bluuebunny/crossref_metadata_2025 huggingface dataset:
A Low-Cost, Passive Release Device for the Surveillance and Control of Mosquitoes
Authors: Kwan Michael W. C. , Bosak Alexander , Kline Jedidiah , Pita Mario A. , Giel Nicholas , Pereira Roberto M. , Koehler Philip G. , Kline Daniel L. , Batich Christopher D. , Willenberg Bradley Jay
Published: April 2019

Mosquitoes continue to be a major threat to global health, and the ability to reliably monitor, catch, and kill mosquitoes via passive traps is of great importance. Global, low-cost, and easy-to-use outdoor devices are needed to augment existing efforts in mosquito control that combat the spread of disease, such as Zika. Thus, we have developed a modular, portable, non-powered (passive), self-contained, and field-deployable device suitable for releasing volatiles with a wide range of applications such as attracting, repelling, and killing mosquitoes. This unique device relies on a novel nested wick and two-reservoir design that achieves a constant release of volatiles over several hundred hours. Devices loaded with one of either two compounds, geraniol or 1-methylpiperazine (MP), were tested in a controlled environment (32 °C and 70% relative humidity), and both compounds achieved a constant release from our devices at a rate of 2.4 mg/h and 47 mg/h, respectively. The liquid payload can be volatile attractants or repellants as well as mosquitocide-containing feeding solutions for capture and surveillance. This low-cost device can be utilized for both civilian and military mosquito control purposes, but it will be particularly important for protecting those in economically repressed environments, such as sub-Saharan Africa and Central and South America.
How Do Neighbourhood Definitions Influence the Associations between Built Environment and Physical Activity?
Authors: Mavoa Suzanne , Bagheri Nasser , Koohsari Mohammad Javad , Kaczynski Andrew T. , Lamb Karen E. , Oka Koichiro , O’Sullivan David , Witten Karen
Published: April 2019

Researchers investigating relationships between the neighbourhood environment and health first need to decide on the spatial extent of the neighbourhood they are interested in. This decision is an important and ongoing methodological challenge since different methods of defining and delineating neighbourhood boundaries can produce different results. This paper explores this issue in the context of a New Zealand-based study of the relationship between the built environment and multiple measures of physical activity. Geographic information systems were used to measure three built environment attributes—dwelling density, street connectivity, and neighbourhood destination accessibility—using seven different neighbourhood definitions (three administrative unit boundaries, and 500, 800, 1000- and 1500-m road network buffers). The associations between the three built environment measures and five measures of physical activity (mean accelerometer counts per hour, percentage time in moderate–vigorous physical activity, self-reported walking for transport, self-reported walking for recreation and self-reported walking for all purposes) were modelled for each neighbourhood definition. The combination of the choice of neighbourhood definition, built environment measure, and physical activity measure determined whether evidence of an association was detected or not. Results demonstrated that, while there was no single ideal neighbourhood definition, the built environment was most consistently associated with a range of physical activity measures when the 800-m and 1000-m road network buffers were used. For the street connectivity and destination accessibility measures, associations with physical activity were less likely to be detected at smaller scales (less than 800 m). In line with some previous research, this study demonstrated that the choice of neighbourhood definition can influence whether or not an association between the built environment and adults’ physical activity is detected or not. This study additionally highlighted the importance of the choice of built environment attribute and physical activity measures. While we identified the 800-m and 1000-m road network buffers as the neighbourhood definitions most consistently associated with a range of physical activity measures, it is important that researchers carefully consider the most appropriate type of neighbourhood definition and scale for the particular aim and participants, especially at smaller scales.
The Role of miRNAs in Zearalenone-Promotion of TM3 Cell Proliferation
Authors: Zheng Wanglong , Fan Wentong , Feng Nannan , Lu Nanyan , Zou Hui , Gu Jianhong , Yuan Yan , Liu Xuezhong , Bai Jianfa , Bian Jianchun , Liu Zongping
Published: April 2019

Zearalenone (ZEA) is a non-steroidal estrogen mycotoxin produced by several Gibberella and Fusarium species. Accumulating evidence has indicated that ZEA strongly stimulates cell proliferation. However the detailed molecular and cellular mechanisms of ZEA-mediated induction of cell proliferation have not yet been completely explained. The aim of this study was to detect the role of miRNAs in ZEA-mediated induction of cell proliferation. The effects of ZEA on cell proliferation were assessed using a cell counting kit assay and xCELLigence system. Micro-RNA sequencing was performed after treatment of TM3 cells with ZEA (0.01 μmol/L) for different time periods (0, 2, 6 and 18 h). Cell function and pathway analysis of the miRNA target genes were performed by Ingenuity Pathway Analysis (IPA). We found that ZEA promotes TM3 cell proliferation at low concentrations. miRNA sequenceing revealed 66 differentially expressed miRNAs in ZEA-treated cells in comparison to the untreated control (p < 0.05). The miRNA sequencing indicated that compared to control group, there were 66 miRNAs significant change (p < 0.05) in ZEA-treated groups. IPA analysis showed that the predicated miRNAs target gene involved in cell Bio-functions including cell cycle, growth and proliferation, and in signaling pathways including MAPK and RAS-RAF-MEK-ERK pathways. Results from flow cytometry and Western Blot analysis validated the predictions that ZEA can affect cell cycle, and the MAPK signaling pathway. Taking these together, the cell proliferation induced ZEA is regulated by miRNAs. The results shed light on the molecular and cellular mechanisms for the mediation of ZEA to induce proliferation.
Comparative Transcriptomic Analysis of Biological Process and Key Pathway in Three Cotton (Gossypium spp.) Species Under Drought Stress
Authors: Hasan Md Mosfeq-Ul , Ma Fanglu , Islam Faisal , Sajid Muhammad , Prodhan Zakaria H. , Li Feng , Shen Hao , Chen Yadong , Wang Xuede
Published: April 2019

Drought is one of the most important abiotic stresses that seriously affects cotton growth, development, and production worldwide. However, the molecular mechanism, key pathway, and responsible genes for drought tolerance incotton have not been stated clearly. In this research, high-throughput next generation sequencing technique was utilized to investigate gene expression profiles of three cotton species (Gossypium hirsutum, Gossypium arboreum, and Gossypium barbadense L.) under drought stress. A total of 6968 differentially expressed genes (DEGs) were identified, where 2053, 742, and 4173 genes were tested as statistically significant; 648, 320, and 1998 genes were up-regulated, and 1405, 422, and 2175 were down-regulated in TM-1, Zhongmian-16, and Pima4-S, respectively. Total DEGs were annotated and classified into functional groups under gene ontology analysis. The biological process was present only in tolerant species(TM-1), indicating drought tolerance condition. The Kyoto encyclopedia of genes and genomes showed the involvement of plant hormone signal transduction and metabolic pathways enrichment under drought stress. Several transcription factors associated with ethylene-responsive genes (ICE1, MYB44, FAMA, etc.) were identified as playing key roles in acclimatizing to drought stress. Drought also caused significant changes in the expression of certain functional genes linked to abscisic acid (ABA) responses (NCED, PYL, PP2C, and SRK2E), reactive oxygen species (ROS) related in small heat shock protein and 18.1 kDa I heat shock protein, YLS3, and ODORANT1 genes. These results will provide deeper insights into the molecular mechanisms of drought stress adaptation in cotton.
Phosphatidylinositol 5 Phosphate (PI5P): From Behind the Scenes to the Front (Nuclear) Stage
Authors: Poli Alessandro , Zaurito Antonio Enrico , Abdul-Hamid Shidqiyyah , Fiume Roberta , Faenza Irene , Divecha Nullin
Published: April 2019

Phosphatidylinositol (PI)-related signaling plays a pivotal role in many cellular aspects, including survival, cell proliferation, differentiation, DNA damage, and trafficking. PI is the core of a network of proteins represented by kinases, phosphatases, and lipases which are able to add, remove or hydrolyze PI, leading to different phosphoinositide products. Among the seven known phosphoinositides, phosphatidylinositol 5 phosphate (PI5P) was the last to be discovered. PI5P presence in cells is very low compared to other PIs. However, much evidence collected throughout the years has described the role of this mono-phosphoinositide in cell cycles, stress response, T-cell activation, and chromatin remodeling. Interestingly, PI5P has been found in different cellular compartments, including the nucleus. Here, we will review the nuclear role of PI5P, describing how it is synthesized and regulated, and how changes in the levels of this rare phosphoinositide can lead to different nuclear outputs.
Prediction of the Auto-Ignition Temperatures of Binary Miscible Liquid Mixtures from Molecular Structures
Authors: Shen Shijing , Pan Yong , Ji Xianke , Ni Yuqing , Jiang Juncheng
Published: April 2019

A quantitative structure-property relationship (QSPR) study is performed to predict the auto-ignition temperatures (AITs) of binary liquid mixtures based on their molecular structures. The Simplex Representation of Molecular Structure (SiRMS) methodology was employed to describe the structure characteristics of a series of 132 binary miscible liquid mixtures. The most rigorous “compounds out” strategy was employed to divide the dataset into the training set and test set. The genetic algorithm (GA) combined with multiple linear regression (MLR) was used to select the best subset of SiRMS descriptors, which significantly contributes to the AITs of binary liquid mixtures. The result is a multilinear model with six parameters. Various strategies were employed to validate the developed model, and the results showed that the model has satisfactory robustness and predictivity. Furthermore, the applicability domain (AD) of the model was defined. The developed model could be considered as a new way to reliably predict the AITs of existing or new binary miscible liquid mixtures, belonging to its AD.
Unappreciated Role of LDHA and LDHB to Control Apoptosis and Autophagy in Tumor Cells
Authors: Urbańska Kaja , Orzechowski Arkadiusz
Published: April 2019

Tumor cells possess a high metabolic plasticity, which drives them to switch on the anaerobic glycolysis and lactate production when challenged by hypoxia. Among the enzymes mediating this plasticity through bidirectional conversion of pyruvate and lactate, the lactate dehydrogenase A (LDHA) and lactate dehydrogenase B (LDHB), are indicated. LDHA has a higher affinity for pyruvate, preferentially converting pyruvate to lactate, and NADH to NAD+ in anaerobic conditions, whereas LDHB possess a higher affinity for lactate, preferentially converting lactate to pyruvate, and NAD+ to NADH, when oxygen is abundant. Apart from the undisputed role of LDHA and LDHB in tumor cell metabolism and adaptation to unfavorable environmental or cellular conditions, these enzymes participate in the regulation of cell death. This review presents the latest progress made in this area on the roles of LDHA and LDHB in apoptosis and autophagy of tumor cells. Several examples of how LDHA and LDHB impact on these processes, as well as possible molecular mechanisms, will be discussed in this article. The information included in this review points to the legitimacy of modulating LDHA and/or LDHB to target tumor cells in the context of human and veterinary medicine.
Insights on the Proteases Involved in Barley and Wheat Grain Germination
Authors: Diaz-Mendoza Mercedes , Diaz Isabel , Martinez Manuel
Published: April 2019

Seed storage proteins must be hydrolyzed by proteases to deliver the amino acids essential for embryo growth and development. Several groups of proteases involved in this process have been identified in both the monocot and the dicot species. This review focuses on the implication of proteases during germination in two cereal species, barley and wheat, where proteolytic control during the germination process has considerable economic importance. Formerly, the participation of proteases during grain germination was inferred from reports of proteolytic activities, the expression of individual genes, or the presence of individual proteins and showed a prominent role for papain-like and legumain-like cysteine proteases and for serine carboxypeptidases. Nowadays, the development of new technologies and the release of the genomic sequences of wheat and barley have permitted the application of genome-scale approaches, such as those used in functional genomics and proteomics. Using these approaches, the repertoire of proteases known to be involved in germination has increased and includes members of distinct protease families. The development of novel techniques based on shotgun proteomics, activity-based protein profiling, and comparative and structural genomics will help to achieve a general view of the proteolytic process during germination.
ARNi: A Novel Approach to Counteract Cardiovascular Diseases
Authors: Volpe Massimo , Rubattu Speranza , Battistoni Allegra
Published: April 2019

Cardiovascular diseases (CVDs) still represent the greatest burden on healthcare systems worldwide. Despite the enormous efforts over the last twenty years to limit the spread of cardiovascular risk factors, their prevalence is growing and control is still suboptimal. Therefore, the availability of new therapeutic tools that may interfere with different pathophysiological pathways to slow the establishment of clinical CVDs is important. Previously, the inhibition of neurohormonal systems, namely the renin–angiotensin–aldosterone system (RAAS) and the sympathetic nervous system, has proven to be useful in the treatment of many CVDs. Attempts have recently been made to target an additional hormonal system, that of the natriuretic peptides (NPs), which, when dysregulated, can also play a role in the development CVDs. Indeed, a new class of drug, the angiotensin receptor–neprilysin inhibitors (ARNi), has the ability to counteract the effects of angiotensin II as well as to increase the activity of NPs. ARNi have already been proven to be effective in the treatment of heart failure with reduced ejection fraction. New evidence has suggested that, in the next years, the field of ARNi application will widen to include other CVDs, such as heart failure, with preserved ejection fraction and hypertension.
The Role of Macrophage in the Pathogenesis of Osteoporosis
Authors: Yang Deng-Ho , Yang Meng-Yin
Published: April 2019

Osteoporosis is a systemic disease with progressive bone loss. The bone loss is associated with an imbalance between bone resorption via osteoclasts and bone formation via osteoblasts. Other cells including T cells, B cells, macrophages, and osteocytes are also involved in the pathogenesis of osteoporosis. Different cytokines from activated macrophages can regulate or stimulate the development of osteoclastogenesis-associated bone loss. The fusion of macrophages can form multinucleated osteoclasts and, thus, cause bone resorption via the expression of IL-4 and IL-13. Different cytokines, endocrines, and chemokines are also expressed that may affect the presentation of macrophages in osteoporosis. Macrophages have an effect on bone formation during fracture-associated bone repair. However, activated macrophages may secrete proinflammatory cytokines that induce bone loss by osteoclastogenesis, and are associated with the activation of bone resorption. Targeting activated macrophages at an appropriate stage may help inhibit or slow the progression of bone loss in patients with osteoporosis.
YY1/BCCIP Coordinately Regulates P53-Responsive Element (p53RE)-Mediated Transactivation of p21Waf1/Cip1
Authors: Sui Yi , Wu Tingting , Li Fuqiang , Wang Fei , Cai Yong , Jin Jingji
Published: April 2019

Transactivation of p21 (cyclin-dependent kinase inhibitor 1A, CDKN1A) is closely related to the recruitment of transcription cofactors at the p53 responsive elements (p53REs) in its promoter region. Human chromatin remodeling enzyme INO80 can be recruited to the p53REs of p21 promoter and negatively regulates p21. As one of the key subunits of the INO80 complex, YY1 has also been confirmed to bind to the p53RE sites of p21 promoter. Importantly, YY1 was recently reported to be bound and stabilized by BCCIP (BRCA2 and CDKN1A-interacting protein). Therefore, we hypothesized that the YY1/BCCIP complex plays an important role in regulating the transactivation of p21. Here we present evidence that the YY1/BCCIP complex coordinatively regulates p53RE-mediated p21 transactivation. We first confirmed the cross-interaction between YY1, BCCIP, and p53, suggesting an intrinsic link between three proteins in the regulation of p21 transcription. In dual luciferase assays, YY1 inhibited p53RE-mediated luciferase activity, whereas BCCIP revealed the opposite effect. More interestingly, the region 146–270 amino acids of YY1, which bound to BCCIP, increased p53-mediated luciferase activity, indicating the complexity of the YY1/BCCIP complex in co-regulating p21 transcription. Further in-depth research confirmed the co-occupancy of YY1/BCCIP with p53 at the p53RE-proximal region of p21. Lentiviral-mediated knockdown of BCCIP inhibited the recruitment of p53 and YY1 at the p53RE proximal region of p21; however, this phenomenon was reversed by expressing exogenous YY1, suggesting the collaborative regulation of YY1/BCCIP complex in p53RE-mediated p21 transcription. These data provide new insights into the transcriptional regulation of p21 by the YY1/BCCIP complex.
Expression of Autotaxin–Lysophosphatidate Signaling-Related Proteins in Breast Cancer with Adipose Stroma
Authors: Cha Yoon Jin , Koo Ja Seung
Published: April 2019

This research aimed to evaluate the expression and clinical implication of autotaxin (ATX)-lysophosphatidate (LPA) signaling-related proteins in breast cancer with adipose stroma. To this end, a tissue microarray (TMA) was constructed from 137 breast cancer tissues with adipose stroma and 329 breast cancer tissues with non-adipose stroma (inflammatory stroma: n = 81, 24.6%; fibrous stroma: n = 246, 75.4%). Immunohistochemical staining for ATX-LPA signaling-related proteins (ATX, LPA1, LPA2, and LPA3) was performed on the TMA. The results showed that LPA2 in tumor cells and LPA3 in stromal cells were highly expressed in breast cancer with adipose stroma and breast cancer with adipose and inflammatory stroma, respectively. Stromal LPA1 positivity (p = 0.017) and stromal LPA3 positivity (p = 0.004) were higher in breast cancer with adipose stroma containing CD68-positive crown-like structures (CLS). Stromal ATX positivity (p = 0.010) and stromal LPA3 positivity (p = 0.009) were higher in breast cancer with adipose tissue containing CD163-positive CLS. In breast cancer with adipose stroma, the number of CD163-positive macrophages was greater with stromal ATX positivity (p = 0.003), and the number of CD68-positive and CD163-positive macrophages were greater in cases with stromal LPA3 positivity. In conclusion, ATX-LPA signaling-related proteins are highly expressed in breast cancer with adipose stroma, with associated macrophage infiltration.
Application of Acyzol in the Context of Zinc Deficiency and Perspectives
Authors: Aliev Gjumrakch , Li Yi , Chubarev Vladimir N. , Lebedeva Svetlana A. , Parshina Lidiya N. , Trofimov Boris A. , Sologova Susanna S. , Makhmutova Alfiya , Avila-Rodriguez Marco F. , Klochkov Sergey G. , Galenko-Yaroshevsky Pavel A. , Tarasov Vadim V.
Published: April 2019

Zinc is one of the most important essential trace elements. It is involved in more than 300 enzyme systems and is an indispensable participant in many biochemical processes. Zinc deficiency causes a number of disorders in the human body, the main ones being the delay of growth and puberty, immune disorders, and cognitive dysfunctions. There are over two billion people in the world suffering from zinc deficiency conditions. Acyzol, a zinc-containing medicine, developed as an antidote against carbon monoxide poisoning, demonstrates a wide range of pharmacological activities: Anti-inflammatory, reparative, detoxifying, immunomodulatory, bacteriostatic, hepatoprotective, adaptogenic, antioxidant, antihypoxic, and cardioprotective. The presence of zinc in the composition of Acyzol suggests the potential of the drug in the treatment and prevention of zinc deficiency conditions, such as Prasad’s disease, immune system pathology, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, and delayed mental and physical development in children. Currently, the efficiency of Acyzol in the cases of zinc deficiency is shown in a large number of experimental studies. So, Acyzol can be used as a highly effective drug for pharmacologic therapy of a wide range of diseases and conditions and it opens up new perspectives in the treatment and prevention of zinc deficiency conditions.
Citrate-Induced p85α–PTEN Complex Formation Causes G2/M Phase Arrest in Human Pharyngeal Squamous Carcinoma Cell Lines
Authors: Hung Kuang-Chen , Wang Shyang-Guang , Lin Meng-Liang , Chen Shih-Shun
Published: April 2019

Citrate is a key intermediate of the tricarboxylic acid cycle and acts as an allosteric signal to regulate the production of cellular ATP. An elevated cytosolic citrate concentration inhibits growth in several types of human cancer cells; however, the underlying mechanism by which citrate induces the growth arrest of cancer cells remains unclear. The results of this study showed that treatment of human pharyngeal squamous carcinoma (PSC) cells with a growth-suppressive concentration of citrate caused cell cycle arrest at the G2/M phase. A coimmunoprecipitation study demonstrated that citrate-induced cell cycle arrest in the G2/M phase was associated with stabilizing the formation of cyclin B1–phospho (p)-cyclin-dependent kinase 1 (CDK1) (Thr 161) complexes. The citrate-induced increased levels of cyclin B1 and G2/M phase arrest were suppressed by the caspase-3 inhibitor Ac-DEVD-CMK and caspase-3 cleavage of mutant p21 (D112N). Ectopic expression of the constitutively active form of protein kinase B (Akt1) could overcome the induction of p21 cleavage, cyclin B1–p-CDK1 (Thr 161) complexes, and G2/M phase arrest by citrate. p85α–phosphatase and tensin homolog deleted from chromosome 10 (PTEN) complex-mediated inactivation of Akt was required for citrate-induced G2/M phase cell cycle arrest because PTEN short hairpin RNA or a PTEN inhibitor (SF1670) blocked the suppression of Akt Ser 473 phosphorylation and the induction of cyclin B1–p-CDK1 (Thr 161) complexes and G2/M phase arrest by citrate. In conclusion, citrate induces G2/M phase arrest in PSC cells by inducing the formation of p85α–PTEN complexes to attenuate Akt-mediated signaling, thereby causing the formation of cyclin B1–p-CDK1 (Thr 161) complexes.
Human Gingival Fibroblasts Exposed to Extremely Low-Frequency Electromagnetic Fields: In Vitro Model of Wound-Healing Improvement
Authors: Costantini Erica , Sinjari Bruna , D’Angelo Chiara , Murmura Giovanna , Reale Marcella , Caputi Sergio
Published: April 2019

Several clinical studies have suggested the impact of sinusoidal and pulsed electromagnetic fields in quickening wound repair processes and tissue regeneration. The clinical use of extremely low-frequency electromagnetic fields could represent a novel frontier in tissue repair and oral health, with an interesting clinical perspective. The present study aimed to evaluate the effect of an extremely low-frequency sinusoidal electromagnetic field (SEMF) and an extremely low-frequency pulsed electromagnetic field (PEMF) with flux densities of 1 mT on a model of oral healing process using gingival fibroblasts. An in vitro mechanical injury was produced to evaluate wound healing, migration, viability, metabolism, and the expression of selected cytokines and protease genes in fibroblasts exposed to or not exposed to the SEMF and the PEMF. Interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-β), metalloproteinase 2 (MMP-2), monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS), and heme oxygenase 1 (HO-1) are involved in wound healing and tissue regeneration, favoring fibroblast proliferation, chemotaxis, and activation. Our results show that the exposure to each type of electromagnetic field increases the early expression of IL-6, TGF-β, and iNOS, driving a shift from an inflammatory to a proliferative phase of wound repair. Additionally, a later induction of MMP-2, MCP-1, and HO-1 was observed after electromagnetic field exposure, which quickened the wound-healing process. Moreover, electromagnetic field exposure influenced the proliferation, migration, and metabolism of human gingival fibroblasts compared to sham-exposed cells. This study suggests that exposure to SEMF and PEMF could be an interesting new non-invasive treatment option for wound healing. However, additional studies are needed to elucidate the best exposure conditions to provide the desired in vivo treatment efficacy.
Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications
Authors: Nagappan Arulkumar , Shin Jooyeon , Jung Myeong Ho
Published: April 2019

Endogenous cannabinoids (ECs) are lipid-signaling molecules that specifically bind to cannabinoid receptor types 1 and 2 (CB1R and CB2R) and are highly expressed in central and many peripheral tissues under pathological conditions. Activation of hepatic CB1R is associated with obesity, insulin resistance, and impaired metabolic function, owing to increased energy intake and storage, impaired glucose and lipid metabolism, and enhanced oxidative stress and inflammatory responses. Additionally, blocking peripheral CB1R improves insulin sensitivity and glucose metabolism and also reduces hepatic steatosis and body weight in obese mice. Thus, targeting EC receptors, especially CB1R, may provide a potential therapeutic strategy against obesity and insulin resistance. There are many CB1R antagonists, including inverse agonists and natural compounds that target CB1R and can reduce body weight, adiposity, and hepatic steatosis, and those that improve insulin sensitivity and reverse leptin resistance. Recently, the use of CB1R antagonists was suspended due to adverse central effects, and this caused a major setback in the development of CB1R antagonists. Recent studies, however, have focused on development of antagonists lacking adverse effects. In this review, we detail the important role of CB1R in hepatic insulin resistance and the possible underlying mechanisms, and the therapeutic potential of CB1R targeting is also discussed.
Ubiquitination-Mediated Inflammasome Activation during Bacterial Infection
Authors: Xu Tao , Guo Yu , Qi Xiaopeng
Published: April 2019

Inflammasome activation is essential for host immune responses during pathogenic infection and sterile signals insult, whereas excessive activation is injurious. Thus, inflammasome activation is tightly regulated at multiple layers. Ubiquitination is an important post-translational modification for orchestrating inflammatory immune responses during pathogenic infection, and a major target hijacked by pathogenic bacteria for promoting their survival and proliferation. This review summarizes recent insights into distinct mechanisms of the inflammasome activation and ubiquitination process triggered by bacterial infection. We discuss the complex regulatory of inflammasome activation mediated by ubiquitination machinery during bacterial infection, and provide therapeutic approaches for specifically targeting aberrant inflammasome activation.
Ouabain Enhances Cell-Cell Adhesion Mediated by β1 Subunits of the Na+,K+-ATPase in CHO Fibroblasts
Authors: Vilchis-Nestor Claudia Andrea , Roldán María Luisa , Leonardi Angelina , Navea Juan G. , Padilla-Benavides Teresita , Shoshani Liora
Published: April 2019

Adhesion is a crucial characteristic of epithelial cells to form barriers to pathogens and toxic substances from the environment. Epithelial cells attach to each other using intercellular junctions on the lateral membrane, including tight and adherent junctions, as well as the Na+,K+-ATPase. Our group has shown that non-adherent chinese hamster ovary (CHO) cells transfected with the canine β1 subunit become adhesive, and those homotypic interactions amongst β1 subunits of the Na+,K+-ATPase occur between neighboring epithelial cells. Ouabain, a cardiotonic steroid, binds to the α subunit of the Na+,K+-ATPase, inhibits the pump activity and induces the detachment of epithelial cells when used at concentrations above 300 nM. At nanomolar non-inhibiting concentrations, ouabain affects the adhesive properties of epithelial cells by inducing the expression of cell adhesion molecules through the activation of signaling pathways associated with the α subunit. In this study, we investigated whether the adhesion between β1 subunits was also affected by ouabain. We used CHO fibroblasts stably expressing the β1 subunit of the Na+,K+-ATPase (CHO β1), and studied the effect of ouabain on cell adhesion. Aggregation assays showed that ouabain increased the adhesion between CHO β1 cells. Immunofluorescence and biotinylation assays showed that ouabain (50 nM) increases the expression of the β1 subunit of the Na+,K+-ATPase at the cell membrane. We also examined the effect of ouabain on the activation of signaling pathways in CHO β1 cells, and their subsequent effect on cell adhesion. We found that cSrc is activated by ouabain and, therefore, that it likely regulates the adhesive properties of CHO β1 cells. Collectively, our findings suggest that the β1 subunit adhesion is modulated by the expression levels of the Na+,K+-ATPase at the plasma membrane, which is regulated by ouabain.
An Update on Interleukin-9: From Its Cellular Source and Signal Transduction to Its Role in Immunopathogenesis
Authors: Chakraborty Sushmita , Kubatzky Katharina F. , Mitra Dipendra Kumar
Published: April 2019

Interleukin-9 (IL-9) is a pleiotropic cytokine and was primarily studied in the context of T helper 2 (TH2)-associated immuno-pathological conditions such as asthma and parasitic infections. There was a paradigm shift in the biology of IL-9 after the recent discovery of TH9 cells, a new subtype of TH cells which secrete IL-9 in copious amounts. This has resulted in renewed interest in this cytokine, which was neglected since discovery because it was considered it to be just another TH2 cytokine. Recent studies have shown that it has multiple cellular sources and is critically involved in the immune-pathogenesis of inflammatory diseases and in guarding immune tolerance. In this review, we will discuss its discovery, gene organization, cellular sources, and signaling pathways. Especially, we will give an update on the recent development regarding its relevance in the immune pathogenesis of human diseases.
The Impact of a Nitric Oxide Synthase Inhibitor (L-NAME) on Ischemia–Reperfusion Injury of Cholestatic Livers by Pringle Maneuver and Liver Resection after Bile Duct Ligation in Rats
Authors: Iwasaki Junji , Afify Mamdouh , Bleilevens Christian , Klinge Uwe , Weiskirchen Ralf , Steitz Julia , Vogt Michael , Yagi Shintaro , Nagai Kazuyuki , Uemoto Shinji , Tolba Rene H.
Published: April 2019

The Pringle maneuver (PM) has been widely used to control blood loss during liver resection. However, hepatic inflow occlusion can also result in hepatic ischemia–reperfusion injury (IRI), especially in patients with a cholestatic, fibrotic, or cirrhotic liver. Here we investigate a nitric oxide synthase (NOS) inhibitor N-Nitroarginine methyl ester (L-NAME) on IRI after the PM and partial hepatectomy of cholestatic livers induced by bile duct ligation (BDL) in rats. Control group (non-BDL/no treatment), BDL + T group (BDL/L-NAME treatment) and BDL group (BDL/no treatment) were analyzed. Cholestasis was induced by BDL in the L-NAME and BDL group and a 50% partial hepatectomy with PM was performed. L-NAME was injected before PM in the BDL + T group. Hepatocellular damage, portal venous flow, microcirculation, endothelial lining, and eNOS, iNOS, interleukin (IL)-6, and transforming growth factor-β (TGF-β) were evaluated. Microcirculation of the liver in the BDL + T group tended to be higher. Liver damage and apoptotic index were significantly lower and Ki-67 labeling index was higher in the BDL + T group while iNOS and TGF-β expression was decreased. This was corroborated by a better preserved endothelial lining. L-NAME attenuated IRI following PM and improved proliferation/regeneration of cholestatic livers. These positive effects were considered as the result of improved hepatic microcirculation, prevention of iNOS formation, and TGF-β mRNA upregulation.
The Possible Role of the Microbiota-Gut-Brain-Axis in Autism Spectrum Disorder
Authors: Srikantha Piranavie , Mohajeri M. Hasan
Published: April 2019

New research points to a possible link between autism spectrum disorder (ASD) and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites, or leaky gut in autistic people are described. Various altered metabolite levels were observed in the blood and urine of autistic children, many of which were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides (LPS). A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients, triggering new body responses or an altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in cells, altered tight junctions in the blood-brain barrier and structural changes in the cortex, hippocampus, amygdala and cerebellum were also detected. Moreover, this paper suggests that ASD is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between ASD and gut microbiota is not yet well established, the consumption of specific probiotics may represent a side-effect free tool to re-establish gut homeostasis and promote gut health. The diagnostic and therapeutic value of bacterial-derived compounds as new possible biomarkers, associated with perturbation in the phenylalanine metabolism, as well as potential therapeutic strategies will be discussed.
Epigenetic Effects of n-3 LCPUFAs: A Role in Pediatric Metabolic Syndrome
Authors: Amatruda Matilde , Ippolito Giulio , Vizzuso Sara , Vizzari Giulia , Banderali Giuseppe , Verduci Elvira
Published: April 2019

Childhood obesity represents an important public health issue worldwide and is strongly linked to metabolic alterations such as hypertension, insulin resistance, and dyslipidemia. The constellation of these conditions is commonly known as Metabolic Syndrome (MetS). Metabolic syndrome is not just a simple cluster of metabolic complications due to excess of adipose tissue, but is considered a risk factor for cardiovascular diseases. Evidence from several human and animal studies suggests that environmental and nutritional exposure during pregnancy may affect the newborn development and future health through epigenetic changes, playing a potential role in determining obesity and obesity-related complications. Understanding how nutritional epigenetic mechanisms contribute to the “transgenerational risk” for obesity and metabolic dysfunction is crucial in order to develop early prevention strategies for children’s health. Nutrigenetics is the science that studies the role of nutrients in gene expression. Long Chain Polyunsaturated Fatty Acids (LCPUFAs) are known for their health benefits, especially in relation to their ability to modulate inflammation and improve some obesity-associated comorbidities, mainly by decreasing plasma triglycerides. Recent nutrigenetic research is focusing on the potential role of LCPUFAs in influencing epigenetic markers. In this review, we present the most recent updates about the possible interaction between n-3 LCPUFAs and epigenetic pathways in metabolic syndrome. Literature from MEDLINE® and the Cochrane database between May 2005 and December 2018 has been scanned.
Characterisation of Gas-Chromatographic Poly(Siloxane) Stationary Phases by Theoretical Molecular Descriptors and Prediction of McReynolds Constants
Authors: D’Archivio Angelo A. , Giannitto Andrea
Published: April 2019

Retention in gas–liquid chromatography is mainly governed by the extent of intermolecular interactions between the solute and the stationary phase. While molecular descriptors of computational origin are commonly used to encode the effect of the solute structure in quantitative structure–retention relationship (QSRR) approaches, characterisation of stationary phases is historically based on empirical scales, the McReynolds system of phase constants being one of the most popular. In this work, poly(siloxane) stationary phases, which occupy a dominant position in modern gas–liquid chromatography, were characterised by theoretical molecular descriptors. With this aim, the first five McReynolds constants of 29 columns were modelled by multilinear regression (MLR) coupled with genetic algorithm (GA) variable selection applied to the molecular descriptors provided by software Dragon. The generalisation ability of the established GA-MLR models, evaluated by both external prediction and repeated calibration/evaluation splitting, was better than that reported in analogous studies regarding nonpolymeric (molecular) stationary phases. Principal component analysis on the significant molecular descriptors allowed to classify the poly(siloxanes) according to their chemical composition and partitioning properties. Development of QSRR-based models combining molecular descriptors of both solutes and stationary phases, which will be applied to transfer retention data among different columns, is in progress.
PhSeZnCl in the Synthesis of Steroidal β-Hydroxy-Phenylselenides Having Antibacterial Activity
Authors: Jastrzebska Izabella , Mellea Stefano , Salerno Valerio , Grzes Pawel Adam , Siergiejczyk Leszek , Niemirowicz-Laskowska Katarzyna , Bucki Robert , Monti Bonifacio , Santi Claudio
Published: April 2019

We report here the reaction of in situ prepared PhSeZnCl with steroid derivatives having an epoxide as an electrophilic functionalization. The corresponding ring-opening reaction resulted to be regio- and stereoselective affording to novel phenylselenium-substituted steroids. Assessment of their antibacterial properties against multidrug-resistant bacteria, such as Pseudomonas aeruginosa Xen 5 strain, indicates an interesting bactericidal activity and their ability to prevent bacterial biofilm formation.
Correction: Langeskov-Christensen, M., et al. Aerobic Capacity Is Not Associated with Most Cognitive Domains in Patients with Multiple Sclerosis—A Cross-Sectional Investigation. Journal of Clinical Medicine 2018, 7, 272
Authors: Langeskov-Christensen Martin , Eskildsen Søren , Stenager Egon , Boye Jensen Henrik , Hvilsted Nielsen Helle , Petersen Thor , Grøndahl Hvid Lars , Hämäläinen Päivi , Marstrand Lisbet , Dalgas Ulrik
Published: April 2019

The authors wish to make the following corrections to this paper [...]
Relevance of Targeting the Distal Renal Artery and Branches with Radiofrequency Renal Denervation Approaches—A Secondary Analysis from a Hypertensive CKD Patient Cohort
Authors: Kiuchi Márcio Galindo , Schlaich Markus P. , Chen Shaojie , Villacorta Humberto , Ho Jan K. , Carnagarin Revathy , Matthews Vance B. , Lugon Jocemir Ronaldo
Published: April 2019

We searched for an association between changes in blood pressure (BP) at 12 and 24 months after renal denervation (RDN) and the different patterns of ablation spots placement along the renal artery vasculature. We performed a post-hoc analysis of a 24-month follow-up evaluation of 30 patients who underwent RDN between 2011 and 2012 using our previous database. Patients who had (i) resistant hypertension, as meticulously described previously, and (ii) Chronic kidney disease (CKD) stages 2, 3 and 4. Correlations were assessed using the Pearson or Spearman correlation tests as appropriate. The mean change in systolic ambulatory BP monitoring (ABPM) compared to baseline was −19.4 ± 12.7 mmHg at the 12th (p < 0.0001) and −21.3 ± 14.1 mmHg at the 24th month (p < 0.0001). There was no correlation between the ABPM Systolic Blood Pressure (SBP)-lowering effect and the total number of ablated spots in renal arteries (17.7 ± 6.0) either at 12 (r = −0.3, p = 0.1542) or at 24 months (r = −0.2, p = 0.4009). However, correlations between systolic BP-lowering effect and the number of ablation spots performed in the distal segment and branches were significant at the 12 (r = −0.7, p < 0.0001) and 24 months (r = −0.8, p < 0.0001) follow-up. Our findings indicate a substantial correlation between the numbers of ablated sites in the distal segment and branches of renal arteries and the systolic BP-lowering effect in the long-term.
Poor Efficacy of L-Acetylcarnitine in the Treatment of Asthenozoospermia in Patients with Type 1 Diabetes
Authors: Condorelli Rosita A. , Calogero Aldo E. , Cannarella Rossella , Giacone Filippo , Mongioi’ Laura M. , Cimino Laura , Aversa Antonio , La Vignera Sandro
Published: April 2019

Introduction. In recent years, research has focused on the impact that diabetes mellitus (DM) has on male reproductive function. The available evidence has mainly considered type 2 DM (DM2). However, we have previously shown that type 1 DM (DM1) also affects male reproductive health. Given the efficacy of carnitine in the treatment of male infertility, a topic that merits further investigation is its role in the treatment of infertile patients with DM1. Aim. To investigate the efficacy of carnitines for the treatment of asthenozoospermia in DM1 patients. Methods. This was a two-arm single-blind, randomized control trial. The patients enrolled in this study were assigned to the group receiving L-acetylcarnitine (LAC) (1.5 g daily for 4 months) or to the group receiving LAC (same dosage) plus L-carnitine (LC) (2 g daily for 4 months). Serum-glycated hemoglobin levels did not differ significantly after either of the two treatments given. Administration of LAC plus LC showed greater efficacy on progressive sperm motility than single therapy (increase 14% vs. 1% after treatment, respectively). Discussion. The results of this study showed that the administration of LAC plus LC is more effective than the administration of LAC alone. The lower efficacy of LAC alone could be due to the lower overall administered dosage. Alternatively, a selective defect of carnitine transporters at an epididymal level could be hypothesized in patients with DM1. Further studies are needed to clarify this point.
Heterogeneous Metabolic Response to Exercise Training in Heart Failure with Preserved Ejection Fraction
Authors: Bahls Martin , Friedrich Nele , Pietzner Maik , Wachter Rolf , Budde Kathrin , Hasenfuß Gerd , Nauck Matthias , Pressler Axel , Felix Stephan , Edelmann Frank , Halle Martin , Dörr Marcus
Published: April 2019

The prevalence of heart failure with preserved ejection fraction (HFpEF) is constantly increasing and no evidence-based pharmacological treatment option is available. While exercise training (ET) improves diastolic function, its metabolic mechanisms in HFpEF are unclear. We assessed the metabolic response to 12 weeks of ET in patients with HFpEF by performing a post hoc analysis of the EX-DHF-P trial (ISRCTN42524037). Plasma concentrations of 188 endogenous metabolites were measured in 44 ET and 20 usual care (UC) patients at baseline and 3-months follow-up. Metabolic differences between ET and UC from baseline to follow-up were compared and differential responses to ET were examined by random forest feature selection. ET prevented the increase of acetylornithine and carnitine as well as the decrease of three glycerophospholipids. After ET, two opposite metabolic response clusters were identified. Cluster belonging was associated with perceived well-being at baseline and changes in low-density lipoprotein but not with cardiorespiratory, ventilatory or echocardiographic parameters. These two ET-induced metabolic response patterns illustrate the heterogeneity of the HFpEF patient population. Our results suggest that other biological parameters might be helpful besides clinical variables to improve HFpEF patient stratification. Whether this approach improves response prediction regarding ET and other treatments should be explored.
Spatial Variability of Coastal Foredune Evolution, Part A: Timescales of Months to Years
Authors: Brodie Katherine , Conery Ian , Cohn Nicholas , Spore Nicholas , Palmsten Margaret
Published: April 2019

Coastal foredunes are topographically high features that can reduce vulnerability to storm-related flooding hazards. While the dominant aeolian, hydrodynamic, and ecological processes leading to dune growth and erosion are fairly well-understood, predictive capabilities of spatial variations in dune evolution on management and engineering timescales (days to years) remain relatively poor. In this work, monthly high-resolution terrestrial lidar scans were used to quantify topographic and vegetation changes over a 2.5 year period along a micro-tidal intermediate beach and dune. Three-dimensional topographic changes to the coastal landscape were used to investigate the relative importance of environmental, ecological, and morphological factors in controlling spatial and temporal variability in foredune growth patterns at two 50 m alongshore stretches of coast. Despite being separated by only 700 m in the alongshore, the two sites evolved differently over the study period. The northern dune retreated landward and lost volume, whereas the southern dune prograded and vertically accreted. At the start of and throughout the study, the erosive site had steeper foredune faces with less overall vegetation coverage, and dune growth varied spatially and temporally within the site. Deposition occurred mainly at or behind the vegetated dune crest and primarily during periods with strong, oblique winds (>∼45 ∘ from shore normal). Minimal deposition was observed on the mostly bare-sand dune face, except where patchy vegetation was present. In contrast, the response of the accretive site was more spatially uniform, with growth focused on the heavily vegetated foredune face. The largest differences in dune response between the two sections of dunes occurred during the fall storm season, when each of the systems’ geomorphic and ecological properties modulated dune growth patterns. These findings highlight the complex eco-morphodynamic feedback controlling dune dynamics across a range of spatial scales.