bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐practice/self‐reflection as an alternative to personal training‐therapy in cognitive behavioural therapy training: A qualitative analysis
Authors: Chigwedere Craig , Thwaites Richard , Fitzmaurice Brian , Donohoe Gary
Published: September 2018

Introduction

The study examined the qualitative impact and credibility of self‐practice/self‐reflection (SP/SR).

Methods

Nineteen participants reflected on the self‐practice of cognitive behavioural therapy techniques. Written reflections were analysed using inductive thematic analysis.

Results

Two superordinate themes (a) Personal‐self and (b) Therapist‐self, with themes and subthemes emerged.

Conclusion

The themes found equivalents in existing goals of traditional therapists' training‐therapy. Though brief, SP/SR may be a credible alternative/adjunctive training‐therapy.
Diversity in the workplace: An overview of disability employment disclosures among UK firms
Authors: Khan Nadeem , Korac‐Kakabadse Nada , Skouloudis Antonis , Dimopoulos Andreas
Published: September 2018

People with disabilities (PWDs) defined as the world's largest minority stakeholder group continue to face significant barriers to labor market entry and corporate inclusion. The associated social and economic costs of supporting non‐working PWDs can be high and long term. Yet, their potential contribution and impact on human capital, firm productivity, and the innovative capacity of business entities are valuable but underutilized. The employment of PWDs has institutional and managerial implications for equitable opportunities, social mobility, and workplace diversity. This study assesses the quality of corporate disclosure on disability issues by firms in the United Kingdom, as a stepping stone for mainstreaming integration of PWDs into labor markets under the scope of corporate social accountability. We benchmark 274 UK sustainability reports against PWDs‐adapted indicators of the Global Reporting Initiative guidelines, highlighting trends pertaining to disability employment. The findings suggest that corporate disclosures on the employment of PWDs are lacking. The implications for PWDs are highlighted considering firm employee and managerial policies and national and transnational regulatory frameworks, towards more meaningful reporting for better alignment between PWD expectations and firm practices.
Biotic and Abiotic Synthesis of Renewable Aliphatic Polyesters from Short Building Blocks Obtained from Biotechnology
Authors: Debuissy Thibaud , Pollet Eric , Avérous Luc
Published: September 2018

Biobased polymers have seen their attractiveness increase in recent decades thanks to the significant development of biorefineries to allow access to a wide variety of biobased building blocks. Polyesters are one of the best examples of the development of biobased polymers because most of them now have their monomers produced from renewable resources and are biodegradable. Currently, these polyesters are mainly produced by using traditional chemical catalysts and harsh conditions, but recently greener pathways with nontoxic enzymes as biocatalysts and mild conditions have shown great potential. Bacterial polyesters, such as poly(hydroxyalkanoate)s (PHA), are the best example of the biotic production of high molar mass polymers. PHAs display a wide variety of macromolecular architectures, which allow a large range of applications. The present contribution aims to provide an overview of recent progress in studies on biobased polyesters, especially those made from short building blocks, synthesized through step‐growth polymerization. In addition, some important technical aspects of their syntheses through biotic or abiotic pathways have been detailed.
Necrobiome framework for bridging decomposition ecology of autotrophically and heterotrophically derived organic matter
Authors: Benbow M. Eric , Barton Philip S. , Ulyshen Michael D. , Beasley James C. , DeVault Travis L. , Strickland Michael S. , Tomberlin Jeffery K. , Jordan Heather R. , Pechal Jennifer L.
Published: September 2018

Decomposition contributes to global ecosystem function by contributing to nutrient recycling, energy flow, and limiting biomass accumulation. The decomposer organisms influencing this process form diverse, complex, and highly dynamic communities that often specialize on different plant or animal resources. Despite performing the same net role, there is a need to conceptually synthesize information on the structure and function of decomposer communities across the spectrum of dead plant and animal resources. A lack of synthesis has limited cross‐disciplinary learning and research in important areas of ecosystem and community ecology. Here we expound on the “necrobiome” concept and develop a framework describing the decomposer communities and their interactions associated with plant and animal resource types within multiple ecosystems. We outline the biotic structure and ecological functions of the necrobiome, along with how the necrobiome fits into a broader landscape and ecosystem context. The expanded necrobiome model provides a set of perspectives on decomposer communities across resource types, and conceptually unifies plant and animal decomposer communities into the same framework, while acknowledging key differences in processes and mechanisms. This framework is intended to raise awareness among researchers, and advance the construction of explicit, mechanistic hypotheses that further our understanding of decomposer community contributions to biodiversity, the structure and function of ecosystems, global nutrient recycling and energy flow.
Duration and onset of action of high dose U‐500 regular insulin in severely insulin resistant subjects with type 2 diabetes
Authors: Shrestha Rupendra T. , Kumar Anjali F. , Taddese Abdisa , Khowaja Ameer A. , Moheet Amir , Olawsky Evan , Eberly Lynn E. , Seaquist Elizabeth R.
Published: September 2018

Aim

Although regular human U‐500 insulin (U‐500) is frequently used for insulin resistant type 2 diabetics, pharmacokinetic and pharmacodynamic studies in these individuals are lacking. We set out to determine the rate of onset, duration of action and total glucose lowering effect of two doses of U‐500 insulin in obese insulin resistant subjects with type 2 diabetes.

Materials and Methods

Randomized double‐blind crossover study was designed to study subjects who were administered either 100 or 200 units SQ of U‐500 insulin once and then were provided intravenous glucose as necessary to maintain euglycaemia.

Results

A total of 12 subjects were studied. The time during which intravenous glucose was required to maintain euglycaemia following a 200‐unit dose of U‐500 insulin was significantly greater than the time following a 100‐unit dose. No differences were found between doses in measures related to the rate of onset or in the total amount of intravenous glucose required to maintain euglycaemia for the duration of the study.

Conclusions

The duration of action of U‐500 increases when dose is increased from 100 to 200 units. Neither dose of U‐500 insulin has an onset of action before 2.5 hours after administration. This suggests that U‐500 should not be used as a premeal bolus insulin to lower glucose two hours after a meal and that dosing intervals might need to be extended as dose is increased to avoid hypoglycaemia.
Growth differentiation factor‐15 is not modified by sacubitril/valsartan and is an independent marker of risk in patients with heart failure and reduced ejection fraction: the PARADIGM‐HF trial
Authors: Bouabdallaoui Nadia , Claggett Brian , Zile Michael R. , McMurray John J.V. , O'Meara Eileen , Packer Milton , Prescott Margarett F. , Swedberg Karl , Solomon Scott D. , Rouleau Jean L. ,   for the PARADIGM‐HF Investigators and Committees
Published: September 2018

Aims

Growth differentiation factor‐15 (GDF‐15) is associated with adverse prognosis in cardiovascular (CV) and non‐CV diseases. We evaluated the association of GDF‐15 with CV and non‐CV outcomes in the PARADIGM‐HF trial.

Methods and results

In 1935 patients with heart failure and reduced ejection fraction (HFrEF) in PARADIGM‐HF, median GDF‐15 values were elevated and similar in sacubitril/valsartan and enalapril patients (1626 ng/L and 1690 ng/L, respectively). Diabetes, age, creatinine, high‐sensitive troponin T, N‐terminal pro‐B‐type natriuretic peptide, and New York Heart Association class III/IV were most strongly associated with elevated GDF‐15 values (all P < 0.001) (adjusted R2 = 0.3857). Baseline GDF‐15 and changes in GDF‐15 at both 1 month and 8 months (log‐transformed) were associated with subsequent mortality and CV events. Each 20% increment in baseline GDF‐15 value was associated with a higher risk of mortality [adjusted hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.08–1.18, P < 0.001], the combined endpoint of CV death or hospitalization for heart failure (adjusted HR 1.09, 95% CI 1.05–1.14, P < 0.001) and heart failure death (adjusted HR 1.16, 95% CI 1.05–1.28, P < 0.001). Changes in GDF‐15 were not influenced by assigned therapy (all P‐values ≥ 0.1).

Conclusion

In patients with ambulatory HFrEF, GDF‐15 is not modified by sacubitril/valsartan and is strongly associated with mortality and CV outcomes, suggesting that GDF‐15 is a marker of poor outcomes in these patients.

Clinical Trial Registration: ClinicalTrials.gov Identifier NCT01035255.
Tuning the Electron Acceptability of the [Mo6S8] Cluster Core by Decorating It with Methyl Groups on the Face‐Bridging µ3‐Sulfides
Authors: Matsumoto Takeshi , Namiki Ryoya , Chang Ho‐Chol
Published: September 2018

Invited for the cover of this issue is the group of Ho‐Chol Chang from Chuo University, Tokyo, Japan. The cover image shows the effect of ligand substitution on the electronic properties of the [Mo6S8] cluster core.
The Reduction Properties of M–Doped (M=Zr, Gd) CeO2/YSZ Scaffolds Co–Infiltrated with Nickel
Authors: Maher R. C. , Kerherve G. , Payne D. J. , Yue X. , Connor P. A. , Irvine J. , Cohen L. F.
Published: September 2018

In recent years infiltration of materials into porous ceramic scaffolds has been shown to be an effective way of creating catalytically active components for solid oxide fuel cells (SOFCs). However, the redox properties of these novel structures are not well understood. Here, we use X‐ray photoelectron spectroscopy (XPS) and in‐situ Raman spectroscopy to investigate the oxidation properties of yttria‐stabilised zirconia (YSZ) scaffolds infiltrated with ceria (CeO2), gadolinium‐doped ceria (GDC) and zirconia‐doped ceria (ZDC), with and without Ni. XPS shows that doping ceria with zirconia increases the ratio of Ce3+ to Ce4+, while gadolinium doping results in a decrease of Ce3+. The presence of Ni increases the Ce3+/Ce4+ ratio for CeO2 and GDC, but had little effect on ZDC. We used the shift of the F2g Raman peak to monitor in‐situ, the oxidation state of ceria. In the as‐made compounds, we show that while the gadolinium and zirconium dopants significantly change the oxidation characteristics of ceria, the resulting materials are only significantly reduced above 500 °C when co‐infiltrated with Ni. In‐situ Raman monitoring during reduction as a function of temperature showed that while ZDC reduces much more readily than undoped ceria or GDC, the presence of Ni dominated the reduction dynamics.
Highly Selective Room‐Temperature Catalyst‐Free Reduction of Alkaline Carbonates to Methane by Metal Hydrides
Authors: Dong Bao-Xia , Wang Lu , Zhao Juan , Teng Yun-Lei , Ping Chao , Zhu Wei , Chen Hua-Bo , Liu Wen-Long
Published: September 2018

The realization of effective CO2 conversion into valuable hydrocarbons is a promising way of addressing the current environmental and energy issues. A convenient, highly selective, and efficient method of CO2 methanation and the synthesis of COx‐free hydrogen/methane fuel mixtures by ball milling‐induced reactions of alkaline carbonates with metal hydrides (MHs) is reported. The natural resources of MgCO3/CaCO3 and MgH2/CaH2 are used as carbon and hydrogen sources, respectively. Mechanochemical investigations of the room‐temperature reactions indicate that some alkaline carbonates can be reduced by MHs under catalyst‐free conditions to selectively afford CH4 as the sole hydrocarbon product in yields of up to 73%. Moreover, the contents of methane in the gaseous products and its yield are shown, which mainly depend on the nature of metal carbonates/hydrides, rate and duration of ball milling, and reaction mixture composition. Thus, this study opens new ways to achieve the CO2 utilization and synthesize of COx‐free hydrogen and methane fuel mixtures.
The Impact of Aberrant Responses and Detection in Forced‐Choice Noncognitive Assessment
Authors: Kim Sooyeon , Moses Tim
Published: September 2018

The purpose of this study is to assess the impact of aberrant responses on the estimation accuracy in forced‐choice format assessments. To that end, a wide range of aberrant response behaviors (e.g., fake, random, or mechanical responses) affecting upward of 20%–30% of the responses was manipulated under the multi‐unidimensional pairwise preference (MUPP) model with forced‐choice format. Under each aberrance condition, we also computed the lz statistic (a common person‐fit index) to determine how well this index can accurately detect aberrant responses without erroneously misidentifying honest examinees. Some aberrant behaviors (e.g., limited responses) were more problematic than others (e.g., omitting) in terms of true trait level recovery. The lz statistic associated with each dimension of the MUPP form led to higher detection rates than did the overall lz statistic. When the dimensional lz approach was used, however, many honest examinees were misclassified as outliers. The detection rates of lz differed as a function of aberrant response types.
Crosscutting Literature on STEAM Ecosystems, Expectancy Value Theory, and Social Emotional Learning: A Metadata Synthesis
Authors: Rikoon Samuel , Finn Bridgid , Jackson Teresa , Inglese Patricia
Published: September 2018

In this report, we describe the initial stages of a crosscutting research effort to characterize literature reviewed across 8 different projects—each with objectives aligned toward improving student engagement in science, technology, engineering, arts, and mathematics (STEAM) fields. These projects sought to identify malleable factors (e.g., motivation, persistence) that could potentially be fostered to improve achievement motivation and build participation among historically underrepresented learners in STEAM pathways. Focusing on both the extent to which different broad and facet‐level constructs are both discussed and assessed in a diverse pool of literature, we developed a standardized reporting structure and catalogued detailed information on 236 unique references. We found that, as a proportion of the number of times constructs in the STEAM, expectancy value (EV) theory, and social emotional learning (SEL) spaces were discussed in the reviewed literature, they were assessed relatively infrequently. We also found high levels of overlap in the literature across the above 3 focal areas, highlighting both the need to document new assessments designed to support STEAM engagement and an opportunity to use them to evaluate expectancy value theory as a holistic model.
Disrupted interactions among the hippocampal, dorsal attention, and central‐executive networks in amnestic mild cognitive impairment
Authors: Chand Ganesh B. , Hajjar Ihab , Qiu Deqiang
Published: September 2018

Neuroimaging investigations consistently demonstrate that the neural processes involve complex interactions between the large‐scale networks. Among those networks, the dorsal attention network (DAN) and the central‐executive network (CEN) have been previously shown to exhibit anti‐correlated activity with the default‐mode network (DMN) in cognitively normal people. In amnestic mild cognitive impairment (MCI) and Alzheimer's disease, the hippocampal network (HCN)—a key memory processing system—and its interactions with other networks have gathered central interest. The current study aims to evaluate the patterns of functional architectures of the HCN with the three networks—DAN, CEN, and DMN—in amnestic MCI and normal controls (NC) to test the hypothesis that the interactions of HCN with other networks alter in MCI. We recorded the resting state functional MRI, assessed patterns of functional architectures between the four networks using dynamical causal modeling, and compared between NC and MCI. Our analysis showed that the DAN modulates the activity between the HCN and the DMN in both MCI and NC. We further uncovered that the DAN modulates the activity between the HCN and the CEN in NC, but such modulation is impaired in MCI. We found an association between impaired modulation and Montreal cognitive assessment (R = 0.349). Overall, our findings provide important insight in understanding the neuroimaging signature of amnestic MCI and/or Alzheimer's disease.
Aberrant structural–functional coupling in adult cannabis users
Authors: Kim Dae‐Jin , Schnakenberg Martin Ashley M. , Shin Yong‐Wook , Jo Hang Joon , Cheng Hu , Newman Sharlene D. , Sporns Olaf , Hetrick William P. , Calkins Eli , O'Donnell Brian F.
Published: September 2018

Cellular studies indicate that endocannabinoid type‐1 retrograde signaling plays a major role in synaptic plasticity. Disruption of these processes by delta‐9‐tetrahydrocannabinol (THC) could produce alterations either in structural and functional brain connectivity or in their association in cannabis (CB) users. Graph theoretic structural and functional networks were generated with diffusion tensor imaging and resting‐state functional imaging in 37 current CB users and 31 healthy non‐users. The primary outcome measures were coupling between structural and functional connectivity, global network characteristics, association between the coupling and network properties, and measures of rich‐club organization. Structural–functional (SC–FC) coupling was globally preserved showing a positive association in current CB users. However, the users had disrupted associations between SC–FC coupling and network topological characteristics, most perturbed for shorter connections implying region‐specific disruption by CB use. Rich‐club analysis revealed impaired SC–FC coupling in the hippocampus and caudate of users. This study provides evidence of the abnormal SC–FC association in CB users. The effect was predominant in shorter connections of the brain network, suggesting that the impact of CB use or predispositional factors may be most apparent in local interconnections. Notably, the hippocampus and caudate specifically showed aberrant structural and functional coupling. These structures have high CB1 receptor density and may also be associated with changes in learning and habit formation that occur with chronic cannabis use.
KSHV viral load and Interleukin‐6 in HIV‐associated pediatric Kaposi sarcoma—Exploring the role of lytic activation in driving the unique clinical features seen in endemic regions
Authors: El‐Mallawany Nader Kim , Mehta Parth S. , Kamiyango William , Villiera Jimmy , Peckham‐Gregory Erin C. , Kampani Coxcilly , Krysiak Robert , Sanders Marcia K. , Caro‐Vegas Carolina , Eason Anthony B. , Ahmed Saeed , Schutze Gordon E. , Martin Stephen C. , Kazembe Peter N. , Scheurer Michael E. , Dittmer Dirk P.
Published: September 2018

Kaposi sarcoma (KS) is among the most common childhood malignancies in central, eastern, and southern Africa. Although its unique clinical features have been established, biological mechanisms related to the causative agent, KS‐associated herpes‐virus (KSHV), have yet to be explored in children. We performed a prospective observational pilot study to explore associations between KSHV viral load (VL), human interleukin‐6 (IL‐6) and IL‐10 levels, and clinical characteristics of 25 children with KS in Lilongwe, Malawi from June 2013–August 2015. The median age was 6.4 years. Lymphadenopathy was the most common site of KS involvement (64%), followed by skin and oral mucosa (44% each), woody edema (12%), and pulmonary (8%). Baseline samples for plasma KSHV VL, IL‐6 and IL‐10 analyses were available for 18/25 patients (72%) at time of KS diagnosis. KSHV VL was detectable at baseline in 12/18 (67%) patients, the median baseline IL‐6 level was 8.53 pg/mL (range 4.31–28.33), and the median baseline IL‐10 level was 19.53 pg/mL (range 6.91–419.69). Seven (39%) patients presented with an IL‐6 level > 10 pg/mL (exceeding twice the upper limit of normal). Detectable KSHV VL was significantly associated with lymphadenopathic KS (p = 0.004), while having undetectable KSHV VL was associated with a higher likelihood of presenting with hyperpigmented skin lesions (p = 0.01). Detectable KSHV VL and elevated IL‐6 levels are present in a subset of children with KS. Lytic activation of KSHV and associated elevation in KSHV VL may contribute to the unique clinical manifestations of pediatric KS in KSHV‐endemic regions of Africa.
Multimodal imaging to explore endogenous fluorescence of fresh and fixed human healthy and tumor brain tissues
Authors: Mehidine Hussein , Sibai Mira , Poulon Fanny , Pallud Johan , Varlet Pascale , Zanello Marc , Devaux Bertrand , Abi Haidar Darine
Published: September 2018

To complement a project toward label‐free optical biopsy and enhanced resection which the overall goal is to develop a multimodal nonlinear endomicroscope, this multimodal approach aims to enhance the accuracy in classifying brain tissue into solid tumor, infiltration and normal tissue intraoperatively. Multiple optical measurements based on one‐ and two‐photon spectral and lifetime autofluorescence, including second harmonic generation imaging, were acquired. As a prerequisite, studying the effect of the time of measurement postexcision on tissue's spectral/lifetime fluorescence properties was warranted, so spectral and lifetime fluorescences of fresh brain tissues were measured using a point‐based linear endoscope. Additionally, a comparative study on tissue's optical properties obtained by multimodal nonlinear optical imaging microscope from fresh and fixed tissue was necessary to test whether clinical validation of the nonlinear endomicroscope is feasible by extracting optical signatures from fixed tissue rather than from freshly excised samples. The former is generally chosen for convenience. Results of this study suggest that an hour is necessary postexcision to have consistent fluorescence intensities\lifetimes. The fresh (a,b,c) vs fixed (d,e,f) tissue study indicates that while all optical signals differ after fixation. The characteristic features extracted from one‐ and two‐photon excitation still discriminate normal brain (a,d) cortical tissue, glioblastoma (GBM) (b,e) and metastases (c,f).
Using Wellness and Resilience to Predict Age Perception in Older Adulthood
Authors: Fullen Matthew C. , Granello Darcy Haag , Richardson Virginia E. , Granello Paul F.
Published: September 2018

The authors surveyed 210 adults ages 56 to 97 to better understand which variables affect perceptions of aging. A correlational design was used to determine whether wellness and resilience predicted positive age perception and internalized ageism among this group. Both variables were found to significantly predict age perception, and the data supported an interaction effect between age and resilience when predicting internalized ageism. Results may inform counselors, counselor educators, and other professionals who work with older adults.
Promoting Wellness in Refugee Populations
Authors: Blount Ashley J. , Acquaye Hannah E.
Published: September 2018

Refugee populations experience risk factors that may influence their wellness. As the number of refugees continues to rise, it is important for professional counselors, counselor educators, and counselors‐in‐training to be aware of techniques for supporting wellness in this population. This article addresses risk factors to refugee wellness within the indivisible self model of wellness (Myers & Sweeney,) and highlights current wellness trends and the importance of a prevention‐based treatment paradigm for helpers working with refugee populations.
Extracellular protease trypsin activates amiloride‐insensitive sodium channels in human leukemia cells
Authors: Sudarikova Anastasia V. , Vasileva Valeria Y. , Vassilieva Irina O. , Negulyaev Yuri A. , Morachevskaya Elena A. , Chubinskiy‐Nadezhdin Vladislav I.
Published: September 2018

Sodium influx is tightly regulated in the cells of blood origin. Amiloride‐insensitive sodium channels were identified as one of the main sodium‐transporting pathways in leukemia cells. To date, all known regulatory pathways of these channels are coupled with intracellular actin cytoskeleton dynamics. Here, to search for physiological mechanisms controlling epithelial Na+ channel (ENaC)‐like channels, we utilized leukemia K562 cells as a unique model to examine single channel behavior in a whole‐cell patch‐clamp experiments. We have shown for the first time that extracellular serine protease trypsin directly activates sodium channels in plasma membrane of K562 cells. The whole‐cell single current recordings clearly demonstrate no inhibition of trypsin‐activated channels by amiloride or benzamil. Involvement of proteolytic cleavage in channel opening was confirmed in experiments with soybean trypsin inhibitor. More importantly, stabilization of F‐actin with intracellular phalloidin did not prevent trypsin‐induced channel activation indicating no implication of cytoskeleton rearrangements in stimulatory effect of extracellular protease. Our data reveals a novel mechanism modulating amiloride‐insensitive ENaC‐like channel activity and integral sodium permeability in leukemia cells.
Perlecan/HSPG2: Signaling role of domain IV in chondrocyte clustering with implications for Schwartz‐Jampel Syndrome
Authors: Martinez Jerahme R. , Grindel Brian J. , Hubka Kelsea M. , Dodge George R. , Farach‐Carson Mary C.
Published: September 2018

Perlecan/heparan sulfate proteoglycan 2 (HSPG2), a large HSPG, is indispensable for the development of musculoskeletal tissues, where it is deposited within the pericellular matrix (PCM) surrounding chondrocytes and disappears nearly completely at the chondro‐osseous junction (COJ) of developing long bones. Destruction of perlecan at the COJ converts an avascular cartilage compartment into one that permits blood vessel infiltration and osteogenesis. Mutations in perlecan are associated with chondrodysplasia with widespread musculoskeletal and joint defects. This study elucidated novel signaling roles of perlecan core protein in endochondral bone formation and chondrocyte behavior. Perlecan subdomains were tested for chondrogenic properties in ATDC5 cells, a model for early chondrogenesis. A region within domain IV of perlecan (HSPG2 IV‐3) was found to promote rapid prechondrocyte clustering. Introduction of the mutation (R3452Q) associated with the human skeletal disorder Schwartz‐Jampel syndrome limited HSPG2 IV‐3‐induced clustering. HSPG2 IV‐3 activity was enhanced when thermally unfolded, likely because of increased exposure of the active motif(s). HSPG2 IV‐3‐induced clustering was accompanied by the deactivation of key components of the focal adhesion complex, FAK and Src, with increased messenger RNA (mRNA) levels of precartilage condensation markers Sox9 and N‐cadherin (
Cdh2), and cartilage PCM components collagen II (
Col2a1) and aggrecan (
Acan). HSPG2 IV‐3 reduced signaling through the ERK pathway, where loss of ERK1/2 phosphorylation coincided with reduced FoxM1 protein levels and increased mRNA levels cyclin‐dependent kinase inhibitor 1C (Cdkn1c) and activating transcription factor 3 (
Atf3), reducing cell proliferation. These findings point to a critical role for perlecan domain IV in cartilage development through triggering chondrocyte condensation.
Catalpol inhibits TGF‐β1‐induced epithelial‐mesenchymal transition in human non–small‐cell lung cancer cells through the inactivation of Smad2/3 and NF‐κB signaling pathways
Authors: Wang Zuopei , Lu Yi , Sheng Bo , Ding Yi , Cheng Xiaoke
Published: September 2018

Catalpol, one of the main active ingredients isolated from Rehmannia glutinosa, was reported to possess anticancer activity. However, the role of catalpol in transforming growth factor β1 (TGF‐β1)‐induced epithelial‐mesenchymal transition (EMT) in human non–small‐cell lung cancer (NSCLC) cells has not been elucidated. The objective of this study was to investigate the effect of catalpol on EMT in human NSCLC cells. Our results showed that catalpol significantly inhibited the TGF‐β1‐induced cell migration and invasion of A549 cells, as well as repressed matrix metalloproteinase (MMP)2 and MMP9 expression induced by TGF‐β1 in A549 cells. In addition, catalpol markedly repressed the EMT process in A549 cells in response to TGF‐β1. Furthermore, catalpol prevented the activation of Smad2/3 and nuclear factor κB (NF‐κB) signaling pathways induced by TGF‐β1 in A549 cells. In conclusion, these findings indicated that catalpol inhibits TGF‐β1‐induced EMT in human NSCLC cells through the inactivation of Smad2/3 and NF‐κB signaling pathways. Thus, catalpol may be a promising agent for the treatment of NSCLC.
NEAT1 contributes to ox‐LDL‐induced inflammation and oxidative stress in macrophages through inhibiting miR‐128
Authors: Chen Dou‐Dou , Hui Liang‐Liang , Zhang Xiang‐Cheng , Chang Qing
Published: September 2018

Long noncoding RNAs (lncRNA) have been recognized as significant regulators in the progression of atherosclerosis (AS). Oxidized low‐density lipoprotein (ox‐LDL) can induce macrophage inflammation and oxidative stress, that serves important roles in AS. However, the exact function of lncRNA NEAT1 and its possible molecular mechanism in AS remain unclear. Here, we concentrated on the roles and molecular mechanisms of NEAT1 in AS development. In our current study, we observed that NEAT1 was elevated by ox‐LDL in a dose‐dependent and time‐dependent manner. RAW264.7 cell survival was greatly enhanced, and cell apoptosis was significantly inhibited by LV‐shNEAT1 transfection. In addition, knockdown of NEAT1 in RAW264.7 cells repressed CD36 expression and foam cell formation while NEAT1 overexpression shown an opposite process. Moreover, NEAT1 downregulation inhibited inflammation molecules including IL‐6, IL‐1β, and TNF‐α. Meanwhile, silencing of NEAT1 can also suppress reactive oxygen species (ROS) and malondialdehyde (MDA) levels with an enhancement of superoxide dismutase (SOD) activity in RAW264.7 cells. MicroRNAs are some short RNAs, and they can regulate multiple biological functions in many diseases including AS. Here, we found that miR‐128 expression was remarkably decreased in ox‐LDL‐incubated RAW264.7 cells. Interestingly, miR‐128 mimics was able to reverse AS‐correlated events induced by overexpression of NEAT1. By using bioinformatics analysis, miR‐128 was predicted as a target of NEAT1 and the correlation between them was validated in our study. Taken these together, it was implied that NEAT1 participated in ox‐LDL‐induced inflammation and oxidative stress in AS development through sponging miR‐128.
Polycistronic expression of the mitochondrial steroidogenic P450scc system in the HEK293T cell line
Authors: Efimova Vera S. , Isaeva Ludmila V. , Labudina Anastasia A. , Tashlitsky Vadim N. , Rubtsov Mikhail A. , Novikova Ludmila A.
Published: September 2018

The cholesterol hydroxylase/lyase (CHL) system, consisting of cytochrome P450scc, adrenodoxin (Adx) and adrenodoxin reductase (AdR), initiates mammalian steroidogenesis, converting cholesterol to pregnenolone. The foot‐and‐mouth disease virus 2A‐based method allows to express multiple proteins from a single transcript. We developed a 2A‐based multicistronic system for the coexpression of three bovine CHL system proteins as the self‐processing polyprotein pCoxIV‐P450scc‐2A‐Adx‐2A‐AdR‐GFP (pCoxIV‐CHL‐GFP), with a cleavable N‐terminal mitochondrial targeting presequence. HEK293T cells transfected with plasmid, containing complementary DNA (cDNA) for pCoxIV‐CHL‐GFP, efficiently performed the expression of P450scc‐2A, targeted to mitochondria, and Adx‐2A, AdR‐GFP and the fusion protein Adx‐2A‐AdR‐GFP, which were predominantly localized in the cytosol. Despite the spatial separation of expressed P450scc and redox partners, the transfected HEK293T cells were able to convert the steroid substrates of cytochrome P450scc to pregnenolone, whereas control HEK293T cells were not catalytically active. The presence of 2А peptide residue on the C‐terminus of P450scc did not preclude its enzymatic activity. HEK293T cells transfected with a vector directing the synthesis of only P450scc‐2A demonstrated cytochrome P450scc activity comparable to that of cells expressing all three CHL system components, and to that of nature steroidogenic cells. Thus, the P450scc activity detected in cells transfected with both constructed plasmids was the result of the effective functional coupling of the bovine cytochrome P450scc and endogenous mitochondrial electron transport proteins of HEK293T cells. The produced pregnenolone did not undergo further conversion to progesterone, which indicates the absence of catalytically active 3β‐hydroxysteroid dehydrogenase. Therefore, HEK293T cells may be suitable for the expression of steroidogenic enzymes and the study of their characteristics.
PlGF knockdown induced apoptosis through Wnt signaling pathway in gastric cancer stem cells
Authors: Akrami Hassan , Mehdizadeh Kiumars , Moradi Behrouz , Borzabadi Farahani Diba , Mansouri Kamran , Ghalib Ibraheem Alnajar Sajjad
Published: September 2018

Despite the fact that much research has focused on gastric cancer, it is still a worldwide concern, because of the difficulties with factors such as signaling pathway crosstalk and gastric cancer stem cell (GCSC). Placental growth factor (PlGF) is one of these factors, and its tumorigenicity potential still remains a question. As a result, we have investigated the effect of PlGF knockdown on apoptosis and genes involved in the Wnt signaling pathway, and apoptosis in cancer stem cells derived from AGS an MKN‐45 gastric cancer cell lines. We isolated GCSCs from MKN‐45 and AGS cell lines on a nonadherent surface. Then the cell viability, the real‐time reverse transcription‐polymerase chain reaction data of the genes involved in the Wnt signaling pathway, and apoptosis were evaluated. Furthermore, DNA laddering was used to show the apoptotic effect and DNA fragmentation caused by the PlGF knockdown. Our investigation revealed that the PlGF knockdown with PlGF‐specific small interfering RNA at 40 pmol for GCSCs derived from MKN‐45 and AGS at 24 hours can significantly affect the cell viability, the Wnt signaling pathway, and the apoptosis‐related genes expression. In conclusion, we showed the PlGF knockdown may induce apoptosis via the Wnt signaling pathway in GCSCs.
Disruption of the redox balance with either oxidative or anti‐oxidative overloading as a promising target for cancer therapy
Authors: Farhood Bagher , Najafi Masoud , Salehi Eniseh , Hashemi Goradel Nasser , Nashtaei Maryam Shabani , Khanlarkhani Neda , Mortezaee Keywan
Published: September 2018

Oxidative stress acts as a double‐edged sword by being both a promoter and a suppressor of cancer. Moderate oxidative stress is beneficial for cancer cell proliferative and invasiveness features, while overexposure of the cells to oxidative insults could induce cancer cell apoptosis and reduce hypoxia along with modulating the immune system for regression of tumor. Cancer cells and cancer stem cells have highly efficient redox systems that make them resistant to oxidative insults. The redox disruptive approach is an area of current research and key for oxidative targeted cancer therapies. This disruption is applicable by using either oxidative or anti‐oxidative overloading strategies, specifically on cancer cells without influencing normal cells or tissues around tumor. The activity of tumor suppressor cells within tumor microenvironment is needed to be maintained in patients receiving such approaches.
Particulate matter 2.5 induced bronchial epithelial cell injury via activation of 5′‐adenosine monophosphate‐activated protein kinase‐mediated autophagy
Authors: Long Fei , Jiang Hong , Yi Hongli , Su Lili , Sun Jian
Published: September 2018

The impact of particulate matter 2.5 (PM2.5) on the respiratory system is a worldwide concern. However, the mechanisms by which PM2.5 causes disease are still unclear. In this study, we investigated the effect of PM2.5 on autophagy and studied the effect of PM2.5‐induced autophagy and 5′‐adenosine monophosphate‐activated protein kinase (AMPK) on cell proliferation, cell cycle, apoptosis, reactive oxygen species (ROS), and airway inflammation using human bronchial epithelial cells 16HBE140 cells. Results showed that exposure of cells to PM2.5 at a concentration of 100 μg/mL for 24 hours was most effective for inhibiting cell viability. PM2.5 induced cell arrest in the G0/G1 phase and increased mitochondrial membrane potential, ROS, and cell apoptosis with increasing concentration. PM2.5 downregulated cyclin D and matrix metallopeptidase‐9 (MMP‐9) expression but upregulated tissue inhibitor of metalloproteinases‐1 (TIMP‐1) expression, significantly promoted interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) production, and enhanced the level and activation of AMPK. The levels of autophagy‐related protein 5 (ATG5), Beclin‐1, and LC3II/I were significantly increased by PM2.5. The activation of Unc‐51‐like autophagy activating kinase 1 was significantly inhibited by PM2.5. Moreover, ATG5 knockdown inhibited PM2.5‐induced autophagy, ROS, and cell apoptosis significantly. The expression of cyclin D, MMP‐9, and TIMP‐1 was reversed by ATG5 suppression. PM2.5‐induction of IL‐6 and TNF‐α was significantly inhibited by knockdown of ATG5. Thus, inhibition of autophagy protected the cells from PM2.5‐induced injury. PM2.5 induced injury in human bronchial epithelial cells via activation of AMPK‐mediated autophagy, suggesting possible therapeutic targets for the treatment of respiratory diseases.
Characterization of the vaginal microbiome during cytolytic vaginosis using high‐throughput sequencing
Authors: Xu Haihong , Zhang Xueying , Yao Wenwu , Sun Yi , Zhang Yanjun
Published: September 2018

Background

Cytolytic vaginosis (CV) is a common disease that results in pruritus, dyspareunia, and vulvar dysuria. However, the pathological mechanisms of the disease are still unclear. Compared to traditional methods, high‐throughput sequencing can obtain more accurate qualitative and quantitative information on the microbiome.

Methods

We collected 75 samples from 32 healthy women (average age 44 ± 8) and 43 patients with CV (average age 38 ± 8). We used high‐throughput sequencing of the 16S rRNA V3‐V4 region to characterize and compare the vaginal microbiota of patients with CV and healthy women and to identify potential biomarkers for CV.

Results

The vaginal pH of patients with CV was ≤3.8, and the vaginal concentration of H2O2 was ≥2 μmol/L. Colony densities of Lactobacillus spp. in patients with CV ranged from +++ (5‐30) to ++++ (>30) and were significantly higher than those in healthy women. High‐throughput sequencing showed that Lactobacillus was the most prominent genus both in patients with CV and in healthy women, with abundances of 83.8% and 97.2%, respectively (P < 0.001). Lactobacillus crispatus was more abundant in patients with CV, whereas Lactobacillus sp. L‐YJ was more abundant in healthy women, with area under the curve (AUC) values of 0.9375 and 0.8379, respectively.

Conclusion

The abundance of Lactobacillus spp. in CV patients was significantly different from that of healthy patients. Two suitable biomarkers, L. crispatus and Lactobacillus sp. L‐YJ, were identified. These results will be useful for the identification of women at risk of serious illness before they develop obvious symptoms.
Glycyrrhizin inactivates toll‐like receptor (TLR) signaling pathway to reduce lipopolysaccharide‐induced acute lung injury by inhibiting TLR2
Authors: Kong Delei , Wang Zanfeng , Tian Jie , Liu Tingwei , Zhou Hui
Published: September 2018

Objective

This study aimed to explore glycyrrhizin on acute lung injury (ALI) and how glycyrrhizin (GL) attenuated lipopolysaccharide (LPS)‐induced ALI.

Methods

Bioinformatics analysis was performed to screen the expressed genes in LPS‐induced ALI mice. The enrichment of functions and signaling pathways of deregulated genes were conducted. Combined with DIGSEE and STICH, the target gene for further investigation was chosen. To verify target gene in mice, we performed experiment in vivo. Forty mice were randomized into NC, LPS, LPS + S, and LPS + GL group. Mice in the LPS + GL group received glycyrrhizin l mg and mice in LPS + S received saline. Then, HE and Masson staining detected pathological changes of lung tissues; enzyme‐linked immunosorbent assay analyzed bronchoalveolar lavage fluid concentrations of MIP‐2, mice growth‐related oncogene homologue (KC), IL‐4, IL‐6, GM‐CSF, IFN‐γ, and IgM; western blot analysis determined the expression of toll‐like receptor (TLR) signaling and NF‐κB pathway‐related proteins.

Results

Tlr2 which was not only upregulated but also closely related to glycyrrhizin. TLR2 was upregulated in following LPS induced in cells and TLR2 overexpression‐activated TLR signaling pathway to promote ALI. After glycyrrhizin treatment, the expression of TLR2 was reduced. Furthermore, it was found out that the number of inflammatory cells, collagen deposition, MIP‐2, KC, IL‐4, IL‐6, GM‐CSF, and IFN‐γ expression increased in ALI mice and glycyrrhizin mitigated it. Similarly, the expression of TLR signaling pathway and NF‐κB pathway‐related protein also increased.

Conclusion

Glycyrrhizin functioned as a suppressor in TLR signaling pathway to reduce LPS‐induced ALI by inhibiting TLR2.
HDAC1/2‐mediated regulation of JNK and ERK phosphorylation in bovine mammary epithelial cells in response to TNF‐α
Authors: Romanick Samantha S. , Morrill Kristen , Hostler Andrew , Evans Levi W. , Shen Yiqiu , Matsumura Allison , Piotrowski Haleigh , Silva Lorrayny G. , Faciola Antonio P. , Ferguson Bradley S.
Published: September 2018

Bovine mammary epithelial cells (MAC‐Ts) are a common cell line for the study of mammary epithelial inflammation; these cells are used to mechanistically elucidate molecular underpinnings that contribute to bovine mastitis. Bovine mastitis is the most prevalent form of disease in dairy cattle that culminates in annual losses of two billion dollars for the US dairy industry. Thus, there is an urgent need for improved therapeutic strategies. Histone deacetylase (HDAC) inhibitors are efficacious in rodent models of inflammation, yet their role in bovine mammary cells remain unclear. HDACs have traditionally been studied in the regulation of nucleosomal DNA, in which deacetylation of histones impact chromatin accessibility and gene expression. Using MAC‐T cells stimulated with tumor necrosis factor α (TNF‐α) as a model for mammary cell inflammation, we report that inhibition of HDACs1 and 2 (HDAC1/2) attenuated TNF‐α‐mediated inflammatory gene expression. Of note, we report that HDAC1/2‐mediated inflammatory gene expression was partly regulated by c‐Jun N‐terminal kinase (JNK) and extracellular signal‐regulated kinase (ERK) phosphorylation. Here, we report that HDAC1/2 inhibition attenuated JNK and ERK activation and thus inflammatory gene expression. These data suggest that HDACs1 and 2 regulate inflammatory gene expression via canonical (i.e., gene expression) and noncanonical (e.g., signaling dependent) mechanisms. Whereas, further studies using primary cell lines and animal models are needed. Our combined data suggest that HDAC1/2‐specific inhibitors may prove efficacious for the treatment of bovine mastitis.
Neratinib augments the lethality of [regorafenib + sildenafil]
Authors: Booth Laurence , Roberts Jane L. , Rais Rumeesa , Cutler Richard E. , Diala Irmina , Lalani Alshad S. , Hancock John F. , Poklepovic Andrew , Dent Paul
Published: September 2018

Regorafenib is approved for the treatment of colorectal cancer and hepatocellular carcinoma. In the trial NCT02466802, we have discovered that regorafenib can be safely combined with the phosphodiesterase 5 inhibitor sildenafil in advanced solid tumor patients. The present studies determined whether the approved ERBB1/2/4 and RAS downregulating drug neratinib, could enhance the lethality of [regorafenib + sildenafil]. Neratinib enhanced [regorafenib + sildenafil] lethality in a greater than additive fashion in colon cancer cells. The drug combination reduced the expression of mutant K‐RAS and of multiple histone deacetylase (HDAC) proteins that required autophagosome formation. It caused green fluorescent protein or red fluorescent protein–tagged forms of K‐RAS V12 to localize into large intracellular vesicles. Compared with [regorafenib + sildenafil], the three‐drug combination caused greater and more prolonged activation of the ATM‐AMPK‐ULK‐1 pathway and caused a greater suppression and prolonged inactivation of mammalian target of rapamycin, AKT, and p70 S6K. Approximately 70% of enhanced lethality caused by neratinib required ataxia‐telangiectasia‐mutated (ATM)–AMP‐dependent protein kinase (AMPK) signaling whereas knockdown of Beclin1, ATG5, FADD, and CD95 completely prevented the elevated killing effect. Exposure of cells to [regorafenib + sildenafil] reduced the expression of the checkpoint immunotherapy biomarkers programmed death‐ligand 1, ornithine decarboxylase, and indoleamine 2,3‐dioxygenase‐1 and increased the expression of major histocompatibility complex A (MHCA), which also required autophagosome formation. Knockdown of specific HDAC proteins recapitulated the effects observed using chemical agents. In vivo, using mouse cancer models, neratinib significantly enhanced the antitumor efficacy of [regorafenib + sildenafil]. Our data support performing a new three drug Phase I trial combining regorafenib, sildenafil, and neratinib.
A meta‐analysis identified genes responsible for distinct immune responses to trivalent inactivated and live attenuated influenza vaccines
Authors: Wen Feng , Guo Jinyue , Huang Shujian
Published: September 2018

Vaccinations are the cornerstone of influenza prevention strategies. We carried out a meta‐analysis of the messenger RNA expression profiles from recipients of trivalent inactivated vaccines (TIV) or live attenuated vaccines (LAIV) to determine the different recipients’ responses to these two types of vaccines, which may provide information to improve the design of future improved vaccines. We executed meta‐analysis on these datasets using a random‐effects model and identified 191 and 195 differentially expressed genes in TIV and LAIV, respectively, with an false discovery rate <0.05. The genes significantly upregulated by TIV were associated with both the innate immune response and the humoral immune response, whereas LAIV mainly activated the innate immune system. The identified genes that responsible for the immune difference between LAIV and TIV might provide new information to improve current vaccines to have better efficacy in children, adults, and the elderly.