bluuebunny/crossref_metadata_2025 huggingface dataset:
A dual voltage clamp technique to study gap junction hemichannels in astrocytes cultured from neonatal rodent spinal cords
Authors: Garré Juan Mauricio , Bukauskas Feliksas F. , Bennett Michael V.L.
Published: November 2021

Astrocytes express surface channels involved in purinergic signaling, and among these channels, pannexin-1 (Px1) and connexin-43 (Cx43) hemichannels (HCs) mediate ATP release that acts directly, or through its derivatives, on neurons and glia via purinergic receptors. Although HCs are functional, i.e., open and close, under physiological and pathological conditions, single channel conductance of Px1 HCs is not well defined. Here, we developed a dual voltage clamp technique in HeLa cells overexpressing human Px1-YFP, and then applied this system to rodent spinal astrocytes. Single channels were recorded in cell attached patches and evoked with ramp cycles of 2 s duration and -/+ 80-100 mV amplitude through another pipette in whole cell clamp. Conductance of Px1 HC openings recorded during ramp stimuli ranged 25-110 pS. Based on their single channel conductances, Px1 HCs could be distinguished from Cx43 HCs and P2X7 receptors (P2X7Rs) in spinal astrocytes during dual voltage clamp experiments. Furthermore, we found that single channel activity of Cx43 HCs and P2X7Rs was increased, and that of Px1 HCs was decreased, in spinal astrocytes treated for 7 h with FGF-1, a growth factor implicated in neurodevelopment, repair and inflammation.
Robust and Efficient Assessment of Potency (REAP): A Quantitative Tool for Dose-response Curve Estimation
Authors: Zhou Shouhao , Liu Xinyi , Fang Xinying , Chinchilli Vernon M. , Wang Michael , Wang Hong-Gang , Dokholyan Nikolay V , Shen Chan , Lee J Jack
Published: November 2021

The median-effect equation has been widely used to describe the dose-response relationship and identify compounds that activate or inhibit specific disease targets in contemporary drug discovery. However, the experimental data often contain extreme responses, which may significantly impair the estimation accuracy and impede valid quantitative assessment in the standard estimation procedure. To improve the quantitative estimation of the dose-response relationship, we introduce a novel approach based on robust beta regression. Substantive simulation studies under various scenarios demonstrate solid evidence that the proposed approach consistently provides robust estimation for the median-effect equation, particularly when there are extreme outcome observations. Moreover, simulation studies illustrate that the proposed approach also provides a narrower confidence interval, suggesting a higher power in statistical testing. Finally, to efficiently and conveniently perform common lab data analyses, we develop a freely accessible web-based analytic tool to facilitate the quantitative implementation of the proposed approach for the scientific community.
A fast variational algorithm to detect the clonal copy number substructure of tumors from single-cell data
Authors: De Falco Antonio , Caruso Francesca , Su Xiao-Dong , Iavarone Antonio , Ceccarelli Michele
Published: November 2021

Here we report Single CEll Variational ANeuploidy analysis (SCEVAN), a fast variational algorithm for the deconvolution of the clonal substructure of tumors from single cell data. It uses a multichannel segmentation algorithm exploiting the assumption that all the cells in a given copy number clone share the same breakpoints. Thus, the smoothed expression profile of every individual cell constitutes part of the evidence of the copy number profile in each subclone. SCEVAN can automatically and accurately discriminate between malignant and non-malignant cells, resulting in a practical framework to analyze tumors and their microenvironment. We apply SCEVAN to several datasets encompassing 106 samples and 93,322 cells from different tumors types and technologies. We demonstrate its application to characterize the intratumor heterogeneity and geographic evolution of malignant brain tumors.
Characterization of Reactive Oxygen Species Signaling changes in a cell culture model of skeletal muscle ageing, and its application to screening pharmacokinetically-relevant exposures of dietary polyphenols for bioactivity
Authors: Hayes N. , Fogarty M. , Sadofsky L. , Jones H.S.
Published: November 2021

Age-related frailty is a significant health and social care burden, however treatment options are limited. There is currently a lack of suitable cell culture model for screening large numbers of test compounds to identifying those which can potentially promote healthy skeletal muscle function. This paper describes the characterization of reactive oxygen and nitrogen species (RONS) signalling changes in young and aged myoblasts and myotubes using the C2C12cell line, and the application of aged myoblast and myotube cultures to assess the effect of dietary polyphenols on RONS signalling. Aged myoblasts and myotubes were observed to have significantly increased reactive oxygen species levels (p<0.01 and p<0.001 respectively), increases in nitric oxide levels (p<0.05 for myoblasts and myotubes), and lipid peroxidation markers (p<0.05 for myoblasts and myotubes). A panel of nine polyphenols were assessed in aged myoblasts and myotubes using concentrations and incubation times consistent with known pharmacokinetic parameters for these compounds. Of these, although several polyphenols were seen to reduce single markers of RONS signalling, only kaempferol and resveratrol consistently reduced multiple markers of RONS signalling with statistical significance in both cell models. Modulation of cellular enzymatic antioxidant activities (superoxide and catalase) was assessed as a possible mechanism of action for these polyphenols, and although both superoxide and catalase activities were significantly reduced in aged (versus young) myotubes (p<0.01 and p<0.05 respectively), no effect of polyphenol treatment on these enzyme activities were observed. Overall, this research has shown the utility of the C2C12model, as both myoblasts and myotubes, as a suitable cell model for screening compounds for modulating RONS signalling in aged muscle, and that resveratrol and kaempferol (using pharmacokinetically-informed exposures) can modulate RONS signalling in skeletal muscle cells after an acute exposure.
Antitumor Effects Of Phytochemicals Of Hot Three Plants On Gastric Adenocarcinoma
Authors: Ragchaasuren Narankhuu , Tumurkhuu Munkhtuya , Byambaa Tserentsoo , Bold Uranbileg , Dagvadorj Enkhmaa , Gendaram Odontuya , Dalkh Tserendagva
Published: November 2021

BACKGROUND

Thymoquinone (TQ) and beta-sitosterol (BS), the bioactive constituents derived from the medicinal plant Atragene sibirica L, Ranunculus repens L, Pulsatilla Bungeana have been used for anti-cancer treatment in Traditional Mongolian Medicine. Recent studies reported that TQ, BS exhibited anti-proliferative effects on several cancer cell lines. This study was performed to investigate the antitumor effects of phytochemicals on gastric adenocarcinoma in vitro.

METHODS

To this aim, we performed a cell apoptosis assay WST1 and several cancer-related gene expressions (Bcl, BIRC5, p53, BAX). NCI-N87, MKN74 cells were seeded at a density of 5×104 cells per well in 96-well culture plates. After overnight incubation, the fresh medium containing different concentrations of TQ (20, 40, 60, 80, and 100 mM/ml) and beta-sitosterol (10, 1, 0.1, 0.001, 0.001 mM/ml) were applied. Following a 24-h incubation, the cell viability was determined by WST-1 assay. We also quantified the expression levels of mRNAs of these genes through qRT-PCR experiments.

RESULTS

Our results showed that TQ induced a higher percentage of cell apoptosis in the human gastric adenocarcinoma cell lines compared to that of control. We observed a significant 4.8-fold change in BAX/BCL2 ratio. These increases were highly correlated with a concentration-dependent manner (p=0.00178). Moreover, the expression of p53 and BIRC5 was downregulated in MKN74 cells after treatment with TQ.

CONCLUSIONS

Our results demonstrate that TQ effectively inhibits cell proliferation through several gene expressions in vitro. Moreover, inhibition of the downstream molecule of these genes would explain the underlying mechanism of the antitumor activity in cancer cell lines.
Stress deceleration theory – chronic adolescent stress exposure results in decelerated neurobehavioral maturation
Authors: Jadhav Kshitij S. , Hoffman Alexander F. , Burgisser Morgane , Rosetti Clara , Aeschlimann Léa , Lupica Carl R. , Boutrel Benjamin
Published: November 2021

Normative development in adolescence indicates that the prefrontal cortex is still under development thereby unable to exert efficient top-down inhibitory control on subcortical regions such as the basolateral amygdala and the nucleus accumbens. This imbalance in the developmental trajectory between cortical and subcortical regions is implicated in expression of the prototypical impulsive, compulsive, reward seeking and risk-taking adolescent behavior. Here we demonstrate that a chronic mild unpredictable stress procedure during adolescence in male Wistar rats arrests the normal behavioral maturation such that they continue to express adolescent-like impulsive, hyperactive, and compulsive behaviors into late adulthood. This arrest in behavioral maturation is associated with the hypoexcitability of prelimbic cortex (PLC) pyramidal neurons and reduced PLC-mediated synaptic glutamatergic control of BLA and nucleus accumbens core (NAcC) neurons that lasts late into adulthood. At the same time stress exposure in adolescence results in the hyperexcitability of the BLA pyramidal neurons sending stronger glutamatergic projections to the NAcC. Chemogenetic reversal of the PLC hypoexcitability decreased compulsivity and improved the expression of goal-directed behavior in rats exposed to stress during adolescence, suggesting a causal role for PLC hypoexcitability in this stress-induced arrested behavioral development.
Miniscope-LFOV: A large field of view, single cell resolution, miniature microscope for wired and wire-free imaging of neural dynamics in freely behaving animals
Authors: Guo Changliang , Blair Garrett J. , Sehgal Megha , Sangiuliano Jimka Federico N. , Bellafard Arash , Silva Alcino J. , Golshani Peyman , Basso Michele A. , Blair H. Tad , Aharoni Daniel
Published: November 2021

Imaging large-population, single-cell fluorescent dynamics in freely behaving animals larger than mice remains a key endeavor of neuroscience. We present a large field of view open-source miniature microscope (MiniLFOV) designed for large-scale (3.6 × 2.7 mm), single cell resolution neural imaging in freely behaving rats. It has an electrically adjustable working distance of up to 3.5 mm±100 μm, incorporates an absolute head-orientation sensor, and weighs only 13.9 grams. The MiniLFOV is capable of both deep brain and cortical imaging and has been validated in freely behaving rats by simultaneously imaging >1000 GCaMP7s expressing neurons in the hippocampal CA1 layer and in head-fixed mice by simultaneously imaging ~2000 neurons in the dorsal cortex through a cranial window. The MiniLFOV also supports optional wire-free operation using a novel, wire-free data acquisition expansion board. We expect this new open-source implementation of the UCLA Miniscope platform will enable researchers to address novel hypotheses concerning brain function in freely behaving animals.
Unravelling the regulation pathway of photosynthetic AB-GAPDH
Authors: Marotta Roberto , Del Giudice Alessandra , Gurrieri Libero , Fanti Silvia , Swuec Paolo , Galantini Luciano , Falini Giuseppe , Trost Paolo , Fermani Simona , Sparla Francesca
Published: November 2021

Oxygenic phototrophs perform carbon fixation through the Calvin–Benson cycle. Different mechanisms adjust the cycle and the light-harvesting reactions to rapid environmental changes. Photosynthetic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a key enzyme of the cycle. In land plants, different photosynthetic GAPDHs exist: the most abundant formed by hetero-tetramers of A and B-subunits, and the homo-tetramer A4. Regardless of the subunit composition, GAPDH is the major consumer of photosynthetic NADPH and for this reason is strictly regulated. While A4-GAPDH is regulated by CP12, AB-GAPDH is autonomously regulated through the C-terminal extension (CTE) of B-subunits. Reversible inactivation of AB-GAPDH occurs via oxidation of a cysteine pair located in the CTE, and substitution of NADP(H) with NAD(H) in the cofactor binding domain. These combined conditions lead to a change in the oligomerization state and enzyme inactivation. SEC-SAXS and single-particle cryoEM analysis disclosed the structural basis of this regulatory mechanism. Both approaches revealed that (A2B2)n-GAPDH oligomers with n=1, 2, 4 and 5 co-exist in a dynamic system. B-subunits mediate the contacts between adjacent A2B2 tetramers in A4B4 and A8B8 oligomers. The CTE of each B-subunit penetrates into the active site of a B-subunit of the adjacent tetramer, while the CTE of this subunit moves in the opposite direction, effectively preventing the binding of the substrate 1,3-bisphosphoglycerate in the B-subunits. The whole mechanism is made possible, and eventually controlled, by pyridine nucleotides. In fact, NAD(H) by removing NADP(H) from A-subunits allows the entrance of the CTE in B-subunits active sites and hence inactive oligomer stabilization.

Significance Statement

In land plants, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) unique sink of reducing power of the entire Calvin-Benson cycle, is finely regulated. Based on the redox state and substrates concentration, its heteromeric form AB-GAPDH oscillates between a fully active heterotetramer (A2B2) and inactive oligomers. Experimental evidence demonstrates that GAPDH inactivation depends on the formation of dimers, tetramers or pentamers of A2B2-modules, linked together by C-terminal extensions (CTE) of B-subunits that extrude from one modular tetramer and occupy two active sites of the adjacent one. This molecular mechanism along with the unexpected observed dynamism of the system, shed light on how the Calvin-Benson cycle is modulated in function of the light environmental changes.
Transient inhibition to light explains stronger V1 responses to dark stimuli
Authors: St-Amand David , Baker Curtis L.
Published: November 2021

Neurons in the primary visual cortex (V1) receive excitation and inhibition from distinct parallel pathways processing lightness (ON) and darkness (OFF). V1 neurons overall respond more strongly to dark than light stimuli, consistent with a preponderance of darker regions in natural images, as well as human psychophysics. However, it has been unclear whether this “dark-dominance” is due to more excitation from the OFF pathway or more inhibition from the ON pathway. To understand the mechanisms behind dark-dominance, we record electrophysiological responses of individual simple-type V1 neurons to natural image stimuli and then train biologically inspired convolutional neural networks to predict the neurons’ responses. Analyzing a sample of 74 neurons (in anesthetized, paralyzed cats) has revealed their responses to be more driven by dark than light stimuli, consistent with previous investigations. We show that this asymmetry is predominantly due to slower inhibition to dark stimuli rather than to stronger excitation from the thalamocortical OFF pathway. Consistent with dark-dominant neurons having faster responses than light-dominant neurons, we find dark-dominance to solely occur in the early latencies of neurons’ responses. Neurons that are strongly dark-dominated also tend to be less orientation selective. This novel approach gives us new insight into the dark-dominance phenomenon and provides an avenue to address new questions about excitatory and inhibitory integration in cortical neurons.

Significance

Neurons in the early visual cortex respond on average more strongly to dark than to light stimuli, but the mechanisms behind this bias have been unclear. Here we address this issue by combining single-unit electrophysiology with a novel machine learning model to analyze neurons’ responses to natural image stimuli in primary visual cortex. Using these techniques, we find slower inhibition to light than to dark stimuli to be the leading mechanism behind stronger dark responses. This slower inhibition to light might help explain other empirical findings, such as why orientation selectivity is weaker at earlier response latencies. These results demonstrate how imbalances in excitation vs. inhibition can give rise to response asymmetries in cortical neuron responses.
Motor plans under uncertainty reflect a trade-off between maximizing reward and success
Authors: Wong Aaron L. , Green Audrey L. , Isaacs Mitchell W.
Published: November 2021

When faced with multiple potential movement options, individuals either reach directly to one of the options, or initiate a reach intermediate between the options. It remains unclear why people generate these two types of behaviors. Using the go-before-you-know task (commonly used to study behavior under choice uncertainty), we examined two key questions. First, do these two types of responses reflect distinct movement strategies, or are they simply examples of a more general response to choice uncertainty? If the former, the relative desirability (i.e., weighing the likelihood of successfully hitting the target versus the attainable reward) of the two target options might be computed differently for direct versus intermediate reaches. We showed that indeed, when exogenous reward and success likelihood (i.e., endogenous reward) differ between the two options, direct reaches were more strongly biased by likelihood whereas intermediate movements were more strongly biased by reward. Second, what drives individual differences in how people respond under uncertainty? We found that risk/reward-seeking individuals generated a larger proportion of intermediate reaches and were more sensitive to trial-to-trial changes in reward, suggesting these movements reflect a strategy to maximize reward. In contrast, risk-adverse individuals tended to generate more direct reaches in an attempt to maximize success. Together, these findings suggest that when faced with choice uncertainty, individuals adopt movement strategies consistent with their risk/reward-seeking tendency, preferentially biasing behavior toward exogenous rewards or endogenous success and consequently modulating the relative desirability of the available options.
Cryo-EM structures of the channelrhodopsin ChRmine in lipid nanodiscs
Authors: Tucker Kyle , Sridharan Savitha , Adesnik Hillel , Brohawn Stephen G.
Published: November 2021

Microbial channelrhodopsins are light-gated ion channels widely used for optogenetic manipulation of neuronal activity. ChRmine is a bacteriorhodopsin-like cation channelrhodopsin (BCCR) more closely related to ion pump rhodopsins than other channelrhodopsins. ChRmine displays unique properties favorable for optogenetics including high light sensitivity, a red-shifted activation spectrum, cation selectivity, and large photocurrents while its slow closing kinetics impede some applications. The structural basis for ChRmine function, or that of any other BCCR, is unknown. Here, we present cryo-EM structures of ChRmine in lipid nanodiscs in apo (opsin) and retinal-bound (rhodopsin) forms. The structures reveal an unprecedented trimeric architecture with a lipid filled central pore. Large electronegative cavities on either side of the membrane facilitate high conductance and selectivity for cations over protons. The retinal binding pocket structure suggests spectral and kinetic properties could be tuned with mutations and we identify ChRmine variants with two-fold increased and ten-fold decreased closing rates. These results provide insight into structural features that generate an ultra-potent microbial opsin and provide a platform for rational engineering of channelrhodopsins with improved properties that could expand the scale, depth, and precision of optogenetic manipulations.
Theoretical Guarantees for Phylogeny Inference from Single-Cell Lineage Tracing
Authors: Wang Robert , Zhang Richard , Khodaverdian Alex , Yosef Nir
Published: November 2021

CRISPR-Cas9 lineage tracing technologies have emerged as a powerful tool for investigating development in single-cell contexts, but exact reconstruction of the underlying clonal relationships in experiment is plagued by data-related complications. These complications are functions of the experimental parameters in these systems, such as the Cas9 cutting rate, the diversity of indel outcomes, and the rate of missing data. In this paper, we develop two theoretically grounded algorithms for reconstruction of the underlying phylogenetic tree, as well as asymptotic bounds for the number of recording sites necessary for exact recapitulation of the ground truth phylogeny at high probability. In doing so, we explore the relationship between the problem difficulty and the experimental parameters, with implications for experimental design. Lastly, we provide simulations validating these bounds and showing the empirical performance of these algorithms. Overall, this work provides a first theoretical analysis of phylogenetic reconstruction in the CRISPR-Cas9 lineage tracing technology.
Reconstructing essential active zone functions within a synapse
Authors: Tan Chao , Wang Shan Shan H. , de Nola Giovanni , Kaeser Pascal S.
Published: November 2021

Active zones are molecular machines that control neurotransmitter release through synaptic vesicle docking and priming, and through coupling of these vesicles to Ca2+ entry. The complexity of active zone machinery has made it challenging to determine which mechanisms drive these roles in release. Here, we induce RIM+ELKS knockout to eliminate active zone scaffolding networks, and then reconstruct each active zone function. Re-expression of RIM1-Zn fingers positioned Munc13 on undocked vesicles and rendered them release-competent. Reconstitution of release-triggering required docking of these vesicles to Ca2+ channels. Fusing RIM1-Zn to CaVβ4-subunits sufficed to restore docking, priming and release-triggering without reinstating active zone scaffolds. Hence, exocytotic activities of the 80 kDa CaVβ4-Zn fusion protein bypassed the need for megadalton-sized secretory machines. These data define key mechanisms of active zone function, establish that fusion competence and docking are mechanistically separable, and reveal that active zone scaffolding networks are not required for release.
Human Biopsies in Nanofibrillar Cellulose Hydrogel – A Novel Method for Long-term Tissue Culture
Authors: Niklander Johanna , Koivuniemi Raili , Stallinger Alexander , Kleinegger Florian , Paasonen Lauri , Schrom Silke , Liegl-Atzwanger Bernadette , Zalaudek Iris , von Campe Gord , Singer Georg , Haybaeck Johannes , Yliperttula Marjo , Rinner Beate
Published: November 2021

Advanced 3D in vitro models are laborious to prepare and susceptible to unintentional design errors due to culture adaptations, cell immaturity, xenofactors or yet incomplete knowledge of the dynamics within tissues or materials. In order to acquire cost-efficient research material with intact in vivo composition, we developed novel tissue culture method with plant-derived scaffolding.

Human skin-, foreskin- and glioblastoma multiforme biopsies were dissected mechanically and cultivated for 28 days in plant-derived nanofibrillar cellulose hydrogel. Comparative cultures were done using mouse sarcoma tumor –derived Matrigel™. Long-term preservation of cultivated tissues was evaluated against typical immunohistochemical biomarkers for each tissue type: skin tissues for cytokeratins 5/6, E-cadherin and vimentin for sustained tissue structures, and brain neoplasia for Olig2, S100, Nestin, NOTCH1, MAP2 and GFAP for preserved disease profile.

Histological analysis from both culture conditions showed that until day 28, all cultivated biopsy types were able to sustain their characteristic protein expressions without signs of necrosis. We here conclude a novel tissue culture model in xeno-free 3D scaffolding, that can enable long-term sample storage in vitro, studies of human tumor tissues and their non-neoplastic microenvironment, and innovations in personalized medicine research.
Comparative transcriptional analysis of the satellite glial cell injury response
Authors: Jager Sara Elgaard , Pallesen Lone Tjener , Lin Lin , Izzi Francesca , Pinheiro Alana Miranda , Villa-Hernandez Sara , Cesare Paolo , Vaegter Christian Bjerggaard , Denk Franziska
Published: November 2021

Satellite glial cells (SGCs) tightly surround and support primary sensory neurons in the peripheral nervous system and are increasingly recognized for their involvement in the development of neuropathic pain following nerve injury. The SGCs are difficult to investigate due to their flattened shape and tight physical connection to neurons in vivo and their rapid changes in phenotype and protein expression when cultured in vitro. Consequently, several aspects of SGC function under normal conditions as well as after a nerve injury remain to be explored. The recent advance in single cell RNAseq technologies has enabled a new approach to investigate SGCs. Here we publish a dataset from mice subjected to sciatic nerve injury as well as a dataset from dorsal root ganglia cells after 3 days in culture. We use a meta-analysis approach to compare the injury response with that in other published datasets and conclude that SGCs share a common signature following sciatic nerve crush and sciatic ligation, involving transcriptional regulation of cholesterol biosynthesis. We also observed a considerable transcriptional change when culturing SGCs, suggesting that some differentiate into a specialised in vitro state, while others start resembling Schwann cell-like precursors. The datasets are available via the Broad Institute Single Cell Portal.
Fine-grained, Nonlinear Image Registration of Live Cell Movies Reveals Spatiotemporal Organization of Diffuse Molecular Processes
Authors: Jiang Xuexia , Isogai Tadamoto , Chi Joseph , Danuser Gaudenz
Published: November 2021

We present an application of non-linear Image registration that allows spatiotemporal analysis of extremely noisy and diffuse molecular processes across the entire cell. To produce meaningful local tracking of the spatially coherent portion of diffuse protein dynamics, we improved upon existing non-linear image registration to compensate for cell movement and deformation. The registration relies on a subcellular fiducial marker, a cell motion mask, and a topological regularization that enforces diffeomorphism on the registration without significant loss of granularity. We demonstrate the potential of this approach in conjunction with stochastic time-series analysis through the discovery of distinct zones of coherent Profillin dynamics in symmetry-breaking U2OS cells. Further analysis of the resulting Profilin dynamics revealed strong relationships with the underlying actin organization. This study thus provides a framework for extracting functional interactions between cell morphodynamics, protein distributions, and signaling in cells undergoing continuous shape changes.

Author Summary

By adapting optical flow based nonlinear image registration we created a method specific for live cell movies that preserves the dynamics of a signal of interest by remapping using a separate measurable subcellular location fiducial. This is an extension as well on our lab’s previously published method of cell edge-based referencing of subcellular locations that was incapable of extracting interpretable subcellular time series more than a few microns away from the cell edge. We showed that our method overcomes this key limitation and allows sampling of subcellular time series from every subcellular location through our discovery of organized profilin dynamics in moving cell and that these profilin dynamics are related to actin dynamics due to their ability to bind growing actin structures likely through actin polymerizing factors. Most importantly, our method is applicable to discovering subcellular organization and coordination in a widely used form of live cell microscopy data that hitherto has been largely limited to anecdotal analysis.
Exogenous estradiol and oxytocin modulate sex differences in hippocampal reactivity and episodic memory
Authors: Coenjaerts Marie , Trimborn Isabelle , Adrovic Berina , Stoffel-Wagner Birgit , Cahill Larry , Philipsen Alexandra , Hurlemann Rene , Scheele Dirk
Published: November 2021

Considerable evidence supports sex differences in episodic memory, which may translate to heightened vulnerability to stress- and trauma-related disorders in women. The hormones estradiol and oxytocin both affect episodic memory, but possible underlying hormonal interactions have not been systemically tested in humans. To this end, healthy women (n = 111) and men (n = 115) received estradiol gel (2 mg) or placebo before the administration of intranasal oxytocin (24 IU) or placebo in a randomized, placebo-controlled, parallel-group functional magnetic resonance imaging (fMRI) study. In the fMRI session, participants viewed positive, neutral, and negative scenes. A surprise recognition task was conducted three days later. Under placebo, women showed a significantly better recognition memory and increased hippocampal responses to subsequently remembered items independent of the emotional valence compared to men. The separate treatments with either hormone significantly diminished this mnemonic sex difference and reversed the hippocampal activation pattern. However, the combined treatments led to a memory performance comparable to that of the placebo group. Collectively, the results suggest that both hormones play a crucial role in modulating sex differences in episodic memory. Furthermore, possible antagonistic interactions between estradiol and oxytocin could explain previously observed opposing hormonal effects in women and men.
Materials on Plant Leaf Surfaces are Deliquescent in a Range of Environments
Authors: Tredenick E. C. , Stuart-Williams H. , Enge T. G.
Published: November 2021

Materials on plant leaf surfaces that attract water impact penetration of foliar-applied agrochemicals, foliar water uptake, gas exchange and stomatal density. Few studies are available on the nature of these substances, and we quantify the hygroscopicity of these materials. Water vapor sorption experiments on twelve leaf washes of sample leaves were conducted and analyzed with inductively coupled plasma-optical emission spectroscopy and X-ray diffraction. All leaf surface materials studied were hygroscopic. Oils were found on the surface of the Eucalyptus studied. For mangroves that excrete salt to the leaf surfaces, significant sorption occurred at high humidity of a total of 316 mg (∼ 0.3 mL) over 6–10 leaves, and fitted a Guggenheim, Anderson, and de Böer sorption isotherm. Materials on the plant leaf surface can deliquesce and form an aqueous solution in a variety of environments where plants grow, including glasshouses and by the ocean, which is an important factor when considering plant-atmosphere relations.
Effect of conjugated system extension on structural features and electron-density distribution in charge–transfer difluoroborates
Authors: Ośmiałowski Borys , Dziuk Błażej , Ejsmont Krzysztof , Chęcińska Lilianna , Dobrzańska Liliana
Published: November 2021

A comparative structural study of two related donor–acceptor pyridine-based BF2 complexes, namely, 3-(dimethylamino)-1,1-difluoro-1H-pyrido[1,2-c][1,3,5,2]oxadiazaborinin-9-ium-1-uide, C8H10BF2N3O (1), and 3-{(1E,3E)-4-[4-(dimethylamino)phenyl]buta-1,3-dien-1-yl}-1,1-difluoro-1H-pyrido[1,2-c][1,3,5,2]oxadiazaborinin-9-ium-1-uide, C18H18BF2N3O (2), containing a dimethylamino group and either the shortest (in 1) or the longest (in 2) charge-transfer path known until now in this family of compounds, is presented. Single-crystal X-ray diffraction analysis supported by computational investigations shed more light on these systems, indicating, among other aspects, the predominance of C—H...F contacts in 1, the formation of antiparallel dimers held together by π–π interactions in both compounds, and the involvement of fused BF2-bearing rings in the charge-transfer process.
Value cocreation in new service development: a process-based view of resource dependency
Authors: Wang Qiang , Oshri Ilan , Zhao Xiande
Published: November 2021

Purpose

This study aims to examine value cocreation in terms of interfirm collaborations between service firms, their business customers and business partners at different stages of a new service development (NSD) process.

Design/methodology/approach

The study develops and tests hypotheses that examine the roles played by business customers and partners in NSD, assuming resource dependency of the focal firm during three NSD stages (ideation, development and deployment). Empirical data were collected from 200 NSD projects and structural equation modelling was used to test the hypotheses.

Findings

The results show that business customer collaboration has a positive effect on ideation performance and development performance, whereas business partner collaboration has a positive effect on deployment performance. These finding support the notion that the value cocreating roles of business customers and partners vary across NSD stages.

Research limitations/implications

Future research should focus on how business partners can be actively involved in the NSD process and how the interests of different parties can be safeguarded. The use of longitudinal data will allow a better examination of the process dynamics.

Practical implications

The study provides managerial implications for service managers in terms of acquiring and allocating resources needed from business customers and partners during different NSD stages.

Originality/value

The study contributes to the growing literature on value cocreation in NSD by empirically demonstrating the respective performance contributions of business customers and partners during different stages of NSD. Moreover, the results also shed light on interfirm collaboration mechanisms from the perspective of resource dependence theory.
Rethinking the strategic management of human resources: lessons learned from Covid-19 and the way forward in building resilience
Authors: Roumpi Dorothea
Published: November 2021

Purpose

Numerous empirical studies and meta-analyses have offered ample evidence for the relationship between the strategic management of human resources and a variety of important organizational outcomes, such as individual- and firm-level performance. The outbreak of the COVID-19 pandemic, however, steered the discussion away from the traditional performance-related outcomes of the strategic human resource management and brought to the fore the importance of resilience. The purpose of this paper is to identify areas in which strategic human resource management can help organizations to become more resilient.

Design/methodology/approach

On the basis of a brief overview of the different phases of the COVID-19 pandemic and its impact on the management of human resources, this conceptual paper uses the Ability-Motivation-Opportunity framework as the backbone for the development of suggestions for the strategic management of employees to create and maintain organizational resilience.

Findings

A series of actionable suggestions regarding the way forward in building organizational resilience through the effective and ethical management of employees are presented and discussed. Specifically, the importance of using flexibility-oriented human resource management systems is highlighted. This “flexibility-orientation” involves all functions of human resource management, such as selection, training and compensation.

Originality/value

The proposed suggestions can benefit organizations by offering actionable recommendations regarding the management of human resources by taking stock of lessons learned during the COVID-19 pandemic.
Opentable as a marketing strategy for modern Muslim funeral product in Indonesia
Authors: Prihatiningsih Witanti , Damayani Ninis Agustini , Suryana Asep , Perbawasari Susie
Published: November 2021

Purpose

The Opentable strategy is considered a taboo because of its ability to take advantage of peoples’ grief. Therefore, this study aims to explore the Opentable (Exhibition) as a marketing strategy for modern Muslim funeral products, considered a luxury by most people in Indonesia.

Design/methodology/approach

This is a qualitative research with a phenomenological approach used to collect data from six Memorial Advisors (MAs) through interviews.

Findings

The result showed that the Opentable strategy was carried out to introduce the concept of a modern Muslim funeral home and its products. Furthermore, MA does not encourage sales during Opentable, rather, it uses the process to obtain complete data from potential customers.

Practical implications

This research serves as a guidance for MA and other similar professions to socialize products uncommon or considered taboo in society. It also provides a repertory of new marketing strategies, especially for targeted and uncommon products.

Originality/value

To the best of the knowledge, this is the first research to explore Opentable (Exhibition) as a marketing strategy for modern Muslim funeral products in Indonesia. Therefore, future research is needed on other marketing strategies.
Cultural differences in deliberate counterfeit purchase behavior
Authors: Sharma Piyush , Chan Ricky Y. K. , Davcik Nebojsa , Ueno Akiko
Published: November 2021

Purpose

This paper explores the moderating effects of four personal cultural orientations or PCOs (independence, interdependence, risk aversion and ambiguity intolerance) on the relationships among counterfeit proneness, subjective norms, ethical judgments, product evaluation and purchase intentions for counterfeit products.

Design/methodology/approach

A field study with 840 consumers in Hong Kong using a self-administered structured questionnaire is used to test all the hypotheses.

Finding

Consumers with high (low) scores on interdependence (independence) show stronger positive effects of counterfeit proneness on subjective norms and its effects on the counterfeit evaluation and purchase intentions. In contrast, consumers with high (low) scores on independence (interdependence) show stronger positive effects of counterfeit proneness on ethical judgments and its effects on counterfeit evaluation and purchase intentions. Consumers with higher scores on risk aversion and ambiguity intolerance show negative moderating effects on most of the relationships in the unified conceptual framework.

Research limitations/implications

The authors collected data in Hong Kong, which is predominantly Chinese in culture. Hence, future research in other parts of the world with more diverse cultural values would help test the validity and generalizability of the results.

Practical implications

The findings would be useful for managers of genuine brands to learn more about the process that explains deliberate counterfeit purchase behavior.

Originality/value

The authors extend the unified conceptual framework for deliberate counterfeit purchase behavior by incorporating four PCOs to explore cultural differences in the socio-psychological decision-making process underlying this behavior.
Digital transformation: “jobocolypse” or empowerment?
Authors: Hizir Zeynep
Published: November 2021

Purpose

The purpose of this paper is to analyse the impact of digital transformation on jobs and to assess whether or not the so-called Fourth Industrial Revolution will lead to mass redundancies. The piece also looks at the role human resources (HR) departments will have to play in the implementation of, and response to, digital transformation within the workplace.

Design/methodology/approach

This paper combines research based on media articles, a parliamentary report and wider digital transformation industry research. The author looks to explain what digital transformation is, deconstruct misconceptions around digital transformation, assess the true evidence-based impact of digital transformation on jobs and advise HR departments on the impact of digital transformation within the workplace.

Findings

This piece finds that there remains a considerable degree of misunderstanding and many misconceptions around digital transformation and that while digital transformation will lead to the loss of some jobs, it will also lead to the change of existing ones and creation of new ones. Furthermore, this piece finds that HR departments will play a crucial role in the implementation of digital transformation, but that they too will need to pivot and adjust to new workplace realities as a result.

Originality/value

Many HR departments face confusion and misconceptions around the impact of digital transformation on the workforce, and there also remains concern among many employers that technology will replace their jobs. This piece seeks to dispel the myths and paint a clearer picture to both HR departments and employees around the impact of digital transformation.
Successful treatment of tumor stage mycosis fungoides with total skin helical tomotherapy
Authors: Yonekura Kentaro , Ichiki Mamoru , Takeda Koichiro , Uchiyama Noriaki , Nishida Hirotoshi , Dokiya Takushi
Published: November 2021

Total skin electron beam therapy (TSEBT) is a treatment option for mycosis fungoides (MF). In Japan, it has been rarely performed because of the time required for each treatment, physical burden on patients, and difficulties in providing uniform dosimetry. In recent years, helical tomotherapy, an intensity‐modulated radiation therapy that applies helical computed tomography technology, has been used to treat cancer. Total skin helical tomotherapy (TSHT) has been suggested as a promising alternative to TSEBT for patients with MF, but there are few reports from Japan. We used TSHT to treat a 28‐year‐old Japanese woman with tumor stage MF. She achieved complete remission with TSHT (12 Gy in six fractions over 6 days) and remained in remission for 32 months without additional treatment. Treatment‐related grade 4 myelosuppression was observed, but resolved with blood transfusions and subcutaneous injection of granulocyte colony stimulating factor. Other adverse events were tolerable. Although careful attention should be paid to myelosuppression, TSHT might be a useful treatment option for MF.
Mobile assessment of decisions to drink in young adults: Examining the role of incentives and disincentives
Authors: Howe Lindy K. , Copeland Savanna , Fisher Lindsey , Farmer Eli , Nemes Luca , Finn Peter R.
Published: November 2021

Background

Research on decision‐making (DM) biases in persons with alcohol use disorder have largely relied on behavioral economic DM tasks, which do not assess the dynamic multitude of factors associated with real‐world decisions about drinking. The current study extends the literature on DM and alcohol use by using a mobile daily diary approach to investigate whether, and how, real‐world incentives and disincentives are associated with actual drinking decisions in college students.

Methods

We assessed current drinking and lifetime alcohol problems in 104 young adults (61.5% female, 84.5% White) who, for 14 days, used a mobile daily diary to respond to questions about drinking decisions from the day prior. Mobile prompts assessed daily data on the timing of drinking decisions, alcohol quantity initially decided to drink, quantity actually decided to drink, and the incentives that influenced drinking decisions.

Results

Users of the app reported high usability, high compliance rates were observed, and incentive responses were reduced to three subtypes: alcohol, social/party, and mood. Daily mobile measures of drinking quantity were strongly correlated with self‐reported drinking 2 weeks prior to the daily assessment. Lifetime alcohol problems were positively related to the average quantity decided to drink per event, drinking more than initially decided, and higher levels of self‐reported drinking‐decision incentives. “Alcohol” and “social/party” incentives were positively related to the quantity the participant decided to drink at drinking events. Mood incentives and disincentives showed little to no significant relationships with drinking decisions.

Conclusions

The results suggest that mobile data collection can be useful for assessing aspects of real‐world drinking decisions and the influence of multiple drinking decision incentives.
Expression pattern of mitochondrial respiratory chain enzymes in skeletal muscle of patients with mitochondrial myopathy associated with the homoplasmic m.14674T>C variant
Authors: Roos Sara , Hedberg‐Oldfors Carola , Visuttijai Kittichate , Stein My , Kollberg Gittan , Elíasdóttir Ólöf , Lindberg Christopher , Darin Niklas , Oldfors Anders
Published: November 2021

Two homoplasmic variants in tRNAGlu (m.14674T>C/G) are associated with reversible infantile respiratory chain deficiency. This study sought to further characterize the expression of the individual mitochondrial respiratory chain complexes and to describe the natural history of the disease. Seven patients from four families with mitochondrial myopathy associated with the homoplasmic m.14674T>C variant were investigated. All patients underwent skeletal muscle biopsy and mtDNA sequencing. Whole‐genome sequencing was performed in one family. Western blot and immunohistochemical analyses were used to characterize the expression of the individual respiratory chain complexes. Patients presented with hypotonia and feeding difficulties within the first weeks or months of life, except for one patient who first showed symptoms at 4 years of age. Histopathological findings in muscle included lipid accumulation, numerous COX‐deficient fibers, and mitochondrial proliferation. Ultrastructural abnormalities included enlarged mitochondria with concentric cristae and dense mitochondrial matrix. The m.14674T>C variant in MT‐TE was identified in all patients. Immunohistochemistry and immunoblotting demonstrated pronounced deficiency of the complex I subunit NDUFB8. The expression of MTCO1, a complex IV subunit, was also decreased, but not to the same extent as NDUFB8. Longitudinal follow‐up data demonstrated that not all features of the disorder are entirely transient, that the disease may be progressive, and that signs and symptoms of myopathy may develop during childhood. This study sheds new light on the involvement of complex I in reversible infantile respiratory chain deficiency, it shows that the disorder may be progressive, and that myopathy can develop without an infantile episode.