt Maximilian , Vogel Alexander , Bolger Anthony , Kozlo Amanda , Enfissi Eugenia MA , Morrel Kris , Regenauer Manuel , Hallab Asis , Ruprecht Colin , Gundlach Heidrun , Spannagl Manuel , Koram Yaw , Mayer Klaus FX , Boerjan Wout , Fraser Paul D. , Persson Staffan , Ivanov Nikolai V. , Fernie Alisdair R.
Published: June 2018

Background

Given its tolerance to stress and its richness in particular secondary metabolites, the tobacco tree, Nicotiana glauca, has been considered a promising biorefinery feedstock that would not be competitive with food and fodder crops.

Results

Here we present a 3.5 Gbp draft sequence and annotation of the genome of N. glauca spanning 731,465 scaffold sequences, with an N50 size of approximately 92 kbases. Furthermore, we supply a comprehensive transcriptome and metabolome analysis of leaf development comprising multiple techniques and platforms.

The genome sequence is predicted to cover nearly 80% of the estimated total genome size of N. glauca. With 73,799 genes predicted and a BUSCO score of 94.9%, we have assembled the majority of gene-rich regions successfully. RNA-Seq data revealed stage-and/or tissue-specific expression of genes, and we determined a general trend of a decrease of tricarboxylic acid cycle metabolites and an increase of terpenoids as well as some of their corresponding transcripts during leaf development.

Conclusion

The N. glauca draft genome and its detailed transcriptome, together with paired metabolite data, constitute a resource for future studies of valuable compound analysis in tobacco species and present the first steps towards a further resolution of phylogenetic, whole genome studies in tobacco.
Speed Control and Force-Vectoring of Blue Bottle Flies in a Magnetically-Levitated Flight Mill
Authors: Hsu Shih-Jung , Thakur Neel , Cheng Bo
Published: June 2018

Flies fly at a broad range of speeds and produce sophisticated aerial maneuvers with precisely controlled wing movements. Remarkably, only subtle changes in wing motion are used by flies to produce aerial maneuvers, resulting in little directional tilt of aerodynamic force vector relative to the body. Therefore, it is often considered that flies fly according to a helicopter model and control speed mainly via force-vectoring enabled primarily by body-pitch change. Here we examine the speed control of blue bottle flies using a magnetically-levitated (MAGLEV) flight mill, as they fly at different body pitch and with different augmented aerodynamic damping. We identify wing kinematic contributors to the changes of estimated aerodynamic force through testing two force-vectoring models. Results show that in addition to body pitch, flies also use a collection of wing kinematic variables to control both force magnitude and direction, the roles of which are analogous to those of throttle, collective and cyclic pitch of helicopters. Our results also suggest that the MAGLEV flight mill system can be potentially used to study the roles of visual and mechanosensory feedback in insect flight control.
OpenPathSampling: A Python framework for path sampling simulations. I. Basics
Authors: Swenson David W.H. , Prinz Jan-Hendrik , Noe Frank , Chodera John D. , Bolhuis Peter G.
Published: June 2018

Transition path sampling techniques allow molecular dynamics simulations of complex systems to focuson rare dynamical events, providing insight into mechanisms and the ability to calculate rates inaccessibleby ordinary dynamics simulations. While path sampling algorithms are conceptually as simple as importancesampling Monte Carlo, the technical complexity of their implementation has kept these techniquesout of reach of the broad community. Here, we introduce an easy-to-use Python framework called Open-PathSampling (OPS) that facilitates path sampling for (bio)molecular systems with minimal effort and yetis still extensible. Interfaces to OpenMM and an internal dynamics engine for simple models are providedin the initial release, but new molecular simulation packages can easily be added. Multiple ready-to-usetransition path sampling methodologies are implemented, including standard transition path sampling (TPS)between reactant and product states, transition interface sampling (TIS) and its replica exchange variant(RETIS), as well as recent multistate and multiset extensions of transition interface sampling (MSTIS, MISTIS).In addition, tools are provided to facilitate the implementation of new path sampling schemes built on basicpath sampling components. In this paper, we give an overview of the design of this framework and illustratethe simplicity of applying the available path sampling algorithms to a variety of benchmark problems.
Retrospective cues mitigate information loss in human cortex during working memory storage
Authors: Ester Edward F. , Nouri Asal , Rodriguez Laura
Published: June 2018

Working memory (WM) enables the flexible representation of information over short intervals. It is well-established that WM performance can be enhanced by a retrospective cue presented during storage, yet the neural mechanisms responsible for this benefit are unclear. Here, we tested several explanations for retro-cue benefits by quantifying changes in spatial WM representations reconstructed from alpha-band (8-12 Hz) EEG activity recorded from human participants (both sexes) before and after presentation of a retrospective cue. This allowed us to track cue-related changes in WM representations with high temporal resolution (tens of milliseconds). Participants encoded the locations of two colored discs for subsequent report. During neutral trials an uninformative cue instructed participants to remember the locations of both discs across a blank delay, and we observed a monotonic decrease in the fidelity of reconstructed spatial WM representations with time. During valid trials a 100% reliable cue indicated the color of the disc participants would be probed to report. Critically, valid cues were presented immediately after termination of the encoding display (“valid early”, or VE trials) or midway through the delay period (“valid late” or VL trials). During VE trials the gradual loss of location-specific information observed during neutral trials was eliminated, while during VL trials it was partially reversed. Our findings suggest that retro-cues engage several different mechanisms that together serve to mitigate information loss during WM storage.

Significance Statement

Working memory (WM) performance can be improved by a cue presented during storage. This effect, termed a retrospective cue benefit, has been used to explore the limitations of attentional prioritization in WM. However, the mechanisms responsible for retrospective cue benefits are unclear. Here we tested several explanations for retrospective cue benefits by examining how they influence WM representations reconstructed from human EEG activity. This approach allowed us to visualize, quantify, and track the effects of retrospective cues with high temporal resolution (on the order of tens of milliseconds). We show that under different circumstances retrospective cues can both eliminate and even partially reverse information loss during WM storage, suggesting that retrospective cue benefits have manifold origins.
Cuticular hydrocarbon divergence in Drosophila melanogaster populations evolving under differential operational sex ratios
Authors: Dutta Rochishnu , Chechi Tejinder Singh , Yadav Ankit , Prasad Nagaraj Guru
Published: June 2018

The ability of interlocus sexual conflict to facilitate reproductive isolation is widely anticipated. However, very few experimental evolutionary studies have convincingly demonstrated the evolution of reproductive isolation due to sexual conflict. Recently a study on replicate populations of Drosophila melanogaster under differential sexual conflict found that divergent mate preference evolved among replicate populations under high sexual conflict regime. The precopulatory isolating mechanism underlying such divergent mate preference could be sexual signals such as cuticular hydrocarbons since they evolve rapidly and are involved in D. melanogaster mate recognition. Using D. melanogaster replicates used in the previous study, we investigate whether cuticular hydrocarbon divergence bears signatures of sexually antagonistic coevolution that led to reproductive isolation among replicates of high sexual conflict regime. We found that D. melanogaster cuticular hydrocarbon profiles are sexually dimorphic. Although replicate populations under high sexual conflict displayed assortative mating, we found no significant differences in the cuticular hydrocarbon profile between the high and low sexual conflict regimes. Instead we find cuticular hydrocarbon divergence patterns to be suggestive of the Buridan’s Ass regime which is one of the six possible mechanisms to resolve sexual conflict. Sexual selection that co-vary between populations under high and low sexual conflict regimes may also have contributed to the evolution of cuticular hydrocarbons. This study indicates that population differentiation as a result of cuticular hydrocarbon divergence cannot be credited to sexual conflict despite high sexual conflict regime evolving divergent cuticular hydrocarbon profiles.
Enzyme Immunoassays May Be Inaccurate: Familiar Correlates of Male Testosterone (T) Replicate in Britons when T is Measured by Mass Spectrometry but Do Not Replicate in Americans When T is Measured by Enzyme Immunoassay
Authors: Mazur Allan , Clifton Soazig
Published: June 2018

Several correlations have been reported between men’s testosterone (T) and other characteristics, e.g., T declines during the day, declines with obesity, and declines with advancing age. We asked if these relationships hold in older men when T is assayed from saliva. Here seven familiar correlations are tested among older American men, their salivary T measured by enzyme immunoassay (EIA). Some correlations can also be tested among older British men, their salivary T assayed by liquid chromatography-tandem mass spectroscopy (LC-MS/MS), a technique noted for its specificity. Most of our attempts at replication failed in the American data but succeeded in the British data. We conclude that failure to replicate in Americans is likely due to inaccuracy of EIA values for T, and that most T correlations hold true in older men when salivary T is accurately measured by LC-MS/MS.
fMRI repetition suppression reveals no sensitivity to trait judgments from faces along the ventral visual stream or in the theory-of-mind network
Authors: Butler Emily E. , Ward Rob , Downing Paul E. , Ramsey Richard
Published: June 2018

The human face cues a wealth of social information, but the neural mechanisms that underpin social attributions from faces are not well known. In the current fMRI experiment, we used repetition suppression to test the hypothesis that populations of neurons in face perception and theory-of-mind neural networks would show sensitivity to faces that cue distinct trait judgments. Although faces were accurately discriminated based on associated traits, our results showed no evidence that face or theory-of-mind networks showed repetition suppression for face traits. Thus, we do not provide evidence for population coding models of face perception that include sensitivity to high and low trait features. Due to aspects of the experimental design, which bolstered statistical power and sensitivity, we have reasonable confidence that we could detect effects of a moderate size, should they exist. The null findings reported here, therefore, add value to models of neural organisation in social perception by showing instances where effects are absent or small. To test the generalisability of our findings, future work should test different types of trait judgment and different types of facial stimuli, in order to further probe the neurobiological bases of impression formation based on facial appearance.
Effects of vitamin D on inflammatory and oxidative stress responses of human bronchial epithelial cells exposed to particulate matter
Authors: Pfeffer Paul E , Lu Haw , Mann Elizabeth H , Chen Yin-Huai , Ho Tzer-Ren , Cousins David J , Corrigan Chris , Kelly Frank J , Mudway Ian S , Hawrylowicz Catherine M
Published: June 2018

Background

Particulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, and vitamin D insufficiency, which compromises immune regulation, are detrimental in asthma.

Objectives

Mechanistic cell culture experiments were undertaken to ascertain whether vitamin D abrogates PM-induced inflammatory responses of human bronchial epithelial cells (HBECs) through enhancement of antioxidant pathways.

Methods

Transcriptome analysis, PCR and ELISA were undertaken to delineate markers of inflammation and oxidative stress; with comparison of expression in primary HBECs from healthy and asthmatic donors cultured with reference urban PM in the presence/absence of vitamin D.

Results

Transcriptome analysis identified over 500 genes significantly perturbed by PM-stimulation, including multiple pro-inflammatory cytokines. Vitamin D altered expression of a subset of these PM-induced genes, including suppressing IL6. Addition of vitamin D suppressed PM-stimulated IL-6 production, although to significantly greater extent in healthy versus asthmatic donor cultures. Vitamin D also differentially affected PM-stimulated GM-CSF, with suppression in healthy HBECs and enhancement in asthmatic cultures. Vitamin D increased HBEC expression of the antioxidant pathway gene G6PD, increased the ratio of reduced to oxidised glutathione, and in PM-stimulated cultures decreased the formation of 8-isoprostane. Pre-treatment with vitamin D decreased CXCL8 and further decreased IL-6 production in PM-stimulated cultures, an effect abrogated by inhibition of G6PD with DHEA, supporting a role for this pathway in the anti-inflammatory actions of vitamin D.

Conclusions

In a study using HBECs from 18 donors, vitamin D enhanced HBEC antioxidant responses and modulated the immune response to PM, suggesting that vitamin D may protect the airways from pathological pollution-induced inflammation.
Beyond Climatic Variation: Human Disturbances Alter the Effectiveness of a Protected Area to Reduce Fires in Tropical Peatlands of Sumatra, Indonesia
Authors: Imron Muhammad Ali , Widyastuti Kirana , Satria Ryan Adi , Prayoga Wiwid , Pradopo Subyantoro Tri , Suryatmojo Hatma , Sopha Bertha Maya , Berger Uta
Published: June 2018

The occurrence of fires has frequently been used to highlight environmental hazards at regional and global scale, and as a proxy for the effectiveness of protected areas. In contrast, the mechanism behind wildfire dynamics in tropical peat land protected areas had been poorly addressed thus far. Our study provides a novel application of assessing fire patterns from a tropical peatland protected area and surrounding landscape. We investigated the importance of both climatic factors (top-down mechanism) and human interventions (bottom-up mechanism) on fire occurrences through analyzing 15-year (2001 - 2015) LANDSAT and MODIS images of the Padang Sugihan Wildlife Reserve (PSWR). Fire density along side road and canal construction were analyzed jointly together with the monthly and annual precipitation, and evidences of climatic anomalies. The reserve was effective in limiting fire occurrences from surrounding landscapes only in wet years. We revealed that peat fire patterns in the protected area and the landscape matrix emerged beyond climatic factors, and the distance from canal system could explain the fire occurrences. Our results show that it is essential to address processes at a landscape level, particularly at the surroundings of the reserve, in order to increase the effectiveness of fire protection, including the development of fire-prone classes maps.
Exploring trend and barriers of antenatal care utilization using data mining:evidence from EDHS of 2000 to 2016
Authors: Abegaz Kedir Hussein
Published: June 2018

Background

The healthcare industry is paying attention to pregnancy and Antenatal care (ANC) for mothers. Thus, the presented study aimed at exploring the trend and identifying the barrier for ANC utilization of mothers in Ethiopia. Data mining is a field of big data science used to discover patterns and knowledge from big data.

Methods

All EDHS datasets from 2000 to 2016 were used for this study. The pooled cross-sectional study was conducted using the knowledge discovery process having steps; selection, cleaning, integration, transformation, and data mining algorithms. These algorithms are; Classification, clustering, association rules, and attribute ranking with pattern prediction.

Results

The proportion of ANC utilization was 27.6%, 28.2%, 34.5%, and 62.9% in 2000, 2005, 2011, and 2016 respectively. The pooled data; contained 28,631 mothers which were included in the study. Of these, more than half (56.09%) of them were not utilizing ANC during a pregnancy. Pregnancy complication, educational status of mothers and husbands, mothers’ residence, economic status, and media exposure had an association with ANC utilization having a confidence level of 95% and above.

Conclusion

ANC utilization in Ethiopia was increased significantly from 27.6%in 2000 to 62.9% in 2016. Despite this increment, the pooled proportion of ANC utilization is still low. The barriers to this low utilization were; Pregnancy complication, poor education of mothers and their husbands, living in rural, poor economic status, and media exposure. This study will recommend; firstly, pregnant mothers have to attend ANC service even though she had no pregnancy complication. Secondly, Education and poverty reduction are key strategic area to be addressed in improving women’s awareness towards ANC during a pregnancy. Thirdly, Expansion of infrastructure among the rural communities having good media coverage needs to be prioritized to improve ANC service utilization.
Phylogenetic relationships in the genus Avena based on the nuclear pgk1 gene
Authors: Peng Yuanying , Zhou Pingping , Zhao Jun , Li Junzhuo , Lai Shikui , Tinker Nicholas A. , Liao Shu , Yan Honghai
Published: June 2018

The phylogenetic relationships among 76 Avena taxa, representing 14 diploids, eight tetraploids, and four hexaploids were investigated by using the nuclear plastid 3-phosphoglycerate kinase gene(pgk1). A significant deletion (131 bp) was detected in all the C genome homoeologues which reconfirmed a major structural divergence between the A and C genomes. Phylogenetic analysis indicated the Cp genome is more closely related to the polyploid species than is the Cv genome. Two haplotypes of pgk1 gene were obtained from most of the AB genome tetraploids. Both types of the barbata group showed a close relationship with the As genome diploid species, supporting the hypothesis that both the A and B genomes are derived from an As genome. Two haplotypes were also detected in A. agadiriana, which showed close relationships with the As genome diploid and the Ac genome diploid, respectively, emphasizing the important role of the Ac genome in the evolution of A. agadiriana. Three homoeologues of thepgK1 gene were detected in five hexaploid accessions. The homoeologues that might represent the D genome were tightly clustered with the tetraploids A. marrocana and A. murphyi, but did not show a close relationship with any extant diploid species.
Variation and diversification of the microbiome ofSchlechtendalia chinensison two alternate host plants
Authors: Wu Haixia , Chen Xiaoming , Chen Hang , Lu Qin , Yang Zixiang , Ren Weibin , Liu Juan , Shao Shuxia , Wang Chao , King-Jones Kirst , Chen Ming-Shun
Published: June 2018

Schlechtendalia chinensis, a gall-inducing aphid, has two host plants in its life cycle. Its wintering host is a moss (typicallyPlagiomnium maximoviczii) and its main host isRhus chinensis(Sumac), on which it forms galls during the summer․. This study investigated bacteria associated withS. chinensisliving on the two different host plants by sequencing 16S rRNAs. A total of 183 Operational Taxonomic Units (OTUs) from 50 genera were identified from aphids living on moss, whereas 182 OTUs from 49 genera were found from aphids living in Sumac galls. The most abundant bacterial genus among identified OTUs from aphids feeding on both hosts wasBuchnera. Despite similar numbers of OTUs, the composition of bacterial taxa showed significant differences between aphids living on moss and those living onR. chinensis. Specifically, there were 12 OTUs from 5 genera (family) unique to aphids living on moss, and 11 OTUs from 4 genera (family) unique to aphids feeding in galls onR. Chinensis. Principal Coordinate Analysis (PCoA) also revealed that bacteria from moss-residing aphids clustered differently from aphids collected from galls. Our results provid a foundation for future analyses on the roles of symbiotic bacteria in plant - aphid interactions in general, and how gall-specific symbionts differ in this respect.
Dissecting PCNA function with a systematically designed mutation library in yeast
Authors: Jiang Qingwen , Zhang Weimin , Liu Chenghao , Lin Yicong , Wu Qingyu , Dai Junbiao
Published: June 2018

Proliferating cell nuclear antigen (PCNA), encoded byPOL30inSaccharomyces cerevisiae, is a key component of DNA metabolism. Here a library consisting of 308 PCNA mutants was designed and synthesized to probe the contribution of each residue to its biological function. Five regions were identified with elevated sensitivity to DNA damaging reagents using high-throughput phenotype screening. Using a series of genetic and biochemical analyses, we demonstrated that one particular mutant, K168A, which displayed severe DNA damage sensitivity, abolished the DNA damage tolerance (DDT) pathway by disrupting interactions between PCNA and Rad5p. Subsequent domain analysis showed that the PCNA/Rad5p interaction is prerequisite for the function of Rad5p in DDT. Our study not only provides a resource in the form of a library of versatile mutants to study PCNA functions, but also reveals a key regulatory function of Rad5p, which highlights the importance of the PCNA-Rad5p interaction.

Author summary

PCNA is regarded as the maestro of DNA replication fork because of the astonishing ability to interact with lots of partner proteins that participate in various DNA metabolism processes. However, it has remained elusive as to how does PCNA orchestrate these functions in harmony. Here, we constructed a systematic mutation library of PCNA, which covers every amino acid to map the functional sites of it. This carefully designed synthetic mutant pool could be generally useful and serve as a flexible resource, such as dissecting the functional mechanism of PCNA by genetic relationship analysis with key proteins through Synthetic genetic array. We further dissected the intrinsic mechanism for damage sensitivity of PCNAK168A, the most severe DNA damage sensitive mutant in our alanine scanning mutation library, this helps us to get better understanding of how PCNA participates in DNA damage tolerance (DDT) pathways. Our findings indicate that K168 site is vital for the interaction between DDT related partner proteins and PCNA, and also highlight the importance of the PCNA-Rad5p interaction.
Structural basis for cholesterol transport-like activity of the Hedgehog receptor Patched
Authors: Zhang Yunxiao , Bulkley David P. , Roberts Kelsey J. , Xin Yao , Asarnow Daniel E. , Sharma Ashutosh , Myers Benjamin R. , Cho Wonhwa , Cheng Yifan , Beachy Philip A.
Published: June 2018

Hedgehog protein signals mediate tissue patterning and maintenance via binding to and inactivation of their common receptor Patched, a twelve-transmembrane protein that otherwise would suppress activity of the seven-transmembrane protein, Smoothened. Loss of Patched function, the most common cause of basal cell carcinoma, permits unregulated activation of Smoothened and of the Hedgehog pathway. A cryo-EM structure of the Patched protein reveals striking transmembrane domain similarities to prokaryotic RND transporters. The extracellular domain mediates association of Patched monomers in an unusual dimeric architecture that implies curvature in the associated membrane. A central conduit with cholesterol-like contents courses through the extracellular domain and resembles that used by other RND proteins to transport substrates, suggesting Patched activity in cholesterol transport. Patched expression indeed reduces cholesterol activity in the inner leaflet of the plasma membrane, in a manner antagonized by Hedgehog stimulation and with implications for regulation of Smoothened.
Separable, Ctf4-mediated recruitment of DNA Polymerase α for initiation of DNA synthesis at replication origins and lagging-strand priming during replication elongation
Authors: Porcella Sarina Y. , Koussa Natasha C. , Tang Colin P. , Kramer Daphne N. , Srivastava Priyanka , Smith Duncan J.
Published: June 2018

During eukaryotic DNA replication, DNA polymerase alpha/primase (Pol α) initiates synthesis on both the leading and lagging strands. It is unknown whether leading- and lagging-strand priming are mechanistically identical, and whether Pol α associates processively or distributively with the replisome. Here, we titrate cellular levels of Pol α inS. cerevisiaeand analyze Okazaki fragments to study both replication initiation and ongoing lagging-strand synthesisin vivo. We observe that both Okazaki fragment initiation and the productive firing of replication origins are sensitive to Pol α abundance, and that both processes are disrupted at similar Pol α concentrations. When the replisome adaptor protein Ctf4 is absent or cannot interact with Pol α, lagging-strand initiation is impaired at Pol α concentrations that still support normal origin firing. Additionally, we observe that activation of the checkpoint becomes essential for viability upon severe depletion of Pol α. Using strains in which the Pol α-Ctf4 interaction is disrupted, we demonstrate that this checkpoint requirement is not solely caused by reduced lagging-strand priming. Our results suggest that Pol α recruitment for replication initiation and ongoing lagging-strand priming are distinctly sensitive to the presence of Ctf4. We propose that the global changes we observe in Okazaki fragment length and origin firing efficiency are consistent with distributive association of Pol α at the replication fork, at least when Pol α is limiting.

Author summary

Half of each eukaryotic genome is replicated continuously as the leading strand, while the other half is synthesized discontinuously as Okazaki fragments on the lagging strand. The bulk of DNA replication is completed by DNA polymerases ε and δ on the leading and lagging strand respectively, while synthesis on each strand is initiated by DNA polymerase α-primase (Pol α). Using the model eukaryoteS. cerevisiae, we modulate cellular levels of Pol α and interrogate the impact of this perturbation on both replication initiation on DNA synthesis and cellular viability. We observe that Pol α can associate dynamically at the replication fork for initiation on both strands. Although the initiation of both strands is widely thought to be mechanistically similar, we determine that Ctf4, a hub that connects proteins to the replication fork, stimulates lagging-strand priming to a greater extent than leading-strand initiation. We also find that decreased leading-strand initiation results in a checkpoint response that is necessary for viability when Pol α is limiting. Because the DNA replication machinery is highly conserved from budding yeast to humans, this research provides insights into how DNA replication is accomplished throughout eukaryotes.
Elucidating the active interaction mechanism of phytochemicals withanolide and withanoside derivatives with human serum albumin
Authors: Dubey Shreya , Kallubai Monika , Sarkar Arijit , Subramanyam Rajagopal
Published: June 2018

Withania somnifera (Ashwagandha) is an efficient plant known in Ayurveda and Chinese medicine since ancient times, whose extracts are consumed orally as food supplement or as a health tonic owing to its several restorative properties for various CNS disorders, inflammation, tumour, stress and rheumatism. In this study, we have analyzed the binding interaction of four derivatives of Withania somnifera (Withanolide A, Withanolide B, Withanoside IV and Withanoside V) with HSA because of their important pharmacological properties. To unravel the binding between derivatives of Withania somnifera and HSA, fluorescence spectroscopy was used. Binding studies were further studied by molecular docking and dynamics studies and results confirmed greater stability upon binding of derivatives with HSA. Circular dichroism data illustrated change in the secondary structure of protein upon interaction with these derivatives, particularly the helical structure was increased and β-sheets and random coils were decreased. Furthermore, morphological and topological changes were observed using AFM and TEM upon binding of ligands with HSA indicating that HSA-withnoside/withanolide complexes were formed. All the results cumulatively demonstrate strong binding of withanosides and withanolides derivatives with serum albumin, which should further be explored to study the pharmacokinetics and pharmacodynamics of these derivatives.
Integrated rural development from a historical and global perspective
Authors: Jacob W. James
Published: June 2018

Purpose

With roots dating back to the early twentieth century, integrated rural development (IRD) is a term that became commonplace in international development circles in the 1960s and afterwards. Based largely on a dual concept of helping to meet basic needs and improve the overall quality of life of poor people from rural and remote regions within national contexts, IRD initiatives have undergone a series of shifts in emphases, approaches and funding schemes. The purpose of this paper is to document the historical background and development of IRD initiatives over time.

Design/methodology/approach

The research design for this study included a series of mixed data collection methods, including case study examples of best practices, interviews and a thorough review of the formal literature, as well as an in-depth examination of alternative and multi-media literature (e.g. project reports, policy reports, government reports, working papers, newspaper articles, internet publications, etc.).

Findings

The findings of this paper are divided into the following sections. First, key terms of IRD are defined. Next, the background and overview of IRD is introduced including addressing how IRD is viewed as an approach to development, its historical evolution over time, some major IRD initiatives and the major development organizations engaged in promoting IRD. Third, an examination of several IRD models is introduced based on recommended methodologies, noting the sequencing of interventions important to successful IRD initiatives, select examples of IRD initiatives built on public-private partnerships, and the positive and negative outcomes and impacts from select IRD approaches.

Originality/value

The final section focuses on conclusions and seven key recommendations (or ingredients) outlined by the author as essential for implementing successful IRD initiatives: first, create an enabling environment that is conducive and supportive of IRD; second, establish a National Policy Framework for Integrated Development, which includes IRD; third, establish supportive policies and a legal framework that is based on the National Policy Framework; fourth, include two or more sectoral approaches in the initiative (e.g. agriculture, education, health, employment, infrastructure and industry, environment, etc.); fifth, garner participation and commitment from all stakeholders during each of the planning, implementation and evaluation stages; sixth, secure initial seed capital and funding and afterwards sustained funding streams; and seventh, conduct continual monitoring and evaluation throughout the lifespan of the entire initiative with specific adherence to the four key principles of good governance: coordination, information flow, transparency and accountability.
The importance of open government data for the private sector and NGOs in Indonesia
Authors: Hermanto Agus , Solimun Solimun , Fernandes Adji Achmad Rinaldo , Wahyono Wahyono , Zulkarnain Zulkarnain
Published: June 2018

Purpose

Open government data (OGD) is making data available free to all by the government with the aim of ensuring accountability and transparency in government besides generating public value by its usage. OGD is an emerging government initiative in Indonesia and there is potential for harnessing OGD for spearheading innovation and improvising services in different economic sectors. This paper aims to investigate the usage of OGD in the private sector and non-governmental organizations (NGOs) in Indonesia.

Design/methodology/approach

Documentary analysis was conducted to review the national OGD portal of Indonesia. Structured interviews were conducted with 49 senior management representatives from the private sector and NGOs to solicit their perspectives regarding the usage of OGD for professional purposes. Also, questions were posed regarding the challenges in harnessing OGD for professional purposes.

Findings

OGD has immense potential for private sector and NGOs; however, more initiatives are required on the part of the government to open their data sets. Further, involvement of stakeholders from the private sector and NGOs and other interested partners is required for an optimum usage of OGD in different economic sectors of Indonesia.

Research limitations/implications

As the research focuses on the private sector and NGOs in Indonesia, the study requires a more broad-based approach to consider the perspectives of different users. Further research is required to appreciate the role of contextual factors in determining the usage of OGD in Indonesia.

Originality/value

The study is one of the first to be conducted in Indonesia about the OGD initiatives of the country. Soliciting views from the key management representatives in the private sector and NGOs, the paper contributes to the extant OGD literature, which is more supply-focused and not demand-driven. While conceding that there are ample usages of OGD for the different economic sectors, the paper underlines the need for refining the OGD initiatives of Indonesia.
Engaging employees with disabilities in Vietnamese business context
Authors: Luu Tuan Trong
Published: June 2018

Purpose

There has been a growing number, though still modest, of organizations in Vietnam context that hire employees with disabilities and build disability inclusive management practices and disability diversity climate for them to engage in their work roles. The purpose of this paper is to investigate how disability inclusive HR practices contribute to work engagement of employees with disabilities working in Vietnam-based information technology (IT) industry.

Design/methodology/approach

The research model was tested through the data collected from employees with disabilities and their direct supervisors from IT companies based in Vietnam.

Findings

The data analysis revealed that disability inclusive HR practices influenced employees with disabilities to engage in their work activities through organizational identification as a mediator. Moral leadership exhibited a positive interactive effect with disability inclusive HR practices in promoting organizational identification of employees with disabilities and, in turn, their work engagement. In addition, employees’ idiosyncratic deals were found to serve as an individual enhancer for the link between their organizational identification and work engagement.

Originality/value

This research sets a milestone for more empirical inquiries on disability-oriented antecedents at both organizational and individual levels that can foster work engagement of employees with disabilities.
Food cold chain management
Authors: Shashi Shashi , Cerchione Roberto , Singh Rajwinder , Centobelli Piera , Shabani Amir
Published: June 2018

Purpose

Since last few years, cold chain management (CCM) has gained growing interest among practitioners, policymakers, researchers and academicians. The purpose of this paper is to provide a review focused on food cold chain management (FCCM) over the last 16 years to identify state of the art in the literature, highlight research gaps and define appropriate research questions (RQs) for future research.

Design/methodology/approach

The paper analyzes the content of 89 research articles published on the topic of food cold chain (FCC) from 2001 to 2016 within different journals. The Scopus and Web of Science databases were taken into consideration to shortlist research articles. Henceforth, the authors scrutinized the FCC industry to offer some effective strategies to tackle the chain complexities. The authors also draw interwoven between FCC infrastructure, integration, stakeholders’ interest, value addition, partners’ performance and overall food cold chain performance (FCCP) into a conceptual framework.

Findings

This paper identifies four research gaps in the literature of FCC concerning the most popular approaches used for the FCCP measurement, the performance measurement metrics, the factors which negatively affect the FCCP and the main sustainability issues in FCC.

Originality/value

This study identifies RQs which represent possible areas of investigation to improve the body of the FCCP evaluation and management. Furthermore, the FCC practitioners, food authorities and researchers might find this review useful, as it draws a clear picture of research in the respective domain.
Do lean manufacturing practices have negative impact on job satisfaction?
Authors: Minh Khaw Sui , Zailani Suhaiza , Iranmanesh Mohammad , Heidari Shima
Published: June 2018

Purpose

Due to the increasing trend of global competitiveness, lean manufacturing has received much attention in the international literature. Although previous studies have indicated the positive effects of lean manufacturing on the performance of the manufacturing firms, the impact of lean practices on two aspects of “job”, namely, characteristics and satisfaction, as of yet remains unclear. As a result, this study aims to evaluate job characteristics to understand the effects of lean manufacturing on job satisfaction.

Design/methodology/approach

Data from a survey of 206 employees in lean manufacturing companies were gathered and analysed using the partial least squares technique.

Findings

The results indicate that customer relationship, human resources and product design practices had positive indirect effects on job satisfaction through job characteristics, whereas, process and equipment practices had a negative indirect effect.

Practical implications

The findings of the study will be useful for the companies that implement lean manufacturing practices. Companies could either adjust their lean initiatives or make a trade-off amongst job characteristics.

Originality/value

This study contributes to the advancement of knowledge on the effects of lean manufacturing practices on job satisfaction through job characteristics.
The perception of corporate social responsibility of the city of Porto
Authors: Borges Ana Pinto , Vieira Elvira Pacheco , Rodrigues Paula
Published: June 2018

Purpose

The purpose of this paper is to assess the perception of the city of Porto as a destination engaged with social responsibility practices. The authors intend to analyse if the national and international tourists know the social responsibility practices of the city and if they associate them to the domains of community, environment and customer presented by Öbersederet al.(2014) and the type of CSR image that is presented (Dean, 2002; Lichtensteinet al., 2004; Menon and Kahn, 2003).

Design/methodology/approach

The authors used a survey to assess the perception of the tourist regarding the social responsibility practices of the city of Porto. The authors applied a factorial analysis and a logistic regression.

Findings

The tourists showed an adequate knowledge regarding the social responsibility practices carried out by the city. The respondents separated the dimensions of perceptions of CSR and revealed that they influence the (re)visit and further recommendation of the city. More specifically, the authors also verified that the CSR image and community, environment and customer domains play an important role in the knowledge of the social responsibility practices engaged by the city of Porto.

Originality/value

It is the first time that the scales of Öbersederet al.(2014) and Dean (2002), Lichtensteinet al.(2004) and Menon and Kahn (2003) were applied in the tourism context. Furthermore, considering that the city of Porto presents a high level of growth in tourism related activities, it is important to study the impact of CSR in the development of a sustainable tourism and its impact on the (re)visit and recommendation.
Incubation and development: an overview of technology incubation innovation system of India
Authors: Lala Kanchan , Sinha Kunal
Published: June 2018

Purpose

The purpose of this paper is to analyze and summarize growth and development of technology business incubation system in India. The study in this route tries to explore factors which include various actors and agencies influencing the process of incubation and innovation.

Design/methodology/approach

The paper in route to access the role of different actors and agencies situated around the incubation process is being executed through the systems of innovation framework. Data have been collected from the secondary sources including government department, ministries and other sources.

Findings

The study besides providing an in-depth analysis of the incubation process in India finds that the process is relatively new in the Indian context and lacks a profound policy for escalating the process of technological incubation. The study also finds that over the years India’s innovation potential has escalated significantly which in a way can be seen as an optimistic result in the growth and development of technology business incubation.

Originality/value

The proposed study is one of the few in this category, especially while analyzing technology business incubation with respect to India. The study also tries to add on literature in the domain of technology incubation especially in the context of India.