bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation is not enough: Graduated drivers licensing benefits from a comprehensive enforcement, education, and awareness campaigns
Authors: Bonne Stephanie , Suber Iesha , Anderson Arnold , Livingston David H.
Published: July 2018

BACKGROUND

Graduated drivers license (GDLs) are required in most states. Graduated drivers licenses are intermediate licenses requiring a supervisory period prior to full licensure. Surveys suggests poor acceptance of GDL restrictions high variability in GDL compliance. New Jersey initiated GDLs in 2002 and introduced a comprehensive public health campaign in 2010. This study analyzed the effect of GDL and the campaign on teen driver–related fatalities and hypothesized that implementation alone was insufficient to decrease deaths.

METHODS

Data were analyzed from 1998 to 2016 from New Jersey’s Fatal Accident Investigation Unit. In 2005, collaboration with state police added total crash fatalities and teen passenger deaths to the data set. Patterns in data before and after GDL implementation in 2002 and a comprehensive campaign in 2010 were evaluated to determine effects in New Jersey. Paired t tests, analysis of variance, and regression analyses were performed, with p value less than 0.05 considered significant.

RESULTS

Little effect was seen after initiation of GDL, with no change in number of dead teen drivers (44 vs. 49, p > 0.05) or fatal accidents (117 vs.115, p > 0.05) in the 4 years before and after implementation. However, after the comprehensive campaign, decreases are seen in dead teenaged drivers (42 vs. 22, p < 0.005) and total fatal accidents involving teens (107 vs. 61, p < 0.005). Comparing 4 years before and 6 years after the campaign demonstrates decreases in total crash fatalities involving teen drivers (112 vs. 66, p < 0.05) and in the number of dead teenaged passengers in a vehicle operated by another teen (19 vs. 11 p < 0.05).

CONCLUSIONS

Implementation of GDLs alone may not be an effective strategy in decreasing the number of teen fatalities. A multipronged approach combining comprehensive, public-health based campaign with targeted enforcement is necessary to decrease the number of teen driver–related deaths. Additional studies are needed to assess the relationship between decreased death and compliance with GDLs.

LEVEL OF EVIDENCE

Retrospective comparative study, level III.
Multimodal Approach to Decision to Treat Critically Ill Patients With Periodic or Rhythmic Patterns Using an Ictal–Interictal Continuum Spectral Severity Score
Authors: Kapinos Gregory , Trinka Eugen , Kaplan Peter W.
Published: July 2018

We propose a comprehensive review of the subject of epileptiform and potentially harmful EEG patterns that lie on the interictal continuum (IIC) to help with therapeutic decision-making and target future research. This approach to “electro-physiological SE” encompasses five dimensions of the IIC: it characterizes a periodic or rhythmic pattern, not only regarding its ictal morphology and potential harm with secondary neuronal injury, but also addresses the “metabolic footprint,” clinical repercussion, and epileptogenic potential. Recent studies have attempted to determine and qualify the ictal nature and the epileptogenic potential (i.e., risk of subsequent acute seizures) of particular IIC patterns and their intrinsic EEG characteristics. Others have correlated non-convulsive seizures with cognitive outcomes beyond mortality; non-convulsive seizures and sporadic, periodic, or rhythmic discharges to encephalopathy severity; and the spectrum of periodic or rhythmic patterns to measurable secondary brain injury. Equivocal periodic or rhythmic patterns on the IIC are frequently encountered in critical care neurology where clinicians often incorporate advanced neuroimaging, metabolic neuromonitoring, and anti-seizure drug short trials, in an effort to gauge these patterns. We propose portraying the IIC with a multiaxial graph to disambiguate each of these risks. Quantification along each axis may help calibrate therapeutic urgency. An adaptable scoring system assesses which quasi-ictal EEG patterns in this spectrum might reach the tipping point toward anti-seizure drug escalation, in neurocritically ill patients.
A wavelet neural control scheme for a quadrotor unmanned aerial vehicle
Authors: Jurado F. , Lopez S.
Published: July 2018

Wavelets are designed to have compact support in both time and frequency, giving them the ability to represent a signal in the two-dimensional time–frequency plane. The Gaussian, the Mexican hat and the Morlet wavelets are crude wavelets that can be used only in continuous decomposition. The Morlet wavelet is complex-valued and suitable for feature extraction using the continuous wavelet transform. Continuous wavelets are favoured when high temporal and spectral resolution is required at all scales. In this paper, considering the properties from the Morlet wavelet and based on the structure of a recurrent high-order neural network model, a novel wavelet neural network structure, here called a recurrent Morlet wavelet neural network, is proposed in order to achieve a better identification of the behaviour of dynamic systems. The effectiveness of our proposal is explored through the design of a decentralized neural backstepping control scheme for a quadrotor unmanned aerial vehicle. The performance of the overall neural identification and control scheme is verified via simulation and real-time results.

This article is part of the theme issue ‘Redundancy rules: the continuous wavelet transform comes of age’.
Tissue-specific degradation of essential centrosome components reveals distinct microtubule populations at microtubule organizing centers
Authors: Sallee Maria D. , Zonka Jennifer C. , Skokan Taylor D. , Raftrey Brian C. , Feldman Jessica L.
Published: July 2018

Non-centrosomal microtubule organizing centers (ncMTOCs) are found in most differentiated cells, but how these structures regulate microtubule organization and dynamics is largely unknown. We optimized a tissue-specific degradation system to test the role of the essential centrosomal microtubule nucleators γ-tubulin ring complex (γ-TURC) and AIR-1/Aurora A at the apical ncMTOC, where they both localize inC. elegansembryonic intestinal epithelial cells. As at the centrosome, the core γ-TURC component GIP-1/GCP3 is required to recruit other γ-TuRC components to the apical ncMTOC including MZT-1/MZT1, characterized here for the first time in animal development. In contrast, AIR-1 and MZT-1 were specifically required to recruit γ-TuRC to the centrosome, but not to centrioles or to the apical ncMTOC. Surprisingly, microtubules remain robustly organized at the apical ncMTOC upon γ-TuRC and AIR-1 co-depletion, and upon depletion of other known microtubule regulators including TPXL-1/TPX2, ZYG-9/chTOG, PTRN-1/CAMSAP, and NOCA-1/Ninein. However, loss of GIP-1 removed a subset of dynamic EBP-2/EB1-marked microtubules, and the remaining dynamic microtubules grew faster. Together, these results suggest that different MTOCs use discrete proteins for their function, and that the apical ncMTOC is composed of distinct populations of γ-TuRC-dependent and independent microtubules that compete for a limited pool of resources.
Simple and rapid separation of diverse neoagaro-oligosaccharides
Authors: Lin Fudi , Huang Yayan , Zhang Na , Ye Jing , Xiao Meitian
Published: July 2018

A rapid and simple method for obtaining pure and well-defined oligosaccharides was established by hydrolyzing agar with β-agarase fromVibrio natriegens. The conditions for enzymolysis were optimized as follows: temperature of 45 °C, pH of 8.5, substrate concentration of 0.3%, enzyme amount of 100 U/g and enzymolysis time of 20 h. Neoagaro-oligosaccharides with different degree of polymerizations were gained by hydrolyzing agar with β-agarase at different enzymolysis time. After removing pigment by activated carbon and salts by dialyzing, the enzyme hydrolysis solution was separated with Bio-Gel P2 column chromatography. Neoagaro-oligosaccharides with different degree of polymerizations were acquired. By comparing with standard substances, along with further confirmation by FTIR, MS and NMR, structures of the purified neoagaro-oligosaccharides were identified as neoagarobiose, neoagaroteraose, neoagarohexaose, neoagarooctaose, neoagarodecaose and neoagarododecaose with purities more than 97.0%, respectively. The present study established a method for rapid preparation of various monomers of neoagaro-oligosaccharides that may be of great significance for further study of bioactivities.
Loss of CG methylation inMarchantia Polymorphacauses disorganization of cell division and reveals unique DNA methylation regulatory mechanisms of non-CG methylation
Authors: Ikeda Yoko , Nishihama Ryuichi , Yamaoka Shohei , Arteaga-Vazquez Mario A. , Aguilar-Cruz Adolfo , Grimanelli Daniel , Pogorelcnik Romain , Martienssen Robert A. , Yamato Katsuyuki T. , Kohchi Takayuki , Hirayama Takashi , Mathieu Olivier
Published: July 2018

DNA methylation is an epigenetic mark that ensures silencing of transposable elements (TEs) and affects gene expression in many organisms. The function of different DNA methylation regulatory pathways has been largely characterized in the model plantArabidopsis thaliana. However, far less is known about DNA methylation regulation and functions in basal land plants. Here we focus on the liverwortMarchantia polymorpha, an emerging model species that represents a basal lineage of land plants. We identified MpMET, theM. polymorphaorthologue of theMETHYLTRANSFERASE 1(MET1) gene required for maintenance of methylation at CG sites in angiosperms. We generated Mpmetmutants using the CRISPR/Cas9 system, which showed a significant loss of CG methylation and severe morphological changes and developmental defects. The mutants developed many adventitious shoot-like structures, suggesting that MpMETis required for maintaining differentiated cellular identities in the gametophyte. Numerous TEs were up-regulated, even though non-CG methylation was highly increased at TEs in the Mpmetmutants. Closer inspection of CHG methylation revealed features unique toM. polymorpha. Methylation of CCG sites inM. polymorphadoes not depend onMET1, unlike inA. thalianaandPhyscomitrella patens. Furthermore, unlikeA. thaliana,M. polymorphashows higher methylation level at CAG sites than at other CHG contexts and CAG/CTG sites are mostly methylated asymmetrically. Interestingly, CAG and CTG methylation reached comparable levels and symmetry upon loss of CG methylation. Our results highlight the diversity of non-CG methylation regulatory mechanisms in plants.
Insulin signalling activates multiple feedback loops to elicit hunger-induced feeding in Drosophila
Authors: Sudhakar Sreesha R. , Varghese Jishy
Published: July 2018

Insulin, a highly conserved peptide hormone, links nutrient availability to metabolism and growth in animals. Besides this, in fed states insulin levels are high and insulin acts as a satiety hormone. In animals that are food deprived insulin levels remain low which facilitates hunger induced feeding. Contrary to expectations, we present evidence for persistent Drosophila insulin-like peptide gene expression and insulin signalling during initial phases of starvation. Maintenance of insulin signalling is crucial to sustain feeding responses during initial stages of starvation. Insulin signalling acts in a feedback loop involving the abdominal fatbody to maintain dilp gene expression in the early stages of food deprivation. Furthermore, another feedback regulatory loop between insulin-producing cells (IPCs) and neurons that produce the orectic hormone short-neuropeptide-F (sNPF), maintains sNPF levels and triggers feeding behavior. Thus, insulin acts through multiple feedback regulatory loops to elicit orexigenic responses and aid in efficient utilization of energy stores during early starvation.
Two essential replicative DNA polymerases exchange dynamically during DNA replication and after replication fork arrest
Authors: Li Yilai , Chen Ziyuan , Matthews Lindsay A. , Simmons Lyle A. , Biteen Julie S.
Published: July 2018

The replisome is the multi-protein complex responsible for faithful replication of chromosomal DNA. Using single-molecule super-resolution imaging, we characterized the dynamics of three replisomal proteins in liveBacillus subtiliscells: the two replicative DNA polymerases, PolC and DnaE, and a processivity clamp loader subunit, DnaX. We quantified the protein mobility and dwell times during normal replication and following both damage-independent and damage-dependent replication fork stress. With these results, we report the dynamic and cooperative process of DNA replication based on changes in the measured diffusion coefficients and dwell times. These experiments show that the replisomal proteins are all highly dynamic and that the exchange rate depends on whether DNA synthesis is active or arrested. Our results also suggest coupling between PolC and DnaX in the DNA replication process, and indicate that DnaX provides an important role in synthesis during repair. Furthermore, our results show that DnaE provides a limited contribution to chromosomal replication and repair.
Personalized expression of bitter ‘taste’ receptors in human skin
Authors: Shaw Lauren , Mansfield Corrine , Colquitt Lauren , Lin Cailu , Ferreira Jaime , Emmetsberger Jaime , Reed Danielle R.
Published: July 2018

The integumentary (i.e., skin) and gustatory systems both function to protect the human body and are a first point of contact with poisons and pathogens. These systems may share a similar protective mechanism because both human taste and skin cells express mRNA for bitter ‘taste’ receptors (TAS2Rs). Here, we used gene-specific methods to measure mRNA from all known bitter receptor genes in adult human skin from freshly biopsied samples and from samples collected at autopsy from the Genotype-Tissue Expression project. Human skin expressed some but not all TAS2Rs, and for those that were expressed, the relative amounts differed markedly among individuals. For some TAS2Rs, mRNA abundance was related to sun exposure (TAS2R14, TAS2R30, TAS2R42, and TAS2R60), sex (TAS2R3, TAS2R4, TAS2R8, TAS2R9, TAS2R14, and TAS2R60), and age (TAS2R5), although these effects were not large. These findings contribute to our understanding of extraoral expression of chemosensory receptors.
De novoTranscriptome Analyses Provide Insights into Opsin-based Photoreception in the Lantern sharkEtmopterus spinax
Authors: Delroisse Jérôme , Duchatelet Laurent , Flammang Patrick , Mallefet Jérôme
Published: July 2018

The velvet belly lantern shark (Etmopterus spinax) is a small deep-sea shark commonly found in the Easter Atlantic and the Mediterranean Sea. In this study, paired-end illumina HiSeqTMtechnology has been employed to analyse transcriptome data from eye and ventral skin tissues of the lantershark species. About 64 and 49 million Illumina reads were generated from skin and eyetissues respectively. The assembly allowed us to predict 119,749 total unigenes including 94,569 for the skin transcriptome and 94,365 for the eye transcriptome while 74,753 were commonly found in both transcriptomes. Among unigenes, 60,322 sequences were annotated using classical public databases. The assembled and annotated transcriptomes provide a valuable resource for further understanding of the shark biology. We identified potential “light-interacting toolkit” genes including multiple genes related to ocular and extraocular light perception processes such as opsins. In particular, a single rhodopsin gene mRNA and its potentially associated peropsin were only detected in the eye transcriptome confirming a monochromatic vision of the lantern-shark. Conversely, an encephalopsin mRNA was mainly detected in the skin transcriptome. The encephalopsin was immunolocalized in various shark tissues confirming its wide expression in the shark skin and pinpointing a possible functional relation with the photophore,i.e. epidermal light organs. We hypothesize that extraocular photoreception might be involved in the bioluminescence control possibly acting on the shutter opening and/or the photocyte activity itself.
Structural connectivity facilitates functional connectivity of auditory prediction error generation within a fronto-temporal network
Authors: Oestreich Lena K. L. , Randeniya Roshini , Garrido Marta I.
Published: July 2018

Auditory prediction errors, i.e. the mismatch between predicted and actual auditory input, are generated by a hierarchical functional network of cortical sources. This network is also interconnected by auditory white matter pathways. Hence it would be reasonable to assume that these structural and functional networks are quantitatively related, which is what the present study set out to investigate. Specifically, whether structural connectivity of auditory white matter pathways enables effective connectivity of auditory prediction error generation. Eighty-nine participants underwent diffusion weighted magnetic resonance imaging. Anatomically-constrained tractography was used to extract auditory white matter pathways, namely the bilateral arcuate fasciculus, the inferior occipito-frontal fasciculi (IOFF), and the auditory interhemispheric pathway, from which Apparent Fibre Density (AFD) was calculated. The same participants also underwent a stochastic oddball paradigm, which was used to elicit prediction error responses, while undergoing electroencephalographic recordings. Dynamic causal modelling (DCM) was used to investigate the effective connectivity of auditory prediction error generation in brain regions interconnected by the above mentioned auditory white matter pathways. Brain areas interconnected by all auditory white matter pathways best explained the dynamics of auditory prediction error responses. Furthermore, AFD in the right IOFF and right arcuate fasciculus significantly predicted the effective connectivity parameters underlying auditory prediction error generation. In conclusion, the generation of auditory prediction errors within an effectively connected, fronto-temporal network was found to be facilitated by the structural connectivity of auditory white matter pathways. These findings build upon the notion that structural connectivity facilitates dynamic interactions within brain regions that are effectively connected.

Significance statement

The brain continuously generates and updates hypotheses that predict forthcoming sensory input. Within the auditory domain, it has repeatedly been reported that these predictions about the auditory environment are facilitated by specific functional cortical connections. These functionally connected brain regions are also structurally connected via auditory white matter pathways. For the first time, this study provides quantitative evidence for a structural basis along which this functional network of auditory prediction error generation operates. This finding provides evidence for the notion that the functional connectivity of dynamically interacting brain areas is facilitated by structural connectivity amongst these brain areas.
DeepStomata: Facial Recognition Technology for Automated Stomatal Aperture Measurement
Authors: Toda Yosuke , Toh Shigeo , Bourdais Gildas , Robatzek Silke , Maclean Dan , Kinoshita Toshinori
Published: July 2018

Stomata are an attractive model for studying the physiological responses of plants to various environmental stimuli1–3. Of the morphological parameters that represent the degree of stomatal opening, the length of the minor axis of the stomatal pore (the stomatal aperture) has been most commonly used to dissect the molecular basis of its regulation. Measuring stomatal apertures is time consuming and labour intensive, preventing their use in large-scale studies. Here, we completely automated this process by developing a program called DeepStomata, which combines stomatal region detection and pore isolation by image segmentation. The former, which comprises histograms of oriented gradients (HOG)-based stomatal detection and the convolutional neural network (CNN)-based classification of open/closed-state stomata, acts as an efficient conditional branch in the workflow to selectively quantify the pores of open stomata. An analysis of batches of images showed that the accuracy of our automated aperture measurements was equivalent to that of manual measurements, however had higher sensitivity (i,e., lower false negative rate) and the process speed was at least 80 times faster. The outstanding performance of our proposed method for automating a laborious and repetitive task will allow researchers to focus on deciphering complex phenomena.
Modeling Zika Virus Spread in Colombia Using Google Search Queries and Logistic Power Models
Authors: Brown Mekenna , Cain Christopher , Whitfield James , Ding Edwin , Del Valle Sara Y , Manore Carrie A
Published: July 2018

Public health agencies generally have a small window to respond to burgeoning disease outbreaks in order to mitigate the potential impact. There has been significant interest in developing forecasting models that can predict how and where a disease will spread. However, since clinical surveillance systems typically publish data with a lag of two or more weeks, there is a need for complimentary data streams that can close this gap. We examined the usefulness of Google Trends search data for analyzing the 2016 Zika epidemic in Colombia and evaluating their ability to predict its spread. We calculated the correlation and the time delay between the reported case data and the Google Trends data using variations of the logistic growth model, and showed that the data sets were systematically offset from each other, implying a lead time in the Google Trends data. Our study showed how Internet data can potentially complement clinical surveillance data and may be used as an effective early detection tool for disease outbreaks.
RNAi screening identifies a new Toll from shrimp that restricts WSSV infection through activating Dorsal to induce antimicrobial peptides
Authors: Li Haoyang , Yin Bin , Wang Sheng , Fu Qihui , Xiao Bang , Lǚ Kai , He Jianguo , Li Chaozheng
Published: July 2018

The function of Toll pathway defense against bacterial infection has been well established in shrimp, however how this pathway responds to viral infection is still largely unknown. In this study, we report the Toll4-Dorsal-AMPs cascade restricts the white spot syndrome virus (WSSV) infection of shrimp. A total of nine Tolls fromLitopenaeus vannameinamely Toll1-9 are identified, and RNAi screeningin vivoreveals the Toll4 is important for shrimp to oppose WSSV infection. Knockdown of Toll4 results in elevated viral loads and renders shrimp more susceptible to WSSV. Furthermore, Toll4 could be a one of upstream pattern recognition receptor (PRR) to detect WSSV, and thereby leading to nuclear translocation and phosphorylation of Dorsal, the known NF-κB transcription factor of the canonical Toll pathway. More importantly, silencing of Toll4 and Dorsal contributes to impaired expression of a specific set of antimicrobial peptides (AMPs) such as anti-LPS-factor (ALF) and lysozyme (LYZ) family, which exert potent anti-WSSV activity. Two AMPs of ALF1 and LYZ1 as representatives are demonstrated to have the ability to interact with several WSSV structural proteins. Taken together, we therefore identify the Toll4-Dorsal pathway mediates strong resistance to WSSV infection by inducing some specific AMPs.

Author summary

The TLR pathway mediated antiviral immune response is well identified in mammals, yet, Toll pathway governing this protection in invertebrates remains unknown. In the present study, we uncover that a shrimp Toll4 from a total of nine Tolls inL. vannameiconfers resistance to WSSV thought inducing the NF-κB transcription factor Dorsal to inspiring the production of some antimicrobial peptides (AMPs) with antiviral activity. The anti-LPS-factor (ALF) and lysozyme (LYZ) family are identified as the Toll4-Dorsal pathway targeted genes with the ability to interact with viral structural proteins in response to WSSV infection. These results suggest that the Toll receptor induces the expression of AMPs with antiviral activity could be a general antiviral mechanism in invertebrates and Toll pathway established antiviral defense could be conserved during evolution.
Effect of NaCl-Stressed Bt Cotton on the Feeding Behaviors and Nutritional Parameters of Helicoverpa armigera
Authors: Luo Jun-Yu , Zhang Shuai , Zhu Xiang-Zhen , Ji Ji-Chao , Zhang Kai-Xin , Wang Chun-Yi , Zhang Li-Juan , Wang Li , Cui Jin-Jie
Published: July 2018

Saline-alkali soil is an arable land resource on which transgenic Bt cotton has been planted on a large scale in accordance with food security strategies, but there are concerns about the insecticidal effects of Bt cotton on target insect pests. In this study, a Bacillus thuringiensis (Bt) cotton variety, GK19, and its nontransgenic parent variety, Simian-3, were used as experimental materials to study the effect of the expression of exogenous insecticidal proteins in Bt cotton under NaCl stress on the feeding behavior and nutritional parameters of Helicoverpa armigera. The results showed that the expression of exogenous insecticidal proteins in GK19 was significantly inhibited under NaCl stress. However, on GK19 Bt cotton, the feeding, crawling, resting and spinning down of the 5th instar H. armigera larvae, as well as the food consumption and feces amount of these larvae, did not markedly differ under different NaCl concentrations. In contrast, the mean relative growth rate (MRGR), relative growth rate (RGR), approximate digestibility (AD), efficiency of conversion of ingested food (ECI) and efficiency of conversion of digested food (ECD) of the larvae decreased markedly in response to NaCl stress. Under the same concentration of NaCl, the nutritional parameters of the bollworm larvae on GK19 Bt cotton or Simian-3 nontransgenic cotton were different. However, the interaction between salt stress and cotton variety had no significant effect on the feeding behavior or nutritional parameters of H. armigera larvae. These results may provide a scientific basis for determining the effect of exogenous insecticidal protein expression in Bt cotton under NaCl stress on H. armigera and can therefore be useful for the effective application of Bt cotton in saline-alkali soils to prevent and control H. armigera.
The short-sequence design of human chromosomes
Authors: Lamolle Guillermo , Sabia Victor , Musto Héctor , Bernardi Giorgio
Published: July 2018

Recent investigations have shown that isochores are characterized by a 3-D structure which is primarily responsible for the topology of chromatin domains. More precisely, an analysis of human chromosome 21 demonstrated that GC-poor isochores are low-heterogeneity sequences characterized by the presence of oligo-Adenines that are intrinsically stiff, curved and unfavorable for nucleosome binding. This leads to a structure of the corresponding chromatin domains, the Lamina Associated Domains, or LADs, which is well suited for interaction with lamina. In contrast, the high-heteorogeneity GC-rich isochores are in the form of compositional peaks characterized by gradients of oligo-Guanines that lead to increasing nucleosome depletions in the corresponding chromatin domains, the Topological Associating Domains, or TADs. These results encouraged us to investigate in detail the di- and tri-nucleotide profiles of 100Kb segments of chromosome 21, as well as those of the di- to octa-Adenines and di- to octa-Guanines in several regions of the chromosome. The results obtained show that the 3-D structures of isochores and chromatin domains depend not only upon oligo-Adenines and oligo-Guanines but also, to a lower but definite extent, upon the majority of di- and tri-nucleotides. This conclusion, which applies to all human chromosome, has strong implications for the biological role of non-coding sequences.
Amyloid-ß promotes neurotoxicity by Cdk5-induced p53 stabilization
Authors: Lapresa Rebeca , Agulla Jesús , Sánchez-Morán Irene , Bolaños Juan P. , Almeida Angeles
Published: July 2018

The p53 tumor suppressor protein, a key regulator of cell apoptosis, has been described to accumulate in affected brain areas from Alzheimer’s disease (AD) patients. However, whether p53 plays any role in AD pathogenesis remains unknown. Here, we found that exposure of neurons to oligomers of the amyloidogenic fragment 25-35 of the Aß peptide (Aβ25-35) activated Cdk5, which promoted p53 protein phosphorylation and stabilization. Moreover, Aβ25-35-mediated mitochondrial dysfunction and neuronal apoptosis were prevented by both genetic and pharmacological inhibition of either p53 or Cdk5 activities. To confirm this mechanism in vivo, Aβ25-35 was stereotaxically injected in the cerebral right ventricle of mice, a treatment that caused p53 protein accumulation, dendrite disruption and neuronal death. Furthermore, these effects were prevented in p53 knockout mice or by pharmacologically inhibiting p53. Thus, Aβ25-35 triggers Cdk5 activation to induce p53 phosphorylation and stabilization, which leads to neuronal damage. Inhibition of the Cdk5-p53 pathway may therefore represent a novel therapeutic strategy against Aβ-induced neurodegeneration.
Connections between freshwater carbon and nutrient cycles revealed through reconstructed population genomes
Authors: Linz Alexandra M. , He Shaomei , Stevens Sarah L. R. , Anantharaman Karthik , Rohwer Robin R. , Malmstrom Rex R. , Bertilsson Stefan , McMahon Katherine D.
Published: July 2018

Metabolic processes at the microbial scale influence ecosystem functions because microbes are responsible for much of the carbon and nutrient cycling in freshwater. One approach to predict the metabolic capabilities of microbial communities is to search for functional marker genes in metagenomes. However, this approach does not provide context about co-occurrence with other metabolic traits within an organism or detailed taxonomy about those organisms. Here, we combine a functional marker gene analysis with metabolic pathway prediction of microbial population genomes (MAGs) assembled from metagenomic time series in eutrophic Lake Mendota and humic Trout Bog to identify how carbon and nutrient cycles are connected in freshwater. We found that phototrophy, carbon fixation, and nitrogen fixation pathways co-occurred in Cyanobacteria MAGs in Lake Mendota and in Chlorobiales MAGs in Trout Bog. Cyanobacteria MAGs also had strong temporal correlations to functional marker genes for nitrogen fixation in several years. Genes encoding steps in the nitrogen and sulfur cycles varied in abundance and taxonomy by lake, potentially reflecting the availability and composition of inorganic nutrients in these systems. We were also able to identify which populations contained the greatest density and diversity of genes encoding glycoside hydrolases. Populations with many glycoside hydrolases also encoded pathways for sugar degradation. By using both MAGs and marker genes, we were better able to link functions to specific taxonomic groups in our metagenomic time series, enabling a more detailed understanding of freshwater microbial carbon and nutrient cycling.
Single-cell transcriptome analysis during cardiogenesis reveals basis for organ level developmental anomalies
Authors: de Soysa T. Yvanka , Ranade Sanjeev S. , Okawa Satoshi , Ravichandran Srikanth , Huang Yu , Salunga Hazel T. , Schricker Amelia , Del Sol Antonio , Gifford Casey A. , Srivastava Deepak
Published: July 2018

Organogenesis involves integration of myriad cell types with reciprocal interactions, each progressing through successive stages of lineage specification and differentiation. Establishment of unique gene networks within each cell dictates fate determination, and mutations of transcription factors that drive such networks can result in birth defects. Congenital heart defects are the most common malformations and are caused by disruption of discrete subsets of progenitors1–3, however, determining the transcriptional changes in individual cells that lead to organ-level defects in the heart, or other organs, has not been tractable. Here, we employed single-cell RNA sequencing to interrogate early cardiac progenitor cells as they become specified during normal and abnormal cardiogenesis, revealing how dysregulation of specific cellular sub-populations can have catastrophic consequences. A network-based computational method for single-cell RNA-sequencing that predicts lineage specifying transcription factors4,5identifiedHand2as a specifier of outflow tract cells but not right ventricular cells, despite failure of right ventricular formation inHand2-null mice6. Temporal single-cell transcriptome analysis ofHand2-null embryos revealed failure of outflow tract myocardium specification, whereas right ventricular myocardium differentiated but failed to migrate into the anterior pole of the developing heart. Dysregulation of retinoic acid signaling, responsible for anterior-posterior patterning7, was associated with posteriorization of anterior cardiac progenitors inHand2-null mutant hearts and ectopic atrial gene expression in outflow tract and right ventricle precursors. This work reveals transcriptional determinants in individual cells that specify cardiac progenitor cell fate and differentiation and exposes mechanisms of disrupted cardiac development at single-cell resolution, providing a framework to investigate congenital heart defects.
Excellence models as complex management systems
Authors: Edgeman Rick
Published: July 2018

Purpose

When appropriately implemented, excellence models such as the Shingo operational excellence model (SOEM), Baldrige performance excellence model and EFQM business excellence model aid enterprise quests for sustained superior results across varied dimensions. Evidence supporting this statement abounds in the literature and in practice. The models, however, tend to be driven by experience, rather than grounded in theory. The purpose of this paper is to explore theoretical underpinnings for such models, with the SOEM used for illustrative purposes.

Design/methodology/approach

Management theory, systems theory and excellence modeling are integrated to yield a complex management systems based operational excellence model. Correspondence of this model with the SOEM is explored. Key elements considered include contextual factors external to the enterprise, diverse stakeholders, mediating forces, enterprise culture and representative enterprise processes.

Findings

Understanding the theoretical underpinnings of excellence models—their elements and the interactions and synergies of these elements—enables more sure adaptation of such models to specific enterprise contexts, and more sure course corrections whenever corrections are needed.

Originality/value

Many excellence models exist, their usefulness largely validated by anecdotal or empirical evidence. Such validation is important, but falls short of theoretically grounding these models. The approach taken herein serves to unify theory, empirical evidence and anecdotes, thus placing excellence models on more solid ground.
Identification and modeling of process barriers
Authors: T. Ramadas , K.P. Satish
Published: July 2018

Purpose

The purpose of this study is to present factors associated with process barriers in implementing lean manufacturing within the small- and medium-sized enterprises (SMEs).

Design/methodology/approach

This study was conducted to identify the process barriers in implementing lean manufacturing in SMEs. Moreover, by a thorough and detailed analysis, process barriers of high rejection rate, employee absenteeism and frequent breakdown with 29 associated variables were identified as the most critical process barriers and were used to develop the questionnaire. Structural equation modeling was used to build the measurement model by drawing on samples of 128 SMEs in Kerala, a state in India. Later, the model was validated using statistical estimates. Data analysis helps to determine whether to accept or reject the hypothesis on the basis of the measurement model.

Findings

Several process barriers that prevent the successful implementation of lean manufacturing within SMEs are identified. These are lack of a training program, lack of periodical maintenance, low-quality standard materials from suppliers, bad vendor inspection, wear and tear of machines, communication gap between supervisors and workers, non-maintenance of a good employee–employer relationship, boredom on the job, overrunning machines beyond the capability, carelessness in work, not replacing worn damage parts periodically, ignoring warning signals of the machine classified as the most critical process barrier among the high rejection rate, employee absenteeism, frequent breakdown factors.

Research limitations/implications

First, the sample size of the study was relatively small (128). Second, data collection was restricted to one geographical area in India, i.e. Kerala, a state in India, giving rise to operational constraints. Third, the study was cross-sectional; a longitudinal study must be performed to reinforce the findings.

Practical implications

The present study has explored an unfocused area of lean implementation in SMEs. The results are expected to help researchers, academics and professionals in the domain of lean manufacturing.

Social implications

Governments of many countries around the world are helping and encouraging the implementation and understanding of the lean manufacturing system by providing financial assistance for training professionals and establishing professional associations. However, many industries have not been successful in lean implementation. This research aims to develop a strategy to tackle process barriers for successful lean implementation.

Originality/value

Very little research has been carried out in exploring process barriers in implementing lean manufacturing in SMEs. This paper will provide value to academics, researchers and practitioners of lean by providing insight into significant process barriers for lean implementation, especially in Indian industries.
Shaping community support for vigilantism: a Nigerian case study
Authors: I. Badiora Adewumi
Published: July 2018

Purpose

In Nigeria, vigilantism appears to be a common response to dissatisfaction about the state police in the recent time. Using survey data of residents in Lagos, Nigeria, the purpose of this paper, therefore, is to explore whether what is already known about perceptions of procedural (in) justice of state police also applies to self-help security groups in Nigeria. This is with a view to influencing community support for and satisfaction with non-state policing in the country.

Design/methodology/approach

The study adopted a case study approach. Lagos, Nigeria was stratified into the high, medium and low densities. Systematic sampling technique was used in selecting 1 out of every 20 buildings (5 percent) in each area. Household representative person on each floor of the selected building who had contact with vigilante corps in the last 12 months were targeted. Of 768 copies of questionnaires administered, a sample of 386 was effectively returned (representing 50 percent response rate). Six categories of variables were analyzed. These are procedural justice, distributive justice, vigilante corps’ performance, legitimacy, residents’ satisfaction with vigilante corps activities and socio-economic characteristics.

Findings

Results reveal that respondents are not primarily instrumental in their support for vigilantisms. Instead, their support is associated with their basic communal values. More than effectiveness in controlling crime, vigilantisms receive community support provided they use procedural justice in dealings with the public. Respondents who perceive vigilantisms use procedural justice also view them as legitimate, and as well satisfy with their activities and services. Besides, results show that support for and satisfaction with vigilantisms are associated with environmental, social and economic characteristics of the residents in the community they serve. The thesis supported in this research paper is that public support for and satisfaction with vigilantisms can be influenced significantly through policing strategies that builds legitimacy.

Originality/value

Vigilantism pervades contemporary policing strategies. It is supported by national crime prevention policies, according to the logic that the use of community self-help security strategies could contribute to sustainable crime prevention. This study extends research on legitimacy, with an empirical focus on Nigerian vigilantism. Understanding factors that shape public support for vigilantism may enhance safer communities.
GAL3 receptor knockout mice exhibit an alcohol‐preferring phenotype
Authors: Genders Shannyn G. , Scheller Karlene J. , Jaehne Emily J. , Turner Bradley J. , Lawrence Andrew J. , Brunner Susanne M. , Kofler Barbara , van den Buuse Maarten , Djouma Elvan
Published: July 2018

Galanin is a neuropeptide which mediates its effects via three G‐protein coupled receptors (GAL1–3). Administration of a GAL3 antagonist reduces alcohol self‐administration in animal models while allelic variation in the GAL3 gene has been associated with an increased risk of alcohol use disorders in diverse human populations. Based on the association of GAL3 with alcoholism, we sought to characterize drug‐seeking behavior in GAL3‐deficient mice for the first time. In the two‐bottle free choice paradigm, GAL3‐KO mice consistently showed a significantly increased preference for ethanol over water when compared to wildtype littermates. Furthermore, male GAL3‐KO mice displayed significantly increased responding for ethanol under operant conditions. These differences in alcohol seeking behavior in GAL3‐KO mice did not result from altered ethanol metabolism. In contrast to ethanol, GAL3‐KO mice exhibited similar preference for saccharin and sucrose over water, and a similar preference for a high fat diet over a low fat diet as wildtype littermates. No differences in cognitive and locomotor behaviors were observed in GAL3‐KO mice to account for increased alcohol seeking behavior. Overall, these findings suggest genetic ablation of GAL3 in mice increases alcohol consumption.
Advances in managing COPD related to α1‐antitrypsin deficiency: An under‐recognized genetic disorder
Authors: Craig Timothy J. , Henao Maria Paula
Published: July 2018

α1‐Antitrypsin deficiency (AATD) predisposes individuals to chronic obstructive pulmonary disease (COPD) and liver disease. Despite being commonly described as rare, AATD is under‐recognized, with less than 10% of cases identified. The following is a comprehensive review of AATD, primarily for physicians who treat COPD or asthma, covering the genetics, epidemiology, clinical presentation, screening and diagnosis, and treatments of AATD. For patients presenting with liver and/or lung disease, screening and diagnostic tests are the only methods to determine whether the disease is related to AATD. Screening guidelines have been established by organizations such as the World Health Organization, European Respiratory Society, and American Thoracic Society. High‐risk groups, including individuals with COPD, nonresponsive asthma, bronchiectasis of unknown etiology, or unexplained liver disease, should be tested for AATD. Current treatment options include augmentation therapy with purified AAT for patients with deficient AAT levels and significant lung disease. Recent trial data suggest that lung tissue is preserved by augmentation therapy, and different dosing schedules are currently being investigated. Effective management of AATD and related diseases also includes aggressive avoidance of smoking and biomass burning, vaccinations, antibiotics, exercise, good diet, COPD medications, and serial assessment.
The end of the Great Khersonian Drying of Eurasia: Magnetostratigraphic dating of the Maeotian transgression in the Eastern Paratethys
Authors: Palcu Dan Valentin , Vasiliev Iuliana , Stoica Marius , Krijgsman Wout
Published: July 2018

Central Eurasia underwent significant palaeoclimatic and palaeogeographic transformations during the middle to late Miocene. The open marine ecosystems of the Langhian and Serravallian seas progressively collapsed and were replaced in the Tortonian by large endorheic lakes. These lakes experienced major fluctuations in water level, directly reflecting the palaeoclimatic conditions of the region. An extreme lowstand of the Eastern Paratethys lake (−300 m) during the regional Khersonian stage reveals a period of intensely dry conditions in Central Eurasia causing a fragmentation of the Paratethys region. This period of “Great Drying” ended by a climate change towards more humid conditions at the base of the Maeotian stage, resulting in a large transgressive event that reconnected most of the Paratethyan basins. The absence of a robust time frame for the Khersonian–Maeotian interval hampers a direct correlation with the global records and complicates a thorough understanding of the underlying mechanisms. Here we present a new chronostratigraphic framework for the Khersonian and Maeotian deposits of the Dacian Basin of Romania, based on integrated magneto‐biostratigraphic studies on long and continuous sedimentary successions. We show the dry climate conditions in the Khersonian start at 8.6–8.4 Ma. The Khersonian/Maeotian transition is dated at 7.65–7.5 Ma, several million years younger than previous estimates. The Maeotian transgression occurs later (7.5–7.4 Ma) in more marginal and shallower basins, in agreement with the time transgressive character of the flooding. In addition, we date a sudden water level drop of the Eastern Paratethys lake, the Intra‐Maeotian Event (IME), at 6.9 Ma, and hypothesize that this corresponds to a reconnection phase with the Aegean basin of the Mediterranean. Finally, we discuss the potential mechanisms explaining the particularities of the Maeotian transgression and conclude that the low salinity and the seemingly “marine influxes” most likely correspond to episodes of intrabasinal mixing in a gradual and pulsating transgressive setting.