bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Indicators of Human Activity During COVID-19 Period Using Digital Trace Data of Population Activities
Authors: Gao Xinyu , Fan Chao , Yang Yang , Lee Sanghyeon , Li Qingchun , Maron Mikel , Mostafavi Ali
Published: February 2021

The spread of pandemics such as COVID-19 is strongly linked to human activities. The objective of this article is to specify and examine early indicators of disease spread risk in cities during the initial stages of outbreak based on patterns of human activities obtained from digital trace data. In this study, the Venables distance (Dv) and the activity density (Da) are used to quantify and evaluate human activities for 193 United States counties, whose cumulative number of confirmed cases was greater than 100 as of March 31, 2020. Venables distance provides a measure of the agglomeration of the level of human activities based on the average distance of human activities across a city or a county (less distance could lead to a greater contact risk). Activity density provides a measure of level of overall activity level in a county or a city (more activity could lead to a greater risk). Accordingly, Pearson correlation analysis is used to examine the relationship between the two human activity indicators and the basic reproduction number in the following weeks. The results show statistically significant correlations between the indicators of human activities and the basic reproduction number in all counties, as well as a significant leader-follower relationship (time lag) between them. The results also show one to two weeks’ lag between the change in activity indicators and the decrease in the basic reproduction number. This result implies that the human activity indicators provide effective early indicators for the spread risk of the pandemic during the early stages of the outbreak. Hence, the results could be used by the authorities to proactively assess the risk of disease spread by monitoring the daily Venables distance and activity density in a proactive manner.
PTEN Reduces BMP9-Induced Osteogenic Differentiation Through Inhibiting Wnt10b in Mesenchymal Stem Cells
Authors: Li Fu-Shu , Li Pei-Pei , Li Ling , Deng Yan , Hu Ying , He Bai-Cheng
Published: February 2021

Bone morphogenetic protein 9 (BMP9) is one of the most efficacious osteogenic cytokines. PTEN and Wnt10b are both implicated in regulating the osteogenic potential of BMP9, but the potential relationship between them is unknown. In this study, we determined whether PTEN could reduce the expression of Wnt10b during the osteogenic process initialized by BMP9 in mesenchymal stem cells (MSCs) and the possible molecular mechanism. We find that PTEN is inhibited by BMP9 in MSCs, but Wnt10b is increased simultaneously. The BMP9-induced osteogenic markers are reduced by PTEN but increased by silencing PTEN. The effects of knockdown PTEN on elevating BMP9-induced osteogenic markers are almost abolished by knockdown of Wnt10b. On the contrary, the BMP9-increased ALP activities and mineralization are both inhibited by PTEN but almost reversed by the combination of Wnt10b. Bone masses induced by BMP9 are enhanced by knockdown of PTEN, which is reduced by knockdown of Wnt10b. The BMP9-increased Wnt10b is decreased by PTEN but enhanced by knockdown of PTEN. Meanwhile, the BMP9-induced Wnt10b is also reduced by a PI3K-specific inhibitor (Ly294002) or rapamycin, respectively. The BMP9-induced phosphorylation of CREB or Smad1/5/9 is also reduced by PTEN, but enhanced by PTEN knockdown. In addition, p-CREB interacts with p-Smad1/5/9 in MSCs, and p-CREB or p-Smad1/5/9 are both enriched at the promoter region of Wnt10b. Our findings indicate that inhibitory effects of PTEN on BMP9's osteogenic potential may be partially mediated through decreasing the expression of Wnt10b via the disturbance of interaction between CREB and BMP/Smad signaling.
Inflammation and Wnt Signaling: Target for Immunomodulatory Therapy?
Authors: Jridi Imen , Canté-Barrett Kirsten , Pike-Overzet Karin , Staal Frank J. T.
Published: February 2021

Wnt proteins comprise a large family of highly conserved glycoproteins known for their role in development, cell fate specification, tissue regeneration, and tissue homeostasis. Aberrant Wnt signaling is linked to developmental defects, malignant transformation, and carcinogenesis as well as to inflammation. Mounting evidence from recent research suggests that a dysregulated activation of Wnt signaling is involved in the pathogenesis of chronic inflammatory diseases, such as neuroinflammation, cancer-mediated inflammation, and metabolic inflammatory diseases. Recent findings highlight the role of Wnt in the modulation of inflammatory cytokine production, such as NF-kB signaling and in innate defense mechanisms as well as in the bridging of innate and adaptive immunity. This sparked the development of novel therapeutic treatments against inflammatory diseases based on Wnt modulation. Here, we summarize the role and function of the Wnt pathway in inflammatory diseases and focus on Wnt signaling as underlying master regulator of inflammation that can be therapeutically targeted.
A Candidate Prognostic Biomarker Complement Factor I Promotes Malignant Progression in Glioma
Authors: Cai Xiaomin , Qiu Wenjin , Qian Mengshu , Feng Shuang , Peng Chenghao , Zhang Jiale , Wang Yi , Wang Yuhai
Published: February 2021

Objectives: Glioma is the most common and aggressive type of primary central nervous system (CNS) tumor in adults and is associated with substantial mortality rates. The aim of our study was to evaluate the prognostic significance and function of the complement factor I (CFI) in glioma.

Materials and Methods: The expression levels of CFI in glioma tissues and the survival of the CFIhigh and CFIlow patient groups were analyzed using The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). The correlation between CFI expression and clinicopathological features of glioma was determined by univariate and multivariate Cox regression analyses in the Chinese Glioma Genome Atlas (CGGA) database. The functional role of CFI in glioma was established through routine in vitro and in vivo assays.

Results: CFI is overexpressed in glioma and its high levels correlated with poor outcomes in both TCGA and CGGA datasets. Furthermore, CFI was identified as an independent prognostic factor of glioma in the CGGA database. CFI knockdown in glioma cell lines inhibited growth in vitro and in vivo, whereas its ectopic expression increased glioma cell proliferation, migration, and invasion in vitro. CFI protein levels were also significantly higher in the glioma tissues resected from patients and correlated to worse prognosis.

Conclusions: CFI is a potential prognostic biomarker in glioma and drives malignant progression.
Long Non-coding RNA LINC01969 Promotes Ovarian Cancer by Regulating the miR-144-5p/LARP1 Axis as a Competing Endogenous RNA
Authors: Chen Jinxin , Li Xiaocen , Yang Lu , Zhang Jingru
Published: February 2021

Accumulating evidence has shown that long non-coding RNAs (lncRNAs) can be used as biological markers and treatment targets in cancer and play various roles in cancer-related biological processes. However, the lncRNA expression profiles and their roles and action mechanisms in ovarian cancer (OC) are largely unknown. Here, we assessed the lncRNA expression profiles in OC tissues from The Cancer Genome Atlas (TCGA) database, and one upregulated lncRNA, LINC01969, was selected for further study. LINC01969 expression levels in 41 patients were verified using quantitative real-time polymerase chain reaction (qRT-PCR). The in vitro effects of LINC01969 on OC cell migration, invasion, and proliferation were determined by the CCK-8, ethynyl-2-deoxyuridine (EdU), wound healing, and Transwell assays. Epithelial–mesenchymal transition (EMT) was evaluated using qRT-PCR and Western blotting. The molecular mechanisms of LINC01969 in OC were assessed through bioinformatics analysis, RNA-binding protein immunoprecipitation (RIP), dual luciferase reporter gene assays, and a rescue experiment. Finally, in vivo experiments were conducted to evaluate the functions of LINC01969. The results of the current study showed that LINC01969 was dramatically upregulated in OC, and patients with lower LINC01969 expression levels tended to have better overall survival. Further experiments demonstrated that LINC01969 promoted the migration, invasion, and proliferation of OC cells in vitro and sped up tumor growth in vivo. Additionally, LINC01969, which primarily exists in the cytoplasm, boosted LARP1 expression by sponging miR-144-5p and promoted the malignant phenotypes of OC cells. In conclusion, the LINC01969/miR-144-5p/LARP1 axis is a newly identified regulatory signaling pathway involved in OC progression.
Structural and Functional Dysbiosis of Fecal Microbiota in Chinese Patients With Alzheimer's Disease
Authors: Ling Zongxin , Zhu Manlian , Yan Xiumei , Cheng Yiwen , Shao Li , Liu Xia , Jiang Ruilai , Wu Shaochang
Published: February 2021

Increasing evidence suggests that gut dysbiosis plays vital roles in a variety of gut–brain disorders, such as Alzheimer's disease (AD). However, alterations of the gut microbiota as well as their correlations with cognitive scores and host immunity have remained unclear in well-controlled trials on Chinese AD patients. In this study, samples from 100 AD patients, and 71 age- and gender-matched, cognitively normal controls were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3–V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with clinical characteristics. Our data demonstrated a remarkably reduction in the bacterial diversity and alterations in the taxonomic composition of the fecal microbiota of the AD patients. Interestingly, the abundant butyrate-producing genera such as Faecalibacterium decreased significantly, where this was positively correlated with such clinical indicators as the MMSE, WAIS, and Barthel scores in the AD patients. On the contrary, abundant lactate-producing genera, such as Bifidobacterium, increased prominently, and were inversely correlated with these indicators. This shift in the gut dysbiosis of the microbiota, from being butyrate producers to lactate producers, contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the controls from the AD patients. Moreover, several predicted functional modules, including the biosynthesis and the metabolism of fatty acids, that were altered in the microbiota of the AD patients could be utilized by the bacteria to produce immunomodulatory metabolites. Our study established the structural and functional dysbiosis of fecal microbiota in AD patients, and the results suggest the potential for use of gut bacteria for the early, non-invasive diagnosis of AD, personalized treatment, and the development of tailor-made probiotics designed for Chinese AD patients.
Estrogen Receptor α Mediates Doxorubicin Sensitivity in Breast Cancer Cells by Regulating E-Cadherin
Authors: Wan Xiaoqing , Hou Jiaxin , Liu Shurong , Zhang Yanli , Li Wenqing , Zhang Yanru , Ding Yi
Published: February 2021

Anthracyclines resistance is commonly seen in patients with estrogen receptor α (ERα) positive breast cancer. Epithelial-mesenchymal transition (EMT), which is characterized with the loss of epithelial cell polarity, cell adhesion and acquisition of new invasive property, is considered as one of the mechanisms of chemotherapy-induced drug resistance. In order to identify factors that associated with doxorubicin resistance, we performed in vitro and in vivo experiments using human and mouse breast cancer cell lines with different ERα status. Cell survival experiments revealed that ERα-positive cells (MCF-7 and MCF-7/ADR cell lines), were less sensitive to doxorubicin than ERα-negative (MDA-MB-231, MDA-MB-468) cells, and mouse mammary carcinoma cells (4T-1). The expression of E-cadherin reduced in low-invasive ERα-positive MCF-7 cells after treatment with doxorubicin, indicating epithelial mesenchymal transition. In contrast, the expression of E-cadherin was upregulated in high-invasive ERα-negative cells, showing mesenchymal-epithelial transition (MET). Moreover, it was found that the growth inhibition of 4T-1 cells by doxorubicin was positively correlated with the expression of E-cadherin. In a mouse breast cancer xenograft model, E-cadherin was overexpressed in the primary tumor tissues of the doxorubicin-treated mice. In ERα-positive MCF-7 cells, doxorubicin treatment upregulated the expression of EMT-related transcription factors Snail and Twist, that regulate the expression of E-cadherin. Following overexpression of ERα in ERα-negative cells (MDA-MB-231 and MDA-MB-468), doxorubicin enhanced the upregulation of Snail and Twist, decreased expression of E-cadherin, and decreased the sensitivity of cells to doxorubicin. In contrast, inhibition of ERα activity increased the sensitivity to doxorubicin in ERα-positive MCF-7 cells. These data suggest that the regulation of Snail and/or Twist varies depends on different ERα status. Therefore, doxorubicin combined with anti-estrogen receptor α therapy could improve the treatment efficacy of doxorubicin in ERα-positive breast cancer.
The BMP2 Signaling Axis Promotes Invasive Differentiation of Human Trophoblasts
Authors: You Jiali , Wang Wei , Chang Hsun-Ming , Yi Yuyin , Zhao Hongjin , Zhu Hua , Sun Yu , Tang Minyue , Wang Chunyan , Sang Yimiao , Feng Guofang , Cheng Shaobing , Leung Peter C. K. , Zhu Yi-Min
Published: February 2021

Embryo implantation and trophoblast invasion are principal limiting factors of pregnancy establishment. Aberrant embryo development or improper trophoblast differentiation and invasion may lead to various unfavorable pregnancy-related outcomes, including early pregnancy loss (EPL). Our clinical data show that the serum BMP2 levels were significantly increased during the first trimester of pregnancy and that the serum and BMP2 expression levels were lower in women with EPL than in women with normal early pregnancies. Moreover, we observed that BMP2 was expressed in oocytes and trophoblast cells of cleaved embryos and blastocysts prior to implantation in both humans and mice. Exogenous BMP2 promoted embryonic development by enhancing blastocyst formation and hatching in mice. LncRNA NR026833.1 was upregulated by BMP2 and promoted SNAIL expression by competitively binding to miR-502-5p. SNAIL induced MMP2 expression and promoted cell invasion in primary extravillous trophoblast cells. BMP2 promotes the invasive differentiation of mouse trophoblast stem cells by downregulating the expression of TS cell marker and upregulating the expression of trophoblast giant cell marker and labyrinthine/spongiotrophoblast marker. Our findings provide significant insights into the regulatory roles of BMP2 in the development of the placenta, which may give us a framework to explore new therapeutic strategies to pregnancy-related complications.
Monocyte/Macrophage Lineage Cells From Fetal Erythromyeloid Progenitors Orchestrate Bone Remodeling and Repair
Authors: Yahara Yasuhito , Ma Xinyi , Gracia Liam , Alman Benjamin A.
Published: February 2021

A third of the population sustains a bone fracture, and the pace of fracture healing slows with age. The slower pace of repair is responsible for the increased morbidity in older individuals who sustain a fracture. Bone healing progresses through overlapping phases, initiated by cells of the monocyte/macrophage lineage. The repair process ends with remodeling. This last phase is controlled by osteoclasts, which are bone-specific multinucleated cells also of the monocyte/macrophage lineage. The slower rate of healing in aging can be rejuvenated by macrophages from young animals, and secreted proteins from macrophage regulate undifferentiated mesenchymal cells to become bone-forming osteoblasts. Macrophages can derive from fetal erythromyeloid progenitors or from adult hematopoietic progenitors. Recent studies show that fetal erythromyeloid progenitors are responsible for the osteoclasts that form the space in bone for hematopoiesis and the fetal osteoclast precursors reside in the spleen postnatally, traveling through the blood to participate in fracture repair. Differences in secreted proteins between macrophages from old and young animals regulate the efficiency of osteoblast differentiation from undifferentiated mesenchymal precursor cells. Interestingly, during the remodeling phase osteoclasts can form from the fusion between monocyte/macrophage lineage cells from the fetal and postnatal precursor populations. Data from single cell RNA sequencing identifies specific markers for populations derived from the different precursor populations, a finding that can be used in future studies. Here, we review the diversity of macrophages and osteoclasts, and discuss recent finding about their developmental origin and functions, which provides novel insights into their roles in bone homeostasis and repair.
Glycans and Glycan-Binding Proteins as Regulators and Potential Targets in Leukocyte Recruitment
Authors: Krautter Franziska , Iqbal Asif J.
Published: February 2021

Leukocyte recruitment is a highly controlled cascade of interactions between proteins expressed by the endothelium and circulating leukocytes. The involvement of glycans and glycan-binding proteins in the leukocyte recruitment cascade has been well-characterised. However, our understanding of these interactions and their regulation has expanded substantially in recent years to include novel lectins and regulatory pathways. In this review, we discuss the role of glycans and glycan-binding proteins, mediating the interactions between endothelium and leukocytes both directly and indirectly. We also highlight recent findings of key enzymes involved in glycosylation which affect leukocyte recruitment. Finally, we investigate the potential of glycans and glycan binding proteins as therapeutic targets to modulate leukocyte recruitment and transmigration in inflammation.
Effect of Physical Training on Exercise-Induced Inflammation and Performance in Mice
Authors: Barcellos Luiz Alexandre Medrado de , Gonçalves William Antonio , Esteves de Oliveira Marcos Paulo , Guimarães Juliana Bohnen , Queiroz-Junior Celso Martins , Resende Carolina Braga de , Russo Remo Castro , Coimbra Cândido Celso , Silva Albená Nunes , Teixeira Mauro Martins , Rezende Barbara Maximino , Pinho Vanessa
Published: February 2021

Acute exercise increases the amount of circulating inflammatory cells and cytokines to maintain physiological homeostasis. However, it remains unclear how physical training regulates exercise-induced inflammation and performance. Here, we demonstrate that acute high intensity exercise promotes an inflammatory profile characterized by increased blood IL-6 levels, neutrophil migratory capacity, and leukocyte recruitment to skeletal muscle vessels. Moreover, we found that physical training amplified leukocyte–endothelial cell interaction induced by acute exercise in skeletal muscle vessels and diminished exercise-induced inflammation in skeletal muscle tissue. Furthermore, we verified that disruption of the gp-91 subunit of NADPH-oxidase inhibited exercise-induced leukocyte recruitment on skeletal muscle after training with enhanced exercise time until fatigue. In conclusion, the training was related to physical improvement and immune adaptations. Moreover, reactive oxygen species (ROS) could be related to mechanisms to limit aerobic performance and its absence decreases the inflammatory response elicited by exercise after training.
TGF-β2 Reduces the Cell-Mediated Immunogenicity of Equine MHC-Mismatched Bone Marrow-Derived Mesenchymal Stem Cells Without Altering Immunomodulatory Properties
Authors: Berglund Alix K. , Long Julie M. , Robertson James B. , Schnabel Lauren V.
Published: February 2021

Allogeneic mesenchymal stem cells (MSCs) are a promising cell therapy for treating numerous diseases, but major histocompatibility complex (MHC)-mismatched MSCs can be rejected by the recipient’s immune system. Pre-treating MSCs with transforming growth factor-β2 (TGF-β2) to downregulate surface expression of MHC molecules may enhance the ability of allogeneic MSCs to evade immune responses. We used lymphocyte proliferation assays and ELISAs to analyze the immunomodulatory potential of TGF-β2-treated equine bone marrow-derived MSCs. T cell activation and cytotoxicity assays were then used to measure thein vitrocell-mediated immunogenicity. Similar to untreated MSCs, TGF-β2-treated MSCs inhibited T cell proliferation and did not stimulate MHC-mismatched T cells to proliferate. Additionally, similar quantities of prostaglandin E2 and TGF-β1 were detected in assays with untreated and TGF-β2-treated MSCs supporting that TGF-β2-treated MSCs retain their strong immunomodulatory propertiesin vitro. Compared to untreated MSCs, TGF-β2-treated MSCs induced less T cell activation and had reduced cell-mediated cytotoxicityin vitro. These results indicate that treating MSCs with TGF-β2 is a promising strategy to reduce the cell-mediated immunogenicity of MHC-mismatched MSCs and facilitate allogeneic MSC therapy.
Compartmentalization of Photoreceptor Sensory Cilia
Authors: Barnes Cassandra L. , Malhotra Himanshu , Calvert Peter D.
Published: February 2021

Functional compartmentalization of cells is a universal strategy for segregating processes that require specific components, undergo regulation by modulating concentrations of those components, or that would be detrimental to other processes. Primary cilia are hair-like organelles that project from the apical plasma membranes of epithelial cells where they serve as exclusive compartments for sensing physical and chemical signals in the environment. As such, molecules involved in signal transduction are enriched within cilia and regulating their ciliary concentrations allows adaptation to the environmental stimuli. The highly efficient organization of primary cilia has been co-opted by major sensory neurons, olfactory cells and the photoreceptor neurons that underlie vision. The mechanisms underlying compartmentalization of cilia are an area of intense current research. Recent findings have revealed similarities and differences in molecular mechanisms of ciliary protein enrichment and its regulation among primary cilia and sensory cilia. Here we discuss the physiological demands on photoreceptors that have driven their evolution into neurons that rely on a highly specialized cilium for signaling changes in light intensity. We explore what is known and what is not known about how that specialization appears to have driven unique mechanisms for photoreceptor protein and membrane compartmentalization.
Review on Stress Tolerance in Campylobacter jejuni
Authors: Kim Se-Hun , Chelliah Ramachandran , Ramakrishnan Sudha Rani , Perumal Ayyappasamy Sudalaiyadum , Bang Woo-Suk , Rubab Momna , Daliri Eric Banan-Mwine , Barathikannan Kaliyan , Elahi Fazle , Park Eunji , Jo Hyeon Yeong , Hwang Su-Bin , Oh Deog Hwan
Published: February 2021

Campylobacter spp. are the leading global cause of bacterial colon infections in humans. Enteropathogens are subjected to several stress conditions in the host colon, food complexes, and the environment. Species of the genus Campylobacter, in collective interactions with certain enteropathogens, can manage and survive such stress conditions. The stress-adaptation mechanisms of Campylobacter spp. diverge from other enteropathogenic bacteria, such as Escherichia coli, Salmonella enterica serovar Typhi, S. enterica ser. Paratyphi, S. enterica ser. Typhimurium, and species of the genera Klebsiella and Shigella. This review summarizes the different mechanisms of various stress-adaptive factors on the basis of species diversity in Campylobacter, including their response to various stress conditions that enhance their ability to survive on different types of food and in adverse environmental conditions. Understanding how these stress adaptation mechanisms in Campylobacter, and other enteric bacteria, are used to overcome various challenging environments facilitates the fight against resistance mechanisms in Campylobacter spp., and aids the development of novel therapeutics to control Campylobacter in both veterinary and human populations.
Detection of Species-Specific Lipids by Routine MALDI TOF Mass Spectrometry to Unlock the Challenges of Microbial Identification and Antimicrobial Susceptibility Testing
Authors: Solntceva Vera , Kostrzewa Markus , Larrouy-Maumus Gerald
Published: February 2021

MALDI-TOF mass spectrometry has revolutionized clinical microbiology diagnostics by delivering accurate, fast, and reliable identification of microorganisms. It is conventionally based on the detection of intracellular molecules, mainly ribosomal proteins, for identification at the species-level and/or genus-level. Nevertheless, for some microorganisms (e.g., for mycobacteria) extensive protocols are necessary in order to extract intracellular proteins, and in some cases a protein-based approach cannot provide sufficient evidence to accurately identify the microorganisms within the same genus (e.g., Shigella sp. vs E. coli and the species of the M. tuberculosis complex). Consequently lipids, along with proteins are also molecules of interest. Lipids are ubiquitous, but their structural diversity delivers complementary information to the conventional protein-based clinical microbiology matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) based approaches currently used. Lipid modifications, such as the ones found on lipid A related to polymyxin resistance in Gram-negative pathogens (e.g., phosphoethanolamine and aminoarabinose), not only play a role in the detection of microorganisms by routine MALDI-TOF mass spectrometry but can also be used as a read-out of drug susceptibility. In this review, we will demonstrate that in combination with proteins, lipids are a game-changer in both the rapid detection of pathogens and the determination of their drug susceptibility using routine MALDI-TOF mass spectrometry systems.
The Absence of Gut Microbiota Alters the Development of the Apicomplexan Parasite Eimeria tenella
Authors: Gaboriaud Pauline , Sadrin Guillaume , Guitton Edouard , Fort Geneviève , Niepceron Alisson , Lallier Nathalie , Rossignol Christelle , Larcher Thibaut , Sausset Alix , Guabiraba Rodrigo , Silvestre Anne , Lacroix-Lamandé Sonia , Schouler Catherine , Laurent Fabrice , Bussière Françoise I.
Published: February 2021

Coccidiosis is a widespread intestinal disease of poultry caused by a parasite of the genus Eimeria. Eimeria tenella, is one of the most virulent species that specifically colonizes the caeca, an organ which harbors a rich and complex microbiota. Our objective was to study the impact of the intestinal microbiota on parasite infection and development using an original model of germ-free broilers. We observed that germ-free chickens presented significantly much lower load of oocysts in caecal contents than conventional chickens. This decrease in parasite load was measurable in caecal tissue by RT-qPCR at early time points. Histological analysis revealed the presence of much less first (day 2pi) and second generation schizonts (day 3.5pi) in germ-free chickens than conventional chickens. Indeed, at day 3.5pi, second generation schizonts were respectively immature only in germ-free chickens suggesting a lengthening of the asexual phase of the parasite in the absence of microbiota. Accordingly to the consequence of this lengthening, a delay in specific gamete gene expressions, and a reduction of gamete detection by histological analysis in caeca of germ-free chickens were observed. These differences in parasite load might result from an initial reduction of the excystation efficiency of the parasite in the gut of germ-free chickens. However, as bile salts involved in the excystation step led to an even higher excystation efficiency in germ-free compared to conventional chickens, this result could not explain the difference in parasite load. Interestingly, when we shunted the excystation step in vivo by infecting chickens with sporozoites using the cloacal route of inoculation, parasite invasion was similar in germ-free and in conventional chickens but still resulted in significantly lower parasite load in germ-free chickens at day 7pi. Overall, these data highlighted that the absence of intestinal microbiota alters E. tenella replication. Strategies to modulate the microbiota and/or its metabolites could therefore be an alternative approach to limit the negative impact of coccidiosis in poultry.
Developing a Modeling Framework to Simulate Compound Flooding: When Storm Surge Interacts With Riverine Flow
Authors: Loveland Mark , Kiaghadi Amin , Dawson Clint N. , Rifai Hanadi S. , Misra Shubhra , Mosser Helena , Parola Alessandro
Published: February 2021

Compound flooding is a physical phenomenon that has become more destructive in recent years. Moreover, compound flooding is a broad term that envelops many different physical processes that can range from preconditioned, to multivariate, to temporally compounding, or spatially compounding. This research aims to analyze a specific case of compound flooding related to tropical cyclones where the compounding effect is on coastal flooding due to a combination of storm surge and river discharge. In recent years, such compound flood events have increased in frequency and magnitude, due to a number of factors such as sea-level rise from warming oceans. Therefore, the ability to model such events is of increasing urgency. At present, there is no holistic, integrated modeling system capable of simulating or forecasting compound flooding on a large regional or global scale, leading to the need to couple various existing models. More specifically, two more challenges in such a modeling effort are determining the primary model and accounting for the effect of adjacent watersheds that discharge to the same receiving water body in amplifying the impact of compound flooding from riverine discharge with storm surge when the scale of the model includes an entire coastal line. In this study, we investigated the possibility of using the Advanced Circulation (ADCIRC) model as the primary model to simulate the compounding effects of fluvial flooding and storm surge via loose one-way coupling with gage data through internal time-dependent flux boundary conditions. The performance of the ADCIRC model was compared with the Hydrologic Engineering Center- River Analysis System (HEC-RAS) model both at the watershed and global scales. Furthermore, the importance of including riverine discharges and the interactions among adjacent watersheds were quantified. Results showed that the ADCIRC model could reliably be used to model compound flooding on both a watershed scale and a regional scale. Moreover, accounting for the interaction of river discharge from multiple watersheds is critical in accurately predicting flood patterns when high amounts of riverine flow occur in conjunction with storm surge. Particularly, with storms such as Hurricane Harvey (2017), where river flows were near record levels, inundation patterns and water surface elevations were highly dependent on the incorporation of the discharge input from multiple watersheds. Such an effect caused extra and longer inundations in some areas during Hurricane Harvey. Comparisons with real gauge data show that adding internal flow boundary conditions into ADCIRC to account for river discharge from multiple watersheds significantly improves accuracy in predictions of water surface elevations during coastal flooding events.
Transitioning From Preclinical Evidence to Advanced Therapy Medicinal Product: A Spanish Experience
Authors: Gastelurrutia Paloma , Prat-Vidal Cristina , Vives Joaquim , Coll Ruth , Bayes-Genis Antoni , Gálvez-Montón Carolina
Published: February 2021

A systematic and ordered product development program, in compliance with current quality and regulatory standards, increases the likelihood of yielding a successful advanced therapy medicinal product (ATMP) for clinical use as safe and effective therapy. As this is a novel field, little accurate information is available regarding the steps to be followed, and the information to be produced to support the development and use of an ATMP. Notably, successful clinical translation can be somewhat cumbersome for academic researchers. In this article, we have provided a summary of the available information, supported by our experience in Spain throughout the development of an ATMP for myocardial infarction, from the pre-clinical stage to phase I clinical trial approval.
Digital Predictors of Morbidity, Hospitalization, and Mortality Among Older Adults: A Systematic Review and Meta-Analysis
Authors: Daniolou Sofia , Rapp Andreas , Haase Celina , Ruppert Alfred , Wittwer Marlene , Scoccia Pappagallo Alessandro , Pandis Nikolaos , Kressig Reto W. , Ienca Marcello
Published: February 2021

The widespread adoption of digital health technologies such as smartphone-based mobile applications, wearable activity trackers and Internet of Things systems has rapidly enabled new opportunities for predictive health monitoring. Leveraging digital health tools to track parameters relevant to human health is particularly important for the older segments of the population as old age is associated with multimorbidity and higher care needs. In order to assess the potential of these digital health technologies to improve health outcomes, it is paramount to investigate which digitally measurable parameters can effectively improve health outcomes among the elderly population. Currently, there is a lack of systematic evidence on this topic due to the inherent heterogeneity of the digital health domain and the lack of clinical validation of both novel prototypes and marketed devices. For this reason, the aim of the current study is to synthesize and systematically analyse which digitally measurable data may be effectively collected through digital health devices to improve health outcomes for older people. Using a modified PICO process and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework, we provide the results of a systematic review and subsequent meta-analysis of digitally measurable predictors of morbidity, hospitalization, and mortality among older adults aged 65 or older. These findings can inform both technology developers and clinicians involved in the design, development and clinical implementation of digital health technologies for elderly citizens.
Primary Pituitary Lymphoma in Immunocompetent Patients: A Report on Two Case Studies and the Review of Literature
Authors: Duan Lian , Liu Jie , Zhang Yan , Cui Lijia , Zhai Xiao , Pan Boju , Lu Lin , Pan Hui , Yao Yong , Zhu Huijuan
Published: February 2021

Primary pituitary lymphoma (PPL) represents an extremely rare entity. Here, we have reported two recently identified cases of immunocompetent PPL having diffuse large B-cell lymphoma by surgical biopsy. Both patients had hypopituitarism, with one patient developing right ptosis. In both patients, MRI and FDG-PET/CT depicted sellar mass that extended into the cavernous sinus with the right sphenoid also present in one of the patients. No systemic disease was found in these two patients. Surprisingly, we found that both patients had infiltrative lesions in sphenoid sinus mucosa pathologically, but the sphenoid bones that composed the sellar base were visually intact during the biopsy procedure. Chemotherapy was administered to both patients, where one patient achieved remission at the recent follow-up, whereas the other one did not respond to the treatment. The diagnosis of PPL is usually difficult if solely dependent on history, clinical presentation, biochemical indexes, and radiographic findings. We have also updated and reviewed the epidemiologic features, clinical presentations, pathological characteristics, potential mechanisms, therapeutic orientation, and prognostic advances of PPL. A total of 40 cases (including ours and four pediatric patients), histologically diagnosed, were analyzed in terms of clinical presentation, endocrine abnormality, radiological features, pathology, treatment, and follow-up. Hypopituitarism and headache were the most common presentation of PPL, while diabetes insipidus was reported in 13 patients (43.3%). B cell lymphoma was the most common type of pathology, followed by T-cell and NK/T cell. PPL was more invasive in nature at the suprasellar region (72.5%), cavernous sinus (52.5%), and sphenoidal sinus (27.5%) in 29, 21, and 11 patients, respectively. Pediatric patients with PPL seem to be different compared to their adult counterparts in terms of pathogenesis, clinical presentation, and radiological features. The management of PPL usually follows the treatment protocols for PCNSL but has a poor prognosis compared to the pituitary involvement of systemic lymphoma.
Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation
Authors: Liu Chien-Liang , Cheng Shih-Ping , Chen Ming-Jen , Lin Chi-Hsin , Chen Shan-Na , Kuo Yi-Hue , Chang Yuan-Ching
Published: February 2021

Perturbed Nicotinamide adenine dinucleotide (NAD+) homeostasis is involved in cancer progression and metastasis. Quinolinate phosphoribosyltransferase (QPRT) is the rate-limiting enzyme in the kynurenine pathway participating in NAD+ generation. In this study, we demonstrated that QPRT expression was upregulated in invasive breast cancer and spontaneous mammary tumors from MMTV-PyVT transgenic mice. Knockdown of QPRT expression inhibited breast cancer cell migration and invasion. Consistently, ectopic expression of QPRT promoted cell migration and invasion in breast cancer cells. Treatment with QPRT inhibitor (phthalic acid) or P2Y11 antagonist (NF340) could reverse the QPRT-induced invasiveness and phosphorylation of myosin light chain. Similar reversibility could be observed following treatment with Rho inhibitor (Y16), ROCK inhibitor (Y27632), PLC inhibitor (U73122), or MLCK inhibitor (ML7). Altogether, these results indicate that QPRT enhanced breast cancer invasiveness probably through purinergic signaling and might be a potential prognostic indicator and therapeutic target in breast cancer.
Signal Transduction Mechanisms for Glucagon-Induced Somatolactin Secretion and Gene Expression in Nile Tilapia (Oreochromis niloticus) Pituitary Cells
Authors: Zhang Chaoyi , Lian Anji , Xu Yue , Jiang Quan
Published: February 2021

Glucagon (GCG) plays a stimulatory role in pituitary hormone regulation, although previous studies have not defined the molecular mechanism whereby GCG affects pituitary hormone secretion. To this end, we identified two distinct proglucagons,GcgaandGcgb, as well as GCG receptors,GcgraandGcgrb, in Nile tilapia (Oreochromis niloticus). Using the cAMP response element (CRE)-luciferase reporter system, tilapia GCGa and GCGb could reciprocally activate the two GCG receptors expressed in human embryonic kidney 293 (HEK293) cells. Quantitative real-time PCR analysis revealed that differential expression of theGcgaandGcgband their cognate receptorsGcgraandGcgrbwas found in the various tissues of tilapia. In particular, theGcgrbis abundantly expressed in the neurointermediate lobe (NIL) of the pituitary gland. In primary cultures of tilapia NIL cells, GCGb effectively stimulated SL release, with parallel rises in the mRNA levels, and co-incubation with the GCG antagonist prevented GCGb-stimulated SL release. In parallel experiments, GCGb treatment dose-dependently enhanced intracellular cyclic adenosine monophosphate (cAMP) accumulation with increasing inositol 1,4,5-trisphosphate (IP3) concentration and the resulting in transient increases of Ca2+signals in the primary NIL cell culture. Using selective pharmacological approaches, the adenylyl cyclase (AC)/cAMP/protein kinase A (PKA) and phospholipase C (PLC)/IP3/Ca2+/calmodulin (CaM)/CaMK-II pathways were shown to be involved in GCGb-induced SL release and mRNA expression. Together, these results provide evidence for the first time that GCGb can act at the pituitary level to stimulate SL release and gene expressionviaGCGRb through the activation of the AC/cAMP/PKA and PLC/IP3/Ca2+/CaM/CaMK-II cascades.
Synergistic Improvement of Carbohydrate and Lignin Processability by Biomimicking Biomass Processing
Authors: Li Man , Liu Zhi-Hua , Hao Naijia , Olson Michelle L. , Li Qiang , Bhagia Samarthya , Shinde Somnath , Kao Katy C. , Ragauskas Arthur J. , Xie Shangxian , Yuan Joshua S.
Published: February 2021

The sustainability and economic feasibility of modern biorefinery depend on the efficient processing of both carbohydrate and lignin fractions for value-added products. By mimicking the biomass degradation process in white-rote fungi, a tailored two-step fractionation process was developed to maximize the sugar release from switchgrass biomass and to optimize the lignin processability for bioconversion. Biomimicking biomass processing using Formic Acid: Fenton: Organosolv (F2O) and achieved high processability for both carbohydrate and lignin. Specifically, switchgrass pretreated by the F2O process had 99.6% of the theoretical yield for glucose release. The fractionated lignin was also readily processable by fermentation via Rhodococcus opacus PD630 with a lipid yield of 1.16 g/L. Scanning electron microscope analysis confirmed the fragmentation of switchgrass fiber and the cell wall deconstruction by the F2O process. 2D-HSQC NMR further revealed the cleavage of aryl ether linkages (β-O-4) in lignin components. These results revealed the mechanisms for efficient sugar release and lignin bioconversion. The F2O process demonstrated effective mimicking of natural biomass utilization system and paved a new path for improving the lignin and carbohydrate processability in next generation lignocellulosic biorefinery.
The Impact of Innovation Activities, Foreign Direct Investment on Improved Green Productivity: Evidence From Developing Countries
Authors: Xu Sa , Li Zejun
Published: February 2021

This paper from the perspective of productivity changes examines the impact of innovation activities and foreign direct investment (FDI) on improved green productivity (IGP) in developing countries. We divide the sample into two sub-groups; the BRICS and the other developing countries so as to account for underlying country heterogeneity. The analysis follows a panel data approach over the period 1991 to 2014, and used the global Malmquist-Luenberger productivity index to measure IGP. The results indicate that IGP in developing countries has declined. Innovation activities have a positive impact on IGP. FDI has a significant negative impact on IGP. Further study finds that there are threshold effects between FDI and IGP based on innovation activities, when the developing countries with a low-level of innovation, FDI has a negative impact on IGP; when the developing countries innovation activities above the threshold, innovation activities and FDI both can promote IGP.
Science and Policy Interactions in Assessing and Managing Marine Ecosystems in the Southern Ocean
Authors: Press Anthony J.
Published: February 2021

Good policy can only be built and implemented using sound advice, and a clear understanding of risk. Scientific advice will often be qualified by the extent of research and knowledge, and uncertainties about the current and future state of the environment. Bodies tasked with protecting the Antarctic environment are required to make decisions based on the best available advice. To not take decisions in the absence of certainty is contrary to clear obligations to protect the Antarctic environment contained in the instruments of the Antarctic Treaty System. The risk of foreclosing future options to protect the environment by indecision is as great, if not greater, than making decisions with incomplete advice, and then actively managing that decision into the future. This “Perspective” explores the relationship between science and policy in the context of the Conference on Marine Ecosystem Assessment for the Southern Ocean held in 2018—it is a perspective from the view of a policy-maker and end user of scientific assessment and advice.
Importance of Small Forest Fragments in Agricultural Landscapes for Maintaining Orangutan Metapopulations
Authors: Ancrenaz Marc , Oram Felicity , Nardiyono Nardiyono , Silmi Muhammad , Jopony Marcie E. M. , Voigt Maria , Seaman Dave J. I. , Sherman Julie , Lackman Isabelle , Traeholt Carl , Wich Serge A. , Santika Truly , Struebig Matthew J. , Meijaard Erik
Published: February 2021

Historically, orangutans (Pongo spp.) lived in large contiguous areas of intact rainforest. Today, they are also found in highly modified and fragmented landscapes dominated by oil palm or industrial timber plantations; a situation that calls for new conservation approaches. Here we report signs of orangutan presence in more than 120 small forest fragments of <500 ha in size and isolated in extensive oil palm plantations across Borneo. We confirmed the long-term presence of adult resident females with dependent young in 42% of the fragments assessed by ground survey (n = 50), and the regular sightings of males traveling across the landscape. We argue that orangutans using and living in small isolated forest patches play an essential part in the metapopulation by maintaining gene flow among larger sub-populations distributed across multiple-use landscapes. In some cases, translocations may be necessary when the animals are in imminent danger of being killed and have no other refuge. However, the impacts of removing animals from spatially dispersed metapopulations could inadvertently decrease critical metapopulation functionality necessary for long-term viability. It is clear that orangutans need natural forest to survive. However, our findings show that forest fragments within agricultural landscapes can also complement conservation areas if they are well-distributed, properly connected and managed, and if orangutan killing is prevented. Efforts to better understand the dynamics and the functionality of an orangutan metapopulation in forest-farmland landscape mosaics characteristic of the Anthropocene are urgently needed to design more efficient conservation strategies for the species across its range.
The Efficacy and Safety of the mTOR Signaling Pathway Activator, MHY1485, for in vitro Activation of Human Ovarian Tissue
Authors: Wu Shuang , Wang Yining , Ding Haixiang , Sun Ningxia , Liu Yan , Wang Liang , Sheng Fei , Zhang Honghong , Yang Fu , Li Wen
Published: February 2021

Background

Premature ovarian insufficiency (POI) is characterized by abnormal ovarian function before the age of 40. POI showed that primordial follicles developed in disorder. mTOR signaling plays a vital role in the process of follicle development. It has been verified that the mTOR signaling pathway activator, MHY1485, can promote primordial follicle development in mice. We considered that MHY1485 would be a promising fertility preservation method for POI patients.

Methods

The fragmented ovarian tissues of normal woman was cultured with activator MHY1485in vitro, and then the control and activated ovaries were transplanted into the kidney capsules of ovariectomized mice. We then used the Infinium Human Methylation EPIC BeadChip to verify the DNA methylation level of ovarian tissues, thus exploring the effectiveness of them.

Results

MHY1485 stimulated mTOR, S6K1, and rpS6 phosphorylation. Cultured with MHY1485, ovarian weights increased and endocrine function was restored. The number of growing follicles was increased. Thein vitroactivation process did not induce histological changes or abnormal DNA methylation occurrence.

Conclusion

MHY1485 forin vitroactivation (IVA) is effective for ovarian rejuvenation and is a potential therapeutic treatment for POI patients.