bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental and Psychosocial Interventions in Age-Friendly Communities and Active Ageing: A Systematic Review
Authors: Sánchez-González Diego , Rojo-Pérez Fermina , Rodríguez-Rodríguez Vicente , Fernández-Mayoralas Gloria
Published: November 2020

Background: The academic literature contains little information regarding the interventions that create age-friendly cities and communities in order to promote active ageing. Objectives: A systematic review was carried out to determine the available empirical evidence in relation to the characteristics, content and effectiveness of interventions aimed at improving environmental and psychosocial risk factors for older people, from the perspective of age-friendly communities and the promotion of active ageing. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the studies retained in this review were identified through a systematic search of the academic literature in selected electronic databases including Web of Science and Scopus. Independent critical appraisal and data extraction were conducted by two reviewers. The checklist was used to assess the quality of the articles. Findings: The search identified 1020 potentially eligible documents, of which 11 satisfied the established criteria. Non-exhaustive practices prevailed over rigorous investigations, with a high proportion of studies observed to be of low methodological quality and at high risk of bias. This reflected the predominance of uncontrolled interventions. Environmental interventions were focused on reducing risk and adapting the everyday environmental setting, while psychosocial interventions prioritised social strategies (behavioural changes, promotion of participation) and training. Interventions were more effective in certain domains of age-friendly cities and communities such as transportation and housing, followed by increased participation as a lifestyle-related behavioural change. The inferred changes were associated with providing information and enhancing skills; modifying access, barriers, exposures, and opportunities; enhancing services and support; continuity and effectiveness of changes over time; and modifying policies based on the bottom-up approach of age-friendly cities and communities (AFCC). Discussion and conclusion: Interventions focused on personal and organisational aspects might have positive effects in the longer term. However, fewer changes would be observed in interventions revolving around changing lifestyles owing to the impact of complex multi-causal factors. The relative effectiveness in terms of health calls into question the design of interventions and the supposed “friendliness” of certain communities. There is a need to encourage sound longitudinal research aimed at providing key knowledge for the implementation and evaluation of public policies, and to encourage age-friendly community programmes to promote active ageing.
Efficacy of an Internet-Based Intervention to Promote a Healthy Lifestyle on the Reproductive Parameters of Overweight and Obese Women: Study Protocol for a Randomised Controlled Trial
Authors: Biviá-Roig Gemma , Blasco-Sanz Ruth , Boldó-Roda Ana , Vara M. Dolores , Escrivá-Martínez Tamara , Herrero Rocío , La Rosa Valentina Lucia , Baños Rosa M. , Lisón Juan Francisco
Published: November 2020

Background: Infertility is estimated to affect 15% of couples of reproductive age. Weight management problems (being obese or overweight) are among the problems that produce infertility, both in women seeking spontaneous pregnancy and in those undergoing assisted reproduction techniques. Over the last few decades, the prevalence of obesity has increased alarmingly in our society and is now considered one of the most important public health problems. The combination of diet and exercise to achieve weight loss are currently considered an effective intervention for the improvement of reproductive parameters in overweight or obese infertile women. In other population groups, it has been shown that Internet-based interventions are just as effective as traditional ones, and these cover a larger population with a good cost–benefit ratio. However, to the best of our knowledge, no studies so far have analysed any specific online interventions for this group of infertile women. Thus, the objective of this project will be to evaluate the effectiveness of an online program to promote a healthy lifestyle among women who are overweight or obese who also have a diagnosis of infertility and are on the waiting list for in vitro fertilisation treatment. Methods: This will be a randomised controlled clinical trial conducted in 94 women which will compare a self-administered Internet-based intervention promoting a healthy lifestyle in terms of diet and exercise (n = 47) to a control group that will receive standard medical care. The online program will comprise nine modules, will last for 3 months, and will be monitored every 3 months after the intervention until the final follow-up at 12 months. The main outcome will be the spontaneous pregnancy rate. Secondary outcomes will include changes in body composition, dietary and physical exercise habits, glycaemic profiles, lipid profiles, hormonal profiles, and patient quality of life related to their fertility problems. The data analysis will be done on an intention-to-treat basis. Discussion: The aim of this study is to increase our knowledge of the effectiveness of online interventions specifically adapted to infertile women who are overweight or obese in the promotion of healthy lifestyles.
Classification of Whole-Body Postural Discomfort Using Cluster Analysis
Authors: Hwang Jaejin , Lee Kyung-Sun
Published: November 2020

The objectives of this study were to evaluate the effect of gender and postures of the neck, trunk, and knee on overall postural discomfort, and to classify combined postures into different postural discomfort groups. A total of 95 participants (42 males and 53 females) performed 45 different static postures, which were a combination of 3 neck angles, 5 trunk angles, and 3 knee angles, and rated the perceived postural discomfort. Non-hierarchical K-means cluster analysis was employed to classify the 45 different combined postures into several postural discomfort groups. Postural discomfort was significantly affected by gender and postures of the neck, trunk, and knee (p < 0.001). Three clusters (high, medium, and low discomfort) were identified and the postural discomfort was significantly different between clusters (p < 0.001). The high discomfort group consisted of mostly males with high knee and trunk flexion angles and a moderate neck flexion angle. The low discomfort group was female-dominant with low neck and trunk flexion angles and a moderate knee flexion angle. The different flexibility (stiffness) of the joint motions between genders may affect the gender difference in postural discomfort. The knee and trunk postures were critical to the postural balance, which may affect the perception of whole-body discomfort. This result will be useful for developing and improving postural observation tools.
Intimate Partner Violence and Resilience: The Experience of Women in Mother-Child Assisted Living Centers
Authors: Rollero Chiara , Speranza Federica
Published: November 2020

Research has largely documented the damaging consequences of intimate partner violence. However, the literature presents an important gap in the identification of factors that may strengthen resilience in the victims, especially in the case of mothers and pregnant women. The present study aimed at investigating the experience of abused mothers engaged in an educative path in a Mother–Child Assisted Living Center. A qualitative descriptive methodology was used. Face-to-face in-depth interviews were conducted with a purposive sample of eight women. Four main themes emerged from the interviews: (1) improvement in the mother–child relationship; (2) a process of personal change during the educative path; (3) the rebuilding of trust relationships; and (4) attitudes and hopes toward the future. Taken together, these findings highlight the process of resilience, conceived from a socioecological perspective as the ability to use resources rooted in interconnected systems. The implications of these findings are discussed.
Estimating the Carcinogenic Potency of Second-Hand Smoke and Aerosol from Cigarettes and Heated Tobacco Products
Authors: Hirano Tomoyasu , Takei Teiji
Published: November 2020

The revised Promotion Act, enforced in April 2020, allows the establishment of dedicated smoking rooms for heated tobacco products (HTPs). Since carcinogenicity assessment is unable to determine the safe level of secondhand smoke, we estimated excess lifetime cancer risk using previously reported risk factors. Assuming that nicotine inhalation is proportional to cancer potency, the lifetime cancer risk for HTP IQOS is expected to be below 10−5 (1/100,000), which is three orders of magnitude lower than that for cigarettes.
Performance Pay in Hospitals: An Experiment on Bonus–Malus Incentives
Authors: Kairies-Schwarz Nadja , Souček Claudia
Published: November 2020

Recent policy reforms in Germany require the introduction of a performance pay component with bonus–malus incentives in the inpatient care sector. We conduct a controlled online experiment with real hospital physicians from public hospitals and medical students in Germany, in which we investigate the effects of introducing a performance pay component with bonus–malus incentives to a simplified version of the German Diagnosis Related Groups (DRG) system using a sequential design with stylized routine cases. In both parts, participants choose between the patient optimal and profit maximizing treatment option for the same eight stylized routine cases. We find that the introduction of bonus–malus incentives only statistically significantly increases hospital physicians’ proportion of patient optimal choices for cases with high monetary baseline DRG incentives to choose the profit maximizing option. Medical students behave qualitatively similar. However, they are statistically significantly less patient oriented than real hospital physicians, and statistically significantly increase their patient optimal decisions with the introduction of bonus–malus incentives in all stylized routine cases. Overall, our results indicate that whether the introduction of a performance pay component with bonus–malus incentives to the (German) DRG system has a positive effect on the quality of care or not particularly depends on the monetary incentives implemented in the DRG system as well as the type of participants and their initial level of patient orientation.
Trans-Ancestral Fine-Mapping and Epigenetic Annotation as Tools to Delineate Functionally Relevant Risk Alleles at IKZF1 and IKZF3 in Systemic Lupus Erythematosus
Authors: Vyse Timothy J. , Cunninghame Graham Deborah S.
Published: November 2020

Background: Prioritizing tag-SNPs carried on extended risk haplotypes at susceptibility loci for common disease is a challenge. Methods: We utilized trans-ancestral exclusion mapping to reduce risk haplotypes at IKZF1 and IKZF3 identified in multiple ancestries from SLE GWAS and ImmunoChip datasets. We characterized functional annotation data across each risk haplotype from publicly available datasets including ENCODE, RoadMap Consortium, PC Hi-C data from 3D genome browser, NESDR NTR conditional eQTL database, GeneCards Genehancers and TF (transcription factor) binding sites from Haploregv4. Results: We refined the 60 kb associated haplotype upstream of IKZF1 to just 12 tag-SNPs tagging a 47.7 kb core risk haplotype. There was preferential enrichment of DNAse I hypersensitivity and H3K27ac modification across the 3′ end of the risk haplotype, with four tag-SNPs sharing allele-specific TF binding sites with promoter variants, which are eQTLs for IKZF1 in whole blood. At IKZF3, we refined a core risk haplotype of 101 kb (27 tag-SNPs) from an initial extended haplotype of 194 kb (282 tag-SNPs), which had widespread DNAse I hypersensitivity, H3K27ac modification and multiple allele-specific TF binding sites. Dimerization of Fox family TFs bound at the 3′ and promoter of IKZF3 may stabilize chromatin looping across the locus. Conclusions: We combined trans-ancestral exclusion mapping and epigenetic annotation to identify variants at both IKZF1 and IKZF3 with the highest likelihood of biological relevance. The approach will be of strong interest to other complex trait geneticists seeking to attribute biological relevance to risk alleles on extended risk haplotypes in their disease of interest.
Tissue Expression of Atrial and Ventricular Myosin Light Chains in the Mechanism of Adaptation to Oxidative Stress
Authors: Banaszkiewicz Marta , Krzywonos-Zawadzka Anna , Olejnik Agnieszka , Bil-Lula Iwona
Published: November 2020

Ischemia/reperfusion (I/R) injury induces post-translational modifications of myosin light chains (MLCs), increasing their susceptibility to degradation by matrix metalloproteinase 2 (MMP-2). This results in the degradation of ventricular light chains (VLC1) in heart ventricles. The aim of the study was to investigate changes in MLCs content in the mechanism of adaptation to oxidative stress during I/R. Rat hearts, perfused using the Langendorff method, were subjected to I/R. The control group was maintained in oxygen conditions. Lactate dehydrogenase (LDH) activity and reactive oxygen/nitrogen species (ROS/RNS) content were measured in coronary effluents. Atrial light chains (ALC1) and ventricular light chains (VLC1) gene expression were examined using RQ-PCR. ALC1 and VLC1 protein content were measured using ELISA tests. MMP-2 activity was assessed by zymography. LDH activity as well as ROS/RNS content in coronary effluents was higher in the I/R group (p = 0.01, p = 0.04, respectively), confirming heart injury due to increased oxidative stress. MMP-2 activity in heart homogenates was also higher in the I/R group (p = 0.04). ALC1 gene expression and protein synthesis were significantly increased in I/R ventricles (p < 0.01, 0.04, respectively). VLC1 content in coronary effluents was increased in the I/R group (p = 0.02), confirming the increased degradation of VLC1 by MMP-2 and probably an adaptive production of ALC1 during I/R. This mechanism of adaptation to oxidative stress led to improved heart mechanical function.
Human Microfibrillar-Associated Protein 4 (MFAP4) Gene Promoter: A TATA-Less Promoter That Is Regulated by Retinol and Coenzyme Q10 in Human Fibroblast Cells
Authors: Lin Ying-Ju , Chen An-Ni , Yin Xi Jiang , Li Chunxiang , Lin Chih-Chien
Published: November 2020

Elastic fibers are one of the major structural components of the extracellular matrix (ECM) in human connective tissues. Among these fibers, microfibrillar-associated protein 4 (MFAP4) is one of the most important microfibril-associated glycoproteins. MFAP4 has been found to bind with elastin microfibrils and interact directly with fibrillin-1, and then aid in elastic fiber formation. However, the regulations of the human MFAP4 gene are not so clear. Therefore, in this study, we firstly aimed to analyze and identify the promoter region of the human MFAP4 gene. The results indicate that the human MFAP4 promoter is a TATA-less promoter with tissue- and species-specific properties. Moreover, the promoter can be up-regulated by retinol and coenzyme Q10 (coQ10) in Detroit 551 cells.
The Function of Oncogene B-Cell Lymphoma 6 in the Regulation of the Migration and Invasion of Trophoblastic Cells
Authors: Ritter Andreas , Safdar Babek Khan , Jasmer Britta , Kreis Nina-Naomi , Friemel Alexandra , Roth Susanne , Solbach Christine , Louwen Frank , Yuan Juping
Published: November 2020

Human placentation is a highly invasive process. Deficiency in the invasiveness of trophoblasts is associated with a spectrum of gestational diseases, such as preeclampsia (PE). The oncogene B-cell lymphoma 6 (BCL6) is involved in the migration and invasion of various malignant cells. Intriguingly, its expression is deregulated in preeclamptic placentas. We have reported that BCL6 is required for the proliferation, survival, fusion, and syncytialization of trophoblasts. In the present work, we show that the inhibition of BCL6, either by its gene silencing or by using specific small molecule inhibitors, impairs the migration and invasion of trophoblastic cells, by reducing cell adhesion and compromising the dynamics of the actin cytoskeleton. Moreover, the suppression of BCL6 weakens the signals of the phosphorylated focal adhesion kinase, Akt/protein kinase B, and extracellular regulated kinase 1/2, accompanied by more stationary, but less migratory, cells. Interestingly, transcriptomic analyses reveal that a small interfering RNA-induced reduction of BCL6 decreases the levels of numerous genes, such as p21 activated kinase 1, myosin light chain kinase, and gamma actin related to cell adhesion, actin dynamics, and cell migration. These data suggest BCL6 as a crucial player in the migration and invasion of trophoblasts in the early stages of placental development through the regulation of various genes associated with the migratory machinery.
CDK5RAP3, a Novel Nucleoplasmic Shuttle, Deeply Regulates HSF1-Mediated Heat Stress Response and Protects Mammary Epithelial Cells from Heat Injury
Authors: Shen Yangyang , Zou Yan , Li Jun , Chen Fanghui , Li Honglin , Cai Yafei
Published: November 2020

CDK5RAP3 was regarded as the most significant regulator of cellular responses against heat stress, which is associated with dysfunctions of the immune system and animal susceptibility to disease. Despite this, little known about how CDK5RAP3 regulates heat stress response. In this study, CDK5RAP3 conditional Knockout (CKO) mice, CDK5RAP3-/- mouse embryo fibroblasts (MEFs) and bovine mammary epithelial cells (BMECs) were used as an in vitro and in vivo model, respectively to reveal the role of CDK5RAP3 in regulating the heat stress response. The deletion of CDK5RAP3 unexpectedly caused animal lethality after 1.5-h heat stimulations. Furthermore, BMECs were re-cultured for eight hours after heat stress and was found that the expression of CDK5RAP3 and HSPs showed a similar fluctuating pattern of increase (0–2, 4–6 h) and decrease (2–4, 6–8 h). In addition to the remarkably enhanced expression of heat shock protein, apoptosis rate and endoplasmic reticulum stress, the deletion of CDK5RAP3 also affected nucleoplasmic translocation and trimer formation of heat shock factor 1 (HSF1). These programs were further confirmed in the mammary gland of CDK5RAP3 CKO mice and CDK5RAP3-/- MEFs as well. Interestingly, genetic silencing of HSF1 downregulated CDK5RAP3 expression in BMECs. Immunostaining and immunoprecipitation studies suggested a physical interaction between CDK5RAP3 and HSF1 being co-localized in the cytoplasm and nucleus. Besides, CDK5RAP3 also interacted with HSP90, suggesting an operative machinery at both transcriptional level and protein functionality of HSP90 per se. Together, our findings suggested that CDK5RAP3 works like a novel nucleoplasmic shuttle or molecular chaperone, deeply participating in HSF1-mediated heat stress response and protecting cells from heat injury.
The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome
Authors: Ilaslan Erkut , Markosyan Renata , Sproll Patrick , Stevenson Brian J. , Sajek Malgorzata , Sajek Marcin P. , Hayrapetyan Hasmik , Sarkisian Tamara , Livshits Ludmila , Nef Serge , Jaruzelska Jadwiga , Kusz-Zamelczyk Kamila
Published: November 2020

Androgen insensitivity syndrome (AIS), manifesting incomplete virilization in 46,XY individuals, is caused mostly by androgen receptor (AR) gene mutations. Therefore, a search for AR mutations is a routine approach in AIS diagnosis. However, some AIS patients lack AR mutations, which complicates the diagnosis. Here, we describe a patient suffering from partial androgen insensitivity syndrome (PAIS) and lacking AR mutations. The whole exome sequencing of the patient and his family members identified a heterozygous FKBP4 gene mutation, c.956T>C (p.Leu319Pro), inherited from the mother. The gene encodes FKBP prolyl isomerase 4, a positive regulator of the AR signaling pathway. This is the first report describing a FKBP4 gene mutation in association with a human disorder of sexual development (DSD). Importantly, the dysfunction of a homologous gene was previously reported in mice, resulting in a phenotype corresponding to PAIS. Moreover, the Leu319Pro amino acid substitution occurred in a highly conserved position of the FKBP4 region, responsible for interaction with other proteins that are crucial for the AR functional heterocomplex formation and therefore the substitution is predicted to cause the disease. We proposed the FKBP4 gene as a candidate AIS gene and suggest screening that gene for the molecular diagnosis of AIS patients lacking AR gene mutations.
3D-Reconstructed Retinal Pigment Epithelial Cells Provide Insights into the Anatomy of the Outer Retina
Authors: Keeling Eloise , Chatelet David S. , Tan Nicole Y. T. , Khan Farihah , Richards Rhys , Thisainathan Thibana , Goggin Patricia , Page Anton , Tumbarello David A. , Lotery Andrew J. , Ratnayaka J. Arjuna
Published: November 2020

The retinal pigment epithelium (RPE) is located between the neuroretina and the choroid, and plays a critical role in vision. RPE cells internalise outer segments (OS) from overlying photoreceptors in the daily photoreceptor renewal. Changes to RPE structure are linked with age and retinopathy, which has been described in the past by conventional 2D electron microscopy. We used serial block face scanning electron microscopy (SBF-SEM) to reconstruct RPE cells from the central mouse retina. Three-dimensional-reconstructed OS revealed the RPE to support large numbers of photoreceptors (90–216 per RPE cell). Larger bi-nucleate RPE maintained more photoreceptors, although their cytoplasmic volume was comparable to smaller mono-nucleate RPE supporting fewer photoreceptors. Scrutiny of RPE microvilli and interdigitating OS revealed the angle and surface area of contact between RPE and photoreceptors. Bi-nucleate RPE contained more mitochondria compared to mono-nucleate RPE. Furthermore, bi-nucleate cells contained larger sub-RPE spaces, supporting a likely association with disease. Use of perfusion-fixed tissues ensured the highest possible standard of preservation, providing novel insights into the 3D RPE architecture and changes linked with retinopathy. This study serves as a benchmark for comparing retinal tissues from donor eyes with age-related macular degeneration (AMD) and other retinopathies.
AK-Score: Accurate Protein-Ligand Binding Affinity Prediction Using an Ensemble of 3D-Convolutional Neural Networks
Authors: Kwon Yongbeom , Shin Woong-Hee , Ko Junsu , Lee Juyong
Published: November 2020

Accurate prediction of the binding affinity of a protein-ligand complex is essential for efficient and successful rational drug design. Therefore, many binding affinity prediction methods have been developed. In recent years, since deep learning technology has become powerful, it is also implemented to predict affinity. In this work, a new neural network model that predicts the binding affinity of a protein-ligand complex structure is developed. Our model predicts the binding affinity of a complex using the ensemble of multiple independently trained networks that consist of multiple channels of 3-D convolutional neural network layers. Our model was trained using the 3772 protein-ligand complexes from the refined set of the PDBbind-2016 database and tested using the core set of 285 complexes. The benchmark results show that the Pearson correlation coefficient between the predicted binding affinities by our model and the experimental data is 0.827, which is higher than the state-of-the-art binding affinity prediction scoring functions. Additionally, our method ranks the relative binding affinities of possible multiple binders of a protein quite accurately, comparable to the other scoring functions. Last, we measured which structural information is critical for predicting binding affinity and found that the complementarity between the protein and ligand is most important.
Phytohormone Abscisic Acid Improves Memory Impairment and Reduces Neuroinflammation in 5xFAD Mice by Upregulation of LanC-Like Protein 2
Authors: Jeon Seung Ho , Kim Namkwon , Ju Yeon-Joo , Gee Min Sung , Lee Danbi , Lee Jong Kil
Published: November 2020

Alzheimer’s disease (AD), a type of dementia, is the most common neurodegenerative disease in the elderly. Neuroinflammation caused by deposition of amyloid β (Aβ) is one of the most important pathological causes in AD. The isoprenoid phytohormone abscisic acid (ABA) has recently been found in mammals and was shown to be an endogenous hormone, acting in stress conditions. Although ABA has been associated with anti-inflammatory effects and reduced cognitive impairment in several studies, the mechanisms of ABA in AD has not been ascertained clearly. To investigate the clearance of Aβ and anti-inflammatory effects of ABA, we used quantitative real-time polymerase chain reaction and immunoassay. ABA treatment inhibited Aβ deposition and neuroinflammation, thus resulting in improvement of memory impairment in 5xFAD mice. Interestingly, these effects were not associated with activation of peroxisome proliferator-activated receptor gamma, well known as a molecular target of ABA, but related with modulation of the LanC-like protein 2 (LANCL2), known as a receptor of ABA. Taken together, our results indicate that ABA reduced Aβ deposition, neuroinflammation, and memory impairment, which is the most characteristic pathology of AD, via the upregulation of LANCL2. These data suggest that ABA might be a candidate for therapeutics for AD treatment.
Terminal Phase Components of the Clotting Cascade in Patients with End-Stage Renal Disease Undergoing Hemodiafiltration or Hemodialysis Treatment
Authors: Pénzes Krisztina , Hurják Boglárka , Katona Éva , Becs Gergely , Balla József , Muszbek László
Published: November 2020

Hemostasis disorder in patients with end-stage renal disease (ESRD) is frequently associated with bleeding diathesis but it may also manifest in thrombotic complications. Analysis of individual coagulation and fibrinolytic factors may shed light on the background of this paradox situation. Here we explored components essential for fibrin formation/stabilization in ESRD patients being on maintenance hemodiafiltration (HDF) or hemodialysis (HD). Pre-dialysis fibrinogen, factor XIII (FXIII) antigen concentrations and FXIII activity were elevated, while α2-plasmin inhibitor (α2PI) activity decreased. The inflammatory status, as characterized by C-reactive protein (CRP) was a key determinant of fibrinogen concentration, but not of FXIII and α2PI levels. During a 4-h course of HDF or HD, fibrinogen concentration and FXIII levels gradually elevated. When compensated for the change in plasma water, i.e., normalized for plasma albumin concentration, only FXIII elevation remained significant. There was no difference between HDF and HD treatments. Individual HDF treatment did not influence α2PI activity, however after normalization it decreased significantly. HD treatment had a different effect, α2PI activities became elevated but the elevation disappeared after normalization. Elevated fibrinogen and FXIII levels in ESRD patients might contribute to the increased thrombosis risk, while decreased α2PI activity might be associated with elevated fibrinolytic potential.
Intracellular Ca2+-Mediated AE2 Is Involved in the Vectorial Movement of HaCaT Keratinocyte
Authors: Hwang Soyoung , Shin Dong Min , Hong Jeong Hee
Published: November 2020

Keratinocyte migration is initiated toward the wound skin barrier as a crucial process in wound healing. However, the migratory machinery used by keratinocytes is relatively unknown. Histamine signaling, including an increase in the Ca2+ signal, mediated the enhanced protein expression and chloride/bicarbonate exchange activity of anion exchanger AE2 in keratinocytes. In this study, we applied an agarose spot assay to induce a vectorial motion. The vectorial stimulation of the histamine-containing agarose spot enhanced the HaCaT keratinocyte migration, compared to non-directional stimulation. AE2 is associated with the vectorial movement of HaCaT keratinocytes. Enhanced expression of AE2 was mainly associated with an increase in Ca2+ and was abolished by the treatment with the Ca2+ chelating agent BAPTA-AM. These findings revealed that the directionality of Ca2+-exerted stimulation can play a prominent role in facilitating migration through the involvement of AE2 as a migratory machinery in HaCaT keratinocytes.
Complementary Transcriptome and Proteome Analyses Provide Insight into the Floral Transition in Bamboo (Dendrocalamus latiflorus Munro)
Authors: Wang Xiaoyan , Wang Yujiao , Yang Guoqian , Zhao Lei , Zhang Xuemei , Li Dezhu , Guo Zhenhua
Published: November 2020

Most woody bamboos bloom only once after long vegetative growth phases and die immediately afterwards. It is difficult, however, to determine the timing of the floral transition, as little information is available on the molecular mechanism of plant maturity in bamboos. To uncover the bamboo floral transition mechanism, its morpho-physiological characteristics, transcriptomes and large-scale quantitative proteomes were investigated in leaves which were collected at different stages during floral transition in a woody bamboo, Dendrocalamus latiflorus. We identified many flowering time-associated genes and the continued increase and decrease genes were screened as flowering biomarker genes (e.g., the MADS14 and bHLH13 genes). These different genes were assigned to specific metabolic pathways by the Kyoto Encyclopedia of Genes and Genomes (KEGG). And the photoperiod pathways depending on the circadian rhythm may play an essential role in the bamboo floral transition. In addition, a total of 721 differently expressed proteins of leaves from the vegetative-to-reproductive stages were identified. Fifty-five genes were specifically differentially expressed at both the transcriptomic and proteomic levels, including genes related to photosynthesis and nucleotide sugar, which may be involved in the floral transition. This work provides insights into bamboo flowers and the management of forest breeding.
Eicosanoids in Skin Wound Healing
Authors: Yasukawa Ken , Okuno Toshiaki , Yokomizo Takehiko
Published: November 2020

Wound healing is an important process in the human body to protect against external threats. A dysregulation at any stage of the wound healing process may result in the development of various intractable ulcers or excessive scar formation. Numerous factors such as growth factors, cytokines, and chemokines are involved in this process and play vital roles in tissue repair. Moreover, recent studies have demonstrated that lipid mediators derived from membrane fatty acids are also involved in the process of wound healing. Among these lipid mediators, we focus on eicosanoids such as prostaglandins, thromboxane, leukotrienes, and specialized pro-resolving mediators, which are produced during wound healing processes and play versatile roles in the process. This review article highlights the roles of eicosanoids on skin wound healing, especially focusing on the biosynthetic pathways and biological functions, i.e., inflammation, proliferation, migration, angiogenesis, remodeling, and scarring.
Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa
Authors: Del Duca Ester , Morelli Paola , Bennardo Luigi , Di Raimondo Cosimo , Nisticò Steven Paul
Published: November 2020

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting areas with a high density of apocrine glands and characterized by subcutaneous nodules that may evolve into fistulas with pus secretion. Methods: The aim of this review is to investigate all current knowledge on cytokine regulation in the pathogenesis of HS. A systematic literature research using the words “cytokine”, “interleukin”, “pathway”, and “hidradenitis suppurativa” was performed in PubMed/Medline and Scopus/Embase databases. A search of the clinicaltrials.gov website for interventional recruiting and completed trials including the term “hidradenitis suppurativa” was also performed up to August 2020. We will discuss the pathogenetic role of various cytokines in HS and potential therapeutic targets for this debilitating disease. Results: The pathophysiology underlying this complex condition has not been clearly defined. An upregulation of various cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, IL-17, IL-23, and other molecules seems to be related to this inflammatory condition. Various cells, such as lymphocytes T Helper 1 and 17 and keratinocytes seem to be involved in the genesis of this condition. Conclusions: Several future studies and clinical trials are necessary in order to have new knowledge about HS and to properly treat this complex condition.
Toxoplasma gondii GRA9 Regulates the Activation of NLRP3 Inflammasome to Exert Anti-Septic Effects in Mice
Authors: Kim Jae-Sung , Mun Seok-Jun , Cho Euni , Kim Donggyu , Son Wooic , Jeon Hye-In , Kim Hyo Keun , Jang Kiseok , Yang Chul-Su
Published: November 2020

Dense granule proteins (GRAs) are essential components in Toxoplasma gondii, which are suggested to be promising serodiagnostic markers in toxoplasmosis. In this study, we investigated the function of GRA9 in host response and the associated regulatory mechanism, which were unknown. We found that GRA9 interacts with NLR family pyrin domain containing 3 (NLRP3) involved in inflammation by forming the NLRP3 inflammasome. The C-terminal of GRA9 (GRA9C) is essential for GRA9–NLRP3 interaction by disrupting the NLRP3 inflammasome through blocking the binding of apoptotic speck-containing (ASC)-NLRP3. Notably, Q200 of GRA9C is essential for the interaction of NLRP3 and blocking the conjugation of ASC. Recombinant GRA9C (rGRA9C) showed an anti-inflammatory effect and the elimination of bacteria by converting M1 to M2 macrophages. In vivo, rGRA9C increased the anti-inflammatory and bactericidal effects and subsequent anti-septic activity in CLP- and E. coli- or P. aeruginosa-induced sepsis model mice by increasing M2 polarization. Taken together, our findings defined a role of T. gondii GRA9 associated with NLRP3 in host macrophages, suggesting its potential as a new candidate therapeutic agent for sepsis.
Aux/IAA14 Regulates microRNA-Mediated Cold Stress Response in Arabidopsis Roots
Authors: Aslam Mohammad , Sugita Kenji , Qin Yuan , Rahman Abidur
Published: November 2020

The phytohormone auxin and microRNA-mediated regulation of gene expressions are key regulators of plant growth and development at both optimal and under low-temperature stress conditions. However, the mechanistic link between microRNA and auxin in regulating plant cold stress response remains elusive. To better understand the role of microRNA (miR) in the crosstalk between auxin and cold stress responses, we took advantage of the mutants of Arabidopsis thaliana with altered response to auxin transport and signal. Screening of the mutants for root growth recovery after cold stress at 4 °C revealed that the auxin signaling mutant, solitary root 1 (slr1; mutation in Aux/IAA14), shows a hypersensitive response to cold stress. Genome-wide expression analysis of miRs in the wild-type and slr1 mutant roots using next-generation sequencing revealed 180 known and 71 novel cold-responsive microRNAs. Cold stress also increased the abundance of 26–31 nt small RNA population in slr1 compared with wild type. Comparative analysis of microRNA expression shows significant differential expression of 13 known and 7 novel miRs in slr1 at 4 °C compared with wild type. Target gene expression analysis of the members from one potential candidate miR, miR169, revealed the possible involvement of miR169/NF-YA module in the Aux/IAA14-mediated cold stress response. Taken together, these results indicate that SLR/IAA14, a transcriptional repressor of auxin signaling, plays a crucial role in integrating miRs in auxin and cold responses.
A Cross between Bread Wheat and a 2D(2R) Disomic Substitution Triticale Line Leads to the Formation of a Novel Disomic Addition Line and Provides Information of the Role of Rye Secalins on Breadmaking Characteristics
Authors: Sestili Francesco , Margiotta Benedetta , Vaccino Patrizia , Moscaritolo Salvatore , Giorgi Debora , Lucretti Sergio , Palombieri Samuela , Masci Stefania , Lafiandra Domenico
Published: November 2020

A bread wheat line (N11) and a disomic 2D(2R) substitution triticale line were crossed and backrossed four times. At each step electrophoretic selection for the seeds that possessed, simultaneously, the complete set of high molecular weight glutenin subunits of N11 and the two high molecular weight secalins of rye, present in the 2D(2R) line, was carried out. Molecular cytogenetic analyses of the BC4F8 generation revealed that the selection carried out produced a disomic addition line (2n = 44). The pair of additional chromosomes consisted of the long arm of chromosome 1R (1RL) from rye fused with the satellite body of the wheat chromosome 6B. Rheological analyses revealed that the dough obtained by the new addition line had higher quality characteristics when compared with the two parents. The role of the two additional high molecular weight secalins, present in the disomic addition line, in influencing improved dough characteristics is discussed.
Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor
Authors: Martínez-Cuesta María Ángeles , Blanch-Ruiz María Amparo , Ortega-Luna Raquel , Sánchez-López Ainhoa , Álvarez Ángeles
Published: November 2020

The P2X7 receptor (P2X7R) possesses a unique structure associated to an as yet not fully understood mechanism of action that facilitates cell permeability to large ionic molecules through the receptor itself and/or nearby membrane proteins. High extracellular adenosine triphosphate (ATP) levels—inexistent in physiological conditions—are required for the receptor to be triggered and contribute to its role in cell damage signaling. The inconsistent data on its activation pathways and the few studies performed in natively expressed human P2X7R have led us to review the structure, activation pathways, and specific cellular location of P2X7R in order to analyze its biological relevance. The ATP-gated P2X7R is a homo-trimeric receptor channel that is occasionally hetero-trimeric and highly polymorphic, with at least nine human splice variants. It is localized predominantly in the cellular membrane and has a characteristic plasticity due to an extended C-termini, which confers it the capacity of interacting with membrane structural compounds and/or intracellular signaling messengers to mediate flexible transduction pathways. Diverse drugs and a few endogenous molecules have been highlighted as extracellular allosteric modulators of P2X7R. Therefore, studies in human cells that constitutively express P2X7R need to investigate the precise endogenous mediator located nearby the activation/modulation domains of the receptor. Such research could help us understand the possible physiological ATP-mediated P2X7R homeostasis signaling.
A Method of Ultra-Large-Scale Matrix Inversion Using Block Recursion
Authors: Wang HouZhen , Guo Yan , Zhang HuanGuo
Published: November 2020

Ultra-large-scale matrix inversion has been applied as the fundamental operation of numerous domains, owing to the growth of big data and matrix applications. Using cryptography as an example, the solution of ultra-large-scale linear equations over finite fields is important in many cryptanalysis schemes. However, inverting matrices of extremely high order, such as in millions, is challenging; nonetheless, the need has become increasingly urgent. Hence, we propose a parallel distributed block recursive computing method that can process matrices at a significantly increased scale, based on Strassen’s method; furthermore, we describe the related well-designed algorithm herein. Additionally, the experimental results based on comparison show the efficiency and the superiority of our method. Using our method, up to 140,000 dimensions can be processed in a supercomputing center.
Effects of Urbanization on Plant–Pollinator Interactions in the Tropics: An Experimental Approach Using Exotic Plants
Authors: Zakardjian Marie , Geslin Benoît , Mitran Valentin , Franquet Evelyne , Jourdan Hervé
Published: November 2020

Land-use changes through urbanization and biological invasions both threaten plant-pollinator networks. Urban areas host modified bee communities and are characterized by high proportions of exotic plants. Exotic species, either animals or plants, may compete with native species and disrupt plant–pollinator interactions. These threats are heightened in insular systems of the Southwest Pacific, where the bee fauna is generally poor and ecological networks are simplified. However, the impacts of these factors have seldom been studied in tropical contexts. To explore those questions, we installed experimental exotic plant communities in urban and natural contexts in New Caledonia, a plant diversity hotspot. For four weeks, we observed plant–pollinator interactions between local pollinators and our experimental exotic plant communities. We found a significantly higher foraging activity of exotic wild bees within the city, together with a strong plant–pollinator association between two exotic species. However, contrary to our expectations, the landscape context (urban vs. natural) had no effect on the activity of native bees. These results raise issues concerning how species introduced in plant–pollinator networks will impact the reproductive success of both native and exotic plants. Furthermore, the urban system could act as a springboard for alien species to disperse in natural systems and even invade them, leading to conservation concerns.
Trade-off Investment between Tonic Immobility and Mate Search in the Sweetpotato Weevil, Cylas formicarius (Coleoptera: Brentidae)
Authors: Ouyang Haoyong , Wu Pengxiang , Zhang Runzhi , Haseeb Muhammad
Published: November 2020

Tonic immobility (TI) is a well-known anti-predator strategy adopted by diverse preys. Numerous studies on the cost–benefit involve in TI have been reported. Although, some studies have reported the effect of mating behavior on TI, few studies highlight the phases of mate search. In the present study, we investigated the relationship between mate search and TI behavior in the sweetpotato weevil (SPW), Cylas formicarius (Coleoptera: Brentidae). First, we found the most active mate search period of male SPW within 24 h. Then, we measured whether the duration of TI of virgin male and female were affected during the mate search. In the end, the Y-tube olfactometer was used to compare the duration of mate search and the proportion of orientation towards the females in two artificial selection groups of the male SPW with longer and shorter duration of TI. Our study confirmed that male mate searching increase after 3 h at night, and up to 73% at midnight, TI was affected by mate search in male, because the duration of TI of the male during mate search (Mean ± SE = 214.53 ± 22.74 s) was significantly shorter duration than the control (679.64 ± 69.77 s). However, mate search did not affect the strength of TI in the females tested. This study determined that mate search was affected by TI due to males from the group with shorter duration of TI who had 28% higher proportion of orientation towards the females than the males with longer duration of TI. Investment trade-off between TI and mate search was confirmed in the males of the SPW.
Deciphering Novel Antimicrobial Peptides from the Transcriptome of Papilio xuthus
Authors: Lee Joon Ha , Chung Hoyong , Shin Yong Pyo , Kim Mi-Ae , Natarajan Sathishkumar , Veerappan Karpagam , Kim Seong Hyun , Park Junhyung , Hwang Jae Sam
Published: November 2020

An insect’s innate immune system is the front line of defense against many invading microorganisms. One of the important components of this defense system is antimicrobial peptides (AMPs). Papiliocin is a well-studied antimicrobial peptide (AMP) isolated from the swallowtail butterfly, Papilio xuthus, and it was previously reported to be effective against Gram-positive bacteria, Gram-negative bacteria, and fungi, particularly in drug resistant Gram-negative bacteria. Hence, we aimed to identify novel AMPs from Papilio xuthus using its transcriptome. We immunized the swallowtail butterfly with Escherichia coli, Staphylococcus aureus, Candida albicans, and the total RNA was isolated. De novo transcriptome assembly and functional annotations were conducted, and AMPs were predicted using an in-silico pipeline. The obtained 344,804,442 raw reads were then pre-processed to retrieve 312,509,806 (90.6%) total clean reads. A total of 38,272 unigenes were assembled with the average length of 1010 bp. Differential gene expression analysis identified 584 and 1409 upregulated and downregulated genes, respectively. The physicochemical, aggregation, and allergen propensity were used as filtration criteria. A total of 248 peptides were predicted using our in-house pipeline and the known AMPs were removed, resulting in 193 novel peptides. Finally, seven peptides were tested in vitro and three peptides (Px 5, 6, and 7) showed stronger antimicrobial activity against Gram-negative bacteria and yeast. All the tested peptides were non-allergens. The identified novel AMPs may serve as potential candidates for future antimicrobial studies.
Changes in Shape, Texture and Airflow Improve Efficiency of Monitoring Traps for Tribolium castaneum (Coleoptera: Tenebrionidae)
Authors: Sajeewani Panamulla A. H. , Dissanayaka Dissanayaka M. S. K. , Wijayaratne Leanage K. W. , Burks Charles S.
Published: November 2020

The red flour beetle, Tribolium castaneum, is an important pest of stored products. We compared an existing standard commercial trap with five experimental trap designs differing from the status quo in shape, surface texture, and in forced air capability provided by fans. We tested the five new traps and a commercial trap with T. castaneum adults with the presence/absence of air flow and the availability of either the pheromone only or both the pheromone and kairomone. Without using the fans and baited with pheromone only, these new trap designs capture beetles three to five times as efficiently as the status quo trap. Use of both pheromone and kairomone doubled the capture efficiency of the status quo trap but did not significantly affect the capture efficiency of the new trap designs, all of which captured significantly more effectively than the status quo trap. Turning on fans for forced ventilation significantly improved trap efficiency of the more effective of the newer traps compared to monitoring with both pheromone and kairomone but no fan. This study provides new insights into factors affecting trap efficiency for monitoring of T. castaneum in grain storage facilities, and suggests ways in which existing traps might be improved.