bluuebunny/crossref_metadata_2025 huggingface dataset:
Managed entry agreementsas a new legal framework for access to medicines
Authors: Zosymenko Oleksandr
Published: July 2021

Key words: managed entry agreements, availability of medicines, original medicines,purchase of medicines, medicinal immunobiological drugs

The article concerns the new provisions of national legislativea legal mechanism for access to medicines, namely managed entry agreements. Theuse of managed entry agreements in European contract practice is widespread.Ukraine, in responding to the COVID-19 pandemic, has reviewed the legal mechanismsfor access to medicines contained in national legislation and had taken the firststeps towards implementing managed access agreements.Ukrainian legislation did not contain such a concept as a managed entry agreementby March 2020, and such agreement was never used in Ukrainian contract practicefor the purchase of medicines. On March 17, 2020, changes were made to the nationallegislation, namely the Law of Ukraine «On amendments to certain laws ofUkraine aimed at increasing the availability of medicines, medical products and theiraccessories, which are purchased by the person authorized to carry out purchases inthe field of health care» which were amended, in particular, to the Law of Ukraine«Fundamentals of the legislation of Ukraine on health care» and supplemented by article791 of which a managed entry agreement to national legislation was introduced.

The provision of Article 79-1 of the Fundamentals of the legislation of Ukraine onhealth care regarding the parties, subject matter, content of managed entry agreementsis analysed.January 27, 2021, the Cabinet of Ministers of Ukraine adopted a decision approvingthe procedure for the negotiation, execution, modification and termination ofmanaged entry agreement. A standard form of agreement for a managed entry agreementhas been approved. The managed entry agreements procedure has been introducedin Ukraine February 15, 2021.The legal and regulatory provisions concerning managed entry agreements havebeen analysed and highlighted their particularities.
Legal framework for the use of intellectual property in sports activities
Authors: Doroshenko Dmytro
Published: July 2021

Key words: sports activities, sports activities legal regulation, temporary laws, ambushmarketing, image rights, local rulemaking

The article analyses the legal regulation of the use of intellectualproperty in sports activities. The relevance of the study is justified by the fact that theincome of the global sports industry is increasingly depending on the use of the intellectualproperty by sports organizations.The author notices that adoption of temporary laws aimed at protecting the intellectualproperty rights of sports organizations who organize major sporting events ina country are distinctive features of sports activities. There were two similar laws inthe Ukrainian legislation. Although these laws contained some gaps, this experienceshould become a basis for the introduction of the concept of ambush marketing on aregular basis in the domestic law.Analysis of international agreements in the sporting sphere shows that nowadaysamong the world sports organizations, only intellectual property of InternationalOlympic Committee has an exclusive basis of protection. At the same time, the factthat in general the use and protection of intellectual property is given too little attentionin international agreements in the field of sports gives greater importance tolocal regulations adopted by sports authorities.According to the established practices of foreign sports organizations, professionalrules and contracts between the athlete and the organization contains mutual restrictionsof the use of a number of intellectual property objects constituting the athlete’simage. To date, in Ukrainian practice, only regulations and contracts of several footballorganizations contain the similar provisions, which at the same time have a numberof shortcomings. One of the issues is terminological ambiguity in image rightslegal phenomena, which is still new to Ukrainian practice, and therefore requires theconsistency of definitions between different sports organizations.Thus, although Ukrainian legislation creates the background for domestic sportsorganizations to benefit from their intellectual property, it still requires the adoptionof some new important definitions.
Yuri A. Shelygin. 70th Anniversary
Authors: Editorial Article
Published: July 2021

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Endoscopic mucosal resection and conventional polypectomy in colon adenomas
Authors: Vaganov Yu. E. , Khomyakov E. A. , Serebry A. B. , Abdulzhalieva E. U.
Published: July 2021

Aim: to compare the early and long-term results of endoscopic mucosal resection (EMR) and conventional polypectomy for benign epithelial colon neoplasms

Patients and methods: the retrospective study included 344 patients with histologically verified adenomas of the size of up to 40 mm in the colon, who underwent EMR or conventional polypectomy. Mucosectomy (EMR) was performed in 207 patients, while conventional polypectomy was performed in 137.

Results: there were no significant differences in the postoperative morbidity rates between the methods (OR = 1.8; 95% CI = 0.7–4.8, p = 0.3). Fragmentation significantly more often occurred in the group of conventional polypectomy (OR = 3.5; 95% CI = 2.3–5.5, p = 0.001, especially when the size of the neoplasm was over 1 cm (OR = 3.1; 95% CI = 1.1–8.9 = 0.037). Recurrence occurred in 19/173 (10.9%) in 12 (8.3%) patients of the EMR group. In the polypectomy group, recurrence developed in 22 (23.1%) patients, in 24/108 (22.2%) cases at the site of the postoperative scar. It was found that the adenoma recurrence in the area of endoscopic excision occurs significantly more often after conventional polypectomy (OR = 2.3; 95% CI = 1.2–4.4; p = 0.016).

Conclusion: EMR and conventional polypectomy both are the safe methods with low morbidity rates. However, the EMR is the preferred method of endoscopic excision for adenomas larger than 1 cm due to the fact that it allows for deeper and more complete resection of the tissue than conventional polypectomy.
Facilitating Digital Transformation in Construction—A Systematic Review of the Current State of the Art
Authors: Olanipekun Ayokunle O. , Sutrisna Monty
Published: July 2021

There is increasing implementation of digital technologies in construction. However, the transformation effects encompassing digital technology implementation are yet to be fully comprehended within the context of construction. Therefore, this study was aimed to provide a holistic understanding of digital transformation in construction. The study drew on extant literature by studying 36 journal publications published between 2016 when digital transformation emerged in construction from the information systems field and 2020. This led to the development of an inductive framework using a grounded theory methodology (GTM) to highlight digital transformation in construction as a process where the implementation of digital technologies creates transformation effects that trigger strategic considerations for putting in place the enablers that facilitate transformation effects and for suppressing the barriers to it. Building on the framework, this study described and presented the strategic considerations for facilitating specific enablers and those for suppressing specific barriers as digital transformation guideline in construction. This study demonstrated how the implementation of digital technologies has increased the understanding of and provided the basis for digital transformation in construction.
Comprehensive Analysis of the Clinical and Biological Significances of Endoplasmic Reticulum Stress in Diffuse Gliomas
Authors: Huang Ruoyu , Li Guanzhang , Wang Kuanyu , Wang Zhiliang , Zeng Fan , Hu Huimin , Jiang Tao
Published: July 2021

Background

As a critical organelle for protein and lipid synthesis, the dysfunction of endoplasmic reticulum has a significant impact on multiple biological processes of cells. Thus, in this study, we constructed an ER stress-related risk signature to investigate the functional roles of ER stress in gliomas.

Methods

A total of 626 samples from TCGA RNA-seq dataset (training cohort) and 310 samples from CGGA RNA-seq dataset (validation cohort) were enrolled in this study. Clinical information and genomic profiles were also obtained. The ER stress signature was developed by the LASSO regression model. The prognostic value of the risk signature was evaluated by Cox regression, Kaplan-Meier and ROC Curve analyses. Bioinformatics analysis and experiment in vitro were performed to explore the biological implication of this signature.

Results

We found that the ER stress-related signature was tightly associated with major clinicopathological features and genomic alterations of gliomas. Kaplan-Meier curve and Cox regression analysis indicated that ER stress activation was an independent prognostic factor for patients with glioma. Besides, we also constructed an individualized prognosis prediction model through Nomogram and ROC Curve analysis. Bioinformatics analysis suggested that ER stress activation also promoted the malignant progression of glioma and participated in the regulation of tumor immune microenvironment, especially the infiltration of macrophages in M2 phase. These results were further validated in IHC analysis and cell biology experiments.

Conclusion

The ER stress activation had a high prognostic value and could serve as a promising target for developing individualized treatment of glioma.
The Actin-Disassembly Protein Glia Maturation Factor γ Enhances Actin Remodeling and B Cell Antigen Receptor Signaling at the Immune Synapse
Authors: Deretic Nikola , Bolger-Munro Madison , Choi Kate , Abraham Libin , Gold Michael R.
Published: July 2021

Signaling by the B cell antigen receptor (BCR) initiates actin remodeling. The assembly of branched actin networks that are nucleated by the Arp2/3 complex exert outward force on the plasma membrane, allowing B cells to form membrane protrusions that can scan the surface of antigen-presenting cells (APCs). The resulting Arp2/3 complex-dependent actin retrograde flow promotes the centripetal movement and progressive coalescence of BCR microclusters, which amplifies BCR signaling. Glia maturation factor γ (GMFγ) is an actin disassembly-protein that releases Arp2/3 complex-nucleated actin filaments from actin networks. By doing so, GMFγ could either oppose the actions of the Arp2/3 complex or support Arp2/3 complex-nucleated actin polymerization by contributing to the recycling of actin monomers and Arp2/3 complexes. We now show that reducing the levels of GMFγ in human B cell lines via transfection with a specific siRNA impairs the ability of B cells to spread on antigen-coated surfaces, decreases the velocity of actin retrograde flow, diminishes the coalescence of BCR microclusters into a central cluster at the B cell-APC contact site, and decreases APC-induced BCR signaling. These effects of depleting GMFγ are similar to what occurs when the Arp2/3 complex is inhibited. This suggests that GMFγ cooperates with the Arp2/3 complex to support BCR-induced actin remodeling and amplify BCR signaling at the immune synapse.
An Opinion Facilitator for Online News Media
Authors: Willaert Tom , Van Eecke Paul , Van Soest Jeroen , Beuls Katrien
Published: July 2021

With more and more voices and opinions entering the public domain, a key challenge facing journalists and editors is maximizing the context of the information that is presented on news websites. In this paper, we argue that systems for exposing readers to the many aspects of societal debates should be grounded in methods and tools that can provide a fine-grained understanding of these debates. The present article thereby explores the conceptual transition from opinion observation to opinion facilitation by introducing and discussing the Penelope opinion facilitator: a proof-of-concept reading instrument for online news media that operationalizes emerging methods for the computational analysis of cultural conflict developed in the context of the H2020 ODYCCEUS project. It will be demonstrated how these methods can be combined into an instrument that complements the reading experience of the news website The Guardian by automatically interlinking news articles on the level of semantic frames. In linguistic theory, semantic frames are defined as coherent structures of related concepts. We thereby zoom in on instances of the “causation” frame, such as “climate change causes global warming,” and illustrate how a reading instrument that links articles based on such frames might reconfigure our readings of climate news coverage, with specific attention to the case of global warming controversies. Finally, we relate our findings to the context of the development of computational social science, and discuss pathways for the evaluation of the instrument, as well as for the future upscaling of qualitative analyses and close readings.
Ore-Forming Fluid Evolution in the Giant Gejiu Sn–Cu Polymetallic Ore Field, SW China: Evidence From Fluid Inclusions
Authors: Chen Yongqing , Wang Zhenyi , Li Jiande
Published: July 2021

The giant Gejiu Sn–Cu polymetallic ore deposit is one of the largest Sn producers in the world, and is related in time and space to highly evolved S type granitic intrusion. The mineralization processes can be divided into four stages: (I) skarnization; (II) greisenization; (III) cassiterite–sulfid; and (IV) cassiterite–tourmaline–quartz. Five types of fluid inclusions were recognized using optical petrography, microthermometry, and Raman spectroscopy. The results of microthermometry revealed the evolution of the ore-forming fluid, from a high temperature with low–to–high salinity to a low temperature with low–to–intermediate salinity. Stage I, skarn Sn–Cu ores were formed by bimetasomatism between the granitic intrusion and the surrounding rock under near–critical conditions with the help of ore-forming fluid. Stage II, the fluid was separated into the coexisting liquid and vapor phases in equilibrium condition, and a large amount of cassiterite–scheelite–beryl–lithium muscovite minerals were formed during greisenization. Stage III, mixing, boiling and immiscibility of different types of fluid solutions took place with a decline in temperature and pressure as well as a change in the Eh–pH, which caused amounts of cassiterites and sulfides to precipitate. Stage IV, stockwork ores characterized by cassiterite–tourmaline–quartz minerals were formed associated with the low temperature and low salinity hydrothermal liqiud activity. The laser Raman spectra identified CH4 in all ore-forming stages, indicating that the ore deposits might have been formed in a relatively reduced environment. CO2 appeared in all stages in addition to Stage I, and might have been formed due to both immiscibility of fluid solutions with dropping pressure as well as temperature and mixing of different types of fluid solutions. In conclusion, the bimetasomatism, mixing, and immiscibility of fluid solutions should have been responsible for the formation of giant Sn–Cu polymetallic deposits.
Analysis of Dam Overtopping Failure Risks Caused by Landslide-Induced Surges Considering Spatial Variability of Material Parameters
Authors: Dong Kai , Li Zefa , Lu Xiang , Chen Chen , Sheng Jinbao , Chen Jiankang , Wu Zhenyu
Published: July 2021

Many of the existing reservoir dams are constructed in alpine and gorge regions, where the topography and geological conditions are complicated, bank slopes are steep, and landslides have a high potential to occur. Surges triggered by landslides in the reservoir are one of the major causes of dam overtopping failures. Many factors affect the slope stability of reservoir banks and the height of surges triggered by landslides, such as spatial variability of material properties, speed of landslides, etc. To reasonably evaluate dam overtopping risk caused by landslide-induced surges is a key technology in engineering that is urgent to be solved. Therefore, a novel risk analysis method for overtopping failures caused by waves triggered by landslides induced by bank instability considering the spatial variability of material parameters is proposed in this study. Based on the random field theory, the simulation method for the spatial variability of material parameters is proposed, and the most dangerous slip surface of the reservoir bank slope is determined with the minimum value of the safety factors. The proxy risk analysis models for both the slope instability and dam overtopping are constructed with the consideration of spatial variability of material parameters, and then the dam overtopping failure risk caused by landslide-induced surges is calculated using the Monte-Carlo sampling. The proposed models are applied to a practical engineering project. Results show that the spatial variability of material properties significantly affects the instability risk of slopes, without considering which the risks of slope instability and dam overtopping may be overestimated. This study gives a more reasonable and realistic risk assessment of dam overtopping failures, which can provide technical support for the safety evaluation and risk control of reservoir dams.
Case Report: A Challenging Localization of a Pulmonary Ectopic ACTH-Secreting Tumor in a Patient With Severe Cushing’s Syndrome
Authors: Serban Andreea Liliana , Rosso Lorenzo , Mendogni Paolo , Cremaschi Arianna , Indirli Rita , Mantovani Beatrice , Rumi Mariagrazia , Castellani Massimo , Chiti Arturo , Croci Giorgio Alberto , Mantovani Giovanna , Nosotti Mario , Ferrante Emanuele , Arosio Maura
Published: July 2021

Background

Ectopic adrenocorticotropic syndrome (EAS) is a rare cause of endogenous ACTH-dependent Cushing’s syndrome, usually associated with severe hypercortisolism as well as comorbidities. Tumor detection is still a challenge and often requires several imaging procedures. In this report, we describe a case of an ectopic ACTH secretion with a misleading localization of the responsible tumor due to a concomitant rectal carcinoma.

Case presentation

A 49-year-old man was referred to our Endocrinology Unit due to suspicion of Cushing’s syndrome. His medical history included metastatic rectal adenocarcinoma, diagnosed 5 years ago and treated with adjuvant chemotherapy, radiotherapy and surgical resection. During follow-up, a thoracic computed tomography scan revealed two pulmonary nodules located in the superior and middle lobes of the right lung with a diameter of 5 and 10 mm, respectively. However, these nodules remained radiologically stable thereafter and were not considered relevant. All biochemical tests were suggestive of EAS (basal ACTH levels: 88.2 ng/L, nv 0–46; basal cortisol levels: 44.2 µg/dl, nv 4.8–19.5; negative response to CRH test and high dose dexamethasone suppression test) and radiological localization of the ectopic ACTH-secreting tumor was scheduled. The CT scan revealed a dimensional increase of the right superior lung nodule (from 5 to 12 mm). [68Ga]-DOTA-TOC PET/CT scan was negative, while [18F]-FDG-PET/CT showed a tracer accumulation in the superior nodule. After a multidisciplinary consultation, the patient underwent thoracic surgery that started with two atypical wedge resections of nodules. Frozen section analyses showed a neuroendocrine tumor on the right middle lobe nodule and a metastatic colorectal adenocarcinoma on the superior lesion. Then, a right superior nodulectomy and a right middle lobectomy with mediastinal lymphadenectomy were performed. The final histopathological examination confirmed a typical carcinoid tumor, strongly positive for ACTH. A post-surgical follow-up showed a persistent remission of Cushing’s syndrome.

Conclusions

The present report describes a case of severe hypercortisolism due to EAS not detected by functional imaging methods, in which the localization of ACTH ectopic origin was puzzled by a concomitant metastatic rectal carcinoma. The multidisciplinary approach was crucial for the management of this rare disease.
Plastic Recovery and Utilization: From Ocean Pollution to Green Economy
Authors: Adelodun Adedeji A.
Published: July 2021

Due to their numerous merits (such as high durability, diverse applicability, ready-availability, low-cost, reusability, and so on), the presumably inevitable use of plastics makes their waste ubiquitously dispersed in our environment, especially in the oceans. The environmental damage posed, especially to the ecosystem, initiated the need for recourse control of these environmentally refractory pollutants. In this review, the various sources, classifications, fate, and control measures of plastic wastes were appraised. Further, of the three primary techniques for resource control, pyrolysis was reviewed in-depth, showing its relevance and superiority over others. Specific case studies showed that liquid and gaseous fuels derived from pyrolyzed plastics are a waste-to-wealth system that requires optimization and intensification. Such an approach would further help rid our planet of the numerous plastic wastes while improving our economy and achieving our energy demand. One approach identified to improve the current pyrolysis technology is catalysis. Further research should devise green methods for organic catalysis, which are environmentally benign.
Evolutionary Perspective and Expression Analysis of Intronless Genes Highlight the Conservation of Their Regulatory Role
Authors: Aviña-Padilla Katia , Ramírez-Rafael José Antonio , Herrera-Oropeza Gabriel Emilio , Muley Vijaykumar Yogesh , Valdivia Dulce I. , Díaz-Valenzuela Erik , García-García Andrés , Varela-Echavarría Alfredo , Hernández-Rosales Maribel
Published: July 2021

The structure of eukaryotic genes is generally a combination of exons interrupted by intragenic non-coding DNA regions (introns) removed by RNA splicing to generate the mature mRNA. A fraction of genes, however, comprise a single coding exon with introns in their untranslated regions or are intronless genes (IGs), lacking introns entirely. The latter code for essential proteins involved in development, growth, and cell proliferation and their expression has been proposed to be highly specialized for neuro-specific functions and linked to cancer, neuropathies, and developmental disorders. The abundant presence of introns in eukaryotic genomes is pivotal for the precise control of gene expression. Notwithstanding, IGs exempting splicing events entail a higher transcriptional fidelity, making them even more valuable for regulatory roles. This work aimed to infer the functional role and evolutionary history of IGs centered on the mouse genome. IGs consist of a subgroup of genes with one exon including coding genes, non-coding genes, and pseudogenes, which conform approximately 6% of a total of 21,527 genes. To understand their prevalence, biological relevance, and evolution, we identified and studied 1,116 IG functional proteins validating their differential expression in transcriptomic data of embryonic mouse telencephalon. Our results showed that overall expression levels of IGs are lower than those of MEGs. However, strongly up-regulated IGs include transcription factors (TFs) such as the class 3 of POU (HMG Box), Neurog1, Olig1, and BHLHe22, BHLHe23, among other essential genes including the β-cluster of protocadherins. Most striking was the finding that IG-encoded BHLH TFs fit the criteria to be classified as microproteins. Finally, predicted protein orthologs in other six genomes confirmed high conservation of IGs associated with regulating neural processes and with chromatin organization and epigenetic regulation in Vertebrata. Moreover, this study highlights that IGs are essential modulators of regulatory processes, such as the Wnt signaling pathway and biological processes as pivotal as sensory organ developing at a transcriptional and post-translational level. Overall, our results suggest that IG proteins have specialized, prevalent, and unique biological roles and that functional divergence between IGs and MEGs is likely to be the result of specific evolutionary constraints.
Melatonin Regulates the Periodic Growth of Cashmere by Upregulating the Expression of Wnt10b and β-catenin in Inner Mongolia Cashmere Goats
Authors: Liu Junyang , Mu Qing , Liu Zhihong , Wang Yan , Liu Jiasen , Wu Zixian , Gong Wendian , Lu Zeyu , Zhao Feifei , Zhang Yanjun , Wang Ruijun , Su Rui , Li Jinquan , Xiao Hongmei , Zhao Yanhong
Published: July 2021

Secondary hair follicle growth in cashmere goats has seasonal cycle changes, and melatonin (MT) has a regulatory effect on the cashmere growth cycle. In this study, the growth length of cashmere was measured by implanting MT in live cashmere goats. The results indicated that the continuous implantation of MT promoted cashmere to enter the anagen 2 months earlier and induce secondary hair follicle development. HE staining of skin tissues showed that the number of secondary hair follicles in the MT-implanted goats was significantly higher than that in the control goats (P < 0.05). Transcriptome sequencing of the skin tissue of cashmere goats was used to identify differentially expressed genes: 532 in February, 641 in October, and 305 in December. Fluorescence quantitative PCR and Western blotting results showed that MT had a significant effect on the expression of Wnt10b, β-catenin, and proteins in the skin tissue of Inner Mongolia cashmere goats. This finding suggested that MT alters the cycle of secondary hair follicle development by changing the expression of related genes. This research lays the foundation for further study on the mechanism by which MT regulates cashmere growth.
Genome-Wide Analysis of PEBP Genes in Dendrobium huoshanense: Unveiling the Antagonistic Functions of FT/TFL1 in Flowering Time
Authors: Song Cheng , Li Guohui , Dai Jun , Deng Hui
Published: July 2021

Dendrobium is a semi-shade epiphytic Orchidaceae herb with important ornamental and medicinal value. Parts of the cultivation of Dendrobium germplasm resources, as well as the identification of medicinal components, are more studied, but the functional characterization of the flowering regulation in Dendrobium plants is less reported. Here, six PEBP family genes (DhFT3, DhFT1, DhMFT, DhTFL1b, DhFT2, and DhTFL1a) were identified from the Dendrobium huoshanense genome. The chromosome-level mapping showed that these genes were sequentially distributed on chromosomes 6, 9, 15, and 17. The paralogous gene DhTFL1b corresponded to DhTFL1a, which was determined through tandem duplication. The gene structure and conserved motif of DhPEBP indicated five PEBP genes apart from DhMFT contained four exons and three introns entirely. The phylogeny analysis showed that the PEBP gene family in A. thaliana, O. sativa, Z. mays, S. lycopersicum, and P. equestris were classified into three subclades, FT, TFL, and MFT, which maintained a high homology with D. huoshanense. The conserved domain of the amino acid demonstrated that two highly conserved short motifs (DPDXP and GXHR) embed in DhPEBPs, which may contribute to the conformation of the ligand binding bag. The 86th position of DhFTs was tyrosine (Y), while the 83th and 87th of DhTFL1s belonged to histidine (H), suggesting they should have distinct functions in flowering regulation. The promoter of six DhPEBPs contained several cis-elements related to hormone induction, light response, and abiotic stress, which indicated they could be regulated by the environmental stress and endogenous signaling pathways. The qRT-PCR analysis of DhPEBPs in short-term days induced by GA indicated the gene expressions of all DhFTs were gradually increased, whereas the expression of DhTFL1 was decreased. The results implied that DhPEBPs have various regulatory functions in modulating flowering, which will provide a scientific reference for the flowering regulation of Dendrobium plants.
Immune-Related Gene Expression Analysis Revealed Three lncRNAs as Prognostic Factors for Colon Cancer
Authors: Xing Xiao-Liang , Zhang Ti , Yao Zhi-Yong , Xing Chaoqun , Wang Chunxiao , Liu Yuan-Wu , Huang Minjiang
Published: July 2021

Colorectal cancer (CRC) is one of the most common cancers. Almost 80% of CRC cases are colon adenocarcinomas (COADs). Several studies have indicated the role of immunotherapy in the treatment of various cancers. Our study aimed to identify immune-related long non-coding RNAs (lncRNAs) and to use them to construct a risk assessment model for evaluating COAD prognosis. Using differential expression, correlation, and Cox regression analyses, we identified three immune-related differentially expressed lncRNAs (IR-DELs) and used them to construct a risk assessment model. The area under the curve (AUC) for each receiver operating characteristic (ROC) curve at 3-, 5-, and 10-years were greater than 0.6. In addition, the risk assessment model was correlated with several immune cells and factors. The three IR-DELs (AC124067.4, LINC02604, and MIR4435-2HG) identified in this study can be used to predict outcomes for patients with COAD and might help in identifying those who can benefit from anti-tumor immunotherapy.
Roles of Phase Separation for Cellular Redox Maintenance
Authors: Saito Yuichi , Kimura Wataru
Published: July 2021

The oxidation reaction greatly alters characteristics of various cellular components. In exchange for efficient energy production, mitochondrial aerobic respiration substantially increases the risk of excess oxidation of cellular biomolecules such as lipids, proteins, nucleic acids, and numerous small molecules. To maintain a physiologically balanced cellular reduction-oxidation (redox) state, cells utilize a variety of molecular machineries including cellular antioxidants and protein degradation complexes such as the ubiquitin-proteasome system or autophagy. In the past decade, biomolecular liquid-liquid phase separation (LLPS) has emerged as a subject of great interest in the biomedical field, as it plays versatile roles in the maintenance of cellular homeostasis. With regard to redox homeostasis, LLPS arose as a major player in both well-characterized and newly emerging redox pathways. LLPS is involved in direct redox imbalance sensing, signal transduction, and transcriptional regulation. Also, LLPS is at play when cells resist redox imbalance through metabolic switching, translational remodeling, activating the DNA damage response, and segregation of vulnerable lipids and proteins. On the other hand, chronic accumulation of phase-separated molecular condensates such as lipid droplets and amyloid causes neurotoxic outcomes. In this review we enumerate recent progress on understanding how cells utilize LLPS to deal with oxidative stress, especially related to cell survival or pathogenesis, and we discuss future research directions for understanding biological phase separation in cellular redox regulation.
Genetic Recombination of the Mantle Color Pattern of Two Boring Giant Clam (Tridacna crocea) Strains
Authors: Wang Junjie , Zhou Zihua , Ma Haitao , Li Jun , Qin Yanping , Wei Jinkuan , Li Xingyou , Liao Qingliang , Li Yunqing , Shi Gongpengyang , Zhou Yinyin , Zhang Yuehuan , Yu Ziniu
Published: July 2021

According to the RGB law display, the polymorphism of the giant clam mantle color pattern is through four iridocytes. The boring giant clam (Tridacna crocea) exhibits diverse mantle colors, including blue, green, purple, gold, and orange. In order to evaluate the genetic laws driving these mantle color patterns, a complete diallel cross between two color strains [blue strain (only blue iridocyte) and the yellow-green strain (yellow and green iridocytes)] was performed. Using a single-to-single mating system, two intra-strain crosses (BB and YY) and two reciprocal inter-strain crosses (BY and YB) were produced in triplicates. Higher fertilization rate and hatching rate were observed in all experimental groups, suggesting that there was no sperm–egg recognition barrier between the two strains. In the grow-out stage, the size of the reciprocal hybrids was larger than that of the two pure strains with a degree of heterosis. In addition, compared with the two pure strains, the hybrids have higher larval metamorphosis rate and higher survival rate. At 1 year of age, the mantle color pattern of pure strains showed 100% stable inheritance, while the reciprocal hybrids exhibited colorful patterns (a combination of blue, yellow, and green), suggesting that there was a genetic recombination of the mantle colors during the stable expression period. These results provide a theoretical basis for the formation of the mantle color of giant clam and its genetic segregation law, as well as provide guidance for genetic breeding of giant clams.
Oceanic Diel Vertical Movement Patterns of Blue Sharks Vary With Water Temperature and Productivity to Change Vulnerability to Fishing
Authors: Vedor Marisa , Mucientes Gonzalo , Hernández-Chan Sofia , Rosa Rui , Humphries Nick , Sims David W. , Queiroz Nuno
Published: July 2021

In the pelagic environment diel vertical movements (DVM) are widespread across taxa, from zooplankton ascending from day-time depths into surface layers at night to avoid visual predators, to apex predators following prey movements to maximise foraging opportunities. The drivers of DVM in large predators such as pelagic sharks have only recently begun to be investigated in detail with the advent of sophisticated archival tags and high-resolution oceanographic datasets. In this study, we satellite tagged adult [>180 cm fork length, (FL)] blue sharks (Prionace glauca) in the North Atlantic Ocean to examine behavioural changes in response to the encountered environment, and therefore, to determine potential risks of capture using pelagic longline fisheries data. Although blue sharks recurrently use surface waters, cyclic diel behaviours were observed, with >95% of night-time spent above 250 m depth and variable day-time depth use. Hence, three different diel behaviours were identified during the tracking period: (i) regular normal DVM (nDVM) (dawn descent – dusk ascent, with over 90% of nighttime spent above 250 m, and between 5 and 50% of the day below this threshold); (ii) surface-oriented behaviour (occupation of surface waters both day and night), and (iii) deep depth-oriented nDVM [dawn descent – dusk ascent, with the majority (>50%) of daytime spent at depth]. Importantly, diel behaviours generally occurred in different ocean regions with nDVM frequently observed in high latitudes, associated with cold, highly productive waters (e.g., North Atlantic Current/Labrador Current convergence zone, West African upwelling area), while depth-oriented nDVM was observed in warm, oligotrophic areas. Thus, day-time occupation of shallow waters significantly increased with lower water temperature at depth (100 m), and with increasing concentration (and decreasing depth) of the chlorophyll a maximum. During nights of full moon blue sharks spent significantly more time in the depth range of longline hooks, while fishing effort and catches were also higher. We demonstrate that increased occupancy of surface layers driven by highly productive, cold waters and greater lunar illumination lead to higher capture risk. Understanding habitat-specific vulnerability to fishing in a commercially important pelagic shark species is essential for improving management and conservation measures.
Virtual Regional Fisheries Management Meetings in the Western and Central Pacific Ocean Region: A Preliminary Appraisal of Performance and Fit
Authors: Campbell Brooke , McIlgorm Alistair , Voyer Michelle
Published: July 2021

Regional fisheries meetings that support the management of Western and Central Pacific Ocean (WCPO) capture fisheries are usually held face-to-face and in-person. In 2020, the travel and gathering bans due to the global COVID-19 pandemic meant that these meetings were held “virtually,” primarily via videoconferencing. But can virtual meetings perform the same functions and deliver the same management outcomes as face-to-face meetings? This study is an initial investigation of the experiences, perceptions and attitudes of WCPO region government participants in a number of virtual regional fisheries meetings in 2020. Results indicate a strong preference for face-to-face regional meetings, with the perception that virtual meetings performed comparatively poorly at supporting a number of key meeting processes and outcomes. However, one-quarter to one-third of study participants consistently found no difference between format performance for many meeting processes and outcomes. Virtual formats were considered more appropriate for smaller and non-regional meetings, and allowed for greater staff attendance at meetings as well as cost and time savings for some, but not all, participants. Study participants believe that virtual regional meetings will be more common in the region in the future, despite nearly half indicating that virtual meeting are not a good fit for the region generally. Many of these experiences and perceptions are consistent with organizational behavior, communications media, and information systems literature. Some results appear unique to the region’s socially and culturally diverse Pacific island countries and territories, which are relative newcomers to the global information and communication technology “revolution.” A greater use of virtual regional fisheries meetings in the future requires meeting hosts and facilitators to carefully consider the potential impacts of virtual meetings on effective communication and inclusive participation in WCPO regional fisheries management and other governance outcomes.
Discovery of Small-Molecule Inhibitors of SARS-CoV-2 Proteins Using a Computational and Experimental Pipeline
Authors: Lau Edmond Y. , Negrete Oscar A. , Bennett W. F. Drew , Bennion Brian J. , Borucki Monica , Bourguet Feliza , Epstein Aidan , Franco Magdalena , Harmon Brooke , He Stewart , Jones Derek , Kim Hyojin , Kirshner Daniel , Lao Victoria , Lo Jacky , McLoughlin Kevin , Mosesso Richard , Murugesh Deepa K. , Saada Edwin A. , Segelke Brent , Stefan Maxwell A. , Stevenson Garrett A. , Torres Marisa W. , Weilhammer Dina R. , Wong Sergio , Yang Yue , Zemla Adam , Zhang Xiaohua , Zhu Fangqiang , Allen Jonathan E. , Lightstone Felice C.
Published: July 2021

A rapid response is necessary to contain emergent biological outbreaks before they can become pandemics. The novel coronavirus (SARS-CoV-2) that causes COVID-19 was first reported in December of 2019 in Wuhan, China and reached most corners of the globe in less than two months. In just over a year since the initial infections, COVID-19 infected almost 100 million people worldwide. Although similar to SARS-CoV and MERS-CoV, SARS-CoV-2 has resisted treatments that are effective against other coronaviruses. Crystal structures of two SARS-CoV-2 proteins, spike protein and main protease, have been reported and can serve as targets for studies in neutralizing this threat. We have employed molecular docking, molecular dynamics simulations, and machine learning to identify from a library of 26 million molecules possible candidate compounds that may attenuate or neutralize the effects of this virus. The viability of selected candidate compounds against SARS-CoV-2 was determined experimentally by biolayer interferometry and FRET-based activity protein assays along with virus-based assays. In the pseudovirus assay, imatinib and lapatinib had IC50 values below 10 μM, while candesartan cilexetil had an IC50 value of approximately 67 µM against Mpro in a FRET-based activity assay. Comparatively, candesartan cilexetil had the highest selectivity index of all compounds tested as its half-maximal cytotoxicity concentration 50 (CC50) value was the only one greater than the limit of the assay (>100 μM).
Sex-Specific Linear Polyubiquitination Is a Critical Regulator of Contextual Fear Memory Formation
Authors: Musaus Madeline , Farrell Kayla , Navabpour Shaghayegh , Ray W. Keith , Helm Richard F. , Jarome Timothy J.
Published: July 2021

Strong evidence supports that protein ubiquitination is a critical regulator of fear memory formation. However, as this work has focused on protein degradation, it is currently unknown whether polyubiquitin modifications that are independent of the proteasome are involved in learning-dependent synaptic plasticity. Here, we present the first evidence that atypical linear (M1) polyubiquitination, the only ubiquitin chain that does not occur at a lysine site and is largely independent of the proteasome, is critically involved in contextual fear memory formation in the amygdala in a sex-specific manner. Using immunoblot and unbiased proteomic analyses, we found that male (49) and female (14) rats both had increased levels of linear polyubiquitinated substrates following fear conditioning, though none of these protein targets overlapped between sexes. In males, target protein functions involved cell junction and axonal guidance signaling, while in females the primary target was Adiponectin A, a critical regulator of neuroinflammation, synaptic plasticity, and memory, suggesting sex-dependent functional roles for linear polyubiquitination during fear memory formation. Consistent with these increases, in vivo siRNA-mediated knockdown of Rnf31, an essential component of the linear polyubiquitin E3 complex LUBAC, in the amygdala impaired contextual fear memory in both sexes without affecting memory retrieval. Collectively, these results provide the first evidence that proteasome-independent linear polyubiquitination is a critical regulator of fear memory formation, expanding the potential roles of ubiquitin-signaling in learning-dependent synaptic plasticity. Importantly, our data identify a novel sex difference in the functional role of, but not a requirement for, linear polyubiquitination in fear memory formation.
Co-creation and User Perspectives for Upper Limb Prosthetics
Authors: Jones Hannah , Dupan Sigrid , Dyson Matthew , Krasoulis Agamemnon , Kenney Laurence P. J. , Donovan-Hall Margaret , Memarzadeh Kaveh , Day Sarah , Coutinho Maxford , Nazarpour Kianoush
Published: July 2021

People who either use an upper limb prosthesis and/or have used services provided by a prosthetic rehabilitation centre, experience limitations of currently available prosthetic devices. Collaboration between academia and a broad range of stakeholders, can lead to the development of solutions that address peoples' needs. By doing so, the rate of prosthetic device abandonment can decrease. Co-creation is an approach that can enable collaboration of this nature to occur throughout the research process. We present findings of a co-creation project that gained user perspectives from a user survey, and a subsequent workshop involving: people who use an upper limb prosthesis and/or have experienced care services (users), academics, industry experts, charity executives, and clinicians. The survey invited users to prioritise six themes, which academia, clinicians, and industry should focus on over the next decade. The prioritisation of the themes concluded in the following order, with the first as the most important: function, psychology, aesthetics, clinical service, collaboration, and media. Within five multi-stakeholder groups, the workshop participants discussed challenges and collaborative opportunities for each theme. Workshop groups prioritised the themes based on their discussions, to highlight opportunities for further development. Two groups chose function, one group chose clinical service, one group chose collaboration, and another group chose media. The identified opportunities are presented within the context of the prioritised themes, including the importance of transparent information flow between all stakeholders; user involvement throughout research studies; and routes to informing healthcare policy through collaboration. As the field of upper limb prosthetics moves toward in-home research, we present co-creation as an approach that can facilitate user involvement throughout the duration of such studies.
Multi-Modal Fusion Emotion Recognition Method of Speech Expression Based on Deep Learning
Authors: Liu Dong , Wang Zhiyong , Wang Lifeng , Chen Longxi
Published: July 2021

The redundant information, noise data generated in the process of single-modal feature extraction, and traditional learning algorithms are difficult to obtain ideal recognition performance. A multi-modal fusion emotion recognition method for speech expressions based on deep learning is proposed. Firstly, the corresponding feature extraction methods are set up for different single modalities. Among them, the voice uses the convolutional neural network-long and short term memory (CNN-LSTM) network, and the facial expression in the video uses the Inception-Res Net-v2 network to extract the feature data. Then, long and short term memory (LSTM) is used to capture the correlation between different modalities and within the modalities. After the feature selection process of the chi-square test, the single modalities are spliced to obtain a unified fusion feature. Finally, the fusion data features output by LSTM are used as the input of the classifier LIBSVM to realize the final emotion recognition. The experimental results show that the recognition accuracy of the proposed method on the MOSI and MELD datasets are 87.56 and 90.06%, respectively, which are better than other comparison methods. It has laid a certain theoretical foundation for the application of multimodal fusion in emotion recognition.
Intracranial Fusiform and Circumferential Aneurysms of the Main Trunk: Therapeutic Dilemmas and Prospects
Authors: Guo Yunbao , Song Ying , Hou Kun , Yu Jinlu
Published: July 2021

Intracranial fusiform and circumferential aneurysms (IFCAs), especially those located on the main trunk, are uncommon and difficult to manage. Currently, literature focused on IFCAs on the main trunk of cerebral arteries is lacking. The treatment of IFCAs is still under debate. Therefore, in this review, we further explore the treatment of this complicated entity. In addition, we also present some interesting cases. Based on the literature review and our experience, we found that IFCAs are often located in the vertebrobasilar system and that ruptured or large symptomatic IFCAs are associated with increased mortality and higher rebleeding rates. The treatment strategies for IFCAs can be classified as deconstructive and reconstructive methods via open surgery and/or endovascular treatment (EVT). Currently, EVT is a popular method and the main therapeutic choice. In particular, flow diversion has revolutionized the treatment of IFCAs. Parent artery occlusion (PAO) with or without revascularization may still be considered a suitable choice. Complex IFCAs that cannot be resolved by EVT can also be treated via open surgery with or without extracranial–intracranial bypass. Targeted embolization for the weak points of IFCAs is a temporary or palliative choice that is rarely used. In summary, despite complications, both surgical treatment and EVT are effective options for appropriately selected cases. Due to the development of endovascular implants, EVT will have better prospects in the future.