bluuebunny/crossref_metadata_2025 huggingface dataset:
Monocolonization with Bacteroides ovatus protects immunodeficient SCID mice from mortality in chronic intestinal inflammation caused by long-lasting dextran sodium sulfate treatment
Authors: Hudcovic T , Kozáková H , Kolínská J , Štěpánková R , Hrnčíř T , Tlaskalová-Hogenová H
Published: February 2021

This study was aimed to evaluate the role of commensal Gramnegative bacterium Bacteroides ovatus in murine model of
chronic intestinal inflammation. The attempt to induce chronic
colitis was done in Bacteroides ovatus-monoassociated, germfree and conventional mice either in immunocompetent (BALB/c)
mice or in mice with severe combined immunodeficiency (SCID),
using 2.5 % dextran-sodium sulfate (DSS) in drinking water
(7 days DSS, 7 days water, 7 days DSS). Conventional mice
developed chronic colitis. Some of germ-free BALB/c and the
majority of germ-free SCID mice did not survive the long-term
treatment with DSS due to massive bleeding into the intestinal
lumen. However, monocolonization of germ-free mice of both
strains with Bacteroides ovatus prior to long-term treatment with
DSS protected mice from bleeding, development of intestinal
inflammation and precocious death. We observed that though
DSS-treated Bacteroides ovatus-colonized SCID mice showed
minor morphological changes in colon tissue, jejunal brushborder enzyme activities such as γ-glutamyltranspeptidase,
lactase and alkaline phosphatase were significantly reduced in
comparison with DSS-untreated Bacteroides ovatus-colonized
mice. This modulation of the enterocyte γ-glutamyltranspeptidase
localized to the brush border membrane has been described for
the first time. This enzyme is known to reflect an imbalance
between pro-oxidant and anti-oxidant mechanisms, which could
be involved in protective effects of colonization of germ-free mice
with Bacteroides ovatus against DSS injury.
Ischemic preconditioning fails to confer additional protection against ischemia-reperfusion injury in the hypothyroid rat heart
Authors: Mourouzis I , Dimopoulos A , Saranteas T , Tsinarakis N , Livadarou E , Spanou D , Kokkinos AD , Xinaris C , Pantos C , Cokkinos DV
Published: February 2021

There is accumulating evidence showing that ischemic
preconditioning (PC) may lose its cardioprotective effect in the
diseased states. The present study investigated whether PC can
be effective in hypothyroidism, a clinical condition which is
common and often accompanies cardiac diseases such as heart
failure and myocardial infarction. Hypothyroidism was induced in
rats by 3-week administration of 6n-propyl-2-thiouracil in water
(0.05 %). Normal and hypothyroid hearts (HYPO) were perfused
in Langendorff mode and subjected to 20 min of zero-flow global
ischemia and 45 min of reperfusion. A preconditioning protocol
(PC) was also applied prior to ischemia. HYPO hearts had
significantly improved post-ischemic recovery of left ventricular
developed pressure, end-diastolic pressure and reduced lactate
dehydrogenase release. Furthermore, phospho-JNK and p38
MAPK levels after ischemia and reperfusion were 4.0 and 3.0 fold
lower in HYPO as compared to normal hearts (P<0.05). A
different response to PC was observed in normal than in HYPO
hearts. PC improved the post-ischemic recovery of function and
reduced the extent of injury in normal hearts but had no
additional effect on the hypothyroid hearts. This response, in the
preconditioned normal hearts, resulted in 2.5 and 1.8 fold smaller
expression of the phospho-JNK and phospho-p38 MAPK levels at
the end of reperfusion, as compared to non-PC hearts (P<0.05),
while in HYPO hearts, no additional reduction in the
phosphorylation of these kinases was observed after PC.
Hypothyroid hearts appear to be tolerant to ischemia-reperfusion
injury. This response may be, at least in part, due to the downregulation of ischemia-reperfusion induced activation of JNKs and
p38 MAPK kinases. PC is not associated with further reduction in
the activation of these kinases in the hypothyroid hearts and fails
to confer added protection in those hearts.
Fibroblast growth factor 21: a novel metabolic regulator with potential therapeutic properties in obesity/type 2 diabetes mellitus
Authors: Dostálová I , Haluzíková D , Haluzík M
Published: February 2021

Fibroblast growth factor 21 (FGF21) is a novel metabolic
regulator produced primarily by the liver that exerts potent
antidiabetic and lipid-lowering effects in animal models of obesity
and type 2 diabetes mellitus. This hormone contributes to body
weight regulation and is strongly involved in the response to
nutritional deprivation and ketogenic state in mice. The principal
sites of metabolic actions of FGF21 are adipose tissue, liver and
pancreas. Experimental studies have shown marked
improvements in diabetes compensation and dyslipidemia after
FGF21 administration in diabetic mice and primates. Positive
metabolic actions of FGF21 without the presence of apparent side
effects make this factor a hot candidate to treat type 2 diabetes
and accompanying metabolic diseases. The aim of this review is
to summarize the current knowledge about the metabolic effects
of FGF21 including some preliminary data on changes of its levels
in humans with a special emphasis on its therapeutic potential in
type 2 diabetes mellitus.
Evaluación de un sistema de andamio móvil en condiciones de uso temporal
Authors: Tanner Peter , Hingorani Ramon , Soriano Rementeria Juan
Published: February 2021

Las normas estructurales actuales, como los Eurocódigos, no proporcionan un marco coherente para el diseño o evaluación de las estructuras en condiciones de uso temporal. Los requisitos de fiabilidad de los sistemas temporales propuestos en el presente estudio pretenden garantizar los mismos niveles de riesgo aceptables por unidad de tiempo que para las estructuras permanentes en las mejores prácticas actuales. Los resultados obtenidos muestran que el índice de fiabilidad para los elementos estructurales aumenta significativamente con la disminución de los tiempos de exposición al riesgo. Por el contrario, los valores de diseño para las acciones variables pueden reducirse en función de la duración de construcción, como se ilustra en un caso práctico: el análisis de un sistema de andamiaje móvil para el montaje de un puente.
Penentuan Centroid Awal Pada Algoritma K-Means Dengan Dynamic Artificial Chromosomes Genetic Algorithm Untuk Tuberculosis Dataset
Authors: Mursalim Mursalim , Purwanto Purwanto , Soeleman M Arief
Published: February 2021

Data merupakan hal penting diera sekarang begitu  juga dengan metode data mining yang dapat mengekstraksi data menghasilkan informasi. Klastering  1 dari 5 peran data mining yang berfungsi untuk mengelompokkan data berdasarkan tingkat kemiripan dan jarak minimum. Algoritma K-Means  termasuk algoritma yang populer banyak digunakan diberbagai bidang seperti bidang pendidikan, kesehatan, sosial, biologi, ilmu komputer. Seringkali metode K-Means dikombinasikan dengan metode optimasi seperti algoritma genetika untuk mengatasi permasalah pada K-Means yaitu sensitif dalam penentuan centroid awal .Namun metode algoritma genetika memiliki kekurangan yaitu mengalamai konvergen prematur sehingga hasil dari algorima genetika terjebak pada optimum lokal. Penelitian ini mengkombinasikan dynamic artificial cromosomes genetic algorithm dengan K-Means dalam menentukan nilai centroid awal pada k-means. Hasil eksperimen menunjukkan bahwa metode DAC GA + K-Means lebih unggul dibandingkan dengan K-Means dan GA + K-Means pada 2 dataset yang diuji dengan optimal nilai klaster sebanyak 2 dan 1 dataset sebanyak 3 klaster. Metode tersebut perolehan nilai DBI sebesar 0.138, 0.279 serta 0.382, nilai Sum Square Error sebesar 92.56, 332,39 dan 1280.68 serta nilai fitness yang tebentuk adalah 7.12, 3.57 dan 2.13.
Addressing Climate Change: What Can Plant Invasion Science and Weed Science Learn From Each Other?
Authors: Sun Yan , Kaleibar Behnaz Pourmorad , Oveisi Mostafa , Müller-Schärer Heinz
Published: February 2021

Plant invasion science and weed science, both dealing with harmful plants, have historically developed in separation. This may also be true for how the two fields are addressing the consequences of future climate change. Here, we first conducted a literature survey to explore how researchers in these two disciplines study the effects of climate change, and then identified their characteristic approaches to determine what the disciplines can learn from each other to better understand, predict, and mitigate the outcomes of responses of harmful plants to climate change. Over the past 20 years, we found a much steeper increase in publications dealing with climate change for invasive alien plants (IAP) than for weeds. However, invasion scientists have to date only rarely investigated climate change effects at the local scale, such as on functional traits and population dynamics. In contrast, weed science could benefit from studies at larger scale, such as using a modeling approach to predict changes in weed distributions. Studies assessing the impacts of the target plants on ecosystem properties and on society, and on their management under climate change are important components of weed studies but remain neglected for IAP. This is despite an urgent need, especially because under climate change, abandoned cropland, and areas of high conservation value are facing increasing risk from IAP. We argue that the strengths and diversity of approaches of these two disciplines in studying the effects of climate change are complementary and that closer ties between them would be highly beneficial for both.
Multiomics Data Collection, Visualization, and Utilization for Guiding Metabolic Engineering
Authors: Roy Somtirtha , Radivojevic Tijana , Forrer Mark , Marti Jose Manuel , Jonnalagadda Vamshi , Backman Tyler , Morrell William , Plahar Hector , Kim Joonhoon , Hillson Nathan , Garcia Martin Hector
Published: February 2021

Biology has changed radically in the past two decades, growing from a purely descriptive science into also a design science. The availability of tools that enable the precise modification of cells, as well as the ability to collect large amounts of multimodal data, open the possibility of sophisticated bioengineering to produce fuels, specialty and commodity chemicals, materials, and other renewable bioproducts. However, despite new tools and exponentially increasing data volumes, synthetic biology cannot yet fulfill its true potential due to our inability to predict the behavior of biological systems. Here, we showcase a set of computational tools that, combined, provide the ability to store, visualize, and leverage multiomics data to predict the outcome of bioengineering efforts. We show how to upload, visualize, and output multiomics data, as well as strain information, into online repositories for several isoprenol-producing strain designs. We then use these data to train machine learning algorithms that recommend new strain designs that are correctly predicted to improve isoprenol production by 23%. This demonstration is done by using synthetic data, as provided by a novel library, that can produce credible multiomics data for testing algorithms and computational tools. In short, this paper provides a step-by-step tutorial to leverage these computational tools to improve production in bioengineered strains.
A High-Efficiency Artificial Synthetic Pathway for 5-Aminovalerate Production From Biobased L-Lysine in Escherichia coli
Authors: Cheng Jie , Tu Wenying , Luo Zhou , Gou Xinghua , Li Qiang , Wang Dan , Zhou Jingwen
Published: February 2021

Bioproduction of 5-aminovalerate (5AVA) from renewable feedstock can support a sustainable biorefinery process to produce bioplastics, such as nylon 5 and nylon 56. In order to achieve the biobased production of 5AVA, a 2-keto-6-aminocaproate-mediated synthetic pathway was established. Combination of L-Lysine α-oxidase from Scomber japonicus, α-ketoacid decarboxylase from Lactococcus lactis and aldehyde dehydrogenase from Escherichia coli could achieve the biosynthesis of 5AVA from biobased L-Lysine in E. coli. The H2O2 produced by L-Lysine α-oxidase was decomposed by the expression of catalase KatE. Finally, 52.24 g/L of 5AVA were obtained through fed-batch biotransformation. Moreover, homology modeling, molecular docking and molecular dynamic simulation analyses were used to identify mutation sites and propose a possible trait-improvement strategy: the expanded catalytic channel of mutant and more hydrogen bonds formed might be beneficial for the substrates stretch. In summary, we have developed a promising artificial pathway for efficient 5AVA synthesis.
Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice
Authors: Sasaki Kazunori , Geribaldi-Doldán Noelia , Wu Qingqing , Davies Julie , Szele Francis G. , Isoda Hiroko
Published: February 2021

Much attention has recently been focused on nutraceuticals, with minimal adverse effects, developed for preventing or treating neurological diseases such as Alzheimer's disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae Aurantiochytrium sp. as a nutraceutical. To test neuroprotection by the ethanol extract of Aurantiochytrium (EEA) and a derivative, the n-Hexane layer of EEA (HEEA), amyloid-β-stimulated SH-SY5Y cells, was used as an in vitro AD model. We then assessed the potential enhancement of neurogenesis by EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to senescence-accelerated mouse-prone 8 (SAMP8) mice, a non-transgenic strain with accelerated aging and AD-like memory loss for evaluation of spatial learning and memory using the Morris water maze test. Finally, we performed immunohistochemical analysis for assessment of neurogenesis in mice administered EEA. Pretreatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, HEEA, ameliorated amyloid-β-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular adenosine triphosphate production. Moreover, EEA treatment significantly increased the number of neurospheres, whereas HEEA treatment significantly increased the number of β-III-tubulin+ young neurons and GFAP+ astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. EEA and HEEA decreased escape latency in the Morris water maze in SAMP8 mice, indicating improved memory. To detect stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU+ cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU+GFAP+ stem cells and their progeny, BrdU+NeuN+ mature neurons. In conclusion, our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against several age-related diseases, particularly AD.
High Dosages of Equine Chorionic Gonadotropin Exert Adverse Effects on the Developmental Competence of IVF-Derived Mouse Embryos and Cause Oxidative Stress-Induced Aneuploidy
Authors: Lin En , Li Zhiling , Huang Yue , Ru Gaizhen , He Pei
Published: February 2021

Gonadotropins play vital roles in the regulation of female reproductive ability and fertility. Our study aimed to determine the effects of superovulation induced by increasing doses of equine chorionic gonadotropin [eCG; also referred to as pregnant mare serum gonadotropin (PMSG)] on the developmental competence of mouse embryos and on aneuploidy formation during in vitro fertilization (IVF). eCG dose-dependently enhanced the oocyte yield from each mouse. Administration of 15 IU eCG significantly reduced the fertilization rate and the formation of four-cell embryos and blastocysts and increased the risk of chromosome aneuploidy. The IVF-derived blastocysts in the 15 IU eCG treatment group had the fewest total cells, inner cell mass (ICM) cells and trophectoderm (TE) cells. Moreover, more blastocysts and fewer apoptotic cells were observed in the 0, 5, and 10 IU eCG treatment groups than in the 15 IU eCG treatment group. We also investigated reactive oxygen species (ROS) levels and variations in several variables: mitochondrial membrane potential (MMP); active mitochondria; mitochondrial superoxide production; adenosine triphosphate (ATP) content; spindle structures; chromosome karyotypes; microfilament distribution; and the expression of Aurora B [an important component of the chromosomal passenger complex (CPC)], the spindle assembly checkpoint (SAC) protein mitotic arrest deficient 2 like 1 (MAD2L1), and the DNA damage response (DDR) protein γH2AX. Injection of 15 IU eCG increased ROS levels, rapidly reduced MMP, increased active mitochondria numbers and mitochondrial superoxide production, reduced ATP content, increased abnormal spindle formation rates, and induced abnormalities in chromosome number and microfilament distribution, suggesting that a high dose of eCG might alter developmental competence and exert negative effects on IVF-obtained mouse embryos. Additionally, the appearance of γH2AX and the significantly increased expression of Aurora B and MAD2L1 suggested that administration of relatively high doses of eCG caused Aurora B-mediated SAC activation triggered by ROS-induced DNA damage in early mouse IVF-derived embryos for self-correction of aneuploidy formation. These findings improve our understanding of the application of gonadotropins and provide a theoretical basis for gonadotropin treatment.
Change in the Single Amino Acid Site 83 in Rabies Virus Glycoprotein Enhances the BBB Permeability and Reduces Viral Pathogenicity
Authors: Li Chunfu , Wang Yongzhi , Liu Huiting , Zhang Xinghua , Baolige Dalai , Zhao Shihua , Hu Wei , Yang Yang
Published: February 2021

Lab-attenuated rabies virus (RABV) is a highly cellular adaptation and less pathogenic than wild-type RABV. However, the molecular mechanisms that regulate the cellular adaptation and pathogenicity remain obscure. In this work, we isolated a wild-type RABV (CNIM1701) from a rabid bovine in northern China. The original CNIM1701 was lethal in adult mice and restricted replication in cell cultures. After 20 serial passages in the brains of suckling mice, the virus was renamed CNIM1701-P20, which was safe in adult mice and replicated well in cell cultures. In addition, sequence comparison analysis of the original CNIM1701 and CNIM1701-P20 identified 2 amino acid substitutions on G protein (Lys83 → Arg83 and Pro367 → Ser 367) related to pathogenesis and cellular adaptation. Using site-directed mutagenesis to exchange Lys83 with Arg83 and Pro367 with Ser 367 in the G protein of the RABV SAD strain, the pathogenicity of rSAD-K83R was significantly decreased. Our data indicate that the decreased pathogenicity of rSAD-K83R is due to increasing the expression of RABV-G, which also induced a higher level of apoptosis in infected cells. Furthermore, the K83 mutation induced high expression of MMP-2 and MMP-9 on DCs and promoted blood–brain barrier (BBB) permeability. These results demonstrate that the pathogenesis of RABV is partially dependent on G expression and BBB permeability, which may help in the design and development of highly safe, live-RABV vaccines.
RETRACTED: Exosomal miR-128-3p Promotes Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells by Targeting FOXO4 via TGF-β/SMAD and JAK/STAT3 Signaling
Authors: Bai Jian , Zhang Xue , Shi Dongdong , Xiang Zhenxian , Wang Shuyi , Yang Chaogang , Liu Qing , Huang Sihao , Fang Yan , Zhang Weisong , Song Jialin , Xiong Bin
Published: February 2021

Epithelial-to-mesenchymal transition (EMT) is a key process that occurs during tumor metastasis, affecting a variety of malignancies including colorectal cancer (CRC). Exosomes mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including microRNAs (miRNAs). Exosomal delivery of miRNAs plays an important role in tumor initiation, development, and progression. In this study, we investigated the effect of exosomal transfer between CRC cells and aimed to identify specific miRNAs and downstream targets involved in EMT and metastasis in CRC cells. High expression of miR-128-3p was identified in exosomes derived from EMT-induced HCT-116 cells. Altered miR-128-3p expression in CRC cells led to distinct changes in proliferation, migration, invasion, and EMT. Mechanistically, miR-128-3p overexpression downregulated the expression of FOXO4 and induced the activation of TGF-β/SMAD and JAK/STAT3 signaling in CRC cells and xenografted tumors, which led to EMT. Clinically, high expression of miR-128-3p was significantly associated with perineural invasion, lymphovascular invasion, tumor stage, and CA 19-9 content in CRC patients. We revealed that exosomal miR-128-3p regulates EMT by directly suppressing its downstream target gene FOXO4 to activate TGF-β/SMAD and JAK/STAT3 signaling, and the properties of the miR-128-3p/FOXO4 axis were horizontally transferred via exosomal delivery. In turn, exosomal miR-128-3p could be considered as a new therapeutic vehicle for CRC.
Eph-Ephrin Signaling Mediates Cross-Talk Within the Bone Microenvironment
Authors: Arthur Agnieszka , Gronthos Stan
Published: February 2021

Skeletal integrity is maintained through the tightly regulated bone remodeling process that occurs continuously throughout postnatal life to replace old bone and to repair skeletal damage. This is maintained primarily through complex interactions between bone resorbing osteoclasts and bone forming osteoblasts. Other elements within the bone microenvironment, including stromal, osteogenic, hematopoietic, endothelial and neural cells, also contribute to maintaining skeletal integrity. Disruption of the dynamic interactions between these diverse cellular systems can lead to poor bone health and an increased susceptibility to skeletal diseases including osteopenia, osteoporosis, osteoarthritis, osteomalacia, and major fractures. Recent reports have implicated a direct role for the Eph tyrosine kinase receptors and their ephrin ligands during bone development, homeostasis and skeletal repair. These membrane-bound molecules mediate contact-dependent signaling through both the Eph receptors, termedforward signaling, and through the ephrin ligands, referred to asreverse signaling. This review will focus on Eph/ ephrin cross-talk as mediators of hematopoietic and stromal cell communication, and how these interactions contribute to blood/ bone marrow function and skeletal integrity during normal steady state or pathological conditions.
Xanthine Oxidoreductase Is Involved in Chondrocyte Mineralization and Expressed in Osteoarthritic Damaged Cartilage
Authors: Nasi Sonia , Castelblanco Mariela , Chobaz Véronique , Ehirchiou Driss , So Alexander , Bernabei Ilaria , Kusano Teruo , Nishino Takeshi , Okamoto Ken , Busso Nathalie
Published: February 2021

Pathologic calcification of cartilage consists of the formation of basic calcium phosphate (BCP) and/or calcium pyrophosphate dihydrate (CPPD) containing calcium crystals in mature hyaline or articular cartilage and is associated with aging, cartilage injury and likely plays a role in accelerating the pathology of osteoarthritis (OA). The pathways regulating joint calcification, in particular cartilage calcification, are not completely understood, but inflammation and the formation of reactive oxygen species (ROS) are contributory factors. The xanthine oxidase (XO) form of xanthine oxidoreductase (XOR), the key enzyme in xanthine and uric acid metabolism, is a major cellular source of superoxide. We hypothesized that XOR could be implicated in chondrocyte mineralization and cartilage calcification and degradation in OA. We showed both in murine primary chondrocyte and chondrogenic ATDC5 cells, that mineralization was inhibited by two different XOR inhibitors, febuxostat and allopurinol. In addition, XOR inhibition reduced the expression of the pro-mineralizing cytokine interleukin-6 (IL-6). We next generated XOR knock-out chondrocyte cell lines with undetectable XOR expression and XO activity. XOR knock-out chondrocyte cells showed decreased mineralization and reduced alkaline phosphatase (Alp) activity. To assess the precise form of XOR involved, primary chondrocytes of XOR mutant mice expressing either the XDH form (XDH ki) or the XO form (XO ki) were studied. We found that XO ki chondrocytes exhibited increased mineralization compared to XDH ki chondrocytes, and this was associated with enhanced Alp activity, ROS generation and IL-6 secretion. Finally, we found increased XOR expression in damaged vs. undamaged cartilage obtained from OA patients and XOR expression partially co-localized with areas showing pathologic calcification. Altogether, our results suggest that XOR, via its XO form, contribute to chondrocyte mineralization and pathological calcification in OA cartilage.
Effect of Quercetin on Lipids Metabolism Through Modulating the Gut Microbial and AMPK/PPAR Signaling Pathway in Broilers
Authors: Wang Mi , Wang Bo , Wang Shanshan , Lu Han , Wu Hao , Ding Manyi , Ying Linlin , Mao Yanjun , Li Yao
Published: February 2021

The present study was conducted to investigate effects and mechanism of quercetin on lipids metabolism in broilers. 480 AA broilers were randomly allotted to four treatments (0, 0.2, 0.4, and 0.6 g/kg quercetin) for 42 days. Compared with the control, 0.6 g/kg quercetin significantly decreased percentage of abdominal fat (P < 0.05); 0.2, 0.4, and 0.6 g/kg quercetin significantly decreased relative abundance of Lachnospiraceae and Desulfovibrionaceae (P < 0.05, P < 0.05, P < 0.01; P < 0.01, P < 0.01, P < 0.01); 0.2 g/kg quercetin significantly increased mRNA expression of PI3K, AMPKα1, AMPKα2, AMPKβ2, LKB1 (P < 0.01, P < 0.01, P < 0.05, P < 0.01, P < 0.05), and significantly reduced mRNA expression of SREBP1 and PPARγ (P < 0.01, P < 0.05); 0.4 g/kg quercetin significantly increased mRNA expression of LKB1 and PKB (P < 0.05, P < 0.01) and significantly reduced mRNA expression of ACC, HMGR, PPARγ, and SREBP1 (P < 0.05, P < 0.01, P < 0.01, P < 0.01); 0.6 g/kg quercetin significantly increased mRNA expression of AMPKγ, LKB1, CPT1, PPARα, PKB (P < 0.01, P < 0.01, P < 0.01, P < 0.05, P < 0.05), and significantly reduced the mRNA expression of PI3K, ACC, HMGR, PPARγ, SREBP1 (P < 0.05, P < 0.05, P < 0.01, P < 0.01, P < 0.01); 0.2 g/kg quercetin significantly increased protein expression of AMPK (P < 0.01); 0.6 g/kg quercetin significantly increased protein expression of LKB1 (P < 0.01), 0.2 and 0.6 g/kg quercetin significantly increased protein expression of PI3K, PKB, CPT1 (P < 0.05, P < 0.01, P < 0.05, P < 0.01, P < 0.01, P < 0.01), and significantly reduced protein expression of ACC and SREBP1 (P < 0.01, P < 0.01, P < 0.01, P < 0.01). In conclusion, quercetin improved lipid metabolism by modulating gut microbial and AMPK/PPAR signaling pathway in broilers.
SNFIMCMDA: Similarity Network Fusion and Inductive Matrix Completion for miRNA–Disease Association Prediction
Authors: Li Lei , Gao Zhen , Zheng Chun-Hou , Wang Yu , Wang Yu-Tian , Ni Jian-Cheng
Published: February 2021

MicroRNAs (miRNAs) that belong to non-coding RNAs are verified to be closely associated with several complicated biological processes and human diseases. In this study, we proposed a novel model that was Similarity Network Fusion and Inductive Matrix Completion for miRNA-Disease Association Prediction (SNFIMCMDA). We applied inductive matrix completion (IMC) method to acquire possible associations between miRNAs and diseases, which also could obtain corresponding correlation scores. IMC was performed based on the verified connections of miRNA–disease, miRNA similarity, and disease similarity. In addition, miRNA similarity and disease similarity were calculated by similarity network fusion, which could masterly integrate multiple data types to obtain target data. We integrated miRNA functional similarity and Gaussian interaction profile kernel similarity by similarity network fusion to obtain miRNA similarity. Similarly, disease similarity was integrated in this way. To indicate the utility and effectiveness of SNFIMCMDA, we both applied global leave-one-out cross-validation and five-fold cross-validation to validate our model. Furthermore, case studies on three significant human diseases were also implemented to prove the effectiveness of SNFIMCMDA. The results demonstrated that SNFIMCMDA was effective for prediction of possible associations of miRNA–disease.
Sulforaphane Protects Against Ethanol-Induced Apoptosis in Human Neural Crest Cells Through Diminishing Ethanol-Induced Hypermethylation at the Promoters of the Genes Encoding the Inhibitor of Apoptosis Proteins
Authors: Li Yihong , Fan Huadong , Yuan Fuqiang , Lu Lanhai , Liu Jie , Feng Wenke , Zhang Huang-Ge , Chen Shao-Yu
Published: February 2021

The neural crest cell (NCC) is a multipotent progenitor cell population that is sensitive to ethanol and is implicated in the Fetal Alcohol Spectrum Disorders (FASD). Studies have shown that sulforaphane (SFN) can prevent ethanol-induced apoptosis in NCCs. This study aims to investigate whether ethanol exposure can induce apoptosis in human NCCs (hNCCs) through epigenetically suppressing the expression of anti-apoptotic genes and whether SFN can restore the expression of anti-apoptotic genes and prevent apoptosis in ethanol-exposed hNCCs. We found that ethanol exposure resulted in a significant increase in the expression of DNMT3a and the activity of DNMTs. SFN treatment diminished the ethanol-induced upregulation of DNMT3a and dramatically reduced the activity of DNMTs in ethanol-exposed hNCCs. We also found that ethanol exposure induced hypermethylation at the promoter regions of two inhibitor of apoptosis proteins (IAP), NAIP and XIAP, in hNCCs, which were prevented by co-treatment with SFN. SFN treatment also significantly diminished ethanol-induced downregulation of NAIP and XIAP in hNCCs. The knockdown of DNMT3a significantly enhanced the effects of SFN on preventing the ethanol-induced repression of NAIP and XIAP and apoptosis in hNCCs. These results demonstrate that SFN can prevent ethanol-induced apoptosis in hNCCs by preventing ethanol-induced hypermethylation at the promoter regions of the genes encoding the IAP proteins and diminishing ethanol-induced repression of NAIP and XIAP through modulating DNMT3a expression and DNMT activity.
Running Against the Wnt: How Wnt/β-Catenin Suppresses Adipogenesis
Authors: de Winter Twan J. J. , Nusse Roeland
Published: February 2021

Mesenchymal stem cells (MSCs) give rise to adipocytes, osteocytes, and chondrocytes and reside in various tissues, including bone marrow and adipose tissue. The differentiation choices of MSCs are controlled by several signaling pathways, including the Wnt/β-catenin signaling. When MSCs undergo adipogenesis, they first differentiate into preadipocytes, a proliferative adipocyte precursor cell, after which they undergo terminal differentiation into mature adipocytes. These two steps are controlled by the Wnt/β-catenin pathway, in such a way that when signaling is abrogated, the next step in adipocyte differentiation can start. This sequence suggests that the main role of Wnt/β-catenin signaling is to suppress differentiation while increasing MSC and preadipocytes cell mass. During later steps of MSC differentiation, however, active Wnt signaling can promote osteogenesis instead of keeping the MSCs undifferentiated and proliferative. The exact mechanisms behind the various functions of Wnt signaling remain elusive, although recent research has revealed that during lineage commitment of MSCs into preadipocytes, Wnt signaling is inactivated by endogenous Wnt inhibitors. In part, this process is regulated by histone-modifying enzymes, which can lead to increased or decreased Wnt gene expression. The role of Wnt in adipogenesis, as well as in osteogenesis, has implications for metabolic diseases since Wnt signaling may serve as a therapeutic target.
Multifaceted Function of Myosin-18, an Unconventional Class of the Myosin Superfamily
Authors: Ouyang Zhaohui , Zhao Shuangshuang , Yao Su , Wang Jing , Cui Yanqin , Wei Ke , Jiu Yaming
Published: February 2021

Myosin is a diverse superfamily of motor proteins responsible for actin-based motility and contractility in eukaryotic cells. Myosin-18 family, including myosin-18A and myosin-18B, belongs to an unconventional class of myosin, which lacks ATPase motor activity, and the investigations on their functions and molecular mechanisms in vertebrate development and diseases have just been initiated in recent years. Myosin-18A is ubiquitously expressed in mammalian cells, whereas myosin-18B shows strong enrichment in striated muscles. Myosin-18 family is important for cell motility, sarcomere formation, and mechanosensing, mostly by interacting with other cytoskeletal proteins and cellular apparatus. Myosin-18A participates in several intracellular transport processes, such as Golgi trafficking, and has multiple roles in focal adhesions, stress fibers, and lamellipodia formation. Myosin-18B, on the other hand, participates in actomyosin alignment and sarcomere assembly, thus relating to cell migration and muscle contractility. Mutations of either Myo18a or Myo18b cause cardiac developmental defects in mouse, emphasizing their crucial role in muscle development and cardiac diseases. In this review, we revisit the discovery history of myosin-18s and summarize the evolving understanding of the molecular functions of myosin-18A and myosin-18B, with an emphasis on their separate yet closely related functions in cell motility and contraction. Moreover, we discuss the diseases tightly associated with myosin-18s, especially cardiovascular defects and cancer, as well as highlight the unanswered questions and potential future research perspectives on myosin-18s.
Bil2 Is a Novel Inhibitor of the Yeast Formin Bnr1 Required for Proper Actin Cable Organization and Polarized Secretion
Authors: Rands Thomas J. , Goode Bruce L.
Published: February 2021

Cell growth in budding yeast depends on rapid and on-going assembly and turnover of polarized actin cables, which direct intracellular transport of post-Golgi vesicles to the bud tip. Saccharomyces cerevisiae actin cables are polymerized by two formins, Bni1 and Bnr1. Bni1 assembles cables in the bud, while Bnr1 is anchored to the bud neck and assembles cables that specifically extend filling the mother cell. Here, we report a formin regulatory role for YGL015c, a previously uncharacterized open reading frame, which we have named Bud6 Interacting Ligand 2 (BIL2). bil2Δ cells display defects in actin cable architecture and partially-impaired secretory vesicle transport. Bil2 inhibits Bnr1-mediated actin filament nucleation in vitro, yet has no effect on the rate of Bnr1-mediated filament elongation. This activity profile for Bil2 resembles that of another yeast formin regulator, the F-BAR protein Hof1, and we find that bil2Δ with hof1Δ are synthetic lethal. Unlike Hof1, which localizes exclusively to the bud neck, GFP-Bil2 localizes to the cytosol, secretory vesicles, and sites of polarized cell growth. Further, we provide evidence that Hof1 and Bil2 inhibitory effects on Bnr1 are overcome by distinct mechanisms. Together, our results suggest that Bil2 and Hof1 perform distinct yet genetically complementary roles in inhibiting the actin nucleation activity of Bnr1 to control actin cable assembly and polarized secretion.
Dynamic Microtubule Arrays in Leukocytes and Their Role in Cell Migration and Immune Synapse Formation
Authors: Kopf Aglaja , Kiermaier Eva
Published: February 2021

The organization of microtubule arrays in immune cells is critically important for a properly operating immune system. Leukocytes are white blood cells of hematopoietic origin, which exert effector functions of innate and adaptive immune responses. During these processes the microtubule cytoskeleton plays a crucial role for establishing cell polarization and directed migration, targeted secretion of vesicles for T cell activation and cellular cytotoxicity as well as the maintenance of cell integrity. Considering this large spectrum of distinct effector functions, leukocytes require flexible microtubule arrays, which timely and spatially reorganize allowing the cells to accommodate their specific tasks. In contrast to other specialized cell types, which typically nucleate microtubule filaments from non-centrosomal microtubule organizing centers (MTOCs), leukocytes mainly utilize centrosomes for sites of microtubule nucleation. Yet, MTOC localization as well as microtubule organization and dynamics are highly plastic in leukocytes thus allowing the cells to adapt to different environmental constraints. Here we summarize our current knowledge on microtubule organization and dynamics during immune processes and how these microtubule arrays affect immune cell effector functions. We particularly highlight emerging concepts of microtubule involvement during maintenance of cell shape and physical coherence.
The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities
Authors: Amôr Nádia Ghinelli , Santos Paulo Sérgio da Silva , Campanelli Ana Paula
Published: February 2021

Squamous cell carcinoma (SCC) is the second most common skin cancer worldwide and, despite the relatively easy visualization of the tumor in the clinic, a sizeable number of SCC patients are diagnosed at advanced stages with local invasion and distant metastatic lesions. In the last decade, immunotherapy has emerged as the fourth pillar in cancer therapy via the targeting of immune checkpoint molecules such as programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). FDA-approved monoclonal antibodies directed against these immune targets have provide survival benefit in a growing list of cancer types. Currently, there are two immunotherapy drugs available for cutaneous SCC: cemiplimab and pembrolizumab; both monoclonal antibodies (mAb) that block PD-1 thereby promoting T-cell activation and/or function. However, the success rate of these checkpoint inhibitors currently remains around 50%, which means that half of the patients with advanced SCC experience no benefit from this treatment. This review will highlight the mechanisms by which the immune checkpoint molecules regulate the tumor microenvironment (TME), as well as the ongoing clinical trials that are employing single or combinatory therapeutic approaches for SCC immunotherapy. We also discuss the regulation of additional pathways that might promote superior therapeutic efficacy, and consequently provide increased survival for those patients that do not benefit from the current checkpoint inhibitor therapies.
Recent Progress of Novel Electrochemiluminescence Nanoprobes and Their Analytical Applications
Authors: Zhang Shiyu , Liu Yang
Published: February 2021

High-performance nanomaterials have been seen as a new generation of electrochemiluminescence (ECL) probes or emitters for their finely tunable structure and concomitant remarkable properties, guaranteeing the prospective applications in the analysis and diagnosis devices with superior performances. The structure–activity relationships of ECL nanoprobes in nanoscale are presenting milestone in understanding of the ECL microscopic behaviors and mechanisms, and guide the exploitation of novel ECL probes. In this mini-review, we summarized the recent development of novel ECL probes based on the nanomaterials. The mechanism and relationships between their structure as well as the active sites and functionality were revealed. In addition, the design and regulation of the ECL nanoprobes were emphasized for the biosensing and imaging application. Finally, the potential prospect of the ECL nanoprobes, design, and their applications were discussed.
Utilizing Ion Mobility-Mass Spectrometry to Investigate the Unfolding Pathway of Cu/Zn Superoxide Dismutase
Authors: Butler Karen E. , Takinami Yoshihiko , Rainczuk Adam , Baker Erin S. , Roberts Blaine R.
Published: February 2021

Native mass spectrometry has emerged as a powerful tool for structural biology as it enables the evaluation of molecules as they occur in their physiological conditions. Ion mobility spectrometry-mass spectrometry (IMS-MS) has shown essential in these analyses as it allows the measurement of the shape of a molecule, denoted as its collision cross section (CCS), and mass. The structural information garnered from native IMS-MS provides insight into the tertiary and quaternary structure of proteins and can be used to validate NMR or crystallographic X-ray structures. Additionally, due to the rapid nature (millisecond measurements) and ability of IMS-MS to analyze heterogeneous solutions, it can be used to address structural questions not possible with traditional structural approaches. Herein, we applied multiple solution conditions to systematically denature bovine Cu/Zn-superoxide dismutase (SOD1) and assess its unfolding pathway from the holo-dimer to the holo-monomer, single-metal monomer, and apo-monomer. Additionally, we compared and noted 1–2% agreement between CCS values from both drift tube IMS and trapped IMS for the SOD1 holo-monomer and holo-dimer. The observed CCS values were in excellent agreement with computational CCS values predicted from the homo-dimer crystal structure, showcasing the ability to use both IMS-MS platforms to provide valuable structural information for molecular modeling of protein interactions and structural assessments.
Informational Nudges to Encourage Pro-environmental Behavior: Examining Differences in Message Framing and Human Interaction
Authors: Nelson Katherine M. , Bauer Mirja Kristina , Partelow Stefan
Published: February 2021

Two natural field experiments were implemented to examine the influence of framing effects on environmental behavior. The first study examined plastic bag use at a convenience store using low cost nudges: an informational message on a sign and interpersonal communication at check-out. We employed a 3 × 2 treatment design (positive message vs. negative message vs. no sign; each paired with both asking for bag vs. not asking for bag) and report the observed plastic bag use behavior. A second study was conducted using a pre-snorkel briefing with two message frames–positive, negative, and no briefing (control). Environmentally damaging snorkel behavior was anonymously observed and recorded. Both experiments show the same general result: a significant and positive difference between subjects that were exposed to an intervention compared to those in the control conditions. However, we do not find significant differences in observed environmental behavior between the negative and positive framing.
Serum S100 Protein Is a Reliable Predictor of Brain Injury After Out-of-Hospital Cardiac Arrest: A Cohort Study
Authors: Kleissner Martin , Sramko Marek , Kohoutek Jan , Kautzner Josef , Kettner Jiri
Published: February 2021

Purpose: To evaluate serum S100 protein at hospital admission and after 48 h in early neuroprognostication of comatose survivors of out-of-hospital cardiac arrest (OHCA).

Methods: The study included 48 consecutive patients after OHCA, who survived for at least 72 h after the event. The patients were divided based on their best cerebral performance category (CPC) achieved over a 30 day follow-up period: favorable neurological outcome (CPC 1–2) vs. unfavorable neurological outcome (CPC 3–4). Predictors of an unfavorable neurological outcome were identified by multivariable regression analysis. Analysis of the receiver operating characteristic curve (ROC) was used to determine the cut-off value for S100, having a 0% false-positive prediction rate.

Results: Of the 48 patients, 30 (63%) had a favorable and 18 (38%) had an unfavorable neurological outcome. Eleven patients (23%) died over the 30 day follow-up. Increased S100 levels at 48 h after OHCA, but not the baseline S100 levels, were independently associated with unfavorable neurological outcome, with an area under the ROC curve of 0.85 (confidence interval 0.74–0.96). A 48 h S100 value ≥0.37 μg/L had a specificity of 100% and sensitivity of 39% in predicting an unfavorable 30 day neurological outcome.

Conclusion: This study showed that S100 values assessed 48 h after an OHCA could independently predict an unfavorable neurological outcome at 30 days.
Safety of Exercise Testing in the Clinical Chinese Population
Authors: Dun Yaoshan , Olson Thomas P. , Ripley-Gonzalez Jeffrey W. , Xie Kangling , Zhang Wenliang , Cai Ying , Liu Yuan , Shen Yanan , Zhou Nanjiang , Gong Xun , Liu Suixin
Published: February 2021

This 18-year cross-sectional study was conducted to provide data on the safety of exercise testing in the clinical Chinese population. We retrospectively identified exercise tests completed at Xiangya Hospital of Central South University from January 1, 2002 to December 31, 2019. From 43,130 unique individuals (50.9% female), a total of consecutive 50,142 tests (standard exercise testing 29,466; cardiopulmonary exercise testing 20,696) were retrieved. Demographics, patients' medical history, exercise testing characteristics, and exercise testing-related adverse events were described. Safety data is expressed as the number of adverse events per 10,000 tests, with 95% confidence interval. The average patients' age was 51 ± 13 years. The majority of patients were diagnosed with at least one disease (N = 44,941, 89.6%). Tests were maximal or symptom-limited. Common clinical symptoms included dizziness (6,822, 13.6%), chest pain or distress (2,760, 5.5%), and musculoskeletal limitations (2,507, 5.0%). Out of 50,142 tests, three adverse events occurred, including one sustained ventricular tachycardia, one sinus arrest with junctional escape rhythm at a rate of 28 bpm, and one syncopal event with fecal and urinary incontinence. The rate of adverse events was 0.8 events per 10,000 tests (95% confidence interval, 0.2–3.0) in men, 0.4 per 10,000 tests (0.7–2.2) in women, and 0.6 per 10,000 tests (0.21.8) total. This study represents the largest dataset analysis of exercise testing in the clinical Chinese population. Our results demonstrate that clinical exercise testing is safe, and the low rate of adverse events related to exercise testing might be due to the overall changes in clinical practice over time.
The 2002–2005 Changbaishan Volcanic Unrest Triggered by the 2002 M 7.2 Wangqing Deep Focus Earthquake
Authors: Liu Guoming , Li Chenyu , Peng Zhigang , Liu Yinan , Zhang Yu , Liu Dongyang , Zhang Maoliang , Pan Bo
Published: February 2021

One of the most active intraplate volcanoes in East Asia, Changbaishan volcano experienced unrest from July 2002 to July 2005. On 2002/06/28, the M 7.2 Wangqing deep-focus earthquake occurred ∼290 km northeast of Changbaishan volcano. While some studies have suggested a possible triggering relationship, the physical mechanism of such distant interaction is still not well understood. Using a template matching technique, which cross-correlates waveform of known events with continuous data, we perform systematic detection of microseismic events recorded by station CBS near Changbaishan volcano from July 1999 to July 2007. The detected earthquakes can be further categorized into three different types: volcano-tectonic (VT) events, long-period (LP) events and harmonic-spectra (HS) events. We detect 3763 VT events between July 2002 and July 2007. The intense VT earthquake swarm during the period from July 2002 to July 2005, along with recurring LPs and HSs and other geodetic/geochemical evidence, suggest magma movement during unrest. Compared with the hand-picked catalogue, the catalogue obtained by template matching technique reveals a delayed-triggering relationship between Wangqing deep-focus earthquake and unrest. The small magnitudes of the VT events and the limited numbers of LP and HS events suggest that the Wangqing mainshock likely triggered bubble excitation in the mid-crust magma system, resulting in overpressure and a small magma injection into the shallow magma chamber at a depth of ∼5 km, leading to the 3-years unrest.