bluuebunny/crossref_metadata_2025 huggingface dataset:
Government data v. ground observation for food-environment assessment: businesses missed and misreported by city and state inspection records
Authors: Lucan Sean C , Maroko Andrew R , Abrams Courtney , Rodriguez Noemi , Patel Achint N , Gjonbalaj Ilirjan , Schechter Clyde B , Elbel Brian
Published: November 2019

Objective:

To assess the accuracy of government inspection records, relative to ground observation, for identifying businesses offering foods/drinks.

Design:

Agreement between city and state inspection records v. ground observations at two levels: businesses and street segments. Agreement could be ‘strict’ (by business name, e.g. ‘Rizzo’s’) or ‘lenient’ (by business type, e.g. ‘pizzeria’); using sensitivity and positive predictive value (PPV) for businesses and using sensitivity, PPV, specificity and negative predictive value (NPV) for street segments.

Setting:

The Bronx and the Upper East Side (UES), New York City, USA.

Participants:

All food/drink-offering businesses on sampled street segments (n 154 in the Bronx, n 51 in the UES).

Results:

By ‘strict’ criteria, sensitivity and PPV of government records for food/drink-offering businesses were 0·37 and 0·57 in the Bronx; 0·58 and 0·60 in the UES. ‘Lenient’ values were 0·40 and 0·62 in the Bronx; 0·60 and 0·62 in the UES. Sensitivity, PPV, specificity and NPV of government records for street segments having food/drink-offering businesses were 0·66, 0·73, 0·84 and 0·79 in the Bronx; 0·79, 0·92, 0·67, and 0·40 in the UES. In both areas, agreement varied by business category: restaurants; ‘food stores’; and government-recognized other storefront businesses (‘gov. OSB’, i.e. dollar stores, gas stations, pharmacies). Additional business categories – ‘other OSB’ (barbers, laundromats, newsstands, etc.) and street vendors – were absent from government records; together, they represented 28·4 % of all food/drink-offering businesses in the Bronx, 22·2 % in the UES (‘other OSB’ and street vendors were sources of both healthful and less-healthful foods/drinks in both areas).

Conclusions:

Government records frequently miss or misrepresent businesses offering foods/drinks, suggesting caveats for food-environment assessments using such records.
Nineteen-year trends in fermented food consumption and sodium intake from fermented foods for Korean adults from 1998 to 2016
Authors: Kim Sang Young , Freeland-Graves Jeanne H , Kim Hyun Ja
Published: November 2019

Objective:

Fermented foods such as kimchi are traditional foods in Korea and could provide beneficial health effects. However, fermented foods also contribute to increased Na intake since salt is added during the fermentation process. The present research aimed to examine trends in the consumption of fermented foods and Na intake over time by Korean adults, using data from the Korea National Health and Nutrition Examination Survey (KNHANES).

Design:

KNHANES is a cross-sectional survey; data from 1998 to 2016 were divided into seven groups from KNHANES I to VII.

Setting:

Demographic information on sex, age, education and income were collected. Assessment of fermented food and Na consumption was conducted via analysis of 24 h dietary recall data. Multivariate linear regressions and logistic regressions were performed to calculate the P for trends by applying strata, cluster and sampling weights by SAS PROC SURVEY.

Participants:

The target population was Korean adults, aged ≥19 years, who participated in a 24 h dietary recall. The total number was 76 199, with 32 324 men and 43 875 women.

Results:

A significant decline in fermented food consumption was observed from 1998 to 2016 in both men and women (P < 0·0001). Among fermented foods, kimchi consumption was greatly reduced while pickled vegetables consumption showed a marked increase. Similarly, Na intake from fermented foods declined significantly over time in both men and women (P < 0·0001).

Conclusions:

The consumption of fermented foods and Na intake from fermented foods by Korean adults decreased significantly over time from 1998 to 2016.
Towards an Explanatory Model of Suicidal Ideation: The Effects of Cognitive Emotional Regulation Strategies, Affectivity and Hopelessness
Authors: Flores-Kanter Pablo Ezequiel , García-Batista Zoilo Emilio , Moretti Luciana Sofía , Medrano Leonardo Adrián
Published: November 2019

Suicide constitutes a public health problem that has a significant economic, social and psychological impact on a global scale. Recently, the American Psychological Association has indicated that suicide prevention should be a public health priority. Suicidal ideation appears as a key variable in suicide prevention. The objective of this research was to verify the adjustment of an explanatory model for suicidal ideation, which considers the effects of cognitive emotion regulation strategies, affectivity and hopelessness. An open mode on-line sample of 2,166 Argentine participants was used and a path analysis was carried out. The results make it possible to conclude that the model presents an optimal fit (χ2 = .10, p = .75, CFI = .99, RMSEA = .01) and predicts 42% of suicidal thoughts. The model proves to be invariant based on age and gender. In conclusion, there is an importance of reducing the use of automatic strategies, such as repetitive negative thoughts of ruminative type, and increasing the use of more controlled strategies, such as reinterpretation or planning.
The Statistics of Replication
Authors: Hedges Larry V.
Published: November 2019

Abstract. The concept of replication is fundamental to the logic and rhetoric of science, including the argument that science is self-correcting. Yet there is very little literature on the methodology of replication. In this article, I argue that the definition of replication should not require underlying effects to be identical, but should permit some variation in true effects to be allowed. I note that different possible analyses could be used to determine whether studies replicate. Finally, I argue that a single replication study is almost never adequate to determine whether a result replicates. Thus, methodological work on the design of replication studies would be useful.
Double or hybrid diabetes: A systematic review on disease prevalence, characteristics and risk factors
Authors: Khawandanah Jomana
Published: November 2019

Diabetes mellitus is a worldwide epidemic affecting the health of millions of people. While type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing beta cells of the pancreas, type 2 diabetes (T2D) results from a combination of insulin resistance and beta cell insulin secretory defect. Clear definition and diagnosis of these two types of diabetes has been increasing more and more difficult, leading to the inclusion of a new category, namely double or hybrid diabetes (DD) that demonstrates symptoms of both T1D and T2D via the accelerator hypothesis. In this review, we discuss the worldwide prevalence of DD, its main physiological characteristics, including beta-cell autoimmunity, insulin resistance, and cardiovascular disease, the main risk factors of developing DD, mainly genetics, obesity and lifestyle choices, as well as potential treatments, such as insulin titration, metformin and behavioural modifications. Increasing awareness of DD among the general population and primary care practitioners is necessary for successfully treating this complex, hybrid disease in the future.
A novel small-molecule inhibitor of trefoil factor 3 (TFF3) potentiates MEK1/2 inhibition in lung adenocarcinoma
Authors: Zhang Mengyi , Wang Baocheng , Chong Qing-Yun , Pandey Vijay , Guo Zhirong , Chen Ru-Mei , Wang Lingzhi , Wang Yanxin , Ma Lan , Kumar Alan P. , Zhu Tao , Wu Zheng-Sheng , Yin Zhinan , Basappa  , Goh Boon-Cher , Lobie Peter E.
Published: November 2019

TFF3 has been identified as a novel biomarker to distinguish between lung adenocarcinoma (ADC) and lung squamous-cell carcinoma (SCC). Herein, we determined the oncogenic functions of TFF3 and demonstrated the potential of pharmacological inhibition of TFF3 in lung ADC using a novel small-molecule inhibitor of TFF3 dimerization (AMPC). Forced expression of TFF3 in lung ADC cells enhanced cell proliferation and survival, increased anchorage-independent growth, cancer stem cell behavior, growth in 3D Matrigel, and cell migration and invasion. In contrast, depleted expression of TFF3 suppressed these cellular functions. Mechanistically, TFF3 exerted its oncogenic function through upregulation of ARAF and hence enhanced downstream activation of MEK1/2 and ERK1/2. Pharmacological inhibition of TFF3 by AMPC, resulted in markedly decreased cell survival, proliferation, 3D growth and foci formation, and impaired tumor growth in a xenograft mouse model. Moreover, the combination of various MEK1/2 inhibitors with AMPC exhibited synergistic inhibitory effects on lung ADC cell growth. In conclusion, this study provides the first evidence that TFF3 is a potent promoter of lung ADC progression. Targeting TFF3 with a novel small-molecule inhibitor alone or in combination with conventional MEK1/2 inhibitors are potential strategies to improve the outcome of lung ADC.
Impaired cellular bioenergetics caused by GBA1 depletion sensitizes neurons to calcium overload
Authors: Plotegher Nicoletta , Perocheau Dany , Ferrazza Ruggero , Massaro Giulia , Bhosale Gauri , Zambon Federico , Rahim Ahad A. , Guella Graziano , Waddington Simon N. , Szabadkai Gyorgy , Duchen Michael R.
Published: November 2019

Heterozygous mutations of the lysosomal enzyme glucocerebrosidase (GBA1) represent the major genetic risk for Parkinson’s disease (PD), while homozygous GBA1 mutations cause Gaucher disease, a lysosomal storage disorder, which may involve severe neurodegeneration. We have previously demonstrated impaired autophagy and proteasomal degradation pathways and mitochondrial dysfunction in neurons from GBA1 knockout (gba1−/−) mice. We now show that stimulation with physiological glutamate concentrations causes pathological [Ca2+]c responses and delayed calcium deregulation, collapse of mitochondrial membrane potential and an irreversible fall in the ATP/ADP ratio. Mitochondrial Ca2+ uptake was reduced in gba1−/− cells as was expression of the mitochondrial calcium uniporter. The rate of free radical generation was increased in gba1−/− neurons. Behavior of gba1+/− neurons was similar to gba1−/− in terms of all variables, consistent with a contribution of these mechanisms to the pathogenesis of PD. These data signpost reduced bioenergetic capacity and [Ca2+]c dysregulation as mechanisms driving neurodegeneration.
Activation of Piezo1 sensitizes cells to TRAIL-mediated apoptosis through mitochondrial outer membrane permeability
Authors: Hope Jacob M. , Lopez-Cavestany Maria , Wang Wenjun , Reinhart-King Cynthia A. , King Michael R.
Published: November 2019

TRAIL specifically induces apoptosis in cancer cells without affecting healthy cells. However, TRAIL’s cancer cytotoxicity was insufficient in clinical trials. Circulatory-shear stress is known to sensitize cancer cells to TRAIL. In this study, we examine the mechanism of this TRAIL sensitization with the goal of translating it to static conditions. GsMTx-4, a Piezo1 inhibitor, was found to reduce shear stress-related TRAIL sensitization, implicating Piezo1 activation as a potential TRAIL-sensitizer. The Piezo1 agonist Yoda1 recreated shear stress-induced TRAIL sensitization under static conditions. A significant increase in apoptosis occurred when PC3, COLO 205, or MDA-MB-231 cells were treated with Yoda1 and TRAIL in combination, but not in Bax-deficient DU145 cells. Calpastatin inhibited apoptosis in Yoda1-TRAIL treated cells, indicating that calpain activation is necessary for apoptosis by Yoda1 and TRAIL. Yoda1 and TRAIL treated PC3 cells showed increased mitochondrial outer membrane permeability (MOMP), mitochondrial depolarization, and activated Bax. This implies that Piezo1 activation sensitizes cancer cells to TRAIL through a calcium influx that activates calpains. The Calpains then induce MOMP by enhancing Bax activation. From these experiments a computational model was developed to simulate apoptosis for cells treated with TRAIL and increased calcium. The computational model elucidated the proapoptotic or antiapoptotic roles of Bax, Bcl-2, XIAP, and other proteins important in the mitochondrial-apoptotic signaling pathway.
Correction: X-chromosome-linked miR548am-5p is a key regulator of sex disparity in the susceptibility to mitochondria-mediated apoptosis
Authors: Matarrese Paola , Tieri Paolo , Anticoli Simona , Ascione Barbara , Conte Maria , Franceschi Claudio , Malorni Walter , Salvioli Stefano , Ruggieri Anna
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Nucleolar stress regulation of endometrial receptivity in mouse models and human cell lines
Authors: Hu Wei , Liang Yu-Xiang , Luo Jia-Mei , Gu Xiao-Wei , Chen Zi-Cong , Fu Tao , Zhu Yu-Yuan , Lin Shuai , Diao Hong-Lu , Jia Bo , Yang Zeng-Ming
Published: November 2019

Embryo implantation is essential to the successful establishment of pregnancy. A previous study has demonstrated that actinomycin D (ActD) could initiate the activation of mouse delayed implantation. However, the mechanism underlying this activation remains to be elucidated. A low dose of ActD is an inducer of nucleolar stress. This study was to examine whether nucleolar stress is involved in embryo implantation. We showed that nucleolar stress occurred when delayed implantation was activated by ActD in mice. ActD treatment also stimulated the Lif-STAT3 pathway. During early pregnancy, nucleolar stress was detected in the luminal epithelial cells during the receptive phase. Blastocyst-derived lactate could induce nucleolar stress in cultured luminal epithelial cells. The inhibition of nucleophosmin1 (NPM1), which was a marker of nucleolar stress, compromised uterine receptivity and decreased the implantation rates in pregnant mice. To translate these mouse data into humans, we examined nucleolar stress in human endometrium. Our data demonstrated that ActD-induced nucleolar stress had positive effects on the embryo attachment by upregulating IL32 expression in non-receptive epithelial cells rather than receptive epithelial cells. Our data should be the first to demonstrate that nucleolar stress is present during early pregnancy and is able to induce embryo implantation in both mice and humans.
Synthetic protein-conductive membrane nanopores built with DNA
Authors: Diederichs Tim , Pugh Genevieve , Dorey Adam , Xing Yongzheng , Burns Jonathan R. , Hung Nguyen Quoc , Tornow Marc , Tampé Robert , Howorka Stefan
Published: November 2019

Nanopores are key in portable sequencing and research given their ability to transport elongated DNA or small bioactive molecules through narrow transmembrane channels. Transport of folded proteins could lead to similar scientific and technological benefits. Yet this has not been realised due to the shortage of wide and structurally defined natural pores. Here we report that a synthetic nanopore designed via DNA nanotechnology can accommodate folded proteins. Transport of fluorescent proteins through single pores is kinetically analysed using massively parallel optical readout with transparent silicon-on-insulator cavity chips vs. electrical recordings to reveal an at least 20-fold higher speed for the electrically driven movement. Pores nevertheless allow a high diffusive flux of more than 66 molecules per second that can also be directed beyond equillibria. The pores may be exploited to sense diagnostically relevant proteins with portable analysis technology, to create molecular gates for drug delivery, or to build synthetic cells.
Author Correction: Disentangling astroglial physiology with a realistic cell model in silico
Authors: Savtchenko Leonid P. , Bard Lucie , Jensen Thomas P. , Reynolds James P. , Kraev Igor , Medvedev Nikolay , Stewart Michael G. , Henneberger Christian , Rusakov Dmitri A.
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Role of innate lymphoid cells and dendritic cells in intradermal immunization of the enterovirus antigen
Authors: Fan Shengtao , Liao Yun , Lian Yaru , Jiang Guorun , Jiang Li , Dong Chenhong , Yang Erxia , Wang Lichun , Xu Xingli , Feng Min , Zhang Ying , Li Qihan
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Scalable Fabrication of Organic Single-Crystalline Wafers for Reproducible TFT Arrays
Authors: Kumagai Shohei , Yamamura Akifumi , Makita Tatsuyuki , Tsurumi Junto , Lim Ying Ying , Wakimoto Takahiro , Isahaya Nobuaki , Nozawa Han , Sato Kayoko , Mitani Masato , Okamoto Toshihiro , Watanabe Shun , Takeya Jun
Published: November 2019

Building on significant developments in materials science and printing technologies, organic semiconductors (OSCs) promise an ideal platform for the production of printed electronic circuits. However, whether their unique solution-processing capability can facilitate the reliable mass manufacture of integrated circuits with reasonable areal coverage, and to what extent mass production of solution-processed electronic devices would allow substantial reductions in manufacturing costs, remain controversial. In the present study, we successfully manufactured a 4-inch (c.a. 100 mm) organic single-crystalline wafer via a simple, one-shot printing technique, on which 1,600 organic transistors were integrated and characterized. Owing to their single-crystalline nature, we were able to verify remarkably high reliability and reproducibility, with mobilities up to 10 cm2 V−1 s−1, a near-zero turn-on voltage, and excellent on-off ratio of approximately 107. This work provides a critical milestone in printed electronics, enabling industry-level manufacturing of OSC devices concomitantly with lowered manufacturing costs.
Deep Neural Network and Monte Carlo Tree Search applied to Fluid-Structure Topology Optimization
Authors: Gaymann Audrey , Montomoli Francesco
Published: November 2019

This paper shows the application of Deep Neural Network algorithms for Fluid-Structure Topology Optimization. The strategy offered is a new concept which can be added to the current process used to study Topology Optimization with Cellular Automata, Adjoint and Level-Set methods. The design space is described by a computational grid where every cell can be in two states: fluid or solid. The system does not require human intervention and learns through an algorithm based on Deep Neural Network and Monte Carlo Tree Search. In this work the objective function for the optimization is an incompressible fluid solver but the overall optimization process is independent from the solver. The test case used is a standard duct with back facing step where the optimizer aims at minimizing the pressure losses between inlet and outlet. The results obtained with the proposed approach are compared to the solution via a classical adjoint topology optimization code.
Computing on actin bundles network
Authors: Adamatzky Andrew , Huber Florian , Schnauß Jörg
Published: November 2019

Actin filaments are conductive to ionic currents, mechanical and voltage solitons. These travelling localisations can be utilised to generate computing circuits from actin networks. The propagation of localisations on a single actin filament is experimentally unfeasible to control. Therefore, we consider excitation waves propagating on bundles of actin filaments. In computational experiments with a two-dimensional slice of an actin bundle network we show that by using an arbitrary arrangement of electrodes, it is possible to implement two-inputs-one-output circuits.
Effect of low doses of biocides on the antimicrobial resistance and the biofilms of Cronobacter sakazakii and Yersinia enterocolitica
Authors: Capita Rosa , Vicente-Velasco María , Rodríguez-Melcón Cristina , García-Fernández Camino , Carballo Javier , Alonso-Calleja Carlos
Published: November 2019

The susceptibility of Cronobacter sakazakii ATCC 29544 (CS) and Yersinia enterocolitica ATCC 9610 (YE) to sodium hypochlorite (10% of active chlorine; SHY), peracetic acid (39% solution of peracetic acid in acetic acid; PAA) and benzalkonium chloride (BZK) was tested. Minimum inhibitory concentration (MIC) values (planktonic cells; microdilution broth method) of 3,800 ppm (SHY), 1,200 ppm (PAA) and 15 ppm (BZK) for CS, and 2,500 ppm (SHY), 1,275 ppm (PAA) and 20 ppm (BZK) for YE, were found. In some instances, an increase in growth rate was observed in presence of sub-MICs (0.25MIC, 0.50MIC or 0.75MIC) of biocides relative to the samples without biocides. The cultures exhibited an acquired tolerance to biocides and an increase in antibiotic resistance after exposure to sub-MICs of such disinfectants. Strains were able to form strong biofilms on polystyrene after 48 hours (confocal laser scanning microscopy), with average biovolumes in the observation field (14,161 µm2) of 242,201.0 ± 86,570.9 µm3 (CS) and 190,184.5 ± 40,860.3 µm3 (YE). Treatment of biofilms for 10 minutes with disinfectants at 1MIC or 2MIC reduced the biovolume of live cells. PAA (YE) and BZK (CS and YE) at 1MIC did not alter the percentage of dead cells relative to non-exposed biofilms, and their effect of countering biofilm was due principally to the detachment of cells. These results suggest that doses of PAA and BZK close to MICs might lead to the dissemination of live bacteria from biofilms with consequent hazards for public health.
Prominin-1 Modulates Rho/ROCK-Mediated Membrane Morphology and Calcium-Dependent Intracellular Chloride Flux
Authors: Hori Akiko , Nishide Kenji , Yasukuni Yuki , Haga Kei , Kakuta Wataru , Ishikawa Yasuyuki , Hayes Matthew J. , Ohnuma Shin-ichi , Kiyonari Hiroshi , Kimura Kazuhiro , Kondo Toru , Sasai Noriaki
Published: November 2019

Membrane morphology is an important structural determinant as it reflects cellular functions. The pentaspan membrane protein Prominin-1 (Prom1/CD133) is known to be localised to protrusions and plays a pivotal role in migration and the determination of cellular morphology; however, the underlying mechanism of its action have been elusive. Here, we performed molecular characterisation of Prom1, focussing primarily on its effects on cell morphology. Overexpression of Prom1 in RPE-1 cells triggers multiple, long, cholesterol-enriched fibres, independently of actin and microtubule polymerisation. A five amino acid stretch located at the carboxyl cytosolic region is essential for fibre formation. The small GTPase Rho and its downstream Rho-associated coiled-coil-containing protein kinase (ROCK) are also essential for this process, and active Rho colocalises with Prom1 at the site of initialisation of fibre formation. In mouse embryonic fibroblast (MEF) cells we show that Prom1 is required for chloride ion efflux induced by calcium ion uptake, and demonstrate that fibre formation is closely associated with chloride efflux activity. Collectively, these findings suggest that Prom1 affects cell morphology and contributes to chloride conductance.
Nanohydroxyapatite Reinforced Chitosan Composite Hydrogel with Tunable Mechanical and Biological Properties for Cartilage Regeneration
Authors: Kumar B. Y. Santosh , Isloor Arun M. , Kumar G. C. Mohan , Inamuddin  , Asiri Abdullah M.
Published: November 2019

With the continuous quest of developing hydrogel for cartilage regeneration with superior mechanobiological properties are still becoming a challenge. Chitosan (CS) hydrogels are the promising implant materials due to an analogous character of the soft tissue; however, their low mechanical strength and durability together with its lack of integrity with surrounding tissues hinder the load-bearing application. This can be solved by developing a composite chitosan hydrogel reinforced with Hydroxyapatite Nanorods (HANr). The objective of this work is to develop and characterize (physically, chemically, mechanically and biologically) the composite hydrogels loaded with different concentration of hydroxyapatite nanorod. The concentration of hydroxyapatite in the composite hydrogel was optimized and it was found that, reinforcement modifies the hydrogel network by promoting the secondary crosslinking. The compression strength could reach 1.62 ± 0.02 MPa with a significant deformation of 32% and exhibits time-dependent, rapid self-recoverable and fatigue resistant behavior based on the cyclic loading-unloading compression test. The storage modulus value can reach nearly 10 kPa which is needed for the proposed application. Besides, composite hydrogels show an excellent antimicrobial activity against Escherichia coli, Staphylococcus aureus bacteria’s and Candida albicans fungi and their cytocompatibility towards L929 mouse fibroblasts provide a potential pathway to developing a composite hydrogel for cartilage regeneration.
Determinants of myocardial function characterized by CMR-derived strain parameters in left ventricular non-compaction cardiomyopathy
Authors: Gastl Mareike , Gotschy Alexander , Polacin Malgorzata , Vishnevskiy Valery , Meyer Dominik , Sokolska Justyna , Tanner Felix C. , Alkadhi Hatem , Kozerke Sebastian , Manka Robert
Published: November 2019

Clinical presentation of left ventricular non-compaction cardiomyopathy (LVNC) can be heterogeneous from asymptomatic expression to congestive heart failure. Deformation indices assessed by cardiovascular magnetic resonance (CMR) can determine subclinical alterations of myocardial function and have been reported to be more sensitive to functional changes than ejection fraction. The objective of the present study was to investigate the determinants of myocardial deformation indices in patients with LVNC. Twenty patients with LVNC (44.7 ± 14.0 years) and twenty age- and gender-matched controls (49.1 ± 12.4 years) underwent functional CMR imaging using an ECG-triggered steady state-free-precession sequence (SSFP). Deformation indices derived with a feature tracking algorithm were calculated including end-systolic global longitudinal strain (GLS), circumferential strain (GCS), longitudinal and circumferential strain rate (SRll and SRcc). Twist and rotation were determined using an in-house developed post-processing pipeline. Global deformation indices (GLS, GCS, SRll and SRcc) were significantly lower in patients with LVNC compared to healthy controls (all, p < 0.01), especially for midventricular and apical regions. Apical rotation and twist were impaired for LVNC (p = 0.007 and p = 0.012), but basal rotation was preserved. Deformation indices of strain, strain rate and twist correlated well with parameters of the non-compacted myocardium, but not with the total myocardial mass or the thinning of the compacted myocardium, e.g. r = 0.595 between GLS and the non-compacted mass (p < 0.001). In conclusion, CMR deformation indices are reduced in patients with LVNC especially in affected midventricular and apical slices. The impairment of all strain and twist parameters correlates well with the extent of non-compacted myocardium.
Role of indoleamine 2,3-dioxygenase in testicular immune-privilege
Authors: Gualdoni Gisela S. , Jacobo Patricia V. , Sobarzo Cristian M. , Pérez Cecilia V. , Matzkin María E. , Höcht Christian , Frungieri Mónica B. , Hill Marcelo , Anegon Ignacio , Lustig Livia , Guazzone Vanesa A.
Published: November 2019

Male meiotic germ cell including the spermatozoa represent a great challenge to the immune system, as they appear long after the establishment of normal immune tolerance mechanisms. The capacity of the testes to tolerate autoantigenic germ cells as well as survival of allogeneic organ engrafted in the testicular interstitium have led to consider the testis an immunologically privileged site. Disruption of this immune privilege following trauma, tumor, or autoimmune orchitis often results in male infertility. Strong evidence indicates that indoleamine 2,3-dioxygenase (IDO) has been implicated in fetal and allograft tolerance, tumor immune resistance, and regulation of autoimmune diseases. IDO and tryptophan 2,3-dioxygenase (TDO) catalyze the same rate-limiting step of tryptophan metabolism along a common pathway, which leads to tryptophan starvation and generation of catabolites collectively known as kynurenines. However, the relevance of tryptophan metabolism in testis pathophysiology has not yet been explored. Here we assessed thein vivorole of IDO/TDO in experimental autoimmune orchitis (EAO), a model of autoimmune testicular inflammation and immunologically impaired spermatogenesis. EAO was induced in adult Wistar rats with testicular homogenate and adjuvants. Control (C) rats injected with saline and adjuvants and normal untreated rats (N) were also studied. mRNA expression of IDO decreased in whole testes and in isolated Sertoli cells during EAO. TDO and IDO localization and level of expression in the testis were analyzed by immunostaining and Western blot. TDO is expressed in granulomas from EAO rats, and similar protein levels were observed in N, C, and EAO groups. IDO was detected in mononuclear and endothelial cells and reduced IDO expression was detected in EAO group compared to N and C rats. This phenomenon was concomitant with a significant reduction of IDO activity in EAO testis measured by tryptophan and kynurenine concentrations (HPLC). Finally,in vivoinhibition of IDO with 1-methyl-tryptophan increased severity of the disease, demonstrating down regulation of IDO-based tolerance when testicular immune regulation was disrupted. We present evidence that an IDO-based mechanism is involved in testicular immune privilege.
Therapeutic effects of methylphenidate for attention-deficit/hyperactivity disorder in children with borderline intellectual functioning or intellectual disability: A systematic review and meta-analysis
Authors: Sun Cheuk-Kwan , Tseng Ping-Tao , Wu Ching-Kuan , Li Dian-Jeng , Chen Tien-Yu , Stubbs Brendon , Carvalho Andre F , Chen Yen-Wen , Lin Pao-Yen , Cheng Yu-Shian , Wu Ming-Kung
Published: November 2019

Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with intellectual disability in children, and may further compromise learning. Methylphenidate is a first-line treatment for ADHD, however no previous meta-analysis has evaluated its overall efficacy for ADHD in children with comorbid intellectual disability (ID) or borderline intellectual functioning. The PubMed/MEDLINE, Cochrane CENTRAL and ScienceDirect databases were systematically searched from inception through 2018/7/15 for clinical studies that investigated the effects of methylphenidate in children with ADHD and ID. A random-effects model meta-analysis was used for data synthesis. Eight studies (average Jadad score = 2.5) enrolling 242 participants receiving methylphenidate and 181 participants receiving placebo were included. The meta-analysis showed that methylphenidate led to a significant improvement in ADHD symptoms relative to placebo (Hedges’ g = 0.878, p < 0.001). Meta-regression analysis pointed to an association between the dose of methylphenidate and overall improvement in ADHD severity (slope = 1.334, p < 0.001). Finally, there was no significant difference in drop-out rate [odds ratio (OR) = 1.679, p = 0.260] or rate of treatment discontinuation due to adverse events (OR = 4.815, p = 0.053) between subjects receiving methylphenidate and those taking placebos. Our study suggests that methylphenidate retains its efficacy in children with ADHD and borderline intellectual functioning or ID.
Tradeoffs in the value of biodiversity feature and cost data in conservation prioritization
Authors: Rodewald Amanda D. , Strimas-Mackey Matt , Schuster Richard , Arcese Peter
Published: November 2019

Decision-support tools are commonly used to maximize return on investments (ROI) in conservation. We evaluated how the relative value of information on biodiversity features and land cost varied with data structure and variability, attributes of focal species and conservation targets, and habitat suitability thresholds for contrasting bird communities in the Pacific Northwest of North America. Specifically, we used spatial distribution maps for 20 bird species, land values, and an integer linear programming model to prioritize land units (1 km2) that met conservation targets at the lowest estimated cost (hereafter ‘efficiency’). Across scenarios, the relative value of biodiversity data increased with conservation targets, as higher thresholds for suitable habitat were applied, and when focal species occurred disproportionately on land of high assessed value. Incorporating land cost generally improved planning efficiency, but at diminishing rates as spatial variance in biodiversity features relative to land cost increased. Our results offer a precise, empirical demonstration of how spatially-optimized planning solutions are influenced by spatial variation in underlying feature layers. We also provide guidance to planners seeking to maximize efficiency in data acquisition and resolve potential trade-offs when setting targets and thresholds in financially-constrained, spatial planning efforts aimed at maximizing ROI in biodiversity conservation.
Analysis of thermochemical energy storage in an elemental configuration
Authors: Malley-Ernewein Alexandre , Lorente Sylvie
Published: November 2019

Here we show theoretically that the design of a thermochemical energy storage system for fast response and high thermal power can be predicted in accord with the constructal law of design. In this fundamental configuration, the walls of the elemental cylinder are impregnated with salt, while humid air is blown through the tube. Cases with constant salt volume or constant fluid volume or both are considered. It is shown that the best design in each case meets the equipartition of imperfections principle. The predictions are confirmed by full numerical experiments, allowing to consider various shape ratios and study their impact on the overall performance.
Isotope effects in self-organization of internal transport barrier and concomitant edge confinement degradation in steady-state LHD plasmas
Authors: Kobayashi T. , Takahashi H. , Nagaoka K. , Sasaki M. , Nakata M. , Yokoyama M. , Seki R. , Yoshinuma M. , Ida K.
Published: November 2019

The isotope effect, which has been a long-standing mystery in the turbulent magnetically confined plasmas, is the phenomena that the plasma generated with heavier hydrogen isotope show a mitigated transport. This is on the contrary to what is predicted with the simple scaling theory, in which the heavier ions easily diffuse because of its larger gyro-radius. Thanks to the newly developed analysis method and a comprehensive parameter scan experiment in the steady-state plasmas in the Large Helical Device (LHD), the isotope effect was clearly observed in the self-organized internal transport barrier (ITB) structure for the first time. Comparing the ITB intensity in deuterium (D) and hydrogen (H) plasmas, two distinct hydrogen isotope effects are found: stronger ITB is formed in D plasmas and a significant edge confinement degradation accompanied by the ITB formation emerges in H plasmas. This observation sheds light on a new aspect of the turbulent plasmas regarding how the basic properties of the fluid material affect the turbulent structure formation in the open-system.
The role of cardiac transcription factor NKX2-5 in regulating the human cardiac miRNAome
Authors: Arasaratnam Deevina , Bell Katrina M. , Sim Choon Boon , Koutsis Kathy , Anderson David J. , Qian Elizabeth L. , Stanley Edouard G. , Elefanty Andrew G. , Cheung Michael M. , Oshlack Alicia , White Anthony J. , Abi Khalil Charbel , Hudson James E. , Porrello Enzo R. , Elliott David A.
Published: November 2019

MicroRNAs (miRNAs) are translational regulatory molecules with recognised roles in heart development and disease. Therefore, it is important to define the human miRNA expression profile in cardiac progenitors and early-differentiated cardiomyocytes and to determine whether critical cardiac transcription factors such as NKX2-5 regulate miRNA expression. We used an NKX2-5eGFP/w reporter line to isolate both cardiac committed mesoderm and cardiomyocytes. We identified 11 miRNAs that were differentially expressed in NKX2-5 -expressing cardiac mesoderm compared to non-cardiac mesoderm. Subsequent profiling revealed that the canonical myogenic miRNAs including MIR1-1, MIR133A1 and MIR208A were enriched in cardiomyocytes. Strikingly, deletion of NKX2-5 did not result in gross changes in the cardiac miRNA profile, either at committed mesoderm or cardiomyocyte stages. Thus, in early human cardiomyocyte commitment and differentiation, the cardiac myogenic miRNA program is predominantly regulated independently of the highly conserved NKX2-5 -dependant gene regulatory network.
The effect of livestock on the physiological condition of roe deer (Capreolus capreolus) is modulated by habitat quality
Authors: Horcajada-Sánchez Fernando , Escribano-Ávila Gema , Lara-Romero Carlos , Virgós Emilio , Barja Isabel
Published: November 2019

Free-range livestock grazing is a widespread human activity that not only modifies natural vegetation but also leads to interactions with wild ungulates. Most commonly, the interactions between cattle and wild ungulates have been studied with a focus on competition for high-quality forage. However, other mechanisms, such as the risk of parasite infection, might better describe this interaction. We aim to determine whether livestock affect roe deer (Capreolus capreolusLinnaeus, 1758) by reducing habitat quality and increasing the probability of infection by shared parasites. We measured noninvasive fecal cortisol metabolites as an indicator of habitat quality as well as the lung nematode larvae burden from theDictyocaulusgenus. A higherDictyocauluslarvae load was found in the presence of livestock in pines, and feces collected in winter had a higher parasite load than feces collected in autumn. Additionally, fecal cortisol metabolite levels in the roe deer were affected by the interaction between habitat quality and livestock presence and were higher in the poorest habitat and when living in sympatry with cattle. Our results suggest that physiological stress responses in roe deer were mediated by the habitat type and the presence of competitors. The long-term implications of altered physiological responses such as those demonstrated here should be considered in management strategies for deer.
The Protein Arginine Methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells
Authors: Favia Annarita , Salvatori Luisa , Nanni Simona , Iwamoto-Stohl Lisa K. , Valente Sergio , Mai Antonello , Scagnoli Fiorella , Fontanella Rosaria Anna , Totta Pierangela , Nasi Sergio , Illi Barbara
Published: November 2019

Protein Arginine (R) methylation is the most common post-translational methylation in mammalian cells. Protein Arginine Methyltransferases (PRMT) 1 and 5 dimethylate their substrates on R residues, asymmetrically and symmetrically, respectively. They are ubiquitously expressed and play fundamental roles in tumour malignancies, including glioblastoma multiforme (GBM) which presents largely deregulated Myc activity. Previously, we demonstrated that PRMT5 associates with Myc in GBM cells, modulating, at least in part, its transcriptional properties. Here we show that Myc/PRMT5 protein complex includes PRMT1, in both HEK293T and glioblastoma stem cells (GSCs). We demonstrate that Myc is both asymmetrically and symmetrically dimethylated by PRMT1 and PRMT5, respectively, and that these modifications differentially regulate its stability. Moreover, we show that the ratio between symmetrically and asymmetrically dimethylated Myc changes in GSCs grown in stem versus differentiating conditions. Finally, both PRMT1 and PRMT5 activity modulate Myc binding at its specific target promoters. To our knowledge, this is the first work reporting R asymmetrical and symmetrical dimethylation as novel Myc post-translational modifications, with different functional properties. This opens a completely unexplored field of investigation in Myc biology and suggests symmetrically dimethylated Myc species as novel diagnostic and prognostic markers and druggable therapeutic targets for GBM.
Age-aware constitutive materials model for a 3D printed polymeric foam
Authors: Maiti A. , Small W. , Lewicki J. P. , Chinn S. C. , Wilson T. S. , Saab A. P.
Published: November 2019

Traditional open or closed-cell stochastic elastomeric foams have wide-ranging applications in numerous industries: from thermal insulation, shock absorbing/gap-filling support cushions, packaging, to light-weight structural and positional components. Recent developments in 3D printing technologies by direct ink-write have opened the possibility of replacing stochastic foam parts by more controlled printed micro-structures with superior stress-distribution and longer functional life. For successful deployment as mechanical support or structural components, it is crucial to characterize the response of such printed materials to long-term external loads in terms of stress-strain behavior evolution and in terms of irreversible structural and load-bearing capacity changes over time. To this end, here we report a thermal-age-aware constitutive model for a 3D printed close-packed foam structure under compression. The model is based on the Ogden hyperfoam strain-energy functional within the framework of Tobolsky two-network scheme. It accurately describes experimentally measured stress-strain response, compression set, and load retention for various aging times and temperatures. Through the technique of time-temperature-superposition the model enables the prediction of long-term changes along with the quantification of uncertainty stemming from sample-to-sample variation and measurement noise. All aging parameters appear to possess the same Arrhenius activation barrier, which suggests a single dominant aging mechanism at the molecular/network level.
Chemical characterization of pterosaur melanin challenges color inferences in extinct animals
Authors: Pinheiro Felipe L. , Prado Gustavo , Ito Shosuke , Simon John D. , Wakamatsu Kazumasa , Anelli Luiz E. , Andrade José A. F. , Glass Keely
Published: November 2019

Melanosomes (melanin-bearing organelles) are common in the fossil record occurring as dense packs of globular microbodies. The organic component comprising the melanosome, melanin, is often preserved in fossils, allowing identification of the chemical nature of the constituent pigment. In present-day vertebrates, melanosome morphology correlates with their pigment content in selected melanin-containing structures, and this interdependency is employed in the color reconstruction of extinct animals. The lack of analyses integrating the morphology of fossil melanosomes with the chemical identification of pigments, however, makes these inferences tentative. Here, we chemically characterize the melanin content of the soft tissue headcrest of the pterosaur Tupandactylus imperator by alkaline hydrogen peroxide oxidation followed by high-performance liquid chromatography. Our results demonstrate the unequivocal presence of eumelanin in T. imperator headcrest. Scanning electron microscopy followed by statistical analyses, however, reveal that preserved melanosomes containing eumelanin are undistinguishable to pheomelanin-bearing organelles of extant vertebrates. Based on these new findings, straightforward color inferences based on melanosome morphology may not be valid for all fossil vertebrates, and color reconstructions based on ultrastructure alone should be regarded with caution.
Intra- and extracellular β-amyloid overexpression via adeno-associated virus-mediated gene transfer impairs memory and synaptic plasticity in the hippocampus
Authors: Forner Stefania , Martini Alessandra C. , Prieto G. Aleph , Dang Cindy T. , Rodriguez-Ortiz Carlos J. , Reyes-Ruiz Jorge Mauricio , Trujillo-Estrada Laura , da Cunha Celia , Andrews Elizabeth J. , Phan Jimmy , Vu Ha Jordan , Chang Allissa V. Z. D. , Levites Yona , Cruz Pedro E. , Ager Rahasson , Medeiros Rodrigo , Kitazawa Masashi , Glabe Charles G. , Cotman Carl W. , Golde Todd , Baglietto-Vargas David , LaFerla Frank M.
Published: November 2019

Alzheimer’s disease (AD), the most common age-related neurodegenerative disorder, is currently conceptualized as a disease of synaptic failure. Synaptic impairments are robust within the AD brain and better correlate with dementia severity when compared with other pathological features of the disease. Nevertheless, the series of events that promote synaptic failure still remain under debate, as potential triggers such as β-amyloid (Aβ) can vary in size, configuration and cellular location, challenging data interpretation in causation studies. Here we present data obtained using adeno-associated viral (AAV) constructs that drive the expression of oligomeric Aβ either intra or extracellularly. We observed that expression of Aβ in both cellular compartments affect learning and memory, reduce the number of synapses and the expression of synaptic-related proteins, and disrupt chemical long-term potentiation (cLTP). Together, these findings indicate that during the progression AD the early accumulation of Aβ inside neurons is sufficient to promote morphological and functional cellular toxicity, a phenomenon that can be exacerbated by the buildup of Aβ in the brain parenchyma. Moreover, our AAV constructs represent a valuable tool in the investigation of the pathological properties of Aβ oligomers both in vivo and in vitro.
Childhood growth hormone treatment in women with Turner syndrome - benefits and adverse effects
Authors: Irzyniec Tomasz , Jeż Wacław , Lepska Katarzyna , Maciejewska-Paszek Izabela , Frelich Jakub
Published: November 2019

Turner syndrome (TS) is characterized by the partial or complete loss of one sex chromosome and results in growth failure, gonadal insufficiency and cardiac anomalies. Treatment with growth hormone (GH) during childhood has indisputable benefits when taking into account the low stature of TS women. Medical records and biochemical findings of 33 TS women treated with GH in childhood (GH+) were compared to those of 124 TS women who did not receive GH (GH−). It seems that the GH-treated group might have had a more severe initial phenotype than the untreated group, as evidenced by higher FSH, more feeding issues in infancy, more lymphedema cases and urinary system malformations. GH+ women were significantly taller and had a better lipid profile and lower prevalence of arterial hypertension than GH− . However, they also had lower thrombocyte counts, a greater prevalence of retrognathism and nail anomalies, especially when the GH treatment was delayed. Long-term GH use was not as effective for growth as GH treatment during the initial period and seemed to have resulted in elevated creatinine levels. GH treatment in childhood has benefits in adulthood; however, adverse effects may occur, especially in individuals with treatment that is delayed or is too long.