bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early immunomodulatory program triggered by pro-tolerogenicBifidobacterium pseudolongumdrives cardiac transplant outcomes
Authors: Gavzy Samuel J , Kensiski Allison , Saxena Vikas , Lakhan Ram , Hittle Lauren , Wu Long , Iyyathurai Jegan , Dhakal Hima , Lee Zachariah L , Li Lushen , Lee Young S , Zhang Tianshu , Lwin Hnin W , Shirkey Marina W , Paluskievicz Christina M , Piao Wenji , Mongodin Emmanuel F , Ma Bing , Bromberg Jonathan S 
Published: October 2022

ABSTRACTBackgroundDespite ongoing improvements in regimens to prevent allograft rejection, most cardiac and other organ grafts eventually succumb to chronic vasculopathy, interstitial fibrosis, or endothelial changes, and eventually graft failure. The events leading to chronic rejection are still poorly understood and the gut microbiota is a known driving force in immune dysfunction. We previously showed that gut microbiota dysbiosis profoundly influences the outcome of vascularized cardiac allografts and subsequently identified biomarker species associated with these differential graft outcomes.MethodsIn this study, we further detailed the multifaceted immunomodulatory properties of pro-tolerogenic and pro-inflammatory bacterial species over time, using our clinically relevant model of allogenic heart transplantation.ResultsIn addition to tracing longitudinal changes in the recipient gut microbiome over time, we observed thatBifidobacterium pseudolongum (Bifido)induced an early anti-inflammatory phenotype within 7 days, whileDesulfovibrio desulfuricans (Desulfo)resulted in a pro-inflammatory phenotype, defined by alterations in leukocyte distribution and lymph node (LN) structure. Indeed,in vitroresults showed thatBifidoandDesulfoacted directly on primary innate immune cells. However, by 40 days after treatment, these two bacterial strains were associated with mixed effects in their impact on LN architecture and immune cell composition and loss of colonization within gut microbiota, despite protection of allografts from inflammation withBifidotreatment.ConclusionsThese dynamic effects suggest a critical role for early microbiota-triggered immunological events such as innate immune cell engagement, T cell differentiation, and LN architectural changes in the subsequent modulation of pro-tolerant versus pro-inflammatory immune responses in organ transplant recipients.
Mitochondrial complex I controls blood brain barrier permeability
Authors: Davis Gavin M. , Juere Estelle , Hayes Jerrard M. , Davey Gavin P. 
Published: October 2022

AbstractMitochondrial electron transport chain (ETC) complexes are key mediators of energy metabolism in astrocytes and neurons, with subsequent effects on memory, behaviour and neurodegeneration. Mitochondrial dysfunction and increased blood brain barrier (BBB) permeability are known pathologies in Parkinson’s and Alzheimer’s diseases. However, knowledge of how ETC activities regulate metabolic flux and influence permeability in the BBB is lacking. Using metabolic flux control analysis we show that complex I is a critical control point for oxidative flux and permeability in brain microvascular endothelial cells derived from human induced pluripotent stem cells. Inhibition of complex I activity immediately reduced the transendothelial electrical resistance (TEER) by 60%, leading to an increase in protein transport across the BBB. These events were accompanied by a transient reduction in ATP that was recovered, along with TEER values, over an extended time period. Furthermore, while inhibition of downstream complexes III or IV decreased oxygen respiration rates, no effects on BBB permeability were identified, due to compensatory glycolytic flux and maintenance of ATP synthesis. These data show that mitochondrial complex I is critical for maintaining energy production in endothelial cells and transiently controls BBB permeability, which may contribute to brain disorders where complex I dysfunction is a hallmark.
Dysfunctional neuro-muscular mechanisms explain gradual gait changes in prodromal spastic paraplegia
Authors: Laßmann Christian , Ilg Winfried , Rattay Tim W. , Schöls Ludger , Giese Martin , Haeufle Daniel F.B. 
Published: October 2022

AbstractIn Hereditary Spastic Paraplegia (HSP) type 4 (SPG4) a length-dependent axonal degeneration in the cortico-spinal tract leads to progressing symptoms of hyperreflexia, muscle weakness, and spasticity of lower extremities. Even before the manifestation of spastic gait, in the prodromal phase, axonal degeneration leads to subtle gait changes. These gait changes – depicted by digital gait recording – are related to disease severity in prodromal and early-to-moderate manifest SPG4 subjects. We hypothesize that dysfunctional neuro-muscular mechanisms such as hyperreflexia and muscle weakness explain these disease severity-related gait changes of prodromal and early-to-moderate manifest SPG4 subjects. We test our hypothesis in computer simulation with a neuro-muscular model of human walking. We introduce neuro-muscular dysfunction by gradually increasing sensory-motor reflex sensitivity based on increased velocity feedback and gradually increasing muscle weakness by reducing maximum isometric force. By increasing hyperreflexia of plantarflexor and dorsiflexor muscles, we found gradual muscular and kinematic changes in neuro-musculoskeletal simulations that are comparable to subtle gait changes found in prodromal SPG4 subjects. Predicting kinematic changes of prodromal and early-to-moderate manifest SPG4 subjects by gradual alterations of sensory-motor reflex sensitivity allows us to link gait as a directly accessible performance marker to emerging neuro-muscular changes for early therapeutic interventions.
Investigating the cause of a 2021 winter wave of COVID-19 in a border region in Eastern Germany: a mixed-methods study, August to November 2021
Authors: Yi Buqing , Laubner Alexa , Stadtmüller Marlena , Patrasová Eva , Šimůnková Lenka , Rost Fabian , Winkler Sylke , Reinhardt Susanne , Dahl Andreas , Dalpke Alexander H. 
Published: October 2022

AbstractIn winter 2020 and 2021 many countries worldwide experienced a COVID-19 pandemic wave which led to severe burdens on healthcare systems and huge economic losses. Yet, it remains unclear how the winter waves started and many debates are ongoing about actions necessary to prevent future winter waves. In this study we deciphered the dynamic course of a winter wave in 2021 in Saxony, a state in Eastern Germany neighboring Czech Republic and Poland. The information we achieved might help future pandemic prevention.The dynamic course of the 2021 winter wave in Saxony was investigated through integration of multiple virus genomic epidemiology approaches and functional evaluations of locally circulating variants. Through international collaborations, we performed genomic epidemiology analysis on a weekly base with samples from Saxony and also from one neighbor region in the Czech Republic. Phylogeny analyses were used to track transmission chains, monitor virus genetic changes and identify emerging variants. Phylodynamic approaches have been applied to track the dynamic changes of transmission clusters. For identified local variants of interest, active viruses were isolated and functional evaluations were performed.Genomic epidemiology studies revealed multiple long-lasting community transmission clusters acting as the major driving forces for the winter wave 2021. Analysis of the dynamic courses of two representative long-lasting community transmission clusters indicated similar dynamic changes. In the first 6-8 weeks, the relevant variant was mainly circulating in a small region among young and middle-aged people; after eight weeks, the ratio of people aged above 60 years in the infected population markedly increased, and the virus got more widely spread to distant regions. On the other hand, the transmission cluster caused by a locally occurring variant showed a different transmission pattern. It got geographically widely distributed within six weeks, with many people aged above 60 years being infected since the beginning of the cluster, indicating a higher risk for escalating healthcare burdens. This variant displayed a relative growth advantage compared to co-circulating Delta sub-lineages. Functional analyses revealed a replication advantage, but no advantage in immune evasion ability.This study indicated that long-lasting community transmission clusters starting between August and October caused by imported variants as well as locally occurring variants all contributed to the development of the 2021 winter wave in Saxony. In particular, the cluster derived from a locally occurring variant with certain growth advantage might have stressed local healthcare systems.
Serological Cross-Reactivity Between Spotted Fever and Typhus Groups of Rickettsia Infection in Japan
Authors: Aita Tetsuro , Sando Eiichiro , Katoh Shungo , Hamaguchi Sugihiro , Fujita Hiromi , Kurita Noriaki 
Published: October 2022

AbstractWe examined the frequency of cross-reactions toRickettsia typhiin patients with Japanese spotted fever and found that approximately 20% of cases were positive. Comparison of antibody titers revealed the difficulty in identifying some positive cases. The frequency of misclassification in serodiagnosis was found to be limited.
Single-cell analysis reveals inter- and intratumour heterogeneity in metastatic breast cancer
Authors: Hamelin Baptiste , Obradović Milan , Sethi Atul , Kloc Michal , Muenst Simone , Beisel Christian , Eschbach Katja , Kohler Hubertus , Soysal Savas , Vetter Marcus , Weber Walter P. , Stadler Michael B. , Bentires-Alj Mohamed 
Published: October 2022

AbstractMetastasis is the leading cause of cancer-related deaths of breast cancer patients. Some cancer cells in a tumour go through successive steps, referred to as the metastatic cascade, and give rise to metastases at a distant site. We know that the plasticity and heterogeneity of cancer cells play critical roles in metastasis but the precise underlying molecular mechanisms remain elusive. Here we aimed to identify molecular mechanisms of metastasis during colonization, one of the most important yet poorly understood steps of the cascade. We performed single-cell RNA-Seq (scRNA-Seq) on tumours and matched lung macrometastases of patient-derived xenografts of breast cancer. After correcting for confounding factors such as the cell cycle and the percentage of detected genes (PDG), we identified cells in three states in both tumours and metastases. Gene-set Enrichment Analysis revealed biological processes specific to proliferation and invasion in two states. Our findings suggest that these states are a balance between epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial transitions (MET) traits that results in so-called partial EMT phenotypes. Analysis of the top Differentially Expressed Genes (DEGs) between these cell states revealed a common set of partial EMT Transcriptions Factors (TFs) controlling gene expression, including ZNF750, OVOL2, TP63, TFAP2C and HEY2. Our data suggest that the TFs related to EMT delineate different cell states in tumours and metastases. The results highlight the marked interpatient heterogeneity of breast cancer but identify common features of single cells from five models of metastatic breast cancer.
Spatiotemporal dynamics of RAD51C between the Golgi and nucleus regulates homologous recombination and genomic stability
Authors: Galea George , Kuodyte Karolina , Khan Muzamil M. , Thul Peter , Neumann Beate , Lundberg Emma , Pepperkok Rainer 
Published: October 2022

AbstractIntra-organelle communication is essential for cellular homeostasis, but the coordination between nuclear processes and cytoplasmic compartments remains poorly understood. Here, we uncover a novel spatiotemporal regulatory pathway linking the Golgi complex to the nucleus upon DNA damage. We show key DNA repair proteins, including RAD51C, dynamically shuttle between these organelles in response to distinct types of DNA damage. Mechanistic analysis reveals that RAD51C is anchored at the Golgi by Giantin. Disrupting this interaction leads to premature RAD51C nuclear localization, impaired homologous recombination signaling, genomic instability, and increased cell proliferation. Our findings establish Golgi-nuclear communication as a critical regulator of DNA repair, offering new insights into genomic integrity maintenance with profound implications for cancer and aging-related genomic instability.
Metabolic clogging of mannose triggers genomic instability via dNTP loss in human cancer cells
Authors: Harada Yoichiro , Mizote Yu , Suzuki Takehiro , Nishida Mikako , Hiratsuka Toru , Ueda Ayaka , Imagawa Yusuke , Maeda Kento , Ohkawa Yuki , Murai Junko , Freeze Hudson H. , Miyoshi Eiji , Higashiyama Shigeki , Udono Heiichiro , Dohmae Naoshi , Tahara Hideaki , Taniguchi Naoyuki 
Published: October 2022

AbstractMannose has anti-cancer activity that inhibits cell proliferation and enhances the efficacy of chemotherapy. How mannose exerts its anti-cancer activity, however, remains poorly understood. Here, using genetically engineered human cancer cells that permit the precise control of mannose metabolic flux, we demonstrate that the large influx of mannose exceeding its metabolic capacity induced metabolic remodeling, leading to the generation of slow-cycling cells with limited deoxyribonucleoside triphosphates (dNTPs). This metabolic remodeling impaired dormant origin firing required to rescue stalled forks by cisplatin, thus exacerbating replication stress. Importantly, pharmacological inhibition ofde novodNTP biosynthesis was sufficient to retard cell cycle progression, sensitize cells to cisplatin, and inhibit dormant origin firing, suggesting dNTP loss-induced genomic instability as a central mechanism for the anti-cancer activity of mannose.
Drivers of mentoring practices in construction related firms: Nigerian quantity surveying firms' perspective
Authors: Otasowie Osamudiamen Kenneth , Oke Ayodeji Emmanuel 
Published: October 2022

PurposeThe paper assessed the required drivers of mentoring practices in construction-related firms: a perspective of the quantity surveying (QS) firms in Nigeria with a view to providing possible drivers for effective mentoring relationships in the respective construction firms.Design/methodology/approachSurvey design was used to assess the level of knowledge, mentoring concept adoption and the required drivers of mentoring relationships in construction-related firms. QS firms in Abuja, Nigeria were sampled through the use of semi-structured questionnaires. A total of 149 questionnaires were administered to principal partners, partners, senior quantity surveyors and quantity surveyors in QS firms in Abuja through personal delivery. A total of 142 of them were returned and found suitable for analysis, representing 95.30% effective response rate. Percentage, mean, Kruskal–Wallis and factor analyses were utilized for the analysis of the data.FindingsThe study revealed an appreciable knowledge of mentoring concept but not so much with the adoption in the respective firms. This connotes that there is a problem with the adoption of mentoring concept in construction-related firms despite knowledge of the concept. Also revealed by the study, are the required drivers of mentoring practices in construction-related firms.Practical implicationsThe findings show the required drivers of mentoring practices in construction-related firms and the recommendations to further the adoption and implementation of these drivers to ensure mentoring practices thrive in construction-related firms in the country.Originality/valueThis paper reveals the required drivers of mentoring practices in Nigerian construction-related firms and provides ways through which the drivers can be implemented in the construction firms.
Eco-friendly and controlled anti-pilling finishing of wool fabric by thiourea dioxide-mediated surface micro-dissolution
Authors: Zhang Ning , Zhang Nan , Zhang Jinfang , Wang Qiang , Zhou Man , Wang Ping , Yu Yuanyuan 
Published: October 2022

PurposeWool, mainly composed of keratin, is a relatively high-grade clothing material. Although woollen textile has the advantages of high wearing comfort and excellent warmth retention property as we have known, its inherent disadvantage of easy pilling has easy puzzled people for a long time. Most of the existing technologies for pilling resistance are not eco-friendly or severely damaged the internal structure of wool.Design/methodology/approachIn this work, a controlled and effective surface treatment method was proposed to controllable micro-dissolution the scale layers of wool with minor damage to its internal structure, thereby improving the anti-pilling property of wool. Thiourea dioxide (TD) is used as a dissolving agent to swell and dissolve wool surface flakes. After TD treatment, the morphology changes of wool fibers were observed by scanning electron microscope (SEM) and methylene blue staining. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) were used to characterize the structural changes of TD wool. At the same time, the anti-pilling properties and wettability of wool fabrics were tested.FindingsThe results show that the wool scale layer is destroyed after TD treatment, which reduces the friction between fibers and improves the anti-pilling performance of wool fabrics. The methylene blue-stained images further demonstrate that low concentrations of TD can damage the superficial scale layer of wool without significant loss of strength.Originality/valueThis method is simple, eco-friendly and economical, and opens up a new direction for the surface treatment of wool fabrics.
Open innovation pathway to firm performance: the role of dynamic marketing capability in Malaysian entrepreneurial firms
Authors: Mostafiz Md Imtiaz , Ahmed Farhad Uddin , Hughes Paul 
Published: October 2022

PurposeThis study investigates how firms build strong dynamic marketing capability (DMC) from open innovation (OI) to enhance the performance of entrepreneurial firms. Moreover, this study unfolds DMC's mediating and moderating mechanisms underlying inbound and outbound OI and performance relationships, respectively.Design/methodology/approachTo test the research model and hypotheses, this study drew a sample of 251 firms operating in Malaysia using the time-lagged survey method. Structural equation modelling was used in this study to investigate the model relationships.FindingsThe findings of this study reveal the positive interplay between inbound OI (knowledge acquisition) and DMC. The outbound OI (knowledge exploitation) in this study is found to mediate the relationship between inbound OI and firm performance. In addition, while the DMC has a mediating effect in the relationship between inbound OI and firm performance, such a capability reinforces the positive relationship between outbound OI and performance.Originality/valueThis study provides a noble insight into the complex interplay between OI and entrepreneurial firms' performance by developing and testing an integrated framework underpinned by a knowledge-based view and dynamic capability theory. The findings highlight the significance of taking an interdisciplinary and integrated approach to better understand the determinants of entrepreneurial firms' performance in an emerging country context.
Competing through international accreditation: cost-benefit analysis and process of AACSB for a business school in Japan
Authors: Ito Hiroshi 
Published: October 2022

PurposeThe current article aims to answer the following research questions: (1) What types of business schools should pursue the Association to Advance Collegiate Schools of Business (AACSB)? and (2) What types of strategic leadership would be necessary for that?Design/methodology/approachA case study approach with archival research and interviews is employed.FindingsThe findings suggest that regional, teaching-oriented business schools at the graduate level with dominance-transformative leaders should consider acquiring AACSB accreditation due to its potential benefits, the most pronounced being an increase in the number of graduate students. Other advantages include improvements in the quality of schools' strategic planning, faculty qualifications, intellectual research contributions and assurance of learning, as well as branding.Research limitations/implicationsGiven its qualitative nature as a single case study with a small sample size, the findings may not be statistically generalizable. Future research could employ multiple case studies to examine several accredited schools, utilizing larger sample sizes to obtain more detailed results about the AACSB acquisition process, as well as the potential benefits and costs of AACSB.Originality/valueFew studies have examined the processes and impacts of acquiring AACSB accreditation, or the associated barriers in the context of an individual, international accreditation-seeking business school, in particular those that are small and regional. Likewise, few studies have addressed management leadership issues in acquiring AACSB accreditation. Our research addressed these research gaps by describing the processes, impacts and issues associated with acquiring AACSB from the perspective of a regional, teaching-oriented institute. Further, the study helped identify kinds of leadership appropriate for the acquisition of AACSB.
The coordination of technology development for complex products and systems innovations
Authors: França José Adalberto , Lakemond Nicolette , Holmberg Gunnar 
Published: October 2022

Purpose
The purpose of this paper is to explore earlier stages of complex products and systems (CoPS) innovations, investigating how technology development can be coordinated.

Design/methodology/approach
This paper uses a case study methodology, adopting an abductive logic, characterized by a nonlinear and iterative process of systematic confrontations between theoretical framework, empirical fieldwork and case analysis. Specifically, the authors study the Swedish aerospace network, which distinctly represents the CoPS characteristics of intense technology development with long-term goals and project-based activities with universities, research institutes, small medium enterprises and leading firms.

Findings
By adding the network perspective in the CoPS literature, the authors found that technology development can be coordinated within the technological and the business dimensions and according to different strategic nets. Also, the authors found that strategic nets co-evolve when their related projects are connected and advance in maturity, and their actors change their network position.

Originality/value
Current research on CoPS often recognizes that the survival and growth of a firm depend on its ability to coordinate innovative projects that are usually implemented during technology development. The findings contribute to this literature by showing how such projects can be implemented through agenda construction and the simultaneous coordination of strategic nets, leading to the synchronization of resources and activities. As such, this study’s framework offers a novel and integrative view of how the short-run and long-run strategies of leading firms can be aligned, and how other actors can contribute to the direction of the innovation path.