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Functionally similar pathways are often seen in biological systems, forming feed-forward controls. The robustness in network motifs such as feed-forward loops (FFLs) has been reported previously. In this work, we studied noise propagation in a development network that has multiple interlinked FFLs. A FFL has the potential of asymmetric noise-filtering (i.e., it works at either the "ON" or the "OFF" state in the target gene). With multiple, interlinked FFLs, we show that the propagated noisesdoi:10.1038/srep23607 pmid:27029397 pmcid:PMC4814832 fatcat:nnyqindy65aire7fruzjklqbge
more »... largely filtered regardless of the states in the input genes. The noise-filtering property of an interlinked FFL can be largely derived from that of the individual FFLs, and with interlinked FFLs, it is possible to filter noises in both "ON" and "OFF" states in the output. We demonstrated the noise filtering effect in the developmental regulatory network of Caenorhabditis elegans that controls the timing of distal tip cell (DTC) migration. The roles of positive feedback loops involving blmp-1 and the degradation regulation of DRE-1 also studied. Our analyses allow for better inference from network structures to noise-filtering properties, and provide insights into the mechanisms behind the precise DTC migration controls in space and time. Most of the cellular processes, which are various biochemical reactions, are inherently "noisy" because of extrinsic and intrinsic fluctuation of various factors. Even in isogenic populations under identical environmental conditions, the cells may show greatly different phenotypes 1-4 . Gene expression can be highly noisy 1,4 , partly due to the burst production in mRNA and proteins, and thereby leading to a large cell-to-cell variations 5-7 . The expression of a gene in one cell can be affected by its upstream noise, other global factors, as well as its own intrinsic noise in the expression 8 . Noise can be both an obstacle for some types of cellular functions 9-11 as well as a useful feature for others 12-18 . Living organisms go through a sequence of decision-making checkpoints that can not be reversed. Thus, cells need ways to cope with those fluctuations. Given the high level of stochastic fluctuations in gene expression at the intracellular level 1,4 it is hard to imagine that stability can be achieved without certain endogenous regulatory mechanism, such as feedback or feed-forward controls 19, 20 . Understanding how cells efficiently and correctly process information in noisy environments is of fundamental importance. In development, organisms grow with the same spatial and temporal patterns, with few variations among individuals. How the precise developmental events are controlled under the noisy condition has been an important question to answer 21, 22 . Gene regulation networks are often composed of a small set of recurring interaction patterns called network motifs 23,24 . Many motifs perform specific dynamic functions (as reviewed in ref. 25). In the cases studied so far, these motifs seem to preserve their autonomous functions even in their natural contexts, wired into the regulatory networks of the cell 25,26 . Therefore, studying the dynamics and fluctuations of biological processes with one particular network may help us to understand many other systems with networks composed of similar motifs. Among the network motifs in biological systems, feed-forward loops (FFLs) play a significant role 27 . All possible FFL architectures have been identified and many were shown to regulate a multitude of cellular processes    27 in a diverse range of organisms, from bacteria to human cells 28-34 . The regulatory interactions in FFL
We have developed a new technique using fluorescent silica nanotubes for simple and sensitive DNA detection. The quantum-dot-embedded silica nanotubes (QD-SNTs) were fabricated by a sol-gel reaction using anodic aluminum silica oxide (AAO) as a template. The fluorescent QD-SNTs of different colors were then immobilized with single-stranded DNA and used as nanoprobes for DNA detection. The optical and structural properties of QD-SNT nanoprobes were examined using photoluminescence spectroscopy,doi:10.1088/0957-4484/22/15/155102 pmid:21389577 fatcat:77ix5ebi5rbfjfzba4i4bbqusa
more »... onfocal microscopy and transmission electron microscopy (TEM). The QD-SNT nanoprobes were applied to detect dye-labeled target DNA in a solution phase. The obvious color change of the QD-SNT nanoprobes was observed visually under a simple microscope after the successful detection with target DNA. The quantitative analyses indicated that ∼100 attomole of target DNA in one nanoprobe can generate a distinguishable and observable color change. The detection results also demonstrated that our assay exhibited high specificity, high selectivity and very low nonspecific adsorption. Our simple DNA assay based on QD-SNT nanoprobes is expected to be quite useful for the needs of fast DNA screening and detection applications.
Iron deficiency (ID) and iron deficiency anemia (IDA) typically occur in developing countries. Notably, ID and IDA can affect an infant's emotion, cognition, and development. Breast milk is considered the best food for infants. However, recent studies have indicated that breastfeeding for more than six months increases the risk of ID. This study investigated the prevalence of ID and IDA, as well as the association between feeding type and iron nutritional status in northern Taiwan. Adoi:10.3390/nu12010139 pmid:31947816 pmcid:PMC7019343 fatcat:pnrtnztat5es7h23zgtw6it76m
more »... onal study was conducted on infants who returned to the well-baby clinic for routine examination from October 2012 to January 2014. Overall, 509 infants aged 1–12 months completed the iron nutritional status analysis, anthropometric measurement, and dietary intake assessment, including milk and complementary foods. The results revealed that 49 (10%) and 21 (4%) infants in their first year of life had ID and IDA, respectively, based on the World Health Organization criteria. Breastfed infants had a higher prevalence rate of ID and IDA than mixed-fed and formula-fed infants (p < 0.001). Regarding biomarkers of iron status, plasma hemoglobin (Hb), ferritin, and transferrin saturation (%) levels were significantly lower in ID and IDA groups. The prevalence of ID and IDA were 3.7% and 2.7%, respectively, in infants under six months of age, but increased to 20.4% and 6.6%, respectively, in infants above six months of age. The healthy group had a higher total iron intake than ID and IDA groups, mainly derived from infant formula. The total dietary iron intake was positively correlated with infants' Hb levels. Compared with formula-fed infants, the logistic regression revealed that the odds ratio for ID was 2.157 (95% confidence interval [CI]: 1.369–3.399) and that for IDA was 4.196 (95% CI: 1.780–9.887) among breastfed infants (p < 0.001) after adjusted for all confounding factors (including gestational week, birthweight, sex, body weight percentile, body length percentile, age of infants, mothers' BMI, gestational weight gain, education level, and hemoglobin level before delivery). In conclusion, our results determined that breastfeeding was associated with an increased the prevalence of ID and/or IDA, especially in infants above six months. This suggests that mothers who prolonged breastfeed after six months could provide high-quality iron-rich foods to reduce the prevalence of ID and IDA.
Mammalian histone deacetylases (HDACs) undergo phosphorylation to regulate their localization, activity and function. However, little is known about the regulation of plant HDAC function and activity by phosphorylation. Here, we report the crystal structure of the Reduced Potassium Dependency3/Histone Deacetylase1 (RPD3/HDA1) type class II histone deacetylase HDA15 in Arabidopsis (Arabidopsis thaliana). The histone deacetylase domain of HDA15 (HDA15HD) assembles as tetrameric forms with eachdoi:10.1104/pp.20.00604 pmid:32878973 pmcid:PMC7608165 fatcat:yijr5sjynzarfjrlvn3hjw7ytq
more »... omer composed of 12 α-helices and 9 β-sheets. The L1 loop and β2 sheet of HDA15HD are the essential interfaces for the tetramer formation. The N-terminal zinc finger domain enhances HDA15HD dimerization and increases its enzymatic activity. Furthermore, HDA15 can also be phosphorylated at Ser448 and Ser452 in etiolated seedlings. The HDA15 phosphorylation status determines its sub-nuclear localization and oligomerization. Phosphomimetics of HDA15 partially disrupt its oligomerization and cause loss of enzymatic activity and translocation from the nucleolus into nucleoplasm. Together, these data indicate that phosphorylation plays a critical role in regulating the structure and function of HDA15.
Acknowledgments: The author wishes to acknowledge the help of Shwu-Chen Kuo and Shwu-Huey Yang in commenting on an early draft of the manuscript. ...doi:10.3390/nu12061859 pmid:32580451 fatcat:igg2esa3unaonmtf3coogt7tq4
Ductal epithelium is primarily detected in porcine neonatal pancreatic cell clusters (NPCCs) bearing grafts, suggesting that transplants might exhibit progenitor-like phenotypes. Here we found that soon after NPCC isolation, PDX1 + /insulin − and SOX9 + pancreatic progenitor-like cells dramatically increased while dual-hormonal progenitor-like cells were routinely observed in NPCC culture. After transplantation (Tx), insulin + cells increased and PDX1 + and SOX9 + cells gradually decreased indoi:10.1038/s41598-018-26404-6 pmid:29844347 pmcid:PMC5974285 fatcat:ntv3x3dwzngb7bvnezokiluz4i
more »... th non-diabetic (NDM) and streptozotocin-induced diabetic (DM) grafts over 2 months. Strikingly, a significantly higher percentage of insulin + cells were detected in 9-day and 16-day, but not in 23-day, 30-day and 60-day grafts implying that hyperglycemia could only facilitate NPCC-derived β cells early post-Tx. A higher percentage of NPCC-derived β cells in early DM grafts was determined via an enhanced neogenic differentiation based on the detection of insulin + cells budding out from PDX1 + / SOX9 + epithelium. Interestingly, a drop in SOX9 + progenitor-like cells was detected 16 days post-Tx in DM grafts whilst PDX1 + cells do not show a significant difference until 60 days post-Tx between DM and NDM grafts, demonstrating that distinct progenitor-like populations fuel new β cells post-Tx. In conclusion, PDX1 + /SOX9 + cells could be quickly activated after NPCC isolation, maintain their multipotency in culture and differentiate into new β cell post-Tx.
Acknowledgments: The authors would like to thank Shao-Yuan Ho from Stanford University and Yi-Hsin Yeh from National Taiwan University of Science and Technology for consulting for the mechanism design ...doi:10.3390/bios11120495 pmid:34940252 pmcid:PMC8699525 fatcat:nbhuwr7g35dmfo6dwfosls66aa
to lead to a shift in the histology from SCC to adenocarcinoma subtypes of lung cancer due to higher exposure and sensitivity of peripheral These authors contributed equally: Fang-Ju Cheng, Chia-Hung Chen ...doi:10.1038/s41388-020-01597-1 pmid:33335306 fatcat:viufgu3mzngyzhxyo7jqpulmji
Echistatin (Ech) is a short disintegrin with a long 42NPHKGPAT C-terminal tail. We determined the 3-D structure of Ech by X-ray crystallography. Superimposition of the structures of chains A and B showed conformational differences in their RGD loops and C-termini. The chain A structure is consistent with our NMR analysis that the GPAT residues of the C-terminus cannot be observed due to high flexibility. The hydrogen bond patterns of the RGD loop and between the RGD loop and C-terminus in Echdoi:10.3390/toxins12110709 pmid:33182321 pmcid:PMC7695343 fatcat:6bfhqnt36beznctjhmia7ajriy
more »... re the same as those of the corresponding residues in medium disintegrins. The mutant with C-terminal HKGPAT truncation caused 6.4-, 7.0-, 11.7-, and 18.6-fold decreases in inhibiting integrins αvβ3, αIIbβ3, αvβ5, and α5β1. Mutagenesis of the C-terminus showed that the H44A mutant caused 2.5- and 4.4-fold increases in inhibiting αIIbβ3 and α5β1, and the K45A mutant caused a 2.6-fold decrease in inhibiting αIIbβ3. We found that Ech inhibited VEGF-induced HUVEC proliferation with an IC50 value of 103.2 nM and inhibited the migration of A375, U373MG, and Panc-1 tumor cells with IC50 values of 1.5, 5.7, and 154.5 nM. These findings suggest that Ech is a potential anticancer agent, and its C-terminal region can be optimized to improve its anticancer activity.
Szu-Chia Chen and Yi-Chun Tsai designed the conceptualization. Szu-Chia Chen, Jiun-Chi Huang, and Pei-Yu Wu curated the data. Hui-Ju Tsai and Yi-Chun Tsai analyzed the data. ... Szu-Chia Chen administrated, supervised, reviewed, and edited this paper. Stem Cells International ...doi:10.1155/2019/5270159 pmid:31781303 pmcid:PMC6874870 fatcat:zab5alzllveslbrsunt7jm6r3a
journalofgastricsurgery.com Chen C-H., et al./ JGS 3 (2021) doi: 10.36159/jgs.v3i1.74 Figure 3 : 3 A. Dilated stomach and straight-line cut-off of the third segment of the duodenum. B. ...doi:10.36159/jgs.v3i1.74 fatcat:mwrdiaebuzc6paq7l4buztd4xm
We study the information design problem in a single-unit auction setting. The information designer controls independent private signals according to which the buyers infer their binary private values. Assuming that the seller adopts the optimal auction due to Myerson (1981) in response, we characterize both the buyer-optimal information structure, which maximizes the buyers' surplus, and the sellerworst information structure, which minimizes the seller's revenue. We translate both informationarXiv:2010.08990v1 fatcat:eydxb5tdfrfdddcalgpniaufkm
more »... sign problems into finite-dimensional, constrained optimization problems in which one can explicitly solve for the optimal information structures. In contrast to the case with one buyer (Roesler and Szentes, 2017 and Du, 2018), we show that with two or more buyers, the symmetric buyer-optimal information structure is different from the symmetric seller-worst information structure. The good is always sold under the seller-worst information structure but not under the buyer-optimal information structure. Nevertheless, as the number of buyers goes to infinity, both symmetric information structures converge to no disclosure. We also show that in an ex ante symmetric setting, an asymmetric information structure is never seller-worst but can generate a strictly higher surplus for the buyers than the symmetric buyer-optimal information structure.
Clean intermittent catheterization (CIC) is one of the methods currently used to prevent overdistention of the bladder in patients with neurogenic bladder dysfunction (NBD). It is also helpful in preventing urinary tract infection and retaining the function of the bladder. Voiding diary and social behavior are necessary for the patients to maintain their physical and mental health, nevertheless there are currently no good assistant systems to help them achieve these goals. Methods: In thisdoi:10.3390/app9071433 fatcat:cysmt45mfnadhpkq4hx4fcppmu
more »... , we propose a CIC assistant system with the functions of recording and tracking the voided volume and accessible lavatory. The aim of this study is to assess the effects from the 12 patients who joined the proposed system. Information collected from participants included their demographics, past medicals, injury characteristics, current and past bladder managements, and any NBD related complications. Results: The results indicate that most patients felt relieved that they could know the voided volume and track their history easily. Moreover, the accessible lavatory function of the proposed system could reduce time consumption by 43.1% in finding the suitable lavatory, thus the desire and willingness of patients to travel increased from 25% to 75% after using the system. Conclusions: The proposed system could help doctors with clinical diagnoses, and help patients to understand more about the history of their catheterization volume and time period. This study provided essential information and design for future investigation.
Chun-Hao Chen, Ping-Hua Chen, Yi-He Tsai, and Yi-Yun Yang performed the experiments. All authors collected and analyzed data together. Hsin-Chiang You and K. S. ... Author Contributions In this paper, Yu-Hsien Lin and Yung-Chun Wu contributed to the design and wrote the manuscript. ...doi:10.3390/en7063653 fatcat:jhn2wf2qkzalpckxif5n5o6ela
Intrahepatic cholangiocarcinoma (ICC) is a relatively rare subtype of cholangiocarcinoma. The study herein gathered experience of surgical treatment for ICC, and aimed to analyze the prognosis of patients who had received curative-intent liver resection. Methods: A total of 216 patients who had undergone curative-intent liver resection for ICC between January 1977 and December 2014 was retrospectively reviewed. Results: Overall, the rates of 5-years recurrence-free survival (RFS) and overalldoi:10.1186/s12876-018-0912-x fatcat:7kiqvg3efjb3bad7gg4crvkcji
more »... vival (OS) were 26.1 and 33.9% respectively. Based on multivariate analysis, four independent adverse prognostic factors including morphology patterns, maximum tumor size > 5 cm, pathological lymph node involvement, and vascular invasion were identified as affecting RFS after curative-intent liver resection for ICC. Among patients with cholangiocarcinoma recurrence, only 27 (16.9%) were able to receive surgical resection for recurrent cholangiocarcinoma that had a significantly better outcome than the remaining patients. Conclusion: Despite curative resection, the general outcome of patients with ICC is still unsatisfactory because of a high incidence of cholangiocarcinoma recurrence after operation. Tumor factors associated with cholangiocarcinoma remain crucial for the prognosis of patients with ICC after curative liver resection. Moreover, aggressive attitude toward repeat resection for the postoperative recurrent cholangiocarcinoma could provide a favorable outcome for patients.
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