bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive Processing dissociation by mental effort manipulation in long demanding tasks
Authors: Alves Marcus Vinicius , Tassini Susanny , Aedo-Jury Felipe , Bueno Orlando F. A.
Published: April 2020

Individuals uses cognitive resources to modulate performance in demanding tasks and a non-invasive and reliable way of measuring mental effort is pupillometry. This study aimed to test the mental effort related to different processing systems in long tasks with controlled and automatic demands. We conducted two experiments with healthy subjects: in Experiment 1 (n=15), using a metronome to ensure control on task pace, participants performed a serial number generation task (Counting; little to no effort tasks), a random number generation (RNG; effortful tasks), and no task (Unfilled interval; no effort at all). In experiment 2, (n=15) participants performed counting tasks with or without additional intermediary beeps produced by a metronome to assess the effect of a possible increase in effort demanded by the distractors. Experiment 1 showed differences between unfilled interval, counting and RNG. Experiment 2 showed that the intermediate beep made the counting tasks more demanding than the normal counting tasks. Notable in both experiments was the tendency of participants to demand mental effort at the beginning of the trial. These results indicate that previously effortless automatic tasks can become controlled, or at least more demanding, with a simple experimental manipulation. They also reveal that tasks that require mental effort over a long period will demand more than automatic ones, but even so the peak of this demand is in the initial trial period. Moreover, they reveal the high sensitivity of pupillometry for the measurement of mental effort employing different processing systems and cognitive resource modulation.
Cancer-specific loss ofTERTactivation sensitizes glioblastoma to DNA damage
Authors: Amen Alexandra M. , Fellmann Christof , Soczek Katarzyna M. , Ren Shawn M. , Lew Rachel J. , Knott Gavin J. , Park Jesslyn E. , McKinney Andrew M. , Mancini Andrew , Doudna Jennifer A. , Costello Joseph F.
Published: April 2020

Most glioblastomas (GBMs) achieve cellular immortality by acquiring a mutation in the telomerase reverse transcriptase (TERT) promoter.TERTpromoter mutations create a binding site for a GA binding protein (GABP) transcription factor complex, whose assembly at the promoter is associated withTERTreactivation and telomere maintenance. Here, we demonstrate increased binding of a specific GABPB1L isoform-containing complex to the mutantTERTpromoter. Furthermore, we find thatTERTpromoter mutant GBM cells, unlike wild-type cells, exhibit a critical near-term dependence on GABPB1L for proliferation, both in cell culture and post-tumor establishmentin vivo. Upregulation of the protein paralogue GABPB2, which is normally expressed at very low levels, can rescue this dependence. More importantly, when combined with frontline temozolomide (TMZ) chemotherapy, inducible GABPB1L knockdown and the associatedTERTreduction led to an impaired DNA damage response that resulted in profoundly reduced growth of intracranial GBM tumors. Together, these findings provide new insights into the mechanism of cancer-specificTERTregulation, uncover rapid effects of GABPB1L-mediatedTERTsuppression in GBM maintenance, and establish GABPB1L inhibition in combination with chemotherapy as a novel therapeutic strategy forTERTpromoter mutant GBM.
Toward Minimally Invasive Therapeutic Ultrasound: Ultrasound-guided Ablation in Neuro-oncology
Authors: Belzberg Micah , Mahapatra Smruti , Chavez Francisco , Morrison Kyle , Xiong Kah Timothy , Gamo Nao J. , Restaino Stephen , Iyer Rajiv , Groves Mari , Thakor Nitish , Theodore Nicholas , Luciano Mark G. , Brem Henry , Cohen Alan R. , Manbachi Amir
Published: April 2020

Introduction

To improve patient outcomes (eg, reducing blood loss and infection), practitioners have gravitated toward noninvasive and minimally invasive surgeries (MIS), which demand specialized toolkits. Focused ultrasound, for example, facilitates thermal ablation from a distance, thereby reducing injury to surrounding tissue. Focused ultrasound can often be performed noninvasively; however, it is more difficult to carry out in neuro-oncological tumors, as ultrasound is dramatically attenuated while propagating through the skull. This shortcoming has prompted exploration of MIS options for intracranial placement of focused ultrasound probes, such as within the BrainPath™(NICO Corporation, Indianapolis, IN). Herein, we present the design, development, andin vitrotesting of an image-guided, focused ultrasound prototype designed for use in MIS procedures. This probe can ablate neuro-oncological lesions despite its small size.

Materials & Methods

Preliminary prototypes were iteratively designed, built, and tested. The final prototype consisted of three 8-mm-diameter therapeutic elements guided by an imaging probe. Probe functionality was validated on a series of tissue-mimicking phantoms.

Results

Lesions were created in tissue-mimicking phantoms with average dimensions of 2.5×1.2×6.5mm and 3.4×3.25×9.36mm after 10- and 30-second sonification, respectively. 30s sonification with 118W power at 50% duty cycle generated a peak temperature of 68°C. Each ablation was visualized in real time by the built-in imaging probe.

Conclusion

We developed and validated an ultrasound-guided focused ultrasound probe for use in MIS procedures. The dimensional constraints of the prototype were designed to reflect those of BrainPath trocars, which are MIS tools used to create atraumatic access to deep-seated brain pathologies.

HIGHLIGHTS

An ultrasound-guided, focused ultrasound prototype was developed and validated

The therapeutic transducer (1.5MHz) consisted of three 8-mm circular elements

Elements were placed on a 9×32mm curved rectangular aperture: 45mm radius curvature

Functionality was examined on tissue-mimicking phantoms

2.5×1.2×6.5mm and 3.4×3.25×9.36mm lesions were seen for 10 and 30s sonification
The case for formal methodology in scientific reform
Authors: Devezer Berna , Navarro Danielle J. , Vandekerckhove Joachim , Buzbas Erkan Ozge
Published: April 2020

Current attempts at methodological reform in sciences come in response to an overall lack of rigor in methodological and scientific practices in experimental sciences. However, most methodological reform attempts suffer from similar mistakes and over-generalizations to the ones they aim to address. We argue that this can be attributed in part to lack of formalism and first principles. Considering the costs of allowing false claims to become canonized, we argue for formal statistical rigor and scientific nuance in methodological reform. To attain this rigor and nuance, we propose a five-step formal approach for solving methodological problems. To illustrate the use and benefits of such formalism, we present a formal statistical analysis of three popular claims in the metascientific literature: (a) that reproducibility is the cornerstone of science; (b) that data must not be used twice in any analysis; and (c) that exploratory projects imply poor statistical practice. We show how our formal approach can inform and shape debates about such methodological claims.
Synchronous spiking associated with high gamma oscillations in prefrontal cortex exerts top-down control over a 5Hz-rhythmic modulation of spiking in locus coeruleus
Authors: Totah Nelson K. , Logothetis Nikos K. , Eschenko Oxana
Published: April 2020

The brainstem noradrenergic locus coeruleus (LC) is reciprocally connected with the prefrontal cortex (PFC). Strong coupling between LC spiking and depolarizing phase of slow (1 – 2 Hz) waves in the PFC field potentials during sleep and anesthesia suggests that the LC drives cortical state transition. Reciprocal LC-PFC connectivity should also allow interactions in the opposing (top-down) direction, but prior work has only studied prefrontal control over LC activity using direct electrical (or optogenetic) stimulation paradigms. Here, we describe the physiological characteristics of naturally occurring top-down prefrontal-coerulear interactions. Specifically, we recorded LC multi-unit activity (MUA) simultaneously with PFC single unit and local field potential (LFP) activity in urethane-anesthetized rats. We observed cross-regional coupling between the phase of ~5 Hz oscillations in LC population spike rate and the power of PFC LFP oscillations within the high Gamma (hGamma) range (60 – 200 Hz). Specifically, transient increases in PFC hGamma power preceded peaks in the ~5 Hz LC-MUA oscillation. Analysis of cross-regional transfer entropy demonstrated that the PFC hGamma transients were predictive of a transient increase in LC-MUA. A ~29 msec delay between these signals was consistent with the conduction velocity from the PFC to the LC. Finally, we showed that PFC hGamma transients are associated with synchronized spiking of a subset (27%) of PFC single units. Our data suggest that, PFC hGamma transients may indicate the timing of the top-down excitatory input to LC, at least under conditions when LC neuronal population activity fluctuates rhythmically at ~5 Hz. Synchronized PFC neuronal spiking that occurs during hGamma transients may provide a previously unknown mode of top-down control over the LC.
Synaptic Plasticity in Correlated Balanced Networks
Authors: Akil Alan Eric , Rosenbaum Robert , Josić Krešimir
Published: April 2020

The dynamics of local cortical networks are irregular, but correlated. Dynamic excitatory– inhibitory balance is a plausible mechanism that generates such irregular activity, but it remains unclear how balance is achieved and maintained in plastic neural networks. In particular, it is not fully understood how plasticity induced changes in the network affect balance, and in turn, how correlated, balanced activity impacts learning. How does the dynamics of balanced networks change under different plasticity rules? How does correlated spiking activity in recurrent networks change the evolution of weights, their eventual magnitude, and structure across the network? To address these questions, we develop a general theory of plasticity in balanced networks. We show that balance can be attained and maintained under plasticity induced weight changes. We find that correlations in the input mildly, but significantly affect the evolution of synaptic weights. Under certain plasticity rules, we find an emergence of correlations between firing rates and synaptic weights. Under these rules, synaptic weights converge to a stable manifold in weight space with their final configuration dependent on the initial state of the network. Lastly, we show that our framework can also describe the dynamics of plastic balanced networks when subsets of neurons receive targeted optogenetic input.
Parkinson Disease-Linked Parkin Mediates Redox Reactions That Lower Oxidative Stress In Mammalian Brain
Authors: El Kodsi Daniel N. , Tokarew Jacqueline M. , Sengupta Rajib , Lengacher Nathalie A. , Ng Andy C. , Boston Heather , Jiang Qiubo , Palmberg Carina , Pileggi Chantal , Shutinoski Bojan , Li Juan , Nguyen Angela P. , Fehr Travis K. , Im Doo Soon , Callaghan Steve , Park David S. , LaVoie Matthew J. , Chan Jennifer A. , Takanashi Masashi , Hattori Nobutaka , Ratan Rajiv R. , Zecca Luigi , Puente Lawrence , Shaw Gary S. , Harper Mary-Ellen , Holmgren Arne , Tomlinson Julianna J. , Schlossmacher Michael G.
Published: April 2020

We recently hypothesized that parkin plays a role in redox homeostasis and provided evidence that it directly reduces hydrogen peroxide (H2O2)in vitro. Here, we examined this anti-oxidant activityin vivo. Informed by findings in human brain, we demonstrate that elevated oxidative stress promotes parkin insolubility in mice. In normal mouse brain parkin was partially oxidized,e.g., at cysteines 195 and 252, which was augmented by oxidative stress. Although under basal conditions H2O2levels were unchanged in adultprkn-/-brain, a parkin-dependent reduction of cytosolic H2O2was observed when mitochondria were impaired, either due to neurotoxicant exposure (MPTP) orSod2haploinsufficiency. In accordance, markers of oxidative stress,e.g., protein carbonylation and nitrotyrosination, were elevated in the cytosol but not in mitochondria fromprkn-/-mice. Nevertheless, this rise in oxidative stress led to changes in mitochondrial enzyme activities and the metabolism of glutathione in cells and mammalian brain. In parkin’s absence reduced glutathione concentrations were increased including in human cortex. This compensation was not due to new glutathione synthesis but attributed to elevated oxidized glutathione (GSSG)-reductase activity. Moreover, we discovered that parkin also recycled GSSG to its reduced form. With this reaction, parkin became S-glutathionylated,e.g., at cysteines 59 and human-specific 95. This oxidative modification was reversed by glutaredoxin. Our results demonstrate that cytosolic parkin mediates anti-oxidant reactions including H2O2reduction and glutathione regeneration. These reducing activities lead to a range of oxidative modifications in parkin itself. In parkin-deficient brain oxidative stress rises despite changes to maintain redox balance.
L-Regulon: A novel “soft-curation” approach supported by a semantic enriched reading for RegulonDB literature
Authors: Lithgow-Serrano Oscar , Gama-Castro Socorro , Ishida-Gutiérrez Cecilia , Collado-Vides Julio
Published: April 2020

Manual curation is a bottleneck in the processing of the vast amounts of knowledge present in the scientific literature in order to make such knowledge available in computational resources e.g., structured databases. Furthermore, the extraction of content is by necessity limited to the pre-defined concepts, features and relationships that conform to the model inherent in any knowledgebase. These pre-defined elements contrast with the rich knowledge that natural language is capable of conveying. Here we present a novel experiment of what we call “soft curation” supported by an ad-hoc tuned robust natural language processing development that quantifies semantic similarity across all sentences of a given corpus of literature. This underlying machine supports novel ways to navigate and read within individual papers as well as across papers of a corpus. As a first proof-of-principle experiment, we applied this approach to more than 100 collections of papers, selected from RegulonDB, that support knowledge of the regulation transcription initiation inE. coli K-12, resulting in L-Regulon (L for “linguistic”) version 1.0. Furthermore, we have initiated the mapping of RegulonDB curated promoters, promoters, to their evidence sentence in the given publication. We believe this is the first step in a novel approach for users and curators, in order to increase the accessibility of knowledge in ways yet to be discovered.
Temporal codes of visual working memory in the human cerebral cortex
Authors: Noguchi Yasuki , Kakigi Ryusuke
Published: April 2020

Visual working memory (vWM) is an important ability required for various cognitive tasks although its neural underpinnings remain controversial. While many studies have focused on theta (4-7 Hz) and gamma (> 30 Hz) rhythms as a substrate of vWM, here we show that temporal signals embedded in alpha (8-12 Hz) and beta (13-30 Hz) bands can be a good predictor of vWM capacity. Neural activity of healthy human participants was recorded with magnetoencephalography when they performed a classical vWM task (change detection). We analyzed changes in inter-peak intervals (IPIs) of oscillatory signals along with an increase in WM load (a number of to-be-memorized items, 1-6). Results showed a load-dependent reduction of IPIs in the parietal and frontal regions, indicating that alpha/beta rhythms became faster when multiple items were stored in vWM. Furthermore, this reduction in IPIs was positively correlated with individual vWM capacity, especially in the frontal cortex. Those results indicate that vWM is represented as a change in oscillation frequency in the human cerebral cortex.
Tinamou egg color displacement at ecoregion co-partitioning
Authors: Li Qin , Wang Silu
Published: April 2020

The divergence of reproductive traits frequently underpins the evolution of reproductive isolation. One of the most enduring puzzles on this subject concerns the variability in egg coloration among species of tinamou (Tinamidae), endemic to neotropics. Here we investigated the hypothesis that tinamou egg coloration is a mating signal and its diversification was driven by reinforcement. For most tinamou species, the male guards the nest that is sequentially visited and laid eggs in by multiple females. The colorations of the existing eggs in the nest could signal mate quality and species identities to the upcoming females, preventing costly hybridization, thus were selected to diverge among species (Mating Signal Character Displacement Hypothesis). If so, two predictions should follow: (1) egg colors should coevolve with known mating signals as the tinamou lineages diverged; (2) species that partition similar ecoregions should display different egg colors. The tinamou songs are important mating signals and are highly divergent among species. We found that the egg luminance was significantly associated with the first principal component of the song variables, which supports prediction (1). In addition, we found support for (2): tinamou species that co-partition ecoregions tend to display different egg colors, controlling for song variation. Egg color and songs could be multimodal mating signals that are divergently selected as different tinamou species diverged. Mating signal evolution could be opportunistic and even exploit post-mating trait as premating signals that undergo character displacement at sympatry.
Specific mutations in SARS-CoV2 RNA dependent RNA polymerase and helicase alter protein structure, dynamics and thus function: Effect on viral RNA replication
Authors: Begum Feroza , Mukherjee Debica , Das Sandeepan , Thagriki Dluya , Tripathi Prem Prakash , Banerjee Arup Kumar , Ray Upasana
Published: April 2020

1.

The open reading frame (ORF) 1ab of SARS-CoV2 encodes non-structural proteins involved in viral RNA functions like translation and replication including nsp1-4; 3C like proteinase; nsp6-10; RNA dependent RNA polymerase (RdRp); helicase and 3’-5’ exonuclease. Sequence analyses of ORF1ab unravelled emergence of mutations especially in the viral RdRp and helicase at specific positions, both of which are important in mediating viral RNA replication. Since proteins are dynamic in nature and their functions are governed by the molecular motions, we performed normal mode analyses of the SARS-CoV2 wild type and mutant RdRp and helicases to understand the effect of mutations on their structure, conformation, dynamics and thus function. Structural analyses revealed that mutation of RdRp (at position 4715 in the context of the polyprotein/ at position 323 of RdRp) leads to rigidification of structure and that mutation in the helicase (at position 5828 of polyprotein/ position 504) leads to destabilization increasing the flexibility of the protein structure. Such structural modifications and protein dynamics alterations might alter unwinding of complex RNA stem loop structures, the affinity/ avidity of polymerase RNA interactions and in turn the viral RNA replication. The mutation analyses of proteins of the SARS-CoV2 RNA replication complex would help targeting RdRp better for therapeutic intervention.
Lsr2 is a nucleoid-associated protein that exerts pleiotropic effects on mycobacterial cellular processes
Authors: Kołodziej Marta , Trojanowski Damian , Bury Katarzyna , Hołówka Joanna , Paściak Mariola , Matysik Weronika , Kąkolewska Hanna , Feddersen Helge , Giacomelli Giacomo , Bramkamp Marc , Konieczny Igor , Zakrzewska-Czerwińska Jolanta
Published: April 2020

Lsr2 is involved in maintaining chromosome structure in asymmetrically dividing mycobacteria and is essential in the tubercle bacillus (M. tuberculosis) during infection. Here, we report that a lack of Lsr2 profoundly impacts the mycobacterial cell morphology and the properties of the cell envelope resulting in the formation of smooth, short and antibiotics sensitive cells. Lsr2 forms large and dynamic nucleoprotein complexesin vivoand deletion oflsr2gene exerts a profound effect on the replication time and replisome dynamics. We suggest that the Lsr2 nucleoprotein complexes may contribute to maintaining the proper organization of the newly synthesized DNA. Moreover, we demonstrate that the N-terminal oligomerization domain of Lsr2 is indispensable for the formation of nucleoprotein complexesin vivo. Collectively, our results indicate that Lsr2 exerts a pleiotropic effect on cellular processes and appears to be an attractive target for the development of a novel antitubercular drugs.
High-throughput organoid screening enables engineering of intestinal epithelial composition
Authors: Mead Benjamin E. , Hattori Kazuki , Levy Lauren , Vukovic Marko , Sze Daphne , Matute Juan D. , Duan Jinzhi , Langer Robert , Blumberg Richard S. , Ordovas-Montanes Jose , Shalek Alex K. , Karp Jeffrey M.
Published: April 2020

Barrier tissue epithelia play an essential role in maintaining organismal homeostasis, and changes in their cellular composition have been observed in multiple human diseases. Within the small intestinal epithelium, adult stem cells integrate diverse signals to regulate regeneration and differentiation, thereby establishing overall cellularity. Accordingly, directing stem cell differentiation could provide a tractable approach to alter the abundance or quality of specialized cells of the small intestinal epithelium, including the secretory Paneth, goblet, and enteroendocrine populations. Yet, to date, there has been a lack of suitable tools and rigorous approaches to identify biological targets and pharmacological agents that can modify epithelial composition to enable causal testing of disease-associated changes with novel therapeutic candidates. To empower the search for epithelia-modifying agents, we establish a first-of-its-kind high-throughput phenotypic organoid screen. We demonstrate the ability to screen thousands of samples and uncover biological targets and associated small molecule inhibitors which translate toin vivo. This approach is enabled by employing a functional, cell-type specific, scalable assay on an organoid model designed to represent the physiological cues ofin vivoPaneth cell differentiation from adult intestinal stem cells. Further, we miniaturize and adapt the organoid culture system to enable automated plating and screening, thereby providing the ability to test thousands of samples. Strikingly, in our screen we identify inhibitors of the nuclear exporter Xpo1 modulate stem cell fate commitment by inducing a pan-epithelial stress response combined with an interruption of mitogen signaling in cycling intestinal progenitors, thereby significantly increasing the abundance of Paneth cells independent of known WNT and Notch differentiation cues. We extend our observationin vivo, demonstrating that oral administration of Xpo1 inhibitor KPT-330 at doses 1,000-fold lower than conventionally used in hematologic malignancies increases Paneth cell abundance. In total, we provide a framework to identify novel biological cues and therapeutic leads to rebalance intestinal stem cell differentiation and modulate epithelial tissue composition via high-throughput phenotypic screening in rationally-designed organoid model of differentiation.
Promoter Choice: Who Should Drive the CAR in T Cells?
Authors: Rad SM Ali Hosseini , Poudel Aarati , Yi Tan Grace Min , McLellan Alexander D.
Published: April 2020

Chimeric antigen receptor (CAR) T cell therapy is an effective treatment for B cell malignancies, with emerging potential for the treatment of other hematologic cancers and solid tumors. The strength of the promoter within the CAR cassette will alter CAR-polypeptide levels on the cell surface of the T cell – impacting on the kinetics of activation, survival and memory cell formation in T cells. In addition to the CAR, promoters can be used to drive other genes of interest to enhance CAR T cell function. Expressing multiple genes from a single RNA transcript can be effectively achieved by linking the genes via a ribosomal skip site. However, promoters may differ in their ability to transcribe longer RNAs, or could interfere with lentiviral production, or transduction frequencies. In this study we compared the ability of the strong well-characterized promoters CMV, EF-1, hPGK and RPBSA to drive functional expression of a single RNA encoding three products: GFP, CAR, plus an additional cell-survival gene, Mcl-1. Although the four promoters produced similarly high lentiviral titres, EF-1 gave the best transduction efficacy of primary T cells. Major differences were found in the ability of the promoters to drive expression of long RNA encoding GFP, CAR and Mcl-1, highlighting promoter choice as an important consideration for gene therapy applications requiring the expression of long and complex mRNA.
An automated homecage system for multiwhisker detection and discrimination learning in mice
Authors: Bernhard Sarah M. , Lee Jiseok , Zhu Mo , Hsu Alex , Erskine Andrew , Hires Samuel A. , Barth Alison L.
Published: April 2020

Automated, homecage behavioral training for rodents has many advantages: it is low stress, requires little interaction with the experimenter, and can be easily manipulated to adapt to different experimental condition. We have developed an inexpensive, Arduino-based, homecage training apparatus for sensory association training in freely-moving mice using multiwhisker air current stimulation coupled to a water reward. Animals learn this task readily, within 1-2 days of training, and performance progressively improves with training. We examined the parameters that regulate task acquisition using different stimulus intensities, directions, and reward valence. Learning was assessed by comparing anticipatory licking for the stimulus compared to the no-stimulus (blank) trials. At high stimulus intensities (>9 psi), animals showed markedly less participation in the task. Conversely, very weak air current intensities (1-2 psi) were not sufficient to generate rapid learning behavior. At intermediate stimulus intensities (5-6 psi), a majority of mice learned that the multiwhisker stimulus predicted the water reward after 24-48 hrs of training. Both exposure to isoflurane and lack of whiskers decreased animals’ ability to learn the task. Perceptual learning was assessed and following training at an intermediate stimulus intensity, perception was likely heightened as mice were able to transfer learning behavior when exposed to the lower stimulus intensity. Mice learned to discriminate between two directions of stimulation rapidly and accurately, even when the angular distance between the stimuli was <15 degrees. Switching the reward to a more desirable reward, aspartame, had little effect on learning trajectory. Our results show that a tactile association task in an automated homecage environment can be monitored by anticipatory licking to reveal rapid and progressive behavioral change. These Arduino-based, automated mouse cages enable high-throughput training that facilitate analysis of large numbers of genetically modified mice with targeted manipulations of neural activity.
Cyclic pentapeptide cRGDfK enhances the inhibitory effect of sunitinib on TGF-β1-induced epithelial-to-mesenchymal transition in human non-small cell lung cancer cells
Authors: Park Kyeong-Yong , Kim Jiyeon
Published: April 2020

In human lung cancer progression, the EMT process is characterized by the transformation of cancer cells into invasive forms that migrate to other organs. Targeting to EMT-related molecules is emerging as a novel therapeutic approach for the prevention of lung cancer cell migration and invasion. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as an anti-proliferative target molecule to regulate the Wnt signaling pathway in several types of cancer cells. In the present study, we evaluated the inhibitory effect of a tyrosine kinase inhibitor sunitinib and the integrin-αVβ3targeted cyclic peptide (cRGDfK) on EMT in human lung cancer cells. Sunitinib strongly inhibited the TGF-β1-activated EMT through suppression of Wnt signaling, Smad and non-Smad signaling pathways. In addition, the cRGDfK also inhibited the expression of TGFβ1-induced mesenchymal marker genes and proteins. The anti-EMT effect of sunitinib was enhanced when cRGDfK was treated together. When sunitinib was treated with cRGDfK, the mRNA and protein expression levels of mesenchymal markers were decreased compared to the treatment with sunitinib alone. Co-treatment of cRGDfK has shown the potential to improve the efficacy of anticancer agents in combination with therapeutic agents that may be toxic at high concentrations. These results provide new and improved therapies for treating and preventing EMT-related disorders, such as lung fibrosis and cancer metastasis, and relapse.
Interleukin-17 pathway activation inEquus caballussupporting limb laminitis
Authors: Cassimeris Lynne , Engiles Julie B. , Galantino-Homer Hannah
Published: April 2020

Supporting Limb Laminitis (SLL) is a painful and crippling secondary complication of orthopedic injuries and infections in horses, often resulting in euthanasia. Due to altered weight bearing, SLL causes structural alternations and inflammation of the interdigitating layers of specialized epidermal and dermal tissues, the lamellae, which suspend the equine distal phalanx from the hoof capsule. Activation of the interleukin-17 (IL-17)-dependent inflammatory pathway is an epidermal stress response that contributes to physiologic cutaneous wound healing as well as pathological skin conditions. To test the hypothesis that IL-17 pathway activation is involved in equine epidermal lamellae in SLL, we analyzed the expression of the IL-17 receptor subunit A and 11 genes upregulated by IL-17 in lamellar tissue isolated from Thoroughbreds euthanized due to naturally occurring SLL and in age and breed matched non-laminitic controls. The IL-17 Receptor A subunit was expressed in both non-laminitic and laminitic tissues. In severe acute SLL (n=7) compared to non-laminitic controls (n=8), quantitative PCR demonstrated ∼20-100 fold upregulation of ß defensin 4 (E. caballusgeneDEFB4B) andS100A9genes.DEFB4Bwas also upregulated in developmental (n=8), moderate acute (n=7), and severe chronic (n=5) samples. By RT-PCR,S100A8, MMP9, andPTSG2(COX2) expression was upregulated in most or all severe acute SLL samples, whereas several other genes,CCL2, CxCL8, TNFα, IL6andMMP1were detected in some, but not all, severe acute samples.PTGS2, CCL2, TNFαandIL6were also expressed in some, but not all, developmental and moderate acute disease stages. Moreover, expression ofDEFB4by in situ hybridization and calprotectin (S100A9/S100A8) protein by immunofluorescence was detected in keratinocytes, primarily in suprabasal cell layers, from SLL samples. These data support the hypothesis that the IL-17 inflammatory pathway is active in equine SLL, and that similarities exist between equine and human epidermal tissue responses to stresses and/or damage.
Remodeling of Chemotaxis is a Cornerstone of Bacterial Swarming
Authors: Partridge Jonathan D. , Nguyen Nhu Q. , Dufour Yann S. , Harshey Rasika M.
Published: April 2020

Many bacteria use flagella-driven motility to swarm or move collectively over a surface terrain. Bacterial adaptations for swarming can include cell elongation, hyper-flagellation, recruitment of special stator proteins and surfactant secretion, among others. We recently demonstrated another swarming adaptation inEscherichia coli, wherein the chemotaxis pathway is remodeled to increase run durations (decrease tumble bias), with running speeds increased as well. We show here that the modification of motility parameters during swarming is not unique toE. coli, but shared by a diverse group of bacteria we examined –Proteus mirabilis, Serratia marcescens, Salmonella enterica, Bacillus subtilis, andPseudomonas aeruginosa– suggesting that altering the chemosensory physiology is a cornerstone of swarming.

Importance

Bacteria within a swarm move characteristically in packs, displaying an intricate swirling motion where hundreds of dynamic packs continuously form and dissociate as the swarm colonizes increasing expanse of territory. The demonstrated property ofE. colito reduce its tumble bias and hence increase its run duration during swarming is expected to maintain/promote side-by-side alignment and cohesion within the bacterial packs. Here we observe a similar low tumble bias in five different bacterial species, both Gram positive and Gram negative, each inhabiting a unique habitat and posing unique problems to our health. The unanimous display of an altered run-tumble bias in swarms of all species examined here suggests that this behavioral adaptation is crucial for swarming.
Structure of the 4-hydroxy-tetrahydrodipicolinate synthase from the thermoacidophilic methanotroph Methylacidiphilum fumariolicum SolV and the phylogeny of the aminotransferase pathway
Authors: Schmitz Rob A. , Dietl Andreas , Müller Melanie , Berben Tom , Op den Camp Huub J. M. , Barends Thomas R. M.
Published: April 2020

The enzyme 4-hydroxy-tetrahydrodipicolinate synthase (DapA) is involved in the production of lysine and precursor molecules for peptidoglycan synthesis. In a multistep reaction, DapA converts pyruvate and L-aspartate-4-semialdehyde to 4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid. In many organisms, lysine binds allosterically to DapA, causing negative feedback, thus making the enzyme an important regulatory component of the pathway. Here, the 2.1 Å resolution crystal structure of DapA from the thermoacidophilic methanotroph Methylacidiphilum fumariolicum SolV is reported. The enzyme crystallized as a contaminant of a protein preparation from native biomass. Genome analysis reveals that M. fumariolicum SolV utilizes the recently discovered aminotransferase pathway for lysine biosynthesis. Phylogenetic analyses of the genes involved in this pathway shed new light on the distribution of this pathway across the three domains of life.
New kind of interference in the case of X-ray Laue diffraction in a single crystal with uneven exit surface under the conditions of the Borrmann effect. Analytical solution
Authors: Kohn V. G. , Smirnova I. A.
Published: April 2020

The analytical solution of the problem of X-ray spherical-wave Laue diffraction in a single crystal with a linear change of thickness on the exit surface is derived. General equations are applied to a specific case of plane-wave Laue diffraction in a thick crystal under the conditions of the Borrmann effect. It is shown that if a thickness increase takes place at the side of the reflected beam, the related reflected wave amplitude is calculated as a sum of three terms, two of which are complex. If all three terms have a comparable modulus, it can lead to an increase in the reflected beam intensity by up to nine times due to interference compared with the value for a plane parallel shape of the crystal. The equation for the related transmitted wave amplitude contains only two terms. Therefore, the possibility to increase intensity is smaller compared with the reflected beam. The analytical solution is obtained after a solution of the integral equations by means of the Laplace transformation. A general integral form of the Takagi equations derived earlier is used. The results of relative intensity calculations by means of analytical equations coincide with the results of direct computer simulations.
Fostering creativity through online creative collaborative group projects
Authors: Raymundo Maria Rowena D.R.
Published: April 2020

Purpose

Higher education institutions (HEIs) frequently overlook the importance of encouraging creative thinking in students. A review of the prevailing practices in a fully online tertiary distance education (DE) institution revealed a lack of learning activities that foster creativity. The study aims to find out whether the creative collaborative group project is a feasible, effective and acceptable learning activity for fostering creativity in students of a fully online graduate-level DE course.

Design/methodology/approach

Seven groups of five to six graduate students each had five weeks to conceptualize, prepare and deliver a creative collaborative group project on lifelong learning using key concepts learned from the course.

Findings

All groups submitted well-crafted creative projects within the given time frame. Reflections on their experience positively correlated with known outcomes associated with creative skills. Students valued the experience and had a better understanding of the concepts. These support the feasibility, effectiveness and acceptability of the project for fostering creativity in a fully online DE institution.

Research limitations/implications

The feasibility, effectiveness and acceptability may vary in different contexts; future iterations in the same and/or other courses are recommended.

Practical implications

The creative collaborative group project is a feasible, effective and acceptable strategy for fostering creativity in online distance education.

Social implications

Creativity can be enhanced through appropriate online collaborative learning activities.

Originality/value

The study adds to the body of literature on the use of creative collaborative group projects to foster creativity in HEIs.
Investigating the managerial ‘‘nuts and bolts’’ for the construction industry
Authors: Yap Jeffrey Boon Hui , Chow Ian Ni
Published: April 2020

Purpose

Managerial shortfalls can considerably undermine the delivery performance of construction projects. This paper appraises the project management essentials (PMEs) for successful construction project delivery.

Design/methodology/approach

Following a detailed literature review, a questionnaire survey was developed encompassing 20 PMEs that were identified. An opinion questionnaire survey was used to facilitate data collection from key construction stakeholders in the Malaysian construction industry. The survey data were subjected to descriptive statistics and exploratory factor analysis.

Findings

Findings indicated that the leading PMEs are competency of the project team, competency of project manager, good leadership, effective planning and control and realistic cost and time estimate. Spearman’s rank correlation tests affirmed a good agreement on the ranking of PMEs across stakeholder groups. The present study found that PMEs for construction have a total of four dimensions, namely: scope, communication and competence management; stakeholder commitment and collaborative engagement; construction time–cost planning and control; and environment, health, safety and quality management.

Practical implications

The findings could potentially contribute to the development of appropriate project management best practices to address managerial shortfalls in Malaysia and other developing countries.

Originality/value

This paper bridges the identified knowledge gap about critical managerial dimensions for successful project management in construction. The present study adds to the existing body of knowledge around this under-explored area in the construction management literature.
Chemical vegetable safety in China: “supermarketisation” and its limits
Authors: Alita Lita , Dries Liesbeth , Oosterveer Peter
Published: April 2020

Purpose

The purpose of this paper is to analyze the process of supermarketization in the vegetable retail sector in China and its impact on food safety.

Design/methodology/approach

Data from food safety reports by the Chinese Food and Drug Administration (CFDA) are used to investigate the degree of vegetable safety in different value chain types. To assess the predictors of the degree of vegetable safety, a logistic regression model is applied.

Findings

Supermarketization has led to the reorganization of the vegetables provision system, through closer coordination along the supply chain and the use of secured production bases. We identify four types of vegetable value chains in China based on their form of coordination. Supermarkets improve vegetable safety even when they rely on external suppliers, but also wet markets perform significantly better than other small-scale retailers in terms of vegetable safety.

Originality/value

The study has expanded the knowledge of the supermarketization in urban China by collecting data from CFDA. Furthermore, the study used the theory of food value chain to understand determinant factors in securing food safety. Moreover, this study reveals that wet markets also have prospects in solving vegetable safety problems in China, especially in underdeveloped areas.
Ambidextrous leadership and employee innovation in public museums
Authors: Kung Ching-Wen , Uen Jin Feng , Lin Shou-Chi
Published: April 2020

Purpose

The purpose of this paper is to explore the impact of ambidextrous leadership on employees’ innovative behaviors in public museums based on the ambidexterity theory of leadership for innovation. It also examines the mediating mechanism of organizational climate for innovation in public museums.

Design/methodology/approach

Multisource survey data were obtained from 30 human resource managers, 74 department managers and 237 employees of Taiwanese public museums. Multilevel path analysis was conducted to test the proposed model.

Findings

Ambidextrous leadership has the most significant effect on employees’ innovative behaviors. Moreover, organizational climate for innovation has a mediating effect on the relationship between ambidextrous leadership and employees’ innovative behaviors.

Practical implications

This study provides a new perspective on dynamic and complementary ambidextrous leadership, thereby providing important practical implications for innovation management in public museums. Specifically, leaders should apply ambidextrous leadership behaviors in their daily operations to develop an organizational climate for innovation and facilitate employees’ innovative behaviors.

Originality/value

This study is the first to explore the influence of ambidextrous leadership in a museum. In addition, it examines the mediating effect of organizational climate for innovation to explain the effect of ambidextrous leadership on employees’ innovative behaviors. The findings provide valuable insights for both researchers and managers of public and private entities.
Dynamic transportation planning for prefabricated component supply chain
Authors: Zhang Hong , Yu Lu
Published: April 2020

Purpose

Prefabricated construction concerns off-site production, multi-mode transportation and on-site installation of the prefabricated components, which are interdependent and dynamically interactive, so coordination among the multiple stages along the prefabricated component supply chain (PCSC) is indispensable. This study aims to solve the dynamic transportation planning problem for the PCSC by addressing the interdependency, dynamic interaction and coordination among the multiple stages and different objectives of the stakeholders.

Design/methodology/approach

The PCSC is analyzed and then the formulation for the dynamic transportation planning problem is developed based on the just-in-time (JIT) strategy. The particle swarm optimization (PSO) algorithm is applied to solve the dynamic optimization problem.

Findings

The proposed dynamic transportation planning method for the PCSC regarding component supplier selection, transportation planning for means, routes and schedule, site layout planning and transportation plan adjustment is able to facilitate coordination among the multiple stages by addressing their interdependencies and dynamic interactions, as well as different economic objectives of the stakeholders such as suppliers or the contractor.

Originality/value

The study helps to achieve the advantages of prefabricated construction by prompting coordination among multiple stages of the PCSC by realizing different benefits of the stakeholders. In addition, it provides the stakeholders with the competitive bidding prices and the evaluation data for the bids quote. Meanwhile, it contributes to the domain knowledge of the PCSC management with regard to the viewpoint of coordination and integration of multiple stages rather than only one stage as well as the dynamic optimization model based on the JIT strategy and the PSO algorithm.
A variety of completely integrable Calogero–Bogoyavlenskii–Schiff equations with time-dependent coefficients
Authors: Wazwaz Abdul-Majid
Published: April 2020

Purpose

The purpose of this paper is to introduce a variety of new completely integrable Calogero–Bogoyavlenskii–Schiff (CBS) equations with time-dependent coefficients. The author obtains multiple soliton solutions and multiple complex soliton solutions for each of the developed models.

Design/methodology/approach

The newly developed models with time-dependent coefficients have been handled by using the simplified Hirota’s method. Moreover, multiple complex soliton solutions are derived by using complex Hirota’s criteria.

Findings

The developed models exhibit complete integrability, for specific determined functions, by investigating the compatibility conditions for each model.

Research limitations/implications

The paper presents an efficient algorithm for handling integrable equations with analytic time-dependent coefficients.

Practical implications

The work presents new integrable equations with a variety of time-dependent coefficients. The author showed that integrable equations with time-dependent coefficients give real and complex soliton solutions.

Social implications

This study presents useful algorithms for finding and studying integrable equations with time-dependent coefficients.

Originality/value

The paper gives new integrable CBS equations which appear in propagation of waves and provide a variety of multiple real and complex soliton solutions.