bluuebunny/crossref_metadata_2025 huggingface dataset:
PANORAMA RECENTE DOS ESTUDOS SOBRE CIDADES PEQUENAS NA GEOGRAFIA BRASILEIRA
Authors: Silva Rafael César , Toledo Márcio
Published: August 2021

Este artigo analisa o estudo das cidades pequenas pela ciência geográfica. A cidade pequena é pouco estudada em todos os níveis de formação universitária e de divulgação do saber científico. O objetivo principal deste trabalho é contribuir com o debate teórico sobre as cidades pequenas, elucidando a importância de estudá-las. Partimos do pressuposto que há uma escassez de pesquisas sobre a temática, justificado por diversos motivos, dentre eles a heterogeneidade de definições. Foi levantada a produção sobre cidades pequenas em dois eventos ligados à Geografia Urbana e em teses e dissertações em Geografia produzidas no Brasil. Apresentaremos as tendências atuais dessas pesquisas e as áreas em que as mesmas estão concentradas. Foi possível detectar que a maior parte das pesquisas sobre pequenas cidades está focada em estudos de casos específicos e não na busca de um aprofundamento teórico para fundamentar os estudos sobre a temática, porém, sempre reservando uma parte do trabalho para uma conceituação, mesmo que breve. Observamos ainda que há um aumento da produção de pesquisas voltadas às pequenas cidades no período analisado.
REPRESENTAÇÕES DE ISOLAMENTO E AFASTAMENTO EM UMA ALDEIA PATAGÔNICA
Authors: Vazquez Alberto
Published: August 2021

O artigo apresenta resultados obtidos em ações de pesquisa realizadas em um pequeno povoado do sul da Argentina. Uma aldeia patagônica de 200 habitantes, distante das cidades que concentram funções e serviços comerciais no setor centro da Patagônia argentino-chilena. O objetivo deste artigo é analisar as representações de seus habitantes sobre o isolamento e o afastamento. Representações que emergiram das entrevistas em profundidade realizadas em 2018 e 2019. Os resultados mostram que as conotações de isolamento ou afastamento em relação às cidades não são apenas negativas e que as distâncias variam em função das relações sociais, as condições materiais e os vínculos afetivos com os lugares. A discussão dos resultados está organizada em duas seções, uma aborda as consequências do isolamento e afastamento físico e a outra enfoca nos outros afastamentos: sociais, emocionais e políticos.
CIDADES PEQUENAS NO INTERIOR PAULISTA: os jovens e as práticas espaciais na praça central em Pompeia - SP
Authors: Souza Karin
Published: August 2021

Este artigo é parte integrante de uma pesquisa de Mestrado onde analisamos as práticas espaciais juvenis e a sociabilidade em cidades pequenas, na elaboração deste artigo em especial, foi elaborado um estudo que tem como objetivo analisar as formas de sociabilidade e as práticas espaciais de jovens de diferentes gerações na praça central de Pompeia-SP, que refletem em apropriações sobre o espaço público, nos momentos de lazer e entretenimento em diferentes dias e horários do cotidiano da pequena cidade. Através de procedimentos de entrevistas e da observação participante, buscamos compreender as práticas dos diferentes grupos juvenis. Entre os resultados de pesquisa demonstra-se a segmentação da frequência de grupos juvenis no espaço público, a partir de questões de renda, faixa etária e horário, também são demonstradas as mudanças e as permanências nas práticas entre as diferentes gerações, destacando que a proximidade da cidade pequena com a cidade média de Marília-SP, certamente nos levou a considerar também as relações interurbanas. Compreendemos que o conjunto das práticas espaciais está também envolvido na produção do espaço e da vida social da cidade.
AS CIDADES PEQUENAS E O ENSINO DE GEOGRAFIA: uma análise a partir do guia do Programa Nacional do Livro Didático (PNLD)
Authors: Silva André , Azevedo Sandra
Published: August 2021

As pequenas cidades vêm cada vez mais se tornando objeto de estudos entre variadas temáticas. No ensino de geografia não é diferente, visto que as pequenas cidades representam boa parte do número de aglomerações urbanas a nível nacional e tem demasiada importância. Por outro lado, existem as políticas educacionais, as quais servem como estruturadores do conhecimento nas instituições escolares, como, por exemplo, os currículos nacionais e estaduais e o Programa Nacional do Livro Didático (PNLD). Assim, torna-se de extrema importância saber se estas realidades vêm sendo abordadas no ensino de geografia. Desse modo, o presente trabalho tem como objetivo tratar como uma política educacional nacional, no caso deste estudo o Guia do PNLD do ano de 2020, trata as cidades pequenas. Para isto foi realizado um levantamento bibliográfico sobre a temática concomitantemente com uma análise investigativa debruçada sobre o Guia do PNLD. Com base em tais análises foi possível constatar que praticamente nenhuma obra se preocupa com as cidades pequenas, tratando em demasia as grandes aglomerações, fugindo das realidades dos alunos que habitam as pequenas aglomerações.
REGULARIZAÇÃO FUNDIÁRIA E AS RELAÇÕES DE PODER E CULTURA NO REORDENAMENTO TERRITORIAL EM PEQUENAS LOCALIDADES: o caso de Porto Camargo, município de Icaraíma/PR
Authors: Moura Evandro , Nicodem Maria Fatima , Oliveira Tarcisio
Published: August 2021

O objetivo deste artigo é apresentar as relações culturais atuais do processo de ocupação histórica ocorrida em pequenas localidades e como essas influenciam o papel que desempenham as instituições utilizando como exemplo a Regularização do Distrito de Porto Camargo, Município de Icaraíma-PR. Está organizado a partir de breve relato histórico da formação do Município de Icaraíma com o seu plano urbanístico, a ocorrência de equívocos, os impactos causados, e a questão cultural do direito de Propriedade. As considerações reforçam a necessidade da implantação da cultura cartográfica sistêmica e periódica para a manutenção do direito de propriedade e redução das tensões sociais causadas por conflitos promovido por informações cartográficas e cadastrais precárias.
PATRIMÔNIO FERROVIÁRIO, TERRITÓRIO E PEQUENAS CIDADES
Authors: Moura Rafael
Published: August 2021

Este trabalho observa a refuncionalização do patrimônio ferroviário no território de pequenas cidades que estão inseridas na rede ferroviária da antiga Companhia Paulista de Estradas de Ferro. O objetivo desta pesquisa é o de compreender os usos destes territórios a partir do patrimônio cultural. Uma vez que as pequenas cidades são localidades que possuem especificidades, este patrimônio possui narrativas que coloca as estações ferroviárias como lugares de memória. Estas estações são espaços privilegiados nas cidades e no período atual apontam para a refuncionalização. A metodologia de pesquisa discute a bibliografia referente ao tema e se respalda na documentação relativa aos processos de tombamento estadual. Ao longo da pesquisa foram realizados trabalhos de campo que auxiliam compreender o patrimônio ferroviário presente nestas localidades. Como resultados são apresentados a diversidade de usos do patrimônio ferroviário em pequenas relacionando-o com os tensionamentos que ocorrem neste território.
Quality Assessment of Protein Docking Models Based on Graph Neural Network
Authors: Han Ye , He Fei , Chen Yongbing , Qin Wenyuan , Yu Helong , Xu Dong
Published: August 2021

Protein docking provides a structural basis for the design of drugs and vaccines. Among the processes of protein docking, quality assessment (QA) is utilized to pick near-native models from numerous protein docking candidate conformations, and it directly determines the final docking results. Although extensive efforts have been made to improve QA accuracy, it is still the bottleneck of current protein docking systems. In this paper, we presented a Deep Graph Attention Neural Network (DGANN) to evaluate and rank protein docking candidate models. DGANN learns inter-residue physio-chemical properties and structural fitness across the two protein monomers in a docking model and generates their probabilities of near-native models. On the ZDOCK decoy benchmark, our DGANN outperformed the ranking provided by ZDOCK in terms of ranking good models into the top selections. Furthermore, we conducted comparative experiments on an independent testing dataset, and the results also demonstrated the superiority and generalization of our proposed method.
Extremophilic Oxidoreductases for the Industry: Five Successful Examples With Promising Projections
Authors: Espina Giannina , Atalah Joaquín , Blamey Jenny M.
Published: August 2021

In a global context where the development of more environmentally conscious technologies is an urgent need, the demand for enzymes for industrial processes is on the rise. Compared to conventional chemical catalysts, the implementation of biocatalysis presents important benefits including higher selectivity, increased sustainability, reduction in operating costs and low toxicity, which translate into cleaner production processes, lower environmental impact as well as increasing the safety of the operating staff. Most of the currently available commercial enzymes are of mesophilic origin, displaying optimal activity in narrow ranges of conditions, which limits their actual application under industrial settings. For this reason, enzymes from extremophilic microorganisms stand out for their specific characteristics, showing higher stability, activity and robustness than their mesophilic counterparts. Their unique structural adaptations allow them to resist denaturation at high temperatures and salinity, remain active at low temperatures, function at extremely acidic or alkaline pHs and high pressure, and participate in reactions in organic solvents and unconventional media. Because of the increased interest to replace chemical catalysts, the global enzymes market is continuously growing, with hydrolases being the most prominent type of enzymes, holding approximately two-third share, followed by oxidoreductases. The latter enzymes catalyze electron transfer reactions and are one of the most abundant classes of enzymes within cells. They hold a significant industrial potential, especially those from extremophiles, as their applications are multifold. In this article we aim to review the properties and potential applications of five different types of extremophilic oxidoreductases: laccases, hydrogenases, glutamate dehydrogenases (GDHs), catalases and superoxide dismutases (SODs). This selection is based on the extensive experience of our research group working with these particular enzymes, from the discovery up to the development of commercial products available for the research market.
Effect of High Hydrostatic Pressure on Human Trabecular Bone Regarding Cell Death and Matrix Integrity
Authors: Waletzko-Hellwig Janine , Pohl Christopher , Riese Janik , Schlosser Michael , Dau Michael , Engel Nadja , Springer Armin , Bader Rainer
Published: August 2021

The reconstruction of critical size bone defects is still clinically challenging. Even though the transplantation of autologous bone is used as gold standard, this therapy is accompanied by donor site morbidities as well as tissue limitations. The alternatively used allografts, which are devitalized due to thermal, chemical or physical processing, often lose their matrix integrity and have diminished biomechanical properties. High Hydrostatic Pressure (HHP) may represent a gentle alternative to already existing methods since HHP treated human osteoblasts undergo cell death and HHP treated bone cylinders maintain their mechanical properties. The aim of this study was to determine the biological effects caused by HHP treatment regarding protein/matrix integrity and type of cell death in trabecular bone cylinders. Therefore, different pressure protocols (250 and 300 MPa for 10, 20 and 30 min) and end point analysis such as quantification of DNA-fragmentation, gene expression, SDS-PAGE, FESEM analysis and histological staining were performed. While both protein and matrix integrity was preserved, molecular biological methods showed an apoptotic differentiation of cell death for lower pressures and shorter applications (250 MPa for 10 and 20 min) and necrotic differentiation for higher pressures and longer applications (300 MPa for 30 min). This study serves as a basis for further investigation as it shows that HHP successfully devitalizes trabecular bone cylinders.
A Potential Method for Rapid Screening of Amphioxus Founder Harboring Germline Mutation and Transgene
Authors: Zou Jiaqi , Wu Xiaotong , Shi Chenggang , Zhong Yanhong , Zhang Lei , Yan Qiuning , Su Liuru , Li Guang
Published: August 2021

Amphioxus is a promising model organism for understanding the origin and evolution of vertebrates due to its basal phylogenetic position among chordates. We here compared the mutation efficacy and mutation type of tail tips and gametes of amphioxus founders injected with Cas9 protein and six different sgRNAs targeting five distinct genes, and revealed a strong correlation for mutation efficacy and a mild correlation for mutation type among the two tissues. In addition, we also observed a positive relationship between gene insertions observed in tail tips and gametes of amphioxus founders injected with Tol2 transposase and two different transgenic constructs. Finally, we showed that amphioxus larvae which had their tail tips cut at the 3–4 gill-slit stage were able to recover within 6 days and developed a normal number of gonads at the adult stage, and that F0 larvae carry similar mutation efficacy and type in the posterior end to that in the tail tips after their metamorphosis. Together, these findings suggest a great potential for obtaining valid amphioxus founders with desired mutations and transgenes at as early as the early larval stage, which will certainly speed up the generation of amphioxus mutants and transgenes and make it more cost- and labor-effective.
The Identification of the Metabolism Subtypes of Skin Cutaneous Melanoma Associated With the Tumor Microenvironment and the Immunotherapy
Authors: Yang Ronghua , Wang Zhengguang , Li Jiehua , Pi Xiaobing , Gao Runxing , Ma Jun , Qing Yi , Zhou Sitong
Published: August 2021

Skin cutaneous melanoma (SKCM) is a highly aggressive and resistant cancer with immense metabolic heterogeneity. Here, we performed a comprehensive examination of the diverse metabolic signatures of SKCM based on non-negative matrix factorization (NMF) categorization, clustering SKCM into three distinct metabolic subtypes (C1, C2, and C3). Next, we evaluated the metadata sets of the metabolic signatures, prognostic values, transcriptomic features, tumor microenvironment signatures, immune infiltration, clinical features, drug sensitivity, and immunotherapy response of the subtypes and compared them with those of prior publications for classification. Subtype C1 was associated with high metabolic activity, low immune scores, and poor prognosis. Subtype C2 displayed low metabolic activity, high immune infiltration, high stromal score, and high expression of immune checkpoints, demonstrating the drug sensitivity to PD-1 inhibitors. The C3 subtype manifested moderate metabolic activity, high enrichment in carcinogenesis-relevant pathways, high levels of CpG island methylator phenotype (CIMP), and poor prognosis. Eventually, a 90-gene classifier was produced to implement the SKCM taxonomy and execute a consistency test in different cohorts to validate its reliability. Preliminary validation was performed to ascertain the role of SLC7A4 in SKCM. These results indicated that the 90-gene signature can be replicated to stably identify the metabolic classification of SKCM. In this study, a novel SKCM classification approach based on metabolic gene expression profiles was established to further understand the metabolic diversity of SKCM and provide guidance on precisely targeted therapy to patients with the disease.
Class I PI3K Provide Lipid Substrate in T Cell Autophagy Through Linked Activity of Inositol Phosphatases
Authors: McLeod Ian X. , Saxena Ruchi , Carico Zachary , He You-Wen
Published: August 2021

Autophagy, a highly conserved intracellular process, has been identified as a novel mechanism regulating T lymphocyte homeostasis. Herein, we demonstrate that both starvation- and T cell receptor-mediated autophagy induction requires class I phosphatidylinositol-3 kinases to produce PI(3)P. In contrast, common gamma chain cytokines are suppressors of autophagy despite their ability to activate the PI3K pathway. T cells lacking the PI3KI regulatory subunits, p85 and p55, were almost completely unable to activate TCR-mediated autophagy and had concurrent defects in PI(3)P production. Additionally, T lymphocytes upregulate polyinositol phosphatases in response to autophagic stimuli, and the activity of the inositol phosphatases Inpp4 and SHIP are required for TCR-mediated autophagy induction. Addition of exogenous PI(3,4)P2 can supplement cellular PI(3)P and accelerate the outcome of activation-induced autophagy. TCR-mediated autophagy also requires internalization of the TCR complex, suggesting that this kinase/phosphatase activity is localized in internalized vesicles. Finally, HIV-induced bystander CD4+ T cell autophagy is dependent upon PI3KI. Overall, our data elucidate an important pathway linking TCR activation to autophagy, via induction of PI3KI activity and inositol phosphatase upregulation to produce PI(3)P.
Opposite Roles for ZEB1 and TMEJ in the Regulation of Breast Cancer Genome Stability
Authors: Prodhomme Mélanie K. , Péricart Sarah , Pommier Roxane M. , Morel Anne-Pierre , Brunac Anne-Cécile , Franchet Camille , Moyret-Lalle Caroline , Brousset Pierre , Puisieux Alain , Hoffmann Jean-Sébastien , Tissier Agnès
Published: August 2021

Breast cancer cells frequently acquire mutations in faithful DNA repair genes, as exemplified by BRCA-deficiency. Moreover, overexpression of an inaccurate DNA repair pathway may also be at the origin of the genetic instability arising during the course of cancer progression. The specific gain in expression of POLQ, encoding the error-prone DNA polymerase Theta (POLθ) involved in theta-mediated end joining (TMEJ), is associated with a characteristic mutational signature. To gain insight into the mechanistic regulation of POLQ expression, this review briefly presents recent findings on the regulation of POLQ in the claudin-low breast tumor subtype, specifically expressing transcription factors involved in epithelial-to-mesenchymal transition (EMT) such as ZEB1 and displaying a paucity in genomic abnormality.
Bioactive Films from Willow Bark Extract and Nanocellulose Double Network Hydrogels
Authors: Lohtander Tia , Grande Rafael , Österberg Monika , Laaksonen Päivi , Arola Suvi
Published: August 2021

In nature, the protection of sensitive components from external threats relies on the combination of physical barriers and bioactive secondary metabolites. Polyphenols and phenols are active molecules that protect organisms from physical and chemical threats such as UV irradiation and oxidative stress. The utilization of biopolymers and natural bioactive phenolic components as protective coating layers in packaging solutions would enable easier recyclability of materials and greener production process compared with the current plastic-based products. Herein, we produce a fully wood-based double network material with tunable bioactive and optical properties consisting of nanocellulose and willow bark extract. Willow bark extract, embedded in nanocellulose, was cross-linked into a polymeric nanoparticle network using either UV irradiation or enzymatic means. Based on rheological analysis, atomic force microscopy, antioxidant activity, and transmittance measurements, the cross-linking resulted in a double network gel with enhanced rheological properties that could be casted into optically active films with good antioxidant properties and tunable oxygen barrier properties. The purely biobased, sustainably produced, bioactive material described here broadens the utilization perspectives for wood-based biomass, especially wood-bark extractives. This material has potential in applications where biodegradability, UV shielding, and antioxidant properties of hydrogels or thin films are needed, for example in medical, pharmaceutical, food, and feed applications, but also as a functional barrier coating in packaging materials as the hydrogel properties are transferred to the casted and dried films.
Difference of Intrahost Dynamics of the Second Human Pegivirus and Hepatitis C Virus in HPgV-2/HCV-Coinfected Patients
Authors: Liang Yuanhao , Hu Fengyu , Fan Hang , Li Linghua , Wan Zhengwei , Wang Haiying , Shui Jingwei , Zhou Yuanping , Tong Yigang , Cai Weiping , Tang Shixing
Published: August 2021

Background

The second human pegivirus (HPgV-2) and hepatitis C virus (HCV) belong to the Flaviviridae family and share some common genome features. However, the two viruses exhibit significantly different genetic diversity. The comparison of intrahost dynamics of HPgV-2 and HCV that mainly reflect virus-host interactions is needed to elucidate their intrahost difference of genetic diversity and the possible mechanisms.

Methods

Intrahost single nucleotide variations (iSNVs) were identified by means of next-generation sequencing from both cross-sectional and longitudinal samples from HPgV-2- and HCV-coinfected patients. The levels of human cytokines were quantified in the patient before and after HCV elimination by the treatment of direct-acting antivirals (DAA).

Results

Unlike HCV, the viral sequences of HPgV-2 are highly conserved among HPgV-2-infected patients. However, iSNV analysis confirmed the intrahost variation or quasispecies of HPgV-2. Almost all iSNVs of HPgV-2 did not accumulate or transmit within host over time, which may explain the highly conserved HPgV-2 consensus sequence. Intrahost variation of HPgV-2 mainly causes nucleotide transition in particular at the 3rd codon position and synonymous substitutions, indicating purifying or negative selection posed by host immune system. Cytokine data further indicate that HPgV-2 infection alone may not efficiently stimulate innate immune responses since proinflammatory cytokine expression dramatically decreased with elimination of HCV.

Conclusion

This study provided new insights into the intrahost genomic variations and evolutionary dynamics of HPgV-2 as well as the impact of host immune selection and virus polymerase on virus evolution. The different genetic diversity of HPgV-2 and HCV makes HPgV-2 a potential new model to investigate RNA virus diversity and the mechanism of viral polymerase in modulating virus replication.
FABP3 Deficiency Exacerbates Metabolic Derangement in Cardiac Hypertrophy and Heart Failure via PPARα Pathway
Authors: Zhuang Lingfang , Mao Ye , Liu Zizhu , Li Chenni , Jin Qi , Lu Lin , Tao Rong , Yan Xiaoxiang , Chen Kang
Published: August 2021

Background: Cardiac hypertrophy was accompanied by various cardiovascular diseases (CVDs), and due to the high global incidence and mortality of CVDs, it has become increasingly critical to characterize the pathogenesis of cardiac hypertrophy. We aimed to determine the metabolic roles of fatty acid binding protein 3 (FABP3) on transverse aortic constriction (TAC)-induced cardiac hypertrophy.

Methods and Results: Transverse aortic constriction or Ang II treatment markedly upregulated Fabp3 expression. Notably, Fabp3 ablation aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction. Multi-omics analysis revealed that Fabp3-deficient hearts exhibited disrupted metabolic signatures characterized by increased glycolysis, toxic lipid accumulation, and compromised fatty acid oxidation and ATP production under hypertrophic stimuli. Mechanistically, FABP3 mediated metabolic reprogramming by directly interacting with PPARα, which prevented its degradation and synergistically modulated its transcriptional activity on Mlycd and Gck. Finally, treatment with the PPARα agonist, fenofibrate, rescued the pro-hypertrophic effects of Fabp3 deficiency.

Conclusions: Collectively, these findings reveal the indispensable roles of the FABP3–PPARα axis on metabolic homeostasis and the development of hypertrophy, which sheds new light on the treatment of hypertrophy.
Interpretation of Nitrogen Isotope Profiles in Petroleum Systems: A Review
Authors: Quan Tracy M. , Adeboye Oyeleye O.
Published: August 2021

Bulk sedimentary nitrogen isotope profiles are often used as proxies for depositional redox conditions, nitrogen cycling, and nutrient uptake in modern and ancient marine systems. The general preference in terms of analysis is that the sediments measured have undergone minimal thermal alteration, as post-depositional processes might have altered the initial δ15N signal, thus complicating the interpretation of these records. Although not a traditional proxy for petroleum evaluation purposes, recently the use of nitrogen isotopes in petroleum systems has been investigated as potential proxies to reconstruct paleoenvironmental conditions such as redox, and for organic matter evaluation. In this paper we review the use of nitrogen isotope data in petroleum systems, their interpretations, and factors that may complicate their use as proxies. We review the evidence for nitrogen isotopic fractionation during diagenesis, catagenesis, and fluid migration as determined by lab experiments, and how these might impact interpretation of δ15N data in petroleum systems. We also analyze the use and interpretation of δ15N data from petroleum-producing reservoir units, including unconventional reservoirs and lacustrine basins. Lastly, we discuss potential applications for nitrogen isotopes in petroleum systems with regards to their use as both geochemical proxies and as tools to evaluate petroleum reservoirs.
SEM Analyses of Fossilized Chondrocytes in the Extinct Birds Yanornis and Confuciusornis: Insights on Taphonomy and Modes of Preservation in the Jehol Biota
Authors: Bailleul Alida M. , Zhou Zhonghe
Published: August 2021

Calcified cartilage is a vertebrate tissue that has unique characteristics, such as a high percentage of calcification, avascularity and cells with apparently delayed autolytic processes after death. All of these factors suggest that fossilized cartilage may be favorable to exceptional cellular preservation, but little is known about chondrocyte fossilization overall in vertebrate paleontology. To further understand the spectrum of cellular preservation in this tissue, we analyze the morphology and the chemistry of some intralacunar content seen in previously published avian cartilage from the Early Cretaceous Jehol biota (in Yanornis and Confuciusornis). For this, we combine standard paleohistology with Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). To better identify some fossilized structures, we compare them with experimentally decayed and biofilm-invaded avian cartilage. Histological images of the cartilage of Yanornis show structures that resemble cell nuclei within chondrocyte lacunae. An SEM analysis on this cartilage shows that some lacunae are filled with a type of in vivo mineralization (similar to micropetrotic lacunae) and others are filled with small and spherical silicified cells surrounded by an amorphous carbonaceous material. These silicified cells apparently underwent postmortem cell shrinkage and do not constitute cell nuclei. Confuciusornis shows filamentous, non-spherical cells that are mostly made of silicon and carbon. This cell morphology does not resemble that of typical healthy chondrocytes, but based on comparison with decaying, biofilm-infiltrated chondrocyte lacunae from extant material, the most plausible conclusion is that the cells of Confuciusornis were partially autolyzed prior to their mineralization. In Yanornis and Confuciusornis respectively, silicification and alumino-silicification were responsible for chondrocyte preservation; while alumino-silicification and ironization occurred in their soft tissues. This shows that alumino-silicification is quite a common mechanism of cellular and soft-tissue preservation in the Jehol biota. Moreover, the two different chondrocyte morphologies (spherical and filamentous) apparently reflect two taphonomical histories, including different timings of postmortem permineralization (one rapid and one much more delayed). This type of analysis paired with more actuotaphonomy experiments will be needed in the future to better understand the preservation potential of chondrocytes and other cell types in the fossil record.
A FACS-Free Purification Method to Study Estrogen Signaling, Organoid Formation, and Metabolic Reprogramming in Mammary Epithelial Cells
Authors: Lacouture Aurélie , Jobin Cynthia , Weidmann Cindy , Berthiaume Line , Bastien Dominic , Laverdière Isabelle , Pelletier Martin , Audet-Walsh Étienne
Published: August 2021

Few in vitro models are used to study mammary epithelial cells (MECs), and most of these do not express the estrogen receptor α (ERα). Primary MECs can be used to overcome this issue, but methods to purify these cells generally require flow cytometry and fluorescence-activated cell sorting (FACS), which require specialized instruments and expertise. Herein, we present in detail a FACS-free protocol for purification and primary culture of mouse MECs. These MECs remain differentiated for up to six days with >85% luminal epithelial cells in two-dimensional culture. When seeded in Matrigel, they form organoids that recapitulate the mammary gland’s morphology in vivo by developing lumens, contractile cells, and lobular structures. MECs express a functional ERα signaling pathway in both two- and three-dimensional cell culture, as shown at the mRNA and protein levels and by the phenotypic characterization. Extracellular metabolic flux analysis showed that estrogens induce a metabolic switch favoring aerobic glycolysis over mitochondrial respiration in MECs grown in two-dimensions, a phenomenon known as the Warburg effect. We also performed mass spectrometry (MS)-based metabolomics in organoids. Estrogens altered the levels of metabolites from various pathways, including aerobic glycolysis, citric acid cycle, urea cycle, and amino acid metabolism, demonstrating that ERα reprograms cell metabolism in mammary organoids. Overall, we have optimized mouse MEC isolation and purification for two- and three-dimensional cultures. This model represents a valuable tool to study how estrogens modulate mammary gland biology, and particularly how these hormones reprogram metabolism during lactation and breast carcinogenesis.
Phalangeal Intra-Articular Osteochondroma Caused a Rare Clinodactyly Deformity in Children: Case Series and Literature Review
Authors: Hao Yun , Guo Jia-Chao , Wang Xiao-Lin , Shao Jing-Fan , Feng Jie-Xiong , He Jin-Peng
Published: August 2021

Background

Various factors are discovered in the development of clinodactyly. The purpose of this retrospective study was to present a group of children with a rare clinodactyly deformity caused by phalangeal intra-articular osteochondroma and evaluate the efficacy of various treatment methods.

Methods

All child patients that were treated for finger problems in our center between Jan 2017 and Dec 2020 were reviewed. A detailed analysis was made of the diagnosis and treatment methods in eight rare cases. X-rays and histopathology were applied.

Results

A preliminary analysis of 405 patients in total was performed, and we included eight cases in our final analysis. This cohort consisted of 2 girls and 6 boys, with a mean age of 5.74 ± 3.22 years (range: 2y5m to 11y). Overall, four patients had their right hand affected and four patients had their left hand affected. One patient was diagnosed as having hereditary multiple osteochondroma (HMO) while the other seven patients were all grouped into solitary osteochondroma. Osteochondroma was proven in all of them by histopathology examination. Preoperative X-rays were used to allow identification and surgery planning in all cases. All osteochondromas were intra-articular and in the distal end of the phalanges, which is located opposite the epiphyseal growth area. All of the osteochondromas developed in half side of the phalanges. The angulation in the finger long axis was measured, and resulted in a mean angulation of 34.63 ± 24.93 degree (range: 10.16-88.91 degree). All of them received surgery, resulting in good appearance and fingers straightening. No recurrence was recorded.

Conclusions

This retrospective analysis indicates that 10 degrees can be selected as the angulation level for diagnosis of clinodactyly deformities. What’s more important, the abnormal mass proven by X-rays should be included as the classical direct sign for diagnosis. The first choice of treatment is surgery in symptomatic osteochondromas.
Adipocyte-Endothelium Crosstalk in Obesity
Authors: Sabaratnam Rugivan , Svenningsen Per
Published: August 2021

Obesity is characterized by pathological adipose tissue (AT) expansion. While healthy AT expansion enhances systemic insulin sensitivity, unhealthy AT expansion through increased adipocyte size is associated with insulin resistance, fibrosis, hypoxia, and reduced adipose-derived adiponectin secretion. The mechanisms causing the unhealthy AT expansion are not fully elucidated; yet, dysregulated crosstalk between cells within the AT is an important contributor. Evidence from animal and human studies suggests a crucial role of the crosstalk between vascular endothelium (the innermost cell type in blood vessels) and adipocytes for metabolic homeostasis. Arterial endothelial cells are directly involved in maintaining normal organ functions through local blood flow regulation. The endothelial-dependent regulation of blood flow in AT is hampered in obesity, which negatively affects the adipocyte. Moreover, endothelial cells secrete extracellular vesicles (EVs) that target adipocytes in vivo. The endothelial EVs secretion is hampered in obesity and may be affected by the adipocyte-derived adipokine adiponectin. Adiponectin targets the vascular endothelium, eliciting organ-protective functions through binding to T-cadherin. The reduced obesity-induced adiponectin binding of T-cadherin reduces endothelial EV secretion. This affects endothelial health and cell-cell communication between AT cells and distant organs, influencing systemic energy homeostasis. This review focuses on the current understanding of endothelial and adipocyte crosstalk. We will discuss how obesity changes the AT environment and how these changes contribute to obesity-associated metabolic disease in humans. Particularly, we will describe and discuss the EV-dependent communication and regulation between adipocytes, adiponectin, and the endothelial cells regulating systemic energy homeostasis in health and metabolic disease in humans.
Beta Cell Function as a Baseline Predictor of Weight Loss After Bariatric Surgery
Authors: Borges-Canha Marta , Neves João Sérgio , Mendonça Fernando , Silva Maria Manuel , Costa Cláudia , M. Cabral Pedro , Guerreiro Vanessa , Lourenço Rita , Meira Patrícia , Salazar Daniela , Ferreira Maria João , Pedro Jorge , Barkoudah Ebrahim , Sande Ana , Lau Eva , B. Souto Selma , Preto John , Freitas Paula , Carvalho Davide
Published: August 2021

Background

Obesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain.

Aim

To evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity.

Methods

Retrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery).

Results

There were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (β = −1.04 [−1.82 to −0.26], p<0.01; β = −1.16 [−2.13 to −0.19], p=0.02; β = −1.29 [−2.64 to 0.06], p=0.061, respectively). This was not observed in the first year post-surgery nor for the other indexes. Glycemia at baseline was positively associated to EWL% at second and third years post-surgery.

Conclusion

β-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice.
Analysis of Human-Building Interactions in Office Environments: to What Extent Energy Saving Boundaries can be Displaced?
Authors: Zaidan Esmat , Ghofrani Ali , Dokaj Ernest
Published: August 2021

Building energy consumption can be enhanced to a certain level, but human-oriented dimensions can open the doors to new opportunities. This article presents an assessment on the interactions between human-driven factors and energy consumption patterns in office buildings based on empirical evidence and a co-simulation. The objective of this work is to evaluate a range for saving capacities as a result of readjusting occupants’ prior habits and engaging them in building operation by determining internal and external factors associated with human-building drivers, needs, actions, and systems. The study is based on a real office building, and according to real behavioral data and subjective measurement to analyze human attitudes and interactions with the building end-uses such as cooling, lighting, and equipment along with factors that directly impact energy use such as fenestrations and window blinds. The survey results are extensively investigated and the correlations between demographic/socioeconomic traits and behavioral factors are examined. The survey results are incorporated into a co-simulation testbed to represent occupant attitudes and behaviors and model human-building interactions accordingly. Different scenarios are designed to perform an assessment on the role of human factors such as attitude, awareness of consequences, habits, ascription of responsibility and personal/social norms on building energy end-uses. The outcomes of this study demonstrate that by adjusting behavioral factors in an office building, an energy saving between 9 and 18% can be achieved without sophisticated technology interface or building retrofit/upgrade. The results are elaborated, and recommendations are explained in detail.
A Systematic Review of Virtual Reality Applications for Automated Driving: 2009–2020
Authors: Riegler Andreas , Riener Andreas , Holzmann Clemens
Published: August 2021

While virtual reality (VR) interfaces have been researched extensively over the last decades, studies on their application in vehicles have only recently advanced. In this paper, we systematically review 12 years of VR research in the context of automated driving (AD), from 2009 to 2020. Due to the multitude of possibilities for studies with regard to VR technology, at present, the pool of findings is heterogeneous and non-transparent. We investigatedN= 176 scientific papers of relevant journals and conferences with the goal to analyze the status quo of existing VR studies in AD, and to classify the related literature into application areas. We provide insights into the utilization of VR technology which is applicable at specific level of vehicle automation and for different users (drivers, passengers, pedestrians) and tasks. Results show that most studies focused on designing automotive experiences in VR, safety aspects, and vulnerable road users. Trust, simulator and motion sickness, and external human-machine interfaces (eHMIs) also marked a significant portion of the published papers, however a wide range of different parameters was investigated by researchers. Finally, we discuss a set of open challenges, and give recommendation for future research in automated driving at the VR side of the reality-virtuality continuum.
Therapeutic Targeting of Nrf2 Signaling by Maggot Extracts Ameliorates Inflammation-Associated Intestinal Fibrosis in Chronic DSS-Induced Colitis
Authors: Wang Rong , Wang Daojuan , Wang Hongwei , Wang Tingyu , Weng Yajing , Zhang Yaling , Luo Yongzheng , Lu Yadong , Wang Yong
Published: August 2021

Intestinal fibrosis is induced by excessive myofibroblast proliferation and collagen deposition, which has been regarded as a general pathological feature in inflammatory bowel disease (IBD). Therefore, identifying clinical markers and targets to treat and prevent intestinal fibrosis is urgently needed. The traditional Chinese medicine maggot, commonly known as “wu gu chong”, has been shown to reduce oxidative stress and alleviate inflammation in chronic colitis. This study investigated the mechanisms underlying the effects of maggot extract (ME) on inflammation-associated intestinal fibrosis in TGF-β1-stimulated human intestinal fibroblasts (CCD-18Co cells) and dextran sodium sulphate (DSS)-induced chronic colitis murine model. To assess the severity of inflammation and fibrosis, histological and macroscopic evaluation were carried out. The results showed that ME was a significant inhibitor of body weight loss and colon length shortening in mice with chronic colitis. In addition, ME suppressed the intestinal fibrosis by downregulating TGF-β1/SMADs pathway via upregulation of Nrf2 expression at both protein and mRNA levels. ME markedly increased the expression of Nrf2, thus resulting in a higher level of HO-1. After treatment with Nrf2 inhibitor (ML385) or siRNA-Nrf2 for deactivating Nrf2 pathway, the protective effects of ME were abolished both in vitro and in vivo. Moreover, the histopathological results for the major organs of DSS mice treated with ME showed no signs of clinically important abnormalities. Treatment with ME had no effect on the viability of CCD-18Co cells, suggesting its low in vitro cytotoxicity. Furthermore, ME could mediate intestine health by keeping the balance of the gut microbes through the enhancement of beneficial microbes and suppression of pathogenic microbes. In conclusion, this is the first ever report demonstrating that ME ameliorates inflammation-associated intestinal fibrosis by suppressing TGF-β1/SMAD pathway via upregulation of Nrf2 expression. Our findings highlight the potential of Nrf2 as an effective therapeutic target for alleviating intestinal fibrosis.
Effects of Multiple Karenia brevis Red Tide Blooms on a Common Bottlenose Dolphin (Tursiops truncatus) Prey Fish Assemblage: Patterns of Resistance and Resilience in Sarasota Bay, Florida
Authors: Berens McCabe Elizabeth J. , Wells Randall S. , Toms Christina N. , Barleycorn Aaron A. , Wilkinson Krystan A. , Palubok Valeriy I.
Published: August 2021

Red tide blooms caused by the toxic dinoflagellate Karenia brevis are natural disturbance events that occur regularly along Florida’s west coast, often resulting in massive fish kills and marine mammal, seabird, and sea turtle mortalities. Limited prior work on the ecological effects of red tides suggests they play an important role in structuring ecosystem dynamics and regulating communities, however specific effects on prey populations and potential alterations to predator-prey interactions are unknown. We surveyed the prey fish assemblage of a top marine predator, the common bottlenose dolphin (Tursiops truncatus), in shallow seagrass habitat in Sarasota Bay, Florida, during 2004–2019, collecting data on prey density, species composition, K. brevis cell densities, and environmental variables. Across eight distinct red tide bloom events, resistance, resilience, and the ecological effects on the prey assemblage varied depending on bloom intensity, season, and frequency. Prey assemblage structure showed significant and distinct short-term shifts during blooms independent of the normal seasonal shifts in prey structure seen during non-bloom conditions. Canonical correspondence analysis indicated a strong influence of K. brevis density on assemblage structure. Blooms occurring primarily in the summer were associated with less initial prey resistance and higher than average annual catch per unit effort (CPUE) 1–3 years following bloom cessation, with bloom frequency prolonging the time needed to reach higher than average annual CPUE. Regardless of season, recovery to pre-bloom prey abundances occurred within 1 year. Sample-based rarefaction and extrapolation indicated significant differences in prey diversity among summer bloom events. This study is a first step in identifying differences in resistance, resilience, and the ecological effects of multiple red tide bloom events of various temporal scales and intensity on a dolphin prey assemblage. Improved understanding of the influence of red tides on estuarine structural dynamics and function can better inform management, and potentially guide mitigation efforts post-bloom.
A Constitutive Model of Clay Considering Structural Failure
Authors: Zhou Biaohe , Tang Bin , Kang Jiashuai
Published: August 2021

Due to the different material composition and deposition conditions, the undisturbed clay presents different degree of structure. Because of the existence of structure, the undisturbed clay has structural yield stress. When the stress level exceeds the structural yield stress, the stress-strain relation of undisturbed clay has typical softening characteristics. To explore the constitutive relation of undisturbed soil, triaxial consolidation, and drainage tests were carried out on undisturbed and remolded soils of structural clay in Zhanjiang Formation in China, and the stress-strain relations under different confining pressures were obtained. By analyzing the structural failure process of undisturbed clay, Weibull distribution was introduced to describe the strength distribution of each point in undisturbed clay, and the structural failure coefficient of undisturbed clay was established during the loading process. Based on the elastic theory and structural failure coefficient, a constitutive model considering the structural failure of clay was proposed, and the method to determine the model parameters was given. The model was used to simulate the experimental data in this paper and the reference, and the validity of the model was verified. The results show that the model can well simulate the softening effect of structural clay during loading.