bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualizing synaptic plasticity in vivo by large-scale imaging of endogenous AMPA receptors
Authors: Graves Austin R. , Roth Richard H. , Tan Han L. , Zhu Qianwen , Bygrave Alexei M. , Lopez-Ortega Elena , Hong Ingie , Spiegel Alina C. , Johnson Richard C. , Vogelstein Joshua T. , Tward Daniel J. , Miller Michael I. , Huganir Richard L.
Published: March 2020

Elucidating how synaptic molecules such as AMPA receptors mediate neuronal communication and tracking their dynamic expression during behavior is crucial to understand cognition and disease, but current technological barriers preclude large-scale exploration of molecular dynamics in vivo. We have developed a suite of innovative methodologies that break through these barriers: a new knockin mouse line with fluorescently tagged endogenous AMPA receptors, two-photon imaging of hundreds of thousands of labeled synapses in behaving mice, and computer-vision-based automatic synapse detection. Using these tools, we can longitudinally track how the strength of synapses changes during behavior. We used this approach to generate an unprecedentedly detailed spatiotemporal map of synaptic plasticity underlying sensory experience. More generally, these tools can be used as an optical probe capable of measuring functional synapse strength across entire brain areas during any behavioral paradigm, describing complex system-wide changes with molecular precision.
Identification and genomic analysis of pedigrees with exceptional longevity identifies candidate rare variants
Authors: Miller Justin B. , Ward Elizabeth , Staley Lyndsay A. , Stevens Jeffrey , Teerlink Craig C , Tavana Justina P. , Cloward Matthew , Page Madeline , Dayton Louisa ,   Alzheimer’s Disease Genetics Consortium, Cannon-Albright Lisa A. , Kauwe John S.K.
Published: March 2020

Background

Longevity as a phenotype entails living longer than average and typically includes living without chronic age-related diseases. Recently, several common genetic components to longevity have been identified. This study aims to identify additional rare genetic variants associated with longevity using unique and powerful pedigree-based analyses of pedigrees with a statistical excess of healthy elderly individuals identified in the Utah Population Database (UPDB).

Methods

From an existing biorepository of Utah pedigrees, four pedigrees were identified which exhibited an excess of healthy elderly individuals; whole exome sequencing (WES) was performed on one set of elderly first- or second-cousins from each pedigree. Rare (<0.01 population frequency) variants shared by at least one elderly cousin pair in a region likely to be identical by descent were identified as candidates. Ingenuity Variant Analysis was used to prioritize putative causal variants based on quality control, frequency, and gain or loss of function. The variant frequency was compared in healthy cohorts and in an Alzheimer’s disease cohort. Remaining variants were filtered based on their presence in genes reported to have an effect on the aging process, aging of cells, or the longevity process. Validation of these candidate variants included tests of segregation to other elderly relatives.

Results

Fifteen rare candidate genetic variants spanning 17 genes shared within cousins were identified as having passed prioritization criteria. Of those variants, six were present in genes that are known or predicted to affect the aging process: rs78408340 (PAM), rs112892337 (ZFAT), rs61737629 (ESPL1), rs141903485 (CEBPE), rs144369314 (UTP4), and rs61753103 (NUP88 and RABEP1). ESPL1 rs61737629 and CEBPE rs141903485 show additional evidence of segregation with longevity in expanded pedigree analyses (p-values=0.001 and 0.0001, respectively).

Discussion

This unique pedigree analysis efficiently identified several novel rare candidate variants that may affect the aging process and added support to seven genes that likely contribute to longevity. Further analyses showed evidence for segregation for two rare variants, ESPL1 rs61737629 and CEBPE rs141903485, in the original longevity pedigrees in which they were originally observed. These candidate genes and variants warrant further investigation.
Switching secretory pathway direction for organelle acquisition in plants
Authors: Kanazawa Takehiko , Morinaka Hatsune , Ebine Kazuo , Shimada Takashi L. , Ishida Sakiko , Minamino Naoki , Yamaguchi Katsushi , Shigenobu Shuji , Kohchi Takayuki , Nakano Akihiko , Ueda Takashi
Published: March 2020

Eukaryotic cells acquired novel organelles during evolution through mechanisms that remain largely obscure. The existence of the unique oil body compartment is a synapomorphy of liverworts that represents lineage-specific acquisition of this organelle during evolution, although its origin, biogenesis, and physiological function are yet unknown. We found that two Syntaxin 1 paralogs in the liverwort,Marchantia polymorpha, are distinctly targeted to forming cell plates and the oil body, suggesting these structures share some developmental similarity. Oil body formation is under the regulation of an ERF/AP2-type transcription factor and loss of the oil body increasedM. polymorphaherbivory. These findings highlight a common strategy for the acquisition of organelles with distinct functions in plants, via periodical switching in secretion direction depending on cellular phase transition.
The Madingley General Ecosystem Model predicts bushmeat yields, species extinction rates and ecosystem-level impacts of bushmeat harvesting
Authors: Barychka Tatsiana , Mace Georgina M. , Purves Drew W.
Published: March 2020

Traditional approaches to guiding decisions about harvesting bushmeat often employ single-species population dynamic models, which require species- and location-specific data, are missing ecological processes such as multi-trophic interactions, cannot represent multi-species harvesting, and cannot predict the broader ecosystem impacts of harvesting. In order to explore an alternative approach to devising sustainable harvesting strategies, we employ the Madingley General Ecosystem Model, which can simulate ecosystem dynamics in response to multi-species harvesting given nothing other than location-specific climate data. We used the model to examine yield, extinctions, and broader ecosystem impacts, for a range of harvesting intensities of duiker-sized ectothermic herbivores. Duiker antelope (such asCephalophus callipygusandCephalophus dorsalis) are the most heavily hunted species in sub-Saharan Africa, contributing 34%-95% of all bushmeat in the Congo Basin. Across a range of harvesting rates, the Madingley model gave estimates for optimal harvesting rate, and extinction rate, that were qualitatively and quantitatively similar to the estimates from single-species Beverton-Holt model. Predicted yields were somewhat greater (around 5 times, on average) for the Madingley model, which would be expected given that the Madingley simulates multi-species harvesting from an initially pristine ecosystem. This match increased the degree of confidence with which we could examine other predictions from the ecosystem model, as follows. At medium and high levels of harvesting of duiker-sized herbivores, there were statistically significant, but moderate, reductions in the densities of the targeted functional group; increases in small-bodied herbivores; decreases in large-bodied carnivores; and minimal ecosystem-level impacts overall. The results suggest that general ecosystem models such as the Madingley model could be used more widely to help estimate sustainable harvesting rates, bushmeat yields and broader ecosystem impacts across different locations and target species.
Amorphous nickel titanium alloy film: a new choice for cryo electron microscopy sample preparation
Authors: Huang Xiaojun , Zhang Lei , Wen Zuoling , Chen Hui , Li Shuoguo , Ji Gang , Yin Chang-cheng , Sun Fei
Published: March 2020

Cryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increase successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including superior electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.
Honey bees solve a multi-comparison ranking task by probability matching
Authors: MaBouDi HaDi , Marshall James A.R. , Barron Andrew B.
Published: March 2020

Honey bees forage on a range of flowers, all of which can vary unpredictably in the amount and type of rewards they offer. In this environment bees are challenged with maximising the resources they gather for their colony. That bees are effective foragers is clear, but how bees solve this type of complex multi-choice task is unknown. Here we challenged bees with a five-comparison choice task in which five colours differed in their probability of offering reward and punishment. The colours were ranked such that high ranked colours were more likely to offer reward, and the ranking was unambiguous. Bees choices in unrewarded tests matched their individual experiences of reward and punishment of each colour, indicating bees solved this test not by comparing or ranking colours but by matching their preferences to their history of reinforcement for each colour. We used a computational model to explore the feasibility of this probability matching strategy for the honey bee brain. The model suggested a structure like the honey bee mushroom body with reinforcement-related plasticity at both input and output was sufficient for this cognitive strategy. We discuss how probability matching enables effective choices to be made without a need to compare any stimuli directly, and the utility and limitations of this simple cognitive strategy for foraging animals.
A DOT1B/Ribonuclease H2 protein complex is involved in R-loop processing, genomic integrity and antigenic variation inTrypanosoma brucei
Authors: Eisenhuth Nicole , Vellmer Tim , Butter Falk , Janzen Christian J.
Published: March 2020

The parasiteTrypanosoma bruceiperiodically changes the expression of protective variant surface glycoproteins (VSGs) to evade its host’s immune system in a process known as antigenic variation. One route to change VSG expression is the transcriptional activation of a previously silent VSG expression site (ES), a subtelomeric region containing theVSGgenes. Homologous recombination of a differentVSGfrom a large reservoir into the active ES represents another route. The conserved histone methyltransferase DOT1B is involved in transcriptional silencing of inactive ES and influences ES switching kinetics. The molecular machinery that enables DOT1B to execute these regulatory functions remains elusive, however. To better understand DOT1B-mediated regulatory processes, we purified DOT1B-associated proteins using complementary biochemical approaches. We identified several novel DOT1B-interactors. One of these was the Ribonuclease H2 complex, previously shown to resolve RNA-DNA hybrids, maintain genome integrity, and play a role in antigenic variation. Our study revealed that DOT1B depletion results in an increase in RNA-DNA hybrids, accumulation of DNA damage and recombination-based ES switching events. Surprisingly, a similar pattern of VSG deregulation was observed in Ribonuclease H2 mutants. We propose that both proteins act together in resolving R-loops to ensure genome integrity and contribute to the tightly-regulated process of antigenic variation.
Early-life social experience shapes social avoidance reactions in larval zebrafish
Authors: Groneberg Antonia H. , Marques João C. , Martins A. Lucas , de Polavieja Gonzalo G. , Orger Michael B.
Published: March 2020

Social experiences greatly define successive social behavior. Lack of such experiences, especially during critical phases of development, can severely impede the ability to behave adequately in social contexts. To date it is not well characterized how early-life social isolation leads to social deficits and impacts development. In many model species, it is challenging to fully control social experiences, because they depend on parental care. Moreover, complex social behaviors involve multiple sensory modalities, contexts, and actions. Hence, when studying social isolation effects, it is particularly important to parse apart social deficits from general developmental effects, such as abnormal motor learning. Here, we characterized how social experiences during early development of zebrafish larvae modulate their social behavior, at one week of age, when social avoidance reactions can be measured as discrete swim events. We show that raising larvae in social isolation leads to enhanced social avoidance, in terms of reaction distance and reaction strength. Specifically, larvae raised in isolation use a high-acceleration escape swim bout, the short latency C-start, more frequently during social interactions. These behavioral differences are absent in non-social contexts. By ablating the lateral line and presenting the fish with local water vibrations, we show that lateral line inputs are both necessary and sufficient to drive enhanced social avoidance reactions. Taken together, our results show that social experience during development is a critical factor in shaping mechanosensory avoidance reactions in larval zebrafish.

Highlights

Larval zebrafish raised in isolation show enhanced social avoidance reactions

Enhanced avoidance is composed of increased avoidance distances and usage of high acceleration escape swims

The lateral line sensory organ is necessary and sufficient for the increased usage of high acceleration escape swims
Unraveling reproducible dynamic states of individual brain functional parcellation
Authors: Boukhdhir Amal , Zhang Yu , Mignotte Max , Bellec Pierre
Published: March 2020

Data-driven parcellations are widely used for exploring the functional organization of the brain, and also for reducing the high dimensionality of fMRI data. Despite the flurry of methods proposed in the literature, functional brain parcellations are not highly reproducible at the level of individual subjects, even with very long acquisitions. Some brain areas are also more difficult to parcellate than others, with association heteromodal cortices being the most challenging. An important limitation of classical parcellations is that they are static, i.e. they neglect dynamic reconfigurations of brain networks. In this paper, we proposed a new method to identify dynamic states of parcellations, which we hypothesized would improve reproducibility over static parcellation approaches. For a series of seed voxels in the brain, we applied a cluster analysis to regroup short (3 minutes) time windows into “states” with highly similar seed parcels. We splitted individual time series of the Midnight scan club sample into two independent sets of 2.5 hours (test and retest). We found that average within-state parcellations, called stability maps, were highly reproducible (over .9 test-retest spatial correlation in many instances) and subject specific (fingerprinting accuracy over 70% on average) between test and retest. Consistent with our hypothesis, seeds in heteromodal cortices (posterior and anterior cingulate) showed a richer repertoire of states than unimodal (visual) cortex. Taken together, our results indicate that static functional parcellations are incorrectly averaging well-defined and distinct dynamic states of brain parcellations. This work calls to revisit previous methods based on static parcellations, which includes the majority of published network analyses of fMRI data. Our method may, thus, impact how researchers model the rich interactions between brain networks in health and disease.
Shape-to-graph Mapping Method for Efficient Characterization and Classification of Complex Geometries in Biological Images
Authors: Pilcher William , Yang Xingyu , Zhurikhina Anastasia , Chernaya Olga , Xu Yinghan , Qiu Peng , Tsygankov Denis
Published: March 2020

With the ever-increasing quality and quantity of imaging data in biomedical research comes the demand for computational methodologies that enable efficient and reliable automated extraction of the quantitative information contained within these images. One of the challenges in providing such methodology is the need for tailoring algorithms to the specifics of the data, limiting their areas of application. Here we present a broadly applicable approach to quantification and classification of complex shapes and patterns in biological or other multi-component formations. This approach integrates the mapping of all shape boundaries within an image onto a global information-rich graph and machine learning on the multidimensional measures of the graph. We demonstrated the power of this method by (1) extracting subtle structural differences from visually indistinguishable images in our phenotype rescue experiments using the endothelial tube formations assay, (2) training the algorithm to identify biophysical parameters underlying the formation of different multicellular networks in our simulation model of collective cell behavior, and (3) analyzing the response of U2OS cell cultures to a broad array of small molecule perturbations.

Author Summary

In this paper, we present a methodology that is based on mapping an arbitrary set of outlines onto a complete, strictly defined structure, in which every point representing the shape becomes a terminal point of a global graph. Because this mapping preserves the whole complexity of the shape, it allows for extracting the full scope of geometric features of any scale. Importantly, an extensive set of graph-based metrics in each image makes integration with machine learning routines highly efficient even for a small data sets and provide an opportunity to backtrack the subtle morphological features responsible for the automated distinction into image classes. The resulting tool provides efficient, versatile, and robust quantification of complex shapes and patterns in experimental images.
Alleviating chronic ER stress by p38-Ire1-Xbp1 pathway and insulin-associated autophagy inC. elegansneurons
Authors: Guan Liying , Zhan Zhigao , Yang Yongzhi , Miao Yue , Huang Xun , Ding Mei
Published: March 2020

ER stress occurs in many physiological and pathological conditions. However, how chronic ER stress is alleviated in specific cells in an intact organism is an outstanding question. Here, overexpressing the gap junction protein UNC-9 (Uncoordinated) inC. elegansneurons triggers the Ire1-Xbp1-mediated stress response in an age-dependent and cell-autonomous manner. The p38 MAPK PMK-3 acts upon the phosphorylation of IRE-1 to regulate chronic stress. Overexpressing gap junction protein also activates autophagy and the insulin pathway functions through autophagy, but not the transcription of genes encoding ER chaperones, to counteract the p38-Ire1-Xbp1-mediated stress response. Together, these results reveal an intricate cellular regulatory network in response to chronic stress in a subset of cells in multicellular organism.

Author Summary

The accumulation of unfolded proteins triggers the ER stress response (UPR), which allows cells to fight against fluctuations in protein expression under both physiological and pathological conditions. Severe acute ER stress responses can be induced by drug treatment. However, such intense ER stress rarely occurs ubiquitously in every cell typein vivo. Here, we designed a genetic system in the nematodeC. elegans, which allows us to induce ER stress in specific cells, without drug treatment or any other external stimuli, and then to monitor the stress response. Using this system, genetic screens identified that the p38 MAPK directly acts through the IRE-1-XBP-1 branch of the UPR to promote the stress response. Meanwhile, the insulin receptor functions through autophagy activation to counteract the p38-IRE-1-XBP-1 pathway. Together, these results reveal an intricate cellular regulatory network in response to chronic stress in multicellular organism.
Long-term associations and insights on social structure of the Humpback whales in Prince William Sound, Alaska
Authors: von Ziegesar Olga , Gill Shelley , Goodwin Beth
Published: March 2020

Humpback whale (Megaptera novaeangliae) social structure is more complex than previously thought. Because of the fluid “fission-fusion” nature of their relationships: individuals foraging, traveling, and socializing with a number of animals, where associations form and are broken numerous times, little has been confirmed about their long-term associations. Humpback whales of the North Pacific Ocean migrate annually between tropical breeding areas to northern latitudes where they congregate and feed. The purpose of this study was to explore the social and feeding habits of the summer population of humpback whales returning to Prince William Sound (PWS) in the south central coast of Alaska. Fluke photographs of pigmentation patterns were used to document individual whales between the years 1983 and 2009 to determine, population characteristics, reproductive rates, long-term associations, feeding habits and spatial partitioning. During the 27 year study period there were 3,017 encounters with 405 unique whales. Forty of these whales (9.88%) had long sighting histories, showing strong site fidelity. Association indices for all pairs of whales were calculated. Long-lasting associations were found between thirty-two of the forty whales. Two distinct groups were determined by the highest association coefficients. Although the overall ranges of the two groups overlapped, they did not often mingle and offspring did not join their maternal group. All but two females had enduring bonds with at least one male. Associate males were sometimes found at a distance from others of their “clan” and would rejoin periodically. Two whales from one of these clans were found together in Hawaiian waters, a male escorting a female with a newborn calf, suggesting these long lasting associations endure through migration and into the southern breeding areas. Optimal observation conditions of a small population of humpback whales in sheltered waters allowed the discovery of two social groups enduring almost three decades.
A 3K Axiom®SNP array from a transcriptome-wide SNP resource sheds new light on the genetic diversity and structure of the iconic subtropical conifer treeAraucaria angustifolia(Bert.) Kuntze
Authors: Silva Pedro I.T. , Silva-Junior Orzenil Bonfim , Resende Lucileide V. , Sousa Valderes A. , Aguiar Ananda V. , Grattapaglia Dario
Published: March 2020

High-throughput SNP genotyping has become a precondition to move to higher precision and wider genome coverage genetic analysis of natural and breeding populations of non-model species. We developed a 44,318 annotated SNP catalog forAraucaria angustifolia, a grandiose subtropical conifer tree, one of the only two native Brazilian gymnosperms, critically endangered due to its valuable wood and seeds. Following transcriptome assembly and annotation, SNPs were discovered from RNA-seq and pooled RAD-seq data. From the SNP catalog, an Axiom®SNP array with 3,038 validated SNPs was developed and used to provide a comprehensive look at the genetic diversity and structure of 15 populations across the natural range of the species. RNA-seq was a far superior source of SNPs when compared to RAD-seq in terms of conversion rate to polymorphic markers on the array, likely due to the more efficient complexity reduction of the huge conifer genome. By matching microsatellite and SNP data on the same set ofA. angustifoliaindividuals, we show that SNPs reflect more precisely the actual genome-wide patterns of genetic diversity and structure, challenging previous microsatellite-based assessments. Moreover, SNPs corroborated the known major north-south genetic cline, but allowed a more accurate attribution to regional versus among-population differentiation, indicating the potential to select ancestry-informative markers. The availability of a public, user-friendly 3K SNP array forA. angustifoliaand a catalog of 44,318 SNPs predicted to provide ∼29,000 informative SNPs across ∼20,000 loci across the genome, will allow tackling still unsettled questions on its evolutionary history, toward a more comprehensive picture of the origin, past dynamics and future trend of the species’ genetic resources. Additionally, but not less importantly, the SNP array described, unlocks the potential to adopt genomic prediction methods to accelerate the still very timid efforts of systematic tree breeding ofA. angustifolia.
Citric Acid Water as an Alternative to Water Restriction for High-Yield Mouse Behavior
Authors: Urai Anne E , Aguillon-Rodriguez Valeria , Laranjeira Inês C , Cazettes Fanny ,   The International Brain Laboratory, Mainen Zachary F , Churchland Anne K
Published: March 2020

Abstract

Powerful neural measurement and perturbation tools have positioned mice as an ideal species for probing the neural circuit mechanisms of cognition. Crucial to this success is the ability to motivate animals to perform specific behaviors. One successful strategy is to restrict their water intake, rewarding them with water during a behavioral task. However, water restriction requires rigorous monitoring of animals’ health and hydration status and can be challenging for some mice.

We present an alternative that allows mice more control over their water intake: free home-cage access to water, made slightly sour by a small amount of citric acid (CA). In a previous study, rats with free access to CA water readily performed a behavioral task for water rewards, although completing fewer trials than under water restriction (Reinagel, 2018). We here extend this approach to mice and confirm its robustness across multiple laboratories.

Mice reduced their intake of CA water while maintaining healthy weights. Continuous home-cage access to CA water only subtly impacted their willingness to perform a decision-making task, in which they were rewarded with sweetened water. When free CA water was used instead of water restriction only on weekends, learning and decision-making behavior were unaffected. CA water is thus a promising alternative to water restriction, allowing animals more control over their water intake without interfering with behavioral performance.

SignificanceStatement

High-throughput, reliable behavioral training is a key requirement for the use of mice in behavioral and systems neuroscience, but depends crucially on ability to motivate animals to perform specific behaviors. Here, we present an alternative method to commonly used methods of water restriction: free home-cage access to water, made slightly sour by a small amount of citric acid. This non-labor-intensive, low-error option benefits animal health without hindering behavioral training progress. Citric acid water can serve as a reliable and standardized strategy to achieve high quality task behavior, further facilitating the use of mice in high-throughput behavioral studies.
Real-time 3D Single Molecule Tracking
Authors: Hou Shangguo , Exell Jack , Welsher Kevin
Published: March 2020

To date, single molecule studies have been reliant on tethering or confinement to achieve long duration and high temporal resolution measurements. Here, we present a 3D single-molecule active real-time tracking method (3D-SMART) which is capable of “locking on” to single fluorophores in solution for minutes at a time with photon limited temporal resolution. As a demonstration, 3D-SMART was applied to actively track single Atto 647N fluorophores in 90% glycerol solution with an average duration of ~16 s at count rates of ~10 kHz. Active feedback tracking was further applied to single proteins and nucleic acids, directly measuring the diffusion coefficient of various lengths (99 to 1385 bp) of single DNA molecules at speeds up to 10 μm2/s. In addition, 3D-SMART was able to quantify to occupancy of single Spinach2 RNA aptamers and capture active transcription on single freely diffusing DNA. 3D-SMART represents a critical step towards the untethering of single molecule spectroscopy.
The K-Cl co-transporter 2 is a point of convergence for multiple autism spectrum disorder and epilepsy risk gene products
Authors: Smalley Joshua L. , Kontou Georgina , Choi Catherine , Ren Qiu , Albrecht David , Abiraman Krithika , Rodriguez Santos Miguel A. , Bope Christopher E. , Deeb Tarek Z. , Davies Paul A. , Brandon Nicholas J. , Moss Stephen J.
Published: March 2020

KCC2 plays a critical role in determining the efficacy of synaptic inhibition and deficits in its activity lead to epilepsy and neurodevelopmental delay. Here we use unbiased proteomic analyses to demonstrate that KCC2 forms stable protein complexes in the neuronal plasma membrane with 96 autism and/or epilepsy risk gene (ASD/Epi) products including ANKB, ANKG, CNTN1, ITPR1, NCKAP1, SCN2A, SHANK3, SPTAN1, and SPTBN1. Many of these proteins are also targets of Fragile-X mental retardation protein (FMRP), the inactivation of which is the leading monogenic cause of autism. Accordingly, the expression of a subset of these KCC2-binding partners was decreased in Fmr1 knockout mice. Fmr1 knockout compromised KCC2 phosphorylation, a key regulatory mechanism for transporter activity and the postnatal development of GABAergic inhibition. Thus, KCC2 is a point of convergence for multiple ASD/Epi risk genes and therapies targeting this transporter may have broad utility in alleviating these heterogeneous disorders and their associated epilepsies.
Pannexin 1 regulates spiny protrusion dynamics in cortical neurons
Authors: Sanchez-Arias Juan C. , Candlish Rebecca C. , Swayne Leigh Anne
Published: March 2020

The integration of neurons into networks relies on the formation of dendritic spines. These specialized structures arise from dynamic filopodia-like spiny protrusions. Recently, it was discovered that cortical neurons lacking the channel protein Pannexin 1 (Panx1) exhibited larger and more complicated neuronal networks, as well as, higher dendritic spine densities. Here, we expanded on those findings to investigate whether the increase in dendritic spine density associated with lack of Panx1 was due to differences in the rates of spine dynamics. Using a fluorescent membrane tag (mCherry-CD9-10) to visualize spiny protrusions in developing neurons (at 10days-in-vitro, DIV10) we confirmed that lack of Panx1 leads to higher spiny protrusion density while transient transfection of Panx1 leads to decreased spiny protrusion density. To quantify the impact of Panx1 expression on spiny protrusion formation, elimination, and motility, we used live cell imaging in DIV10 neurons (1 frame every 5 seconds for 10 minutes). We discovered, that at DIV10, lack of Panx1 KO stabilized spiny protrusions. Notably, re-expression of Panx1 in Panx1 knockout neurons resulted in a significant increase in spiny protrusion motility and turnover. In summary, these new data revealed that Panx1 regulates the development of dendritic spines by controlling protrusion dynamics.

Significance statement

Cells in the brain form intricate and specialized networks -neuronal networks- in charge of processing sensations, executing movement commands, and storing memories. To do this, brain cells extend microscopic protrusions -spiny protrusions- which are highly dynamic and survey the local environment to contact other cells. Those contact sites are known as synapses and undergo further stabilization and maturation establishing the function and efficiency of neuronal networks. Our work shows that removal of Panx1 increases the stability and decreases the turnover of spiny protrusion on young neurons.
Unexpected formation of a co-crystal containing the chalcone (E)-1-(5-chlorothiophen-2-yl)-3-(3-methylthiophen-2-yl)prop-2-en-1-one and the keto–enol tautomer (Z)-1-(5-chlorothiophen-2-yl)-3-(3-methylthiophen-2-yl)prop-1-en-1-ol
Authors: Al-Refai Mahmoud , Ali Basem F. , Geyer Armin , Harms Klaus , Marsch Michael
Published: March 2020

The title crystal structure is assembled from the superposition of two molecular structures, (E)-1-(5-chlorothiophen-2-yl)-3-(3-methylthiophen-2-yl)prop-2-en-1-one, C12H9ClOS2 (93%), and (Z)-1-(5-chlorothiophen-2-yl)-3-(3-methylthiophen-2-yl)prop-1-en-1-ol, C12H11ClOS2 (7%), 0.93C12H9ClOS2·0.07C12H11ClOS2. Both were obtained from the reaction of 3-methylthiophene-2-carbaldehyde and 1-(5-chlorothiophen-2-yl)ethanone. In the extended structure of the major chalcone component, molecules are linked by a combination of C—H...O/S, Cl...Cl, Cl...π and π–π interactions, leading to a compact three-dimensional supramolecular assembly.
Crystal structure of ethyl 2-(5-amino-1-benzenesulfonyl-3-oxo-2,3-dihydro-1H-pyrazol-2-yl)acetate
Authors: Metwally Nadia H. , Elgemeie Galal H. , Jones Peter G.
Published: March 2020

In the title compound, C13H15N3O5S, the two rings face each other in a `V′ form at the S atom, with one N—H...O=S and one C—H...O=S contact from the pyrazolyl substituents to the sulfonyl group. Two classical hydrogen bonds from the amine group, one of the form N—H...O=S and one N—H...O=Coxo, link the molecules to form layers parallel to the bc plane.
Accounting to ensure healthy lives: critical perspective from the Italian National Healthcare System
Authors: Pizzi Simone , Caputo Fabio , Venturelli Andrea
Published: March 2020

Purpose

The aim of the paper is to understand the differences between “talking” and “walking” about sustainable development goals (SDGs) in state-owned enterprises (SOEs). Specifically, the authors have conducted an analysis on 202 entities that operate within the Italian National Healthcare System (INHS) to evaluate the overall degree of transparency in term of contribution to the SDG3.

Design/methodology/approach

The research evaluates the degree of contribution to SDG3 by INHS through the adoption of the theoretical framework proposed by Beck et al. (2010). Specifically, the authors assess the degree of contribution to this goal using an interpretive content analysis that combines the theoretical framework with the 13 targets that composed the SDG3. For the authors’ purposes, they analyze all INHS’s website to evaluate the presence/absence of social reports produced in the periods 2015-2018.

Findings

Although the great contribution to the SDG3, the INHS is characterized by a low degree of accountability. In fact, only 12.21 per cent of INHS’s entities disclosed at least one social report during the observed period. Moreover, the authors’ results denote how the approach of INHS’s entities to social reporting is different both in term of “quality” and “quantity.”

Research limitations/implications

The SOEs play a central role within the Agenda 2030 strategies. However, public managers are less oriented than private managers to adopt non-financial reporting tools. Furthermore, the authors’ results highlight the existence of asymmetric information between SOEs and citizens even if in presence of best practices such as the INHS. In this sense, the adoption of non-financial reports tool to engage in a more effective way with citizens could be a strategic driver for the achievement of highest degree of social legitimacy to operate.

Practical implications

The paper is of use to public managers operating in countries characterized by a high level of contribution to SDGs. Specifically, the authors’ results suggest how the adoption of reporting tools could impact positively in terms of stakeholder’s awareness to SDG themes.

Originality/value

This paper contributes to the understanding of the central role covered by academics, practitioners and public sectors to SDGs through the adoption of social reporting tools.
Developing a framework to revolutionise the 4D BIM process: IPD-based solution
Authors: Elghaish Faris , Abrishami Sepehr
Published: March 2020

Purpose

The integration of building information modelling (BIM) and integrated project delivery (IPD) is highly recommended for better project delivery. Although there is a methodology for this integration, the BIM requires some improvements to foster the adoption of IPD. The purpose of this paper is to present an innovative way to support 4D BIM automation/optimisation within the IPD approach. Similar to structural and architectural design libraries, this research proposes a planning library to enable automating the formulation of schedule, as well as embedding the multi-objective optimisation into the 4D BIM.

Design/methodology/approach

The literature review was used to highlight the existing attempts to support the automation process for 4D BIM and the multi-objective schedule optimisation for construction projects. A case study was done to validate the developed framework and measure its applicability.

Findings

The results show that there is a cost-saving of 22.86 per cent because of using the proposed automated multi-objective optimisation. The case study shows the significance of integrating activity-based costing into 4D BIM to configure the hierarchy level of overhead activities with the IPD approach; therefore, the maximum level of contribution in managing the IPD project is 33.33 per cent by the trade package level and the minimum contribution is around 8.33 per cent by the project level.

Originality/value

This research presents a new philosophy to develop the 4D BIM model – planning and scheduling – a BIM library of the project activities is developed to enable the automation of the creation of the project schedule with respect to the 3D BIM design sequence. The optimisation of the project duration is considered to be automated within the creation process by using the proposed genetic algorithm model.
Don’t you (forget about me)
Authors: Mo Ce (Jacky) , Yu Ting , de Ruyter Ko
Published: March 2020

Purpose

To advance research on channel relationship management, this study aims to test for the impacts of a channel member’s perception of exclusion from a supplier’s distribution channel networks (i.e. out-of-the-channel-loop perceptions [OCLP]) on supplier–channel partner relationships. The authors also systematically develop and empirically validate a scale to measure OCLP.

Design/methodology/approach

This paper reports two empirical studies. The first develops a new scale for OCLP, following established approaches. The second tests the hypotheses. Survey data from a sample of channel firms operating in four industries were subjected to partial least squares modelling in the test of the hypothesized main and moderating effects.

Findings

The authors developed the new scale, including eight items, that capture OCLP from both social and economic perspectives. The results also show that OCLP has negative impacts on channel members’ psychological and behavioural outcomes (satisfaction, information sharing, positive word of mouth), after controlling for the effect of perceived unfairness. Channel partner perceived peer support emerges as a boundary condition of the impact; perceived informational support attenuates, whereas emotional support amplifies, the impact of OCLP.

Research limitations/implications

This study suggests new research opportunities for explaining business-to-business marketing relationships using newly conceptualized OCLP.

Practical implications

This study highlights that suppliers must recognize the potential for negative consequences of OCLP and manage these perceptions to minimize the negative implications. For suppliers, this study also offers several tools for managing OCLP.

Originality/value

This study introduces ostracism concepts to marketing channel literature to study a potential detriment to channel relationships. The proposed scale captures channel partners’ sense of exclusion from supplier relationships. It provides initial insights into the direct impacts on channel relational outcomes and associated boundary conditions.
Future study of operations research based on scenario planning and soft systems methodology
Authors: Fathi Mohammad Reza , Maleki Mohammad Hasan , Sobhani Seyed Mohammad , Koksal Can Deniz
Published: March 2020

Purpose

The purpose of this study is to formulate exploratory scenarios of Operations Research through the critical uncertainty approach and Soft Systems Methodology.

Design/methodology/approach

In this study, to formulate plausible scenarios, the discipline of operation research internal and external experts’ opinions of this field have been gathered through Delphi approach and uncertainty questionnaires. After use of the most important uncertainties, plausible scenarios of operations research have been mapped with the help of experts through co-thinking workshops.

Findings

Four scenarios are presented in this study. These scenarios include Solar System, Esfandiar's Eye, Rival’s Setraps and Legendary Simurgh. Naturally, the imagination of such a unitary future for all academic communities is an expectation far from reality, and given the conditions of each of these futures or any integration of them is imaginable.

Originality/value

Operations Research models have been faced with variously multiple changes since its emergence until now. Investigation into the future of operations research on the necessity for his planning has not received a reasonable notice in the literature. Sporadic activities that have been carried out are also lacking in the necessary methodology. Also, there has been no research about future study using the soft Operation Research tools (Soft Systems Methodology).
Preventing supplier non-conformance: extending the agency theory perspective
Authors: Shevchenko Anton , Pagell Mark , Lévesque Moren , Johnston David
Published: March 2020

Purpose

The supply chain management literature and agency theory suggest that preventing supplier non-conformance—a supplier's failure to conform to the requirements of the buyer—requires monitoring supplier behavior. However, case studies collected to explore how buyers monitored suppliers revealed an unexpected empirical phenomenon. Some buyers believed they could prevent non-conformance by either trusting their suppliers or relying on a third party, without monitoring their behavior. The purpose of this article is to examine conditions when buyers should monitor supplier behavior to prevent non-conformance.

Design/methodology/approach

This article employs a mixed-method design by formulating an agent-based simulation grounded in the case-study findings and agency theory to reconcile observed unexpected behaviors with scholarly suggestions.

Findings

The simulation results indicate that buyers facing severe consequences from non-conformance should opt to monitor supplier behavior. Sourcing from trusted suppliers should only be reserved for buyers that lack competence and have a small number of carefully selected suppliers. Moreover, buyers facing minor consequences from non-conformance should generally favor sourcing from trusted suppliers over monitoring their behavior. The results also suggest that having a third-party involved in monitoring suppliers is an effective path to preventing non-conformance.

Originality/value

By combining a simulation with qualitative case studies, this article examines whether buyers were making appropriate decisions, thereby offering contributions to theory and practice that would not have been possible using either methodological approach alone.
Savouring place: cheese as a food tourism destination landmark
Authors: Fusté-Forné Francesc
Published: March 2020

Purpose

Cheeses convey the identity of a region. The origin of milk, the pastures, the land, the cheesemakers and the traditional recipes transmit the ways a cheese is produced and consumed. This background links to food tourism practices, particularly to cheese-oriented tourism. In this sense, people can buy cheese at a range of selling points, and markets are being one of the most appreciated social, leisure and experience spaces. From a tourist and marketing perspective, the purpose of this paper is to explore the relationship between cheese consumption and place identity, drawing from a study into the cheeses sold in a medium-sized European city.

Design/methodology/approach

Drawing on 17 semi-structured interviews with cheese vendors in markets and specialist food shops, the provenances of cheeses sold in the city of Reus – south-eastern Catalonia, northeastern Spain – were studied.

Findings

Local, national and international cheeses were analysed. Results show the type of identity that derives from cheese offer and its opportunities for food tourism planning and development.

Practical implications

Outcomes of this paper may lead cheese producers to explore new arenas of cheesemaking and cheese distribution. Also, the results inform food tourism stakeholders of what consumers – both locals and tourists – gather when they buy cheese in a medium-sized European city.

Originality/value

This research offers an innovative approach to the study of the links between food and place. Based on the understanding of the origin of products, this paper leads to further comprehension of specialist food tourisms from the offer perspective, which may also drive to the development of a more robust destination gastronomic identity – in this case, through the particular provision of cheeses.
Perceptual versus institutional determinants of entrepreneurial entry
Authors: Amini Sedeh Amirmahmood , Beck Joseph , Forghani Bajestani Mahdi
Published: March 2020

Purpose

This cross-national study of entrepreneurship seeks to investigate the perceptual and institutional determinants of entrepreneurial entry. To do so, the authors distinguish between social and commercial entrepreneurial activities, taking the position that the concept of entrepreneurship is not a monolithic one.

Design/methodology/approach

The authors construct a large cross-national data set and employ hierarchical linear modeling (HLM) to run a multi-level analysis on individual-level data from Global Entrepreneurship Monitor (GEM) and country-level data from Polity IV and GLOBE, representing 47 countries.

Findings

Individuals' perceptual characteristics (i.e. perceived self-efficacy, opportunity perception, and fear of failure) and informal institutions in the form of supportive cultures impact social entrepreneurship more strongly than commercial entrepreneurship. On the other hand, the formal institution of the rule of law, specifically the protection of property rights, is more conducive to commercial entrepreneurship.

Originality/value

The results of this study contribute to theory by illuminating the complicated relationships between environmental conditions, individual-level psychological factors, and entrepreneurial decisions. Furthermore, the authors’ multi-level model contributes to a more detailed conceptualization of entrepreneurial entry by identifying institutional settings that facilitate commercial versus social entrepreneurship. The authors also clarify why commercial entrepreneurship and social entrepreneurship attract different types of individuals.