bluuebunny/crossref_metadata_2025_split huggingface dataset:
A large lipoprotein mediates target specificity for T6SS-dependent killing
Authors: Speare Lauren , Woo Madison , Dunn Anne K. , Septer Alecia N. 
Published: April 2021

AbstractInterbacterial competition is prevalent in host-associated microbiota, where it can shape community structure and function, impacting host health in both positive and negative ways. However, the factors that permit bacteria to discriminate among their various neighbors for targeted elimination of competitors remain elusive. We identified a specificity factor inVibriospecies that is used to target specific competitors for elimination. Here, we describe this specificity factor, which is associated with the broadly-distributed type VI secretion system (T6SS), by studying symbioticVibrio fischeri, which use the T6SS to compete for colonization sites in their squid host. We demonstrate that a large lipoprotein (TasL) allowsV. fischericells to restrict T6SS-dependent killing to certain genotypes by selectively integrating competitor cells into aggregates while excluding other cell types. TasL is also required for T6SS-dependent competition within juvenile squid, indicating the adhesion factor is active in the host. Because TasL homologs are found in other host-associated bacterial species, this newly-described specificity factor has the potential to impact microbiome structure within diverse hosts.
A chromosome-level genome assembly and annotation of a maize elite breeding line Dan340
Authors: Zhao Yikun , Wang Yuancong , Ma De , Feng Guang , Huo Yongxue , Liu Zhihao , Zhou Ling , Zhang Yunlong , Xu Liwen , Wang Liang , Zhao Han , Zhao Jiuran , Wang Fengge 
Published: April 2021

AbstractBackgroundMaize is not only one of the most important crops grown worldwide for food, forage, and biofuel, but also an important model organism for fundamental research in genetics and genomics. Owing to its importance in crop science, genetics and genomics, several reference genomes of common maize inbred line (genetic material) have been released, but some genomes of important genetic germplasm resources in maize breeding research are still lacking. The maize cultivar Dan340 is an excellent backbone inbred line of the Luda Red Cob Group with several desirable characteristics, such as disease resistance, lodging resistance, high combining ability, and wide adaptability.FindingsIn this study, we constructed a high-quality chromosome-level reference genome for Dan340 by combining PacBio long HiFi sequencing reads, Illumina short reads and chromosomal conformational capture (Hi-C) sequencing reads. The final assembly of the Dan340 genome was 2,348.72 Mb, including 2,738 contigs and 2,315 scaffolds with N50 of 41.49 Mb and 215.35 Mb, respectively. Repeat sequences accounted for 73.40% of the genome size and 39,733 protein-coding genes were annotated. Analysis of genes in the Dan340 genome, together with those from B73, Mo17 and SK, were clustered into 27,654 gene families. There were 1,806 genes from 359 gene families that were specific to Dan340, of which many had functional gene ontology annotations relating to “porphyrin-containing compound metabolic process”, “tetrapyrrole biosynthetic process”, and “tetrapyrrole metabolic process”.ConclusionsThe completeness and continuity of the genome were comparable to those of other important maize inbred lines. The assembly and annotation of this genome not only facilitates our understanding about of intraspecific genome diversity in maize, but also provides a novel resource for maize breeding improvement.Research AreasGenetics and Genomics; Agriculture, Plant GeneticsData Description
Intrinsic Lipid Curvatures of Mammalian Plasma Membrane Outer Leaflet Lipids and Ceramides
Authors: Kaltenegger Michael , Kremser Johannes , Frewein Moritz P. , Ziherl Primož , Bonthuis Douwe J. , Pabst Georg 
Published: April 2021

AbstractWe developed a global X-ray data analysis method to determine the intrinsic curvatures of lipids hosted in inverted hexagonal phases. In particular, we combined compositional modelling with molecular shape-based arguments to account for non-linear mixing effects of guest-in-host lipids on intrinsic curvature. The technique was verified by all-atom molecular dynamics simulations and applied to sphingomyelin and a series of phosphatidylcholines and ceramides with differing composition of the hydrocarbon chains. We report positive lipid curvatures for sphingomyelin and all phosphatidylcholines with disaturated and monounsaturated hydrocarbons. Substitution of the second saturated hydrocarbon with an unsaturated acyl chain in turn shifted the intrinsic lipid curvatures to negative values. All ceramides, with chain lengths varying between C2:0 and C24:0, displayed significant negative lipid curvature values. Moreover, we re-port non-additive mixing for C2:0 ceramide and sphingomyelin. Our findings manifest the high and manifold potential of lipids to modulate physiological membrane function.HighlightsMolecular shape based theory for non-linear lipid curvature mixingGlobal analysis of SAXS patterns inverted hexagonal phases using compositional modelling and Bayesian probability theoryMD simulations of inverted hexagonal phasesNon-additive mixing of palmitoyl sphingomyelin and C2:0 ceramide
Dorsal striatum and the temporal expectancy of an aversive event in Pavlovian odor fear learning
Authors: Boulanger-Bertolus Julie , Parrot Sandrine , Doyère Valérie , Mouly Anne-Marie 
Published: April 2021

AbstractInterval timing, the ability to encode and retrieve the memory of intervals from seconds to minutes, guides fundamental animal behaviors across the phylogenetic tree. In Pavlovian fear conditioning, an initially neutral stimulus (conditioned stimulus, CS) predicts the arrival of an aversive unconditioned stimulus (US, generally a mild foot-shock) at a fixed time interval. Although some studies showed that temporal relations between CS and US events are learned from the outset of conditioning, the question of the memory of time and its underlying neural network in fear conditioning is still poorly understood. The aim of the present study was to investigate the role of the dorsal striatum in timing intervals in odor fear conditioning in male rats. To assess the animal’s interval timing ability in this paradigm, we used the respiratory frequency. This enabled us to detect the emergence of temporal patterns related to the odor-shock time interval from the early stage of learning, confirming that rats are able to encode the odor-shock time interval after few training trials. We carried out reversible inactivation of the dorsal striatum before the acquisition session and before a shift in the learned time interval, and measured the effects of this treatment on the temporal pattern of the respiratory rate. In addition, using intracerebral microdialysis, we monitored extracellular dopamine level in the dorsal striatum throughout odor-shock conditioning and in response to a shift of the odor-shock time interval. Contrary to our initial predictions based on the existing literature on interval timing, we found evidence suggesting that transient inactivation of the dorsal striatum may favor a more precocious buildup of the respiratory frequency’s temporal pattern during the odor-shock interval in a manner that reflected the duration of the interval. Our data further suggest that the conditioning and the learning of a novel time interval were associated with a decrease in dopamine level in the dorsal striatum, but not in the nucleus accumbens. These findings prompt a reassessment of the role of the striatum and striatal dopamine in interval timing, at least when considering Pavlovian aversive conditioning.
RETRACTED: Pentoxifylline prevents epileptic seizure via modulating HMGB1/RAGE/TLR4 signalling pathway and improves memory in pentylenetetrazol kindling rats
Authors: Badawi Ghada A. , Shokr Mustafa M. , Zaki Hala F. , Mohamed Ahmed F. 
Published: April 2021

AbstractEpilepsy is a chronic widely prevalent neurologic disorder, affecting brain functions with a broad spectrum of deleterious consequences. High mobility group box1 (HMGB1) is a nuclear non‐histone protein that targets vital cell receptor of toll‐like receptor 4 (TLR4) and advanced glycation end products (RAGE). HMGB1 mediated TLR4/RAGE cascade has been scored as a key culprit in neuroinflammatory signalling that critically evokes development of impaired cognition and epilepsy. The current study aimed to investigate the neuroprotective effect of pentoxifylline (PTX) on pentylenetetrazol (PTZ)‐kindling rats by its anti‐inflammatory/antioxidant capacity and its impact on memory and cognition were investigated, too. PTZ was intraperitoneally injected 35 mg/kg, every 48 h, for 14 doses, to evoke kindling model. Phenytoin (30 mg/kg, i.p.) and PTX (60 mg/kg, i.p.) or their combination were given once daily for 27 days. PTX treatment showed a statistically significant effect on behavioural, histopathological and neurochemical analysis. PTX protected the PTZ kindling rats from epileptic seizures and improved memory and cognitive impairment through the Morris water maze (MWM) test. Furthermore, PTX reversed PTZ hippocampal neuronal loss by decreasing protein expression of amyloid‐β peptide (Aβ), Tau and β site‐amyloid precursor protein cleavage enzyme 1 (BACE1), associated with a marked reduction in expression of inflammatory mediators such as HMGB1, TL4, and RAGE proteins. Furthermore, PTX inhibited hippocampal apoptotic caspase 1 protein, total reactive oxygen species (TROS) along with upregulated erythroid 2‐related factor 2 (Nrf2) content. In conclusion, PTX or its combination with phenytoin represent a promising drug to inhibit the epilepsy progression via targeting the HMGB1/TLR4/RAGE signalling pathway.
Assessment of the safety and anti‐inflammatory effects of three Bacillus strains in the respiratory tract
Authors: Kim Hye‐Shin , Arellano Karina , Park Haryung , Todorov Svetoslav D. , Kim Bobae , Kang Hyeji , Park Yu Jin , Suh Dong Ho , Jung Eun Sung , Ji Yosep , Holzapfel Wilhelm H. 
Published: April 2021

SummaryChronic respiratory diseases are part of accumulating health problems partly due to worldwide increase in air pollution. By their antimicrobial and immunomodulatory properties, some probiotics constitute promising alternatives for the prevention and treatment of chronic respiratory diseases. We have isolated Bacillus strains from Korean fermented foods and selected three potentially probiotic strains (two Bacillus subtilis and one Bacillus amyloliquefaciens) based on safety, antimicrobial efficacy, activity against airborne pathogens and their immunomodulatory properties in vivo. Safety evaluation included in silico analysis for confirming absence of virulence genes. Safety for the respiratory tract was confirmed by an in vivo pathogenicity test using a murine model. Antimicrobial activity was displayed against several airborne pathogens. Potential antimicrobial metabolites such as 2,3‐butanediol and propylene glycol were identified as possible antagonistic agents. Immunomodulatory properties in vitro were confirmed by upregulation of IL‐10 expression in a macrophage cell line. Intranasal instillation and inhalation in an ovalbumin (OVA)‐induced lung inflammation murine model reduced T helper type 2 (Th2) cytokines at transcriptional and protein levels in the lungs. The safety and potentially beneficial role of these Bacillus strains could be demonstrated for the respiratory tract of a murine model.
Effects of differences in whey composition on the physicochemical properties of whey butter
Authors: Kasapcopur Eren , Mohammed Aram M , Colakoglu Abdullah S 
Published: April 2021

The objective of this work was to determine the effects of whey composition on the physicochemical properties of whey butter and compare with milk butter based on these properties. Whey samples were obtained from the whey processing plants located in different regions of Turkey. Whey composition influenced the major and minor components of whey butters. Differences among the whey butters were observed on titratable acidy (TA, 0.43–0.55%), acid value (AV, 0.75–0.90 mg KOH/g), moisture (17.33–19.05%), fat (80.23–81.47%), nonfat solid (0.66–1.20%), NaCl (0.10–0.23%), peroxide value (PV, 1.08–1.50 meq O2/kg), total carotenoids (1.78–2.21 mg/kg), γ‐ and total tocopherols (1.06–1.41 and 27.02–27.33 mg/kg, respectively), Ca (73.12–94.72 mg/kg), P (56.03–72.20 mg/kg), K (73.36–140.10 mg/kg), Mg (12.83–18.12 mg/kg), Na (63.95–165.85 mg/kg), total minerals (283.32–485.53 mg/kg), colour (L*, 86.46–89.52 and b*, 12.21–15.52) and certain fatty acids. The milk butters were one‐ to threefold lower in TA, AV, moisture, NaCl and PV and one‐ to 3.4‐fold higher in fat, nonfat solids, protein, total carotenoids, α‐, γ‐ and total tocopherols, Ca, P, K, Mg and total minerals. Whey butters were distinctly brighter and less yellower. Butter source had no effect on iodine value (35.39 ± 0.15 g I2/100 g), saponification value (225.22 ± 0.17 mg KOH/g), β‐tocopherol (0.41 ± 0.02 mg/kg), certain fatty acids, melting characteristic and thermo‐oxidative stability. The cluster analysis enabled the division of whey and milk butters into two separate groups. These results highlighted that partial transfer of certain compounds from milk to whey during cheese manufacturing and biochemical and chemical changes such as lipolysis, hydrolysis and oxidation that occur in the period from the whey production to butter processing were largely responsible for the differences in the whey and milk butter properties.
The Role of Moral Devaluation in Phasing Out Fossil Fuels: Limits for a Socioecological Fix
Authors: Furnaro Andrea 
Published: April 2021

AbstractBy putting into conversation theories of capital devaluation, the scholarship on the socioecological fix, and critical energy studies, this paper offers a conceptual framework to study the phase‐out of fossil fuel energy infrastructure. The concept of moral devaluation is presented, which emphasises the interaction of economic, political, and socioecological dimensions shaping the main forces, constraints, and regulatory mechanisms to devalue emission‐intensive fixed capital. This notion of moral devaluation is useful to inform empirical research on the institutional arrangements through which the devaluation of fixed fossil fuel capital is resisted and organised. Moreover, this notion complements current studies about the possibility of a capital switch to renewable energies as a socioecological fix to the climate and other entangled crises of capitalism, by emphasising that the devaluation of fixed capital represents a constraining condition for the rapid emergence of a socioecological fix based on fixed capital formation in the low‐carbon energy sector.
Pharmacological HIF‐PHD inhibition reduces renovascular resistance and increases glomerular filtration by stimulating nitric oxide generation
Authors: Burmakin Mikhail , Fasching Angelica , Kobayashi Hanako , Urrutia Andrés A. , Damdimopoulos Anastasios , Palm Fredrik , Haase Volker H. 
Published: April 2021

AbstractAimHypoxia‐inducible factors (HIFs) are O2‐sensitive transcription factors that regulate multiple biological processes which are essential for cellular adaptation to hypoxia. Small molecule inhibitors of HIF‐prolyl hydroxylase domain (PHD) dioxygenases (HIF‐PHIs) activate HIF‐dependent transcriptional programs and have broad clinical potential. HIF‐PHIs are currently in global late‐stage clinical development for the treatment of anaemia associated with chronic kidney disease. Although the effects of hypoxia on renal haemodynamics and function have been studied in animal models and in humans living at high altitude, the effects of pharmacological HIF activation on renal haemodynamics, O2 metabolism and metabolic efficiency are not well understood.MethodsUsing a cross‐sectional study design, we investigated renal haemodynamics, O2 metabolism, gene expression and NO production in healthy rats treated with different doses of HIF‐PHIs roxadustat or molidustat compared to vehicle control.ResultsSystemic administration of roxadustat or molidustat resulted in a dose‐dependent reduction in renovascular resistance (RVR). This was associated with increased glomerular filtration rate (GFR), urine flow and tubular sodium transport rate (TNa). Although both total O2 delivery and TNa were increased, more O2 was extracted per transported sodium in rats treated with high‐doses of HIF‐PHIs, suggesting a reduction in metabolic efficiency. Changes in RVR and GFR were associated with increased nitric oxide (NO) generation and substantially suppressed by pharmacological inhibition of NO synthesis.ConclusionsOur data provide mechanistic insights into dose‐dependent effects of short‐term pharmacological HIF activation on renal haemodynamics, glomerular filtration and O2 metabolism and identify NO as a major mediator of these effects.
Promoting children's inquiry performances in alternate reality games: A mobile concept mapping‐based questioning approach
Authors: Liang Hsin‐Yi , Hsu Tien‐Yu , Hwang Gwo‐Jen 
Published: April 2021

AbstractActive inquiry plays a key role in science education. To facilitate children's motivation, alternate reality games are applied to engage children actively in inquiry in authentic learning contexts. However, the complexity of real‐world contexts and the ambiguity of game puzzles increase the difficulty for children to conduct effective inquiries. To achieve successful inquiry‐based learning, concept mapping is an effective learning strategy to guide children to organise related information as well as to brainstorm for possible solutions. Accordingly, this study proposes a mobile concept mapping‐based questioning approach for environmental education. A quasi‐experimental study was conducted to evaluate the effectiveness of the proposed approach and the conventional questioning approach in game‐based inquiry‐based learning. The results showed that the proposed approach had a more significant effect on learning achievement, critical thinking, and learning attitude than the conventional questioning approach. However, cognitive overload negatively affected the children's learning. Besides, it was found that improper use of concept maps could limit their creative problem‐solving performances.
Practitioner notesWhat is already known about this topic

Alternate reality game (ARG) significantly promotes children’s learning motivation and engagement of game‐based inquiry learning activities.
Most children have difficulties in learning with ARGs due to the complexity of real‐world contexts and the ambiguity of the puzzles.
Children cannot construct knowledge effectively without proper learning supports in their cognitive process; however, it is challenge to provide proper learning supports without distracting children from gaming.
What this paper adds

An ARG with a mobile concept mapping‐based questioning approach (ARG‐CMQ) was applied to facilitate meaningful inquiry‐based learning for children in different real environments (school campuses and in science museums).
Both quantitative and qualitative analyses were examined to identify the effect of different learning strategies to support children learning with ARGs.
ARG‐CMQ improved children’s learning achievement, critical thinking and learning attitude better than conventional ARGs.
ARG‐CMQ might limit children’s divergent thinking and influences their creative problem‐solving performance.
Implications for practice and/or policy

ARG‐CMQ is a potential approach for inquiry‐based learning in real environments, especially in improving learning perceptions and higher‐order cognitive abilities.
ARG‐CMQ can be used to support competency‐based education.
Efficacy and safety of intravitreal methotrexate for vitreo‐retinal lymphoma – 20 years of experience
Authors: Habot‐Wilner Zohar , Frenkel Shahar , Pe’er Jacob 
Published: April 2021

SummaryVitreo‐retinal lymphoma (VRL) is the most common intraocular lymphoma and is highly associated with central nervous system (CNS) lymphoma (CNSL), both posing a therapeutic challenge. We investigated patients’ characteristics, efficacy and safety of intravitreal methotrexate (MTX) injections and their outcomes over 20 years. The records of 129 patients diagnosed between 1997 and 2018 were retrospectively reviewed. Lymphoma involved both the CNS and vitreo‐retina (49%), solely the CNS (37%) or solely the vitreo‐retina (14%). In all, 45·5% of the patients with CNSL either presented with VRL or developed it after a mean (±SE) of 85·7 (7·3) months. In all, 66·0% of the patients diagnosed with VRL either presented with CNSL or developed it after a mean (±SE) 42·6 (7·6) months. The 81 patients with VRL (134 eyes) received a mean (±SD) of 19 (7) injections; however, only 5 (4) injections were needed to reach complete remission. Local recurrence occurred in two of the 81 patients. Overall, 80·2% of eyes had an initial moderate–severe visual loss, and >50% of them improved. Reversible keratopathy was the most prevalent side‐effect. A total of 18·5% developed intraocular pressure (IOP) elevation due to angle neovascularisation after 16 injections, which could be reversed with prompt intravitreal injection of bevacizumab. Intravitreal MTX injections are a safe and effective treatment for VRL. Fewer injections (15) may offer similar results with fewer side‐effects.
Protective properties of GLP‐1 and associated peptide hormones in neurodegenerative disorders
Authors: Hölscher Christian 
Published: April 2021

Type 2 diabetes mellitus and the associated desensitisation of insulin signalling has been identified as a risk factor for progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and others. Glucagon‐like peptide 1 (GLP‐1) is a hormone that has growth factor‐like and neuroprotective properties. Several clinical trials have been conducted, testing GLP‐1 receptor agonists in patients with Alzheimer's disease, Parkinson's disease or diabetes‐induced memory impairments. The trials showed clear improvements in Alzheimer's disease, Parkinson's disease and diabetic patients. Glucose‐dependent insulinotropic polypeptide/gastric inhibitory peptide (GIP) is the ‘sister’ incretin hormone of GLP‐1. GIP analogues have shown neuroprotective effects in animal models of disease and can improve on the effects of GLP‐1. Novel dual GLP‐1/GIP receptor agonists have been developed that can enter the brain at an enhanced rate. The improved neuroprotective effects of these drugs suggest that they are superior to single GLP‐1 receptor agonists and could provide disease‐modifying care for Alzheimer's disease and Parkinson's disease patients.LINKED ARTICLESThis article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc