bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-thrombotic treatment enhances antibiotic efficiency in a humanized model of meningococcemia
Authors: Corre Jean-Philippe , Obino Dorian , Nivoit Pierre , Yatim Aline , Schmitt Taliah , Duménil Guillaume 
Published: January 2022

AbstractMeningococcal infections remain particularly difficult to treat. Despite antibiotic therapy, the state of the patients often rapidly deteriorates. Early clinical studies suggest that meningococci acquire a form of resistance to antibiotic treatments during infections. Taking advantage of a humanized animal model of infection, we confirm that adherent bacteria become highly resistant to antibiotic treatments as early as 3-6 hours post infection, although fully sensitivein vitro. Within this time frame, meningococci adhere to the endothelium via their type IV pili, proliferate and eventually fill the vessel lumen. Using intravital imaging, we show that rapidly upon infection blood flow is dramatically decreased, thus limiting antibiotic access to infected vessels. Concomitantly, fibrin is deposited inside infected vessels in proximity to bacterial aggregates. Pharmacologically impairing thrombin generation by inhibiting Factor X activity not only improves blood flow in infected vessels, but also enhances the efficacy of the antibiotic treatment. Our results indicate that the combined administration of anticoagulants together with antibiotics might represent a therapeutic approach to treat meningococcal sepsis more efficiently.
Establishment of a transparent soil system to study Bacillus subtilis chemical ecology
Authors: Lozano-Andrade Carlos N. , Nogueira Carla G. , Wibowo Mario , Kovács Ákos T. 
Published: January 2022

AbstractBacterial secondary metabolites are structurally diverse molecules that drive microbial interaction by altering growth, cell differentiation, and signaling. Bacillus subtilis, a Gram-positive soil-dwelling bacterium, produces a wealth of secondary metabolites, among them, lipopeptides have been vastly studied by their antimicrobial, antitumor, and surfactant activities. However, the natural functions of secondary metabolites in the lifestyles of the producing organism remain less explored under natural conditions, i.e. in soil. Here, we describe a hydrogel-based transparent soil system to investigate B. subtilis chemical ecology under controllable soil-like conditions. The transparent soil matrix allows the growth of B. subtilis and other isolates gnotobiotically and under nutrient-controlled conditions. Additionally, we show that transparent soil allows the detection of lipopeptides production and dynamics by HPLC-MS and MALDI-MS imaging, along with fluorescence imaging of 3-dimensional bacterial assemblages. We anticipate that this affordable and highly controllable system will promote bacterial chemical ecology research and help to elucidate microbial interactions driven by secondary metabolites.
Bacterial lifestyle switch in response to algal metabolites
Authors: Barak-Gavish Noa , Dassa Bareket , Kuhlisch Constanze , Nussbaum Inbal , Rosenberg Gili , Avraham Roi , Vardi Assaf 
Published: January 2022

AbstractUnicellular algae, termed phytoplankton, greatly impact the marine environment by serving as the basis of marine food webs and by playing central roles in biogeochemical cycling of elements. The interactions between phytoplankton and heterotrophic bacteria affect the fitness of both partners. It is becoming increasingly recognized that metabolic exchange determines the nature of such interactions, but the underlying molecular mechanisms remain underexplored. Here, we investigated the molecular and metabolic basis for the bacterial lifestyle switch, from coexistence to pathogenicity, in Sulfitobacter D7 during its interaction with Emiliania huxleyi, a cosmopolitan bloom-forming phytoplankter. To unravel the bacterial lifestyle switch, we profiled bacterial transcriptomes in response to infochemicals derived from algae in exponential and stationary growth, which induced the Sulfitobacter D7 coexistence and pathogenicity lifestyles, respectively. We found that algal dimethylsulfoniopropionate (DMSP) was a pivotal signaling molecule that mediated the transition between the lifestyles. However, the coexisting and pathogenic lifestyles were evident only in the presence of additional algal metabolites. In the pathogenic mode, Sulfitobacter D7 upregulated flagellar motility and many transport systems, presumably to maximize assimilation of E. huxleyi-derived metabolites released by algal cells upon cell death. Specifically, we discovered that algae-produced benzoate promoted the growth of Sulfitobacter D7, and negated the DMSP-inducing lifestyle switch to pathogenicity, demonstrating that benzoate is important for maintaining the coexistence of algae and bacteria. We propose that bacteria can sense the physiological status of the algal host through changes in the metabolic composition, which will determine the bacterial lifestyle during the interactions.Significance StatementMicroorganisms in the marine environment play crucial roles in the regulation of Earth’s climate and elemental cycling. Understanding microbial interactions and the metabolic exchange that drives them is necessary for disentangling the complexity of the marine ecosystem. Here we demonstrate how the opportunistic pathogen Sulfitobacter D7 switches its lifestyle from coexistence to pathogenicity in response to metabolites released by Emiliania huxleyi, a bloom-forming unicellular alga. By mapping bacterial transcriptional profiles, we show that the algal metabolite dimethylsulfoniopropionate (DMSP), an important signaling molecule in the marine environment, is essential for the bacterial lifestyle switch. However, the activity of DMSP depended on additional algal signals. This work emphasizes how metabolic crosstalk can influence the nature and fate of microbial interactions, which have cascading effects on large-scale oceanic processes.
A pleiotropic chemoreceptor facilitates the functional coupling of pheromone production and perception
Authors: Vernier Cassondra , Zelle Kathleen M. , Leitner Nicole , Liang Xitong , Halloran Sean , Millar Jocelyn G. , Ben-Shahar Yehuda 
Published: January 2022

SUMMARYOptimal mating decisions depend on the robust coupling of signal production and perception because independent changes in either could carry a fitness cost. However, since the perception and production of mating signals are often mediated by different tissues and cell types, the mechanisms that drive and maintain their coupling remain unknown for most animal species. Here, we show that inDrosophila,sensory perception and production of an inhibitory mating pheromone are co-regulated byGr8a,a member of theGustatory receptorgene family. Specifically, we found that the pleiotropic action ofGr8aindependently regulates the perception of pheromones by the chemosensory systems of males and females, as well as their production in the fat body and oenocytes of males. These findings provide a relatively simple molecular explanation for how pleiotropic receptors maintain robust mating signaling systems at the population and species levels.
unc-37/Groucho and lsy-22/AES repress Wnt target genes in C. elegans asymmetric cell divisions
Authors: Bekas Kimberly N. , Phillips Bryan T. 
Published: January 2022

AbstractAsymmetric cell division (ACD) is a fundamental mechanism of cell fate specification and adult tissue homeostasis. In C. elegans, the Wnt/β-catenin asymmetry (WβA) pathway regulates ACDs throughout embryonic and larval development. Under control of Wnt ligand-induced polarity, the transcription factor POP-1/TCF functions with the coactivator SYS-1/β-catenin to activate gene expression in the signaled cell or, in absence of the coactivator, to repress Wnt target genes in the unsignaled daughter cell. To date, investigation of Groucho function in WβA is lacking, and the function of LSY-22/AES has only been evaluated in C. elegans neurons. Further, conflicting evidence shows TCF utilizing Groucho-mediated repression may be either aided or repressed by AES addition. Here we demonstrate a genetic interaction between Groucho corepressors and POP-1/TCF in the distal tip cells (DTCs), seam cells (SCs) and embryonic endoderm development. In the DTCs, signaled cell fate increases after individual and double Groucho loss of function, representing the first demonstration of Groucho function in wildtype WβA ACDs. Further, WβA target gene misexpression occurs more frequently than DTC fate changes, suggesting derepression generates an intermediate cell fate. In the SCs, loss of UNC-37/Groucho or LSY-22/AES in a POP-1/TCF hypomorphic background enhances SC expansion and target gene misregulation. Moreover, while POP-1/TCF depletion in lsy-22/AES nulls yielded an expected increase in SCs we observed a surprising SC decrease in unc-37/Groucho nulls subjected to POP-1/TCF depletion. This phenotype correlates with UNC-37/Groucho regulation of pop-1/tcf expression since POP-1/TCF levels are increased in unc-37/Groucho null SCs. Lastly, Groucho functions in embryonic endoderm development since we observe ectopic endoderm transgene expression in unc-37/Groucho and lsy-22/AES knockdown in a HDA-1 background. Together, these data indicate Groucho-mediated modulation of cell fate via regulation of POP-1/TCF repression is widespread in WβA ACDs and suggests a novel role of LSY-22/AES as a bona fide TCF repressor.
A non-canonical RNA-binding domain of the Fragile X protein, FMRP, elicits translational repression independent of mRNA G-quadruplexes
Authors: Scarpitti MaKenzie R. , Warrick Julia E. , Yoder Evelyn L. , Kearse Michael G. 
Published: January 2022

ABSTRACTLoss of functional fragile X mental retardation protein (FMRP) causes fragile X syndrome, the leading form of inherited intellectual disability and the most common monogenic cause of autism spectrum disorders. FMRP is an RNA-binding protein that controls neuronal mRNA localization and translation. FMRP is thought to inhibit translation elongation after being recruited to target transcripts via binding RNA G-quadruplexes (G4s) within the coding sequence. Here, we directly test this model and report that FMRP inhibits translation independent of mRNA G4s.Furthermore, we found that the RGG box motif together with its natural C-terminal domain forms a non-canonical RNA-binding domain (ncRBD) that is essential for translational repression. The ncRBD elicits broad RNA binding ability and binds to multiple reporter mRNAs and all four homopolymeric RNAs. Serial deletion analysis of the ncRBD identified that the regions required for mRNA-binding and translational repression overlap but are not identical. Consistent with FMRP stalling elongating ribosomes and causing the accumulation of slowed 80S ribosomes, transcripts bound by FMRP via the ncRBD co-sediment with heavier polysomes and were present in puromycin-resistant ribosome complexes. Together, this work identifies a ncRBD and translational repression domain that shifts our understanding of how FMRP inhibits translation independent of mRNA G4s.
WNK kinases sense molecular crowding and rescue cell volume via phase separation
Authors: Boyd-Shiwarski Cary R. , Shiwarski Daniel J. , Griffiths Shawn E. , Beacham Rebecca T. , Norrell Logan , Morrison Daryl E. , Wang Jun , Mann Jacob , Tennant William , Anderson Eric N. , Franks Jonathan , Calderon Michael , Connolly Kelly A. , Weaver Claire J. , Weckerly Claire C. , Pandey Udai Bhan , Donnelly Christopher J. , Sun Dandan , Rodan Aylin R. , Subramanya Arohan R. 
Published: January 2022

AbstractWhen challenged by hypertonicity, dehydrated cells must defend their volume to survive. This process requires the phosphorylation-dependent regulation of SLC12 cation chloride transporters by WNK kinases, but how these kinases are activated by cell shrinkage remains unknown. Within seconds of cell exposure to hypertonicity, WNK1 concentrates into membraneless droplets, initiating a phosphorylation-dependent signal that drives net ion influx via the SLC12 cotransporters to rescue volume. The formation of WNK1 condensates is driven by its intrinsically disordered C-terminus, whose evolutionarily conserved signatures are necessary for efficient phase separation and volume recovery. This disorder-encoded phase behavior occurs within physiological constraints and is activated in vivo by molecular crowding rather than changes in cell size. This allows WNK1 to bypass a strengthened ionic milieu that favors kinase inactivity and reclaim cell volume through condensate-mediated signal amplification. Thus, WNK kinases are physiological crowding sensors that phase separate to coordinate a cell volume rescue response.
Closed-loop recruitment of striatal parvalbumin interneurons prevents the onset of compulsive behaviours
Authors: Mondragón-González Sirenia Lizbeth , Schreiweis C Christiane , Burguière E Eric 
Published: January 2022

ABSTRACTA prominent electrophysiological feature of compulsive behaviours is striatal hyperactivity, yet, its underlying regulatory processes still need to be characterised. Within the striatum, parvalbumin-positive interneurons (PVI) exert a powerful feed-forward inhibition essential for the regulation of striatal activity and are implied in the suppression of prepotent inappropriate actions. To investigate the potential role of striatal PVI in regulating striatal activity and compulsive behaviours, we used the Sapap3 knockout mice (Sapap3-KO), which exhibit compulsive-like self-grooming. We first showed that the number of compulsive-like events in Sapap3-KO mice was reduced to normal levels by continuous optogenetic activation of striatal PVI in the centromedial striatum. To narrow down the critical time window of striatal PVI recruitment for regulating compulsive-like grooming, we then developed a novel closed-loop optogenetic stimulation pipeline. Upon a predictive biomarker of grooming onsets, characterised by a transient power increase of 1-4 Hz frequency band in the orbitofrontal cortex, we provided real-time closed-loop stimulation of striatal PVI. This targeted closed-loop optogenetics approach reduced grooming events as efficiently as continuous recruitment of striatal PVI with a reduction of stimulation time of 87%. Together, these results demonstrated that recruitment of striatal PVI at the initiation of the compulsive events is sufficient to drastically reduce compulsive-like behaviours and pave the way for targeted closed-loop therapeutic protocols.
A human fetal lung cell atlas uncovers proximal-distal gradients of differentiation and key regulators of epithelial fates
Authors: He Peng , Lim Kyungtae , Sun Dawei , Pett Jan Patrick , Jeng Quitz , Polanski Krzysztof , Dong Ziqi , Bolt Liam , Richardson Laura , Mamanova Lira , Dabrowska Monika , Wilbrey-Clark Anna , Madissoon Elo , Tuong Zewen Kelvin , Dann Emma , Suo Chenqu , Goh Isaac , Yoshida Masahiro , Nikolić Marko Z , Janes Sam M , He Xiaoling , Barker Roger A , Teichmann Sarah A , Marioni John C. , Meyer Kerstin B , Rawlins Emma L 
Published: January 2022

AbstractWe present a multiomic cell atlas of human lung development that combines single cell RNA and ATAC sequencing, high throughput spatial transcriptomics and single cell imaging. Coupling single cell methods with spatial analysis has allowed a comprehensive cellular survey of the epithelial, mesenchymal, endothelial and erythrocyte/leukocyte compartments from 5-22 post conception weeks. We identify new cell states in all compartments. These include developmental-specific secretory progenitors and a new subtype of neuroendocrine cell related to human small cell lung cancer. Our datasets are available through our web interface (https://lungcellatlas.org). Finally, to illustrate its general utility, we use our cell atlas to generate predictions about cell-cell signalling and transcription factor hierarchies which we test using organoid models.HighlightsSpatiotemporal atlas of human lung development from 5-22 post conception weeks identifies 144 cell types/states.Tracking the developmental origins of multiple cell compartments, including new progenitor states.Functional diversity of fibroblasts in distinct anatomical signalling niches.Resource applied to interrogate and experimentally test the transcription factor code controlling neuroendocrine cell heterogeneity and the origins of small cell lung cancer.
Crystal structures of bacterial Small Multidrug Resistance transporter EmrE in complex with structurally diverse substrates
Authors: Kermani Ali A. , Burata Olive E. , Koff B. Ben , Koide Akiko , Koide Shohei , Stockbridge Randy B. 
Published: January 2022

AbstractProteins from the bacterial small multidrug resistance (SMR) family are proton-coupled exporters of diverse antiseptics and antimicrobials, including polyaromatic cations and quaternary ammonium compounds. The transport mechanism of the Escherichia coli transporter, EmrE, has been studied extensively, but a lack of high-resolution structural information has impeded a structural description of its molecular mechanism. Here we apply a novel approach, multipurpose crystallization chaperones, to solve several structures of EmrE, including a 2.9 Å structure at low pH without substrate. We report five additional structures in complex with structurally diverse transported substrates, including quaternary phosphonium, quaternary ammonium, and planar polyaromatic compounds. These structures show that binding site tryptophan and glutamate residues adopt different rotamers to conform to disparate structures without requiring major rearrangements of the backbone structure. Structural and functional comparison to Gdx-Clo, an SMR protein that transports a much narrower spectrum of substrates, suggests that in EmrE, a relatively sparse hydrogen bond network among binding site residues permits increased sidechain flexibility.
Examining the influential factors of consumer purchase intentions for blockchain traceable coffee using the theory of planned behaviour
Authors: Dionysis Symeon , Chesney Thomas , McAuley Derek 
Published: January 2022

PurposeGiven the increasing industry interest in blockchain technologies for supply chain management and product traceability, this paper aims to investigate consumer purchasing intentions for blockchain traceable coffee and their psychosocial antecedents, utilising an extended model of the theory of planned behaviour (TPB).Design/methodology/approachAn online questionnaire study of 123 participants was deployed, using two traceability systems (one based on blockchain and one on a more established traceability certification) for organic coffee.FindingsAdding variables such as environmental protections, trust and habits significantly increased the predictive power of TPB. The results suggest that attitude, perceived behavioural control and environmental protections drive intentions to purchase blockchain traceable coffee.Research limitations/implicationsApart from establishing the factors affecting consumer intentions for blockchain traceable coffee, this study validates the TPB as a model of explaining coffee purchasing intentions and provides evidence of new variables that can significantly increase the model's predictive power.Practical implicationsThe proposed format of presenting traceability information along with the significant variables revealed in our study can function as a guide for designing product features and marketing strategies for blockchain traceable organic coffee. Increasing consumer awareness on product traceability will also play a crucial role in the success of these products.Originality/valueThis study is the first to explore consumer purchasing intentions for blockchain traceable coffee and establish the psychosocial variables behind them contributing, in that way, to an understudied area in academic literature as well as providing insights for a more consumer-centric design of such products.
Economic analysis of the environmental sustainability of agriculture: recent studies using quasi-experimental methods
Authors: Zhang Wei 
Published: January 2022

PurposeThe purpose of this review article is to demonstrate how the quasi-experimental approach has been used to study environmental and natural resource issues related to agricultural production.Design/methodology/approachThis review article first provides a short introduction to the quasi-experimental approach using the potential outcomes framework and then uses studies on the environmental sustainability of agricultural production to illustrate how quasi-experimental methods have been applied. Papers reviewed consist of studies that estimate the environmental externalities from agricultural production, evaluate agri-environmental and other related policies and programs, and demonstrate issues related to on-farm resource use and climate adaptation.FindingsDifference-in-differences (DID) and two-way fixed effects methods that utilize the spatial and temporal variation in panel data are widely used to estimate the causal impact of changes in agricultural production and policy on the environment. Utilizing the discontinuities and limits created by agricultural policies and regulations, local treatment effects on land and other input use are estimated using regression discontinuity (RD) or instrumental variable (IV) methods with cross-sectional data.Originality/valueChallenges faced by the food systems have made agricultural sustainability more critical than ever. Over the past three decades, the quasi-experimental approach has become the powerhouse of applied economic research. This review article focuses on quasi-experimental studies on the environmental sustainability of agriculture to provide methodological insights and to highlight gaps in the economics literature of agricultural sustainability.
Are the macroeconomic effects on oil price asymmetric? An asymmetric quantile regression approach
Authors: Alqaralleh Huthaifa 
Published: January 2022

Purpose
This paper aims to contribute to the clarification of whether the dependence and causality between oil and the macrofundamentals change across different quantiles of the distribution function.

Design/methodology/approach
Within the context of an asymmetric quantile approach, we drop the assumption that variables operate at the upper tails of the distribution in the way that they operate at the mean.

Findings
Our innovative approach indicates that the response of oil prices not only differs according to the underlying source of the variables shock but also differs across the quantiles.

Originality/value
Although a number of recent studies are closely related to our present research, our novel findings offer some important insights that foreshadow the empirical results. The current research addresses to answer the following questions, in sequence: (i) Is there any extreme value dependence between the crude oil and macroeconomic variables? If yes, (ii) is the dependence symmetric or asymmetric? Finally, (iii) can this dependence be driven by the phases of the economic cycle?