bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological consequences of invasion across the freshwater–marine transition in a warming world
Authors: Crespo Daniel , Solan Martin , Leston Sara , Pardal Miguel A. , Dolbeth Marina
Published: January 2018

The freshwater–marine transition that characterizes an estuarine system can provide multiple entry options for invading species, yet the relative importance of this gradient in determining the functional contribution of invading species has received little attention. The ecological consequences of species invasion are routinely evaluated within a freshwater versus marine context, even though many invasive species can inhabit a wide range of salinities. We investigate the functional consequences of different sizes ofCorbicula fluminea—an invasive species able to adapt to a wide range of temperatures and salinity—across the freshwater–marine transition in the presence versus absence of warming. Specifically, we characterize howC. flumineaaffect fluid and particle transport, important processes in mediating nutrient cycling (NH4‐N,NO3‐N,PO4‐P). Results showed that sediment particle reworking (bioturbation) tends to be influenced by size and to a lesser extent, temperature and salinity; nutrient concentrations are influenced by different interactions between all variables (salinity, temperature, and size class). Our findings demonstrate the highly context‐dependent nature of the ecosystem consequences of invasion and highlight the potential for species to simultaneously occupy multiple components of an ecosystem. Recognizing of this aspect of invasibility is fundamental to management and conservation efforts, particularly as freshwater and marine systems tend to be compartmentalized rather than be treated as a contiguous unit. We conclude that more comprehensive appreciation of the distribution of invasive species across adjacent habitats and different seasons is urgently needed to allow the true extent of biological introductions, and their ecological consequences, to be fully realized.
Bottom‐up processes drive reproductive success in an apex predator
Authors: Schmidt Joshua H. , McIntyre Carol L. , Roland Carl A. , MacCluskie Margaret C. , Flamme Melanie J.
Published: January 2018

One of the central goals of the field of population ecology is to identify the drivers of population dynamics, particularly in the context of predator–prey relationships. Understanding the relative role of top‐down versus bottom‐up drivers is of particular interest in understanding ecosystem dynamics. Our goal was to explore predator–prey relationships in a boreal ecosystem in interior Alaska through the use of multispecies long‐term monitoring data. We used 29 years of field data and a dynamic multistate site occupancy modeling approach to explore the trophic relationships between an apex predator, the golden eagle, and cyclic populations of the two primary prey species available to eagles early in the breeding season, snowshoe hare and willow ptarmigan. We found that golden eagle reproductive success was reliant on prey numbers, but also responded prior to changes in the phase of the snowshoe hare population cycle and failed to respond to variation in hare cycle amplitude. There was no lagged response to ptarmigan populations, and ptarmigan populations recovered quickly from the low phase. Together, these results suggested that eagle reproduction is largely driven by bottom‐up processes, with little evidence of top‐down control of either ptarmigan or hare populations. Although the relationship between golden eagle reproductive success and prey abundance had been previously established, here we established prey populations are likely driving eagle dynamics through bottom‐up processes. The key to this insight was our focus on golden eagle reproductive parameters rather than overall abundance. Although our inference is limited to the golden eagle–hare–ptarmigan relationships we studied, our results suggest caution in interpreting predator–prey abundance patterns among other species as strong evidence for top‐down control.
Dispersion Makes a Difference – The Solid‐State Structure of Hg[N(SiMe3)2]2
Authors: Bresien Jonas , Hering‐Junghans Christian , Kumm Peter , Schulz Axel , Thomas Max , Villinger Alexander
Published: January 2018

The solid‐state structure and Raman spectrum of Wannagat's mercurane, Hg[N(SiMe3)2]2 (1), are reported. Crystals were grown from the pure substance by slow cooling to –24 °C. Compound 1 crystallizes in the monoclinic space group P21/c as discrete monomers, which do not display intermolecular mercurophilic interactions. The molecular structure features a nearly linear N–Hg–N scaffold, while the (Me3Si)2N groups are in a staggered conformation with a dihedral angle of 58.3° (average) to each other. This can be attributed to intramolecular dispersion interactions according to DFT calculations.
Properties of Liposomes Containing Natural and Synthetic Lipids Formed by Microfluidic Mixing
Authors: Zheng Mengxiu , Fyles Thomas M.
Published: January 2018

Vesicle formation by a staggered herringbone microfluidic mixer is investigated in comparison to a sonication‐extrusion method. Experiments focused on the incorporation efficiency of lipid components, on dye entrapment efficiency, and on the barrier properties of the vesicle bilayers produced. The microfluidic method produces vesicles largely under the control of thermodynamic factors. As a result, the molecular parameters of the lipids (chain length, chain volume, head group area) directly control vesicle diameter. A hydrophobic branched chain sulfonate lipid is incorporated by microfluidic mixing but not by sonication‐extrusion. The vesicles produced by microfluidic mixing can be used to study ion transport by known ionophores and appear to have directly comparable barrier properties to those produced by sonication‐extrusion. Vesicles containing the branched chain sulfonate are highly permeable. The microfluidic mixing method produces predominantly unilamellar vesicles.

Practical Applications: The microfluidic device examined offers a new method to reproducibly produce vesicles that are directly controlled by the molecular components of the lipid mixture. The authors show that this method produces vesicles that are equivalent to currently used methods in the study of synthetic ion channels and carriers. Looking forward, thermodynamically controlled self‐assembly will find application in the creation of new membrane systems and assemblies where the vesicles themselves are the building blocks in more extensive structures, and the active components in inter‐vesicle functions.

A staggered herringbone microfluidic mixer reproducibly gives size‐controlled unilamellar vesicles having low‐permeability bilayer membranes.
Fluorescent Recognition of 1,3‐Diaminopropane in the Fluorous Phase – Greatly Enhanced Sensitivity and Selectivity
Authors: Shi Dan , Wang Xinjing , Yu Shanshan , Zhao Feng , Wang Yachen , Tian Jun , Hu Lingling , Yu Xiaoqi , Pu Lin
Published: January 2018

A 1,1′‐binaphthyl‐based dialdehyde, which is soluble in the fluorous phase, is synthesized. The fluorescence of this compound is greatly enhanced by 1,3‐diaminopropane (DAP) in perfluorohexane (FC‐72) but not by other amines and diamines. Thus, this compound can be used as a fluorescent sensor for the detection of the biologically important DAP at submicromolar concentrations. The selectivity and sensitivity of this fluorescent probe in this fluorous solvent are much greater than those in the common organic solvent dichloromethane.
Chemoselective Synthesis of Arylpyridines through Suzuki–Miyaura Cross‐Coupling Reactions
Authors: Perdomo Rivera Rodisnel , Ehlers Peter , Ohlendorf Lars , Torres Rodríguez Eugenio , Villinger Alexander , Langer Peter
Published: January 2018

4‐Bromo‐2,3,5‐trichloro‐6‐iodopyridine has been synthesized for the first time and applied in chemo‐ and site‐selective Suzuki–Miyaura cross‐coupling reactions. This novel starting material allows the selective synthesis of pentaarylpyridines with up to four different aryl substituents.
Synthesis of Triazolium Inner Salts by Thiocyanation of Aldehyde‐Derived Hydrazones
Authors: Mondal Susmita , Samanta Sadhanendu , Hajra Alakananda
Published: January 2018

An ammonium persulfate mediated thiocyanation reaction of aldehyde‐derived hydrazones has been carried out under metal‐free conditions at ambient temperature to afford the corresponding 5‐thioxo‐1,2,4‐triazolium inner salts. A library of triazolium inner salts that contain a wide range of functional groups were synthesized in high yields. The reaction proceeds through a thiocyanation followed by isomerization to give the isothiocyanate and subsequent cyclization steps.
Prediction analysis and quality assessment of microwell array images
Authors: Mazumdar Hirak , Kim Tae Hyeon , Lee Jong Min , Ha Jang Ho , Ahrberg Christian D. , Chung Bong Geun
Published: January 2018

Microwell arrays are widely used for the analysis of fluorescent‐labelled biomaterials. For rapid detection and automated analysis of microwell arrays, the computational image analysis is required. Support Vector Machines (SVM) can be used for this task. Here, we present a SVM‐based approach for the analysis of microwell arrays consisting of three distinct steps: labeling, training for feature selection, and classification into three classes. The three classes are filled, partially filled, and unfilled microwells. Next, the partially filled wells are analyzed by SVM and their tendency towards filled or unfilled tested through applying a Gaussian filter. Through this, all microwells can be categorized as either filled or unfilled by our algorithm. Therefore, this SVM‐based computational image analysis allows for an accurate and simple classification of microwell arrays.
Social Media May Empower Fisheries Students via Learning Networks
Authors: Orth Donald J
Published: January 2018

Social media has great, unrealized potential to improve student learning and engagement. Whereas some traditional face-to-face instruction may encourage “cram, pass, and forget” learning strategies, a holistic approach to student learning requires smart use of social media to facilitate long-term personal, professional, and scholarly development. In this paper, I advocate the alignment of learning objectives with assignments and learning environments that encourage a high level of involvement by the student in a community of practice. These learning activities are enhanced by use of social media in teaching. Five pedagogies that will benefit fisheries students and enhance social networks include public writing, Twitter and infographics, digital storytelling, online communities, and electronic portfolios. Social media application in a holistic, multi-modal approach respects student differences and enables more engaging, open learning networks.
Subclinical depressive symptoms during late midlife and structural brain alterations: A longitudinal study of Danish men born in 1953
Authors: Osler Merete , Sørensen Lauge , Rozing Maarten , Calvo Oriol Puig , Nielsen Mads , Rostrup Egill
Published: January 2018

We explored whether depressive symptoms measured three times during midlife were associated with structural brain alterations quantified using magnetic resonance imaging measurements of volume, cortical thickness, and intensity texture. In 192 men born in 1953 with depressive symptoms measured at age 51, 56, and 59 years, magnetic resonance imaging was performed at age 59. All data processing was performed using the Freesurfer software package except for the texture‐scores that were computed using in‐house software. Structural brain alterations and associations between depressive symptoms and brain structure outcomes were tested using Pearson's correlation, t test, and linear regression. Depressive symptoms at age 51 showed clear inverse correlations with total gray matter, pallidum, and hippocampal volume with the strongest estimate for hippocampal volume (r = −.22, p < .01). After exclusion of men (n = 3) with scores in the range of clinical depression the inverse correlation between depressive symptoms and hippocampal volume became insignificant (r = −13, p = .08). Depressive symptoms at age 59 correlated positively with hippocampal and amygdala texture‐potential early markers of atrophy. Inverse relations with total gray matter and pallidum volumes lost significance when the analysis was adjusted for intracranial volume. In men, depressive symptoms at age 51 were associated with a reduced volume of the hippocampus at age 59 independent of later symptoms. Amygdala and hippocampal textures might be the early markers for brain alterations associated with depression in midlife.
Abnormal fronto‐striatal activation as a marker of threshold and subthreshold Bulimia Nervosa
Authors: Cyr Marilyn , Yang Xiao , Horga Guillermo , Marsh Rachel
Published: January 2018

This study aimed to determine whether functional disturbances in fronto‐striatal control circuits characterize adolescents with Bulimia Nervosa (BN) spectrum eating disorders regardless of clinical severity. FMRI was used to assess conflict‐related brain activations during performance of a Simon task in two samples of adolescents with BN symptoms compared with healthy adolescents. The BN samples differed in the severity of their clinical presentation, illness duration and age. Multi‐voxel pattern analyses (MVPAs) based on machine learning were used to determine whether patterns of fronto‐striatal activation characterized adolescents with BN spectrum disorders regardless of clinical severity, and whether accurate classification of less symptomatic adolescents (subthreshold BN; SBN) could be achieved based on patterns of activation in adolescents who met DSM5 criteria for BN. MVPA classification analyses revealed that both BN and SBN adolescents could be accurately discriminated from healthy adolescents based on fronto‐striatal activation. Notably, the patterns detected in more severely ill BN compared with healthy adolescents accurately discriminated less symptomatic SBN from healthy adolescents. Deficient activation of fronto‐striatal circuits can characterize BN early in its course, when clinical presentations are less severe, perhaps pointing to circuit‐based disturbances as useful biomarker or risk factor for the disorder, and a tool for understanding its developmental trajectory, as well as the development of early interventions.
Narrow band imaging versus laryngovideostroboscopy in precancerous and malignant vocal fold lesions
Authors: Rzepakowska Anna , Sielska‐Badurek Ewelina , Cruz Raul , Sobol Maria , Osuch‐Wójcikiewicz Ewa , Niemczyk Kazimierz
Published: January 2018

Background

This is a comparative analysis of the diagnostic accuracy of narrow band imaging (NBI) and laryngovideostroboscopy (LVS) in the assessment of premalignant and malignant vocal fold lesions.

Methods

A prospective analysis was performed on 105 consecutive patients with vocal fold lesions. The NBI and LVS were obtained before the microsurgery.

Results

The NBI and LVS showed no significant differences in identifying premalignant and malignant pathologies. However, in analysis restricted to identification of only malignant lesions, the specificity (88.9% vs 20.6%), accuracy (90.5% vs 51.4%), and positive predictive value (PPV; 84.8% vs 45.1%) were significantly higher for NBI (P value < .001; .015; and .045, respectively). A comparison of LVS scored results relative to each NBI type revealed statistically significant differences (P < .001). A moderate positive correlation between NBI and LVS was demonstrated (P = .54).

Conclusion

The NBI and LVS are useful, complementary tools in evaluating early potential vocal fold malignancies. The NBI was superior to LVS on several statistical analyses.
Learning to Talk Back to Texts
Authors: Leland Christine , Ociepka Anne , Kuonen Kate , Bangert Sara
Published: January 2018

This article describes an informal study that focused on teaching eighth graders to take a critical stance and talk back to texts. In this era of “fake news,” “alternative facts,” and what has been called a “post‐truth” culture, it is imperative that students do not simply accept everything they read, see, or hear at face value. They must be made aware that information presented as fact is not necessarily true and that it is up to them to identify the messages embedded in texts before deciding whether they agree with them, disagree with them, or need more information to make a decision. Data sources include students’ responses to three sophisticated picture books, their responses to questions about what talking back means and why people do it, examples of students talking back to common sayings, and examples of them talking back to an instance of administrative censorship.
Biochemical and molecular study on interleukin‐1β gene expression and relation of single nucleotide polymorphism in promoter region with Type 2 diabetes mellitus
Authors: Tayel Safaa I. , Fouda Eman A. M. , Elshayeb Elsayed I. , Eldakamawy Asmaa R. A. , El‐kousy Salah M.
Published: January 2018

Interleukin‐1β (IL‐1β) assumes a centric role in the regulation of immune and inflammatory responses and thus has been recognized in immune mediated diseases like type 2 diabetes mellitus (T2DM). We aimed to investigate expressed level of IL‐1β and its relation with IL‐1β −511T>C polymorphism in T2DM patients. This study enrolled 80 subjects (50 patients with T2DM and 30 healthy control subjects). Laboratory investigations included fasting (FBG) and 2 h postprandial blood sugar (2 h PBG), HBA1c, lipid profile, and renal function tests. Genotyping of IL‐1β −511T>C (rs16944) SNP assay by real‐time PCR and relative quantitation of IL‐1β gene expression transcript by real‐time PCR. Results: T2DM patients had significantly higher FBG and 2 h PBG, HBA1c, LDLc, TC, TG, systolic, and diastolic BP while lower HDLc compared with control group. IL 1‐ β −511 T>C, CC genotype and C allele were significantly associated with risk of T2DM with odds ratio (OR) 4.73, 95%CI (1.21‐18.39) and OR 2.27, 95%CI (1.72‐4.40), respectively. Moreover, diabetic patients had significantly higher IL 1‐ β gene transcript compared with control group (P < 0.001). CC genotype of IL 1‐ β −511 T > C had the highest significant level of IL 1‐ β gene transcript demonstrated compared with C/T and T/T genotypes (P < 0.001) in patients. Conclusion: C allele of IL‐1 β −511 T >C could be considered risk factor contributor to T2DM and excess level of IL‐1 β transcript may disclose to some degree the inflammatory role of cytokines in T2DM.
An epididymis‐specific secretory protein Clpsl2 critically regulates sperm motility, acrosomal integrity, and male fertility
Authors: Lu Xiaosheng , Ding Fei , Lian Zizhen , Chen Lei , Cao Zuowu , Guan Yiqing , Chen Ran , Cai Dongqing , Yu Yanhong
Published: January 2018

The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. Here we report that Clpsl2, a novel colipase homology, is exclusively expressed in the caupt epididymis and conserved in mammalian. Clpsl2 was secreted into the lumen and covered the acrosome region and principal piece of spermatozoa tail. And during epididymal transit, the binding rate between Clpsl2 protein and the spermatozoa gradually decreased. Though Clpsl2 had the highest identifies with pancreatic colipase (Clps), Clpsl2 lacked those conserved amino acids in pancreatic Clps that interacting with lipase, correspondingly, the recombinant Clpsl2 protein did not possess the Clps function such as promoting the hydrolysis of lipase to its substrate glycerine trioleate. However, sequence analysis showed that Clpsl2 has the potency to bind with lipid. Knockdown expression of Clpsl2 by lentivirus‐mediated RNAi in vivo caused an attenuation of spermatozoa motility, a suppressed acrosomal reaction, a decrease of cauda spermatozoa number, and subfertility. This study identified a novel and conserved molecule, Clpsl2, was specifically expressed in epididymis and involved in the regulation of spermatozoa motility, acrosomal integrity, and male fertility.
MicroRNA‐193b‐3p regulates matrix metalloproteinase 19 expression in interleukin‐1β‐induced human chondrocytes
Authors: Chang Zong‐kun , Meng Fan‐gang , Zhang Zhi‐qi , Mao Gu‐ping , Huang Zhi‐yu , Liao Wei‐ming , He Ai‐shan
Published: January 2018

Micro(mi)RNAs are small, non‐coding RNA molecules known to play a significant role in osteoarthritis (OA) initiation and development, and similar to matrix metalloproteinases (MMPs), they participate in cartilage degeneration and cleave multiple extracellular matrices. The aim of this study was to determine whether the expression of MMP‐19 in interleukin (IL)‐1β‐induced human chondrocytes is directly regulated by miR‐193b‐3p. Expression levels of miR‐193b‐3p and MMP‐19 in normal and osteoarthritis (OA) human cartilage, and interleukin‐1 β (IL‐1β)‐induced human chondrocytes were determined by real‐time polymerase chain reaction. Additionally, expression level of MMP‐19 in IL‐1β‐induced human chondrocytes was estimated by Western blotting and immunohistochemistry analyses. The effect of miR‐193b‐3p on MMP‐19 expression was evaluated using transient transfection of normal human chondrocytes with miR‐193b‐3p mimic or its antisense inhibitor (miR‐193b‐3p inhibitor), and siMMP‐19. The putative binding site of miR‐193b‐3p in the 3′‐untranslated region (UTR) of MMP‐19 mRNA was validated by luciferase reporter assay. miR‐193b‐3p expression was reduced in OA cartilage compared to that in normal chondrocytes, while the opposite was observed for MMP‐19. Upregulation of MMP‐19 expression was correlated with downregulation of miR‐193b‐3p in IL‐1β‐stimulated normal chondrocytes. Increase in miR‐193b‐3p levels was associated with silencing of MMP‐19. Overexpression of miR‐193b‐3p suppressed the activity of the reporter construct containing the 3′‐UTR of human MMP‐19 mRNA and inhibited the IL‐1β‐induced expression of MMP‐19 and iNOS in chondrocytes, while treatment with miR‐193b‐3p inhibitor enhanced MMP‐19 expression. MiR‐193b‐3p is an important regulator of MMP‐19 in human chondrocytes and may relieve the inflammatory response in OA.
Differential expression profile of long non‐coding RNAs in human thoracic aortic aneurysm
Authors: Li Yang , Liu Yang , Liu Suxuan , Wu Feng , Li Songhua , Yang Fan , Gu Ying , Xu Zhiyun , Wang Guokun
Published: January 2018

Thoracic aortic aneurysm (TAA) is progressive fatal aortic pathological dilation, which is characterized by increased proteoglycans and loss of elastic fibers. Recent advances in long non‐coding RNAs (lncRNAs), an important regulator in many biological processes, suggested the close correlation between expression patterns and disease progression. In the present study, the ascending aortic tissues were collected from ascending TAA patients (n = 33) and organ donors (n = 16). Microarray analysis and real‐time PCR were then applied to detect the lncRNA expression profiles. A total of 147 differentially expressed lncRNAs were determined, including 104 upregulated and 43 downregulated lncRNAs. Bioinformatics analysis showed 51.7% of differentially expressed lncRNAs were sense‐overlapping, and most of the down‐regulated lncRNAs were located on chromosome 1, 7, and 12. Subgroup analysis of TAA patients indicated that the expression of lnc‐HLTF‐5 was significantly higher in hypertension group than non‐hypertension group (P < 0.05). Spearman correlation analysis further confirmed that the lnc‐HLTF‐5 level was positively correlated with the expanded ascending aortic diameter (rs = 0.483, P = 0.004) and MMP9 level (rs = 0.465, P = 0.006). Our results expanded the lncRNA expression patterns in aortic disease, and provided experimental basis for future investigation on TAA pathogenesis.
Retracted: Long non‐coding RNA ASBEL promotes osteosarcoma cell proliferation, migration, and invasion by regulating microRNA‐21
Authors: Zhao Jianhui , Zhang Chao , Gao Zhongli , Wu Han , Gu Rui , Jiang Rui
Published: January 2018

Osteosarcoma is the most common malignant bone tumor in children and adolescents with high rate of incidence, high frequency of recurrence, and high degree of metastasis. This study aimed to investigate the effects of long noncoding RNA antisense ncRNA in the abundant in neuroepithelium area (ANA)/B‐cell translocation gene 3 (BTG3) locus (lncRNA ASBEL) on the pathogenesis of osteosarcoma. The expression levels of ASBEL in human osteoblast cells and human osteosarcoma cells were evaluated using qRT‐PCR. Effects of ASBEL knockdown on cell viability, migration, and invasion were detected using trypan blue exclusion assay, cell migration, and cell invasion assay, respectively. The regulatory effects of ASBEL on microRNA‐21 (miR‐21) were analyzed using qRT‐PCR. The roles of miR‐21 and protein phosphatase 2A (PP2A), the possible downstream factor of miR‐21, in osteosarcoma cell proliferation, migration, and invasion were also explored. The results showed that ASBEL was highly expressed in osteosarcoma cells. Knockdown of ASBEL inhibited osteosarcoma cell viability, migration, and invasion, as well as the expression level of miR‐21. PP2A was a direct target of miR‐21, which participated in the effects of ASBEL and miR‐21 on the activation of phosphatidylinositol 3‐kinase/protein kinase 3/glycogen synthase kinase‐3β (PI3K/AKT/GSK3β) and mitogen‐activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathways as well as the enhancement of osteosarcoma cell proliferation, migration, and invasion. In conclusion, we verified that ASBEL‐miR‐21‐PP2A pathway might play critical regulatory effects on the pathogenesis of osteosarcoma and could be as the potential therapeutic target and biomarker for osteosarcoma treatment.
A fully analytical integration of properties over the 3D volume of the β sphere in topological atoms
Authors: Popelier Paul L. A.
Published: January 2018

Atomic multipole moments associated with a spherical volume fully residing within a topological atom (i.e., the β sphere) can be obtained analytically. Such an integration is thus free of quadrature grids. A general formula for an arbitrary rank spherical harmonic multipole moment is derived, for an electron density comprising Gaussian primitives of arbitrary angular momentum. The closed expressions derived here are also sufficient to calculate the electrostatic potential, the two types of kinetic energy, as well as the potential energy between atoms. Some integrals have not been solved explicitly before but through recursion and substitution are broken down to more elementary listed integrals. The proposed method is based on a central formula that shifts Gaussian primitives from one center to another, which can be derived from the well‐known plane‐wave expansion (or Rayleigh equation). © 2018 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.
Predicting reduction potentials of 1,3,6‐triphenyl fulvenes using molecular electrostatic potential analysis of substituent effects
Authors: Anjali Bai Amutha , Suresh Cherumuttathu H.
Published: January 2018

The influence of mono‐ and multiple substituent effect on the reduction potential (E0) of 1,3,6‐triphenyl fulvenes is investigated using B3LYP‐SMD/6‐311+G(d,p) level density functional theory. The molecular electrostatic potential (MESP) minimum at the fulvene π‐system (Vmin) and the change in MESP at any of the fulvene carbon atoms (ΔVC) for both neutral and reduced forms are used as excellent measures of substituent effect from the para and meta positions of the 1,3 and 6‐phenyl moieties. Substitution at 6‐phenyl para position has led to significant change in E0 than any other positions. By applying the additivity rule of substituent effects, an equation in ΔVC is derived to predict E0 for multiply substituted fulvenes. Further, E0 is predicted for a set of 2000 hexa‐substituted fulvene derivatives where the substituents and their positions in the system are chosen in a random way. The calculated E0 agreed very well with the experimental E0 reported by Godman et al. Predicting E0 solely by substituent effect offers a simple and powerful way to select suitable combinations of substituents on fulvene system for light harvesting applications. © 2018 Wiley Periodicals, Inc.
Sirtuin 3 silencing improves oxaliplatin efficacy through acetylation of MnSOD in colon cancer
Authors: Torrens‐Mas Margalida , Hernández‐López Reyniel , Oliver Jordi , Roca Pilar , Sastre‐Serra Jorge
Published: January 2018

Sirtuin 3 (SIRT3) is the major mitochondria deacetylase and regulates ROS levels by targeting several key proteins, such as those involved in mitochondrial function and antioxidant defenses. This way, SIRT3 balances ROS production and scavenging and promotes cell survival. The aim of this study was to analyze the effect of SIRT3 silencing on the antioxidant response in SW620 colon cancer cell line, and whether this intervention could improve efficacy of oxaliplatin, a common drug used to treat colon cancer. For this purpose, we obtained stable clones of SW620 with SIRT3 knockdown and determined parameters such as ROS levels and ROS production, levels of several antioxidant enzymes, cell viability, and apoptosis. Results showed that after SIRT3 silencing, both ROS levels and production were increased, and antioxidant enzymes gene expression was significantly reduced. Furthermore, manganese superoxide dismutase levels and enzymatic activity were reduced. Combination of SIRT3 knockdown with oxaliplatin treatment further increased ROS production and apoptosis, reducing cell viability. Finally, survival curves on colon cancer patients suggested that SIRT3 expression is related to a poorer prognosis. In conclusion, SIRT3 could be a target for colon cancer, since it regulates the antioxidant response and its knockdown improves the efficacy of oxaliplatin treatment.
XIST accelerates neuropathic pain progression through regulation of miR‐150 and ZEB1 in CCI rat models
Authors: Yan Xue‐Tao , Lu Jing‐Min , Wang Yu , Cheng Xiao‐Li , He Xiang‐Hu , Zheng Wen‐Zhong , Chen Hu , Wang Yan‐Lin
Published: January 2018

LncRNAs are reported to participate in neuropathic pain development. LncRNA X‐inactive specific transcript (XIST) is involved in the progression of various cancers. However, the role of XIST in neuropathic pain remains unclear. In our present study, we established a chronic constriction injury (CCI) rat model and XIST was found to be greatly upregulated both in the spinal cord tissues and in the isolated microglias of CCI rats. Inhibition of XIST inhibited neuropathic pain behaviors including mechanical and thermal hyperalgesia. Moreover, decrease of XIST repressed neuroinflammation through inhibiting COX‐2, tumor necrosis factor (TNF)‐α and IL‐6 and in CCI rats. Previously, miR‐150 has been reported to restrain neuropathic pain by targeting TLR5. Currently, miR‐150 was predicted to be a microRNA target of XIST, which indicated a negative correlation between miR‐150 and XIST. miR‐150 was remarkably decreased in CCI rats and overexpression of miR‐150 can significantly suppress neuroinflammation‐related cytokines. Furthermore, ZEB1 was exhibited to be a direct target of miR‐150 and we found it was overexpressed in CCI rats. Silencing ZEB1 was able to inhibit neuropathic pain in vivo and downreguation of XIST decreased ZEB1, which can be reversed by miR‐150 inhibitors. Taken these together, we indicated that XIST can induce neuropathic pain development in CCI rats via upregulating ZEB1 by acting as a sponge of miR‐150. It was revealed that XIST/miR‐150/ZEB1 axis can be provided as a therapeutic target in neuropathic pain.
Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus
Authors: Frinchi Monica , Scaduto Pietro , Cappello Francesco , Belluardo Natale , Mudò Giuseppa
Published: January 2018

The cholinergic system plays a crucial role in modulating in the central nervous system physiological responses such as neurogenesis, neuronal differentiation, synaptic plasticity, and neuroprotection. In a recent study, we showed that Oxotremorine‐M, a non‐selective muscarinic acetylcholine receptor agonist, is able to transactivate the fibroblast growth factor receptor and to produce a significant increase in the hippocampal primary neurite outgrowth. In the present study we aimed to explore in the rat hippocampus the possible effect of acute or chronic treatment with Oxotremorine‐M on some heat shock proteins (Hsp60, Hsp70, Hsp90) and on activation of related transcription factor heat shock factor 1 (HSF1). Following single injection of Oxotremorine‐M (0.4 mg/kg) all Hsps examined were significantly increased in at least one of the time points studied (24, 48, and 72 hr). Treatment with Oxotremorine‐M significantly increased the level of phosphorylated HSF1 in all time points studied, without change of protein levels. Similar pattern of Hsps changes was obtained following chronic Oxotremorine‐M treatment (0.2 mg/kg) for 5 days. Surprisingly, following chronic treatment for 10 days no changes were observed in Hsps. The muscarinic acetylcholine receptor antagonist scopolamine (1 mg/kg) was able to completely block Oxotremorine‐M effects on Hsps. In conclusion, considering the function of Hsps in protecting neuronal cells from deleterious proteotoxic stress, for example, protein mis‐folding and aggregation, the results obtained indicate that muscarinic acetylcholine receptor activation may have implications in potential treatment of neurodegenerative disorders linked to protein aggregation, such as Alzheimer disease.
Leukotriene B4 receptor 2 regulates the proliferation, migration, and barrier integrity of bronchial epithelial cells
Authors: Liu Min , Shen Juan , Yuan Huimin , Chen Fengling , Song Huaidong , Qin Hui , Li Yanqin , Xu Jiabo , Ye Qing , Li Shenxian , Saeki Kazuko , Yokomizo Takehiko
Published: January 2018

The airway epithelium plays a crucial role in the pathogenesis of asthma. The functions of leukotriene B4 receptor 2 (BLT2) on the airway epithelial cells remains unknown. In our study, BLT2 expression in 16HBE bronchial epithelial cells were manipulated by transfection with BLT2 overexpression plasmid or BLT2 small interference RNA. 16HBE cells were then exposed to BLT2 antagonist (LY255283) or BLT2 agonist (12(S)‐hydroxyheptadeca‐5Z,8E,10E‐trienoic acid [12‐HHT] or CAY10583). The results showed that BLT2 overexpression, 12‐HHT stimulation, or CAY10583 treatment resulted in the enhanced proliferation and migration of 16HBE cells. In addition, BLT2 showed an inhibitory effect on epithelial permeability as illustrated by the measurement of transepithelial electrical resistance (TER) and epithelial permeability, and a promoting effect on the levels of tight junction proteins (occludin and claudin‐4) and phosphorylated p38 as demonstrated by real‐time PCR and Western blotting analyses. These results suggest BLT2 as a key determinant of airway epithelial barrier integrity. On the contrary, RNAi‐mediated knockdown or LY255283 treatment had reversed effects on the proliferation, migration, and epithelial barrier integrity. Together, our findings suggest the critical roles of BLT2 on the functions of bronchial epithelial cells and that BLT2 agonists are potential therapeutic agents for asthma treatment.
Serum IgG antibodies from healthy subjects up to 100 years old react to JC polyomavirus
Authors: Bononi Ilaria , Mazzoni Elisa , Pietrobon Silvia , Manfrini Marco , Torreggiani Elena , Rossini Marika , Lotito Francesca , Guerra Giovanni , Rizzo Paola , Martini Fernanda , Tognon Mauro
Published: January 2018

JC polyomavirus (JCPyV) was identified in 1971 in the brain tissue of a patient (J.C.) affected by the progressive multifocal leukoencephalopathy (PML). JCPyV encodes for the oncoproteins large T antigen (Tag) and small t‐antigen (tag). These oncoproteins are responsible of the cell transformation and tumorigenesis in experimental animals. JCPyV is ubiquitous in human populations. After the primary infection, which is usually asymptomatic, JCPyV remains lifelong in the host in a latent phase. Its reactivation may occur in heathy subjects and immunocompromised patients. Upon reactivation, JCPyV could reach (i) the CNS inducing the PML, (ii) the kidney of transplant patients causing the organ rejection. Association between JCPyV, which is a small DNA tumor virus, and gliomas and colorectal carcinomas has been published. In the present investigation, we report on a new indirect ELISA with two specific synthetic peptides mimicking JCPyV VP1 immunogenic epitopes to detect specific serum IgG antibodies against JCPyV. Serum samples of healthy subjects (n = 355) ranging 2–100 years old, were analyzed by this new indirect ELISA. The linear peptides VP1 K and VP1 N resemble the natural JCPyV VP1 capsidic epitopes constituting a docking site for serum antibodies. Data from this innovative immunologic assay indicate that the overall prevalence of JCPyV‐VP1 antibodies in healthy subjects is at 39%. The innovative indirect ELISA with JCPyV VP1 mimotopes seems to be a useful method to detect specific IgG antibodies against this virus, without cross‐reactivity with the closely related SV40 and BKPyV polyomaviruses.
Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post‐traumatic osteoarthritis
Authors: Lin Chuangxin , Shao Yan , Zeng Chun , Zhao Chang , Fang Hang , Wang Liping , Pan Jianying , Liu Liangliang , Qi Weizhong , Feng Xiaofeng , Qiu Hong , Zhang Haiyang , Chen Yuhui , Wang Hong , Cai Daozhang , Xian Cory J.
Published: January 2018

PI3K/AKT signaling is essential in regulating pathophysiology of osteoarthritis (OA). However, its potential modulatory role in early OA progression has not been investigated yet. Here, a mouse destabilization OA model in the tibia was used to investigate roles of PI3K/AKT signaling in the early subchondral bone changes and OA pathological process. We revealed a significant increase in PI3K/AKT signaling activation which was associated with aberrant bone formation in tibial subchondral bone following destabilizing the medial meniscus (DMM), which was effectively prevented by treatment with PI3K/AKT signaling inhibitor LY294002. PI3K/AKT signaling inhibition attenuated articular cartilage degeneration. Serum and bone biochemical analyses revealed increased levels of MMP‐13, which was found expressed mainly by osteoblastic cells in subchondral bone. However, this MMP‐13 induction was attenuated by LY294002 treatment. Furthermore, PI3K/AKT signaling was found to enhance preosteoblast proliferation, differentiation, and expression of MMP‐13 by activating NF‐κB pathway. In conclusion, inhibition of PI3K/AKT/NF‐κB axis was able to prevent aberrant bone formation and attenuate cartilage degeneration in OA mice.
The origins and homeostasis of monocytes and tissue‐resident macrophages in physiological situation
Authors: Zhao Yang , Zou Weilong , Du Junfeng , Zhao Yong
Published: January 2018

Monocytes and macrophages are critical effectors and regulators of innate immune response. They not only play crucial and distinctive roles in homeostasis, but also contribute to some pathologic processes. The heterogeneity of the macrophage lineage has been widely recognized and, in part, is a result of the specialization of resident macrophages in particular tissue microenvironments. Monocytes are usually known to originate in the bone marrow from a common myeloid progenitor that is shared with neutrophils, and they are then released into the peripheral blood. However, the origin of tissue‐resident macrophages, crucial for homeostasis and immunity, has remained controversial until recently. During embryonic organogenesis, macrophages derived from yolk sac and fetal liver precursors are seeded throughout tissues, persisting in the adulthood as resident, self‐maintaining populations. After birth, bone marrow‐derived monocytes can replenish tissue resident macrophages following injury, infection and inflammation. In this review, we will mainly summarize our current understanding on the origin, ontogeny and fates of tissue macrophages and will briefly discuss the molecular regulation of resident macrophage homeostasis in physiological situation.
HIV‐1 increases extracellular amyloid‐beta levels through neprilysin regulation in primary cultures of human astrocytes
Authors: Martínez‐Bonet Marta , Muñoz‐Fernández M. Ángeles , Álvarez Susana
Published: January 2018

Since the success of combined antiretroviral therapy, HIV‐1‐infected individuals are now living much longer. This increased life expectancy is accompanied by a higher prevalence of HIV‐1 associated neurocognitive disorders. Rising too is the incidence in these patients of pathological hallmarks of Alzheimer's disease such as increased deposition of amyloid beta protein (Aβ). Although neurons are major sources of Aβ in the brain, astrocytes are the most numerous glial cells, therefore, even a small level of astrocytic Aβ metabolism could make a significant contribution to brain pathology. Neprilysin (NEP) is a decisive/crucial regulator of Aβ levels. We evaluated the effects of HIV‐1 on Aβ deposition and the expression and activity of NEP in primary human astrocytes. Specifically, no differences in intracellular amyloid deposits were found between infected and control cells. However, primary cultures of infected astrocytes showed more extracellular Aβ levels compared to controls. This was accompanied by reduced expression of NEP and to a significant decrease in its activity. These results indicate that the presence of HIV‐1 in the brain could contribute to the increase in the total burden of cerebral Aβ.
Alleviation of palmitic acid‐induced endoplasmic reticulum stress by augmenter of liver regeneration through IP3R‐controlled Ca2+ release
Authors: Xiao Wei‐chun , Zhang Jing , Chen Si‐li , Shi Yi‐jun , Xiao Fan , An Wei
Published: January 2018

The aberrant release of Ca2+ from the endoplasmic reticulum (ER) contributes to the onset of ER stress, which is closely related to the pathogenesis of non‐alcoholic fatty liver disease. We previously reported that augmenter of liver regeneration (ALR) alleviates ER stress and protects hepatocytes from lipotoxicity. However, the link between ALR protection and the suppression of ER stress remains unclear. In this study, we investigated whether the protection against liver steatosis afforded by ALR is related to its inhibition of calcium overflow from the ER to the mitochondria. The treatment of HepG2 cells with palmitic acid (PA) upregulated IP3R expression, triggering ER‐luminal Ca2+ release and inducing ER stress. However, in ALR‐transfected (ALR‐Tx) HepG2 cells, PA‐induced cell injury was clearly alleviated compared with that in vector‐Tx cells. After exposure to PA, IP3R expression was downregulated and ER stress was effectively inhibited in the ALR‐Tx cells, and ER‐Ca2+ release and simultaneous mitochondrial Ca2+ uptake were lower than those in vector‐Tx cells. The knockdown of ALR expression with shRNA abolished the protective effects afforded by ALR transfection. PA treatment also suppressed the interaction between BCL‐2 and IP3R in HepG2 cells, whereas this interaction was massively enhanced in the ALR‐Tx cells, effectively reducing the IP3R‐mediated ER‐Ca2+ release and thus mitochondrial Ca2+ influx. Our results suggest that the inhibition of ER stress by ALR is related to the interruption of the interaction between BCL2 and IP3R, demonstrating a novel mechanism of ER stress resistance in ALR‐Tx cells.
Osteosarcoma‐derived extracellular vesicles induce a tumor‐like phenotype in normal recipient cells
Authors: Urciuoli Enrica , Giorda Ezio , Scarsella Marco , Petrini Stefania , Peruzzi Barbara
Published: January 2018

Osteosarcoma is the most common primary bone cancer and the most frequent cause of bone cancer‐related deaths in children and adolescents. Osteosarcoma cells are able to establish a crosstalk with resident bone cells leading to the formation of a deleterious vicious cycle. We hypothesized that osteosarcoma cells can release, in the bone microenvironment, transforming Extracellular Vesicles (EVs) involved in regulating bone cell proliferation and differentiation, thereby promoting tumor growth. We assessed EV production by three osteosarcoma cell lines with increasing aggressiveness in order to investigate their roles in the communication between osteosarcoma cells and normal recipient cells. Osteosarcoma‐derived EVs were used to treat the murine fibroblast cell line NIH3T3 and to study the induction of tumor‐like phenotypes. Our results showed that osteosarcoma cell lines are able to produce EVs that fuse to recipient cells, with a very high uptake efficiency. The treatment of recipient NIH3T3 with osteosarcoma‐derived EVs induced substantial biological and functional effects, as an enhanced proliferation and survival capability under starved conditions, high levels of activated survival pathways, an increased migration, adhesion, and 3D sphere formation and the acquired capability to grow in an anchorage‐independent manner. Moreover, in murine NIH3T3 we found human mRNAs of TNF‐α, IL‐6, and TGF‐β, as well as a de novo expression of murine MMP‐9 and TNF‐α following the treatment of human osteosarcoma‐derived EVs.
Paradoxical side effects of bisphosphonates on the skeleton: What do we know and what can we do?
Authors: Vargas‐Franco Jorge W. , Castaneda Beatriz , Rédiní Françoise , Gómez David F. , Heymann Dominique , Lézot Frédéric
Published: January 2018

Bisphosphonates are considered the most effective drugs for controlling adult and pediatric osteolytic diseases. Although they have been used successfully for many years, several side effects, such as osteonecrosis of the jaw, delayed dental eruption, atypical femoral fracture, and alterations to the bone growth system, have been described. After an overview of nitrogenous bisphosphonate, the purpose of this article is to describe their mechanisms of action and current applications, review the preclinical and clinical evidence of their side effects in the skeleton (“what we know”), and describe current recommendations for preventing and managing these effects (“what we can do”). Finally, promising future directions on how to limit the occurrence of these side effects will be presented.
Oxidative burden in familial hypercholesterolemia
Authors: Mollazadeh Hamid , Carbone Federico , Montecucco Fabrizio , Pirro Matteo , Sahebkar Amirhossein
Published: January 2018

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high serum levels of low‐density lipoprotein cholesterol (LDL‐c). FH is characterized by accelerated development of atherosclerosis and represents the most frequent hereditary cause of premature coronary heart disease. Mutations of the LDL receptor gene are the genetic signature of FH, resulting in abnormal levels of circulating LDLs. Moreover, FH promotes the generation of reactive oxygen species (ROS) which is another key mechanism involved in atherosclerosis development and progression. The aim of this narrative review is to update the current knowledge on the pathophysiological mechanisms linking FH to ROS generation and their detrimental impact on atherosclerotic pathophysiology. With this purpose, we reviewed experimental and clinical data on the association between FH and OS and the functional role of OS as a promoter of inflammation and atherosclerosis. In this regard, oxidant species such as oxidized LDL, malondialdehyde, ROS, and isoprostanes emerged as leading mediators of the oxidative injury in FH. In conclusion, targeting oxidative stress may be a promising therapeutic strategy to reduce atherogenesis in patients with FH.