bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of TGF‐β1/Smad2/3 pathway in platelet‐rich plasma in retarding intervertebral disc degeneration
Authors: Yang Huilin , Yuan Chenxi , Wu Chunshen , Qian Jiale , Shi Qing , Li Xuefeng , Zhu Xuesong , Zou Jun
Published: April 2016

Recent studies have suggested that platelet‐rich plasma (PRP) injections are an effective way to retard intervertebral disc degeneration, but the mechanism of action is unclear. Activated platelets release some growth factors, such as transforming growth factor‐β1 (TGF‐β1), which positively modulate the extracellular matrix of nucleus pulposus cells. The purpose of this study was to explore the mechanism underlying the PRP‐mediated inhibition of intervertebral disc degeneration. In an in vitro study, we found that the proliferation of nucleus pulposus cells was greatly enhanced with 2.5% PRP treatment. The TGF‐β1 concentration was much higher after PRP treatment. PRP administration effectively increased the collagen II, aggrecan and sox‐9 mRNA levels and decreased collagen X levels. However, Western blotting demonstrated that specifically inhibiting TGF‐β1 signalling could significantly prevent nucleus pulpous cellular expression of Smad2/3 and matrix protein. In a rabbit study, magnetic resonance imaging revealed significant recovery signal intensity in the intervertebral discs of the PRP injection group compared with the very low signal intensity in the control groups. Histologically, the PRP plus inhibitor injection group had significantly lower expression levels of Smad2/3 and collagen II than the PRP group. These results demonstrated that a high TGF‐β1 content in the platelets retarded disc degeneration in vitro and in vivo. Inhibiting the TGF‐β1/Smad2/3 pathway could prevent this recovery by inactivating Smad2/3 and down‐regulating the extracellular matrix. Therefore, the TGF‐β1/Smad2/3 pathway might play a critical role in the ability of PRP to retard intervertebral disc degeneration.
Identification of multiple nursery habitats of skates in the eastern Bering Sea
Authors: Hoff G. R.
Published: April 2016

The use of more than a single nursery habitat type is examined for oviparous elasmobranchs using data summarized from studies conducted on the Alaska skate Bathyraja parmifera and the Aleutian skate Bathyraja aleutica in the eastern Bering Sea. The eastern Bering Sea skate species use two discrete areas as nurseries, one for egg deposition and a second for newly emergent juveniles. Egg deposition sites were located along the outer shelf and upper slope near canyons in the eastern Bering Sea. Newly emergent juveniles were found along the outer and middle shelf for B. parmifera and deep‐slope for B. aleutica, suggesting that habitat used by newly emergent juvenile skates is distinct from habitat used for egg deposition and embryo development. In reviewing many studies on oviparous elasmobranchs, similar patterns emerge of habitat use during their early life history. To distinguish these distinct habitats, appropriate terminology is proposed. Egg case nursery is suggested for areas of egg deposition and juvenile nursery is suggested for areas where juveniles aggregate after emergence. Criteria to describe each habitat type are outlined.
Using genetic inference to re‐evaluate the minimum longevity of the lemon shark Negaprion brevirostris
Authors: Brooks J. L. , Guttridge T. L. , Franks B. R. , Grubbs R. D. , Chapman D. D. , Gruber S. H. , Dibattista J. D. , Feldheim K. A.
Published: April 2016

A combination of mark–recapture and genetic sampling was used to extend the minimum longevity of an elasmobranch species and the life span estimate of the lemon shark Negaprion brevirostris was increased conservatively from 20·2 to 37 years. This increase in longevity means higher vulnerability and a longer recovery time from exploitation.
Pluvial flooding in urban areas: the role of surface drainage efficiency
Authors: Palla A. , Colli M. , Candela A. , Aronica G.T. , Lanza L.G.
Published: April 2016

Pluvial flooding in urban areas may derive from the limited or temporarily reduced efficiency of surface drainage, even when the underlying storm sewers are properly designed. This study focuses on the impact of uncertainties in the operational condition of the surface drainage system on pluvial flood hazard. The flood propagation model FLURB‐2D is implemented on a selected study area in the town of Genoa (Italy). Synthetic hyetographs based on the Chicago and bivariate copula methods with suitable return periods are used as input. While simulating the design rainfall, inlet operational conditions are varied stochastically using a Monte Carlo approach. Results confirm that microtopography has the potential to impact the efficiency of surface drainage and consequently to produce local flooding, with significant water depth in zones of flow concentration. Furthermore, the derived inundation maps allow the highlighting of areas with insufficient design of the surface drainage system (inlet size and positioning).
The Influence of Group Versus Individual Prenatal Care on Phase of Labor at Hospital Admission
Authors: Tilden Ellen L. , Emeis Cathy L. , Caughey Aaron B. , Weinstein Sarah R. , Futernick Sarah B. , Lee Christopher S.
Published: April 2016

Introduction

Group prenatal care, an alternate model of prenatal care delivery, has been associated with various improved perinatal outcomes in comparison to standard, individual prenatal care. One important maternity care process measure that has not been explored among women who receive group prenatal care versus standard prenatal care is the phase of labor (latent vs active) at hospital admission.

Methods

A retrospective case‐control study was conducted comparing 150 women who selected group prenatal care with certified nurse‐midwives (CNMs) versus 225 women who chose standard prenatal care with CNMs. Analyses performed included descriptive statistics to compare groups and multivariate regression to evaluate the contribution of key covariates potentially influencing outcomes. Propensity scores were calculated and included in regression models.

Results

Women within this sample who received group prenatal care were more likely to be in active labor (≥ 4 cm of cervical dilatation) at hospital admission (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.03‐2.99; P = .049) and were admitted to the hospital with significantly greater cervical dilatation (mean [standard deviation, SD] 5.7 [2.5] cm vs. 5.1 [2.3] cm, P = .005) compared with women who received standard prenatal care, controlling for potential confounding variables and propensity for group versus individual care selection.

Discussion

Group prenatal care may be an effective and safe intervention for decreasing latent labor hospital admission among low‐risk women. Neither group prenatal care nor active labor hospital admission was associated with increased morbidity.
cGMP/cGMP‐dependent protein kinase pathway modulates nicotine‐induced currents through the activation of α‐bungarotoxin‐insensitive nicotinic acetylcholine receptors from insect neurosecretory cells
Authors: Mannai Safa , Bitri Lofti , Thany Steeve H.
Published: April 2016

Insect neurosecretory cells, called dorsal unpaired median neurons, are known to express two α‐bungarotoxin‐insensitive nicotinic acetylcholine receptor (nAChR) subtypes, nAChR1 and nAChR2. It was demonstrated that nAChR1 was sensitive to cAMP/cAMP‐dependent protein kinase (PKA) regulation, resulting in a modulation of nicotine currents. In this study, we show that cyclic guanosine monophosphate (cGMP)/cGMP‐dependent protein kinase (PKG) pathway modulates nicotine‐induced currents, as increased cGMP affects the second compound of the biphasic current–voltage curve, corresponding to the nAChR2 receptors. Indeed, maintaining the guanosine triphosphate level with 100 μM guanosine triphosphate‐γ‐S increased nicotine currents through nAChR2. We also demonstrated that inhibition of PKG activity with 0.2 μM (8R,9S,11S)‐(‐)‐9‐methoxy‐carbamyl‐8‐methyl‐2,3,9,10‐tetrahydro‐8,11‐epoxy‐1H,8H,11H‐2,7b,11a‐trizadibenzo‐(a,g)‐cycloocta‐(c,d,e)‐trinden‐1‐one (KT5823), a PKG specific inhibitor, reduced nicotine‐induced current amplitudes. KT5823 effect on nicotine currents is associated with calcium (Ca2+) activity because inhibition of Ca2+ concentration with cadmium chloride (CdCl2) abolished KT5823‐induced inhibition mediated by nAChR2. However, specific inhibition of nitric oxide‐guanylyl cyclase (GC) complex by 10 μM 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) significantly increased nicotine‐induced current amplitudes on both nAChR1 and nAChR2. These results suggest that nicotine‐induced currents mediated by both α‐bungarotoxin‐insensitive nAChR1 and nAChR2 are coupled to the cGMP/PKG pathway.

image

We propose that nicotinic acetylcholine receptor activation induces an increase in intracellular calcium (Ca2+) concentration. Elevation of intracellular Ca2+ results in the formation of Ca2+‐calmodulin (CaM) complex, which activates guanylyl cyclase (GC) and/or adenylyl cyclase (AC). Ca2+‐CaM complex could activate Ca2+ calmodulin kinase II which could directly or indirectly modulate the nicotinic response. The mechanisms by which cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) interact remain unclear. We demonstrate that nicotine‐induced currents are coupled to the cGMP/PKG pathway.
The function and performance of aqueous aerosol devices for inhalation therapy
Authors: Carvalho Thiago C , McConville Jason T
Published: April 2016

Objectives

In this review paper, we explore the interaction between the functioning mechanism of different nebulizers and the physicochemical properties of the formulations for several types of devices, namely jet, ultrasonic and vibrating-mesh nebulizers; colliding and extruded jets; electrohydrodynamic mechanism; surface acoustic wave microfluidic atomization; and capillary aerosol generation.

Key findings

Nebulization is the transformation of bulk liquids into droplets. For inhalation therapy, nebulizers are widely used to aerosolize aqueous systems, such as solutions and suspensions. The interaction between the functioning mechanism of different nebulizers and the physicochemical properties of the formulations plays a significant role in the performance of aerosol generation appropriate for pulmonary delivery. Certain types of nebulizers have consistently presented temperature increase during the nebulization event. Therefore, careful consideration should be given when evaluating thermo-labile drugs, such as protein therapeutics. We also present the general approaches for characterization of nebulizer formulations.

In conclusion, the interplay between the dosage form (i.e. aqueous systems) and the specific type of device for aerosol generation determines the effectiveness of drug delivery in nebulization therapies, thus requiring extensive understanding and characterization.
Effect of permeability enhancers on paracellular permeability of acyclovir
Authors: Ates Muge , Kaynak Mustafa Sinan , Sahin Selma
Published: April 2016

Objectives

According to Biopharmaceutics Classification System (BCS), acyclovir is a class III (high solubility, low permeability) compound, and it is transported through paracellular route by passive diffusion. The aim of this study was to investigate the effect of various pharmaceutical excipients on the intestinal permeability of acyclovir.

Methods

The single-pass in-situ intestinal perfusion (SPIP) method was used to estimate the permeability values of acyclovir and metoprolol across different intestinal segments (jejunum, ileum and colon). Permeability coefficient (Peff) of acyclovir was determined in the absence and presence of a permeation enhancer such as dimethyl β-cyclodextrin (DM-β-CD), sodium lauryl sulfate (SLS), sodium caprate (Cap-Na) and chitosan chloride.

Key findings

All enhancers increased the permeability of paracellularly transported acyclovir. Although Cap-Na has the highest permeability-enhancing effect in all segments, permeation-enhancing effect of chitosan and SLS was only significant in ileum. On the other hand, DM-β-CD slightly decreased the permeability in all intestinal segments.

Conclusions

These findings have potential implication concerning the enhancement of absorption of paracellularly transported compounds with limited oral bioavailability. In the case of acyclovir, Cap-Na either alone or in combination with SLS or chitosan has the potential to improve its absorption and bioavailability and has yet to be explored.
Preliminary Assessment of Biofouling on Offshore Mussel Farms
Authors: Atalah Javier , Fletcher Lauren M. , Hopkins Grant A. , Heasman Kevin , Woods Chris M. C. , Forrest Barrie M.
Published: April 2016

Biofouling is a significant operational problem for the aquaculture industry globally; however, options for on‐farm management are limited. In New Zealand, the green‐lipped mussel,Perna canaliculus, has historically been cultivated at inshore locations, but increased competition for space has led the industry to develop offshore farming sites several kilometers from the coast. We hypothesize that the distance to these farm sites from coastal locations, and their placement over extensive soft‐sediment habitats, may provide a barrier to colonization by biofouling species with limited natural dispersal abilities. A study of two offshore mussel farms revealed that they supported relatively impoverished biofouling communities by comparison with inshore mussel farms and other artificial structures. Offshore sites had a relatively low number of taxa and a low prevalence of short‐dispersing organisms such as ascidians, which are a problematic group of fouling organisms in aquaculture. We suggest that newly established offshore marine farms have the potential to be kept free of a range of problematic fouling organisms, provided the introduction of such species via human transport pathways can be mitigated.
Evaluation of Soy Protein Concentrate and Meat and Bone Meal as a Replacement for Fish Meal in the Diet of Nile Tilapia Fingerlings
Authors: Ribeiro Manoel Joaquim Peres , Vidotti Rose M. , Ferreira Leandro A. , Gonçalves Giovani Sampaio
Published: April 2016

This experiment evaluated soy protein concentrate (SPC) and meat and bone meal as a replacement for fish meal protein (FP) in the diet of Nile tilapia fingerlings. Five diets were evaluated including a control diet (50.0% crude protein [CP], of which half the protein came from fish meal [FM]), and four diets in which FM was replaced by increasing amounts of SPC (25.5, 50.0, 75.5, and 100.0%) in combination with meat and bone meal. At the conclusion of a 60‐d growth trial, the following parameters were determined: final weight (FW), final length (FL), weight gain (WG), feed intake (FI), apparent feed conversion (AFC), survival (SUR), and production cost. The estimate of the best replacement value was determined by polynomial regression and the linear response plateau. The results showed significant (P < 0.05) improvement for WG and AFC ratio as FM was gradually replaced by SPC. The parameters FL and FI reached their optimum value at a replacement level of 100% SPC. These results show that it is feasible to use a combination of SPC and meat and bone meal in a balanced feed formulation as an alternative protein source in the diets of Nile tilapia fingerlings.
The HopF family of Pseudomonas syringae type III secreted effectors
Authors: Lo Timothy , Koulena Noushin , Seto Derek , Guttman David S. , Desveaux Darrell
Published: April 2016

Pseudomonas syringae is a bacterial phytopathogen that utilizes the type III secretion system to inject effector proteins into plant host cells. Pseudomonas syringae can infect a wide range of plant hosts, including agronomically important crops such as tomatoes and beans. The ability of P. syringae to infect such numerous hosts is caused, in part, by the diversity of effectors employed by this phytopathogen. Over 60 different effector families exist in P. syringae; one such family is HopF, which contains over 100 distinct alleles. Despite this diversity, research has focused on only two members of this family: HopF1 from P. syringae pathovar phaseolicola 1449B and HopF2 from P. syringae pathovar tomato DC3000. In this study, we review the research on HopF family members, including their host targets and molecular mechanisms of immunity suppression, and their enzymatic function. We also provide a phylogenetic analysis of this expanding effector family which provides a basis for a proposed nomenclature to guide future research. The extensive genetic diversity that exists within the HopF family presents a great opportunity to study how functional diversification on an effector family contributes to host specialization.
Non‐dermatophytic onychomycosis diagnostic criteria: an unresolved question
Authors: Bombace Francesca , Iovene Maria Rosaria , Galdiero Marilena , Martora Francesca , Nicoletti Giovanni Francesco , D'Andrea Mirella , Della Pepa Maria Elena , Vitiello Mariateresa
Published: April 2016

Non‐dermatophytic moulds (NDMs) have been increasingly recognised as causative agents of onychomycosis. The diagnosis of onychomycosis is most often obtained by microscopic observation of nail specimens where fungal elements can be detected and cultured by standard mycological techniques. Direct microscopic examination does not always result positive in NDM onychomycosis; therefore to perform a correct diagnosis, a proper mycological culture is often required. The purpose of our study was to evaluate the role of direct microscopic examination in the NDM onychomycosis diagnosis. The results show that only 57.2% of the specimens from onychomycosis patients could be properly diagnosed showing positivity to both direct microscopic examination and NDMs culture isolation in two or more subsequent inoculations, while 42.8% of analysed specimens with a negative direct microscopic examination, showed NDMs growth after three or more subsequent inoculations. The large proportion of false negatives (more than 42%) could be related to the duration of the infection and/or to the experience and skills of the personnel dedicated to specimen collection. We point out the need for thoroughly evaluating all specimens showing cultural growth in at least three subsequent medium inoculations, whatever the result of the microscopic examination, in order to reduce false‐negative rates. This strategy would allow for more accurate diagnosis of this mycosis.
How Superior–Subordinate Relationship Quality and Conflict Management Styles Influence an Employee's Use of Upward Dissent Tactics
Authors: Redmond Valeska , Jameson Jessica Katz , Binder Andrew R.
Published: April 2016

This study examined employees’ use of upward dissent tactics to express disagreement with organizational policies or practices to their supervisors. Employees (N = 242) from three organizations completed a survey instrument in which they reported the types of upward dissent tactics and types of conflict management styles they used with their supervisors as well as their perceptions of the quality of those relationships. The integrating conflict management style was positively correlated with the prosocial dissent tactic and negatively correlated with the threatening resignation dissent tactic. The dominating conflict management style was positively correlated with threatening resignation, circumvention, and repetition dissent tactics. When looking at relationships between the use of upward dissent tactics, superior–subordinate relationship quality, and conflict management styles, we found that conflict management styles were a stronger predictor of the use of upward dissent tactics than superior–subordinate relationship quality. Implications for employee voice are discussed.
An Exploration of the Structure of Effective Apologies
Authors: Lewicki Roy J. , Polin Beth , Lount Robert B.
Published: April 2016

Violations of trust are an unfortunate but common occurrence in conflict and negotiation settings: negotiators make promises that they do not keep; parties in conflict behave in unexpected ways, escalating tensions and breaking past trust. What often follows these violations is some form of an account, specifically an apology, in an effort to repair that trust. But are some apologies more effective than others? Two studies reported here examine the structural components of apologies. Six components of an apology were defined from previous research and presented to subjects—singly and in combination—in the form of component definitions and in the context of a trust violation scenario. Results indicate that not all apologies are viewed equally; apologies with more components were more effective than those with fewer components, and certain components were deemed more important than others. Moreover, apologies following competence‐based trust violations were seen as more effective than apologies following integrity‐based violations. Implications and future directions for research in the structure of effective apologies are presented.
Yersinochloa gen. nov. (Gramineae: Bambusoideae‐Bambusineae) endemic to the Lam Vien Plateau, southern Vietnam
Authors: Nguyen Hoang Nghia , Tran Van Tien
Published: April 2016

A clambering bamboo endemic to the Lam Vien plateau, southern Vietnam and representing a new monotypic endemic genus, Yersinochloa H. N. Nguyen & V. T. Tran (Gramineae–Bambusoideae–Bambusinae), is described and illustrated. It has an indeterminate inflorescence, terminate leafy branches, pseudo‐spikelets with only one perfect floret, unkeeled palea, three lodicules, six stamens with free filaments, anther apices with tiny spines, glabrous ovary with a long style, 3 plumose stigmas, and an oblong caryopsis with a relatively thin pericarp.
Adverse childhood experiences are associated with irritable bowel syndrome and gastrointestinal symptom severity
Authors: Park S. H. , Videlock E. J. , Shih W. , Presson A. P. , Mayer E. A. , Chang L.
Published: April 2016

Background

Early adverse life events (EALs) are associated with irritable bowel syndrome (IBS). Exposure to EALs as assessed by the Adverse Childhood Experiences (ACE) questionnaire is associated with greater disease prevalence, but ACE has not been studied in gastrointestinal disorders. Study aims were to: (i) Estimate the prevalence of EALs in the IBS patients using the ACE questionnaire; (ii) Determine correlations between ACE and Early Trauma Inventory Self Report‐Short Form (ETI‐SR) scores to confirm its validity in IBS; and (iii) Correlate ACE scores with IBS symptom severity.

Methods

A total of 148 IBS (73% women, mean age = 31 years) and 154 HCs (59% women, mean age = 30 years) completed the ACE and ETI‐SR between June 2010 and April 2015. These surveys measured EALs before age 18 in the domains of physical, sexual, and emotional abuse, and general trauma. IBS and abdominal pain severity was measured by a 20‐point scale (0 = none, 20 = worst symptoms).

Key Results

The ACE score increased the odds of having IBS (odds ratio [OR] = 2.05, 95% confidence interval [CI]: 1.21–3.48, p = 0.008). Household mental illness (p < 0.001), emotional abuse (p = 0.004), and incarcerated household member (p = 0.019) were significant predictors of IBS. Adverse childhood experiences and ETI‐SR scores were strongly correlated (r = 0.59, p < 0.001). ACE, but not ETI‐SR, modestly correlated with IBS severity (r = 0.17, p = 0.036) and abdominal pain (r = 0.20, p = 0.015).

Conclusions & Inferences

The ACE questionnaire is a useful instrument to measure EALs in IBS based on its use in large studies, its ability to measure prevalence across different EAL domains, and its correlation with symptom severity.
Subcutaneous Double “Purse String Suture”—A Safe Method for Femoral Vein Access Site Closure after Leadless Pacemaker Implantation
Authors: KYPTA ALEXANDER , BLESSBERGER HERMANN , LICHTENAUER MICHAEL , KAMMLER JUERGEN , LAMBERT THOMAS , KELLERMAIR JOERG , NAHLER ALEXANDER , KIBLBOECK DANIEL , SCHWARZ STEFAN , STEINWENDER CLEMENS
Published: April 2016

Background

Leadless cardiac pacemaker (LCP) requires large‐caliber venous sheaths for device placement. Sheath sizes for these procedures vary from 18‐ to 23‐French (F). The most common complications are hematomas, pseudoaneurysms, and arteriovenous fistulas. Complete and secure closure of the venous access is an important step at the end of such a procedure.

Methods

We performed a retrospective analysis of all patients who had undergone LCP implantation at our institution. Patients and procedural characteristics as well as groin complications at 30 days and 3 months were evaluated. After sheath removal venous access sites were closed performing a so‐called “purse‐string” suture (PSS).

Results

Seventy‐seven patients received an LCP at our institution. In 27 (35%) of these patients a heparin bolus was given at the beginning of the procedure. Anticoagulation therapy with phenprocoumon was present in 32 (40%) of patients. In 76 (98.7%) patients, the LCP was implanted without complications. In one (1.3%) patient a perforation occurred during implantation, which required surgical intervention. Access site complications occurred in three (3.9%) patients, two (2.6%) groin hematomas, and one (1.3%) arteriovenous fistula. The hematomas disappeared completely after 3 weeks, and the fistula was not detectable by ultrasound anymore after 4 weeks.

Conclusion

Use of subcutaneous absorbable double PSS closure after removal of large‐caliber venous sheaths is a safe technique to achieve immediate postprocedural hemostasis. Especially for sheath sizes with an inner diameter of 23F, this technique creates a very secure and also cosmetically appealing closure.
'SUPRANATIONALISM' IN QUESTION: BELIEFS, VALUES, AND THE SOCIALIZING POWER OF THE EUROPEAN COMMISSION REVISITED
Authors: CONNOLLY SARA , KASSIM HUSSEIN
Published: April 2016

Do international organizations affect the views of the people who work for them? Although increasingly sophisticated methods have been used to address this question, disagreement persists about whether the beliefs of staff are formed before they join, after they enter the institution, or are shaped by instrumental calculation. Drawing on an original dataset based on the first fully representative survey of the European Commission's workforce, this article breaks new ground by putting different definitions of ‘supranationalism’ to the test and by capturing multiple ways in which individuals may be affected by the experience of working for the organization. For the first time, it demonstrates that commitment to ‘supranationalism’ varies between Commission staff groupings, that the influences on belief vary with the measure of ‘supranationalism’ used, and that both post‐recruitment experience and pre‐recruitment roles play a part in shaping beliefs.
The assessment of HER2 status in breast cancer: the past, the present, and the future
Authors: Nitta Hiroaki , Kelly Brian D. , Allred Craig , Jewell Suzan , Banks Peter , Dennis Eslie , Grogan Thomas M.
Published: April 2016

Humanized monoclonal anti‐human growth factor receptor 2 (HER2) antibody trastuzumab was approved for HER2 positive breast cancer patient treatment 11 years after the demonstration of HER2 gene amplification associated with the HER2 protein overexpression in breast cancer in 1987. HER2 positive status of breast cancer patients is assessed by HER2 gene amplification with in situ hybridization (ISH) and/or HER2 protein overexpression with immunohistochemistry (IHC). Because the discordance between quantitative HER2 ISH and subjective, semi‐quantitative HER2 IHC assay results is a well‐recognized issue of HER2 testing, we developed an assay combining HER2 ISH and HER2 IHC assays (HER2 gene‐protein assay; HER2 GPA) as one test on the same tissue section. HER2 GPA allows pathologists to score the HER2 gene and HER2 protein status simultaneously at the individual cell level. The possibility that HER2 GPA may become the next generation of HER2 testing is discussed, particularly for cases in which it is difficult to assess the HER2 status of breast cancer patients due to the HER2 heterogeneity.
Impact of interspecific competition and drought on the allocation of new assimilates in trees
Authors: Hommel R. , Siegwolf R. , Zavadlav S. , Arend M. , Schaub M. , Galiano L. , Haeni M. , Kayler Z. E. , Gessler A.
Published: April 2016

In trees, the interplay between reduced carbon assimilation and the inability to transport carbohydrates to the sites of demand under drought might be one of the mechanisms leading to carbon starvation. However, we largely lack knowledge on how drought effects on new assimilate allocation differ between species with different drought sensitivities and how these effects are modified by interspecific competition. We assessed the fate of 13C labelled assimilates in above‐ and belowground plant organs and in root/rhizosphere respired CO2 in saplings of drought‐tolerant Norway maple (Acer platanoides) and drought‐sensitive European beech (Fagus sylvatica) exposed to moderate drought, either in mono‐ or mixed culture. While drought reduced stomatal conductance and photosynthesis rates in both species, both maintained assimilate transport belowground. Beech even allocated more new assimilate to the roots under moderate drought compared to non‐limited water supply conditions, and this pattern was even more pronounced under interspecific competition. Even though maple was a superior competitor compared to beech under non‐limited soil water conditions, as indicated by the changes in above‐ and belowground biomass of both species in the interspecific competition treatments, we can state that beech was still able to efficiently allocate new assimilate belowground under combined drought and interspecific competition. This might be seen as a strategy to maintain root osmotic potential and to prioritise root functioning. Our results thus show that beech tolerates moderate drought stress plus competition without losing its ability to supply belowground tissues. It remains to be explored in future work if this strategy is also valid during long‐term drought exposure.
Colonization of the vegetative stage of rice plants by the false smut fungus Villosiclava virens, as revealed by a combination of species‐specific detection methods
Authors: Tanaka E. , Kumagawa T. , Ito N. , Nakanishi A. , Ohta Y. , Suzuki E. , Adachi N. , Hamada A. , Ashizawa T. , Ohara T. , Tsuda M.
Published: April 2016

Rice false smut disease caused by the ascomycete fungus Villosiclava virens (Clavicipitaceae) reduces rice yield worldwide. It invades rice panicles and forms dark‐green false smut balls composed of thick‐walled conidia. Although the infection process during the booting stage is well studied, its infection route before this is unclear. It was hypothesized that the thick‐walled conidia in soil penetrate rice roots, and the fungus latently colonizes roots and tiller buds at the vegetative stage. This hypothesis was tested using species‐specific detection methods. First, real‐time PCR with species‐specific primers and probe was used to estimate thick‐walled conidial number in the paddy field soil. Secondly, nested PCR with species‐specific primers showed that fungal DNA was detected in roots and shoot apices of rice plants in the vegetative stage. Thirdly, colourimetric in situ hybridization with a species‐specific oligonucleotide probe targeting 18S rRNA suggested that sparse mycelia or tightly condensed mycelia were present on the external surface of tiller buds enveloped by juvenile leaf sheaths at the vegetative stage. Thin hyphae were found around leaf axils at the surface of elongated stems at the heading stage, and the fungal hyphae grew in the rice root tissues. In addition, it was demonstrated that eGFP‐tagged transformants of the fungus invaded rice roots and colonized the surface of roots and leaf sheaths under artificial conditions.
A Boundary Value Problem for Conjugate Conductivity Equations
Authors: Chaabi S. , Rigat S. , Wielonsky F.
Published: April 2016

We give explicit integral formulas for the solutions of planar conjugate conductivity equations in a circular domain of the right half‐plane with conductivity , . The representations are obtained via the so‐called unified transform method or Fokas method, involving a Riemann–Hilbert problem on the complex plane when p is even and on a two‐sheeted Riemann surface when p is odd. They are given in terms of the Dirichlet and Neumann data on the boundary of the domain. For even exponent p, we also show how to make the conversion from one type of conditions to the other by using the global relation that follows from the closedness of some differential form. The method used to derive our integral representations could be applied in any bounded simply connected domain of the right half‐plane with a smooth boundary.
Postoperative complications after dental extraction in liver pretransplant patients
Authors: Pereira Thaís dos Santos Fontes , Pelinsari Fernanda Cristina Melo , Ruas Bruna Mara , Avelar Luanne Priscila Pereira , da Fonseca Vitor José , de Abreu Mauro Henrique Nogueira , Salomão Ulisses Eliezer , Lima Agnaldo Soares , de Souza e Silva Maria Elisa , Gomez Ricardo Santiago
Published: April 2016

Objectives

The liver pretransplant phase requires the interaction of ­multidisciplinary teams for optimal patient outcomes, including dental ­professionals. In this study, we sought to estimate the prevalence of complications related to dental extraction in liver transplant candidates.

Material and methods

This study is a case series of patients eligible for liver transplants referred for dental treatment between 2012 and 2014. Eligible patients for this study underwent at least one tooth extraction, had a complete blood count at the time of the procedure, and were candidates for liver transplantation.

Results

Forty‐three patients, 12 women (28%) and 31 men (72%), with an ­average age of 50.9 ± 11.4 years, had received a total of 116 dental extractions. The prevalence of postoperative complications was 1.7% including two bleeding episodes in the same patient. Seven patients presented a platelet count below 50 × 10³/μL and received platelet transfusions preoperatively.

Conclusions

Postoperative complications following dental extractions in liver transplant candidates are unusual.

Clinical Relevance

Low postoperative complications prevalence indicates that dental surgical procedures may be safety performed in patients eligible for liver transplantation after careful ­preoperative evaluation.
Sedimentological and palaeohydrological characterization of Late Pleistocene and Holocene tufa mound palaeolakes using trenching methods in the Spanish Pyrenees
Authors: Pellicer Xavier M. , Corella Juan Pablo , Gutiérrez Francisco , Roqué Carles , Linares Rogelio , Carbonel Domingo , Zarroca Mario , Guerrero Jesús , Comas Xavier
Published: April 2016

Lakes developed in the inner depressions of tufa mounds are rare geomorphic features and still poorly understood. Sedimentation in this unusual type of endorheic lake with a very restricted catchment area is highly sensitive to environmental and hydrological changes. The Isona tufa mound complex, north‐eastern Iberian Peninsula, is associated with the discharge zone of a confined artesian aquifer and comprises 11 tufa mounds consisting of an annular rimstone enclosing a central depression filled with lake deposits. Data gathered from trenches excavated in four palaeolakes located within three different morphostratigraphic units permitted a precise analysis of the geometrical characteristics and stratigraphic relationships of the deposits and provided a sedimentation model for the Late Quaternary infilling of the spring‐fed lakes. The work illustrates that trenches allow a precise characterization of the stratigraphic arrangements, lateral facies changes and deformation structures, which are not apparent in studies relying solely on borehole records, and facilitate sampling for dating and geochemical analyses. The five sedimentary facies described represent different evolutionary stages of the lakes, including: (i) carbonate‐rich palustrine deposits probably related to periods with strong hydrological seasonality; (ii) massive highly bioturbated organic ooze; (iii) banded organic carbonate‐rich facies associated with an increase in the regional effective moisture; (iv) fine‐grained quartz‐rich aeolian/slope‐wash sediments; and (v) colluvial facies deposited following the desiccation of the lakes located at higher altitudes. Geochemical and sedimentological analyses of the lacustrine sequences provided information on the palaeohydrological evolution of the Isona tufa mound complex and the palaeoenvironmental conditions of the area over the last 28 ka. Radiometric dating suggests that deposition occurred simultaneously at ca 22 ka in palaeolakes situated at different elevations. A drop in the piezometric level prompted by the opening of springs at lower altitudes probably caused the deactivation of the upper springs and the desiccation of the lakes. Arid conditions prevailed in the area during the Late Glacial and the early Holocene (28·0 to 8·5 ka bp). More humid conditions recorded from 8·5 to 4·2 ka and again since 1·7 ka are in accordance with palaeoenvironmental reconstructions available in the Western Mediterranean since the Last Glacial Maximum.
From Social Capital to Inequality: Migrant Networks in Different Stages of Labor Incorporation
Authors: Morales Maria Cristina
Published: April 2016

How does social capital vary in the distinct stages (prehiring, hiring, and posthiring) of labor incorporation? Based on interviews with 71 Latino migrant workers engaged in residential construction in Las Vegas, Nevada, and 30 transnational migrants who returned to Mexico after working in the United States, I examined two primary issues: first, the structural labor mechanisms that create hyperexploitation, and second, how, in turn, such processes shape social capital. I discovered, at the prehiring phase, social networks connected to subcontractors and those who attempt to form a labor crew function as social capital, despite what may appear to be bonded labor. At the hiring stage, social capital continues to play a role, yet posthiring labor structures create hyperexploitation and immigrants experience inequality in social capital. In such contexts, undocumented Latinos are unable to retain their social capital as U.S. labor structures such as subcontracting and piece‐rate compensation lead to the subjugation of workers, who can become “ghost workers” and bonded laborers. I conclude that in the posthiring stage, such labor structures create what Lin (2000, 2001) refers to as capital deficit and return deficit in social capital that greatly limit the economic incorporation of Latino immigrants.
Cytomegalovirus pre‐emptive therapy after hematopoietic stem cell transplantation in the era of real‐time quantitative PCR: comparison with recipients of solid organ transplants
Authors: Panagou E. , Zakout G. , Keshani J. , Smith C. , Irish D. , Mackinnon S. , Kottaridis P. , Fielding A. , Griffiths P.D.
Published: April 2016

Background

Cytomegalovirus (CMV) continues to be an important complication of hematopoietic stem cell transplantation and solid organ transplantation.

Methods

In this study, 314 patients who underwent hematopoietic stem cell transplantation between January 2003 and October 2011 were tested serially for CMV DNA by real‐time quantitative polymerase chain reaction (qPCR) for 90 days post transplantation. Patients with CMV viremia >3000 genomes/mL (equivalent to 2520 IU/mL) received pre‐emptive therapy and were compared with previously published data from solid organ transplant (SOT) patients monitored and treated in exactly the same way.

Results

After stem cell transplant (SCT), 48% of patients developed at least 1 episode of viremia. The median duration of a viremic episode was 25 days and the peak viral load (VL) was 4784 genomes/mL whole blood (equivalent to 4019 IU/mL). The data demonstrated that recipients with positive CMV serostatus were at increased risk of developing viremia, with 0% of donor‐negative/recipient‐negative (D−R−), 3.7% of D+R−, 79.5% of D−R+, and 74.2% of D+R+ groups developing viremia over follow‐up (adjusted hazard ratio for D+R− vs. D+R+ group 0.03; 95% confidence interval 0.004, 0.18; P = 0.0013). In contrast with SOT patients, where 58/74 (78%) D+R− patients had viremia, a low risk of CMV infection was seen after stem cell transplantation (1/27; 3.7%).

Conclusion

As both groups of patients, the previously published SOT patients and the present hematopoietic SCT patients, were monitored using the same protocol and qPCR assay with pre‐emptive therapy administered at the same VL cutoffs, the distinct differences seen cannot be explained by differences in testing or management and thus emphasize distinct aspects of the natural history of CMV infection post transplant in these 2 patient groups.
The transcriptomic signature of developing soybean seeds reveals the genetic basis of seed trait adaptation during domestication
Authors: Lu Xiang , Li Qing‐Tian , Xiong Qing , Li Wei , Bi Ying‐Dong , Lai Yong‐Cai , Liu Xin‐Lei , Man Wei‐Qun , Zhang Wan‐Ke , Ma Biao , Chen Shou‐Yi , Zhang Jin‐Song
Published: April 2016

Cultivated soybean has undergone many transformations during domestication. In this paper we report a comprehensive assessment of the evolution of gene co‐expression networks based on the analysis of 40 transcriptomes from developing soybean seeds in cultivated and wild soybean accessions. We identified 2680 genes that are differentially expressed during seed maturation and established two cultivar‐specific gene co‐expression networks. Through analysis of the two networks and integration with quantitative trait locus data we identified two potential key drivers for seed trait formation, GA20OX and NFYA. GA20OX encodes an enzyme in a rate‐limiting step of gibberellin biosynthesis, and NFYA encodes a transcription factor. Overexpression of GA20OX and NFYA enhanced seed size/weight and oil content, respectively, in seeds of transgenic plants. The two genes showed significantly higher expression in cultivated than in wild soybean, and the increases in expression were associated with genetic variations in the promoter region of each gene. Moreover, the expression of GA20OX and NFYA in seeds of soybean accessions correlated with seed weight and oil content, respectively. Our study reveals transcriptional adaptation during soybean domestication and may identify a mechanism of selection by expression for seed trait formation, providing strategies for future breeding practice.
Use of a Grant Writing Class in Training PhD Students
Authors: Kahn Richard A. , Conn Graeme L. , Pavlath Grace K. , Corbett Anita H.
Published: April 2016

A well‐written application for funding in support of basic biological or biomedical research or individual training fellowship requires that the author perform several functions well. They must (i) identify an important topic, (ii) provide a brief but persuasive introduction to highlight its significance, (iii) identify one or two key questions that if answered would impact the field, (iv) present a series of logical experiments and convince the reader that the approaches are feasible, doable within a certain period of time and have the potential to answer the questions posed, and (v) include citations that demonstrate both scholarship and an appropriate command of the relevant literature and techniques involved in the proposed research study. In addition, preparation of any compelling application requires formal scientific writing and editing skills that are invaluable in any career. These are also all key components in a doctoral dissertation and encompass many of the skills that we expect graduate students to master. Almost 20 years ago, we began a grant writing course as a mechanism to train students in these specific skills. Here, we describe the use of this course in training of our graduate students as well as our experiences and lessons learned.
N‐Cadherin Regulates Cell Migration Through a Rab5‐Dependent Temporal Control of Macropinocytosis
Authors: Wen Meng‐Hsuan , Wang Jen‐Yeu , Chiu Yu‐Ting , Wang Mei‐Pin , Lee Sue‐Ping , Tai Chin‐Yin
Published: April 2016

Macropinocytosis is a clathrin‐independent endocytic pathway implicated in fluid uptake, pathogen invasion and cell migration. During collective cell migration, macropinocytosis occurs primarily at membrane ruffles arising from the leading edges of migrating cells. We report here that N‐cadherin (Ncad) regulates the tempo of macropinocytosis and thereby influences wound‐induced collective cell migration. Using live‐cell and super‐resolution imaging techniques, we observed that Ncad formed clusters at the membrane ruffles and macropinosomes. De‐clustering of Ncad by an interfering antibody impaired the recruitment of Rab5‐an early endosomal marker‐to the macropinosomes. Moreover, we demonstrated that Ncad interacts with Rab5, and laser ablation of Ncad caused Rab5 to dissociate from the macropinosomes. Although Rab5 detached from macropinosomes upon the de‐clustering of Ncad, the recruitment of late endosomal marker Rab7 occurred earlier. Consequently, both centripetal trafficking of macropinosomes and collective migration were accelerated due to de‐clustering of Ncad. Thus, our results suggest that Ncad is involved in the maturation of macropinocytosis through Rab5 recruitment, linking macropinocytosis and cell migration through a novel function of Ncad.
Monomerization and ER Relocalization of GRASP Is a Requisite for Unconventional Secretion of CFTR
Authors: Kim Jiyoon , Noh Shin Hye , Piao He , Kim Dong Hee , Kim Kuglae , Cha Jeong Seok , Chung Woo Young , Cho Hyun‐Soo , Kim Joo Young , Lee Min Goo
Published: April 2016

Induction of endoplasmic reticulum (ER)‐to‐Golgi blockade or ER stress induces Golgi reassembly stacking protein (GRASP)‐mediated, Golgi‐independent unconventional cell‐surface trafficking of the folding‐deficient ΔF508‐cystic fibrosis transmembrane conductance regulator (CFTR). However, molecular mechanisms underlying this process remain elusive. Here, we show that phosphorylation‐dependent dissociation of GRASP homotypic complexes and subsequent relocalization of GRASP to the ER play a critical role in the unconventional secretion of CFTR. Immunolocalization analyses of mammalian cells revealed that the Golgi protein GRASP55 was redistributed to the ER by stimuli that induce unconventional secretion of ΔF508‐CFTR, such as induction of ER‐to‐Golgi blockade by the Arf1 mutant. Notably, the same stimuli also induced phosphorylation of regions near the C‐terminus of GRASP55 and dissociation of GRASP homomultimer complexes. Furthermore, phosphorylation‐mimicking mutations of GRASP55 induced the monomerization and ER relocalization of GRASP55, and these changes were nullified by phosphorylation‐inhibiting mutations. These results provide mechanistic insights into how GRASP accesses the ER‐retained ΔF508‐CFTR and mediates the ER stress‐induced unconventional secretion pathway.