The bipyridyl herbicide paraquat-induced toxicity in human neuroblastoma SH-SY5Y cells: relevance to dopaminergic pathogenesis

Paraquat (PQ) is a cationic non-selective bipyridyl herbicide widely used in agriculture to control weeds and grasses. Epidemiologic studies indicate that exposure to pesticides can be a risk factor in the incidence of Parkinson`s disease (PD). A strong correlation has been reported between exposure to paraquat and PD incidence in Canada, Taiwan, and United States. This correlation is supported by animal studies showing that paraquat produces toxicity in dopaminergic neurons of the rat and mouse brain. However, it is unclear how paraquat triggers toxicity in dopaminergic neurons. Based on the previous reports, it was hypothesized that paraquat may induce oxidative stress and proteasomal dysfunction-mediated toxicity in dopaminergic neurons. To explore this possibility, dopaminergic SH-SY5Y human neuroblastoma cells were treated with paraquat, and several biomarkers of oxidative stress or proteasomal dysfunction were investigated. First, a specific dopamine transporter inhibitor GBR12909 significantly protected SY5Y cells against the toxicity of paraquat, indicating that paraquat exerts its toxicity by a mechanism involving the dopamine transporter (DAT). Second, paraquat increased the levels of reactive oxygen species (ROS) in SY5Y cells, but decreased the levels of glutathione. Third, paraquat inhibited glutathione peroxidase activity, but did not affect glutathione reductase activity. On the other hand, paraquat increased GST activity by 24 hr, after which GST activity returned to the control value at 48 hr. Fourth, paraquat decreased mitochondrial transmembrane potential (MTP). Fifth, paraquat produced the increases in malondialdehyde (MDA) and protein carbonyls, as well as DNA fragmentation, indicating oxidative damage to major cellular components. Sixth, paraquat decreased proteasomal activity, the activities of mitochondrial complex I and V, and intracellular ATP levels, but increased the activities of caspase 3 and 9, indicating that proteasomal inhibition is linked to mitochondrial dysfunction accompanied by the activation of apoptotic signaling pathway. Seventh, paraquat increased the protein levels of heme oxygenase-1 (HO-1), p53, Bax, ñ-synuclein and ubiquitinated proteins. Eighth, paraquat induced nuclear condensation. Taken together, these findings support the hypothesis that paraquat produces oxidative stress and proteasomal dysfunctionmediated toxicity in SY5Y cells. Thus, current findings suggest that paraquat may induce the pathogenesis of dopaminergic neurons through oxidative stress and proteasomal dysfunction

Fashion Style Editing with Generative Human Prior

Image editing has been a long-standing challenge in the research community with its far-reaching impact on numerous applications. Recently, text-driven methods started to deliver promising results in domains like human faces, but their applications to more complex domains have been relatively limited. In this work, we explore the task of fashion style editing, where we aim to manipulate the fashion style of human imagery using text descriptions. Specifically, we leverage a generative human prior and achieve fashion style editing by navigating its learned latent space. We first verify that the existing text-driven editing methods fall short for our problem due to their overly simplified guidance signal, and propose two directions to reinforce the guidance: textual augmentation and visual referencing. Combined with our empirical findings on the latent space structure, our Fashion Style Editing framework (FaSE) successfully projects abstract fashion concepts onto human images and introduces exciting new applications to the field.Comment: 5 page

Annealing of focused ion beam damage in gold microcrystals: an in situ Bragg coherent X-ray diffraction imaging study

Focused ion beam (FIB) techniques are commonly used to machine, analyse and image materials at the micro- and nanoscale. However, FIB modifies the integrity of the sample by creating defects that cause lattice distortions. Methods have been developed to reduce FIB-induced strain; however, these protocols need to be evaluated for their effectiveness. Here, non-destructive Bragg coherent X-ray diffraction imaging is used to study the in situ annealing of FIB-milled gold microcrystals. Two non-collinear reflections are simultaneously measured for two different crystals during a single annealing cycle, demonstrating the ability to reliably track the location of multiple Bragg peaks during thermal annealing. The thermal lattice expansion of each crystal is used to calculate the local temperature. This is compared with thermocouple readings, which are shown to be substantially affected by thermal resistance. To evaluate the annealing process, each reflection is analysed by considering facet area evolution, cross-correlation maps of the displacement field and binarized morphology, and average strain plots. The crystal's strain and morphology evolve with increasing temperature, which is likely to be caused by the diffusion of gallium in gold below ∼280°C and the self-diffusion of gold above ∼280°C. The majority of FIB-induced strains are removed by 380–410°C, depending on which reflection is being considered. These observations highlight the importance of measuring multiple reflections to unambiguously interpret material behaviour

Flexible Acceptance Condition of Generics from a Probabilistic Viewpoint: Towards Formalization of the Semantics of Generics

Formalization of the semantics of generics has been considered extremely challenging for their inherent vagueness and context-dependence that hinder a single fixed truth condition. The present study suggests a way to formalize the semantics of generics by constructing flexible acceptance conditions with comparative probabilities. Findings from our in-depth psycholinguistic experiment show that two comparative probabilities—cue validity and prevalence—indeed construct the flexible acceptance conditions for generics in a systematic manner that can be applied to a diverse types of generics: Acceptability of IS_A relational generics is mostly determined by prevalence without interaction with cue validity; feature-describing generics are endorsed acceptable with high cue validity, albeit mediated by prevalence; and acceptability of feature-describing generics with low cue validity is mostly determined by prevalence irrespective of cue validity. Such systematic patterns indicate a great potential for the formalization of the semantics of generics

Refinements for Bragg coherent X-ray diffraction imaging: electron backscatter diffraction alignment and strain field computation

Bragg coherent X-ray diffraction imaging (BCDI) allows the 3D measurement of lattice strain along the scattering vector for specific microcrystals. If at least three linearly independent reflections are measured, the 3D variation of the full lattice strain tensor within the microcrystal can be recovered. However, this requires knowledge of the crystal orientation, which is typically attained via estimates based on crystal geometry or synchrotron microbeam Laue diffraction measurements. Presented here is an alternative method to determine the crystal orientation for BCDI measurements using electron backscatter diffraction (EBSD) to align Fe–Ni and Co–Fe alloy microcrystals on three different substrates. The orientation matrix is calculated from EBSD Euler angles and compared with the orientation determined using microbeam Laue diffraction. The average angular mismatch between the orientation matrices is less than ∼6°, which is reasonable for the search for Bragg reflections. The use of an orientation matrix derived from EBSD is demonstrated to align and measure five reflections for a single Fe–Ni microcrystal via multi-reflection BCDI. Using this data set, a refined strain field computation based on the gradient of the complex exponential of the phase is developed. This approach is shown to increase accuracy, especially in the presence of dislocations. The results demonstrate the feasibility of using EBSD to pre-align BCDI samples and the application of more efficient approaches to determine the full lattice strain tensor with greater accuracy

Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes. An Individual-Participant Data Meta-Analysis

IMPORTANCE: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. OBJECTIVE: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. DESIGN, SETTING, AND PARTICIPANTS: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. EXPOSURES: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). MAIN OUTCOMES AND MEASURES: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. RESULTS: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). CONCLUSIONS AND RELEVANCE: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations

Pano-AVQA: Grounded Audio-Visual Question Answering on 360◦ Videos

© 2021 IEEE360◦ videos convey holistic views for the surroundings of a scene. It provides audio-visual cues beyond predetermined normal field of views and displays distinctive spatial relations on a sphere. However, previous benchmark tasks for panoramic videos are still limited to evaluate the semantic understanding of audio-visual relationships or spherical spatial property in surroundings. We propose a novel benchmark named Pano-AVQA as a large-scale grounded audio-visual question answering dataset on panoramic videos. Using 5.4K 360◦ video clips harvested online, we collect two types of novel question-answer pairs with bounding-box grounding: spherical spatial relation QAs and audio-visual relation QAs. We train several transformer-based models from Pano-AVQA, where the results suggest that our proposed spherical spatial embeddings and multimodal training objectives fairly contribute to a better semantic understanding of the panoramic surroundings on the dataset.N