bluuebunny/crossref_metadata_2025_split huggingface dataset:
Task-Evoked Functional Connectivity Does Not Explain Functional Connectivity Differences Between Rest and Task Conditions
Authors: Lynch Lauren K. , Lu Kun-Han , Wen Haiguang , Zhang Yizhen , Saykin Andrew J. , Liu Zhongming 
Published: January 2018

AbstractDuring complex tasks, patterns of functional connectivity (FC) differ from those in the resting state. What accounts for such differences remains unclear. Brain activity during a task reflects an unknown mixture of spontaneous activity and task-evoked responses. The difference in FC between a task state and resting state may reflect not only task-evoked connectivity, but also changes in spontaneously emerging networks. Here, we characterized the difference in apparent functional connectivity between the resting state and when human subjects were watching a naturalistic movie. Such differences were marginally (3-15%) explained by the task-evoked networks directly involved in processing the movie content, but mostly attributable to changes in spontaneous networks driven by ongoing activity during the task. The execution of the task reduced the correlations in ongoing activity among different cortical networks, especially between the visual and non-visual sensory cortices. Our results suggest that the interaction between spontaneous and task-evoked activities is not mutually independent or linearly additive, and that engaging in a task may suppress ongoing activity.
Highly efficient chondrogenic differentiation of human iPSCs and purification via a reporter allele generated by CRISPR-Cas9 genome editing
Authors: Adkar Shaunak S. , Wu Chia-Lung , Willard Vincent P. , Dicks Amanda , Ettyreddy Adarsh , Steward Nancy , Bhutani Nidhi , Gersbach Charles A. , Guilak Farshid 
Published: January 2018

SummaryThe differentiation of human induced pluripotent stem cells (hiPSCs) to prescribed cell fates enables the engineering of patient-specific tissue types, such as hyaline cartilage, for applications in regenerative medicine, disease modeling, and drug screening. In many cases, however, these differentiation approaches are poorly controlled and generate heterogeneous cell populations. Here we demonstrate robust cartilaginous matrix production in three unique hiPSC lines using a highly efficient and reproducible differentiation protocol. To purify chondroprogenitors produced by this protocol, we engineered a COL2A1-GFP knock-in reporter hiPSC line by CRISPR-Cas9 genome editing. Purified chondroprogenitors demonstrated an improved chondrogenic capacity compared to unselected populations. The ability to enrich for chrondroprogenitors and generate homogenous matrix without contaminating cell types will be essential for regenerative and disease modeling applications.
Electron Paramagnetic Resonance Investigation of Nitrite Binding in Myoglobin
Authors: Bawn Matthew , MacMillan Fraser 
Published: January 2018

ABSTRACTIt has been proposed that myoglobin (Mb) may act as a nitrite reductase under hypoxic conditions. Any mechanism describing such activity should take into account the binding geometry of the ligand to the heme. Crystal structures of horse-heart Mb and human hemoglobin-nitrite complexes suggest that the anion adopts an uncommonO-nitrito binding mode. Electron Paramagnetic Resonance (EPR) spectroscopy was employed to investigate the nature of nitrite binding to Mb at pH values ranging from 6.5 to 10.8. Results suggest that for ferric Mb at low pH, nitrite binds in theO-bound nitrito mode resulting in a low-spin (LS) iron center. Further a high-spin (HS) iron center is observed at high pH in Mb-Nitrite with spectral values different to that of purely HS-Mb that is proposed to be due to anN-bound nitrite. The yields of these two species were found to be influenced by pH.BackgroundMyoglobin has been theorized to have a role as a nitrite reductase.ResultsO-bound nitrite produces a low-spin ferric heme complex, whilst at high pH a high-spin species is found proposed to be theN-bound form.ConclusionNitrite may bind to heme in myoglobin via N-nitro or O-nitrito mode.SignificanceThe mechanism of any nitrite reduction will depend on its binding to the heme cofactor.
Species richness, habitat association and odonata diversity of the south-western region of Bangladesh
Authors: Tuhin Sajjad Hossain , Khan Md Kawsar 
Published: January 2018

AbstractOdonata survey was conducted throughout the south-western region of Bangladesh, concentrated on eight districts and the Sundarban (the largest mangrove forest of the world) from August 2014 to August 2016. A total of 50 species under 30 genera belonging to six families were recorded during the study period. Among the 50 species, 31 species belong to Anisoptera whereas 19 species were recorded from the Zygoptera suborder. Libellulidae and Coenagrionidae were most dominant Anisoptetran and Zygopteran families with 28 and 17 species respectively. One Zygoptera speciesMortonagrion varalliwas newly added to the Odonata fauna of Bangladesh. Among surveyed habitats, species richness was highest in marshland with 38 species followed by 34 species in the lakeside. On the other hand, odonata diversity was lowest in the mangrove area. Our study shows a positive correlation between environmental variables (such as average rainfall, relative humidity, and average temperature) and species richness in the study area. Species richness is highest during monsoon and lowest in winter.
SlARF10, an auxin response factor, is required for chlorophyll and sugar accumulation during tomato fruit development
Authors: Mei Lihua , Yuan Yujin , Wu Mengbo , Gong Zehao , Zhang Qian , Yang Fengqing , Zhang Qiang , Luo Yingqing , Xu Xin , Zhang Wenfa , Miao Mingjun , Li Zhengguo , Deng Wei 
Published: January 2018

AbstractTomato green fruits photosynthesis contributes to fruit growth and carbon economy. Tomato auxin response factor 10 (SlARF10) is one of the members of ARF family. Our results showed that SlARF10 locates in the nucleus and has no transcriptional activity. SlARF10 was expressed in various tomato tissues, but highly expressed in green fruit. Up-regulation of SlARF10 produced dark green phenotype of fruits, whereas down-regulation of SlARF10 had light green phenotype. Autofluorescence and chlorophyll content analysis confirmed the phenotypes, which indicated that SlARF10 plays an important role in chlorophyll accumulation in tomato fruits. Up-regulation of SlARF10 increased the photochemical potential in tomato leaves and fruits. Furthermore, the SlARF10 up-regulating lines displayed improved accumulation of starch in fruits, whereas SlARF10 suppressed lines had inhibited starch accumulation. Up-regulation of SlARF10 increased the expression of AGPases, the starch biosynthesis genes. SlARF10 up-regulating lines had increased accumulation of SlGLK1 and SlGLK2 transcripts in fruits. The promoter sequence of SlGLK1 gene had two conserved ARF binding sites. SlARF10 may regulate the expression of SlGLK1, thus controlling chlorophyll accumulation, photosynthesis rates and sugars synthesis in fruits. Our study provided more insight on the link between auxin signaling, chloroplastic activity and sugar metabolism during the development of tomato fruits.AbbreviationsARFsAuxin Response FactorsRNAiRNA interferenceGLKGOLDEN2-LIKEDET1/hp2The DE-ETIOLATED 1DDB1UV-DAMAGED DNA-BINDING PROTEIN 1KNOXsClass I KNOTTED1-LIKE HOMEOBOXGC-MSGas Chromatography-Mass SpectrometryqRT-PCRQuantitative real time PCRTFsTranscription factorsWTWild-typeMRMiddle regionDB domainDNA binding domainCTDC-terminal interaction domainADTranscriptional activatorsRDTranscriptional repressorsB3N-terminal DNA-binding domainHighlightSlARF10 played an important role in the chlorophyll accumulation and photosynthesis in tomato fruits. SlARF10 was involved in starch accumulation by controlling the expression of starch synthesis related enzyme genes. SlARF10 may regulate the expression of SlGLK1, thus controlling chlorophyll accumulation, photosynthesis rates and sugars synthesis in tomato fruits.
Loss of E-cadherin enhances IGF1-IGF1R pathway activation and sensitizes breast cancers to anti-IGF1R inhibitors
Authors: Nagle Alison M. , Levine Kevin M. , Tasdemir Nilgun , Scott Julie A. , Burlbaugh Kara , Kehm Justin , Katz Tiffany A. , Boone David N. , Jacobsen Britta M. , Atkinson Jennifer M. , Oesterreich Steffi , Lee Adrian V. 
Published: January 2018

ABSTRACTPurposeInsulin-like growth factor I (IGF1) signaling regulates breast cancer initiation and progression and associated cancer phenotypes. We previously identified E-cadherin (CDH1) as a repressor of IGF1 signaling and in this study examined how loss of E-cadherin affects IGF1R signaling and response to anti-IGF1R therapies in breast cancer.Experimental DesignBreast cancer cell lines were used to assess how altered E-cadherin levels regulate IGF1R signaling and response to two anti-IGF1R therapies. In situ proximity ligation assay (PLA) was used to define interaction between IGF1R and E-cadherin. TCGA RNA-seq and RPPA data was used to compare IGF1R activation in estrogen receptor positive (ER+) invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) tumors. ER+ ILC cell lines and xenograft tumor explant cultures were used to evaluate efficacy to IGF1R pathway inhibition in combination with endocrine therapy.ResultsDiminished functional E-cadherin increased both activation of IGF1R signaling and efficacy to anti-IGF1R therapies. PLA demonstrated a direct endogenous interaction between IGF1R and E-cadherin at points of cell-cell contact. Increased expression of IGF1 ligand and levels of IGF1R phosphorylation were observed in E-cadherin deficient ER+ ILC compared to IDC tumors. IGF1R pathway inhibitors were effective in inhibiting growth in ER+ ILC cell lines and synergized with endocrine therapy and similarly IGF1R inhibition reduced proliferation in ILC tumor explant culture.ConclusionsWe provide evidence that loss of E-cadherin hyperactivates the IGF1R pathway and increases sensitivity to IGF1R targeted therapy, thus identifying the IGF1R pathway as a potential novel target in E-cadherin deficient breast cancers.STATEMENT OF SIGNIFICANCEIGF1R signaling is an attractive therapeutic target in breast cancer due to its regulation of proliferation, migration, and invasion. However, clinical trials targeting IGF1R have largely been unsuccessful due to lack of biomarkers to stratify patients for therapeutic response. In this study, we demonstrate loss of E-cadherin as a potential biomarker for response to anti-IGF1R therapy, and show efficacy of IGF1R inhibition in ER+ ILC in combination with endocrine therapy. Patients with ER+ ILC have poorer long-term outcomes than patients with ER+ IDC and have a propensity for increased late recurrences, highlighting the need for improved therapeutic strategies for this subtype of breast cancer. Here, we credential IGF1R inhibition as a novel therapeutic strategy in combination with endocrine therapy for the treatment of ER+ ILC.
Gene Expression-Based Drug Repurposing to Target Ageing
Authors: Dönertaş Handan Melike , Valenzuela Matías Fuentealba , Partridge Linda , Thornton Janet M. 
Published: January 2018

SummaryAgeing is the largest risk factor for a variety of non-communicable diseases. Model organism studies have shown that genetic and chemical perturbations can extend both life- and health-span. Ageing is a complex process, with parallel and interacting mechanisms contributing to its aetiology, posing a challenge for the discovery of new pharmacological candidates to ameliorate its effects. In this study, instead of a target-centric approach, we adopt a systems level drug repurposing methodology to discover drugs that could combat ageing in human brain. Using multiple gene expression datasets from brain tissue, taken from patients of different ages, we first identified the expression changes that characterise ageing. Then, we compared these changes in gene expression with drug perturbed expression profiles in the Connectivity Map. We thus identified 24 drugs with significantly associated changes. Some of these drugs may function as anti-ageing drugs by reversing the detrimental changes that occur during ageing, others by mimicking the cellular defense mechanisms. The drugs that we identified included significant number of already identified pro-longevity drugs, indicating that the method can discover de novo drugs that meliorate ageing. The approach has the advantages that, by using data from human brain ageing data it focuses on processes relevant in human ageing and that it is unbiased, making it possible to discover new targets for ageing studies.
Role of IQGAP1 in Head and Neck Carcinogenesis
Authors: Wei Tao , Choi Suyong , Buehler Darya , Rapraeger Alan C. , Anderson Richard A. , Lambert Paul F. 
Published: January 2018

ABSTRACTHead and neck squamous cell carcinoma (HNSCC) is a common cancer in humans. Phosphoinositide 3-kinase (PI3K)/AKT signaling, along with its downstream effector mTOR, is one of the most frequently altered pathways in HNSCC, and is downstream of growth factor signaling including that mediated by epidermal growth factor receptor (EGFR), which is also commonly upregulated in HNSCC. Recently, IQ motif-containing GTPase activation protein 1 (IQGAP1) has been reported to function as a scaffold for the enzymes involved in the PI3K/AKT signaling pathway. Iqgap1 gene expression is increased in human HNSCCs, raising the hypothesis that it acts as an oncogene in this cancer. Whether IQGAP1 is necessary for HNSCC development as well as what is its underlying mechanism are both unknown. Here we report on the role of IQGAP1 in HNSCC by performing a combination of in vitro studies using human cancer cell lines, and in vivo studies using a well-validated preclinical mouse model for HNSCC that is known to depend upon EGFR signaling. Cells knocked out for IQGAP1 lost AKT signaling. Disruption of IQGAP1-scaffolded PI3K/AKT signaling using a peptide that interferes with the ability of IQGAP1 to bind to PI3K reduced HNSCC cell survival. In vivo studies utilizing Iqgap1-null (Iqgap1-/-) mice demonstrated that IQGAP1 is necessary for efficient PI3K signaling upon EGF-stimulation. Treatment of Iqgap1-/- mice with the oral carcinogen, 4-nitroquinoline 1-oxide (4NQO), Iqgap1-/- led to significantly lower multiplicities of cancer foci as well as significantly lower numbers of high grade cancers than observed in similarly treated Iqgap1+/+ mice. IQGAP1 protein was increased in its expression in HNSCCs arising in the Iqgap1+/+ mice, consistent with that seen in human HNSCCs. We also observed a significant down-regulation of PI3K signaling in 4NQO-induced HNSCCs arising in the Iqgap1-/- mice, consistent with IQGAP1 contributing to carcinogenesis by promoting PI3K signaling. Our studies, therefore, support the hypothesis that IQGAP1 acts as an oncogene in head and neck carcinogenesis, and provide mechanistic insight into its role.
Knowledge exchange and management research: barriers and potentials
Authors: Bager Torben 
Published: January 2018

Purpose
The growing involvement of management researchers in knowledge exchange activities and collaborative research does not seem to be reflected in a growing academic output. The purpose of this paper is to explore barriers for the limited academic output from these activities as well as the potential for ‘interesting’ papers.

Design/methodology/approach
The paper uses secondary data and statistics as well as an illustrative case study to trace knowledge exchange activities and barriers for academic output based on these activities.

Findings
The paper identifies a number of barriers for the turning of data derived from knowledge exchange activities into academic papers such as low priority of case study research in leading management journals, a growing practice orientation in the research funding systems, methodological challenges because of limited researcher control and disincentives for researcher involvement in knowledge exchange activities. The paper also identifies a potential for ‘interesting’ research and discoveries through collaborative research.

Research limitations/implications
Diminishing the barriers for collaborative and case-based research and exploring the potential for ‘interesting’ discoveries has the potential to increase the number of published papers with a high level of scientific rigor as well as a high level of relevance for practice.

Originality/value
An outcome focus on the relationship between knowledge exchange activities and management research is to the author’s knowledge new in the debate about weak practical relevance of management research.
Bridging the relevance-ranking chasm: mission impossible?
Authors: Zolkiewski Judy 
Published: January 2018

Purpose
This paper aims to debate the challenges related to balancing relevance and ranking in management research.

Design/methodology/approach
This is a commentary on and review of challenges faced by twenty-first century management academics.

Findings
There is a chasm between managerial relevance and current managerial research; however, with academic buy-in, there are ways in which the chasm can be crossed.

Research limitations/implications
The implications of this are wide reaching for management researchers. They are challenged to consider different methodologies, strategies and dissemination avenues for their research.

Practical implications
Researchers need to consider not only collaboration with practitioners, as they pursue solutions to managerial problems, but also more inter-disciplinary research that addresses the wicked problems of management in practice.

Social implications
Solving the challenge of managerial relevance of business research has the potential to allow the contribution of business academia to be fully appreciated by practitioners.

Originality/value
The value of this thought-piece is that it challenges business and management academics to challenge the status quo and fight to make their research relevant to and valued by the business world.
Questionable research practices in academia: antecedents and consequences
Authors: Grant David B. , Kovács Gyöngyi , Spens Karen 
Published: January 2018

Purpose
The purpose of this paper is to discuss questionable research practices (QRPs) in business research, particularly in the logistics and supply chain management discipline, in light of antecedents influenced by the current academic environment and the consequences for academic rigour and relevance to stimulate thinking and debate among the academic community.

Design/methodology/approach
A literature review and autoethnographic approach were used to examine these issues based on over 60 years’ collective academic experience of the authors. Data were collected from discussions among the paper’s authors as well as recounting open discussions with other academics and journal editors to collate their observations.

Findings
Evidence is provided of issues the authors have seen first-hand where antecedents in the academic environment influences QRPs, which then detrimentally affect research rigour and relevance, integrity and proper contributions to ground-breaking research and knowledge advancement.

Research limitations/implications
This paper is based on personal observations and experiences of the three authors as well as open-ended discussions with others in the academic community. Suggestions are provided for various academic stakeholders to address these issues.

Practical implications
Practical implications are only provided for academics in their roles as authors, journal editors and reviewers.

Social implications
Encouraging the academic community to eliminate QRPs to improve the rigour, relevance and quality of research will provide more credibility and integrity resulting in better impact and outcomes for society at large.

Originality/value
The value of this paper is in stimulating thinking and debate among academics to return to core issues and values in academia opposed to focusing on narrow university goals focussed on other antecedents of QRPs.
Smart tourism destination triggers consumer experience: the case of Porto
Authors: Liberato Pedro , Alen Elisa , Liberato Dalia 
Published: January 2018

Purpose
The purpose of this paper is to emphasize the increasing importance of information and communication technologies (ICTs) in smart tourism destinations, in their integration in the activity of the tourism companies, and in their interaction with visitors/tourists. In summary, it is intended to evaluate in the city of Porto how the use of technology before, during and after the visit influences the tourist experience.

Design/methodology/approach
The authors empirically investigate the importance of using ICTs during tourism experience, assess the access/availability of ICT at the destination and its importance in tourist’s decisions. It is analyzed if the applications and/or information available on the internet are important and positively influence the tourism experience in Porto, that is, the degree of tourist satisfaction. The empirical evidence is based on a quantitative analysis, using a data set involving 423 tourists in the city of Porto.

Findings
The importance of the internet access at the destination, especially in places like airports and hotels, since most tourists are primarily using their mobile devices and computers during the trip, and the existing information technologies available in the destination (internet, smartphones or other mobile devices and applications) are considered very important in explaining tourists’ experience.

Originality/value
This study identifies the strengths and weaknesses of the technological strategies, providing useful information for destination management, discussing innovation in tourism, and proposing a framework that empirically evaluates how technological components used in smart tourism destinations can improve tourists’ experiences.