bluuebunny/crossref_metadata_2025 huggingface dataset:
TRPV5, TRPV6, TRPM6, and TRPM7 do not contribute to hair-cell mechanotransduction
Authors: Morgan Clive P. , Zhao Hongyu , LeMasurier Meredith , Xiong Wei , Pan Bifeng , Avenarius Matthew R. , Bateschell Michael , Larisch Ruby , Ricci Anthony J. , Müller Ulrich , Barr-Gillespie Peter G.
Published: October 2017

The hair-cell mechanotransduction channel remains unidentified. We tested whether four transient receptor channel (TRP) family members, TRPV5, TRPV6, TRPM6, and TRPM7, participated in transduction. Using cysteine-substitution mouse knock-ins and methanethiosulfonate reagents selective for those alleles, we found that inhibition of TRPV5 or TRPV6 had no effect on transduction in mouse cochlear hair cells. TRPM6 and TRPM7 each interacted with the tip-link component PCDH15 in cultured eukaryotic cells, which suggested they could participate in transduction. Cochlear hair cell transduction was insensitive to shRNA knockdown ofTrpm6orTrpm7, however, and was not affected by manipulations of Mg2+, which normally perturbs TRPM6 and TRPM7. To definitively examine the role of these two channels in transduction, we showed that deletion of either or both of their genes selectively in hair cells had no effect on auditory function. We suggest that TRPV5, TRPV6, TRPM6, and TRPM7 are unlikely to be the pore-forming subunit of the hair-cell transduction channel.
Effect of cellular de-differentiation on the dynamics and evolution of tissue and tumor cells in mathematical models with feedback regulation
Authors: Wodarz Dominik
Published: October 2017

Tissues are maintained by adult stem cells that self-renew and also differentiate into functioning tissue cells. Homeostasis is achieved by a set of complex mechanisms that involve regulatory feedback loops. Similarly, tumors are believed to be maintained by a minority population of cancer stem cells, while the bulk of the tumor is made up of more differentiated cells, and there is indication that some of the feedback loops that operate in tissues continue to be functional in tumors. Mathematical models of such tissue hierarchies, including feedback loops, have been analyzed in a variety of different contexts. Apart from stem cells giving rise to differentiated cells, it has also been observed that more differentiated cells can de-differentiate into stem cells, both in healthy tissue and tumors, aspects of which have also been investigated mathematically. This paper analyses the effect of de-differentiation on the basic and evolutionary dynamics of cells in the context of tissue hierarchy models that include negative feedback regulation of the cell populations. The models predict that in the presence of dedifferentiation, the fixation probability of a neutral mutant is lower than in its absence. Therefore, if de-differentiation occurs, a mutant with identical parameters compared to the wild-type cell population behaves like a disadvantageous mutant. Similarly, the process of de-differentiation is found to lower the fixation probability of an advantageous mutant. These results indicate that the presence of de-differentiation can lower the rates of tumor initiation and progression in the context of the models considered here.
A control theoretic model of adaptive behavior in dynamic environments
Authors: Ritz Harrison , Nassar Matthew R. , Frank Michael J. , Shenhav Amitai
Published: October 2017

To behave adaptively in environments that are noisy and non-stationary, humans and other animals must monitor feedback from their environment and adjust their predictions and actions accordingly. An under-studied approach for modeling these adaptive processes comes from the engineering field of control theory, which provides general principles for regulating dynamical systems, often without requiring a generative model. The proportional-integral-derivative (PID) controller is one of the most popular models of industrial process control. The proportional term is analogous to the “delta rule” in psychology, adjusting estimates in proportion to each successive error in prediction. The integral and derivative terms augment this update to simultaneously improve accuracy and stability. Here, we tested whether the PID algorithm can describe how people sequentially adjust their predictions in response to new information. Across three experiments, we found that the PID controller was an effective model of participants’ decisions in noisy, changing environments. In Experiment 1, we re-analyzed a change-point detection experiment, and showed that participants’ behavior incorporated elements of PID updating. In Experiments 2-3 we developed a task with gradual transitions that we optimized to detect PID-like adjustments. In both experiments, the PID model offered better descriptions of behavioral adjustments than both the classical delta-rule model and its more sophisticated variant, the Kalman filter. We further examined how participants weighted different PID terms in response to salient environmental events, finding that these control terms were modulated by reward, surprise, and outcome entropy. These experiments provide preliminary evidence that adaptive behavior in dynamic environments resembles PID control.
Antagonism in olfactory receptor neurons and its implications for the perception of odor mixtures
Authors: Reddy Gautam , Zak Joseph , Vergassola Massimo , Murthy Venkatesh N.
Published: October 2017

Natural environments feature mixtures of odorants of diverse quantities, qualities and complexities. Olfactory receptor neurons (ORNs) are the first layer in the sensory pathway and transmit the olfactory signal to higher regions of the brain. Yet, the response of ORNs to mixtures is strongly non-additive, and exhibits antagonistic interactions among odorants. Here, we model the processing of mixtures by mammalian ORNs, focusing on the role of inhibitory mechanisms. Theoretically predicted response curves capture experimentally determined glomerular responses imaged by a calcium indicator expressed in ORNs of live, breathing mice. Antagonism leads to an effective “normalization” of the ensemble glomerular response, which arises from a novel mechanism involving the distinct statistical properties of receptor binding and activation, without any recurrent neuronal circuitry. Normalization allows our encoding model to outperform noninteracting models in odor discrimination tasks, and to explain several psychophysical experiments in humans.
Modulation of target recollection and recollection rejection networks due to retrieval facilitation and interference
Authors: Bowman Caitlin R. , Sine Shalome L. , Dennis Nancy A.
Published: October 2017

To better understand neural recollection processing, we induced interference in target recollection by presenting related lures before their respective targets and facilitated recollection rejection of lures by presenting targets before their related lures. Target recollection following interference recruited visual and prefrontal cortices, showing that these regions support recollection when related information has disrupted target representations. Recollection rejection following target presentation recruited angular gyrus, indicating that this region supports recollection rejection when target representations are strong and highly accessible. Thus, recollection networks are sensitive to the accessibility of target representations that are affected by the presentation of related information during retrieval.
Context memory formation requires activity-dependent protein degradation in the hippocampus
Authors: Cullen Patrick K. , Ferrara Nicole C. , Pullins Shane E. , Helmstetter Fred J.
Published: October 2017

Numerous studies have indicated that the consolidation of contextual fear memories supported by an aversive outcome like footshock requires de novo protein synthesis as well as protein degradation mediated by the ubiquitin–proteasome system (UPS). Context memory formed in the absence of an aversive stimulus by simple exposure to a novel environment requires de novo protein synthesis in both the dorsal (dHPC) and ventral (vHPC) hippocampus. However, the role of UPS-mediated protein degradation in the consolidation of context memory in the absence of a strong aversive stimulus has not been investigated. In the present study, we used the context preexposure facilitation effect (CPFE) procedure, which allows for the dissociation of context learning from context–shock learning, to investigate the role of activity-dependent protein degradation in the dHPC and vHPC during the formation of a context memory. We report that blocking protein degradation with the proteasome inhibitor clasto-lactacystin β-lactone (βLac) or blocking protein synthesis with anisomycin (ANI) immediately after context preexposure significantly impaired context memory formation. Additionally, we examined 20S proteasome activity at different time points following context exposure and saw that the activity of proteasomes in the dHPC increases immediately after stimulus exposure while the vHPC exhibits a biphasic pattern of proteolytic activity. Taken together, these data suggest that the requirement of increased proteolysis during memory consolidation is not driven by processes triggered by the strong aversive outcome (i.e., shock) normally used to support fear conditioning.
The synthesis, crystal structure and thermal properties of an energetic compound: the hydrated azanium salt of 3,6-bis[(1H-1,2,3,4-tetrazol-5-yl)amino]-1,2,4,5-tetrazine
Authors: Liu Qing , Chen Xiang , Cao Wenli , Yang Jin , Zhang Wenhui , Ren Yinghui , Ma Haixia , Zhao Fengqi , Hu Rongzu
Published: October 2017

The energetic ionic salt bis(1-aminoguanidin-2-ium) 5,5′-[1,2,4,5-tetrazine-3,6-diylbis(azanediyl)]bis(1H-1,2,3,4-tetrazol-1-ide) dihydrate, 2CH7N4+·C4H2N142−·2H2O, (I), with a high nitrogen content, has been synthesized and examined by elemental analysis, Fourier transform IR spectrometry,1H NMR spectroscopy and single-crystal X-ray crystallography. Compound (I) crystallizes in the monoclinic space groupP21/cwith two water molecules. However, the water molecules are disordered about an inversion centre and were modelled as half-occupancy molecules in the structure. The crystal structure reveals a three-dimensional network of molecules linked through N—H...N, N—H...O, O—H...N and O—H...O hydrogen bonds. Thermal decomposition was investigated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The exothermic peak temperature is 509.72 K, which indicates that hydrated salt (I) exhibits good thermal stability. Non-isothermal reaction kinetic parameters were calculatedviaboth the Kissinger and the Ozawa methods to yield activation energies ofEk= 239.07 kJ mol−1, lgAk= 22.79 s−1andEO= 235.38 kJ mol−1for (I). Additionally, the thermal safety was evaluated by calculating critical temperatures and thermodynamic values,viz.TSADT,TTIT,Tb, ΔS≠, ΔH≠and ΔG≠. The results reveal that (I) exhibits good thermal safety compared to other ion salts of 3,6-bis[(1H-1,2,3,4-tetrazol-5-yl)amino]-1,2,4,5-tetrazine (BTATz).
Investigating feedback effects in the field of brand extension using brand concept maps
Authors: Kottemann Pascal , Plumeyer Anja , Decker Reinhold
Published: October 2017

Purpose

The purpose of this paper is to apply the (advanced) brand concept maps (BCM) approach to reinvestigate previous findings on feedback effects resulting from brand extension information (BEI) and to explore whether this information affects the structure of a brand’s associative network.

Design/methodology/approach

This research builds on the associative network memory model, as well as Keller’s conceptualization of customer-based brand equity, and uses a series of empirical studies with a total of 839 respondents in two different countries.

Findings

The findings reveal that BEI has no significant impact on the structure of the parent brand’s associative network at the individual level. Furthermore, key brand image dimensions (i.e. favorability, strength, and uniqueness of brand associations) are not affected.

Research limitations/implications

By applying the (advanced) BCM approach, this paper is able to address shortcomings that are incorporated with the use of Likert scales for measuring a brand’s image and for investigating feedback effects in the field of brand extension. As the results indicate that the identification of feedback effects might be influenced by the approach used to measure a brand’s image, this paper calls for further investigations of feedback effects on a brand’s image.

Originality/value

Data from three empirical studies provide insights into the cognitive processing of BEI and their impact on a brand’s associative network.
Influences of workplace environment factors on employees’ training transfer
Authors: Na-nan Khahan , Chaiprasit Kanokporn , Pukkeeree Peerapong
Published: October 2017

Purpose

The purpose of this paper is to investigate the direct and indirect influences of workplace environment factors on the motivation to transfer the acquired training (MT) and the transfer of training. The workplace environment factors under study encompass the organizational support, supervisor support, peer support, technological support and the opportunity to use the acquired training.

Design/methodology/approach

In the study, the empirical data were garnered from a sample of 220 business school students, using a 52-question questionnaire. A research framework was first proposed and the structural equation modeling subsequently utilized to test the research framework and determine the direct influence of the workplace environment factors on the transfer of training and also their indirect influence on TT through the MT variable.

Findings

The structural equation modeling model is congruent with the empirical data, with the χ2 statistic of 24.414, the degree of freedom of 21, the p-value of 0.273, the goodness of fit index of 0.977 and the root mean square error of approximation of 0.027. The findings revealed that the workplace environment factors directly influenced the training transfer behavior of the participants and indirectly through the MT of the individuals. Most importantly, the proposed model could achieve the coefficient of prediction (R2) as high as 82 percent.

Originality/value

Workplace environment is important to motivation to transfer and transfer of training. To enhance the training transfer effectiveness, businesses should take into account the contributions associated with each environment factor in the design and implementation of training programs.
Negotiating barriers: prisoner and staff perspectives on mental wellbeing in the open prison setting
Authors: Danks Kara , Bradley Alexandria
Published: October 2017

Purpose

The purpose of this paper is to explore the perspectives of prisoners and prison staff in relation to mental wellbeing and the negotiation of barriers to accessing and providing support. This small-scale study includes the experiences of 11 prison staff and 9 prisoners within a Category D male prison.

Design/methodology/approach

A focus group was conducted with the prisoners and interviews with prison staff. Thematic analysis identified three core themes: “context enabling factors”, “barriers to accessing support for mental wellbeing” and “peer support roles”.

Findings

Prisoners conveyed a reluctance in reporting mental health issues due to the fear of being transferred to closed conditions. All staff indicated the benefits of peer support roles.

Research limitations/implications

Further research is required on a wider scale, as it is acknowledged that the findings of this study are from one prison and may not apply to other settings. Although there are barriers that may impact the reporting of mental wellbeing issues, there may be small relational steps that can be taken to address these.

Originality/value

Few studies exist that explore the nuances and barriers within open prisons, perhaps due to the overwhelming need within closed conditions. A context-specific approach considering early prevention strategies to support a safer prison system and successful rehabilitation is explored. The combination of prisoner and staff experiences is of value to both academia and policymakers.
Cold-formed steel columns at both ambient and fire conditions
Authors: Craveiro Hélder , Rodrigues João Paulo Correia , Laim Luis
Published: October 2017

Purpose

The use of cold-formed steel members has increased significantly in the past few years; however, its design is only briefly addressed in the current design codes, such as the EN 1993-1-3. To evaluate the compressive behavior of single and built-up cold-formed steel members, at ambient and simulated fire conditions with restrained thermal elongation, experimental and numerical tests were undertaken.

Design/methodology/approach

Four cross-section shapes were tested, namely, one single (lipped channel), one open built-up (I) and two closed built-up (R and 2R), considering two end support conditions, pinned and fixed. Two test set-ups were specifically developed for these tests. Based on the experimental results finite element models were developed and calibrated to allow future parametric studies.

Findings

This paper showed that increasing the level of restraint to thermal elongation and the initially applied load led to lower critical temperatures. Increasing the level of restraint to thermal elongation, the failure is governed by the generated axial restraining forces, whereas for lower levels of restraint to thermal elongation, the failure is controlled by the temperature increasing.

Originality/value

This paper is a contribution to the knowledge on the behavior of cold-formed steel columns subjected to fire, especially on the ones with a built-up cross-section, where results on thermal restrained ones are still scarce. It presented a set of experimental and numerical results useful for the development of numerical and analytical analysis concerning the development of new simplified calculation methods.
Does omalizumab modify a course of recalcitrant chronic spontaneous urticaria?: A retrospective study in Asian patients
Authors: Kulthanan Kanokvalai , Tuchinda Papapit , Likitwattananurak Chayanee , Weerasubpong Puncharas , Chularojanamontri Leena
Published: October 2017

Omalizumab has been approved for the treatment of recalcitrant chronic spontaneous urticaria (CSU). However, it remains unanswered whether omalizumab modifies a CSU course. We aimed to study a course of CSU after omalizumab treatment in an Asian population. Medical records of recalcitrant CSU patients who attended Siriraj Hospital between 2013 and 2017 were reviewed. All patients receiving omalizumab treatment were followed after the first injection for at least 1 year. Of 15 patients receiving omalizumab treatment, 11 patients (73.3%) responded well to 150 mg while the rest required 300 mg. The median follow‐up period was 18 months (range, 13.5–25.3). Three patterns of response were proposed and measured: excellent (disease remission over than 6 months) was found in 20%; good (injection interval extended longer than 6 months) was found in 27%; and modest (frequently required injections) was found in 53%. The mean duration of complete remission was 33 weeks (range, 26–38). Two‐thirds of patients had disease relapse and required omalizumab injections to control symptoms. The other third did not show relapses for at least 69 weeks of the follow‐up period. After 1 year of treatment, Kaplan–Meier curves estimated that a higher percentage (86.7%) of recalcitrant CSU patients receiving omalizumab treatment would be free of symptoms (weekly Urticaria Activity Score = 0) without prednisolone and/or cyclosporin as compared with 42% of patients not receiving omalizumab treatment. In conclusion, patients seem to be easily and safely manageable with omalizumab. Prednisolone and cyclosporin could be discontinued in all patients. Further studies are needed to conclude whether omalizumab can exactly modify CSU.
Involvement of NF‐κB in the upregulation of cystathionine‐γ‐lyase, a hydrogen sulfide‐forming enzyme, and bladder pain accompanying cystitis in mice
Authors: Ozaki Tomoka , Tsubota Maho , Sekiguchi Fumiko , Kawabata Atsufumi
Published: October 2017

Hydrogen sulfide (H2S) is generated from l‐cysteine by multiple enzymes including cystathionine‐γ‐lyase (CSE), and promotes nociception by targeting multiple molecules such as Cav3.2 T‐type Ca2+ channels. Bladder pain accompanying cyclophosphamide (CPA)‐induced cystitis in mice has been shown to involve the functional upregulation of the CSE/H2S/Cav3.2 pathway. Therefore, we investigated whether NF‐κB, as an upstream signal of the CSE/H2S system, contributes to bladder pain in mice with CPA‐induced cystitis. Bladder pain‐like nociceptive behaviour was observed in CPA‐treated mice, and referred hyperalgesia was evaluated by the von Frey test. Isolated bladder weights were assessed to estimate bladder swelling, and protein levels were measured by Western blotting. CPA, administered intraperitoneally, induced nociceptive behaviour, referred hyperalgesia and increased bladder weights in mice. β‐Cyano‐l‐alanine, a reversible selective CSE inhibitor, prevented CPA‐induced nociceptive behaviour, referred hyperalgesia, and, in part, increases in bladder weight. CPA markedly increased phosphorylated NF‐κB p65 levels in the bladder, an effect that was prevented by pyrrolidine dithiocarbamate (PDTC), an NF‐κB inhibitor. PDTC and curcumin, which inhibits NF‐κB signals, abolished CPA‐induced nociceptive behaviour, referred hyperalgesia and, in part, increases in bladder weight. CPA caused the overexpression of CSE in the bladder, and this was prevented by PDTC or curcumin. The CPA‐induced activation of NF‐κB signals appeared to cause CSE overexpression in the bladder, contributing to bladder pain and in part swelling, possibly through H2S/Cav3.2 signaling. Therefore, NF‐κB‐inhibiting compounds including curcumin may be useful for the treatment of cystitis‐related bladder pain.
Housing and the Tax System: How Large Are the Distortions in the Euro Area?*
Authors: Fatica Serena , Prammer Doris
Published: October 2017

This paper presents new evidence on the impact of the preferential treatment of owner‐occupied housing in the euro area. We find that tax benefits to homeowners reduce the user cost of housing capital by almost 40 per cent compared with the efficient level under neutral taxation. On average, the tax subsidy translates into an excess consumption of housing services equivalent to 7.8 per cent of the value of owner‐occupied housing, or about 30 per cent of financial asset holdings in household portfolios. The bulk of the subsidy stems from undertaxation of the return to home equity, while the average contribution of the tax rebate for mortgage interest payments is driven down by relatively low loan‐to‐value ratios in the data. However, at the margin, the tax‐induced incentive to use mortgage debt to finance the purchase of the main residence is sizeable.
Household Determinants of the Adoption of Improved Cassava Varieties using DNA Fingerprinting to Identify Varieties in Farmer Fields: A Case Study in Colombia
Authors: Floro Victorino O. , Labarta Ricardo A. , Becerra López‐Lavalle Luis A. , Martinez Jose M. , Ovalle Tatiana M.
Published: October 2017

We examine factors affecting the adoption of improved cassava varieties of 217 households in the Cauca Department in southwest Colombia. Using DNA fingerprinting through Single Nucleotide Polymorphisms (SNPs), we identified different cultivars in farmers fields. We also used this information to remove possible bias in the adoption model that could have resulted from a misclassification of improved varieties (IVs). As a result, we found that farmers substantially overestimate their use of IVs and there are important differences in the determinants of adoption between farmer self‐identification and DNA fingerprinting. This finding implies that the incorporation of DNA fingerprinting in IV adoption studies is important to ensure the accuracy of future agricultural economic research and the relevance of subsequent policy recommendations.
Authentication of Surveillance Videos: Detecting Frame Duplication Based on Residual Frame
Authors: Fadl Sondos M. , Han Qi , Li Qiong
Published: October 2017

Nowadays, surveillance systems are used to control crimes. Therefore, the authenticity of digital video increases the accuracy of deciding to admit the digital video as legal evidence or not. Inter‐frame duplication forgery is the most common type of video forgery methods. However, many existing methods have been proposed for detecting this type of forgery and these methods require high computational time and impractical. In this study, we propose an efficient inter‐frame duplication detection algorithm based on standard deviation of residual frames. Standard deviation of residual frame is applied to select some frames and ignore others, which represent a static scene. Then, the entropy of discrete cosine transform coefficients is calculated for each selected residual frame to represent its discriminating feature. Duplicated frames are then detected exactly using subsequence feature analysis. The experimental results demonstrated that the proposed method is effective to identify inter‐frame duplication forgery with localization and acceptable running time.
Myocardial Bridging: A Meta‐Analysis of Prevalence
Authors: Hostiuc Sorin , Negoi Ionuț , Rusu Mugurel C. , Hostiuc Mihaela
Published: October 2017

The main objective of this article was to analyze prevalence data about myocardial bridging (MB) in published studies. To this purpose, we performed a meta‐analysis of studies published in English literature that contained data about the prevalence of MB and its anatomical characteristics. The overall prevalence was 19% (CI: 17–21%); autopsy studies revealed an overall prevalence of 42% (CI: 30–55%), CT studies 22% (CI: 18–25%), and coronary angiography 6% (CI: 5–8%). Most bridges were located on the left anterior descending artery (82% overall, 63% on autopsy studies), had a mean thickness of 2.47 mm and a mean length of 19.3 mm. In conclusion, autopsy studies should be the gold standard in evaluating the actual prevalence of myocardial bridges, while in vivo high‐resolution CT scanning should be preferred to coronary angiography studies.
An Automated Two‐Dimensional Form Registration Method for Osteological Pair‐Matching
Authors: Lynch Jeffrey James
Published: October 2017

This study introduces an automated method for osteological pair‐matching using two‐dimensional outline form data extracted from photographs. A procedure for acquiring photographs that improve the differentiation of specimens from the background is presented along with an extraction procedure that allows the capture of form data from photographs. The raw form data are used in a two‐dimensional registration procedure, which combines iterative closest point, K‐nearest neighbor search, and iterations around an estimated mean. Form data are used in optimized distance calculations that minimize true‐pair difference and maximize false‐pair difference. The sample consists of 122 calcanei and 110 tali from the UI‐Stanford collection. Performance statistics are provided for the maximum and average Segmented‐Hausdorff, Hausdorff, and Procrustes distances to show the comparative statistical results for matching. Results indicate 98.36% and 98.2% accuracy in pinpointing true‐pairs for the calcanei and tali, respectively, using a shortlist of one‐lowest‐distance.
Flexible work arrangements, national culture, organisational characteristics, and organisational outcomes: A study across 21 countries
Authors: Peretz Hilla , Fried Yitzhak , Levi Ariel
Published: October 2017

Using a contingency perspective, we investigated two complementary topics: (a) the influence of the GLOBE national cultural values and key organisational variables on employee use of flexible work arrangements (FWAs), and (b) the contribution of the level of congruence between cultural values and FWA use on absenteeism and turnover. The results, based on Cranfield Network on Comparative Human Resource Management—a large data set across multiple countries—supported the hypothesised effects of the cultural values on employee use of FWAs and the moderating effects of these cultural values on FWA use and organisational outcomes. Specifically, we found that national cultural values and organisational characteristics were related to outcomes via FWA use; and employees' use of FWAs had the overall effect of reducing absenteeism and turnover, but this effect was weakened when the FWAs were not consistent with cultural values. Theoretically, our results add to our knowledge and understanding of the effects of FWA use on absenteeism and turnover under different degrees of “fit” with cultural context. From a practical perspective, our results suggest that organisations should consider national cultural characteristics before implementing FWAs. A misfit between national culture and FWAs would potentially reduce employee use of FWAs and increase the likelihood of absenteeism and turnover.
Anti‐inflammaging effects of human alpha‐1 antitrypsin
Authors: Yuan Ye , DiCiaccio Benedetto , Li Ying , Elshikha Ahmed S. , Titov Denis , Brenner Brian , Seifer Lee , Pan Hope , Karic Nurdina , Akbar Mohammad A. , Lu Yuanqing , Song Sihong , Zhou Lei
Published: October 2017

Inflammaging plays an important role in most age‐related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha‐1 antitrypsin (hAAT) has immune‐regulatory, anti‐inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti‐inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT. Surprisingly, the lifespan of hAAT‐expressing lines was significantly longer than that of genetically matched controls. To understand the mechanism underlying the anti‐aging effect of hAAT, we monitored the expression of aging‐associated genes and found that aging‐induced expressions of Relish (NF‐ĸB orthologue) and Diptericin were significantly lower in hAAT lines than in control lines. RNA‐seq analysis revealed that innate immunity genes regulated by NF‐kB were significantly and specifically inhibited in hAAT transgenic Drosophila lines. To confirm this anti‐inflammaging effect in human cells, we treated X‐ray‐induced senescence cells with hAAT and showed that hAAT treatment significantly decreased the expression and maturation of IL‐6 and IL‐8, two major factors of senescence‐associated secretory phenotype. Consistent with results from Drosophila,RNA‐seq analysis also showed that hAAT treatment significantly inhibited inflammation related genes and pathways. Together, our results demonstrated that hAAT significantly inhibited inflammaging in both Drosophila and human cell models. As hAAT is a FDA‐approved drug with a confirmed safety profile, this novel therapeutic potential may make hAAT a promising candidate to combat aging and aging‐related diseases.
The impact diverging public opinion on cannabis and tobacco regulation has on constructive engagement between advocates
Authors: Arnott Deborah
Published: October 2017

Commentary to: The diverging trajectories of cannabis and tobacco policies in the United States: reasons and possible implications
A Study of Biodeterioration and Chromatic Alterations of Painted and Gilded Mummy Cartonnage at the Saqqara Museum Storeroom, Egypt
Authors: Ali M. F. , Mansour M. M. A. , Badr N. M. , Salem M. Z. M.
Published: October 2017

Microbial biofilms have developed on the surfaces and within the painted and gilded layers of mummy cartonnage at the Saqqara museum storeroom in Giza, Egypt. SEM–EDX, XRD and FT–IR–ATR techniques were applied to analyse the coloured and gilded materials, ground layer, textile support and binder used for the cartonnage. Aspergillus niger (24.8%), Penicillium chrysogenum (21.5%) and a novel cartonnage‐biodegrading bacterium, Bacillus sonorensis (23.7%), were the most abundant microbes growing over the cartonnage surface. In addition, Aspergillus tamari (15.4%), A. fumigates (8.1%) and Fusarium solani (6.5%) were identified. The pigments comprised Egyptian blue (cuprorivaite), cinnabar (red), orpiment (yellow) and green pigment made from a mixture of cuprorivaite and orpiment. Gold leaf was used for the gilded layer, calcium carbonate and gypsum comprised the ground layer, gum arabic was the binding medium and the fibre base was a fine linen textile. Microbial colonization tests were performed on aged cartonnage replica samples made from linen and pigments of similar composition to ancient pigments found in the cartonnage. Each sample was inoculated separately with A. niger, P. chrysogenum and B. sonorensis. Yellow orpiment samples were the exception, as no colour change was detected after colonization by the examined micro‐organisms.
Feasibility of laparoscopic surgery after stent insertion for obstructive colorectal cancer
Authors: Shimizu Hideharu , Yamazaki Ryoto , Ohtsuka Hideo , Osaka Itaru , Takuma Kunio , Morita Yasuhiro
Published: October 2017

Introduction

A growing number of patients with obstructive colorectal cancer are being treated with self‐expanding metallic stents (SEMS) followed by laparoscopic resection. The aim of this study was to assess the feasibility of stent insertion and laparoscopic surgery for obstructive colorectal cancer and to compare these outcomes to regular laparoscopic surgery for non‐obstructive colorectal cancer.

Methods

We retrospectively analyzed the outcomes of patients with a malignant colonic obstruction who underwent SEMS placement followed by elective laparoscopic resection. The comparison was made between stent‐laparoscopy and laparoscopy alone for non‐obstructive colorectal cancer.

Results

Colonic stenting as a bridge to surgery was successful in 97.1% of all cases. Fifteen patients underwent an elective laparoscopic surgery for left‐sided colon and rectal cancer after SEMS. The mean interval from SEMS insertion to laparoscopic surgery was 21.5 days. There was no conversion to open surgery and no need for a diverting stoma. One patient (6.7%) experienced paralytic ileus. Our comparison of stent‐laparoscopy to regular laparoscopy for non‐obstructive colorectal cancer treatment showed comparable short‐term postoperative outcomes with the exception of blood loss, which was greater in the stent‐laparoscopy group.

Conclusion

Elective laparoscopic surgery after colonic stenting is a safe and feasible strategy for the treatment of an acute malignant colonic obstruction.
The influence of time units on the flexibility of the spatial numerical association of response codes effect
Authors: Zhao Tingting , He Xianyou , Zhao Xueru , Huang Jianrui , Zhang Wei , Wu Shuang , Chen Qi
Published: October 2017

The Spatial Numerical/Temporal Association of Response Codes (SNARC/STEARC) effects are considered evidence of the association between number or time and space, respectively. As the SNARC effect was proposed by Dehaene, Bossini, and Giraux in 1993, several studies have suggested that different tasks and cultural factors can affect the flexibility of the SNARC effect. This study explored the influence of time units on the flexibility of the SNARC effect via materials with Arabic numbers, which were suffixed with time units and subjected to magnitude comparison tasks. Experiment 1 replicated the SNARC effect for numbers and the STEARC effect for time units. Experiment 2 explored the flexibility of the SNARC effect when numbers were attached to time units, which either conflicted with the numerical magnitude or in which the time units were the same or different. Experiment 3 explored whether the SNARC effect of numbers was stable when numbers were near the transition of two adjacent time units. The results indicate that the SNARC effect was flexible when the numbers were suffixed with time units: Time units influenced the direction of the SNARC effect in a way which could not be accounted for by the mathematical differences between the time units and numbers. This suggests that the SNARC effect is not obligatory and can be easily adapted or inhibited based on the current context.
Anticancer activity of VmCT1 analogs against MCF‐7 cells
Authors: Pedron Cibele Nicolaski , Andrade Gislaine Patricia , Sato Roseli Hiromi , Torres Marcelo Der Torossian , Cerchiaro Giselle , Ribeiro Anderson Orzari , Oliveira Vani Xavier
Published: October 2017

Antimicrobial peptides are considered promising drug candidates due to their broad range of activity. VmCT1 (Phe–Leu–Gly–Ala–Leu–Trp–Asn–Val–Ala–Lys–Ser–Val–Phe–NH2) is an α‐helical antimicrobial peptide that was obtained from the Vaejovis mexicanus smithi scorpion venom. Some of its analogs showed to be as antimicrobial as the wild type, and they were designed for understanding the influence of physiochemical parameters on antimicrobial and hemolytic activity. Some cationic antimicrobial peptides exhibit anticancer activity so VmCT1 analogs were tested to verify the anticancer activity of this family of peptides. The analogs were synthesized, purified, characterized, and the conformational studies were performed. The anticancer activity was assessed against MCF‐7 mammary cancer cells. The results indicated that [Glu]7‐VmCT1‐NH2, [Lys]3‐VmCT1‐NH2, and [Lys]7‐VmCT1‐NH2 analogs presented moderated helical tendency (0.23–0.61) and tendency of anticancer activity at 25 μmol/L in 24 hr of experiment; and [Trp]9‐VmCT1‐NH2 analog that presented low helical tendency and moderated anticancer activity at 50 μmol/L. These results demonstrated that single substitutions on VmCT1 led to different physicochemical features and could assist on the understanding of anticancer activity of this peptide family.
Ensemble‐based ADME–Tox profiling and virtual screening for the discovery of new inhibitors of the Leishmania mexicana cysteine protease CPB2.8ΔCTE
Authors: Scala Angela , Rescifina Antonio , Micale Nicola , Piperno Anna , Schirmeister Tanja , Maes Louis , Grassi Giovanni
Published: October 2017

In an effort to identify novel molecular warheads able to inhibit Leishmania mexicana cysteine protease CPB2.8ΔCTE, fused benzo[b]thiophenes and β,βʹ‐triketones emerged as covalent inhibitors binding the active site cysteine residue. Enzymatic screening showed a moderate‐to‐excellent activity (12%–90% inhibition of the target enzyme at 20 μm). The most promising compounds were selected for further profiling including in vitro cell‐based assays and docking studies. Computational data suggest that benzo[b]thiophenes act immediately as non‐covalent inhibitors and then as irreversible covalent inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3ʹ‐triketones with a Y‐topology. Based on the predicted physicochemical and ADME–Tox properties, compound 2b has been identified as a new drug‐like, non‐mutagen, non‐carcinogen, and non‐neurotoxic lead candidate.
An inverse association between serum resistin levels and n‐3 polyunsaturated fatty acids intake was strongest in the SNP‐420 G/G genotype in the Japanese cohort: The Toon Genome Study
Authors: Noumi Yukinobu , Kawamura Ryoichi , Tabara Yasuharu , Maruyama Koutatsu , Takata Yasunori , Nishida Wataru , Okamoto Ai , Nishimiya Tatsuya , Onuma Hiroshi , Saito Isao , Tanigawa Takeshi , Osawa Haruhiko
Published: October 2017

Objective

Resistin is secreted by monocytes/macrophages and is associated with insulin resistance, inflammation and cardiovascular diseases. In the Japanese cohort, serum resistin is tightly associated with a single‐nucleotide polymorphism (SNP) at ‐420 (rs1862513) in the promoter region of the human resistin gene. However, interactions betweenSNP‐420 and environmental factors remain to be elucidated. The aim of this study was to investigate the association between serum resistin levels and nutrient intake, and the effect ofSNP‐420 on this association.

Design, Participants and Measurements

The Toon Genome Study is a cohort study of Japanese community‐dwelling subjects. A total of 1981 participants were cross‐sectionally analysed. Each nutrient intake was assessed using the semiquantitative food frequency questionnaire and categorized into the quartiles (Q1‐Q4). Serum resistin was measured byELISA.

Results

Serum resistin tended to be inversely associated with fish intake and positively associated with meat intake after adjustment for age, sex,BMIand energy intake. Serum resistin was inversely associated with n‐3 polyunsaturated fatty acids (PUFA) intake after adjustment for age, sex,BMIand energy intake (Q1 12.5, Q2 12.5, Q3 12.2, Q4 11.5 ng/mL;Pfor trend = .007). This inverse association was strongest in the G/G genotype ofSNP‐420, followed by C/G and C/C (G/G, Q1 18.9, Q2 19.5, Q3 18.4, Q4 14.5 ng/mL,P = .001; C/G, 14.4, 13.3, 13.1, 12.9,P = .015; C/C, 9.5, 9.5, 9.2, 8.8,P = .020;Pfor interaction = .004).

Conclusions

The inverse association between serum resistin and n‐3PUFAintake was strongest inSNP‐420 G/G genotype in the Japanese cohort.
Real‐world visual outcomes in patients with neovascular age‐related macular degeneration receiving aflibercept at fixed intervals as per UK licence
Authors: Ozturk Mehmet , Harris Martin L , Nguyen Vuong , Barthelmes Daniel , Gillies Mark C , Mehta Hemal
Published: October 2017

Importance

To assess the impact of injection frequency on visual outcomes in patients with neovascular age‐related macular degeneration (nAMD) treated with intravitreal aflibercept.

Background

The UK licence for treatment of nAMD with aflibercept is based on the VIEW protocol. We tested the hypothesis that patients receiving fewer than the eight recommended injections in the first year would experience worse visual outcomes.

Design

Retrospective, single‐centre observational study.

Participants

There were 42 eyes from 42 patients included.

Methods

Fight Retinal Blindness! software was used to record real‐world outcomes of all treatment‐naïve eyes receiving aflibercept for at least 1 year.

Main Outcome Measures

Visual acuity (VA) at 1 year in eyes which received the recommended eight injections versus those receiving seven or fewer injections.

Results

There were 21 eyes (50%) that received the recommended eight aflibercept injections in the first year of treatment, whilst 14 eyes received seven injections, five received six injections and two received only five injections, with median VA change +7.0, +5.0, −4.0 and −6.5 LogMAR letters, respectively. Those eyes receiving seven or fewer injections had worse baseline vision. The main reasons for patients being undertreated were insufficient clinic capacity and non‐attendance due to illness.

Conclusions and Relevance

Patients in the real‐world receiving aflibercept for nAMD at fixed intervals as per UK licence could achieve similar visual improvement at 1 year compared with phase III clinical trials. Undertreated patients had worse visual outcomes. Measures need to be introduced to increase clinic capacity and closely follow non‐attenders to improve future outcomes.
Finding a routine that works: A mixed methods study of foster parents
Authors: Helton Jesse J. , Schreiber Jill C. , Wiley Janet , Schweitzer Rachel
Published: October 2017

Although it is well established that daily routines are important for family well‐being, very little research has been done on how foster parents establish and integrate new foster children into family routines. We used a mixed‐methods, cross‐sectional design, focused on qualitative results to explore how foster parents utilize routines. Twenty‐three foster parents were recruited from a private child welfare agency in a large city in the United States. Surveys were administered to obtain demographic information, overall home atmosphere, and the importance and prevalence of different routines, including mealtimes and sleep schedules. Nine foster parents received a semistructured interview with open‐ended questions. Foster parents reported that routines such as bedtimes, mealtimes, chores, and homework were essential to family well‐being. Because both parents and children had to adjust to living together in an intimate family environment, it was important to establish routines quickly. Foster parents modified routines depending on their child's needs. Along with typical family routines, foster parents reported additional tasks, such as visits with biological parents, meetings with caseworkers, and trainings that affected their family schedule. Results imply that training foster care workers and foster parents about routines can engender stability and emotional belonging for children.
Improvements in health‐related quality of life over 3 years with liraglutide 3.0 mg compared with placebo in participants with overweight or obesity
Authors: Kolotkin R. L. , Smolarz B. G. , Meincke H. H. , Fujioka K.
Published: October 2017

Previously in the SCALE Obesity and Prediabetes trial, at 1 year, participants with obesity (or overweight with comorbidities) and prediabetes receiving liraglutide 3.0 mg experienced greater improvements in health‐related quality of life (HRQoL) than those receiving placebo. The current study extends these findings by examining 3‐year changes in HRQoL. HRQoL was assessed using the obesity‐specific Impact of Weight on Quality of Life‐Lite (IWQOL‐Lite) questionnaire, as well as the Short‐Form 36 v2 (SF‐36) health survey. At 3 years, mean change (±standard deviation) in IWQOL‐Lite total score from baseline for liraglutide (n = 1472) was 11.0 ± 14.2, vs. 8.1 ± 14.7 for placebo (n = 738) (estimated treatment difference [ETD] 3.4 [95% confidence interval (CI): 2.0, 4.7], P < 0.0001). Mean change in SF‐36 physical component summary (PCS) score from baseline for liraglutide was 3.1 ± 7.3, vs. 2.6 ± 7.6 for placebo (ETD 0.87 [95% CI: 0.17, 1.6], P = 0.0156). Mean change in SF‐36 mental component summary score did not significantly differ between groups. Both IWQOL‐Lite total score and PCS score demonstrated an association between greater HRQoL improvement with higher weight loss. Liraglutide 3.0 mg was also associated with improved health utility (Short‐Form‐6D and EuroQol‐5D, mapped from IWQOL‐Lite and/or SF‐36) vs. placebo. Liraglutide 3.0 mg, plus diet and exercise, is associated with long‐term improvements in HRQoL with obesity or overweight with comorbidity vs. placebo.
Contact dermatitis caused by a new rubber compound detected in canvas shoes
Authors: Hulstaert Eva , Bergendorff Ola , Persson Christina , Goossens An , Gilissen Liesbeth , Engfeldt Malin , Bruze Magnus , Schuttelaar Marie L. , Meijer Joost M. , Lapeere Hilde
Published: October 2017

Background

In 2015 and 2016, female patients in Flanders consulted a dermatologist because they developed skin lesions after wearing a specific brand of canvas shoes.

Objectives

To identify the culprit allergen in the shoes.

Methods

Eighteen young females aged 14–22 years presented with itching and erythematous to purple‐coloured eczematous lesions on both feet. They were patch tested by 10 dermatologists with the European baseline series. Some patients underwent testing with additional series. Pieces of the shoe fabrics were tested in 11 of 18 patients. Chemical analysis of the shoe materials was performed. Finally, patients were tested with a thin‐layer chromatogram of the shoe extracts and dilutions of the suspected rubber compound.

Results

All 18 patients showed positive reactions to thiuram mix. Ten of 11 patients reacted to a piece of shoe fabric. Chemical analysis showed the presence of dimethylthiocarbamylbenzothiazole sulfide (DMTBS). No thiurams were detected. Four patients tested with the chromatogram developed positive reactions to DMTBS. Positive reactions to low concentrations were observed in the 4 patients tested with a DMTBS dilution series; one patient reacted to 0.00001% in acetone.

Conclusions

DMTBS, the culprit allergen, is a component formed during rubber vulcanization that probably cross‐reacts with the thiuram mix.