bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlling swelling and release of hyaluronic acid during aqueous storage by in situ cross-linking during spray drying with alginate
Authors: Wong Dana E. , Cunniffe Julia C. , Scher Herbert B. , Jeoh Tina 
Published: July 2019

AbstractThe success of hyaluronic acid in over-the-counter cosmetics has been limited by its poor storage stability in aqueous environments due to premature swelling and hydrolysis. Here, hyaluronic acid was prepared in dry microparticles, encapsulated by spray-drying in patented in situ calcium cross-linked alginate microcapsules (CLAMs) to minimize swelling and release in aqueous formulations. CLAMs prepared with 61% (d.b.) hyaluronic acid (HA-CLAMs) demonstrated restricted plumping, limited water absorption capacity, and reduced leaching; retaining up to 49 % hyaluronic acid after 2 hrs in water. A new method using chelated soluble calcium resulted in particles with significantly improved hyaluronic acid retention in water. ‘Chelate HA-CLAMs’ exhibited nearly full retention of hyaluronic acid over 2 hr incubation in water, and remained visibly insoluble after 1 year of storage in water at 4°C. Successful hyaluronic acid retention in CLAMs is likely due to the ability of hyaluronic acid to participate in calcium cross-linking.
Mechanics of MTOC clustering and spindle positioning in budding yeast Cryptococcus neoformans
Authors: Chatterjee Saptarshi , Som Subhendu , Varshney Neha , Satyadev PVS , Sanyal Kaustuv , Paul Raja 
Published: July 2019

AbstractThe dynamic process of mitotic spindle assembly depends on multitudes of inter-dependent interactions involving kinetochores (KTs), microtubules (MTs), spindle pole bodies (SPBs), and molecular motors. Before forming the mitotic spindle, multiple visible microtubule organizing centers (MTOCs) coalesce into a single focus to serve as a SPB in the pathogenic budding yeast, Cryptococcus neoformans. To explain this unusual phenomenon in the fungal kingdom, we propose a ‘search and capture’ model, in which cytoplasmic MTs (cMTs) nucleated by MTOCs grow and capture each other to promote MTOC clustering. Our quantitative modeling identifies multiple redundant mechanisms mediated by a combination of cMT-cell cortex interactions and inter-cMT coupling to facilitate MTOC clustering within the physiological time limit as determined by time-lapse live-cell microscopy. Besides, we screen various possible mechanisms by computational modeling and propose optimal conditions that favor proper spindle positioning - a critical determinant for timely chromosome segregation. These analyses also reveal that a combined effect of MT buckling, dynein pull, and cortical push maintains spatiotemporal spindle localization.
Two Forms of Knowledge Representations in the Human Brain
Authors: Wang Xiaoying , Men Weiwei , Gao Jiahong , Caramazza Alfonso , Bi Yanchao 
Published: July 2019

AbstractSensory experience shapes what and how knowledge is stored in the brain -- our knowledge about the color of roses depends in part on the activity of color-responsive neurons based on experiences of seeing roses. We study the brain basis of color knowledge in congenitally blind individuals whose color knowledge can only be obtained through language descriptions. We found that some regions support color knowledge only in the sighted. More importantly, a region in the left dorsal anterior temporal lobe supports object color knowledge in both the blind and sighted groups, indicating the existence of a sensory-independent knowledge coding system in both groups. Thus, there are (at least) two forms of object knowledge representations in the human brain: sensory-derived and cognitively-derived knowledge, supported by different brain systems.
Widespread remodelling of proteome solubility in response to different protein homeostasis stresses
Authors: Sui Xiaojing , Pires Douglas E. V. , Nie Shuai , Vecchi Giulia , Vendruscolo Michele , Ascher David B. , Reid Gavin E. , Hatters Danny M. 
Published: July 2019

ABSTRACTThe accumulation of protein deposits in neurodegenerative diseases involves the presence of a metastable subproteome vulnerable to aggregation. To investigate this subproteome and the mechanisms that regulates it, we measured the proteome solubility of the Neuro2a cell line under protein homeostasis stresses induced by Huntington Disease proteotoxicity; Hsp70, Hsp90, proteasome and ER-mediated folding inhibition; and oxidative stress. We found one-quarter of the proteome extensively changed solubility. Remarkably, almost all the increases in insolubility were counteracted by increases in solubility of other proteins. Each stress directed a highly specific pattern of change, which reflected the remodelling of protein complexes involved in adaptation to perturbation, most notably stress granule proteins, which responded differently to different stresses. These results indicate that the robustness of protein homeostasis relies on the absence of proteins highly vulnerable to aggregation and on large changes in aggregation state of regulatory mechanisms that restore protein solubility upon specific perturbations.
Molecular mechanism for the recognition of sequence-divergent CIF peptides by the plant receptor kinases GSO1/SGN3 and GSO2
Authors: Okuda Satohiro , Fujita Satoshi , Moretti Andrea , Hohmann Ulrich , Doblas Verónica G. , Ma Yan , Pfister Alexandre , Brandt Benjamin , Geldner Niko , Hothorn Michael 
Published: July 2019

AbstractPlants use leucine-rich repeat receptor kinases (LRR-RKs) to sense sequence diverse peptide hormones at the cell surface. A 3.0 Å crystal structure of the LRR-RK GSO1/SGN3 regulating Casparian strip formation in the endodermis reveals a large spiral-shaped ectodomain. The domain provides a binding platform for 21 amino-acid CIF peptide ligands, which are tyrosine sulfated by the tyrosylprotein sulfotransferase TPST/SGN2. GSO1/SGN3 harbors a binding pocket for sulfotyrosine and makes extended backbone interactions with CIF2. Quantitative biochemical comparisons reveal that GSO1/SGN3 – CIF2 represents one of the strongest receptor-ligand pairs known in plants. Multiple missense mutations are required to block CIF2 binding in vitro, and GSO1/SGN3 function in vivo. Using structure-guided sequence analysis we uncover novel CIF peptides conserved among higher plants. Quantitative binding assays with known and novel CIFs suggest that the homologous LRR-RKs GSO1/SGN3 and GSO2 have evolved unique peptide binding properties to control different developmental processes. A quantitative biochemical interaction screen, a CIF peptide antagonist and genetic analyses together implicate SERK LRR-RKs as essential co-receptor kinases required for GSO1/SGN3 and GSO2 receptor activation. 0ur work provides a mechanistic framework for the recognition of sequence-divergent peptide hormones in plants.Significance StatementTwo sequence-related plant membrane receptor kinases and their shape-complementary co-receptors are shown to selectively sense members of a small family of secreted peptide hormones to control formation of an important diffusion barrier in the plant root.
Examining the relationship between prenatal depression, amygdala-prefrontal structural connectivity and behaviour in preschool children
Authors: Hay Rebecca E. , Reynolds Jess E. , Grohs Melody , Paniukov Dmitrii , Giesbrecht Gerald F. , Letourneau Nicole , Dewey Deborah , Lebel Catherine 
Published: July 2019

AbstractPrenatal depression is a common, underrecognized, and undertreated condition with negative consequences on child behaviour and brain development. Neurological dysfunction of the amygdala, cingulate cortex and hippocampus are associated with the development of depression and stress disorders in youth and adults. Although prenatal depression is associated with both child behaviour and neurological dysfunction, the relationship between these variables remains unclear. In this study, fifty-four mothers completed the Edinburgh Depression Scale (EDS) during the second and third trimester of pregnancy and 3 months postpartum. Their children’s behaviour was assessed using the Child Behaviour Checklist (CBCL), and the children had diffusion magnetic resonance imaging (MRI) at age 4.1 +/− 0.8 years. Associations between prenatal depressive symptoms, child behaviour, and child brain structure were investigated. Third trimester EDS scores were associated with altered white matter in the amygdala-frontal tract and the cingulum, controlling for postpartum depression. Externalizing behaviour was sexually differentiated in the amygdala-frontal pathway. Altered structural connectivity between the amygdala and frontal cortex mediated the relationship between third trimester maternal depressive symptoms and child externalizing behaviour in males, but not females. These findings suggest that altered brain structure is a possible mechanism via which prenatal depressive symptoms can impact child behaviour, highlighting the importance of both recognition and intervention in prenatal depression.
Neurology-related protein biomarkers are associated with general fluid cognitive ability and brain volume in older age
Authors: Harris Sarah E. , Cox Simon R. , Bell Steven , Marioni Riccardo E. , Prins Bram P , Pattie Alison , Corley Janie , Muñoz Maniega Susana , Valdés Hernández Maria , Morris Zoe , John Sally , Bronson Paola G. , Tucker-Drob Elliot M. , Starr John M. , Bastin Mark E. , Wardlaw Joanna M. , Butterworth Adam S , Deary Ian J. 
Published: July 2019

AbstractIdentifying the biological correlates of late life cognitive function is important if we are to ascertain biomarkers for, and develop treatments to help reduce, age-related cognitive decline. This study investigated the associations between plasma levels of 91 neurology-related proteins (Olink® Proteomics) and general fluid cognitive ability in the Lothian Birth Cohort 1936 (LBC1936, N=798), the Lothian Birth Cohort 1921 (LBC1921, N=165), and the INTERVAL BioResource, (N=4,451). In LBC1936, we also examined mediation of protein-cognitive ability associations by MRI-derived indices of brain structure. In the LBC1936, 22 of the proteins and the first principal component (PC) created from a PC analysis of the 91 proteins, were associated with general fluid cognitive ability (β between −0.11 and −0.17, p<0.0029). Total brain volume partially mediated the association between 10 of these proteins and general fluid cognitive ability. Effect sizes for the 22 proteins, although smaller, were all in the same direction as in LBC1936 in an age-matched subsample of INTERVAL. Similar effect sizes were found for the majority of these 22 proteins in the older LBC1921. The associations were not replicated in a younger subset of INTERVAL. In conclusion, we identified plasma levels of a number of neurology-related proteins that were associated with general fluid cognitive ability in later life, some of which were mediated by brain volume.
Reconciling Dimensional and Categorical Models of Autism Heterogeneity: a Brain Connectomics & Behavioral Study
Authors: Tang Siyi , Sun Nanbo , Floris Dorothea L. , Zhang Xiuming , Di Martino Adriana , Yeo B.T. Thomas 
Published: July 2019

AbstractBackgroundHeterogeneity in autism spectrum disorder (ASD) has hindered the development of biomarkers, thus motivating subtyping efforts. Most subtyping studies divide ASD individuals into non-overlapping (categorical) subgroups. However, continuous inter-individual variation in ASD suggests the need for a dimensional approach.MethodsA Bayesian model was employed to decompose resting-state functional connectivity (RSFC) of ASD individuals into multiple abnormal RSFC patterns, i.e., categorical subtypes henceforth referred to as “factors”. Importantly, the model allowed each individual to express one or more factors to varying degrees (dimensional subtyping). The model was applied to 306 ASD individuals (age 5.2-57 years) from two multisite repositories. Posthoc analyses associated factors with symptoms and demographics.ResultsAnalyses yielded three factors with dissociable whole-brain hypo/hyper RSFC patterns. Most participants expressed multiple (categorical) factors, suggestive of a mosaic of subtypes within individuals. All factors shared abnormal RSFC involving the default network, but the directionality (hypo/hyper RSFC) differed across factors. Factor 1 was associated with core ASD symptoms, while factor 2 was associated with comorbid symptoms. Older males preferentially expressed factor 3. Factors were robust across multiple control analyses and not associated with IQ, nor head motion.ConclusionsThere exist at least three ASD factors with dissociable patterns of whole-brain RSFC, behaviors and demographics. Heterogeneous default network hypo/hyper RSFC across the factors might explain previously reported inconsistencies. The factors differentiated between core ASD and comorbid symptoms - a less appreciated domain of heterogeneity in ASD. These factors are co-expressed in ASD individuals with different degrees, thus reconciling categorical and dimensional perspectives of ASD heterogeneity.
Decision-making flexibility in New Caledonian crows, young children and adult humans in a multi-dimensional tool-use task
Authors: Miller Rachael , Gruber Romana , Frohnwieser Anna , Schiestl Martina , Jelbert Sarah A. , Gray Russell D. , Boeckle Markus , Taylor Alex H. , Clayton Nicola S. 
Published: July 2019

AbstractThe ability to make profitable decisions in natural foraging contexts may be influenced by an additional requirement of tool-use, due to increased levels of relational complexity and additional work-effort imposed by tool-use, compared with simply choosing between an immediate and delayed food item. We examined the flexibility for making the most profitable decisions in a multi-dimensional tool-use task, involving different apparatuses, tools and rewards of varying quality, in 3-5-year-old children, adult humans and tool-making New Caledonian crows (Corvus moneduloides). We also compared our results to previous studies on habitually tool-making orangutans (Pongo abelii) and non-tool-making Goffin’s cockatoos (Cacatua goffiniana). Adult humans, cockatoos and crows, though not children and orangutans, did not select a tool when it was not necessary, which was the more profitable choice in this situation. Adult humans, orangutans and cockatoos, though not crows and children, were able to refrain from selecting non-functional tools. By contrast, the birds, though not primates tested, struggled to attend to multiple variables - where two apparatuses, two tools and two reward qualities were presented simultaneously - without extended experience. These findings indicate: (1) in a similar manner to humans and orangutans, New Caledonian crows and Goffin’s cockatoos can flexibly make profitable decisions in some decision-making tool-use tasks, though the birds may struggle when tasks become more complex; (2) children and orangutans may have a bias to use tools in situations where adults and other tool-making species do not.
Burden analysis of missense variants in 1,330 disease-associated genes on 3D provides insights into the mutation effects
Authors: Iqbal Sumaiya , Jespersen Jakob B. , Perez-Palma Eduardo , May Patrick , Hoksza David , Heyne Henrike O. , Ahmed Shehab S. , Rifat Zaara T. , Rahman M. Sohel , Lage Kasper , Palotie Aarno , Cottrell Jeffrey R. , Wagner Florence F. , Daly Mark J. , Campbell Arthur J. , Lal Dennis 
Published: July 2019

AbstractInterpretation of the colossal number of genetic variants identified from sequencing applications is one of the major bottlenecks in clinical genetics, with the inference of the effect of amino acid-substituting missense variants on protein structure and function being especially challenging. Here we evaluated the burden of amino acids affected in pathogenic variants (n=32,923) compared to the variants (n=164,915) from the general population in 1,330 disease-associated genes on forty protein features using over 14,000 experimentally-solved 3D structures. By analyzing the whole gene/variant set jointly, we identified 18 features associated with 3D mutational hotspots that are generally important for protein fitness and stability. Individual analyses performed for twenty-four protein functional classes further revealed 240 characteristics of mutational hotspots in total, including new associations recapitulating the sheer diversity across proteins essential structural regions. We demonstrated that the function-specific features of variants correspond to the readouts of mutagenesis experiments and positively correlate with clinically-interpreted pathogenic and benign missense variants. Finally, we made our results available through a web server to foster accessibility and downstream research. Our findings represent a crucial step towards translational genetics, from highlighting the impact of mutations on protein structure to rationalizing the pathogenicity of variants in terms of the perturbed molecular mechanisms.
Single-cell glycolytic activity regulates membrane tension and HIV-1 fusion
Authors: Coomer Charles A. , Carlon-Andres Irene , Iliopoulou Maro , Dustin Michael L. , Compeer Ewoud B. , Compton Alex A. , Padilla-Parra Sergi 
Published: July 2019

ABSTRACTThere has been resurgence in determining the role of host metabolism in viral infection yet deciphering how the metabolic state of single cells affects viral entry and fusion remains unknown. Here, we have developed a novel assay multiplexing genetically encoded biosensors with single virus tracking (SVT) to evaluate the influence of global metabolic processes on the success rate of virus entry in single cells. We found that cells with a lower ATP:ADP ratio prior to virus addition were less permissive to virus fusion and infection. These results indicated a relationship between host metabolic state and the likelihood for virus-cell fusion to occur. SVT revealed that HIV-1 viruses were arrested at hemifusion in glycolytically-inactive cells. Interestingly, cells acutely treated with glycolysis inhibitor 2-deoxyglucose (2-DG) become resistant to virus infection and also display less surface membrane cholesterol. Addition of cholesterol in these in glycolytically-inactive cells rescued the virus entry block at hemifusion and enabled completion of HIV-1 fusion. Further investigation with FRET-based membrane tension and membrane-order reporters revealed a link between host cell glycolytic activity and host membrane order and tension. Indeed, cells treated with 2-DG possessed lower plasma membrane lipid order and higher tension values, respectively. Our novel imaging approach that combines lifetime imaging (FLIM) and SVT revealed not only changes in plasma membrane tension at the point of viral fusion, but also that HIV is less likely to enter cells at areas of higher membrane tension. We therefore have identified a connection between host cell glycolytic activity and membrane tension that influences HIV-1 fusion in real-time at the single-virus fusion level in live cells. As glycolytic activity sets membrane tension levels by altering cellular cholesterol surface levels, our results suggest additional previously unknown benefits of cholesterol-lowering medication in HIV-1 infection.
Extracellular signal‐regulated kinase activation of self‐healing Langerhans cell histiocytosis: A case report
Authors: Kaneshima Akiko , Yamaguchi Sayaka , Miyagi Takuya , Kariya Yoshiyuki , Awazawa Tsuyoshi , Ohshiro Tokiko , Hyakuna Nobuyuki , Nakanishi Koichi , Takahashi Kenzo 
Published: July 2019

AbstractA 3‐month‐old boy developed small papules on his trunk. After the papules increased in number, the patient was diagnosed with Langerhans cell histiocytosis based on the pathological findings. He was referred to our department for further examination. Upon initial examination, the papules and nodules were scattered on his back, abdomen and lumbar region. Because he did not present with any organ involvement except the skin, he was diagnosed with single‐system and skin‐limited Langerhans cell histiocytosis. Skin rashes were treated with a topical steroid and started regressing 3 months after onset. All papules disappeared 6 months after onset. In this boy, the Langerhans cell histiocytosis tumor cells expressed phosphorylated extracellular signal‐regulated kinases. In Langerhans cell histiocytosis, BRAF V600E and other genes are known to mutate to act as driver mutations in stem cells of the myeloid dendritic cell lineage. Consequently, extracellular signal‐regulated kinases are continuously activated, which contributes to Langerhans cell histiocytosis carcinogenesis.
Contrasting levels of genotype by environment interaction for life history and morphological traits in invasive populations of Zaprionus indianus (Diptera: Drosophilidae)
Authors: Lavagnino Nicolás J. , Imberti Marcos , Ortiz Victoria E. , Flaibani Nicolás , Fanara Juan José 
Published: July 2019

AbstractIt has been demonstrated that phenotypic plasticity and genotype by environment interaction are important for coping with new and heterogeneous environments during invasions. Zaprionus indianus Gupta (Diptera: Drosophilidae) is an Afrotropical invasive fly species introduced to the South American continent in 1999. This species is generalist and polyphagous, since it develops and feeds in several different fruit species. These characteristics of Z. indianus suggest that phenotypic plasticity and genotype by environment interaction may be important in this species invasion process. In this sense, our aim was to investigate the role of genetic variation for phenotypic plasticity (genotype by environment interaction) in Z. indianus invasion of the South American continent. Specifically, we quantified quantitative genetic variation and genotype by environment interactions of morphological and life history traits in different developmental environments, that is, host fruits. This was done in different populations in the invasive range of Z. indianus in Argentina. Results showed that Z. indianus populations have considerable amounts of quantitative genetic variation. Also, genotype by environment interactions was detected for the different traits analyzed in response to the different developmental environments. Interestingly, the amounts and patterns of these parameters differed between populations. We interpreted these results as the existence of differences in evolutionary potential between populations that have an important role in the short‐ and long‐term success of the Z. indianus invasion process.
Scaled‐up biotechnological production of individual betalains in a microbial system
Authors: Guerrero‐Rubio María Alejandra , López‐Llorca Rosalía , Henarejos‐Escudero Paula , García‐Carmona Francisco , Gandía‐Herrero Fernando 
Published: July 2019

SummaryThe recent interest in plant pigment betalains as bioactive compounds and chemopreventive agents has led to the search for a reliable and scalable process to obtain them. The cloning of the novel and efficient enzyme 4,5‐DOPA‐extradiol dioxygenase from Gluconacetobacter diazotrophicus in an expression vector, and the subsequent heterologous expression in Escherichia coli cultures has led to the start‐up of a biotechnological production system of individual pigments. The aim of this study was to search for the optimal conditions for the production of betalamic acid in microbial factories and the scaled‐up obtention of the derived pigments. Four different betaxanthins and two betacyanins were obtained after the addition of non‐transformable amines and amino acids and their condensation with the betalamic acid produced by the dioxygenase. The scaled‐up obtention and purification of betalains improved the yields of the previous methodologies reaching quantities by up to 150 mg of pure compounds.