bluuebunny/crossref_metadata_2025 huggingface dataset:
FUS P525L mutation causing amyotrophic lateral sclerosis and movement disorders
Authors: Zhou Binbin , Wang Huan , Cai Yu , Wen Han , Wang Lulu , Zhu Min , Chen Yunqing , Yu Yanyan , Lu Xi , Zhou Meihong , Fang Pu , Li Xiaobing , Hong Daojun
Published: April 2020

Background

Mutations in the fused in sarcoma (FUS) gene have been associated with amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and essential tremor. Among the FUS mutations, p.P525L as a hot spot variant has been reported in more than 20 patients with ALS. Apart from the typical ALS phenotype, patients with p.P525L mutation exhibit some atypical symptoms. However, movement disorders related to p.P525L mutation have not been emphasized currently.

Methods

Two unrelated patients with ALS were evaluated through a set of clinical and laboratory tests. The genetic screening was performed through next‐generation sequencing. Muscle biopsies were performed on the 2 patients. Muscle samples were stained according to standard histological and immunohistochemical procedures.

Results

The first patient presented with juvenile‐onset neurogenic weakness and wasting and simultaneously had dropped head, ophthalmoplegia, tremor, involuntary movements, and cognitive impairments. The second patient showed a typical ALS phenotype and prominent adventitious movements. Genetic screening disclosed de novo p.P525L FUS mutation in the 2 patients by family cosegregation analysis. Muscle biopsy showed neurogenic patterns and numerous lipid droplets aggregating in the fibers.

Conclusion

Apart from the typical ALS phenotype, patients with p.P525L mutation in the FUS gene can present with great clinical heterogeneity including multiple movement disorders. Numerous lipid droplets in muscle fibers indicate that skeletal muscle is likely an important therapeutic target for ALS.
Gene–disease association study of tumor necrosis factor‐α G‐308A gene polymorphism with risk of major depressive disorder: A systematic review and meta‐analysis
Authors: Wang Xin , Zhang Hongxiu , Cao Xianling , Shi Wei , Zhou Xiaoyu , Chen Qian , Ma Ke
Published: April 2020

Introduction

The single nucleotide polymorphism (SNP) of the tumor necrosis factor‐α (TNF‐α) G‐308A gene is the most studied regarding susceptibility to major depressive disorder (MDD). However, results have been controversial perhaps due to the heterogeneous genetic backgrounds influenced by race as well as subtypes of depression.

Methods and materials

A systematic MEDLINE search was performed to retrieve all published studies that identified the connection between the TNF‐α G‐308A gene polymorphism and the risk of MDD.

Results

There was no statistical difference between the allele frequencies or genotypes of TNF‐α G‐308A gene and the depressive patients or healthy subjects in the five models tested. Further, subgroup analyses showed that the TNF‐α G‐308A gene polymorphism also did not confer susceptibility to poststroke, late‐life, maternal, or major depression. Publication bias analysis showed p values were more than .05, suggesting that the 9 articles included in the current analysis had no publication bias.

Conclusion

Neither the allele frequencies nor genotypes of TNF‐α G‐308A gene could be served as an independent risk factor of depression.
Elemental metal variance in cell culture raw materials for process risk profiling
Authors: Grinnell Chris , Bareford Lisa , Matthews Thomas E. , Brantley Tim , Moore Brandon , Kolwyck David
Published: April 2020

Elemental metals are critical raw material attributes which can impact cell culture performance and associated therapeutic protein product quality profiles. Metals such as copper and manganese act as cofactors and reagents for numerous metabolic pathways which govern cell growth, protein expression, and glycosylation, thus mandating elemental monitoring. The growing complexity of modern cell culture media formulations adds additional opportunities for elemental variance and its associated impact risks. This article describes an analytical technique applying inductively coupled plasma mass spectrometry to characterize a list of common raw materials and media powders used in mammalian cell culture and therapeutic protein production. We aim to describe a method qualification approach suitable for biopharmaceutical raw materials. Furthermore, we present detailed profiles of many common raw materials and discuss trends in raw material subtypes. Finally, a case study demonstrating the impact of an unexpected source of raw material variation is presented along with recommendations for raw material elemental risk profiling and control.
Variations of Flavonoid Composition and Antioxidant Properties among Different Cultivars, Fruit Tissues and Developmental Stages of Citrus Fruits
Authors: Zhu Chunhua , Zhou Xianyan , Long Chunrui , Du Yuxia , Li Jinxue , Yue Jianqiang , Pan Siyi
Published: April 2020

A large number of biologically active compounds are present in ripe citrus fruits. However, few studies have been focused on the changes in flavonoids and the evolution of antioxidant activity during citrus fruit growth. In this study, fruits of five citrus cultivars cultivated in China were sampled at 60–210 days post‐anthesis (DPA) at intervals of 30 days. The amounts of main flavonoids in the peel and pulp were analyzed by HPLC and their activities were studied by DPPH, ABTS and FRAP. The results showed that the contents of hesperidin, diosmin, eriodictyol, rutin and nobiletin increased before 90 DPA and then decreased with the growth and development of fruits, but an opposite tendency was observed for naringin and narirutin. The antioxidant activities in citrus peel and pulp were found to be significantly correlated with some flavonoids. The results may be of guiding values in citrus production and utilization of citrus fruit by‐products.
CircRNA‐0077930 from hyperglycaemia‐stimulated vascular endothelial cell exosomes regulates senescence in vascular smooth muscle cells
Authors: Wang Sha , Zhan Junkun , Lin Xiao , Wang Yanjiao , Wang Yi , Liu Youshuo
Published: April 2020

Vascular smooth muscle aging leads to diabetic complications such as cardiovascular and kidney diseases or diabetic foot. Therefore, understanding the mechanism of smooth muscle cell senescence in a high‐glucose (HG) environment is essential. The purpose of this study was to determine whether and how circRNA from human umbilical vein endothelial cell exosomes (HUVEC‐Exos) under HG conditions regulates the senescence of vascular smooth muscle cells (VSMCs). Combining circRNA array analysis and bioinformatics, we postulated that the circRNA‐0077930‐miR‐622‐Kras CeRNA network plays an important role in inducing senescence in VSMCs. CircRNA‐0077930 transmitted by HG‐HUVEs‐Exos induced senescence of VSMCs by down‐regulation of miR‐622 expression and up‐regulation of Kras, p21, p53 and p16 expression. Moreover, the lactate dehydrogenase (LDH) activity was significantly increased while anti‐oxidative stress marker (superoxide dismutase, SOD) activity was reduced in HG‐HUVEC‐Exos treatment VSMCs. Finally, HG‐HUVEC‐Exos with depleted‐circRNA‐0077930 is no longer able to induce cellular senescence in VSMCs. These findings provided a new light on the effective treatment of VSMC senescence.

Significance of the study

Previous studies have shown that endothelial cell senescence is closely related to smooth muscle cell aging. Here, for the first time, we proved that the HG‐HUVECs derived exosomes induced the VSMCs senescence by circRNA0077930‐miR622‐Kras CeRNA network. The circRNA‐0077930‐depleted exosomes would lose the ability to promote cellular senescence of VSMCs.
Critical roles of tyrosyl‐DNA phosphodiesterases in cell tolerance to carnosol‐induced DNA damage
Authors: Feng Xiaoyu , Wu Xiaohua , Wu Yang , Zhao Zilu , Xiang Cuifang , Bai Xin , Liu Xin , Zhao Jingxia , Takeda Shunichi , Qing Yong
Published: April 2020

Carnosol is a natural compound with pharmacological action due to its anti‐cancer properties. However, the precise mechanism for its anti‐carcinogenic effect remains elusive. In this study, we used lymphoblastoid TK6 cell lines to identify the DNA damage and repair mechanisms of carnosol. Our results showed that carnosol induced DNA double‐strand breaks (DSBs). We also found that cells lacking tyrosyl‐DNA phosphodiesterase 1 (TDP1), an enzyme related to topoisomerase 1 (TOP1), and tyrosyl‐DNA phosphodiesterase 2 (TDP2), an enzyme related to topoisomerase 2 (TOP2), were supersensitive to carnosol. Carnosol was found to induce the formation of the TOP1‐DNA cleavage complex (TOP1cc) and TOP2‐DNA cleavage complex (TOP2cc). When comparing the accumulation of γ‐H2AX foci and the number of chromosomal aberrations (CAs) with wild‐type (WT) cells, the susceptivity of the TDP1−/− and TDP2−/− cells were associated with an increased DNA damage. Our results provided evidence of carnosol inducing DNA lesions in TK6 cells and demonstrated that the damage induced by carnosol was associated with abnormal topoisomerase activity. We conclude that TDP1 and TDP2 play important roles in the anti‐cancer effect of carnosol.
Two‐Dimensional Layered Metallic VSe2/SWCNTs/rGO Based Ternary Hybrid Materials for High Performance Energy Storage Applications
Authors: Sree Raj K. A. , Shajahan Afsal S. , Chakraborty Brahmananda , Rout Chandra Sekhar
Published: April 2020

In this work, the ternary hybrid structure VSe2/SWCNTs/rGO is reported for supercapacitor applications. The ternary composite exhibits a high specific capacitance of 450 F g−1 in a symmetric cell configuration, with maximum energy density of 131.4 Wh kg−1 and power density of 27.49 kW kg−1. The ternary hybrid also shows a cyclic stability of 91 % after 5000 cycles. Extensive density functional theory (DFT) simulations on the structure as well as on the electronic properties of the binary hybrid structure VSe2/SWCNTs and the ternary hybrid structure VSe2/SWCNTs/rGO have been carried out. Due to a synergic effect, there are enhanced density of states near the Fermi level and higher quantum capacitance for the hybrid ternary structure compared to VSe2/SWCNTs, leading to higher energy and power density for VSe2/SWCNTs/rGO, supporting our experimental observation. Computed diffusion energy barrier of electrolyte ions (K+) predicts that ions move faster in the ternary structure, providing higher charge storage performance.
Evidence for Genuine Bimetallic Frustrated Lewis Pair Activation of Dihydrogen with Gold(I)/Platinum(0) Systems
Authors: Hidalgo Nereida , Moreno Juan José , Pérez‐Jiménez Marina , Maya Celia , López‐Serrano Joaquín , Campos Jesús
Published: April 2020

Invited for the cover of this issue is the group of Joaquín López‐Serrano and Jesús Campos at the Consejo Superior de Investigaciones Científicas and the University of Sevilla. The image depicts the importance of balancing the degree of frustration/interaction in the splitting of H2 by AuI/Pt0. Read the full text of the article at 10.1002/chem.201905793.
Post‐Metalation Modification of a Macrocyclic Dicobalt(III) Metallohost by Site‐Selective Ligand Exchange for Guest Recognition Control
Authors: Sakata Yoko , Okada Masahiro , Tamiya Munehiro , Akine Shigehisa
Published: April 2020

We propose post‐metalation modification as a useful strategy to control the guest recognition behavior of a metal‐containing macrocyclic host. This is based on the ligand exchange of the axial ligands of a cobalt(III) dinuclear macrocyclic host, [LCo2X4]2+ (X=axial amine ligand). Four piperidine ligands in [LCo2(pip)4]2+ (pip=piperidine) were site‐selectively replaced with primary amines. The competitive experiments revealed that the order of the affinity toward the cobalt centers in [LCo2X4]2+ is primary amine > secondary amine > tertiary amine and that the piperidine‐coordinating complex, [LCo2(pip)4]2+, was reasonably reactive among the isolable complexes. Indeed, two piperidine ligands at the diagonal positions in [LCo2(pip)4]2+ were site‐selectively replaced with pyridine or acetate ion. The replacement of piperidine with acetate ion significantly enhanced the recognition ability towards Na+.
Highly Efficient Luminescent Solar Concentrators Based on Benzoheterodiazole Dyes with Large Stokes Shifts
Authors: Gao Sheng , Balan Bamisha , Yoosaf Karuvath , Monti Filippo , Bandini Elisa , Barbieri Andrea , Armaroli Nicola
Published: April 2020

Five extended π‐conjugated systems with electron donor (D) and acceptor (A) moieties have been synthesized. Their basic D‐A‐D structural motif is a benzothiadiazole unit symmetrically equipped with two thiophene rings (S2T). Its variants include 1) the same molecular framework in which sulfur is replaced by selenium (Se2T), also with four thiophene units (Se4T) and 2) a D’‐D‐A‐D system having a N‐carbazole donor moiety at one end (CS2T) and a D’‐D‐A‐D‐A’ array with a further acceptor carbonyl unit at the other extremity (CS2TCHO). The goal is taking advantage of the intense luminescence and large Stokes shifts of the five molecules for use in luminescent solar concentrators (LSCs). All of them exhibit intense absorption spectra in the UV/Vis region down to 630 nm, which are fully rationalized by DFT. Emission properties have been studied in CH2Cl2 (298 and 77 K) as well as in PMMA and PDMS matrices, measuring photoluminescence quantum yields (up to 98 %) and other key optical parameters. The dye–PMMA systems show performances comparable to the present state‐of‐the‐art, in terms of optical and external quantum efficiencies (OQE=47.6 % and EQE=31.3 %, respectively) and flux gain (F=10.3), with geometric gain close to 90. LSC devices have been fabricated and tested in which the five emitters are embedded in PDMS and their wave‐guided VIS luminescence feeds crystalline silicon solar cells.
Iridium‐Catalyzed Enantioselective Hydroarylation of Alkenes through C−H bond Activation: Experiment and Computation
Authors: Shinde Valmik S. , Mane Manoj V. , Cavallo Luigi , Rueping Magnus
Published: April 2020

A new catalytic enantioselective hydroarylation of unactivated olefins is developed that provides rapid access to functionalized chiral dihydrobenzofurans with good yields and excellent enantioselectivities. Simple aromatic ketones or amides act as a directing group allowing the regioselective reaction at the more hindered ortho position. Tertiary benzylic stereocenters are obtained directly under mild reaction conditions and with complete atom economy from readily available starting materials.
The Transient Complex of Cytochrome c and Cytochrome c Peroxidase: Insights into the Encounter Complex from Multifrequency EPR and NMR Spectroscopy
Authors: van Son Martin , Schilder Jesika T. , Di Savino Antonella , Blok Anneloes , Ubbink Marcellus , Huber Martina
Published: April 2020

We present a novel approach to study transient protein‐protein complexes with standard, 9 GHz, and high‐field, 95 GHz, electron paramagnetic resonance (EPR) and paramagnetic NMR at ambient temperatures and in solution. We apply it to the complex of yeast mitochondrial iso‐1‐cytochrome c (Cc) with cytochrome c peroxidase (CcP) with the spin label [1‐oxyl‐2,2,5,5‐tetramethyl‐Δ3‐pyrroline‐3‐methyl)‐methanethiosulfonate] attached at position 81 of Cc (SL−Cc). A dissociation constant KD of 20±4×10−6 M (EPR and NMR) and an equal amount of stereo‐specific and encounter complex (NMR) are found. The EPR spectrum of the fully bound complex reveals that the encounter complex has a significant population (60 %) that shares important features, such as the Cc‐interaction surface, with the stereo‐specific complex.
Analysis of Tomato Post‐Harvest Properties: Fruit Color, Shelf Life, and Fungal Susceptibility
Authors: Thole Vera , Vain Philippe , Yang Ray‐Yu , Almeida Barros da Silva Juliana , Enfissi Eugenia M. A. , Nogueira Marilise , Price Elliott J. , Alseekh Saleh , Fernie Alisdair R. , Fraser Paul D. , Hanson Peter , Martin Cathie
Published: April 2020

A wide variety of fresh market and processing tomatoes (Solanum lycopersicum) is grown and consumed worldwide. Post‐harvest losses are a major contributing factor to losses in crop productivity and can account for up to 50% of the harvest. To select and breed elite tomato varieties, it is important to characterize fruit quality and evaluate the post‐harvest properties of tomato fruits. This includes the analysis of shelf life (the period during which a fruit remains suitable for consumption without qualitative deterioration), color, and pathogen susceptibility. Tomato shelf life depends upon the rate of fruit softening which accompanies fruit ripening and exacerbates damage during transport and handling. Furthermore, the susceptibility of tomatoes to fruit pathogens is also often linked to fruit ripening, especially for necrotrophic fungi such as Botrytis cinerea, also known as gray mold. The methods described here are critical for determining fruit quality and fungal susceptibility during storage. © 2020 The Authors.

Basic Protocol 1: Fruit color as a determinant of fruit quality

Basic Protocol 2: Shelf life test of tomato fruits

Basic Protocol 3: Botrytis cinerea pathogen test of tomato fruits

Support Protocol: Preparation of Botrytis spore inoculum
Genetic transfer from several apomictic tetraploid Paspalum species to an elite group of sexual plants
Authors: Novo Patricia E. , Acuña Carlos A. , Urbani Mario H. , Galdeano Florencia , Espinoza Francisco , Quarin Camilo L.
Published: April 2020

Basic findings from classical genetic studies are available for exploiting apomixis in the breeding of several forage grass genera. Most Paspalum species are multiploid with a sexual diploid cytotype and conspecific apomictic polyploid (mainly tetraploid) cytotypes. Experimental tetraploidized diploids reproduce sexually and, when crossed with natural apomictic tetraploids, yield hybrid populations that segregate for reproductive mode. Genetic studies indicated that apomixis is inherited as a monogenic dominant factor. We recombined 50 selected sexual hybrids obtained from crosses between a tetraploidized sexual genotype of P. plicatulum and 9 natural apomictic tetraploid accessions of 6 species of the Plicatula group. A synthetic sexual tetraploid population (SSTP) of 600 individuals from mixed seed of the 50 intercrossed hybrids was space‐planted in the field. Based on evaluations of plant vigor, seed set, ergot tolerance, regrowth after flowering, and cold tolerance, 31 plants were selected. Crosses between most selected plants and two testers, which belonged to P. guenoarum, were performed, and the generated progeny was planted into the field following a randomized block design with 3 replications. The progeny test was evaluated for seed fertility, biomass yield, and cold tolerance. This procedure allowed selection of 10 elite plants from the SSTP. These plants should contain genes recombined from six apomictic species, without the genetic determinants for apomixis. They may be polycrossed to generate an improved sexual population, or crossed with other apomictic genotypes to obtain improved apomictic hybrids.
Bidirectional isolated three‐phase dc‐dc converter using coupled inductor for dc microgrid applications
Authors: Berrehil El Kattel Menaouar , Mayer Robson , Douglas Possamai Maicon , Vidal Garcia Oliveira Sergio
Published: April 2020

The main objective of this project is to study the analysis and design of an isolated three‐phase bidirectional dc‐dc converter connected to the dc microgrid system. The proposed topology achieves efficient power conversion with a wide input voltage range, continuous input current, and bidirectional operation. In forward mode operation, the topology acts as a three‐phase push‐pull converter to reach a step‐up voltage conversion ratio (90 to 450 V). In backward mode operation, the converter acts as an interleaved flyback converter to provide a step‐down voltage conversion ratio (450 to 90 V). Over and above that, in both operation senses, the dc voltage gain is presented. The main advantages of this topology are high‐switching frequency, the three‐phase transformer that provides galvanic isolation between the dc voltage link bus to the battery or ultra‐capacitor storage, and input/output filters size reduction. Besides, a fewer number of power switches, the frequency of output voltage, and input current ripple are three times higher than the switching frequency. The three active switches are connected to the same reference, which simplifies the gate drive circuit. Ultimately, the theoretical analysis of the proposed topology is carefully confirmed with the experimental results of the 4 kW converter prototype.
The cytoskeleton as a modulator of tension driven axon elongation
Authors: Sousa Sara C. , Sousa Mónica M.
Published: April 2020

Throughout development, neurons are capable of integrating external and internal signals leading to the morphological changes required for neuronal polarization and axon growth. The first phase of axon elongation occurs during neuronal polarization. At this stage, membrane remodeling and cytoskeleton dynamics are crucial for the growth cone to advance and guide axon elongation. When a target is recognized, the growth cone collapses to form the presynaptic terminal. Once a synapse is established, the growth of the organism results in an increased distance between the neuronal cell bodies and their targets. In this second phase of axon elongation, growth cone‐independent molecular mechanisms and cytoskeleton changes must occur to enable axon growth to accompany the increase in body size. While the field has mainly focused on growth‐cone mediated axon elongation during development, tension driven axon growth remains largely unexplored. In this review, we will discuss in a critical perspective the current knowledge on the mechanisms guiding axon growth following synaptogenesis, with a particular focus on the putative role played by the axonal cytoskeleton.
Development and validation of a simple online‐SPE method coupled to high‐resolution mass spectrometry for the analysis of stanozolol‐N‐glucuronides in urine samples
Authors: Göschl Lorenz , Gmeiner Günter , Enev Valentin , Kratena Nicolas , Gärtner Peter , Forsdahl Guro
Published: April 2020

Stanozolol is still the most commonly used illicit anabolic‐androgenic steroid (AAS) in professional sports. Therefore, accurate and fast analysis and long detection windows are of great interest in the field of antidoping analysis. In this work, a very simple, fast, and highly sensitive online solid‐phase extraction method coupled with liquid chromatography–high‐resolution tandem mass spectrometry (HPLC‐HRMSMS) for the analysis of stanozolol‐N‐glucuronides was developed. This fully validated procedure is characterized by only a few manual steps (dilution and addition of internal standard) in the sample preparation. A limit of identification (LOI) of 75 pg/mL, high accuracy (87.1%–102.1%), precision (3.1%–7.8%), and sensitivity was achieved. Furthermore, good linearity (> 0.99) and robustness, as well as no carry‐over effects, could be observed. In addition to excellent confirmation analysis performance, this method shows sufficient potential for the identification and characterization of unknown metabolites. Using this method, it was possible to unambiguously confirm the presence of 1′N‐ and 2′N‐stanozolol‐glucuronide in human urine for the first time due to the access to reference material.
Adulterants in selected dietary supplements and their detection methods
Authors: Muschietti Liliana , Redko Flavia , Ulloa Jerónimo
Published: April 2020

At present, there is a growing trend toward the intentional adulteration of dietary supplements (DS) with synthetic pharmaceuticals, which represents an alarming emerging risk to consumers and a serious problem for regulatory agencies. An amazing array of synthetic drugs and their analogues have been reported as adulterants in DS. Mainly, the presence of analogues represents a serious health risk as their efficacy and toxic effects have not been clinically assessed yet and may result in unpredictable adverse effects. The purpose of this review is to provide an overview, over the period 2009–2019, of the most frequently reported adulterants in DS for the treatment of erectile dysfunction, obesity/overweight, diabetes mellitus, and hypertension and the analytical methods used for their detection.
In vitro and in vivo metabolism and detection of 3‐HO‐PCP, a synthetic phencyclidine, in human samples and pooled human hepatocytes using high resolution mass spectrometry
Authors: Davidsen Anders Bork , Mardal Marie , Johansen Sys Stybe , Dalsgaard Petur Weihe , Linnet Kristian
Published: April 2020

The new psychoactive substance (NPS) 3‐HO‐PCP, a phencyclidine (PCP) analog, was detected in a law enforcement seizure and in forensic samples in Denmark. Compared with PCP, 3‐HO‐PCP is known to be a more potent dissociative NPS, but no toxicokinetic investigations of 3‐HO‐PCP are yet available. Therefore, 3‐HO‐PCP was quantified in in vivo samples, and the following were investigated: plasma protein binding, in vitro and in vivo metabolites, and metabolic targets. All samples were separated by liquid chromatography and analyzed by mass spectrometry. The unbound fraction in plasma was determined as 0.72 ± 0.09. After in vitro incubation with pooled human hepatocytes, four metabolites were identified: a piperidine‐hydroxyl‐and piperidine ring opened N‐dealkyl‐COOH metabolite, and O‐glucuronidated‐ and O‐sulfate‐conjugated metabolites. In vivo, depending on the sample and sample preparation, fewer metabolites were detected, as the O‐sulfate‐conjugated metabolite was not detected. The N‐dealkylated‐COOH metabolite was the main metabolite in the deconjugated urine sample. in vivo analytical targets in blood and brain samples were 3‐HO‐PCP and the O‐glucuronidated metabolite, with 3‐HO‐PCP having the highest relative signal intensity. The drug levels of 3‐HO‐PCP quantified in blood were 0.013 and 0.095 mg/kg in a living and a deceased subject, respectively. The 3‐HO‐PCP concentrations in deconjugated urine in a sample from a living subject and in post‐mortem brain were 7.8 and 0.16 mg/kg, respectively. The post mortem results showed a 1.5‐fold higher concentration of 3‐HO‐PCP in the brain tissue than in the post mortem blood sample.
Indigenous tenure security and local participation in climate mitigation programs: Exploring the institutional gaps of REDD+ implementation in the Peruvian Amazon
Authors: Dupuits Emilie , Cronkleton Peter
Published: April 2020

The Reduction of Emissions from Deforestation and forest Degradation (REDD+) mechanism faces implementation challenges related to tenure security and governance institutions. In response, multiple regional climate mitigation initiatives have emerged. In Peru, indigenous networks have created their own Indigenous Amazonian REDD (RIA), an initiative aiming to strengthen property rights for native peoples. At roughly the same time, the Peruvian government launched the National Forest Conservation Program (PNCB), a conditional payment scheme aiming to encourage sustainable forest management. However, these initiatives must still overcome fragmented institutional governance of forests at the regional scale and continued challenges related to indigenous tenure security. This article examines how indigenous federations and the Peruvian government are attempting to implement these initiatives in the Amazonian region of Madre de Dios to examine how challenges play out in practice. These cases illustrate the institutional gaps between national policies, regional capacities, and local needs and expectations. However, it also demonstrates how an innovative institutional partnership at the subnational scale may be overcoming some of these challenges.
Cost and health effects of case management compared with outpatient clinic follow‐up in a Dutch heart failure cohort
Authors: van Voorst Henk , Arnold Alfred Ernest Reiner
Published: April 2020

Aims

Heart failure reduces quality of life and life expectancy; hospital admissions are frequent and create a burden on public resources. This study aims to quantify the benefits in terms of health effects [quality‐adjusted life years (QALYs)] and costs when heart failure patients receive case management at home compared with outpatient cardiology clinic follow‐up.

Methods and results

A health state transition (Markov) model was written, and transition probabilities were derived from a cohort of 1114 patients and available literature. QALYs in different health states of heart failure patients were retrieved from the literature, and costs were estimated with data from the financial department of the Noordwest Ziekenhuisgroep and public cost sources. Monthly simulation cycles were repeated 60 times to generate 5 years of virtual follow‐up data. Baseline willingness to pay is assumed €50 000 per QALY. Sensitivity analyses were performed in a one‐way deterministic and a multiway probabilistic approach; the probabilistic approach used uniform and more plausible distributions of the model parameters.

Case management reduced costs by €382 and increased QALYs by 0.261 for the baseline simulation; this results in a net monetary benefit of €13 428. Probabilistic sensitivity analysis based on uniform and most plausible distributions of parameters resulted in 96.2% and 83.3% of the simulations, favouring a treatment strategy of case management.

Conclusions

Case management is cost effective in 83.3% of the probabilistic simulations and has a tendency towards reducing costs and increasing QALYs when considering a real‐world cohort of heart failure patients in the Netherlands.
Impact of H2 and Consecutive H2O2 Exposures on the Oxidative Dissolution of (U1–xGdx)O2 Pellets Under Deep Repository Conditions for Spent Nuclear Fuel
Authors: Maier Annika Carolin , Barreiro Fidalgo Alexandre , Jonsson Mats
Published: April 2020

The reactivity of H2O2 towards (U1–xGdx)O2 (x = 0.03, 0.045, 0.08) in the presence of H2 was studied experimentally to assess the effect of H2 on oxidative dissolution of Gd‐doped UO2 under deep repository conditions for spent nuclear fuel. Gd‐doped UO2 was chosen as a model substance for spent nuclear fuel due to its chemical similarity but low radiotoxicity. While H2O2 is a radiolysis product capable of driving fuel matrix dissolution, H2, which is expected to evolve mainly through the corrosion of cast iron canisters encapsulating the fuel, might limit or even suppress fuel dissolution. Commercial (U1–xGdx)O2 pellets were immersed in 10 mm HCO3– solutions and consecutively exposed to 2 mm H2O2 in an autoclave under either 40 bar H2 or 5 bar N2 atmosphere. The results indicate that H2 does not influence the oxidative dissolution of (U1–xGdx)O2. Instead, the reactivity of the pellets decreases with increasing H2O2 exposure due to an irreversible alteration of the pellet surfaces resulting in decreased redox reactivity.
Synthesis of Functionalized Bridged Bicyclic Sulfonamides with a Bridgehead Nitrogen Atom
Authors: Blahun Oleksandr P. , Melnychenko Heorhii , Kuchkovska Yuliya O. , Zhersh Serhii , Tolmachev Andrey A. , Grygorenko Oleksandr O.
Published: April 2020

Two approaches to the synthesis of functionalized bridged bicyclic sulfonamides with a bridgehead nitrogen atom were developed. The target compounds were obtained either by introduction of a CH2SO2 bridge into functionalized monocyclic substrates or by final‐step carboxylation of parent bicyclic cores. The described methods allowed preparation of the final products on a multigram scale.
Mindfulness meditation is related to sensory‐affective uncoupling of pain in trained novice and expert practitioners
Authors: Zorn Jelle , Abdoun Oussama , Bouet Romain , Lutz Antoine
Published: April 2020

Background

Mindfulness meditation can alleviate acute and chronic pain. It has been proposed that mindfulness meditation reduces pain by uncoupling sensory and affective pain dimensions. However, studies to date have reported mixed results, possibly due to a diversity of styles of and expertise in mindfulness meditation. Furthermore, the interrelations between mindfulness meditation and pain catastrophizing during acute pain remain little known.

Methods

This cross‐sectional study investigated the effect of a style of mindfulness meditation called Open Monitoring (OM) on sensory and affective pain experience by comparing novice (2‐day formal training; average ~20 hr practice) to expert practitioners (>10.000 hr practice). We implemented a paradigm that was designed to amplify the cognitive‐affective aspects of pain experience by the manipulation of pain anticipation and uncertainty of stimulus length (8 or 16 s thermal pain stimuli). We collected pain intensity and unpleasantness ratings and assessed trait pain catastrophizing with the Pain Catastrophizing Scale (PCS).

Results

Across groups, mindfulness meditation reduced unpleasantness, but not intensity ratings compared to attentional distraction. Experts reported a lower score on PCS, reduced amplification of unpleasantness by long painful stimuli, and larger sensory‐affective uncoupling than novices particularly during long painful stimuli. In experts, meditation‐induced uncoupling spilled over the control condition. Across groups and task conditions, a higher score on PCS predicted lower sensory‐affective uncoupling during long painful stimuli and higher ratings of pain intensity during short painful stimuli.

Conclusion

These findings suggest that mindfulness meditation specifically down‐regulates pain affect as opposed to pain intensity, and that pain catastrophizing undermines sensory‐affective uncoupling of pain.

Significance

In this study, we found that a style of mindfulness meditation referred to as OM reduced unpleasantness but not intensity ratings compared to attentional distraction in trained novice (state effect) and expert meditators (state and trait effects). We also observed that trait pain catastrophizing scores predicted this sensory‐affective uncoupling. These findings advance our understanding of the cognitive mechanisms underlying mindfulness meditation and can inform treatment strategies for chronic pain.
Orange peel volatile oil: A green solvent for propolis extraction, enhanced α‐amylase inhibition activity
Authors: Keskin Şaban
Published: April 2020

Orange peel oil contains high amount of d‐limonene which is reported to have antidiabetic activity. Propolis contains many biologically active compounds like phenolic acids, flavonoids and terpenes. Because of its rich phenolic composition, antidiabetic activity of propolis has also been shown in literature. Consumption of raw propolis is limited because of its resinous nature. It should be extracted to convert it into consumable form. Ethanol is the most used solvent for this purpose. Ethanol is the limiting factor for propolis consumption either for religious concerns or being harmful for human health. There is an increasing need for new, compatible and healthier solvents for propolis extraction. This is the first paper describing the extraction of propolis with orange peel oil. 1:10 (g/v) ratio was used for extraction. Orange peel oil (OPO), orange peel oil propolis extract (OPOPE) and ethanol propolis extract (EPE) were separately analysed by using GC‐MS technique. Total phenolic content of oil and propolis extract was also carried out. Inhibition of α‐amylase from barley malt with new extract was also reported. It was found that OPOPE was rich in volatile compounds of propolis, phenolic acid derivatives and free fatty acids. It was observed that OPOPE showed higher inhibition on α‐amylase enzyme (IC50 0.196 mg/mL). It can be concluded that orange peel oil could be used as solvent for preparing propolis extract. Propolis extract obtained with orange peel oil could also be used as complementary medicine for the treatment of type 2 diabetes.
Separation of saturated fatty acids from docosahexaenoic acid‐rich algal oil by enzymatic ethanolysis in tandem with molecular distillation
Authors: He Jianlin , Hong Bihong , Lu Rong , Zhang Ruoqi , Fang Hua , Huang Wenwen , Bai Kaikai , Sun Jipeng
Published: April 2020

Algal oil, rich in docosahexaenoic acid (DHA) and an environmentally sustainable source of ω‐3 fatty acids, is receiving increasing attention. In the present study, a novel approach combining ethanolysis with a 1,3‐specific immobilized lipase (Lipozyme® TL IM) and molecular distillation was investigated to increase the DHA content of algal oil. Algal oil with a 45.94% DHA content was mixed with ethanol, pumped into a column filled with Lipozyme® TL IM, and then circulated for 4 hr at room temperature. The ethanol was then recycled by vacuum distillation. At an evaporator temperature of 150°C, the residue was separated by molecular distillation into a heavy component enriched with DHA glycerides (in the form of triglyceride (TG), diglyceride (DG), and monoglyceride (MG)) and a light component enriched with palmitic acid (PA) and DHA ethyl ester (EE). As a result, 76.55% of the DHA from the algal oil was present in the heavy component, whose DHA content was 70.27%. DHA‐MG was collected in the heavy component mostly in the form of 1‐MG. Lipozyme® TL IM appeared to specifically target PA rather than DHA at the sn‐1(3) position. The Lipozyme® TL IM allowed 90.03% of the initial DHA yield to be retained after seven reaction cycles. Therefore, an eco‐friendly and simple method for increasing the DHA content in algal oil has been developed.
Effects of Agaricus blazei Murrill polysaccharides on hyperlipidemic rats by regulation of intestinal microflora
Authors: Li Yuxin , Lu Xuechun , Li Xiao , Guo Xiao , Sheng Yu , Li Yingna , Xu Guangyu , Han Xiao , An Liping , Du Peige
Published: April 2020

The present research envisaged the effects of Agaricus blazei Murrill polysaccharides (ABPs) on blood lipids and its role in regulation of the intestinal microflora in hyperlipidemic rats. The acidic polysaccharide fraction of Agaricus blazei Murrill was obtained by DEAE‐cellulose ion exchange column chromatography. The sugar content of ABP was 75.1%. Compared with the model group (MG), the serum TC, TG, and LDL‐C levels decreased (p < .05 or p < .01) and the HDL‐C levels increased (p < .01) significantly in the ABP group. Expression of CYP7A1 was up‐regulated (p < .01), and that of SREBP‐1C (p < .05) was down‐regulated significantly in the liver tissue of rats in the ABP group. Additionally, the disordered hepatic lobules and the steatosis of hepatocytes were found to be significantly alleviated in the ABP group. We believe that ABP can reduce the ratio of Firmicutes/Bacteroidetes and reduce the relative abundance of Firmicutes, Ruminococcaceae_unclassified, and Ruminococcaceae, increasing the relative abundance of Proteobacteria, Clostridium_sensu_stricto, Allobaculum, Peptostreptococcaceae, Clostridiaceae_1, and Erysipelotrichaceae as targets to regulate blood lipids. The results showed ABP could regulate the dyslipidemia in rats with hyperlipidemia. The mechanism may be through the regulation of the imbalance of intestinal microflora induced by the high‐fat diet in rats, which may be one of the important ways of its intervention on the dyslipidemia induced by high‐fat diet.
Effect of fish paste products “Hanpen” intake in Sprague‐Dawley rats
Authors: Kadokura Kazunari , Tomita Tsuyoshi , Kobayashi Masakazu , Mitsui Tadahiko , Suruga Kohei
Published: April 2020

Fish paste product, “Hanpen,” is a traditional type of Japanese food made from minced fish as well as imitation crab and kamaboko, and a marshmallow‐like soft texture is characteristic of hanpen. Hanpen is known as a high‐protein and low‐fat food. However, there is a lack of evidence on its health benefits. The aim of this study was to investigate the effects of hanpen intake on organ weight and biomarker levels in Sprague‐Dawley rats with diets consisting of hanpen for 84 days as an initial study. Male, 6‐week‐old Sprague‐Dawley rats were divided into two groups: group I, fed normal diets, and group II, fed normal diets with 5% dried hanpen. Throughout the 84‐day treatment period, we checked body weight and food intake, and after 84 days, we performed organ weight and blood biochemical analyses. No significant differences were seen in body weight, food intake, organ weight, and most biochemical parameters between group I and group II. Interestingly, total cholesterol (T‐CHO) and high‐density lipoprotein cholesterol (HDL‐C) levels of group II were significantly higher than those of group I after administration for 84 days. Moreover, lactate dehydrogenase (LDH) level of group II was marked lower than that of group I, and other liver function parameters of group II tended to be lower than those of group I. As conclusion, “Hanpen,” a Japanese traditional food, could be effective as a functional food for human health management worldwide.
The timing of brittle deformation: An example from the Cenozoic faults in the Youjiang fold‐thrust belt in southwestern China
Authors: Qiu Liang , Yan Dan‐Ping , Yang Wen‐Xin , Cao Wentao , Ren Minghua , Gao Tian , Dong Jianmeng , Wang Fang‐Yue
Published: April 2020

The Cenozoic evolution of SE Asia is marked by thousands of kilometres extension on the continental margin, including normal faults, half‐grabens, and volcanic rocks, but dating of brittle faults in the shallow crust is difficult because of a lack of synkinematic minerals. The Cenozoic extension in the Youjiang fold‐thrust belt in southwest China is marked by brittle normal faults and half‐grabens filled with Paleogene sediments in the region. Here, we identified a strongly weathered mafic sill that was truncated by normal faults in the fold‐thrust belt and present the age and chemistry of zircons from a weathered sill. The zircons from the sill yielded a mean age of ~35 Ma. Integrating cross‐cutting relationship and zircon U–Pb dating suggest that the Cenozoic extension was initiated later than ~35 Ma in Youjiang fold‐thrust belt in southwest China. Combined with structural analysis and previous fission track data in the region, we suggest that the normal faults in this study provide evidence of surface fault activity of Cenozoic extension in SE Asia caused by retreat of a trench system. Furthermore, this study provides a case study to discuss how to decipher brittle normal faulting using zircon geochronology and structural and textural analysis from the mesoscale to the microscale.
ENIGMA‐DTI: Translating reproducible white matter deficits into personalized vulnerability metrics in cross‐diagnostic psychiatric research
Authors: Kochunov Peter , Hong L. Elliot , Dennis Emily L. , Morey Rajendra A. , Tate David F. , Wilde Elisabeth A. , Logue Mark , Kelly Sinead , Donohoe Gary , Favre Pauline , Houenou Josselin , Ching Christopher R. K. , Holleran Laurena , Andreassen Ole A. , van Velzen Laura S. , Schmaal Lianne , Villalón‐Reina Julio E. , Bearden Carrie E. , Piras Fabrizio , Spalletta Gianfranco , van den Heuvel Odile A. , Veltman Dick J. , Stein Dan J. , Ryan Meghann C. , Tan Yunlong , van Erp Theo G. M. , Turner Jessica A. , Haddad Liz , Nir Talia M. , Glahn David C. , Thompson Paul M. , Jahanshad Neda
Published: April 2020

The ENIGMA‐DTI (diffusion tensor imaging) workgroup supports analyses that examine the effects of psychiatric, neurological, and developmental disorders on the white matter pathways of the human brain, as well as the effects of normal variation and its genetic associations. The seven ENIGMA disorder‐oriented working groups used the ENIGMA‐DTI workflow to derive patterns of deficits using coherent and coordinated analyses that model the disease effects across cohorts worldwide. This yielded the largest studies detailing patterns of white matter deficits in schizophrenia spectrum disorder (SSD), bipolar disorder (BD), major depressive disorder (MDD), obsessive–compulsive disorder (OCD), posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and 22q11 deletion syndrome. These deficit patterns are informative of the underlying neurobiology and reproducible in independent cohorts. We reviewed these findings, demonstrated their reproducibility in independent cohorts, and compared the deficit patterns across illnesses. We discussed translating ENIGMA‐defined deficit patterns on the level of individual subjects using a metric called the regional vulnerability index (RVI), a correlation of an individual's brain metrics with the expected pattern for a disorder. We discussed the similarity in white matter deficit patterns among SSD, BD, MDD, and OCD and provided a rationale for using this index in cross‐diagnostic neuropsychiatric research. We also discussed the difference in deficit patterns between idiopathic schizophrenia and 22q11 deletion syndrome, which is used as a developmental and genetic model of schizophrenia. Together, these findings highlight the importance of collaborative large‐scale research to provide robust and reproducible effects that offer insights into individual vulnerability and cross‐diagnosis features.
Metastable neural dynamics underlies cognitive performance across multiple behavioural paradigms
Authors: Alderson Thomas H. , Bokde Arun L. W. , Kelso J. A. Scott , Maguire Liam , Coyle Damien
Published: April 2020

Despite resting state networks being associated with a variety of cognitive abilities, it remains unclear how these local areas act in concert to express particular cognitive operations. Theoretical and empirical accounts indicate that large‐scale resting state networks reconcile dual tendencies towards integration and segregation by operating in a metastable regime of their coordination dynamics. Metastability may confer important behavioural qualities by binding distributed local areas into large‐scale neurocognitive networks. We tested this hypothesis by analysing fMRI data in a large cohort of healthy individuals (N = 566) and comparing the metastability of the brain's large‐scale resting network architecture at rest and during the performance of several tasks. Metastability was estimated using a well‐defined collective variable capturing the level of 'phase‐locking' between large‐scale networks over time. Task‐based reasoning was principally characterised by high metastability in cognitive control networks and low metastability in sensory processing areas. Although metastability between resting state networks increased during task performance, cognitive ability was more closely linked to spontaneous activity. High metastability in the intrinsic connectivity of cognitive control networks was linked to novel problem solving or fluid intelligence, but was less important in tasks relying on previous experience or crystallised intelligence. Crucially, subjects with resting architectures similar or 'pre‐configured' to a task‐general arrangement demonstrated superior cognitive performance. Taken together, our findings support a key linkage between the spontaneous metastability of large‐scale networks in the cerebral cortex and cognition.