bluuebunny/crossref_metadata_2025 huggingface dataset:
N‐Linked Glycans in the Variable Domain of IgG Anti–Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis
Authors: Hafkenscheid Lise , de Moel Emma , Smolik Irene , Tanner Stacey , Meng Xiaobo , Jansen Bas C. , Bondt Albert , Wuhrer Manfred , Huizinga Tom W. J. , Toes Rene E. M. , El‐Gabalawy Hani , Scherer Hans U.
Published: May 2019

Objective

Anti–citrullinated protein antibodies (ACPAs) are disease‐specific biomarkers in rheumatoid arthritis (RA). More than 90% of IgG ACPAs harbor N‐linked glycans in the antibody variable (V) domain. The corresponding N‐glycosylation sites in ACPA V‐region sequences result from somatic hypermutation, a T cell–dependent process. As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.

Methods

We analyzed 2 independent sets of serum samples obtained from 126 ACPA‐positive first‐degree relatives (FDRs) of RA patients. Both sets originated from an Indigenous North American population and comprised cross‐sectional and longitudinal samples of individuals who did or did not develop inflammatory arthritis. Serum IgG ACPAs were affinity‐purified and subjected to ultra high‐performance liquid chromatography–based glycan analysis.

Results

In both data sets, FDR‐derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients. Notably, FDRs who later developed RA showed extensive V‐domain glycosylation before the onset of arthritis. Moreover, IgG ACPA V‐domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46–25.2]; P = 0.013).

Conclusion

Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients. The presence of this feature substantially increases the risk of RA development. Based on these findings, we propose that glycosylation of the IgG ACPA V domain represents a predictive marker for RA development in ACPA‐positive individuals and may serve to better target prevention measures.
GMPP tracking based on model reference LPV control for a PV system with buck converter modelled on bond graph
Authors: Galindo Orozco René , Villa Villaseñor Noé
Published: May 2019

A PhotoVoltaic (PV) system with a Linear Parametric Varying (LPV) average model of a buck converter modelled by bond graph methodology, is considered. It is assumed that the voltage generated by the PV panel is a smooth function of time under changes in atmospheric conditions. A model reference is proposed representing the PV system with buck converter operating at the Global Maximum Power Point (GMPP). An LPV control is designed, and an algorithm is proposed in a model reference tracking control configuration assuring that the PV system with buck converter tracks the proposed model reference and hence guaranteeing that this system operates at the GMPP. The proposed algorithm changes the voltage reference based on the power measurement of the PV system assuring that this reference represents the GMPP under shading conditions. The LPV control is designed for an average model of the buck converter solving a feasibility problem based on linear matrix inequalities that assure quadratic stability and minimize a quadratic criterion. The feedback system is tested under shading conditions, and its performance is compared with a standard Perturb and Observe method and with an ideal algorithm based on the irradiance measurement in each section of the PV system.
Aberrant brain network topology in fronto‐limbic circuitry differentiates euthymic bipolar disorder from recurrent major depressive disorder
Authors: Dvorak Jannis , Hilke Marietheres , Trettin Marco , Wenzler Sofia , Hagen Marleen , Ghirmai Naddy , Müller Maximilian , Kraft Dominik , Reif Andreas , Oertel Viola
Published: May 2019

Introduction

Previous studies have established graph theoretical analysis of functional network connectivity (FNC) as a potential tool to detect neurobiological underpinnings of psychiatric disorders. Despite the promising outcomes in studies that examined FNC aberrancies in bipolar disorder (BD) and major depressive disorder (MDD), there is still a lack of research comparing both mood disorders, especially in a nondepressed state. In this study, we used graph theoretical network analysis to compare brain network properties of euthymic BD, euthymic MDD and healthy controls (HC) to evaluate whether these groups showed distinct features in FNC.

Methods

We collected resting‐state functional magnetic resonance imaging (fMRI) data from 20 BD patients, 15 patients with recurrent MDD as well as 30 age‐ and gender‐matched HC. Graph theoretical analyses were then applied to investigate functional brain networks on a global and regional network level.

Results

Global network analysis revealed a significantly higher mean global clustering coefficient in BD compared to HC. We further detected frontal, temporal and subcortical nodes in emotion regulation areas such as the limbic system and associated regions exhibiting significant differences in network integration and segregation in BD compared to MDD patients and HC. Participants with MDD and HC only differed in frontal and insular network centrality.

Conclusion

In conclusion, our findings indicate that a significantly altered brain network topology in the limbic system might be a trait marker specific to BD. Brain network analysis in these regions may therefore be used to differentiate euthymic BD not only from HC but also from patients with MDD.
Interethnic differences in pancreatic cancer incidence and risk factors: The Multiethnic Cohort
Authors: Huang Brian Z. , Stram Daniel O. , Le Marchand Loic , Haiman Christopher A. , Wilkens Lynne R. , Pandol Stephen J. , Zhang Zuo‐Feng , Monroe Kristine R. , Setiawan Veronica Wendy
Published: May 2019

While disparity in pancreatic cancer incidence between blacks and whites has been observed, few studies have examined disparity in other ethnic minorities. We evaluated variations in pancreatic cancer incidence and assessed the extent to which known risk factors account for differences in pancreatic cancer risk among African Americans, Native Hawaiians, Japanese Americans, Latino Americans, and European Americans in the Multiethnic Cohort Study. Risk factor data were obtained from the baseline questionnaire. Cox regression was used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for pancreatic cancer associated with risk factors and ethnicity. During an average 16.9‐year follow‐up, 1,532 incident pancreatic cancer cases were identified among 184,559 at‐risk participants. Family history of pancreatic cancer (RR 1.97, 95% CI 1.50‐2.58), diabetes (RR 1.32, 95% CI 1.14‐1.54), body mass index ≥30 kg/m2 (RR 1.25, 95% CI 1.08‐1.46), current smoking (<20 pack‐years RR 1.43, 95% CI 1.19‐1.73; ≥20 pack‐years RR 1.76, 95% CI 1.46‐2.12), and red meat intake (RR 1.17, 95% CI 1.00‐1.36) were associated with pancreatic cancer. After adjustment for these risk factors, Native Hawaiians (RR 1.60, 95% CI 1.30‐1.98), Japanese Americans (RR 1.33, 95% CI 1.15‐1.54), and African Americans (RR 1.20, 95% CI 1.01‐1.42), but not Latino Americans (RR 0.90, 95% CI 0.76‐1.07), had a higher risk of pancreatic cancer compared to European Americans. Interethnic differences in pancreatic cancer risk are not fully explained by differences in the distribution of known risk factors. The greater risks in Native Hawaiians and Japanese Americans are new findings and elucidating the causes of these high rates may improve our understanding and prevention of pancreatic cancer.
The role of microRNAs in the involvement of vascular smooth muscle cells in the development of atherosclerosis
Authors: Li Linqing , Li Yongjun , Tang Chengchun
Published: May 2019

MicroRNAs (miRNAs) are a class of nonprotein‐encoding RNAs of ~22 nucleotides in length that bind to or complement each other with a target gene messenger RNA (mRNA) to promote mRNA degradation or inhibit translation of the target mRNA. The protein required [such as Toll‐like receptor (TLR) proteins] is controlled at an optimal level. By affecting protein translation, miRNAs have become powerful regulators of biological processes, including development, differentiation, cell proliferation, and apoptosis. MiRNAs are involved in the regulation of proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs), thereby affecting the formation of atherosclerosis (AS). In recent years, the role and mechanism of miRNAs involved in AS development in VSMCs have been studied extensively. In the current study, the results and progress in miRNA research are reviewed.
Comparison of drug eluting versus bare metal stents for pulmonary vein stenosis in childhood
Authors: Khan Asra , Qureshi Athar M. , Justino Henri
Published: May 2019

Objective

Comparison of outcomes using bare metal (BMS) and drug‐eluting (DES) stents in pulmonary vein stenosis (PVS).

Background

PVS is a serious condition with frequent restenosis after surgical and percutaneous interventions. After experiencing encouraging results with DES, we sought to compare outcomes of BMS and DES in native and post‐surgical PVS.

Methods and Results

A retrospective review of all patients who underwent stent implantation between 08/93 and 11/17 for PVS at Texas Children's Hospital was performed. BMS were used to treat 58 lesions in 37 patients and 105 DES used to treat 105 lesions in 41 patients. Mean age at first stent implant was 2.9 ± 3.5 years in BMS and 16.2 ± 18.8 months in DES group. Of those with follow‐up catheterization, mean lumen loss rate from stent implant to first follow‐up catheterization was 0.85 ± 1.47 mm/month over 6.4 ± 6.4 months in the BMS group (n = 44 lesions) compared to 0.16 ± 0.31 mm/month over 6.8 ± 7.4 months in the DES group (n = 86 lesions), p < .01. Follow‐up for the BMS group was 14 months (6 days–22.3 years), with 13 mortalities, eight lesions were re‐stented and six complete occlusions were noted. Follow‐up for DES group (including four cross‐overs) was 17.5 months (3 days‐9 years), with 10 mortalities, seven lesions were re‐stented, 11 had complete occlusion, 20 new adjacent lesions in the same vessel underwent stenting and 12 stents were intentionally fractured.

Conclusion

DES have significantly lowered lumen loss rate when compared to BMS at medium term follow‐up and can be fractured to enable larger diameters. Availability of larger diameter DES would be ideal.
Light chain lambda myeloma with fatal AL cardiac amyloidosis in a 21‐year‐old patient: A case report and review
Authors: Camus Vincent , Dubois Sydney , Thiébaut Pierre‐Alain , Lepretre Stéphane , Lenain Pascal , Picquenot Jean‐Michel , Veresezan Elena‐Liana , François Arnaud , Penther Dominique , Bauer Fabrice , Jaccard Arnaud , Jardin Fabrice
Published: May 2019

Abstract

Multi‐organ AL amyloidosis is a therapeutic challenge because of light chain deposits severely damaging the function of concerned organs. Cardiac involvement, which leads to concentric hypertrophy of both ventricles, is particularly severe and leads to poor prognosis regardless of combination chemotherapy. This case pinpoints the relevance of combining clinical, histological, and echocardiographic information in the management of this complex and life‐threatening disease.
Mesoporous Aluminosilicate Nanofibers with a Low Si/Al Ratio as Acidic Catalyst for Hydrodeoxygenation of Phenol
Authors: Haynes Tommy , D'hondt Thibaut , Morritt Alexander L. , Khimyak Yaroslav Z. , Desmecht Didier , Dubois Vincent , Hermans Sophie
Published: May 2019

Mesoporous aluminosilicate nanofibers (mASNF) were prepared using hard and soft dual templates approach. The mesoporous material was fully characterized and its acidic nature was confirmed by FTIR spectroscopy of pyridine adsorption and 27Al/29Si solid state NMR. Thanks to the incorporated aluminum atoms, the acidic material showed high hydrothermal stability which is an essential property for biomass conversion applications. The catalytic performance of Pd supported on mASNF for hydrodeoxygenation (HDO) of lignin model compound was also investigated. A complete conversion and a high selectivity towards cyclohexane (up to 95 %) starting from phenol were achieved with this bifunctional catalyst. In comparison, no cyclohexane has been produced with a non‐acidic material which underlines the importance of acidic sites in HDO process selectivity control. Moreover, the catalyst can be recycled without losing its initial structure.
Magnetization Slow Dynamics in Ferrocenium Complexes
Authors: Ding Mei , Hickey Anne K. , Pink Maren , Telser Joshua , Tierney David L. , Amoza Martin , Rouzières Mathieu , Ozumerzifon Tarik J. , Hoffert Wesley A. , Shores Matthew P. , Ruiz Eliseo , Clérac Rodolphe , Smith Jeremy M.
Published: May 2019

The single‐molecule magnet (SMM) properties of a series of ferrocenium complexes, [Fe(η5‐C5R5)2]+ (R=Me, Bn), are reported. In the presence of an applied dc field, the slow dynamics of the magnetization in [Fe(η5‐C5Me5)2]BArF are revealed. Multireference quantum mechanical calculations show a large energy difference between the ground and first excited states, excluding the commonly invoked, thermally activated (Orbach‐like) mechanism of relaxation. In contrast, a detailed analysis of the relaxation time highlights that both direct and Raman processes are responsible for the SMM properties. Similarly, the bulky ferrocenium complexes, [Fe(η5‐C5Bn5)2]BF4 and [Fe(η5‐C5Bn5)2]PF6, also exhibit magnetization slow dynamics, however an additional relaxation process is clearly detected for these analogous systems.
Manganese‐Mediated Formic Acid Dehydrogenation
Authors: Anderson Nickolas H. , Boncella James , Tondreau Aaron M.
Published: May 2019

A robust and rapid manganese formic acid (FA) dehydrogenation catalyst is reported. The manganese is supported by the recently developed, hybrid backbone chelate ligand tBuPNNOP (tBuPNNOP=2,6‐(di‐tert‐butylphosphinito)(di‐tert‐butylphosphinamine)pyridine) (1) and the catalyst is readily prepared with MnBrCO5 to form [(tBuPNNOP)Mn(CO)2][Br] (2). Dehydrohalogenation of 2 generated the neutral five coordinate complex (tBuPNNOP)Mn(CO)2 (3). Dehydrogenation of FA by 2 and 3 was found to be highly efficient, exhibiting turnover frequencies (TOFs) exceeding 8500 h−1, rivaling many noble metal systems. The parent chelate, tBuPONOP (tBuPONOP=2,6‐bis(di‐tert‐butylphosphinito)pyridine) or tBuPNNNP (tBuPNNNP=2,6‐bis (di‐tert‐butylphosphinamine)pyridine), coordination complexes of Mn were synthesized, respectively affording [(tBuPONOP)Mn(CO)2][Br] (4) and [(tBuPNNNP)Mn(CO)2][Br] (5). FA dehydrogenation with the hybrid‐ligand supported 2 exhibits superior catalysis to 4 and 5.
N‐Substituted Benzene‐1‐Urea‐3,5‐Biscarboxamide (BUBA): Easily Accessible C2‐Symmetric Monomers for the Construction of Reversible and Chirally Amplified Helical Assemblies
Authors: Li Yan , Dubreucq Ludovic , Alvarenga Bruno G. , Raynal Matthieu , Bouteiller Laurent
Published: May 2019

Non‐C3‐symmetric supramolecular helices are gaining interest for the design of hierarchical assemblies, for the compartmentalisation or the self‐assembly of polymer chains and for application in asymmetric catalysis. Herein, N‐substituted benzene‐1‐urea‐3,5‐biscarboxamide (BUBA) monomers, which consist of one urea and two carbon‐connected amide functions linked to an aromatic ring, are introduced as an easily accessible class of C2‐symmetric supramolecular synthons. In apolar solvents, BUBA monomers assemble into long helical assemblies by means of hydrogen‐bonding and aromatic interactions, as assessed by several analytical techniques. To probe the influence of the urea function, BUBA and related benzene‐1,3,5‐tricarboxamide (BTA) helical polymers have been compared, in terms of their thermodynamics of formation, stability, reversibility and chiral amplification properties. Similar to BTA, BUBA monomers form long helices reversibly through a highly cooperative mechanism and the helicity of their assemblies is governed by chiral amplification effects. However, precise quantification of their properties reveals that BUBA monomers assemble in a more cooperative manner. Also, chiral amplification operates to a higher extent in BUBA helices, as probed by both sergeants‐and‐soldiers and majority‐rules experiments. Compatibility between urea and amide functions also allows the formation of co‐assemblies that incorporate both BUBA and BTA monomers. Importantly, a small amount of chiral BUBA monomers in these co‐assemblies is sufficient to obtain single‐handed helices; thus paving the way towards the development of functional supramolecular helices.
Bioinspired Metal‐Free Formal Decarbonylation of α‐Branched Aliphatic Aldehydes at Ambient Temperature
Authors: Richter Sven C. , Oestreich Martin
Published: May 2019

A sequence of a Baeyer–Villiger oxidation and a Lewis acid‐promoted reduction of the resulting formate with Et3SiH enabled the metal‐free formal decarbonylation of tertiary and secondary aliphatic aldehydes. The new methodology mimics the biosynthetic decarbonylation pathway through oxidative C−C bond cleavage rather than the C(O)−H bond activation known from conventional Tsuji–Wilkinson‐type reactions. The substrate scope is complementary to existing transition‐metal‐catalyzed protocols.
The Effect of Thermal Treatment on the Hydrogen‐Storage Properties of PIM‐1
Authors: Ramimoghadam Donya , Boyd Sue E. , Brown Christopher L. , Mac A. Gray Evan , Webb C. J.
Published: May 2019

There has been recent interest in polymers of intrinsic microporosity (PIMs) for solid‐state hydrogen‐storage materials; however, the gas‐sorption properties and conditions for hydrogen uptake are relatively unexplored. PIM‐1 has been synthesised using the condensation reaction between 3,3,3,3‐tetramethyl‐1,1‐spirobisindane‐5,5,6,6‐tetraol and 2,3,5,6‐tetrafluorophthalonitrile as precursors. The synthesised PIM‐1 was annealed at different temperatures for varying times and then characterised for hydrogen uptake at both ambient and cryogenic temperatures. The excess hydrogen PCT isotherms have been measured to high pressure (320 bar) for the first time and the effect of different annealing conditions on the hydrogen capacity is reported.
Shared Genetic Risk Factors Across Carbamazepine‐Induced Hypersensitivity Reactions
Authors: Nicoletti Paola , Barrett Sarah , McEvoy Laurence , Daly Ann K. , Aithal Guruprasad , Lucena M. Isabel , Andrade Raul J. , Wadelius Mia , Hallberg Pär , Stephens Camilla , Bjornsson Einar S. , Friedmann Peter , Kainu Kati , Laitinen Tarja , Marson Anthony , Molokhia Mariam , Phillips Elizabeth , Pichler Werner , Romano Antonino , Shear Neil , Sills Graeme , Tanno Luciana K. , Swale Ashley , Floratos Aris , Shen Yufeng , Nelson Matthew R. , Watkins Paul B. , Daly Mark J. , Morris Andrew P. , Alfirevic Ana , Pirmohamed Munir
Published: May 2019

Carbamazepine (CBZ) causes life‐threating T‐cell‐mediated hypersensitivity reactions, including serious cutaneous adverse reactions (SCARs) and drug‐induced liver injury (CBZ‐DILI). In order to evaluate shared or phenotype‐specific genetic predisposing factors for CBZ hypersensitivity reactions, we performed a meta‐analysis of two genomewide association studies (GWAS) on a total of 43 well‐phenotyped Northern and Southern European CBZ‐SCAR cases and 10,701 population controls and a GWAS on 12 CBZ‐DILI cases and 8,438 ethnically matched population controls. HLA‐A*31:01 was identified as the strongest genetic predisposing factor for both CBZ‐SCAR (odds ratio (OR) = 8.0; 95% CI 4.10–15.80; P = 1.2 × 10−9) and CBZ‐DILI (OR = 7.3; 95% CI 2.47–23.67; P = 0.0004) in European populations. The association with HLA‐A*31:01 in patients with SCAR was mainly driven by hypersensitivity syndrome (OR = 12.9; P = 2.1 × 10−9) rather than by Stevens‐Johnson syndrome/toxic epidermal necrolysis cases, which showed an association with HLA‐B*57:01. We also identified a novel risk locus mapping to ALK only for CBZ‐SCAR cases, which needs replication in additional cohorts and functional evaluation.
Sustainable development and human resource management: A science mapping approach
Authors: Santana Monica , Lopez‐Cabrales Alvaro
Published: May 2019

This manuscript presents a systematic review of “sustainable human resource management” (HRM), highlighting its major themes and the evolution and tendencies observed in this field. It contributes to the development of this relatively new topic, offering a critical evaluation and identifying the highest impact research strands. The Web of Science database returned 111 documents spanning the period 1997–2018, and a conceptual science mapping analysis based on co‐word bibliographic networks was developed, using SciMAT as an analytical tool. The motor themes (well developed and important for the structure of the discipline) in the field of sustainable HRM are environmental management, socially responsible HRM, and turnover. Employee engagement is a specialised theme (well developed but less important for the structure of the research field), human resource practices is a basic or transversal theme (important for the discipline but not developed), and sustainable leadership and environmental performance are emerging themes (both weakly developed and marginal to the field).
Non‐Solvent Fractionation of Lignin Enhances Carbon Fiber Performance
Authors: Li Qiang , Li Mengjie , Lin Hao‐Sheng , Hu Cheng , Truong Phuc , Zhang Tan , Sue Hung‐Jue , Pu Yunqiao , Ragauskas Arthur J. , Yuan Joshua S.
Published: May 2019

Even though lignin carbon fiber has been sought after for several decades, the poor mechanical performance remains to be a major barrier for commercial applications. The low mechanical performance is attributed to the heterogeneity of lignin polymer. Recent advances in fractionation technologies showed the great potential to reduce lignin heterogeneity, but current fractionation methods often depend on costly chemicals and materials such as enzymes, organic solvents, membranes, and dialysis tubes. Here, a new non‐solvent strategy was developed to fractionate lignin by autohydrolysis. By using only water, lignin was efficiently fractionated into water‐soluble and ‐insoluble fractions. The latter fraction had increased molecular weight and uniformity and resulted in more β‐O‐4 interunitary linkages as analyzed by size‐exclusion chromatography and 2D heteronuclear single quantum coherence NMR spectroscopy, respectively. In particular, the water‐insoluble fraction significantly enhanced the mechanical performances of the resultant carbon fibers. Mechanistic study by differential scanning calorimetry (DSC) revealed that the miscibility of lignin with guest polyacrylonitrile molecules was improved with the reduced lignin heterogeneity. Crystallite analyses by XRD and Raman spectroscopy revealed that the crystallite size and content of the pre‐graphitic turbostratic carbon structure were increased. The fundamental understanding revealed how lignin fractionation could modify lignin chemical features to enhance the mechanical performance of resultant carbon fibers. The autohydrolysis fractionation thus represents a green, economic, and efficient methodology to process lignin waste and boost lignin carbon fiber quality, which could open new horizons for lignin valorization.
Preferential sampling for presence/absence data and for fusion of presence/absence data with presence‐only data
Authors: Gelfand Alan E. , Shirota Shinichiro
Published: May 2019

Presence/absence data and presence‐only data are the two customary sources for learning about species distributions over a region. We present an ambitious agenda with regard to the analysis of such data. We illuminate the fundamental modeling differences between the two types of data. Most simply, locations are considered to be fixed under presence/absence data; locations are random under presence‐only data. The definition of “probability of presence” is incompatible between the two. We are not comfortable with modeling strategies in the literature that ignore this incompatibility and that assume that presence/absence modeling can be induced from presence‐only specifications and, therefore, that fusion of presence‐only and presence/absence data sources is routine. While, in some cases, data collection may not support this, we propose that, since, in nature, presence/absence is seen at the point locations, presence/absence data should be modeled at point level. If so, we need to specify two surfaces. The first provides the probability of presence at any location in the region. The second provides a realization from this surface in the form of a binary map yielding the results of Bernoulli trials across all locations; this surface is only partially observed. On the other hand, presence‐only data should be modeled as a (partially observed) point pattern, arising from a random number of individuals seen at random locations, driven by specification of an intensity function. There is no notion of Bernoulli trials; events are associated with areas. We further suggest that, with just presence/absence data, preferential sampling of locations may arise. Accounting for this, using a shared process perspective, can improve our estimated presence/absence surface as well as prediction of presence. We further propose that preferential sampling can enable a probabilistically coherent fusion of the two data types. We illustrate with two real data sets, one presence/absence, one presence‐only, for invasive species presence in New England in the United States. We demonstrate that potential bias in sampling locations can affect inference with regard to presence/absence and show that inference can be improved with preferential sampling ideas. We also provide a probabilistically coherent fusion of the two data sets again with the goal of improving inference for presence/absence. The importance of our work is to encourage more careful modeling when studying species distributions. Ignoring incompatibility between data types and adopting nongenerative modeling specifications results in invalid inference; the quantitative ecological community should benefit from this recognition.
Synthesis and Electrochemical Investigations of [Ru(η5‐Ferrocenyl‐Thiophene)(η5‐C5R5)]+ Sandwich Compounds
Authors: Speck J. Matthäus , Korb Marcus , Hildebrandt Alexander , Lang Heinrich
Published: May 2019

The synthesis of [Ru(η5‐2‐Fc‐3‐R3‐4‐R2‐5‐R1‐cC4S)(η5‐C5R5)]+[PF6]– (R = H, Me; R1–R3 = H; R1 = Me, R2 = R3 = H; R1–R3 = Me; R1 = Fc, R2 = R3 = OCH2CH2O; Fc = Fe(η5‐C5H4)(η5‐C5H5)) is reported with the aim of a better understanding of the influence of π‐thiophene‐bonded transition metal units on the thermodynamic stabilities and charge transfer interactions of the resulting compounds and their oxidized intermediates. Within the electrochemical studies, reversible one‐electron Fe‐based redox events were found for the mono‐Fc Ru species, whereby the Fc/Fc+ redox potential increases as the degree of methylation of the thiophene and the Ru‐cyclopentadienyl moiety decreases. For [Ru(η5‐2,5‐Fc2‐cC4H2S)(η5‐C5R5)]+[PF6]– a hindered 2nd Fc‐based electrode reaction was observed under “weak‐coordinating” conditions. Two separated Fc/Fc+ redox events were detected by the use of stronger solvating solvents or (smaller) anions. With regard to the non complexed 2,5‐Fc2 thiophenes, the thermodynamic stabilities of the appropriate mixed‐valent species decrease, when the thiophene is η5‐coordinated to [Ru(η5‐C5R5)]+. Contrary to the redox potential, the substitution of the [Ru(η5‐C5R5)]+ moiety does not have a major impact on the thermodynamic stabilities of the mixed‐valent species. The related decrease of electronic coupling between the Fc unit(s) via the thiophene in the corresponding oxidized states, could be verified during UV/Vis/NIR spectroelectrochemical studies.
Iodocyclization of Propargyl Alcohols: Highly Facile Approach to Hetero/Carbocyclic Iodides
Authors: Khan Tabassum , Yaragorla Srinivasarao
Published: May 2019

Iodocyclization of propargyl alcohols is an active area for the construction of hetero/carbocyclic iodides. Ambiphilic reactivity of propargyl alcohols made it more attractive to tune their reactivity towards the development of regioselective synthetic strategies. In general, iodocyclization reactions are atom and step economic, promoted by simple and readily available inexpensive electrophilic iodine reagents at ambient temperature. These compounds find potential applications in pharmaceutical and material sciences, because of the presence of a preinstalled reactive iodide functionality. Therefore, many researchers are actively involved in developing synthetic strategies towards iodocyclizations from propargyl alcohols for various applications. In this mini‐review, we emphasize the full list of synthetic endeavors made towards the “iodocyclization of propargyl alcohols, propargyl ethers and homopropargyl alcohols”.
Diastereoselective Synthesis of Spiro[2.3]hexanes from Methylenecyclopropane and Cyanoalkenes Catalyzed by a Tin‐Ate Complex
Authors: Suzuki Itaru , Shimazu Jun‐ya , Tsunoi Shinji , Shibata Ikuya
Published: May 2019

A diastereoselective synthesis of spiro[2.3]hexane catalyzed by Sn and Mg halides was developed from a combination of methylenecyclopropane and cyanoalkene bearing an ester group. The selectivity was affected by the size of the halogen in the catalyst and by an electron deficiency in the alkene. Once synthesized only with a Pd catalyst, the spirocarbocycle was easily transformed into cyclopentene under transition metal‐free conditions.
Direct Hydroheteroarylation of Ynamides with 2H‐Tetrazoles: Regio‐ and Stereoselective Synthesis of (Z)‐α‐Tetrazole Enamides
Authors: Zhu Jiekun , Wang Qingbo , Meng Xin , Zhao Changyin , Sun Xuejun , Tian Laijin , Cao Ziping
Published: May 2019

We herein report the direct reaction of ynamides with 2H‐tetrazoles under metal‐free conditions to provide a variety of functionalized (Z)‐α‐tetrazole enamide products in high yields, including the N‐2 and N‐1 adducts that are easily separated. The reaction proceeds via a key keteniminium ion intermediate, generated in situ from ynamides with acidic 2H‐tetrazoles, leading to the formation of C‐N bonds efficiently. The present reaction features simple experimental operations and mild reaction conditions, high chemo‐, regio‐, and stereoselectivities, and high reaction efficiencies. Without using any catalyst, the reaction protocol should facilitate the modification of tetrazole‐containing molecules for the discovery of new potentially bioactive compounds.
The Selective N‐Functionalization of Indoles via aza‐Michael Addition in the Ligand Sphere of a Chiral Nickel(II) Complex: Asymmetric Synthesis of (S)‐1H‐Indole‐Alanine Derivatives
Authors: Larionov Vladimir A. , Savel'yeva Tat'yana F. , Medvedev Michael G. , Stoletova Nadezhda V. , Smol'yakov Alexander F. , Gugkaeva Zalina T. , Cruchter Thomas , Maleev Victor I.
Published: May 2019

The selective addition of electrophilic C=C double bonds to the N–H bond of indoles is a challenging task due to the high nucleophilicity of indoles at their C3‐position. Herein, we report the successful selective intermolecular N‐functionalization of various indoles via aza‐Michael addition of C=C double bond of a dehydroalanine Schiff base, which takes place in the ligand sphere of a chiral NiII complex in the presence of sodium hydride. The resulting hydroaminated NiII complexes were isolated in 55–82 % yields with excellent diastereoselectivity (dr > 99:1) (8 examples). And the actual products of interest, namely (S)‐2‐amino‐3‐(1H‐indol‐1‐yl)propanoic acids, were subsequently released from the NiII complexes via aqueous HCl treatment of the NiII complexes and isolated with excellent enantioselectivity (> 99 % ee). The chiral auxiliary [(S)‐BPB = (S)‐2‐(N‐benzylprolyl)aminobenzophenone] and NiII ions can be easily recovered after the acidic complex cleavage step and reused for the synthesis of the starting NiII complex. Moreover, the indole′s preference for nucleophilic attack via its N1‐ over its C3‐position was rationalized by DFT calculations.
Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma
Authors: Gómez‐Tomás Álvaro , Pumarega José , Alguacil Juan , Amaral André F. S. , Malats Núria , Pallarès Natàlia , Gasull Magda , Porta Miquel ,   for the PANKRAS II Study Group
Published: May 2019

Trace elements are a possible risk factor for pancreatic ductal adenocarcinoma (PDAC). However, their role in the occurrence and persistence of KRAS mutations remains unstudied. There appear to be no studies analyzing biomarkers of trace elements and KRAS mutations in any human cancer. We aimed to determine whether patients with KRAS mutated and nonmutated tumors exhibit differences in concentrations of trace elements. Incident cases of PDAC were prospectively identified in five hospitals in Spain. KRAS mutational status was determined through polymerase chain reaction from tumor tissue. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Concentrations of trace elements were compared in 78 PDAC cases and 416 hospital‐based controls (case–control analyses), and between 17 KRAS wild‐type tumors and 61 KRAS mutated tumors (case–case analyses). Higher levels of iron, arsenic, and vanadium were associated with a statistically nonsignificant increased risk of a KRAS wild‐type PDAC (OR for higher tertile of arsenic = 3.37, 95% CI 0.98–11.57). Lower levels of nickel and manganese were associated with a statistically significant higher risk of a KRAS mutated PDAC (OR for manganese = 0.34, 95% CI 0.14–0.80). Higher levels of selenium appeared protective for both mutated and KRAS wild‐type PDAC. Higher levels of cadmium and lead were clear risk factors for both KRAS mutated and wild‐type cases. This is the first study analyzing biomarkers of trace elements and KRAS mutations in any human cancer. Concentrations of trace elements differed markedly between PDAC cases with and without mutations in codon 12 of the KRAS oncogene, thus suggesting a role for trace elements in pancreatic and perhaps other cancers with such mutations. Environ. Mol. Mutagen., 60:693–703, 2019. © 2019 Wiley Periodicals, Inc.
The influence of yeast level and fermentation temperature on Ochratoxin A decrement during bread making
Authors: Mozaffary Payman , Milani Jafar M. , Heshmati Ali
Published: May 2019

Ochratoxin A (OTA) occurrence in cereals is a permanent challenge in human health. In recent years, some studies have focused on the role of yeasts as adsorbing tools to eliminate OTA. The aim of the current research was to study the effects of different variables including Saccharomyces cerevisiae amount and the fermentation temperature on the reduction of OTA during bread baking. For this purpose, the OTA was spiked to the flour and then the bread was prepared. OTA levels in flour, dough, and bread were measured by the high‐performance liquid chromatography with fluorescence detector (HPLC‐FD). The results revealed that yeast level and fermentation temperature had a significant effect on OTA reduction. The increase of the amount of S. cerevisiae from 1% to 2% w/w and the fermentation temperature from 25ºC to 30ºC resulted in the increment of OTA reduction from 31.17% to 59.41%. During baking, OTA reduction was 19.21%. In general, the utilization of 2% w/w S. cerevisiae and the fermentation temperature of 35 ºC could reduce considerable amount of OTA in the wheat bread.
Thyroid disruption properties of three indoor dust chemicals tested in Silurana tropicalis tadpoles
Authors: Carlsson Gunnar , Pohl Johannes , Athanassiadis Ioannis , Norrgren Leif , Weiss Jana
Published: May 2019

Indoor dust contains a multitude of industrial chemicals, and ingestion of dust is considered an important exposure route to organic contaminants. Some of these contaminants have been shown to interfere with the thyroid system, which may result in significant consequences on public health. The amphibian metamorphosis is a thyroid hormone‐dependent process, which can be used as an in vivo model for studies on thyroid hormone‐disrupting potency. Three contaminants of indoor dust were tested on metamorphosing Silurana (Xenopus) tropicalis tadpoles. The tested chemicals were Tris (1,3‐dichloroisopropyl) phosphate (TDCiPP), tetrabromobisphenol‐A (TBBPA) and propylparaben (PrP). Measurements reflecting general growth, development progress and thyroid epithelial cell height were performed on the exposed tadpoles as well as chemical analyses of the exposure water. It was shown that TDCiPP acts as a thyroid hormone‐disrupting chemical in metamorphosing tadpoles by causing increased epithelial cell height in thyroid glands after exposure to a nominal concentration of 0.010 mg/L and in higher concentrations. TBBPA caused reductions in general growth of tadpoles at the nominal concentration 0.125 mg/L, and PrP caused acute toxicity at the nominal concentration 12.5 mg/L. However, no evident indications of specific thyroid‐disrupting effects caused by TBBPA or PrP were observed.
CTLA4-Ig Directly Inhibits Osteoclastogenesis by Interfering With Intracellular Calcium Oscillations in Bone Marrow Macrophages
Authors: Okada Hiroyuki , Kajiya Hiroshi , Omata Yasunori , Matsumoto Takumi , Sato Yuiko , Kobayashi Tami , Nakamura Satoshi , Kaneko Yosuke , Nakamura Shinya , Koyama Takuma , Sudo Shunichi , Shin Masashi , Okamoto Fujio , Watanabe Hisato , Tachibana Naohiro , Hirose Jun , Saito Taku , Takai Toshiyuki , Matsumoto Morio , Nakamura Masaya , Okabe Koji , Miyamoto Takeshi , Tanaka Sakae
Published: May 2019

CTLA4-Ig (cytotoxic T-lymphocyte antigen 4-immunoglobulin; Abatacept) is a biologic drug for rheumatoid arthritis. CTLA4 binds to the CD80/86 complex of antigen-presenting cells and blocks the activation of T cells. Although previous reports showed that CTLA4-Ig directly inhibited osteoclast differentiation, the whole inhibitory mechanism of CTLA4-Ig for osteoclast differentiation is unclear. Bone marrow macrophages (BMMs) from WT mice were cultured with M-CSF and RANKL with or without the recombinant mouse chimera CTLA4-Ig. Intracellular calcium oscillations of BMMs with RANKL were detected by staining with calcium indicator fura-2 immediately after administration of CTLA4-Ig or after one day of treatment. Calcium oscillations were analyzed using Fc receptor gamma- (FcRγ-) deficient BMMs. CTLA4-Ig inhibited osteoclast differentiation and reduced the expression of the nuclear factor of activated T cells NFATc1 in BMMs in vitro. Calcium oscillations in BMMs were suppressed by CTLA4-Ig both immediately after administration and after one day of treatment. CTLA4-Ig did not affect osteoclastogenesis and did not cause remarkable changes in calcium oscillations in FcRγ-deficient BMMs. Finally, to analyze the effect of CTLA4-Ig in vivo, we used an LPS-induced osteolysis model. CTLA4-Ig suppressed LPS-induced bone resorption in WT mice, not in FcRγ-deficient mice. In conclusion, CTLA4-Ig inhibits intracellular calcium oscillations depending on FcRγ and downregulates NFATc1 expression in BMMs. © 2019 American Society for Bone and Mineral Research.
Association of IL1RL1 rs3771180 and TSLP rs1837253 variants with asthma in the Guangxi Zhuang population in China
Authors: Sun Yan , Wei Xuan , Deng Jingmin , Zhang Jianquan , He Zhiyi , Yang Meiling , Liang Siqiao , Chen Zhangrong , Qin Huajiao
Published: May 2019

Objective

IL‐1 receptor‐like 1 (IL1RL1) and thymic stromal lymphopoietin (TSLP) play important roles in asthma in various ways. IL1RL1 rs3771180 and TSLP rs1837253 single nucleotide polymorphisms (SNPs) are associated with asthma in some European nationals but not in Zhuang people. Accordingly, this study aimed to determine the associations of IL1RL1 rs3771180 and TSLP rs1837253 with asthma in Zhuang people.

Methods

We performed a case‐control study to observe the association between the two polymorphisms and asthma in a Guangxi Zhuang cohort consisting of 123 asthmatic patients and 100 healthy controls. These individuals were recruited from the Department of Respiration of the First Affiliated Hospital of Guangxi Medical University. Multiplex PCR assay was used to identify the genotype of rs3771180 and rs1837253. Data were analyzed with SPSS 22.0 and SHEsis.

Results

rs1837253 showed significant differences between asthmatic and control groups in allele comparison (OR = 2.15; 95% CI = 1.27‐3.63; P = 0.004), as well as in the homozygote (OR = 4.83; 95% CI = 1.47‐16.47; P = 0.012), heterozygote (OR = 2.69; 95% CI = 1.20‐6.00; P = 0.016), and dominant (OR = 3.01; 95% CI = 1.39‐6.52; P = 0.005) genetic models. However, the genotype frequencies of rs3771180 did not obviously differ.

Conclusion

rs1837253 is associated with asthma susceptibility and may increase the risk of asthma in Zhuang people in Guangxi.
Family processes among Latino Early Head Start families: Understanding the role of caregiver acculturation
Authors: Hurwich‐Reiss Eliana , Watamura Sarah E.
Published: May 2019

The Family Stress Model (FSM) provides a framework for how economic pressure can impact family processes and outcomes, including parent's mental health, parenting, and child problem behaviors. Although the FSM has been widely replicated, samples disproportionately impacted by poverty, including early childhood samples and in particular Latino families with young children, have been largely excluded from FSM research. Therefore, among a sample of Latino Early Head Start children (N = 127), the current study evaluated a modified FSM to understand the direct and indirect pathways among economic pressure, parental depression, parenting self‐efficacy, the parent–child relationship, child problem behaviors, and parental acculturation. Results showed that the majority of the direct FSM pathways were well‐replicated among Latino caregivers of young children. Further analyses illuminated how some pathways were replicated among more but not among less‐acculturated Latino parents. Implications for future FSM research with Latino families as well as for parent‐focused interventions are discussed.
Retracted: CCR5 silencing reduces inflammatory response, inhibits viability, and promotes apoptosis of synovial cells in rat models of rheumatoid arthritis through the MAPK signaling pathway
Authors: Lan You‐Yu , Wang You‐Qiang , Liu Yi
Published: May 2019

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that can, in severe cases, lead to disability. CC chemokine receptor (CCR), an integral membrane protein, has been suggested to play a key role in the RA developmentThis study is to explore the role of CCR5 silencing in inflammatory response, viability, and apoptosis of synovial cells in RA rats by inactivating the mitogen‐activated protein kinase (MAPK) signaling pathway. Microarray analysis was conducted to screen out differentially expressed genes from RA‐related chips. The rat model was established by injection of siRNA‐CCR5 and PD98059 (inhibitor of mitogen‐activated protein kinase kinase 1) to evaluate the role of CCR5 silencing in RA, with the involvement of inflammatory response, synovial cell viability, apoptosis, and cycle. CCR5 was predicted to participate in RA by regulating the MARK pathway. In animal experiments, reduction was identified in arthritis index (AI), CCR5 positive expression rate, levels of tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), matrix metalloproteinase (MMP)‐1, and MMP‐3 in serum of RA rats after CCR5 siRNA and PD98059 injections. RA rats treated with CCR5 siRNA, and PD98059 presented with inhibition in cell viability, promotion of apoptosis, increase in cell proportion in G0/G1 phase, and shortened the S phase. In addition, the treatment of CCR5 siRNA, and PD98059 resulted in downregulated JNK1, ERK1, p38, Cyclin D1, Cyclin E1, Cyclin B1, and Bcl‐2 and upregulated Bax and Cas3. These findings reveal that CCR5 silencing suppresses inflammatory response, inhibits viability, and promotes apoptosis of synovial cells in RA rats by inhibiting MAPK pathway. Therefore, CCR5 silencing may provide a novel therapeutic target for RA.
Lin28B regulates the fate of grafted mesenchymal stem cells and enhances their protective effects against Alzheimer's disease by upregulating IGF‐2
Authors: Wu Kaimin , Zhang Ruiyi , Lu Yanhui , Wen Lulu , Li Yanfei , Duan Ranran , Yao Yaobing , Jia Yanjie
Published: May 2019

Mesenchymal stem cells (MSCs) transplantation has emerged as a potential therapeutic approach for Alzheimer's disease (AD). However, the poor proliferation capacity and low survival rate of engrafted MSCs in the hostile microenvironment of AD limit their therapeutic efficiency. Lin28B is a conserved RNA‐binding protein associated with cell self‐renewal and survival. The purpose of the present study was to explore whether lin28B might influence the functions of implanted MSCs and strengthen their neuroprotective potential in AD. A gain‐of‐function assay was used to upregulate lin28B expression in MSCs by lentiviral transfection. Our in vitro results indicated that lin28B promoted MSCs proliferation and migration, and protected MSCs against Aβ1–42‐induced cell death by upregulating insulin‐like growth factor‐2 (IGF‐2). Blockage of IGF‐2 partially abrogated the above effects of lin28B. After intracerebroventricular injection into amyloid precursor protein/presenilin 1 mice, implanted MSCs were monitored using bioluminescence imaging. We observed that administration of MSCs transfected with lin28B significantly stimulated their proliferation and prolonged cell retention after delivery. Moreover, administration of the transfected MSCs markedly mitigated cognitive deficits, promoted amyloid plaque clearance, decreased the activation of microglia, and reduced neuronal cell death. The data above confirmed our hypothesis that lin28B is a crucial modulator determining the fate of transplanted MSCs by regulating IGF‐2‐associated pathways and thereby enhancing their protective effects against AD.
LncRNAs associated with multiple sclerosis expressed in the Th1 cell lineage
Authors: Hosseini Aref , Teimuri Shohreh , Ehsani Marzieh , Rasa Seyed Mohammad Mahdi , Etemadifar Masoud , Nasr Esfahani Mohammad Hossein , Megraw Timothy L. , Ghaedi Kamran
Published: May 2019

Multiple sclerosis (MS) is a type of inflammatory and demyelinating disorder of the central nervous system in which immune‐mediated inflammatory processes are elicited by secreted cytokines from T helper (Th)‐1 and Th17 cells. While some protein‐coding genes expressed in T cell types have established involvement in MS disease progression, little is understood about the roles of long noncoding RNAs (lncRNAs) within the disease landscape. LncRNAs, noncoding RNAs longer than 200 nucleotides, likely control gene expression and function of Th1 cells, and offer the potential to act as therapeutic and biomarker candidates for MS. We identified lncRNAs in Th1 cells linked to MS. Expression levels of candidate lncRNAs and genes were evaluated in 50 MS patients and 25 healthy controls using quantitative real‐time polymerase chain reaction, and their correlations were assessed. LncRNAs encoded by AC007278.2 and IFNG‐AS1‐001 showed significantly higher expression in relapsing Phase MS patients whereas IFNG‐AS1‐003 was elevated in patients in the remitting phase compared with relapsing patients. Collectively, these misregulated lncRNAs may provide valuable tools to understand the relationships between lncRNAs and MS, and possibly other related disorders.