bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photoreceptor alteration in intermediate age-related macular degeneration
Authors: Borrelli Enrico , Sacconi Riccardo , Zuccaro Biancamaria , Cavalleri Michele , Bordato Alessandro , Zucchiatti Ilaria , Querques Lea , Bandello Francesco , Querques Giuseppe 
Published: December 2020

AbstractThe aim of this study was to analyze photoreceptor alterations occurring in eyes with intermediate age-related macular degeneration (AMD) and to investigate their associations with choriocapillaris (CC) flow. In this retrospective case–control study, we collected data from 35 eyes with intermediate AMD from 35 patients who had swept source optical coherence tomography structural and angiography imaging obtained. A control group of 35 eyes from 35 healthy subjects was included for comparison. Our main outcome measure for comparison between groups was the normalized reflectivity of en face image segmented at the ellipsoid zone (EZ) level, which was calculated to quantify the photoreceptor damage. OCTA metrics to quantify CC flow signal were also computed. These metrics were measured in a circle centered on the fovea and with a diameter of 5 mm. In intermediate AMD eyes, the macular area occupied by drusen was identified. Therefore, the EZ reflectivity and CC flow signal were separately measured in regions without drusen (“drusen-free” region). Measurements were generated using previously published algorithms. Mean ± SD age was 74.1 ± 6.8 years in the intermediate AMD group and 72.1 ± 6.0 years in the control group (p = 0.206). The normalized EZ reflectivity was 0.76 ± 0.10 in the intermediate AMD group and 0.85 ± 0.08 in the control group (p < .0001). In the “drusen-free” region, the normalized EZ reflectivity was 0.77 ± 0.10 (p < .0001 vs. healthy controls) and was positively correlated with the CC flow signal density (ρ = − 0.340 and p = 0.020). In conclusion, eyes with intermediate AMD exhibit a diffuse reduced EZ normalized reflectivity, and this reduction is correlated with CC flow signal in the regions without drusen. This study supports the concept of the damage of the unit comprised of photoreceptor, CC, and intervening tissues as an early event in AMD.
Maternal proteomic profiling reveals alterations in lipid metabolism in late-onset fetal growth restriction
Authors: Paules Cristina , Youssef Lina , Miranda Jezid , Crovetto Francesca , Estanyol Josep Maria , Fernandez Guerau , Crispi Fatima , Gratacós Eduard 
Published: December 2020

AbstractFetal growth restriction defined as the failure to achieve the fetal genetic growth potential is a major cause of perinatal morbidity and mortality. The role of maternal adaptations to placental insufficiency in this disorder is still not fully understood. We aimed to investigate the biological processes and protein–protein interactions involved in late-onset fetal growth restriction in particular. We applied 2D nano LC–MS/MS proteomics analysis on maternal blood samples collected at the time of delivery from 5 singleton pregnancies with late-onset fetal growth restriction and 5 uncomplicated pregnancies. Data were analyzed using R package “limma” and Ingenuity Pathway Analysis. 25 proteins showed significant changes in their relative abundance in late-onset fetal growth restriction (p value < 0.05). Direct protein–protein interactions network demonstrated that Neurogenic locus notch homolog protein 1 (NOTCH1) was the most significant putative upstream regulator of the observed profile. Gene ontology analysis of these proteins revealed the involvement of 14 canonical pathways. The most significant biological processes were efflux of cholesterol, efflux of phospholipids, adhesion of blood cells, fatty acid metabolism and dyslipidemia. Future studies are warranted to validate the potential role of the detected altered proteins as potential therapeutic targets in the late-onset form of fetal growth restriction.
Generation, analysis, and transformation of macro-chloroplast Potato (Solanum tuberosum) lines for chloroplast biotechnology
Authors: Occhialini Alessandro , Pfotenhauer Alexander C. , Frazier Taylor P. , Li Li , Harbison Stacee A. , Lail Andrew J. , Mebane Zachary , Piatek Agnieszka A. , Rigoulot Stephen B. , Daniell Henry , Stewart C. Neal , Lenaghan Scott C. 
Published: December 2020

AbstractChloroplast biotechnology is a route for novel crop metabolic engineering. The potential bio-confinement of transgenes, the high protein expression and the possibility to organize genes into operons represent considerable advantages that make chloroplasts valuable targets in agricultural biotechnology. In the last 3 decades, chloroplast genomes from a few economically important crops have been successfully transformed. The main bottlenecks that prevent efficient transformation in a greater number of crops include the dearth of proven selectable marker gene-selection combinations and tissue culture methods for efficient regeneration of transplastomic plants. The prospects of increasing organelle size are attractive from several perspectives, including an increase in the surface area of potential targets. As a proof-of-concept, we generatedSolanum tuberosum(potato) macro-chloroplast lines overexpressing the tubulin-like GTPase protein geneFtsZ1fromArabidopsis thaliana. Macro-chloroplast lines exhibited delayed growth at anthesis; however, at the time of harvest there was no significant difference in height between macro-chloroplast and wild-type lines. Macro-chloroplasts were successfully transformed by biolistic DNA-delivery and efficiently regenerated into homoplasmic transplastomic lines. We also demonstrated that macro-chloroplasts accumulate the same amount of heterologous protein than wild-type organelles, confirming efficient usage in plastid engineering. Advantages and limitations of using enlarge compartments in chloroplast biotechnology are discussed.
The dorsal arcopallium of chicks displays the expression of orthologs of mammalian fear related serotonin receptor subfamily genes
Authors: Fujita Toshiyuki , Aoki Naoya , Mori Chihiro , Fujita Eiko , Matsushima Toshiya , Homma Koichi J. , Yamaguchi Shinji 
Published: December 2020

AbstractFear is an adaptive emotion that elicits defensive behavioural responses against aversive threats in animals. In mammals, serotonin receptors (5-HTRs) have been shown to modulate fear-related neural circuits in the basolateral amygdala complex (BLA). To understand the phylogenetic continuity of the neural basis for fear, it is important to identify the neural circuit that processes fear in other animals. In birds, fear-related behaviours were suggested to be processed in the arcopallium/amygdala complex and modulated by the serotonin (5-HT) system. However, details about the distribution of 5-HTRs in the avian brain are very sparsely reported, and the 5-HTR that is potentially involved in fear-related behaviour has not been elucidated. In this study, we showed that orthologs of mammalian 5-HTR genes that are expressed in the BLA, namely 5-HTR1A, 5-HTR1B, 5-HTR2A, 5-HTR2C, 5-HTR3A, and 5-HTR4, are expressed in a part of the chick arcopallium/amygdala complex called the dorsal arcopallium. This suggests that serotonergic regulation in the dorsal arcopallium may play an important role in regulating fear-related behaviour in birds. Our findings can be used as a basis for comparing the processing of fear and its serotonergic modulation in the mammalian amygdala complex and avian arcopallium/amygdala complex.
Single-cell RNA-seq reveals CD16- monocytes as key regulators of human monocyte transcriptional response to Toxoplasma
Authors: Patir Anirudh , Gossner Anton , Ramachandran Prakash , Alves Joana , Freeman Tom C. , Henderson Neil C. , Watson Mick , Hassan Musa A. 
Published: December 2020

AbstractMonocytes are among the major myeloid cells that respond toToxoplasma, a ubiquitous foodborne that infects ≥ 1 billion people worldwide, in human peripheral blood. As such, a molecular understanding of human monocyte-Toxoplasmainteractions can expedite the development of novel human toxoplasmosis control strategies. Current molecular studies on monocyte-Toxoplasmainteractions are based on average cell or parasite responses across bulk cell populations. Although informative, population-level averages of monocyte responses toToxoplasmahave sometimes produced contradictory results, such as whether CCL2 or IL12 define effective monocyte responses to the parasite. Here, we used single-cell dual RNA sequencing (scDual-Seq) to comprehensively define, for the first time, the monocyte and parasite transcriptional responses that underpin human monocyte-Toxoplasmaencounters at the single cell level. We report extreme transcriptional variability between individual monocytes. Furthermore, we report thatToxoplasma-exposed and unexposed monocytes are transcriptionally distinguished by a reactive subset of CD14+CD16-monocytes. Functional cytokine assays on sorted monocyte populations show that the infection-distinguishing monocytes secrete high levels of chemokines, such as CCL2 and CXCL5. These findings uncover theToxoplasma-induced monocyte transcriptional heterogeneity and shed new light on the cell populations that largely define cytokine and chemokine secretion in human monocytes exposed toToxoplasma.
Common and personal target genes of the micronutrient vitamin D in primary immune cells from human peripheral blood
Authors: Hanel Andrea , Neme Antonio , Malinen Marjo , Hämäläinen Emmi , Malmberg Henna-Riikka , Etheve Stéphane , Tuomainen Tomi-Pekka , Virtanen Jyrki K. , Bendik Igor , Carlberg Carsten 
Published: December 2020

AbstractVitamin D is essential for the function of the immune system. In this study, we treated peripheral blood mononuclear cells (PBMCs) of healthy adults with the biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) using two different approaches: single repeats with PBMCs obtained from a cohort of 12 individuals and personalized analysis based on triplicates of five study participants. This identified 877 (cohort approach) and 3951 (personalized approach) genes that significantly (p < 0.05) changed their expression 24 h after 1,25(OH)2D3 stimulation. From these, 333 and 1232 were classified as supertargets, a third of which were identified as novel. Individuals differed largely in their vitamin D response not only by the magnitude of expression change but also by their personal selection of (super)target genes. Functional analysis of the target genes suggested the overarching role of vitamin D in the regulation of metabolism, proliferation and differentiation, but in particular in the control of functions mediated by the innate and adaptive immune system, such as responses to infectious diseases and chronic inflammatory disorders. In conclusion, immune cells are an important target of vitamin D and common genes may serve as biomarkers for personal responses to the micronutrient.
Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae
Authors: Hanasaki Miki , Yaku Keisuke , Yamauchi Motohiro , Nakagawa Takashi , Masumoto Hiroshi 
Published: December 2020

AbstractCellular metabolism is directly or indirectly associated with various cellular processes by producing a variety of metabolites. Metabolic alterations may cause adverse effects on cell viability. However, some alterations potentiate the rescue of the malfunction of the cell system. Here, we found that the alteration of glucose metabolism suppressed genome instability caused by the impairment of chromatin structure. Deletion of the TDH2 gene, which encodes glyceraldehyde 3-phospho dehydrogenase and is essential for glycolysis/gluconeogenesis, partially suppressed DNA damage sensitivity due to chromatin structure, which was persistently acetylated histone H3 on lysine 56 in cells with deletions of both HST3 and HST4, encoding NAD+-dependent deacetylases. tdh2 deletion also restored the short replicative lifespan of cells with deletion of sir2, another NAD+-dependent deacetylase, by suppressing intrachromosomal recombination in rDNA repeats increased by the unacetylated histone H4 on lysine 16. tdh2 deletion also suppressed recombination between direct repeats in hst3∆ hst4∆ cells by suppressing the replication fork instability that leads to both DNA deletions among repeats. We focused on quinolinic acid (QUIN), a metabolic intermediate in the de novo nicotinamide adenine dinucleotide (NAD+) synthesis pathway, which accumulated in the tdh2 deletion cells and was a candidate metabolite to suppress DNA replication fork instability. Deletion of QPT1, quinolinate phosphoribosyl transferase, elevated intracellular QUIN levels and partially suppressed the DNA damage sensitivity of hst3∆ hst4∆ cells as well as tdh2∆ cells. qpt1 deletion restored the short replicative lifespan of sir2∆ cells by suppressing intrachromosomal recombination among rDNA repeats. In addition, qpt1 deletion could suppress replication fork slippage between direct repeats. These findings suggest a connection between glucose metabolism and genomic stability.
Autophagy: a necessary defense against extreme cadmium intoxication in a multigenerational 2D experiment
Authors: Babczyńska Agnieszka , Nowak Agnieszka , Kafel Alina , Łozowski Bartosz , Rost-Roszkowska Magdalena , Tarnawska Monika , Augustyniak Maria , Sawadro Marta , Molenda Agnieszka 
Published: December 2020

AbstractAutophagy is a natural process that aims to eliminate malfunctioning cell parts, organelles or molecules under physiological conditions. It is also induced in response to infection, starvation or oxidative stress to provide energy in case of an energy deficit. The aim of this 2-dimensional study was to test if, and if so, how, this process depends on the concentration of cadmium in food (with Cd concentrations from 0 to 352 μg of Cd per g of food (dry weight)—D1 dimension) and the history of selection pressure (160 vs 20 generations of exposure to Cd—D2 dimension). For the study, the 5th instar larvae of a unique strain of the moth Spodoptera exigua that was selected for cadmium tolerance for 160 generations (44 μg of Cd per g of food (dry weight)), as well as 20-generation (11, 22 and 44 μg of Cd per g of food (dry weight)) and control strains, were used. Autophagy intensity was measured by means of flow cytometry and compared with life history parameters: survivability and duration of the 3rd larval stage. The highest values of autophagy markers were found in the groups exposed to the highest Cd concentration and corresponded (with a significant correlation coefficient) to an increased development duration or decreased survivorship in the respective groups. In conclusion, autophagy is probably initiated only if any other defense mechanisms, e.g., antioxidative mechanisms, are not efficient. Moreover, in individuals from pre-exposed populations, the intensity of autophagy is lower.
Effect of immunosuppressants on a mouse model of osteogenesis imperfecta type V harboring a heterozygous Ifitm5 c.-14C > T mutation
Authors: Hanagata Nobutaka , Takemura Taro , Kamimura Keiko , Koda Toshiaki 
Published: December 2020

AbstractOsteogenesis imperfecta (OI) type V is an autosomal dominant disorder caused by the c.-14C > T mutation in the interferon-induced transmembrane protein 5 gene (IFITM5), however, its onset mechanism remains unclear. In this study, heterozygous c.-14C > T mutant mice were developed to investigate the effect of immunosuppressants (FK506 and rapamycin) on OI type V. Among the mosaic mice generated by Crispr/Cas9-based technology, mice with less than 40% mosaic ratio of c.-14C > T mutation survived, whereas those with more than 48% mosaic ratio exhibited lethal skeletal abnormalities with one exception. All heterozygous mutants obtained by mating mosaic mice with wild-type mice exhibited a perinatal lethal phenotype due to severe skeletal abnormalities. Administration of FK506, a calcineurin inhibitor, in the heterozygous fetuses improved bone mineral content (BMC) of the neonates, although it did not save the neonates from the lethal effects of the mutation, whereas rapamycin, an mTOR inhibitor, reduced BMC, suggesting that mTOR signaling is involved in the bone mineralization of heterozygous mutants. These findings could clarify certain aspects of the onset mechanism of OI type V and enable development of therapeutics for this condition.
Muscle and epidermal contributions of the structural protein β-spectrin promote hypergravity-induced motor neuron axon defects in C. elegans
Authors: Kalichamy Saraswathi S. , Alcantara Alfredo V. , Kim Ban-Seok , Park Junsoo , Yoon Kyoung-hye , Lee Jin I. 
Published: December 2020

AbstractBiology is adapted to Earth’s gravity force, and the long-term effects of varying gravity on the development of animals is unclear. Previously, we reported that high gravity, called hypergravity, increases defects in the development of motor neuron axons in the nematode Caenorhabditis elegans. Here, we show that a mutation in the unc-70 gene that encodes the cytoskeletal β-spectrin protein suppresses hypergravity-induced axon defects. UNC-70 expression is required in both muscle and epidermis to promote the axon defects in high gravity. We reveal that the location of axon defects is correlated to the size of the muscle cell that the axon traverses. We also show that mutations that compromise key proteins of hemidesmosomal structures suppress hypergravity-induced axon defects. These hemidesmosomal structures play a crucial role in coupling mechanical force between the muscle, epidermis and the external cuticle. We speculate a model in which the rigid organization of muscle, epidermal and cuticular layers under high gravity pressure compresses the narrow axon migration pathways in the extracellular matrix hindering proper axon pathfinding of motor neurons.
Sustained blood glutamate scavenging enhances protection in ischemic stroke
Authors: Zaghmi Ahlem , Dopico-López Antonio , Pérez-Mato María , Iglesias-Rey Ramón , Hervella Pablo , Greschner Andrea A. , Bugallo-Casal Ana , da Silva Andrés , Gutiérrez-Fernández María , Castillo José , Pérez Francisco Campos , Gauthier Marc A. 
Published: December 2020

AbstractStroke is a major cause of morbidity, mortality, and disability. During ischemic stroke, a marked and prolonged rise of glutamate concentration in the brain causes neuronal cell death. This study explores the protective effect of a bioconjugate form of glutamate oxaloacetate transaminase (hrGOT), which catalyzes the depletion of blood glutamate in the bloodstream for ~6 days following a single administration. When treated with this bioconjugate, a significant reduction of the infarct volume and a better retention of sensorimotor function was observed for ischemic rats compared to those treated with saline. Moreover, the equivalent dose of native hrGOT yielded similar results to the saline treated group for some tests. Targeting the bioconjugate to the blood-brain-barrier did not improve its performance. The data suggest that the bioconjugates draw glutamate out of the brain by displacing homeostasis between the different glutamate pools of the body.
The intracellular lipid-binding domain of human Na+/H+ exchanger 1 forms a lipid-protein co-structure essential for activity
Authors: Hendus-Altenburger Ruth , Vogensen Jens , Pedersen Emilie Skotte , Luchini Alessandra , Araya-Secchi Raul , Bendsoe Anne H. , Prasad Nanditha Shyam , Prestel Andreas , Cardenas Marité , Pedraz-Cuesta Elena , Arleth Lise , Pedersen Stine F. , Kragelund Birthe B. 
Published: December 2020

AbstractDynamic interactions of proteins with lipid membranes are essential regulatory events in biology, but remain rudimentarily understood and particularly overlooked in membrane proteins. The ubiquitously expressed membrane protein Na+/H+-exchanger 1 (NHE1) regulates intracellular pH (pHi) with dysregulation linked to e.g. cancer and cardiovascular diseases. NHE1 has a long, regulatory cytosolic domain carrying a membrane-proximal region described as a lipid-interacting domain (LID), yet, the LID structure and underlying molecular mechanisms are unknown. Here we decompose these, combining structural and biophysical methods, molecular dynamics simulations, cellular biotinylation- and immunofluorescence analysis and exchanger activity assays. We find that the NHE1-LID is intrinsically disordered and, in presence of membrane mimetics, forms a helical αα-hairpin co-structure with the membrane, anchoring the regulatory domain vis-a-vis the transport domain. This co-structure is fundamental for NHE1 activity, as its disintegration reduced steady-state pHi and the rate of pHi recovery after acid loading. We propose that regulatory lipid-protein co-structures may play equally important roles in other membrane proteins.
C1QTNF6 regulates cell proliferation and apoptosis of NSCLC in vitro and in vivo
Authors: Zhang Wei , Feng Ganzhu 
Published: December 2020

Abstract
Objectives: Lung cancer has been reported as the leading cause of cancer-associated deaths in humans, and its incidence continues to increase in the world. A growing number of studies have shown that dysregulated genes are associated with the occurrence and poor prognosis of a variety of tumors, including non-small cell lung cancer (NSCLC). C1q/tumor necrosis factor-related protein 6 (C1QTNF6), a member of the C1q/tumor necrosis factor-related protein (CTRP) family, has been revealed to play a role in carcinogenesis and cancer progression. Nevertheless, the effects and mechanisms of C1QTNF6 in NSCLC remain unrevealed. Materials and methods: MTT (3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide) and colony formation, flow cytometric and transwell assays were performed to explore the cell function. Real-time PCR (RT-PCR) and Western blot were used to analyze the mRNA and protein expression. Results: In the present study, we found that C1QTNF6 significantly promoted the proliferation of SPCA1 and A549 cells by MTT and colony formation assays. In addition, down-regulation of C1QTNF6 weakened the tumor growth in vivo. Besides, C1QTNF6 remarkably reduced apoptosis by flow cytometric analysis and TUNEL assay. Furthermore, the capability of migration and invasion was obviously enhanced on C1QTNF6 overexpression. Conclusion: Overall, our results demonstrated that inhibition of C1QTNF6 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and in vivo of NSCLC. Based on the above results, our study provided us with a new and key perspective in understanding and treating NSCLC.