bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of biofilm dispersal approaches in Pseudomonas aeruginosa and evaluation of dispersed cells in acute infection mouse model
Authors: Ruhal Rohit , De Winter Fien , de Jonger Bart , Xavier Basil Britto , lammens Christine , Goossens Herman , Singh Samir Kumar , Malhotra-Kumar Surbhi
Published: July 2019

Biofilm dispersal is biologically significant process to fully understand its consequences during biofilm based infections. The mechanism for biofilm dispersal may involve response to environmental cues and changes in intracellular secondary messengers. Considering range of cues for biofilm dispersal, it is significant to study if dispersed cells generated by different methods have similar phenotype. In the present study, we have compared four type of biofilm dispersal in P. aeruginosa based in response to environment cues (starvation and nutrient rich), c-di-GMP knockdown and signaling molecule NO. We have determined their dispersal efficiency, susceptibility of dispersed cells for antibiotics, their transcriptomic changes compared to planktonic and biofilm. We also determined if dispersed cells can cause acute infections in mouse models. In vitro experiments showed that NO and c-di-GMP based dispersal methods had high biofilm reduction efficiency of 50 and 75% respectively, however, the nutrient induced dispersion showed low efficiency (≈30%) and more tolerance to colistin. We also showed that in vitro dispersed cells induced >10-fold transcriptomic expression of genes (at significance level of p < 0.005) related to efflux pumps (mexCD-oprJ), antibiotic resistance (arnDET) in dispersed cells induced by NO and nutrient change, while denitrification pathway and virulence (T3SS, VreI, T2SS) genes in all dispersed cells compared to planktonic and biofilm state. When the ability of the dispersed cells was tested in mouse model of lung infection, c-di-GMP and NO based dispersed cells displayed enhanced infections and haematogenous spread to liver and spleen and higher mortality. Although degree of immune response (cytokines) does not differ based on phenotypes inoculated in our experimental conditions. Based on our data most efficient dispersal methods increase murine mortality. This indicates their capability of making biofilm associated infection more complicated. Our data encourage to be more careful for studies suggesting biofilm dispersal during treatment of biofilm infections.
Modulation of RNA condensation by the DEAD-box protein eIF4A
Authors: Tauber Devin , Tauber Gabriel , Khong Anthony , Van Treeck Briana , Pelletier Jerry , Parker Roy
Published: July 2019

Stress granules are condensates of non-translating mRNAs and proteins involved in the stress response and neurodegenerative diseases. Stress granules form in part through intermolecular RNA-RNA interactions, although the process of RNA condensation is poorly understood. In vitro, we demonstrate that RNA is effectively recruited to the surfaces of RNA or RNP condensates. We demonstrate that the DEAD-box protein eIF4A reduces RNA condensation in vitro and limits stress granule formation in cells. This defines a purpose for eIF4A to limit intermolecular RNA-RNA interactions in cells, thereby allowing for proper RNP function. These results establish an important role for DEAD-box proteins as ATP-dependent RNA chaperones that can limit the intermolecular condensation and entanglement of RNA, analogous to the function of proteins like HSP70 in combatting protein aggregates.

eTOC Blurb

Stress granules are formed in part by the process of RNA condensation, which is mediated by and promotes trans RNA-RNA interactions. The essential DEAD-box protein and translation initiation factor eIF4A limits stress granule formation by reducing RNA condensation through its function as an ATP-dependent RNA binding protein, behaving analogously to how protein chaperones like HSP70 combat protein aggregates.

Highlights

RNA condensates promote intermolecular RNA-RNA interactions at their surfaces

eIF4A limits the recruitment of RNAs to stress granules in cells

eIF4A reduces the nucleation of stress granules in cells

Recombinant eIF4A1 inhibits the condensation of RNA in vitro in an ATP-dependent manner
In vitro testing of flash-frozen sublingual membranes for storage and reproducible permeability studies of macromolecular drugs from solution or nanofiber mats
Authors: Berka Pavel , Stránská Denisa , Semecký Vladimír , Berka Karel , Doležal Pavel
Published: July 2019

Sublingual drug delivery allows systemic delivery of drug without difficulties connected with the gastrointestinal pathway. We developed a new simple protocol for easy-to-use processing and storage of porcine sublingual mucosal membrane for in vitro studies using “flash freezing” in liquid nitrogen. All the dextrans used as mucosal membrane integrity and permeability markers permeated only slowly through sublingual mucosa illustrating usability both the “fresh” and “flash frozen” sublingual membranes whereas conventional cold storage “frozen” membranes have shown significantly higher permeabilities for macromolecules due to the sustained damage. The permeability values were too low to expect dextrans to be potential carriers at this context. To test albumin as a drug carrier we compared FITC-albumin permeation from solutions vs. nanofiber mats donors. To increase the amounts and prolong the transport, we manufactured nanofiber mats loaded with fluorescently marked albumin using well-scalable electrospinning technology. Nanofiber mats have allowed albumin passage through the sublingual membrane in similar amounts as from the pure artificial saliva solution. Since salivary washout strictly limits the duration of liquid dosages, nanofiber mats may thus permit prolonged sublingual administration.

Graphical abstract
Exploiting Heterogeneous Time Scale of Dynamics to Enhance 2D HETCOR Solid-State NMR Sensitivity
Authors: Zhang Rongchun , Nishiyama Yusuke , Ramamoorthy Ayyalusamy
Published: July 2019

Multidimensional solid-state NMR spectroscopy plays a significant role in offering atomic-level insights into molecular systems. In particular, heteronuclear chemical shift correlation (HETCOR) experiments could provide local chemical and structural information in terms of spatial heteronuclear proximity and through-bond connectivity. In solid state, the transfer of magnetization between heteronuclei, a key step in HETCOR experiments, is usually achieved using cross-polarization (CP) or INEPT (insensitive nuclei enhanced by polarization transfer) depending on the sample characteristics and magic-angle-spinning (MAS) frequency. But, for a multiphase system constituting molecular components that differ in their time scales of mobilities, CP efficiency is pretty low for mobile components because of the averaging of heteronuclear dipolar couplings whereas INEPT is inefficient due to the short T2 of immobile components and can be non-selective due to strong proton spin diffusion for immobile components especially under moderate spinning speeds. Herein, in this study we present two 2D pulse sequences that enable the sequential acquisition of 13C/1H HETCOR NMR spectra for the rigid and mobile components by taking full advantage of the abundant proton magnetization in a single experiment with barely increasing the overall experimental time. In particular, the 13C-detected HETCOR experiment could be applied under slow MAS conditions, where a multiple-pulse sequence is typically employed to enhance 1H spectral resolution in the indirect dimension. In contrast, the 1H-detected HETCOR experiment should be applied under ultrafast MAS, where CP and transient heteronuclear nuclear Overhauser effect (NOE) polarization transfer are combined to enhance 13C signal intensities for mobile components. These pulse sequences are experimentally demonstrated on two model systems to obtain 2D 13C/1H chemical shift correlation spectra of rigid and mobile components independently and separately. These pulse sequences can be used for dynamics difference based spectral editing and resonance assignments. Therefore, we believe the proposed 2D HETCOR NMR pulse sequences will be beneficial for the structural studies of heterogeneous systems containing molecular components that differ in their time scale of motions for understanding the interplay of structures and properties.
Mutant ACTB mRNA 3′UTR Promotes Hepatocellular Carcinoma Development by Regulating miR-1 and miR-29a
Authors: Li Yong , Ma Hong-Bin , Shi Chang-Ying , Feng Fei-Ling , Yang Liang
Published: July 2019

In recent years, mounting studies have shown that ACTB is closely related to various tumors. Although ACTB is dysregulated in numerous cancer types, limited data are available on the potential function and mechanism of ACTB in hepatocellular carcinoma (HCC). This study evaluated the expression and biological roles of mutant ACTB mRNA 3′UTR in HCC. Transcriptome sequence and qRT-PCR analysis determined that mutant ACTB mRNA 3′UTR was high expression in HCC tissues. Luciferase reporter assay showed that the ACTB mRNA 3′UTR mutations made it easier to interact with miR-1 and miR-29a. Moreover, mutant ACTB mRNA 3′UTR regulated miR-1 and miR-29a degradation via AGO2. Furthermore, mutant ACTB mRNA 3′UTR promoted hepatocellular carcinoma cells migration and invasionin vitroandin vivoby up-regulating miR-1 target gene MET and miR-29a target gene MCL1. In a word, our study demonstrates that 3′UTR of ACTB plays a key role in the tumor growth of hepatocellular carcinoma (HCC) and highlights the molecular mechanisms of ACTB-involved cancer growth and development.
Phenotypic plasticity, but not genetic adaptation, underlies seasonal variation in the cold hardening response ofDrosophila melanogaster
Authors: Stone Helen M. , Erickson Priscilla A. , Bergland Alan O.
Published: July 2019

In temperate regions, an organism’s ability to rapidly adapt to seasonally varying environments is essential for its survival. In response to seasonal changes in selection pressure caused by variation in temperature, humidity, and food availability, some organisms exhibit plastic changes in phenotype. In other cases, seasonal variation in selection pressure can rapidly increase the frequency of genotypes that offer survival or reproductive advantages under the current conditions. Little is known about the relative influences of plastic and genetic changes in short lived organisms experiencing seasonal environmental fluctuations. Cold hardening is a seasonally relevant plastic response in which exposure to cool, but nonlethal, temperatures significantly increases the organism’s ability to later survive at freezing temperatures. In the present study, we demonstrate seasonal variation in cold hardening inDrosophila melanogasterand test the extent to which plasticity and adaptive tracking underlie that seasonal variation. We measured the cold hardening response of flies from outdoor mesocosms over the summer, fall, and winter. We bred outdoor mesocosm-caught flies for two generations in the lab and matched each outdoor cohort to an indoor control cohort of similar genetic background. We measured the cold hardening response of indoor and field-caught flies and their laboratory-reared F1 and F2 progeny to determine the roles of seasonal environmental plasticity, parental effects, and genetic changes on cold hardening. We also tested the relationship between cold hardening and other factors, including age, developmental density, food substrate, presence of antimicrobials, and supplementation with live yeast. We found strong plastic responses to a variety of field- and lab-based environmental effects, but no evidence of seasonally varying parental or genetic effects on cold hardening. We therefore conclude that seasonal variation in the cold hardening response results from environmental influences and not genetic changes.
Metformin inhibits high glucose‐induced mesangial cell proliferation, inflammation and ECM expression through the SIRT1‐FOXO1‐autophagy axis
Authors: Xu Jiang , Chen Yan , Xing Yan , Ye Shandong
Published: July 2019

The aim of this study was to investigate the role of metformin in high glucose‐induced mesangial cell proliferation, inflammation and extracellular matrix (ECM) accumulation and to elucidate the underlying mechanism of metformin function. An MTT assay was used to examine rat mesangial cell (RMC) proliferation. The levels of TNF‐α, IL‐6 and TGF‐β in RMCs were determined by ELISA. The protein expression of fibronectin, collagen IV and autophagy‐related proteins (Beclin‐1, LC3‐I and LC3‐II) in RMCs was detected using western blot. Fluorescence microscopy analysis was carried out to evaluate RMC autophagy. Our results showed that high glucose‐induced RMC proliferation, inflammation and ECM expression, but these effects were markedly reduced by metformin. We confirmed that metformin suppressed high glucose‐induced RMC proliferation, inflammation and ECM expression via induction of autophagy. Mechanistic investigation demonstrated an axis of SIRT1‐FOXO1 in RMC autophagy. Our data indicated that metformin inhibits high glucose‐induced mesangial cell proliferation, inflammation and ECM expression through a SIRT1‐FOXO1‐autophagy axis.
Communal metabolism by Methylococcaceae and Methylophilaceae is driving rapid aerobic methane oxidation in sediments of a shallow seep near Elba, Italy
Authors: Taubert Martin , Grob Carolina , Crombie Andrew , Howat Alexandra M. , Burns Oliver J. , Weber Miriam , Lott Christian , Kaster Anne‐Kristin , Vollmers John , Jehmlich Nico , von Bergen Martin , Chen Yin , Murrell John Colin
Published: July 2019

The release of abiotic methane from marine seeps into the atmosphere is a major source of this potent greenhouse gas. Methanotrophic microorganisms in methane seeps use methane as carbon and energy source, thus significantly mitigating global methane emissions. Here, we investigated microbial methane oxidation at the sediment–water interface of a shallow marine methane seep. Metagenomics and metaproteomics, combined with 13C‐methane stable isotope probing, demonstrated that various members of the gammaproteobacterial family Methylococcaceae were the key players for methane oxidation, catalysing the first reaction step to methanol. We observed a transfer of carbon to methanol‐oxidizing methylotrophs of the betaproteobacterial family Methylophilaceae, suggesting an interaction between methanotrophic and methylotrophic microorganisms that allowed for rapid methane oxidation. From our microcosms, we estimated methane oxidation rates of up to 871 nmol of methane per gram sediment per day. This implies that more than 50% of methane at the seep is removed by microbial oxidation at the sediment–water interface, based on previously reported in situ methane fluxes. The organic carbon produced was further assimilated by different heterotrophic microbes, demonstrating that the methane‐oxidizing community supported a complex trophic network. Our results provide valuable eco‐physiological insights into this specialized microbial community performing an ecosystem function of global relevance.
Combining Cupuassu (Theobroma grandiflorum) Puree, Pectin, and Chitosan Nanoparticles into Novel Edible Films for Food Packaging Applications
Authors: Melo Pamela Thais S. , Nunes Juliana C. , Otoni Caio G. , Aouada Fauze A. , de Moura Marcia R.
Published: July 2019

Every year, the residues generated by the disposal of packaging materials produced from fossil fuels have been growing, denoting a major environmental problem that can be mitigated by the development of biodegradable materials from natural polymers, particularly edible films. This work aimed at the development of pectin films added by cupuassu puree and chitosan nanoparticles and to evaluate the improvement of the physical–mechanical performance of the composite films. The nanostructures displayed an average size of 110 nm and a zeta potential of approximately +40 mV. The films were produced by casting, and they exhibited manageability, homogeneity, and continuity. Based upon the mechanical analysis of maximum stress and elongation, it was concluded that the nanoparticles functioned as fillers, increasing the toughness of the pectin films. Water vapor permeability assays demonstrated that the nanostructured films containing cupuassu exhibited improved barrier properties. The glass transition temperature of the films was not strongly affected by the addition of nanoparticles. Conversely, the initial degradation temperature decreased with the addition of nanoparticles and cupuassu puree. The outcomes of this research pave a new route for the development of nonconventional food packaging materials.
The impact of different voxels and exposure parameters of CBCT for the assessment of external root resorptions: A phantom study
Authors: Goller Bulut Duygu , Uğur Aydın Zeliha
Published: July 2019

This study aimed to compare the effectiveness of the different voxel sizes and imaging parameters of cone beam computed tomography (CBCT) on the determination of external root resorption (ERR). ERRs were created in coronal, middle and apical regions. Depths (0.62–0.73 mm) and diameters (0.68–0.81 mm) of ERRs were measured using a digital calliper. Images were obtained in 0.125, 0.2, 0.25, 0.3 and 0.4 mm3 voxel sizes and at different currents. Data were analysed using Friedman and Wilcoxon signed‐rank tests at a level of P < 0.05. There was a difference between the parameters in determining the size of the ERR in coronal and middle regions (P < 0.05), but there was no difference in the apical region (P > 0.05). The change in current and exposure time did not make a difference in determining the dimensions of the ERRs (P > 0.05). Some voxel dimensions were more reliable in determining the depth and diameter of ERR in the coronal and middle region.
Trade Blocs and Trade Wars during the Interwar Period
Authors: Jacks David S. , Novy Dennis
Published: July 2019

What precisely were the causes and consequences of the trade wars in the 1930s? Were there perhaps deeper forces at work in reorienting global trade prior to the outbreak of World War II? And what lessons may this particular historical episode provide for the present day? To answer these questions, we distinguish between long‐run secular trends in the period from 1920 to 1939 related to the formation of trade blocs and short‐run disruptions associated with the trade wars of the 1930s. We argue that the trade wars mainly served to intensify pre‐existing efforts toward the formation of trade blocs which dated from at least 1920. More speculatively, we argue that the trade wars of the present day may serve a similar purpose as those in the 1930s, that is, the intensification of China‐ and US‐centric trade blocs.
Impact of reduced P‐glycoprotein function on digoxin concentrations in patients with dementia
Authors: Ali Izna , Guidone Daniel , Nicolazzo Joseph A. , Brouwer Kim L.R.
Published: July 2019

Aims

Patients with Alzheimer's disease (AD), the most common form of dementia, have reduced P‐glycoprotein (P‐gp) function at the blood–brain barrier. However, the effect of AD on P‐gp function in peripheral organs, and the impact on medication efficacy and toxicity is unknown. In this study, clinical chart review and physiologically based pharmacokinetic (PBPK) modelling were employed to determine whether disease‐associated changes in P‐gp could be assessed from clinically measured digoxin concentrations in patients without and with dementia.

Methods

A retrospective chart review was conducted to compare digoxin dose and concentrations between cohorts. A PBPK model was developed to simulate changes in digoxin concentrations at single and multiple 62.5 and 125 μg/d doses due to reduced P‐gp function in peripheral organs.

Results

Digoxin concentrations were similar between the nondementia (n = 75) and dementia (n = 72) cohorts (mean ± standard deviation; 0.64 ± 0.31 and 0.60 ± 0.34 ng/mL, respectively; −0.06 to 0.15, 95% confidence interval of difference). PBPK simulations showed that reduced P‐gp function resulted in a significant increase in digoxin exposure (AUC), but not in Cmax. For example, when a 2‐fold reduction in P‐gp function was simulated in older people following multiple 125 μg/d digoxin doses, the AUC over the last dosing interval was increased compared to baseline (24.29 ± 3.94 vs 17.04 ± 3.46 ng/mL*h; 4.52 to 9.98); however, Cmax was similar (1.38 ± 0.20 vs 0.99 ± 0.18 ng/mL; −2.33 to 3.13).

Conclusion

Clinically measured digoxin concentrations were not statistically different in patients with dementia. Based on PBPK simulations, digoxin AUC may need to be evaluated to adequately assess the impact of reduced P‐gp function in peripheral organs.
The impact of the guideline for pain management in Japanese neonatal intensive care units: A 5‐year follow‐up
Authors: Ozawa Mio
Published: July 2019

Background

This study presented the guidelines for the prevention and management of procedural pain management in Japan and investigated the impact of these guidelines on Japanese neonatal intensive care units (NICUs). The aim of this study was to investigate whether the published national guidelines influenced organizational factors that could lead to improved pain management and, if so, whether the number of units that perform pain assessments, the administration of local guidelines and collaboration among health care professionals had improved in the 5‐year period from 2012 to 2017.

Method

An anonymous questionnaire was sent to 106 Level 3 NICUs across Japan.

Results

The response rate was 78% (81 units). In almost all cases, the implementation of organizational factors had increased. Forty‐seven units (47%) reported that health care professionals collaborated in pain management, compared with 11 units (17.7%) in 2012. In addition, compliance with the guidelines for pain assessment improved over the 5‐year period. Twenty‐four units (30%) reported that they used a structured scale for pain measurement, compared with nine units (15%) in 2012.

Conclusion

The current study suggested that the national guidelines published in 2014 influenced the organizational factors that could lead to improved pain management in Japanese NICUs. The number of units that used a structured scale for pain measurement, the development of local guidelines, and collaboration among health care professionals increased over the 5‐year period from 2012 to 2017.
A network approach to prioritize conservation efforts for migratory birds
Authors: Xu Yanjie , Si Yali , Takekawa John , Liu Qiang , Prins Herbert H. T. , Yin Shenglai , Prosser Diann J. , Gong Peng , de Boer Willem F.
Published: July 2019

Habitat loss can trigger migration network collapse by isolating migratory bird breeding grounds from nonbreeding grounds. Theoretically, habitat loss can have vastly different impacts depending on the site's importance within the migratory corridor. However, migration‐network connectivity and the impacts of site loss are not completely understood. We used GPS tracking data on 4 bird species in the Asian flyways to construct migration networks and proposed a framework for assessing network connectivity for migratory species. We used a node‐removal process to identify stopover sites with the highest impact on connectivity. In general, migration networks with fewer stopover sites were more vulnerable to habitat loss. Node removal in order from the highest to lowest degree of habitat loss yielded an increase of network resistance similar to random removal. In contrast, resistance increased more rapidly when removing nodes in order from the highest to lowest betweenness value (quantified by the number of shortest paths passing through the specific node). We quantified the risk of migration network collapse and identified crucial sites by first selecting sites with large contributions to network connectivity and then identifying which of those sites were likely to be removed from the network (i.e., sites with habitat loss). Among these crucial sites, 42% were not designated as protected areas. Setting priorities for site protection should account for a site's position in the migration network, rather than only site‐specific characteristics. Our framework for assessing migration‐network connectivity enables site prioritization for conservation of migratory species.
New leaf and fruit disease of Juglans regia caused by Juglanconis juglandina in Xinjiang, China
Authors: Ma Rong , Ye Shuanghua , Zhao Ying , Michailides Themis J. , Tian Chengming
Published: July 2019

Juglans regia L. is an important and scarce natural resource that grows in the part of the western Tianshan Mountains and the Pamir Alai Mountains in Central Asia. They only distribute in Gongliu County, Yili, Xinjiang Uygur Autonomous Region in China. However, the healthy growth of J. regia was seriously affected by a fungal disease affecting leaves, branches and fruit in 2016. Sixty isolates were obtained from diseased branches, leaves and fruit collected. The pathogenicity of the isolates was confirmed by inoculating shoots and fruit collected from healthy J. regia in Gongliu County and by inoculating the leaves of J. regia seedlings. The pathogen was re‐isolated from all inoculated shoots, leaves and fruits, thereby fulfilling Koch's postulates. Furthermore, isolates from leaves were able to infect fruit and shoots and vice versa. The isolate 1429‐1 was more pathogenic to the branches than HG and HY, no significant difference between the other isolates from leaves and fruits. Based on morphological, cultural characteristics and multilocus analyses using the internal transcribed spacer region, the RNA polymerase II subunit 2 gene, the calmodulin gene, the guanine nucleotide‐binding protein subunit beta gene, the translation elongation factor 1‐alpha gene and the β‐tubulin gene sequences, the fungus was identified as Juglanconis juglandina. Although J. juglandina has been reported previously as the causal agent of stem disease, this is the first description of J. juglandina as the causal agent of a leaf and fruit disease of J. regia.
Association between decrease in frequency of going out and oral function in older adults living in major urban areas
Authors: Mikami Yurie , Watanabe Yutaka , Motokawa Keiko , Shirobe Maki , Motohashi Yoshiko , Edahiro Ayako , Nakajima Junko , Osuka Yosuke , Inagaki Hiroki , Fujiwara Yoshinori , Shinkai Shoji , Awata Shuichi
Published: July 2019

Aim

To examine the association between a decrease in the frequency of going out and oral function in independent older adults living in the urban area of Tokyo.

Methods

The participants analyzed were 785 older adults from the “Takashimadaira Study” (344 men and 441 women, age 77.0 ± 4.6 years). This study investigated the following items: decrease in frequency of going out; basic characteristics (sex, age); physical factors, such as oral function (difficulty chewing, difficulty swallowing, dry mouth); body pain; the Japan Science and Technology Agency Index of Competence; physical activities; psychological factors, such as the Geriatric Depression Scale‐15 score; and social and environmental factors, such as the presence or absence of participation in organization activities.

Results

To investigate the factors associated with a decrease in frequency of going out, logistic regression analysis showed an association with age (OR 1.08, 95% CI 1.03–1.13), difficulty chewing (OR 2.41, 95% CI 1.52–3.83), dry mouth (OR 1.68, 95% CI 1.07–2.64), body pain (OR 1.78, 95% CI 1.14–2.78), Japan Science and Technology Agency Index of Competence scores (OR 0.91, 95% CI 0.84–0.99), physical activities (OR 0.99, 95% CI 0.98–1.00), Geriatric Depression Scale‐15 scores (OR 1.13, 95% CI 1.05–1.21) and organization activities (OR 1.94, 95% CI 1.22–3.07). Covariance structural analyses showed that both “difficulty chewing” and “dry mouth” significantly affected “decrease in frequency of going out.” In addition, decrease in frequency of going out was significantly affected by “ Geriatric Depression Scale‐15 scores” through oral function.

Conclusions

The relationship between oral function and decrease in frequency of going out was clarified, after the multifaceted factors were adjusted. Geriatr Gerontol Int 2019; 19: 792–797.
Heterogeneity in the local employment multipliers in the United States
Authors: Osei Michael J. , Sengupta Shruti
Published: July 2019

Recent studies have found evidence of a local employment multiplier’s effect. For the most part, these studies provide an average estimate for all labor markets. In this paper, we examine how the average local employment multiplier, the effect of an exogenous increase in employment in the tradable sector on total employment, depends on the characteristics of the local labor market. Specifically, we estimate the average multipliers for coastal, noncoastal, large, and small metropolitan statistical areas (MSAs) across different time periods using the data of 333 US MSAs. Overall, we find a reduced form of local employment multiplier ranging from 1.38 to 2.24, which is within the range of typically estimated local employment multipliers. In addition, the characteristics of the local labor market matter. The local multipliers appear larger in noncoastal and large MSAs. For small and coastal metros, the multiplier is closer to 1.5 than to 2.0 while in the case of large and noncoastal metros, it is closer to 2.0 than to 1.5. The local multipliers are also sensitive to the time period considered.
Peri‐implant tissue management after immediate implant placement using a customized healing abutment
Authors: Ruales‐Carrera Edwin , Pauletto Patrícia , Apaza‐Bedoya Karin , Volpato Claudia A. M. , Özcan Mutlu , Benfatti César A. M.
Published: July 2019

Objective

The unavoidable extraction of teeth in the esthetic area can be overcome through different treatment modalities. Recently, immediate implants appeared as a minimally invasive approach to resolving these cases; however, immediate implant loading is not always possible or indicated. In these cases, an innovative approach through customized healing abutments could be used to preserve the soft tissue contour, eliminating the need for reopening surgery and the use of provisional restorations to condition the mucosal contour.

Clinical Considerations

The present cases describe a simplified chairside approach to use customized healing abutments for immediate implants placed after tooth extraction in the anterior and posterior areas in order to maintain the soft tissue contours while reducing the clinical steps until delivering the final restorations.

Conclusions

This technique seems to be effective to guide the soft tissue healing around dental implants allowing a natural emergence profile with implant‐supported restorations, reducing the number of treatment steps.

Clinical Significance

The use of customized healing abutments prepares soft tissue for the prosthetic stage preserving its contours and eliminating the need for reopening surgery.
Occurrence and molecular characterization of zoonotic Anisakis simplex sensu stricto and Anisakis pegreffii larvae in retail‐marketed fish
Authors: Arafa Waleed M. , Hassan Abdelrahim H. A. , Mahrous Lilian N. , Abdel‐Ghany Ahmed E. , Aboelhadid Shawky M.
Published: July 2019

The study aimed at investigating the occurrence and molecular characterization of zoonotic Anisakis larvae in imported, retail‐marketed smoked herring (Clupea harengus) and frozen mackerel (Scomber scombrus) in Egypt. A total of 154 fishes (84 ready‐to‐eat smoked herring and 70 frozen mackerel) were collected. The prevalence of Anisakis larvae Type I in the whole specimen of smoked herring and frozen mackerel was 19.05 and 42.86% with mean intensities of 4.71 and 1.83. While the prevalence in muscles was 8.33 and 5.71% with mean intensities of 4.29 and 5, respectively. The sequencing of 11 larval PCR products from fish muscles revealed the presence of two zoonotic species; Anisakis simplex sensu stricto and Anisakis pegreffii. The recovered strains showed high identities to GenBank Anisakis isolates of fish from the North Sea, nearby waters and from China. More surveillance studies are recommended on those areas to ensure food safety and minimize public health risks.

Practical Application

Frozen fish imports by Egypt have been growing significantly since 2009 to cover the progressive elevation in fish consumption there. Anisakis is one of the commonly reported zoonotic parasites infecting humans through fish consumption. This study provides important information on the prevalence and molecular characteristics of zoonotic Anisakis species in edible muscles of imported, retail‐marketed frozen mackerel and ready‐to‐eat herring fish in Egypt. The study outlined some recommendations to reduce the public health risks from that biological hazard.
Colloidal particle aggregation in three dimensions
Authors: HÄBEL HENRIKE , SÄRKKÄ AILA , RUDEMO MATS , BLOMQVIST CHARLOTTE HAMNGREN , OLSSON EVA , NORDIN MATIAS
Published: July 2019

Colloidal systems are of importance not only for everyday products, but also for the development of new advanced materials. In many applications, it is crucial to understand and control colloidal interaction. In this paper, we study colloidal particle aggregation of silica nanoparticles, where the data are given in a three‐dimensional micrograph obtained by high‐angle annular dark field scanning transmission electron microscopy tomography. We investigate whether dynamic models for particle aggregation, namely the diffusion limited cluster aggregation and the reaction limited cluster aggregation models, can be used to construct structures present in the scanning transmission electron microscopy data. We compare the experimentally obtained silica aggregate to the simulated postaggregated structures obtained by the dynamic models. In addition, we fit static Gibbs point process models, which are commonly used models for point patterns with interactions, to the silica data. We were able to simulate structures similar to the silica structures by using Gibbs point process models. By fitting Gibbs models to the simulated cluster aggregation patterns, we saw that a smaller probability of aggregation would be needed to construct structures similar to the observed silica particle structure.
Multiple failures in the lutenising hormone surge generating system in GABAB1KO female mice
Authors: Di Giorgio Noelia P. , Bizzozzero Hiriart Marianne , Surkin Pablo N. , López Paula V. , Bourguignon Nadia S. , Dorfman Verónica B. , Bettler Bernhard , Libertun Carlos , Lux‐Lantos Victoria
Published: July 2019

Female mice lacking GABAB receptors, GABAB1KO, show disrupted oestrous cycles, reduced pregnancies and increased hypothalamic Gnrh1 mRNA expression, whereas anteroventral periventricular/periventricular preoptic nucleus (AVPV/PeN) Kiss1 mRNA was not affected. In the present study, we characterise the important components of the gonadotrophic preovulatory surge, aiming to unravel the origin of this reproductive impairment. In GABAB1KO and wild‐type (WT) females, we determined: (i) hypothalamic oestrogen receptor (ER)α and β and aromatase mRNA and protein expression; (ii) ovulation index and oestrus serum follicle‐stimulating hormone (FSH) and pituitary Gnrh1r expression; (iii) in ovariectomised‐oestradiol valerate‐treated mice, we evaluated ex vivo hypothalamic gonadotrophin‐releasing hormone (GnRH) pulsatility in the presence/absence of kisspeptin (Kiss‐10, constant or pulsatile) and oestradiol (constant); and (iv) in ovariectomised‐oestradiol silastic capsule‐treated mice (proestrous‐like environment), we evaluated morning and evening kisspeptin neurone activation (c‐Fos+) and serum luteinising homrone (LH). In the medial basal hypothalamus of oestrus GABAB1KOs, aromatase and ERα mRNA and protein were increased, whereas ERβ was decreased. In GABAB1KOs, the ovulation index was decreased together with decreased first oestrus serum FSH and increased pituitary Gnrh1r mRNA. Under constant Kiss‐10 stimulation, hypothalamic GnRH pulse frequency did not vary, although GnRH mass/pulse was increased in GABAB1KOs. In WTs, pulsatile Kiss‐10 together with constant oestradiol significantly increased GnRH pulsatility, whereas, in GABAB1KOs, oestradiol alone increased GnRH pulsatility and this was reversed by pulsatile Kiss‐10 addition. In GABAB1KOs AVPV/PeN kisspeptin neurones were similarly activated (c‐Fos+) in the morning and evening, whereas WTs showed the expected, marked evening stimulation. LH correlated with activated kisspeptin cells in WT mice, whereas GABAB1KO mice showed high, similar LH levels both in the morning and evening. Taken together, all of these alterations point to impairment in the trigger of the preovulatory GnRH surge that entails the reproductive alterations described.
The supplementation of nutrient additives in broad bean‐based diet improved the growth of “crisped” grass carp, Ctenopharyngodon idellus
Authors: Jiang Weibo , Li Xiaoqin , Xu Xiaoying , Ma Min , Leng Xiangjun
Published: July 2019

To investigate the effects of supplemental nutrient additives in broad bean‐based diets on growth, flesh quality, and collagen gene expression of grass carp, five diets were prepared, including complete formula diet (control), soaked broad bean (SBB), and three broad bean‐based diets containing 80% broad bean without (BBD1) or with the supplementation of methionine (BBD2), and methionine+vitamins+minerals (BBD3), and were fed to grass carp (171.9 ± 1.1 g), Ctenopharyngodon idellus, for 84 days. The results showed that broad bean‐based diets significantly increased weight gain (WG) and reduced the feed conversion ratio (FCR) of grass carp when compared to the SBB (p < .05). The BBD3 group reached levels similar to the WG and FCR of the control group (p > .05). Grass carp fed the BBD3 diet had lower steaming loss of flesh, higher muscle fiber density, and higher collagen content in muscle and skin than the control (p < .05). The relative expressions of COL1A1 and COL1A2 mRNA in muscle and skin were significantly higher in the BBD3 and SBB groups than in other groups (p < .05). In conclusion, the combination of methionine, vitamins, and minerals in broad bean‐based diets promoted the growth of “crisped” grass carp and improved flesh quality and collagen gene expression when compared to the control formula diet.
Probability and interval hybrid reliability analysis based on adaptive local approximation of projection outlines using support vector machine
Authors: Zhang Jinhao , Xiao Mi , Gao Liang , Chu Sheng
Published: July 2019

This paper investigates structural reliability analysis with both random and interval variables, which is defined as a three‐classification problem and handled by support vector machine (SVM). First, it is determined that projection outlines on the limit‐state surface are crucial for describing separating hyperplanes of the three‐classification problem. Compared with the whole limit‐state surface, the region of projection outlines are much smaller. It will be beneficial to reduce the number of update points and the computational cost if SVM update concentrates on refining the approximate projection outlines. An adaptive local approximation method is developed to realize that the initial built SVM model is sequentially updated by adding new training samples located around the projection outlines. Using this method, the separating hyperplanes can be accurately and efficiently approximated by SVM. Finally, a new method is proposed to evaluate the failure probability interval based on Monte Carlo simulation and the refined SVM.
Tomato chlorosis virus, an emergent plant virus still expanding its geographical and host ranges
Authors: Fiallo‐Olivé Elvira , Navas‐Castillo Jesús
Published: July 2019

Tomato chlorosis virus (ToCV) causes an important disease that primarily affects tomato, although it has been found infecting other economically important vegetable crops and a wide range of wild plants. First described in Florida (USA) and associated with a ‘yellow leaf disorder’ in the mid‐1990s, ToCV has been found in 35 countries and territories to date, constituting a paradigmatic example of an emergent plant pathogen. ToCV is transmitted semipersistently by whiteflies (Hemiptera: Aleyrodidae) belonging to the genera Bemisia and Trialeurodes. Whitefly transmission is highly efficient and cases of 100% infection are frequently observed in the field. To date, no resistant or tolerant tomato plants are commercially available and the control of the disease relies primarily on the control of the insect vector.

Taxonomy

Tomato chlorosis virus is one of the 14 accepted species in the genus Crinivirus, one of the four genera in the family Closteroviridae of plant viruses.

Virion and genome properties

The genome of ToCV is composed of two molecules of single‐stranded positive‐sense RNA, named RNA1 and RNA2, separately encapsidated in long, flexuous, rod‐like virions. As has been shown for other closterovirids, ToCV virions are believed to have a bipolar structure. RNA1 contains four open reading frames (ORFs) encoding proteins associated with virus replication and suppression of gene silencing, whereas RNA2 contains nine ORFs encoding proteins putatively involved in encapsidation, cell‐to‐cell movement, gene silencing suppression and whitefly transmission.

Host range

In addition to tomato, ToCV has been found to infect 84 dicot plant species belonging to 25 botanical families, including economically important crops.

Transmission

Like all species within the genus Crinivirus, ToCV is semipersistently transmitted by whiteflies, being one of only two criniviruses transmitted by members of the genera Bemisia and Trialeurodes.

Disease symptoms

Tomato ‘yellow leaf disorder’ syndrome includes interveinal yellowing and thickening of leaves. Symptoms first develop on lower leaves and then advance towards the upper part of the plant. Bronzing and necrosis of the older leaves are accompanied by a decline in vigour and reduction in fruit yield. In other hosts the most common symptoms include interveinal chlorosis and mild yellowing on older leaves.

Control

Control of the disease caused by ToCV is based on the use of healthy seedlings for transplanting, limiting accessibility of alternate host plants that can serve as virus reservoirs and the spraying of insecticides for vector control. Although several wild tomato species have been shown to contain genotypes resistant to ToCV, there are no commercially available resistant or tolerant tomato varieties to date.
Efficacy of alteplase 1 versus 2 mg dose in restoring haemodialysis catheter function (Alte‐dose 2): A randomized double‐blind controlled study
Authors: El‐Masri Maher M , El Nekidy Wasim S , Soong Derrick , Kadri Albert
Published: July 2019

Aim

Data about the optimal alteplase dose required to treat haemodialysis catheter occlusion (HDC) are scarce. The purpose of the clinical trial was to examine the effectiveness of alteplase 2 mg as compared with 1 mg in restoring HDC function.

Methods

A double‐blind, randomized, controlled clinical trial was conducted in a single‐centre in southwestern Ontario, Canada. Rate of clot resolution, catheter replacements, catheter stripping, and mean catheter survival time were assessed using Kaplan–Meier, Cox‐proportional hazard and clustered logic regression analyses.

Results

On a sample of 48 haemodialysis patients who provided 252 catheter occlusion events, the rate of clot resolution at the catheter site in the 2 mg group was 85.7% as opposed to 84.9% in the 1 mg group. There were only six catheter removals and 10 catheter stripping events. Cox regression analysis revealed no difference between the two groups in the hazard of occlusion on the primary 48 observations after the initial alteplase management (P = 0.267; hazard ratio = 0.72; 95% confidence interval 0.40–1.3). Correlated logistic regression on all 252 observations indicated no difference in the rate of post alteplase clot resolution (P = 0.336; odds ratio = 2.4, 95% confidence interval 0.399–14.6) between the two groups.

Conclusion

Alteplase 1 mg is as effective as 2 mg in restoring HDC malfunction and may result in cost reduction in haemodialysis units.
Vagal innervation of the stomach reassessed: brain−gut connectome uses smart terminals
Authors: Powley Terry L. , Jaffey Deborah M. , McAdams Jennifer , Baronowsky Elizabeth A. , Black Diana , Chesney Logan , Evans Charlene , Phillips Robert J.
Published: July 2019

Brain−gut neural communications have long been considered limited because of conspicuous numerical mismatches. The vagus, the parasympathetic nerve connecting brain and gut, contains thousands of axons, whereas the gastrointestinal (GI) tract contains millions of intrinsic neurons in local plexuses. The numerical paradox was initially recognized in terms of efferent projections, but the number of afferents, which comprise the majority (≈ 80%) of neurites in the vagus, is also relatively small. The present survey of recent morphological observations suggests that vagal terminals, and more generally autonomic and visceral afferent arbors in the stomach as well as throughout the gut, elaborate arbors that are extensive, regionally specialized, polymorphic, polytopic, and polymodal, commonly with multiplicities of receptors and binding sites—smart terminals. The morphological specializations and dynamic tuning of one‐to‐many efferent projections and many‐to‐one convergences of contacts onto afferents create a complex architecture capable of extensive peripheral integration in the brain−gut connectome and offset many of the disparities between axon and target numbers. Appreciating this complex architecture can help in the design of therapies for GI disorders.
Genetic Contribution in Low Back Pain: A Prospective Genetic Association Study
Authors: Margarit César , Roca Reyes , Inda María‐del‐Mar , Muriel Javier , Ballester Pura , Moreu Rocío , Conte Anna Lucia , Nuñez Angela , Morales Domingo , Peiró Ana M
Published: July 2019

Objectives

Chronic pain is one of the most common reasons individuals seek medical attention. It is a major issue because of the wide interindividual variability in the analgesic response. This might be partly explained by the presence of variants in genes encoding molecules involved in pharmacodynamics and pharmacokinetics. The aim was to analyze opioid effectiveness in chronic low back pain (CLBP) relief after opioid titration, unveiling the impact of pharmacogenetics.

Methods

The study included 231 opioid‐naïve patients from the Spine Unit; age 63 ± 14 years, 64% female, body mass index 29 ± 6 kg/m2, visual analog scale pain intensity score 73 ± 16 mm. Clinical data were collected at baseline, 3 months after opioid titration, and after 2 to 4 years of follow‐up concerning pain (intensity and relief), quality of life, disability, comorbidities, and drug prescription (opioid dose, rotations, and adverse events). The genotype influence ofOPRM1,COMT,UGT2B7,ABCB1,KCNJ6, andCYP3A5*3Ain analgesic response was analyzed by reverse‐transcription polymerase chain reaction genotyping.

Results

Patients with theCOMTG472A‐AAgenotype (rs4680) andKCNJ6A1032G‐A allele (rs2070995)CLBPresponded differently to opioid titration, with higher pain intensity requiring higher dosing. Furthermore,GG‐ genotypes of A118G (OPRM1, rs1799971) and A854G (UGT2B7, rs776746) influenced the neuropathic component. After opioid titration,CLBPintensity, neuropathic component, low back pain disability, anxiety, and depression significantly decreased, while quality of life improved.

Conclusion

Single‐nucleotide polymorphisms in genes involved in pain transmission and opioid metabolism might predispose to exaggerated sensitivity and differences in the opioid analgesic effect in patients withCLBP. We encourage clinical trials for their clinical application in chronic pain management.