bluuebunny/crossref_metadata_2025_split huggingface dataset:
Function of the bacteriophage P2 baseplate central spike Apex domain in the infection process
Authors: Miller John-Mark , Knyazhanskaya Ekaterina S. , Buth Sergii A. , Prokhorov Nikolai S. , Leiman Petr G. 
Published: February 2023

AbstractThe contractile tail of bacteriophage P2 functions to drive the tail tube across the outer membrane of its host bacterium, a prerequisite event for subsequent translocation of phage genomic DNA into the host cell. The tube is equipped with a spike-shaped protein (product of P2 geneV, gpV or Spike) that contains a membrane-attacking Apex domain carrying a centrally positioned Fe ion. The ion is enclosed in a histidine cage that is formed by three symmetry-related copies of a conserved HxH (histidine, any residue, histidine) sequence motif. Here, we used solution biophysics and X-ray crystallography to characterize the structure and properties of Spike mutants in which the Apex domain was either deleted or its histidine cage was either destroyed or replaced with a hydrophobic core. We found that the Apex domain is not required for the folding of full-length gpV or its middle intertwined β-helical domain. Furthermore, despite its high conservation, the Apex domain is dispensable for infection in laboratory conditions. Collectively, our results show that the diameter of the Spike but not the nature of its Apex domain determines the efficiency of infection, which further strengthens the earlier hypothesis of a drill bit-like function of the Spike in host envelope disruption.
Cell-type-specific regulation of APOE levels in human neurons by the Alzheimer’s disease risk gene SORL1
Authors: Lee Hyo , Aylward Aimee J. , Pearse Richard V. , Hsieh Yi-Chen , Augur Zachary M. , Benoit Courtney R. , Chou Vicky , Knupp Allison , Pan Cheryl , Goberdhan Srilakshmi , Duong Duc M. , Seyfried Nicholas T. , Bennett David A. , Klein Hans-Ulrich , De Jager Philip L. , Menon Vilas , Young Jessica E. , Young-Pearse Tracy L. 
Published: February 2023

SummarySORL1 is strongly implicated in the pathogenesis of Alzheimer’s disease (AD) through human genetic studies that point to an association of reduced SORL1 levels with higher risk for AD. To interrogate the role(s) of SORL1 in human brain cells, SORL1 null iPSCs were generated, followed by differentiation to neuron, astrocyte, microglia, and endothelial cell fates. Loss of SORL1 led to alterations in both overlapping and distinct pathways across cell types, with the greatest effects in neurons and astrocytes. Intriguingly, SORL1 loss led to a dramatic neuron-specific reduction in APOE levels. Further, analyses of iPSCs derived from a human aging cohort revealed a neuron-specific linear correlation between SORL1 and APOE RNA and protein levels, a finding validated in human post-mortem brain. Pathway analysis implicated intracellular transport pathways and TGF- β/SMAD signaling in the function of SORL1 in neurons. In accord, enhancement of retromer-mediated trafficking and autophagy rescued elevated phospho-tau observed in SORL1 null neurons but did not rescue APOE levels, suggesting that these phenotypes are separable. Stimulation and inhibition of SMAD signaling modulated APOE RNA levels in a SORL1-dependent manner. These studies provide a mechanistic link between two of the strongest genetic risk factors for AD.
Active zone protein SYD-2/Liprin-α acts downstream of LRK-1/LRRK2 to regulate polarized trafficking of synaptic vesicle precursors through clathrin adaptor protein complexes
Authors: Nadiminti Sravanthi S P , Dixit Shirley B , Ratnakaran Neena , Hegde Sneha , Swords Sierra , Grant Barth D , Koushika Sandhya P 
Published: February 2023

AbstractSynaptic vesicle proteins (SVps) are thought to travel in heterogeneous carriers dependent on the motor UNC-104/KIF1A. InC. elegansneurons, we found that some SVps are transported along with lysosomal proteins by the motor UNC-104/KIF1A. LRK-1/LRRK2 and the clathrin adaptor protein complex AP-3 are critical for the separation of lysosomal proteins from SVp transport carriers. Inlrk-1mutants, both SVp carriers and SVp carriers containing lysosomal proteins are independent of UNC-104, suggesting that LRK-1 plays a key role in ensuring UNC-104-dependent transport of SVps. Additionally, LRK-1 likely acts upstream of the AP-3 complex and regulates the membrane localization of AP-3. The action of AP-3 is necessary for the active zone protein SYD-2/Liprin-α to facilitate the transport of SVp carriers. In the absence of the AP-3 complex, SYD-2/Liprin-α acts with UNC-104 to instead facilitate the transport of SVp carriers containing lysosomal proteins. We further show that the mistrafficking of SVps into the dendrite inlrk-1andapb-3mutants depends on SYD-2, likely by regulating the recruitment of the AP-1/UNC-101. We propose that SYD-2 acts in concert with both the AP-1 and AP-3 complexes to ensure polarized trafficking of SVps.
Stromal depletion by TALEN-edited universal hypoimmunogenic FAP-CAR T cells enables infiltration and anti-tumor cytotoxicity of tumor antigen-targeted CAR-T immunotherapy
Authors: Das Shipra , Valton Julien , Duchateau Philippe , Poirot Laurent 
Published: February 2023

AbstractAdoptive cell therapy based on chimeric antigen receptor-engineered T (CAR-T) cells has proven to be lifesaving for many cancer patients. However, its therapeutic efficacy has so far been restricted to only a few malignancies, with solid tumors proving to be especially recalcitrant to efficient therapy. Poor intra-tumor infiltration by T cells and T cell dysfunction due to a desmoplastic, immunosuppressive microenvironment are key barriers for CAR T-cell success against solid tumors.Cancer-associated fibroblasts (CAFs) are critical components of the tumor stroma, evolving specifically within the tumor microenvironment in response to tumor cell cues. The CAF secretome is a significant contributor to the extracellular matrix and a plethora of cytokines and growth factors that induce immune suppression. Together they form a physical and chemical barrier which induces a T cell-excluding ‘cold’ TME. CAF depletion in stroma rich solid tumors can thus provide an opportunity to convert immune evasive tumors susceptible to tumor-antigen CAR T-cell cytotoxicity.Using our TALEN-based gene editing platform we engineered non-alloreactive, immune evasive CAR T-cells (termed UCAR T-cells) targeting the unique CAF marker Fibroblast Activation Protein, alpha (FAP). In an orthotopic mouse model of triple-negative breast cancer (TNBC) composed of patient derived-CAFs and tumor cells, we demonstrate the efficacy of our engineered FAP UCAR T-cells in CAF depletion, reduction of desmoplasia and successful tumor infiltration. Furthermore, while previously resistant, pre-treatment with FAP UCAR T-cells now sensitized these tumors to Mesothelin (Meso) UCAR T-cell infiltration and anti-tumor cytotoxicity. Combination therapy of FAP UCAR, Meso UCAR T cells and the checkpoint inhibitor anti-PD-1 significantly reduced tumor burden and prolonged mice survival. Our study thus proposes a novel treatment paradigm for successful CAR-T immunotherapy against stroma-rich solid tumors.
Local administration of a novel siRNA modality into the CNS extends survival and improves motor function in the SOD1G93Amouse model for ALS
Authors: Duan Chunling , Kang Moorim , Pan Xiaojie , Gan Zubao , Huang Vera , Li Guanlin , Place Robert F. , Li Long-Cheng 
Published: February 2023

ABSTRACTAntisense oligonucleotides (ASOs) were the first modality to pioneer targeted gene knockdown in the treatment of ALS caused by mutant superoxide dismutase 1 (SOD1). RNA interference (RNAi) is another mechanism of gene silencing with historically superior potency in which short interfering RNAs (siRNAs) guide the RNA-induced silencing complex (RISC) to cleave complementary transcripts. However, delivery to extrahepatic tissues like the central nerve system (CNS) has been a bottleneck in the clinical development of RNAi. Herein, we identify potent siRNA duplexes for the knockdown of human SOD1 (hSOD1) in which medicinal chemistry and conjugation to an accessory oligonucleotide (ACO) enables durable and potent activity in CNS tissues. Local delivery via intracerebroventricular (ICV) or intrathecal (IT) injection into SOD1G93Amice delayed disease progression and extended animal survival with superior efficacy compared to an ASO compound resembling Tofersen in sequence and chemistry. Treatment also prevented disease-related declines in motor function including improvements in animal mobility, muscle strength, and coordination. The ACO itself does not target any specific complementary nucleic acid sequence; rather, it imparts benefits conducive to bioavailability and delivery through its chemistry. The complete conjugate (i.e., siRNA-ACO) represents a novel modality for delivery of RNAi to the CNS in which we aim to pursue ALS as an exemplary indication for clinical development.
Using social media to analyze consumers' attitude toward natural food products
Authors: Fatemi Hajar , Kao Erica , Schillo R. Sandra , Li Wanyu , Du Pan , Jian-Yun Nie , Dube Laurette 
Published: February 2023

PurposeThis paper examines user generated social media content bearing on consumers’ attitude and belief systems taking the domain of natural food product as illustrative case. This research sheds light on how consumers think and talk about natural food within the context of food well-being and health.Design/methodology/approachThe authors used a keyword-based approach to extract user generated content from Twitter and used both food as well-being and food as health frameworks for analysis of more than two million tweets.FindingsThe authors found that consumers mostly discuss food marketing and less frequently discuss food policy. Their results show that tweets regarding naturalness were significantly less frequent in food categories that feature naturalness to an extent, e.g. fruits and vegetables, compared to food categories dominated by technologies, processing and man-made innovation, such as proteins, seasonings and snacks.Research limitations/implicationsThis paper provides numerous implications and contributions to the literature on consumer behavior, marketing and public policy in the domain of natural food.Practical implicationsThe authors’ exploratory findings can be used to guide food system stakeholders, farmers and food processors to obtain insights into consumers' mindset on food products, novel concepts, systems and diets through social media analytics.Originality/valueThe authors’ results contribute to the literature on the use of social media in food marketing on understanding consumers' attitudes and beliefs toward natural food, food as the well-being literature and food as the health literature, by examining the way consumers think about natural (versus man-made) food using user generated content of Twitter, which has not been previously used.
Macro investigation on China's engineering insurance industry: based on industrial organization theories
Authors: Zhou Xiaowei , Wang Yousong , Zhang Yangbing , Liu Fangfang 
Published: February 2023

PurposeIn China, engineering insurance has been questioned as not being beneficial as expected. This paper seeks to further understand how China's engineering insurance industry functions and to provide a macro perspective explanation for engineering insurance's underdevelopment.Design/methodology/approachThree industrial organization hypotheses were extended to the engineering insurance context: structure conduct performance (SCP), relative market power (RMP) and efficiency structure (ES) hypotheses. This paper employed the Generalized Method of Moments (GMM) and Data Envelopment Analysis (DEA) bootstrap to test the hypotheses using panel data from 2008 to 2017.FindingsThe results suggest that the SCP paradigm is validated in China's engineering insurance market, indicating a concentrated market where the welfare of consumers (e.g. owners, contractors and designers) may be eroded. Several factors are identified to have significant impacts on engineering insurers' performance, such as the investment return, percentage of engineering business, the ratio of outstanding claims, the number of large contractors, market rivalry and entry barriers.Originality/valueDespite the sheer size of China's construction industry and the urgent need to improve risk management, the insurance industry that serves construction firms engineering insurance is underdeveloped. Engineering insurance is yet to be understood from a macro perspective, which may reveal the underlying reasons for engineering insurance's underdevelopment. The industrial organization theories provided a theoretical framework to test the functioning of this specific industry. The disaggregated data (engineering line specific) is employed to ensure effective regulation and policymaking.
When is research and development more effective in times of crisis? The role of environmental policies
Authors: Petti Claudio , Lepore Dominique , Liakh Olena , Elia Gianluca 
Published: February 2023

PurposeIn times of crisis, innovation management and specifically Research and Development (R&D) investments are critical to temper company losses and stimulate higher revenues. Environmental policies, for their potential to stimulate environmental innovations and efficient management of resources, may hold a magnifying role in this relationship. By relying on the distinction between regulatory policies and institutional incentives, this paper argues about the moderating role of environmental policies between a firm's R&D expenses and its performance.Design/methodology/approachHypotheses are tested on data collected from a sample of small and medium-sized Chinese enterprises after the 2008 financial crisis.FindingsFindings reveal positive moderating effects of both regulatory pressures and institutional incentives, with a more significant effect of government support. The highest impact is reached when both these types of policies are present.Originality/valueThe theoretical and methodological relevance of this distinction, the importance of an appropriate mix of environmental policies in policymaking and their resilience building role in stimulating environmental innovations in the aftermath of crises are discussed.
The impact of innovation orientation and knowledge management on business services performance moderated by technological readiness
Authors: Borodako Krzysztof , Berbeka Jadwiga , Rudnicki Michał , Łapczyński Mariusz 
Published: February 2023

PurposeThis work aims to determine how innovation orientation (IO), built from six dimensions (strategic, structural-process, human resources, technological, organizational culture and market) affects organizational performance (OP) with the inclusion of knowledge management (KM) as a mediator and technological readiness (TR) as a moderator in the model.Design/methodology/approachQuestionnaires completed by business service companies were analyzed using multiple regression analysis (path analysis), including the mediating variable (KM) and moderating variable (TR). The construct was validated with positive outcomes.FindingsOf the eight hypotheses, six were supported. The study results show that strategic, technological, organizational culture and market dimensions of IO positively influence KM. On the other hand, KM plays an important role as a mediator in supporting the relationship between the four dimensions of IO and performance. Moreover, TR, as a moderator, positively affects the relationship between KM and OP.Originality/valueThe study is the first to explore the relationship between six dimensions of IO and KM in business service sector. Furthermore, this study provides evidence that TR can be beneficial for companies with respect to effective KM, which leads to the better performance.
Research trends on guest experience with service robots in the hospitality industry: a bibliometric analysis
Authors: Yörük Tayfun , Akar Nuray , Özmen Neslihan Verda 
Published: February 2023

PurposeThe purpose of this study is to reveal the research trends in guest experiences of service robots in the hospitality industry.Design/methodology/approachIn this study, a review was carried out on the Web of Science (WoS) database with the assistance of bibliometric analysis techniques. Cluster analysis was also employed for this to group important data to determine the relationships and to visualize the areas in which the studies are concentrated. The thematic content analysis method was used to reveal on which customer experiences and on which methods the focuses were.FindingsOn the subject of experiences of service robots, the greatest number of publications was in 2021. In terms of country, China has come to the fore in the distribution of publications. As a result of thematic content analysis, it was determined that the leading factor was the main dimension of emotional experience. In terms of sub-dimensions, social interactions attracted more attention. Most of the studies discussed were not based on any theory. Apart from these, the Technology Acceptance Model (TAM), the Service Quality Model (SERVQUAL) and Perceived Value Theory (PVT) were featured more prominently among other studies.Research limitations/implicationsIn this study, only the WoS database was reviewed. In future studies, it would be possible to make contextual comparisons by scanning other databases. In addition to quantitative research designs, social dimensions may be examined in depth following qualitative research methods. Thus, various comparisons can be made on the subject with mixed-method research designs. Experimental research designs can also be applied to where customers have experienced human-robot interactions (HRIs).Originality/valueIn the hospitality industry, it is critical to uncover every dimension of guests' robot acceptance. This study, which presents the current situation on this basis, guides future projections for the development of guest experiences regarding service robots in the hospitality industry.
AEC/FM performance in adaptive reuse projects: investigation of challenges and development of practical guidelines
Authors: Hassanain Mohammad A. , Hamida Mohammad B. 
Published: February 2023

Purpose
This paper aims to provide architecture, engineering, construction and facilities management (AEC/FM) practitioners with a guiding tool for overcoming the challenges affecting their performance in adaptive reuse project.

Design/methodology/approach
Literature review was conducted to comprehend the challenges affecting the AEC/FM performance during the implementation of adaptive reuse projects. A case study was conducted on an adaptively reused building, located in Saudi Arabia. The case study building was converted from a bookstore into an amusement center. Document review of the as-built drawings, and a structured interview with the project manager were conducted. The study concluded with the development of AEC/FM practical guidelines, pertaining to the different involved domains.

Findings
This study indicated that the potential challenges are interrelated among the three domains. These challenges pertained to the spatial, legislative, technical, administrative and operational aspects. The findings emphasized the vital role of the integration among the AEC/FM domains, at the early project planning phases. Based on the findings, three sets of AEC/FM guidelines were developed.

Research limitations/implications
Theoretically, to the best of the authors’ knowledge, this is the first study that provides a case-specific investigation of the challenges affecting the AEC/FM performance in adaptive reuse projects.

Practical implications
The developed practical guidelines could potentially enhance the AEC/FM performance in future adaptive reuse projects.

Originality/value
This study contributes to the practice of adaptive reuse projects through providing practical guidelines for mitigating the challenges that affect the AEC/FM performance in these projects.
An energy performance baseline scenario for 19thC listed dwellings in the UK
Authors: Menconi Michela , Painting Noel , Piroozfar Poorang 
Published: February 2023

PurposeThe inclusion of heritage dwellings in the UK decarbonization policies can contribute to cut operational carbon emissions from the building stock; this needs to be made a priority if net zero carbon targets are to be achieved. However, the energy and carbon savings potential of suitable retrofit interventions on this part of the stock is extremely variable and strictly intertwined with the range of baseline conditions of such dwellings. This study aims to propose a framework for interventions in traditional listed dwellings (TLDs) to improve their energy performance utilizing dynamic energy simulation (DES) of selected case studies (CSs) in the city of Brighton and Hove (South-East England).Design/methodology/approachTo achieve this aim, the study established a baseline scenario which provides a basis for the assessment of energy performance and thermo-hygrometric behaviour pre- and post-interventions and allows for comparison between different CSs under comparable conditions.FindingsPresenting a brief overview of the methodology adopted in this study, the paper describes the approach devised to generate such baseline scenario. The paper then compares the results obtained from simulation of normalized and baseline models with the status-quo energy consumption of the dwellings investigated (based on meter readings).Originality/valueThis analysis finally allows to highlight some key physical determinants of the baseline HEC which, in the following stage of research, proved to have a considerable effect also on the amount of energy and carbon savings achievable post retrofit interventions.
Achievement to adaptive reuse strategies of industrial heritage: learning from Iranian cases
Authors: Porkar Mohammad Javad , Khakzand Mehdi , Mardanlou Nima 
Published: February 2023

PurposeThe adaptability of multi-functional industrial buildings can be an important factor in their reuse. This utility requires the evaluation of factors that are effective apart from physical interventions. Therefore, this study used a combined method to investigate the factors affecting the reuse of the case studies of Iran and their adaptation to the theories proposed in the field of industrial heritage. This study aims to achieve effective strategies in adaptive reuse of industrial heritage buildings.Design/methodology/approachHence, six factors in the economic, social, technological, environmental and legal sectors were analyzed based on PESTEL analysis and the interactions of the proposed matrix factors were evaluated. The results from this evaluation were integrated based on conceptual similarities and examined by SWOT technique as the main factors. Finally the criteria obtained from SWOT analysis has been approved by a Delphi survey.FindingsConsequently, the interaction of the findings to determine the strategy was multiplied in a matrix and the resulting concepts were identified. Finally, 23 strategies were extracted as the factors affecting the reuse of industrial heritage buildings and dealing with future issues. According to the results, the most important strategies are government policies and interventions. Also, the determination of the status of ownership, supervision by the Ministry of Cultural Heritage over the preservation and revitalization of industrial heritage buildings and intervention policies for defining the uses related to an industrial building fall into this category.Originality/valueThe findings of this study indicate that an adaptive view of the above strategies and the indicators of each factor could affect the adaptive reuse of the industrial heritage.