bluuebunny/crossref_metadata_2025_split huggingface dataset:
A human mitofusin 2 mutation causes mitophagic cardiomyopathy
Authors: Franco Antonietta , Li Jiajia , Kelly Daniel P. , Hershberger Ray E. , Marian Ali J. , Lewis Renate M. , Song Moshi , Dang Xiawei , Schmidt Alina D. , Mathyer Mary E. , de Guzman Strong Cristina , Dorn Gerald W. 
Published: November 2022

AbstractCardiac muscle has the highest mitochondrial density of any human tissue, but mitochondrial dysfunction is not a recognized cause of isolated cardiomyopathy. Here, we determined that the rare mitofusin (MFN) 2 R400Q mutation is ~20x over-represented in clinical cardiomyopathy, whereas this specific mutation is not reported as a cause of the MFN2 mutant-induced peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Accordingly, we interrogated the enzymatic, biophysical and functional characteristics of MFN2 Q400 versus wild-type and representative CMT2A-causing MFN2 mutants. All MFN2 mutants we studied suppressed mitochondrial fusion, the canonical MFN2 function. Compared to CMT2A mutants MFN2 R94Q and T105M that lacked catalytic GTPase activity and exhibited normal activation-induced changes in conformation, MFN2 Q400 had normal GTPase activity with impaired conformational shifting. GTPase-defective MFN2 mutants, but not MFN2 Q400, suppressed mitochondrial motility, provoked mitochondrial depolarization and reduced mitochondrial respiration. By contrast, MFN2 Q400 was uniquely defective in recruiting Parkin to mitochondria. CRISPR editing of the R400Q mutation into the mouseMfn2gene induced perinatal cardiomyopathy with no other organ involvement. RNA sequencing and metabolomics of cardiomyopathic Mfn2 Q400 hearts revealed signature abnormalities recapitulating experimental mitophagic cardiomyopathy. Indeed, cardiomyoblasts expressing MFN2 Q400 exhibited multiple mitophagy defects, but normal mitochondrial respiration. MFN2 Q400 is the first known natural mitophagy- and shape change-defective MFN2 mutant. Its unique profile of dysfunction evokes mitophagic cardiomyopathy, suggesting a mechanism for its enrichment in clinical cardiomyopathy.
A termination-aware vector design improves heterologous gene expression inPseudomonas putida
Authors: de Siqueira Guilherme Marcelino Viana , Guazzaroni María-Eugenia 
Published: November 2022

AbstractTranscriptional terminators are key players in the flow of genetic information, but are often overlooked in circuit design. In this work, we used the Standard European Vector Architecture (SEVA) as a scaffold to investigate the effects of different terminators in the output of a reporter construct expressed in two bacterial species and found that replacing the conventional T1 and T0 transcriptional terminators of the SEVA vector format with a set of broad-host metagenomic terminators resulted in a significant improvement in the signal of a fluorescent device inPseudomonas putidaKT2440. Interestingly, this new vector design displayed the same performance as pSEVA231 inEscherichia coliDH10B. Our results support the notion that transcriptional terminators may affect the interconnected mesh of biological processes taking place in gene expression, leading to a host-dependent output that should be heeded for optimal circuit expression in different microbial hosts.
Influence of pump laser fluence on ultrafast structural changes in myoglobin
Authors: Barends Thomas R.M. , Bhattacharyya Swarnendu , Gorel Alexander , Schiro Giorgio , Bacellar Camila , Cirelli Claudio , Colletier Jacques-Philippe , Foucar Lutz , Grünbein Marie Luise , Hartmann Elisabeth , Hilpert Mario , Johnson Philip J.M. , Kloos Marco , Knopp Gregor , Marekha Bogdan , Nass Karol , Kovacs Gabriela Nass , Ozerov Dmitry , Stricker Miriam , Weik Martin , Doak R. Bruce , Shoeman Robert L. , Milne Christopher J. , Huix-Rotllant Miquel , Cammarata Marco , Schlichting Ilme 
Published: November 2022

SummaryHigh-intensity femtosecond pulses from an X-ray free-electron laser enable pump probe experiments for investigating electronic and nuclear changes during light-induced reactions. On time scales ranging from femtoseconds to milliseconds and for a variety of biological systems, time-resolved serial femtosecond crystallography (TR-SFX) has provided detailed structural data for light-induced isomerization, breakage or formation of chemical bonds and electron transfer1. However, all ultra-fast TR-SFX studies to date have employed such high pump laser energies that several photons were nominally absorbed per chromophore2-14. As multiphoton absorption may force the protein response into nonphysiological pathways, it is of great concern15whether this experimental approach16allows valid inferences to be drawn vis-à-vis biologically relevant single-photon-induced reactions17. Here we describe ultrafast pump-probe SFX experiments on photodissociation of carboxymyoglobin, showing that different pump laser fluences yield markedly different results. In particular, the dynamics of structural changes and observed indicators of the mechanistically important coherent oscillations of the Fe-CO bond distance (predicted by recent quantum wavepacket dynamics15) are seen to depend strongly on pump laser energy. Our results confirm both the feasibility and necessity of performing TR-SFX pump probe experiments in the linear photoexcitation regime. We consider this to be a starting point for reassessing design and interpretation of ultrafast TR-SFX pump probe experiments16such that biologically relevant insight emerges.
Exaptation of inactivated host enzymes for structural roles in orthopoxviruses and novel protein folds revealed by protein structure modeling
Authors: Mutz Pascal , Resch Wolfgang , Faure Guilhem , Senkevich Tatiana G. , Koonin Eugene V. , Moss Bernard 
Published: November 2022

AbstractViruses with large double-stranded DNA genomes appear to have captured the majority of their genes from the hosts at different stages of evolution. The origin of many virus genes is readily detected through highly significant sequence similarity with cellular homologs. This is the case, in particular, for virus enzymes, such as DNA and RNA polymerases or nucleotide kinases, that retain their catalytic activity after capture by an ancestral virus. However, a large fraction of virus genes have no readily detectable cellular homologs so that their origin remains enigmatic. We sought to explore potential origins of proteins of unknown provenance encoded in the genomes of orthopoxviruses, a thoroughly studied virus genus which includes major human pathogens. To this end, we used AlphaFold2, to predict the structures of all 214 proteins encoded by orthopoxviruses. Among the proteins of unknown provenance, structure prediction yielded a clear indication of origin for 14, along with validating several inferences previously made by sequence analysis. The major trend that emerges from these findings is the exaptation of enzymes from cellular organisms for non-enzymatic, structural roles in virus reproduction which is accompanied by disruption of catalytic sites and overall drastic divergence which precludes detection of homology at the sequence level. Among the 16 orthopoxvirus proteins found to be inactivated enzyme derivatives, are the poxvirus replication processivity factor A20, an inactivated derivative of bacterial NAD-dependent DNA ligase; major core protein A3, an inactivated deubiquitinase; F11, an inactivated prolyl hydroxylase; and more similar cases. However, for nearly one third of the orthopoxvirus virion proteins, no significantly similar structures were identified, suggesting exaptation with subsequent major structural rearrangement, yielding novel protein folds.
Golgi-IP, a novel tool for multimodal analysis of Golgi molecular content
Authors: Fasimoye Rotimi , Dong Wentao , Nirujogi Raja S. , Rawat Eshaan S. , Iguchi Miharu , Nyame Kwamina , Phung Toan K. , Bagnoli Enrico , Prescott Alan , Alessi Dario R. , Abu-Remaileh Monther 
Published: November 2022

AbstractThe Golgi is a membrane-bound organelle that is essential for protein and lipid biosynthesis. It represents a central trafficking hub that sorts proteins and lipids to various destinations or for secretion from the cell. The Golgi has emerged as a docking platform for cellular signalling pathways including LRRK2 kinase whose deregulation leads to Parkinson disease. Golgi dysfunction is associated with a broad spectrum of diseases including cancer, neurodegeneration, and cardiovascular diseases. To allow the study of the Golgi at high resolution, we report a rapid immunoprecipitation technique (Golgi-IP) to isolate intact Golgi mini-stacks for subsequent analysis of their content. By fusing the Golgi resident protein TMEM115 to three tandem HA epitopes (GolgiTAG), we purified the Golgi using Golgi-IP with minimal contamination from other compartments. We then established an analysis pipeline using liquid chromatography coupled with mass spectrometry to characterize the human Golgi proteome, metabolome and lipidome. Subcellular proteomics confirmed known Golgi proteins and identified novel ones. Metabolite profiling established the first known human Golgi metabolome and revealed the selective enrichment of uridine-diphosphate (UDP) sugars and their derivatives, which is consistent with their roles in protein and lipid glycosylation. Furthermore, targeted metabolomics validated SLC35A2 as the subcellular transporter for UDP-hexose. Finally, lipidomics analysis showed that phospholipids including phosphatidylcholine, phosphatidylinositol and phosphatidylserine are the most abundant Golgi lipids and that glycosphingolipids are enriched in this compartment. Altogether, our work establishes a comprehensive molecular map of the human Golgi and provides a powerful method to study the Golgi with high precision in health and disease states.SignificanceThe Golgi is central to protein and lipid processing. It senses and responds to diverse cell states to allow trafficking of macromolecules based on cellular demands. Traditional techniques for purifying the Golgi shaped our understanding of its functions, however such methods are too slow to preserve the labile Golgi metabolome and transient protein interactions. Here, we overcome this issue through the development of a method for the rapid capture of intact Golgi from human cells using organelle-specific immunoprecipitation (Golgi-IP). Using high resolution mass spectrometry, we demonstrate that our approach allows the unbiased characterization of the Golgi proteome, metabolome and lipidome. Thus, we believe that the Golgi-IP will be useful for the study of the Golgi in health and disease states.
A systematic review of near-infrared spectroscopy in dementia
Authors: Butters Emilia , Srinivasan Sruthi , O’Brien John T , Su Li , Bale Gemma 
Published: November 2022

AbstractObjectivesThis review aimed to evaluate previous studies using Near-infrared spectroscopy (NIRS) in dementia by summarising the results, determining the consensus in the literature, and delineating if, and how, NIRS experimental and analysis methods may be improved for future studies in dementia.MethodsThree databases (PsychINFO, Medline, Embase) were searched for original research studies using NIRS in dementia and prodromal disease stages. We included both observational and randomised control trials, and studies published in English. Animal studies, conference abstracts, and reviews were excluded.ResultsFrom 759 identified records, 80 studies using NIRS in dementia and prodromal populations across a range of activation tasks testing memory (28), word retrieval (22), and motor (7) and visuo-spatial function (4), as well as in the resting state (29) were evaluated. Across these cognitive domains, dementia patients generally showed a blunted haemodynamic response, often localised to frontal regions of interest, and a lack of task-appropriate frontal lateralisation. Prodromal stages, such as Mild Cognitive Impairment, revealed mixed results and were associated with either diminished responses or hyperactivity, accompanied by reduced cognitive function, the latter suggesting a possible compensatory neural response which is not present at the dementia stage.ConclusionThere is clear evidence of alterations in brain oxygenation in both dementia and prodromal stages across a range of cognitive domains and in the resting state, indicating an ability of NIRS to distinguish dementia from healthy ageing, or at-risk populations. A consensus as to the nature of these changes, however, is difficult to reach due to a lack of standardisation in optical techniques and processing methods. Further studies are required exploring more naturalistic settings and in a wider range of dementia subtypes.
Do CSR awards enhance firms’ market value? Evidence from China
Authors: Zhang Min , Long Ruixi , Tan Qingmei , Wei Keke 
Published: November 2022

Purpose
This study aims to examine the impact of corporate social responsibility (CSR) awards on firms’ market value considering these awards as a signal and proxy for the effectiveness of CSR practice.

Design/methodology/approach
There are 342 announcements of CSR awards in China from 2006 to 2017 screened and analyzed using the event study methodology.

Findings
The stock market reacts significantly negatively to CSR award announcements in the short term. Firms that are state-owned, belong to the manufacturing industry, outside east China, repeatedly win awards and are listed in the Chinese H-share market, experience a stronger stock market reaction. Interestingly, the long-term stock returns of award winners are significantly positive for multiyear holding periods.

Practical implications
The findings offer stakeholders clear guidelines on how to manage communications in the market to extract enhanced financial performance from CSR award announcements.

Originality/value
This study chooses CSR awards as a proxy for the effectiveness of excellent CSR practice. This study also contributes to the CSR literature by analyzing how investors use the award information to make investment decisions.
Influence of psychosocial safety climate on construction workers’ intent to stay, taking job satisfaction as the intermediary
Authors: Xie Linlin , Luo Ziyuan , Xia Bo 
Published: November 2022

PurposeFrom a psychosocial perspective, this study aims to understand the impact of psychosocial safety climate (PSC) on the intent to stay of construction workers and provides practical recommendations for construction enterprises to retain construction workers.Design/methodology/approachThis study proposes the conceptual framework explained by the conservation of resources (COR) theory and develops a mediation model of “PSC – job satisfaction – intent to stay” within the framework supported by the stimulus–organism–response (SOR) model. Then, a questionnaire survey of 489 construction workers in Guangzhou was conducted and structural equation modeling (SEM) analysis was performed on the data collected.FindingsResults show that PSC has a significant and positive effect on job satisfaction and intent to stay. In addition, job satisfaction partially mediates the effect of PSC on intent to stay. Hence, the theoretical model of “PSC – job satisfaction – intent to stay” has been empirically tested and supported.Originality/valueThis study is the first to investigate the effect of PSC on intent to stay and enriches the research on the retention of construction workers. The COR theory explains well the mechanism of PSC influence on intent to stay, thus expanding its application to the construction field. Moreover, this study provides practical recommendations for construction enterprises to retain workers so as to build a stable and productive workforce.
Backer funding intention in reward-based crowdfunding: service-dominant logic and stimulus-organism-response perspectives
Authors: Wu Cedric Hsi-Jui , Atmaja Ferry Tema , Ko Yu-Chien , Guttena Revanth Kumar 
Published: November 2022

PurposeThe new age of entrepreneurs recognizes crowdfunding as an innovative and effective means of obtaining funding from backers. However, attracting backers is challenging and related scholarly knowledge lacking. Therefore, this study investigates the diverse factors influencing backer funding intention in reward-based crowdfunding.Design/methodology/approachThis study conducted an online survey of 401 registered backers from two reward-based crowdfunding platforms in Taiwan. Data were analyzed using covariance-based structural equation modeling.FindingsResults show that entrepreneur activeness has a negative effect on perceived risk but positively, while entrepreneur activeness and platform interactivity have a positive effect on backer engagement and backer value creation. Although it had no significant impact on backer engagement, project novelty positively influenced backer value creation. Perceived risk had no influence on either backer engagement or backer value creation. Backer engagement positively influenced backer value creation and backer funding intention, with the former having a positive impact on the latter.Originality/valueThis study provides a multi-perceptual lens by proposing an integration of diverse factors such as entrepreneurial- (entrepreneur activeness), project- (project novelty and perceived risk) and platform-related characteristics (platform interactivity) as antecedents to backer funding intention. By integrating a service-dominant logic perspective into the stimulus-organism-response model, this study highlights the essence of value creation by perceiving backers as value co-creators.
Airborne cues accelerate flowering and promote photosynthesis in Brassica rapa
Authors: Brosset Agnès , Yu Hao , Blande James D. 
Published: November 2022

Abstract

Volatile cues can induce and/or prime plant defences, but it is less well known if plants also respond by altering growth and reproduction‐related parameters.

Here, we evaluated whether plant volatile cues can elicit changes in growth, flower production, net photosynthesis rate and defences in receiver plants and whether those responses are similar to those elicited in response to direct herbivore‐feeding.

Our results demonstrate that exposure to volatiles emitted from damaged neighbours accelerated the time to first flowering, increased the number of flowers produced and the net photosynthesis rate, but did not alter the fresh harvested plant biomass and volatile defences, compared to non‐exposed plants. Earlier flowering was also observed for plants exposed to volatiles from undamaged plants.

These responses differed from those of plants exposed to actual herbivore‐feeding for which feeding enhanced net photosynthesis rate but reduced growth and had no effect on reproduction and defence in response to subsequent herbivory.

Synthesis. These findings document that plant airborne cues can influence floral traits of receiver plants. In particular, the flower phenology is modulated, and photosynthesis is enhanced, suggesting that carbon allocation could be directed toward reproduction.
Biogas digestate as a sustainable phytosterol source for biotechnological cascade valorization
Authors: Weckerle Tim , Ewald Helen , Guth Patrick , Knorr Klaus‐Holger , Philipp Bodo , Holert Johannes 
Published: November 2022

AbstractEvery year, several million tonnes of anaerobic digestate are produced worldwide as a by‐product of the biogas industry, most of which is applied as agricultural fertilizer. However, in the context of a circular bioeconomy, more sustainable uses of residual digestate biomass would be desirable. This study investigates the fate of the sterol lipids β‐sitosterol and cholesterol from the feedstocks to the final digestates of three agricultural and one biowaste biogas plants to assess if sterols are degraded during anaerobic digestion or if they remain in the digestate, which could provide a novel opportunity for digestate cascade valorization. Gas chromatographic analyses showed that feedstock sterols were not degraded during anaerobic digestion, resulting in their accumulation in the digestates to up to 0.15% of the dry weight. The highest concentrations of around 1440 mg β‐sitosterol and 185 mg cholesterol per kg dry weight were found in liquid digestate fractions, suggesting partial sterol solubilization. Methanogenic batch cultures spiked with β‐sitosterol, cholesterol, testosterone and β‐oestradiol confirmed that steroids persist during anaerobic digestion. Mycobacterium neoaurum was able to transform digestate sterols quantitatively into androstadienedione, a platform chemical for steroid hormones, without prior sterol extraction or purification. These results suggest that digestate from agricultural and municipal biowaste is an untapped resource for natural sterols for biotechnological applications, providing a new strategy for digestate cascade valorization beyond land application.
GPCR signaling regulates severe stress‐induced organismic death in Caenorhabditis elegans
Authors: Wang Changnan , Long Yong , Wang Bingying , Zhang Chao , Ma Dengke K. 
Published: November 2022

AbstractHow an organism dies is a fundamental yet poorly understood question in biology. An organism can die of many causes, including stress‐induced phenoptosis, also defined as organismic death that is regulated by its genome‐encoded programs. The mechanism of stress‐induced phenoptosis is still largely unknown. Here, we show that transient but severe freezing‐thaw stress (FTS) in Caenorhabditis elegans induces rapid and robust phenoptosis that is regulated by G‐protein coupled receptor (GPCR) signaling. RNAi screens identify the GPCR‐encoding fshr‐1 in mediating transcriptional responses to FTS. FSHR‐1 increases ligand interaction upon FTS and activates a cyclic AMP‐PKA cascade leading to a genetic program to promote organismic death under severe stress. FSHR‐1/GPCR signaling up‐regulates the bZIP‐type transcription factor ZIP‐10, linking FTS to expression of genes involved in lipid remodeling, proteostasis, and aging. A mathematical model suggests how genes may promote organismic death under severe stress conditions, potentially benefiting growth of the clonal population with individuals less stressed and more reproductively privileged. Our studies reveal the roles of FSHR‐1/GPCR‐mediated signaling in stress‐induced gene expression and phenoptosis in C. elegans, providing empirical new insights into mechanisms of stress‐induced phenoptosis with evolutionary implications.
Reciprocal associations between peer victimization and depressive symptoms among Chinese children and adolescents: Between‐ and within‐person effects
Authors: Shen Zijiao , Xiao Jiale , Su Shaobing , Tam Cheuk Chi , Lin Danhua 
Published: November 2022

AbstractPeer victimization is detrimental to child mental health. Research has indicated a reciprocal relationship between peer victimization and mental health problems. Yet limited evidence was from children and adolescents in China. The present study used the random intercepts cross‐lagged panel model (RI‐CLPM) to examine both between‐person and within‐person associations between peer victimization and depressive symptoms among Chinese children and adolescents. Participants were 1205 Chinese students (Mage = 11.27 years; ranged from 9 to 15 years; SD = 1.75; 55% boys) who completed four surveys (Time 1 to Time 4) between 2017 and 2019 on demographics, peer victimization, and depressive symptoms. At the between‐person level, peer victimization was positively associated with depressive symptoms. Controlling for between‐person effects, RI‐CLPM suggested positive within‐person effects from peer victimization to depressive symptoms across adjacent waves. The model also suggested a positive within‐person effect from Time 2 depressive symptoms to Time 3 peer victimization. The multi‐group analysis showed that these effects did not differ by gender, age, or subjective socioeconomic status. Peer victimization and depression appear to be reciprocally related at the transitioning period between late childhood and early adolescence in Chinese students. Mental health interventions should attend to peer victimization for children and adolescents in China.