Miracle-dz/UniFAR-FTUs huggingface dataset:
Hazardous effects of sanguinarine on maturation of mouse oocytes, fertilization, and fetal development through apoptotic processes

Previously, we reported that sanguinarine, a phytoalexin with antimicrobial, anti‐oxidant, anti‐inflammatory and pro‐apoptotic effects, is a risk factor for normal embryonic development that triggers apoptotic processes in the inner cell mass of mouse blastocysts, causing decreased embryonic development and cell viability. In the current study, we investigated the deleterious effects of sanguinarine on mouse oocyte maturation, in vitro fertilization (IVF), and subsequent pre‐ and postimplantation development both in vitro and in vivo. Notably, sanguinarine significantly impaired mouse oocyte maturation, decreased IVF rates, and inhibited subsequent embryonic development in vitro. Preincubation of oocytes with sanguinarine during in vitro maturation induced an increase in postimplantation embryo resorption and a decrease in mouse fetal weight. In an in vivo animal model, 1 to 5 μM sanguinarine, provided in drinking water, caused a decrease in oocyte maturation and IVF, and led to deleterious effects on early embryonic development. Importantly, preincubation of oocytes with a caspase‐3‐specific inhibitor effectively blocked sanguinarine‐triggered deleterious effects, clearly implying that embryonic injury induced by sanguinarine is mediated by a caspase‐dependent apoptotic mechanism. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 946–955, 2015.
Direct Ubiquitination of Pattern Recognition Receptor FLS2 Attenuates Plant Innate Immunity

Targeted degradation of bacterial sensing proteins keeps plant defenses from running amok. Innate immune responses are triggered by the activation of pattern-recognition receptors (PRRs). The Arabidopsis PRR FLAGELLIN-SENSING 2 (FLS2) senses bacterial flagellin and initiates immune signaling through association with BAK1. The molecular mechanisms underlying the attenuation of FLS2 activation are largely unknown. We report that flagellin induces recruitment of two closely related U-box E3 ubiquitin ligases, PUB12 and PUB13, to FLS2 receptor complex in Arabidopsis. BAK1 phosphorylates PUB12 and PUB13 and is required for FLS2-PUB12/13 association. PUB12 and PUB13 polyubiquitinate FLS2 and promote flagellin-induced FLS2 degradation, and the pub12 and pub13 mutants displayed elevated immune responses to flagellin treatment. Our study has revealed a unique regulatory circuit of direct ubiquitination and turnover of FLS2 by BAK1-mediated phosphorylation and recruitment of specific E3 ligases for attenuation of immune signaling.
Determining surface curvature with photometric stereo

A method is described to compute dense representations of the intrinsic curvature at each point on a visible surface, based on photometric stereo. The idea of photometric stereo is to use the intensity values recorded from multiple images obtained from the same viewpoint but under different conditions of illumination. Previously, photometric stereo has been used to obtain local estimates of surface orientation. Here, an extension to photometric stereo is described in which the spatial derivatives of the intensity values are used to determine the principal curvatures and associated directions, at each point on a visible surface. The result shows that it is possible to obtain reliable local estimates of intrinsic surface curvature. The method is demonstrated using images of two pottery vases, one of which is used for calibration purposes. <<ETX>>
Efficacy of Injury Prevention Training Is Greater for High-Risk vs Low-Risk Elite Female Youth Soccer Players

Background: The efficacy of robustness training for high- versus low-risk individuals within high-risk groups is currently unknown. Purpose: To explore the efficacy of robustness training on injury risk factors among female youth soccer players and to examine if high-risk athletes are greater responders to such training. Study Design: Controlled laboratory study. Methods: A total of 125 elite youth female soccer players on the English FA talent pathway were randomly selected into a training group (n = 71) or a control group (n = 54). Relative leg stiffness, 2-dimensional knee valgus and knee flexion range of motion from a single-legged countermovement jump, and probability of high knee abduction moment (pKAM) risk were all determined before and after a 16-week robustness training program. For further analysis, participants in the training group were split into groups based on risk: high risk (pKAM >0.80, n = 33) and low risk (pKAM <0.55, n = 33). Magnitude-based inferences were used to explore differences between the control and intervention groups and the high- and low-risk groups. Results: Magnitude-based inferences demonstrated significant beneficial effects in the training group for knee valgus, pKAM, and leg stiffness as compared with the control group. The control group demonstrated possible worthwhile differences in knee flexion range of motion as compared with the intervention group. The high-risk group demonstrated likely/very likely worthwhile differences versus the low-risk group for all parameters. Conclusion/Clinical Relevance: Robustness training induces significant beneficial improvements in injury risk factors among female youth soccer players. The beneficial effects of this multidimensional program are greater for those classified as high risk.
Ice Volume and Sea Level During the Last Interglacial

More Melting The last interglacial period, around 125,000 years ago, was 1° to 2°C warmer than the present, and the sea level was thought to be 4 to 6 meters higher. However, Dutton and Lambeck (p. 216), now suggest that sea level was possibly as much as 10 meters above current levels. Such a large excess of seawater would mean that the Greenland and Antarctic ice sheets melted much more than previously assumed, which has implications for how much sea-level rise we should expect with anthropogenic climate warming. Global average sea level during the last interglacial period was 6 to 10 meters higher than it is today. During the last interglacial period, ~125,000 years ago, sea level was at least several meters higher than at present, with substantial variability observed for peak sea level at geographically diverse sites. Speculation that the West Antarctic ice sheet collapsed during the last interglacial period has drawn particular interest to understanding climate and ice-sheet dynamics during this time interval. We provide an internally consistent database of coral U-Th ages to assess last interglacial sea-level observations in the context of isostatic modeling and stratigraphic evidence. These data indicate that global (eustatic) sea level peaked 5.5 to 9 meters above present sea level, requiring smaller ice sheets in both Greenland and Antarctica relative to today and indicating strong sea-level sensitivity to small changes in radiative forcing.
Inhibition of HeLa cells metastasis by bioactive compounds in crocodile (Crocodylus siamensis) white blood cells extract

Matrix metalloproteinases (MMPs) play a key role in cancer progression, including cell invasion, metastasis, cell growth, apoptosis, angiogenesis, and cell adhesion. Thus, suppression of the MMPs activities is crucial for inhibiting cancer cells metastasis. Herein, bioactive agents from crocodile (Crocodylus siamensis) leukocyte extracts (WBCex) showed the anticancer activity with HeLa cells and inhibited the migration and invasion process by reducing gelatinases (MMP‐2, MMP‐9) activity and their protein levels. This mechanism is regulated via interfering Ras and p38 signal transduction. Moreover, disrupting VEGF and integrin‐signaling cascade by bioactive agents are the predictable mechanisms that cause the decreasing of MMP‐2 and MMP‐9 activity. Hence, bioactive substances in WBCex may play the mode of action similar with MMPs inhibitor due to HeLa cell metastasis being suppressed in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1329–1336, 2016.
Knowledge-Based System for Managing Complex Clinical Trials

Clinical trials are formal patient studies that serve as the gold standard method for establishing the efficacy of medical treatments. There is an enormous requirement to specify the knowledge used at all stages of clinical trials, including planning, implementation, and analysis, so that they can be faithfully executed by a clinical research organization. We are building Epoch, a knowledge-based system, to help a large research consortium, the immune tolerance network (ITN), undertake trials to advance new therapeutics in immune-mediated disorders. We are currently targeting two application areas essential to the successful implementation of a trial: (1) tracking study participants as they advance through a study, and (2) tracking biological specimens as they are processed at laboratories. In this paper, we discuss our use of the Web ontology language (OWL) to create a suite of ontologies that conceptualize the clinical trial domain and show how they can inform our system. We show that our ontological framework provides a stable, consistent platform to define, maintain, and distribute the knowledge requirements used in clinical trial management
Suppression of the migration and invasion is mediated by triptolide in B16F10 mouse melanoma cells through the NF‐kappaB‐dependent pathway

Melanoma cancer is one of the major causes of death in humans worldwide. Triptolide is one of the active components of Tripterygium wilfordii Hook F, and has biological activities including induced cell cycle arrest and induction of apoptosis but its antimetastatic effects on murine melanoma cells have not yet been elucidated. Herein, we investigated the effect of triptolide on the inhibition of migration and invasion and possible associated signal pathways in B16F10 murine melanoma cancer cells. Wound healing assay and Matrigel Cell Migration Assay and Invasion System demonstrated that triptolide marked inhibiting the migration and invasion of B16F10 cells. Gelatin zymography assay demonstrated that triptolide significantly inhibited the activities of matrix metalloproteinases‐2 (MMP‐2). Western blotting showed that triptolide markedly reduced CXCR4, SOS1, GRB2, p‐ERK, FAK, p‐AKT, Rho A, p‐JNK, NF‐κB, MMP‐9, and MMP‐2 but increased PI3K and p‐p38 and COX2 after compared to the untreated (control) cells. Real time PCR indicated that triptolide inhibited the gene expression of MMP‐2, FAK, ROCK‐1, and NF‐κB but did not significantly affect TIMP‐1 and ‐2 gene expression in B16F10 cells in vitro. EMSA assay also showed that triptolide inhibited NF‐κB DNA binding in a dose‐dependent manner. Confocal laser microscopy examination also confirmed that triptolide inhibited the expression of NF‐κB in B16F10 cells. Taken together, we suggest that triptolide inhibited B16F10 cell migration and invasion via the inhibition of NF‐κB expression then led to suppress MMP‐2 and ‐9 expressions. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1974–1984, 2016.
Associations of arsenic metabolites, methylation capacity, and skin lesions caused by chronic exposure to high arsenic in tube well water

To investigate the interaction between skin lesion status and arsenic methylation profiles, the concentrations and proportions of arsenic metabolites in urine and arsenic methylation capacities of study subjects were determined. The results showed that the mean urinary concentrations of iAs (inorganic arsenic), MMA (monomethylarsonic acid), DMA (dimethylarsinic acid), and TAs (total arsenic) were 75.65, 68.78, 265.81, and 410.24 μg/L, respectively, in the skin lesions subjects. The highest values were observed in the multiple skin lesions subjects. Higher %iAs and %MMA, and lower %DMA, PMI (primary methylation index), and SMI (secondary methylation index) were found in skin lesions subjects. The multiple skin lesions subjects had highest %iAs and %MMA, and lowest %DMA, PMI, and SMI. The prevalence of skin lesions strongly, positively correlated with arsenic levels in drinking water. The elder persons also had higher frequency of skin lesions compared with younger persons. It can be concluded that arsenic levels in drinking water significantly affected the prevalence of skin lesions. Male subjects usually had higher proportions of skin lesions when compared with female subjects. Moreover, it may be concluded that MMA was significantly related to single skin lesion, whereas DMA and iAs were associated with multiple skin lesions. It seemed that MMA had greater toxicity to hyperkeratosis, whereas DMA and iAs had higher toxicity to depigmentation or pigmentation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 28–36, 2017.
Adult Neural Function Requires MeCP2

An epigenetic program regulated by MeCP2 needs to be maintained throughout life for normal neurological function. Rett syndrome (RTT) is a postnatal neurological disorder caused by mutations in MECP2, encoding the epigenetic regulator methyl-CpG-binding protein 2 (MeCP2). The onset of RTT symptoms during early life together with findings suggesting neurodevelopmental abnormalities in RTT and mouse models of RTT raised the question of whether maintaining MeCP2 function exclusively during early life might protect against disease. We show by using an inducible model of RTT that deletion of Mecp2 in adult mice recapitulates the germline knock-out phenotype, underscoring the ongoing role of MeCP2 in adult neurological function. Moreover, unlike the effects of other epigenetic instructions programmed during early life, the effects of early MeCP2 function are lost soon after its deletion. These findings suggest that therapies for RTT must be maintained throughout life.
Initiation Complex Structure and Promoter Proofreading

RNA polymerase II transcription complexes reveal the basis of abortive initiation and its role in promoter control. The initiation of transcription by RNA polymerase II is a multistage process. X-ray crystal structures of transcription complexes containing short RNAs reveal three structural states: one with 2- and 3-nucleotide RNAs, in which only the 3′-end of the RNA is detectable; a second state with 4- and 5-nucleotide RNAs, with an RNA-DNA hybrid in a grossly distorted conformation; and a third state with RNAs of 6 nucleotides and longer, essentially the same as a stable elongating complex. The transition from the first to the second state correlates with a markedly reduced frequency of abortive initiation. The transition from the second to the third state correlates with partial “bubble collapse” and promoter escape. Polymerase structure is permissive for abortive initiation, thereby setting a lower limit on polymerase-promoter complex lifetime and allowing the dissociation of nonspecific complexes. Abortive initiation may be viewed as promoter proofreading, and the structural transitions as checkpoints for promoter control.
Global Network Reorganization During Dynamic Adaptations of Bacillus subtilis Metabolism

Outside In Acquisition and analysis of large data sets promises to move us toward a greater understanding of the mechanisms by which biological systems are dynamically regulated to respond to external cues. Now, two papers explore the responses of a bacterium to changing nutritional conditions (see the Perspective by Chalancon et al.). Nicolas et al. (p. 1103) measured transcriptional regulation for more than 100 different conditions. Greater amounts of antisense RNA were generated than expected and appeared to be produced by alternative RNA polymerase targeting subunits called sigma factors. One transition, from malate to glucose as the primary nutrient, was studied in more detail by Buescher et al. (p. 1099) who monitored RNA abundance, promoter activity in live cells, protein abundance, and absolute concentrations of intracellular and extracellular metabolites. In this case, the bacteria responded rapidly and largely without transcriptional changes to life on malate, but only slowly adapted to use glucose, a shift that required changes in nearly half the transcription network. These data offer an initial understanding of why certain regulatory strategies may be favored during evolution of dynamic control systems. A vertical analysis reveals that a simple switch of one food for another evokes changes at many levels. Adaptation of cells to environmental changes requires dynamic interactions between metabolic and regulatory networks, but studies typically address only one or a few layers of regulation. For nutritional shifts between two preferred carbon sources of Bacillus subtilis, we combined statistical and model-based data analyses of dynamic transcript, protein, and metabolite abundances and promoter activities. Adaptation to malate was rapid and primarily controlled posttranscriptionally compared with the slow, mainly transcriptionally controlled adaptation to glucose that entailed nearly half of the known transcription regulation network. Interactions across multiple levels of regulation were involved in adaptive changes that could also be achieved by controlling single genes. Our analysis suggests that global trade-offs and evolutionary constraints provide incentives to favor complex control programs.
The Dynamic Architecture of Hox Gene Clusters

Sequential activation of Hox genes correlates with a transition of negative to positive three-dimensional chromosome structure. The spatial and temporal control of Hox gene transcription is essential for patterning the vertebrate body axis. Although this process involves changes in histone posttranslational modifications, the existence of particular three-dimensional (3D) architectures remained to be assessed in vivo. Using high-resolution chromatin conformation capture methodology, we examined the spatial configuration of Hox clusters in embryonic mouse tissues where different Hox genes are active. When the cluster is transcriptionally inactive, Hox genes associate into a single 3D structure delimited from flanking regions. Once transcription starts, Hox clusters switch to a bimodal 3D organization where newly activated genes progressively cluster into a transcriptionally active compartment. This transition in spatial configurations coincides with the dynamics of chromatin marks, which label the progression of the gene clusters from a negative to a positive transcription status. This spatial compartmentalization may be key to process the colinear activation of these compact gene clusters.
Twenty‐eight‐day repeated inhalation toxicity study of nano‐sized lanthanum oxide in male sprague‐dawley rats

Although the use of lanthanum has increased in field of high‐tech industry worldwide, potential adverse effects to human health and to the environment are largely unknown. The present study aimed to investigate the potential toxicity of nano‐sized lanthanum oxide (La2O3) following repeated inhalation exposure in male Sprague‐Dawley rats. Male rats were exposed nose‐only to nano‐sized La2O3 for 28 days (5 days/week) at doses of 0, 0.5, 2.5, and 10 mg/m3. In the experimental period, we evaluated treatment‐related changes including clinical signs, body weight, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology findings. We also analyzed lanthanum distribution in the major organs and in the blood, bronchoalveolar lavage fluids (BALF), and oxidative stress in lung tissues. Lanthanum level was highest in lung tissues and showed a dose‐dependent relation. Alveolar proteinosis was observed in all treatment groups and was accompanied by an increase in lung weight; moreover, lung inflammation was observed in the 2.5 mg/m3 and higher dose groups and was accompanied by an increase in white blood cells. In the BALF, total cell counts including macrophages and neutrophils, lactate dehydrogenase, albumin, nitric oxide, and tumor necrosis factor‐alpha increased significantly in all treatment groups. Furthermore, these changes tended to deteriorate in the 10 mg/m3 group at the end of the recovery period. In the present experimental conditions, we found that the lowest‐observed‐adverse‐effect level of nano‐sized La2O3 was 0.5 mg/m3 in male rats, and the target organ was the lung. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1226–1240, 2017.
Autonomous navigation of a mobile robot using custom-designed qualitative reasoning VLSI chips and boards

Two types of computer boards including custom-designed VLSI chips have been developed to add a qualitative reasoning capability to the real-time control of autonomous mobile robots. The design and operation of these boards are first described, and an example of their use for the autonomous navigation of a mobile robot is presented. The development of qualitative reasoning schemes emulating human-like navigation in a priori unknown environments is discussed. The efficiency of such schemes, which can consist of as little as a dozen qualitative rules, is illustrated in experiments involving an autonomous mobile robot navigating on the basis of very sparse and inaccurate sensor data. <<ETX>>
Assessing the utility of targeted outreach to intervene with 18 to 24 year old non-treatment seeking tobacco users

Objective: This pilot study assessed the utility of a targeted outreach approach to intervene with non-treatment seeking 18 to 24 year old tobacco users to quit smoking. Methods: A total of 184 tobacco users were recruited from community settings and completed a structured interview assessing tobacco use patterns. Interest in quitting tobacco was measured with an analog scale (1 = none to 10 = highest). Participants (N = 145) who reported any interest (2 or greater) in quitting were provided a brief tobacco intervention. Results: Overall 78/145 (54%) completed a 6 month follow-up of which 14 (17.9%) reported no tobacco use in the past 30 days. Also, a service utilization assessment found that 19.2% used a Nicotine Replacement Therapy (NRT) and 19.2% enrolled in a tobacco cessation program during the past 6 months. Conclusions: The pilot targeted outreach program is an acceptable public health technique to recruit non-treatment seeking tobacco users and help them to quit smoking and engage in cessation services.
Automatic Proposition Extraction from Dependency Trees: Helping Early Prediction of Alzheimer's Disease from Narratives

Idea Density (ID) was originally proposed as a way of measuring the memory load of narratives, by representing the underlying content of the text as a series of semantic units, called propositions or ideas. From a clinical perspective, this notion has been shown to correlate with several cognitive aspects, such as memory, readability, aging, and dementia onset and progress. Traditionally, propositions are extracted manually from texts. There is a tool that can automate ID extraction [1], but it uses shallow information as input, and doesn't produce the propositions themselves as output. We propose a novel approach to obtaining the ID automatically from a text. Our method is an automation of Chand et al.'s ID manual [2], and consists of a rule-based system acting upon dependency trees. Initially, for each sentence in a text, a dependency parser is used to elicit the dependency relations between words. Then, a set of rules is recursively applied in order to process these relations to yield the corresponding propositions. We analyze preliminary results of our system using a well-formed journalistic text, and speech transcriptions of dementia patients.