bluuebunny/crossref_metadata_2025 huggingface dataset:
A Meta-Analysis of Executive Functions in Frontal Cortex: Comparing Healthy and Neuropsychiatric Groups
Authors: Waters Abigail B. , Swenson Lance P. , Gansler David A.
Published: May 2018

Background

The neural architecture of executive functions remains a topic of considerable clinical and academic interest in the clinical neurosciences, given its strength as a transdiagnostic predictor of adaptive functioning with high heritability. In recent years, meta-analyses have shown a consistent relationship between prefrontal cortex size and executive functioning task performance in healthy adults and lesion patients, with increases in measures of cortical size (i.e., volume or thickness) associated with better executive functioning performance. There is a gap in meta-analytic literature assessing these relationships in neuropsychiatric populations, their effects relative to healthy controls, and differential contributions of brains regions and neuropsychological paradigms.

Methods

We conducted a meta-analysis of published studies (k =30) that assessed the relationship between executive functions and frontal regions in vivo (N = 1935) for both healthy (20 samples) and neuropsychiatric (21 samples) adults. Random effects modeling was used to calculate mean effect sizes and CIs.

Results

Larger volumes and thickness were associated with better executive functioning in both healthy (r =.35, 95% CI =.29 -.39) and neuropsychiatric populations (r =.47, 95% CI =.40 -.51), with the effect size for neuropsychiatric populations being significantly larger compared to healthy controls. While there was variability between tasks, there were no significant differences in effect size between neuropsychological paradigms or brain region classification.

Conclusions

These results indicate the relationship between healthy adult performance on neuropsychological testing is less associated with cortical size compared to neuropsychiatric adults.
Speciation with gene flow via cycles of isolation and migration: Insights from multiple mangrove taxa
Authors: He Ziwen , Li Xinnian , Yang Ming , Wang Xinfeng , Zhong Cairong , Duke Norman C. , Shi Suhua , Wu Chung-I
Published: May 2018

Allopatric speciation requiring an unbroken period of geographical isolation has been the standard model of neo-Darwinism. While doubts have been repeatedly raised, strict allopatry without any gene flow remains a plausible mechanism in most cases. To rigorously reject strict allopatry, genomic sequences superimposed on the geological records of a well-delineated geographical barrier will be necessary. The Strait of Malacca, narrowly connecting the Pacific and Indian Ocean coasts, serves at different times either as a geographical barrier or a conduit of gene flow for coastal/marine species. We surveyed 1,700 plants from 29 populations of five common mangrove species by large scale DNA sequencing and added several whole-genome assemblies. Speciation between the two oceans is driven by cycles of isolation and gene flow due to the fluctuations in sea level leading to the opening/closing of the Strait to ocean currents. Because the time required for speciation in mangroves is longer than the isolation phases, speciation in these mangroves has proceeded through many cycles of mixing-isolation-mixing, or MIM cycles. The MIM mechanism, by relaxing the condition of no gene flow, can promote speciation in many more geographical features than strict allopatry can. Finally, the MIM mechanism of speciation is also efficient, potentially yielding mn(m>1) species after n cycles.

Significance statement

Mechanisms of species formation have always been a conundrum. Speciation between populations that are fully geographically isolated, or allopatric speciation, has been the standard solution in the last 50 years. Complete geographical isolation with no possibility of gene flow, however, is often untenable and is inefficient in generating the enormous biodiversity. By studying mangroves on the Indo-Malayan coasts, a global hotspot of coastal biodiversity, we were able to combine genomic data with geographical records on the Indo-Pacific barrier that separates Pacific and Indian Ocean coasts. We discovered a novel mechanism of speciation, that we call mixing-isolation-mixing (MIM) cycles. By permitting intermittent gene flow during speciation, MIM can potentially generate species at an exponential rate, thus combining speciation and biodiversity in a unified framework.
M-current regulates firing mode and spike reliability in a collision detecting neuron
Authors: Dewell Richard B. , Gabbiani Fabrizio
Published: May 2018

All animals must detect impending collisions to escape them, and they must reliably discriminate them from non-threatening stimuli to prevent false alarms. Therefore, it is no surprise that animals have evolved highly selective and sensitive neurons dedicated to such tasks. We examined a well-studied collision detection neuron in the grasshopperSchistocerca americanausingin vivoelectrophysiology, pharmacology, and computational modeling. This lobula giant movement detector (LGMD) neuron is excitable by inputs originating from each ommatidia of the compound eye, and it has many intrinsic properties that increase its selectivity to objects approaching on a collision course, including switching between burst and non-burst firing. Here, we demonstrate that the LGMD neuron exhibits a large M current, generated by non-inactivating K+channels, that narrows the window of dendritic integration, regulates a firing mode switch between burst and isolated spiking, increases the precision of spike timing, and increases the reliability of spike propagation to downstream motor centers. By revealing how the M current increases the LGMD’s ability to detect impending collisions our results suggest that it may play an analogous role in other collision detection circuits.

New & Noteworthy

The ability to reliably detect impending collisions is a critical survival skill. The nervous systems of many animals have developed dedicated neurons for accomplishing this task. We used a mix ofin vivoelectrophysiology and computational modeling to investigate the role of M potassium channels within one such collision detecting neuron and showed that through regulation of burst firing and increasing spiking reliability the M current increases the ability to detect impending collisions.
Epidemiologal investigation of anAcinetobacter baumanniioutbreak using Core Genome Multilocus Sequence Typing
Authors: Venditti Carolina , Vulcano Antonella , D’Arezzo Silvia , Maria Gruber Cesare Ester , Selleri Marina , Antonini Mario , Lanini Simone , Marani Alessandra , Puro Vincenzo , Nisii Carla , Caro Antonino Di
Published: May 2018

Carbapenem-resistant (CR)Acinetobacter baumanniiis a serious nosocomial pathogen able to cause a variety of serious, often life-threatening infections and outbreaks. We aimed to investigate the molecular epidemiology of clinical isolates of CR-A. baumanniifrom an outbreak occurred in the intensive care unit (ICU) of our hospital.

From January to April 2017, 13 CR-A. baumanniiisolates were collected at the “L. Spallanzani” hospital, Rome, Italy; typing was performed by repetitive extragenetic palindromic-based (rep)- PCR-based DiversiLab system and WGS data were used for insilicoanalysis of traditional MLST types, for identifying resistance genes and for core genome multi locus sequence typing (cgMLST) analysis. Epidemiological data were obtained from hospital records.

Strains were cultured from 7 patients treated in the ICU of our hospital; all isolates showed a multi-drug resistant (MDR) profile, carrying theblaOXA-23carbapenemase. Typing performed by rep-PCR and MLST showed that the isolates clustered into one group while the cgMLST approach, which uses 2690 gene targets to characterize the gene-by-gene allelic profile ofA. baumannii,highlighted the presence of two cluster types. These results allowed us to identify two patients who entered the ICU already colonized by two different strains of CR-A. baumannii; we hypothesize that these two patients could be the source of two separate transmission chains.

Our results show that whole-genome-DNA sequencing by cgMLST is a valuable tool, better suited for prompt epidemiological investigations than traditional typing methods because of its higher discriminatory ability in determining clonal relatedness.
Characterizing the Effects of Glutathione as an Immunoadjuvant in the Treatment of Tuberculosis
Authors: Cao Ruoqiong , Teskey Garrett , Islamoglu Hicret , Abrahem Rachel , Gyurjian Karo , Zhong Li , Venketaraman Vishwanath
Published: May 2018

Mycobacteriumtuberculosis(M.tb) is the etiological agent that is responsible for causing tuberculosis (TB), which continues to affect millions of people worldwide, with an ever-increasing resistance to antibiotics. We tested the synergistic effects of N-acetyl cysteine (NAC, the precursor molecule for the synthesis of glutathione) and individual first-line antibiotics typically given for the treatment of TB such as Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB) and Pyrazinamide (PZA) to improve the ability of macrophages to control intracellularM.tbinfection. Glutathione (GSH), a pleiotropic antioxidant molecule has been previously shown to display both antimycobacterial and immune-enhancing effects. Our results indicate that there was not only an increase in beneficial immunomodulatory effects, but a greater reduction in the intracellular viability ofM. tbwhen macrophages were treated with the combination of antibiotics (INH/RIF/EMB or PZA) and NAC.
Barcoded Rational AAV Vector Evolution enables systematicin vivomapping of peptide binding motifs
Authors: Davidsson Marcus , Wang Gang , Aldrin-Kirk Patrick , Cardoso Tiago , Nolbrant Sara , Hartnor Morgan , Parmar Malin , Björklund Tomas
Published: May 2018

Engineering of Adeno-associated viral (AAV) vector capsids through directed evolution has been used to generate novel capsids with altered tropism and function1-9. This approach, however, involves a selection process that requires multiple generations of screenings to identify real functional capsids2-4. Due to the random nature of this process, it is also inherently unreproducible, and the resulting capsid variants provide little mechanistic insights into the molecular targets engaged. To overcome this, we have developed a novel method for rational capsid evolution named Barcoded Rational AAV Vector Evolution (BRAVE). The key to this method is a novel viral production approach where each virus particle displays a protein-derived peptide on the surface which is linked to a unique barcode in the packaged genome10. Through hidden Markov model-based clustering11, we were able to identify novel consensus motifs for cell-type specific retrograde transport in neurons in vivo in the brain. The BRAVE approach enables the selection of novel capsid structures using only a single-generation screening. Furthermore, it can be used to map, with high resolution, the putative binding sequences of large protein libraries.
Computational analysis of the Plasmodiophora brassicae genome: mitochondrial sequence description and metabolic pathway database design
Authors: Daval S. , Belcour A. , Gazengel K. , Legrand L. , Gouzy J. , Cottret L. , Lebreton L. , Aigu Y. , Mougel C. , Manzanares-Dauleux M.J.
Published: May 2018

Plasmodiophora brassicae is an obligate biotrophic pathogenic protist responsible for clubroot, a root gall disease of Brassicaceae species. In addition to the reference genome of the P. brassicae European e3 isolate and the draft genomes of Canadian or Chinese isolates, we present the genome of eH, a second European isolate. Refinement of the annotation of the eH genome led to the identification of the mitochondrial genome sequence, which was found to be bigger than that of Spongospora subterranea, another plant parasitic Plasmodiophorid phylogenetically related to P. brassicae. New pathways were also predicted, such as those for the synthesis of spermidine, a polyamine up-regulated in clubbed regions of roots. A P. brassicae pathway genome database was created to facilitate the functional study of metabolic pathways in transcriptomics approaches. These available tools can help in our understanding of the regulation of P. brassicae metabolism during infection and in response to diverse constraints.
CRISPR/Cas9-mediated knock-out of dUTPase in mice leads to early embryonic lethality
Authors: Pálinkás Hajnalka Laura , Rácz Gergely , Gál Zoltán , Hoffmann Orsolya , Tihanyi Gergely , Gócza Elen , Hiripi László , Vértessy Beáta G.
Published: May 2018

Sanitization of nucleotide pools is essential for genome maintenance. Among the enzymes significant in this mechanism, deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) performs cleavage of dUTP into dUMP and inorganic pyrophosphate. By this reaction the enzyme efficiently prevents uracil incorporation into DNA and provides dUMP, the substrate for de novo thymidylate biosynthesis. Despite its physiological significance, knock-out models of dUTPase have not yet been investigated in mammals, only in unicellular organisms, such as bacteria and yeast. Here we generate CRISPR/Cas9-mediated dUTPase knock-out in mice. We find that heterozygous dut +/-animals are viable while the decreased dUTPase level is clearly observable. We also show that the enzyme is essential for embryonic development. Based on the present results, early dut -/-embryos can still reach the blastocyst stage, however, they die shortly after implantation. Analysis of preimplantion embryos indicate perturbed growth of both inner cell mass (ICM) and trophectoderm (TE). We conclude that dUTPase is indispensable for post-implantation development in mice. The gene targeting model generated in the present study will allow further detailed studies in combination with additional gene knock-outs.
Humanized Mcl-1 mice enable accurate pre-clinical evaluation of MCL-1 inhibitors destined for clinical use
Authors: Brennan Margs S. , Chang Catherine , Dewson Grant , Tai Lin , Lessene Guillaume , Strasser Andreas , Kelly Gemma L. , Herold Marco J.
Published: May 2018

MCL-1 is a pro-survival BCL-2 protein required for the sustained growth of many cancers. Recently a highly specific MCL-1-inhibitor, S63845, showing 6-fold higher affinity to human compared to mouse MCL-1 has been described. To accurately test efficacy and tolerability of this BH3 mimetic drug in pre-clinical cancer models, we developed a humanized Mcl-1 (huMcl-1) mouse in which MCL-1 was replaced with its human homologue. HuMcl-1 mice are phenotypically indistinguishable from wild-type mice but are more sensitive to MCL-1 inhibition. Importantly, non-transformed cells and lymphomas from huMcl-1;Eμ-Myc mice are more sensitive to S63845 in vitro than their control counterparts. When huMcl-1;Eμ-Myc lymphoma cells are transplanted into huMcl-1 mice, treatment with S63845 alone or alongside cyclophosphamide leads to long-term remission in ~60% or almost 100% of mice, respectively. These results demonstrate the potential of our huMCL-1 mouse model to test MCL-1 inhibitors, allowing precise predictions of efficacy and tolerability for clinical translation.
Integrated Cognitive Assessment: Speed and Accuracy of Visual Processing as a Reliable Proxy to Cognitive Performance
Authors: Khaligh-Razavi Seyed-Mahdi , Habibi Sina , Sadeghi Maryam , Marefat Haniye , Khanbagi Mahdiyeh , Nabavi Seyed Massood , Sadeghi Elham , Kalafatis Chris
Published: May 2018

Various mental disorders are accompanied by some degree of cognitive impairment. Particularly in neurodegenerative disorders, cognitive impairment is the phenotypical hallmark of the disease. Effective, accurate and timely cognitive assessment is key to early diagnosis of this family of mental disorders. Current standard-of-care techniques for cognitive assessment are primarily paper-based, and need to be administered by a healthcare professional; they are additionally language and education-dependent and typically suffer from a learning bias. These tests are thus not ideal for large-scale pro-active cognitive screening and disease progression monitoring. We developed the Integrated Cognitive Assessment (ICA), a 5-minute computerized cognitive assessment tool based on a rapid visual categorization task, in which a series of carefully selected natural images of varied difficulty are presented to participants. Overall 448 participants, across a wide age-range with different levels of education took the ICA test. We compared participants’ ICA test results with a variety of standard pen-and-paper tests that are routinely used to assess cognitive performance. ICA had excellent test-retest reliability, and was significantly correlated with all the reference cognitive tests used here, demonstrating ICA’s ability as one unified test that can assess various cognitive domains.
Tissue growth factor β stimulates fibroblast-like synovial cells to produce extra domain A fibronectin in osteoarthritis
Authors: Kragstrup TW , Sohn DH , Lepus CM , Onuma K , Wang Q , Robinson WH , Sokolove J
Published: May 2018

Introduction

The pathophysiology of osteoarthritis (OA) involves wear and tear, and a state of low-grade inflammation. Wear and tear leads to tissue degradation and tissue repair responses, including tissue growth factor beta (TGFβ)-induced myofibroblast production of extracellular matrix (ECM). Fibronectins are an essential part of the ECM, and injection of fibronectin fragments into rabbit joints is a previously established animal model of OA. Alternatively-spliced fibronectin contains the ED-A domain (ED-A FN) and has been shown to activate Toll-like receptor 4. In this study, we tested the hypothesis that FN fragments containing the ED-A domain could be one mechanism transducing mechanical events into inflammatory signals in OA.

Methods

Samples of synovial membrane and cartilage were obtained from patients with knee OA undergoing joint replacement surgery. Immunostaining for ED-A FN and the myofibroblast marker alpha smooth muscle actin (αSMA) was performed on synovial membranes and fibroblast-like synovial cells (FLS). FLS were stimulated with TGFβ, TNFα, lipopolysaccharide, IL-6, OA synovial fluid, or chondrocyte lysate, and analyzed for ED-A FN. Synovial cells isolated by enzymatic digestion and human monocyte-derived macrophages (MDM) were incubated with recombinant ED-A FN, plasmin, cellular FN, or cellular FN digested with plasmin; and culture supernatants were analyzed for MCP-1 and TNFα.

Results

We hypothesized that ED-A FN is produced by OA FLS in response to factors found in the OA synovial joint. Indeed, the production of ED-A FN by OA FLS was increased by TGFβ, OA synovial fluid, and lysed chondrocytes in all experiments (n=3). ED-A FN co- localized with the myofibroblast marker αSMA in both the OA FLS (n=3) and in the OA synovial membranes (n=8). We further hypothesized that ED-A FN expression is associated with cellular density and expression of inflammatory molecules in OA. ED-A FN staining was associated with both number of lining layer cells (rho=0.85 and p=0.011) and sublining cells (rho=0.88 and p=0.007) in the OA synovium (n=8), and co-localized with both MCP-1 and TNFα (n=5). Recombinant ED-A FN increased the production of both MCP-1 and TNFα by MDM (n=3) and OA FLS (n=3). Finally, we demonstrated that the FN fragments containing the ED-A domain generated the same production of both MCP-1 and TNFα as recombinant ED-A FN.

Conclusion

The disease process in OA shares features with the chronic wound healing response including myofibroblast differentiation and production of mediators that promote myofibroblast production of ED-A FN. We show that recombinant and plasmin-derived ED-A fragments stimulate FLS and MDM to produce pro-inflammatory mediators. Our findings support utilizing ED-A FN for drug delivery or therapeutic targeting of the formation of ED- A FN or the enzymatic fragmentation of FN to reduce pro-inflammatory responses in OA.
Proteome and microbiota analysis reveals alterations of liver-gut axis under different stocking density of Peking ducks
Authors: Wu Yuqin , Li Jianhui , Qin Xin , Sun Shiqiang , Xiao Zhibin , Dong Xiaoyu , Shahid Muhammad Suhaib , Yin Dafei , Lei Zhao , Guo Yuming , Yuan Jianmin
Published: May 2018

The aim of this study was to determine the impact of stocking density on the liver proteome and cecal microbiota of Peking ducks. A total of 1,200 ducks with 21-day old were randomly allotted into 5 stocking density groups of 5, 6, 7, 8 and 9 ducks/m2, with 6 replicates for each group. At 40 days of age, duck serum and pectorals were collected for biochemical tests; liver and cecal contents of ducks were gathered for proteome and microbiota analysis, respectively. Serum MDA increased while pectorals T-AOC reduced linearly with enhancing stocking density. Duck lipid metabolism was altered under different stocking density as well. Serum LDL-C increased linearly with increasing stocking density. Proteome analysis revealed fatty acid biosynthesis proteins such as acyl-CoA synthetase family member 2 and fatty acid oxidation related proteins including acyl-CoA dehydrogenase long chain and acyl-coenzyme A oxidase were enriched in high stocking density group. Additionally, high stocking density increased oxidative response related proteins such as DDRGK domain containing 1 while diminished anti-oxidant capacity related proteins including regucalcin and catalase. 16S rDNA analysis revealed that higher stocking density was accompanied with decreased microbial diversity, as well as depletion of anti-inflammatory bacterial taxa, including Bacteroidales, Butyricimonas and Alistipe. In addition, decreased bile acid metabolism-associated bacteria such as Ruminococcaceae, Clostridiales and Desulfovibrionaceae were found in the high-density group. Both proteome and 16S rDNA results showed inflammation and chronic liver disease trend in the high-density group, which suggests the involvement of the liver-gut axis in oxidative stress.
Longitudinal increase in sleep problems is related to amyloid deposition in cortical regions with high HOMER1 gene expression
Authors: Fjell Anders M , Sederevicius Donatas , Sneve Markus H , de Lange Ann-Marie Glasø , Sjøli Bråthen Anne Cecilie , Walhovd Kristine B ,   for The Alzheimer’s Disease Neuroimaging Initiative
Published: May 2018

Older adults who report more sleep problems tend to have elevated levels of the Alzheimer’s disease (AD) biomarker β-amyloid (Aβ), but the mechanisms responsible for this relationship are largely unknown. Molecular markers of sleep problems are now emerging from rodent research, yielding opportunities to generate hypotheses about the causes of the sleep-Aβ relationship. A major molecular marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, involved in control of sleep homeostasis and also implied in Aβ accumulation. Here, in a sample of 109 cognitively healthy middle-aged and older adults, we tested whether the relationship between cortical Aβ accumulation and self-reported sleep quality, as well as changes in sleep quality over three years, was stronger in cortical regions with high HOMER1 mRNA expression levels. Aβ correlated with poorer sleep quality cross-sectionally and longitudinally. This relationship was stronger in the younger (50-67 years) than the older (68-81 years) participants. Effects were mainly found in regions with high expression of HOMER1, suggesting a possible molecular pathway between sleep problems and Aβ accumulation. The anatomical distribution of the sleep-Aβ relationships followed closely the Aβ accumulation pattern in 69 patients with mild cognitive impairment (MCI) or AD. Thus, the results indicate that the relationship between sleep problems and Aβ-accumulation may involve Homer1 activity in the cortical regions that harbor Aβ in AD. Analysis of cortical gene expression patterns represent a promising avenue to unveil molecular mechanisms behind the relationship between sleep problems and AD risk.
Endoplasmic Reticulum Retention Motif Fused to Recombinant Anti-cancer Monoclonal Antibody (mAb) CO17-1A Affects mAb Expression and Plant Stress Response
Authors: Song Ilchan , Kang Yang Joo , Lee Young Koung , Myung Soon-chul , Ko Kisung
Published: May 2018

The endoplasmic reticulum (ER) is the main site of protein synthesis, folding, and secretion to other organelles. The capacity of the ER to process proteins is limited, and excessive accumulation of unfolded and misfolded proteins can induce ER stress, which is associated with plant diseases. Here, a transgenicArabidopsissystem was established to express anti-cancer monoclonal antibodies (mAbs) that recognize the tumor-associated antigen GA733-2. The ER retention Lys-Asp-Glu-Leu (KDEL) motif sequence was added to the C-terminus of the heavy chain to retain anti-colorectal cancer mAbs in the ER, consequently boosting mAb production.Agrobacterium-mediated floral dip transformation was used to generate T1transformants, and homozygous T4seeds obtained from transgenicArabidopsisplants expressing anti-colorectal cancer mAbs were used to confirm the physiological effects of KDEL tagging. Germination rates were not significantly different between mAb CO and mAb COK. However, mAb COK primary root lengths were shorter than those of mAb CO plants and non-transgenicArabidopsisplants inin vitromedia. Most ER stress-related genes, with the exception ofbZIP28andIRE1a, were upregulated in mAb COK plants compared to mAb CO plants. Western blot and SDS-PAGE analyses showed that mAb COK plants exhibited up to five-times higher expression and mAb amounts than mAb CO plants. Enhanced expression in mAb COK plants was confirmed by immunohistochemical analyses. mAb COK was distributed across most of the area of leaf tissues, whereas mAb CO was mainly distributed in extracellular areas. Surface plasmon resonance analyses revealed that both mAb CO and mAb COK possessed equivalent or slightly better binding activities to antigen EpCAM compared to a commercially available parental antibody. These results suggest that the introduction of the KDEL motif is a promising strategy for obtaining enhanced amounts of recombinant therapeutic proteins, but the KDEL sequence may induce ER stress and slightly reduce plant biomass.
Cerebellar contribution to preparatory activity in motor neocortex
Authors: Chabrol Francois P. , Blot Antonin , Mrsic-Flogel Thomas D.
Published: May 2018

In motor neocortex, preparatory activity predictive of specific movements is maintained by a positive feedback loop with the thalamus. Motor thalamus receives excitatory input from the cerebellum, which learns to generate predictive signals for motor control. The contribution of this pathway to neocortical preparatory signals remains poorly understood. Here we show that in a virtual reality conditioning task, cerebellar output neurons in the dentate nucleus exhibit preparatory activity similar to that in anterolateral motor cortex prior to reward acquisition. Silencing activity in dentate nucleus by photoactivating inhibitory Purkinje cells in the cerebellar cortex caused robust, short-latency suppression of preparatory activity in anterolateral motor cortex. Our results suggest that preparatory activity is controlled by a learned decrease of Purkinje cell firing in advance of reward under supervision of climbing fibre inputs signalling reward delivery. Thus, cerebellar computations exert a powerful influence on preparatory activity in motor neocortex.
Comparison of large-scale citizen science data and long-term study data for phenology modeling
Authors: Taylor Shawn D. , Meiners Joan M. , Riemer Kristina , Orr Michael C. , White Ethan P.
Published: May 2018

Large-scale observational data from citizen science efforts are becoming increasingly common in ecology, and researchers often choose between these and data from intensive local-scale studies for their analyses. This choice has potential trade-offs related to spatial scale, observer variance, and inter-annual variability. Here we explored this issue with phenology by comparing models built using data from the large-scale, citizen science National Phenology Network (NPN) effort with models built using data from more intensive studies at Long Term Ecological Research (LTER) sites. We built process based phenology models for species common to each dataset. From these models we compared parameter estimates, estimates of phenological events, and out-of-sample errors between models derived from both NPN and LTER data. We found that model parameter estimates for the same species were most similar between the two datasets when using simple models, but parameter estimates varied widely as model complexity increased. Despite this, estimates for the date of phenological events and out-of-sample errors were similar, regardless of the model chosen. Predictions for NPN data had the lowest error when using models built from the NPN data, while LTER predictions were best made using LTER-derived models, confirming that models perform best when applied at the same scale they were built. Accordingly, the choice of dataset depends on the research question. Inferences about species-specific phenological requirements are best made with LTER data, and if NPN or similar data are all that is available, then analyses should be limited to simple models. Large-scale predictive modeling is best done with the larger-scale NPN data, which has high spatial representation and a large regional species pool. LTER datasets, on the other hand, have high site fidelity and thus characterize inter-annual variability extremely well. Future research aimed at forecasting phenology events for particular species over larger scales should develop models which integrate the strengths of both datasets.
Kinetic sculpting of the seven stripes of theDrosophila even-skippedgene
Authors: Berrocal Augusto , Lammers Nicholas , Garcia Hernan G. , Eisen Michael B.
Published: May 2018

We used live imaging to visualize the transcriptional dynamics of theDrosophila melanogaster even-skippedgene at single-cell and high temporal resolution as its seven stripe expression pattern forms, and developed tools to characterize and visualize how transcriptional bursting varies over time and space. We find that despite being created by the independent activity of five enhancers,even-skippedstripes are sculpted by the same kinetic phenomena: a coupled increase of burst frequency and amplitude. By tracking the position and activity of individual nuclei, we show that stripe movement is driven by the exchange of bursting nuclei from the posterior to anterior stripe flanks. Our work provides a conceptual, theoretical and computational framework for dissecting pattern formation in space and time, and reveals how the coordinated transcriptional activity of individual nuclei shape complex developmental patterns.
Multimodal transcriptional control of pattern formation in embryonic development
Authors: Lammers Nicholas C , Galstyan Vahe , Reimer Armando , Medin Sean A , Wiggins Chris H , Garcia Hernan G
Published: May 2018

Predicting developmental outcomes from regulatory DNA sequence and transcription factor patterns remains an open challenge in physical biology. Using stripe 2 of theeven-skippedgene inDrosophilaembryos as a case study, we dissect the regulatory forces underpinning a key step along the developmental decision-making cascade: the generation of cytoplasmic mRNA patterns via the control of transcription in individual cells. Using live imaging and computational approaches, we found that the transcriptional burst frequency is modulated across the stripe to control the mRNA production rate. However, we discovered that bursting alone cannot quantitatively recapitulate the formation of the stripe, and that control of thewindow of timeover which each nucleus transcribeseven-skippedplays a critical role in stripe formation. Theoretical modeling revealed that these regulatory strategies—bursting and the time window—obey different kinds of regulatory logic, suggesting that the stripe is shaped by the interplay of two distinct underlying molecular processes.
Performance of quartz- and sapphire-based double-crystal high-resolution (∼10 meV) RIXS monochromators under varying power loads
Authors: Gog Thomas , Casa Diego M. , Knopp Jonathan , Kim Jungho , Upton Mary H. , Krakora Richard , Jaski Alan , Said Ayman , Yavaş Hasan , Gretarsson Hlynur , Huang Xian Rong
Published: May 2018

In the context of a novel, high-resolution resonant inelastic X-ray scattering spectrometer, a flat-crystal-based quartz analyzer system has recently been demonstrated to provide an unprecedented intrinsic-energy resolution of 3.9 meV at the Ir L
3 absorption edge (11.215 keV) [Kim et al. (2018) Sci. Rep.
8, 1958]. However, the overall instrument resolution was limited to 9.7 meV because of an 8.9 meV incident band pass, generated by the available high-resolution four-bounce Si(844) monochromator. In order to better match the potent resolving power of the novel analyzer with the energy band pass of the incident beam, a quartz(309)-based double-bounce, high-resolution monochromator was designed and implemented, expected to yield an overall instrument resolution of 6.0 meV. The choice of lower-symmetry quartz is very attractive because of its wealth of suitable near-backscattering reflections. However, it was found that during room-temperature operation typical levels of incident power, barely affecting the Si monochromator, caused substantial thermal distortions in the first crystal of the quartz monochromator, rendering it practically unusable. Finite-element analyses and heat-flow analyses corroborate this finding. As a high-flux, lower resolution (15.8 meV) alternative, a two-bounce sapphire(078) version was also tested and found to be less affected than quartz, but notably more than silicon.
Structure and analysis of nucleoside diphosphate kinase fromBorrelia burgdorferiprepared in a transition-state complex with ADP and vanadate moieties
Authors: Dumais Mitchell , Davies Douglas R. , Lin Tao , Staker Bart L. , Myler Peter J. , Van Voorhis Wesley C.
Published: May 2018

Nucleoside diphosphate kinases (NDKs) are implicated in a wide variety of cellular functions owing to their enzymatic conversion of NDP to NTP. NDK fromBorrelia burgdorferi(BbNDK) was selected for functional and structural analysis to determine whether its activity is required for infection and to assess its potential for therapeutic inhibition. The Seattle Structural Genomics Center for Infectious Diseases (SSGCID) expressed recombinantBbNDK protein. The protein was crystallized and structures were solved of both the apoenzyme and a liganded form with ADP and vanadate ligands. This provided two structures and allowed the elucidation of changes between the apo and ligand-bound enzymes. Infectivity studies withndktransposon mutants demonstrated that NDK function was important for establishing a robust infection in mice, and provided a rationale for therapeutic targeting ofBbNDK. The protein structure was compared with other NDK structures found in the Protein Data Bank and was found to have similar primary, secondary, tertiary and quaternary structures, with conserved residues acting as the catalytic pocket, primarily using His132 as the phosphohistidine-transfer residue. Vanadate and ADP complexes model the transition state of this phosphoryl-transfer reaction, demonstrating that the pocket closes when bound to ADP, while allowing the addition or removal of a γ-phosphate. This analysis provides a framework for the design of potential therapeutics targetingBbNDK inhibition.
Divided we stand? Occupational boundary work among human resource managers and external organization development practitioners
Authors: Kuna Shani , Nadiv Ronit
Published: May 2018

Purpose

Understanding occupational boundaries is vital in the contemporary economy, in which knowledge-based work is a central feature. The purpose of this paper is to identify and decipher boundary work which affects the cooperation and demarcation between human resource (HR) managers and external organization development (OD) practitioners during organization change processes.

Design/methodology/approach

Data are based on in-depth interviews with HR managers and external OD practitioners in the Israeli business sector.

Findings

Encounters between HR managers and external OD practitioners are potentially volatile given mutual experiences of occupational threat. Three distinct patterns of boundary work for negotiating OD-HR jurisdiction are identified. These yield differential occupational and organizational outcomes.

Research limitations/implications

This study is based on a medium-sized sample of practitioners of HRM and OD in the Israeli business sector. The data focused on one-sided descriptions of occupational relations.

Practical implications

The findings shed light on boundary work associated with fruitful HRM-OD partnerships. This may greatly advance the success of costly organization change and development interventions which demand the collaboration of both parties. Implications are offered regarding the academic education and practical daily management of both groups of practitioners.

Originality/value

Despite their growing relevance, empirical investigations of daily HRM-OD interfaces are scarce. This exploratory research addresses this gap in the literature and offers theoretical and practical insights.
Subjective and objective financial literacy, opinion leadership, and the use of retail banking services
Authors: Nejad Mohammad G. , Javid Katayon
Published: May 2018

Purpose

The purpose of this paper is to explore the relationship between consumers’ subjective and objective financial literacy (OFL) – the necessary knowledge and skills to make effective personal financial decisions – and their effects on opinion leadership and the use of retail financial services.

Design/methodology/approach

In total, 486 US participants were surveyed. The demographical profile of the sample roughly resembled that of the USA population.

Findings

On average, consumers with moderate levels of OFL report lower subjective financial literacy (SFL) compared to those with low or high levels of OFL. Moreover, while SFL and opinion leadership are positively correlated, consumers with moderate levels of OFL reported lower opinion leadership compared to those with high or low levels of OFL. The paper introduces financial literacy miscalibration as the discrepancy between consumers’ objective and SFL. Financially illiterate respondents who perceived themselves as financially knowledgeable reported high opinion leadership. Finally, a greater percentage of financially – literate consumers reported owning checking and savings accounts, using online and mobile banking for diverse purposes, and making fewer phone calls to customer services, compared to others.

Research limitations/implications

The paper integrates literature from financial literacy, consumer knowledge, and opinion leadership to explain these findings and to further enhance our theoretical and empirical understanding of objective vs SFL.

Practical implications

The discrepancies between objective and SFL may significantly influence consumers’ financial decisions and the degree to which they expose themselves to the pertinent risks. The paper discusses implications for public policy makers as well as marketing managers and researchers.

Originality/value

The study is the first to empirically explore the research questions following the conceptual development.
Does information asymmetry lead to higher debt financing? Evidence from China during the NTS Reform period
Authors: Qu Wenzhou , Wongchoti Udomsak , Wu Fei , Chen Yanming
Published: May 2018

Purpose

The purpose of this paper is to test an implication of the pecking order theory to explain capital structure decisions among Chinese listed companies during the 2005-2007 NTS Reform transition period.

Design/methodology/approach

The authors utilize direct proxies for information asymmetry based on microstructure models including Probability of the arrival of informed trades (PIN), Adverse selection component of the bid-ask spread (λ), Illiquidity ratio (ILLIQ) and liquidity ratio, and Information asymmetry index (InfoAsy) to examine their relation with firms’ debt financing.

Findings

Consistent with the prediction of Pecking Order Theory, the authors find that companies for which stock investors are challenged with more severe informational disadvantages are associated with higher degree of leverage use.

Originality/value

The study provides a more direct test on the positive relation between information asymmetry and financial leverage of Chinese firms. In contrast to previous findings by Chen (2004), the results suggest that capital structure choices among Chinese firms progressively conform to conventional finance theories (e.g. Pecking Order Theory) with the decline of non-tradable shares.
A peer approach to the evaluation of adult support and protection processes in North Ayrshire
Authors: Burns John
Published: May 2018

Purpose

By adopting a “peer approach,” the purpose of this paper is to evaluate the adult support and protection process in North Ayrshire from the perspective of patients, service users and carers.

Design/methodology/approach

A research design was co-produced by health and social care staff and people with lived experience of ASP processes and experiences. The semi-structured interview design explored the ASP inquiry, investigation and case conference stages of the ASP process.

Findings

The study found some examples of good practice as well as some areas for improvement. The variability of experience, the provision of information, use of advocacy services and plans for future systematic evaluation of experiences were identified for possible improvement.

Research limitations/implications

The design somewhat limits generalizability; the sample size is small and although the findings and innovative approach involving those with lived experience may have wider appeal, the specific recommendations pertain to a specific local authority area in Scotland though these too may interest practitioners and researchers in other authorities.

Practical implications

The recommendations stand to improve services and process accessed and experienced by adults at risk of harm. Working with people with lived experience takes services closer to co-producing, designing and evaluating services and processes.

Originality/value

This study has high originality. Local value is high and is also likely to be valuable to those interested in adult support in protection generally and peer approaches across fields.
Organizational learning, knowledge management capability and supply chain management practices in the Saudi food industry
Authors: Attia Ahmed , Essam Eldin Ingy
Published: May 2018

Purpose

The purpose of this paper is to examine the effect of knowledge management capabilities (KMCs) on organizational learning (OL) and supply chain management practices (SCMPs). In addition, to study the effect of OL, KMC and supply chain management on organizational performance (OP).

Design/methodology/approach

To study the relationships between KMC, OL, SCMP and OP, different techniques such as factor analysis, correlation analysis and structural equation modeling were used to verify the validity of the proposed conceptual model, and to test the suggested hypotheses, data collected from 165 companies in the Saudi food industry (representing a response rate of 64.9 per cent) were used.

Findings

According to the study’s findings, SCMP and OL are positively affected by KMC. Moreover, OP is directly affected by KMC, OL and SCMP.

Research limitations/implications

Owing to the specific nature of the sample, the findings of the current research are applicable only to the food industry.

Originality/value

The current research introduced a conceptual model, which has been tested and verified in the Saudi food industry. The findings recommend that both KMC and OL as well as SCMP will contribute to improving the OP. In addition, KMC will improve the SCMP and OL.
Societal impact of university innovation
Authors: Yeo Benjamin
Published: May 2018

Purpose

This study aims to use university patent and regional economic data to investigate the current and future impact of university innovation, measured using multiple variables, on real economic productivity.

Design/methodology/approach

Using university patent and regional economic data, regression models are built to determine the impact of university innovation on current and future regional economic performance.

Findings

The findings demonstrate that university innovation generates sustained impact on economic performance, but by itself, is insufficient in driving economic performance; and different measures of university innovation have different degrees of impact. University innovation makes up a small, albeit significant, proportion of the drivers of economic performance.

Research limitations/implications

There are four implications. First, developing countries can leverage university–industry collaborations for economic growth. Second, innovation management must encourage continuous university innovation for sustainable economic productivity. Third, Science, Technology, Engineering and Mathematics (STEM) and non-STEM innovation warrant attention. Fourth, successful innovation policies should be tailored to their unique societal contexts.

Originality/value

Although innovation is a driver of economic performance, there is a lack of studies that focus specifically on universities, operationalize performance using gross domestic product measures and take into account impact lags by exploring universities’ current and future impacts.
Using functional electrical stimulation with stroke survivors: A survey of Victorian occupational therapists and physiotherapists
Authors: Howlett Owen , McKinstry Carol , Lannin Natasha A.
Published: May 2018

Background/aim

Functional electrical stimulation (FES) improves active movement of the hemiplegic upper and lower limbs following stroke. The use of FES by Australian allied health clinicians in stroke rehabilitation is, however, unknown. The purpose of this study was to understand the use of FES in clinical practice. Reasons for the use of FES and potential variables that influence decision‐making were also investigated.

Methods

Cross‐sectional study of Victorian allied health clinicians, using a snowball recruitment method. Ninety‐seven eligible therapists completed the anonymous online survey. Data were analysed using frequency distributions.

Results

The majority of respondents were occupational therapists (n = 60; 62%). Approximately half of the respondents (n = 50; 52%) reported using FES in the past two years to improve a stroke survivor's ability to use their arm in daily activities. Respondents suggested that receiving workplace training from colleagues to learn how to use FES is the preferred method of education. Of those who received education (n = 80), 50 participants reported using FES in their practice.

Conclusion

There is variable use of FES in stroke rehabilitation to increase active movement after stroke. While there was moderate agreement about when to use FES and useful education approaches for learning to use FES, further research is needed to better understand strategies which could be implemented to support increased FES use in stroke rehabilitation.