bluuebunny/crossref_metadata_2025 huggingface dataset:
Affordability and Availability of Child Restraints in an Under-Served Population in South Africa
Authors: Puvanachandra Prasanthi , Janmohammed Aliasgher , Mtambeka Pumla , Prinsloo Megan , Van As Sebastian , Peden Margaret M.
Published: March 2020

Background: Child road traffic injuries are a major global public health problem and the issue is particularly burdensome in middle-income countries such as South Africa where injury death rates are 41 per 100,000 for under 5′s and 24.5 per 100,000 for 5–14-year-old. Despite their known effectiveness in reducing injuries amongst children, the rates of use of child restraint systems (CRS) remains low in South Africa. Little is known about barriers to child restraint use especially in low- and middle-income countries. Methods: We carried out observation studies and parent/carer surveys in 7 suburbs of Cape Town over a three month period to assess usage rates and explore the knowledge and perceptions of parents towards child restraint legislation, ownership and cost; Results: Only 7.8% of child passengers were observed to be properly restrained in a CRS with driver seatbelt use and single child occupancy being associated with higher child restraint use. 92% of survey respondents claimed to have knowledge of current child restraint legislation, however, only 32% of those parents/carers were able to correctly identify the age requirements and penalty. Reasons given for not owning a child seat included high cost and the belief that seatbelts were a suitable alternative. Conclusions: These findings indicate the need for a tighter legislation with an increased fine paired with enhanced enforcement of both adult seatbelt and child restraint use. The provision of low-cost/subsidised CRS or borrowing schemes and targeted social marketing through online fora, well baby clinics, early learning centres would be beneficial in increasing ownership and use of CRS.
Genotoxicity and Oxidative Stress in Experimental Hybrid Catfish Exposed to Heavy Metals in a Municipal Landfill Reservoir
Authors: Neeratanaphan Lamyai , Kamollerd Chuchart , Suwannathada Pimchanok , Suwannathada Pongthorn , Tengjaroenkul Bundit
Published: March 2020

This study aimed to investigate the concentrations of Cr, Cd and Pb in the water, sediment and experimental hybrid catfish muscles, and to compare the genetic differentiation and the levels of oxidative stress biomarkers (malondialdehyde and protein carbonyl) between the catfish from the contaminated reservoir near a municipal landfill and the reference area after chronic exposure. The concentrations of all metals in the water and the concentration of Cd in the sediment exceeded Thailand’s surface water quality and soil quality standards, respectively, whereas the concentrations of these metals in fish muscles did not exceed Thailand’s food quality standards. Dendrogram results in terms of genetic similarity values of the catfish from the reference and the landfill areas were 0.90 to 0.96 and 0.79 to 0.86, respectively, implying that the genetic differentiation of the fish from the landfill was greater than of those from the reference area. The fish in the landfill reservoir had slightly increased protein carbonyl levels. The results indicate that chronic heavy metal exposure can cause genotoxicity of the hybrid catfish and induce protein carbonyl as an oxidative stress biomarker in the reservoir near a municipal landfill.
Extension of the Theory of Planned Behavior (TPB) to Predict Patterns of Marijuana Use among Young Iranian Adults
Authors: Jalilian Farzad , Mirzaei-Alavijeh Mehdi , Ahmadpanah Mohammad , Mostafaei Shayan , Kargar Mehdi , Pirouzeh Razieh , Sadeghi Bahmani Dena , Brand Serge
Published: March 2020

Background: Marijuana use is increasing among adolescents and young adults. Long-term marijuana use magnifies the risk of a wide variety of behavioral, cognitive-emotional, and neurological problems, and can be a gateway to use of other drugs. In the present study, we investigated the cognitive-emotional and behavioral predictors of marijuana use. To this end, young Iranian adults answered questions based on an extended Theory of Planned Behavior (TPB) and related it to marijuana use. We hypothesized that cognitive-emotional and behavioral factors would predict intention to use marijuana, and that this, in turn, would predict actual consumption. Methods: A total of 166 young Iranian adults (mean age: 20.51 years; 15.7% females) attending a walk-in center for drug use took part in this cross-sectional study. Participants completed questionnaires covering sociodemographic information, frequency of marijuana use per week, along with questionnaires assessing the following dimensions of the TPB: attitude towards marijuana use, subjective norms, self-efficacy to resist marijuana use, environmental constraints, problem-solving skills, and behavioral intention for marijuana use. Results: Mean marijuana use was found to be 4.6 times/week. Attitude towards marijuana use, subjective norms, environmental constraints, and behavioral intention to use marijuana were positively correlated to each other and with marijuana use/week. In contrast, higher self-efficacy and problem-solving skills were associated with lower marijuana use/week. The multiple regression analysis showed that a positive attitude to marijuana use, lower self-efficacy in resisting its use, higher behavioral intention, and poorer problem-solving skills predicted actual use. Conclusion: The pattern of results suggests that dimensions of TPB can explain marijuana use among young Iranian adults self-admitted to a walk-in center for drug use. Specifically, poor problem-solving skills, low self-efficacy in resisting marijuana use, and positive labelling of its use appeared to be the best predictors of actual use. It follows that prevention programs aimed at improving problem-solving skills and raising self-efficacy, along with educational interventions aimed at highlighting the negative effects of marijuana might decrease the risk of its use among young adults in Iran.
The Risk of Depression in Patients with Pemphigus: A Nationwide Cohort Study in Taiwan
Authors: Hsu Yi-Min , Fang Hsin-Yu , Lin Cheng-Li , Shieh Shwn-Huey
Published: March 2020

Pemphigus is a chronic dermatological disorder caused by an autoimmune response and is associated with a high proportion of comorbidities and fatalities. The aim of this study was to investigate the risk of depression in patients with pemphigus. Data were derived from the National Health Insurance Research Database recorded during the period 2000–2010 in Taiwan. Multivariate Cox proportional hazards regression models were used to analyze the data and assess the effects of pemphigus on the risk of depression after adjusting for demographic characteristics and comorbidities. Patients with pemphigus were 1.98 times more likely to suffer from depression than the control group (pemphigus, adjusted HR: 1.99, 95% CI = 1.37–2.86). People aged ≥65 years were 1.69 times more likely to suffer from depression than those aged 20–49 years (≥65 years, adjusted HR: 1.42, 95% CI = 0.92–2.21). Female and male patients with pemphigus were respectively 2.02 and 1.91 times more likely to suffer from depression than the control group (female, adjusted HR: 2.09, 95% CI = 1.24–3.54; male, adjusted HR: 1.87, 95% CI = 0.97–3.60). People with HTN, hyperlipidemia, asthma/COPD, and chronic liver disease were respectively 1.73, 2.3, 2.2, and 1.69 times more likely to suffer from depression than those without these comorbidities (HTN, adjusted HR: 0.75, 95% CI = 0.41–1.42; hyperlipidemia, adjusted HR: 1.48, 95% CI = 0.78–2.82; asthma/COPD, adjusted HR: 1.4, 95% CI = 0.72–2.69; and chronic liver disease, adjusted HR: 1.61, 95% CI = 1.07–2.43). There was a significant association between pemphigus and increased risk of depression. Female patients had a higher incidence of depression.
Benchmarking Community Disaster Resilience in Nepal
Authors: Aksha Sanam K. , Emrich Christopher T.
Published: March 2020

Building disaster resilience is a stated goal of disaster risk reduction programs. Recent research emphasizes a need for a greater understanding of community disaster response and recovery capacity so that communities can absorb shocks and withstand severe conditions and progress through the recovery period more efficiently. Nepal, which is prone to a multitude of hazards and having recently experienced a large earthquake in 2015, provides a unique opportunity for exploring disaster resilience in the developing world context. To date, no study investigating community disaster resilience across the entire country of Nepal exists. This study quantifies disaster resilience at Nepal’s village level, primarily using census data. Guided by the Disaster Resilience of Place (DROP) model, 22 variables were selected as indicators of social, economic, community, infrastructure, and environmental resilience. Community resilience was assessed for 3971 village development communities (VDCs) and municipalities while using a principal component analysis. Additionally, a cluster analysis was performed to distinguish spatial patterns of resilience. Analyses reveal differential community disaster resilience across the country. Communities in the capital city Kathmandu and in the western and far western Hill are relatively resilient. While the entire Tarai region, which holds the greatest proportion of Nepal’s population, exhibits relatively low levels of resilience when compared to the rest of the county. The results from this analysis provide empirical evidence with the potential to help decision-makers in the allocation of scarce resources to increase resilience at the local level.
Prevention of Cognitive Decline in Alzheimer’s Disease by Novel Antioxidative Supplements
Authors: Tadokoro Koh , Ohta Yasuyuki , Inufusa Haruhiko , Loon Alan Foo Nyuk , Abe Koji
Published: March 2020

Oxidative stress plays a crucial role in Alzheimer’s disease (AD) from its prodromal stage of mild cognitive impairment. There is an interplay between oxidative stress and the amyloid β (Aβ) cascade via various mechanisms including mitochondrial dysfunction, lipid peroxidation, protein oxidation, glycoxidation, deoxyribonucleotide acid damage, altered antioxidant defense, impaired amyloid clearance, inflammation and chronic cerebral hypoperfusion. Based on findings that indicate that oxidative stress plays a major role in AD, oxidative stress has been considered as a therapeutic target of AD. In spite of favorable preclinical study outcomes, previous antioxidative components, including a single antioxidative supplement such as vitamin C, vitamin E or their mixtures, did not clearly show any therapeutic effect on cognitive decline in AD. However, novel antioxidative supplements can be beneficial for AD patients. In this review, we summarize the interplay between oxidative stress and the Aβ cascade, and introduce novel antioxidative supplements expected to prevent cognitive decline in AD.
Mitophagy in the Retinal Pigment Epithelium of Dry Age-Related Macular Degeneration Investigated in the NFE2L2/PGC-1α-/- Mouse Model
Authors: Sridevi Gurubaran Iswariyaraja , Viiri Johanna , Koskela Ali , Hyttinen Juha M.T. , Paterno Jussi J. , Kis Gréta , Antal Miklós , Urtti Arto , Kauppinen Anu , Felszeghy Szabolcs , Kaarniranta Kai
Published: March 2020

Increased oxidative stress and mitochondrial damage are observed in protein aggregation diseases, such as age-related macular degeneration (AMD). We have recently reported elevated levels of oxidative stress markers, damaged mitochondria, accumulating lysosomal lipofuscin and extracellular drusen-like structures in the retinal pigment epithelial cells (RPE) of the dry AMD-resembling NFE2L2/PGC1α double knockout (dKO) mouse model. Here, we provide evidence of a disturbance in the autolysosomal machinery handling mitochondrial clearance in the RPE cells of one-year-old NFE2L2/PGC1α-deficient mice. Confocal immunohistochemical analysis revealed an upregulation of autophagosome marker microtubule-associated proteins 1A/1B light chain 3B (LC3B) as well as numerous mitophagy markers, such as PTE-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (PARKIN) together with damaged mitochondria. However, we detected no evidence of increased autolysosome formation in transmission electron micrographs or of colocalization of lysosomal marker LAMP2 (lysosome-associated membrane protein 2) and the mitochondrial marker ATP synthase β in confocal micrographs. Interestingly, we observed an upregulation of late autolysosomal fusion Ras-related protein (Rab7) in the perinuclear space of RPE cells together with autofluorescence aggregates. Our results reveal that there is at least a relative decrease of mitophagy in the RPE cells of NFE2L2/PGC1α dKO mice. This further supports the hypothesis that mitophagy is a putative therapy target in AMD-like pathology.
Identification and Characterization of NPR1 and PR1 Homologs in Cymbidium orchids in Response to Multiple Hormones, Salinity and Viral Stresses
Authors: Ren Rui , Wei Yonglu , Ahmad Sagheer , Jin Jianpeng , Gao Jie , Lu Chuqiao , Zhu Genfa , Yang Fengxi
Published: March 2020

The plant nonexpressor of pathogenesis-related 1 (NPR1) and pathogenesis-associated 1 (PR1) genes play fundamental roles in plant immunity response, as well as abiotic-stress tolerance. Nevertheless, comprehensive identification and characterization of NPR1 and PR1 homologs has not been conducted to date in Cymbidium orchids, a valuable industrial crop cultivated as ornamental and medicinal plants worldwide. Herein, three NPR1-like (referred to as CsNPR1-1, CsNPR1-2, and CsNPR1-3) and two PR1-like (CsPR1-1 and CsPR1-2) genes were genome-widely identified from Cymbidium orchids. Sequence and phylogenetic analysis revealed that CsNPR1-1 and CsNPR1-2 were grouped closest to NPR1 homologs in Zea mays (sharing 81.98% identity) and Phalaenopsis (64.14%), while CsNPR1-3 was classified into a distinct group with Oryza sativa NPR 3 (57.72%). CsPR1-1 and CsPR1-2 were both grouped closest to Phalaenopsis PR1 and other monocot plants. Expression profiling showed that CsNPR1 and CsPR1 were highly expressed in stem/pseudobulb and/or flower. Salicylic acid (SA) and hydrogen peroxide (H2O2) significantly up-regulated expressions of CsNPR1-2, CsPR1-1 and CsPR1-2, while CsNPR1-3, CsPR1-1 and CsPR1-2 were significantly up-regulated by abscisic acid (ABA) or salinity (NaCl) stress. In vitro transcripts of entire Cymbidium mosaic virus (CymMV) genomic RNA were successfully transfected into Cymbidium protoplasts, and the CymMV infection up-regulated the expression of CsNPR1-2, CsPR1-1 and CsPR1-2. Additionally, these genes were transiently expressed in Cymbidium protoplasts for subcellular localization analysis, and the presence of SA led to the nuclear translocation of the CsNPR1-2 protein, and the transient expression of CsNPR1-2 greatly enhanced the expression of CsPR1-1 and CsPR1-2. Collectively, the CsNPR1-2-mediated signaling pathway is SA-dependent, and confers to the defense against CymMV infection in Cymbidium orchids.
Association between Pericytes in Intraplaque Neovessels and Magnetic Resonance Angiography Findings
Authors: Ogata Atsushi , Wakamiya Tomihiro , Nishihara Masashi , Tanaka Tatsuya , Mizokami Taichiro , Masuoka Jun , Momozaki Nobuaki , Sakata Shuji , Irie Hiroyuki , Abe Tatsuya
Published: March 2020

(1) Background: Pericytes are involved in intraplaque neovascularization of advanced and complicated atherosclerotic lesions. However, the role of pericytes in human carotid plaques is unclear. An unstable carotid plaque that shows high-intensity signals on time-of-flight (TOF) magnetic resonance angiography (MRA) is often a cause of ischemic stroke. The aim of the present study is to examine the relationship between the pericytes in intraplaque neovessels and MRA findings. (2) Methods: A total of 46 patients with 49 carotid artery stenoses who underwent carotid endarterectomy at our hospitals were enrolled. The patients with carotid plaques that were histopathologically evaluated were retrospectively analyzed. Intraplaque hemorrhage was evaluated using glycophorin A staining, and intraplaque neovessels were evaluated using CD34 (Cluster of differentiation) stain as an endothelial cell marker or NG2 (Neuron-glial antigen 2) and CD146 stains as pericyte markers. Additionally, the relationships between the TOF-MRA findings and the carotid plaque pathologies were evaluated. (3) Results: Of the 49 stenoses, 28 had high-intensity signals (TOF-HIS group) and 21 had iso-intensity signals (TOF-IIS group) on TOF-MRA. The density of the CD34-positive neovessels was equivalent in both groups. However, the NG2- and CD146-positive neovessels had significantly higher densities in the TOF-HIS group than in the TOF-IIS group. (4) Conclusion: The presence of a high-intensity signal on TOF-MRA in carotid plaques was associated with intraplaque hemorrhage and few pericytes in intraplaque neovessels. These findings may contribute to the development of new therapeutic strategies focusing on pericytes.
Maternal N-Acetyl Cysteine Intake Improved Glucose Tolerance in Obese Mice Offspring
Authors: Michlin Michal , Argaev-Frenkel Lital , Weinstein-Fudim Liza , Ornoy Asher , Rosenzweig Tovit
Published: March 2020

Exposure to certain environmental factors during the early stages of development was found to affect health in adulthood. Among other environmental factors, oxidative stress has been suggested to be involved in fetal programming, leading to elevated risk for metabolic disorders, including type 2 diabetes; however, the possibility that antioxidant consumption during early life may affect the development of diabetes has scarcely been studied. The aim of this study was to investigate the effects of N-acetyl-l-cysteine (NAC) given during pregnancy and lactation on the susceptibility of offspring to develop glucose intolerance at adulthood. C57bl6/J mice were given NAC during pregnancy and lactation. High fat diet (HFD) was given to offspring at an age of 6 weeks for an additional 9 weeks, till the end of the study. Isolated islets of NAC-treated offspring (6 weeks old, before HFD feeding) had an increased efficacy of glucose-stimulated insulin secretion and a higher resistance to oxidative damage. Following HFD feeding, glucose tolerance and insulin sensitivity of NAC-treated offspring were improved. In addition, islet diameter was lower in male offspring of NAC-treated mice compared to their HFD-fed littermates. NAC consumption during early life improves glucose tolerance in adulthood in mice.
Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients
Authors: Gryp Tessa , Huys Geert R.B. , Joossens Marie , Van Biesen Wim , Glorieux Griet , Vaneechoutte Mario
Published: March 2020

In chronic kidney disease (CKD), impaired kidney function results in accumulation of uremic toxins, which exert deleterious biological effects and contribute to inflammation and cardiovascular morbidity and mortality. Protein-bound uremic toxins (PBUTs), such as p-cresyl sulfate, indoxyl sulfate and indole-3-acetic acid, originate from phenolic and indolic compounds, which are end products of gut bacterial metabolization of aromatic amino acids (AAA). This study investigates gut microbial composition at different CKD stages by isolating, identifying and quantifying PBUT precursor-generating bacteria. Fecal DNA extracts from 14 controls and 138 CKD patients were used to quantify total bacterial number and 11 bacterial taxa with qPCR. Moreover, isolated bacteria from CKD 1 and CKD 5 fecal samples were cultured in broth medium supplemented with AAA under aerobic and anaerobic conditions, and classified as PBUT precursor-generators based on their generation capacity of phenolic and indolic compounds, measured with U(H)PLC. In total, 148 different fecal bacterial species were isolated, of which 92 were PBUT precursor-generators. These bacterial species can be a potential target for reducing PBUT plasma levels in CKD. qPCR indicated lower abundance of short chain fatty acid-generating bacteria, Bifidobacterium spp. and Streptococcus spp., and higher Enterobacteriaceae and E. coli with impaired kidney function, confirming an altered gut microbial composition in CKD.
Docking and Molecular Dynamics Predictions of Pesticide Binding to the Calyx of Bovine β-Lactoglobulin
Authors: Cortes-Hernandez Paulina , Vázquez Nuñez Roberto , Domínguez-Ramírez Lenin
Published: March 2020

Pesticides are used extensively in agriculture, and their residues in food must be monitored to prevent toxicity. The most abundant protein in cow’s milk, β-lactoglobulin (BLG), shows high affinity for diverse hydrophobic ligands in its central binding pocket, called the calyx. Several of the most frequently used pesticides are hydrophobic. To predict if BLG may be an unintended carrier for pesticides, we tested its ability to bind 555 pesticides and their isomers, for a total of 889 compounds, in a rigid docking screen. We focused on the analysis of 60 unique molecules belonging to the five pesticide classes defined by the World Health Organization, that docked into BLG’s calyx with ΔGs ranging from −8.2 to −12 kcal mol−1, chosen by statistical criteria. These “potential ligands” were further analyzed using molecular dynamic simulations, and the binding energies were explored with Molecular Mechanics/Generalized Born/Surface Area (MMGBSA). Hydrophobic pyrethroid insecticides, like cypermethrin, were found to bind as deeply and tightly into the calyx as BLG’s natural ligand, palmitate; while polar compounds, like paraquat, were expelled. Our results suggest that BLG could be a carrier for pesticides, in particular for pyrethroid insecticides, allowing for their accumulation in cow’s milk beyond their solubility restrictions. This analysis opens possibilities for pesticide biosensor design based on BLG.
Oxidative Stress and Mitochondrial Abnormalities Contribute to Decreased Endothelial Nitric Oxide Synthase Expression and Renal Disease Progression in Early Experimental Polycystic Kidney Disease
Authors: Kahveci Alp S. , Barnatan Tania T. , Kahveci Ali , Adrian Alexis E. , Arroyo Jennifer , Eirin Alfonso , Harris Peter C. , Lerman Amir , Lerman Lilach O. , Torres Vicente E. , Irazabal Maria V.
Published: March 2020

Vascular abnormalities are the most important non-cystic complications in Polycystic Kidney Disease (PKD) and contribute to renal disease progression. Endothelial dysfunction and oxidative stress are evident in patients with ADPKD, preserved renal function, and controlled hypertension. The underlying biological mechanisms remain unknown. We hypothesized that in early ADPKD, the reactive oxygen species (ROS)-producing nicotinamide adenine dinucleotide phosphate hydrogen (NAD(P)H)-oxidase complex-4 (NOX4), a major source of ROS in renal tubular epithelial cells (TECs) and endothelial cells (ECs), induces EC mitochondrial abnormalities, contributing to endothelial dysfunction, vascular abnormalities, and renal disease progression. Renal oxidative stress, mitochondrial morphology (electron microscopy), and NOX4 expression were assessed in 4- and 12-week-old PCK and Sprague-Dawley (wild-type, WT) control rats (n = 8 males and 8 females each). Endothelial function was assessed by renal expression of endothelial nitric oxide synthase (eNOS). Peritubular capillaries were counted in hematoxylin–eosin (H&E)-stained slides and correlated with the cystic index. The enlarged cystic kidneys of PCK rats exhibited significant accumulation of 8-hydroxyguanosine (8-OHdG) as early as 4 weeks of age, which became more pronounced at 12 weeks. Mitochondria of TECs lining cysts and ECs exhibited loss of cristae but remained preserved in non-cystic TECs. Renal expression of NOX4 was upregulated in TECs and ECs of PCK rats at 4 weeks of age and further increased at 12 weeks. Contrarily, eNOS immunoreactivity was lower in PCK vs. WT rats at 4 weeks and further decreased at 12 weeks. The peritubular capillary index was lower in PCK vs. WT rats at 12 weeks and correlated inversely with the cystic index. Early PKD is associated with NOX4-induced oxidative stress and mitochondrial abnormalities predominantly in ECs and TECs lining cysts. Endothelial dysfunction precedes capillary loss, and the latter correlates with worsening of renal disease. These observations position NOX4 and EC mitochondria as potential therapeutic targets in PKD.
The Aggregation Conditions Define Whether EGCG is an Inhibitor or Enhancer of α-Synuclein Amyloid Fibril Formation
Authors: Sternke-Hoffmann Rebecca , Peduzzo Alessia , Bolakhrif Najoua , Haas Rainer , Buell Alexander K.
Published: March 2020

The amyloid fibril formation by α -synuclein is a hallmark of various neurodegenerative disorders, most notably Parkinson’s disease. Epigallocatechin gallate (EGCG) has been reported to be an efficient inhibitor of amyloid formation by numerous proteins, among them α -synuclein. Here, we show that this applies only to a small region of the relevant parameter space, in particular to solution conditions where EGCG readily oxidizes, and we find that the oxidation product is a much more potent inhibitor compared to the unmodified EGCG. In addition to its inhibitory effects, EGCG and its oxidation products can under some conditions even accelerate α -synuclein amyloid fibril formation through facilitating its heterogeneous primary nucleation. Furthermore, we show through quantitative seeding experiments that, contrary to previous reports, EGCG is not able to re-model α -synuclein amyloid fibrils into seeding-incompetent structures. Taken together, our results paint a complex picture of EGCG as a compound that can under some conditions inhibit the amyloid fibril formation of α -synuclein, but the inhibitory action is not robust against various physiologically relevant changes in experimental conditions. Our results are important for the development of strategies to identify and characterize promising amyloid inhibitors.
Ralstonia solanacearum elicitor RipX Induces Defense Reaction by Suppressing the Mitochondrial atpA Gene in Host Plant
Authors: Sun Tingyan , Wu Wei , Wu Haoxiang , Rou Wei , Zhou Yinghui , Zhuo Tao , Fan Xiaojing , Hu Xun , Zou Huasong
Published: March 2020

RipX of Ralstonia solanacearum is translocated into host cells by a type III secretion system and acts as a harpin-like protein to induce a hypersensitive response in tobacco plants. The molecular events in association with RipX-induced signaling transduction have not been fully elucidated. This work reports that transient expression of RipX induced a yellowing phenotype in Nicotiana benthamiana, coupled with activation of the defense reaction. Using yeast two-hybrid and split-luciferase complementation assays, mitochondrial ATP synthase F1 subunit α (ATPA) was identified as an interaction partner of RipX from N. benthamiana. Although a certain proportion was found in mitochondria, the YFP-ATPA fusion was able to localize to the cell membrane, cytoplasm, and nucleus. RFP-RipX fusion was found from the cell membrane and cytoplasm. Moreover, ATPA interacted with RipX at both the cell membrane and cytoplasm in vivo. Silencing of the atpA gene had no effect on the appearance of yellowing phenotype induced by RipX. However, the silenced plants improved the resistance to R. solanacearum. Moreover, qRT-PCR and promoter GUS fusion experiments revealed that the transcript levels of atpA were evidently reduced in response to expression of RipX. These data demonstrated that RipX exerts a suppressive effect on the transcription of atpA gene, to induce defense reaction in N. benthamiana.
GsMAS1 Encoding a MADS-box Transcription Factor Enhances the Tolerance to Aluminum Stress in Arabidopsis thaliana
Authors: Zhang Xiao , Li Lu , Yang Ce , Cheng Yanbo , Han Zhenzhen , Cai Zhandong , Nian Hai , Ma Qibin
Published: March 2020

The MADS-box transcription factors (TFs) are essential in regulating plant growth and development, and conferring abiotic and metal stress resistance. This study aims to investigate GsMAS1 function in conferring tolerance to aluminum stress in Arabidopsis. The GsMAS1 from the wild soybean BW69 line encodes a MADS-box transcription factor in Glycine soja by bioinformatics analysis. The putative GsMAS1 protein was localized in the nucleus. The GsMAS1 gene was rich in soybean roots presenting a constitutive expression pattern and induced by aluminum stress with a concentration-time specific pattern. The analysis of phenotypic observation demonstrated that overexpression of GsMAS1 enhanced the tolerance of Arabidopsis plants to aluminum (Al) stress with larger values of relative root length and higher proline accumulation compared to those of wild type at the AlCl3 treatments. The genes and/or pathways regulated by GsMAS1 were further investigated under Al stress by qRT-PCR. The results indicated that six genes resistant to Al stress were upregulated, whereas AtALMT1 and STOP2 were significantly activated by Al stress and GsMAS1 overexpression. After treatment of 50 μM AlCl3, the RNA abundance of AtALMT1 and STOP2 went up to 17-fold and 37-fold than those in wild type, respectively. Whereas the RNA transcripts of AtALMT1 and STOP2 were much higher than those in wild type with over 82% and 67% of relative expression in GsMAS1 transgenic plants, respectively. In short, the results suggest that GsMAS1 may increase resistance to Al toxicity through certain pathways related to Al stress in Arabidopsis.
Photochemical Printing of Plasmonically Active Silver Nanostructures
Authors: Szalkowski Marcin , Sulowska Karolina , Jönsson-Niedziółka Martin , Wiwatowski Kamil , Niedziółka-Jönsson Joanna , Maćkowski Sebastian , Piątkowski Dawid
Published: March 2020

In this paper, we demonstrate plasmonic substrates prepared on demand, using a straightforward technique, based on laser-induced photochemical reduction of silver compounds on a glass substrate. Importantly, the presented technique does not impose any restrictions regarding the shape and length of the metallic pattern. Plasmonic interactions have been probed using both Stokes and anti-Stokes types of emitters that served as photoluminescence probes. For both cases, we observed a pronounced increase of the photoluminescence intensity for emitters deposited on silver patterns. By studying the absorption and emission dynamics, we identified the mechanisms responsible for emission enhancement and the position of the plasmonic resonance.
The Role of Autophagy and Autophagy Receptor NDP52 in Microbial Infections
Authors: Fan Shuangqi , Wu Keke , Zhao Mengpo , Zhu Erpeng , Ma Shengming , Chen Yuming , Ding Hongxing , Yi Lin , Zhao Mingqiu , Chen Jinding
Published: March 2020

Autophagy is a general protective mechanism for maintaining homeostasis in eukaryotic cells, regulating cellular metabolism, and promoting cell survival by degrading and recycling cellular components under stress conditions. The degradation pathway that is mediated by autophagy receptors is called selective autophagy, also named as xenophagy. Autophagy receptor NDP52 acts as a ‘bridge’ between autophagy and the ubiquitin-proteasome system, and it also plays an important role in the process of selective autophagy. Pathogenic microbial infections cause various diseases in both humans and animals, posing a great threat to public health. Increasing evidence has revealed that autophagy and autophagy receptors are involved in the life cycle of pathogenic microbial infections. The interaction between autophagy receptor and pathogenic microorganism not only affects the replication of these microorganisms in the host cell, but it also affects the host’s immune system. This review aims to discuss the effects of autophagy on pathogenic microbial infection and replication, and summarizes the mechanisms by which autophagy receptors interact with microorganisms. While considering the role of autophagy receptors in microbial infection, NDP52 might be a potential target for developing effective therapies to treat pathogenic microbial infections.
Potential Mechanisms of AtNPR1 Mediated Resistance against Huanglongbing (HLB) in Citrus
Authors: Qiu Wenming , Soares Juliana , Pang Zhiqian , Huang Yixiao , Sun Zhonghai , Wang Nian , Grosser Jude , Dutt Manjul
Published: March 2020

Huanglongbing (HLB), a bacterial disease caused by Candidatus Liberibacter asiaticus (CLas), is a major threat to the citrus industry. In a previous study conducted by our laboratory, several citrus transgenic trees expressing the Arabidopsis thaliana NPR1 (AtNPR1) gene remained HLB-free when grown in a field site under high HLB disease pressure. To determine the molecular mechanisms behind AtNPR1-mediated tolerance to HLB, a transcriptome analysis was performed using AtNPR1 overexpressing transgenic trees and non-transgenic trees as control, from which we identified 57 differentially expressed genes (DEGs). Data mining revealed the enhanced transcription of genes encoding pathogen-associated molecular patterns (PAMPs), transcription factors, leucine-rich repeat receptor kinases (LRR-RKs), and putative ankyrin repeat-containing proteins. These proteins were highly upregulated in the AtNPR1 transgenic line compared to the control plant. Furthermore, analysis of protein–protein interactions indicated that AtNPR1 interacts with CsNPR3 and CsTGA5 in the nucleus. Our results suggest that AtNPR1 positively regulates the innate defense mechanisms in citrus thereby boosting resistance and effectively protecting the plant against HLB.
Adiponectin and Cognitive Decline
Authors: Rizzo Maria Rosaria , Fasano Renata , Paolisso Giuseppe
Published: March 2020

Adiponectin (ADPN) is a plasma protein secreted by adipose tissue showing pleiotropic effects with anti-diabetic, anti-atherogenic, and anti-inflammatory properties. Initially, it was thought that the main role was only the metabolism control. Later, ADPN receptors were also found in the central nervous system (CNS). In fact, the receptors AdipoR1 and AdipoR2 are expressed in various areas of the brain, including the hypothalamus, hippocampus, and cortex. While AdipoR1 regulates insulin sensitivity through the activation of the AMP-activated protein kinase (AMPK) pathway, AdipoR2 stimulates the neural plasticity through the activation of the peroxisome proliferator-activated receptor alpha (PPARα) pathway that inhibits inflammation and oxidative stress. Overall, based on its central and peripheral actions, ADPN appears to have neuroprotective effects by reducing inflammatory markers, such as C-reactive protein (PCR), interleukin 6 (IL6), and Tumor Necrosis Factor a (TNFa). Conversely, high levels of inflammatory cascade factors appear to inhibit the production of ADPN, suggesting bidirectional modulation. In addition, ADPN appears to have insulin-sensitizing action. It is known that a reduction in insulin signaling is associated with cognitive impairment. Based on this, it is of great interest to investigate the mechanism of restoration of the insulin signal in the brain as an action of ADPN, because it is useful for testing a possible pharmacological treatment for the improvement of cognitive decline. Anyway, if ADPN regulates neuronal functioning and cognitive performances by the glycemic metabolic system remains poorly explored. Moreover, although the mechanism is still unclear, women compared to men have a doubled risk of developing cognitive decline. Several studies have also supported that during the menopausal transition, the estrogen reduction can adversely affect the brain, in particular, verbal memory and verbal fluency. During the postmenopausal period, in obese and insulin-resistant individuals, ADPN serum levels are significantly reduced. Our recent study has evaluated the relationship between plasma ADPN levels and cognitive performances in menopausal women. Thus, the aim of this review is to summarize both the mechanisms and the effects of ADPN in the central nervous system and the relationship between plasma ADPN levels and cognitive performances, also in menopausal women.
The Fibroblast Growth Factor Receptors in Breast Cancer: from Oncogenesis to Better Treatments
Authors: Sobhani Navid , Fan Chunmei , O. Flores-Villanueva Pedro , Generali Daniele , Li Yong
Published: March 2020

Breast cancer (BC) is the most frequent form of malignancy and second only to lung cancer as cause of deaths in women. Notwithstanding many progresses made in the field, metastatic BC has a very poor prognosis. As therapies are becoming more personalized to meet the needs of patients, a better knowledge of the molecular biology leading to the disease unfolds the possibility to project more precise compounds or antibodies targeting definite alteration at the molecular level and functioning on such cancer-causing molecules expressed in cancer cells of patients, or present as antigens on the surface of cancer cell membranes. Fibroblast growth factor receptor (FGFR) is one of such druggable targets, activated by its own ligands -namely the Fibroblast Growth Factors (FGFs). This pathway provides a vast range of interesting molecular targets pursued at different levels of clinical investigation. Herein we provide an update on the knowledge of genetic alterations of the receptors in breast cancer, their role in tumorigenesis and the most recent drugs against this particular receptor for the treatment of the disease.
Norepinephrine Regulation of Ventromedial Hypothalamic Nucleus Metabolic-Sensory Neuron 5′-AMP-Activated Protein Kinase Activity: Impact of Estradiol
Authors: Mahmood A. S. M. Hasan , Uddin Md. Main , Ibrahim Mostafa M. H. , Briski Karen P.
Published: March 2020

The mediobasal hypothalamus (MBH) shapes the neural regulation of glucostasis by 5′-AMP-activated protein kinase (AMPK)-dependent mechanisms. Yet, the neurochemical identity and neuroanatomical distribution of MBH neurons that express glucoprivic-sensitive AMPK remain unclear. The neurotransmitters γ-aminobutyric acid (GABA) and nitric oxide (NO) act within the MBH to correspondingly inhibit or stimulate glucose counter-regulation. The current review highlights recent findings that GABA and NO, neurons located in the ventromedial hypothalamic nucleus (VMN), a distinct important element of the MBH, are direct targets of noradrenergic regulatory signaling, and thereby, likely operate under the control of hindbrain metabolic-sensory neurons. The ovarian hormone estradiol acts within the VMN to govern energy homeostasis. Discussed here is current evidence that estradiol regulates GABA and NO nerve cell receptivity to norepinephrine and moreover, controls the noradrenergic regulation of AMPK activity in each cell type. Future gains in insight on mechanisms underpinning estradiol’s impact on neurotransmitter communication between the hindbrain and hypothalamic AMPKergic neurons are expected to disclose viable new molecular targets for the therapeutic simulation of hormonal enhancement of neuro-metabolic stability during circumstances of diminished endogenous estrogen secretion or glucose dysregulation.
Overexpression of NRF1-742 or NRF1-772 Reduces Arsenic-Induced Cytotoxicity and Apoptosis in Human HaCaT Keratinocytes
Authors: Wang Shuai , Cheng Hao , Wang Linlin , Zhao Rui , Guan Dawei
Published: March 2020

Increasing evidence indicates that human exposure to inorganic arsenic causes cutaneous diseases and skin cancers. Nuclear factor erythroid 2-like 1 (NRF1) belongs to the cap “n” collar (CNC) basic-region leucine zipper (bZIP) transcription factor family and regulates antioxidant response element (ARE) genes. The human NRF1 gene is transcribed into multiple isoforms, which contain 584, 616, 742, 761, or 772 amino acids. We previously demonstrated that the long isoforms of NRF1 (i.e., NRF1-742, NRF1-761 and NRF1-772) are involved in the protection of human keratinocytes from acute arsenic cytotoxicity by enhancing the cellular antioxidant response. The aim of the current study was to investigate the roles of NRF1-742 and NRF1-772 in the arsenic-induced antioxidant response and cytotoxicity. We found that overexpression of NRF1-742 or NRF1-772 in human HaCaT keratinocytes decreased susceptibility to arsenic-induced apoptosis and cytotoxicity. In addition, we characterized the different protein bands observed for NRF1-742 and NRF1-772 by western blotting. The posttranslational modifications and nuclear translocation of these isoforms differed and were partially affected by arsenic exposure. Antioxidant protein levels were increased in the NRF1-742 and NRF1-772-overexpressing cell lines. The upregulation of antioxidant protein levels was partly due to the translation of nuclear factor erythroid 2-like 2 (NRF2) and its increased nuclear transport. Overall, overexpression of NRF1-742 and NRF1-772 protected HaCaT cells from arsenic-induced cytotoxicity, mainly through translational modifications and the promotion of antioxidant gene expression.
Lysophosphatidic Acid and Hematopoiesis: From Microenvironmental Effects to Intracellular Signaling
Authors: Lin Kuan-Hung , Chiang Jui-Chung , Ho Ya-Hsuan , Yao Chao-Ling , Lee Hsinyu
Published: March 2020

Vertebrate hematopoiesis is a complex physiological process that is tightly regulated by intracellular signaling and extracellular microenvironment. In recent decades, breakthroughs in lineage-tracing technologies and lipidomics have revealed the existence of numerous lipid molecules in hematopoietic microenvironment. Lysophosphatidic acid (LPA), a bioactive phospholipid molecule, is one of the identified lipids that participates in hematopoiesis. LPA exhibits various physiological functions through activation of G-protein-coupled receptors. The functions of these LPARs have been widely studied in stem cells, while the roles of LPARs in hematopoietic stem cells have rarely been examined. Nonetheless, mounting evidence supports the importance of the LPA-LPAR axis in hematopoiesis. In this article, we have reviewed regulation of hematopoiesis in general and focused on the microenvironmental and intracellular effects of the LPA in hematopoiesis. Discoveries in these areas may be beneficial to our understanding of blood-related disorders, especially in the context of prevention and therapy for anemia.
Affinity-Bead Assisted Mass Spectrometry (Affi-BAMS): A Multiplexed Microarray Platform for Targeted Proteomics
Authors: Hamza Ghaith M. , Bergo Vladislav B. , Mamaev Sergey , Wojchowski Don M. , Toran Paul , Worsfold Camilla R. , Castaldi M. Paola , Silva Jeffrey C.
Published: March 2020

The ability to quantitatively probe diverse panels of proteins and their post-translational modifications (PTMs) across multiple samples would aid a broad spectrum of biological, biochemical and pharmacological studies. We report a novel, microarray analytical technology that combines immuno-affinity capture with Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS), which is capable of supporting highly multiplexed, targeted proteomic assays. Termed “Affinity-Bead Assisted Mass Spectrometry” (Affi-BAMS), this LC-free technology enables development of highly specific and customizable assay panels for simultaneous profiling of multiple proteins and PTMs. While affinity beads have been used previously in combination with MS, the Affi-BAMS workflow uses enrichment on a single bead that contains one type of antibody, generally capturing a single analyte (protein or PTM) while having enough binding capacity to enable quantification within approximately 3 orders of magnitude. The multiplexing capability is achieved by combining Affi-BAMS beads with different protein specificities. To enable screening of bead-captured analytes by MS, we further developed a novel method of performing spatially localized elution of targets from individual beads arrayed on a microscope slide. The resulting arrays of micro spots contain highly concentrated analytes localized within 0.5 mm diameter spots that can be directly measured using MALDI MS. While both intact proteins and protein fragments can be monitored by Affi-BAMS, we initially focused on applying this technology for bottom-up proteomics to enable screening of hundreds of samples per day by combining the robust magnetic bead-based workflow with the high throughput nature of MALDI MS acquisition. To demonstrate the variety of applications and robustness of Affi-BAMS, several studies are presented that focus on the response of 4EBP1, RPS6, ERK1/ERK2, mTOR, Histone H3 and C-MET to stimuli including rapamycin, H2O2, EPO, SU11274, Staurosporine and Vorinostat.
Comprehensive Genome Analysis on the Novel Species Sphingomonas panacis DCY99T Reveals Insights into Iron Tolerance of Ginseng
Authors: Kim Yeon-Ju , Park Joon Young , Balusamy Sri Renukadevi , Huo Yue , Nong Linh Khanh , Thi Le Hoa , Yang Deok Chun , Kim Donghyuk
Published: March 2020

Plant growth-promoting rhizobacteria play vital roles not only in plant growth, but also in reducing biotic/abiotic stress. Sphingomonas panacis DCY99T is isolated from soil and root of Panax ginseng with rusty root disease, characterized by raised reddish-brown root and this is seriously affects ginseng cultivation. To investigate the relationship between 159 sequenced Sphingomonas strains, pan-genome analysis was carried out, which suggested genomic diversity of the Sphingomonas genus. Comparative analysis of S. panacis DCY99T with Sphingomonas sp. LK11 revealed plant growth-promoting potential of S. panacis DCY99T through indole acetic acid production, phosphate solubilizing, and antifungal abilities. Detailed genomic analysis has shown that S. panacis DCY99T contain various heavy metals resistance genes in its genome and the plasmid. Functional analysis with Sphingomonas paucimobilis EPA505 predicted that S. panacis DCY99T possess genes for degradation of polyaromatic hydrocarbon and phenolic compounds in rusty-ginseng root. Interestingly, when primed ginseng with S. panacis DCY99T during high concentration of iron exposure, iron stress of ginseng was suppressed. In order to detect S. panacis DCY99T in soil, biomarker was designed using spt gene. This study brings new insights into the role of S. panacis DCY99T as a microbial inoculant to protect ginseng plants against rusty root disease.
On the Trail of Tetu1: Genome-Wide Discovery of CACTA Transposable Elements in Sunflower Genome
Authors: Ventimiglia Maria , Pugliesi Claudio , Vangelisti Alberto , Usai Gabriele , Giordani Tommaso , Natali Lucia , Cavallini Andrea , Mascagni Flavia
Published: March 2020

Much has been said about sunflower (Helianthus annuus L.) retrotransposons, representing the majority of the sunflower’s repetitive component. By contrast, class II transposons remained poorly described within this species, as they present low sequence conservation and are mostly lacking coding domains, making the identification and characterization of these transposable elements difficult. The transposable element Tetu1, is a non-autonomous CACTA-like element that has been detected in the coding region of a CYCLOIDEA (CYC) gene of a sunflower mutant, tubular ray flower (turf). Based on our knowledge of Tetu1, the publicly available genome of sunflower was fully scanned. A combination of bioinformatics analyses led to the discovery of 707 putative CACTA sequences: 84 elements with complete ends and 623 truncated elements. A detailed characterization of the identified elements allowed further classification into three subgroups of 347 elements on the base of their terminal repeat sequences. Only 39 encode a protein similar to known transposases (TPase), with 10 TPase sequences showing signals of activation. Finally, an analysis of the proximity of CACTA transposons to sunflower genes showed that the majority of CACTA elements are close to the nearest gene, whereas a relevant fraction resides within gene-encoding sequences, likely interfering with sunflower genome functionality and organization.