bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life in keratoconus: evaluation with Keratoconus Outcomes Research Questionnaire (KORQ)
Authors: Pinto Roberto Damian Pacheco , Abe Ricardo Yuji , Gomes Flávia Cid , Barbisan Paulo Rodolfo Tagliari , Martini Alexandre Fattah , de Almeida Borges Daniel , Fernandes Arthur Gustavo , Arieta Carlos Eduardo Leite , Alves Monica 
Published: June 2021

AbstractTo assess the quality of life of keratoconus patients using the Keratoconus Outcomes Research Questionnaire (KORQ), translated and validated in Portuguese language. The KORQ is the only validated keratoconus specific questionnaire and has a high rating for its psychometric properties. This cross-sectional study enrolled 100 keratoconus patients from a tertiary referral eye hospital between April 2018 and June 2019. Associations between age, sex, allergic conjunctivitis, keratoconus stage, best-corrected visual acuity (BCVA), maximum simulated keratometry (Kmax), steep keratometry (K2), pachymetry, treatments performed, hydrops, and KORQ scores were evaluated using univariate (Wilcoxon test and the Kruskal Wallis test) and multivariate linear regression with stepwise backward modeling. Lower KORQ scores are associated with better quality of life, whereas, higher scores are associated with greater impairment of functional activities and symptoms. Among the 100 patients, mild, moderate, and severe keratoconus were observed in 15%, 46% and 39% of participants, respectively. Univariate analysis showed lower function scores values, with male sex (p < 0.05) and both functional and symptom scores were significantly associated with BCVA < 0.3 (LogMAR) (p < 0.05). Multivariate analysis indicated significantly lower functional scores in individuals with BCVA < 0.3 (LogMAR) (p < 0.001) and those with a history of crosslinking treatment (p = 0.022), while symptom scores were only significantly associated with only BCVA < 0.3 (LogMAR) (p < 0.001). In patients with keratoconus, BCVA in the better eye and history of crosslinkig were factors associated with better quality of life scores using the KORQ.
Ocular pigmentation in humans, great apes, and gibbons is not suggestive of communicative functions
Authors: Caspar Kai R. , Biggemann Marco , Geissmann Thomas , Begall Sabine 
Published: June 2021

AbstractPigmentation patterns of the visible part of the eyeball, encompassing the iris and portions of the sclera, have been discussed to be linked to social cognition in primates. The cooperative eye hypothesis suggests the white sclera of humans to be a derived adaptive trait that enhances eye-mediated communication. Here, we provide a comparative analysis of ocular pigmentation patterns in 15 species of hominoids (humans, great apes & gibbons) that show marked differences in social cognition and quantify scleral exposure at the genus level. Our data reveals a continuum of eye pigmentation traits in hominoids which does not align with the complexity of gaze-mediated communication in the studied taxa. Gibbons display darker eyes than great apes and expose less sclera. Iridoscleral contrasts in orangutans and gorillas approach the human condition but differ between congeneric species. Contrary to recent discussions, we found chimpanzee eyes to exhibit a cryptic coloration scheme that resembles gibbons more than other apes. We reevaluate the evidence for links between social cognition and eye pigmentation in primates, concluding that the cooperative eye hypothesis cannot explain the patterns observed. Differences in scleral pigmentation between great apes and humans are gradual and might have arisen via genetic drift and sexual selection.
Multiscale modelling of cerebrovascular injury reveals the role of vascular anatomy and parenchymal shear stresses
Authors: Farajzadeh Khosroshahi Siamak , Yin Xianzhen , K. Donat Cornelius , McGarry Aisling , Yanez Lopez Maria , Baxan Nicoleta , J. Sharp David , Sastre Magdalena , Ghajari Mazdak 
Published: June 2021

AbstractNeurovascular injury is often observed in traumatic brain injury (TBI). However, the relationship between mechanical forces and vascular injury is still unclear. A key question is whether the complex anatomy of vasculature plays a role in increasing forces in cerebral vessels and producing damage. We developed a high-fidelity multiscale finite element model of the rat brain featuring a detailed definition of the angioarchitecture. Controlled cortical impacts were performed experimentally and in-silico. The model was able to predict the pattern of blood–brain barrier damage. We found strong correlation between the area of fibrinogen extravasation and the brain area where axial strain in vessels exceeds 0.14. Our results showed that adjacent vessels can sustain profoundly different axial stresses depending on their alignment with the principal direction of stress in parenchyma, with a better alignment leading to larger stresses in vessels. We also found a strong correlation between axial stress in vessels and the shearing component of the stress wave in parenchyma. Our multiscale computational approach explains the unrecognised role of the vascular anatomy and shear stresses in producing distinct distribution of large forces in vasculature. This new understanding can contribute to improving TBI diagnosis and prevention.
CB1R activation in nucleus accumbens core promotes stress-induced reinstatement of cocaine seeking by elevating extracellular glutamate in a drug-paired context
Authors: Guzman Andrea S. , Avalos Maria P. , De Giovanni Laura N. , Euliarte Pia V. , Sanchez Marianela A. , Mongi-Bragato Bethania , Rigoni Daiana , Bollati Flavia A. , Virgolini Miriam B. , Cancela Liliana M. 
Published: June 2021

AbstractPreclinical models of stress-induced relapse to drug use have shown that the dysregulation of glutamatergic transmission within the nucleus accumbens (NA) contributes notably to the reinstatement of cocaine-seeking behavior in rodents. In this sense, there has been increasing interest in the cannabinoid type-1 receptor (CB1R), due to its crucial role in modulating glutamatergic neurotransmission within brain areas involved in drug-related behaviors. This study explored the involvement of CB1R within the NA subregions in the restraint stress-induced reinstatement of cocaine-conditioned place preference (CPP), as well as in the regulation of glutamatergic transmission, by using a pharmacological approach and the in vivo microdialysis sampling technique in freely moving rats. CB1R blockade by the antagonist/inverse agonist AM251 (5 nmol/0.5 μl/side) or CB1R activation by the agonist ACEA (0.01 fmol/0.5 μl/side), prevented or potentiated restraint stress-induced reinstatement of cocaine-CPP, respectively, after local administration into NAcore, but not NAshell. In addition, microdialysis experiments demonstrated that restraint stress elicited a significant increase in extracellular glutamate in NAcore under reinstatement conditions, with the local administration of AM251 or ACEA inhibiting or potentiating this, respectively. Interestingly, this rise specifically corresponded to the cocaine-associated CPP compartment. We also showed that this context-dependent change in glutamate paralleled the expression of cocaine-CPP, and disappeared after the extinction of this response. Taken together, these findings demonstrated the key role played by CB1R in mediating reinstatement of cocaine-CPP after restraint stress, through modulation of the context-specific glutamate release within NAcore. Additionally, CB1R regulation of basal extracellular glutamate was demonstrated and proposed as the underlying mechanism.
Pathogenesis of hemorrhagic disease caused by elephant endotheliotropic herpesvirus (EEHV) in Asian elephants (Elephas maximus)
Authors: Guntawang Thunyamas , Sittisak Tidaratt , Kochagul Varankpicha , Srivorakul Saralee , Photichai Kornravee , Boonsri Kittikorn , Janyamethakul Thittaya , Boonprasert Khajohnpat , Langkaphin Warangkhana , Thitaram Chatchote , Pringproa Kidsadagon 
Published: June 2021

AbstractElephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD) is an acute fatal disease in elephants. Despite the fact that the underlying pathogenesis of EEHV-HD has been proposed, it remains undetermined as to what mechanisms drive these hemorrhagic and edematous lesions. In the present study, we have investigated and explained the pathogenesis of acute EEHV-HD using blood profiles of EEHV-HD and EEHV-infected cases, hematoxylin and eosin (H&E) stain, special stains, immunohistochemistry, quantitative polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT-PCR). It was found that EEHV genomes were predominantly detected in various internal organs of EEHV-HD cases. Damage to endothelial cells, vasculitis and vascular thrombosis of the small blood vessels were also predominantly observed. Increases in platelet endothelial cell adhesion molecules-1 (PECAM-1)- and von Willebrand factor (vWF)-immunolabeling positive cells were significantly noticed in injured blood vessels. The expression of pro-inflammatory cytokine mRNA was significantly up-regulated in EEHV-HD cases when compared to EEHV-negative controls. We have hypothesized that this could be attributed to the systemic inflammation and disruption of small blood vessels, followed by the disseminated intravascular coagulopathy that enhanced hemorrhagic and edematous lesions in EEHV-HD cases. Our findings have brought attention to the potential application of effective preventive and therapeutic protocols to treat EEHV infection in Asian elephants.
Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia
Authors: Colado Ana , Elías Esteban Enrique , Sarapura Martínez Valeria Judith , Cordini Gregorio , Morande Pablo , Bezares Fernando , Giordano Mirta , Gamberale Romina , Borge Mercedes 
Published: June 2021

AbstractHypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.
Whimbrel populations differ in trans-atlantic pathways and cyclone encounters
Authors: Watts Bryan D. , Smith Fletcher M. , Hines Chance , Duval Laura , Hamilton Diana J. , Keyes Tim , Paquet Julie , Pirie-Dominix Lisa , Rausch Jennie , Truitt Barry , Winn Brad , Woodard Paul 
Published: June 2021

AbstractEach year hundreds of millions of birds cross the Atlantic Ocean during the peak of tropical cyclone activity. The extent and consequences of migrant-storm interactions remain unknown. We tracked whimbrels from two populations (Mackenzie Delta; Hudson Bay) to examine overlap between migration routes and storm activity and both the frequency and consequence of storm encounters. Here we show that Mackenzie Delta and Hudson Bay whimbrels follow different routes across the ocean and experience dramatically different rates of storm encounters. Mackenzie Delta whimbrels departed North America from Atlantic Canada, made long ($$\bar{x}$$x¯ = 5440 ± 120.3 km) nonstop flights far out to sea that took several days ($$\bar{x}$$x¯ = 6.1 ± 0.18) to complete and encountered storms during 3 of 22 crossings. Hudson Bay whimbrels departed North America from the south Atlantic Coast, made shorter ($$\bar{x}$$x¯ = 3643 ± 196.2 km) nonstop flights across the Caribbean Basin that took less time ($$\bar{x}$$x¯ = 4.5 ± 0.29) to complete and encountered storms during 13 of 18 crossings. More than half of Hudson Bay storm encounters resulted in groundings on Caribbean islands. Grounded birds required longer ($$\bar{x}$$x¯ = 30.4 ± 5.32 days) to complete trans-Atlantic crossings and three were lost including 2 to hunters and 1 to a predator. One of the Mackenzie Delta whimbrels was lost at sea while crossing the Intertropical Convergence Zone. Whimbrels use two contrasting strategies to cross the Atlantic including (1) a long nonstop flight around the core of storm activity with a low likelihood of encountering storms but no safety net and (2) a shorter flight through the heart of Hurricane Alley with a high likelihood of encountering storms and a safety network of islands to use in the event of an encounter. Demographic consequences of storm encounters will likely play a role in the ongoing evolution of trans-Atlantic migration pathways as global temperatures continue to rise.
SIRT2 promotes murine melanoma progression through natural killer cell inhibition
Authors: Zhang Manchao , Acklin Scarlett , Gillenwater John , Du Wuying , Patra Mousumi , Yu Hao , Xu Bo , Yu Jianhua , Xia Fen 
Published: June 2021

AbstractSIRT2, an NAD+-dependent histone deacetylase, has been shown to play a pivotal role in various physiological processes, however, its role in cancer is currently controversial. In recent years, SIRT2 has been described as both a tumor suppressor and oncogene with divergent expression and function in various malignancies. Using murine allograft melanoma models, our results suggest increased systemic expression of SIRT2 promotes tumor progression. In this study, SIRT2-overexpressing mice exhibited enhanced tumor growth and larger tumor volumes compared to their wild-type littermates. Mechanistically, systemic overexpression of SIRT2 reduces the number of tumor-infiltrating natural killer (NK) cells and suppresses NK cell function and proliferation within the tumor microenvironment (TME). Furthermore, despite the enhancing effect of NK cell depletion on tumor volume and growth rate in wild-type littermate mice, this effect was diminished in SIRT2-overexpressing mice. Lastly, pharmacological inhibition of SIRT2 increases NK cell tumor infiltration and suppresses allograft melanoma tumor growth. The findings of this study identify a dynamic functional interaction between systemic SIRT2 and NK cell activity, which controls melanoma tumor progression. Given the recent renewed interest in NK-cell-mediated immunotherapy response, SIRT2 could present a new opportunity to mediate immunotherapy response and resistance.
A metabolomic study of Gomphrena agrestis in Brazilian Cerrado suggests drought-adaptive strategies on metabolism
Authors: Melo Geraldo Aclécio , Abreu Ilka Nacif , de Oliveira Maíra Baista , Budzinski Ilara Gabriela Frasson , Silva Lucinélia Vieira , Pimenta Marcio Antônio Silva , Moritz Thomas 
Published: June 2021

AbstractDrought is the main factor that limits the distribution and productivity of plant species. In the Brazilian Cerrado, the vegetation is adapted to a seasonal climate with long- and short-term periods of drought. To analyze the metabolic strategies under such conditions, a metabolomic approach was used to characterize Gomphrena agrestis Mart. (Amaranthaceae) a native species that grows under natural conditions, in a rock-field area. Roots and leaves material from native specimens were sampled along different seasons of the year and LC–MS and GC–MS analyzed for multiple chemical constituents. The datasets derived from the different measurements were combined and evaluated using multivariate analysis. Principal component analysis was used to obtain an overview of the samples and identify outliers. Later, the data was analyzed with orthogonal projection to latent structures discriminant analysis to obtain valid models that could explain the metabolite variations in the different seasons. Two hundred and eighty metabolites were annotated, generating a unique database to characterize metabolic strategies used to cope with the effects of drought. The accumulation of fructans in the thickened roots is consistent with the storage of carbons during the rainy season to support the energy demand during a long period of drought. The accumulation of Abscisic acid, sugars and sugar alcohols, phenolics, and pigment in the leaves suggests physiological adaptations. To cope with long-term drought, the data suggests that tissue water status and storage of reserves are important to support plant survival and regrowth. However, during short-term drought, osmoregulation and oxidative protection seems to be essential, probably to support the maintenance of active photosynthesis.
Lymphödem: Anatomie, Physiologie und Pathophysiologie
Authors: Brenke Rainer 
Published: June 2021

ZusammenfassungDie Ursachen für Ödeme sind vielfältig. Bei deren Entstehung spielt das Lymphgefäßsystem eine entscheidende Rolle. Jedem Ödem liegt eine Überlastung des Lymphgefäßsystems zugrunde. Zur Behandlung wird die Manuelle Lymphdrainage als Massagetechnik geschätzt. Die noch relativ neue Massagetechnik wurde als Teil der „Komplexen Physikalischen Entstauungstherapie“ zur Behandlung des Lymphödems entwickelt. Jedoch sind nicht bei jedem Ödem Lymphdrainage und Kompression angezeigt, bei einigen sind sie sogar kontraindiziert. Der Beitrag gibt einen Überblick zu den anatomischen Grundlagen und der Pathophysiologie des Lymphsystems, die die Basis für die Auswahl der Behandlungsoptionen bilden.
The Diet‐microbiota‐mucus Layer Axis as a Mediator of Intestinal Health and Disease
Authors: Martens Eric 
Published: June 2021

Despite the accepted health benefits of consuming dietary fiber, little is known about the precise mechanisms by which fiber levels impact the gut microbiota and alters disease risk or how the precise chemistry of fiber polysaccharides interfaces with the hundreds of gut microbiota species. Using gnotobiotic mouse models, functional genomics, biochemical and genetic studies we have explored these interactions in mechanistic depth. In recent studies in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we have elucidated the functional interactions between dietary fiber, the gut microbiota and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. During chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host‐secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber‐deprived, mucus‐eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium, or inflammatory disease in the absence of pathogen in IL‐10‐deficient mice. Our work has begun to unravel the intricate pathways linking diet, the gut microbiome and intestinal barrier dysfunction, which could be exploited to improve health using dietary fiber or prebiotic therapeutics. As such, it is anticipated that our research will provide direct paths to future dietary intervention studies in humans, which are built on a firm foundation of functional and mechanistic knowledge of fiber‐microbiota interactions gathered in tractable model systems.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Context‐dependent and Disease‐specific Diversity in Stress Granules Formed from Pre‐existing Protein Interactions
Authors: Markmiller Sebastian , Soltanieh Sahar , Server Kari L. , Mak Raymond , Jin Wenhao , Fang Mark Y. , Luo En‐Ching , Yeo Gene W. , Krach Florian , Yang Dejun , Sen Anindya , Fulzele Amit , Wozniak Jacob M. , Gonzalez David J. , Kankel Mark W. , Gao Fen‐Biao , Bennett Eric J. , Lécuyer Eric 
Published: June 2021

Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration‐linked mutations, we used APEX proximity labeling, mass spectrometry and immunofluorescence to identify ~150 previously unknown human SG components. SG proteins form a dense interaction network in unstressed cells, facilitating rapid coalescence into larger SGs. About 20% of SG diversity is stress‐ or cell type‐dependent, with neuronal SGs displaying a particularly complex repertoire of proteins enriched in chaperones and autophagy factors. Strengthening the link between SGs and neurodegeneration, we demonstrate aberrant dynamics, composition and subcellular distribution of SGs in cells from ALS patients. Using three Drosophila ALS/FTD models, we identify ~30 SG‐associated modifiers of neurotoxicity in vivo. Altogether, our results highlight SG proteins as central to understanding and ultimately targeting neurodegeneration.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The muscle‐specific ubiquitin ligase MuRF1 regulates autophagy via FOXO1/3 ubiquitination to inhibit NF‐κB signaling and protect against cardiac inflammation in vivo
Authors: Parry Traci L. , Schisler Jonathan C. , Mwiza Jean Marie , Durand Joel K. , Baldwin Albert S. , Willis Monte S. 
Published: June 2021

The muscle‐specific ubiquitin ligase MuRF1 (muscle ring finger‐1) has recently been shown to regulate signal transduction by modulating transcription factor activity through ubiquitin‐mediated post‐translational modification. Therefore, we investigated the ability of MuRF1 to regulate autophagy. MuRF1−/− hearts exhibited decreased autophagic flux (decrease in LC3II and VPS34 protein levels), while MuRF1Tg+ hearts exhibited increased autophagic flux (increase in last phase autophagosomes and VPS34 protein levels). Interestingly, the FOXO1/3a transcription factors, known supporters of autophagy, correlated with MuRF1 expression. MuRF1−/− hearts expressed significantly less of the FOXO‐regulated P62, while MuRF1Tg+ expressed significantly more P62 by immunoblot analysis. Since P62 supports NF‐κB signaling by IKKβ phosphorylation, MuRF1−/− and MuRF1Tg+ mice were challenged with LPS to determine resistance to endotoxin‐induced cardiac dysfunction to identify the role of MuRF1‐P62 in inhibiting cardiac NF‐κB signaling. MuRF1−/− mice were significantly protected against LPS‐induced systolic dysfunction, while MuRF1 Tg+ mice were more susceptible to LPS‐induced heart failure. NF‐κB activity was significantly inhibited in MuRF1−/− mice at the level of the IKK complex, consistent with decreased FOXO‐regulated P62 to reduce downstream NF‐κB signaling. These studies identify the first ubiquitin ligase to regulate autophagy in the heart and describe novel therapeutic targets that could be used to block myocyte‐specific inflammationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.