bluuebunny/crossref_metadata_2025_split huggingface dataset:
SEX DIFFERENCES IN BLOOD PRESSURE RESPONSE TO CONTINUOUS ANG II INFUSION: ARE ONLY SEX HORMONES TO BLAME?
Authors: Dadam Florencia , Godino Andrea , Vivas Laura , Caeiro Ximena E. 
Published: October 2021

ABSTRACTTo investigate the involvement of the sex chromosome complement (SCC), organizational and activational hormonal effects in changes in mean arterial pressure during acute Ang II infusion, we used gonadectomized (GDX) mice of the “four core genotypes” model, which dissociates the effect of gonadal sex and SCC, allowing comparisons of sexually dimorphic traits between XX and XY females as well as XX and XY males. Additionally, β-estradiol and testosterone propionate (2ug/g) were daily injected for 4 days to evaluate activational hormonal effects.Statistical analysis of the changes in mean arterial pressure revealed an interaction of SCC, organizational and activational hormonal effects during Ang II infusion {F(7,39=2,60 p<0.01)}. Our results indicate that, in absence of activational hormonal effects, interaction between the SCC and organizational hormonal action differentially modulates changes in arterial pressure. In GDX mice without hormone replacement, Ang II infusion resulted in an increase in mean arterial pressure in XX-male, XX-female and XY-female mice, while no changes were observed in XY-male mice. Furthermore, β-estradiol replacement (GDX+E2 group) resulted in a decrease in blood pressure in XX-males, XX-females and XY-females (indicating an activational β-estradiol effect), while no changes were observed in the XY-male group. Moreover, testosterone propionate replacement (GDX+TP group) showed a greater increase in blood pressure in XY-male mice than in XX-males and XX-females, demonstrating an activational hormonal effect of testosterone in XY-male mice.Our data isolates and highlights the contribution and interaction of SCC, activational and organizational hormonal effects in sex differences in Ang II blood pressure regulation.
findPC: An R package to automatically select number of principal components in single-cell analysis
Authors: Zhuang Haotian , Ji Zhicheng 
Published: October 2021

AbstractSummaryPrincipal component analysis (PCA) is widely used in analyzing single-cell genomic data. Selecting the optimal number of PCs is a crucial step for downstream analyses. The elbow method is most commonly used for this task, but it requires one to visually inspect the elbow plot and manually choose the elbow point. To address this limitation, we developed six methods to automatically select the optimal number of PCs based on the elbow method. We evaluated the performance of these methods on real single-cell RNA-seq data from multiple human and mouse tissues. The perpendicular line method with 20 PCs has the best overall performance, and its results are highly consistent with the numbers of PCs identified manually. We implemented the six methods in an R package, findPC, that objectively selects the number of PCs and can be easily incorporated into any automatic analysis pipeline.Availability and ImplementationfindPC R package is freely available at https://github.com/haotian-zhuang/findPCContactzhicheng.ji@duke.eduSupplementary informationSupplementary data are available at Bioinformatics online.
Network-based analysis on pharmacological mechanisms underlying the anti-diabetic property of Coix lacryma-jobi
Authors: Taquiqui Arvin , Ferrer Angelu Mae , David Janella Rayne , Deocaris Custer C. , Alinsug Malona V. 
Published: October 2021

AbstractDiabetes mellitus (DM) is the most common endocrine disorder and among the top 10 leading diseases causing death worldwide. Coicis semen [CS] (Coix lacryma-jobi), also known as adlay have been reported to display anti-diabetic properties. Unfortunately, studies on the pharmacological mechanisms involving adlay for the treatment of diabetes are nil. Thus, this study was conducted to evaluate the interactions and mechanisms of the bioactive compound targets of adlay in the treatment of diabetes using network analysis. Adlay bioactive compounds and potential target genes were obtained from SymMap. Diabetes related target genes were collected from CTD. Protein-Protein Interaction Network was analyzed using the STRING database. GO and KEGG pathway enrichment analyses were performed using DAVID to further explore the mechanisms of adlay in treating diabetes. PPI and compound-target-pathway were visualized using Cytoscape. A total of 25 bioactive compounds, 201 corresponding targets, and 35839 diabetes mellitus associated targets were obtained while 200 were considered potential therapeutic targets. The 9 bioactive compounds studied were berberine, oleic acid, beta-sitosterol, sitosterol, linoleic acid, berberrubine, jatrorrhizine, thalifendine, and stigmasterol. The identified 5 core targets were ESR1, JUN, MAPK14, and RXRA. Adlai targets enriched in GO terms were mostly involved with positive regulation of transcription, response to drugs, and negative regulation of apoptosis. This study provides novel research insights into the clinical properties of adlay in diabetes melitus treatment.
Genetic and environmental influences on the evolution of virulence in the HIV-associated opportunistic human fungal pathogen Cryptococcus neoformans
Authors: Yu Yiwu , Wang Yuanyuan , Li Linghua , Chen Xiaoqing , Huang Xinhua , Liang Huaping , Jiang Tong , Liao Guojian , Chen Min , Zhu Liping , Li Muyuan , Zhou Tao , Tang Qinyu , Zhao Jingjun , Chen Changbin 
Published: October 2021

AbstractThe fungus Cryptococcus neoformans is considered the leading cause of death in immunocompromised patients. Despite numerous investigations concerning its molecular epidemiology, there are only a few studies addressing the impacts of varying factors on genotype-phenotype correlations. It remains largely unknown whether genetic and environmental variabilities among isolates from different sources may have dramatic consequences on virulence. In this study, we analyzed 105 Chinese C. neoformans isolates, including 54 from HIV-infected patients, 44 from HIV-uninfected individuals and 7 from a natural environment, to investigate factors influencing the outcome of C. neoformans infection. MLST analysis clearly identified sequence type (ST) 5 as the prevalent sequence type in all clinical isolates and interestingly, genotypic diversities were observed in isolates from both HIV-uninfected individual and natural environment but not those from HIV-infected patients. Moreover, we found that compared to those from HIV-infected patients, the isolates from HIV-uninfected individuals exhibited enhanced virulence-associated traits including significantly elevated capsule production and melanin formation, increases in survival in human cerebrospinal fluid (CSF), less effective uptake by host phagocytes, and higher mortality in a mouse model of cryptococcosis. Consistently, pathogenic phenotypes were associated with CD4 counts of patients, implying environmental impact on within-host C. neoformans virulence. Importantly, a large-scale whole-genome sequencing analysis revealed that genomic variations within genes related to specific functions may act as a vital driving force of host intrinsic virulence evolution. Taken together, our results support a strong genotype-phenotype correlation suggesting that the pathogenic evolution of C. neoformans could be heavily affected by both genetic and environmental factors.
Propionate ameliorates diabetes-induced neurological dysfunction through regulating the PI3K/Akt/eNOS signaling pathway
Authors: Wu Qin , Dong Jiajun , Cheng Yahong , Jiang Gaofeng 
Published: October 2021

AbstractA large body of research has established diabetes-related cognitive deterioration, sometimes known as “diabetic encephalopathy.” Current evidence supports that oxidative stress, neuronal apoptosis, and cerebral microcirculation weakness are associated with cognition deficits induced by diabetes. The present study explores the effect of propionate on neurological deficits, cerebral blood flow, and oxidative stress in diabetic mice. Propionate can markedly improve neurological function, which is correlated with its capabilities of stimulating nitric oxide (NO) production, increasing cerebral microcirculation, suppressing oxidative stress and reducing neuron loss in the hippocampus. In addition, the results of Western Blotting indicated that the brain-protective function of propionate in streptozocin (STZ)-induced insulin-dependent diabetes mellitus (IDDM) mice is related to phosphoinositide 3-kinase (PI3K)/serine-threonine protein kinase (Akt)/endothelial nitric oxide synthase(eNOS) signaling pathway. In a diabetic mouse model, propionate reduces cerebral microcirculation, hippocampus apoptosis, and neurological impairment. Thus, propionate, now employed as a food preservative, may also help slow diabetes-induced cognitive loss.Graphical AbstractHighlightsPropionate ameliorates diabetic-induced depression-like behavior, spatial learning and memory deficits.Propionate increases cerebral microcirculation by enhancing NO production in diabetic mice.Propionate suppresses oxidative stress and reduces neuron loss in the hippocampus.The brain-protective function of propionate is related to PI3K/Akt/eNOS signaling pathway.
City climate and landscape structure shape pollinators, nectar and transported pollen along a gradient of urbanization
Authors: Biella Paolo , Tommasi Nicola , Guzzetti Lorenzo , Pioltelli Emiliano , Labra Massimo , Galimberti Andrea 
Published: October 2021

AbstractUrbanization gradients influence both landscape and climate and provide opportunity for understanding how species, especially plants and pollinators, respond to artificially driven environmental transitions.Here, we investigated several aspects of pollination along an urbanization gradient in landscape and climate. We quantified wild hoverfly and bee abundances with trapping, standing crop of nectar with spectrophotometer, and the pollen transported by flower-visitors with DNA-metabarcoding, in 40 independent sites from seminatural to built-up areas in Northern Italy.Linear and nonlinear relationships were detected along the urbanization gradient. Pollinator abundances increased until 22% of impervious surface, dropping by 34% after that, and it also decreased with green patch distance and urban park size. Thus, suburban landscapes host more pollinators than highly cemented or seminatural areas. Moreover, pollinators diminished by up to 45% in areas with low temperature seasonality: urbanized areas likely posing thermic stress. Furthermore, the sugar mass available in nectar increased by 91% with impervious cover, indicating that city nectars were less consumed or flowers more productive. Furthermore, the species richness of pollen decreased by 32% in highly urbanized areas, and with a high incidence of exotic plants, hinting for anthropized plant communities.Synthesis and applications. Urbanization influences pollinator abundances, nectar resources and transported pollen. Pollinators are negatively affected by a thermally harsh climate in highly urbanized areas with isolated green areas and large parks. Suburban landscapes demonstrated the highest pollinator presence. In the city core, flowers contained more nectary sugar, while pollinators collected pollen from a small number of plants, mainly exotic. These findings highlight the influence of urban landscape structure and climate on pollinators and plants, showing that cities are heterogenous realities. Patterns from this study will serve as basis for pollinator-friendly planning and management of urban landscapes.
Cofilin regulates actin network homeostasis and microvilli length in mouse oocytes
Authors: Bourdais Anne , Dehapiot Benoit , Halet Guillaume 
Published: October 2021

AbstractHow multiple actin networks coexist in a common cytoplasm, while competing for a shared pool of monomers, is still an ongoing question. This is exemplified by meiotic maturation in the mouse oocyte, which relies on the dynamic remodeling of distinct cortical and cytoplasmic F-actin networks. Here we show that the conserved actin-depolymerizing factor cofilin is activated in a switch-like manner at meiosis resumption from prophase arrest. Interfering with cofilin activation during maturation resulted in widespread microvilli elongation, while cytoplasmic F-actin was depleted, leading to defects in spindle migration and polar body extrusion. In contrast, cofilin inactivation in metaphase II-arrested oocytes resulted in a shutdown of F-actin dynamics, along with a dramatic overgrowth of the polarized actin cap. However, inhibition of the Arp2/3 complex to promote actin cap disassembly elicited ectopic microvilli outgrowth in the polarized cortex. These data establish cofilin as a key player in actin network homeostasis in oocytes, and reveal that microvilli can act as a sink for monomers upon disassembly of a competing network.
Remarkable Adsorption Performance of Rutile TiO2 (110) Nanosheet for DNA Nucleobases: A First-Principles Study
Authors: Yang Jin , Liu Wen , Hu Qiang , Hu Shuhuan , Chi Zonglin , Han Yizhang , Meng Fanchao 
Published: October 2021

AbstractThe remarkable biocompatibility and supreme physical properties of nanostructured TiO2 have promised itself a strong future for biomedical applications. The present study reported a theoretical study on the adsorption of rutile TiO2 (110) nanosheet for DNA nucleobases using first-principles calculations. The calculations of the binding energy and work function demonstrate that the TiO2 nanosheet has remarkable adsorption strength to the DNA nucleobases, being more than 20 times larger than that of graphene and its derivatives. Further electronic band structure and density of state calculations elucidate the interaction mechanisms, which originate from dramatically reduced energy levels and strong hybridization of the 2p orbital of C, N and/or O with 3d orbital of Ti atoms near the Fermi level. The study directs a promising material at applications in DNA sensors and sequencers.
Microtubule disassembly by caspases is the rate-limiting step of cell extrusion
Authors: Villars Alexis , Matamoro-Vidal Alexis , Levillayer Florence , Levayer Romain 
Published: October 2021

AbstractEpithelial cell death is essential for tissue homeostasis, robustness and morphogenesis. The expulsion of epithelial cells following caspase activation requires well-orchestrated remodeling steps leading to cell elimination without impairing tissue sealing. While numerous studies have provided insight about the process of cell extrusion, we still know very little about the relationship between caspase activation and the remodeling steps of cell extrusion. Moreover, most studies of cell extrusion focused on the regulation of actomyosin and steps leading to the formation of a supracellular contractile ring. However, the contribution of other cellular factors to cell extrusion has been poorly explored. Using the Drosophila pupal notum, a single layer epithelium where most extrusion events are caspase-dependent, we first showed that the initiation of cell extrusion and apical constriction are surprisingly not associated with the modulation of actomyosin concentration/dynamics. Instead, cell apical constriction is initiated by the disassembly of a medio-apical mesh of microtubules which is driven by effector caspases. We confirmed that local and rapid increase/decrease of microtubules is sufficient to respectively expand/constrict cell apical area. Importantly, the depletion of microtubules is sufficient to bypass the requirement of caspases for cell extrusion. This study shows that microtubules disassembly by caspases is a key rate-limiting steps of extrusion, and outlines a more general function of microtubules in epithelial cell shape stabilisation.
DAF-2/insulin IGF-1 receptor regulates motility during ageing by integrating opposite signaling from muscle and neuronal tissues
Authors: Roy Charline , Molin Laurent , Alcolei Allan , Solyga Mathilde , Bonneau Benjamin , Vachon Camille , Bessereau Jean-Louis , Solari Florence 
Published: October 2021

SUMMARYDuring ageing, preservation of locomotion is generally considered an indicator of sustained good health, in elderlies and in animal models. In C. elegans, mutants of the insulin-IGF-1 receptor DAF-2/IIRc represent a paradigm of healthy ageing, as their increased lifespan is accompanied by a delay in age-related loss of motility. However, these animals are less mobile than wild-type animals in early adulthood. Here we investigated the DAF-2/IIRc- dependent relationship between longevity and motility using an auxin-inducible degron to trigger tissue-specific degradation of endogenous DAF-2/IIRc. As previously reported, inactivation of DAF-2/IIRc in neurons or intestine was sufficient to extend the lifespan of worms, whereas depletion in epidermis, germline or muscle was not. However, neither intestinal nor neuronal depletion of DAF-2/IIRc prevented the age-related loss of motility. In 1-day-old adults, DAF-2/IIRc depletion in neurons reduced motility in a DAF-16/FOXO dependent manner, while muscle depletion had no effect. By contrast, DAF-2 depletion in the muscle of middleage animals improved their motility independently of DAF-16/FOXO but required UNC-120/SRF.Yet, neuronal or muscle DAF-2/IIRc depletion both preserved the mitochondria network in ageing muscle. Overall, these results show that the motility pattern of daf-2 mutants is determined by the sequential and opposing impact of neurons and muscle tissues and can be dissociated from the regulation of the lifespan. This work also provides the characterization of a versatile tool to analyze the tissue-specific contribution of insulin-like signaling in integrated phenotypes at the whole organism level.
Spatial signatures of anesthesia-induced burst-suppression differ between primates and rodents
Authors: Sirmpilatze Nikoloz , Mylius Judith , Ortiz-Rios Michael , Baudewig Jürgen , Paasonen Jaakko , Golkowski Daniel , Ranft Andreas , Ilg Rüdiger , Gröhn Olli , Boretius Susann 
Published: October 2021

AbstractDuring deep anesthesia, the electroencephalographic (EEG) signal of the brain alternates between bursts of activity and periods of relative silence (suppressions). The origin of burst-suppression and its distribution across the brain remain matters of debate. In this work, we used functional magnetic resonance imaging (fMRI) to map the brain areas involved in anesthesia-induced burst-suppression across four mammalian species: humans, long-tailed macaques, common marmosets, and rats. At first, we determined the fMRI signatures of burst-suppression in human EEG-fMRI data. Applying this method to animal fMRI datasets, we found distinct burst-suppression signatures in all species. The burst-suppression maps revealed a marked inter-species difference: in rats the entire neocortex engaged in burst-suppression, while in primates most sensory areas were excluded—predominantly the primary visual cortex. We anticipate that the identified species-specific fMRI signatures and whole-brain maps will guide future targeted studies investigating the cellular and molecular mechanisms of burst-suppression in unconscious states.
Astrocytic urea cycle detoxifies Aβ-derived ammonia while impairing memory in Alzheimer’s disease
Authors: Ju Yeon Ha , Bhalla Mridula , Hyeon Seung Jae , Oh Ju Eun , Yoo Seonguk , Chae Uikyu , Kwon Jae , Koh Wuhyun , Lim Jiwoon , Park Yongmin Mason , Lee Junghee , Cho Il-Joo , Lee Hyunbeom , Ryu Hoon , Lee C. Justin 
Published: October 2021

SummaryAlzheimer’s disease (AD) is one of the foremost neurodegenerative diseases, characterized by beta-amyloid (Aβ) plaques and significant progressive memory loss. In AD, astrocytes are known to take up and clear Aβ plaques. However, how Aβ induces pathogenesis and memory impairment in AD remains elusive. We report that normal astrocytes show non-cyclic urea metabolism, whereas Aβ-treated astrocytes show switched-on urea cycle with upregulated enzymes and accumulated entering-metabolite aspartate, starting-substrate ammonia, end-product urea, and side-product putrescine. Gene-silencing of astrocytic ornithine decarboxylase-1 (ODC1), facilitating ornithine-to-putrescine conversion, boosts urea cycle and eliminates aberrant putrescine and its toxic by-products ammonia, H2O2, and GABA to recover from reactive astrogliosis and memory impairment in AD model. Our findings implicate that astrocytic urea cycle exerts opposing roles of beneficial Aβ detoxification and detrimental memory impairment in AD. We propose ODC1-inhibition as a promising therapeutic strategy for AD to facilitate removal of toxic molecules and prevent memory loss.
Eyeblink conditioning performance and brain-wide C-fos expression in male and female mice
Authors: Oyaga Maria Roa , Serra Ines , Kurup Devika , Koekkoek Sebastiaan K.E. , Badura Aleksandra 
Published: October 2021

AbstractThe functional and molecular sources of behavioral variability in mice are not fully understood. As a consequence, the predominant use of male mice has become a standard in animal research, under the assumption that males are less variable than females. Similarly, to homogenize genetic background, neuroscience studies have almost exclusively used the C57BL/6 (B6) strain. Here, we examined individual differences in performance in the context of associative learning. We performed delayed eyeblink conditioning while recording locomotor activity in mice from both sexes in two strains (B6 and B6CBAF1). Further, we used a C-FOS immunostaining approach to explore brain areas involved in eyeblink conditioning across subjects and correlate them with behavioral performance. We found that B6 male and female mice show comparable variability in this task and that females reach higher learning scores. We found a strong positive correlation across sexes between learning scores and voluntary locomotion. C-FOS immunostainings revealed positive correlations between C-FOS positive cell density and learning in the cerebellar cortex, as well as multiple previously unreported extra-cerebellar areas. We found consistent and comparable correlations in eyeblink performance and C-fos expression in B6 and B6CBAF1 females and males. Taken together, we show that differences in motor behavior and activity across brain areas correlate with learning scores during eyeblink conditioning across strains and sexes.