bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent MEK/ERK and AMPK signaling dictate lipogenic plasticity and dependence on fatty acid synthesis in Glioblastoma
Authors: Eyme Katharina M. , Sammarco Alessandro , Jha Roshani , Mnatsakanyan Hayk , Neustadt Rudolph , Moses Charlotte , Alnasser Ahmad , Tardiff Daniel , Su Baolong , Williams Kevin J , Bensinger Steven J. , Chung Chee Yeun , Badr Christian E. 
Published: April 2022

AbstractDeregulated de novo lipid synthesis (DNLS) is a potential druggable vulnerability in Glioblastoma (GBM), a highly lethal and incurable cancer. Yet the molecular mechanisms that determine susceptibility to DNLS-targeted therapies remain unknown, and the lack of brain-penetrant inhibitors of DNLS has prevented their clinical evaluation as GBM therapeutics. Here, we report that YTX-7739, a clinical-stage, brain-penetrant inhibitor of stearoyl CoA desaturase (SCD), triggers lipotoxicity in patient-derived GBM stem-like cells (GSCs) and inhibits fatty acid desaturation in GSCs orthotopically implanted in mice. When administered as a single agent, or particularly in combination with the first line GBM chemotherapy, Temozolomide (TMZ), YTX-7739 showed therapeutic efficacy in orthotopic GSC mouse models owing to its lipotoxicity and its ability to impair DNA damage repair. Leveraging genetic, pharmacological, and physiological manipulation of key signaling nodes in gliomagenesis, we uncover that aberrant MEK/ERK signaling and its repression of the energy sensor AMP-activated protein kinase (AMPK) primarily drives therapeutic vulnerability to SCD and other DNLS inhibitors. Conversely, AMPK activation mitigates lipotoxicity and renders GSCs impervious to the loss of DNLS, both in culture and in vivo, by decreasing the saturation state of phospholipids and diverting toxic lipids into lipid droplets. Altogether, our findings reveal mechanisms of metabolic plasticity in GSCs and provide a framework for rational integration of DNLS-targeted therapies for the treatment of GBM.
Intestinal microbiota dysbiosis and liver metabolomic changes during brain death
Authors: Tao R. , Guo W. , Li T. , Wang Y. , Wang P. 
Published: April 2022

ABSTRACTBackgroundThe causative link between brain death and intestinal microbiota dysbiosis is unclear, and the distortion in liver metabolism caused by brain death requires further exploration.Material and MethodsA rat model of brain death was constructed and sustained for 9 hours. Intestinal contents and portal vein plasma were collected for microbiota sequencing and microbial metabolite detection. Liver tissue was resected to investigate metabolic alterations, and the results were compared with those of a sham group.ResultsMicrobiota dysbiosis occurred at the family and genus levels after 9 hours of brain death. Microbial metabolites remained unchanged in both the intestinal contents and portal vein plasma. Liver metabolic function deteriorated, and the levels of 80% of the differential metabolites decreased in the brain-dead rats. Most of the differential metabolites were related to energy metabolism.ConclusionsBrain death resulted in microbiota dysbiosis in rats; however, this dysbiosis did not alter microbial metabolites. Deterioration in liver metabolic function during extended periods of brain death may reflect a continuous worsening in energy deficiency.
The concordance of signals based on irregular incremental lines in the human tooth cementum with documented pregnancies: Results from a systematic approach
Authors: Mani-Caplazi Gabriela , Vach Werner , Wittwer-Backofen Ursula , Hotz Gerhard 
Published: April 2022

ABSTRACTBackground and ObjectiveThere is evidence from previous studies that pregnancies and diseases are recorded in the tooth cementum. This study aims to assess the degree of concordance between signals based on irregular incremental lines (ILs) and reported pregnancies.Material and Methods23 recent and 24 archaeological human teeth with known birth history were included in this investigation. 129 histological sections of tooth roots were assessed for irregularities in appearance and width using a standardized protocol. Similarity of observed irregularities at the section level allowed us to define signals at the tooth level. The sensitivity of signals to detect pregnancies was determined and related to the signal prevalence.ResultsPregnancy signals were frequently visually observed. However, applying a standardized process we could only reach signal sensitivities to identify pregnancies up to 20 percentage points above chance level.ConclusionsBased on a standardized and reproducible method it could be confirmed that some pregnancies leave visible signals in the tooth cementum. The results show the potential of the tooth cementum to support reconstruction of life courses in paleopathology. However, it seems that not all pregnancies affect the cementogenesis in such a way that irregular ILs are identifiable. Further research is needed to better understand which type of pregnancies and other conditions are recorded in the tooth cementum.
A method for stabilising the XX karyotype in female mESC cultures
Authors: Keniry Andrew , Jansz Natasha , Hickey Peter F. , Breslin Kelsey A. , Iminitoff Megan , Beck Tamara , Ritchie Matthew E. , Blewitt Marnie E. 
Published: April 2022

AbstractFemale mouse embryonic stem cells (mESCs) present differently to male mESCs in several fundamental ways, however complications with their in vitro culture have resulted in an underrepresentation of female mESCs in the literature. Recent studies show that the second X chromosome in female, and more specifically the transcriptional activity from both of these chromosomes due to absent X chromosome inactivation, sets female mESCs apart from males. To avoid this undesirable state, female mESCs in culture preferentially adopt an XO karyotype, with this adaption leading to loss of their unique properties in favour of a state near indistinguishable from male. If female pluripotency is to be studied effectively in this system, it is critical that high quality cultures of XX mESCs are available. Here we report a method for better maintaining XX female mESCs in culture, which also stabilises the male karyotype, and makes study of female specific pluripotency more feasible.
Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas
Authors: Lee Sanghoon , Osmanbeyoglu Hatice Ulku 
Published: April 2022

AbstractBackgroundInvasive lobular breast carcinoma (ILC), the second most prevalent histological subtype of breast cancer, exhibits unique molecular features compared with the more common invasive ductal carcinoma (IDC). While genomic and transcriptomic features of ILC and IDC have been characterized, genome-wide chromatin accessibility pattern differences between ILC and IDC remain largely unexplored.MethodsHere, we characterized tumor-intrinsic chromatin accessibility differences between ILC and IDC using primary tumors from The Cancer Genome Atlas (TCGA) breast cancer assay for transposase-accessible chromatin with sequencing (ATAC-seq) dataset.ResultsWe identified distinct patterns of genome-wide chromatin accessibility in ILC and IDC. Inferred patient-specific transcription factor (TF) motif activities revealed regulatory differences between and within ILC and IDC tumors. EGR1, RUNX3, TP63, STAT6, SOX family, and TEAD family TFs were higher in ILC, while ATF4, PBX3, SPDEF, PITX family, and FOX family TFs were higher in IDC.ConclusionsThis study reveals the distinct epigenomic features of ILC and IDC and the active TFs driving cancer progression that may provide valuable information on patient prognosis.
DOT1L activity affects cell lineage progression in the developing brain by controlling metabolic programs
Authors: Appiah Bismark , Fullio Camilla L. , Haffner Christiane , Zeis Patrice , Treppner Martin , Bovio Patrick , Cheffer Arquimedes , Bertani Ilaria , Binder Harald , Grün Dominic , Kalebic Nereo , Taverna Elena , Vogel Tanja 
Published: April 2022

AbstractCortical neurogenesis depends on the tight balance between self-renewal and differentiation of apical progenitors (APs), the key progenitor type generating all other neural cells including neocortical neurons. We here report the activity of the histone methyltransferase DOT1L as a gatekeeper for AP cell identity. Combining lineage tracing with single-cell RNA sequencing of clonally related cells, we explore consequences of DOT1L inhibition on AP lineage progression during neurogenesis in the embryonic mouse neocortex. At the cellular level, DOT1L inhibition led to increased neurogenesis driven by a shift from asymmetric self-renewing to symmetric neurogenic divisions of APs. At the molecular level, we show that DOT1L activity preserved AP identity by promoting transcription of a gene set involved in AP metabolism. On a mechanistic level, DOT1L inhibition increased expression of metabolic genes, including microcephaly-associated Asparagine synthetase (Asns) and overexpression of ASNS in APs resulted in increased neuronal differentiation.Asnsexpression was predicted to be controlled through EZH2 and we show that DOT1L activity allows PRC2-mediated repression ofAsnsexpression. Importantly, inhibition of ASNS activity rescued increased AP differentiation upon DOT1L inhibition. Our data show that DOT1L activity/PRC2 crosstalk controls AP lineage progression by regulating AP metabolism, and they provide a mechanistic view on how DOT1L activity might affect neocortical neurogenesis.
Hydrogens and hydrogen-bond networks in macromolecular MicroED data
Authors: Clabbers Max T.B. , Martynowycz Michael W. , Hattne Johan , Gonen Tamir 
Published: April 2022

AbstractMicrocrystal electron diffraction (MicroED) is a powerful technique utilizing electron cryo-microscopy (cryo-EM) for protein structure determination of crystalline samples too small for X-ray crystallography. Electrons interact with the electrostatic potential of the sample, which means that scattered electrons carry informing about the charged state of atoms and can provide strong contrast for visualizing hydrogen atoms. Accurately identifying the positions of hydrogen atoms, and by extension the hydrogen bonding networks, is of importance for drug discovery and electron microscopy can enable such visualization. Using subatomic resolution MicroED data obtained from triclinic hen egg-white lysozyme, we identified hundreds of individual hydrogen atom positions and directly visualize hydrogen bonding interactions and the charged states of residues. Over a third of all hydrogen atoms are identified from strong difference peaks, the most complete view of a macromolecular hydrogen network visualized by electron diffraction to date. These results show that MicroED can provide accurate structural information on hydrogen atoms and non-covalent hydrogen bonding interactions in macromolecules. Furthermore, we find that the hydrogen bond lengths are more accurately described by the inter-nuclei distances than the centers of mass of the corresponding electron clouds. We anticipate that MicroED, coupled with ongoing advances in data collection and refinement, can open further avenues for structural biology by uncovering and understanding the hydrogen bonding interactions underlying protein structure and function.
Dictyostelium discoideum cells sense their local density and retain nutrients when the cells are about to overgrow their food source
Authors: Rijal Ramesh , Kirolos Sara A. , Rahman Ryan J. , Gomer Richard H. 
Published: April 2022

AbstractDictyostelium discoideum is a unicellular eukaryote that eats bacteria, and eventually overgrows the bacteria. D. discoideum cells accumulate extracellular polyphosphate (polyP), and the polyP concentration increases as the local cell density increases. At high cell densities, the correspondingly high extracellular polyP concentrations allow cells to sense that they are about to overgrow their food supply and starve, causing the D. discoideum cells to inhibt their proliferation. In this report, we show that high extracellular polyP inhibits exocytosis of undigested or partially digested nutrients. PolyP decreases cell membrane fluidity and plasma membrane recycling, and this requires the G protein-coupled polyP receptor GrlD, the polyphosphate kinase Ppk1, and the inositol hexakisphosphate kinase I6kA. PolyP did not affect random cell motility, cell speed, or F-actin levels. PolyP decreased membrane saturated fatty acids and altered lipid and protein contents in detergent-insoluble lipid microdomains. Together, these data suggest that D. discoideum cells use polyP as a signal to sense their local cell density and reduce cell membrane fluidity and membrane recycling, perhaps as a mechanism to retain ingested food when the cells are about to starve.
Analysis of the influence factors of VSC–HVDC on AC three-phase short-circuit current level
Authors: Zhao Jingbo , Tao Yan , Sun Zhiming 
Published: April 2022

Purpose
This paper aims to clarify voltage sourced converter’s (VSC’s) influence rules on the alternating current (AC) short-circuit current and identify the key factors, so as to propose the short-circuit current suppression strategy.

Design/methodology/approach
This paper investigates the key factors which impact the short-circuit current supplied by the VSC based on the equivalent current source model. This study shows that the phase of the VSC equivalent current source is mainly affected by the type of fault, whereas the amplitude is mainly decided by the control mode, the amplitude limiter and the electrical distance. Based on the above influence mechanism, the dynamic limiter with short-circuit current limiting function is designed. The theoretical analysis is verified by simulations on PSCAD.

Findings
The short-circuit current feeding from VSC is closely related to the control mode and control parameters of the VSC, fault type at AC side and the electrical distance of the fault point. The proposed dynamic limiter can make VSC absorb more reactive power to suppress the short-circuit current.

Research limitations/implications
The dynamic limiter proposed in this paper is limited to suppress three-phase short-circuit fault current. The future work will focus more on improving and extending the dynamic limiter to the fault current suppression application in other fault scenarios.

Practical implications
The research results provide a reference for the design of protection system.

Originality/value
The key influence factors are conducive to put forward the measures to suppress the fault current, eliminate the risk of short-circuit current exceeding the standard and reduce the difficulty of protection design.
Under domination of oil and gas: future scenarios of renewable energy development in Iran
Authors: Fartash Kiarash , Ghorbani Amir 
Published: April 2022

PurposeScenario planning is a useful approach that helps policymakers to better understand the complexity and uncertainties that lie in the future and to choose the right policy mix to support the development of renewable and affordable energy sources. In this regard, this paper aims to present renewable energy (RE) development scenarios in Iran in the horizon of 2030.Design/methodology/approachFollowing the intuitive logic school and the Global Business Network model, the authors identified seven driving forces, according to the expert’s judgment, by brainstorming techniques which influence REs development in the horizon of 2030. By prioritizing driving forces based on their importance and uncertainty, “sustainable and green economy” and “emerging technology development” are the most instrumental uncertainties and the authors formed a two-axis scenario matrix with each representing an axis.FindingsThe results suggest four main scenarios of “Transition to Sustainability with Green Gold,” “Towards Sustainability with Green Gold,” “Productivity with Black Gold” and “Desperation with Black Gold.” They include a wide range of possible situations of energy basket in the future ranging from dominance of fossil fuels to dominance of REs. The “Productivity with Black Gold” and the “Towards Sustainability with Green Gold” are the most probable scenarios of RE development by 2030 in Iran.Originality/valueThis paper indicates that the dominance of oil and gas resources would impede or at least slow down the development of renewable and affordable energy sources. Although the economic and environmental potentials and the inevitability of REs are well-understood, path dependence created by fossil fuels in Iran’s energy regime, either partially or fully, hinders the widespread development of REs which is the case in other resource-based countries as well.
A conceptualization of the privacy concerns of cloud users
Authors: Peras Dijana , Mekovec Renata 
Published: April 2022

Purpose
The purpose of this paper is to improve the understanding of cloud service users’ privacy concerns, which are anticipated to considerably hinder cloud service market growth. The researchers have explored privacy concerns from dimensions that were identified as relevant in the cloud context.

Design/methodology/approach
Content analysis was used to identify privacy problems that were most often raised in previous cloud research. Multidimensional developmental theory (MDT) was used to build a conceptual model of cloud privacy concerns. Literature review was made to identify the privacy-related constructs used to measure privacy concerns in previous cloud research.

Findings
The paper provides systematization of recent cloud privacy research, proposal of a conceptual model of cloud privacy concerns, identification of measuring instruments that were used to measure privacy concerns in previous cloud research and identification of categories of problems that need to be addressed in future cloud research.

Originality/value
This paper has identified the categories of privacy problems and dimensions that have not yet been measured in the cloud context, to the best of the authors’ knowledge. Their simultaneous examination could clarify the effects of different dimensions on the privacy concerns of cloud users. The conceptual model of cloud privacy concerns will allow cloud service providers to focus on key cloud problems affecting users’ privacy concerns and use the most appropriate privacy protection communication and preservation approaches.
Gatekeeper perceptions on adopting environmentally sound information and communication technology-enhanced live performances to improve the sustainability of music festivals
Authors: Bossey Adrian 
Published: April 2022

PurposeThe purpose of this paper is to consider perceptions of sustainability, information communication technologies (ICTs)-enhanced performances, authenticity, COVID-19 and performance futures in relation to digital content for use on-site and off-site at music festivals/events. It responds to the UN Sustainable Development Goal 9 – Industries, Innovation and Infrastructure. The research analyses existing literature to inform a dialogue among music festival organisers, consultants and performers. It addresses the thesis that: industry gatekeepers’ opinions on the authenticity of environmentally sound ICT-generated live content will influence its adoption at music festivals.Design/methodology/approachPrimary research was carried out using purposive sampling of 50 live music industry professionals to collect and interpret expert empirical evidence through informed narrative. Using a mixed-methods approach, respondents completed a structured e-mail questionnaire comprising closed questions, a five-point Likert scale and additional qualitative open questions.FindingsPredominantly positive quantitative responses relating to the live music industry's role in advocating sustainability contrasted with negative responses to virtual festivals. Responses adopting and rejecting environmentally sound ICT for live content were evident in qualitative results, with significant proportions of undecided or uncertain respondents. The prevalence of postponement and rejection responses around authenticity may prevent adoption at some music festivals.Research limitations/implicationsThe limitations of this research include the relatively small sample size and limited scope in terms of the artform.Originality/valueThe “snapshot” of digital aspects of sustainability at music festivals within this research is of particular value due to the paucity of research in this area, rapid change in virtual music festival provision prompted by COVID-19 and its narrative from varied industry professionals. The paper makes recommendations to artists, music festival organisers, consultants, academics and public funders to attempt to advance sustainability.
Drivers of showrooming behaviour: insights from integrated perspectives
Authors: Arora Sourabh , Sahney Sangeeta , Parida Rashmi Ranjan 
Published: April 2022

PurposeThe paper investigates shoppers' justification behind the showrooming behaviour and proposes an integrated SOR-MOA framework and a SAP-LAP model for a better understanding of the showrooming phenomenon.Design/methodology/approachThe study adopts a qualitative approach. A narrative-based examination followed by an inductive thematic analysis was employed to discover consumers' reasoning behind showrooming.FindingsThe results of the study affirmed the distinction between situational and intentional showrooming conduct. Situational factors have been classified across two categories: store-related (mismanagement at the store, assortment issues) and sales-personal related factors (disrespectful, rude, poor response and dishonest behaviour of the sales staff). However, factors corresponding to intentional showrooming conduct have been characterized as motivational (perceived value, past experience and perceived relative advantage), opportunity (retailer's support and services, channel availability and consumer empowerment) and ability (consumer skills)-related factors in aggregation with the stimulus organism response ideology. In addition, the study also highlights the consequences associated with the showrooming conduct of the shoppers.Research limitations/implicationsThe findings of the study need further exploration and examination through the adoption of a quantitative approach on a large sample size.Practical implicationsThe findings of the study can be utilized by offline retailers for devising strategies to counter showrooming customers and retain them as buyers.Originality/valueThe study emerges as the first piece of research to account for the ability and opportunity perspectives for better understanding of showrooming.