bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Multi-Omics Data Reveals the Molecular Subtypes of Prostate Cancer
Authors: Meng Jialin , Lu Xiaofan , Jin Chen , Zhou Yujie , Ge Qintao , Zhang Meng , Zhou Jun , Hao Zongyao , Yan Fangrong , Liang Chaozhao 
Published: June 2021

AbstractProstate cancer (PCa), the second most common male malignancy, is the fifth leading cause of cancer-related death and places notable burdens on medical resources. Most of the previous subtypes only focused on one or fewer types of data or ignored the genomic heterogeneity among PCa patients with diverse genetic backgrounds. Therefore, it is essential to precisely identify the specific molecular features and judge potential clinical outcomes based on multi-omics data. In the current study, we first identified the PCa multi-omics classification (PMOC) system based on the multi-omics, including mRNA, miRNA, lncRNA, DNA methylation, and gene mutation, using a total of ten state-of-the-art clustering algorithms. The PMOC1 subtype, also called the inflammatory subtype, contains the highest expression levels of immune checkpoint proteins, moderate activated immune-associated pathways. The PMOC2 tumor-activated subtype demonstrated the worst prognosis, which might be impacted by the activated cell cycle and DNA repair pathways, and also characterized by the most genetic alterations of mutant TP53, mutant APC and copy number alteration of 8q24.21 region. The PMOC3 subtype is likely to be a balance subtype, with the activated oncogenic signaling pathways, including hypoxia, angiogenesis, epithelial mesenchymal transition, and PI3K/AKT pathways. As well as with the activated proinflammatory pathways, including IL6/JAK/STAT3, IL2/STAT5, Notch and TNF-α signaling. Additionally, PMOC3 subtype also linked with the activation of the androgen response and the high response rate of ARSI treatment. Taken together, we defined the PMOC system for PCa patients via multi-omics data and consensus results of ten algorithms, this multi-omics consensus PCa molecular classification can further assist in the precise clinical treatment and development of targeted therapy.
Skeletal Muscle Histidine Containing Dipeptide Contents are Increased in Freshwater Turtles (Chrysemys picta bellii) with Cold-Acclimation
Authors: Dolan Eimear , Warren Daniel E. , Harris Roger C. , Sale Craig , Gualano Bruno , Saunders Bryan 
Published: June 2021

AbstractFreshwater turtles found in higher latitudes can experience extreme challenges to acid-base homeostasis while overwintering, due to a combination of cold temperatures along with the potential for environmental hypoxia. Histidine containing dipeptides (HCDs; carnosine, anserine and balenine) may facilitate pH regulation in response to these challenges, through their role as pH buffers. We measured the HCDs content of three tissues (liver, cardiac muscle and skeletal muscle) from the anoxia-tolerant painted turtle (Chrysemys picta bellii) acclimated to either 3 or 20°C. HCDs were detected in all tissues, with the highest content shown in the skeletal muscle. Turtles acclimated to 3°C had more HCD in their skeletal muscle than those acclimated to 20°C (carnosine = 20.8±4.5 vs 12.5±5.9 mmol·kg DM-1; ES = 1.59 (95%CI: 0.16 – 3.00), P = 0.013). The higher HCD content observed in the skeletal muscle of the cold-acclimated turtles suggests a role in acid-base regulation in response to physiological challenges associated with living in the cold, with the increase possibly related to the temperature sensitivity of carnosine’s dissociation constant and buffering power of the skeletal muscle during anoxic submergence.HighlightspH regulation is a major challenge for overwintering freshwater turtles.Histidine containing dipeptides are important intracellular buffers.Turtles acclimated to 3°C had higher HCD content than those at 20°C.HCDs may be important pH regulators in cold-acclimated turtles.
An olfactory pattern generator for on-demand combinatorial control of receptor activities
Authors: Si Guangwei , Baron Jacob , Feng Yu , Samuel Aravinthan D.T. 
Published: June 2021

ABSTRACTOlfactory systems employ combinatorial receptor codes for odors. Systematically generating stimuli that address the combinatorial possibilities of an olfactory code poses unique challenges. Here, we present a stimulus method to probe the combinatorial code, demonstrated using the Drosophila larva. This method leverages a set of primary odorants, each of which targets the activity of one olfactory receptor neuron (ORN) type at an optimal concentration. Our setup uses microfluidics to mix any combination of primary odorants on demand to activate any desired combination of ORNs. We use this olfactory pattern generator to demonstrate a spatially distributed olfactory representation in the dendrites of a single interneuron in the antennal lobe, the first olfactory neuropil of the larva. In the larval mushroom body, the next processing layer, we characterize diverse receptive fields of a population of Kenyon cells. The precision and flexibility of the olfactory pattern generator will facilitate systematic studies of processing and transformation of the olfactory code.
Role of the G-Protein Coupled Receptor 3-Salt Inducible Kinase 2 Pathway in Human β Cell Proliferation
Authors: Iorio Caterina , Rourke Jillian L. , Wells Lisa , Sakamaki Jun-Ichi , Moon Emily , Hu Queenie , Kin Tatsuya , Screaton Robert A. 
Published: June 2021

AbstractLoss of pancreatic β cells is the hallmark of type 1 diabetes (T1D) 1, for which provision of insulin is the standard of care. While regenerative and stem cell therapies hold the promise of generating single-source or host-matched tissue to obviate immune-mediated complications2–4, these will still require surgical intervention and immunosuppression. Thus, methods that harness the innate capacity of β-cells to proliferate to increase β cell mass in vivo are considered vital for future T1D treatment5, 6. However, early in life β cells enter what appears to be a permanent state of quiescence 7–10, directed by an evolutionarily selected genetic program that establishes a β cell mass setpoint to guard against development of fatal endocrine tumours. Here we report the development of a high-throughput RNAi screening approach to identify upstream pathways that regulate adult human β cell quiescence and demonstrate in a screen of the GPCRome that silencing G-protein coupled receptor 3 (GPR3) leads to human pancreatic β cell proliferation. Loss of GPR3 leads to activation of Salt Inducible Kinase 2 (SIK2), which is necessary and sufficient to drive cell cycle entry, increase β cell mass, and enhance insulin secretion in mice. Taken together, targeting the GPR3-SIK2 pathway represents a novel avenue to stimulate the regeneration of β cells.
TORC1 and PKA activity towards ribosome biogenesis oscillates in synchrony with the budding yeast cell cycle
Authors: Guerra Paolo , Vuillemenot Luc-Alban P.E. , Been Marije , Milias-Argeitis Andreas 
Published: June 2021

SummaryRecent studies have revealed that the growth rate of budding yeast and mammalian cells varies during the cell cycle. By linking a multitude of signals to cell growth, the highly conserved Target of Rapamycin Complex 1 (TORC1) and Protein Kinase A (PKA) pathways are prime candidates for mediating the dynamic coupling between growth and division. However, measurements of TORC1 and PKA activity during the cell cycle are still lacking. Following the localization dynamics of two TORC1 and PKA targets via time-lapse microscopy in hundreds of yeast cells, we found that the activity of these pathways towards ribosome biogenesis fluctuates in synchrony with the cell cycle even under constant external conditions. Mutations of upstream TORC1 and PKA regulators suggested that internal metabolic signals partially mediate these activity changes. Our study reveals a new aspect of TORC1 and PKA signaling, which will be important for understanding growth regulation during the cell cycle.
Direct Energy Transfer from Allophycocyanin-Free Rod-Type CpcL-Phycobilisome to Photosystem I
Authors: Noji Tomoyasu , Watanabe Mai , Dewa Takehisa , Itoh Shigeru , Ikeuchib Masahiko 
Published: June 2021

ABSTRACTPhycobilisomes (PBSs) are photosynthetic antenna megacomplexes comprised of pigment-binding proteins (cores and rods) joined with linker proteins. A rod-type PBS that does not have a core is connected to photosystem I (PSI) by a pigment-free CpcL linker protein, which induces a red-shift of the absorption band of phycocyanobilin (PCB) in the rod (red-PCB). Herein, the isolated supercomplex of the rod-type PBS and the PSI tetramer from Anabaena sp. PCC 7120 were probed by picosecond laser spectroscopy at 77 K and by decay-associated spectral analysis to show that red-PCB mediates the fast (time constant = 90 ps) and efficient (efficiency = 95%) transfer of excitation energy from PCB in rod to chlorophyll a (Chl a) in PSI. According to the Förster energy transfer mechanism, this high efficiency corresponds to a 4-nm distance between red-PCB and Chl a, suggesting that β-84 PCB in rod acts as red-PCB.TOC GRAPHIC
High-fat diet induced loss of GABAergic inhibition decouples intrinsic and synaptic excitability in AgRP neurons
Authors: Korgan Austin C. , Wei Wei , Martin Sophie L. A. , Kaczorowski Catherine C. , O’Connell Kristen M.S. 
Published: June 2021

AbstractObesity is a progressive, relapsing disease with few therapies. Diet and lifestyle interventions are effective but are often temporary and many individuals regain weight. High-fat diet increases the excitability of AgRP neurons, a critical neuronal population for the regulation of food intake and body weight. Here we investigate the plasticity of AgRP neurons and the impact of high-fat diet on modulation by synaptic input. We find that diet-induced hyperexcitability of AgRP neurons is not reversed by a lower-fat diet intervention. High-fat diet is associated with changes in the synaptic modulation of AgRP neurons, with a paradoxical increase in inhibitory input accompanied by a loss of GABA-mediated inhibition due to a depolarizing shift in the reversal potential of the GABA-evoked Cl− current. These findings reveal that high-fat diet leads to decoupling of intrinsic and synaptic excitability in AgRP neurons, such that hyperexcitability of AgRP neurons persists despite an increase in inhibitory input, revealing a mechanism for the difficulty in sustaining weight loss.
RNA surveillance controls 3D genome structure via stable cohesin-chromosome interaction
Authors: Chun Yujin , Han Sungwook , Kim Taemook , Choi Yoonjung , Lee Daeyoup 
Published: June 2021

SummaryThe 3D architecture that the genome is folded into is regulated by CTCF, which determines domain borders, and cohesin, which generates interactions within domains. However, organisms lacking CTCF have been reported to still have cohesin-mediated 3D structures with strong borders. How this can be achieved and precisely regulated are yet unknown. Using in situ Hi-C, we found that 3’-end RNA processing factors coupled with proper transcription termination are a cis-acting determinant that regulates the localization and dynamics of cohesin on the chromosome arms. Loss of RNA processing factors, including nuclear exosome and Pfs2, destabilizes cohesin from the 3’-ends of convergent genes and results in decreased cohesin-mediated domain boundaries. We observed the co-localization between Rad21 and a wide range of 3’end RNA processing/termination factors. Further, deletion of Rrp6 leads to cohesin redistribution to facultative heterochromatin, resulting in improper domain boundaries. Importantly, we observed that knockdown of Rrp6Exosc10 caused a defect in cohesin binding and loss of local topologically associating domains (TADs) interactions in mouse embryonic stem cells. Based on these findings, we propose a novel function of the RNA surveillance pathway in 3D genome organization via cohesin complex, which provides the molecular basis underlying the dynamics of cohesin function.
Reverse engineering of a mechanistic model of gene expression using metastability and temporal dynamics
Authors: Ventre Elias 
Published: June 2021

AbstractDifferentiation can be modeled at the single cell level as a stochastic process resulting from the dynamical functioning of an underlying Gene Regulatory Network (GRN), driving stem or progenitor cells to one or many differentiated cell types. Metastability seems inherent to differentiation process as a consequence of the limited number of cell types. Moreover, mRNA is known to be generally produced by bursts, which can give rise to highly variable non-Gaussian behavior, making the estimation of a GRN from transcriptional profiles challenging. In this article, we present CARDAMOM (Cell type Analysis from scRna-seq Data achieved from a Mixture MOdel), a new algorithm for inferring a GRN from timestamped scRNA-seq data, which crucially exploits these notions of metastability and transcriptional bursting. We show that such inference can be seen as the successive resolution of as many regression problem as timepoints, after a preliminary clustering of the whole set of cells with regards to their associated bursts frequency. We demonstrate the ability of CARDAMOM to infer a reliable GRN from in silico expression datasets, with good computational speed. To the best of our knowledge, this is the first description of a method which uses the concept of metastability for performing GRN inference.
CDK12 is Necessary to Promote Epidermal Differentiation through Transcription Elongation
Authors: Li Jingting , Tiwari Manisha , Chen Yifang , Sen George L. 
Published: June 2021

ABSTRACTProper differentiation of the epidermis is essential to prevent water loss and to protect the body from the outside environment. Perturbations in this process can lead to a variety of skin diseases that impacts 1 in 5 people. While transcription factors that control epidermal differentiation have been well characterized, other aspects of transcription control such as elongation are poorly understood. Here we show that of the two cyclin dependent kinases (CDK12 and CDK13), that are known to regulate transcription elongation, only CDK12 is necessary for epidermal differentiation. Depletion of CDK12 led to loss of differentiation gene expression and absence of skin barrier formation in regenerated human epidermis. CDK12 binds to genes that code for differentiation promoting transcription factors (GRHL3, KLF4, and OVOL1) and is necessary for their elongation. CDK12 is necessary for elongation by promoting Ser2 phosphorylation on the C-terminal domain of RNA polymerase II and the binding of the elongation factor SPT6 to target genes. Our results suggest that control of transcription elongation by CDK12 plays a prominent role in adult cell fate decisions.
High-quality complete genome resource of plant pathogenic bacteriumPectobacterium atrosepticumstrain Green1 isolated from potato (Solanum tuberosumL.) in Greenland
Authors: Czajkowski Robert , Rabalski Lukasz , Kosinski Maciej , de Neergaard Eigil , Harding Susanne 
Published: June 2021

AbstractPectobacterium atrosepticumis a narrow host range pectinolytic plant pathogenic bacterium causing blackleg of potato (Solanum tuberosumL.) worldwide. Till present, severalP. atrosepticumgenomes have been sequenced and characterized in detail; all of these genomes have come, however, fromP. atrosepticumstrains isolates from plants grown in temperate zones, not from hosts cultivated under different climatic conditions. Herewith, we present the first complete, high-quality genome of theP. atrosepticumstrain Green1 isolated from potato plants grown under subarctic climate in Greenland. The genome ofP. atrosepticumstrain Green1 consists of one chromosome of 4,959,719 bp., with a GC content of 51% and no plasmids. The genome contains 4531 annotated features, including 4179 protein-coding genes (CDSs), 22 rRNA genes, 70 tRNA genes, 8 ncRNA genes, 2 CRISPRs and 126 pseudogenes. We believe that the information of this first, high-quality, complete, closed genome ofP. atrosepticumstrain isolated from host plant grown in subarctic agricultural region will provide resources for comparative genomic studies and for analyses targeting climatic adaptation and ecological fitness mechanisms present inP. atrosepticum.
Stat3 co-operates with mutantEzh2Y641Fto regulate gene expression and limit the anti-tumor immune response in melanoma
Authors: Zimmerman Sarah M. , Nixon Samantha J. , Chen Pei Yu , Raj Leela , Smith Sofia , Paolini Rachel L. , Lin Phyo Nay , Souroullas George P. 
Published: June 2021

ABSTRACTOne of the most frequently genetically altered chromatin modifiers in melanoma is the Enhancer of Zeste Homolog 2 (EZH2), the catalytic component of the Polycomb Repressive Complex 2 (PRC2), which methylates lysine 27 on histone 3 (H3K27me3), a chromatin mark associated with transcriptional repression. Genetic alterations inEZH2in melanoma include amplifications and activating point mutations at tyrosine 641 (Y641). The oncogenic role of EZH2 in melanoma has previously been identified; however, its downstream mechanisms remain underexplored. We found that in genetically engineered mouse models,Ezh2Y641Fexpression causes upregulation of a subset of interferon-regulated genes in melanoma cells, suggesting a potential role of the immune system in the pathogenesis of these mutations. Upregulation of these interferon genes was not a result of changes in H3K27me3, but through a direct and non-canonical interaction between Ezh2 and Signal Transducer and Activator of Transcription 3 (Stat3). Ezh2 directly binds Stat3, and, in the presence of Ezh2Y641F, Stat3 protein is hypermethylated. Expression of Stat3 was required to maintain an anti-tumor immune response and its depletion resulted in faster melanoma progression and disease recurrence. Molecularly, Stat3 and Ezh2 bind together at many genomic loci, and can both activate and repress gene expression in association with the rest of the PRC2 complex. These results suggest that Ezh2 can mediate melanomagenesis through evasion of the anti-tumor immune response, and that the immunomodulatory properties of Stat3 are context dependent.
Design stage evaluation tools for residential dementia care environments
Authors: Quirke Martin , Ostwald Michael J. , Fleming Richard , Taylor Mark , Williams Anthony 
Published: June 2021

Purpose
The independence and well-being of people with dementia can be significantly influenced by the design of the physical environments around them. Several assessment tools exist to evaluate the dementia design quality of existing residential aged care facilities but, to date, none have been formally identified as suitable for use during the design process. This paper aims to examine the feasibility of re-purposing existing post-occupancy tools for use during the design process, while mapping the influence of design stages on resulting dementia design quality.

Design/methodology/approach
Literature searches identified audit tools for residential aged care settings. After reliability screening, three tools were analysed in-depth, mapping their suitability for use during the design process.

Findings
The study confirmed that existing tools can be re-purposed for design stage use and identified that early design stages have a larger influence on overall dementia design quality than previously thought.

Research limitations/implications
Non-English language publications were not reviewed. Searches may not have identified other existing audit tools for residential care environments.

Practical implications
The ability to assess proposals at key stages of design may help improve the dementia design quality of future residential aged care environments – potentially enhancing the lives of ever-larger numbers of people with dementia.

Originality/value
According to the authors’ knowledge, this is the first known paper to consider formal design-stage evaluation of dementia design quality and the first to identify the relative influence of key stages of design on the resulting dementia design quality.
Loyalty programs: the vital safety feature for airlines to survive COVID-19
Authors: Pascual Manuel E. , Cain Lisa Nicole 
Published: June 2021

PurposeThe airline industry has been severely impacted by COVID-19 due to widespread travel restrictions. Its current response is crucial to ensure continued operations after the global pandemic is resolved. One resource the airlines are leveraging is loyalty programs. This study aims to examine the viability of leveraging loyalty programs in times of crisis.Design/methodology/approachThis study employs a case study methodology to examine how one company, American Airlines, has used its loyalty program to survive a pandemic and alleviate the financial costs associated with limited and restricted travel.FindingsAmerican Airlines' AAdvantage loyalty program structure may be used as a benchmark to understand how airlines can anchor their loyalty base to reinvigorate travel interest and use these programs as safeguards in critical instances that may arise in the future.Research limitations/implicationsThe case was bound by the fact that the pandemic was still a threat during the time of analysis. The findings of this case study go beyond the airline industry and may inform other hospitality and tourism organizations on the benefits of loyalty programs in times of financial distress.Originality/valueThis is the first known case study examining the strengths and opportunities of the structure of the American Airlines' AAdvantage program as a means for surviving in a time of crisis. Moreover, understanding how to mitigate the long-term effects of crises may help to inform future short-term strategies of airlines and other hospitality and tourism organizations for navigating unexpected shocks to their ecosystem.
An intelligence optimization method based on crowd intelligence for IoT devices
Authors: Wang Ke , Yang Zheming , Liang Bing , Ji Wen 
Published: June 2021

Purpose
The rapid development of 5G technology brings the expansion of the internet of things (IoT). A large number of devices in the IoT work independently, leading to difficulties in management. This study aims to optimize the member structure of the IoT so the members in it can work more efficiently.

Design/methodology/approach
In this paper, the authors consider from the perspective of crowd science, combining genetic algorithms and crowd intelligence together to optimize the total intelligence of the IoT. Computing, caching and communication capacity are used as the basis of the intelligence according to the related work, and the device correlation and distance factors are used to measure the improvement level of the intelligence. Finally, they use genetic algorithm to select a collaborative state for the IoT devices.

Findings
Experimental results demonstrate that the intelligence optimization method in this paper can improve the IoT intelligence level up to ten times than original level.

Originality/value
This paper is the first study that solves the problem of device collaboration in the IoT scenario based on the scientific background of crowd intelligence. The intelligence optimization method works well in the IoT scenario, and it also has potential in other scenarios of crowd network.