bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of MAML1 inhibits proliferation and induces apoptosis of T‐cell acute lymphoblastic leukemia cells through SP1‐dependent inactivation of TRIM59
Authors: Cheng Hui , Chen Li , Hu Xiaoxia , Qiu Huiying , Xu Xiaoqian , Gao Lei , Tang Gusheng , Zhang Weiping , Wang Jianmin , Yang Jianmin , Huang Chongmei
Published: October 2018

Notch exerts important functions in cell proliferation, survival, and differentiation, which plays a critical role in tumor development when aberrantly activated. Mastermind‐like protein 1 (MAML1) has been functioning as crucial coactivators of Notch receptors and is required for stable formation of Notch transcriptional complexes. However, the mechanism whereby MAML1 induces T‐cell acute lymphoblastic leukemia (T‐ALL) tumorigenesis is largely unknown. The CCK‐8 and flow cytometry assay were performed to examine the effect of MAML1 knockdown on T‐ALL cell proliferation, apoptosis, and cell cycle. The expression of MAML1, cell cycle, and apoptosis‐related gene, as well as TRIM family members and specific protein 1 (SP1) was measured by western blot analysis and qPCR. Our results showed that MAML1 knockdown significantly inhibited cell proliferation and induced G0/G1 cell cycle arrest and apoptosis in Jurkat and MOLT‐4 cells. Cell cycle and apoptosis‐related gene expression, including CDK2, Bcl‐2, Bax, and Bad, was modified by the MAML1 knockdown. MAML1 knockdown obviously inhibited the CDK2 and Bcl‐2 expression and increased the Bax, p53, and Bad expression. Moreover, the TRIM family members, including TRIM13, TRIM32, TRIM44, and TRIM59, were significantly decreased by the MAML1 knockdown, with the highest decrease detected in TRIM59 expression. Interesting, overexpression of SP1 not only increased the expression of MAML1 and TRIM59, but also promoted the promoter activation of TRIM59. Taken together, knockdown of MAML1 inhibits proliferation and induces apoptosis of T‐ALL cells through SP1‐dependent inactivation of TRIM59, and therefore suggest that MAML1‐SP1‐TRIM59 axis may serve as potentially interesting therapeutic targets for treatment of T‐ALL.
Curcumin nanofibers for the purpose of wound healing
Authors: Fereydouni Narges , Darroudi Majid , Movaffagh Jebrail , Shahroodi Azadeh , Butler Alexandra E. , Ganjali Shiva , Sahebkar Amirhossein
Published: October 2018

Poor wound healing is a highly prevalent clinical problem with, as yet, no entirely satisfactory solution. A new technique, termed electrospinning, may provide a solution to improve wound healing. Due to their large surface area to volume ratio and porosity, the nanofibers created by electrospinning are able to deliver sustained drug release and oxygen to the wound. Using different types of polymers with varying properties helps strengthening nanofiber and exudates absorption. The nanofibers appear to have an ideal structure applicable for wound healing and, in combination with curcumin, can blend the anti‐inflammatory and antioxidant properties of curcumin into a highly effective wound dressing. The use of suitable curcumin solvents and the slow release of curcumin from the nanofiber help in overcoming the known limitations of curcumin, specifically its low stability and limited bioavailability. Here, we review the studies which have been done on synthesized nanofibers containing curcumin, produced by the electrospinning technique, for the purpose of wound healing.
Regulating ferroportin‐1 and transferrin receptor‐1 expression: A novel function of hydrogen sulfide
Authors: Zhang Meng‐Wan , Yang Guang , Zhou Yu‐Fu , Qian Christopher , Mu Ming‐Dao , Ke Ya , Qian Zhong‐Ming
Published: October 2018

Hydrogen sulfide (H2S) has a significant effect on the regulation of interleukin‐6 (IL‐6) and signal transducer and activator of transcription 3 (STAT3) activities, while IL‐6 directly regulates hepcidin expression via STAT3. We therefore hypothesized that H
2S has a role in body iron homeostasis by regulating the expression of iron transport proteins via the IL‐6/STAT3/Hepcidin pathway. Here, we investigated the effects of two H
2S donors sodium hydrosulfide and GYY4137 on the expression of ferroportin‐1 (Fpn1), transferrin receptor‐1 (TfR1), hepcidin, IL‐6 and pSTAT3 in the spleen of mice in vivo and peritoneal macrophage in vitro. We also examined the effects of H
2S on serum iron, transferrin saturation, and ferritin light chain contents in the spleen, and on nitrite content, nuclear factor erythroid 2‐related factor‐2 (Nrf2) and iron regulatory protein 1 (IRP1) in the macrophages. We demonstrated that H
2S regulates the expression of TfR1 and Fpn1 in the spleen in vivo and in peritoneal macrophages in vitro predominantly via the IL‐6/pSTAT3/hepcidin pathway, under the conditions of inflammation induced by lipopolysaccharides. We also provide evidence that under uninflamed conditions, the regulation of Fpn1 and TfR1 expression by H
2S, both in vivo and in vitro, are mediated by the nitric oxide (NO)/Nrf2 and iron regulatory protein/iron responsive element pathways, respectively, which are independent of IL‐6/pSTAT3/hepcidin signals. These findings show that H
2S is a key player in iron homeostasis under not only the inflamed conditions but also uninflamed conditions.
Promoter methylation as biomarkers for diagnosis of melanoma: A systematic review and meta‐analysis
Authors: Guo Yu , Long Jianhong , Lei Shaorong
Published: October 2018

Melanoma is one of the most common skin cancer that is characterized by rapid growth, early metastasis, high malignant, and mortality. Accumulating evidence demonstrated that promoter methylation of tumor‐suppressor genes is implicated in the pathogenesis of melanoma. In the current study, we performed a meta‐analysis to identify promising methylation biomarkers in the diagnosis of melanoma. We carried out a systematic literature search using Pubmed, Embase, and ISI web knowledge database and found that gene promoter methylation of 50 genes was reported to be associated with the risk of melanoma. Meta‐analysis revealed that hypermethylation of claudin 11 (CLDN11; odds ratio [OR], 16.82; 95% confidence interval [CI], 1.97–143.29; p = 0.010), O‐6‐methylguanine‐DNA methyltransferase (MGMT; OR, 5.59; 95% CI, 2.51–12.47; p < 0.0001), cyclin‐dependent kinase inhibitor 2A (p16; OR, 6.57; 95% CI, 2.19–19.75; p = 0.0008), retinoic acid receptor β (RAR‐β2; OR, 24.31; 95% CI, 4.58–129.01; p = 0.0002), and Ras association domain family member (RASSF1A; OR, 9.35; 95% CI, 4.73–18.45; p < 0.00001) was significantly higher in melanoma patients compared with controls. CLDN11 (OR, 14.52; 95% CI, 1.84–114.55; p = 0.01), MGMT (OR, 8.08; 95% CI, 1.84–35.46; p = 0.006), p16 (OR, 9.44; 95% CI, 2.68–33.29; p = 0.0005), and RASSF1A (OR, 7.72; 95% CI, 1.05–56.50; p = 0.04) hypermethylation was significantly increased in primary melanoma compared with controls. Methylation frequency of CLDN11 (OR, 25.56; 95% CI, 2.32–281.66; p = 0.008), MGMT (OR, 4.64; 95% CI, 1.98–10.90; p = 0.0004), p16 (OR, 4.31; 95% CI, 1.33–13.96; p = 0.01), and RASSF1A (OR, 10.10; 95% CI, 2.87–35.54; p = 0.0003) was significantly higher in metastasis melanoma compared with controls. These findings indicated that CLDN11, MGMT, p16, RAR‐β2, and RASSF1A hypermethylation is a risk factor and a potential biomarker for melanoma. CLDN11, MGMT, p16, and RASSF1A promoter methylation may take part in the development of melanoma and become useful biomarkers in the early diagnosis of the disease.
Molecular insights into development of Trichoderma interfusants for multistress tolerance enhancing antagonism against Sclerotium rolfsii Sacc
Authors: Hirpara Darshna G. , Gajera H. P. , Patel Abha K. , Katakpara Zinkal A. , Golakiya B. A.
Published: October 2018

The current study aimed at developing diverse Trichoderma fusants for fungicides, drought, and salt tolerance with enhanced antagonistic activity against Sclerotium rolfsii Sacc. Trichoderma virens NBAII Tvs12 (mycoparasitic) and Trichoderma koningii MTCC796 (multistress tolerant) were used as parental strains for development of interspecific protoplast fusants. A total of 36 stable fusants were used for mycoparasitism, fungicides, and abiotic stresses (drought and salt) tolerance. The results revealed 20 homozygous progenies showing characteristics of either one parental strain and 14 heterozygous mutants depicting traits of both parental strains. A novel concept of inhibition coefficient was established using growth‐related key parameters that represent the pathogen biology and the biocontrol‐related biophysics of Trichoderma fusants. The results indicated a differential inhibition coefficient of the test pathogen and the highest (92.88%) inhibition coefficient of S. rolfsii was observed by interstable fusant Fu21. It also grew better under fungicides and abiotic stress (drought and salt) conditions. The molecular characterization and heterozygosity analysis evidenced the highest observed heterozygosity (0.5441) and gene flow (0.3872) in stable heterozygous Fu21. Principal coordinates analysis exhibited 62.7% of total variability. The ecofriendly heterozygous Trichoderma fusant (Fu21) might be useful for biocontrol of stem rot disease under adverse conditions or as a part of integrated disease management.
OxLDL induces vascular endothelial cell pyroptosis through miR‐125a‐5p/TET2 pathway
Authors: Zhaolin Zeng , Jiaojiao Chen , Peng Wu , Yami Liu , Tingting Zhang , Jun Tao , Shiyuan Wu , Jinyan Xiao , Dangheng Wei , Zhisheng Jiang , Zuo Wang
Published: October 2018

Pyroptosis participates in the formation and development of atherosclerosis (As) by promoting inflammatory factor release and is closely related to the stability of atherosclerotic plaque. MicroRNAs can regulate the expression of target genes at the posttranscriptional level. Previous studies have shown that miR‐125a‐5p increases in hyperlipidemic–hyperglycemic conditions and is involved in apoptosis, but its specific role in pyroptosis and As remains unclear. We propose that miR‐125a‐5p may be implicated in oxidized low‐density lipoprotein (oxLDL)‐induced vascular endothelial cells (VECs) pyroptosis and therefore conducted the current study. We observed that miR‐125a‐5p can inhibit tet methylcytosine dioxygenase 2 (TET2) expression at the posttranscription level, resulting in abnormal DNA methylation, mitochondrial dysfunction, and increased reactive oxygen species production, activated nuclear factor‐κB that induces activation of inflammasome and maturation, release of proinflammatory cytokines interleukin (IL)‐1β and IL‐18, and pyroptosis. Given the role of VECs in vascular physiology, oxLDL‐induced VEC pyroptosis may promote the development of As. Our current study reveals a novel pathway associated with pyroptosis program regulation, which comprises miR‐125a‐5p and TET2 in VECs. Modulation of their expression levels may serve as a potential target for therapeutic strategies of As.
Multiomics analysis on DNA methylation and the expression of both messenger RNA and microRNA in lung adenocarcinoma
Authors: Yang Zhaoyang , Liu Bao , Lin Tie , Zhang Yingli , Zhang Limin , Wang Meng
Published: October 2018

Lung adenocarcinoma (LUAD) poses a significant threat to public health worldwide, while the genetic and epigenetic abnormalities involved in the oncogenesis of LUAD remains unknown. This study aimed to identify and validate key genes during the development and progression of LUAD by multiomics analysis. First, Empirical Analysis of Digital Gene Expression Data in R (EdgeR) was used to identify differentially regulated genes between normal samples and LUAD samples. Then significance analysis of microarrays (SAM) was used to identify differentially methylated genes and regulated microRNAs (miRNAs) between normal samples and LUAD samples. Following that, Kyoto Encyclopedia of Genes and Genomes (KEGG)‐enrichment analysis was used to analyze the function that these genes enriched in. A total of 4,816 genes, 419 miRNAs, and 4,476 methylated genes that were significantly differentially expressed corresponding to the normal tissues in LUAD were obtained, and some of the pathways these genes enriched in were the same. Moreover, 255 genes differentially methylated and expressed at the same time were also found, and these 255 genes were the target genes of the miRNAs differentially expressed in LUAD. Finally, nine genes (BRCA1, COL1A1, ESR1, FGFR2, HNF4A, IGFBP3, MET, MMP3, and PAK1) network analysis, and two of which were found to be related to the survival of LUAD patients. In summary, a total of nine genes that may play important roles in the development of LUAD were identified, and two (PAK1 and FGFR2) of them can be served as prognostic biomarkers for LUAD patients. The genes found in this study played different roles in the tumor progression of LUAD, indicating these genes may be considered as potential target genes for LUAD treatment.
HDAC6 inhibition induces the failure of mouse early embryonic development
Authors: Wang Hui , Ling Li , Ai Limei , Bai Liping
Published: October 2018

Histone deacetylases (HDACs) have been implicated in numerous biological events. However, to date, the role of HDAC6 in early embryos remains unknown. In the current study, Tubastatin A (TubA), a potent HDAC6 inhibitor, was used to block HDAC6 activity in mouse embryos. We found that TubA exposure significantly reduced the blastocyst formation of early embryos. Confocal microscopy revealed the markedly increased chromosomal congression failure in the mouse embryos treated with the HDAC6 inhibitor. Moreover, the HDAC6 inhibition resulted in the overproduction of reactive oxygen species (ROS) in embryos. In addition, we observed the accumulation of phosphorylated γH2AX in TubA‐treated embryos, indicative of the increased DNA damage. In line with this, cell apoptosis of blastocysts was frequently detected in HDAC6‐deficient embryos compared with their controls. Altogether, our data indicate that HDAC6 may serve as an important regulator of chromatin structure and mitochondrial function, determining the developmental potential of the early embryos of mouse.
Retracted: Effects of IGFBP3 gene silencing mediated inhibition of ERK/MAPK signaling pathway on proliferation, apoptosis, autophagy, and cell senescence in rats nucleus pulposus cells
Authors: Chen Gang , Zhou Xiaopeng , Xu Zhengkuan
Published: October 2018

Objective

Disc degeneration is the common life‐threatening disease characterized by flank pain. The gene expression of insulin‐like growth factor binding protein 3 (IGFBP3) is increased in patients with disc degeneration, however, its mechanism is still unknown. This study aimed to investigate the influence of IGFBP3 gene silencing mediated inhibition of extracellular signal‐related kinase (ERK)/mitogen‐activated protein kinase (MAPK) signaling on proliferation, apoptosis, autophagy, and cell senescence in rats nucleus pulposus (NP) cells.

Methods

The expression of IGFBP3 in disc NP of patients was assessed by real‐time PCR (RT‐PCR) and western blot. RT‐PCR, transwell assay, immunohistochemical staining, SA‐β‐Gal staining, and western blot were performed to explore the molecular mechanism of IGFBP3 in NP cell migration and invasion.

Results

In this study, IGFBP3 was highly expressed in disc NP of patients. With RT‐PCR, transwell assay, immunohistochemical staining, SA‐β‐Gal staining, and western blot, downregulated IGFBP3 could inhibit NP cells' migration and invasion by targeting the ERK/MAPK signaling pathway.

Conclusion

Our findings revealed that the inhibition of the ERK/MAPK pathway was mediated by IGFBP3 silencing that had effects on proliferation, apoptosis, autophagy, and cell senescence. Furthermore, our findings suggested the underlying mechanism of disc degeneration.
Gymnemic acid I triggers mechanistic target of rapamycin‐mediated β cells cytoprotection through the promotion of autophagy under high glucose stress
Authors: Wu Yanyang , Hu Yongquan , Yuan Yuju , Luo Yushuang , lai Dengni , Zhou Haiyan , Tong Zhongyi , Liu Dongbo
Published: October 2018

Gymnemic acid I (GA I) is a bioactive component of Gymnema sylvestre. It is an Indian traditional medicinal herb which has antidiabetic effect. However, the molecular mechanism is remaining to be elucidated. Here, we showed that high glucose promoted the rate of apoptosis, GA I decreased the apoptosis under the high glucose stress. Our further study explored that GA I increased the number of autophagosome and the ratio of light chain 3‐I (LC3‐I)/LC3‐II in MIN‐6 cells under the normal or high glucose stress by the methods of western blot analysis and immunofluorescence. It induced autophagy flux and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase β‐1 (p70 S6K/S6K1), which is a substrate of mTOR. GA I decreased the rate of apoptosis and the activity of caspase‐3 under the high glucose stress. The inhibition of apoptosis and caspase‐3 activity by GA I were increased after treating with autophagy inhibitor in mouse islet β cells MIN‐6. Our data suggested that GA I‐induced autophagy protected MIN‐6 cells from apoptosis under high glucose stress via inhibition the phosphorylation activity of mTOR.
Transmembrane protein 215 promotes angiogenesis by maintaining endothelial cell survival
Authors: Liu Yuan , Zheng Qijun , He Guangbin , Zhang Mei , Yan Xianchun , Yang Ziyan , Zhang Peiran , Wang Lili , Liu Jiankang , Liang Liang , Han Hua
Published: October 2018

Sprouting angiogenesis is a major form of neovascularization of tissues suffering from hypoxia and other related stress. Endothelial cells (ECs) undergo proliferation, differentiation, programmed death, and migration during angiogenic sprouting, but the underlying molecular mechanisms regulating ECs in angiogenesis have been incompletely elucidated. Here we report that the transmembrane protein 215 (TMEM215) is involved in angiogenesis by regulating EC survival. The murine TMEM215 gene, which possesses two transcriptional starting sites as determined by 5′‐rapid amplification of complementary DNA (cDNA) ends (RACE), encodes a two‐pass TMEM. The TMEM215 transcripts were detected in ECs in addition to other tissues by quantitative reverse transcription‐polymerase chain reaction. Immunofluorescence showed that TMEM215 was expressed in the vasculature in retina, liver, and tumor, and colocalized with EC markers. We show that knockdown of TMEM215 in ECs induced strong cell death of ECs in vitro without affecting cell proliferation and migration, suggesting that TMEM215 was required for EC survival. Downregulation of TMEM215 expression compromised lumen formation and sprouting capacities of ECs in vitro. Moreover, intravitreous injection of TMEM215 small interfering RNA resulted in delayed and abnormal development of retinal vasculature with poor perfusion. These results identified TMEM215 as a novel molecule involved in angiogenesis by regulating the survival of ECs.
Evidence for calpains in cancer metastasis
Authors: Chen Jiaxin , Wu Yizheng , Zhang Lumin , Fang Xiao , Hu Xiaotong
Published: October 2018

Metastatic dissemination represents the final stage of tumor progression as well as the principal cause of cancer‐associated deaths. Calpains are a conserved family of calcium‐dependent cysteine proteinases with ubiquitous or tissue‐specific expression. Accumulating evidence indicates a central role for calpains in tumor migration and invasion via participating in several key processes, including focal adhesion dynamics, cytoskeletal remodeling, epithelial‐to‐mesenchymal transition, and apoptosis. Activated after the increased intracellular calcium concentration () induced by membrane channels and extracellular or intracellular stimuli, calpains induce the limited cleavage or functional modulation of various substrates that serve as metastatic mediators. This review covers established literature to summarize the mechanisms and underlying signaling pathways of calpains in cancer metastasis, making calpains attractive targets for aggressive tumor therapies.
Hyperinsulinemia is associated with increasing insulin secretion but not with decreasing insulin clearance in an age‐related metabolic dysfunction mice model
Authors: Kurauti Mirian A. , Ferreira Sandra M. , Soares Gabriela M. , Vettorazzi Jean F. , Carneiro Everardo M. , Boschero Antonio C. , Costa‐Júnior José M.
Published: October 2018

Human life expectancy is increasing faster lately and, consequently, the number of patients with age‐related diseases such as type 2 diabetes (T2D) is rising every year. Cases of hyperinsulinemia have been extensively reported in elderly subjects and this alteration in blood insulin concentration is postulated to be a cause of insulin resistance, which in some cases triggers T2D onset. Thus, it is important to know the underlying mechanisms of age‐dependent hyperinsulinemia to find new strategies to prevent T2D in elderly subjects. Two processes control blood insulin concentration: Insulin secretion by the endocrine portion of the pancreas and insulin clearance, which occurs mainly in the liver by the action of the insulin‐degrading enzyme (IDE). Here, we demonstrated that 10‐month‐old mice (old) display increased body and fat pad weight, compared with 3‐month‐old mice (control), and these alterations were accompanied by glucose and insulin intolerance. We also confirm hyperinsulinemia in the old mice, which was related to increased insulin secretion but not to reduced insulin clearance. Although no changes in insulin clearance were observed, IDE activity was lower in the liver of old compared with the control mice. However, this decreased IDE activity was compensated by increased expression of IDE protein in the liver, thus explaining the similar insulin clearance observed in both groups. In conclusion, at the beginning of aging, 10‐month‐old mice do not display any alterations in insulin clearance. Therefore, hyperinsulinemia is initiated primarily due to a higher insulin secretion in the age‐related metabolic dysfunction in mice.
An Evaluation of Vancomycin Area Under the Curve Estimation Methods for Children Treated for Acute Pulmonary Exacerbations of Cystic Fibrosis Due to Methicillin‐Resistant Staphylococcus aureus
Authors: Stockmann Chris , Olson Jared , Rashid Jahidur , Lubsch Lisa , Young David C. , Hersh Adam L. , Frymoyer Adam , Ampofo Krow , Liu Xiaoxi , Wang Yuhuan , Sherwin Catherine M.T. , Zobell Jeffery T.
Published: October 2018

The prevalence of pulmonary methicillin‐resistant Staphylococcus aureus infections in patients with cystic fibrosis (CF) has increased over the last 2 decades. Two concentrations—a postdistributive and a trough—are currently used to estimate the area under the curve (AUC) of vancomycin, an antibiotic routinely used to treat these infections, to achieve the target AUC/minimum inhibitory concentration of ≥400 mg·h/L in ensuring optimal dosing of this drug. This study evaluated precision and bias in estimating vancomycin AUCs obtained either from a population pharmacokinetic (PK) model by using a single trough concentration or from standard PK equation–based 2‐point monitoring approach. AUCs were either obtained from a single trough concentration–fitted model or derived from a model fitted by 2 concentration points. Children ≥2 years of age with CF received intravenous vancomycin at 2 centers from June 2012 to December 2014. A population PK model was developed in Pmetrics to quantify the between‐subject variability in vancomycin PK parameters, define the sources of PK variability, and leverage information from the population to improve individual AUC estimates. Twenty‐three children with CF received 27 courses of vancomycin. The median age was 12.3 (interquartile range [IQR] 8.5–16.6) years. From the individual vancomycin PK parameter estimates from the population PK model, median AUC was 622 (IQR 529–680) mg·h/L. Values were not significantly different from the AUC calculated using the standard PK equation‐based approach (median 616 [IQR 540–663] mg·h/L) (P = .89). A standard PK equation‐based approach using 2 concentrations and a population PK model‐based approach using a single trough concentration yielded unbiased and precise AUC estimates. Findings suggest that options exist to implement AUC‐based pediatric vancomycin dosing in patients with CF. The findings of this study reveal that several excellent options exist for centers to implement AUC‐based pediatric vancomycin dosing for patients with CF.
How Financial Constraints Influence Consumer Behavior: An Integrative Framework
Authors: Hamilton Rebecca W. , Mittal Chiraag , Shah Anuj , Thompson Debora V. , Griskevicius Vladas
Published: October 2018

Financial constraints are economic limitations on behavior. Given that millions of people experience chronic or episodic financial constraints, we sought to review research that provides insight into how they affect consumer behavior. We propose an integrative framework that draws insights from multiple literatures that have examined financial constraints from different perspectives. The framework distinguishes between four perspectives, which are rooted in literatures on resource scarcity, choice restriction, social comparison, and environmental uncertainty and highlights different temporal stages of responding to financial constraints, distinguishing between reacting, coping, and adapting. Beyond the obvious negative effects of financial constraints, our framework emphasizes consumer resilience, highlighting that consumers often successfully cope with and devise adaptive strategies to deal with financial constraints. By broadening the behavioral and temporal scope of financial constraints considered within consumer psychology, this framework helps us to understand the often strong and sometimes counterintuitive effects of financial constraints on consumer behavior.
Reconstruction from the deck of ‐vertex induced subgraphs
Authors: Spinoza Hannah , West Douglas B
Published: October 2018

The ‐
deck of a graph is its multiset of subgraphs induced by vertices; we study what can be deduced about a graph from its ‐deck. We strengthen a result of Manvel by proving for that when is large enough ( suffices), the ‐deck determines whether an ‐vertex graph is connected ( suffices when , and cannot suffice). The reconstructibility of a graph with vertices is the largest such that is determined by its ‐deck. We generalize a result of Bollobás by showing for almost all graphs. As an upper bound on , we have . More generally, we compute whenever , which involves extending a result of Stanley. Finally, we show that a complete ‐partite graph is reconstructible from its ‐deck.
Improper coloring of graphs on surfaces
Authors: Choi Ilkyoo , Esperet Louis
Published: October 2018

A graph is ‐colorable if its vertex set can be partitioned into sets , such that for each , the subgraph of induced by has maximum degree at most . The Four Color Theorem states that every planar graph is ‐colorable, and a classical result of Cowen, Cowen, and Woodall shows that every planar graph is ‐colorable. In this paper, we extend both of these results to graphs on surfaces. Namely, we show that every graph embeddable on a surface of Euler genus is ‐colorable and ‐colorable. Moreover, these graphs are also ‐colorable and ‐colorable. We also prove that every triangle‐free graph that is embeddable on a surface of Euler genus is ‐colorable. This is an extension of Grötzsch's Theorem, which states that triangle‐free planar graphs are ‐colorable. Finally, we prove that every graph of girth at least 7 that is embeddable on a surface of Euler genus is ‐colorable. All these results are best possible in several ways as the girth condition is sharp, the constant maximum degrees cannot be improved, and the bounds on the maximum degrees depending on are tight up to a constant multiplicative factor.
GILZ restrains neutrophil activation by inhibiting the MAPK pathway
Authors: Ricci Erika , Ronchetti Simona , Gabrielli Elena , Pericolini Eva , Gentili Marco , Roselletti Elena , Vecchiarelli Anna , Riccardi Carlo
Published: October 2018

Glucocorticoid-induced leucine zipper (GILZ) exerts anti-inflammatory effects on the immune cells. However, less is known about GILZ function in neutrophils. We aimed to define the specific role of GILZ in basal neutrophil activity during an inflammatory response. GILZ knockdown resulted in a persistent activation state of neutrophils, as evidenced by increased phagocytosis, killing activity, and oxidative burst in GILZ-knockout (KO) neutrophils. This enhanced response caused severe disease in a dinitrobenzene sulfonic acid (DNBS)-induced colitis model, where GILZ-KO mice had prominent granulocytic infiltrate and excessive inflammatory state. We used a Candida albicans intraperitoneal infection model to unravel the intracellular pathways affected by GILZ expression in activated neutrophils. GILZ-KO neutrophils had stronger ability to clear the infectious agent than the wild-type (WT) neutrophils, and there was more activation of the NOX2 (NADPH oxidase 2) and p47phox proteins, which are directly involved in oxidative burst. Similarly, the MAPK pathway components, that is, ERK and p38, which are involved in the oxidative burst pathway, were highly phosphorylated in GILZ-KO neutrophils. Evaluation of GILZ expression kinetics during C. albicans infection revealed down-regulation that correlated inversely with the state of neutrophil activation, which was evaluated as oxidative burst. Overall, our findings define GILZ as a regulator of neutrophil functions, as its expression contributes to limiting neutrophil activation by reducing the activation of the signaling pathways that control the basal neutrophil functions. Controlling GILZ expression could help regulate a continuous inflammatory state that can result in chronic inflammatory and autoimmune diseases.

GILZ expression contributes to the inhibition of neutrophil activation by reducing MAPK pathway protein and NOX2 activity that control basal neutrophil functions.
Genetic characterization of human metapneumovirus identified through community and facility‐based surveillance of infants in Dhaka, Bangladesh
Authors: Rahman Mohammed Ziaur , Sumiya Mariya , Sahabuddin Mohammed , Pell Lisa G , Gubbay Jonathan B , Rahman Rajibur , Momtaz Farhana , Azmuda Nafisa , Shanta Shaila S , Jahan Ishrat , Rahman Mustafizur , Mahmud Abdullah A , Roth Daniel E , Morris Shaun K
Published: October 2018

Background

Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children in low and middle‐income countries. Human metapneumovirus (hMPV) is one of the most common viral etiological agents for ARIs in children.

Objectives

In this study, we explored the genotypic diversity and the epidemiology of hMPV among infants in Dhaka, Bangladesh.

Study Design

Between December 2014 and August 2016, a total of 3810 mid‐turbinate nasal swab samples were collected from infants (0 to 6 months of age) who met clinical ARI criteria, as a part of a prospective ARI cohort study. hMPV was detected using polymerase chain reaction, and genotyped by sequencing and phylogenetic analysis.

Results

hMPV was identified in 206 (5.4%) nasal swab specimens. One‐tenth of the hMPV‐positive swabs (n = 19) were also positive for other respiratory viruses. hMPV activity peaked in January and September in 2015; however, no seasonal pattern of hMPV infection was detected. Phylogenetic analyses of the N and F gene‐fragments revealed that the hMPV strains circulating in Dhaka, Bangladesh, belonged to three genotypes: A2b, A2c, and B1. Genotype A (57%) was the predominant hMPV genotype circulating in Bangladesh during the study period.

Conclusion

This study describes both the epidemiology of hMPV infection and its genotypic strain diversity in Dhaka, Bangladesh.
Nano and micro biomechanical alterations of annulus fibrosus after in situ immobilization revealed by atomic force microscopy
Authors: Liang Ting , Che Yan‐Jun , Chen Xi , Li Hai‐Tao , Yang Hui‐Lin , Luo Zong‐Ping
Published: October 2018

Annulus fibrosus is critical to bear loads and resist fluid flow in the intervertebral disc. However, the detailed biomechanical mechanism of annulus fibrosus under abnormal loading is still ambiguous, especially at the micro and nano scales. This study aims to characterize the alterations of modulus at the nano scale of individual collagen fibrils in annulus fibrosus after in‐situ immobilization, and the corresponding micro‐biomechanics of annulus fibrosus. An immobilization model was used on the rat tail with an external fixation device. The elastic modulus of annulus fibrosus at both the nano‐ and micro‐scale was examined using atomic force microscopy after fixation for 4 and 8 weeks, respectively. The fibrils in inner layer showed an alteration in elastic modulus from 91.38 ± 20.19 MPa in the intact annulus fibrosus to 110.64 ± 15.58 MPa (p < 0.001) at the nano scale after immobilization for 8 weeks, while the corresponding modulus at the micro scale also underwent a change from 0.33 ± 0.04 MPa to 0.47 ± 0.04 MPa (p < 0.001). The fibril disorder after immobilization was observed by hematoxylin/eosin staining. The gene expression of annulus fibrosus was also measured by real‐time reverse transcription‐polymerase chain reaction, which showed the upregulation of collagen II (p = 0.003) after immobilization. The results indicated that the immobilization not only influenced the individual fibril at the nanoscale, but also the micro‐biomechanical property of annulus fibrosus which is critical to define the cell response to surrounding biomechanical environment. These alterations may also lead to the change in the mechanical property of the whole disc and the load‐bearing function. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1–7, 2018.
Fibronectin induced ITGβ1/FAK‐dependent apoptotic pathways determines the fate of degenerative NP cells
Authors: Wu Xinghuo , Wang Kun , Hua Wenbin , Li Shuai , Liu Xianzhe , Song Yu , Zhang Yukun , Shao Zengwu , Li Suyun , Yang Cao
Published: October 2018

Intervertebral disc (IVD) degeneration is caused by a decrease in nucleus pulposus (NP) cells, due mainly to apoptosis. Focal adhesion kinase (FAK) is involved in the integrin (ITG)‐mediated control of cell adhesion and anoikis (apoptosis). To explore the involvement of ITGβ1/FAK‐dependent apoptotic pathways in disc degeneration, histological, and molecular biological studies on the protein expression of fibronectin (FN), ITGβ1, and syndecan 4 (SYND4) in non‐degenerative and degenerative NP tissues were conducted. Degenerative NP cells were isolated and cultured in the presence of SYND4 and/or ITGβ1, with or without an FAK inhibitor. The effects of upregulation or knockdown of ITGβ1 gene expression were also examined. The TUNEL assay was used to determine the percentage of apoptotic cells. Western blotting was used to detect the expression of SYND4, ITGβ1, FAK, and downstream pathway proteins. The results showed that extracellular FN was degraded during the IVD degeneration process, detrimentally affecting the function, and survival of NP cells. The apoptotic rate was increased by ITGβ1 activation, but partially reduced by FN. After ITGβ1 knockdown, the FAK/PI3 K/AKT axis was activated in the ITGβ1/FAK‐dependent pathways, resulting in increased cell adherence capacity and decreased anoikis. FN rescued the degenerative NP cells from anoikis through the FAK‐dependent signaling pathways. In conclusion, the extracellular matrix protein FN is essential for maintaining the function and survival of NP cells through ITGβ1/FAK‐dependent apoptotic pathways during disc degeneration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:439–448, 2019.
Cellular biology of fracture healing
Authors: Bahney Chelsea S. , Zondervan Robert L. , Allison Patrick , Theologis Alekos , Ashley Jason W. , Ahn Jaimo , Miclau Theodore , Marcucio Ralph S. , Hankenson Kurt D.
Published: October 2018

The biology of bone healing is a rapidly developing science. Advances in transgenic and gene‐targeted mice have enabled tissue and cell‐specific investigations of skeletal regeneration. As an example, only recently has it been recognized that chondrocytes convert to osteoblasts during healing bone, and only several years prior, seminal publications reported definitively that the primary tissues contributing bone forming cells during regeneration were the periosteum and endosteum. While genetically modified animals offer incredible insights into the temporal and spatial importance of various gene products, the complexity and rapidity of healing—coupled with the heterogeneity of animal models—renders studies of regenerative biology challenging. Herein, cells that play a key role in bone healing will be reviewed and extracellular mediators regulating their behavior discussed. We will focus on recent studies that explore novel roles of inflammation in bone healing, and the origins and fates of various cells in the fracture environment. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Characterizing Exclusively Breastfed Infant Stool via a Novel Infant Stool Scale
Authors: Gustin Jennifer , Gibb Roger , Kenneally Dianna , Kutay Ben , Waimin Siu Susana , Roe Don
Published: October 2018

Analysis of stool has long been a diagnostic tool across a number of disease states. Currently, there are two stool scales in clinical use, the Bristol Stool Scale and the Amsterdam Infant Stool Scale. However, the existing categorizations for stool may not sufficiently cover the broad range of stool output for exclusively breastfed infants. The Bristol Stool Scale is not age specific to cover children who are not toilet trained and the Amsterdam Infant Stool Scale, though developed for children who are not toilet trained, does not sufficiently cover the wide variety of consistencies of exclusively breastfed infant stools. Through a robust understanding of exclusively breastfed infant stool characteristics, a new stool scale has been developed. It is proposed that this stool scale may better assist in observing and recording exclusively breastfed infant stool in a more accurate manner, which may aid in diagnostic capabilities.
Does Lupinus angustifolius L. need sulfur fertilization under central European conditions?
Authors: Pötzsch Frank , Lux Guido , Lewandowska Sylwia , Schmidtke Knut
Published: October 2018

In order to answer the question of whether narrow‐leaf lupin (Lupinus angustifolius L.) needs sulfur (S) fertilization under central European conditions, field trials were carried out at several sites in Germany on long‐term (> 10 years) organically cultivated arable land from 2012 to 2014. The effect of S‐containing fertilizers kieserite, gypsum, epsom salt, and elemental sulfur on S accumulation, yield, yield structure, and nitrogen (N) accumulation in narrow leaf lupin as well as the recovery of fertilized S was investigated. Under the given conditions, the fertilization did not influence seed yields. The S accumulation in shoots ranged from 11.8 kg ha−1 to 14.1 kg ha−1. The bulk of the absorbed S was accumulated in the straw (average S harvest index: 0.40). The N : S ratio in the youngest open leaf at BBCH 60–65 was about 20 and the corresponding S concentration was 0.24% in the leaf dry mass. The apparent recovery efficiency of S (RE) of kieserite, gypsum, and epsom salt, whose S form is generally plant‐available, was low with 4.0%, –2.1%, and 6.6%, respectively. The S requirement of the lupin was obviously completely filled by plant‐available S from the soil as well as atmospheric S deposition in all tested environments. Application of kieserite, gypsum, and epsom salt resulted in a partially significant increase in S concentration of seeds and straw, and also partly significantly narrowed the N : S ratios in the plants but did not increase yield. Application of elemental S did not lead to an increase in plant S concentration in the year of application.
A hydrophobic deep eutectic solvent‐based vortex‐assisted dispersive liquid–liquid microextraction combined with HPLC for the determination of nitrite in water and biological samples
Authors: Zhang Kaige , Li Shuangying , Liu Chuang , Wang Qi , Wang Yunhe , Fan Jing
Published: October 2018

In recent years, hydrophobic deep eutectic solvents as new generation of green solvents have attracted wide attention in liquid microextraction technique. In this article, four hydrophobic deep eutectic solvents composed of trioctylmethylammonium chloride and oleic acid were designed and prepared firstly. Combined with high‐performance liquid chromatography, these deep eutectic solvents were used as an extraction solvent in vortex‐assisted dispersive liquid–liquid microextraction for the selective enrichment and indirect determination of trace nitrite from real water and biological samples. This method is based on the diazotization‐coupling reaction of nitrite with p‐nitroaniline and diphenylamine in acidic water, and then the nitrite is quantified indirectly by measuring the obtained azo compounds. Some factors influencing the extraction efficiency, including the reaction and extraction conditions, were investigated. Under the optimized conditions, the method has a linear range of 1–300 μg/L with a correlation coefficient of 0.9924, limit of detection of 0.2 μg/L, limit of quantitation of 1 μg/L, intraday and interday relative standard deviations of 4.0 and 6.0%. This method was successfully applied in determination of nitrite from three environmental water and two biological samples with the recovery in the range of 90.5–115.2%. In addition, these results were well agreement with those obtained by the conventional Griess method.
Numerical study on CP of RC structures regarding the significance of the 100 mV decay criterion considering time dependent processes
Authors: Helm Christian , Raupach Michael
Published: October 2018

Cathodic protection (CP) is an electrochemical repair method for reinforced concrete (RC) structures. It has been subject to numerous research projects and has proven its capabilities in countless repair measures around the world. Nevertheless, due to the uniqueness of each application as well as the large number of influencing factors (e.g., geometry, concrete resistivity distribution, kinetics of rebar, and CP anode system) the design and operation of CP systems is still governed by the use of (semi‐) empirical calculations and criteria. Within this study, numerical simulation has been used to determine the current and potential distribution during the application of CP. On the basis of this data, which are not measurable on site, the significance of the most important criterion for the operation of CP systems, the so called 100 mV decay criterion, shall be discussed. In particular, the correlation of the criterion with the corrosion state of the active reinforcement against a backdrop of time dependent effects of CP is within the scope of this study.
The challenges of peptidomics in complementing proteomics in a clinical context
Authors: Maes Evelyne , Oeyen Eline , Boonen Kurt , Schildermans Karin , Mertens Inge , Pauwels Patrick , Valkenborg Dirk , Baggerman Geert
Published: October 2018

Naturally occurring peptides, including growth factors, hormones, and neurotransmitters, represent an important class of biomolecules and have crucial roles in human physiology. The study of these peptides in clinical samples is therefore as relevant as ever. Compared to more routine proteomics applications in clinical research, peptidomics research questions are more challenging and have special requirements with regard to sample handling, experimental design, and bioinformatics. In this review, we describe the issues that confront peptidomics in a clinical context. After these hurdles are (partially) overcome, peptidomics will be ready for a successful translation into medical practice.
Funding project meets early goals to support consumers, produce cost savings
Authors: Canady Valerie A.
Published: October 2018

A little more than a year into its six‐year operation, a mental health Pay for Success (PFS) program designed to deliver publicly funded services to consumers with serious mental illness in Santa Clara County in California is reaping benefits in cost savings by helping its targeted population reduce usage of psychiatric emergency visits and state hospital days. The PFS program, the ninth used in the United States, is the first to work in the mental health arena.
Dance/movement therapy aids clients' MH treatment plan
Authors: Canady Valerie A.
Published: October 2018

Dance/movement therapy remains a growing field for therapists who seek to help patients connect with their mind, body and spirit, even though that form of therapy has been around for more than 50 years, observers say. The use of movement and dance as a holistic form of therapy to support the cognitive, emotional and physical aspects of treatment plans for clients with mental health conditions is at the core of one Chicago‐based practice.
NRDR inhibits estradiol synthesis and is associated with changes in reproductive traits in pigs
Authors: Liu Ying , Yang Yalan , Li Wentong , Zhang Yanmin , Yang Yanzhao , Li Hua , Geng Zhaoyu , Ao Hong , Zhou Rong , Li Kui
Published: October 2018

Cumulus cells secreting steroid hormones have important functions in oocyte development. Several members of the short‐chain dehydrogenase/reductase (SDR) family are critical to the biosynthesis of steroid hormones. NADPH‐dependent retinol dehydrogenase/reductase (
NRDR), a member of the SDR superfamily, is overexpressed in pig breeds that also show high levels of androstenone. However, the potential functions and regulatory mechanisms of
NRDR in pig ovaries have not been reported to date. The present study demonstrated that
NRDR is highly expressed in pig ovaries and is specifically located in cumulus granulosa cells. Functional studies showed that
NRDR inhibition increased estradiol synthesis. Both pregnant mare serum gonadotropin and human chorionic gonadotropin downregulated the expression of
NRDR in pig cumulus granulosa cells. When the relationship between reproductive traits and single‐nucleotide polymorphisms (SNPs) of the
NRDR gene was examined, we found that two SNPs affected reproductive traits. SNP rs701332503 was significantly associated with a decrease in the total number of piglets born during multiparity, and rs326982309 was significantly associated with an increase in the average birth weight during primiparity. Thus,
NRDR has an important role in steroid hormone biosynthesis in cumulus granulosa cells, and
NRDR SNPs are associated with changes in porcine reproduction traits.
Optimal E2 (reference) electrode placement in fibular motor nerve conduction studies recording from the tibialis anterior muscle
Authors: Escorcio‐Bezerra Marcio Luiz , Abrahao Agessandro , Nunes Karlo Faria , de Castro Sparapani Fabio Veiga , de Oliveira Braga Nadia Iandoli , Robinson Lawrence R. , Zinman Lorne , Manzano Gilberto Mastrocola
Published: October 2018

Introduction: In this study we aimed to determine the contribution of the E2 (reference electrode) to the compound muscle action potential (CMAP) amplitude during fibular motor recording to the tibialis anterior (TA) when E2 is placed over routine referential vs. alternative sites. Methods: The CMAP was obtained from 10 healthy subjects, using the active electrode (E1) over sites routinely used as E2 for the TA, whereas the E2 was over the contralateral knee. The same procedure was performed with the E1 over alternative E2 sites. Results: Significant electrical signal was captured over routine E2 placement sites. Among the tested alternative E2 sites, the ipsilateral patella (especially its medial aspect) was the most electrically silent. Discussion: Using alternative E2 sites with near isoelectric recordings can optimize near‐field potential measurement in the fibular motor recording to the TA and represents a more accurate way of measuring nerve and muscle function. Muscle Nerve 59:249–253, 2019