Miracle-dz/UniFAR-FTUs huggingface dataset:
ASK1 contributes to fibrosis and dysfunction in models of kidney disease

Oxidative stress is an underlying component of acute and chronic kidney disease. Apoptosis signal–regulating kinase 1 (ASK1) is a widely expressed redox-sensitive serine threonine kinase that activates p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase kinases, and induces apoptotic, inflammatory, and fibrotic signaling in settings of oxidative stress. We describe the discovery and characterization of a potent and selective small-molecule inhibitor of ASK1, GS-444217, and demonstrate the therapeutic potential of ASK1 inhibition to reduce kidney injury and fibrosis. Activation of the ASK1 pathway in glomerular and tubular compartments was confirmed in renal biopsies from patients with diabetic kidney disease (DKD) and was decreased by GS-444217 in several rodent models of kidney injury and fibrosis that collectively represented the hallmarks of DKD pathology. Treatment with GS-444217 reduced progressive inflammation and fibrosis in the kidney and halted glomerular filtration rate decline. Combination of GS-444217 with enalapril, an angiotensin-converting enzyme inhibitor, led to a greater reduction in proteinuria and regression of glomerulosclerosis. These results identify ASK1 as an important target for renal disease and support the clinical development of an ASK1 inhibitor for the treatment of DKD.
Randomized clinical trial on the comparison of bleaching outcomes using either ozone or hydrogen peroxide.

OBJECTIVE To evaluate the efficacy of in-office tooth bleaching following application of either ozone (O3) or hydrogen peroxide (H2O2). METHOD AND MATERIALS 32 participants were randomly distributed into two groups (n = 16 each). Participants' maxillary anterior teeth were treated with ozone (produced via a healOzone X4 device; Curozone) for 60 seconds in Group 1, or with 38% H2O2 for 20 minutes in Group 2. Tooth shades were evaluated by means of a colorimeter (CR-400, Minolta) measuring Vita classic shades in addition to L*a*b* shade values before and following bleaching in each group. A visual analog scale was used to evaluate tooth sensitivity before and after bleaching. Statistically significant differences were identified at P < . 05. RESULTS Teeth obtained lighter shades (increased L* and reduced a* and b* values) following bleaching in both groups (P < .001). Both groups revealed comparable bleaching outcomes (P > .05). However, bleaching with ozone did not result in tooth sensitivity, whilst using H2O2 was accompanied with significantly increased bleaching sensitivity (P < .001). CONCLUSION Similar bleaching outcomes and lighter tooth shades (both for Vita shades and L*a*b* values) were obtained following in-office bleaching with either 60 seconds of ozone or 20 minutes of 38% H2O2. Notwithstanding, tooth sensitivity was significantly increased following bleaching with H2O2 in comparison to ozone. Ozone obviously does reduce the regularly clinically observed inconveniences of bleaching by means of H2O2; thus, ozone would seem worth considering for patients asking for in-office tooth bleaching.
Biochemical studies evaluating the chemopreventive potential of brucine in chemically induced mammary carcinogenesis of rats

Abstract The present study was aimed to investigate the dose dependent chemopreventive activity of brucine against 7, 12-dimethylbenz (a) anthracene induced mammary gland tumorigenesis in rats. The mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near the mammary gland. We observed reduced body weight and increase in tumor incidence, the total number of tumors, and tumor volume in DMBA alone injected rats and also observed decreased antioxidant status (SOD, CAT, GPX, and GSH) and increased lipid peroxidation (TBARS and LOOH) in plasma and mammary tissues. Increased levels of CYP450, Cyt-b5 and decreased levels of phase II (GST and GR) biotransformation enzymes were noticed in the liver and mammary tissues. Further, increased levels of lipid profile (TC, TG, PL, and FFA) and lipoprotein (LDL and VLDL) were noticed. Whereas, decrease in the levels of HDL in plasma and decreased levels of PL and FFA in mammary tissues were observed. Oral administration of brucine in different doses (2, 4 and 8 mg/kg bw) inhibited the tumor incidence and restored the levels of biochemical markers near to normal in dose responsive manner. Biochemical findings are supported by histopathological studies. The results suggest that brucine at a dose of 8 mg/kg bw shows more significant chemopreventive activity in DMBA-induced mammary carcinogenesis.
Autism‐related behaviors in the cyclooxygenase‐2‐deficient mouse model

Prostaglandin E2 (PGE2) is an endogenous lipid molecule involved in normal brain development. Cyclooxygenase‐2 (COX2) is the main regulator of PGE2 synthesis. Emerging clinical and molecular research provides compelling evidence that abnormal COX2/PGE2 signaling is associated with autism spectrum disorder (ASD). We previously found that COX2 knockout mice had dysregulated expression of many ASD genes belonging to important biological pathways for neurodevelopment. The present study is the first to show the connection between irregular COX2/PGE2 signaling and autism‐related behaviors in male and female COX2‐deficient knockin, (COX)‐2−, mice at young (4‐6 weeks) or adult (8‐11 weeks) ages. Autism‐related behaviors were prominent in male (COX)‐2− mice for most behavioral tests. In the open field test, (COX)‐2− mice traveled more than controls and adult male (COX)‐2− mice spent less time in the center indicating elevated hyperactive and anxiety‐linked behaviors. (COX)‐2− mice also buried more marbles, with males burying more than females, suggesting increased anxiety and repetitive behaviors. Young male (COX)‐2− mice fell more frequently in the inverted screen test revealing motor deficits. The three‐chamber sociability test found that adult female (COX)‐2− mice spent less time in the novel mouse chamber indicative of social abnormalities. In addition, male (COX)‐2− mice showed altered expression of several autism‐linked genes: Wnt2, Glo1, Grm5 and Mmp9. Overall, our findings offer new insight into the involvement of disrupted COX2/PGE2 signaling in ASD pathology with age‐related differences and greater impact on males. We propose that (COX)‐2− mice might serve as a novel model system to study specific types of autism.
Origin of Equisetum: Evolution of horsetails (Equisetales) within the major euphyllophyte clade Sphenopsida.

PREMISE OF THE STUDY Equisetum is the sole living representative of Sphenopsida, a clade with impressive species richness, a long fossil history dating back to the Devonian, and obscure relationships with other living pteridophytes. Based on molecular data, the crown group age of Equisetum is mid-Paleogene, although fossils with possible crown synapomorphies appear in the Triassic. The most widely circulated hypothesis states that the lineage of Equisetum derives from calamitaceans, but no comprehensive phylogenetic studies support the claim. Using a combined approach, we provide a comprehensive phylogenetic analysis of Equisetales, with special emphasis on the origin of genus Equisetum. METHODS We performed parsimony phylogenetic analyses to address relationships of 43 equisetalean species (15 extant, 28 extinct) using a combination of morphological and molecular characters. KEY RESULTS We recovered Equisetaceae + Neocalamites as sister to Calamitaceae + a clade of Angaran and Gondwanan horsetails, with the four groups forming a clade that is sister to Archaeocalamitaceae. The estimated age for the Equisetum crown group is mid-Mesozoic. CONCLUSIONS Modern horsetails are not nested within calamitaceans; instead, both groups have explored independent evolutionary trajectories since the Carboniferous. Diverse fossil taxon sampling helps to shed light on the position and relationships of equisetalean lineages, of which only a tiny remnant is present within the extant flora. Understanding these relationships and early character configurations of ancient plant clades as Equisetales provide useful tests of hypotheses about overall phylogenetic relationships of euphyllophytes and foundations for future tests of molecular dates with paleontological data.
Adaptive Memory: Survival Processing and Social Isolation

Social isolation was examined to assess its potential influence on the survival processing effect, which shows that individuals are more likely to remember something when it is processed with regard to their survival. Participants imagined being stranded in the grasslands, going on a space mission, or moving to a foreign land while alone or with a group of friends and rated a list of words for their relevance to the assigned scenario. An incidental memory test showed the typical survival processing effect on recall memory, with a significant interaction showing that the effect occurred in the isolated condition but not in the group condition. A second experiment examined rates of recognition for an isolated and group condition for the grasslands and moving scenarios and found a marginally significant effect of isolation in addition to the typical survival processing effect. Further, in both experiments, the perceived isolation of the isolated and group survival grasslands scenarios was significantly higher than the other conditions. The results are discussed with regard to the self-reference effect and the object-function account of the survival processing effect.
Automated quantitative analysis of multiple cardiomyocytes at the single‐cell level with three‐dimensional holographic imaging informatics

Cardiomyocytes derived from human pluripotent stem cells are a promising tool for disease modeling, drug compound testing, and cardiac toxicity screening. Bio‐image segmentation is a prerequisite step in cardiomyocyte image analysis by digital holography (DH) in microscopic configuration and has provided satisfactory results. In this study, we quantified multiple cardiac cells from segmented 3‐dimensional DH images at the single‐cell level and measured multiple parameters describing the beating profile of each individual cell. The beating profile is extracted by monitoring dry‐mass distribution during the mechanical contraction‐relaxation activity caused by cardiac action potential. We present a robust two‐step segmentation method for cardiomyocyte low‐contrast image segmentation based on region and edge information. The segmented single‐cell contains mostly the nucleus of the cell since it is the best part of the cardiac cell, which can be perfectly segmented. Clustering accuracy was assessed by a silhouette index evaluation for k‐means clustering and the Dice similarity coefficient (DSC) of the final segmented image. 3D representation of single of cardiomyocytes. The cell contains mostly the nucleus section and a small area of cytoplasm.
Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells

Mounting evidence implicates chronic oxidative stress as a critical driver of the aging process. Down syndrome (DS) is characterized by a complex phenotype, including early senescence. DS cells display increased levels of reactive oxygen species (ROS) and mitochondrial structural and metabolic dysfunction, which are counterbalanced by sustained Nrf2‐mediated transcription of cellular antioxidant response elements (ARE). Here, we show that caspase 3/PKCδdependent activation of the Nrf2 pathway in DS and Dp16 (a mouse model of DS) cells is necessary to protect against chronic oxidative damage and to preserve cellular functionality. Mitochondria‐targeted catalase (mCAT) significantly reduced oxidative stress, restored mitochondrial structure and function, normalized replicative and wound healing capacity, and rendered the Nrf2‐mediated antioxidant response dispensable. These results highlight the critical role of Nrf2/ARE in the maintenance of DS cell homeostasis and validate mitochondrial‐specific interventions as a key aspect of antioxidant and antiaging therapies.
DNA electromagnetic properties and interactions -An investigation on intrinsic bioelectromagnetism within DNA

ABSTRACT The question whether intrinsic bioelectromagnetism exists within DNA or not is an important and so far unexplored area of biology. We carried out a study of isolated genetic material, utilizing both prokaryotic and eukaryotic DNA, to measure any possible intrinsic electromagnetic effects or fields emanated within the molecules. Studies were carried out with extremely sensitive ultra-low-noise trans-impedance amplifiers and a high-precision data acquisition system to record any possible faintest electromagnetic signals from the concentrated, as well as diluted DNA, in vitro. Some experiments were performed to investigate any possible electromagnetic effects of high-frequency (HF) RF fields on the DNA under test. However, after extensive testing and careful measurements, we failed to detect any possible intrinsic or induced electromagnetic activity from the DNA as compared to simple water or empty chambers. We reached a conclusion that there does not seem to be any measurable intrinsic electromagnetic activity or fields present in the DNA material, whether in concentrated or diluted form, and if there were, any such activity or fields would be extremely minuscule to be detected with scientific precision by current human measurement methods.
3-Hydroxypyruvate Destabilizes Hypoxia Inducible Factor and Induces Angiostasis

Purpose Transcriptional analysis of retina protected by hypoxia-inducible factor (HIF) stabilization demonstrates an increase in genes associated with aerobic glycolysis. We hypothesized that since protection is associated with a change in metabolism, oxygen-induced metabolites might transduce oxygen toxicity. We used global metabolic profiling to identify retinal metabolites increased in hyperoxia compared to normoxia. Methods Untargeted gas chromatography mass spectroscopy (GC-MS) was performed on both mouse retina samples collected in hyperoxia and on primary human retinal endothelial cells, each with and without HIF stabilization. After identifying 3-hydropxypyruvate (3OH-pyruvate) as a unique hyperoxic metabolite, endothelial cells in culture and choroidal explants were challenged with 3OH-pyruvate in order to determine how this glycolytic intermediate was metabolized, and whether it had an effect on angiogenesis. Results 3OH-pyruvate was one of five metabolites at least 2.0-fold elevated in hyperoxia with a P value < 0.1. Once metabolized by endothelial cells, 3OH-pyruvate led to a 20-fold increase in 3-phosphoglycerate and a 4-fold increase in serine when cells were treated with Roxadustat to induce HIF stabilization. 3OH-pyruvate, but not pyruvate, destabilized HIF in endothelial cells with an increase in proline hydroxylation. 3OH-pyruvate was angiostatic in choroidal explant assays. Conclusions 3OH-pyruvate is a unique metabolite induced by hyperoxia that destabilizes HIF at least in part by a canonical pathway. 3OH-pyruvate induces angiostasis in vitro. HIF stabilization increases serine biosynthesis in vitro and in vivo.
Extracellular mycosynthesis of gold nanoparticles using Trichoderma hamatum: optimization, characterization and antimicrobial activity

Synthesis of gold nanoparticles (AuNPs) has become a needed domain of applied science. Biological method for synthesis of AuNPs by Trichoderma hamatum SU136 aqueous mycelial extract was achieved. The culture filtrate of the fungus was exposed to three different concentrations of gold chloride. The culture filtrate of the fungus was exposed to three different concentrations of gold chloride (0·25, 0·5 and 1·0 mmol l−1). In all cases, the gold ions (Au3+) were reduced to Au0, leading to the formation of stable AuNPs. The AuNPs were identified by UV–visible spectrometry, TEM and FT‐IR. The presence of a surface plasmon band around 530 nm indicates AuNPs synthesis. Trichoderma hamatum SU136 synthesized 5–30 nm sized; spherical, pentagonal and hexagonal morphologies of AuNPs by TEM. The existence and binding of proteins with nanoparticles was approved by FT‐IR study. Parameters optimization showed the smallest size of AuNPs was obtained with (0·5 mmol l−1 gold chloride, pH 7 at 38°C). Interestingly, AuNPs exhibited antimicrobial activity against four pathogenic bacterial strains in the presence of the standard antibiotic, streptomycin.
Take a Deep Breath - Monitoring of Inhaled Nanoparticles with Magnetic Particle Imaging

Magnetic Particle Imaging (MPI) is a new imaging modality based on the visualization of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) using magnetic fields. The potential of MPI was recently evaluated in numerous ex vivo and in vivo studies and the technique can now be considered as an established preclinical imaging modality with a promising perspective of clinical applications.
HUWE1 controls the development of non-small cell lung cancer through down-regulation of p53

Lung cancer is the most frequent cancer type and the leading cause of tumor-associated deaths worldwide. TP53 is an important tumor suppressor gene and is frequently inactivated in lung cancer. E3 ligases targeting p53, such as MDM2, are involved in the development of lung cancer. The E3 ligase HUWE1, which targets many tumor-associated proteins including p53, has been reported to be highly expressed in lung cancer; however, its role in lung tumorigenesis is unclear. Methods: The expression of HUWE1 and p53 in lung cancer cells was modulated and the phenotypes were assessed by performing soft agar colony forming assays, cell cycle analysis, BrdU incorporation assays, and xenograft tumor growth assays. The effect on tumorigenesis in genetically-engineered mice was also analyzed. The mechanism through which HUWE1 sustained lung cancer cell malignancy was confirmed by western blotting. HUWE1 expression in clinical lung cancer was identified by immunohistochemistry and validated by analyzing lung adenocarcinoma and lung squamous carcinoma samples from the Cancer Genome Atlas (TCGA) database. Finally, we assessed the association between HUWE1 expression and patient outcome using online survival analysis software including survival information from the caBIG, GEO, and TCGA database. Results: Inactivation of HUWE1 in a human lung cancer cell line inhibited proliferation, colony-forming capacity, and tumorigenicity. Mechanistically, this phenotype was driven by increased p53, which was due to attenuated proteasomal degradation by HUWE1. Up-regulation of p53 inhibited cancer cell malignancy, mainly through the induction of p21 expression and the down-regulation of HIF1α. Huwe1 deletion completely abolished the development of EGFRVIII-induced lung cancer in Huwe1 conditional knockout mice. Furthermore, survival analysis of lung cancer patients showed that increased HUWE1 expression is significantly associated with worse prognosis. Conclusion: Our data suggest that HUWE1 plays a critical role in lung cancer and that the HUWE1-p53 axis might be a potential target for lung cancer therapy.
Understanding Mechanisms of Genetic Risk for Adolescent Internalizing and Externalizing Problems: The Mediating Role of Parenting and Personality

Genetic predispositions play an important role in the development of internalizing and externalizing behaviors. Understanding the mechanisms through which genetic risk unfolds to influence these developmental outcomes is critical for developing prevention and intervention efforts, capturing key elements of Irv's research agenda and scientific legacy. In this study, we examined the role of parenting and personality in mediating the effect of genetic risk on adolescents’ major depressive disorder and conduct disorder symptoms. Longitudinal data were drawn from a sample of 709 European American adolescents and their mothers from the Collaborative Studies on Genetics of Alcoholism. Results from multivariate path analysis indicated that adolescents’ depressive symptoms genome-wide polygenic scores (DS_GPS) predicted lower parental knowledge, which in turn was associated with more subsequent major depressive disorder and conduct disorder symptoms. Adolescents’ DS_GPS also had indirect effects on these outcomes via personality, with a mediating effect via agreeableness but not via other dimensions of personality. Findings revealed that the pattern of associations was similar across adolescent gender. Our findings emphasize the important role of evocative gene–environment correlation processes and intermediate phenotypes in the pathways of risk from genetic predispositions to complex adolescent outcomes.
Selective effects of specificity inductions on episodic details: evidence for an event construction account

ABSTRACT Prior research has suggested that an episodic specificity induction – brief training in recollecting the details of a past event – affects downstream performance on remembering past and imagining future events, solving problems, and thinking creatively. We have hypothesised that a process common to these tasks that the induction may target is event construction – assembling and maintaining a mental scenario filled with details related to settings, people, and actions. We test this hypothesis by having participants receive a memory specificity induction, imagination specificity induction, or control induction not requiring event construction prior to memory and imagination tasks that involve event construction, and a picture description task that involves describing but not mentally constructing an event. We predicted that induction effects would be specific to episodic detail production on subsequent memory and imagination because these details assay critical elements of a constructed event. In line with an event construction account, the two specificity inductions produced significant and indistinguishable increases in the number of episodic – but not semantic – details generated during memory and imagination relative to the control. Induction did not increase detail generation on picture description. The findings provide novel evidence that event construction is a key process targeted by specificity inductions.
EAACI position paper on how to classify cutaneous manifestations of drug hypersensitivity

Drug hypersensitivity reactions (DHRs) are common, and the skin is by far the most frequently involved organ with a broad spectrum of reaction types. The diagnosis of cutaneous DHRs (CDHR) may be difficult because of multiple differential diagnoses. A correct classification is important for the correct diagnosis and management. With these guidelines, we aim to give precise definitions and provide the background needed for doctors to correctly classify CDHR.