bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apolipoprotein E4 modulates astrocyte neuronal support functions in the presence of amyloid-β
Authors: Fleeman Rebecca M , Kuhn Madison K , Chan Dennis C , Proctor Elizabeth A 
Published: October 2022

AbstractApolipoprotein E (APOE) is a lipid transporter produced predominantly by astrocytes in the brain. The ε4 variant of APOE (APOE4) is the strongest and most common genetic risk factor for Alzheimer’s disease (AD). Although the molecular mechanisms of this increased risk are unclear, APOE4 is known to alter immune signaling and lipid and glucose metabolism. Astrocytes provide various forms of support to neurons, including regulating neuron metabolism and immune responses through cytokine signaling. Changes in astrocyte function due to APOE4 may therefore decrease neuronal support, leaving neurons more vulnerable to stress and disease insults. To determine whether APOE4 alters astrocyte neuronal support functions, we measured glycolytic and oxidative metabolism of neurons treated with conditioned media from APOE4 or APOE3 (the common, risk-neutral variant) primary astrocyte cultures. We found that APOE4 neurons treated with conditioned media from resting APOE4 astrocytes had similar metabolism to APOE3 astrocytes, but treatment with ACM from astrocytes challenged with amyloid-β (Aβ), a key pathological protein in AD, caused APOE4 neurons to increase their basal mitochondrial and glycolytic metabolic rates more than APOE3 neurons. These changes were not due to differences in astrocytic lactate production or glucose utilization, but instead correlated with increased glycolytic ATP production and a lack of cytokine secretion response to Aβ. Together, these findings suggest that in the presence of Aβ, APOE4 astrocytes alter immune and metabolic functions that result in a compensatory increase in neuronal metabolic stress.
Tixagevimab-cilgavimab as an early treatment for COVID-19 in kidney transplant recipients
Authors: Benotmane Ilies , Olagne Jérôme , Vargas Gabriela Gautier , Cognard Noëlle , Heibel Francoise , Braun-Parvez Laura , Keller Nicolas , Martzloff Jonas , Perrin Peggy , Pszczolinski Romain , Moulin Bruno , Fafi-Kremer Samira , Caillard Sophie 
Published: October 2022

AbstractObjectiveThis single-center retrospective study evaluated the use of tixagevimab-cilgavimab as an early treatment for COVID-19 in kidney transplant recipients (KTRs) during the omicron wave.MethodsKTRs were deemed at high risk for moderate-to-severe COVID-19 in presence of at least one comorbidity (age >60 years, diabetes, obesity, or cardiovascular disease) associated with a weak humoral response (<264 BAU/mL). All other KTRs were considered at low risk. The two groups were stratified according to the administration of tixagevimab-cilgavimab and compared in terms of COVID-19-related hospitalization, oxygen need, ICU admission, and mortality.ResultsOf the 61 KTRs at high risk, 26 received tixagevimab-cilgavimab. COVID-19-related hospitalizations (3.8% versus 34%, p=0.006) and oxygen need (3.8% versus 23%, p=0.04) were significantly less frequent in patients who received tixagevimab-cilgavimab. In addition, non-significant trends towards a lower number of ICU admissions (3.8% versus 14.3% p=0.17) and deaths (0 versus 3, p=0.13) were observed after administration of tixagevimab-cilgavimab. Ten of the 73 low-risk KTRs received tixagevimab-cilgavimab, and no significant clinical benefit was observed in this subgroup.ConclusionEarly administration of tixagevimab-cilgavimab may be clinically useful in high-risk KTRs with COVID-19; however, no major benefit was observed for low-risk patients.
High-content phenotypic screen to identify small molecule enhancers of Parkin-dependent ubiquitination and mitophagy
Authors: Tufi Roberta , Clark Emily H. , Hoshikawa Tamaki , Tsagkaraki Christiana , Stanley Jack , Takeda Kunitoshi , Staddon James M. , Briston Thomas 
Published: October 2022

ABSTRACTMitochondrial dysfunction and aberrant mitochondrial homeostasis are key aspects of Parkinson’s disease (PD) pathophysiology. Mutations in PINK1 and Parkin proteins lead to autosomal recessive PD, suggesting that defective mitochondrial clearance via mitophagy is key in PD etiology. Accelerating the identification and/or removal of dysfunctional mitochondria could therefore provide a disease-modifying approach to treatment. To that end, we performed a high-content phenotypic screen (HCS) of ~125,000 small molecules to identify compounds that positively modulate mitochondrial accumulation of the PINK1-Parkin-dependent mitophagy initiation marker p-Ser65-Ub in Parkin haploinsufficiency (Parkin +/R275W) human fibroblasts. Following confirmatory counter-screening and orthogonal assays, we selected compounds of interest that enhance mitophagy-related biochemical and functional endpoints in patient-derived fibroblasts. Identification of inhibitors of the ubiquitin-specific peptidase and negative regulator of mitophagy USP30 within our hits further validated our approach. The compounds identified provide a novel starting point for further investigation and optimisation.
Mechanisms of insertions at a DNA double-strand break
Authors: Min Jaewon , Zhao Junfei , Zagelbaum Jennifer , Takahashi Sho , Cummings Portia , Schooley Allana , Dekker Job , Gottesman Max E. , Rabadan Raul , Gautier Jean 
Published: October 2022

AbstractInsertions and deletions (indels) are common sources of structural variation, and insertions originating from spontaneous DNA lesions are frequent in cancer. We developed a highly sensitive assay in human cells (Indel-Seq) to monitor rearrangements at the TRIM37 acceptor locus which reports indels stemming from experimentally-induced and spontaneous genome instability. Templated insertions derive from sequences genome-wide and are enriched within 100 kb of donor regions flanking a DSB. Insertions require contact between donor and acceptor loci as well as DNA-PK catalytic activity. Notably, these templated insertions originate from actively transcribed loci, underscoring transcription as a critical source of spontaneous genome instability. Transcription-coupled insertions involve a DNA/RNA hybrid intermediate and are stimulated by DNA end-processing. Using engineered Cas9 breaks, we establish that ssDNA overhangs at the acceptor site greatly stimulate insertions. Indel-Seq revels that insertions are generated via at least three distinct pathways. Our studies indicate that insertions result from movement and subsequent contact between acceptor and donor loci followed invasion or annealing, then by non-homologous end-joining at the acceptor site.
The structure of a Plasmodium vivax Tryptophan Rich Antigen suggests a lipid binding function for a pan-Plasmodium multi-gene family
Authors: Kundu Prasun , Naskar Deboki , McKie Shannon , Dass Sheena , Kanjee Usheer , Introini Viola , Ferreira Marcelo U. , Duraisingh Manoj , Deane Janet , Rayner Julian C. 
Published: October 2022

AbstractTryptophan Rich Antigens (TRAgs) are encoded by a multi-gene family in all Plasmodium species, significantly expanded in P. vivax, but their function is not currently known. We show that multiple P. vivax TRAgs are expressed on the merozoite surface and that one, PVP01_0000100 binds red blood cells with a strong preference for reticulocytes. Solving the structure of the C-terminal tryptophan rich domain that defines the TRAg family revealed a three-helical bundle that is conserved across Plasmodium and has homology with lipid-binding BAR domains involved in membrane remodelling. Biochemical assays confirmed that this domain has lipid binding activity with preference for sulfatide, a glycosphingolipid present in the outer leaflet of plasma membranes. Deletion of the putative orthologue in P. knowlesi, PKNH_1300500, impacts invasion in reticulocytes, suggesting a role for membrane remodelling during this essential process. Together, this work suggests a molecular function for the TRAg family for the first time.
McIdas localizes at centrioles and controls centriole numbers through PLK4-dependent phosphorylation
Authors: Arbi Marina , Skamnelou Margarita , Bournaka Spyridoula , Zitouni Sihem , Tsaridou Stavroula , Karayel Ozge , Vasilopoulou Catherine G. , Tsika Aikaterini C. , Giakoumakis Nikolaos N. , Spyroulias Georgios A. , Mann Matthias , Bettencourt-Dias Mónica , Taraviras Stavros , Lygerou Zoi 
Published: October 2022

SUMMARYThe centriole duplication cycle must be tightly controlled and coordinated with the chromosome cycle. Aberrations in centriole biogenesis can lead to cancer, developmental disorders and ciliopathies. Here, we show that McIdas -previously implicated in cell cycle control and centriole amplification in multiciliated cells-is critical to maintain centriole numbers. Using expansion microscopy, we demonstrate that McIdas is present at the middle part of centrioles, where it exhibits a differential localization during the cell cycle. McIdas loss perturbs daughter centriole biogenesis and centrosomal SAS6 recruitment, whereas its overexpression induces centriole overduplication. Consistently, McIdas depletion reduces PLK4-induced centriole amplification. McIdas interacts with and is phosphorylated by PLK4 in multiple sites identified by mass spectrometry. Mutational analysis shows that McIdas phosphorylation is important for centriole number control. Overall, our results identify a novel, direct role of McIdas on centriole duplication that can link its previously characterized roles in the chromosome cycle and multiciliogenesis.
Barcoding populations ofPseudomonas fluorescensSBW25
Authors: Theodosiou Loukas , Farr Andrew D. , Rainey Paul B. 
Published: October 2022

AbstractIn recent years evolutionary biologists have developed increasing interest in the use of barcoding strategies to study eco-evolutionary dynamics of lineages within evolving populations and communities. Although barcoded populations can deliver unprecedented insight into evolutionary change, barcoding microbes presents specific technical challenges. Here, strategies are described for barcoding populations of the model bacteriumPseudomonas fluorescensSBW25, including the design and cloning of barcoded regions, preparation of libraries for amplicon sequencing, and quantification of resulting barcoded lineages. In so doing, we hope to aid the design and implementation of barcoding methodologies in a broad range of model and non-model organisms.
Nucleotide metabolism is linked to cysteine availability
Authors: Allen Annamarie E. , Sun Yudong , Wei Fangchao , Reid Michael A. , Locasale Jason W. 
Published: October 2022

AbstractThe small molecule erastin inhibits the cystine-glutamate antiporter, system xc-, which leads to intracellular cysteine and glutathione depletion. This can cause ferroptosis, which is an oxidative cell death process characterized by uncontrolled lipid peroxidation. Erastin and other ferroptosis inducers have been shown to affect metabolism but the metabolic effects of these drugs have not been systematically studied. To this end, we investigated how erastin impacts global metabolism in cultured cells and compared this metabolic profile to that caused by the ferroptosis inducer RSL3 or in-vivo cysteine deprivation. Common among the metabolic profiles were alterations in nucleotide and central carbon metabolism. Supplementing nucleosides to cysteine-deprived cells rescued cell proliferation in certain contexts, showing that these alterations to nucleotide metabolism can affect cellular fitness. While GPX4 inhibition caused a similar metabolic profile as cysteine deprivation, nucleoside treatment did not rescue cell viability or proliferation under RSL3 treatment, suggesting that these metabolic changes have varying importance in different scenarios of ferroptosis. Together, our study shows how global metabolism is affected during ferroptosis, and points to nucleotide metabolism as an important target of cysteine deprivation.
Engineered RecA constructs reveal the minimal SOS activation complex
Authors: Cory Michael B. , Li Allen , Hurley Christina M. , Hostetler Zachary M. , Venkatesh Yarra , Jones Chloe M. , Petersson E. James , Kohli Rahul M. 
Published: October 2022

ABSTRACTThe SOS response is a bacterial DNA damage response pathway that has been heavily implicated in bacteria’s ability to evolve resistance to antibiotics. Activation of the SOS response is dependent on the interaction between two bacterial proteins, RecA and LexA. RecA acts as a DNA damage sensor by forming lengthy oligomeric filaments (RecA*) along single-stranded DNA (ssDNA) in an ATP-dependent manner. RecA* can then bind to LexA, the repressor of SOS response genes, triggering LexA degradation and leading to induction of the SOS response. Formation of the RecA*-LexA complex therefore serves as the key ‘SOS activation signal’. Given the challenges associated with studying a complex involving multiple macromolecular interactions, the essential constituents of RecA* that permit LexA cleavage are not well defined. Here, we leverage head-to-tail linked and end-capped RecA constructs as tools to define the minimal RecA* filament that can engage LexA. In contrast to previously postulated models, we found that as few as three linked RecA units are capable of ssDNA binding, LexA binding, and LexA cleavage. We further demonstrate that RecA oligomerization alone is insufficient for LexA cleavage, with an obligate requirement for ATP and ssDNA binding to form a competent SOS activation signal with the linked constructs. Our minimal system for RecA* highlights the limitations of prior models for the SOS activation signal and offers a novel tool that can inform efforts to slow acquired antibiotic resistance by targeting the SOS response.Abstract Figure
Restriction Endonuclease-based Modification-Dependent Enrichment (REMoDE) of DNA for Metagenomic Sequencing
Authors: Enam Syed Usman , Cherry Joshua L. , Leonard Susan R. , Zheludev Ivan N. , Lipman David J. , Fire Andrew Z. 
Published: October 2022

AbstractMetagenomic sequencing is a swift and powerful tool to ascertain the presence of an organism of interest in a sample. However, sequencing coverage of the organism of interest can be insufficient due to an inundation of reads from irrelevant organisms in the sample. Here, we report a nuclease-based approach to rapidly enrich for DNA from certain organisms, including enterobacteria, based on their differential endogenous modification patterns. We exploit the ability of taxon-specific methylated motifs to resist the action of cognate methylation-sensitive restriction endonucleases that thereby digest unwanted, unmethylated DNA. Subsequently, we use a distributive exonuclease or electrophoretic separation to deplete or exclude the digested fragments, thus, enriching for undigested DNA from the organism of interest. As a proof-of-concept, we apply this method to enrich for the enterobacteria Escherichia coli and Salmonella enterica by 11- to 142-fold from mock metagenomic samples and validate this approach as a versatile means to enrich for genomes of interest in metagenomic samples.ImportancePathogens that contaminate the food supply or spread through other means can cause outbreaks that bring devastating repercussions to the health of a populace. Investigations to trace the source of these outbreaks are initiated rapidly but can be drawn out due to the labored methods of pathogen isolation. Metagenomic sequencing can alleviate this hurdle but is often insufficiently sensitive. The approach and implementations detailed here provide a rapid means to enrich for many pathogens involved in foodborne outbreaks, thereby improving the utility of metagenomic sequencing as a tool in outbreak investigations. Additionally, this approach provides a means to broadly enrich for otherwise minute levels of modified DNA which may escape unnoticed in metagenomic samples.
People want to see people? Personalization on Facebook as a tool for corporate communications
Authors: Denner Nora , Schneider Hannah 
Published: October 2022

PurposeSocial networks were created to connect with friends. Therefore, communication in social networks allows addressing individual contacts of each user and is often rather private by nature. Organizations can use this to communicate frequently and personally with their stakeholders. Therefore, this study investigates how organizations use personalization in their social media communication.Design/methodology/approachThis study uses a quantitative content analysis of Facebook posts from ten large companies (N = 500). The posts were analyzed regarding the sub dimensions of personalization, individualization and privatization, as well as type of post, tonality, emotions, user reactions and topics.FindingsCompanies at least partially personalize their communication on Facebook. Overall, 28% of all posts were personalized. Personalized posts were almost always positive regarding tonality and mostly positive regarding emotions. While the personalized posts in this study have fewer user reactions than non-personalized posts, they still have a rather high absolute number of reactions. Regarding personal characteristics, results show that professional competence and appearance were mainly addressed. Concerning privatization, only very few posts showed an individual in a private setting.Originality/valueThe present work gives an overview of how personalized posts differ from non-personalized posts and looks at depicted individuals as well as the use of private elements. By applying the conceptualization of Van Aelst et al. (2012) and by looking at organizations’ use of personalization on the social media platform Facebook, it sheds light on an area that has not been the center of attention so far and helps to expand the current state of personalization research.
Macroeconomic risk factors and Chinese FDIs in real estate: evidence from the Asia-Pacific public real estate markets
Authors: Coën Alain , Lecomte Patrick , Zaiter Saadallah 
Published: October 2022

PurposeThe aim of this study is to shed light on the relative importance of Chinese (Mainland China and Hong Kong: CH-HK) foreign direct investments (FDIs) in real estate (FDIRE) on the dynamics of Asia-Pacific (APAC) public real estate markets after the Global Financial Crisis.Design/methodology/approachUsing a parsimonious real estate asset-pricing model including macroeconomic risk factors, the authors develop a metric to measure FDIs in the real estate sector. The authors use a panel VAR approach based on robust econometric methodology (generalized method of moments) and deal with potential endogeneity and an eventual causality problem. The authors also compute multiple metrics to measure the Chinese, US and Japanese FDIs in the real estate sector.FindingsThe study results report a positive significant impact of CH-HK FDIRE on APAC public real estate returns, while FDIRE originating from outside China are not significant. The authors also show that Chinese investors use the channel of FDIs in Diversified Listed Property Companies (LPCs) and Hotel and Family LPCs to gain exposure to the APAC real estate markets. The study results suggest that APAC property markets are mainly impacted and emphasize the importance of an intercontinental diversification strategy for investors in LPCs in the APAC region.Practical implicationsContrary to Bond et al. (2003) who identified that APAC public real estate markets were overwhelmingly idiosyncratic in the decade preceding China's WTO membership (1990–2001), the study findings underline that Chinese FDIRE became a common factor affecting all eight markets in this study in the decade following the global financial crisis (2007–2017). The results emphasize the importance of an intercontinental diversification strategy for investors in LPCs in the APAC region.Originality/valueThe authors use a parsimonious model, introduce metrics to measure FDIRE and apply a panel VAR approach based on a robust econometric methodology to shed light on China's economic globalization strategy on Asia-Pacific public real estate markets after the GFC. The study results highlighting the major impact of CH-HK FDIRE on securitized real estate market returns dynamics, identify the existence of an Asian common factor driven by Chinese FDI inflows into neighbouring countries.
Description of crystal defect properties in BCC Cr with extended Finnis–Sinclair potential
Authors: Wei Limin , Zhou Fei , Wang Shuo , Hao Weixun , Liu Yong , Zhu Jingchuan 
Published: October 2022

PurposeThe purpose of this study is to propose extended potentials and investigate the applicability of extended Finnis–Sinclair (FS) potential to Cr with the unit cell structure of body-centered cubic (BCC Cr).Design/methodology/approachThe parameters of each potential are determined by fitting the elastic constants, cohesive energy and mono-vacancy formation energy. Furthermore, the ability of the extended FS potential to describe the crystal defect properties is tested. Finally, the applicability of reproducing the thermal properties of Cr is discussed.FindingsThe internal relationship between physical properties and potential function is revealed. The mathematical relationship between physical properties and potential function is derived in detail. The extended FS potential performs well in reproducing physical properties of BCC Cr, such as elastic constants, cohesive energy, surface energy and the properties of vacancy et al. Moreover, good agreement is obtained with the experimental data for predicting the melting point, specific heat and coefficient of thermal expansion.Originality/valueIn this study, new extended potentials are proposed. The extended FS potential is able to reproduce the physical and thermal properties of BCC Cr. Therefore, the new extended potential can be used to describe the crystal defect properties of BCC Cr.
The Most Beloved Cow in Gokulpur
Authors: Maitra Amrapali 
Published: October 2022

SUMMARYDuring ethnographic fieldwork in West Bengal, India, I witnessed the comingling of disgust and desire in shaping religious identity, the effervescent force of crowds, and moments of ordinary ethics enacted through labor. This short story is set in a fictional town: Gokulpur is a microcosm of the tension between rural idiosyncrasies and urban aspirations in India, permeated by growing right‐wing Hindu sentiments. Through the evolving relationship between a boy and his family's revered cow, I explore what it means to navigate companionship, community, and everyday life in an increasingly politicized village—and the reverberations of our choices. The piece originates from a desire to inhabit unfamiliar perspectives through closely observed characters and scenes, testing the potential and limits of imaginative empathy as a tool for social understanding. This work of fiction engages with anthropological scholarship on cross‐species friendship, nonhuman agency, religious ritual, and the ethics of care. [fiction, religion, India, animals, agency, ethics of care]