bluuebunny/crossref_metadata_2025 huggingface dataset:
FoxA expression pattern in two polychaete species, Alitta virens and Platynereis dumerilii: Examination of the conserved key regulator of the gut development from cleavage through larval life, postlarval growth, and regeneration
Authors: Kostyuchenko Roman P. , Kozin Vitaly V. , Filippova Nadezhda A. , Sorokina Ekaterina V.
Published: December 2018

Background

foxA orthologs are involved in various processes from embryo patterning to regulation of metabolism. Since foxA conserved role in the development of the gut of errant annelids has never been thoroughly studied, we used a candidate gene approach to unravel the molecular profile of the alimentary canal in two closely related nereid worms with a trochophore‐type lecithotrophic larva.

Results

The character of foxA expression in the two polychaetes was similar but not identical. The genes were successively activated first in blastoporal cells, then in the stomodeum, the midgut, and hindgut primordia, and in the cells of central and peripheral nervous system. Before the start of active feeding of nectochaetes, we observed a short phase of foxA expression in the entire digestive tract. After amputation of posterior segments, foxA expression was established de novo in the new terminal part of the intestine, and then in the developing hindgut and the anus.

Conclusions

We discovered an early marker of endoderm formation previously unknown in errant annelids. Its expression dynamics provided valuable insights into the gut development. Comparative analysis of foxA activity suggests its primary role in gastrulation morphogenesis independently of its type and in midgut and foregut specification. Developmental Dynamics 248:728–743, 2019. © 2018 Wiley Periodicals, Inc.
Land tenure shapes black bear density and abundance on a multi‐use landscape
Authors: Loosen Anne E. , Morehouse Andrea T. , Boyce Mark S.
Published: December 2018

Global biodiversity is decreasing rapidly. Parks and protected lands, while designed to conserve wildlife, often cannot provide the habitat protection needed for wide‐ranging animals such as the American black bear (Ursus americanus). Conversely, private lands are often working landscapes (e.g., farming) that have high human footprints relative to protected lands. In southwestern Alberta, road densities are highest on private lands and black bears can be hunted year‐round. On protected lands, road densities are lowest, and hunting is prohibited. On public lands under the jurisdiction of the provincial government (Crown lands), seasonal hunting is permitted. Population estimates are needed to calculate sustainable harvest levels and to monitor population trends. In our study area, there has never been a robust estimate of black bear density and spatial drivers of black bear density are poorly understood. We used non‐invasive genetic sampling and indices of habitat productivity and human disturbance to estimate density and abundance for male and female black bears in 2013 and 2014 using two methods: spatially explicit capture–recapture (SECR) and resource‐selection functions (RSF). Land tenure best explained spatial variation in black bear density. Black bear densities for females and males were highest on parkland and lowest on Crown lands. Sex ratios were female‐biased on private lands, likely a result of lower harvests and movement of females out of areas with high male density. Synthesis and application: Both SECR and RSF methods clearly indicate spatial structuring of black bear density, with a strong influence based on how lands are managed. Land tenure influences the distribution of available foods and risk from humans. We emphasize the need for improved harvest reporting, particularly for non‐licensed hunting on private land, to estimate the extent of black bear harvest mortality.
IL‐10 signaling in dendritic cells is required for tolerance induction in a murine model of allergic airway inflammation
Authors: Dolch Anja , Kunz Stefanie , Dorn Britta , Alessandrini Francesca , Müller Werner , Jack Robert S. , Martin Stefan F. , Roers Axel , Jakob Thilo
Published: December 2018

Allergen specific tolerance induction efficiently ameliorates subsequent allergen induced inflammatory responses. The underlying regulatory mechanisms have been attributed mainly to interleukin (IL)‐10 produced by diverse hematopoietic cells, while targets of IL‐10 in allergen specific tolerance induction have not yet been well defined. Here, we investigate potential cellular targets of IL‐10 in allergen specific tolerance induction using mice with a cell type specific inactivation of the IL‐10 receptor gene. Allergic airway inflammation was effectively prevented by tolerance induction in mice with IL‐10 receptor (IL‐10R) deficiency in T or B cells. Similarly, IL‐10R on monocytes/macrophages and/or neutrophils was not required for tolerance induction. In contrast, tolerance induction was impaired in mice that lack IL‐10R on dendritic cells: those mice developed an allergic response characterized by a pronounced neutrophilic lung infiltration, which was not ameliorated by tolerogenic treatment. In conclusion, our results show that allergen specific tolerance can be effectively induced without a direct impact of IL‐10 on cells of the adaptive immune system, and highlight dendritic cells, but not macrophages nor neutrophils, as the main target of IL‐10 during tolerance induction.
A New Statistical Approach to Describe the Quality of Extra Virgin Olive Oils Using Near Infrared Spectroscopy (NIR) and Traditional Analytical Parameters
Authors: Willenberg Ina , Matthäus Bertrand , Gertz Christian
Published: December 2018

NIR prediction models are developed for the determination of relevant parameters to evaluate olive oil quality such as acidity (FFA), peroxide value (PV), UV‐absorption at 232 and at 268/270 nm, p‐anisidine value (AnV), isomeric diacylglycerols (DG), and pyropheophytin A (PPP). In addition a new NIR method to estimate the age of olive oil is presented. The relevant wavenumbers are given for the calculation of the parameters and the precision data are presented in comparison to the chemical reference methods. The calibration and validation of the methods are executed with independent data sets (test in test instead of cross‐validation) to cover the wide range of variability of the analytical parameters including the corresponding accurate analytical results from the reference chemical methods. The correctness and accuracy of the developed NIR methods are verified by analyzing certified materials. Finally, a simple statistical approach has been developed to describe the quality of olive oils using the parameters FFA, PV, K232 and K270, DG and PPP. The probability of presence of a sensory defect (100% ≙ 1; 0% ≙ 0) is calculated using the following equation: Pred (BIN) = 1/(1 + exp(−(−9 + 37 × FFA‐0.9 × PV‐2.9 × K232 + 14 × K270 + 3.7 × PPP‐0.17 × DG))).

Practical Applications: The use of NIR allows the analysis of different parameters relevant for the quality of olive oil in one run in comparison to the individual chemical reference methods. That allows saving time and money, and a skilled operator is not necessary, making the method interesting for routine analysis. The use of a simple equation developed from the logistic regression using FFA, PV, K‐values, DG, and PPP measured by NIR as variables enables for the first time to describe the sensory quality of olive oils without making sensory testing. This criterion without setting limits for the individual parameters estimates the probability of the presence of sensory defects on basis of chemical parameters. This tool can easily be used to differentiate the two categories extra virgin and virgin olive oils both using the traditional laboratory methods and the corresponding NIR‐methods.

In the present study, NIR prediction models are developed for the determination of free fatty acids, peroxide value, UV‐absorption at 232 and at 268/270 nm, p‐anisidine value, isomeric di‐acyl‐glycerols, and pyropheophytin A to evaluate olive oil quality. On basis of NIR, a new method is developed to estimate the age of olive oil. The parameters FFA, PV, K232 and K270, DG and PPP have been used to describe the quality of olive oils by a simple statistical approach.
Making scenario interventions matter: Exploring issues of power and rationality
Authors: Cairns George , Wright George
Published: December 2018

In this article, we consider prospects for long‐term impact from scenario projects, specifically for sustained positive change. We outline scenario methods intended to actively engage scenario development team members who will be directly impacted by the “focal issue” of the scenario exercise, in particular those who are remote and by and large excluded from the central decision‐making processes of the powerful. We consider possibilities for building capacity for them to envisage and enact alternative futures for themselves and their communities. However, we see a need to consider how current powerful actors might respond to the wishes and actions of less powerful stakeholders, positing that the potential for action by these less powerful groups may be disrupted by the rationality of the more powerful, where any intended action is against the latter's interests. We argue that understanding and appreciating issues of power and rationality are central to how such participatory approaches might elicit coordinated and articulated action in response to positive scenarios. We discuss this issue by reference to contemporary interpretations of Aristotelian phronēsis, or “practical wisdom.” We outline steps involved in enacting an augmented scenario model that responds to this critique.
Relative impact of indels versus SNPs on complex disease
Authors: Gagliano Sarah A. , Sengupta Sebanti , Sidore Carlo , Maschio Andrea , Cucca Francesco , Schlessinger David , Abecasis Gonçalo R.
Published: December 2018

It is unclear whether insertions and deletions (indels) are more likely to influence complex traits than abundant single‐nucleotide polymorphisms (SNPs). We sought to understand which category of variation is more likely to impact health. Using the SardiNIA study as an exemplar, we characterized 478,876 common indels and 8,246,244 common SNPs in up to 5,949 well‐phenotyped individuals from an isolated valley in Sardinia. We assessed association between 120 traits, resulting in 89 nonoverlapping‐associated loci.We evaluated whether indels were enriched among credible sets of potential causal variants. These credible sets included 1,319 SNPs and 88 indels. We did not find indels to be significantly enriched. Indels were the most likely causal variant in seven loci, including one locus associated with monocyte count where an indel with causality and mechanism previously demonstrated (rs200748895:TGCTG/T) had a 0.999 posterior probability. Overall, our results show a very modest and nonsignificant enrichment for common indels in associated loci.
Targeting microglia attenuates neuroinflammation‐related neural damage in mice carrying human PLP1 mutations
Authors: Groh Janos , Klein Dennis , Berve Kristina , West Brian L. , Martini Rudolf
Published: December 2018

Genetically caused neurological disorders of the central nervous system (CNS) usually result in poor or even fatal clinical outcome and few or no causative treatments are available. Often, these disorders are associated with disease‐amplifying neuroinflammation, a feature shared by progressive forms of multiple sclerosis (PMS), another poorly treatable disorder of the CNS. We have previously generated two mouse lines carrying distinct mutations in the oligodendrocytic PLP1 gene that have initially been identified in patients fulfilling clinical criteria for multiple sclerosis (MS). These mutations cause a loss of function of the gene product resulting in a histopathological and clinical phenotype common to both PMS and genetic CNS disorders, like hereditary spastic paraplegias. Importantly, neuroinflammation comprising adaptive immune reactions promotes disease progression in these PLP1 mutant models, opening the possibility to improve disease outcome of the respective disorders by targeting/modulating inflammation. We here show that PLX3397, a potent inhibitor of the CSF‐1R and targeting innate immune cells, attenuates neuroinflammation in our models by reducing numbers of resident microglia and attenuating T‐lymphocyte recruitment in the CNS. This leads to an amelioration of demyelination, axonopathic features and neuron loss in the retinotectal system, also reflected by reduced thinning of the inner retinal composite layer in longitudinal studies using noninvasive optical coherence tomography. Our findings identify microglia as important promoters of neuroinflammation‐related neural damage and CSF‐1R inhibition as a possible therapeutic strategy not only for PMS but also for inflammation‐related genetic diseases of the nervous system for which causal treatment options are presently lacking.
Uniquely folded shapes, photophysical properties, and recognition abilities of macrocyclic BODIPY oligomers
Authors: Hojo Tomohiro , Nakamura Takashi , Matsuoka Ryota , Nabeshima Tatsuya
Published: December 2018

Macrocyclic BODIPY/dipyrrin tetramers and pentamers connected by m‐phenylene linkers were synthesized. Their uniquely folded shapes were revealed by a single‐crystal X‐ray diffraction analysis, and their dynamic structural behaviors in solution were investigated by variable‐temperature NMR measurements. The BODIPY oligomers exhibited strong emission properties without quenching. Furthermore, the BODIPY pentamer interacted with an ammonium cation utilizing the negatively charged binding pockets in which the polarized Bδ+–Fδ− bonds are present.
Overweight in midlife and risk of cancer in late life: A nationwide Swedish twin study
Authors: Bao Cuiping , Yang Rongrong , Pedersen Nancy L , Xu Weige , Xu Hui , Song Ruixue , Qi Xiuying , Xu Weili
Published: December 2018

Our study examined whether midlife overweight (body mass index [BMI] ≥25) is associated with late‐life cancer risk and explored the role of genetic and early‐life environmental factors in this association. The study included 14,766 individuals from the Swedish Twin Registry, whose midlife (30–50 years) height and weight were recorded. Information on cancer diagnoses in late life (>65 years) was derived from the National Patient Registry and Cancer Registry. Generalized estimating equation (GEE) models were used to analyze unmatched case–control data (controlled for the clustering of twins within a pair). A co‐twin matched case–control analysis used conditional logistic regression to compare cancer‐discordant twins. Of all participants, 3968 (26.9%) were overweight and 4253 (28.8%) had cancer. In multi‐adjusted GEE models using normal‐weight (BMI 18.5–24.9) participants as the reference group, overweight was related to higher risk of colon cancer (OR 1.36, 95% CI: 1.00–1.84, p = 0.049), liver cancer (OR 2.00, 95% CI: 1.11–3.62), cervix uteri cancer (OR 2.86, 95% CI: 1.19–6.91) and corpus uteri cancer (OR 1.78, 95% CI: 1.14–2.78) but lower risk of nonmelanoma skin cancer (OR 0.77, 95% CI: 0.66–0.90). In conditional logistic regression analysis, these associations were attenuated becoming nonsignificance. The difference in ORs from the unmatched and matched analyses was not significant. In conclusion, midlife overweight is associated with increased risk of late‐life colon, liver and uterine cancer but reduced risk of late‐life nonmelanoma skin cancer. Further investigations are warranted to explore the role of genetic and early‐life environmental factors in these associations.
Alterations in the gut microbiota and metabolite profiles of thyroid carcinoma patients
Authors: Feng Jing , Zhao Fuya , Sun Jiayu , Lin Baiqiang , Zhao Lei , Liu Yang , Jin Ye , Li Shengda , Li Aidong , Wei Yunwei
Published: December 2018

The aim of our study was to investigate the relationship among the gut microbiota community, metabolite profiles and thyroid carcinoma (TC). First, 30 TC patients and 35 healthy controls (HCs) fecal samples were applied to characterize the gut microbial community using 16S rRNA gene sequencing. Differential microbiota compositions were observed, with significant enrichment of 19 and depletion of 8 genera in TC samples compared to those in HCs (Q value <0.05), and some genera were correlated with various clinical parameters, such as lipoprotein A and apolipoprotein B. Furthermore, 6 different genera distinguished TC patients from HCs with the AUC of 0.94. The PICRUSt analysis showed 12 remarkably different metabolic pathways (Q value <0.05). Subsequently, we systematically analyzed the gut microbiota and metabolites in the same TC patients (n = 15) and HCs (n = 15). The characteristics of the gut microbiota community were mostly consistent with the above results (30 TC patients and 35 HCs), and liquid chromatography mass spectrometry analysis was performed to characterize the metabolite profiles. In total, 21 different genera (Q value <0.05) and 72 significantly changed metabolites (VIP > 1.0 and p < 0.05) were observed and correlated to each other. Eight metabolites combined with 5 genera were more effective in distinguishing TC patients from HCs (AUC = 0.97). In conclusion, our study presents a comprehensive landscape of the gut microbiota and metabolites in TC patients, and provides a research direction of the mechanism of interaction between gut microbiota alteration and TC pathogenesis.
An effective dendritic cell‐based vaccine containing glioma stem‐like cell lysate and CpG adjuvant for an orthotopic mouse model of glioma
Authors: Zhu Shan , Lv Xinping , Zhang Xuhao , Li Tete , Zang Guoxia , Yang Ning , Wang Xue , Wu Jing , Chen Wei , Liu Yong‐Jun , Chen Jingtao
Published: December 2018

Owing to the limited therapeutic efficacy of glioma vaccines, new strategies are required to improve cancer vaccines. Our study aimed to assess the therapeutic efficacy of a glioma vaccine called STDENVANT. This vaccine, comprising glioma stem‐like cell (GSC) lysate, dendritic cells (DCs), and Toll‐like receptor (TLR) 9 agonist CpG motif‐containing oligodeoxynucleotides (CpG ODNs), was assessed using a GL261‐C57BL/6 orthotopic mouse model of glioma. STDENVANT markedly improved survival and tumor regression by enhancing anti‐tumor immune function. Moreover, STDENVANT upregulated programmed death 1 (PD‐1) and its ligand PD‐L1 on effector T cells, DCs, and glioma tissues, resulting in the accumulation of regulatory T (Treg) cells in the brain and lymph nodes. Combinatorial administration of anti‐PD‐L1 antibody and STDENVANT conferred a greater survival advantage and decreased the Treg cell population in the brain. The present results indicate that PD‐L1 blockade can promote tumor regression via STDENVANT in a mouse model of glioma, and combinatorial administration of anti‐PD‐L1 antibody and STDENVANT increases the therapeutic anti‐tumor efficacy of treatment.
Coexpression network analysis linked H2AFJ to chemoradiation resistance in colorectal cancer
Authors: Wang Xiaojie , Ghareeb Waleed M. , Lu Xingrong , Huang Ying , Huang Shenghui , Chi Pan
Published: December 2018

Neoadjuvant chemoradiotherapy (CRT) resistance is a complex phenomenon and it remains a major problem for patients with a priori resistant tumor. Therefore, there is a strong need to investigate molecular biomarkers which may guide for treatment decision‐making. In our study, weighted gene coexpression network analysis was applied to identify CRT‐resistance hub modules in 12 colorectal cancer (CRC) cell lines with different CRT sensitivities from GSE20298 data set. The green module and purple module had the highest correlations with CRT resistance. Gene ontology enrichment analysis indicated that the function of these two modules focused on interferon‐mediated signaling pathway, immune response, chromatin modulation, Rho GTPases activities, and regulation of apoptotic process. Then, 15 hub genes in both the coexpression and protein‐protein interaction networks were selected. Among these hub genes, higher H2A histone family member J (H2AFJ) expression was independently validated in patient cohorts from two testing data sets of GSE46862 and GSE68204 to be related to CRT resistance. The receiver operating characteristic curve showed that H2AFJ could efficiently distinguish CRT‐resistance cases from CRT‐sensitive cases in another two testing data sets. Furthermore, meta‐analysis of 12 Gene Expression Omnibus–sourced data sets showed that H2AFJ messenger RNA levels were significantly higher in CRC tissues than in normal colon tissues. High H2AFJ expression was correlated with a significant worse event‐ and relapse‐free survival by analyzing the data from the R2: Genomics Analysis and Visualization Platform. Gene set enrichment analysis determined that the mechanism of H2AFJ‐mediated CRT resistance might involve the ERK5 (MAPK7), human immunodeficiency virus Nef (HIV Nef), and inflammatory pathways. This study is the first, to the best of our knowledge, to implicate and verify H2AFJ as an effective new marker for CRT response prediction.
microRNA‐802 inhibits cell proliferation and induces apoptosis in human cervical cancer by targeting serine/arginine‐rich splicing factor 9
Authors: Zhang Qianwen , Lv Rui , Guo Wenjia , Li Xiaoning
Published: December 2018

microRNAs (miRNAs) play crucial roles in cancer development and progression by targeting mRNAs for degradation and/or translational repression. microRNA‐802 (miR‐802) has been reported as a tumor suppressor and its deregulation is observed in various human cancers. However, the prognostic value of miR‐802 and its underlying mechanisms involved in human cervical cancer are poorly investigated. The purposes of this study were to explore the role of miR‐802 in cervical cancer and to clarify the regulation of serine/arginine‐rich splicing factor 9 (SRSF9) by miR‐802. Here, we found that miR‐802 was downregulated in both cervical cancer tissues and cell lines. Transfection of a miR‐802 mimic into cervical cancer cells inhibited their proliferation and colony formation, and promoted cell cycle arrest at the G0/G1 phase and cell apoptosis. In addition, we found that miR‐802 could directly target the 3′‐untranslated region of SRSF9 and suppress SRSF9 expression. Rescue experiments revealed that overexpression of SRSF9 partially reversed the inhibition effect of miR‐802 in cervical cancer cells. Overall, these findings demonstrate that miR‐802 functions as a tumor suppressor in cervical cancer by targeting SRSF9, suggesting that miR‐802 might serve as a potential therapeutic target in cervical cancer.
Benchmark study of popular density functionals for calculating binding energies of three‐center two‐electron bonds
Authors: Cui Cheng‐Xing , Xu Dongdong , Ding Bo‐Wen , Qu Ling‐Bo , Zhang Yu‐Ping , Lan Yu
Published: December 2018

Density functional theory (DFT) can be used to study the three‐center two‐electron (3c2e) bonding mode, which is universal in catalysts containing alkaline‐earth (Ae) and boron‐group (Bg) elements. However, because of the delocalization pattern of the 3c2e bond, the wavefunction cannot be accurately described by DFT methods. The calculated energies of Ae and Bg catalysts therefore fluctuate greatly when different functionals are used, largely because of inconsistent DFT‐calculated binding energies of 3c2e bonds. Nevertheless, with the development of supercomputers and theoretical calculation software, the DFT method is becoming increasingly popular for studying Ae and Bg catalysts. In this study, we compared the performances of 21 functionals with the high‐level composite G3B3 method in calculations for the binding energies of 3c2e bonds. Several frequently used post‐Hartree–Fock methods were also tested. The calculation results indicate that the M06‐2X, MN12‐L, and MN15 functionals give consistent and reliable binding energies for common 3c2e bonds. © 2018 Wiley Periodicals, Inc.
Efficient implementation of periodic boundary conditions in Monte Carlo simulation
Authors: Shakhno Dzmitry V. , Shakhno Aleh V. , Paulechka Eugene
Published: December 2018

Determination of the shortest distances between particles is one of the most time‐consuming parts of molecular simulation by the Monte Carlo method. In this work, we demonstrate that the use of signed‐integer storage of coordinates in a scaled box allows one to skip multiple conditional statements in realization of periodic boundary conditions in cubic and rectangular boxes, which, in turn, increases the performance. Performance of the improved procedure was tested in NVT Monte Carlo simulations for liquid krypton and water. © 2018 Wiley Periodicals, Inc.
Retracted: MicroRNA‐1271 functions as a potential tumor suppressor in hepatitis B virus–associated hepatocellular carcinoma through the AMPK signaling pathway by binding to CCNA1
Authors: Chen Yang , Zhao Zhen‐Xian , Huang Fei , Yuan Xiao‐Wei , Deng Liang , Tang Di
Published: December 2018

Hepatocellular carcinoma (HCC) is mainly associated with hepatitis B virus (HBV) infection and characterized by metastasizing and infiltrating adjacent and distant tissues. Notably, microRNA‐1271 (miR‐1271) is a tumor suppressor in various cancers. Therefore, we evaluate the ability of miR‐1271 to influence cell proliferation, migration, invasion, and apoptosis in HBV‐associated HCC through the Adenosine monophosphate–activated protein kinase (AMPK) signaling pathway via targeting CCNA1. HBV‐associated HCC and adjacent normal tissues were collected to identify the expression of miR‐1271 and CCNA1. To verify the relationship between miR‐1271 and CCNA1, we used bioinformatics prediction and the dual‐luciferase reporter gene assay. The effects of miR‐1271 on HBV‐associated HCC cell behaviors were investigated by treatment of the miR‐1271 mimic, the miR‐1271 inhibitor, or small interfering RNA against CCNA1. The HBV‐DNA quantitative assay, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromid assay, scratch test, transwell assay, and flow cytometry were used to detect HBV‐DNA replication, cell proliferation, invasion, migration, and apoptosis. MiR‐1271 showed a low expression, whereas CCNA1 showed a high expression in HBV‐associated HCC tissues. We identified that miR‐1271 targeted and negatively regulated CCNA1. Upregulated miR‐1271 and downregulated CCNA1 inhibited the HBV‐associated HCC cell HBV‐DNA replication, proliferation, migration, and invasion, while accelerating apoptosis by activating the AMPK signaling pathway. MiR‐1271 promotes the activation of the AMPK signaling pathway by binding to CCNA1, whereby miR‐1271 suppresses HBV‐associated HCC progression. This study points to a potential therapeutic approach of downregulation of miR‐1271 in HBV‐associated HCC treatment.
Leukemia inhibitory factor inhibits the proliferation of gastric cancer by inducing G1‐phase arrest
Authors: Xu Guoxing , Wang Haibin , Li Weizheng , Xue Zengfu , Luo Qi
Published: December 2018

Leukemia inhibitory factor (LIF), a member of the interleukin‐6 cytokine family, plays a complex role in cancer. LIF inhibits the proliferation and survival of several myeloid leukemia cells but promotes tumor progression and metastasis in many solid tumors. However, the relationship between LIF and gastric cancer has not been well understood. LIF was downregulated in gastric cancer as detected by western blot analysis and immunohistochemistry (IHC). Notably, LIF was downregulated in approximately 70% (56/80) of primary gastric cancers, in which it was significantly associated with advanced clinical stage, lymph node metastasis, and poor overall survival (median 5‐year survival = 26 vs. 43 months for patients with high LIF expression and low LIF expression gastric cancer, respectively). To study the potential function of LIF in the downregulation of gastric cancer, we monitored the behavior using proliferation, cell cycle, and flow cytometry analysis. Overexpression of LIF inhibited the gastric cancer cell cycle in the G1 phase. In our experiment, overexpression of LIF by lentivirus upregulated P21 and downregulated cyclin D1. Recombinant human LIF also downregulated P21 and cyclin D1 at various times. A further in vivo tumor formation study in nude mice indicated that overexpression of LIF in gastric cancer significantly delayed the progress of tumor formation. These findings indicate that LIF may serve as a negative regulator of gastric cancer.
The role of microRNAs regulating the expression of matrix metalloproteinases (MMPs) in breast cancer development, progression, and metastasis
Authors: Javadian Mahsa , Gharibi Tohid , Shekari Najibeh , Abdollahpour‐Alitappeh Meghdad , Mohammadi Ali , Hossieni Arezoo , Mohammadi Hamed , Kazemi Tohid
Published: December 2018

MicroRNAs (miRNAs) regulate several biological and physiological processes in mammalian cells, including cellular proliferation, differentiation, apoptosis, and metabolism. Recent studies have confirmed the alteration of them during the cancer development. Matrix metalloproteinases (MMPs), belonging to the large family of proteases, have also been demonstrated to play crucial roles in tissue remodeling, and to support cancer progression and metastasis. There are several known miRNAs which regulate the MMP family and their expression. The expression profiles of miRNAs involved in MMP regulation, change during cancer progression, and metastasis. The present review focuses on important miRNAs capable of targeting MMPs through direct and indirect interactions during the breast cancer development, progression, and metastasis.
IL‐17 and IL‐22 elicited by a DNA vaccine encoding ROP13 associated with protection againstToxoplasma gondiiin BALB/c mice
Authors: Alizadeh Paria , Ahmadpour Ehsan , Daryani Ahmad , Kazemi Tohid , Spotin Adel , Mahami‐Oskouei Mahmoud , Flynn Robin J , Azadi Yaghob , Rajabi Saba , Sandoghchian Siamak
Published: December 2018

Toxoplasma gondii,an intracellular parasitic protozoan, is capable of infecting man and all warm‐blooded animals. Cell‐mediated immunity is vital in mounting protective responses againstT. gondiiinfection. Recent studies have shown that T‐helper (Th) 17 responses may play a key role in parasite control. In this current study, we constructed a DNA vaccine encodingT. gondiiROP13 in a pcDNA vector. Groups of BALB/c mice were immunized intramuscularly with pcROP13 or controls and challenged with the RH strain ofT. gondii. The results showed that immunization with pcROP13 could elicit an antibody response againstT. gondii. The expression of the canonical Th17 cytokines, interleukin (IL)‐17 and IL‐22, were significantly increased after immunization with pcROP13 compared with control groups (p < 0.05). Furthermore, vaccination resulted in a significant decrease in parasite load (p < 0.05). The induction of Th17 related cytokines, using a ROP13 DNA vaccine, againstT. gondiishould be considered as a potential vaccine approach for the control of toxoplasmosis.
Molecular aspects of pancreatic β‐cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA
Authors: Saeedi Borujeni Mohammad Javad , Esfandiary Ebrahim , Baradaran Azar , Valiani Ali , Ghanadian Mustafa , Codoñer‐Franch Pilar , Basirat Reyhane , Alonso‐Iglesias Eulalia , Mirzaei Hamed , Yazdani Amid
Published: December 2018

Metabolic syndrome is known as a frequent precursor of type 2 diabetes mellitus (T2D). This disease could affect 8% of the people worldwide. Given that pancreatic β‐cell dysfunction and loss have central roles in the initiation and progression of the disease, the understanding of cellular and molecular pathways associated with pancreatic β‐cell dysfunction can provide more information about the underlying pathways involved in T2D. Multiple lines evidence indicated that oxidative stress, microRNA, and long noncoding RNA play significant roles in various steps of diseases. Oxidative stress is one of the important factors involved in T2D pathogenesis. This could affect the function and survival of the β cell via activation or inhibition of several processes and targets, such as receptor‐signal transduction, enzyme activity, gene expression, ion channel transport, and apoptosis. Besides oxidative stress, microRNAs and noncoding RNAs have emerged as epigenetic regulators that could affect pancreatic β‐cell dysfunction. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in T2D pathogenesis. Here, we summarized the molecular aspects of pancreatic β‐cell dysfunction. Moreover, we highlighted the roles of oxidative stress, microRNAs, and noncoding RNAs in pancreatic β‐cell dysfunction.
Biomaterial aided differentiation and maturation of induced pluripotent stem cells
Authors: Velmurugan Bharath Kumar , Bharathi Priya Lohanathan , Poornima Paramasivan , Lee Li‐Jen , Baskaran Rathinasamy
Published: December 2018

Engineering/reprogramming differentiated adult somatic cells to gain the ability to differentiate into any type of cell lineage are called as induced pluripotent stem cells (iPSCs). Offering unlimited self‐renewal and differentiation potential, these iPSC are aspired to meet the growing demands in the field of regenerative medicine, tissue engineering, disease modeling, nanotechnology, and drug discovery. Biomaterial fabrication with the rapid evolution of technology increased their versatility and utility in regenerative medicine and tissue engineering, revolutionizing the stem cell biology research with the property to guide the process of proliferation, differentiation, and morphogenesis. Combining traditional culture platforms of iPSC with biomaterials aids to overcome the limitations associated with derivation, proliferation, and maturation, thereby could improve the clinical translation of iPSC. The present review discusses in brief about the reprogramming techniques for the derivation iPSC and details on several biomaterial guided differentiation of iPSC to different cell types with specific relevance to tissue engineering/regenerative medicine.
CircRNA fibroblast growth factor receptor 3 promotes tumor progression in non‐small cell lung cancer by regulating Galectin‐1‐AKT/ERK1/2 signaling
Authors: Qiu Bai‐Quan , Zhang Peng‐Fei , Xiong Dian , Xu Jian‐Jun , Long Xiang , Zhu Shu‐Qiang , Ye Xu‐Dong , Wu Yin , Pei Xu , Zhang Xue‐Mei , Wu Yong‐Bing
Published: December 2018

The dysregulation of circular RNA (circRNA) expression is involved in the progression of several cancers, including non‐small cell lung cancer (NSCLC). However, the role and underlying molecular mechanisms of circRNA FGFR3 (circFGFR3) in NSCLC progression remains unknown. Here, we used quantitative real‐time polymerase chain reaction to validate that circFGFR3 expression was higher in NSCLC tissues than in the paratumor tissues. Furthermore, our study indicated that the forced circFGFR3 expression promoted NSCLC cell invasion and proliferation. Mechanistically, we found that circFGFR3 promoted NSCLC cell invasion and proliferation via competitively combining with miR‐22‐3p to facilitate the galectin‐1 (Gal‐1), p‐AKT, and p‐ERK1/2 expressions. Clinically, we revealed that the high circFGFR3 expression correlates with the poor clinical outcomes in patients with NSCLC. Together, these data provide mechanistic insights into the circFGFR3‐mediated regulation of both the AKT and ERK1/2 signaling pathways by sponging miR‐22‐3p and increasing Gal‐1 expression.
Flavonoid genistein protects bone marrow sinusoidal blood vessels from damage by methotrexate therapy in rats
Authors: Hassanshahi Mohammadhossein , Su Yu‐Wen , Khabbazi Samira , Fan Chia‐Ming , Chen Ke‐Ming , Wang Ju‐Fang , Qian Airong , Howe Peter R. , Yan De‐Wen , Zhou Hou‐De , Xian Cory J.
Published: December 2018

Cancer chemotherapy can cause significant damage to the bone marrow (BM) microvascular (sinusoidal) system. Investigations must now address whether and how BM sinusoidal endothelial cells (SECs) can be protected during chemotherapy. Herein we examined the potential protective effects of genistein, a soy‐derived flavonoid, against BM sinusoidal damage caused by treatment with methotrexate (MTX). The groups of young adult rats were gavaged daily with genistein (20 mg/kg) or placebo. After 1 week, rats also received daily injections of MTX (0.75 mg/kg) or saline for 5 days and were killed after a further 4 days. Histological analyses showed that BM sinusoids were markedly dilated (
p < 0.001) in the MTX‐alone group but were unaffected or less dilated in the genistein+MTX group. In control rats, genistein significantly enhanced expression of vascular endothelial growth factor (VEGF;
p < 0.01), particularly in osteoblasts, and angiogenesis marker CD31 (
p < 0.001) in bone. In MTX‐treated rats, genistein suppressed MTX‐induced apoptosis of BM SECs (
p < 0.001 vs MTX alone group) and tended to increase expression of CD31 and VEGF (
p < 0.05). Our in vitro studies showed that genistein in certain concentrations protected cultured SECs from MTX cytotoxic effects. Genistein enhanced tube formation of cultured SECs, which is associated with its ability to induce expression of endothelial nitric oxide synthase and production of nitric oxide. These data suggest that genistein can protect BM sinusoids during MTX therapy, which is associated, at least partially, with its indirect effect of promoting VEGF expression in osteoblasts and its direct effect of enhancing nitric oxide production in SECs.
A new and simple kinetic model for assessing the dynamic behavior and simulating the biochemical methane potential (BMP) of sewage sludge in the presence of fly ash
Authors: Huiliñir César , Montalvo Silvio , Borja Rafael
Published: December 2018

BACKGROUND

The modeling of anaerobic digestion of sewage sludge including the effect of fly ash has been studied only scarcely and has focused mainly on the accumulated methane (CH4). The present work was aimed at assessing the complete dynamic behavior of the biochemical methane potential (BMP) of sewage sludge in the presence of fly ash, including both the liquid and gas phases. The model was calibrated and validated for BMPs using eight fly ash concentrations (10, 40, 25, 50 150, 250, 350 and 500 mg L−1).

RESULTS

The calibration showed that the model fits well with the experimental data, with the values of the parameters falling in the range reported in the literature. The calibrated model was able to describe properly the behavior of soluble chemical oxygen demand (COD) and volatile solids in the liquid phase, with normalized root mean square error (NRMSE) and correlation coefficients (CC) ranging from 0.4052 to 0.2729 and 0.6246 to 0.8172, respectively. For the gas phase, the model was able to represent accurately the daily CH4 production and accumulated CH4, with NRMSE and CC ranging from 0.8915 to 0.07194 and 0.5051 to 0.9736, respectively.

CONCLUSIONS

The proposed model is robust and valid for all the tested conditions. © 2018 Society of Chemical Industry
Synthesis, characterization and use of iron oxide nano particles for antibacterial activity
Authors: Saqib Saddam , Munis Muhammad Farooq Hussain , Zaman Wajid , Ullah Fazal , Shah Syed Nasar , Ayaz Asma , Farooq Muhammad , Bahadur Saraj
Published: December 2018

In this decade, the use of nano particles (NPs) against bacterial growth is increasing day by day due to remarkable alternative properties compared to molecular antibiotics. Thus, the use of iron oxide nanoparticles (IONPs) has proven one of the most important transition metals oxide‐based remedy in nanotechnological advances and biological applications due to enriched biocompatibility of iron. In this study synthesis of IONPs was carried out via co‐precipitation method. The crystallographic morphology of the synthesized particles was studied via X‐ray diffraction which revealed cubic structure of the particles, whereas, the spinal shaped morphology of the prepared NPs was confirmed from scanning electron microscopy. Likewise, the presence of the major elements in the sample was determined through energy dispersive X‐ray analysis characterization. Bactericidal effect of the NPs was assessed at pre‐defined concentrations (50 and 100 μg/ml) against Gram +ve bacteria Staphylococcus aureus, Gram −ve bacteria Shigella dysentry and Escherichia coli. Bacterial strains, which demonstrate the potential of NPs. The purpose of this study was assessing the structure of the synthesized NPs for protective effect against harmful bacterial activity.
Bipartite spanning sub(di)graphs induced by 2‐partitions
Authors: Bang‐Jensen J. , Bessy S. , Havet F. , Yeo A.
Published: December 2018

For a given ‐partition of the vertices of a (di)graph , we study properties of the spanning bipartite subdigraph of induced by those arcs/edges that have one end in each . We determine, for all pairs of nonnegative integers , the complexity of deciding whether has a 2‐partition such that each vertex in (for ) has at least (out‐)neighbours in . We prove that it is ‐complete to decide whether a digraph has a 2‐partition such that each vertex in has an out‐neighbour in and each vertex in has an in‐neighbour in . The problem becomes polynomially solvable if we require to be strongly connected. We give a characterisation of the structure of ‐complete instances in terms of their strong component digraph. When we want higher in‐degree or out‐degree to/from the other set, the problem becomes ‐complete even for strong digraphs. A further result is that it is ‐complete to decide whether a given digraph has a ‐partition such that is strongly connected. This holds even if we require the input to be a highly connected eulerian digraph.
Novel Nano‐sized bis‐indoline Derivatives as Antitumor Agents
Authors: Althagafi Ismail I. , Abouzied Amr S. , Farghaly Thoraya A. , Al‐Qurashi Nadia T. , Alfaifi Mohammad Y. , Shaaban Mohamed R. , Abdel Aziz Mohamed R.
Published: December 2018

A facile access to novel bis‐(indoline‐2,3‐dione) was achieved via reactions of isatin with 1,3‐dibromopropane. The utility of the versatile bis‐(indoline‐2,3‐dione) in the design of new multifunctional building blocks using condensation with hydrazine derivatives was demonstrated. Moreover, a new series of bis‐thiazoles and bis‐thiazol‐4(5H)‐ones were synthesized by the reaction of bis‐thiosemicarbazone derivative with various derivatives of hydrazonoyl halides. The calculations derived from X‐ray diffraction patterns indicated the nanosize of the newly designed compounds. The spectral data of the formed compounds were established their structures. Also, the cytotoxic activity of the produced derivatives was screened against line MCF‐7 (breast cancer cell). It was found that four derivatives from nine investigated compounds showed activity more potent than the standard drug used by 20 times in some cases.
Noncontrast MR angiography: An update
Authors: Edelman Robert R. , Koktzoglou Ioannis
Published: December 2018

Both computed tomography (CT) angiography (CTA) and contrast‐enhanced MR angiography (CEMRA) have proven to be useful and accurate cross‐sectional imaging modalities over a wide range of vascular territories and vascular disorders. A key advantage of MRA is that, unlike CTA, it can be performed without the administration of a contrast agent. In this review article we consider the motivations for using noncontrast MRA, potential contrast mechanisms, imaging techniques, advantages, and drawbacks with respect to CTA and CEMRA, and the level of evidence for using the various MRA techniques. In addition, we explore new developments that promise to expand the reliability and range of clinical applications for noncontrast MRA, along with functional MRA capabilities not available with CTA or CEMRA.

Level of Evidence: 1

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2019;49:355–373.
Surrogate‐assisted tolerance analysis of low‐sidelobe linear arrays with microstrip corporate feeds
Authors: Koziel Slawomir , Ogurtsov Stanislav
Published: December 2018

This paper addresses the problem of fast statistical analysis of low‐sidelobe linear arrays with microstrip corporate feeds using surrogate‐assisted methods. Tolerances normally lead to a degradation of array performance with respect to circuit and radiation pattern characteristics. Tolerances may be pertinent to array elements, spacing, feed dimensions, and microstrip substrate parameters. Sidelobe level (SLL) is affected by these parameter deviations in case of low sidelobe designs. Accurate evaluation of an SLL requires full‐wave electromagnetic (EM) simulations, which can be very computationally expensive. Consequently, performing statistical analysis directly at the level of the EM model of the array is impractical. Here, we discuss techniques that permits fast tolerance analysis yet at the high‐fidelity level of EM modeling. These include various surrogate modeling and correction techniques that are used to align the fast surrogates with the respective EM models.
Exploring a temporal relationship between biofilm microbiota and inflammatory mediators during resolution of naturally occurring gingivitis
Authors: Stone Simon J. , Kumar Purnima S. , Offenbacher Steven , Heasman Peter A. , McCracken Giles I.
Published: December 2018

Background

This study uses multiple, contemporary methodologies to expand our knowledge of the temporal relationship between host‐microbial interactions and clinical signs of gingivitis.

Methods

Subgingival plaque and crevicular fluid samples were collected from 31 systemically healthy adults with naturally occurring plaque‐induced gingivitis. Professional prophylaxis was administered and participants were followed over 7 weeks. Microbial characterization was performed using a bead‐based hybridization assay and cytokine analysis using bead‐based flow cytometry.

Results

The provision of sequential interventions, oral hygiene instruction, and subsequent professional prophylaxis brought about significant reduction of plaque and resolution of gingivitis at all post baseline time points (P < 0.0001). Candidate cytokines that increased significantly (95% level) were interleukin (IL)‐1β, matrix metalloproteinases (MMP)‐1, MMP‐3, MMP‐8, MMP‐9, from baseline to week 2; regulated on activation, normal T cell expressed and secreted (RANTES) at week 4 and week 8; macrophage inflammatory protein (MIP)‐1α and MIP‐1β at week 8. Resolution of inflammation was accompanied by a shift in the microbiological flora toward those species associated with health.

Conclusions

This study provides further evidence of the dynamic relationships that exist between the overt clinical signs, the microbial biofilm, and the host response in gingivitis and upon resolution following clinical interventions. Understanding the interactions between the host immune system and subgingival microbial communities during the resolution of established gingivitis continues to evolve as additional knowledge is achieved through using new analytical technologies. The present study confirms a critical effect of oral hygiene measures on restoration of microbial eubiosis in subgingival communities, confirming the important role for home care and professional intervention in maintaining oral health.