bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scanning ultrasound-mediated memory and functional improvements do not require amyloid-β reduction
Authors: Leinenga Gerhard , To Xuan Vinh , Bodea Liviu-Gabriel , Yousef Jumana , Richter-Stretton Gina , Palliyaguru Tishila , Chicoteau Antony , Dagley Laura , Nasrallah Fatima , Götz Jürgen 
Published: June 2023

AbstractA prevalent view in treating age-dependent disorders including Alzheimer’s disease (AD) is that the underlying amyloid plaque pathology must be targeted for cognitive improvements. In contrast, we report here that repeated scanning ultrasound (SUS) treatment at 1 MHz frequency can ameliorate memory deficits in the APP23 mouse model of AD without reducing amyloid-β (Aβ) burden. Different from previous studies that had shown Aβ clearance as a consequence of blood-brain barrier (BBB) opening, here, the BBB was not opened as no microbubbles were used. Quantitative proteomics and functional magnetic resonance imaging revealed that ultrasound induced long-lasting functional changes that correlate with the improvement in memory. Intriguingly, the treatment was more effective at a higher frequency (1MHz) than at a frequency within the range currently explored in clinical trials in AD patients (286 kHz). Together, our data suggest frequency-dependent bio-effects of ultrasound and a dissociation of cognitive improvement and Aβ clearance, with important implications for the design of trials for AD therapies.SummaryThe therapeutic effect of ultrasound on memory in AD mice leads to altered protein expression and improved functional connectivity in the absence of amyloid-β removal. Of two frequencies explored, the higher ultrasound frequency (1 MHz) is more effective.
Aryl hydrocarbon receptor (AHR) and IL-13 signaling crosstalk in human keratinocytes and atopic dermatitis
Authors: Proper Steven P. , Dwyer Alexander T. , Appiagyei Andrews , Felton Jennifer M. , Morgenstern Netali Ben-Baruch , Marlman Justin M. , Kotliar Michael , Barski Artem , Troutman Ty D. , Rothenberg Marc E. , Mersha Tesfaye B. , Azouz Nurit P. 
Published: June 2023

AbstractAtopic dermatitis (AD) is an allergic skin disease mediated by skin barrier impairment and IL-13-driven immune response. Activation of the aryl hydrocarbon receptor (AHR) has shown promise in early clinical trials for AD, however, the mechanism by which AHR mediates this function is unknown. Herein, AHR signaling is shown to be dysregulated in AD patients using publicly available gene expression data from biopsies of patients with AD compared with controls. AHR target genes,CYP1A1,CYP1A2andNFE2L2were decreased in lesional skin compared with healthy control skin (p=0.001, p<1.0*10-10and p=6.1*10-6respectively). Single cell RNA sequencing studies demonstrated increased expression ofAHR(p<1.0*10-4and p=0.049) and decreased expression ofCYP1A1in lesional AD keratinocytes compared with healthy control keratinocytes (p=5.0*10-4and p=0.21). AHR activation reversed IL-13-dependent gene expression of several key genes in AD pathogenesis, most notably the eosinophil chemoattractant,CCL26(Eotaxin-3). There was substantial overlap between differentially expressed genes in keratinocytes of patients with atopic dermatitis and AHR-regulated genes. Mechanistically, there was evidence for direct transcriptional effects of AHR as its binding motifs were identified in the differentially expressed genes from lesional AD keratinocytes compared to control keratinocytes and AHR activation did not modify IL-13-dependent signal transducer and activator of transcription 6 (STAT6) translocation to the nucleus. Together these data imply that AHR modulates IL-13 downstream signaling in keratinocytes through genome-wide direct transcriptional regulatory effects.
Deep intravital brain tumor imaging enabled by tailored three-photon microscopy and analysis
Authors: Schubert Marc Cicero , Soyka Stella Judith , Tamimi Amr , Maus Emanuel , Denninger Robert , Wissmann Niklas , Reyhan Ekin , Tetzlaff Svenja Kristin , Beretta Carlo , Drumm Michael , Schroers Julian , Steffens Alicia , Walshon Jordain , McCortney Kathleen , Heiland Sabine , Golebiewska Anna , Kurz Felix Tobias , Wick Wolfgang , Winkler Frank , Kreshuk Anna , Kuner Thomas , Horbinski Craig , Prevedel Robert , Venkataramani Varun 
Published: June 2023

AbstractIntravital two-photon microscopy has emerged as a powerful technology to study brain tumor biology and its temporal dynamics, including invasion, proliferation and therapeutic resistance in the superficial layers of the mouse cortex. However, intravital microscopy of deeper cortical layers and especially the subcortical white matter, an important route of glioblastoma invasion and recurrence, has not yet been feasible due to low signal-to-noise ratios, missing spatiotemporal resolution and the inability to delineate myelinated axonal tracts. Here, we present a tailored intravital microscopy and artificial intelligence-based analysis methodology and workflow that enables routine deep imaging of glioblastoma over extended time periods, named Deep3P. We show that three-photon microscopy, adaptive optics, as well as customized deep learning-based denoising and machine learning segmentation together allow for deep brain intravital investigation of tumor biology up to 1.2 mm depth. Leveraging this approach, we find that perivascular invasion is a preferred invasion route into the corpus callosum as compared to intracortical glioblastoma invasion and uncover two vascular mechanisms of glioblastoma migration in the white matter. Furthermore, we can define an imaging biomarker of white matter disruption during early glioblastoma colonization. Taken together, Deep3P allows for an efficient and non-invasive investigation of brain tumor biology and its tumor microenvironment in unprecedented deep white and gray matter of the living mouse, opening up novel opportunities for studying the neuroscience of brain tumors and other model systems.
Dynamic X-chromosomal reactivation enhances female brain resilience
Authors: Käseberg S , Bertin M , Menon R , Gabassi E , Todorov H , Frank S , Brennenstuhl H , Lohrer B , Winter J , Krummeich J , Winkler J , Winner B , Weis E , Hartwich D , Diederich S , Luck K , Gerber S , Lunt P , Berninger B , Falk S , Schweiger S , Karow M 
Published: June 2023

SummaryWhile random X-chromosome inactivation in female cells of placental mammalians silences one allele of the majority of X-chromosomal genes, a considerable fraction is only incompletely and variably inactivated resulting in a tissue-specific pattern of mono- and biallelic expression. Here we used clonal human female induced pluripotent stem cells (iPSCs) allowing to trace the (in)activation status of the two X-chromosomes individually along neural differentiation trajectories. We discovered X-chromosome-wide locus- and lineage-specific dynamic usage of the two X-chromosomal alleles in female cells induced by differentiation. Leveraging iPSCs derived from patients with an X-linked neurodevelopmental disorder, we demonstrate that activation of alleles on the inactive X-chromosome can exert protective effects on the manifestation of disease phenotypes in female neural cells and tissue. Taken together, our data demonstrate that alleles on the inactive X-chromosome can serve as a critical reservoir reactivated during differentiation, thereby enhancing resilience of female neural tissue.
Dating the bacterial tree of life based on ancient symbiosis
Authors: Wang Sishuo , Luo Haiwei 
Published: June 2023

AbstractObtaining a timescale for bacterial evolution is crucial to understand early life evolution but is difficult owing to the scarcity of bacterial fossils and absence of maximum age constraints of the available fossils. Here, we introduce multiple new time constraints to calibrate bacterial evolution based on ancient symbiosis. This idea is implemented using a bacterial tree constructed with mitochondria-originated genes where the mitochondrial lineage representing eukaryotes is embedded within Proteobacteria, such that the date constraints of eukaryotes established by their abundant fossils are propagated to ancient co-evolving bacterial symbionts and across the bacterial tree of life. Importantly, we formulate a new probabilistic framework that considers uncertainty in inference of the ancestral lifestyle of modern symbionts to apply 19 relative time constraints (RTC) each informed by host-symbiont association to constrain bacterial symbionts no older than their eukaryotic host. Moreover, we develop an approach to incorporating substitution mixture models that better accommodate substitutional saturation and compositional heterogeneity for dating deep phylogenies. Our analysis estimates that the last bacterial common ancestor (LBCA) occurred approximately 4.0-3.5 billion years ago (Ga), followed by rapid divergence of major bacterial clades. It is robust to alternative root ages, root positions, tree topologies, fossil ages, ancestral lifestyle reconstruction, gene sets, among other factors. The timetree obtained enables the validation of various hypotheses, such as the survival of life during the late heavy bombardment, the absence of a connection between ancient stromatolites and cyanobacteria, and the presence of aerobic enzymes before the oldest geochemical records of molecular oxygen.Significance StatementBacteria, with their vast diversity and ancient history, play a crucial role in shaping Earth’s biogeochemistry. However, the scarcity of fossils complicates the determination of their evolution timescale and its link to Earth’s history. To address this issue, we have devised and implemented novel methods that utilize ancient symbiosis and eukaryotic fossils to calibrate bacterial evolution by molecular clock. We obtain a comprehensive genus-level evolutionary timeline of bacteria that sheds light on their profound influence on the development and diversity of life on our planet, as well as its environmental dynamics. This research greatly contributes to our understanding of microbial evolution and its implications for Earth’s past and present.
Combination therapy with oral antiviral and anti-inflammatory drugs improves the efficacy of delayed treatment in severe COVID-19
Authors: Sasaki Michihito , Sugi Tatsuki , Iida Shun , Hirata Yuichiro , Kusakabe Shinji , Konishi Kei , Itakura Yukari , Tabata Koshiro , Kishimoto Mai , Kobayashi Hiroko , Ariizumi Takuma , Intaruck Kittiya , Nobori Haruaki , Toba Shinsuke , Sato Akihiko , Matsuno Keita , Yamagishi Junya , Suzuki Tadaki , Hall William W. , Orba Yasuko , Sawa Hirofumi 
Published: June 2023

AbstractPulmonary infection with SARS-CoV-2 stimulates host immune responses and can also result in the progression of dysregulated and critical inflammation. Throughout the pandemic, the management and treatment of COVID-19 has been continuously updated with a range of antiviral drugs and immunomodulators. Monotherapy with oral antivirals has proven to be effective in the treatment of COVID-19. However, the treatment should be initiated in the early stages of infection to ensure beneficial therapeutic outcomes, and there is still room for further consideration on therapeutic strategies using antivirals. Here, we show that the oral antiviral ensitrelvir combined with the anti-inflammatory corticosteroid methylprednisolone has higher therapeutic effects and better outcomes in a delayed dosing model of SARS-CoV-2 infected hamsters compared to the monotherapy with ensitrelvir or methylprednisolone alone. Combination therapy with these drugs improved respiratory conditions and the development of pneumonia in hamsters even when the treatment was started after 2 days post infection. The combination therapy led to a differential histological and transcriptomic pattern in comparison to either of the monotherapies, with reduced lung damage and down-regulated expressions of genes involved in inflammatory response. Furthermore, we found that the combination treatment is effective in infection with both highly pathogenic delta and circulating omicron variants. Our results demonstrate the advantage of combination therapy with antiviral and corticosteroid drugs in COVID-19 treatment. Since both drugs are available as oral medications, this combination therapy could provide a clinical and potent therapeutic option for COVID-19.
Green supplier selection and environmental performance of firms in the Chinese manufacturing industry: the roles of behavior and outcome controls
Authors: Lee Hanna , Wu Xiaobo 
Published: June 2023

PurposeGreen supplier selection (GSS) is acknowledged as important governance in green supply chain management (GSCM). However, this paper argues that GSS is not a stand-alone GSCM governance mode that determines manufacturers' environmental performance but rather one that needs to be aligned with contractual governance, particularly contractual control and adaptation, to promote environmental performance effects. This paper adopts GSS as ex ante governance and introduces behavior and outcome controls as ex post contractual control and adaptation, respectively. Thus, this paper addresses how GSS affects environmental performance directly and indirectly through behavior and outcome controls within transaction cost economics (TCE) theory.Design/methodology/approachThis research model was tested on 300 Chinese manufacturing firms, and multiple regression analysis was used to validate our hypotheses.FindingsA direct relationship was observed between GSS and environmental performance. This direct relationship is positively mediated by behavior and outcome controls.Originality/valueThis paper develops and elucidates an integrative green supply chain process proceeding from the implementation of ex ante GSS and ex post contractual governance to the realization of environmental performance. Furthermore, this paper considers two different forms of contractual governance, specifically contractual control and adaptation, and explains how they can be implemented using behavior and outcome controls from the perspective of TCE theory.
Too much psychological capital? Exploring curvilinear relationships between OPsyCap and performance prior to and after the COVID-19 crisis
Authors: Jancenelle Vivien 
Published: June 2023

PurposePast research has generally purported and tested for a positive linear relationship between psychological capital and organizational outcomes such as firm performance. Yet, recent conceptual work has started to recognize that for certain outcomes, too much psychological capital can be as detrimental as too little. In this study, the author hypothesizes that during a major crisis, organizational psychological capital (OPsyCap) may in fact exhibit an inverted U-shaped relationship with performance.Design/methodology/approachT leverages the revelatory power of a recent major crisis (the COVID-19 pandemic) to gather a pre-crisis and post-crisis matching sample of 952 earnings conference calls held by 476 S&P 500 firms with corresponding market performance data and use computer-assisted text analysis (CATA) methodology to assess OPsyCap from call transcripts.FindingsT finds that OPsyCap has a statistically significant inverted U-shaped relationship with market performance after the crisis, but not prior—thereby suggesting that moderate OPsyCap is more beneficial to market performance than either insufficient or excessive OPsyCap in times of crisis.Practical implicationsTop managers should not display overly excessive psychological capital after a major crisis, as shareholders may interpret such cues as unwarranted optimism, overconfidence and an inability to accept the new reality brought about by the crisis.Originality/valueThis study's findings contribute to extant literature by being the first to empirically highlight a curvilinear relationship between psychological capital and an important outcome variable—market performance. Furthermore, this study's lack of results prior to a major crisis, but not after, may suggest a new boundary condition.
Performance feedback and firms’ strategic actions: a cross-national meta-analysis
Authors: Xue Shan , Chen Honghui , Wu Jintao 
Published: June 2023

Purpose Although previous research has investigated how performance feedback may affect firms’ strategic actions, their findings has been inconsistent. The relationship between performance feedback and firms’ strategic activities thus appears complex. Moreover, the authors contend that it may vary with the measurement strategies employed (i.e. social or historical feedback, operationalizations of strategic actions or accounting- and market-based performance indicators) and the national contexts.Design/methodology/approach Therefore, the current article presents a comprehensive meta-analysis of prior research, including 1,637,817 sample observations from 101 studies that span more than 18 countries.Findings The results indicate that (1) performance that are below or above aspirational levels generally has a positive relationship with firms’ strategic actions; (2) these relationships are contingent on the implementation forms taken by the key variables, such as performance feedback, strategic actions and performance indicators; and (3) the relationships are much stronger in countries where managerial discretion is greater.Originality/value The findings contribute to the clarification of long-standing theoretical and empirical debates regarding the relationship between performance feedback and strategic actions, as well as some pertinent directions for future research.
The internationalization performance of Indonesian SMEs during COVID-19 pandemic: exploring a mediation model
Authors: Anggadwita Grisna , Indarti Nurul , Sinha Paresha , Manik Hardo Firmana Given Grace 
Published: June 2023

Purpose
Small and medium enterprises (SMEs) in emerging economies face significant challenges in formulating effective strategies to enter international markets, particularly amid uncertain conditions such as the COVID-19 pandemic. Consequently, there is a pressing need to examine the performance of these SMEs and evaluate their internationalization process. This study aims to examine the effects of international entrepreneurial orientation on the internationalization performance of SMEs and the mediating effects of organizational dynamic capability and organizational culture in Indonesia.

Design/methodology/approach
This study used a quantitative method with a survey approach by distributing questionnaires to 206 SMEs in Indonesia that have implemented internationalization practices. Partial least squares-structural equation modeling (PLS-SEM) was used to predict and estimate relationships.

Findings
This study finds that one of the SMEs’ strategies to encounter the new normal era of COVID-19 is to improve their internationalization performance, especially by actively participating in international markets. The empirical results show that organizational dynamic capabilities and organizational culture are proven to fully mediate the relationship between international entrepreneurial orientation and the internationalization performance of SMEs. Meanwhile, international entrepreneurial orientation does not directly affect SMEs’ internationalization performance. This study confirms the mediating role of organizational dynamic capabilities and organizational culture in dynamic capabilities theory and their relevance to internationalization.

Originality/value
This study provides valuable insights and encourages owner-managers and policy-makers in emerging economies, particularly Indonesia, to develop organizational dynamic capabilities and organizational culture that align with the demands of internationalization.
Does uncertainty promote exchange rate volatility? Global evidence
Authors: Aftab Muhammad , Naeem Maham , Tahir Muhammad , Ismail Izlin 
Published: June 2023

Purpose
Exchange rate volatility is an important factor affecting investors and policymakers. This study aims to examine the impact of uncertainties, in terms of changes in economic policy, monetary policy and global financial markets, on exchange rate volatility.

Design/methodology/approach
The study uses the GARCH (1,1) univariate model to calculate exchange rate volatility. Economic and monetary policy uncertainties are measured using news-based indices, while global financial market volatility is measured using the implied volatility index. Panel autoregressive distributed lag modeling is used to analyze the impact of uncertainty on exchange rate volatility in the short and long run. The sample consists of 26 developed and emerging markets from 2005 to 2020.

Findings
The study finds that economic policy uncertainty significantly increases exchange rate volatility. Similarly, global financial market uncertainty leads to increased exchange rate volatility. The effect of US monetary policy uncertainty reduces exchange rate volatility.

Originality/value
This research contributes to the existing literature on exchange rate fluctuations by examining the impact of uncertainties on exchange rate volatility. The study uses novel news-based indices for measuring economic and monetary policy uncertainties and includes a broader sample of emerging and advanced markets. The findings have important implications for investors and policymakers.
Survey of glyphosate- and dicamba-resistant kochia (Bassia scoparia) in Saskatchewan
Authors: Sharpe Shaun M. , Leeson Julia Y. , Geddes Charles M. , Willenborg Christian J. , Beckie Hugh J. 
Published: June 2023

Kochia ( Bassia scoparia (L.) A.J. Scott) is a problematic tumbleweed, which infests row crops and ruderal areas within western Canada. Herbicide resistance makes kochia management challenging for producers. Widespread resistance to acetolactate synthase-inhibitors, evolution and spread of glyphosate resistance, and the occurrence of dicamba resistance has been previously noted in Saskatchewan. This study's objective was to evaluate the occurrence and distribution of glyphosate- and dicamba-resistant kochia in central and southern Saskatchewan. A randomized, stratified survey was conducted in the fall of 2019 at 303 sites. Rotational history was obtained using the Agriculture and Agri-Food Canada Annual Crop Inventory. Kochia samples were collected from cropped fields (78%), ditches (17%), oil well sites (2%), and railway grades (3%). Glyphosate resistance was detected in 87% of samples ( n = 275) within 137 Rural Municipalities (RMs). Dicamba resistance was detected in 45% of kochia samples ( n = 255) in 87 RMs. Crops infested with herbicide-resistant kochia included wheat ( Triticum aestivum L. and T. durum Desf.), canola ( Brassica napus L.), lentils ( Lens culinaris Medik.), barley ( Hordeum vulgare L.), flax ( Linum usitatissimum L.), and peas ( Pisum sativum L.). Reducing the soil seedbank and preventing dispersal will be critical to mitigating resistance. Good herbicide stewardship including mixing multiple modes of action is paramount. Cultural strategies to increase canopy closure and crop competitiveness to limit biomass and seed production are recommended. Kochia occupies many environments outside of cropped fields, and a community-wide management approach may be necessary to reduce dispersal potential of tumbling plants that disperse seed.