Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Insights into the Role of the Cyclic Backbone in a Squash Trypsin Inhibitor*

Background: MCoTI-II is a potent serine protease inhibitor with a cyclic protein backbone. Results: Its three-dimensional structure and dynamics in complex with trypsin were determined using x-ray and NMR methods. Conclusion: The cyclic backbone of MCoTI-II participates in favorable interactions with trypsin. Significance: We demonstrate a new role for backbone cyclization in enhancing enzyme inhibitory activity. MCoTI-II is a head-to-tail cyclic peptide with potent trypsin inhibitory activity and, on the basis of its exceptional proteolytic stability, is a valuable template for the design of novel drug leads. Insights into inhibitor dynamics and interactions with biological targets are critical for drug design studies, particularly for protease targets. Here, we show that the cyclization and active site loops of MCoTI-II are flexible in solution, but when bound to trypsin, the active site loop converges to a single well defined conformation. This finding of reduced flexibility on binding is in contrast to a recent study on the homologous peptide MCoTI-I, which suggested that regions of the peptide are more flexible upon binding to trypsin. We provide a possible explanation for this discrepancy based on degradation of the complex over time. Our study also unexpectedly shows that the cyclization loop, not present in acyclic homologues, facilitates potent trypsin inhibitory activity by engaging in direct binding interactions with trypsin.
Using the mixed model for interval mapping of quantitative trait loci in outbred line crosses.

Interval mapping by simple regression is a powerful method for the detection of quantitative trait loci (QTLs) in line crosses such as F2 populations. Due to the ease of computation of the regression approach, relatively complex models with multiple fixed effects, interactions between QTLs or between QTLs and fixed effects can easily be accommodated. However, polygenic effects, which are not targeted in QTL analysis, cannot be treated as random effects in a least squares analysis. In a cross between true inbred lines this is of no consequence, as the polygenic effect contributes just to the residual variance. In a cross between outbred lines, however, if a trait has high polygenic heritability, the additive polygenic effect has a large influence on variation in the population. Here we extend the fixed model for the regression interval mapping method to a mixed model using an animal model. This makes it possible to use not only the observations from progeny (e.g. F2), but also those from the parents (F1) to evaluate QTLs and polygenic effects. We show how the animal model using parental observations can be applied to an outbred cross and so increase the power and accuracy of QTL analysis. Three estimation methods, i.e. regression and an animal model either with or without parental observations, are applied to simulated data. The animal model using parental observations is shown to have advantages in estimating QTL position and additive genotypic value, especially when the polygenic heritability is large and the number of progeny per parent is small.
Neurobehavioral phenotype in carriers of the fragile X premutation.

There have been contradictory findings in the fragile X (fraX) literature about possible neurocognitive and psychological symptoms due to the fraX premutation (pM). The purpose of the present study was to investigate the relationship between CGG repeat length and neurobehavioral functioning in carriers of the fraX pM. Eighty-five female carriers of the pM with allele sizes ranging from 59-166 were administered a comprehensive IQ test (WAIS-III) and completed a questionnaire designed to measure psychopathology (Symptom Checklist (SCL)-90-R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and age was found, as well as a positive relationship between allele size and depression. Follow-up analyses separating small and large allele sizes (below and above 100 CGG repeats) indicated that individuals with larger allele sizes scored significantly higher on the Interpersonal Sensitivity and Depression subscales of the SCL-90-R. Despite the limitation of few individuals with high CGG repeat lengths, our findings suggest that females with larger premutated alleles (> or = 100 repeats) display some clinical manifestations of fraX syndrome.
Visualization and characterization of interleukin 1 receptors in brain.

Interleukin 1 (IL 1) is a polypeptide hormone produced by macrophages, keratinocytes, and brain glial cells which acts as a soluble mediator in immunological and inflammatory reactions. Although its best known effect on the central nervous system is its ability to cause fever, it has been found to influence cell growth, food intake, and slow-wave sleep. We have developed a binding assay for 125I-labeled recombinant murine IL 1 and show it to be highly specific. Additionally, affinity cross-linking studies indicate that the rat brain IL 1 receptor has a m.w. of approximately 80,000, which is similar to the previously described recognition molecule on T cells and fibroblasts. Using autoradiographic techniques, we visualized the distribution of 125I-IL 1 binding in sections of fresh frozen rat brain. IL 1 receptors were found to be widespread throughout the brain, forming a distinctive pattern of distribution. Areas especially dense in receptors were typically neuron-rich sites of the brain such as granule cell layer of the dentate gyrus, the pyramidal cell layer of the hippocampus, and the granule cell layer of the cerebellum as well as in the hypothalamus. The pattern of IL 1 receptor distribution indicates the presence of receptors on neuron cell bodies and the localization to numerous discrete brain areas other than those hypothalamic sites involved in temperature regulation, suggesting a broader role for IL 1 in brain functioning than previously recognized. IL 1, derived from local or systemic sources, may function in the brain to coordinate behavioral and neuroendocrine activities with immunological and inflammatory reactions throughout the body.
Signal transduction in endothelium-dependent vasodilatation.

Modulation of vascular tone is one important function of the endothelium. This can occur via two principal mechanisms: by modulating the local concentration of circulating vasoactive substances (e.g. adenine nucleotides, angiotensin II, biogenic amines, bradykinin), and by synthesizing and releasing vasoactive autacoids. The most important endothelium-derived vasodilator autacoids are nitric oxide (NO) and prostacyclin (PGI2). By counteracting neuro- and myogenic vasoconstriction, the continuous release of these autacoids from the vascular endothelium represents a sensitive and highly effective local system for maintaining an adequate blood flow to the organs. Impaired production of NO (and PGI2), either as a result of endothelial injury or dysfunction, has been implicated in the pathology of a variety of cardiovascular diseases, such as hypertension, hypercholesterolaemia, atherosclerosis and diabetes. Therefore, the prevention and/or reversal of the functional and morphological changes of the endothelium associated with these diseases is an important therapeutic goal. This brief overview covers current knowledge concerning the intracellular pathways that link endothelial activation by receptor-dependent and -independent stimuli to the formation of NO and PGI2.
Cardiorespiratory Response to Different Exercise Tests in Interstitial Lung Disease.

INTRODUCTION The 6-min stepper test (6MST) has been used as an alternative to the 6-min walk test (6MWT) to assess exercise tolerance in patients with interstitial lung disease (ILD). Recent data suggest that the tests may involve different energy pathways and cardiorespiratory responses. We thus aimed to compare the cardiorespiratory responses of ILD patients during the 6MWT and the 6MST. METHODS Thirty-one patients with ILD were randomized to perform both tests in the order 6MST → 6MWT (n = 16) or 6MWT → 6MST (n = 15). Gas exchange, HR, and pulse O2 saturation (SpO2) were measured continuously, and dyspnoea, leg discomfort, and blood lactate concentration were assessed before and immediately after each test. RESULTS Oxygen uptake (V˙O2) was lower (P = 0.002) and respiratory equivalent ratio for O2 (V˙E/V˙O2) and RER were higher (both P < 0.001) during the 6MST compared with the 6MWT. The 6MST was also associated with higher blood lactate concentrations (6MST, 4.16 ± 1.95 mmol·L; 6MWT, 2.84 ± 1.17 mmol·L; P = 0.01), higher leg discomfort scores (6MST 5 ± 3 points, 6MWT 3 ± 2 points; P < 0.001), and smaller decreases in SpO2 (6MST -5% ± 5%, 6MWT -9% ± 6%; P < 0.001). CONCLUSIONS ILD patients exhibited greater ventilatory responses and lower arterial O2 desaturation during the 6MST compared with the 6MWT. The higher lactate concentrations and perceived muscle fatigue observed during the 6MST may indicate the presence of intertest differences in active muscle metabolism that could contribute to the distinct cardiorespiratory responses.
Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy

• Although neonatal glucocorticoid therapy is an effective measure to prevent and treat chronic lung disease in premature infants, it can cause long‐term adverse effects on the cardiovascular system secondary to oxidative stress and reduced nitric oxide (NO) bioavailability. • Here, we report that neonatal dexamethasone therapy using human clinically relevant doses resulted in increased mortality, and that surviving offspring had significantly lower NO bioavailability and impaired cardiac function at adulthood. Combined neonatal treatment of dexamethasone with antioxidant vitamins prevented these adverse side‐effects in offspring. • The data give insight into the mechanisms underlying the adverse effects of neonatal dexamethasone on the cardiovascular system. Further, the findings are of significant clinical importance in helping to modify current perinatal practice to minimise adverse side‐effects while maintaining the benefits of potent neonatal steroid therapy.
Selective Enrichment and Sequencing of Whole Mitochondrial Genomes in the Presence of Nuclear Encoded Mitochondrial Pseudogenes (Numts)

Numts are an integral component of many eukaryote genomes offering a snapshot of the evolutionary process that led from the incorporation of an α-proteobacterium into a larger eukaryotic cell some 1.8 billion years ago. Although numt sequence can be harnessed as molecular marker, these sequences often remain unidentified and are mistaken for genuine mtDNA leading to erroneous interpretation of mtDNA data sets. It is therefore indispensable that during the process of amplifying and sequencing mitochondrial genes, preventive measures are taken to ensure the exclusion of numts to guarantee the recovery of genuine mtDNA. This applies to mtDNA analyses in general but especially to studies where mtDNAs are sequenced de novo as the launch pad for subsequent mtDNA-based research. By using a combination of dilution series and nested rolling circle amplification (RCA), we present a novel strategy to selectively amplify mtDNA and exclude the amplification of numt sequence. We have successfully applied this strategy to de novo sequence the mtDNA of the Black Field Cricket Teleogryllus commodus, a species known to contain numts. Aligning our assembled sequence to the reference genome of Teleogryllus emma (GenBank EU557269.1) led to the identification of a numt sequence in the reference sequence. This unexpected result further highlights the need of a reliable and accessible strategy to eliminate this source of error.
In vitro toxicity of silver nanoparticles on murine peritoneal macrophages

Silver nanoparticles, the new generation of antimicrobial agents, are becoming one of the progressively growing products in nanotechnology. Meanwhile, the potential side effects of these nanoparticles have not been studied thoroughly yet. Macrophages, one of the most important immune cells in innate and acquired immune responses, are a key component of the clearance mechanisms in semi-open interfaces of human body against nanosilver (nano-Ag). In this experimental study, we assessed the effect of commercial colloidal nano-Ag on murine peritoneal macrophages by MTT and nitric oxide (NO) production assay in vitro. A significant decrease in cell viability was observed for 1 ppm (part per million) to 25 ppm of nano-Ag concentrations compared to the control group (P < 0.01) after 24 h of cell culture. Also, a significant decrease in the cell viability was observed for 2–25 ppm of nano-Ag concentrations after 48–72 h, respectively (P < 0.05). In our study, exposure to 0.4–25 ppm of colloidal nano-Ags brought about a considerable decline (P < 0.05) in NO production by macrophages. Nevertheless, there is no evidence of substantial difference at lower concentrations. This acute cytotoxic dose-dependent effect of nano-Ag particles on peritoneal macrophages which declines cell viability and NO production urges caution about the usage for sensitive surfaces. It is highly recommended to carry out the in vivo investigation for human to confirm its use.
A robust, real-time control scheme for multifunction myoelectric control

This paper represents an ongoing investigation of dexterous and natural control of upper extremity prostheses using the myoelectric signal (MES). The scheme described within uses pattern recognition to process four channels of MES, with the task of discriminating multiple classes of limb movement. The method does not require segmentation of the MES data, allowing a continuous stream of class decisions to be delivered to a prosthetic device. It is shown in this paper that, by exploiting the processing power inherent in current computing systems, substantial gains in classifier accuracy and response time are possible. Other important characteristics for prosthetic control systems are met as well. Due to the fact that the classifier learns the muscle activation patterns for each desired class for each individual, a natural control actuation results. The continuous decision stream allows complex sequences of manipulation involving multiple joints to be performed without interruption. Finally, minimal storage capacity is required, which is an important factor in embedded control systems.
Constraint factor graph cut–based active contour method for automated cellular image segmentation in RNAi screening

Image‐based, high throughput genome‐wide RNA interference (RNAi) experiments are increasingly carried out to facilitate the understanding of gene functions in intricate biological processes. Automated screening of such experiments generates a large number of images with great variations in image quality, which makes manual analysis unreasonably time‐consuming. Therefore, effective techniques for automatic image analysis are urgently needed, in which segmentation is one of the most important steps. This paper proposes a fully automatic method for cells segmentation in genome‐wide RNAi screening images. The method consists of two steps: nuclei and cytoplasm segmentation. Nuclei are extracted and labelled to initialize cytoplasm segmentation. Since the quality of RNAi image is rather poor, a novel scale‐adaptive steerable filter is designed to enhance the image in order to extract long and thin protrusions on the spiky cells. Then, constraint factor GCBAC method and morphological algorithms are combined to be an integrated method to segment tight clustered cells. Compared with the results obtained by using seeded watershed and the ground truth, that is, manual labelling results by experts in RNAi screening data, our method achieves higher accuracy. Compared with active contour methods, our method consumes much less time. The positive results indicate that the proposed method can be applied in automatic image analysis of multi‐channel image screening data.
Extending the Validity of the Personality Assessment Inventory's (PAI) Level of Care Index (LOCI) in Multiple Psychiatric Settings

The purpose of this study was to extend the validity and clinical application of the Level of Care Index (LOCI) from the Personality Assessment Inventory (PAI) in 2 independent psychiatric samples. In Study 1 (N = 201), the LOCI effectively differentiated level of care (inpatients from outpatients), and was also meaningfully associated with risk factors for psychiatric admission (e.g., suicidal ideation, self-harming behavior, previous psychiatric admission, etc.), even after controlling for other demographic variables (range of Cohen's ds = 0.57–1.00). Likewise, the LOCI also incremented other risk indicators (suicide and violence history) and relevant PAI indexes (i.e., Mean Clinical Elevation, and Suicide and Violence Potential) in predicting level of care, and explained an additional 6% to 12% of variance in the target variable. Diagnostic efficiency analyses indicated LOCI scores in the range of 15 to 18 optimize positive and negative predictive power, and classification rate. In Study 2 (N = 96), the LOCI was found to be significantly higher in those with a recent psychiatric admission within the past 6 months (d = 0.64), as compared to those without an admission. Similarly, those who were admitted for suicide risk had significantly higher mean LOCI scores as compared to those who did not (d = 0.70). The clinical implications of these findings and potential application of the LOCI are discussed.
Olfactory sensory neurons are trophically dependent on the olfactory bulb for their prolonged survival

In most neural systems, developing neurons are trophically dependent on contact with their synaptic target for their survival and for some features of their differentiation. However, in the olfactory system, it is unclear whether or not the survival and differentiation of olfactory sensory neurons depend on contact with the olfactory bulb (normally the sole synaptic target for these neurons). In order to address this issue, we examined neuronal life-span and differentiation in adult rats subjected to unilateral olfactory bulb ablation at least 1 month prior to use. Life-span of a newly generated cohort of olfactory neurons was determined by labeling them at their “birth” via the incorporation of 3H-thymidine. In the absence of the bulb, neurons are continually produced at a twofold greater rate. However, the epithelium on the ablated side is thinner, indicating that average neuronal life-span must be reduced in the targetless epithelium. Indeed, nearly 90% of the labeled neurons disappear from the bulbectomized side between 5 d and 2 weeks of neuronal age. Moreover, on electron microscopic examination, olfactory axons are degenerating in large numbers on the ablated side. Since labeled neurons migrate apically through the width of the epithelium during this same period, it appears that most, if not all, neurons on the ablated side have a life-span on the order of 2 weeks or less. In contrast, there is a more moderate degree of neuronal loss on the unoperated side of the same animals during the first 2 weeks after tracer injection, and that occurs while the neurons are concentrated in the deeper half of the epithelium, suggesting that there is a preexisting population of neurons in the control epithelium that does not die during this period. Likewise, degenerating axons are much less frequent on the unoperated side. We conclude that life-span is significantly shorter for olfactory neurons born in the targetless epithelium and that olfactory neurons are trophically dependent on the presence of the bulb for their prolonged survival. Neuronal differentiation in the absence of the bulb was assessed according to ultrastructural criteria and the pattern of protein expression using antisera to the growth associated protein GAP-43 and the olfactory marker protein. By both measures, most neurons in the epithelium on the bulbectomized side, but not all, are immature. (ABSTRACT TRUNCATED AT 400 WORDS)
Reduction of fat storage in mice fed a high‐fat diet long term by treatment with saponins prepared from Kochia scoparia fruit

The fresh fruit (Japanese name, Tonburi) of Kochia scoparia has been used as a food garnish in Japanese‐style dishes from ancient times, and may prevent metabolic syndromes such as hyperlipidemia, hypertension, obesity and atherosclerosis. This study was performed to clarify whether an ethanol extract of K. scoparia fruit prevented obesity induced in mice by a high‐fat diet for 9 weeks. The ethanol extract of K. scoparia fruit prevented the increases in body weight and parametrial adipose tissue weight induced by the high‐fat diet. Furthermore, consumption of a high‐fat diet containing 1% or 3% K. scoparia extract significantly increased the fecal content and the fecal triacylglycerol level at day 3 compared with those in the high‐fat diet group. The ethanol extract (250 mg/kg) and total saponins (100 mg/kg) of K. scoparia inhibited the elevation of the plasma triacylglyccerol level 2 or 3 h after the oral administration of the lipid emulsion. Total saponins, momordin Ic, 2′‐O‐β‐d‐glucopyranosyl momordin Ic and 2′‐O‐β‐d‐glucopyranosyl momordin IIc isolated from K. scoparia fruit inhibited the pancreatic lipase activity (in vitro). These findings suggest that the anti‐obesity actions of K. scoparia extract in mice fed a high‐fat diet may be partly mediated through delaying the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity. Copyright © 2006 John Wiley & Sons, Ltd.
A Method to Enhance Face Biometric Security

In cancelable biometrics, a template undergoes a random-like transformation process such that it is disposable and a new template for the same identity can be re-generated for new usage. However, existing works do not consider control of verification performance and identity concealment at the same time. In this paper, we propose a method which can boost the verification performance of face biometric via two steps: using an efficient feature extraction transformation, and using an error minimizing template transformation. An extended Random Projection of face data improves the feature extraction efficiency in the first step. A near optimal transformation of the face template is next generated from iterative steps of gradient descent algorithm based on an error rate formulation. For experimentation, we adopted face images from AR and BERC databases where the face images were collected under various external conditions. From these face databases, we show an improved verification performance in terms of test equal error rate (EER), at the same time hiding the face identity based on template transformation. This work contributes to establishment of an algorithm for effective cancelable face template generation as well as verification performance enhancement.