bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Foreign Direct Investment on Environmental Pollution in China: Corruption Matters
Authors: Wang Shi , Wang Hua , Sun Qian
Published: September 2020

This research investigates the interaction effect between corruption and foreign direct investment (FDI) on environmental pollution by applying the spatial econometric model to the panel data of China’s 29 provinces from 1994 to 2015 and analyzes the differences between China’s eastern, central and western regions. Results show that (a) FDI inflow deteriorates the environmental quality, validating the pollution haven hypothesis (PHH); (b) by weakening the environmental standards, corruption enables the inflow of low-quality FDI, weakens the spillover effect of FDI and indirectly causes further environmental pollution; (c) the interaction effect between corruption and FDI on environmental pollution is less significant in the eastern region than in the central and western regions.
Effect of Passive Stretching of Respiratory Muscles on Chest Expansion and 6-Minute Walk Distance in COPD Patients
Authors: Rehman Asma , Ganai Jyoti , Aggarwal Rajeev , Alghadir Ahmad H. , Iqbal Zaheen A.
Published: September 2020

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Hyperinflation of the lungs leads to a remodeling of the inspiratory muscles that causes postural deformities and more labored breathing. Postural changes include elevated, protracted, or abducted scapulae with medially rotated humerus, and kyphosis that leads to further tightening of respiratory muscles. As the severity of the disease progresses, use of the upper limbs for functional tasks becomes difficult due to muscle stiffness. There are various studies that suggest different rehabilitation programs for COPD patients; however, to the best of our knowledge none recommends passive stretching techniques. The aim of this study was to assess the effect of respiratory muscle passive stretching on chest expansion and 6-min walk distance (6MWD) in patients with moderate to severe COPD. Methods: Thirty patients were divided into two groups, experimental (n = 15) and control (n = 15). The experimental group received a hot pack followed by stretching of the respiratory muscles and relaxed passive movements of the shoulder joints. The control group received a hot pack followed by relaxed passive movements of the shoulder joints. Results: In the control group, there was no difference in chest expansion at the levels of both the axilla and the xiphisternum or in 6MWD between baseline and post treatment (p > 0.05). In the experimental group, chest expansion at the level of the axilla (p < 0.05) and 6MWD (p < 0.001) were significantly higher post treatment, while there was no difference in chest expansion at the level of the xiphisternum (p > 0.05). A comparison between control and experimental groups showed that chest expansion at the level of the axilla (p < 0.05) and 6MWD (p < 0.01) were significantly higher in the experimental group, while there was no difference in chest expansion at the level of the xiphisternum (p > 0.05). Conclusions: Although COPD is an irreversible disease, results of this study indicate that passive stretching of respiratory muscles can clinically improve the condition of such patients, especially in terms of chest expansion and 6MWD. Given the good effects of muscle stretching and the fact that such an exercise is harmless, clinicians and physiotherapists should consider including passive stretching of respiratory muscles in the rehabilitation plan of COPD patients.
A Design Strategy for Energy-Efficient Rural Houses in Severe Cold Regions
Authors: Pan Wente , Mei Hongyuan
Published: September 2020

In the past decade, Chinese urban areas have seen rapid development, and rural areas are becoming the next construction hotspot. The development of rural buildings in China has lagged behind urban development, and there is a lack of energy-efficient rural buildings. Rural houses in severe cold regions have the characteristics of large energy exchange, a long heating cycle, and low construction costs. Energy consumption is a crucial issue for rural houses in severe cold regions. How to balance the energy efficiency and building cost become a crucial problem. To solve this problem, we investigate the energy consumption of rural housing in cold regions, using Longquan Village in Heilongjiang Province, northeast China, as a case study. A low-energy design framework is established that considers the spatial layout, building type, enclosure system, and heating system. With the support of project funds, a demonstration house is constructed, and the energy savings performance of the building is investigated during the heating period. The results indicate that the energy savings rate of the demonstration house is 66%. The demonstration building enables local residents to learn construction methods for low-energy houses and promotes energy efficiency.
Erratum: Murrell, A., et al. Measuring Food Insecurity Using the Food Abundance Index: Implications for Economic, Health and Social Well-Being. Int. J. Environ. Res. Public Health 2020, 17, 2434
Authors: Murrell Audrey , Jones Ray
Published: September 2020

Since no human subjects were included in this research review [...]
Transcultural Differences in Risk Factors and in Triggering Reasons of Suicidal and Self-Harming Behaviour in Young People with and without a Migration Background
Authors: Özlü-Erkilic Zeliha , Wenzel Thomas , Kothgassner Oswald D. , Akkaya-Kalayci Türkan
Published: September 2020

Minors with and without migration background can have different risk factors and triggering reasons for self-harming and suicidal behaviour. We retrospectively analysed the data of 192 children and adolescents to investigate the transcultural differences in self-harming, as well as suicidal behaviour in Austrian, Turkish, and Bosnian/Croatian/Serbian (BCS)-speaking patients, who were treated in an emergency out-patient clinic in Vienna. Our results showed transcultural differences in both behaviours. In all groups, females had higher rates of suicide attempts and self-harming behaviour than males. While Turkish-speaking patients received treatment more often, after attempted suicide, Austrians and BCS-speaking patients needed treatment more often for acute stress disorder. Suicide attempts and self-harming behaviours were triggered most frequently by intrafamilial problems, but more frequently in migrant patients. Turkish-speaking patients were at a more than 2 times (OR = 2.21, 95%CI: 1.408–3.477) higher risk for suicide attempts, and were triggered almost 3 times (OR = 2.94, 95%CI: 1.632–5.304) more often by interfamilial conflicts. The suicide attempts of BCS-speaking minors were more often caused by relationship and separation crises (OR = 2.56, 95%CI: 1.148–5.705). These transcultural differences in suicidal and self-harming behaviour of minors, demand an increase of transcultural competence to provide optimal treatment of migrant children.
The Contribution of Avoidable Mortality to the Life Expectancy Gains in Korea between 1998 and 2017
Authors: Bahk Jinwook , Jung-Choi Kyunghee
Published: September 2020

This study evaluated the contribution of avoidable causes of death to gains in life expectancy between 1998 and 2017 in Korea. This is a multi-year, cross-sectional study using national data. Death certificate data from 1998 to 2017 were obtained from Statistics Korea. The difference in life expectancy between 1998 and 2017 by age and cause of death were decomposed using Arriaga’s method. Life expectancy rose 7.73 years over 20 years in Korea, which was largely (more than 50%) due to changes in avoidable causes of death. As age increased, the contribution to changes in life expectancy increased, and the gain in life expectancy due to avoidable causes also tended to increase. The major factors that drove that gain in life expectancy were avoidable causes such as cerebrovascular diseases and traffic accidents. The gain in life expectancy from preventable diseases was greater in men than in women. The results of this study indicate that active public health programs have been effective in improving life expectancy in Korea. Moreover, avoidable mortality could be further improved with good public health policy. Health policy aimed at reducing amenable and preventable deaths should be further implemented to promote population health.
Dating Apps and Their Sociodemographic and Psychosocial Correlates: A Systematic Review
Authors: Castro Ángel , Barrada Juan Ramón
Published: September 2020

The emergence and popularization of dating apps have changed the way people meet and interact with potential romantic and sexual partners. In parallel with the increased use of these applications, a remarkable scientific literature has developed. However, due to the recency of the phenomenon, some gaps in the existing research can be expected. Therefore, the objective of this study was to conduct a systematic review of the empirical research of the psychosocial content published in the last five years (2016–2020) on dating apps. A search was conducted in different databases, and we identified 502 articles in our initial search. After screening titles and abstracts and examining articles in detail, 70 studies were included in the review. The most relevant data (author/s and year, sample size and characteristics, methodology) and their findings were extracted from each study and grouped into four blocks: user dating apps characteristics, usage characteristics, motives for use, and benefits and risks of use. The limitations of the literature consulted are discussed, as well as the practical implications of the results obtained, highlighting the relevance of dating apps, which have become a tool widely used by millions of people around the world.
The Shifting Risk of Homelessness among Persons with a Disability: Insights from a National Policy Intervention
Authors: Beer Andrew , Daniel Lyrian , Baker Emma , Lester Laurence
Published: September 2020

Persons with a disability are at a far higher risk of homelessness than those without. The economic, social and health challenges faced by disabled people are addressed, in Australia, by the recently implemented National Disability Insurance Scheme (NDIS). Using nationally representative, longitudinal household panel data, we construct the Index of Relative Homelessness Risk (IRHR) to track how the risk of homelessness for disabled persons has changed since the introduction of the NDIS. We find that, overall, fewer persons with a disability face moderate risk of homelessness but that many more face high risk. We conclude that the NDIS has not effectively protected disabled people from the risk of homelessness. We reflect on the implications of these findings for policy interventions.
XGBoost-Based Framework for Smoking-Induced Noncommunicable Disease Prediction
Authors: Davagdorj Khishigsuren , Pham Van Huy , Theera-Umpon Nipon , Ryu Keun Ho
Published: September 2020

Smoking-induced noncommunicable diseases (SiNCDs) have become a significant threat to public health and cause of death globally. In the last decade, numerous studies have been proposed using artificial intelligence techniques to predict the risk of developing SiNCDs. However, determining the most significant features and developing interpretable models are rather challenging in such systems. In this study, we propose an efficient extreme gradient boosting (XGBoost) based framework incorporated with the hybrid feature selection (HFS) method for SiNCDs prediction among the general population in South Korea and the United States. Initially, HFS is performed in three stages: (I) significant features are selected by t-test and chi-square test; (II) multicollinearity analysis serves to obtain dissimilar features; (III) final selection of best representative features is done based on least absolute shrinkage and selection operator (LASSO). Then, selected features are fed into the XGBoost predictive model. The experimental results show that our proposed model outperforms several existing baseline models. In addition, the proposed model also provides important features in order to enhance the interpretability of the SiNCDs prediction model. Consequently, the XGBoost based framework is expected to contribute for early diagnosis and prevention of the SiNCDs in public health concerns.
Episodic Ataxias: Faux or Real?
Authors: Giunti Paola , Mantuano Elide , Frontali Marina
Published: September 2020

The term Episodic Ataxias (EA) was originally used for a few autosomal dominant diseases, characterized by attacks of cerebellar dysfunction of variable duration and frequency, often accompanied by other ictal and interictal signs. The original group subsequently grew to include other very rare EAs, frequently reported in single families, for some of which no responsible gene was found. The clinical spectrum of these diseases has been enormously amplified over time. In addition, episodes of ataxia have been described as phenotypic variants in the context of several different disorders. The whole group is somewhat confused, since a strong evidence linking the mutation to a given phenotype has not always been established. In this review we will collect and examine all instances of ataxia episodes reported so far, emphasizing those for which the pathophysiology and the clinical spectrum is best defined.
Extracellular Vesicles: New Endogenous Shuttles for miRNAs in Cancer Diagnosis and Therapy?
Authors: Martellucci Stefano , Orefice Nicola Salvatore , Angelucci Adriano , Luce Amalia , Caraglia Michele , Zappavigna Silvia
Published: September 2020

Extracellular Vesicles (EVs) represent a heterogeneous population of membranous cell-derived structures, including cargo-oriented exosomes and microvesicles. EVs are functionally associated with intercellular communication and play an essential role in multiple physiopathological conditions. Shedding of EVs is frequently increased in malignancies and their content, including proteins and nucleic acids, altered during carcinogenesis and cancer progression. EVs-mediated intercellular communication between tumor cells and between tumor and stromal cells can modulate, through cargo miRNA, the survival, progression, and drug resistance in cancer conditions. These consolidated suggestions and EVs’ stability in bodily fluids have led to extensive investigations on the potential employment of circulating EVs-derived miRNAs as tumor biomarkers and potential therapeutic vehicles. In this review, we highlight the current knowledge about circulating EVs-miRNAs in human cancer and the application limits of these tools, discussing their clinical utility and challenges in functions such as in biomarkers and instruments for diagnosis, prognosis, and therapy.
Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma
Authors: Ferreira Mendes Jéssica Mariane , de Faro Valverde Ludmila , Torres Andion Vidal Manuela , Paredes Bruno Diaz , Coelho Paulo , Allahdadi Kyan James , Coletta Ricardo Della , Souza Bruno Solano de Freitas , Rocha Clarissa Araújo Gurgel
Published: September 2020

(1) Background: Activation of the PI3K-AKT pathway controls most hallmarks of cancer, and the hedgehog (HH) pathway has been associated with oral squamous cell carcinoma (OSCC) development and progression. We hypothesized that fibroblast-derived insulin-like growth factor-1 (IGF-1) acts in oral squamous cell carcinoma (OSCC) cells, leading to the non-canonical activation of the HH pathway, maintaining AKT activity and promoting tumor aggressiveness. (2) Methods: Primary fibroblasts (MF1) were genetically engineered for IGF-1 overexpression (MF1-IGF1) and CRISPR/Cas9-mediated IGF1R silencing was performed in SCC-4 cells. SCC-4 cells were co-cultured with fibroblasts or incubated with fibroblast conditioned medium (CM) or rIGF-1 for functional assays and the evaluation of AKT and HH pathways. (3) Results: Gene expression analysis confirmed IGF-1 overexpression in MF1-IGF1 and the absence of IGF-1 expression in SCC-4, while elevated IGF1R expression was detected. IGF1R silencing was associated with decreased survival of SCC-4 cells. Ihh was expressed in both MF1 and MF1-IGF1, and increased levels of GLI1 mRNA were observed in SCC-4 after stimulation with CM-MF1. Activation of both PI3K-AKT and the HH pathway (GLI1, Ihh and SMO) were identified in SCC-4 cells cultured in the presence of MF1-IGF1-CM. rIGF-1 promoted tumor cell proliferation, migration, invasion and tumorsphere formation, whereas CM-MF1 significantly stimulated angiogenesis. (4) Conclusions: IGF-1 exerts pro-tumorigenic effects by stimulating SCC-4 cell proliferation, migration, invasion and stemness. AKT and HH pathways were activated by IGF-1 in SCC-4, reinforcing its influence on the regulation of these signaling pathways.
The Role of Epac in Cancer Progression
Authors: Wehbe Nadine , Slika Hasan , Mesmar Joelle , Nasser Suzanne A. , Pintus Gianfranco , Baydoun Serine , Badran Adnan , Kobeissy Firas , Eid Ali H. , Baydoun Elias
Published: September 2020

Cancer continues to be a prime contributor to global mortality. Despite tremendous research efforts and major advances in cancer therapy, much remains to be learned about the underlying molecular mechanisms of this debilitating disease. A better understanding of the key signaling events driving the malignant phenotype of cancer cells may help identify new pharmaco-targets. Cyclic adenosine 3′,5′-monophosphate (cAMP) modulates a plethora of biological processes, including those that are characteristic of malignant cells. Over the years, most cAMP-mediated actions were attributed to the activity of its effector protein kinase A (PKA). However, studies have revealed an important role for the exchange protein activated by cAMP (Epac) as another effector mediating the actions of cAMP. In cancer, Epac appears to have a dual role in regulating cellular processes that are essential for carcinogenesis. In addition, the development of Epac modulators offered new routes to further explore the role of this cAMP effector and its downstream pathways in cancer. In this review, the potentials of Epac as an attractive target in the fight against cancer are depicted. Additionally, the role of Epac in cancer progression, namely its effect on cancer cell proliferation, migration/metastasis, and apoptosis, with the possible interaction of reactive oxygen species (ROS) in these phenomena, is discussed with emphasis on the underlying mechanisms and pathways.
The Role of Losartan as a Potential Neuroregenerative Pharmacological Agent after Aneurysmal Subarachnoid Haemorrhage
Authors: Wanderer Stefan , Andereggen Lukas , Mrosek Jan , Kashefiolasl Sepide , Marbacher Serge , Konczalla Jürgen
Published: September 2020

Background: Cerebral vasospasm (CVS) remains a major cause of delayed cerebral ischaemia following aneurysmal subarachnoid haemorrhage (SAH), making it a life-threatening type of stroke with high morbidity and mortality. Endothelin-1 is known as key player mediating a strong vasocontractile effect. Interestingly, losartan restores the impaired vasorelaxative ET(B1) receptor function in a non-competitive direct fashion. With this study, we aimed to investigate a potential losartan-dependent vasodilatory effect vice versa by inhibiting NO release through L-NAME, thus pushing forward concepts to alleviate vasospasm and possibly prevent ischaemia and neurodegeneration. Methods: Cerebral vasospasm was induced by the use of an established double-injection rat model. Sprague-Dawley rats were culled on Day 3 after the ictus, and the vasospastic basilar artery was harvested for isometric investigations of the vessel tone. Ring segments were preincubated with and without L-NAME and/or losartan. Results: Preincubation with L-NAME induced dose-dependent vasoconstriction via endothelin-1 in the non-SAH cohort, which was dose-dependently reduced by losartan. After SAH and dose-dependent endothelin-1 administration, maximal contraction was achieved in the control group without losartan. Furthermore, this maximal contraction was significantly decreased in the losartan group and was reversed by L-NAME. Conclusions: After SAH, losartan was shown to positively influence the ET(B1) receptor pathway in a non-competitive direct agonistic and indirect fashion. Losartan alleviated the maximum contraction triggered by endothelin-1. This effect was resolved due to NO inhibition by L-NAME. Considering this spasmolytic effect of losartan besides its already well-known effects (attenuating cerebral inflammation, restoring cerebral autoregulation and reducing epileptogenic activity) and alleviating early brain injury, losartan seems to have potential as a promising pharmacological agent after SAH.
The Transcription Factor TCF1 in T Cell Differentiation and Aging
Authors: Kim Chulwoo , Jin Jun , Weyand Cornelia M. , Goronzy Jörg J.
Published: September 2020

The transcription factor T cell factor 1 (TCF1), a pioneer transcription factor as well as a downstream effector of WNT/β-catenin signaling, is indispensable for T cell development in the thymus. Recent studies have highlighted the additional critical role of TCF1 in peripheral T cell responses to acute and chronic infections as well as cancer. Here, we review the regulatory functions of TCF1 in the differentiation of T follicular helper cells, memory T cells and recently described stem-like exhausted T cells, where TCF1 promotes less differentiated stem-like cell states by controlling common gene-regulatory networks. These studies also provide insights into the mechanisms of defective T cell responses in older individuals. We discuss alterations in TCF1 expression and related regulatory networks with age and their consequences for T cell responses to infections and vaccination. The increasing understanding of the pathways regulating TCF1 expression and function in aged T cells holds the promise of enabling the design of therapeutic interventions aiming at improving T cell responses in older individuals.
Insight into Molecular Mechanism for Activin A-Induced Bone Morphogenetic Protein Signaling
Authors: Xie Chen , Jiang Wenjuan , Lacroix Jerome J. , Luo Yun , Hao Jijun
Published: September 2020

Activins transduce the TGF-β pathway through a heteromeric signaling complex consisting of type I and type II receptors, and activins also inhibit bone morphogenetic protein (BMP) signaling mediated by type I receptor ALK2. Recent studies indicated that activin A cross-activates the BMP pathway through ALK2R206H, a mutation associated with Fibrodysplasia Ossificans Progressiva (FOP). How activin A inhibits ALK2WT-mediated BMP signaling but activates ALK2R206H-mediated BMP signaling is not well understood, and here we offer some insights into its molecular mechanism. We first demonstrated that among four BMP type I receptors, ALK2 is the only subtype able to mediate the activin A-induced BMP signaling upon the dissociation of FKBP12. We further showed that BMP4 does not cross-signal TGF-β pathway upon FKBP12 inhibition. In addition, although the roles of type II receptors in the ligand-independent BMP signaling activated by FOP-associated mutant ALK2 have been reported, their roles in activin A-induced BMP signaling remains unclear. We demonstrated in this study that the known type II BMP receptors contribute to activin A-induced BMP signaling through their kinase activity. Together, the current study provided important mechanistic insights at the molecular level into further understanding physiological and pathophysiological BMP signaling.
MiR-581/SMAD7 Axis Contributes to Colorectal Cancer Metastasis: A Bioinformatic and Experimental Validation-Based Study
Authors: Zhao Xiaojuan , Liu Shuzhen , Yan Bianbian , Yang Jin , Chen Erfei
Published: September 2020

Metastasis is a well-known poor prognostic factor and primary cause of mortality in patients with colorectal cancer (CRC). Recently, with the progress of high through-put sequencing, aberrantly expressed non-coding RNAs (ncRNAs) were found to participate in the initiation and development of cancer. However, the mechanisms of ncRNA-mediated regulation of metastasis in CRC remain largely unknown. In this study, we systematically analyzed the expression network of microRNAs (miRNAs) and genes in CRC metastasis using bioinformatics, and discovered that the miR-581/SMAD7 axis could be a potential factor that drives CRC metastasis. A dual luciferase report assay and protein analysis confirmed the binding relationship between miR-581 and SMAD7. Further functional assays revealed that miR-581 inhibition could suppress cell proliferation and induce apoptosis in SW480 cells. Up-regulation or down-regulation of miR-581 could both affect cell invasion capacity and modulate epithelial to mesenchymal transition (EMT) via a SMAD7/TGFβ signaling pathway. In conclusion, our findings elucidated that miR-581/SMAD7 could be essential for CRC metastasis, and may serve as a potential therapeutic target for CRC patients.
Functional Grading of a Transversely Isotropic Hyperelastic Model with Applications in Modeling Tricuspid and Mitral Valve Transition Regions
Authors: Roy Rajarshi , Warren Eric , Xu Yaoyao , Yow Caleb , Madhurapantula Rama S. , Orgel Joseph P. R. O. , Lister Kevin
Published: September 2020

Surgical simulators and injury-prediction human models require a combination of representative tissue geometry and accurate tissue material properties to predict realistic tool–tissue interaction forces and injury mechanisms, respectively. While biological tissues have been individually characterized, the transition regions between tissues have received limited research attention, potentially resulting in inaccuracies within simulations. In this work, an approach to characterize the transition regions in transversely isotropic (TI) soft tissues using functionally graded material (FGM) modeling is presented. The effect of nonlinearities and multi-regime nature of the TI model on the functional grading process is discussed. The proposed approach has been implemented to characterize the transition regions in the leaflet (LL), chordae tendinae (CT) and the papillary muscle (PM) of porcine tricuspid valve (TV) and mitral valve (MV). The FGM model is informed using high resolution morphological measurements of the collagen fiber orientation and tissue composition in the transition regions, and deformation characteristics predicted by the FGM model are numerically validated to experimental data using X-ray diffraction imaging. The results indicate feasibility of using the FGM approach in modeling soft-tissue transitions and has implications in improving physical representation of tissue deformation throughout the body using a scalable version of the proposed approach.
Cataract-Associated New Mutants S175G/H181Q of βΒ2-Crystallin and P24S/S31G of γD-Crystallin Are Involved in Protein Aggregation by Structural Changes
Authors: Song In-Kang , Na Seungjin , Paek Eunok , Lee Kong-Joo
Published: September 2020

β/γ-Crystallins, the main structural protein in human lenses, have highly stable structure for keeping the lens transparent. Their mutations have been linked to cataracts. In this study, we identified 10 new mutations of β/γ-crystallins in lens proteomic dataset of cataract patients using bioinformatics tools. Of these, two double mutants, S175G/H181Q of βΒ2-crystallin and P24S/S31G of γD-crystallin, were found mutations occurred in the largest loop linking the distant β-sheets in the Greek key motif. We selected these double mutants for identifying the properties of these mutations, employing biochemical assay, the identification of protein modifications with nanoUPLC-ESI-TOF tandem MS and examining their structural dynamics with hydrogen/deuterium exchange-mass spectrometry (HDX-MS). We found that both double mutations decrease protein stability and induce the aggregation of β/γ-crystallin, possibly causing cataracts. This finding suggests that both the double mutants can serve as biomarkers of cataracts.
Construction of Gossypium barbadense Mutant Library Provides Genetic Resources for Cotton Germplasm Improvement
Authors: Abid Muhammad Ali , Wang Peilin , Zhu Tao , Liang Chengzhen , Meng Zhigang , Malik Waqas , Guo Sandui , Zhang Rui
Published: September 2020

Allotetraploid cotton (Gossypium hirsutum and Gossypium barbadense) are cultivated worldwide for its white fiber. For centuries, conventional breeding approaches increase cotton yield at the cost of extensive erosion of natural genetic variability. Sea Island cotton (G. barbadense) is known for its superior fiber quality, but show poor adaptability as compared to Upland cotton. Here, in this study, we use ethylmethanesulfonate (EMS) as a mutagenic agent to induce genome-wide point mutations to improve the current germplasm resources of Sea Island cotton and develop diverse breeding lines with improved adaptability and excellent economic traits. We determined the optimal EMS experimental procedure suitable for construction of cotton mutant library. At M6 generation, mutant library comprised of lines with distinguished phenotypes of the plant architecture, leaf, flower, boll, and fiber. Genome-wide analysis of SNP distribution and density in yellow leaf mutant reflected the better quality of mutant library. Reduced photosynthetic efficiency and transmission electron microscopy of yellow leaf mutants revealed the effect of induced mutations at physiological and cellular level. Our mutant collection will serve as the valuable resource for basic research on cotton functional genomics, as well as cotton breeding.
An Iatrogenic Model of Brain Small-Vessel Disease: Post-Radiation Encephalopathy
Authors: Moretti Rita , Caruso Paola
Published: September 2020

We studied 114 primitive cerebral neoplasia, that were surgically treated, and underwent radiotherapy (RT), and compared their results to those obtained by 190 patients diagnosed with subcortical vascular dementia (sVAD). Patients with any form of primitive cerebral neoplasia underwent whole-brain radiotherapy. All the tumor patients had regional field partial brain RT, which encompassed each tumor, with an average margin of 2.6 cm from the initial target tumor volume. We observed in our patients who have been exposed to a higher dose of RT (30–65 Gy) a cognitive and behavior decline similar to that observed in sVAD, with the frontal dysexecutive syndrome, apathy, and gait alterations, but with a more rapid onset and with an overwhelming effect. Multiple mechanisms are likely to be involved in radiation-induced cognitive impairment. The active site of RT brain damage is the white matter areas, particularly the internal capsule, basal ganglia, caudate, hippocampus, and subventricular zone. In all cases, radiation damage inside the brain mainly focuses on the cortical–subcortical frontal loops, which integrate and process the flow of information from the cortical areas, where executive functions are “elaborated” and prepared, towards the thalamus, subthalamus, and cerebellum, where they are continuously refined and executed. The active mechanisms that RT drives are similar to those observed in cerebral small vessel disease (SVD), leading to sVAD. The RT’s primary targets, outside the tumor mass, are the blood–brain barrier (BBB), the small vessels, and putative mechanisms that can be taken into account are oxidative stress and neuro-inflammation, strongly associated with the alteration of NMDA receptor subunit composition.
Understanding the Interaction Modes and Reactivity of Trimedoxime toward MmAChE Inhibited by Nerve Agents: Theoretical and Experimental Aspects
Authors: de Castro Alexandre , Polisel Daniel , Pereira Bruna , da Cunha Elaine , Kuca Kamil , Nepovimova Eugenie , Ramalho Teodorico
Published: September 2020

Organophosphorus (OP) compounds are used as both chemical weapons and pesticides. However, these agents are very dangerous and toxic to humans, animals, and the environment. Thus, investigations with reactivators have been deeply developed in order to design new antidotes with better efficiency, as well as a greater spectrum of action in the acetylcholinesterase (AChE) reactivation process. With that in mind, in this work, we investigated the behavior of trimedoxime toward the Mus musculus acetylcholinesterase (MmAChE) inhibited by a range of nerve agents, such as chemical weapons. From experimental assays, reactivation percentages were obtained for the reactivation of different AChE–OP complexes. On the other hand, theoretical calculations were performed to assess the differences in interaction modes and the reactivity of trimedoxime within the AChE active site. Comparing theoretical and experimental data, it is possible to notice that the oxime, in most cases, showed better reactivation percentages at higher concentrations, with the best result for the reactivation of the AChE–VX adduct. From this work, it was revealed that the mechanistic process contributes most to the oxime efficiency than the interaction in the site. In this way, this study is important to better understand the reactivation process through trimedoxime, contributing to the proposal of novel antidotes.
Human Natural Antibodies Recognizing Glycan Galβ1-3GlcNAc (LeC)
Authors: Dobrochaeva Kira , Khasbiullina Nailya , Shilova Nadezhda , Antipova Nadezhda , Obukhova Polina , Galanina Oxana , Gorbach Mikhail , Popova Inna , Khaidukov Sergey , Grishchenko Natalia , Tupitsyn Nikolai , Pendu Jacques Le , Bovin Nicolai
Published: September 2020

The level of human natural antibodies of immunoglobulin M isotype against LeC in patients with breast cancer is lower than in healthy women. The epitope specificity of these antibodies has been characterized using a printed glycan array and enzyme-linked immunosorbent assay (ELISA), the antibodies being isolated from donors’ blood using LeC-Sepharose (LeC is Galβ1-3GlcNAcβ). The isolated antibodies recognize the disaccharide but do not bind to glycans terminated with LeC, which implies the impossibility of binding to regular glycoproteins of non-malignant cells. The avidity (as dissociation constant value) of antibodies probed with a multivalent disaccharide is 10−9 M; the nanomolar level indicates that the concentration is sufficient for physiological binding to the cognate antigen. Testing of several breast cancer cell lines showed the strongest binding to ZR 75-1. Interestingly, only 7% of the cells were positive in a monolayer with a low density, increasing up to 96% at highest density. The enhanced interaction (instead of the expected inhibition) of antibodies with ZR 75-1 cells in the presence of Galβ1-3GlcNAcβ disaccharide, indicates that the target epitope of anti-LeC antibodies is a molecular pattern with a carbohydrate constituent rather than a glycan.
Non-Coding RNAs in the Brain-Heart Axis: The Case of Parkinson’s Disease
Authors: Acharya Shubhra , Salgado-Somoza Antonio , Stefanizzi Francesca Maria , Lumley Andrew I. , Zhang Lu , Glaab Enrico , May Patrick , Devaux Yvan
Published: September 2020

Parkinson’s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data.
Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest
Authors: Huang Boyan , Chen Qingmei , Wang Lingling , Gao Xiaojuan , Zhu Wenya , Mu Peiqiang , Deng Yiqun
Published: September 2020

Aflatoxin B1 (AFB1) is a mycotoxin widely distributed in a variety of food commodities and exhibits strong toxicity toward multiple tissues and organs. However, little is known about its neurotoxicity and the associated mechanism. In this study, we observed that brain integrity was markedly damaged in mice after intragastric administration of AFB1 (300 μg/kg/day for 30 days). The toxicity of AFB1 on neuronal cells and the underlying mechanisms were then investigated in the neuroblastoma cell line IMR-32. A cell viability assay showed that the IC50 values of AFB1 on IMR-32 cells were 6.18 μg/mL and 5.87 μg/mL after treatment for 24 h and 48 h, respectively. ROS levels in IMR-32 cells increased significantly in a time- and AFB1 concentration-dependent manner, which was associated with the upregulation of NOX2, and downregulation of OXR1, SOD1, and SOD2. Substantial DNA damage associated with the downregulation of PARP1, BRCA2, and RAD51 was also observed. Furthermore, AFB1 significantly induced S-phase arrest, which is associated with the upregulation of CDKN1A, CDKN2C, and CDKN2D. Finally, AFB1 induced apoptosis involving CASP3 and BAX. Taken together, AFB1 manifests a wide range of cytotoxicity on neuronal cells including ROS accumulation, DNA damage, S-phase arrest, and apoptosis—all of which are key factors for understanding the neurotoxicology of AFB1.
Combination of Linkage Mapping, GWAS, and GP to Dissect the Genetic Basis of Common Rust Resistance in Tropical Maize Germplasm
Authors: Kibe Maguta , Nyaga Christine , Nair Sudha K. , Beyene Yoseph , Das Biswanath , M Suresh L. , Bright Jumbo M. , Makumbi Dan , Kinyua Johnson , Olsen Michael S. , Prasanna Boddupalli M. , Gowda Manje
Published: September 2020

Common rust (CR) caused by Puccina sorghi is one of the destructive fungal foliar diseases of maize and has been reported to cause moderate to high yield losses. Providing CR resistant germplasm has the potential to increase yields. To dissect the genetic architecture of CR resistance in maize, association mapping, in conjunction with linkage mapping, joint linkage association mapping (JLAM), and genomic prediction (GP) was conducted on an association-mapping panel and five F3 biparental populations using genotyping-by-sequencing (GBS) single-nucleotide polymorphisms (SNPs). Analysis of variance for the biparental populations and the association panel showed significant genotypic and genotype x environment (GXE) interaction variances except for GXE of Pop4. Heritability (h2) estimates were moderate with 0.37–0.45 for the individual F3 populations, 0.45 across five populations and 0.65 for the association panel. Genome-wide association study (GWAS) analyses revealed 14 significant marker-trait associations which individually explained 6–10% of the total phenotypic variances. Individual population-based linkage analysis revealed 26 QTLs associated with CR resistance and together explained 14–40% of the total phenotypic variances. Linkage mapping revealed seven QTLs in pop1, nine QTL in pop2, four QTL in pop3, five QTL in pop4, and one QTL in pop5, distributed on all chromosomes except chromosome 10. JLAM for the 921 F3 families from five populations detected 18 QTLs distributed in all chromosomes except on chromosome 8. These QTLs individually explained 0.3 to 3.1% and together explained 45% of the total phenotypic variance. Among the 18 QTL detected through JLAM, six QTLs, qCR1-78, qCR1-227, qCR3-172, qCR3-186, qCR4-171, and qCR7-137 were also detected in linkage mapping. GP within population revealed low to moderate correlations with a range from 0.19 to 0.51. Prediction correlation was high with r = 0.78 for combined analysis of the five F3 populations. Prediction of biparental populations by using association panel as training set reveals positive correlations ranging from 0.05 to 0.22, which encourages to develop an independent but related population as a training set which can be used to predict diverse but related populations. The findings of this study provide valuable information on understanding the genetic basis of CR resistance and the obtained information can be used for developing functional molecular markers for marker-assisted selection and for implementing GP to improve CR resistance in tropical maize.
Total Recall: Lateral Habenula and Psychedelics in the Study of Depression and Comorbid Brain Disorders
Authors: Vitkauskas Matas , Mathuru Ajay S.
Published: September 2020

Depression impacts the lives and daily activities of millions globally. Research into the neurobiology of lateral habenula circuitry and the use of psychedelics for treating depressive states has emerged in the last decade as new directions to devise interventional strategies and therapies. Several clinical trials using deep brain stimulation of the habenula, or using ketamine, and psychedelics that target the serotonergic system such as psilocybin are also underway. The promising early results in these fields require cautious optimism as further evidence from experiments conducted in animal systems in ecologically relevant settings, and a larger number of human studies with improved spatiotemporal neuroimaging, accumulates. Designing optimal methods of intervention will also be aided by an improvement in our understanding of the common genetic and molecular factors underlying disorders comorbid with depression, as well as the characterization of psychedelic-induced changes at a molecular level. Advances in the use of cerebral organoids offers a new approach for rapid progress towards these goals. Here, we review developments in these fast-moving areas of research and discuss potential future directions.
Regulation of Anti-Oxidative, Anti-Inflammatory, and Anti-Apoptotic Activity of Advanced Cooling Composition (ACC) in UVB-Irradiated Human HaCaT Keratinocytes
Authors: Park Jungha , Woo Yong-Kyu , Cho Hyun-Jeong
Published: September 2020

We recently demonstrated that advanced cooling composition (ACC) has effective ingredients that exhibit anti-inflammatory effects in RAW 264.7 cells stimulated with lipopolysaccharide (LPS) and exhibit strong antimicrobial effects on Pseudomonas aeruginosa, Staphylococcus aureus, MRSA (methicillin-resistant Staphylococcus aureus), Candida albicans, and Streptococcus mutans. To further investigate whether ACC has beneficial effects in ultraviolet B (UVB)-irradiated human keratinocytes (HaCaT cells), HaCaT cells were pretreated with ACC prior to UVB irradiation. Our data showed that ACC, which is effective at 100 µg/mL, is nontoxic and has an antioxidative effect against UVB-induced intracellular reactive oxygen species (ROS) in HaCaT cells. In addition, ACC exerts cytoprotective effects against UVB-induced cytotoxicity in HaCaT cells by inhibiting abnormal inflammation and apoptosis through the regulation of mitogen-activated protein kinase (MAPK) signals, such as jun-amino-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). Therefore, these results indicate that ACC is a potentially beneficial raw material that possesses antioxidative, anti-inflammatory, and antiapoptotic effects against UVB-induced keratinocytes and may have applications in skin health.
Multiple Known Mechanisms and a Possible Role of an Enhanced Immune System in Bt-Resistance in a Field Population of the Bollworm, Helicoverpa zea: Differences in Gene Expression with RNAseq
Authors: Lawrie Roger D. , Mitchell III Robert D. , Deguenon Jean Marcel , Ponnusamy Loganathan , Reisig Dominic , Pozo-Valdivia Alejandro Del , Kurtz Ryan W. , Roe R. Michael
Published: September 2020

Several different agricultural insect pests have developed field resistance to Bt (Bacillus thuringiensis) proteins (ex. Cry1Ac, Cry1F, etc.) expressed in crops, including corn and cotton. In the bollworm, Helicoverpa zea, resistance levels are increasing; recent reports in 2019 show up to 1000-fold levels of resistance to Cry1Ac, a major insecticidal protein in Bt-crops. A common method to analyze global differences in gene expression is RNA-seq. This technique was used to measure differences in global gene expression between a Bt-susceptible and Bt-resistant strain of the bollworm, where the differences in susceptibility to Cry1Ac insecticidal proteins were 100-fold. We found expected gene expression differences based on our current understanding of the Bt mode of action, including increased expression of proteases (trypsins and serine proteases) and reduced expression of Bt-interacting receptors (aminopeptidases and cadherins) in resistant bollworms. We also found additional expression differences for transcripts that were not previously investigated, i.e., transcripts from three immune pathways-Jak/STAT, Toll, and IMD. Immune pathway receptors (ex. PGRPs) and the IMD pathway demonstrated the highest differences in expression. Our analysis suggested that multiple mechanisms are involved in the development of Bt-resistance, including potentially unrecognized pathways.
The Emerging Relevance of AIM2 in Liver Disease
Authors: Lozano-Ruiz Beatriz , González-Navajas José M.
Published: September 2020

Absent in melanoma 2 (AIM2) is a cytosolic receptor that recognizes double-stranded DNA (dsDNA) and triggers the activation of the inflammasome cascade. Activation of the inflammasome results in the maturation of inflammatory cytokines, such as interleukin (IL)-1 β and IL-18, and a form of cell death known as pyroptosis. Owing to the conserved nature of its ligand, AIM2 is important during immune recognition of multiple pathogens. Additionally, AIM2 is also capable of recognizing host DNA during cellular damage or stress, thereby contributing to sterile inflammatory diseases. Inflammation, either in response to pathogens or due to sterile cellular damage, is at the center of the most prevalent and life-threatening liver diseases. Therefore, during the last 15 years, the study of inflammasome activation in the liver has emerged as a new research area in hepatology. Here, we discuss the known functions of AIM2 in the pathogenesis of different hepatic diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), hepatitis B, liver fibrosis, and hepatocellular carcinoma (HCC).
Advanced Bioluminescence System for In Vivo Imaging with Brighter and Red-Shifted Light Emission
Authors: Endo Mizuki , Ozawa Takeaki
Published: September 2020

In vivo bioluminescence imaging (BLI), which is based on luminescence emitted by the luciferase–luciferin reaction, has enabled continuous monitoring of various biochemical processes in living animals. Bright luminescence with a high signal-to-background ratio, ideally red or near-infrared light as the emission maximum, is necessary for in vivo animal experiments. Various attempts have been undertaken to achieve this goal, including genetic engineering of luciferase, chemical modulation of luciferin, and utilization of bioluminescence resonance energy transfer (BRET). In this review, we overview a recent advance in the development of a bioluminescence system for in vivo BLI. We also specifically examine the improvement in bioluminescence intensity by mutagenic or chemical modulation on several beetle and marine luciferase bioluminescence systems. We further describe that intramolecular BRET enhances luminescence emission, with recent attempts for the development of red-shifted bioluminescence system, showing great potency in in vivo BLI. Perspectives for future improvement of bioluminescence systems are discussed.