bluuebunny/crossref_metadata_2025 huggingface dataset:
Pure-Tone Masking Patterns for Monopolar and Phantom Electrical Stimulation in Cochlear Implants
Authors: Saoji Aniket A. , Koka Kanthaiah , Litvak Leonid M. , Finley Charles C.
Published: July 2017

Objectives:

Monopolar stimulation of the most apical electrode produces the lowest pitch sensation in cochlear implants clinically. A phantom electrode that uses out-of-phase electrical stimulation between the most apical and the neighboring basal electrode can produce a lower pitch sensation than that associated with the most apical electrode. However, because of the absence of contacts beyond the apical tip of the array, the ability to assess the spread of electrical excitation associated with phantom stimulation is limited in the typical cochlear implant subject with no residual hearing. In the present study, the spread of electrical excitation associated with monopolar and phantom stimulation of the most apical electrode was assessed using electrical masking of acoustic thresholds in cochlear implant subjects with residual, low-frequency, acoustic hearing.

Design:

Eight subjects with an Advanced Bionics cochlear implant and residual hearing in the implanted ear participated in this study (nine ears in total). Unmasked and masked thresholds for acoustic pure tones were measured at 125, 250, 500, 750, 1000, and 2000 Hz in the presence of monopolar and phantom electrode stimulation presented at the apical-most end of the array. The current compensation for phantom electrode stimulation was fixed at 50%. The two electrical maskers were loudness balanced. Differences between the unmasked and masked acoustic thresholds can be attributed to (1) the electrical stimulus–induced interference in the transduction/conduction of the acoustic signal through cochlear periphery and the auditory nerve and/or (2) masking at the level of the central auditory system.

Results:

The results show a significant elevation in pure-tone thresholds in the presence of the monopolar and phantom electrical maskers. The unmasked thresholds were subtracted from the masked thresholds to derive masking patterns as a function of the acoustic probe frequency. The masking patterns show that phantom stimulation was able to produce more masking than that associated with the monopolar stimulation of the most apical electrode.

Conclusion:

These results suggest that for some cochlear implant subjects, phantom electrode stimulation can shift the neural stimulation pattern more apically in the cochlea, which is consistent with reports that phantom electrode stimulation produces lower pitch sensations than those associated with monopolar stimulation of the most apical electrode alone.
Impact of Hearing Aid Technology on Outcomes in Daily Life III: Localization
Authors: Johnson Jani A. , Xu Jingjing , Cox Robyn M.
Published: July 2017

Objective:

Compared to basic-feature hearing aids, premium-feature hearing aids have more advanced technologies and sophisticated features. The objective of this study was to explore the difference between premium-feature and basic-feature hearing aids in horizontal sound localization in both laboratory and daily life environments. We hypothesized that premium-feature hearing aids would yield better localization performance than basic-feature hearing aids.

Design:

Exemplars of premium-feature and basic-feature hearing aids from two major manufacturers were evaluated. Forty-five older adults (mean age 70.3 years) with essentially symmetrical mild to moderate sensorineural hearing loss were bilaterally fitted with each of the four pairs of hearing aids. Each pair of hearing aids was worn during a 4-week field trial and then evaluated using laboratory localization tests and a standardized questionnaire. Laboratory localization tests were conducted in a sound-treated room with a 360°, 24-loudspeaker array. Test stimuli were high frequency and low frequency filtered short sentences. The localization test in quiet was designed to assess the accuracy of front/back localization, while the localization test in noise was designed to assess the accuracy of locating sound sources throughout a 360° azimuth in the horizontal plane.

Results:

Laboratory data showed that unaided localization was not significantly different from aided localization when all hearing aids were combined. Questionnaire data showed that aided localization was significantly better than unaided localization in everyday situations. Regarding the difference between premium-feature and basic-feature hearing aids, laboratory data showed that, overall, the premium-feature hearing aids yielded more accurate localization than the basic-feature hearing aids when high-frequency stimuli were used, and the listening environment was quiet. Otherwise, the premium-feature and basic-feature hearing aids yielded essentially the same performance in other laboratory tests and in daily life. The findings were consistent for both manufacturers.

Conclusions:

Laboratory tests for two of six major manufacturers showed that premium-feature hearing aids yielded better localization performance than basic-feature hearing aids in one out of four laboratory conditions. There was no difference between the two feature levels in self-reported everyday localization. Effectiveness research with different hearing aid technologies is necessary, and more research with other manufacturers’ products is needed. Furthermore, these results confirm previous observations that research findings in laboratory conditions might not translate to everyday life.
Bile acids upregulate BRCA1 and downregulate estrogen receptor 1 gene expression in ovarian cancer cells
Authors: Jin Qunyan , Noel Olivier , Nguyen Mai , Sam Lionel , Gerhard Glenn S.
Published: July 2017

Two major risk factors for ovarian cancer include loss-of-function mutations in the BRCA1 (breast cancer 1, early onset) gene and aspects of estrogen metabolism. Modulation of the levels of the normal BRCA1 allele and estrogen receptor expression may therefore be a preventive strategy. Consensus binding motifs for the bile acid-responsive transcription factor farnesoid X receptor were identified in the BRCA1 and estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) genes, supported by chromatin immunoprecipitation sequencing data. Two major bile acids, deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA), resulted in a greater than four-fold induction of BRCA1 transcript levels at 10 μmol/l and a greater than six-fold induction at 50 μmol/l relative to untreated control OVCAR3 ovarian cancer cells. Conversely, CDCA and DCA at 10 μmol/l resulted in about a 75% decrease in ESR1 expression in response to 10 μmol/l CDCA and DCA and close to 90% reduction with 50 μmol/l CDCA and DCA. Bile acids had no effects on ESR2 gene transcript levels. The inverse regulation of BRCA1 and ESR1 gene expression in response to physiological levels of bile acids could have important implications for disease penetrance and chemoprevention strategies in carriers of BRCA1 mutations.
Effects of D1 and D2 receptor antagonists on the discriminative stimulus effects of methylendioxypyrovalerone and mephedrone in male Sprague-Dawley rats trained to discriminate d-amphetamine
Authors: Harvey Eric L. , Burroughs Rachel L. , Baker Lisa E.
Published: July 2017

Psychopharmacology research has amassed substantial evidence for similarities between synthetic cathinones and other commonly abused psychostimulants. Few studies have utilized drug discrimination methods to investigate synthetic cathinones, and the precise neurochemical substrates underlying their interoceptive effects have not been examined. The present study assessed the involvement of D1 and D2 dopaminergic receptors in the stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) and mephedrone (MEPH) in rats trained to discriminate d-amphetamine. Eight male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg d-amphetamine (AMPH) from saline. Dose–response curves were then generated with AMPH (0.0–1.0 mg/kg), MDPV (0.0–1.0 mg/kg), and MEPH (0.0–2.0 mg/kg). Subsequently, Sch 39166 (0.3 mg/kg) and haloperidol (0.5 mg/kg) were administered in combination with select doses of MDPV and MEPH. Both MDPV and MEPH produced full substitution for AMPH. Sch 39166 produced a downward shift in the MDPV and MEPH dose–response curves and haloperidol produced similar results with MDPV. These preliminary findings indicate that MDPV and MEPH produce interoceptive stimuli that are similar to those produced by AMPH and that D1 and D2 dopamine receptors contribute to these effects. Additional studies are warranted to investigate the contribution of other receptor mechanisms involved in the interoceptive stimuli produced by synthetic cathinones.
Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in Rheumatoid Arthritis
Authors: Medina Frédéric , Plasencia Chamaida , Goupille Philippe , Ternant David , Balsa Alejandro , Mulleman Denis
Published: July 2017

The treatment of rheumatoid arthritis (RA) has largely improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor (TNF) inhibitors, are effective, but some patients may show poor response, sometimes because of the presence of antidrug antibodies (ADAs). In some instances, clinicians may increase or taper the dose depending on the clinical response. Besides the current clinical-based practice, a tailored strategy based on drug monitoring has emerged as a way to improve the use of these drugs. However, the relevance of this therapeutic drug monitoring (TDM) of biopharmaceuticals in RA is still unknown. In this literature review, we examine the most relevant articles dealing with the concentration–response relationship, ADA detection and pharmacokinetics in RA patients receiving biopharmaceuticals. A concentration–response relationship was clearly established for TNF inhibitors. Moreover, ADA positivity was associated with low drug concentrations, poor clinical outcome, and reduced drug survival for TNF-inhibitor monoclonal antibodies. Concomitant use of disease-modifying antirheumatic drugs, especially methotrexate, is associated with good clinical outcome, increased drug concentrations, and reduced immunogenicity. Strategies based on TDM of TNF inhibitors seem promising for RA, but randomized controlled trials are required to support this. A concentration–response relationship may exist with tocilizumab, and immunogenicity seems rare. Finally, the relevance of TDM for RA patients receiving rituximab and abatacept remains unclear.
Interrelationships Between 3 Keratoconic Cone Parameters
Authors: Tu Kyaw L. , Tourkmani Abdo K. , Srinivas Singaram
Published: July 2017

Purpose:

To find out the interrelationships between 3 parameters of the keratoconic cone.

Methods:

A total of 101 keratoconic eyes of 58 patients were included in this retrospective case series study. A complete eye examination was performed. Kmax (K) and pachymetry at the thinnest point (T) were obtained from the Pentacam tomographer. The vertex to thinnest pachymetry distance (D for decentration) was calculated using trigonometry. Pearson correlation coefficients between T and D, between T and K, and between D and K were calculated.

Results:

There is a statistically significant positive correlation between thinnest point pachymetry and decentration (R = 0.366, P = 0.0002) and also statistically significant negative correlation between thinnest point pachymetry and Kmax (R = −0.719, P < 0.00001) and decentration and Kmax (R = −0.281, P = 0.0044).

Conclusions:

The interrelationships between the 3 keratoconic cone parameters suggest that the thinner cones are largely central, that is, decenter less, but show greater steepening.
Observation of Retrocorneal Plaques in Patients With Infectious Keratitis Using Anterior Segment Optical Coherence Tomography
Authors: Takezawa Yuki , Suzuki Takashi , Shiraishi Atsushi
Published: July 2017

Purpose:

Endothelial plaques are a typical characteristic in patients with fungal keratitis. However, bacterial keratitis and herpetic keratouveitis are rarely associated with fibrin formation on the retrocorneal surface. This study was conducted to examine plaques attached to the endothelium in patients with infectious keratitis using anterior segment optical coherence tomography (AS-OCT).

Methods:

Seventeen patients (10 women and 7 men; mean age, 75 ± 15.5 years) suspected to have infectious keratitis with retrocorneal plaques were included. AS-OCT was used to acquire a scan of the retrocorneal plaque at the patient's first visit.

Results:

Based on the culture results and detection of viral DNA, the patients were diagnosed with fungal keratitis (6 patients), bacterial keratitis (8 patients), and herpetic keratouveitis (3 patients). Examination of the cornea using AS-OCT showed a clear boundary between the corneal endothelial surface and plaque in 8 patients with bacterial keratitis and in all patients with herpetic keratitis. Moreover, a space between the corneal endothelial surface and plaque was found in 3 patients with bacterial keratitis. In 5 patients with fungal keratitis, the AS-OCT images showed an unclear boundary between the corneal endothelial surface and plaque, and high reflection of the plaque was extended from the corneal lesion.

Conclusions:

Endothelial plaques in patients with fungal keratitis could continue from the corneal lesion. Observation of retrocorneal plaques using AS-OCT could be used in the diagnosis of infectious keratitis.
Suppression of scratching-induced pleasurable sensation by compression nerve blocking and its association with itch relief
Authors: Mochizuki Hideki , Shevchenko Alina , Nattkemper Leigh A. , Valdes-Rodriguez Rodrigo , Yosipovitch Gil
Published: July 2017

Itch can be suppressed by scratching. At the same time, scratching evokes a pleasurable sensation. In the present study, we investigated the peripheral mechanism of scratching-induced pleasurability and its association with itch relief using compression nerve block. We found that myelinated nerve fibers (Aβ-fibers and possibly Aδ-fibers), are involved in transmission of scratching-induced pleasurability. We observed that itch relief effect was the same regardless of whether the pleasurable sensation was evoked by scratching an itch, indicating that pleasure is not a necessary component to induce itch relief. This is the first study to investigate the peripheral mechanism of scratching-induced pleasurability and itch relief.
Psychosocial factors and their influence on the experience of pain
Authors: Tracy Lincoln M.
Published: July 2017

Over the past 20 years, our understanding of social factors on pain experience has increased. Edwards et al observed that the presence of a friend resulted in an increased pain threshold and tolerance to experimentally induced pain (cold pressor test and pressure algometry). Having a male friend present had the most prominent effect on male participants' reporting of pain. However, the effects of psychosocial traits known to effect pain experience (eg, catastrophising) were not considered.
Refining the Policy for Timing of Kidney Transplant Waitlist Qualification
Authors: Lee Benjamin J. , McCulloch Charles E. , Grimes Barbara A. , Chandran Sindhu , Allen Isabel Elaine , Delgado Cynthia , Hsu Chi-yuan
Published: July 2017

Background

Earlier qualification for the kidney transplant waitlist expedites transplant and is therefore associated with improved outcomes. U.S. Organ Procurement and Transplantation Network policies state that “measured or calculated creatinine clearance or glomerular filtration rate less than or equal to 20 mL/min” triggers waitlist time accrual. The choice of qualification method is somewhat arbitrary, and the policy implies that decline in renal function is monotonic.

Methods

(1) We used survival analysis to quantify temporal differences in waitlist qualification by applying 3 kidney-function-estimating equations (Cockcroft-Gault, Modification of Diet in Renal Disease study, Chronic Kidney Disease Epidemiology Collaboration) to serial creatinine measurements from 3 patient cohorts: 1 of waitlisted patients at a major U.S. academic center and 2 national, multicenter cohorts of chronic kidney disease patients (African American Study of Kidney Disease and Hypertension, Modification of Diet in Renal Disease). (2) Survival analysis assessed whether requiring patients to demonstrate persistently reduced renal function on 2 occasions at least 90 days apart would meaningfully change qualification order.

Results

On average, time to waitlist qualification would be delayed on the order of 1 to 2 years by using calculated creatinine clearance (per the Cockcroft-Gault equation). Compared with current policy, requiring demonstration of persistently reduced renal function delayed qualification by 0.6 to 2.1 years and caused 40% to 50% of patients to switch the order in which they qualify by 6 months or more.

Conclusions

The kidney transplantation policies should be revised, such that timing of waitlist qualification is more standardized. We suggest that mention of using calculated creatinine clearance be dropped from the Organ Procurement and Transplantation Network policy wording and the units to quantify kidney function be changed to mL/min per 1.73 m2. Some consideration should be given to whether requiring persistently reduced renal function would better identify patients most likely to benefit from earlier waitlist qualification.
Renal Outcomes in Patients With IgA Nephropathy Undergoing Liver Transplant: A Retrospective Cohort Study
Authors: Hommos Musab S. , El-Zoghby Ziad M.
Published: July 2017

Background

End-stage liver disease (ESLD) is the most common cause of secondary immunoglobulin A nephropathy (IgAN). Multiple mechanisms have been proposed to explain the association between liver disease and IgAN. Although some mechanisms are expected to reverse in patients after liver transplant, the long-term renal prognosis is unclear for these patients.

Methods

This observational retrospective cohort study examined the renal outcomes of 14 patients who had IgAN with end-stage liver disease and subsequently underwent either liver transplant alone or combined liver and kidney transplant at a single tertiary care center.

Results

Of the 7 patients who underwent liver transplant alone, hematuria persisted in 2, 4 had progressive loss of kidney function with worsening proteinuria in 3 but only 1 reached end-stage renal disease 5 years posttransplant. Among 7 combined liver and kidney transplant recipients, 1 had histologic and 1 had histologic and clinical recurrence of IgAN without kidney allograft loss.

Conclusions

IgAN in patients with advanced liver disease does not necessarily resolve after liver transplant but has overall favorable renal outcomes.
Modelling the host–pathogen interactions of macrophages and
Candida albicans
using Game Theory and dynamic optimization
Authors: Dühring Sybille , Ewald Jan , Germerodt Sebastian , Kaleta Christoph , Dandekar Thomas , Schuster Stefan
Published: July 2017

The release of fungal cells following macrophage phagocytosis, called non-lytic expulsion, is reported for several fungal pathogens. On one hand, non-lytic expulsion may benefit the fungus in escaping the microbicidal environment of the phagosome. On the other hand, the macrophage could profit in terms of avoiding its own lysis and being able to undergo proliferation. To analyse the causes of non-lytic expulsion and the relevance of macrophage proliferation in the macrophage–
Candida albicans
interaction, we employ Evolutionary Game Theory and dynamic optimization in a sequential manner. We establish a game-theoretical model describing the different strategies of the two players after phagocytosis. Depending on the parameter values, we find four different Nash equilibria and determine the influence of the systems state of the host upon the game. As our Nash equilibria are a direct consequence of the model parameterization, we can depict several biological scenarios. A parameter region, where the host response is robust against the fungal infection, is determined. We further apply dynamic optimization to analyse whether macrophage mitosis is relevant in the host–pathogen interaction of macrophages and
C. albicans
. For this, we study the population dynamics of the macrophage–
C. albicans
interactions and the corresponding optimal controls for the macrophages, indicating the best macrophage strategy of switching from proliferation to attacking fungal cells.
Degradation and erosion mechanisms of bioresorbable porous acellular vascular grafts: an
in vitro
investigation
Authors: Gade Piyusha S. , Lee Keewon , Pfaff Blaise N. , Wang Yadong , Robertson Anne M.
Published: July 2017

A fundamental mechanism of
in situ
tissue regeneration from biodegradable synthetic acellular vascular grafts is the effective interplay between graft degradation, erosion and the production of extracellular matrix. In order to understand this crucial process of graft erosion and degradation, we conducted an
in vitro
investigation of grafts (
n
= 4 at days 1, 4, 7, 10 each) exposed to enzymatic degradation. Herein, we provide constitutive relationships for mass loss and mechanical properties based on much-needed experimental data. Furthermore, we formulate a mathematical model to provide a physics-based framework for understanding graft erosion. A novel finding is that despite their porous nature, grafts lost mass exponentially via surface erosion demonstrating a 20% reduction in outer diameter and no significant change in apparent density. A diffusion based, concentration gradient-driven mechanistic model of mass loss through surface erosion was introduced which can be extended to an
in vivo
setting through the use of two degradation parameters. Furthermore, notably, mechanical properties of degrading grafts did not scale with mass loss. Thus, we introduced a damage function scaling a neo-Hookean model to describe mechanical properties of the degrading graft; a refinement to existing mass-dependent growth and remodelling (G&R) models. This framework can be used to improve accuracy of well-established G&R theories in biomechanics; tools that predict evolving structure–function relationships of neotissues and guide graft design.
microRNA-206modulates an Rtn4a/Cxcr4a/Thbs3a axis in newly forming somites to maintain and stabilize the somite boundary formation of zebrafish embryos
Authors: Lin Cheng-Yung , He Jun-Yu , Zeng Chih-Wei , Loo Moo-Rumg , Chang Wen-Yen , Zhang Po-Hsiang , Tsai Huai-Jen
Published: July 2017

AlthoughmicroRNA-206(miR-206) is known to regulate proliferation and differentiation of muscle fibroblasts, the role ofmiR-206in early-stage somite development is still unknown. During somitogenesis of zebrafish embryos,reticulon4a(rtn4a) is specifically repressed bymiR-206.The somite boundary was defective, and actin filaments were crossing over the boundary in eithermiR-206-knockdown orrtn4a-overexpressed embryos. In these treated embryos, C–X–C motif chemokine receptor 4a (cxcr4a) was reduced, while thrombospondin 3a (thbs3a) was increased. The defective boundary was phenocopied in eithercxcr4a-knockdown orthbs3a-overexpressed embryos. Repression ofthbs3aexpression bycxcr4areduced the occurrence of the boundary defect. We demonstrated thatcxcr4ais an upstream regulator ofthbs3aand that defective boundary cells could not process epithelialization in the absence of intracellular accumulation of the phosphorylated focal adhesion kinase (p-FAK) in boundary cells. Therefore, in the newly forming somites,miR-206-mediated downregulation ofrtn4aincreasescxcr4a.This activity largely decreasesthbs3aexpression in the epithelial cells of the somite boundary, which causes epithelialization of boundary cells through mesenchymal–epithelial transition (MET) and eventually leads to somite boundary formation. Collectively, we suggest thatmiR-206mediates a novel pathway, the Rtn4a/Cxcr4a/Thbs3a axis, that allows boundary cells to undergo MET and form somite boundaries in the newly forming somites of zebrafish embryos.
DictyosteliumAMPKα regulates aggregate size and cell-type patterning
Authors: Maurya Ranjana , Kumar Rakesh , Saran Shweta
Published: July 2017

StarvedDictyosteliumcells aggregate into groups of nearly 105cells. AMPK is a highly conserved serine/threonine protein kinase consisting of a catalytic and two regulatory subunits. As multi-cellular development inDictyosteliumis initiated upon starvation, we explored the role of the energy sensor, AMPK, which shows significant similarity to human AMPK and is expressed throughout development. Deletion of theampkαgene results in the formation of numerous small-sized aggregates that develop asynchronously to form few fruiting bodies with small sori and long stalks. On the other hand,ampkαOEcells form fruiting bodies with small stalks and large sori when compared with wild-type, Ax2. A minimum of 5%ampkα−cells in a chimaera with Ax2 cells was sufficient to reduce the aggregate size. Also, the conditioned media collected fromampkα−cells triggered Ax2 cells to form smaller aggregates. The starvedampkα−cells showed low glucose levels and formed large aggregates when glucose was supplied exogenously. Interestingly,ampkα−cells exhibit abnormal cell-type patterning with increased prestalk region and a concomitant reduction of prespore region. In addition, there was a loss of distinct prestalk/prespore boundary in the slugs.
Bending of the BST-2 coiled-coil during viral budding
Authors: Ozcan Kadir A. , Berndsen Christopher E.
Published: July 2017

BST-2/tetherin is a human extracellular transmembrane protein that serves as a host defense factor against HIV-1 and other viruses by inhibiting viral spreading. Structurally, BST-2 is a homodimeric coiled-coil that is connected to the host cell membrane by N and C terminal transmembrane anchors. The C-terminal membrane anchor of BST-2 is inserted into the budding virus while the N-terminal membrane anchor remains in the host cell membrane creating a viral tether. The structural mechanism of viral budding and tethering as mediated by BST-2 is not clear. To more fully describe the mechanism of viral tethering, we created a model of BST-2 embedded in a membrane and used steered molecular dynamics to simulate the transition from the host cell membrane associated BST-2 and the cell-virus membrane bridging form. We observed that BST-2 did not transition as a rigid structure, but instead bent at sites with a reduced interface between the helices of the coiled-coil. The simulations for the human BST-2 were then compared with simulations on the mouse homolog, which has a more stable coiled-coil. We observed that the mouse homolog spread the bending across the ectodomain, rather than breaking at discrete points as observed with the human homolog. These simulations support previous biochemical and cellular work suggesting some flexibility in the coiled-coil is necessary for viral tethering, while also highlighting how subtle changes in protein sequence can influence the dynamics and stability of proteins with overall similar structure.
Agrochemical pollution increases risk of human exposure to schistosome parasites
Authors: Halstead Neal T. , Hoover Christopher M. , Arakala Arathi , Civitello David J. , De Leo Giulio A. , Gambhir Manoj , Johnson Steve A. , Loerns Kristin A. , McMahon Taegan A. , Nguyen Karena , Raffel Thomas R. , Remais Justin V. , Sokolow Susanne H. , Rohr Jason R.
Published: July 2017

Roughly 10% of the global population is at risk of schistosomiasis, a snail-borne parasitic disease that ranks among the most important water-based diseases of humans in developing countries1–3. Increased prevalence, infection intensity, and spread of human schistosomiasis to non-endemic areas has been consistently linked with water resource management related to agricultural expansion, such as dam construction, which has resulted in increased snail habitat1,4–6. However, the role of agrochemical pollution in human schistosome transmission remains unexplored, despite strong evidence of agrochemicals increasing snail-borne diseases of wildlife7–9and a projected 2- to 5-fold increase in global agrochemical use by 205010that will disproportionately occur in schistosome-endemic regions. Using a field mesocosm experiment, we show that environmentally relevant concentrations of fertilizer, the common herbicide atrazine, and the common insecticide chlorpyrifos, individually and as mixtures, increase densities of schistosome-infected snails by increasing the algae snails eat (fertilizer and atrazine) and decreasing densities of snail predators (chlorpyrifos). Epidemiological models indicate that these agrochemical effects can increase transmission of schistosomiasis. Hence, the rapid agricultural changes occurring in schistosome-endemic regions11,12that are driving increased agrochemical use and pollution could potentially increase the burden of schistosomiasis in these areas. Identifying agricultural practices or agrochemicals that minimize disease risk will be critical to meeting growing food demands while improving human wellbeing13,14.
When rarity has costs: coexistence under positive frequency-dependence and environmental stochasticity
Authors: Schreiber Sebastian J. , Yamamichi Masato , Strauss Sharon Y.
Published: July 2017

Stable coexistence relies on negative frequency-dependence, in which rarer species invading a patch benefit from a lack of conspecific competition experienced by residents. In nature, however, rarity can have costs, resulting in positive frequency-dependence (PFD) particularly when species are rare. Many processes can cause positive frequency-dependence, including a lack of mates, mutualist interactions, and reproductive interference from heterospecifics. When species become rare in the community, positive frequency-dependence creates vulnerability to extinction, if frequencies drop below certain thresholds. For example, environmental fluctuations can drive species to low frequencies where they are then vulnerable to PFD. Here, we analyze deterministic and stochastic mathematical models of two species interacting through both PFD and resource competition in a Chessonian framework. Reproductive success of individuals in these models is reduced by a product of two terms: the reduction in fecundity due to PFD, and the reduction in fecundity due to competition. Consistent with classical coexistence theory, the effect of competition on individual reproductive success exhibits negative frequency-dependence when individuals experience greater intraspecific competition than interspecific competition i.e., niche overlap is less than one. In the absence of environmental fluctuations, our analysis reveals that (1) a synergistic effect of PFD and niche overlap that hastens exclusion, (2) trade-offs between susceptibility to PFD and maximal fecundity can mediate coexistence, and (3) coexistence, when it occurs, requires that neither species is initially rare. Analysis of the stochastic model highlights that environmental fluctuations, unless perfectly correlated, coupled with PFD ultimately drive one species extinct. Over any given time frame, this extinction risk decreases with the correlation of the demographic responses of the two species to the environmental fluctuations, and increases with the temporal autocorrelation of these fluctuations. For species with overlapping generations, these trends in extinction risk persist despite the strength of the storage effect decreasing with correlated demographic responses and increasing with temporal autocorrelations. These results highlight how the presence of PFD may alter the outcomes predicted by modern coexistence mechanisms.
Sympathetic Transmitters Controlling Thermogenic Efficacy of Brown Adipocytes by Modulating Mitochondrial Complex V
Authors: Xie Tao-Rong , Liu Chun-Feng , Kang Jian-Sheng
Published: July 2017

Obesity is epidemic worldwide as the results of excessive energy intake or inefficient energy expenditure. It is promising to utilize the thermogenic function of brown adipose tissue for obesity intervention. However, the mechanisms controlling the efficacy of norepinephrine-induced thermogenesis in brown adipocytes remain elusive. Here, we demonstrate that the proton ATPase activity of mitochondrial complex V is a key factor, which antagonizes proton leak by UCP1 and determines the efficacy of norepinephrine-induced thermogenesis in brown adipocytes. Furthermore, to avoid unnecessary and undesired heat production, we reveal that ATP as a sympathetic cotransmitter is necessary for the high efficacy and specificity of norepinephrine-induced thermogenesis in brown adipocytes by upregulating the ATP synthase activity of complex V. Thus, we demonstrate the modulation mechanism of thermogenic efficacy in brown adipocytes. These findings imply new strategies for efficiently utilizing brown adipocytes thermogenic capacity, and therapeutic targets for the treatments of obesity and diabetes.

Highlights

1. Norepinephrine (NE) induces heterogeneous responses in brown adipocytes

2. NE activates the H+-ATPase activity of mitochondrial complex V

3. Mitochondrial complex V is a key factor in NE-induced thermogenic efficacy

4. ATP as a sympathetic cotransmitter enhances the NE-induced thermogenic efficacy
PRKCI promotes immune suppression in ovarian cancer
Authors: Sarkar Sharmistha , Bristow Christopher A. , Dey Prasenjit , Rai Kunal , Perets Ruth , Ramirez-Cardenas Alejandra , Malasi Shruti , Huang-Hobbs Emmet , Haemmerle Monika , Wu Sherry Y. , McGuire Michael , Protopopov Alexei , Jiang Shan , Liu Joyce F. , Hirsch Michelle S. , Chang Qing , Lazar Alexander J. , Sood Anil K. , Drapkin Ronny , DePinho Ronald , Draetta Giulio , Chin Lynda
Published: July 2017

A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring PRKC-ι (PRKCI). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called serous tubal intraepithelial carcinoma. Transgenic mouse studies establish PRKCI as an ovarian cancer-specific oncogene. Mechanistically, we show that the oncogenic activity of PRKCI relates in part to the up-regulation of TNFα to promote an immune-suppressive tumor microenvironment characterized by an abundance of myeloid-derived suppressor cells and inhibition of cytotoxic T-cell infiltration. Furthermore, system-level and functional analyses identify YAP1 as a downstream effector in tumor progression. In human ovarian cancers, high PRKCI expression also correlates with high expression of TNFα and YAP1 and low infiltration of cytotoxic T cells. The PRKCI–YAP1 regulation of the tumor immunity provides a therapeutic strategy for highly lethal ovarian cancer.
Kinetochores accelerate or delay APC/C activation by directing Cdc20 to opposing fates
Authors: Kim Taekyung , Lara-Gonzalez Pablo , Prevo Bram , Meitinger Franz , Cheerambathur Dhanya K. , Oegema Karen , Desai Arshad
Published: July 2017

Mitotic duration is determined by activation of the anaphase-promoting complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the microtubule-interacting machines on chromosomes, restrain mitotic exit when not attached to spindle microtubules by generating a Cdc20-containing complex that inhibits the APC/C. Here, we show that flux of Cdc20 through kinetochores also accelerates mitotic exit by promoting its dephosphorylation by kinetochore-localized protein phosphatase 1, which allows Cdc20 to activate the APC/C. Both APC/C activation and inhibition depend on Cdc20 fluxing through the same binding site at kinetochores. The microtubule attachment status of kinetochores therefore optimizes mitotic duration by controlling the balance between opposing Cdc20 fates.
Do anticipated emotions influence behavioural intention and behaviour to consume filled chocolates?
Authors: De Pelsmaeker Sara , Schouteten Joachim J. , Gellynck Xavier , Delbaere Claudia , De Clercq Nathalie , Hegyi Adrienn , Kuti Tünde , Depypere Frédéric , Dewettinck Koen
Published: July 2017

Purpose

The purpose of this paper is to examine the influence of anticipated emotions (AE) on behavioural intention and behaviour to consume filled chocolates and to give an indication on the possible differences in consumer behaviour between two countries.

Design/methodology/approach

The theory of planned behaviour (TPB) was used to explain the consumption of chocolate. In this study, TPB is extended with a construct for AE.

Findings

A total of 859 consumers in Belgium and Hungary participated in the study and results showed that including AE increases the predicted variance of the TPB. Moreover, AE have a positive effect on the intention and the actual behaviour of consumers. Next, the study suggests that Belgian consumers are more influenced by their emotional and control beliefs and that Hungarian consumers are also driven by opinion of family and friends and some behavioural beliefs.

Practical implications

Overall, TPB can contribute to the understanding of behavioural intention and behaviour towards eating filled chocolate. Moreover, it can help to develop a marketing plan for specific consumer segments as it can identify influencing factors and consumer beliefs towards a product.

Originality/value

This is the first study that compares the fit of the TPB model with and without the construct of AE. The work contributes to the growing literature on emotions as it does not focus on emotions elicited during or after consumption, but explores if the AE also play a significant role in behaviour.
Personal values and pro-social behaviour
Authors: Coppola Adele , Verneau Fabio , Caracciolo Francesco , Panico Teresa
Published: July 2017

Purpose

The purpose of this paper is to investigate the role of socio-economic context in affecting the relationship between personal values and the purchase of fair trade (FT) products.

Design/methodology/approach

The study was based on data and information collected by means of a web-administered survey and was performed in two steps. First, an explanatory factor analysis on the Schwartz value system and a confirmatory factor analysis on socio-economic context variables were carried out. Second, the per capita GDP at provincial level and the predicted factor scores were used in an ordered probit model to explain the expenditure level of FT products.

Findings

The results provide evidence that the value system has an effect on the consumption of FT products, but the economic context, in particular the average wealth at province level, is also relevant and plays a role by either affecting FT product purchasing levels directly or interacting with personal values.

Research limitations/implications

Because of the electronic submission and the specific channel used in the survey, the sample cannot be considered as representative of Italian consumers, and thus the analysis has a merely descriptive (non-inferential) function.

Originality/value

While several studies investigated how personal values affect consumers’ behaviour directly or indirectly, very few studies analysed the way socio-economic context interacts with the value structure and the way both aspects influence ethical consumption. The present study analyses this last aspect and provides evidence of the role economic context plays in affecting the relationship between personal values and FT products consumption.
Impact of human resource management practices on employee turnover intentions
Authors: Santhanam Nivethitha , T.J. Kamalanabhan , Dyaram Lata , Ziegler Hans
Published: July 2017

Purpose

This paper aims to explore the relationship between human resource management practices, breach of psychological contract and employee turnover intentions among hotel frontline employees, considering the scant research attention to frontline employee’s perspectives in Indian hospitality industry.

Design/methodology/approach

A survey design was used to collect responses from 294 frontline employees (front-office and food and beverage services). Multiple regression analyses have been used to test the hypothesized relationships.

Findings

Selection, training and compensation practices were found to influence employee’s turnover intentions. In addition, psychological contract breach was found to enhance employee’s turnover intentions, despite the implementation of effective human resource management practices.

Originality/value

This study examines the role of psychological contract breach as a moderator in the relationship between human resource management practices and turnover intentions in a highly labour-intensive context, the hospitality industry.
Using UTAUT 2 model to predict mobile app based shopping: evidences from India
Authors: Tak Preeti , Panwar Savita
Published: July 2017

Purpose

The purpose of this paper is to understand antecedents of app-based shopping in an Indian context. The paper has used unified theory of acceptance and use of technology (UTAUT) 2 model for examining the impact of various constructs on behavioral intention and usage behavior of smart phone users toward the mobile shopping apps.

Design/methodology/approach

The constructs were tested and validated by means of a structured questionnaire which was administered on a sample of 350 mobile app shoppers in Delhi. AMOS 20 was used to analyze the collected data.

Findings

The study revealed that hedonic and habit are the strongest predictors of users’ behavioral intention to use mobile apps for shopping. Respondents are also influenced by the deals that are being offered by the marketers. The research also suggests that facilitating conditions help in usage of mobile apps for shopping.

Research limitations/implications

Managerial implications simplifying the interface which would encourage the less technologically advanced individuals to use mobile apps. Hedonic element of shopping through mobile apps should also be enhanced.

Originality/value

This study contributes to the research on intentions and usage behavior of consumer technologies by adopting UTAUT 2 model to explain the intentions and usage behavior toward mobile apps for shopping. The paper also measured the role of deals in influencing the consumers.
How IT controls improve the control environment
Authors: Rubino Michele , Vitolla Filippo , Garzoni Antonello
Published: July 2017

Purpose

The purpose of this paper is to analyze how Information technology (IT) controls influence the control environment’s components and the internal control system.

Design/methodology/approach

This paper aims to highlight how IT controls enable to improve the control environment assessment and implementation.

Findings

The analysis indicates that the implementation of the IT controls (IT organizational controls, IT process controls and IT soft variables controls) provides some indications for managers and auditors, who must implement or assess internal control system. A joint use of the three dimensions of IT control contributes to a better assessment of the individual components of the control environment. IT controls help managers to develop the design of the organizational structure and to identify the key processes to achieve the internal control objectives and to mitigate firm’s risk.

Practical implications

The examination of three IT control dimensions allows managers to expand their knowledge about these types of controls and change the way they approach technology-based processes and associated risks. This improves the understanding of the key aspects connected to the control environment. The paper provides a list of the relevant activities that affect the three types of IT controls. This is useful for managers to begin to frame the specific controls inside the three dimensions of IT control.

Originality/value

This paper addresses an area of relevance to both practitioners and academics. This analysis focuses on accounting information systems themes and, through the examination of the IT controls, allows a better understanding of the hard and soft elements of the control environment.
Unsticking the status quo
Authors: Martin Brittany Harker
Published: July 2017

Purpose

Managerial mindset and cognitive bias can be barriers to any transformation strategy. In the case of telework, most employees express willingness to telework, yet, few firms formally enable it during regular business hours. The status quo is a daily commute to the traditional workplace. The purpose of this paper is to test framing interventions designed to harness cognitive biases through choice architecture.

Design/methodology/approach

Drawing upon behavioral strategy and prospect theory, this paper presents two studies: quasi-experiments with 146 senior business students and experiments in the field (replication using random assignment and extension) with 84 senior decision makers. Both studies use a one-way between-subjects design and chi-square analysis.

Findings

Findings support the proposition that, although cognitive biases can act as barriers to transformation, they can be re-framed through strategic interventions. Specifically, in both studies, there was a drastic increase in adoption simply by changing the way the choice was presented. Findings in the lab were cross-validated in the field. Observed shifts in preferences provide evidence that embedding the right reference point within communications can frame a decision choice more favorably. Findings also support that a bias for an implicitly perceived status quo can be overruled through an explicitly stated reference point.

Research limitations/implications

It is an assumption of behavioral strategy that most individuals simply respond to the gains/loss framing without being influenced by other psychological or contextual factors, and though these effects dissipate through aggregation, it is a limitation nonetheless. Indeed, using an individual construct to explain an organizational phenomenon is a well-debated topic in the field of strategy, with proponents on both sides. The distinguishing factor, here, is that behavioral strategists are only interested in results at the aggregated level.

Practical implications

Practitioners attempting to roll out telework adoption, or any transformation, now have proven strategies for designing frames of reference that intervene against and harness the power of loss aversion and the status quo.

Social implications

This paper measures micro processes that have an effect at the macro level. It explains systematic aversion to adoption as an aggregation of decision-making behavior that is seemingly subconscious. In doing so, it highlights the impact of bounded rationality perpetuated through social systems, while measuring effective interventions designed to make systematic behavior more predictable.

Originality/value

A novel contribution is made in designing/testing a new frame for systematic resistance to change that frames the status quo as the losing prospect. In this frame, the perceived loss is in the choice not to change, and loss aversion proves to be an effective tool for facilitating systematic change.
Dopamine D1 receptors induce apoptosis of osteosarcoma cells via changes of MAPK pathway
Authors: Gao Jun , Gao Feng
Published: July 2017

This study explored the effects and mechanisms of dopamine D1 receptors (DR1) activation on the apoptosis of osteosarcoma cells (OS732).The DR1 agonist SKF‐38393 decreased the viability of OS732 cells and increased their rate of apoptosis, whereas the DR1 antagonist SCH‐23390 abolished the effects of SKF‐38393. In OS732 cells, overexpression of DR1 increased the rate of apoptosis, caspase‐9 and ‐3 expression, and the release of cytochrome c (Cyt c), reduced Bcl‐2 expression, inhibited extracellular signal‐regulated kinase 1/2 (ERK1/2) phosphorylation, and induced phosphorylation of p38 mitogen‐activated protein kinase (p38 MAPK) and c‐Jun N‐terminal kinase (JNK). These results suggest that activation of DR1 induces osteosarcoma cell apoptosis via changes to the MAPK pathway.