bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering of Nucleic Acids and Synthetic Cofactors as Holo Sensors for Probing Signaling Molecules in the Cellular Membrane Microenvironment
Authors: Feng Guangfu , Luo Xingyu , Lu Xu , Xie Shiyi , Deng Lu , Kang Wenyuan , He Fang , Zhang Jiaheng , Lei Chunyang , Lin Bin , Huang Yan , Nie Zhou , Yao Shouzhuo 
Published: March 2019

AbstractThe comprehensive understanding of the mechanisms underlying the interaction of cells with their membrane microenvironment is of great value for fundamental biological research; however, tracking biomolecules on cell surfaces with high temporal and spatial resolution remains a challenge. Herein, a modular strategy is presented for the construction of cell surface DNA‐based sensors by engineering DNA motifs and synthetic cofactors. In this strategy, a stimuli‐reactive organic molecule is employed as the cofactor for the DNA motif, and the self‐assembly of them forms a FRET‐based holo DNA‐based sensor. With the use of the DNA‐based sensors, the versatility of this modular strategy has been demonstrated in the ratiometric imaging of the cellular extrusion process of endogenous signaling molecules, including sulfur dioxide derivatives and nitric oxide.
Identification of Chemokine Ligands by Biochemical Fragmentation and Simulated Peptide Evolution
Authors: Fuchs Jens‐Alexander , Brunner Cyrill , Schineis Philipp , Hiss Jan A. , Schneider Gisbert 
Published: March 2019

AbstractShort linear peptides can overcome certain limitations of small molecules for targeting protein–protein interactions (PPIs). Herein, the interaction between the human chemokine CCL19 with chemokine receptor CCR7 was investigated to obtain receptor‐derived CCL19‐binding peptides. After identifying a linear binding site of CCR7, five hexapeptides binding to CCL19 in the low micromolar to nanomolar range were designed, guided by pharmacophore and lipophilicity screening of computationally generated peptide libraries. The results corroborate the applicability of the computational approach and the chosen selection criteria to obtain short linear peptides mimicking a protein–protein interaction site.
Quality of Sunflower Oil Obtained in the Main Producing Region of Brazil: Adherence to the Codex Alimentarius
Authors: de Carvalho Claudio Guilherme Portela , Mazzola Luana Fernanda , Caldeira Andressa , Dalchiavon Flávio Carlos , Mandarino José Marcos Gontijo 
Published: March 2019

AbstractThe objective of this work was to evaluate the quality of the oil extracted from sunflower achenes grown in Campo Novo de Parecis, the main producing region of Brazil, to optimize its use by the processing and food industries. In addition, the fatty acid profiles of the oil were checked for their adherence to the CODEX STAN 210–1999. Traditional and high‐oleic genotypes were grown between 2014 and 2017 during trials with a randomized complete block experimental design with four replications. The contents of oleic, linoleic, palmitic, and stearic acids were determined using gas chromatography. The fatty acid profiles of traditional genotypes were observed to be outside the ranges established by the CODEX, with an oleic acid content above 39.4% and linoleic, palmitic, and stearic acid values lower than 48.3%, 2.7%, and 5.0%, respectively, as well as high‐oleic sunflower oil with a stearic acid content of less than 2.6%. The availability of this information can, on the one hand, positively impact industries and encourage the use of better quality raw materials that are more technologically and nutritionally adequate. On the other hand, the commercialization of sunflower oil with a fatty acid profile outside the ranges established by CODEX can be difficult, because the contents are out of specification due to the climatic conditions in the cropping region.
Fuel‐Free Micro‐/Nanomotors as Intelligent Therapeutic Agents
Authors: Liu Lu , Gao Junbin , Wilson Daniela A. , Tu Yingfeng , Peng Fei 
Published: March 2019

AbstractThere are many efficient biological motors in Nature that perform complex functions by converting chemical energy into mechanical motion. Inspired by this, the development of their synthetic counterparts has aroused tremendous research interest in the past decade. Among these man‐made motor systems, the fuel‐free (or light, magnet, ultrasound, or electric field driven) motors are advantageous in terms of controllability, lifespan, and biocompatibility concerning bioapplications, when compared with their chemically powered counterparts. Therefore, this review will highlight the latest biomedical applications in the versatile field of externally propelled micro‐/nanomotors, as well as elucidating their driving mechanisms. A perspective into the future of the micro‐/nanomotors field and a discussion of the challenges we need to face along the road towards practical clinical translation of external‐field‐propelled micro‐/nanomotors will be provided.
Optimal cue aggregation in the absence of criterion knowledge
Authors: Zhao Wenjia Joyce , Davis‐Stober Clintin P. , Bhatia Sudeep 
Published: March 2019

AbstractThe study of multi‐cue judgment investigates how decision makers aggregate cues to predict the value of a criterion variable. We consider a multi‐cue judgment task in which decision makers have prior knowledge of inter‐cue relationships but are ignorant of how the cues correlate with the criterion. In this setting, a naive judgment strategy prescribes weighting the cues equally. Although many participants are well described via an equal weighting scheme, we find that a substantial minority of participants make predictions consistent with a weighting scheme based on a low‐dimensional projection of the cue space that optimally takes into account inter‐cue correlations. The use of such a weighting scheme is consistent with minimizing maximal error in prediction when the cue‐criterion relationships are unknown.
The effect of ketogenic diet on behaviors and synaptic functions of naive mice
Authors: Huang Jie , Li Yuan‐Quan , Wu Cui‐Hong , Zhang Yun‐Long , Zhao Shen‐Ting , Chen Yong‐Jun , Deng Yu‐Hong , Xuan Aiguo , Sun Xiang‐Dong 
Published: March 2019

AbstractIntroductionBeyond its application as an epilepsy therapy, the ketogenic diet (KD) has been considered a potential treatment for a variety of other neurological and metabolic disorders. However, whether KD promotes functional restoration by reducing the pathological processes underlying individual diseases or through some independent mechanisms is not clear.MethodsIn this study, we evaluated the effect of KD on a series of behaviors and synaptic functions of young adult naive mice. Wild‐type C57BL/6J mice at age of 2–3 months were fed with control diet or KD for three months. Body weight and caloric intake were monitored throughout the experiments. We assessed behavioral performance with seizure induction, motor coordination and activity, anxiety level, spatial learning and memory, sociability, and depression. Synaptic transmission and long‐term potentiation were also recorded.ResultsKD‐fed mice performed equivalent to control‐diet‐fed mice in the behavioral tests and electrophysiological assays except exhibiting slower weight gain and increased seizure threshold.ConclusionsOur results contribute to the better understanding of effects of the KD on physiological behaviors and synaptic functions.
Identification of mNeonGreen as a pH‐Dependent, Turn‐On Fluorescent Protein Sensor for Chloride
Authors: Tutol Jasmine N. , Kam Hiu C. , Dodani Sheel C. 
Published: March 2019

AbstractChloride‐sensitive fluorescent proteins generated from laboratory evolution have a characteristic tyrosine residue that interacts with a chloride ion and π‐stacks with the chromophore. However, the engineered yellow‐green fluorescent protein mNeonGreen lacks this interaction but still binds chloride, as seen in a recently reported crystal structure. Based on its unique coordination sphere, we were curious if chloride could influence the optical properties of mNeonGreen. Here, we present the structure‐guided identification and spectroscopic characterization of mNeonGreen as a turn‐on fluorescent protein sensor for chloride. Our results show that chloride binding lowers the chromophore pKa and shifts the equilibrium away from the weakly fluorescent phenol form to the highly fluorescent phenolate form, resulting in a pH‐dependent, turn‐on fluorescence response. Moreover, through mutagenesis, we link this sensing mechanism to a non‐coordinating residue in the chloride binding pocket. This discovery sets the stage to further engineer mNeonGreen as a new fluorescent protein‐based tool for imaging cellular chloride.
[Co(TPP)]‐Catalyzed Formation of Substituted Piperidines
Authors: Lankelma Marianne , Olivares Astrid M. , de Bruin Bas 
Published: March 2019

AbstractRadical cyclization via cobalt(III)‐carbene radical intermediates is a powerful method for the synthesis of (hetero)cyclic structures. Building on the recently reported synthesis of five‐membered N‐heterocyclic pyrrolidines catalyzed by CoII porphyrins, the [Co(TPP)]‐catalyzed formation of useful six‐membered N‐heterocyclic piperidines directly from linear aldehydes is presented herein. The piperidines were obtained in overall high yields, with linear alkenes being formed as side products in small amounts. A DFT study was performed to gain a deeper mechanistic understanding of the cobalt(II)‐porphyrin‐catalyzed formation of pyrrolidines, piperidines, and linear alkenes. The calculations showed that the alkenes are unlikely to be formed through an expected 1,2‐hydrogen‐atom transfer to the carbene carbon. Instead, the calculations were consistent with a pathway involving benzyl‐radical formation followed by radical‐rebound ring closure to form the piperidines. Competitive 1,5‐hydrogen‐atom transfer from the β‐position to the benzyl radical explained the formation of linear alkenes as side products.
A Neutral Germanium/Phosphorus Frustrated Lewis Pair and Its Contrasting Reactivity Compared to Its Silicon Analogue
Authors: Kinder Timo A. , Pior René , Blomeyer Sebastian , Neumann Beate , Stammler Hans‐Georg , Mitzel Norbert W. 
Published: March 2019

AbstractChlorogermane (C2F5)3GeCl with very electronegative pentafluoroethyl groups was converted with LiCH2P(tBu)2 to obtain the intramolecular frustrated Lewis pair (FLP) (C2F5)3GeCH2P(tBu)2, a neutral, germanium‐based FLP. Its reactivity was compared to its silicon homologue (C2F5)3SiCH2P(tBu)2. Both FLPs cleave NO but give cyclic (Si) and open‐chain oxides (Ge). In reactions with HCl both FLPs gave the same adduct type in the solid state, while the proton seems more mobile in solution in the germanium case. Reactions with PhCNO and Me3SiCHN2 result in ring‐type adducts. The structures of (C2F5)3GeCH2P(tBu)2 and of five adducts with substrates were elucidated by X‐ray diffraction. The study clearly showed the germanium compound to have a more moderate Lewis acidity compared to the silicon analogue.
Regioselective Oxidative Ring Cleavage of Antiaromatic Nickel(II) Norcorrole to Dialkoxybis(dipyrrin)s
Authors: Shafie Siham A. , Kawashima Hiroyuki , Miyake Yoshihiro , Shinokubo Hiroshi 
Published: March 2019

AbstractThe Ni(II) complex of meso‐dimesitylnorcorrole is a stable 16π antiaromatic porphyrinoid. We have previously reported that the reaction of the norcorrole Ni(II) complex with m‐chloroperbenzoic acid resulted in oxygen insertion to afford the corresponding 10‐ oxacorrole Ni(II) complex, which is an 18π aromatic porphyrinoid. In sharp contrast, we have found that treatment of the norcorrole Ni(II) complex with bis[(trifluoroacetoxy)iodo]benzene in the presence of a variety of alcohols induced a ring‐opening reaction to furnish the corresponding dialkoxybis(dipyrrin)s through regioselective oxidative C−C bond cleavage. Furthermore, dihydroxybis(dipyrrin) exhibited solvent‐dependent absorption and emission behavior through keto−enol tautomerization of the hydroxy groups.
Effects of prenatal alcohol exposure on social competence: Asymmetry in play partner preference among heterogeneous triads of male and female rats
Authors: Holman Parker J. , Baglot Samantha L. , Morgan Erin , Weinberg Joanne 
Published: March 2019

AbstractSocial behavior deficits associated with prenatal alcohol exposure (PAE) are frequently described in terms of impaired social competence, which can be defined as the effectiveness in social interaction and the ability to employ social skills successfully within different interpersonal contexts. Play behavior—which peaks during adolescence—is critical for developing social competence, as well as for motor, cognitive, and emotional development. Studies of play behavior typically utilize protocols where animals interact in dyads. However, less is understood about how the social environment may shape PAE‐related social behavior deficits, particularly in more complex social contexts. Here, we assess play partner preference utilizing a novel approach in which adolescent male and female animals interact within same‐sex triads comprised of animals from mixed prenatal treatments to determine how play partner identity and social group composition interact to shape behavior. When triads included one PAE animal and two control animals (i.e., control animals had the option to play either with a fellow control or a PAE playmate), we observed play target asymmetry whereby controls preferentially played with fellow controls. Notably, these results were consistent for triads of both males and females, with subtle differences in frequency of initiations versus reciprocations. We found no play target asymmetry, however, when triads included two PAE animals and one control animal or different configurations of control and pair‐fed animals. Taken together, play target asymmetry resulting from ineffective social interactions, including a failure to engage with, respond to, and/or solicit play from control play partners appropriately, suggests that PAE negatively impacts the development of social competence.
Kidney organoids in translational medicine: Disease modeling and regenerative medicine
Authors: Miyoshi Tomoya , Hiratsuka Ken , Saiz Edgar Garcia , Morizane Ryuji 
Published: March 2019

AbstractThe kidney is one of the most complex organs composed of multiple cell types, functioning to maintain homeostasis by means of the filtering of metabolic wastes, balancing of blood electrolytes, and adjustment of blood pressure. Recent advances in 3D culture technologies in vitro enabled the generation of “organoids” which mimic the structure and function of in vivo organs. Organoid technology has allowed for new insights into human organ development and human pathophysiology, with great potential for translational research. Increasing evidence shows that kidney organoids are a useful platform for disease modeling of genetic kidney diseases when derived from genetic patient iPSCs and/or CRISPR‐mutated stem cells. Although single cell RNA‐seq studies highlight the technical difficulties underlying kidney organoid generation reproducibility and variation in differentiation protocols, kidney organoids still hold great potential to understand kidney pathophysiology as applied to kidney injury and fibrosis. In this review, we summarize various studies of kidney organoids, disease modeling, genome‐editing, and bioengineering, and additionally discuss the potential of and current challenges to kidney organoid research.
LPA1, LPA2, LPA4, and LPA6 receptor expression during mouse brain development
Authors: Suckau Olga , Gross Isabel , Schrötter Sandra , Yang Fan , Luo Jiankai , Wree Andreas , Chun Jerold , Baska David , Baumgart Jan , Kano Kuniyuki , Aoki Junken , Bräuer Anja U. 
Published: March 2019

AbstractBackgroundLPA is a small bioactive phospholipid that acts as an extracellular signaling molecule and is involved in cellular processes, including cell proliferation, migration, and differentiation. LPA acts by binding and activating at least six known G protein–coupled receptors: LPA1–6. In recent years, LPA has been suggested to play an important role both in normal neuronal development and under pathological conditions in the nervous system.ResultsWe show the expression pattern of LPA receptors during mouse brain development by using qRT‐PCR, in situ hybridization, and immunocytochemistry. Only LPA
1, LPA
2, LPA
4, and LPA
6 mRNA transcripts were detected throughout development stages from embryonic day 16 until postnatal day 30 of hippocampus, neocortex, cerebellum, and bulbus olfactorius in our experiments, while expression of LPA
3 and LPA
5 genes was below detection level. In addition to our qRT‐PCR results, we also analyzed the cellular protein expression of endogenous LPA receptors, with focus on LPA1 and LPA2 within postnatal brain slices and primary neuron differentiation with and without cytoskeleton stabilization and destabilization.ConclusionsThe expression of LPA receptors changes depends on the developmental stage in mouse brain and in cultured hippocampal primary neurons. Interestingly, we found that commercially available antibodies for LPA receptors are largely unspecific.
Diet and macronutrient niche of Asiatic black bear (Ursus thibetanus) in two regions of Nepal during summer and autumn
Authors: Panthi Saroj , Aryal Achyut , Coogan Sean C. P. 
Published: March 2019

AbstractRelatively little is known about the nutritional ecology of omnivorous Asiatic black bears (Ursus thibetanus) in Nepal. We characterized the diet of black bears in two seasons (June–July, “summer”; and October–November “autumn”) and two study areas (Dhorpatan Hunting Reserve [DHR]; and Kailash Sacred Landscape [KSL]). We then conducted nutritional analysis of species consumed by black bears in each study area, in combination with nutritional estimates from the literature, to estimate the proportions of macronutrients (i.e., protein [P], lipid [L], and carbohydrate [C]) in the seasonal bear foods and diets, as well as their macronutrient niche breadth. We found that bamboo (Arundinaria spp.) had the highest relative frequency in both study areas and seasons. Ants and termites were found in DHR diets, but not KSL diets. One anthropogenic crop was found in DHR summer diets (Zea mays) and two were found in KSL summer diets (Z. mays; and Kodo millet [Paspalum scrobiculatum]). Other than insects, no animal prey was found in either diet. The proportions of macronutrients in diets (i.e., realized macronutrient niches) were relatively high in carbohydrate for both study areas and seasons: DHRsummer 24.1P:8.7L:67.2C; KSLsummer 16.7P:8.2L:75.1C; DHRautumn 21.1P:10.5L:68.4C; KSHautumn 19.0P:11.0L:70.0C. Macronutrient niche breadth was 3.1 × greater in the DHR than KSL during summer, and 4.0 × greater in the autumn, primarily due to the higher proportion of lipid in ants and termites relative to plant foods. Within‐study area differences in niche breadth were greater during summer than autumn; in the KSH the macronutrient breadth was 1.4 × greater in summer, while in the DHR it was 1.1 × greater in summer. Similarity in dietary macronutrient proportions despite differences in foods consumed and niche breadth are suggestive of foraging to reach a preferred macronutrient balance.
Sampling related individuals within ponds biases estimates of population structure in a pond‐breeding amphibian
Authors: O'Connell Kyle A. , Mulder Kevin P. , Maldonado Jose , Currie Kathleen L. , Ferraro Dennis M. 
Published: March 2019

AbstractEffective conservation and management of pond‐breeding amphibians depends on the accurate estimation of population structure, demographic parameters, and the influence of landscape features on breeding‐site connectivity. Population‐level studies of pond‐breeding amphibians typically sample larval life stages because they are easily captured and can be sampled nondestructively. These studies often identify high levels of relatedness between individuals from the same pond, which can be exacerbated by sampling the larval stage. Yet, the effect of these related individuals on population genetic studies using genomic data is not yet fully understood. Here, we assess the effect of within‐pond relatedness on population and landscape genetic analyses by focusing on the barred tiger salamanders (Ambystoma mavortium) from the Nebraska Sandhills. Utilizing genome‐wide SNPs generated using a double‐digest RADseq approach, we conducted standard population and landscape genetic analyses using datasets with and without siblings. We found that reduced sample sizes influenced parameter estimates more than the inclusion of siblings, but that within‐pond relatedness led to the inference of spurious population structure when analyses depended on allele frequencies. Our landscape genetic analyses also supported different models across datasets depending on the spatial resolution analyzed. We recommend that future studies not only test for relatedness among larval samples but also remove siblings before conducting population or landscape genetic analyses. We also recommend alternative sampling strategies to reduce sampling siblings before sequencing takes place. Biases introduced by unknowingly including siblings can have significant implications for population and landscape genetic analyses, and in turn, for species conservation strategies and outcomes.
Offspring mass variation in tree swallows: A case of bet‐hedging?
Authors: Gossieaux Philippine , Leclerc Martin , Van de Walle Joanie , Poisson Yoanna , Toni Pauline , Landes Julie , Bourret Audrey , Garant Dany , Pelletier Fanie , Bélisle Marc 
Published: March 2019

AbstractThe evolution of reproductive strategies is affected by the ability of organisms to deal with future environmental conditions. When environments are temporally unpredictable, however, it is difficult to anticipate optimal offspring phenotype. Diversification of offspring phenotypes, a strategy called diversified bet‐hedging, may allow parents to maximize their fitness by reducing between‐year variation in reproductive success. The link between diversification of offspring phenotypes and individual reproductive success, however, has rarely been documented empirically. We used an eight‐year dataset (1215 broods, 870 females) on individually marked tree swallows (Tachycineta bicolor) to assess whether intra‐brood mass variation was compatible with a diversified bet‐hedging strategy. Intra‐brood mass variation was weakly, but significantly repeatable within females, suggesting consistent individual differences. Greater intra‐brood mass variation, however, was not associated with reduced between‐year variation in reproductive success or increased female reproductive success. Moreover, contrary to diversified bet‐hedging expectations, fledging success of large broods was greater when hatchlings had similar rather than variable masses. Our results suggest that intra‐brood mass variation may not result from diversified bet‐hedging, but rather from complex interactions between environmental, brood, and maternal characteristics.