bluuebunny/crossref_metadata_2025 huggingface dataset:
Intratendinous Injection of Hydrogel for Reseeding Decellularized Human Flexor Tendons
Authors: Long Chao , Galvez Michael G. , Legrand Anais , Joubert Lydia-Marie , Wang Zhen , Chattopadhyay Arhana , Chang James , Fox Paige M.
Published: May 2017

Background:

Decellularized cadaveric tendons are a potential source for reconstruction. Reseeding to enhance healing is ideal; however, cells placed on the tendon surface result in inadequate delivery. The authors used an injection technique to evaluate intratendinous cell delivery.

Methods:

Decellularized tendons were reseeded with adipose-derived stem cells in culture, and injected with fetal bovine serum or hydrogel. PKH26-stained cells in cross-section were quantified. To evaluate cell viability, the authors delivered luciferase-labeled cells and performed bioluminescent imaging. To evaluate synthetic ability, the authors performed immunohistochemistry of procollagen. Adipose-derived stem cells’ ability to attract tenocytes was assessed using transwell inserts. Cell-to-cell interaction was assessed by co-culturing, measuring proliferation and collagen production, and quantifying synergy. Finally, tensile strength was tested.

Results:

Both fetal bovine serum (p < 0.001) and hydrogel (p < 0.001) injection led to more cells inside the tendon compared with culturing. Hydrogel injection initially demonstrated greater bioluminescence than culturing (p < 0.005) and fetal bovine serum injection (p < 0.05). Injection groups demonstrated intratendinous procollagen staining correlating with the cells’ location. Co-culture led to greater tenocyte migration (p < 0.05). Interaction index of proliferation and collagen production assays were greater than 1 for all co-culture ratios, demonstrating synergistic proliferation and collagen production compared with controls (p < 0.05). There were no differences in tensile strength.

Conclusions:

Hydrogel injection demonstrated the greatest intratendinous seeding efficiency and consistency, without compromising tensile strength. Intratendinous cells demonstrated synthetic capabilities and can potentially attract tenocytes inside the tendon, where synergy would promote intrinsic tendon healing.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Pursuing Mirror Image Reconstruction in Unilateral Microtia: Customizing Auricular Framework by Application of Three-Dimensional Imaging and Three-Dimensional Printing
Authors: Chen Hsin-Yu , Ng Li-Shia , Chang Chun-Shin , Lu Ting-Chen , Chen Ning-Hung , Chen Zung-Chung
Published: May 2017

Background:

Advances in three-dimensional imaging and three-dimensional printing technology have expanded the frontier of presurgical design for microtia reconstruction from two-dimensional curved lines to three-dimensional perspectives. This study presents an algorithm for combining three-dimensional surface imaging, computer-assisted design, and three-dimensional printing to create patient-specific auricular frameworks in unilateral microtia reconstruction.

Methods:

Between January of 2015 and January of 2016, six patients with unilateral microtia were enrolled. The average age of the patients was 7.6 years. A three-dimensional image of the patient’s head was captured by 3dMDcranial, and virtual sculpture carried out using Geomagic Freeform software and a Touch X Haptic device for fabrication of the auricular template. Each template was tailored according to the patient’s unique auricular morphology. The final construct was mirrored onto the defective side and printed out with biocompatible acrylic material.

Results:

During the surgery, the prefabricated customized template served as a three-dimensional guide for surgical simulation and sculpture of the MEDPOR framework. Average follow-up was 10.3 months. Symmetric and good aesthetic results with regard to auricular shape, projection, and orientation were obtained. One case with severe implant exposure was salvaged with free temporoparietal fascia transfer and skin grafting.

Conclusions:

The combination of three-dimensional imaging and manufacturing technology with the malleability of MEDPOR has surpassed existing limitations resulting from the use of autologous materials and the ambiguity of two-dimensional planning. This approach allows surgeons to customize the auricular framework in a highly precise and sophisticated manner, taking a big step closer to the goal of mirror-image reconstruction for unilateral microtia patients.

CLINCIAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Buccal Fat Pad Augmentation for Facial Rejuvenation
Authors: Cohen Steven R. , Fireman Emily , Hewett Sierra , Saad Ahmad
Published: May 2017

The buccal space, with its fat pad, is a valuable, overlooked target in facial rejuvenation procedures. The authors identified a specific group of patients who have normal or prominent malar projection in the presence of atrophy of the buccal fat pad, with or without prominent gonial angles. Eight of 24 prospectively studied patients (Biomedical Research Institute of America) who had fat grafts and face lifts received an average of 2.7 ml of fat transferred into the buccal space. Immediate visual correction of the buccal depression was noted. No overcorrection was carried out. None of the eight patients suffered an adverse event from transoral buccal space fat grafting. Persistent facial volume in this area has been noted up to 24 months after treatment. In patients with buccal fat pad atrophy, fat grafting into the buccal space can be safely performed through an intraoral approach.
Safety of Outpatient Circumferential Body Lift: Evidence from 42 Consecutive Cases
Authors: Makipour J. John , Nuveen Erik , Abbott Diana
Published: May 2017

Background:

Circumferential lower body lifts have become more prevalent with the rise of massive weight loss surgery. This has historically required inpatient admission. Only three previous groups have published their experience with outpatient lower body lifts.

Methods:

The authors reviewed their experience with 42 consecutive outpatient circumferential body lifts from 2010 to 2016, and report patient demographics, operative details, and postoperative outcomes. Several variables are evaluated for statistical associations with complications and revisions. In addition, the three largest published accounts of inpatient lower body lifts are summarized and presented for comparison, with the data from this group pooled with the three previously published accounts of outpatient circumferential lower body lifts.

Results:

Forty-two consecutive circumferential lower body lifts were performed with and without a diverse array of other procedures. Average follow-up was 10.4 months. No patients required hospitalization. A complication rate of 36 percent and a revision rate of 26 percent were similar to those for inpatient groups. As with inpatient cohorts, the vast majority of complications were related to minor incisional separations. No statistical association was made between complications or revisions and the presence of (1) multiple surgeons, (2) fleur-de-lis modification, (3) concurrent cosmetic procedures, (4) liposuction, or (5) body mass index greater than 25 kg/m2. An association was identified between venous thromboembolic events and admission for circumferential body lift.

Conclusions:

The authors report the third largest, and fourth ever, published account of circumferential lower body lift in the English language literature. Based on these data, it safe to offer outpatient lower body lifts to appropriately chosen patients.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Multidisciplinary Point-of-Care Testing in South African Primary Health Care Clinics Accelerates HIV ART Initiation but Does Not Alter Retention in Care
Authors: Stevens Wendy S. , Gous Natasha M. , MacLeod William B. , Long Lawrence C. , Variava Ebrahim , Martinson Neil A. , Sanne Ian , Osih Regina , Scott Lesley E.
Published: May 2017

Background:

Lack of accessible laboratory infrastructure limits HIV antiretroviral therapy (ART) initiation, monitoring, and retention in many resource-limited settings. Point-of-care testing (POCT) is advocated as a mechanism to overcome these limitations. We executed a pragmatic, prospective, randomized, controlled trial comparing the impact of POCT vs. standard of care (SOC) on treatment initiation and retention in care.

Methods:

Selected POC technologies were embedded at 3 primary health clinics in South Africa. Confirmed HIV-positive participants were randomized to either SOC or POC: SOC participants were venesected and specimens referred to the laboratory with patient follow-up as per algorithm (∼3 visits); POC participants had phlebotomy and POCT immediately on-site using Pima CD4 to assess ART eligibility followed by hematology, chemistry, and tuberculosis screening with the goal of receiving same-day adherence counseling and treatment initiation. Participant outcomes measured at recruitment 6 and 12 months after initiation.

Results:

Four hundred thirty-two of 717 treatment eligible participants enrolled between May 2012 and September 2013: 198 (56.7%) SOC; 234 (63.6%) POC. Mean age was 37.4 years; 60.5% were female. Significantly more participants were initiated using POC [adjusted prevalence ratio (aPR) 0.83; 95% confidence interval (CI): 0.74 to 0.93; P < 0.0001], the median time to initiation was 1 day for POC and 26.5 days for SOC. The proportion of patients in care and on ART was similar for both arms at 6 months (47 vs. 50%) (aPR 0.96; 95% CI: 0.79 to 1.16) and 12 months (32 vs. 32%) (aPR 1.05; 95% CI: 0.80 to 1.38), with similar mortality rates. Loss to follow-up at 12 months was higher for POC (36% vs. 51%) (aPR 0.82; 95% CI: 0.65 to 1.04).

Conclusions:

Adoption of POCT accelerated ART initiation but once on treatment, there was unexpectedly higher loss to follow-up on POC and no improvement in outcomes at 12 months over SOC.
De novo indels within introns contribute to ASD incidence
Authors: Munoz Adriana , Yamrom Boris , Lee Yoon-ha , Andrews Peter , Marks Steven , Lin Kuan-Ting , Wang Zihua , Krainer Adrian R. , Darnell Robert B. , Wigler Michael , Iossifov Ivan
Published: May 2017

Copy number profiling and whole-exome sequencing has allowed us to make remarkable progress in our understanding of the genetics of autism over the past ten years, but there are major aspects of the genetics that are unresolved. Through whole-genome sequencing, additional types of genetic variants can be observed. These variants are abundant and to know which are functional is challenging. We have analyzed whole-genome sequencing data from 510 of the Simons Simplex Collections quad families and focused our attention on intronic variants. Within the introns of 546 high-quality autism target genes, we identified 63 de novo indels in the affected and only 37 in the unaffected siblings. The difference of 26 events is significantly larger than expected (p-val = 0.01) and using reasonable extrapolation shows that de novo intronic indels can contribute to at least 10% of simplex autism. The significance increases if we restrict to the half of the autism targets that are intolerant to damaging variants in the normal human population, which half we expect to be even more enriched for autism genes. For these 273 targets we observe 43 and 20 events in affected and unaffected siblings, respectively (p-value of 0.005). There was no significant signal in the number of de novo intronic indels in any of the control sets of genes analyzed. We see no signal from de novo substitutions in the introns of target genes.
The Proteolytic Landscape of an Arabidopsis Separase-Deficient Mutant Reveals Novel Substrates Associated With Plant Development
Authors: Liu Chen , Stael Simon , Gevaert Kris , Van Breusegem Frank , Bozhkov Peter V , Moschou Panagiotis N
Published: May 2017

Digestive proteolysis executed by the proteasome plays an important role in plant development. Yet, the role of limited proteolysis in this process is still obscured due to the absence of studies. Previously, we showed that limited proteolysis by the caspase-related protease separase (EXTRA SPINDLE POLES [ESP]) modulates development in plants through the cleavage of unknown substrates. Here we used a modified version of the positional proteomics method COmbined FRActional DIagonal Chromatography (COFRADIC) to survey the proteolytic landscape of wild-type and separase mutantRADIALLY SWOLLEN 4(rsw4) root tip cells, as an attempt to identify targets of separase. We have discovered that proteins involved in the establishment of pH homeostasis and sensing, and lipid signalling in wild-type cells, suggesting novel potential roles for separase. We also observed significant accumulation of the protease PRX34 inrsw4which negatively impacts growth. Furthermore, we observed an increased acetylation of N-termini ofrsw4proteins which usually comprise degrons identified by the ubiquitin-proteasome system, suggesting that separase intersects with additional proteolytic networks. Our results hint to potential pathways by which separase could regulate development suggesting also novel proteolytic functions.
Image Memorability in the Eye of the Beholder: Tracking the Decay of Visual Scene Representations
Authors: Võ Melissa Le-Hoa , Bylinskii Zoya , Oliva Aude
Published: May 2017

Some images stick in your mind for days or even years, while others seem to vanish quickly from memory. We tested whether differences in image memorability 1) are already evident immediately after encoding, 2) produce different rates of forgetting, and 3) whether the retrieval of images with different memorability scores affords differential degrees of cognitive load, mirrored by graded pupillary and blink rate responses. We monitored participants’ eye activity while they viewed a sequence of >1200 images in a repetition detection paradigm. 240 target images from 3 non-overlapping memorability classes were repeated at 4 different lags. Overall, performance decreased log-linearly with time. Differences in memorability were already visible at the shortest lag (~ 20 sec) and became more pronounced as time passed on. The rate of forgetting was steepest for low memorable images. We found that pupils dilated significantly more to correctly identified targets than correctly rejected distractors. Importantly, this “pupil old/new effect” increased with increasing number of lags and decreasing image memorability. A similar modulation of blink rates corroborated these findings. These results suggest that during memory retrieval of scenes, image inherent characteristics pose differential degrees of cognitive load on observers as seen in their eyes.
Matriarchy and prehistory: a statistical method for testing an old theory
Authors: d’Huy Julien
Published: May 2017

Mythological data and statistical methods have been used to reconstruct the phylogeny of matriarchal tales and its relationship to genetic trees. The results show a correlation between the two trees and allow to identify the proto-forms of this mythology. This makes it possible to reject some assumptions about rock art.
Cancer progression models and fitness landscapes: a many-to-many relationship
Authors: Diaz-Uriarte Ramon
Published: May 2017

The identification of constraints, due to gene interactions, in the order of accumulation of mutations during cancer progression can allow us to single out therapeutic targets. Cancer progression models (CPMs) use genotype frequency data from cross-sectional samples to try to identify these constraints, and return Directed Acyclic Graphs (DAGs) of genes. On the other hand, fitness landscapes, which map genotypes to fitness, contain all possible paths of tumor progression. Thus, we expect a correspondence between DAGs from CPMs and the fitness landscapes where evolution happened. But many fitness landscapes —e.g., those with reciprocal sign epistasis— cannot be represented by CPMs. Using simulated data under 500 fitness landscapes, I show that CPMs’ performance (prediction of genotypes that can exist) degrades with reciprocal sign epistasis. There is large variability in the DAGs inferred from each landscape, which is also affected by mutation rate, detection regime, and fitness landscape features, in ways that depend on CPM method. And the same DAG is often observed in very different landscapes, which differ in more than 50% of their accessible genotypes. Using a pancreatic data set, I show that this many-to-many relationship affects the analysis of empirical data. Fitness landscapes that are widely different from each other can, when evolutionary processes run repeatedly on them, both produce data similar to the empirically observed one, and lead to DAGs that are very different among themselves. Because reciprocal sign epistasis can be common in cancer, these results question the use and interpretation of CPMs.
Coordinated shifts in allocation among reproductive tissues across 14 coexisting plant species
Authors: Wenk E. H. , Abramowicz K. , Westoby M. , Falster D. S.
Published: May 2017

Plant species differ in the amounts of energy allocated to different reproductive tissues, driving differences in their ecology and energy flows within ecosystems. While it is widely agreed that energy allocation is key to reproductive outcomes, few studies have estimated how reproductive effort (RE) is partitioned among different pools, for multiple species in a community. In plants, RE can be partitioned in several meaningful ways: seed versus non-seed tissues; into flowers that form seeds and those that fail to develop; into pre-versus post-pollination tissues, and into successful versus aborted ovules. Evolutionary theory suggests several hypotheses about how these tissues should be coordinated across species. To quantify variation in allocation to different reproductive tissues, we collected detailed RE measurements for a year from 14 perennial species in a recurrent-fire coastal heath community in eastern Australia. Overall we found that total accessory costs – the proportion of RE not directly invested in provisioning the seed – were very large, varying from 95.8% to 99.8% across the study species. These results suggest that studies using seed or fruit production as measures of RE may underestimate it by 10-to 500-fold. We propose a suitable alternative that well-approximates true RE. When comparing species, we found strong support for three evolutionary trade-offs that are predicted to arise when a given energy pool is divided into different tissue masses and counts across species: 1) between successful pollen-attraction costs and mature ovule count, 2) between total reproductive costs and seed count, and 3) between seedset and relative investment in pollen-attraction costs. As a result of these trade-offs, species were also predicted to show coordinated shifts in the amounts invested in floral construction, in seedset and seed size. These shifts in investment were indeed observed, with the amount allocated to discarded tissues increasing with seed size and the amount allocated to pollen-attraction decreasing with seed size. It is already well-established that the seed size axis aligns with the colonization-competition life history spectrum; here we show that relative construction costs of pollen-attraction versus provisioning tissues and seedset are also part of this trajectory, expanding our understanding of the relatives sizes of floral and fruiting structures observed across angiosperms.
Stratification of TAD boundaries identified in reproducible Hi-C contact matrices reveals preferential insulation of super-enhancers by strong boundaries
Authors: Gong Yixiao , Lazaris Charalampos , Sakellaropoulos Theodore , Lozano Aurelie , Kambadur Prabhanjan , Ntziachristos Panagiotis , Aifantis Iannis , Tsirigos Aristotelis
Published: May 2017

The metazoan genome is compartmentalized in megabase-scale areas of highly interacting chromatin known as topologically associating domains (TADs), typically identified by computational analyses of Hi-C sequencing data. TADs are demarcated by boundaries that are largely conserved across cell types and even across species, although, increasing evidence suggests that the seemingly invariant TAD boundaries may exhibit plasticity and their insulating strength can vary. However, a genome-wide characterization of TAD boundary strength in mammals is still lacking. A systematic classification and characterization of TAD boundaries may generate new insights into their function. In this study, we first use fused two-dimensional lasso as a machine learning method to improve Hi-C contact matrix reproducibility, and, subsequently, we categorize TAD boundaries based on their insulation score. We demonstrate that higher TAD boundary insulation scores are associated with elevated CTCF levels and that they may differ across cell types. Intriguingly, we observe that super-enhancer elements are preferentially insulated by strong boundaries, i.e. boundaries of higher insulation score. Furthermore, we perform a pan-cancer analysis to demonstrate that strong TAD boundaries and super-enhancer elements are frequently co-duplicated in cancer patients. Taken together, our findings suggest that super-enhancers insulated by strong TAD boundaries may be exploited, as a functional unit, by cancer cells to promote oncogenesis.
Natural mismatch repair mutations mediate phenotypic diversity and drug resistance inCryptococcus deuterogattii
Authors: Billmyre R. Blake , Clancey Shelly Applen , Heitman Joseph
Published: May 2017

Pathogenic microbes confront a constant evolutionary conflict between the pressure to maintain genome stability and the need to adapt to mounting external stresses. Prokaryotes often respond with elevated mutation rates, but to date little evidence exists of stable eukaryotic hypermutators in nature. Whole genome resequencing of the human fungal pathogenCryptococcus deuterogattiiidentified an outbreak lineage characterized by a nonsense mutation inMSH2. This defect in mismatch repair results in a moderate mutation rate increase in typical genes, and a larger increase in genes containing homopolymer runs. This allows facile inactivation of genes with coding homopolymer runs includingFRR1, which encodes the target of the immunosuppresive antifungal drugs FK506 and rapamycin. Our study identifies a eukaryotic hypermutator lineage spread over two continents and suggests that pathogenic eukaryotic microbes may experience similar selection pressures on mutation rate as bacterial pathogens, particularly during long periods of clonal growth or while expanding into new environments.
Genome-wide SNP discovery in field and laboratory colonies of AustralianPlutellaspecies
Authors: Perry K.D. , Pederson S.M. , Baxter S.W.
Published: May 2017

Understanding dispersal and gene flow is an important focus of evolutionary biology, conservation biology and pest management. The diamondback moth,Plutella xylostella, is a worldwide pest ofBrassicavegetable and oilseed cropping systems. This insect has high dispersal ability, which has important consequences for population dynamics and the potential spread of insecticide resistance genes. Population genetic studies of the diamondback moth have found little evidence of population structure, suggesting that frequent intermixing occurs within regions, however the patterns of local and regional dispersal remain to be identified. For this and many other pest species, understanding dispersal is crucial for developing integrated management tactics such as forecasting systems and insecticide resistance management plans. In recent years, next generation sequencing (NGS) methods have provided previously unparalleled resolution for population genetic studies in a wide range of species. Here, we assessed the potential of NGS-derived molecular markers to provide new insights about population structure in the diamondback moth. We use restriction-site-associated DNA sequencing (RAD-Seq) to discover hundreds to thousands of single nucleotide polymorphism (SNP) markers in nine field and laboratory-reared populations collected from Australia. Genotypic data from RAD-Seq markers identified a cryptic species,P. australiana, among individuals collected from a wild host,Diplotaxissp., indicating strong divergence in the nuclear genomes of two AustralianPlutellalineages. Significant genetic differentiation was detected among populations ofP. xylostellaused in our study, however this could be explained by reduced heterozogosity and genetic drift in laboratory-reared populations founded by relatively few individuals. This study demonstrates that RAD-Seq is a powerful method for generating SNP markers for population genetic studies in this species.
The peach RGF/GLV signalling peptide pCTG134 is involved in a regulatory circuit that sustains auxin and ethylene actions
Authors: Busatto Nicola , Salvagnin Umberto , Resentini Francesca , Quaresimin Silvia , Navazio Lorella , Marin Oriano , Pellegrini Maria , Costa Fabrizio , Mierke Dale F. , Trainotti Livio
Published: May 2017

Peach is a climacteric species whose ripening is regulated by the plant hormone ethylene. A crosstalk mechanism with auxin is necessary to support climacteric ethylene synthesis. The homeostasis control of auxin is regulated also by the activity of peptide hormones (PHs), acting both as short and long distant ligands. In this work, we investigated the role ofCTG134, a peach gene encoding a GOLVEN-like PH isolated in mesocarp at the onset of ripening.

In peach fruit,CTG134was expressed during the climacteric transition and its mRNA level was induced by auxin and 1-methylcyclopropene (1-MCP) treatments, whereas it was minimally affected by ethylene. To better elucidate its function,CTG134was overexpressed inArabidopsisand tobacco, which showed abnormal root hair growth, similar to wild-type plants treated with a synthetic form of the peptide. Molecular surveys demonstrated an impaired hormonal crosstalk, resulting in a re-modulated expression of a set of genes involved in both ethylene and auxin domains. In addition, the promoter of pCTG134 fused with GUS reporter highlighted gene activity in plant organs in which the auxin-ethylene interplay is known to occur. These data support the role of pCTG134 as mediator in an auxin-ethylene regulatory circuit.

Highlight

The role of the peach RGF/GLV peptide during root hair formation inArabidopsisand tobacco supports its involvement in a cross-hormonal auxin-ethylene regulatory circuit.
Cross-cultural effects on ensemble coding of emotion in facial crowds
Authors: Im Hee Yeon , Chong Sang Chul , Sun Jisoo , Steiner Troy G. , Albohn Daniel N. , Adams Reginald B. , Kveraga Kestutis
Published: May 2017

In many social situations, we make a snap judgment about crowds of people relying on their overall mood (termed “crowd emotion”). Although reading crowd emotion is critical for interpersonal dynamics, the sociocultural aspects of this process have not been explored. The current study examined how culture modulates the processing of crowd emotion in Korean and American observers. Korean and American participants were briefly presented with two groups of faces that were individually varying in emotional expressions and asked to choose which group between the two they would rather avoid. We found that Korean participants were more accurate than American participants overall, in line with the framework on cultural viewpoints: Holistic versus analytic processing in East Asians versus Westerners. Moreover, we found a speed advantage for other-race crowds in both cultural groups. Finally, we found different hemispheric lateralization patterns: American participants were more accurate for angry crowds presented in the left visual field and happy crowds presented in the right visual field, replicating previous studies, whereas Korean participants did not show an interaction between emotional valence and visual field. This work suggests that culture plays a role in modulating our crowd emotion perception of groups of faces and responses to them.
A kinetically-driven free exchange mechanism of EmrE antiport sacrifices coupling efficiency in favor of promiscuity
Authors: Robinson Anne E. , Thomas Nathan E. , Morrison Emma A. , Balthazor Bryan , Henzler-Wildman Katherine A.
Published: May 2017

EmrE is a small multidrug resistance transporter found inE. colithat confers resistance to toxic polyaromatic cations due to its proton-coupled antiport of these substrates. Here we show that EmrE breaks the rules generally deemed essential for coupled antiport. NMR spectra reveal that EmrE can simultaneously bind and cotransport proton and drug. The functional consequence of this finding is an exceptionally promiscuous transporter: Not only can EmrE export diverse drug substrates, it can couple antiport of a drug to either one or two protons, performing both electrogenic and electroneutral transport of a single substrate. We present a new kinetically-driven free exchange model for EmrE antiport that is consistent with these results and recapitulates ΔpH-driven concentrative drug uptake. Our results suggest that EmrE sacrifices coupling efficiency for initial transport speed and multidrug specificity.

SIGNIFICANCE

EmrE facilitatesE. colimultidrug resistance by coupling drug efflux to proton import. This antiport mechanism has been thought to occur via a pure exchange model which achieves coupled antiport by restricting when the single binding pocket can alternate access between opposite sides of the membrane. We test this model using NMR titrations and transport assays and find it cannot account for EmrE antiport activity. We propose a new kinetically-driven free exchange model of antiport with fewer restrictions that better accounts for the highly promiscuous nature of EmrE drug efflux. This model expands our understanding of coupled antiport and has implications for transporter design and drug development.
Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism
Authors: Putzbach William , Gao Quan Q. , Patel Monal , van Dongen Stijn , Haluck-Kangas Ashley , Sarshad Aishe A. , Bartom Elizabeth , Kim Kwang-Youn A. , Scholtens Denise M. , Hafner Markus , Zhao Jonathan C. , Murmann Andrea E. , Peter Marcus E.
Published: May 2017

Over 80% of multiple tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3’UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death. By testing 4666 shRNAs derived from the CD95 and CD95L mRNA sequences and an unrelated control gene, Venus, we have identified many toxic sequences - most of them located in the open reading frame of CD95L. We propose that using specific toxic RNAi-active sequences present in the genome can kill cancer cells.
Supramolecular architectures in two 1:1 cocrystals of 5-fluorouracil with 5-bromothiophene-2-carboxylic acid and thiophene-2-carboxylic acid
Authors: Mohana Marimuthu , Thomas Muthiah Packianathan , McMillen Colin D.
Published: May 2017

In solid-state engineering, cocrystallization is a strategy actively pursued for pharmaceuticals. Two 1:1 cocrystals of 5-fluorouracil (5FU; systematic name: 5-fluoro-1,3-dihydropyrimidine-2,4-dione), namely 5-fluorouracil–5-bromothiophene-2-carboxylic acid (1/1), C5H3BrO2S·C4H3FN2O2, (I), and 5-fluorouracil–thiophene-2-carboxylic acid (1/1), C4H3FN2O2·C5H4O2S, (II), have been synthesized and characterized by single-crystal X-ray diffraction studies. In both cocrystals, carboxylic acid molecules are linked through an acid–acid R
2
2(8) homosynthon (O—H...O) to form a carboxylic acid dimer and 5FU molecules are connected through two types of base pairs [homosynthon, R
2
2(8) motif] via a pair of N—H...O hydrogen bonds. The crystal structures are further stabilized by C—H...O interactions in (II) and C—Br...O interactions in (I). In both crystal structures, π–π stacking and C—F...π interactions are also observed.
Establishment path and management innovation of mutually beneficial nonprofit organization (MBNPO)
Authors: Shin Kwang-yong , Ge Fa-quan , Qin Peng-fei
Published: May 2017

Purpose

Research about the modern mutually beneficial nonprofit organizations (MBNPOs) has great value because of the increasingly important role that the MBNPO plays in society. The establishment and management of MBNPOs are critical for its development.

Design/methodology/approach

Integrated marketing communications (IMC) theory is applied to the research on establishment and management innovation. The establishment of MBNPOs needs four sequential steps: identifying the target group, providing services to meet the demand of stakeholders, designing appropriate communication tactics and deploying proper organizational structure to accomplish efficient communication.

Findings

Three types of approach enable traditional enterprises to transform into MBNPOs: product innovation, operational innovation and synergetic development. The application of IMC theory accomplishes management innovation of MBNPOs in three aspects: leading market-orientation specific to stakeholder-orientation, making management innovation systematic in MBNPOs and clarifying targets of management innovation in MBNPOs.

Originality/value

This is one of the first examinations of establishment path and management innovation of MBNPO based on IMC theory.
Nation image and its dynamic changes in Wikipedia
Authors: Lee Youngwhan , Chun Heuiju
Published: May 2017

Purpose

In this volatile and increasingly fast-revolving world, it has become crucially important to monitor, measure and manage nation image and its dynamic changes in real time. However, few studies have been conducted on a model to measure the image and/or its changes. The purpose of this paper is to find an economically affordable methodology to measure nation image and its changes online in real time.

Design/methodology/approach

The study took an approach to build dynamic ontology that may reflect to change nation image in real-time. With it, the authors attempted to measure nation image in real time.

Findings

Among many social media, the authors found that Wikipedia is particularly suitable for the purpose of measuring nation image. An ontology of nation image was built from the keywords collected from the pages directly related to the big three exporting countries in East Asia, i.e. Korea, Japan and China. The click views on the pages of the countries in two different language editions of Wikipedia, Vietnamese and Indonesian were counted.

Originality/value

The study confirms the objective: the data from a social media service, Wikipedia, may work very well as an economically affordable real-time supplement to offline nation image indices that are currently used.
The contribution of environmental regulation to technological innovation and quality competitiveness
Authors: Cao Yuhong , You Jianxin
Published: May 2017

Purpose

This paper aims to explore the relationship between environmental regulation, technological innovation and manufacturing quality competitiveness to provide some references for emission reduction activities and improvements in manufacturing quality competitiveness to achieve environmental protection targets and economic development as part of a win–win situation.

Design/methodology/approach

Based on the structure-behavior-performance paradigm and Grabowski’s research, a new empirical model was provided. The software, EViews 6.0, was used for econometric analysis. Regression analysis was adopted to explore the three indicators’ relationships.

Findings

First, environmental regulation can promote technological innovation effectively. Second, compared with wasted gas and wasted solids, investment in wasted water control promotes Chinese technological innovation most. Third, the impact of research and development investment, induced by environmental regulation, on manufacturing quality competitiveness is greater than that induced by non-environmental regulation. Fourth, the impact of lagged two-phase environmental regulation on manufacturing quality competitiveness is similar to that of lagged one-phase regulation.

Practical implications

The issue that Chinese manufacturing is facing is how to manage the trade-off between pollution control investment and improved quality competitiveness. This study enables managers to understand how to better implement environmental regulation initiatives while achieving environmental protection and quality competitiveness as part of a win–win situation.

Originality/value

This paper analyzes the relationships between environmental regulation, technological innovation and manufacturing quality competitiveness for the first time and provides the basic argument for integrating Chinese environmental regulation with quality competitiveness to reveal the uniqueness of the circumstances determining China’s economic development.
Theorizing with managers: how to achieve both academic rigor and practical relevance?
Authors: Nenonen Suvi , Brodie Roderick J. , Storbacka Kaj , Peters Linda D.
Published: May 2017

Purpose

The aim of the paper is to address the widening theory-praxis gap in marketing. The authors propose that one viable solution to this challenge is involving practitioners in research processes as active, reflective and empowered participants. Most extant discussions addressing the inclusion of managers as partners in theorizing restrain themselves to an “if” question, arguing whether or not it is possible to create sufficiently rigorous knowledge in collaboration with practitioners. This leaves the “how” question unanswered, i.e. how should such gap-bridging research be conducted in practice.

Design/methodology/approach

Based on a literature review of collaborative theorizing processes, the authors develop a conceptual framework highlighting the main research design decisions when theorizing with managers. The use of the framework is illustrated with four research program examples.

Findings

Most accounts of theorizing with managers use – explicitly or implicitly – abduction as the main mode of inference. In addition to this philosophical commonality, our literature review identified 12 themes that should be considered when designing collaborative research processes. The four illustrative examples indicate that theorizing with managers is an effective way of producing and socializing both academically sound and managerially relevant knowledge. On the other hand, collaborative theorizing processes are time-consuming and studies using abductive reasoning may be more challenging to publish in top-tier journals.

Originality/value

This paper makes two contributions. First, the authors go beyond the extensive academic literature which provides a plethora of explanations and ideas for potential remedies for bridging the theory-praxis gap by offering a detailed description how one particular solution, theorizing with managers, unfolds in practice. Second, the authors ground collaborative theorizing processes in the philosophy of science and put abduction forward as a common nominator for such studies.
Theorizing with managers to bridge the theory-praxis gap
Authors: Brodie Roderick J. , Nenonen Suvi , Peters Linda D. , Storbacka Kaj
Published: May 2017

Purpose

The purpose of this paper is to refine an agenda concerning the theory–praxis gap to develop a foundation for a research tradition.

Design/methodology/approach

The paper synthesizes and builds on the suggestions in commentary articles by Kohli (2017), Leeflang (2017) and Möller (2017).

Findings

The authors develop a research agenda consisting of the following issues: the need for a systemic view of business practice; the need for innovative and meaningful theoretical understanding; the need to identify conditions and approaches for collaborative theorizing; to further define and instruct the abductive approach; and to explore pragmatic realism to ensure both practical outcomes and truthful theories.

Originality/value

These five issues are a step towards developing a theory–praxis research tradition.
Systematic response errors in self-reported category buying frequencies
Authors: Ludwichowska Gosia , Romaniuk Jenni , Nenycz-Thiel Magda
Published: May 2017

Purpose

Despite the growing availability of scanner-panel data, surveys remain the most common and inexpensive method of gathering marketing metrics. The purpose of this paper is to explore the size, direction and correction of response errors in retrospective reports of category buying.

Design/methodology/approach

Self-reported purchase frequency data were validated using British household panel records and the negative binomial distribution (NBD) in six packaged goods categories. The log likelihood theory and the fit of the NBD model were used to test an approach to adjusting the errors post-data collection.

Findings

The authors found variations in systematic response errors according to buyer type. Specifically, lighter buyers tend to forward telescope their buying episodes. Heavier buyers tend either to over-use a rate-based estimation of once-a-month buying and over-report purchases at multiples of six or to use round numbers. These errors lead to overestimates of penetration and average purchase frequency. Adjusting the aggregate data for the NBD, however, improves the accuracy of these metrics.

Practical implications

In light of the importance of purchase data for decision making, the authors describe the inaccuracy problem in frequency reports and offer practical suggestions regarding the correction of survey data.

Originality/value

Two novel contributions are offered here: an investigation of errors in different buyer groups and use of the NBD in survey accuracy research.
Does unit pricing influence store price image dimensions and shopping intentions for retail stores?
Authors: Roth Stefan , Himbert Lena , Zielke Stephan
Published: May 2017

Purpose

While previous literature focusses on the impact of unit pricing on the customer level by analysing customer awareness and product choice, the present research aims to highlight the impact unit pricing has at the store level.

Design/methodology/approach

The impact of unit pricing on the store price image is investigated in two experiments. While the first experiment assesses the general influence of unit price presence and unit price prominence on store price image, the second experiment provides further insights into the influence of unit price prominence on store price image and shopping intentions under consideration of moderating variables.

Findings

This research demonstrates that the availability of unit prices influences several store price image dimensions positively, namely, price processibility, price perceptibility and evaluation certainty. There is also an indirect positive effect on value-for-money perception. Furthermore, unit price prominence has a positive effect on the dimension price processibility. There is a positive influence of unit price presence and unit price prominence on the consumers’ intention to shop at a given store through the store price image.

Originality/value

This paper adds to the existing unit price and store price image literature and derives implications for retailers as well as for policymakers regarding the presentation of unit prices on price labels. Policymakers can use the results for motivating retailers to use unit price information more actively and present it more prominently beyond the minimum regulatory standards.
The role of geographical distance and its efficacy on global purchasing practices
Authors: Wiengarten Frank , Ambrose Eamonn
Published: May 2017

Purpose

The purpose of this paper is to investigate the extent to which the geographical location of and thus the geographical distance between buyer and supplier impact on the efficacy of purchasing practices (i.e. strategic purchasing management, tactical purchasing management, relational purchasing management) in terms of operational performance.

Design/methodology/approach

The authors utilise cross-country data collected through the International Purchasing Survey group across a variety of countries and industry sectors. The authors conduct exploratory factor analysis to assess construct validity and regression analysis to test the varying effects of purchasing practices on operational performance. The authors split the sample to compare potential differences in the efficacy of purchasing practices between buyers and suppliers through geographical characteristics.

Findings

The results indicate that the efficacy of purchasing practices does indeed vary depending on differences in geographical location. Specifically, the authors identify that in cases where the buyer and supplier are located in the same country tactical and relational purchasing tools have a positive impact on operational performance. However, in cases where they are situated in different countries none of the purchasing tools seems to significantly improve operational performance.

Originality/value

Research that has taken a cross-country perspective on the efficacy of supply chain practices is surprisingly sparse. Since most supply chains are becoming more and more global it is important to consider the geographical location of the supply chain members when assessing the performance benefits of supply chain practices such as purchasing tools. Thus, the authors introduce and test the concept of geographical distance on the efficacy of purchasing practices at the dyadic level. To test the implications of geographical distance for purchasing practices the authors use a large-scale cross-country survey.