bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short- and long-term high-fat diet exposure differentially alters phasic and tonic GABAergic signaling onto lateral orbitofrontal pyramidal neurons
Authors: Seabrook L.T , Peterson C , Noble D , Sobey M , Tayyab T , Kenney T , Judge A.K , Armstrong M , Lin S , Borgland S.L. 
Published: May 2023

AbstractThe chronic consumption of caloric dense high-fat foods is a major contributor to increased body weight, obesity, and other chronic health conditions. The orbitofrontal cortex (OFC) is critical in guiding decisions about food intake and is altered with diet-induced obesity. Obese rodents have altered morphological and synaptic electrophysiological properties in the lateral orbitofrontal cortex (lOFC). Yet the time course by which exposure to a high-fat diet (HFD) induces these changes is poorly understood. Here male mice are exposed to either short- (7 day) or long-term (90 day) HFD. Long-term HFD exposure increases body weight, and glucose signaling compared to short-term HFD or a standard chow control diet (SCD). Both short and long-term HFD exposure increased the excitability of lOFC pyramidal neurons. However, phasic and tonic GABAergic signalling was differentially altered depending on HFD exposure length, such that tonic GABAergic signaling was decreased with early exposure to the HFD and phasic signaling was changed with long-term diet exposure. Furthermore, alterations in the short-term diet exposure were transient, as removal of the diet restored electrophysiological characteristics similar to mice fed SCD whereas long-term HFD electrophysiological changes were persistent and remained after HFD removal. Finally, we demonstrate that changes in reward devaluation occur early with diet exposure. Together, these results suggest that the duration of HFD exposure differentially alters lOFC function and provides mechanistic insights into the susceptibility of the OFC to impairments in outcome devaluation.Significant statementThis study provides mechanistic insight on the impact of short- and long-term high fat diet (HFD) exposure on GABAergic function in the lateral orbitofrontal cortex (lOFC), a region known to guide decision making. We find short-term HFD exposure induces transient changes in firing and tonic GABA action on lOFC pyramidal neurons, whereas long-term HFD induces obesity and has lasting changes on firing, tonic GABA and inhibitory synaptic transmission onto lOFC neurons. Given that GABAergic signaling in the lOFC can influence decision making around food, these results have important implications in present society as palatable energy dense foods are abundantly available.
Slit-independent guidance of longitudinal axons byDrosophilaRobo3
Authors: Carranza Abigail , Howard LaFreda J. , Brown Haley E. , Ametepe Ayawovi Selom , Evans Timothy A. 
Published: May 2023

AbstractDrosophilaRobo3 is a member of the evolutionarily conserved Roundabout (Robo) receptor family and one of threeDrosophilaRobo paralogs. During embryonic ventral nerve cord development, Robo3 does not participate in canonical Slit-dependent midline repulsion, but instead regulates the formation of longitudinal axon pathways at specific positions along the medial-lateral axis. Longitudinal axon guidance by Robo3 is hypothesized to be Slit dependent, but this has not been directly tested. Here we create a series of Robo3 variants in which the N-terminal Ig1 domain is deleted or modified, in order to characterize the functional importance of Ig1 and Slit binding for Robo3’s axon guidance activity. We show that Robo3 requires its Ig1 domain for interaction with Slit and for proper axonal localization in embryonic neurons, but deleting Ig1 from Robo3 only partially disrupts longitudinal pathway formation. Robo3 variants with modified Ig1 domains that cannot bind Slit retain proper localization and fully rescue longitudinal axon guidance. Our results indicate that Robo3 guides longitudinal axons independently of Slit, and that sequences both within and outside of Ig1 contribute to this Slit-independent activity.
SGRN: A Cas12a-driven Synthetic Gene Regulatory Network System
Authors: Kang HyunJin , Fitch John C. , Varghese Reeba P. , Thorne Curtis A. , Cusanovich Darren A. 
Published: May 2023

AbstractGene regulatory networks, which control gene expression patterns in development and in response to stimuli, use regulatory logic modules to coordinate inputs and outputs. One example of a regulatory logic module is the gene regulatory cascade (GRC), where a series of transcription factor genes turn on in order. Synthetic biologists have derived artificial systems that encode regulatory rules, including GRCs. Furthermore, the development of single-cell approaches has enabled the discovery of gene regulatory modules in a variety of experimental settings. However, the tools available for validating these observations remain limited. Based on a synthetic GRC using DNA cutting-defective Cas9 (dCas9), we designed and implemented an alternative synthetic GRC utilizing DNA cutting-defective Cas12a (dCas12a). Comparing the ability of these two systems to express a fluorescent reporter, the dCas9 system was initially more active, while the dCas12a system was more streamlined. Investigating the influence of individual components of the systems identified nuclear localization as a major driver of differences in activity. Improving nuclear localization for the dCas12a system resulted in 1.5-fold more reporter-positive cells and a 15-fold increase in reporter intensity relative to the dCas9 system. We call this optimized system the “Synthetic Gene Regulatory Network” (SGRN, pronounced “sojourn”).
Remodeling the central metabolism ofEscherichia colienables a universal chassis
Authors: Liu Min , Guo Likun , Huo Meitong , Feng Xinjun , Zhao Zhe , Qi Qingsheng , Xian Mo , Zhao Guang 
Published: May 2023

AbstractE. coliis the host of choice to produce a wide variety of chemicals and proteins. Overflow metabolism is considered as the widespread and major obstacle in microbial synthesis, and overcoming this common bottleneck may enable a universal chassis. Here, we constructed anE. coliuniversal chassis (ABKS strain) with significantly suppressed overflow metabolism, presenting similar growth rate, decreased glucose consumption, and increased production of desired chemicals and proteins when compared with wild-type BL21(DE3) strain. Furthermore, we demonstrated that metabolic flux of ABKS strain was reprogrammed from TCA cycle to glyoxylate bypass at isocitrate node via the synergistic effect of multi-layer regulation in gene transcription and protein modification. This metabolic reconfiguration alleviates overflow metabolism, avoids CO2release in TCA cycle, finally improving the carbon atom economy in bioprocess. Our chassis has widespread and practical use for elevating the production and yield of multiple desired chemicals and proteins from different carbon source. The metabolic reconfiguration also provides theoretical basis for rational design of efficient bioproduction strains.
Cysteine synthase: multiple structures of a key enzyme in cysteine synthesis and a potential drug target for Chagas disease and leishmaniasis
Authors: Sowerby Kate , Freitag-Pohl Stefanie , Murillo Ana Milena , Silber Ariel Mariano , Pohl Ehmke 
Published: May 2023

Chagas disease is a neglected tropical disease (NTD) caused by Trypanosoma cruzi, whilst leishmaniasis, which is caused by over 20 species of Leishmania, represents a group of NTDs endemic to most countries in the tropical and subtropical belt of the planet. These diseases remain a significant health problem both in endemic countries and globally. These parasites and other trypanosomatids, including T. theileri, a bovine pathogen, rely on cysteine biosynthesis for the production of trypanothione, which is essential for parasite survival in hosts. The de novo pathway of cysteine biosynthesis requires the conversion of O-acetyl-L-serine into L-cysteine, which is catalysed by cysteine synthase (CS). These enzymes present potential for drug development against T. cruzi, Leishmania spp. and T. theileri. To enable these possibilities, biochemical and crystallographic studies of CS from T. cruzi (TcCS), L. infantum (LiCS) and T. theileri (TthCS) were conducted. Crystal structures of the three enzymes were determined at resolutions of 1.80 Å for TcCS, 1.75 Å for LiCS and 2.75 Å for TthCS. These three homodimeric structures show the same overall fold and demonstrate that the active-site geometry is conserved, supporting a common reaction mechanism. Detailed structural analysis revealed reaction intermediates of the de novo pathway ranging from an apo structure of LiCS and holo structures of both TcCS and TthCS to the substrate-bound structure of TcCS. These structures will allow exploration of the active site for the design of novel inhibitors. Additionally, unexpected binding sites discovered at the dimer interface represent new potential for the development of protein–protein inhibitors.
Applying means-end to hospitality hosts: a study of winery tasting rooms
Authors: Lease Terry , Goldenberg Marni , Haberland Matt , Wallan Sam 
Published: May 2023

PurposeThe paper has a twofold purpose: (1) to test the application of means-end theory to providers of hospitality goods and services, and (2) to explore this question in the context of winery tasting rooms when they had a unique opportunity to restructure their hospitality experience due to government restrictions in response to COVID.Design/methodology/approachA qualitative approach was adopted, and a convenience sample was used to conduct semi-structured laddering interviews. Forty interview transcripts were coded as means-end ladders, which were analyzed using a custom computer program to develop the implication matrix and the hierarchical value map.FindingsThis paper demonstrates that means-end is a useful approach to investigate the values and behaviors of the producer, specifically hospitality hosts. It finds that the principal goal of tasting rooms is to generate sales, and offering a compelling guest experience is the characteristic that contributes the most to achieving that goal. The staff and the atmosphere created for the guests are the two factors with the greatest influence on the guest experience.Originality/valueThis is the first paper to use means-end theory to study the hospitality host, or the producer of goods and services in general, and the first to study winery hospitality primarily through the lens of means-end theory. The study also helps fill a gap in research on tasting room sales focused on the winery’s goals.
FDI and productivity: facts versus fiction of high growth
Authors: Sokhanvar Amin 
Published: May 2023

PurposeThis paper aims to study the role of foreign direct investment (FDI) channels in improving local firms' productivity. Two transmission channels of knowledge spillovers are empirically investigated. The study focuses on the role of high-growth firms (HGFs) that are assumed to have a higher absorptive capacity.Design/methodology/approachA threshold regression model that considers country and sector fixed effects is applied to investigate 8525 firms across 50 sectors in 12 developing countries in the East Asia and Pacific (EAP) region.FindingsThe author's findings indicate that first, larger firms with external market linkages are more productive. Second, high-growth enterprises are powerful engines of job creation; however, the firms do not outperform other firms in terms of capacity in absorbing FDI spillovers and do not have higher productivity.Research limitations/implicationsThe findings highlight the necessity of rethinking public policy priorities to support firm growth. Policies to maximize the gains from FDI spillovers are discussed.Originality/valueThis is the first study to investigate the strength of FDI spillover channels across different sectors, and the channels' impact on the productivity of local enterprises in the EAP region. This study also explores the potential role of high-growth firms (HGFs) in this interaction via job creation and improving output growth rate.
Exploring fire for financial independence retire early (FIRE): a netnography approach
Authors: Khan Abdul Wahid , Pandey Jatin 
Published: May 2023

Purpose
Consumers’ lifestyle and financial decision-making affects their overall well-being. This paper aims to explore the factors that motivate consumers to pursue the goal of financial independence and retiring early (FIRE).

Design/methodology/approach
Qualitative netnography was used to analyze FIRE-related discussions by FIRE-specific online communities. The findings were triangulated using inputs from in-depth interviews with 13 financial advisors.

Findings
Using conservation of resources as a theoretical lens, two factors were found to be the primary motivators driving FIRE attitude and subsequent adoption of FIRE behavior – “escapism & freedom from the current workplace & life space” and “concern for physical & mental well-being.” Four factors were found to influence the adoption of FIRE attitude and behavior: “individual characteristics” [do-it-yourself (DIY) and proactive attitude, the capability of frugal living and ability to plan, track, and review], “well-paying job,” “support from spouse” and “resistance from social groups.”

Research limitations/implications
Due to the nature of netnography, demographic details of the sample cannot be completely ascertained.

Practical implications
The findings suggest marketing strategies primarily to wealth managers for: shifting to need-based segmentation of FIRE participants, modifying offerings to involve co-creation and low-touch products, innovating pricing models, increasing distribution reach through digitization and increasing sales and lead generation through engagement.

Originality/value
This is one of the first studies to explore the factors driving the adoption of FIRE by general FIRE consumers and presents a conceptual model.
Financial inclusion and financial development: implications for monetary policy effectiveness and economic growth in sub-Saharan Africa
Authors: Takyi Paul Owusu , Sakyi Daniel , Yusif Hadrat , Asante Grace Nkansa , Osei-Fosu Anthony Kofi , Mensah Gideon 
Published: May 2023

PurposeThis paper explores the implications of financial inclusion and financial development for the conduct of monetary policy in achieving price stability and economic growth in sub-Saharan Africa (SSA).Design/methodology/approachThe paper employs the system-generalized methods of moment (GMM) estimation technique using panel data spanning 2004 to 2019 and sourced from Databases of (International Monetary Fund's) IMF's Financial Access Survey (FAS), IMF's International Financial Statistics (IFS), World Bank's Global Financial Development Database (GFDD) and World Bank's World Development Indicators (WDI).FindingsThe authors find that financial inclusion has a double-edge effect in SSA. That is, it increases economic growth and lowers inflation in SSA. Furthermore, the results show that a simultaneous increase in financial inclusion and financial development have restrictive effects on economic growth. On the evidence provided, the authors conclude that financial inclusion is an important predictor of economic growth and the conduct of monetary policy in the sub-region.Originality/valueThis paper expands and contributes to the frontier of knowledge how financial inclusion is important for the conduct of monetary policy by monetary authorities in achieving its intended objectives in SSA. The paper highlights the need for ongoing enhancement of financial inclusion of many governments in the sub-region to achieving high economic growth and price stability. Thus, there is the need for policy makers to ensure that a more stringent, effective and appropriate policies and measures are put in place to enhance financial inclusion while taking into consideration the extent of financial development in SSA.
Exploring knowledge management enablers for blockchain-enabled food supply chain implementations
Authors: Pham Chi Minh , Lokuge Sachithra , Nguyen Thanh-Thuy , Adamopoulos Arthur 
Published: May 2023

Purpose
With the advent of new technologies, the integration of blockchain-enabled food supply chain (FSC) implementations is on the rise. Considering the multilateral, comprehensive and complex nature of the whole blockchain-enabled FSC implementation process, understanding knowledge management (KM) practices will add value. Prior literature shows that only a few studies have focused on this topic. As such, this study aims to identify and establish key KM enablers for blockchain-enabled FSC implementations.

Design/methodology/approach
This study conducted a qualitative research approach. By conducting 22 in-depth interviews with experienced blockchain implementation experts in FSC contexts, this study provides interesting insights for academics and practitioners.

Findings
The results of the analysis highlighted eight critical KM enablers that directly influence blockchain-enabled FSC implementations. They include external enablers (i.e. regulation and market competition) as well as internal enablers (i.e. people – organizational learning, strategy and leadership, culture, information technology, organizational infrastructure, processes and activities).

Originality/value
This study is one of the few studies that identify KM enablers for blockchain-enabled FSC implementations. Considering the novelty of decentralized blockchain implementations in FSC and its importance in transforming silo-based knowledge exchange to a decentralized operational structure, this study attempts to identify factors that increase the efficiency of blockchain implementations in FSC contexts.
A taxonomy of competition-based approaches as innovation policy measures to foster external knowledge search
Authors: Landoni Paolo , Franzò Simone , Viglialoro Davide , Laspia Alessandro , Verganti Roberto 
Published: May 2023

Purpose
This paper aims to provide a comprehensive view of the different competition-based approaches that policymakers can exploit to foster external knowledge search and their positioning among innovation policy measures. A growing number of companies have implemented initiatives to access external knowledge to increase their innovativeness, consistently with the open innovation paradigm. Competition-based approaches have received increasing attention by the private sector as a way to access external knowledge. However, despite their potential role as innovation policy measures, a limited attention has been devoted so far to investigate them from the policymakers’ perspective.

Design/methodology/approach
To this aim, a two-stage empirical analysis has been carried out to develop a taxonomy of competition-based approaches. The first stage leveraged a multiple case study methodology including a sample of 20 competition-based approaches, while the second one leveraged interviews with Italian and European key informants.

Findings
This paper proposes a novel taxonomy including eight competition-based approaches, which differ among each other in terms of policy strategy, scope breadth and output required. Moreover, this paper enriches a well-established taxonomy of innovation policy instruments with the identified competition-based approaches.

Originality/value
This study contributes to the current debate on innovation policy by providing a taxonomy that includes eight competition-based approaches that can be exploited by policymakers to foster external knowledge search as well as their positioning among the innovation policy instruments. The taxonomy will hopefully support policymakers in identifying of the most suitable instruments in the light of their policy strategy and objectives.
Seasonal shifts in Fe‐acquisition strategies in Southern Ocean microbial communities revealed by metagenomics and autonomous sampling
Authors: Zhang Rui , Debeljak Pavla , Blain Stephane , Obernosterer Ingrid 
Published: May 2023

AbstractIron (Fe) governs the cycling of organic carbon in large parts of the Southern Ocean. The strategies of diverse microbes to acquire the different chemical forms of Fe under seasonally changing organic carbon regimes remain, however, poorly understood. Here, we report high‐resolution seasonal metagenomic observations from the region off Kerguelen Island (Indian Sector of the Southern Ocean) where natural Fe‐fertilization induces consecutive spring and summer phytoplankton blooms. Our data illustrate pronounced, but distinct seasonal patterns in the abundance of genes implicated in the transport of different forms of Fe and organic substrates, of siderophore biosynthesis and carbohydrate‐active enzymes. The seasonal dynamics suggest a temporal decoupling in the prokaryotic requirements of Fe and organic carbon during the spring phytoplankton bloom and a concerted access to these resources after the summer bloom. Taxonomic assignments revealed differences in the prokaryotic groups harbouring genes of a given Fe‐related category and pronounced seasonal successions were observed. Using MAGs we could decipher the respective Fe‐ and organic substrate‐related genes of individual taxa assigned to abundant groups. The ecological strategies related to Fe‐acquisition provide insights on how this element could shape microbial community composition with potential implications on organic matter transformations in the Southern Ocean.
Identification of complement factor H variants that predispose to pre‐eclampsia: A genetic and functional study
Authors: Lokki A. Inkeri , Ren Zhen , Triebwasser Michael , Daly Emma ,   FINNPEC, Perola Markus , Auro Kirsi , Burwick Richard , Salmon Jane E. , Daly Mark , Laivuori Hannele , Atkinson John P. , Java Anuja , Meri Seppo 
Published: May 2023

AbstractObjectiveThe objective of the study was to investigate the role of genetic variants in complement proteins in pre‐eclampsia.DesignIn a case–control study involving 609 cases and 2092 controls, five rare variants in complement factor H (CFH) were identified in women with severe and complicated pre‐eclampsia. No variants were identified in controls.SettingPre‐eclampsia is a leading cause of maternal and fetal morbidity and mortality. Immune maladaptation, in particular, complement activation that disrupts maternal‐fetal tolerance leading to placental dysfunction and endothelial injury, has been proposed as a pathogenetic mechanism, but this remains unproven.PopulationWe genotyped 609 pre‐eclampsia cases and 2092 controls from FINNPEC and the national FINRISK cohorts.MethodsComplement‐based functional and structural assays were conducted in vitro to define the significance of these five missense variants and each compared with wild type.Main outcome measuresSecretion, expression and ability to regulate complement activation were assessed for factor H proteins harbouring the mutations.ResultsWe identified five heterozygous rare variants in complement factor H (L3V, R127H, R166Q, C1077S and N1176K) in seven women with severe pre‐eclampsia. These variants were not identified in controls. Variants C1077S and N1176K were novel. Antigenic, functional and structural analyses established that four (R127H, R166Q, C1077S and N1176K) were deleterious. Variants R127H and C1077S were synthesised, but not secreted. Variants R166Q and N1176K were secreted normally but showed reduced binding to C3b and consequently defective complement regulatory activity. No defect was identified for L3V.ConclusionsThese results suggest that complement dysregulation due to mutations in complement factor H is among the pathophysiological mechanisms underlying severe pre‐eclampsia.