bluuebunny/crossref_metadata_2025_split huggingface dataset:
White matter damage as a consequence of vascular dysfunction in a spontaneous mouse model of chronic mild chronic hypoperfusion with eNOS deficiency
Authors: Chen Xingyong , Chen Ling , Lin Geng , Wang Zhengjun , Kodali Mahesh C. , Li Mingqi , Chen Huimin , Lebovitz Sarah G. , Ortyl Tyler C. , Li Lexiao , Ismael Saifudeen , Singh Purnima , Malik Kafait U. , Ishrat Tauheed , Zhou Fu-Ming , Zheng Wei , Liao Francesca-Fang 
Published: August 2022

AbstractVascular cognitive impairment and dementia (VCID) is the second most common form of dementia after Alzheimer’s disease (AD). Currently, the mechanistic insights into the evolution and progression of VCID remain elusive. White matter change represents an invariant feature. Compelling clinical neuroimaging and pathological evidence suggest a link between white matter changes and neurodegeneration. Our prior study detected hypoperfused lesions in mice with partial deficiency of endothelial nitric oxide (eNOS) at very young age, precisely matching to those hypoperfused areas identified in preclinical AD patients. White matter tracts are particularly susceptible to the vascular damage induced by chronic hypoperfusion. Using immunohistochemistry, we detected severe demyelination in the middle-aged eNOS-deficient mice. The demyelinated areas were confined to cortical and subcortical areas including the corpus callosum and hippocampus. The intensity of demyelination correlated with behavioral deficits of gait and associative recognition memory performances. By Evans blue angiography, we detected blood–brain barrier (BBB) leakage as another early pathological change affecting frontal and parietal cortex in eNOS-deficient mice. Sodium nitrate fortified drinking water provided to young and middle-aged eNOS-deficient mice completely prevented non-perfusion, BBB leakage, and white matter pathology, indicating that impaired endothelium-derived NO signaling may have caused these pathological events. Furthermore, genome-wide transcriptomic analysis revealed altered gene clusters most related to mitochondrial respiratory pathways selectively in the white matter of young eNOS-deficient mice. Using eNOS-deficient mice, we identified BBB breakdown and hypoperfusion as the two earliest pathological events, resulting from insufficient vascular NO signaling. We speculate that the compromised BBB and mild chronic hypoperfusion trigger vascular damage, along with oxidative stress and astrogliosis, accounting for the white matter pathological changes in the eNOS-deficient mouse model. We conclude that eNOS-deficient mice represent an ideal spontaneous evolving model for studying the earliest events leading to white matter changes, which will be instrumental to future therapeutic testing of drug candidates and for targeting novel/specific vascular mechanisms contributing to VCID and AD.
Measuring corporate Paris Compliance using a strict science-based approach
Authors: Rekker S. , Ives M. C. , Wade B. , Webb L. , Greig C. 
Published: August 2022

AbstractThe achievement of the Paris Agreement climate goals of well-below 2 degrees of warming requires companies to align their greenhouse gas emission reductions with this goal. To measure whether companies are compliant with the Paris targets we propose several strict conditions that any emissions allocation methodology must meet before it can be classified as Paris-Compliant. Our conditions focus on the need for a common, and early as practicable, base year for all companies and consistency with an underlying Paris-aligned decarbonisation pathway. Additionally, we propose four operationalisation requirements to ensure companies can declare they are on a Paris Compliant Pathway including calculations of their carbon budgets and re-alignment pathways. Applying example Paris-Compliant Pathways and associated metrics to ten high emission electric utility companies and ten cement companies, we find that all but one of these companies are not currently Paris-compliant, with every year of delayed action increasing their required rate of decarbonisation and hence the exposure of billions of investment dollars to transition risk. Applying this proposed method will ensure the Paris carbon budget is met and that progress can be tracked accurately - an imperative for any companies and stakeholders seeking to align their decision-making with the Paris Agreement.
N-Heterocyclic carbene-based C-centered Au(I)-Ag(I) clusters with intense phosphorescence and organelle-selective translocation in cells
Authors: Lei Zhen , Endo Mizuki , Ube Hitoshi , Shiraogawa Takafumi , Zhao Pei , Nagata Koichi , Pei Xiao-Li , Eguchi Tomoya , Kamachi Toshiaki , Ehara Masahiro , Ozawa Takeaki , Shionoya Mitsuhiko 
Published: August 2022

AbstractPhotoluminescent gold clusters are functionally variable chemical modules by ligand design. Chemical modification of protective ligands and introduction of different metals into the gold clusters lead to discover unique chemical and physical properties based on their significantly perturbed electronic structures. Here we report the synthesis of carbon-centered Au(I)-Ag(I) clusters with high phosphorescence quantum yields using N-heterocyclic carbene ligands. Specifically, a heterometallic cluster [(C)(AuI-L)6AgI2]4+, where L denotes benzimidazolylidene-based carbene ligands featuring N-pyridyl substituents, shows a significantly high phosphorescence quantum yield (Φ = 0.88). Theoretical calculations suggest that the carbene ligands accelerate the radiative decay by affecting the spin-orbit coupling, and the benzimidazolylidene ligands further suppress the non-radiative pathway. Furthermore, these clusters with carbene ligands are taken up into cells, emit phosphorescence and translocate to a particular organelle. Such well-defined, highly phosphorescent C-centered Au(I)-Ag(I) clusters will enable ligand-specific, organelle-selective phosphorescence imaging and dynamic analysis of molecular distribution and translocation pathways in cells.
Reduced synaptic activity and dysregulated extracellular matrix pathways in midbrain neurons from Parkinson’s disease patients
Authors: Stern Shani , Lau Shong , Manole Andreea , Rosh Idan , Percia Menachem Mendel , Ben Ezer Ran , Shokhirev Maxim N. , Qiu Fan , Schafer Simon , Mansour Abed AlFatah , Mangan Kile P. , Stern Tchelet , Ofer Polina , Stern Yam , Diniz Mendes Ana Paula , Djamus Jose , Moore Lynne Randolph , Nayak Ritu , Laufer Sapir Havusha , Aicher Aidan , Rhee Amanda , Wong Thomas L. , Nguyen Thao , Linker Sara B. , Winner Beate , Freitas Beatriz C. , Jones Eugenia , Sagi Irit , Bardy Cedric , Brice Alexis , Winkler Juergen , Marchetto Maria C. , Gage Fred H. 
Published: August 2022

AbstractSeveral mutations that cause Parkinson’s disease (PD) have been identified over the past decade. These account for 15–25% of PD cases; the rest of the cases are considered sporadic. Currently, it is accepted that PD is not a single monolithic disease but rather a constellation of diseases with some common phenotypes. While rodent models exist for some of the PD-causing mutations, research on the sporadic forms of PD is lagging due to a lack of cellular models. In our study, we differentiated PD patient-derived dopaminergic (DA) neurons from the induced pluripotent stem cells (iPSCs) of several PD-causing mutations as well as from sporadic PD patients. Strikingly, we observed a common neurophysiological phenotype: neurons derived from PD patients had a severe reduction in the rate of synaptic currents compared to those derived from healthy controls. While the relationship between mutations in genes such as theSNCAandLRRK2and a reduction in synaptic transmission has been investigated before, here we show evidence that the pathogenesis of the synapses in neurons is a general phenotype in PD. Analysis of RNA sequencing results displayed changes in gene expression in different synaptic mechanisms as well as other affected pathways such as extracellular matrix-related pathways. Some of these dysregulated pathways are common to all PD patients (monogenic or idiopathic). Our data, therefore, show changes that are central and convergent to PD and suggest a strong involvement of the tetra-partite synapse in PD pathophysiology.
A conformational switch controlling the toxicity of the prion protein
Authors: Frontzek Karl , Bardelli Marco , Senatore Assunta , Henzi Anna , Reimann Regina R. , Bedir Seden , Marino Marika , Hussain Rohanah , Jurt Simon , Meisl Georg , Pedotti Mattia , Mazzola Federica , Siligardi Giuliano , Zerbe Oliver , Losa Marco , Knowles Tuomas , Lakkaraju Asvin , Zhu Caihong , Schwarz Petra , Hornemann Simone , Holt Matthew G. , Simonelli Luca , Varani Luca , Aguzzi Adriano 
Published: August 2022

AbstractPrion infections cause conformational changes of the cellular prion protein (PrPC) and lead to progressive neurological impairment. Here we show that toxic, prion-mimetic ligands induce an intramolecular R208-H140 hydrogen bond (‘H-latch’), altering the flexibility of the α2–α3 and β2–α2 loops of PrPC. Expression of a PrP2Cys mutant mimicking the H-latch was constitutively toxic, whereas a PrPR207A mutant unable to form the H-latch conferred resistance to prion infection. High-affinity ligands that prevented H-latch induction repressed prion-related neurodegeneration in organotypic cerebellar cultures. We then selected phage-displayed ligands binding wild-type PrPC, but not PrP2Cys. These binders depopulated H-latched conformers and conferred protection against prion toxicity. Finally, brain-specific expression of an antibody rationally designed to prevent H-latch formation prolonged the life of prion-infected mice despite unhampered prion propagation, confirming that the H-latch is an important reporter of prion neurotoxicity.
The unique second wave phenomenon in contrast enhanced ultrasound imaging with nanobubbles
Authors: Chen Chuan , Perera Reshani , Kolios Michael C. , Wijkstra Hessel , Exner Agata A. , Mischi Massimo , Turco Simona 
Published: August 2022

AbstractInvestigation of nanobubble (NB) pharmacokinetics in contrast-enhanced ultrasound (CEUS) at the pixel level shows a unique phenomenon where the first pass of the contrast agent bolus is accompanied by a second wave. This effect has not been previously observed in CEUS with microbubbles. The objective of this study was to investigate this second-wave phenomenon and its potential clinical applications. Seven mice with a total of fourteen subcutaneously-implanted tumors were included in the experiments. After injecting a bolus of NBs, the NB-CEUS images were acquired to record the time-intensity curves (TICs) at each pixel. These TICs are fitted to a pharmacokinetic model which we designed to describe the observed second-wave phenomenon. The estimated model parameters are presented as parametric maps to visualize the characteristics of tumor lesions. Histological analysis was also conducted in one mouse to compare the molecular features of tumor tissue with the obtained parametric maps. The second-wave phenomenon is evidently shown in a series of pixel-based TICs extracted from either tumor or tissues. The value of two model parameters, the ratio of the peak intensities of the second over the first wave, and the decay rate of the wash-out process present large differences between malignant tumor and normal tissue (0.04 < Jessen-Shannon divergence < 0.08). The occurrence of a second wave is a unique phenomenon that we have observed in NB-CEUS imaging of both mouse tumor and tissue. As the characteristics of the second wave are different between tumor and tissue, this phenomenon has the potential to support the diagnosis of cancerous lesions.
Potentiation of combined p19Arf and interferon-beta cancer gene therapy through its association with doxorubicin chemotherapy
Authors: Medrano Ruan F. V. , Salles Thiago A. , Dariolli Rafael , Antunes Fernanda , Feitosa Valker A. , Hunger Aline , Catani João P. P. , Mendonça Samir A. , Tamura Rodrigo E. , Lana Marlous G. , Rodrigues Elaine G. , Strauss Bryan E. 
Published: August 2022

AbstractBalancing safety and efficacy is a major consideration for cancer treatments, especially when combining cancer immunotherapy with other treatment modalities such as chemotherapy. Approaches that induce immunogenic cell death (ICD) are expected to eliminate cancer cells by direct cell killing as well as activation of an antitumor immune response. We have developed a gene therapy approach based on p19Arf and interferon-β gene transfer that, similar to conventional inducers of ICD, results in the release of DAMPS and immune activation. Here, aiming to potentiate this response, we explore whether association between our approach and treatment with doxorubicin (Dox), a known inducer of ICD, could further potentiate treatment efficacy without inducing cardiotoxicity, a critical side effect of Dox. Using central composite rotational design analysis, we show that cooperation between gene transfer and chemotherapy killed MCA205 and B16F10 cells and permitted the application of reduced viral and drug doses. The treatments also cooperated to induce elevated levels of ICD markers in MCA205, which correlated with improved efficacy of immunotherapy in vivo. Treatment of subcutaneous MCA205 tumors associating gene transfer and low dose (10 mg/kg) chemotherapy resulted in inhibition of tumor progression. Moreover, the reduced dose did not cause cardiotoxicity as compared to the therapeutic dose of Dox (20 mg/kg). The association of p19Arf/interferon-β gene transfer and Dox chemotherapy potentiated antitumor response and minimized cardiotoxicity.
Hydrogel-extraction technique for non-invasive detection of blue fluorescent substances in plant leaves
Authors: Iwasa Shigeyuki , Kobara Yuso , Maeda Katsumi , Nagamine Kuniaki 
Published: August 2022

AbstractThis paper reports a new hydrogel extraction technique for detecting blue fluorescent substances in plant leaves. These blue fluorescent substances were extracted by placing a hydrogel film on the leaf of a cherry tomato plant infected withRalstonia solanacearum; herein, chlorogenic acid was confirmed to be a blue fluorescent substance. The wavelength at the maximum fluorescence intensity of the film after the hydrogel extraction was similar to that of the methanolic extract obtained from the infected cherry tomato leaves. Chlorophyll was not extracted from the hydrogel film because no fluorescence peak was observed at 680 nm. Accordingly, the blue fluorescence of the substances extracted from the hydrogel film was not quenched by the strong absorption of chlorophyll in the blue light region. This hydrogel extraction technique can potentially detect small amounts of blue fluorescent substances and the changes in its amount within the leaves of infected plants. These changes in the amount of blue fluorescent substances in the early stages of infection can be used to detect presymptomatic infections. Therefore, hydrogel extraction is a promising technique for the noninvasive detection of infections before onset.
Changes in soil carbon mineralization related to earthworm activity depend on the time since inoculation and their density in soil
Authors: Garnier Patricia , Makowski David , Hedde Mickael , Bertrand Michel 
Published: August 2022

AbstractEarthworms play a key role in soil carbon mineralization, but their effect is highly uncertain and suspected to vary as a function of several factors, particularly the earthworm density and time from earthworm inoculation. We conducted a meta-analysis considering these factors based on 42 experiments comparing carbon mineralization in the absence and presence of earthworms at different times. The results reveal an average carbon mineralization increase of 24% (sd 41%) in the presence of earthworms with an initial median earthworm density of 1.95 mg/g soil DM (Dry Mass) (sd 48%). We show that carbon mineralization due to earthworms was related to their density and time from inoculation. From a simple regression model using these two variables, the estimated impact of earthworms on carbon mineralization was 20% increase from 0 to 60 days and 14% decrease at day 350 for a density of worms commonly found in soils (0.5 mg/g soil DM). Finally, we proposed a simple equation that could be used in organic matter decomposition models that do not take macrofauna into account.
The mediating effect of parenting style on the relationship between first-born children’s temperament and psychological adaptation
Authors: Qian Guoying , Yang Sijie , Li Ruonan , Dou Gang 
Published: August 2022

AbstractChinese first-born children need to learn how to get along with their siblings after the implementation of the universal two-child policy in 2016. We investigated the relationships between temperament, parenting style, and psychological adjustment among firstborns. The current study employed a questionnaire survey conducted in four regions in China. A total of 524 Chinese two-child families participated in the study; the firstborns were between 3 and 8 years old and their younger siblings were between 1 month and 5 years old. The results indicated that (1) children’s temperament subscales were significantly related to parenting style subscales and psychological adaptation. Moreover, the parenting style subscales were significantly related to psychological adaptation, and (2) authoritarian parenting partially mediated the relationship between approach or withdrawal and psychological adjustment.
Anti-tumor activity of a T-helper 1 multiantigen vaccine in a murine model of prostate cancer
Authors: Cecil Denise L. , Curtis Benjamin , Gad Ekram , Gormley Michael , Timms Andrew E. , Corulli Lauren , Bos Rinke , Damle Rajendra N. , Sepulveda Manuel A. , Disis Mary L. 
Published: August 2022

AbstractProstate cancer is one of the few malignancies that includes vaccination as a treatment modality. Elements of an effective cancer vaccine should include the ability to elicit a Type I T-cell response and target multiple antigenic proteins expressed early in the disease. Using existing gene datasets encompassing normal prostate tissue and tumors with Gleason Score ≤ 6 and ≥ 8, 10 genes were identified that were upregulated and conserved in prostate cancer regardless of the aggressiveness of disease. These genes encoded proteins also expressed in prostatic intraepithelial neoplasia. Putative Class II epitopes derived from these proteins were predicted by a combination of algorithms and, using human peripheral blood, epitopes which selectively elicited IFN-γ or IL-10 dominant antigen specific cytokine secretion were determined. Th1 selective epitopes were identified for eight antigens. Epitopes from three antigens elicited Th1 dominant immunity in mice; PSMA, HPN, and AMACR. Each single antigen vaccine demonstrated significant anti-tumor activity inhibiting growth of implanted Myc-Cap cells after immunization as compared to control. Immunization with the combination of antigens, however, was superior to each alone in controlling tumor growth. When vaccination occurred simultaneously to tumor implant, multiantigen immunized mice had significantly smaller tumors than controls (p = 0.002) and a significantly improved overall survival (p = 0.0006). This multiantigen vaccine shows anti-tumor activity in a murine model of prostate cancer.
Insect cuticular compounds affect Conidiobolus coronatus (Entomopthorales) sporulation and the activity of enzymes involved in fungal infection
Authors: Włóka Emilia , Boguś Mieczysława Irena , Wrońska Anna Katarzyna , Drozdowski Mikołaj , Kaczmarek Agata , Sobich Justyna , Gołębiowski Marek 
Published: August 2022

AbstractMycoses are a global problem that affects humans and animals. In the present study, the entomopathogenic soil fungus Conidiobolus coronatus (Entomophthorales), infecting in tropics also humans, sheep and horses, was cultivated with the addition of insect cuticular compounds (CCs) previously detected in the cuticle of C. coronatus—resistant fly species (C10–C30 fatty alcohols, butyl oleate, butyl stearate, glycerol oleate, squalene, tocopherol acetate). Our findings indicate that CCs have diversified and complex effects on the growth and sporulation of C. coronatus and its ability to infect the larvae of Galleria mellonella (Lepidoptera). The CCs affected protein content and cuticle-degrading enzymes (CDEs) activity in the conidia. Some CCs inhibited fungal growth (0.1% C10), decreased sporulation (C12, C16, C24, C28, C30, butyl stearate, squalene), virulence (C12, C14, butyl oleate, butyl stearate) and protein content (C18). They also reduced conidial CDE activity: elastase (C24, butyl oleate, butyl stearate, squalene, tocopherol acetate), chitobiosidase (C12, C14, C20) and lipase (C12, C18, C26, squalene, tocopherol acetate). Several CCs enhanced sporulation (C14, C18, C22, C26, C30), virulence (C18, C26, squalene), conidial protein content (C16, C24, C30, squalene) and CDE activity: elastase (C10, C16, C18), NAGase (C16, C20), chitobiosidase (C16) and lipase (C10, C14, C16, C20, butyl oleate). Our findings indicate that C. coronatus colonies grown on media supplemented with CCs employ various compensation strategies: colonies grown with C16 alcohol demonstrated reduced sporulation but greater conidial protein accumulation and increased elastase, NAGase, chitobiosidase and lipase activity, thus preserving high virulence. Also, colonies supplemented with C18 alcohol demonstrated high virulence and enhanced sporulation and elastase activity but slightly decreased conidial protein content. CCs that inhibit the activity of lipases and proteases show promise in the fight against conidiobolomycosis.
The a subunit isoforms of vacuolar-type proton ATPase exhibit differential distribution in mouse perigastrulation embryos
Authors: Sun-Wada Ge-Hong , Wada Yoh 
Published: August 2022

AbstractVacuolar-type H+-ATPases (V-ATPases) are large multi-subunit complexes that play critical roles in the acidification of a variety of intracellular or extracellular compartments. Mammalian cells contain four isoforms of the membrane integral subunit a (a1–a4); these isoforms contain the information necessary to target the enzyme to different cellular destinations. They are also involved in regulating the efficiency of ATP hydrolysis and proton transport. Previously, we showed that early embryogenesis requires V-ATPase function, and the luminal acidic endocytic and lysosomal compartments in the visceral endoderm of mouse embryos at the pre-gastrulation stage (E6.5) are essential for both nutrition and signal transduction during early embryogenesis. In this study, we examined the expression and distribution of a subunit isoforms in mouse embryos at E6.5. We found that all four isoforms expressed and exhibited differential distribution in the E6.5 embryo. At this developmental stage, the embryos establish highly elaborate endocytic compartments called apical vacuoles, on which the a3 isoform specifically accumulated.