bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of leukemia-associated immunophenotypes by database-guided flow cytometry provides a highly sensitive and reproducible strategy for the study of measurable residual disease in acute myeloblastic leukemia
Authors: Pinero P , Morillas M , Gutiérrez N , Barragán E , Such E , Breña J , Gil C , García C , Botella C , Navajas JM , Zapater P , Montesinos P , Sempere A , Tarín F 
Published: July 2022

ABSTRACTBackgroundMultiparametric Flow Cytometry (MFC) is an essential tool to study the involved cell lineages, the aberrant differentiation/maturation patterns and the expression of aberrant antigens in acute myeloid leukemia (AML). The characterization of leukemia-associated immunophenotypes (LAIPs) at the moment of diagnosis is critical to establish reproducible strategies for the study of measurable residual disease using MFC (MFC-MRD).MethodsIn this study, we identified and characterized LAIPs by comparing the leukemic populations of 145 AML patients, using the EuroFlow AML/ MDS MFC panel, with 6 databases of normal myeloid progenitors (MPCs). Principal component analysis was used to identify and characterize the LAIPs, which were then used to generate individual profiles for MFC-MRD monitoring. Furthermore, we investigated the relationship between the expression patterns of LAIPs and the different subtypes of AML.The MFC-MRD study was performed by identifying residual AML populations that matched with the LAIPs at diagnosis. To further validate this approach, the presence of MRD was also assessed by qPCR (qPCR-MRD). Finally, we studied the association between MFC-MRD and progression-free survival (PFS).ResultsThe strategy used in this study allowed us to describe more than 300 different LAIPs and facilitated the association of specific phenotypes with certain subtypes of AML. The MFC-MRD monitoring based on LAIPs with good/strong specificity was applicable to virtually all patients and showed a good correlation with qPCR-MRD and PFS.ConclusionsThe described methodology provides an objective method to identify and characterize LAIPs. Furthermore, it provides a theoretical basis to develop highly sensitive MFC-MRD strategies.
Circadian regulation of hippocampal function is disrupted with chronic corticosteroid treatment
Authors: Birnie Matthew T. , Claydon Matthew D.B. , Flynn Benjamin P. , Yoshimura Mitsuhiro , Kershaw Yvonne M. , Demski-Allen Rebecca C.R. , Barker Gareth R.I. , Warburton E. Clea , Bortolotto Zuner A. , Lightman Stafford L. , Conway-Campbell Becky L. 
Published: July 2022

AbstractNeuropsychiatric disorders such as major depression and schizophrenia are highly prevalent and contribute substantially to disease burden worldwide. Despite this, progress understanding the pathophysiology has remained largely elusive, yet these disorders often exhibit a loss of regulation of biological rhythms, such as sleep/wake cycles and hormonal rhythms. Cushing’s disease, a condition characterized by chronic corticosteroid (cortisol) hypersecretion is associated with psychiatric and neurocognitive disorders and disruption to the circadian release of cortisol can result in depression and neurocognitive impairment. In rats, we report that circadian regulation of the hippocampal transcriptome integrates crucial functional networks that link corticosteroid-inducible gene regulation to synaptic plasticity regulation via an intra-hippocampal circadian transcriptional clock. During the early active period, when corticosteroid availability is high, CA1 region excitatory and inhibitory post-synaptic currents were augmented along with long-term potentiation. In contrast, chronic corticosteroid exposure disturbed hippocampal function. The hippocampal transcriptome, as well as circadian regulation of synaptic plasticity were ablated, resulting in memory loss during hippocampal-dependent behavior. These findings identify how exposure to elevated levels of corticosteroid, that is often seen in neuropsychiatric illness, results in adverse critical hippocampal function. These data provide novel insights into the molecular mechanisms of neurocognitive disorders and provides evidence for corticosteroid-mediated intervention in disabling mental illnesses.
Tex2 is required for lysosomal functions at TMEM55-dependent ER membrane contact sites
Authors: Du Yuanjiao , Chang Weiping , Deng Lin , Ji Wei-Ke 
Published: July 2022

ABSTRACTER tubules form and maintain membrane contact sites (MCSs) with late endosomes/lysosomes (LE/lys). The molecular composition and cellular functions of these MCSs are poorly understood. Here we find that Tex2, an SMP domain-containing lipid transfer protein conserved in metazoen and yeast, is a tubular ER protein, and enriches at ER-LE/lys MCSs dependent on TMEM55, phosphatases that convert PI(4,5)P2 to PI5P on LE/lys. We show that the Tex2-TMEM55 interaction occurs between a N-terminal region of Tex2 and a catalytic motif in PTase domain of TMEM55. The Tex2-TMEM55 interaction can be regulated by endosome-resident type 2 PI4K activities. Functionally, Tex2 knockout results in severe defects in lysosomal digestive capacity and blocked autophagic flow, as well as an aberrant accumulation of PI3P on the LE/lys membranes. These defects can be substantially rescued by wild type Tex2 other than a lipid transfer-defective Tex2 mutant, indicating an important role of lipid transfer in these processes. Together our data identify Tex2 as a tubular ER protein that resides at TMEM55-depedent ER-LE/lys MCSs required for lysosomal functions.
Neural Distinctiveness and Reinstatement of Hippocampal Representations Support Unitization for Associations
Authors: Ricupero S. , Carpenter C.M. , Steinkrauss A.C. , Gerver C.R. , Chamberlain J.D. , Monkman R.G. , Overman A.A. , Dennis N.A. 
Published: July 2022

AbstractThe medial temporal lobe (MTL) is critical to associative memory success. Yet not all types of associations may be processed in a similar manner within MTL subregions. In particular, work suggests that intra- and inter-item associations not only exhibit differences in overall rates of recollection, but also recruit different MTL subregions. Whereas intra-item associations, akin to unitization, take advantage of associations between within-item features, inter-item associations form links across discrete items. The current work aimed to examine the neural differences between these two types of associations using multivariate neural analyses. Specifically, the current study examined differences across face-occupation as a function of whether the pairing was viewed as a person performing the given job (intra-item binding) or a person saying that they knew someone who had a particular job (inter-item binding). The results show that at encoding, successfully recollected intra- and inter-item associations are discriminable from one another in the hippocampus, parahippocampal cortex, and perirhinal cortex. Additionally, the two trial types are reinstated distinctly such that inter-item trials have higher neural reinstatement from encoding to retrieval compared to intra-item trials in the hippocampus. We conclude that intra- and inter-associative pairs may utilize similar neural regions that represent patterns of activation differentially at encoding. However, in order to reinstate information to the same degree (i.e., subsequently successfully recollected) inter-item associations may act in a compensatory manner, while it is not necessary for intra-item associations to be reinstated to the same degree. This may indicate that intra-item associations promote more efficient reinstatement.
MukBEF-dependent chromosomal organization in widened Escherichia coli
Authors: Japaridze Aleksandre , van Wee Raman , Gogou Christos , Kerssemakers Jacob W. J. , Dekker Cees 
Published: July 2022

AbstractThe bacterial chromosome is spatially organized through protein-mediated compaction, supercoiling, and cell-boundary confinement. Structural Maintenance of Chromosomes (SMC) complexes are a major class of chromosome-organizing proteins present throughout all domains of life. Here, we study the role of the Escherichia coli SMC complex MukBEF in chromosome architecture and segregation. Using quantitative live-cell imaging of shape-manipulated cells, we show that MukBEF is crucial to preserve the toroidal topology of the E. coli chromosome and that it is non-uniformly distributed along the chromosome: it prefers locations towards the origin and away from the terminus of replication, and it is unevenly distributed over the origin of replication along the two chromosome arms. Using an ATP hydrolysis-deficient MukB mutant, we find that MukBEF translocation along the chromosome is ATP-dependent, in contrast to its loading onto DNA. MukBEF and MatP are furthermore found to be essential for sister chromosome decatenation. We propose a model that explains how MukBEF, MatP, and their interacting partners organize the chromosome and contribute to sister segregation and recombination. The combination of bacterial cell-shape modification and quantitative fluorescence microscopy paves way to investigating chromosome-organization factors in vivo.
Kindlin-2 inhibits TNF/NF-κB-caspase 8 pathway in hepatocytes to maintain liver development and function
Authors: Gao Huanqing , Zhong Yiming , Zhou Liang , Lin Sixiong , Hou Xiaoting , Ding Zhen , Li Yan , Yao Qing , Cao Huiling , Zou Xuenong , Chen Di , Bai Xiaochun , Xiao Guozhi 
Published: July 2022

AbstractInflammatory liver diseases are a major cause of morbidity and mortality worldwide; however, underlying mechanisms are incompletely understood. Here we show that deleting the focal adhesion protein Kindlin-2 in hepatocytes using the Alb-Cre transgenic mice causes a severe inflammation, resulting in premature death. Kindlin-2 loss accelerates hepatocyte apoptosis with subsequent compensatory cell proliferation and accumulation of the collagenous extracellular matrix, leading to massive liver fibrosis and dysfunction. Mechanistically, Kindlin-2 loss abnormally activates the tumor necrosis factor (TNF) pathway. Blocking activation of the TNF signaling pathway by deleting TNF receptor or deletion of caspase 8 expression in hepatocytes essentially restores liver function and prevents premature death caused by Kindlin-2 loss.Finally, of translational significance, adeno-associated virus mediated overexpression of Kindlin-2 in hepatocytes attenuates the D-galactosamine and lipopolysaccharide-induced liver injury and death in mice. Collectively, we establish that Kindlin-2 acts as a novel intrinsic inhibitor of the TNF pathway to maintain liver homeostasis and may define a useful therapeutic target for liver diseases.
Newborn chicks prefer stimuli that move against gravity
Authors: Bliss Larry , Vasas Vera , Freeland Laura , Roach Robyn , Ferrè Elisa Raffaella , Versace Elisabetta 
Published: July 2022

AbstractAt the beginning of life, inexperienced animals use evolutionary-given preferences (predispositions) to decide what stimuli attend and approach. Stimuli that contain cues of animacy, such as face-like stimuli, biological motion and changes in speed, are particularly attractive across vertebrate taxa. A strong cue of animacy is upward movement against terrestrial gravity, because only animate objects consistently move upward. To test whether upward movement is spontaneously considered attractive already at birth, we tested the early preferences of dark-hatched chicks (Gallus gallus) for upward vs downward moving visual stimuli. We found that, without any previous visual experience, chicks consistently exhibited a preference to approach upward moving stimuli, that move against gravity. A control experiment showed that these preferences are not driven by avoidance of downward stimuli. These results show that newborn animals are spontaneously attracted by upward movement, indicating that movement against gravity can be used as a cue of animacy to orient early approach responses in the absence of previous visual experience.
Gaps in megaproject management system literature: a systematic overview
Authors: Ashkanani Salman , Franzoi Robert 
Published: July 2022

PurposeThis paper aims to present a structured and comprehensive review of relevant works, collected through a systematic methodology and clustered into nine meaningful categories on megaproject management systems and the current requirements for improved industrial megaprojects.Design/methodology/approachThe methodology employed in this paper retrieves relevant works from available online citation indexes that are published in peer-reviewed journals and other reliable sources from 2000 to 2021.FindingsIt has been observed that the literature on megaproject management is still premature and requires further research to understand better the main gaps and effects of large-scale and typically complex megaprojects. Significant improvements are needed towards covering gaps to address the project management system holistically over the entire project life cycle. There are no clear guidelines for achieving a complete and conclusive project management system and enhancing future megaprojects' management capabilities.Originality/valueThis paper provides a clear picture of the existing literature on megaproject management systems, contributing insights for successful megaproject projects. Additionally, the holistic analysis identifies gaps in the body of knowledge, revealing avenues for future research.
Entrepreneurial mentoring, financial support and incubator patent licensing: evidence from Chinese incubators
Authors: Chang Yanru , Cheng Qiang 
Published: July 2022

PurposeBased on Chinese incubators as the research sample, this paper aims to examine whether and how incubators' entrepreneurial mentoring and financial support affect incubator patent licensing. Entrepreneurial mentoring functions through the buffering mechanism and financial support functions through the bridging and curating mechanisms.Design/methodology/approachA negative binomial model is used to empirically explain the relation between entrepreneurial mentoring or financial support and incubator patent licensing. In addition, a cross-sectional test is performed to explore whether province-level incubator support policies strengthen the effect of entrepreneurial mentoring and financial support on incubator patent licensing.FindingsThe results reveal that incubators' entrepreneurial mentoring positively affects patent licensing. In contrast, incubators' financial support has an inverted U-shaped relationship with patent licensing. In addition, the two relations are stronger when an incubator locates in a province with more incubator support policies.Originality/valueThe authors contribute to the literature on incubator performance by identifying an important but less discussed factor: entrepreneurial mentoring. Through the connection with mentors, tenants efficiently commercialize the value of their patents, facilitate patent licensing and expand the product market. Furthermore, the inverted U-shaped association between financial support and patent licensing shows that incubation support does not always have a linear effect on incubator patent licensing. Overall, this study provides evidence on the effect of incubator support on incubator patent licensing.
An analysis of climate change and health hazards: results from an international study
Authors: Leal Filho Walter , Ternova Linda , Fayyaz Muhammad Muddassir , Abubakar Ismaila Rimi , Kovaleva Marina , Donkor Felix Kwabena , Anuga Samuel Weniga , Matamanda Abraham R. , Djekic Ilija , Umar Ibrahim Abatcha , Olooto Felicia Motunrayo , Meirelles Maria , Nagy Gustavo J. , May Julia , May Marta , Ebhuoma Eromose , Begum Halima 
Published: July 2022

PurposeThe interconnections between climate change and health are well studied. However, there is a perceived need for studies that examine how responses to health hazards (e.g. cardiovascular diseases, ozone layer effects, allergens, mental health and vector-borne diseases) may assist in reducing their impacts. The purpose of this paper is to review the evidence on health responses to climate hazards and list some measures to address them.Design/methodology/approachA mixed literature review, bibliometric analysis and an original online survey were undertaken on 140 participants from 55 countries spread across all geographical regions.FindingsThe bibliometric analysis identified that most climate-related health hazards are associated with extreme weather events. However, only one-third of the investigated papers specifically analysed the connections between climate change and health hazards, revealing a thematic gap. Also, although Africa is highly affected by climate change, only 5% of the assessed studies focused on this continent. Many respondents to the survey indicated “heat distress” as a significant vulnerability. The survey also identified social determinants relevant to climate-induced health vulnerabilities, such as socioeconomic and environmental factors, infrastructure and pre-existing health conditions. Most respondents agree that policies and regulations are the most effective adaptation tools to address the public health hazards triggered by climate change. This paper presents some suggestions for optimising public health responses to health hazards associated with climate change, such as the inclusion of climate-related components in public health policies, setting up monitoring systems to assess the extent to which specific climate events may pose a health threat, establishing plans to cope with the health implications of heatwaves, increased measures to protect vulnerable groups and education and awareness-raising initiatives to reduce the overall vulnerability of the population to climate-related health hazards. These measures may assist the ongoing global efforts to understand better – and cope with – the impacts of climate change on health.Originality/valueThe combination of a literature review, bibliometric analysis and an original world survey identified and presented a wide range of responses.
Economic policy uncertainty and investment-cash flow sensitivity: evidence from India
Authors: Gupta Gaurav , Mahakud Jitendra , Singh Vishal Kumar 
Published: July 2022

PurposeThis study examines the impact of economic policy uncertainty (EPU) on the investment-cash flow sensitivity (ICFS) of Indian manufacturing firms.Design/methodology/approachThis study uses the fixed-effect method to investigate the effect of EPU on ICFS from 2004 to 2019.FindingsThis study finds that EPU increases ICFS, which is more (less) during the crisis (before and post-crisis) period. The authors also find that the effect of EPU on ICFS is more for smaller, younger and standalone (SA) firms than the larger, matured and business group affiliated (BGA) firms. This study also reveals that EPU reduces corporate investment (CI). Further, the authors find that cash flow is more significant for the investment of financially constrained firms and the negative effect of EPU is more for these firms.Research limitations/implicationsThis study considers the Indian manufacturing sector. Therefore, this study can be extended by analyzing the relationship between EPU and ICFS for the service sector.Practical implicationsFirst, this study can be useful for corporates, academicians and government bodies to understand the effect of EPU on ICFS and CI. Second, this study will help corporates to focus on internal funds to finance corporates' investment during the crisis period because EPU increases the cost of external finance which may increase ICFS and reduce CI. Third, lending agencies, investors and stakeholders should also focus on the firm's nature, ownership, size and age because these factors play a crucial role to reduce or increase the negative effect of EPU on ICFS. Fourth, the Government should make appropriate policy measures in terms of concessional interest rates to increase the easy availability of external finance for SA, small size, and young firms to reduce the negative effect of EPU on CI because these firms are considered as more financially constrained firms.Originality/valueThis study adds new inputs to the current literature of EPU in several ways. First, this study is one of the main studies focused on the relationship between EPU and ICFS (CI). Especially in emerging countries like India, examining this relationship extends previous research. Second, this study also examines the impact of EPU on ICFS for BGA, SA, small, large, matured and young firms as well as crisis and non-crisis periods. Third, this study uses the sample of the Indian manufacturing sector which has emerged the qualities to become a global manufacturing hub and attracting global investors. Therefore, examining the effect of EPU on ICFS for these firms will be more interesting.
Impact of merger on stock returns and economic value added (EVA) of the acquiring firms: a study from Indian corporate sector
Authors: Gulati Puja Aggarwal , Garg Sonia 
Published: July 2022

PurposeThis paper attempts to examine the impact of merger on the stock returns and economic value added (EVA) of acquiring firms to know if the mergers are successful corporate restructuring strategies for the firms.Design/methodology/approachIn total, 108 Indian firms are studied using paired sample t-test and Wilcoxon signed rank test for comparing the EVA of acquiring firms in short, medium and long term after merger. The effect of merger announcements on stock returns is analyzed by way of event study. An event window of −20 to +20 is taken and an estimation window of 256 (-276 -20) days is used in the study.FindingsThe authors find that mergers lead to significant improvement in the EVA of acquiring firms. However, the increase in financial performance and EVA is witnessed only in long term. The authors did not find any significant impact of merger announcement on the stock returns of acquiring firms.Originality/valueThe study is a first of study's kind, which evaluates both short-term (using event study methodology) and long-term (using EVA) impact of value addition to an acquirer after Merger & Acquisition (M&A). The study contributes to existing literature on the signaling theory of announcement of M&As and synergy gain theory of completed M&As by providing evidence from the context of an emerging market like India.