bluuebunny/crossref_metadata_2025 huggingface dataset:
Complementary Maps for Location and Environmental Structure in CA1 and Subiculum
Authors: Olson Jacob M , Johnson Alexander B , Chang Lillian , Tao Emily L , Wang Xuefei , Nitz Douglas A
Published: February 2021

The dorsal subiculum lies among a network of interconnected brain regions that collectively map multiple spatial and orientational relationships between an organism and the boundaries and pathways composing its environment. A unique role of the subiculum in spatial information processing has yet to be defined despite reports of small neuron subpopulations that encode relationships to specific boundaries, axes of travel, or locations. We examined the activity patterns among populations of subiculum neurons during performance of a spatial working memory task performed within a complex network of interconnected pathways. Compared to neurons in hippocampal sub-region CA1, a major source of its afferents, subiculum neurons were far more likely to exhibit multiple firing fields at locations that were analogous with respect to path structure and function. Subiculum neuron populations were also found to exhibit a greater dynamic range in scale of spatial representation and for persistent patterns of spiking activity to be aligned to transitions between maze segments. Together, the findings indicate that the subiculum plays a unique role in spatial mapping, one that complements the location-specific firing of CA1 neurons with the encoding of emergent and recurring structural features of a complex path network.
Quality control strategies for brain MRI segmentation and parcellation: practical approaches and recommendations - insights from The Maastricht Study
Authors: Sánchez Jennifer Monereo , de Jong Joost J.A. , Drenthen Gerhard S. , Beran Magdalena , Backes Walter H. , Stehouwer Coen D.A. , Schram Miranda T. , Linden David E.J. , Jansen Jacobus. F.A.
Published: February 2021

Background

Quality control of brain segmentation is a fundamental step to ensure data quality. Manual quality control is the current gold standard, despite unfeasible in large neuroimaging samples. Several options for automated quality control have been proposed, providing potential time efficient and reproducible alternatives. However, those have never been compared side to side, which prevents to reach consensus in the appropriate QC strategy to use. This study aims to elucidate the changes manual editing of brain segmentations produce in morphological estimates, and to analyze and compare the effects of different quality control strategies in the reduction of the measurement error.

Methods

We used structural MR images from 259 participants of The Maastricht Study. Morphological estimates were automatically extracted using FreeSurfer 6.0. A subsample of the brain segmentations with inaccuracies was manually edited, and morphological estimates were compared before and after editing. In parallel, 11 quality control strategies were applied to the full sample. Those included: a manual strategy, manual-QC, in which images were visually inspected and manually edited; five automated strategies where outliers were excluded based on the tools MRIQC and Qoala-T, and the metrics morphological global measures, Euler numbers and Contrast-to-Noise ratio; and five semi-automated strategies, were the outliers detected through the mentioned tools and metrics were not excluded, but visually inspected and manually edited. We used a regression of morphological brain measures against age as a test case to compare the changes in relative unexplained variance that each quality control strategy produces, using the reduction of relative unexplained variance as a measure of increase in quality.

Results

Manually editing brain surfaces produced changes particularly high in subcortical brain volumes and moderate in cortical surface area, thickness and hippocampal volumes. The exclusion of outliers based on Euler numbers yielded a larger reduction of relative unexplained variance for measurements of cortical area, subcortical volumes and hippocampal subfields, while manual editing of brain segmentations performed best for cortical thickness. MRIQC produced a lower, but consistent for all types of measures, reduction in relative unexplained variance. Unexpectedly, the exclusion of outliers based on global morphological measures produced an increase of relative unexplained variance, potentially removing more morphological information than noise from the sample.

Conclusion

Overall, the automatic exclusion of outliers based on Euler numbers or MRIQC are reliable and time efficient quality control strategies that can be applied in large neuroimaging cohorts.
OmicsTIDE: Interactive Exploration of Trends in Multi-Omics Data
Authors: Harbig Theresa , Fratte Julian , Krone Michael , Nieselt Kay
Published: February 2021

Motivation

The increasing amount of data produced by omics technologies has significantly improved the understanding of how biological information is transferred across different omics layers and to which extent it is involved in the manifestation of a given phenotype. Besides data-driven analysis strategies, interactive visualization tools have been developed to make the analysis in the multi-omics field more transparent. However, most state-of-the-art tools do not reconstruct the impact of a given omics layer on the final integration result. In general, the amount of omics data analyses strategies and the fields of applications lack a clearer classification of the different approaches.

Results

We developed a classification for omics data focusing on different aspects of multi-omics data sets, such as data type and experimental design. Based on this classification we developed the Omics Trend-comparing Interactive Data Explorer (OmicsTIDE), an interactive visualization tool developed to address the limitations of current visualization approaches in the multi-omics field. The tool consists of an automated part that clusters omics data to determine trends and an interactive visualization. The trends are visualized as profile plots and are connected by a Sankey diagram that allows an interactive pairwise trend comparison to discover concordant and discordant trends. Moreover, large-scale omics data sets are broken down into small subsets of concordant and discordant regulatory trends within few analysis steps. We demonstrate the interactive analysis usingOmicsTIDEwith two case studies focusing on different types of experimental designs.

Availability

OmicsTIDEis a web tool and available viahttp://tuevis.informatik.uni-tuebingen.de/

Contact

kay.nieselt@uni-tuebingen.de
Associations of weather fronts with pig reproduction and mortality
Authors: Reibling Tamás , Hagstrand Linnea , Maróti-Agóts Ákos , Barcza Zoltán , Solymosi Norbert
Published: February 2021

Farmers and practising veterinarians have long suspected the impact of weather fronts on production and animal health. A common impression is that sows will farrow earlier in connection with a cold front. There might be a correlation between daily mortality and the occurrence of a strong atmospheric front. Population-based quantitative studies on weather fronts’ effects on animal health and production are very sparse in the scientific literature. In this study, the associations between the weather fronts and daily farrowing incidence, the pregnancy length and the daily death incidence were analysed. The results show that cold front increased the odds of more than daily six farrowings on the day of the front (with at least 3°C cooling OR: 4.79, 95%CI: 1.08-21.21, p=0.039). On the day of the front, with at least 3°C temperature change both the cold and the warm front increased the odds of the farrowing on the day ≥ 118th day of the gestation (OR: 3.10, 95%CI: 1.04-9.30, p=0.43 and OR: 4.39, 95%CI: 1.73-11.15, p=0.002, respectively). On the day after the day of front, the odds of farrowing on the ≤ 113th day of gestation are increased, if the temperature decrease was at least 2°C the OR: 2.30 (95%CI: 1.04-5.06, p=0.039). On the day after the warm front with at least 1°C temperature increase the odds of more than daily three deaths is increased (OR: 5.44, 95%CI: 1.23-24.05, p=0.025).
Wrinkle force microscopy: a new machine learning based approach to predict cell mechanics from images
Authors: Li Honghan , Matsunaga Daiki , Matsui Tsubasa S. , Aosaki Hiroki , Inoue Koki , Doostmohammadi Amin , Deguchi Shinji
Published: February 2021

Combining experiments with artificial intelligence algorithms, we propose a new machine learning based approach to extract the cellular force distributions from the microscope images. The full process can be divided into three steps. First, we culture the cells on a special substrate allowing to measure both the cellular traction force on the substrate and the corresponding substrate wrinkles simultaneously. The cellular forces are obtained using the traction force microscopy (TFM), at the same time that cell-generated contractile forces wrinkle their underlying substrate. Second, the wrinkle positions are extracted from the microscope images. Third, we train the machine learning system with GAN (generative adversarial network) by using sets of corresponding two images, the traction field and the input images (raw microscope images or extracted wrinkle images), as the training data. The network understands the way to convert the input images of the substrate wrinkles to the traction distribution from the training. After sufficient training, the network is utilized to predict the cellular forces just from the input images. Our system provides a powerful tool to evaluate the cellular forces efficiently because the forces can be predicted just by observing the cells under the microscope, which is a way simpler method compared to the TFM experiment. Additionally, the machine learning based approach presented here has the profound potential for being applied to diverse cellular assays for studying mechanobiology of cells.

Significance Statement

Cell-generated forces are indispensable determinants of fundamental cell functions such as motility and cell division. As such, quantifying how the forces change upon perturbations to the cells such as gene mutations and drug administration is of profound importance. Here we present a novel machine learning based system that allows for efficient estimations of the forces that are determined only by “observing” microscope images. Given that the cellular traction forces are regulated downstream of diverse signaling pathways, our system – that helps significantly improve the throughput of the measurements – presents a new, high throughput platform for real time analysis of the effects of a massive number of genetic and molecular perturbations on the forces and resulting cell mechanics.
Cubam receptor-mediated endocytosis in hindgut-derived pseudoplacenta of a viviparous teleost Xenotoca eiseni
Authors: Iida Atsuo , Sano Kaori , Inokuchi Mayu , Nomura Jumpei , Suzuki Takayuki , Kuriki Mao , Sogabe Maina , Susaki Daichi , Tonosaki Kaoru , Kinoshita Tetsu , Hondo Eiichi
Published: February 2021

Nutrient transfer from mother to the embryo is essential for reproduction in viviparous animals. In the viviparous teleost Xenotoca eiseni belonging to the family Goodeidae, the intraovarian embryo intakes the maternal component secreted into the ovarian fluid via the trophotaenia. Our previous study reported that the epithelial layer cells of the trophotaenia incorporate a maternal protein via vesicle trafficking. However, the molecules responsible for the absorption were still elusive. Here, we focused on Cubam (Cubilin-Amnionless) as a receptor involved in the absorption, and cathepsin L as a functional protease in the vesicles. Our results indicated that the Cubam receptor is distributed in the apical surface of the trophotaenia epithelium and then is taken into the intracellular vesicles. The trophotaenia possesses acidic organelles in epithelial layer cells and cathepsin L-dependent proteolysis activity. This evidence does not conflict with our hypothesis that receptor-mediated endocytosis and proteolysis play roles in maternal macromolecule absorption via the trohotaenia in viviparous teleosts. Such nutrient absorption involving endocytosis is not a specific trait in viviparous fish. Similar processes have been reported in the larval stage of oviparous fish or the suckling stage of viviparous mammals. Our findings suggest that the viviparous teleost acquired trophotaenia-based viviparity from a modification of the intestinal absorption system common in vertebrates. This is a fundamental study to understand the strategic variation of the reproductive system in vertebrates.

Summary statement

Here, we report that an endocytic pathway is a candidate for nutrient absorption in pseudoplacenta of a viviparous teleost. The trait may have developed from common intestinal mechanism among vertebrates.
Verapamil/Curcumin treatment attenuates the behavioral alterations observed in Williams Syndrome mice by regulation of MAPK pathway and Microglia overexpression
Authors: Ortiz-Romero Paula , Egea Gustavo , Pérez-Jurado Luis A , Campuzano Victoria
Published: February 2021

Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by a distinctive cognitive phenotype for which there currently are not any effective treatments. We investigated the progression of behavioral deficits present in CD (complete deletion) mice, a rodent model of WBS, after chronic treatment with curcumin, verapamil and a combination of both. These compounds have been proven to have beneficial effects over different cognitive aspects of various murine models and thus, may have neuroprotective effects in WBS. Treatment was administered orally dissolved in drinking water. A set of behavioral tests demonstrated the efficiency of combinatorial treatment. Some histological and molecular analyses were performed to analyze the effects of treatment and its underlying mechanism in CD mice. Behavioral improvement correlates with the molecular recovery of several affected pathways regarding MAPK signaling, in tight relation with the control of synaptic transmission. Moreover, CD mice showed an increased activated microglia density in different brain regions, which was prevented by treatment. Therefore, results show that treatment prevented behavioral deficits by recovering altered gene expression in cortex of CD mice, reducing activated microglia and normalizingBdnfexpression levels. These findings unravel the mechanisms underlying the beneficial effects of this novel treatment on behavioral deficits observed in CD mice, and suggest that the combination of curcumin and verapamil could be a potential candidate to treat the cognitive impairments in WBS patients.
Metabolomic profiling of pancreatic adenocarcinoma reveals fundamental clinical features
Authors: Kaoutari Abdessamad El , Fraunhoffer Nicolas A , Hoare Owen , Teyssedou Carlos , Soubeyran Philippe , Gayet Odile , Roques Julie , Lomberk Gwen , Urrutia Raul , Dusetti Nelson , Iovanna Juan
Published: February 2021

In this study, we perform the metabolomics profiling of 77 PDAC patient-derived tumor xenografts (PDTX) to investigate the relationship of metabolic profiles with overall survival (OS) in PDAC patients, tumor phenotypes and resistance to five anticancer drugs (gemcitabine, oxaliplatin, docetaxel, SN-38 and 5-Fluorouracil). We identified a metabolic signature that was able to predict the clinical outcome of PDAC patients (p < 0.001, HR=2.68 [95% CI: 1.5-4.9]). The correlation analysis showed that this metabolomic signature was significantly correlated with the PDAC molecular gradient (PAMG) (R = 0.44 and p < 0.001) indicating significant association to the transcriptomic phenotypes of tumors. Resistance score established, based on growth rate inhibition metrics using 35 PDTX-derived primary cells, allowed to identify several metabolites related to drug resistance which was globally accompanied by accumulation of several diacy-phospholipids and decrease in lysophospholipids. Interestingly, targeting glycerophospholipid synthesis improved sensitivity to the three tested cytotoxic drugs indicating that interfering with metabolism could be a promising therapeutic strategy to overcome the challenging resistance of PDAC.

Short abstract

Targeting metabolism of cancer cells gives a precious opportunity to overcome challenges related to the high mortality and chemoresistance in PDAC.

Metabolic profiling of PDAC patient-derived tumor xenografts used in this study allowed highlighting the strong link between metabolism and both clinical outcome of the patients and chemoresistance.

Metabolic signature was able to discriminate between good and bad prognosis groups of patients based on their level of key metabolites.

Identification of key metabolic markers associated to chemoresistance allowed to improve sensitivity to anticancer drugs.

These results provide new insights to help to predict patient survival and elaborate new combinatory therapies against chemoresistance in PDAC patients attesting of the important clinical value of this work.
Catechin complexed with lysine has potent antitumor activities in human breast cancer xenograft model
Authors: Katsoulieris Elias N , Rodriguez Amanda Canas
Published: February 2021

bioRxiv has withdrawn this preprint as it was posted without proper authorization therefore violating confidentiality agreements between involved parties.
Tomato roots sense horizontal/vertical mechanical impedance and divergently modulate root/shoot metabolome
Authors: Kumari Alka , Nongmaithem Sapana , Devulapalli Sameera , Sreelakshmi Yellamaraju , Sharma Rameshwar
Published: February 2021

Plant roots encounter coarse environs right after emergence from the seeds. Little is known about metabolic changes enabling roots to overcome the soil impedance. Tomato seedlings grown vertically or horizontally, at increasing hardness, exhibited lateral roots proliferation, shorter hypocotyls, and primary roots. In primary root tips, hardness-elicited loss of amyloplasts staining; induced ROS and NO accumulation. The levels of IBA, zeatin, jasmonates, and salicylic acids markedly differed in roots and shoots exposed to increasing hardness. Hardness lowered IAA and elevated ABA levels, while increased ethylene emission was confined to horizontally-impeded seedlings. The trajectories of metabolomic shifts distinctly differed between vertically/horizontally-impeded roots/shoots. In horizontal roots, amino acids were the major affected group, while in vertical roots, sugars were the major group. Commonly affected metabolites in roots and shoots, trehalose, dopamine, caffeoylquinic acid, and suberic acid, hallmarked the signature for hardness. Increasing hardness loweredSnRK1aexpression in roots/shoots implying regulation of metabolic homeostasis by the SnRK1 signalling module. Our data suggest that though hardness is a common denominator, roots sense the horizontal/vertical orientation and correspondingly modulate metabolite profiles.

Significance statement

We show that the tomato roots sense the magnitude of hardness as well as the horizontal and vertical orientation. The hardness divergently modulates the phytohormone and metabolite levels in roots and shoots. The trajectory of the metabolic shift in vertically-grown seedling distinctly differs from horizontally-grown seedlings. ABA and trehalose were the hallmark of hardness stress and may influence metabolic alteration via the SNRK signalling pathway.
The evolution of the metazoan Toll receptor family and its expression during protostome development
Authors: Orús-Alcalde Andrea , Lu Tsai-Ming , Hejnol Andreas
Published: February 2021

Background

Toll-like receptors (TLRs) play a crucial role in immunity and development. They contain leucine-rich repeat domains, one transmembrane domain, and one Toll/IL-1 receptor domain. TLRs have been classified into V-type/scc and P-type/mcc TLRs, based on differences in the leucine-rich repeat domain region. Although TLRs are widespread in animals, detailed phylogenetic studies of this gene family are lacking. Here we aim to uncover TLR evolution by conducting a survey and a phylogenetic analysis in species across Bilateria. To discriminate between their role in development and immunity we furthermore analyzed stage-specific transcriptomes of the ecdysozoansPriapulus caudatusandHypsibius exemplaris, and the spiraliansCrassostrea gigasandTerebratalia transversa.

Results

We detected a low number of TLRs in ecdysozoan species, and multiple independent radiations within the Spiralia. V-type/scc and P-type/mcc type-receptors are present in cnidarians, protostomes and deuterostomes, and therefore they emerged early in TLR evolution, followed by a loss in xenacoelomorphs. Our phylogenetic analysis shows that TLRs cluster into three major clades: clade α is present in cnidarians, ecdysozoans, and spiralians; clade β in deuterostomes, ecdysozoans, and spiralians; and clade γ is only found in spiralians. Our stage-specific transcriptome andin situhybridization analyses show that TLRs are expressed during development in all species analyzed, which indicates a broad role of TLRs during animal development.

Conclusions

Our findings suggest that the bilaterian TLRs likely emerged by duplication from a single TLR encoding gene (proto-TLR) present in the last common cnidarian-bilaterian ancestor. Thisproto-TLR gene duplicated before the split of protostomes and deuterostomes; a second duplication occurred in the lineage to the Trochozoa. While all three clades further radiated in several spiralian lineages, specific TLRs clades have been presumably lost in others. Furthermore, the expression of the majority of these genes during protostome ontogeny suggests their involvement in immunity and development.
Integrated spatial models foster complementarity between monitoring programs in producing large-scale bottlenose dolphin indicators
Authors: Lauret Valentin , Labach Hélène , Turek Daniel , Laran Sophie , Gimenez Olivier
Published: February 2021

Over the last decades, large-scale ecological projects have emerged that require collecting ecological data over broad spatial and temporal coverage. Yet, obtaining relevant information about large-scale population dynamics from a single monitoring program is challenging, and often several sources of data, possibly heterogeneous, need to be integrated. In this context, integrated models combine multiple data types into a single analysis to quantify population dynamics of a targeted population. When working at large geographical scales, integrated spatial models have the potential to produce spatialised ecological estimates that would be difficult to obtain if data were analysed separately.

In this paper, we illustrate how spatial integrated modelling offers a relevant framework for conducting ecological inference at large scales. Focusing on the Mediterranean bottlenose dolphins (Tursiops truncatus), we combined 21,464 km of photo-identification boat surveys collecting spatial capture-recapture data with 24,624 km of aerial line-transect following a distance-sampling protocol. We analysed spatial capture-recapture data together with distance-sampling data to estimate abundance and density of bottlenose dolphins. We compared the performances of the distance sampling model and the spatial capture-recapture model fitted independently, to our integrated spatial model.

The outputs of our spatial integrated models inform bottlenose dolphin ecological status in the French Mediterranean Sea and provide ecological indicators that are required for regional scale ecological assessments like the EU Marine Strategy Framework Directive. We argue that integrated spatial models are widely applicable and relevant to conservation research and biodiversity assessment at large spatial scales.
Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons
Authors: Haddjeri-Hopkins Alexis , Tapia Mónica , Ramirez-Franco Jorge , Tell Fabien , Marqueze-Pouey Béatrice , Amalric Marianne , Goaillard Jean-Marc
Published: February 2021

Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons display a peculiar electrical phenotype characterized in vitro by a spontaneous tonic regular activity (pacemaking activity), a broad action potential and a biphasic post-inhibitory response. Several studies in rodents have underlined the central role played by the transient A-type current (IA) in the control of pacemaking activity and post-inhibitory rebound properties, thereby influencing both DA release and the physiological response of SNc neurons to incoming inhibitory inputs. Kv4.3 potassium channels were considered to be fully responsible for IA in these neurons, their density being tightly related to pacemaking frequency. In spite of this crucial electrophysiological role, we show that Kv4.3-/- transgenic mice exhibit minor alterations in locomotion and motor learning, although no compensation by functionally overlapping ion channels is observed in Kv4.3-/- SNc DA neurons. Using antigen retrieval immunohistochemistry, we further demonstrate that Kv4.2 potassium channels are also expressed in SNc DA neurons, even though their contribution to IA appears significant only in a minority of neurons (~5-10%). Using correlative analysis on recorded electrophysiological parameters and multi-compartment modeling, we then demonstrate that, rather than its conductance level, IA gating kinetics (inactivation time constant) appear as the main biophysical property defining post-inhibitory rebound delay and pacemaking frequency. Moreover, we show that the hyperpolarization-activated current (IH) has an opposing and complementary influence on the same firing features, and that the biophysical properties of IA and IH are likely coregulated in mouse SNc DA neurons.

SIGNIFICANCE STATEMENT

Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons are characterized by pacemaking activity, a broad action potential and biphasic post-inhibitory response. The A-type transient potassium current (IA) plays a central role in both pacemaking activity and post-inhibitory response. While it was thought so far that Kv4.3 ion channels were fully responsible for IA, using a Kv4.3-/- transgenic mouse and antigen retrieval immunohistochemistry we demonstrate that Kv4.2 channels are also expressed in SNc DA neurons, although their contribution is significant in a minority of neurons only. Using electrophysiological recordings and computational modeling, we then demonstrate that IA gating kinetics and its functional complementarity with the hyperpolarization-activated current are major determinants of both pacemaking activity and post-inhibitory response in SNc DA neurons.
Early, color-specific neural responses to object color knowledge
Authors: Retter Talia L. , Gao Yi , Jiang Fang , Rossion Bruno , Webster Michael A.
Published: February 2021

Some familiar objects are associated with specific colors, e.g., rubber ducks with yellow. Whether and at what stage neural responses occur to these color associations remain open questions. We tested for frequency-tagged electroencephalogram (EEG) responses to periodic presentations of yellow-associated objects, shown among sequences of non-periodic blue-, red-, and green-associated objects. Both color and grayscale versions of the objects elicited yellow-specific responses, indicating an automatic activation of color knowledge from object shape. Follow-up experiments replicated these effects with green-specific responses, and demonstrated modulated responses for incongruent color-object associations. Importantly, the onset of color-specific responses was as early to grayscale as actually colored stimuli (before 100 ms), the latter additionally eliciting a conventional later response (approximately 140-230 ms) to actual stimulus color. This suggests that the neural representation of familiar objects includes both diagnostic shape and color properties, such that shape can elicit associated color-specific responses before actual color-specific responses occur.
Molecular basis for two stereoselective Diels-Alderases that produce decalin skeletons
Authors: Fujiyama Keisuke , Kato Naoki , Re Suyong , Kinugasa Kiyomi , Watanabe Kohei , Takita Ryo , Nogawa Toshihiko , Hino Tomoya , Osada Hiroyuki , Sugita Yuji , Takahashi Shunji , Nagano Shingo
Published: February 2021

Molecular chirality, discovered by Louis Pasteur in the middle of the 19th century1, is found in most primary and secondary metabolites. Particularly, the so-called natural products are rich in chiral centres2. The stereochemistry of natural products is strictly recognized in living organisms, and is thus closely related to their biological functions. The Diels–Alder (DA) reaction, which forms a six-membered ring with up to four chiral centres, is a fundamental practical reaction for C–C bond formation in synthetic chemistry3. Nature has also adopted this reaction to elaborate the complex structures of natural products using enzymes derived from various progenitor proteins4-7. Although enzymes catalysing the DA reaction, Diels–Alderases (DAases), have attracted increasing attention, little is known about the molecular mechanism by which they control the stereochemistry and perform catalysis. Here, we solved the X-ray crystal structures of a pair of decalin synthases, Fsa2 and Phm7, that catalyse intramolecular DA reactions to form enantiomeric decalin scaffolds during biosynthesis of the HIV-1 integrase inhibitor equisetin and its stereochemical opposite, phomasetin8,9. Based on the crystal structures, docking simulations followed by all-atom molecular dynamics simulations provided dynamic binding models demonstrating the folding of linear polyenoyl tetramic acid substrates in the binding pocket of these enzymes, explaining the stereoselectivity in the construction of decalin scaffolds. Site-directed mutagenesis studies verified the binding models and, in combination with density functional theory calculations, clarified how hydrophilic amino acid residues in the Phm7 pocket regulate and catalyse the stereoselective DA reaction. This study highlights the distinct molecular mechanisms of the enzymatic DA reaction and its stereoselectivity experimentally and computationally. We anticipate that clarified molecular mechanism herein provides not only the basic understanding how these important enzymes work but also the guiding principle to create artificial enzymes that produce designer bioactive molecules.
Structural analysis of viral ExoN domains reveals polyphyletic hijacking events
Authors: Cruz-González A. , Muñoz-Velasco I. , Cottom-Salas W. , Becerra A. , Campillo-Balderas J.A. , Hernández-Morales R. , Vázquez-Salazar A. , Jácome R. , Lazcano A.
Published: February 2021

Nidoviruses and arenaviruses are the only known RNA viruses encoding a 3’-5’ exonuclease domain (ExoN). The proofreading activity of the ExoN domain has played a key role in the growth of nidoviral genomes, while in arenaviruses this domain partakes in the suppression of the host innate immune signaling. Sequence and structural homology analyses suggest that these proteins have been hijacked from cellular hosts many times. Analysis of the available nidoviral ExoN sequences reveals a high conservation level comparable to that of the viral RNA-dependent RNA polymerases (RdRp), which are the most conserved viral proteins. Two highly preserved zinc fingers are present in all nidoviral exonucleases, while in the arenaviral protein only one zinc finger can be identified. This is in sharp contrast with the reported lack of zinc fingers in cellular ExoNs, and opens the possibility of therapeutic strategies in the struggle against COVID-19.
Genome-scale metabolic modelling ofP. thermoglucosidasiusNCIMB 11955 reveals metabolic bottlenecks in anaerobic metabolism
Authors: Mol Viviënne , Bennett Martyn , Sánchez Benjamín J. , Lisowska Beata K. , Herrgård Markus J. , Nielsen Alex Toftgaard , Leak David J. , Sonnenschein Nikolaus
Published: February 2021

Parageobacillus thermoglucosidasiusrepresents a thermophilic, facultative anaerobic bacterial chassis, with several desirable traits for metabolic engineering and industrial production. To further optimize strain productivity, a systems level understanding of its metabolism is needed, which can be facilitated by a genome-scale metabolic model. Here, we presentp-thermo, the most complete, curated and validated genome-scale model (to date) ofParageobacillus thermoglucosidasiusNCIMB 11955. It spans a total of 890 metabolites, 1175 reactions and 917 metabolic genes, forming an extensive knowledge base forP. thermoglucosidasiusNCIMB 11955 metabolism. The model accurately predicts aerobic utilization of 22 carbon sources, and the predictive quality of internal fluxes was validated with previously published13C-fluxomics data. In an application case,p-thermowas used to facilitate more in-depth analysis of reported metabolic engineering efforts, giving additional insight into fermentative metabolism. Finally,p-thermowas used to resolve a previously uncharacterised bottleneck in anaerobic metabolism, by identifying the minimal required supplemented nutrients (thiamin, biotin and iron(III)) needed to sustain anaerobic growth. This highlights the usefulness ofp-thermofor guiding the generation of experimental hypotheses and for facilitating data-driven metabolic engineering, expanding the use ofP. thermoglucosidasiusas a high yield production platform.
Single-component optogenetic tools for inducible RhoA GTPase signaling
Authors: Berlew Erin E. , Kuznetsov Ivan A. , Yamada Keisuke , Bugaj Lukasz J. , Boerckel Joel D. , Chow Brian Y.
Published: February 2021

We created optogenetic tools to control RhoA GTPase, a central regulator of actin organization and actomyosin contractility. RhoA GTPase, or its upstream activating GEF effectors, were fused to BcLOV4, a photoreceptor that can be dynamically recruited to the plasma membrane by a light-regulated protein-lipid electrostatic interaction with the inner leaflet. Direct membrane recruitment of these effectors induced potent contractile signaling sufficient to separate adherens junctions in response to as little as one pulse of blue light. Cytoskeletal morphology changes were dependent on the alignment of the spatially patterned stimulation with the underlying cell polarization. RhoA-mediated cytoskeletal activation induced YAP nuclear localization within minutes and subsequent mechanotransduction, verified by YAP- TEAD transcriptional activity. These single-component tools, which do not require protein binding partners, offer spatiotemporally precise control over RhoA signaling that will advance the study of its diverse regulatory roles in cell migration, morphogenesis, and cell cycle maintenance.
Mouse oocytes do not contain a Balbiani body
Authors: Dhandapani Laasya , Salzer Marion C. , Duran Juan M. , Zaffagnini Gabriele , De Guirior Cristian , Martínez-Zamora Maria Angeles , Böke Elvan
Published: February 2021

Oocytes spend the majority of their lifetime in a primordial, dormant state. Unlike many somatic cell types and mature oocytes, the cellular and molecular biology of primordial oocytes is largely unexplored. Yet, studying their cellular biology is necessary to understand the mechanisms through which oocytes maintain cellular fitness for decades, and why they eventually fail with age.

A hallmark of primordial oocytes in many species is the Balbiani body, a non-membrane bound compartment that contains the majority of mitochondria in the oocyte cytoplasm. The Balbiani body has been proposed to be essential for maintaining mitochondria in a healthy state during long-lasting dormancy, however, the architecture and function of the mammalian Balbiani body remains unknown.

Here, we develop enabling methods for live-imaging based comparative characterization ofXenopus, mouse and human primordial oocytes. We show that primordial oocytes in all three vertebrate species contain active mitochondria, Golgi apparatus and lysosomes. We further demonstrate that human andXenopusoocytes have a Balbiani body characterized by a dense accumulation of mitochondria in their cytoplasm. However, despite previous reports, we did not find a Balbiani body in mouse oocytes. Instead, we demonstrate what was previously used as a marker for the Balbiani body in mouse primordial oocytes is in fact a ring-shaped Golgi apparatus that is not functionally associated with oocyte dormancy. Our work provides the first insights into the organisation of the cytoplasm in mammalian primordial oocytes, and clarifies relative advantages and limitations of choosing different model organisms for studying oocyte dormancy.
MESOMELIC DYSPLASIAS ASSOCIATED WITH THEHOXDLOCUS ARE CAUSED BY REGULATORY REALLOCATIONS
Authors: Bolt Christopher Chase , Lopez-Delisle Lucille , Mascrez Bénédicte , Duboule Denis
Published: February 2021

Some human families display severe shortening and bending of the radius and ulna, a condition referred to as mesomelic dysplasia. Many of these families contain chromosomal rearrangements at 2q31, where the humanHOXDlocus maps. In mice, the dominant X-ray-inducedUlnalessinversion of theHoxDgene cluster produces a similar phenotype suggesting that the same mechanism is responsible for this pathology in humans and mice. Amongst the proposed explanations, the various alterations to the genomic structure ofHOXDcould exposeHoxd13to proximal limb enhancers, leading to its deleterious gain-of-expression in the embryonic forelimb. To assess this hypothesis, we used an engineered 1Mb large inversion including theHoxDgene cluster, in order to positionHoxd13within a chromatin domain rich in proximal limb enhancers. We show that these enhancers contact and activateHoxd13in proximal cells, concomitant to the formation of a mesomelic dysplasia phenotype. A secondary mutation in the coding frame of the HOXD13 protein in-ciswith the inversion completely rescued the limb alterations, demonstrating that ectopic HOXD13 is indeed the unique cause of this bone anomaly. Single cell expression analysis and evaluation of HOXD13 binding sites in cells from this ectopic expression domain suggests that the phenotype arises primarily by acting through genes normally controlled by HOXD13 in distal limb cells. Altogether, these results provide a conceptual and mechanistic framework to understand and unify the molecular origins of human mesomelic dysplasia associated with 2q31.
2-(2,4-Dinitrophenyl)-1-(pyridin-4-yl)ethanol monohydrate
Authors: Huang Houshi , Wu Zhichao
Published: February 2021

In the title compound, C13H11N3O5·H2O, the dihedral angle between the aromatic rings is 9.60 (7)° and the chain linking the rings has an anti conformation with a torsion angle of −178.28 (12)°. In the crystal, the components are linked by O—H...O and O—H...N hydrogen bonds, generating (010) sheets.
Premium versus affordable clothing retailers: what are customer expectations for satisfaction and repurchase intentions?
Authors: Cunningham Nicole , De Meyer-Heydenrych Christine
Published: February 2021

Purpose

Within the highly competitive clothing retail industry, retailers (both affordable and premium) need to consider which customer experience elements drive customer satisfaction and repurchase intentions. The purpose of this study is to determine whether customer expectations are different for various types of clothing retailers, and what customers specifically expect when purchasing from a retailer.

Design/methodology/approach

For this study, a positivistic quantitative research design and a non-probability convenience sampling method were used. A total of 222 useable questionnaires were used to conduct descriptive statistics. Confirmatory factor analysis, structural equation modelling and multi-group analysis were run to test the hypotheses.

Findings

The results indicate that customers expect affordable retailers to provide them with convenience and to create a positive shopping experience, while premium clothing retailers should offer added-value and convenience. In addition, the presence of other customers influences the experience. For both groups, satisfaction was a predictor of loyalty, which, in turn, was a predictor of repurchase intentions.

Originality/value

The study is unique as it compares the customer expectations for satisfaction and repurchase intentions for both affordable retailers and premium retailers. The study is conducted in an emerging market context where the growth of the retailing industry is visible. By conducting this study, both affordable and premium clothing retailers are more informed with regards to their customer's expectations and how those expectations should be managed in order to ensure satisfaction and repurchase intention.
Entrepreneurial leadership: the key to develop creativity in organizations
Authors: Mehmood Muhammad Shahid , Jian Zhang , Akram Umair , Tariq Adeel
Published: February 2021

Purpose

Entrepreneurial leadership has been developed from the existing leadership and entrepreneurship literature as a new leadership theory to meet the dynamic changes in the 21st century. Accordingly, the main purpose of this study is to investigate the effect of entrepreneurial leadership on employee creativity and the mediating influence of psychological empowerment and psychological safety, with the lens of social learning theory.

Design/methodology/approach

Data were collected from the manufacturing sector of Pakistan with a sample size of 280 dyads of managers and employees. A two-step analytical strategy was adopted through which the measurement model was validated by using confirmatory factor analysis and structural equation modeling to estimate the structural model to fit the data. The bootstrapping method was applied for testing the mediation analysis.

Findings

The current study found that entrepreneurial leadership positively related to employee creativity. Moreover, it was found that psychological empowerment and psychological safety mediated the relationships between entrepreneurial leadership and employee creativity.

Research limitations/implications

The findings of the current study provide guidance to managers and businessmen on how to develop the creative skills of employees by adopting entrepreneurial leadership behaviors. Besides, this study enriches the literature by exploring the performance mechanism of entrepreneurial leadership to develop employee creativity.

Originality/value

The current study is considered the first to examine the role of entrepreneurial leaders in stimulating employee creativity through psychological safety and psychological empowerment. As such, it enriches the creativity literature by exploring the employee creativity mechanism through entrepreneurial leadership and validating the importance of psychological factors in the development of creativity compared to previous studies, which have focused primarily on the concept or scale development of entrepreneurial leadership. Furthermore, it provides several theoretical and managerial implications along with future opportunities.
Employee engagement constructs: “CARE” model of engagement – need to look beyond the obvious
Authors: Mani Swaminathan , Mishra Mridula
Published: February 2021

Purpose

The purpose of this article is to identify new variables that form the core building blocks of employee engagement model which can be leveraged by human resources' (HR) practitioners to develop HR strategies to drive employee engagement initiatives in their companies.

Design/methodology/approach

The authors have undertaken extensive literature review to identify the variables that enhances engagement. These variables are yet to be leveraged fully in engagement models that have been developed but have the potential to impact the motivation levels of the employees. Exploratory survey to validate the relevance of these variables was conducted and subsequently these variables were grouped into a Context, Altruistic, Resonance and Enable (“CARE”) framework that can be leveraged by HR practitioners.

Findings

The changing nature of workforce, increasing diversity and tenure of jobs has resulted in changing aspirations of employees as well. The building blocks hitherto adopted by companies to craft their employee engagement strategies have to undergo a perceptible change as well. This paper offers an alternative perspective of relooking the engagement levers currently adopted by firms (work environment, autonomy, appreciation, organization support, etc.) and proposes 15 new building blocks (resonant connections, value congruence, socialization practices, micro-moments of connections, fit amongst others) which are logically grouped under CARE model over which employee engagement strategies can be built by companies.

Originality/value

This paper provides insights into this important concept of employee engagement using a set of newer constructs that can form the foundation of newer models that will drive future HR strategies to enhance engagement.
Long‐term efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 5‐year extension of a phase 3 study (reSURFACE 1)
Authors: Imafuku Shinichi , Nakagawa Hidemi , Igarashi Atsuyuki , Morita Akimichi , Okubo Yukari , Sano Shigetoshi , Tada Yayoi , Nemoto Osamu , Rozzo Stephen J. , Kawamura Masaki , Ohtsuki Mamitaro
Published: February 2021

The three part, double‐blind, randomized, controlled reSURFACE 1 trial and extension study (NCT01722331) evaluated efficacy and safety of tildrakizumab in adults with moderate to severe plaque psoriasis. Patients with ≥50% improvement from baseline in Psoriasis Area and Severity Index (PASI 50) following treatment with tildrakizumab 100 mg (TIL100) or 200 mg (TIL200) could enter the optional long‐term extension study and continue treatment at the same dose for an additional 192 weeks. This subgroup analysis assessed the long‐term efficacy and safety of tildrakizumab treatment for Japanese patients enrolled in reSURFACE 1 for up to 5 years of treatment. The primary efficacy outcomes were the proportions of patients who maintained PASI 75 and Physician Global Assessment (PGA) clear or minimal with ≥2‐grade reduction from baseline (PGA 0/1) from base study week 64 to extension week 192. Secondary outcomes were the proportion of patients who maintained PASI 90/100 from base study week 64 to extension week 192. Adverse events (AEs) were monitored throughout the study and for up to 20 weeks after the last study visit. Of the 120 Japanese patients who entered the reSURFACE 1 extension study, 43 (79.6%) patients receiving tildrakizumab 100 mg and 58 (87.9%) patients receiving tildrakizumab 200 mg completed the extension study. Of all Japanese patients with PASI 75/90/100 and PGA 0/1 at week 64, 85%/88% receiving TIL100/TIL200 maintained PASI 75, 70%/96% maintained PASI 90, 63%/67% maintained PASI 100, and 68%/72% maintained PGA 0/1 at extension week 192. AEs led to discontinuation in 1.7 patients per 100 patient‐years (P100PY) receiving tildrakizumab 100 mg and 0.8 P100PY receiving tildrakizumab 200 mg. Incidences of severe infections, malignancies, confirmed major adverse cardiac events, and hypersensitivity reactions were low in both treatment groups. Through 5 years of treatment, tildrakizumab maintained efficacy and was well tolerated with low rates of AEs of special interest.