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Decoding your PTM unique codes with the cancer suppressor p53.
Exogenous application of human epidermal growth factor (hEGF) stimulates epidermal wound healing. The aim of this study was to develop bioconjugates based on hEGF mimicking the protein in its native state and thus suitable for tissue engineering applications, in particular for treating skin-related disorders as burns. Ribonuclease A (RNase A) was used to investigate a number of different activated-agarose carriers cyanogen bromide (CNBr)-activated-agarose and glyoxyl-agarose showed to preserve the appropriate orientation of the protein for receptor binding. EGF was immobilized on these carriers and immobilization yield was evaluated (100% and 12%, respectively). A peptide mapping of unbound protein regions was carried out by LC-MS to take evidence of the residues involved in the immobilization and, consequently, the flexibility and surface accessibility of immobilized EGF. To assess cell proliferative activities, 10, 25, 50, and 100 ng/mL of each immobilized EGF sample were seeded on fibroblast cells and incubated for 24, 48 and 72 h. The immobilized growth factor showed significantly high cell proliferative activity at 50 and 100 ng/mL compared to control and soluble EGF. Although both of the immobilized samples show dose-dependency when seeded with high number of fibroblast cells, CNBr-agarose-EGF showed a significantly high activity at 100 ng/mL and 72 h incubation, compared to glyoxyl-agarose-EGF.In neurophysiology, nonhuman primates represent an important model for studying the brain. Typically, monkeys are moved from their home cage to an experimental room daily, where they sit in a primate chair and interact with electronic devices. Refining this procedure would make the researchers' work easier and improve the animals' welfare. To address this issue, we used home-cage training to train two macaque monkeys in a non-match-to-goal task, where each trial required a switch from the choice made in the previous trial to obtain a reward. The monkeys were tested in two versions of the task, one in which they acted as the agent in every trial and one in which some trials were completed by a "ghost agent". We evaluated their involvement in terms of their performance and their interaction with the apparatus. Both monkeys were able to maintain a constant involvement in the task with good, stable performance within sessions in both versions of the task. https://www.selleckchem.com/products/AC-220.html Our study confirms the feasibility of home-cage training and demonstrates that even with challenging tasks, monkeys can complete a large number of trials at a high performance level, which is a prerequisite for electrophysiological studies of monkey behavior.Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells. We show that FANCD2, a master regulator of CFS stability, dampens the activation of the mitochondrial stress response and prevents mitochondrial dysfunction. Genetic or pharmacological activation of mitochondrial stress signaling induces CFS gene expression and concomitant relocalization to CFSs of FANCD2. FANCD2 attenuates CFS gene transcription and promotes CFS gene stability. Mechanistically, we demonstrate that the mitochondrial stress-dependent induction of CFS genes is mediated by ubiquitin-like protein 5 (UBL5), and that a UBL5-FANCD2 dependent axis regulates the mitochondrial UPR in human cells. We propose that FANCD2 coordinates nuclear and mitochondrial activities to prevent genome instability.Stochastic differential equations (SDEs) are ubiquitous across disciplines, and uncovering SDEs driving observed time series data is a key scientific challenge. Most previous work on this topic has relied on restrictive assumptions, undermining the generality of these approaches. We present a novel technique to uncover driving probabilistic models that is based on kernel density estimation. The approach relies on few assumptions, does not restrict underlying functional forms, and can be used even on non-Markov systems. When applied to El Niño-Southern Oscillation (ENSO), the fitted empirical model simulations can almost perfectly capture key time series properties of ENSO. This confirms that ENSO could be represented as a two-variable stochastic dynamical system. Our experiments provide insights into ENSO dynamics and suggest that state-dependent noise does not play a major role in ENSO skewness. Our method is general and can be used across disciplines for inverse and forward modeling, to shed light on structure of system dynamics and noise, to evaluate system predictability, and to generate synthetic datasets with realistic properties.Water inrush is one of the major mining disasters that may lead to numerous casualties. The development of information techniques makes it possible to monitor the occurrence and evolution of water inrush. Then, locating monitors for water inrush becomes a primary problem. This study presents a method of optimal location of water level sensors by constructing a set covering model. The monitoring scope of the water level sensor at each location in a given time is computed first based on the numerical simulation of water spreading along mine tunnels. In this simulation, the water inrush quantity is assigned using the mine drainage capability over which an accident may occur. Then the greedy algorithm is used to optimize the number and positions of water level sensors. As results, a mine water disaster can be monitored in the given time after it happened. The proposed method is then verified in the Beiyangzhuang coal mine in the North China. The results show that at least 22, 36, 42, 64 and 106 water level sensors are needed to monitor water disasters in the whole mine within 60, 30, 20, 10 and 5 min, respectively.Structured light with spatial degrees of freedom (DoF) is considered a potential solution to address the unprecedented demand for data traffic, but there is a limit to effectively improving the communication capacity by its integer quantization. We propose a data transmission system using fractional mode encoding and deep-learning decoding. Spatial modes of Bessel-Gaussian beams separated by fractional intervals are employed to represent 8-bit symbols. Data encoded by switching phase holograms is efficiently decoded by a deep-learning classifier that only requires the intensity profile of transmitted modes. Our results show that the trained model can simultaneously recognize two independent DoF without any mode sorter and precisely detect small differences between fractional modes. Moreover, the proposed scheme successfully achieves image transmission despite its densely packed mode space. This research will present a new approach to realizing higher data rates for advanced optical communication systems.No studies have investigated the influence of ethnicity in a multi-ethnic middle-income country with a long-standing history of co-habitation. Stool samples from 214 Malaysian community members (46 Malay, 65 Chinese, 49 Indian, and 54 Jakun) were collected. The gut microbiota of the participants was investigated using 16S amplicon sequencing. Ethnicity exhibited the largest effect size across participants (PERMANOVA Pseudo-F = 4.24, R2 = 0.06, p = 0.001). Notably, the influence of ethnicity on the gut microbiota was retained even after controlling for all demographic, dietary factors and other covariates which were significantly associated with the gut microbiome (PERMANOVA Pseudo-F = 1.67, R2 = 0.02, p = 0.002). Our result suggested that lifestyle, dietary, and uncharacterized differences collectively drive the gut microbiota variation across ethnicity, making ethnicity a reliable proxy for both identified and unidentified lifestyle and dietary variation across ethnic groups from the same community.The right ventricle´s (RV) characteristics-thin walls and trabeculation-make it challenging to evaluate extracellular volume (ECV). We aimed to assess the feasibility of RV ECV measurements in congenital heart disease (CHD), and to introduce a novel ECV analysis tool. Patients (n = 39) and healthy controls (n = 17) underwent cardiovascular magnetic resonance T1 mapping in midventricular short axis (SAX) and transverse orientation (TRANS). Regions of interest (ROIs) were evaluated with regard to image quality and maximum RV wall thickness per ROI in pixels. ECV from plane ROIs was compared with values obtained with a custom-made tool that derives the mean T1 values from a "line of interest" (LOI) centered in the RV wall. In CHD, average image quality was good (no artifacts in the RV, good contrast between blood/myocardium), and RV wall thickness was 1-2 pixels. RV ECV was not quantifiable in 4/39 patients due to insufficient contrast or wall thickness  less then  1 pixel. RV myocardium tended to be more clearly delineated in SAX than TRANS. ECV from ROIs and corresponding LOIs correlated strongly in both directions (SAX/TRANS r = 0.97/0.87, p  less then  0.001, respectively). In conclusion, RV ECV can be assessed if image quality allows sufficient distinction between myocardium and blood, and RV wall thickness per ROI is ≥ 1 pixel. T1 maps in SAX are recommended for RV ECV analysis. LOI application simplifies RV ECV measurements.GetUsPPE.org has built a centralized platform to facilitate matches for PPE donations, with an active role in matching donors with the appropriate recipients. A manual match process was limited by volunteer hours, thus we developed an open-access matching algorithm using a linear programming-based transportation model. From April 14, 2020 to April 27, 2020, the algorithm was used to match 83,136 items of PPE to 135 healthcare facilities in need across the United States with a median of 214.3 miles traveled, 100% of available donations matched, met the full quantity of requested PPE for 67% of recipients matched, and with 46% matches under 30 miles traveled. Compared with the period April 1, 2020 to April 13, 2020, when PPE matching was manual, the algorithm resulted in a 280% increase in matches/day. This publicly available automated algorithm could be deployed in future situations when the healthcare supply chain is insufficient.Prunus mume (also known as Mei) is an important ornamental plant that is popular with Asians. The weeping trait in P. mume has attracted the attention of researchers for its high ornamental value. However, the formation of the weeping trait of woody plants is a complex process and the molecular basis of weeping stem development is unclear. Here, the morphological and histochemical characteristics and transcriptome profiles of upright and weeping stems from P. mume were studied. Significant alterations in the histochemical characteristics of upright and weeping stems were observed, and the absence of phloem fibres and less xylem in weeping stems might be responsible for their inability to resist gravity and to grow downward. Transcriptome analysis showed that differentially expressed genes (DEGs) were enriched in phenylpropanoid biosynthesis and phytohormone signal transduction pathways. To investigate the differential responses to hormones, upright and weeping stems were treated with IAA (auxin) and GA3 (gibberellin A3), respectively, and the results revealed that weeping stems had a weaker IAA response ability and reduced upward bending angles than upright stems.
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