bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex dependence of opioid-mediated responses to subanesthetic ketamine
Authors: Di Ianni Tommaso , Azadian Matine M. , Ewbank Sedona N. , Michaelides Michael , Airan Raag D. 
Published: September 2022

AbstractSubanesthetic ketamine rapidly and robustly reduces depressive symptoms in patients with treatment-resistant depression. While it is commonly classified as an N-methyl D-aspartate receptor (NMDAR) antagonist, our picture of ketamine’s mechanistic underpinnings is incomplete. Recent clinical evidence has indicated, controversially, that a component of the efficacy of ketamine in depression may be opioid dependent. Using pharmacological functional ultrasound imaging in rats, we found that blocking opioid receptors suppressed neurophysiologic changes evoked by ketamine, but not by a more selective NMDAR antagonist, in regions implicated in the pathophysiology of depression and in reward processing. Importantly, this opioid-dependent response was strongly sex dependent, as it was not evident in female subjects and was fully reversed by surgical removal of the male gonads. We observed similar opioid-mediated sex-dependent effects in ketamine-evoked structural plasticity and behavioral sensitization. Together, these results underscore the potential for ketamine to induce its affective responses via opioid signaling, and indicate that this opioid dependence may be strongly influenced by subject sex. These factors should be more directly assessed in future clinical trials.One-Sentence SummarySubanesthetic ketamine evokes opioid-mediated behavioral and neurophysiological effects in male, but not female, rats.
Tracking N- and C-termini of C. elegans polycystin-1 reveals their distinct targeting requirements and functions in cilia and extracellular vesicles
Authors: Walsh Jonathon D. , Wang Juan , DeHart Molly , Nikonorova Inna A. , Srinivasan Jagan , Barr Maureen M. 
Published: September 2022

AbstractThe cilium acts as an antenna receiving and sending signals, the latter via extracellular vesicles (EVs). In C. elegans and mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 (PC1) and polycystin-2 (PC2) localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation. However, the functions of the polycystins on cilia and EVs remain enigmatic. We used our C. elegans model and endogenously fluorescent-tagged LOV-1/polycystin-1 to study LOV-1 processing, trafficking, transport, EV biogenesis, and function in living animals. Super resolution, real time imaging reveals that LOV-1 is processed into N-terminal and C-terminal forms via a conserved GPCR proteolytic site (GPS). The LOV-1 NTM is secreted into the extracellular matrix and not localized to ciliary tip EVs. In contrast, LOV-1 CTM and PKD-2 are co-trafficked, co-transported, and co-localized in cilia and on environmentally-released ciliary EVs. LOV-1 CTM requires PKD-2 for ciliary EV localization, while PKD-2 localizes to ciliary EVs independent of LOV-1. We find that LOV-1 but not PKD-2 is required for chemosensation of an ascaroside mating pheromone. These findings indicate that the polycystins LOV-1 and PKD-2 function together and independently and provide insight to how cargo selected and packaged in ciliary EVs.
Platform-Agnostic CellNet (PACNet) enables cross-study meta-analysis of cell fate engineering protocols
Authors: Lo Emily K.W. , Velazquez Jeremy , Peng Da , Kwon Chulan , Ebrahimkhani Mo R. , Cahan Patrick 
Published: September 2022

SummaryThe optimization of cell fate engineering protocols requires evaluating their fidelity, efficiency, or both. We previously adopted CellNet, a computational tool to quantitatively assess the transcriptional fidelity of engineered cells and tissues as compared to their in vivo counterparts based on bulk RNA-Seq. However, this platform and other similar approaches are sensitive to experimental and analytical aspects of transcriptomics methodologies. This makes it challenging to capitalizing on the expansive, publicly available sets of transcriptomic data that reflect the diversity of cell fate engineering protocols. Here, we present Platform-Agnostic CellNet (PACNet), which extends the functionality of CellNet by enabling the assessment of transcriptional profiles in a platform-agnostic manner, and by enabling the comparison of user-supplied data to panels of engineered cell types from state-of-the-art protocols. To demonstrate the utility of PACNet, we evaluated a range of cell fate engineering protocols for cardiomyocytes and hepatocytes. Through this analysis, we identified the best-performing methods, characterized the extent of intra-protocol and inter-lab variation, and identified common off-target signatures, including a surprising neural and neuroendocrine signature in primary liver-derived organoids. Finally, we made our tool accessible as a user-friendly web application that allows users to upload their own transcriptional profiles and assess their protocols relative to our database of reference engineered samples.Highlights•The development of Platform-Agnostic CellNet (PACNet) that classifies engineered cell populations from transcriptome data regardless of profiling method or transcript abundance estimation method•PACNet enables cross-study comparisons of cell fate engineering protocols•Comparison of cardiomyocyte engineering protocols emphasizes metabolic selection as a key step in achieving a strong cardiomyocyte fate.•PACNet identifies an unexpected off-target neural and neuroendocrine signature in primary liver-derived organoids.eTOC BlurbCahan and colleagues created a computational resource, PACNet, which evaluates the fidelity of cell engineering expression profiles in a platform-agnostic manner to facilitate cross-protocol benchmarking. Examining state-of-the-field cardiomyocyte and hepatocyte derivation protocols, they identified that two techniques in cardiomyocyte engineering best increase cardiac identity and that an off-target neural/neuroendocrine signature in primary liver-derived organoids may reflect a cholangiopathic signature.Graphical abstract
Differential gene expression analysis and physiological response characteristics of passion fruit (Passiflora edulis) buds under high-temperature stress
Authors: Wang Hongli , Zhao Jiucheng , Lai Miao , Zhang Yingqing , Qiu Wenwu , Li Yanyan , Tu Hailian , Ling Qichang , Fu Xinfeng 
Published: September 2022

ABSTRACTHigh temperature in summer is an unfavorable factor for passion fruit (Passiflora edulis), which can lead to restricted growth, short flowering period, few flower buds, low fruit setting rate, severe fruit drop, and more deformed fruit. To explore the molecular physiology mechanism of passion fruit responding to high-temperature stress, we use ‘Zhuangxiang Mibao’, a hybrid passion fruit cultivar, as the test material. Several physiological indicators were measured and compared between high-temperature (average temperature 38°C) and nonmoral temperature (average temperature 25°C) conditions, including photosynthesis, chlorophyll fluorescence parameters, POD, SOD activity and malondialdehyde content. We performed RNA-seq analysis combined with biochemistry experiment to investigate the gene and molecular pathways that respond to high-temperature stress. The results showed that some physiological indicators in the high-temperature group, including the net photosynthetic rate, stomatal conductance, intercellular CO2 concentration, transpiration rate, and the maximum chemical quantum yield of PS∥, were significantly lower than those of the control group. Malondialdehyde content was substantially higher than the control group, while superoxide dismutase and superoxide dismutase activities decreased to different degrees. Transcriptome sequencing analysis showed that 140 genes were up-regulated and 75 genes were down-regulated under high-temperature stress. GO and KEGG annotation analysis of differentially expressed genes revealed many metabolic pathways related to high-temperature stress. Further investigation revealed that 30 genes might be related to high-temperature stress, such as CAO, GSH, WRKY, and HSP, which have also been reported in other species. The results of real-time fluorescence quantitative PCR and RNA-seq of randomly selected ten genes are consistent, which suggests that the transcriptome sequencing results were reliable. Our study provides a theoretical basis for the mechanism of passion fruit response to high-temperature stress. Also, it gives a theoretical basis for the subsequent breeding of new heat-resistant passion fruit varieties.
Image-based phenomic prediction can provide valuable decision support in wheat breeding
Authors: Roth Lukas , Fossati Dario , Krähenbühl Patrick , Walter Achim , Hund Andreas 
Published: September 2022

AbstractTraditionally, breeders’ selection decisions in early generations are largely based on visual observations in the field. With the advent of affordable genome sequencing and high-throughput phenotyping technologies, enhancing breeders’ ratings with such information became attractive. In this research, it is hypothesized that G×E interactions of secondary traits (i.e., growth dynamics’ traits) are less complex than those of related target traits (e.g., yield). Thus, phenomic selection (PS) may allow selecting for genotypes with beneficial response-pattern in a defined population of environments. A set of 45 winter wheat varieties was grown at five year-sites and analyzed with linear and factor-analytic (FA) mixed models to estimate G×E interactions of secondary and target traits. The dynamic development of drone-derived plant height, leaf area and tiller density estimations was used to estimate the timing of key stages, quantities at defined time points, and temperature dose-response curve parameters. Most of these secondary traits and grain protein content showed little G×E interactions. In contrast, the modeling of G×E for yield required a FA model with two factors. A trained PS model predicted overall yield performance, yield stability and grain protein content with correlations of 0.43, 0.30 and 0.34. While these accuracies are modest and do not outperform well-trained GS models, PS additionally provided insights into the physiological basis of target traits. An ideotype was identified that potentially avoids the negative pleiotropic effects between yield and protein content.Key messageGenotype-by-environment interactions of secondary traits based on high-throughput field phenotyping are less complex than those of target traits, allowing for a phenomic selection in unreplicated early generation trials.
Microglia protect fungi against copper starvation and promote brain infection
Authors: Mohamed Sally H. , Fu Man Shun , Hain Sofia , Alselami Alanoud , Vanhoffelen Eliane , Li Yanjian , Bojang Ebrima , Lukande Robert , Ballou Elizabeth R. , May Robin C. , Ding Chen , Velde Greetje Vande , Drummond Rebecca A. 
Published: September 2022

AbstractMicroglia provide protection against a range of brain infections, but how these glial cells respond to fungi is poorly understood. We investigated the role of microglia in the context of cryptococcal meningitis, the most common cause of fungal brain infections in humans. Using a series of transgenic- and chemical-based microglia depletion methods we found that, contrary to their protective role during other infections, microglia supported cryptococcal fungal brain infection. We show that microglia become hosts for intracellular fungal growth and are a site in which the fungus accesses the restricted micronutrient copper. We developed a reporter fungal strain to track copper starvation responses by the fungus and found that yeast were protected from copper starvation within microglia. Lastly, we show that stimulation of microglia with IFNγ causes restriction of phagosomal copper to intracellular fungi. These data provide a mechanistic explanation for why microglia depletion has a therapeutic effect in the context of this life-threatening fungal infection and is one of the few examples of microglia acting to promote infection. Our data demonstrate how tissue-resident phagocytes can support cryptococcal infections by acting as intracellular reservoirs and sites of microbial nutrient acquisition, and how these mechanisms may be blocked by IFNγ immunotherapy.
Noradrenergic cross-modular reciprocal inhibition within the locus coeruleus
Authors: Davy Oscar , Perrins Ray , Lavigne Marina , Kremer Eric , Tsaneva-Atanasova Krasimira , Ashby Michael , Pickering Anthony E 
Published: September 2022

AbstractThe Locus Coeruleus (LC) is the primary noradrenergic nucleus in the brain with widespread projections driving changes in cognitive state and animal behaviour. The LC is composed of multiple “modules” with specific efferent target domains enabling discretional neuromodulation. LC neuronal activity releases noradrenaline within the nucleus as a local feedback mechanism, but it is not known how this influences modular output. We address this question using whole-cell recordings and calcium imaging in rat pontine slices in combination with LC neuronal ensemble modelling to assess the influence of local noradrenaline release on cross-modular interactions.Electrophysiological recordings of LC neurons from rats transduced with the optogenetic actuator ChR2 showed auto-inhibition and lateral inhibition (of surrounding non-transduced neurons). This inhibition was strongly frequency dependent and was mediated by noradrenaline acting on alpha2-adrenceptors (α2R). To allow calcium-imaging of LC neuronal ensembles a Canine-Adenoviral vector strategy was developed using the PRS promoter to drive selective expression GCaMP6s. Calcium imaging allowed resolution of both increases and decreases in LC activity (to TTX / clonidine or high potassium). Selective chemogenetic-activation of subsets of LC neurons (expressing the ionotropic actuator PSAM) revealed both a direct excitation (after application of PSEM308, 3-30µM) and an α2R-mediated inhibition of neighbouring LC cells (non-transduced). Differential retrograde targeting of PSAM or GCaMP6s to specific LC modules showed the presence of strong, reciprocal cross-modular inhibition (shown for the LC-olfactory bulb vs LC bulbospinal modules) and a subsequent rebound activity inversion.This represents a preferential, targeted, cross-modular, lateral inhibition within the LC rather than a non-specific surround inhibition. Computational modelling showed the emergence of lateral inhibition and biphasic responses to modular activation when α2R signalling and noradrenergic reuptake saturation were included. This interaction may facilitate recruitment of neuronal ensembles by coherent inputs and represents a bottom-up differential contrast-enhancement mechanism within the LC to produce a modality specific focus.
Fluid flow sensitizes bacterial pathogens to chemical stress
Authors: Padron Gilberto C. , Shuppara Alexander M. , Sharma Anuradha , Koch Matthias D. , Palalay Jessica-Jae S. , Radin Jana N. , Kehl-Fie Thomas E. , Imlay James A. , Sanfilippo Joseph E. 
Published: September 2022

AbstractCells regularly experience fluid flow in natural systems. However, most experimental systems rely on batch cell culture and fail to consider the effect of flow-driven dynamics on cell physiology. Using microfluidics and single-cell imaging, we discover that the interplay of physical shear rate (a measure of fluid flow) and chemical stress trigger a transcriptional response in the human pathogenPseudomonas aeruginosa. In batch cell culture, cells protect themselves by quickly scavenging the ubiquitous chemical stressor hydrogen peroxide (H2O2) from the media. In microfluidic conditions, we observe that cell scavenging generates spatial gradients of H2O2. High shear rates replenish H2O2, abolish gradients, and generate a stress response. Combining mathematical simulations and biophysical experiments, we find that cells in flow are sensitive to a H2O2concentration that is 100-1000 times lower than traditionally studied in batch cell culture. Surprisingly, the shear rate and H2O2concentration required to trigger a transcriptional response closely match their respective values in the human bloodstream. Thus, our results explain a long-standing discrepancy between H2O2levels in experimental and natural systems. Finally, we demonstrate that the shear rate and H2O2concentration found in the human bloodstream trigger gene expression in the blood-relevant human pathogenStaphylococcus aureus, suggesting that flow sensitizes bacteria to chemical stress in natural environments.
β-arrestin-independent endosomal cAMP signaling by a polypeptide hormone GPCR
Authors: Blythe Emily E. , von Zastrow Mark 
Published: September 2022

AbstractMany GPCRs are now recognized to initiate a second phase of G protein (Gs) -dependent signaling through the cAMP cascade after endocytosis. A prevailing current view is that endocytosis-promoted signaling from GPCRs is inherently β-arrestin-dependent because β-arrestin is necessary for receptors to internalize and, for some GPCRs, it also promotes Gsactivation on endosomes. Here we revise this view by showing that the vasoactive intestinal peptide receptor 1 (VIPR1), a prototypic secretin-family polypeptide hormone receptor, remains bound to β-arrestin after endocytosis but does not require β-arrestin either to internalize or to generate an endosomal signal. β-arrestin instead resolves the endosomal signal into a temporally separated cAMP peak, and it does so by attenuating signaling from the plasma membrane without detectably affecting the endosomal response. The mechanistic basis for this location-specific difference in β-arrestin function is the formation of distinct VIPR1/β-arrestin complexes at each location. The signal-attenuating complex formed at the plasma membrane does not require GRK-mediated phosphorylation of receptors, while the signaling-neutral complex present on the endosome membrane, in contrast, is GRK-dependent. To our knowledge, the present results provide the first direct demonstration that endosomal GPCR signaling can occur in the complete absence of β-arrestin. They also reveal a discrete role of β-arrestin in sculpting the spatiotemporal profile of cellular GPCR - G protein signaling through the location-specific formation or remodeling of GPCR/β-arrestin complexes.
Multi-block RNN Autoencoders Enable Broadband ECoG Signal Reconstruction
Authors: Nolan Michael , Pesaran Bijan , Shlizerman Eli , Orsborn Amy 
Published: September 2022

AbstractObjectiveNeural dynamical models reconstruct neural data using dynamical systems. These models enable direct reconstruction and estimation of neural time-series data as well as estimation of neural latent states. Nonlinear neural dynamical models using recurrent neural networks in an encoder-decoder architecture have recently enabled accurate single-trial reconstructions of neural activity for neuronal spiking data. While these models have been applied to neural field potential data, they have only so far been applied to signal feature reconstruction (e.g. frequency band power), and have not yet produced direct reconstructions of broadband time-series data preserving signal phase and temporal resolution.ApproachHere we present two encoder-decoder model architectures - the RNN autoencoder (RAE) and multi-block RAE (MRAE) for direct time-series reconstruction of broadband neural data. We trained and tested models on multi-channel micro-Electricorticography (μECoG) recordings from non-human primate motor corticies during unconstrained behavior.Main ResultsWe show that RAE reconstructs micro-electrocorticography recordings, but has reconstruction accuracy that is band-limited to model scale. The MRAE architecture overcomes these time-bandwidth restrictions, yielding broadband (0-100 Hz), accurate reconstructions of μECoG data.SignificanceRAE and MRAE reconstruct broadband μECoG data through multiblock dynamical modeling. The MRAE overcomes time-bandwitdh restrictions to provide improved accuracy for long time duration signals. The reconstruction capabilities provided by these models for broadband neural signals like μECoG may enable the development of improved tools and analysis for basic scientific research and applications like brain-computer interfaces.
Robust induction of functional astrocytes using NGN2 expression in human pluripotent stem cells
Authors: Berryer Martin H. , Tegtmeyer Matthew , Binan Loïc , Valakh Vera , Nathanson Anna , Trendafilova Darina , Crouse Ethan , Klein Jenny , Meyer Daniel , Pietiläinen Olli , Rapino Francesca , Farhi Samouil L. , Rubin Lee L. , McCarroll Steven A. , Nehme Ralda , Barrett Lindy E. 
Published: September 2022

ABSTRACTAstrocytes play essential roles in normal brain function, with dysfunction implicated in diverse developmental and degenerative disease processes. Emerging evidence of profound species divergent features of astrocytes coupled with the relative inaccessibility of human brain tissue underscore the utility of human pluripotent stem cell (hPSC) technologies for the generation and study of human astrocytes. However, existing approaches for hPSC-astrocyte generation are typically lengthy, incompletely characterized, or require intermediate purification steps, limiting their utility for multi-cell line, adequately powered functional studies. Here, we establish a rapid and highly scalable method for generating functional human induced astrocytes (hiAs) based upon transient Neurogenin 2 (NGN2) induction of neural progenitor-like cells followed by maturation in astrocyte media, which demonstrate remarkable homogeneity within the population and across 11 independent cell lines in the absence of additional purification steps. These hiAs express canonical astrocyte markers, respond to pro-inflammatory stimuli, exhibit ATP-induced calcium transients and support neuronal maturation in vitro. Moreover, single-cell transcriptomic analyses reveal the generation of highly reproducible cell populations across individual donors, most closely resembling human fetal astrocytes, and highly similar to hPSC-derived astrocytes generated using more complex approaches. Finally, the hiAs capture key molecular hallmarks in a trisomy 21 disease model. Thus, hiAs provide a valuable and practical resource well-suited for study of basic human astrocyte function and dysfunction in disease.
Timing, paths and contents of the intergenerational inheritance of family firm from the perspective of HeXie theory
Authors: Wang Lixia , Zhang Xin , Yan Beibei , Boasson Vigdis 
Published: September 2022

Purpose
This paper aims to examine the internal logical relationship between two intergenerational inheritance ways of passing property rights and residual control rights (RCR) and to construct a conceptual model comprising transfer elements, paths and timing of succession in this process.

Design/methodology/approach
Driven by the cases of Haixin, Tianyijiao and Changhe Group, this paper applies research methods of copying and expanding analysis logic, progressive deduction, content analysis and comparative research based on the perspective of HeXie theory to explore the deep interrelation of transfer elements, paths and timing during family business succession.

Findings
The findings present that the content of intergenerational inheritance of a family firm is the inheritance of property rights and RCR. First, the inheritance of property rights is a static inheritance of time-point delivery, whereas the inheritance of RCR is a dynamic inheritance process for a period of time. Second, the inheritance of property rights and RCR are not independent; only a “HeXie” succession of both rights can realize a successful inheritance of family firms.

Originality/value
This paper constructs the paths and timing model of intergenerational inheritance of property rights and RCR in family firms. This paper integrates the current literature studies on the family inheritance of property rights and RCR and explains their internal mechanisms. This paper also provides a theoretical foundation and empirical evidence for family business transitions in the business world.