bluuebunny/crossref_metadata_2025 huggingface dataset:
Range and Consistency of Outcomes Reported in Randomized Trials Conducted in Kidney Transplant Recipients: A Systematic Review
Authors: Sautenet Bénédicte , Tong Allison , Chapman Jeremy R. , Warrens Anthony N. , Rosenbloom David , Wong Germaine , Gill John , Budde Klemens , Rostaing Lionel , Marson Lorna , Josephson Michelle A , Reese Peter P. , Pruett Timothy L. , Evangelidis Nicole , Craig Jonathan C.
Published: May 2018

Background

The potential for clinical trials to impact patient care may be limited if the outcomes reported vary by trial and lack direct relevance to patients. Despite the many trials conducted in kidney transplantation, premature death due to cardiovascular disease, infection, and malignancy remains high. We aimed to assess the range and consistency of outcomes reported in trials in kidney transplantation.

Methods

We searched for randomized trials conducted in kidney transplantation. We extracted the outcome measures, classified them into outcome domains, and into categories (clinical, surrogate or patient-reported outcome [PRO]). We assessed the measures used for the top 4 domains.

Results

Overall, 397 trials reported 12 047 outcomes measures and time points (median, 19 per trial; interquartile range, 9-42) across 106 different domains, of which 55 (52%) were surrogate, 35 (33%) clinical, and 16 (15%) PRO. The 4 most frequently reported were graft function (322 [81%] trials, 118 outcome measures), acute rejection (234 [59%], 93 measures), graft loss (215 [54%], 48 measures), and mortality (204 [51%], 51 measures). The remaining 102 domains were reported in less than 50% of trials.

Conclusions

Mortality- and graft-related outcome domains were frequently reported and assessed with a multiplicity of measures. Most outcome domains were surrogate outcomes, and the reporting of relevant life-threatening complications and PRO were uncommon. Establishing core outcomes based on the shared priorities of patients/caregivers and health professionals in kidney transplantation may improve the relevance and consistency of outcome reporting in trials to better inform clinical decision making.
Optimizing Temperature and Oxygen Supports Long-term Culture of Human Islets
Authors: Komatsu Hirotake , Rawson Jeffrey , Medrano Leonard , Cook Colin A. , Barriga Alyssa , Gonzalez Nelson , Salgado Mayra , Omori Keiko , Kandeel Fouad , Tai Yu-Chong , Mullen Yoko
Published: May 2018

Background

Islet transplantation is a promising treatment for type-1 diabetes; however, donor shortage is a concern. Even when a pancreas is available, low islet yield limits the success of transplantation. Islet culture enables pooling of multiple low-yield isolations into an effective islet mass, but isolated islets rapidly deteriorate under conventional culture conditions. Oxygen (O2) depletion in the islet core, which leads to central necrosis and volume loss, is one of the major reasons for this deterioration.

Methods

To promote long-term culture of human islets in PIM-R medium (used for islet research), we adjusted temperature (12°C, 22°C, and 37°C) and O2 concentration (21% and 50%). We simulated the O2 distribution in islets based on islet O2 consumption rate and dissolved O2 in the medium. We determined the optimal conditions for O2 distribution and volume maintenance in a 2-week culture and assessed viability and insulin secretion compared to noncultured islets. In vivo islet engraftment was assessed by transplantation into diabetic nonobese diabetic-severe combined immunodeficiency mouse kidneys. We validated our results using CMRL 1066 medium (used for clinical islet transplantation).

Results

Simulation revealed that 12°C of 50% O2 PIM-R culture supplied O2 effectively into the islet core. This condition maintained islet volume at greater than 90% for 2 weeks. There were no significant differences in viability and function in vitro or diabetic reversal rate in vivo between 2-week cultured and noncultured islets. Similar results were obtained using CMRL 1066.

Conclusions

By optimizing temperature and O2 concentration, we cultured human islets for 2 weeks with minimal loss of volume and function.
Impact of CMV PCR Blips in Recipients of Solid Organ and Hematopoietic Stem Cell Transplantation
Authors: Lodding Isabelle P. , Mocroft Amanda , da Cunha Bang Caspar , Gustafsson Finn , Iversen Martin , Kirkby Nikolai , Perch Michael , Rasmussen Allan , Sengeløv Henrik , Sørensen Søren S. , Lundgren Jens D.
Published: May 2018

Background

Viral blips reflecting polymerase chain reaction (PCR) artefacts or transient low-level replication are well described in the human immunodeficiency virus setting. However, the epidemiology of such blips in transplant recipients screened for cytomegalovirus (CMV) with PCR remains uncertain and was investigated in a cohort of solid organ and hematopoietic stem cell recipients.

Methods

Eligible recipients had known donor/recipient CMV IgG serostatus, and 3 CMV PCRs ≥. The CMV PCR triplicates (3 consecutive CMV PCRs) were defined; the first CMV PCR was always negative, and the time between the second and third samples was 7 days ≤. A positive second but negative third sample represented a blip. Odds ratio (OR) for factors associated with a triplicate being a blip was estimated by binomial regression adjusted for repeated measurements. Whether blips affected the hazard ratio (HR) for subsequent CMV infection was determined with a Cox model.

Results

851 recipients generated 3883 CMV PCR triplicates. The OR of a triplicate representing a blip decreased with increasing viral load of the second sample (vs 273 IU/mL; >273-910 IU/mL: odds ratio [OR], 0.2; 95% confidence interval [CI], 0.1-0.5; >910 IU/mL: OR, 0.08; 95% CI, 0.02-0.2; P ≤ 0.0002) and increased with intermediary-/low-risk serostatus (vs high risk) (OR, 2.8; 95% CI, 1.2-5.5; P = 0.01). Cumulative exposure to DNAemia in the CMV blips greater than 910 IU/mL indicated increased HR of subsequent CMV infection (HR, 4.6; 95% CI, 1.2-17.2; P = 0.02).

Conclusions

Cytomegalovirus blips are frequent; particularly when the viral load of the first positive PCR is < 910 IU/mL, and serostatus risk is intermediary/low. Accumulating blips suggest intermittent low-level replication. If blips are suspected, confirmation of ongoing replication before initiation of treatment is prudent.
The expanding spectrum of paroxysmal movement disorders: update from clinical features to therapeutics
Authors: McGovern Eavan M. , Roze Emmanuel , Counihan Timothy J.
Published: May 2018

Purpose of review

This review will discuss the expanding clinical spectrum of paroxysmal movement disorders and therapeutic options in light of emerging genotypic heterogeneity in these conditions.

Recent findings

Paroxysmal movement disorders comprise a heterogeneous group of rare neurological conditions characterized by intermittent episodes of abnormal movement associated with various triggers. As the clinical and genotypic spectrum of these disorders evolves, so also has the range of therapeutic options. Triheptanoin has recently been shown to be a very promising alternative to the ketogenic diet in paroxysmal exercise-induced dyskinesia. Four-aminopyridine is now considered first-line symptomatic therapy for episodic ataxia type-2, with pre-clinical findings indicating cerebellar neuroprotection.

In light of the newly emerging therapies, careful clinical phenotyping is needed to ensure diagnostic precision and timely initiation of appropriate therapies.
Multi-omic profiling of tyrosine kinase inhibitor-resistant K562 cells suggests metabolic reprogramming to promote cell survival
Authors: Noel Brett M. , Ouellette Steven B. , Marholz Laura , Dickey Deborah , Navis Connor , Yang Tzu-Yi , Nguyen Vinh , Parker Sarah J. , Bernlohr David , Sachs Zohar , Parker Laurie L.
Published: May 2018

Resistance to chemotherapy can occur through a wide variety of mechanisms. Resistance to tyrosine kinase inhibitors (TKIs) often arises from kinase mutations-however, “off-target” resistance occurs but is poorly understood. Previously, we established cell line resistance models for three TKIs used in chronic myeloid leukemia treatment, and found that resistance was not attributed entirely to failure of kinase inhibition. Here, we performed global, integrated proteomic and transcriptomic profiling of these cell lines to describe mechanisms of resistance at the protein and gene expression level. We used whole transcriptome sequencing and SWATH-based data-independent acquisition mass spectrometry (DIA-MS), which does not require isotopic labels and provides quantitative measurements of proteins in a comprehensive, unbiased fashion. The proteomic and transcriptional data were correlated to generate an integrated understanding of the gene expression and protein alterations associated with TKI resistance. We defined mechanisms of resistance and two novel markers, CA1 and alpha-synuclein, that were common to all TKIs tested. Resistance to all of the TKIs was associated with oxidative stress responses, hypoxia signatures, and apparent metabolic reprogramming of the cells. Metabolite profiling and glucose-dependence experiments showed that resistant cells had routed their metabolism through glycolysis (particularly through the pentose phosphate pathway) and exhibited disruptions in mitochondrial metabolism. These experiments are the first to report a global, integrated proteomic, transcriptomic and metabolic analysis of TKI resistance. These data suggest that although the mechanisms are complex, targeting metabolic pathways along with TKI treatment may overcome pan-TKI resistance.

Key Points:

Alterations to metabolism are a common feature of target-mutation-independent resistance in CML cells across multiple clinically relevant TKIs.

Carbonic anhydrase 1 (CA1) and a-synuclein (SNCA) are novel markers of metabolic reprogramming in TKI resistant CML cells.
The effect of dream report collection and dream incorporation on memory consolidation during sleep
Authors: Schoch Sarah F. , Cordi Maren J. , Schredl Michael , Rasch Bjöern
Published: May 2018

Waking up during the night to collect dream reports is a commonly used method to study dreams. This method has also been applied in studies on the relationship between dreams and memory consolidation. However, it is unclear if these awakenings influence ongoing memory consolidation processes. Furthermore, only few studies have examined if task incorporation into dreams is related to enhanced performance in the task. Here we compare memory performance in a word-picture association learning task after a night with (up to six awakenings) and without awakenings in 22 young and healthy participants. We then examine if the task is successfully incorporated into the dreams and if this incorporation is related to the task performance the next morning. We show that while the awakenings impair both subjective and objective sleep quality, these awakenings did not impair ongoing memory consolidation during sleep. When dreams were collected during the night by awakenings, memories of the learning task were successfully incorporated into dreams. No incorporation occurred in dreams collected only in the morning. Task incorporation into NREM sleep dreams, but not REM sleep dreams showed a relationship with task performance the next morning.

We conclude that the method of awakenings to collect dream reports is suitable for dream and memory studies, and is even crucial to uncover task incorporations. Furthermore, our study suggests that dreams in NREM rather than REM sleep might be related to processes of memory consolidation during sleep.
Cis-nonProline Peptides: Genuine Occurrences and their Functional Roles
Authors: Richardson Jane S. , Videau Lizbeth L. , Williams Christopher J. , Hintze Bradley J. , Lewis Steven M. , Richardson David C.
Published: May 2018

Whilecispeptides preceding proline can occur about 5% of the time,cispeptides preceding any other residue (“cis-nonPro” peptides) are an extremely rare feature in protein structures, of considerable importance for two opposite reasons. On one hand, their genuine occurrences are mostly found at sites critical to biological function, from the active sites of carbohydrate enzymes to rare adjacent-residue disulfide bonds. On the other hand, acis-nonPro can easily be misfit into weak or ambiguous electron density, which led to a high incidence of unjustifiedcis-nonPro over the 2006-2015 decade. This paper uses high-resolution crystallographic data and especially stringent quality-filtering at the residue level to identify genuine occurrences ofcis-nonPro, and to survey both individual examples and broad patterns of their functionality.

We explain the procedure developed to identify genuinecis-nonPro examples with almost no false positives. We then survey a large sample of the varied functional roles and structural contexts ofcis-nonPro, including the uses of specific amino acids for particular purposes. We emphasize aspects not previously covered: thatcis-nonPro always (except for vicinal disulfides) occur in highly ordered structure, and especially the great concentration of occurrence in proteins that process or bind carbohydrates (identified by occurrence on the CAZy website).
New interfaces on MiD51 for Drp1 recruitment and regulation
Authors: Ma Jun , Zhai Yujia , Chen Ming , Zhang Kai , Chen Quan , Pang Xiaoyun , Sun Fei
Published: May 2018

Mitochondrial fission is facilitated by dynamin-related protein Drp1 and a variety of its receptors. However, the molecular mechanism of how Drp1 is recruited to the mitochondrial surface by receptors MiD49 and MiD51 remains elusive. Here, we showed that the interaction between Drp1 and MiD51 is regulated by GTP binding and depends on the polymerization of Drp1. We identified two regions on MiD51 that directly bind to Drp1, and found that dimerization of MiD51 via an intermolecular disulfide bond between C452 residues is required for MiD51 to directly interact with Drp1. Our Results have suggested a multi-faceted regulatory mechanism for the interaction between Drp1 and MiD51 that illustrates the potentially complicated and tight regulation of mitochondrial fission.
Combined effect of matrix quality and spatial heterogeneity on biodiversity decline
Authors: Ramos Irene , González González Cecilia , Urrutia Ana L. , Mora Van Cauwelaert Emilio , Benítez Mariana
Published: May 2018

The land-sparing/land-sharing debate remains an oversimplified framework to evaluate landscape management strategies that aim to reconcile food production and biodiversity conservation. Still, biodiversity-yield curves, on which the framework has relied, provide valuable qualitative information on biodiversity’s sensitivity to agricultural practices, and much research has studied this relationship. But the potential effect of landscape configuration on biodiversity’s response to intensification has rarely been considered; besides, studies have often taken yield as an indicator of agricultural management and have generalized conclusions from studying particular taxonomic groups. In this work we adapt a metacommunity model to analyze factors that shape biodiversity’s response to agricultural intensification while addressing some of the simplifications of the land-sparing/land-sharing dichotomy. In particular, we study species richness decline in landscapes encompassing a combined gradient in matrix quality and configurational heterogeneity of habitat patches, and considering community dynamics. We found that species richness along an intensification gradient shifts from following a robust response to presenting an abrupt decline, as landscape heterogeneity increases, as stricter survival thresholds are applied to species or as habitat area is reduced. Our work highlights the interdependent effects of heterogeneity, habitat availability and matrix quality on biodiversity and contributes to a nuanced understanding of ecological and landscape factors that enable a robust response of biodiversity in the face of spatiotemporal perturbations.
4-hydroxyphenylpyruvate dioxygenase thermolability is responsible for temperature-dependent melanogenesis inAeromonas salmonicidasubsp.salmonicida
Authors: Qiao Yunqian , Wang Jiao , Wang He , Chai Baozhong , Rao Chufeng , Chen Xiangdong , Du Shishen
Published: May 2018

Aeromonas salmonicidasubsp.salmonicida(A.s.s) is a major pathogen affecting fisheries worldwide. It is a well-known member of the pigmentedAeromonasspecies, which produces melanin at ≤ 22 °C. However, melanogenesis decreases as the culture temperature increases and is completely suppressed at 30-35 °C while bacterial growth is not affected. The mechanism and biological significance of this temperature-dependent melanogenesis are not clear. Heterologous expression of anA.s.s.4-hydroxyphenylpyruvate dioxygenase (HppD), the most crucial enzyme in the HGA-melanin synthesis pathway, results in thermosensitive pigmentation inEscherichia coli, suggesting that HppD plays a key role in this process. In the current study, we demonstrated that the extreme thermolability of HppD is responsible for the temperature-dependent melanization ofA.s.s.Substitutions in three residues, Ser18, Pro103, or Leu119 of HppD fromA.s.sincreases the thermolability of this enzyme and results in temperature-independent melanogenesis. Moreover, replacing the corresponding residues of HppD fromAeromonasmedia strain WS, which forms pigment independent of temperature, with those ofA.s.sHppD leads to thermosensitive melanogenesis. Structural analysis suggested that mutations at these sites, especially at position P103, can strengthen the secondary structure of HppD and greatly improve its thermal stability. In addition, we found that HppD sequences of allA.s.sisolates are identical and that two of the three residues are completely conserved withinA.s.sisolates, which clearly distinguishes these from otherAeromonasstrains. We suggest that this property represents an adaptive strategy to the psychrophilic lifestyle ofA.s.s.

Importance

Aeromonas salmonicidasubsp.salmonicida(A.s.s) is the causative agent of furunculosis, a bacterial septicemia of cold water fish of theSalmonidaefamily. As it has a well-defined host range,A.s.shas become an ideal model to investigate the co-evolution of host and pathogen. For many pathogens, melanin production is associated with virulence. Although other species ofAeromonascan produce melanin,A.s.sis the only member of this genus that has been reported to exhibit temperature-dependent melanization. Here we demonstrate that thermosensitive melanogenesis inA.s.sstrains is due to the thermolability of 4-hydroxyphenylpyruvate dioxygenase (HppD). The strictly conservedhppDsequences amongA.s.sand the exclusive thermosensitive pigmentation of these strains might provide insight into the role of melanin in the adaptation to a particular host, and offer a novel molecular marker to readily differentiateA.s.sstrains from otherA. salmonicidasubspecies andAeromonasspecies.
starmap: Immersive visualisation of single cell data using smartphone-enabled virtual reality
Authors: Yang Andrian , Yao Yu , Li Jianfu , Ho Joshua W. K.
Published: May 2018

We report a new smartphone-enabled virtual reality (VR) program, starmap (https://vccri.github.io/starmap/), that enables immersive visualisation of single-cell data for hundreds of thousands of cells using a mobile-enabled web browser and low-cost VR head mount device.
Radiopotentiation of Enzalutamide Over Human Prostate Cancer Cells as Assessed by Real-Time Cell Monitoring
Authors: Barrado Marta , Blanco-Luquin Idoia , Paola Andrea Navarrete , Visus Ignacio , Guerrero-Setas David , Escors David , Kochan Grazyna , Arias Fernando
Published: May 2018

While radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen blockade will potentiate the cytotoxic activities of radiotherapy. Here we tested the potential synergistic effects of these two treatments over two human metastatic prostate cancer cells by real time growth monitoring (RTCA), androgen-sensitive LNCaP cells and androgen-resistant PC-3. Both cell lines were highly resistant to high doses of radiotherapy. A pre-treatment of LNCaP cells with IC50 concentrations of enzalutamide significantly sensitized them to radiotherapy through enhanced apoptosis. In contrast, enzalutamide resistant PC-3 cells were not sensitized to radiotherapy by androgen blockade. These results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.
Mechanisms of Kinesin-1 activation by Ensconsin/MAP7in vivo
Authors: Métivier Mathieu , Monroy Brigette Y. , Gallaud Emmanuel , Caous Renaud , Pascal Aude , Richard-Parpaillon Laurent , Guichet Antoine , Ori-McKenney Kassandra M. , Giet Régis
Published: May 2018

Centrosome separation inDrosophilalarval neuroblasts and asymmetric transport of embryonic determinants in oocytes are both microtubule-dependent processes that require Kinesin-1 activation by Ensconsin/microtubule-associated protein 7 (MAP7). However, the molecular mechanism used by Ensconsin to activate Kinesin-1 remains elusive. Ensconsin/ MAP7 contains an N-terminal microtubule-binding domain (MBD) and a C-terminal Kinesin-binding domain (KBD). Using rescue experiments in live flies, we show that KBD expression alone is sufficient to fully rescue Ensconsin-dependent centrosome separation defects, but not the fast oocyte streaming and the localization patterns of Staufen and Gurken proteins. Interestingly, we show here for the first time that KBD binds and stimulates Kinesin-1 binding to Mtsin vivoandin vitro. We propose that the KBD/Kinesin-1 motor represents a minimal activation module that stimulates Kinesin-1 binding to Mts. Addition of the MBD, present in the full length Ensconsin allows this activation to occur directly on the Mt. Our data also suggest that in a very large cell with a complex microtubule network, but not in smaller cells, this dual activation by Ensconsin is essential for optimal Kinesin-1 targeting to the microtubule cytoskeleton.
Sedimentation and soil carbon accumulation in degraded mangrove forests of North Sumatra, Indonesia
Authors: Murdiyarso Daniel , Hanggara Bayu Budi , Lubis Ali Arman
Published: May 2018

Mangrove ecosystems are often referred to as “land builders” because of their ability to trap sediments transported from the uplands as well as from the oceans. The sedimentation process in mangrove areas is influenced by hydro-geomorphic settings that represent the tidal range and coastal geological formation. We estimated the sedimentation rate in North Sumatran mangrove forests using the210Pb radionuclide technique, also known as the constant rate supply method, and found that mudflats, fringes, and interior mangroves accreted 4.3 ± 0.2 mm yr−1, 5.6 ± 0.3 mm yr1, and 3.7 ± 0.2 mm yr−1, respectively. Depending on the subsurface changes, these rates could potentially keep pace with global sea level rise of 2.6−3.2 mm yr−1, except the interior mangrove they would also be able to cope with regional sea-level rise of 4.2 ± 0.4 mm yr−1. The mean soil carbon accumulation rates in the mudflats, fringes, and interior areas were 40.1 ± 6.9 g C m−2yr−1, 50.1 ± 8.8 g C m−2yr−1, and 47.7 ± 12.5 g C m−2yr−1, respectively, much lower than the published global average of 226 ± 39 g C m−2yr−1. We also found that based on the excess of radioactive elements derived from atomic bomb fallout, the sediment in the mudflat area was deposited since over 28 years ago, and is much younger than the sediment deposited in the interior and fringe areas that are 43 years 54 years old, respectively.
Cohesin interacts with a panoply of splicing factors required for cell cycle progression and genomic organization
Authors: Kim Jung-Sik , He Xiaoyuan , Liu Jie , Duan Zhijun , Kim Taeyeon , Gerard Julia , Kim Brian , Lane William S. , Noble William S. , Budnik Bogdan , Waldman Todd
Published: May 2018

The cohesin complex regulates sister chromatid cohesion, chromosome organization, gene expression, and DNA repair. Here we report that endogenous human cohesin interacts with a panoply of splicing factors and RNA binding proteins, including diverse components of the U4/U6.U5 tri-snRNP complex and several splicing factors that are commonly mutated in cancer. The interactions are enhanced during mitosis, and the interacting splicing factors and RNA binding proteins follow the cohesin cycle and prophase pathway of regulated interactions with chromatin. Depletion of cohesin-interacting splicing factors results in stereotyped cell cycle arrests and alterations in genomic organization. These data support the hypothesis that splicing factors and RNA binding proteins control cell cycle progression and genomic organization via regulated interactions with cohesin and chromatin.

One Sentence Summary

Endogenous tagging reveals that cohesin interacts with diverse chromatin-bound splicing factors that regulate cell cycle progression and genomic organization in human cells.
Mammalian stringent-like response mediated by the cytosolic NADPH phosphatase MESH1
Authors: Ding Chien-Kuang Cornelia , Rose Joshua , Wu Jianli , Sun Tianai , Chen Kai-Yuan , Chen po-Han , Xu Emily , Tian Sarah , Akinwuntan Jadesola , Guan Ziqiang , Zhou Pei , Chi Jen-Tsan
Published: May 2018

Nutrient deprivation triggers stringent response in bacteria, allowing rapid reallocation of resources from proliferation toward stress survival. Critical to this process is the accumulation/degradation of (p)ppGpp regulated by the RelA/SpoT homologues. While mammalian genomes encode MESH1, a homologue of the bacterial (p)ppGpp hydrolase SpoT, neither (p)ppGpp nor its synthetase has been identified in mammalian cells. Therefore, the function of MESH1 remains a mystery. Here, we report that human MESH1 is an efficient cytosolic NADPH phosphatase, an unexpected enzymatic activity that is captured by the crystal structure of the MESH1-NADPH complex. MESH1 depletion promotes cell survival under ferroptosis-inducing conditions by sustaining the level of NADPH, an effect that is reversed by the simultaneous depletion of the cytosolic NAD(H) kinase, NADK, but not its mitochondrial counterpart NADK2. Importantly, MESH1 depletion also triggers extensive transcriptional changes that are distinct from the canonical integrated stress response but resemble the bacterial stringent response, implicating MESH1 in a previously uncharacterized stress response in mammalian cells.
The RhoGAP myosin 9/HUM-7 integrates membrane signals to modulate Rho/RHO-1 during embryonic morphogenesis inC. elegans
Authors: Wallace Andre G. , Raduwan Hamidah , Carlet John , Soto Martha C.
Published: May 2018

During embryonic morphogenesis, cells and tissues undergo dramatic movements under the control of F-actin regulators. Our studies of epidermal cell migrations in developingC. elegansembryos have identified multiple plasma membrane signals that regulate the Rac GTPase, thus regulating WAVE and Arp2/3 complexes, to promote branched F-actin formation and polarized enrichment. We describe here a pathway that acts in parallel to Rac to transduce membrane signals to control epidermal F-actin through the GTPase Rho. Rho contributes to epidermal migrations through effects on underlying neuroblasts. Here we identify signals to regulate Rho in the epidermis. HUM-7, theC. eleganshomolog of human Myo9A and Myo9B, regulates F-actin dynamics during epidermal migrations, by controlling Rho. Genetics and biochemistry support that HUM-7 behaves as GAP for the Rho GTPase, so that loss of HUM-7 enhances Rho-dependent epidermal cell behaviors. We identify SAX-3/ROBO as an upstream signal that contributes to attenuated Rho activation through its regulation of HUM-7/Myo9. These studies identify a new role for Rho during epidermal cell migrations, and suggest that Rho activity is regulated by SAX-3/ROBO acting on the RhoGAP HUM-7.
DNA-segment-capture model for loop extrusion by structural maintenance of chromosome (SMC) protein complexes
Authors: Marko John F. , De Los Rios Paolo , Barducci Alessandro , Gruber Stephan
Published: May 2018

Cells possess remarkable control of the folding and entanglement topology of long and flexible chromosomal DNA molecules. It is thought that structural maintenance of chromosome (SMC) protein complexes play a crucial role in this, by organizing long DNAs into series of loops. Experimental data suggest that SMC complexes are able to translocate on DNA, as well as pull out lengths of DNA via a “loop extrusion” process. We describe a Brownian loop-capture-ratchet model for translocation and loop extrusion based on known structural, catalytic, and DNA-binding properties of theBacillus subtilisSMC complex. Our model provides an example of a new class of molecular motor where large conformational fluctuations of the motor ‘track’ - in this case DNA - are involved in the basic translocation process. Quantitative analysis of our model leads to a series of predictions for the motor properties of SMC complexes, most strikingly a strong dependence of SMC translocation velocity and step size on tension in the DNA track that it is moving along, with “stalling” occuring at subpiconewton tensions. We discuss how the same mechanism might be used by structurally related SMC complexes (E. coliMukBEF and eukaryote condensin, cohesin and SMC5/6) to organize genomic DNA.
On the design of treatment schedules that avoid chemotherapeutic resistance
Authors: Ma Y. , Newton P.K.
Published: May 2018

We introduce a method of designing treatment schedules for a model three-component replicator dynamical system that avoids chemotherapeutic resistance by controlling and managing the competitive release of resistant cells in the tumor. We use an evolutionary game theory model with prisoner’s dilemma payoff matrix that governs the competition among healthy cells, chemo-sensitive cells, and chemo-resistant cells and the goal is to control the evolution of chemo-resistance via the competitive release mechanism. The method is based on nonlinear trajectory design and energy transfer methods first introduced in the orbital mechanics literature for Hamiltonian systems. By using the structure of the trajectories defined by solutions of the replicator system for different constant chemotherapeutic concentrations (which produces a curvilinear coordinate system spanning the full region), we construct periodic (closed) orbits by switching the chemo-dose at carefully chosen times and appropriate levels to design schedules that are superior to both maximum tolerated dose (MTD) schedules and low-dose metronomic (LDM) schedules, both of which ultimately lead to fixation of either sensitive cells or resistant cells. By keeping the three sub-populations of cells in competition with each other, neither the sensitive cell population nor the resitant cell population are able to dominate as we balance the populations indefinitely (closed periodic orbits), thereby avoiding fixation of the cancer cell population and re-growth of a resistant tumor. The schedules we design have the feature that they maintain a higher average population fitness than either the MTD or the LDM schedules.

PACS numbers: 87.23.Kg; 87.55.de; 87.19.Xj; 87.19.lr
Crystal structure of an inactive variant of the quorum-sensing master regulator HapR from the protease-deficient non-O1, non-O139Vibrio choleraestrain V2
Authors: Cruite Justin , Succo Patrick , Raychaudhuri Saumya , Kull F. Jon
Published: May 2018

HapR is a TetR-family transcriptional regulator that controls quorum sensing inVibrio cholerae, the causative agent of cholera. HapR regulates the expression of hemagglutinin protease, virulence and biofilm genes. The crystal structure of wild-type HapR fromV. choleraestrain O1 El Tor C6706 has previously been solved. In this study, the structure of a DNA-binding-deficient variant of HapR (HapRV2) derived from the protease-deficientV. choleraeserotype O37 strain V2 is reported. The structure reveals no structural differences compared with wild-type HapR. However, structural alignment of HapRV2with the TetR-family member QacR in complex with its operator DNA suggests that the aspartate residue located between the regulatory and DNA-binding domains may clash with and electrostatically repel the phosphate backbone of DNA to prevent binding.
Foreign exchange exposure in Latin America: evidence for Spanish firms
Authors: Vivel-Búa María Milagros , Lado-Sestayo Rubén
Published: May 2018

Objective

The purpose of this paper is to analyse the Spanish business sector’s economic exposure to currency risk in Latin America between 2010 and 2016, testing the effectiveness of hedging with derivatives for the reduction of this risk.

Methodology

Economic exposure is tested with the Jorion model (1990) using both a currency basket and an individualised analysis for the main currencies sustaining business activities between Spain and Latin America: the Mexican peso, Brazilian real, Argentine peso, Chilean peso, and Colombian peso. For the hedging analysis, dynamic panel data models were estimated using a generalised method of moments.

Results

The results reveal that the number of firms with significant economic exposure is sensitive to the temporal frequency of the observations. The evidence denotes that the firms’ export profile is predominant, both when considering a basket of Latin American currencies and when individually considering the five main pairs of currencies. The only exception is the Argentine peso, where firms’ import profile is slightly higher. The Chilean peso stands out as the currency with the greatest number of firms with significant exposure.

Originality

This work provides unpublished evidence on economic exposure to currency risk in Latin America in a recent period characterised by two main aspects: an important devaluation of some Latin American currencies with respect to the euro; and an enhancement of Spanish business activities in the region to favour growth during the recent recession of the Spanish economy.
A new index to measure ease of doing business at the sub-national level
Authors: Tan Khee Giap , Amri Mulya , Merdikawati Nurina
Published: May 2018

Purpose

The purpose of this paper is to propose a novel framework to measure ease of doing business (EDB) that undertakes a holistic approach incorporating three distinct environments: attractiveness to investors, business friendliness, and competitive policies (ABC). This is offered as an alternative to existing popular indicators of doing business (DB), allowing for better approximation of investment and economic growth at the sub-national level.

Design/methodology/approach

The proposed “EDB Index ABC” aggregates 74 indicators into five sub-environments, three environments, and ultimately into the overall EDB Index ABC. Values are standardised using the standardised score method. The framework is applied to 33 Indonesian provinces using a combination of primary data from surveying the business community and government departments as well as secondary data from formal government statistics.

Findings

The findings suggest a positive association between the proposed EDB Index ABC and competitiveness as well as investments into Indonesian provinces. In terms of explanatory power, attractiveness to investors and business friendliness seem to be stronger and more consistent, while the role of competitive policies is more ambiguous.

Originality/value

This research departs significantly from conventional approaches to the study of DB that tend to overwhelmingly focus on formal regulatory aspects by including macroeconomic factors such as market potential and infrastructure resilience as well as micro-level variables such as profitability and cost effectiveness, and the role of government in managing competition. Responding to calls for a bottom-up approach in understanding the EDB, the EDB Index ABC is applied to 33 Indonesian provinces.
Firm CSR implementation and societal moral degradation
Authors: Li Zhiqiang , Zheng Qinqin
Published: May 2018

Purpose

This paper aims to examine how firms respond to societal moral degradation in a transition economy from the corporate social responsibility (CSR) perspective.

Design/methodology/approach

Based on a survey of 302 firms operating in China and using hierarchical regression, this study explores the effect of societal moral degradation on firm CSR implementation.

Findings

The study finds that the amount of CSR performed by firms in a transition market will reduce when they face increased moral degradation in the business field. The authors also find that CSR philanthropy is more significantly deterred by societal moral degradation than CSR sustainability.

Practical implications

These findings reveal that firms conducting CSR initiatives need to strategically consider the great influence of environment. Meanwhile, strategic CSR decisions should be fully aware of the different characters of different CSR forms.

Originality/value

This paper draws on the strategic choice theory and contributes to understanding of the influence of specific environmental factors in transition economies on CSR implementation. Based on two main categories of CSR, this study develops a framework that explores how firms choose different CSR forms when they encounter severe moral degradation in business sector.
On business short-termism: the case of CVS’s discontinuing tobacco sales
Authors: Gooding Chase , Stephenson E. Frank
Published: May 2018

Purpose

The purpose of this paper is to examine the effect of CVS’s decision to stop tobacco sales on the company’s share price.

Design/methodology/approach

The paper uses event study methodology to examine the same day effect of CVS’s announcement and the one-year later effect of CVS’s announcement. Competing pharmacy retail chains’ stock performance is included for comparison purposes.

Findings

CVS’s shares fell by about one percentage point on the day of the company’s announcement while competitors’ share prices increased. A year later, however, CVS’s share price had increased by about twice as much as competitors’ share prices.

Originality/value

The finding that a company can make a decision that harms its short-run share price in exchange for a long-run share appreciation suggests that short-termism may not be as significant a concern as some critics of corporate management suggest.
Bargaining over crowdfunding benefits
Authors: Bade Marco
Published: May 2018

Purpose

Crowdfunding creates multifaceted benefits for different agents who all desire to extract some of these benefits. The purpose of this paper is to analyze the allocation of crowdfunding benefits among crowdfunders, entrepreneurs, and venture capitalists.

Design/methodology/approach

The present paper develops a multi-stage bargaining model with a double-sided moral hazard.

Findings

It is demonstrated that higher entrepreneurial bargaining power vis-à-vis the crowd may not always be beneficial for the venture. Most importantly, this is due to the reduced success probability of crowdfunding resulting from higher bargaining power of the entrepreneur. Bargaining power and the value of outside options determine the equilibrium allocation of crowdfunding benefits, expected venture value, and thus expected wealth of all agents.

Practical implications

Entrepreneurs face a tradeoff between venture quality gains and worse outcomes from crowdfunding campaigns. Crowdfunding success and thus venture quality gains are the ultimate goal of policy makers if they aim to enhance the overall social welfare.

Originality/value

This paper is the first to investigate how multifaceted crowdfunding benefits are allocated between the crowd, entrepreneurs, and venture capitalists. The paper furthers the development of an appropriate regulatory framework for crowdfunding by depicting new and original effects related to crowdfunding.
Effects of multi-brand company’s CSR activities on purchase intention through a mediating role of corporate image and brand image
Authors: Lee Jihyun , Lee Yuri
Published: May 2018

Purpose

The purpose of this paper is to examine the effect of the corporate social responsibility (CSR) activities of a fashion company with multiple brands. In particular, the aim is to determine the differences in the impact of corporate-level and brand-level CSR.

Design/methodology/approach

The data were collected using an online survey from the consumer panel of a marketing research firm in South Korea. The subjects were presented with the following stimuli of a fashion company with multiple brands: describing corporate-level CSR activities of a company (n=109) and describing brand-level CSR activities of a company (n=113). After processing the information, the participants were asked to evaluate their reciprocity perception, corporate image, brand image, and purchase intention.

Findings

Regarding corporate-level CSR, participants’ reciprocity perception positively and directly affected purchase intention. It also positively affected corporate image, and corporate image affected brand image, and brand image positively affected purchase intention. Regarding brand-level CSR, reciprocity perception did not affect purchase intention directly, but positively affected purchase intention through mediation of corporate image. This study found a construct where reciprocity perception influences purchase intention with a mediating role of corporate image and brand image. The effect of reciprocity perception shaped by corporate-level CSR is greater than that shaped by brand-level CSR.

Originality/value

The outcome of this study provides meaningful insights and practical implications for companies that have multiple brands.
Consumer online purchase behavior of local fashion clothing brands
Authors: Rahman Muhammad Sabbir , Mannan Mahafuz
Published: May 2018

Purpose

The purpose of this paper is to investigate the influence of information adoption, e-WOM, online brand experience and online brand familiarity on consumer online purchase behavior of local fashion clothing brands. The study also examines the influence of central and peripheral route on the consumer information adoption process.

Design/methodology/approach

The research design was cross-sectional. A total of 300 respondents from Bangladesh participated in the self-administered survey who have experienced of purchasing local fashion clothing brand online. Only 273 questionnaires were used in final data analysis after discarding incomplete questionnaires. The study applied PLS-SEM to test the proposed model.

Findings

Central and peripheral route were found to have positive influences on the consumer information adoption process in the context of online purchasing of local fashion clothing brands. Consumer information adoption was found to influence consumer online purchase behavior positively. The information adoption-consumer purchase behavior relationship was found to be partially mediated by e-WOM. Online brand experience was found to influence consumer online purchase behavior positively. The online brand experience-consumer purchase behavior relationship was found to be partially mediated by online brand familiarity.

Originality/value

So far, no studies have investigated how information adoption, e-WOM, online brand experience and online brand familiarity influence consumer purchase behavior of local fashion clothing brand, in a virtual environment under the perspective of a developing country like Bangladesh. This study is also a pioneer in exploring which dimensions have more leverage on central and peripheral route in information adoption in the context of local fashion clothing brand of Bangladesh.
Should I stay or should I go? A systematic literature review about the conceptualization and measurement of international relocation mobility readiness
Authors: Weisheit Jil
Published: May 2018

Purpose

Employees’ readiness to relocate abroad plays a crucial role for the success or failure of expatriate assignments. Hence, companies should consider employees’ international relocation mobility readiness (IRMR) when selecting candidates for international postings. However, past research has conceptualized and measured IRMR heterogeneously, hampering the interpretation and comparability of IRMR research results. Hence, the purpose of this paper is to provide a new conceptualization of IRMR and to give recommendations for its measurement.

Design/methodology/approach

Based on the business, psychological and sociological literature, this paper reviews and categorizes how IRMR has been conceptualized and measured. To structure the findings, a directed content analysis was applied. The sample comprises 88 journal articles.

Findings

The results reveal that studies seldom provide a conceptualization of IRMR. While the authors often find a misfit between the studies’ explicit conceptualization and the actual measurement of IRMR, most scales actually measure willingness (i.e. usually a predictor of risky and spontaneous behavior).

Research limitations/implications

Based on the results and the Rubicon model of action phases (Heckhausen and Gollwitzer, 1987), the authors recommend future research to conceptualize IRMR as a dynamic multidimensional construct, covering the different phases of an individual’s decision to relocate internationally. Future, IRMR measurements should also cover the complexity of IRMR, e.g. regarding specific location characteristics.

Practical implications

Companies should consider the whole decision-making process regarding IRMR to apply specific measures at the best possible time.

Originality/value

This paper investigates IRMR scales according to their scientific validity and hence provides the basic ground for future scale development studies.
Mental health and policing interventions: implementation and impact
Authors: Kane Eddie , Evans Emily
Published: May 2018

Purpose

Interactions between individuals experiencing mental health (MH) problems and the police are complex and may affect the way in which both parties react to and experience the interactions. The purpose of this paper is to examine three commonly used interventions to improve these interactions.

Design/methodology/approach

Mixed methods were used to examine embedded MH professionals in command and control rooms, Liaison and Diversion Teams and Street Triage. The authors also reviewed the use of Section 136 (s136) of the Mental Health Act 1983 (2007) during the period these interventions were deployed.

Findings

There was strong support for these interventions but also gaps, resource and operational issues that need to be addressed if they are to have optimal effect on delivering appropriate diversion from the justice system, reduce reoffending and improve MH outcomes for individuals. The use of s136 remained relatively constant.

Originality/value

Despite a recent increase in the level of investment related to these interventions the evidence base remains limited. This study provides baseline of research evidence for those who commission and provide services for individuals experiencing mental ill health and who are in contact with the justice system.