Relevant bibliographies by topics / RAS wild type

Academic literature on the topic 'RAS wild type'

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Published: 10 December 2022
Last updated: 29 January 2023

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Journal articles on the topic "RAS wild type"

1

Anastassiadis, Theonie, and Eric J. Brown. "Wild-Type RAS: Keeping Mutant RAS in CHK." Cancer Cell 25, no. 2 (February 2014): 137–38. http://dx.doi.org/10.1016/j.ccr.2014.01.029.

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Fotiadou, Poppy P., Chiaki Takahashi, Hasan N. Rajabi, and Mark E. Ewen. "Wild-Type NRas and KRas Perform Distinct Functions during Transformation." Molecular and Cellular Biology 27, no. 19 (July 16, 2007): 6742–55. http://dx.doi.org/10.1128/mcb.00234-07.

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ABSTRACT The ras proto-oncogenes, of which there are four isoforms, are molecular switches that function in signal transduction pathways to control cell differentiation, proliferation, and survival. How the Ras isoforms orchestrate cellular processes that affect behavior is poorly understood. Further, why cells express two or more Ras isoforms is unknown. Here, using a genetically defined system, we show that the presence of both wild-type KRas and NRas isoforms is required for transformation because they perform distinct nonoverlapping functions: wild-type NRas regulates adhesion, and KRas coordinates motility. Remarkably, we find that Ras isoforms achieve functional specificity by engaging different signaling pathways to affect the same cellular processes, thereby coordinating cellular outcome. Although we find that signaling from both isoforms intersects in actin and microtubule cytoskeletons, our results suggest that KRas signals through Akt and Cdc42 while NRas signals through Raf and RhoA. Our analyses suggest a previously unappreciated convergence of different Ras isoforms on the dynamics of the processes involved in transformation.
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Singh, Arvind, A. Pavani Sowjanya, and Gayatri Ramakrishna. "The wild‐type Ras: road ahead." FASEB Journal 19, no. 2 (February 2005): 161–69. http://dx.doi.org/10.1096/fj.04-2584hyp.

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Henry, Jason, Jason Willis, Christine Megerdichian Parseghian, Kanwal Pratap Singh Raghav, Benny Johnson, Arvind Dasari, David Stone, et al. "NeoRAS: Incidence of RAS reversion from RAS mutated to RAS wild type." Journal of Clinical Oncology 38, no. 4_suppl (February 1, 2020): 180. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.180.

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180 Background: RAS mutations are found in ~50% of patients (pts) with metastatic colorectal cancer (mCRC) and associated with resistance to anti-EGFR. Circulating tumor DNA (ctDNA) enables detection of resistant RASMUT arising from RASWT. Recently there has been interest in defining the converse: RASMUT tumors that revert to RASWT, with early results suggesting rates of ~7%. Clinical trials in this population are in development, though the incidence has not been validated with robust methodologies. Methods: 1) We identified 74 mCRC pts with baseline RASMUT and longitudinal ctDNA or tissue data enrolled in ATTACC (NCT01196130), a prospective genomic matching protocol utilizing paired tissue/ctDNA samples at baseline. We evaluated serial samples for RAS loss. 2) Using an external cohort of pts with mCRC and serial ctDNA with a targeted NGS assay sequencing all KRAS/ NRAS exons (Guardant360, Guardant Health), we screened pts for baseline RASMUT with no evidence of prior anti-EGFR exposure and evaluated for RAS loss. Results: 74 pts met criteria of RASMUT CRC with serial samples in ATTACC. Of these, 51 retained RASMUT. 22 pts had very low or absent levels of other clonal alterations such as APC or TP53 and are therefore unable to reliably detect RAS loss. One patient had true RAS loss with NRAS G13R, APC and TP53 mutations at baseline and persistent high-level APC and TP53 mutations without a detectable NRAS mutation, for an overall rate of RAS loss of 2% (1/52). In the second cohort we identified 162 pts, 34 of which had insufficient ctDNA to assess RAS loss on the serial sample as defined by loss of clonal alterations like APC and TP53. Of the remaining 128 patients, 11 had RAS loss (8.5%, with 1 NRAS, 10 KRAS). We next compared the relative mutant allele frequency (rMAF) between RAS retainers and RAS loss. The median baseline rMAF for pts who lost RAS was 0.74, compared to 0.86 in pts retaining RAS (p = 0.045). Conclusions: RAS reversion in mCRC from RASMUT to RASWT is uncommon and occurs at a rate between 2-8% in our two cohorts. RAS reversion is associated with a lower rMAF at baseline, suggesting subclonality. Liquid biopsies must be interpreted carefully, such that a determination of RAS mutation status is most informative in the presence of truncal APC and/or TP53 mutations.
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Sheffels, Erin, and Robert L. Kortum. "The Role of Wild-Type RAS in Oncogenic RAS Transformation." Genes 12, no. 5 (April 28, 2021): 662. http://dx.doi.org/10.3390/genes12050662.

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The RAS family of oncogenes (HRAS, NRAS, and KRAS) are among the most frequently mutated protein families in cancers. RAS-mutated tumors were originally thought to proliferate independently of upstream signaling inputs, but we now know that non-mutated wild-type (WT) RAS proteins play an important role in modulating downstream effector signaling and driving therapeutic resistance in RAS-mutated cancers. This modulation is complex as different WT RAS family members have opposing functions. The protein product of the WT RAS allele of the same isoform as mutated RAS is often tumor-suppressive and lost during tumor progression. In contrast, RTK-dependent activation of the WT RAS proteins from the two non-mutated WT RAS family members is tumor-promoting. Further, rebound activation of RTK–WT RAS signaling underlies therapeutic resistance to targeted therapeutics in RAS-mutated cancers. The contributions of WT RAS to proliferation and transformation in RAS-mutated cancer cells places renewed interest in upstream signaling molecules, including the phosphatase/adaptor SHP2 and the RasGEFs SOS1 and SOS2, as potential therapeutic targets in RAS-mutated cancers.
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Roy, Sandrine, Bruce Wyse, and John F. Hancock. "H-Ras Signaling and K-Ras Signaling Are Differentially Dependent on Endocytosis." Molecular and Cellular Biology 22, no. 14 (July 15, 2002): 5128–40. http://dx.doi.org/10.1128/mcb.22.14.5128-5140.2002.

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ABSTRACT Endocytosis is required for efficient mitogen-activated protein kinase (MAPK) activation by activated growth factor receptors. We examined if H-Ras and K-Ras proteins, which are distributed across different plasma membrane microdomains, have equal access to the endocytic compartment and whether this access is necessary for downstream signaling. Inhibition of endocytosis by dominant interfering dynamin-K44A blocked H-Ras but not K-Ras-mediated PC12 cell differentiation and selectively inhibited H-Ras- but not K-Ras-mediated Raf-1 activation in BHK cells. H-Ras- but not K-Ras-mediated Raf-1 activation was also selectively dependent on phosphoinositide 3-kinase activity. Stimulation of endocytosis and endocytic recycling by wild-type Rab5 potentiated H-Ras-mediated Raf-1 activation. In contrast, Rab5-Q79L, which stimulates endocytosis but not endocytic recycling, redistributed activated H-Ras from the plasma membrane into enlarged endosomes and inhibited H-Ras-mediated Raf-1 activation. Rab5-Q79L expression did not cause the accumulation of wild-type H-Ras in enlarged endosomes. Expression of wild-type Rab5 or Rab5-Q79L increased the specific activity of K-Ras-activated Raf-1 but did not result in any redistribution of K-Ras from the plasma membrane to endosomes. These results show that H-Ras but not K-Ras signaling though the Raf/MEK/MAPK cascade requires endocytosis and endocytic recycling. The data also suggest a mechanism for returning Raf-1 to the cytosol after plasma membrane recruitment.
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Wen, Zhi, and Jing Zhang. "Wild-Type Kras Inhibits NrasQ61R/+-Induced Leukemias." Blood 126, no. 23 (December 3, 2015): 1249. http://dx.doi.org/10.1182/blood.v126.23.1249.1249.

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Ras proteins belong to the super family of small GTPases. Although RAS mutations are oncogenic, it remains highly controversial whether wild-type (WT) RAS facilitates or inhibits tumorigenesis in the presence of oncogenic RAS. Previous studies suggest that this might depend on cell type, specific RAS isoforms, and/or stage of tumorigenesis (e.g. tumor initiation versus tumor progression). Recently, we found that deletion of WT Kras in oncogenic Kras mice promotes myeloidproliferative neoplasm (MPN) in a cell-autonomous manner. This is through promoting activation of all Ras isoforms and thus enhancing cytokine signaling in vivo. However, it remains unknown whether WT Kras plays a similar role in oncogenic Nras-induced leukemogenesis. To address this issue, we conditionally down-regulated WT Kras expression in a novel leukemia model induced by endogenous NrasQ61R/+. Detailed characterization of NrasQ61R allele reveals that NrasQ61R/+ displays an intermediate leukemogenic activity between NrasG12D/+ and NrasG12D/G12D. NrasQ61R/+ mice developed MPN (100%) and acute T-cell lymphoblastic leukemia/lymphoma (T-ALL) (~10%) at the moribund stage with a median survival of 197 days. Therefore, NrasQ61R/+ mice provide an excellent experimental system to test genetic lesions promoting or inhibiting oncogenic Nras-induced leukemogenesis. We observed that 3-weeks after activation of NrasQ61R/+ and deletion of WT Kras, the double mutant mice displayed more severe MPN phenotypes than NrasQ61R/+ mice, as demonstrated by more prominent hepatosplenomegaly and further expanded myeloid compartment in bone marrow and spleen. Consistent with these MPN phenotypes, NrasQ61R/+; Kras-/- myeloid progenitor and precursor cells showed prolonged and hyperactivated GM-CSF signaling compared to NrasQ61R/+ cells. In addition, NrasQ61R/+; Kras-/- mice displayed further expanded common lymphoid progenitor compartment and a less differentiated phenotype in thymic T-cells than NrasQ61R/+ mice. In NrasQ61R/+; Kras-/- mice, early thymic T cell progenitors demonstrated enhanced cell proliferation and stronger ERK1/2 signaling compared to NrasQ61R/+ cells. Consequently, NrasQ61R/+; Kras-/- mice survived significantly shorter than NrasQ61R/+ mice (median survival: 97 days; P < 0.001) and 100% of them developed both MPN and T-ALL at the moribund stage. Preliminary results from bone marrow transplantation assay indicate that loss of WT Kras expression promoted NrasQ61R/+-induced MPN and T-ALL in a cell-autonomous manner. Taken together, our results suggest that loss of WT Kras promotes leukemogenesis in NrasQ61R/+ mice. We are currently studying on the underlying mechanisms. Disclosures No relevant conflicts of interest to declare.
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Graham, S. M., A. B. Vojtek, S. Y. Huff, A. D. Cox, G. J. Clark, J. A. Cooper, and C. J. Der. "TC21 causes transformation by Raf-independent signaling pathways." Molecular and Cellular Biology 16, no. 11 (November 1996): 6132–40. http://dx.doi.org/10.1128/mcb.16.11.6132.

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Although the Ras-related protein TC21/R-Ras2 has only 55% amino acid identity with Ras proteins, mutated forms of TC21 exhibit the same potent transforming activity as constitutively activated forms of Ras. Therefore, like Ras, TC21 may activate signaling pathways that control normal cell growth and differentiation. To address this possibility, we determined if regulators and effectors of Ras are also important for controlling TC21 activity. First, we determined that Ras guanine nucleotide exchange factors (SOS1 and RasGRF/CDC25) synergistically enhanced wild-type TC21 activity in vivo and that Ras GTPase-activating proteins (GAPs; p120-GAP and NF1-GAP) stimulated wild-type TC21 GTP hydrolysis in vitro. Thus, extracellular signals that activate Ras via SOS1 activation may cause coordinate activation of Ras and TC21. Second, we determined if Raf kinases were effectors for TC21 transformation. Unexpectedly, yeast two-hybrid binding analyses showed that although both Ras and TC21 could interact with the isolated Ras-binding domain of Raf-1, only Ras interacted with full-length Raf-1, A-Raf, or B-Raf. Consistent with this observation, we found that Ras- but not TC21-transformed NIH 3T3 cells possessed constitutively elevated Raf-1 and B-Raf kinase activity. Thus, Raf kinases are effectors for Ras, but not TC21, signaling and transformation. We conclude that common upstream signals cause activation of Ras and TC21, but activated TC21 controls cell growth via distinct Raf-independent downstream signaling pathways.
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Dent, P., D. B. Reardon, D. K. Morrison, and T. W. Sturgill. "Regulation of Raf-1 and Raf-1 mutants by Ras-dependent and Ras-independent mechanisms in vitro." Molecular and Cellular Biology 15, no. 8 (August 1995): 4125–35. http://dx.doi.org/10.1128/mcb.15.8.4125.

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The serine/threonine kinase Raf-1 functions downstream from Ras to activate mitogen-activated protein kinase kinase, but the mechanisms of Raf-1 activation are incompletely understood. To dissect these mechanisms, wild-type and mutant Raf-1 proteins were studied in an in vitro system with purified plasma membranes from v-Ras- and v-Src-transformed cells (transformed membranes). Wild-type (His)6- and FLAG-Raf-1 were activated in a Ras- and ATP-dependent manner by transformed membranes; however, Raf-1 proteins that are kinase defective (K375M), that lack an in vivo site(s) of regulatory tyrosine (YY340/341FF) or constitutive serine (S621A) phosphorylation, that do not bind Ras (R89L), or that lack an intact zinc finger (CC165/168SS) were not. Raf-1 proteins lacking putative regulatory sites for an unidentified kinase (S259A) or protein kinase C (S499A) were activated but with apparently reduced efficiency. The kinase(s) responsible for activation by Ras or Src may reside in the plasma membrane, since GTP loading of plasma membranes from quiescent NIH 3T3 cells (parental membranes) induced de novo capacity to activate Raf-1. Wild-type Raf-1, possessing only basal activity, was not activated by parental membranes in the absence of GTP loading. In contrast, Raf-1 Y340D, possessing significant activity, was, surprisingly, stimulated by parental membranes in a Ras-independent manner. The results suggest that activation of Raf-1 by phosphorylation may be permissive for further modulation by another membrane factor, such as a lipid. A factor(s) extracted with methanol-chloroform from transformed membranes or membranes from Sf9 cells coexpressing Ras and SrcY527F significantly enhanced the activity of Raf-1 Y340D or active Raf-1 but not that of inactive Raf-1. Our findings suggest a model for activation of Raf-1, wherein (i) Raf-1 associates with Ras-GTP, (ii) Raf-1 is activated by tyrosine and/or serine phosphorylation, and (iii) Raf-1 activity is further increased by a membrane cofactor.
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Tang, Y., Z. Chen, D. Ambrose, J. Liu, J. B. Gibbs, J. Chernoff, and J. Field. "Kinase-deficient Pak1 mutants inhibit Ras transformation of Rat-1 fibroblasts." Molecular and Cellular Biology 17, no. 8 (August 1997): 4454–64. http://dx.doi.org/10.1128/mcb.17.8.4454.

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Among the mechanisms by which the Ras oncogene induces cellular transformation, Ras activates the mitogen-activated protein kinase (MAPK or ERK) cascade and a related cascade leading to activation of Jun kinase (JNK or SAPK). JNK is additionally regulated by the Ras-related G proteins Rac and Cdc42. Ras also regulates the actin cytoskeleton through an incompletely elucidated Rac-dependent mechanism. A candidate for the physiological effector for both JNK and actin regulation by Rac and Cdc42 is the serine/threonine kinase Pak (p65pak). We show here that expression of a catalytically inactive mutant Pak, Pak1(R299), inhibits Ras transformation of Rat-1 fibroblasts but not of NIH 3T3 cells. Typically, 90 to 95% fewer transformed colonies were observed in cotransfection assays with Rat-1 cells. Pak1(R299) did not inhibit transformation by the Raf oncogene, indicating that inhibition was specific for Ras. Furthermore, Rat-1 cell lines expressing Pak1(R299) were highly resistant to Ras transformation, while cells expressing wild-type Pak1 were efficiently transformed by Ras. Pak1(L83,L86,R299), a mutant that fails to bind either Rac or Cdc42, also inhibited Ras transformation. Rac and Ras activation of JNK was inhibited by Pak1(R299) but not by Pak1(L83,L86,R299). Ras activation of ERK was inhibited by both Pak1(R299) and Pak1(L83,L86,R299), while neither mutant inhibited Raf activation of ERK. These results suggest that Pak1 interacts with components essential for Ras transformation and that inhibition can be uncoupled from JNK but not ERK signaling.
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Dissertations / Theses on the topic "RAS wild type"

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Ferguson, Robert. "Wild-type N-Ras complements mutant K-Ras in pancreatic cancer cell lines but K-Ras has a specific role in cell cycle independent regulation of G2 cyclins." Thesis, University of Liverpool, 2015. http://livrepository.liverpool.ac.uk/2032380/.

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Pancreatic Ductal Adenocarcinoma (PDAC) is nearly always associated with mutant K-Ras. Nevertheless, targeting oncogenic K-Ras has so far proved ineffective in treating this form of cancer and pancreatic cancer cell lines can become K-Ras independent. Other forms of Ras are rarely mutated but wild type N-Ras and H-Ras have been shown to be present alongside functional K-Ras mutations and have been demonstrated to increase responsiveness to growth factors. Beyond this little evidence had previously been gathered on the activity or function of N-Ras and H-Ras in PDAC. Therefore, this thesis aimed to determine if other Ras isoforms are active in PDAC cell lines and what effect they may have on controlling cell division, oxidative metabolism, cytokine expression and the phospholipid composition of the membrane. The presence of active N-Ras and K-Ras was identified in three of the four human PDAC cell lines tested. Only active K-Ras was detected in a cell line derived from a mouse model of pancreatic cancer driven by heterologous expression of mutant KRAS. N-Ras was shown to be functioning alongside K-Ras to control the relative level of oxidative metabolism in the Suit-2 and a faster growing variant of the Panc-1 cell lines, but K-Ras acts alone in the slow growing Panc-1 cell line that does not contain N-Ras. N-Ras and K-Ras were shown to have different effects on the levels of cytokines, although K-Ras is largely independent of N-Ras in its regulation of phospholipid composition. A novel N-Ras independent mechanism for K-Ras transcriptional control of cyclin B1 was demonstrated. When K-Ras is depleted cyclin B1 and cyclin A are decreased. Cyclin B1 transcription can be rescued by inhibition of the Proteasome. A model is proposed whereby an unknown protein or proteins activates cyclin B1 transcription in a cell-cycle independent fashion and is protected from proteasomal degradation by K-Ras. These results suggest that mutant K-Ras can act in conjunction with wild-type N-Ras, but also can function independently to regulate G2 cyclins.
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Zanucco, Emanuele [Verfasser], and Ulf Rüdiger [Akademischer Betreuer] Rapp. "Role of oncogenic and wild type B-RAF in mouse lung tumor models / Emanuele Zanucco. Betreuer: Ulf R. Rapp." Würzburg : Universitätsbibliothek der Universität Würzburg, 2012. http://d-nb.info/1022061216/34.

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Weyandt, Jamie Dawn. "Investigatiing the Role of the Wild-Type Ras Isoforms in KRas-driven Cancer." Diss., 2015. http://hdl.handle.net/10161/11392.

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The RAS family is a group of small GTPases that can become constitutively activated by point mutations that are found in about 30% of all cancer patients. There are three well-characterized RAS family members: HRAS, NRAS, and KRAS, the latter of which is alternatively spliced at the C-terminus into KRAS4A and KRAS4B. The RAS proteins are all nearly identical at their N-termini and core effector binding domains, but have divergent C-terminal membrane-binding regions that impart different subcellular localization and subtle differences in signaling. Although the role of constitutively activated oncogenic RAS has been well established to play a role in cancer, recent work has suggested that wild-type RAS signaling may also be important in tumorigenesis. Wild-type RAS proteins have been shown to be activated in the presence of oncogenic KRAS. However, the consequences of this activation are context-dependent, as signaling through the wild-type RAS proteins has been shown to both suppress neoplastic growth and promote tumorigenesis under different circumstances.

I sought to investigate the role of the wild-type RAS proteins in two clinically –relevant models of cancer: pancreatic, the type of cancer most frequently associated with KRAS mutations, and lung cancer, the cancer in which KRAS mutations affect the highest number of patients. First, I tested whether a loss of wild type Hras altered tumorigenesis in a mouse model of pancreatic cancer driven by oncogenic Kras. Hras homozygous null mice (Hras-/- ) exhibited more precancerous lesions of the pancreas as well as more off-target skin papillomas compared to their wild type counterparts, indicating that Hras suppresses early Kras-driven pancreatic tumorigenesis. Loss of Hras also reduced the survival of mice engineered to develop aggressive pancreatic cancer by the additional disruption of one allele of the tumor suppressor p53 (Trp53R172H/+). However, this survival advantage was lost when both alleles of Trp53 were mutated, suggesting that wild-type HRas inhibits tumorigenesis in a p53-dependant manner.

Next, I investigated the role that wild-type Hras and Nras play in a chemical carcinogen-induced model of lung cancer. In mice treated with urethane, a carcinogen that induces Kras-mutation positive lung lesions, Hras-/ mice once again developed more tumors than wild-type mice. Interestingly, however, this effect was not observed in mice lacking wild-type Nras. Mice lacking both Hras and Nras alleles developed approximately the same number of tumors as Hras-/- mice, thus the additional loss of Nras does not appear to enhance the tumor-promoting effects of loss of Hras. In summary, signaling through wild-type Hras, but not Nras, suppresses tumorigenesis in a carcinogen-induced model of lung cancer.

The tumor-suppressive effects of wild-type Ras signaling were traced to the earliest stages of pancreatic tumorigenesis, suggesting that wild-type Ras signaling may suppress tumorigenesis as early as the time of initiation. These findings suggest that differences in expression of the wild-type Ras isoforms could potentially play a role in an individual’s predisposition for developing cancer upon oncogenic insult.


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Chun-ILi and 李俊毅. "The effect of miR-146a and target gene vimentin on tumorigenesis of esophageal squamous cell carcinoma cell lines overexpressing wild-type K-Ras gene." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/b64k4e.

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Zanucco, Emanuele. "Role of oncogenic and wild type B-RAF in mouse lung tumor models." Doctoral thesis, 2011. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-69603.

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Von Wachstumsfaktoren regulierte Signalkaskaden sind Schlüsselelemente in der Gewebeentwicklung und Geweberegeneration. Eine Deregulation dieser Kaskaden führt zu Entwicklungsstörungen und neoplastischen Krankheiten. Für viele humane Krebsformen sind aktivierende Mutationen der Kinasen der RAF Familie verantwortlich. Das erste Projekt dieser Doktorarbeit fokussiert auf der Rolle des B-RAF V600E, welches als eine der am häufigsten vorkommenden Mutantionen in humanen Krebszellen identifiziert worden ist. Um die onkogene Funktion des B-RAF V600E zu untersuchen, haben wir transgene Mauslinien hergestellt, welche das aktivierte Onkogen spezifisch in alveolaren Lungenepithelzellen des Typ II exprimieren. Konstitutive Expression des B-RAF V600E führte zu einer abnormen alveolaren Epithelzellbildung und zu Emphysem-ähnlichen Läsionen. Diese Läsionen wiesen Zeichen einer Gewebsumstrukturierung auf, oft in Assoziation mit chronischer Inflammation und geringer Inzidenz von Lungentumoren. Die Infiltration der entzündlichen Zellen erfolgte erst nach der Entstehung von Emphysem-ähnlichen Läsionen und könnte zur späteren Tumorbildung beigetragen haben. Diese Ergebnisse unterstützen ein Modell, in welchem der kontinuierliche regenerative Prozess eine tumorfördernde Umgebung schafft. Dabei induziert die Aktivität des onkogenen B-RAF eine alveolare Störung, welche ursächlich verantwortlich ist für den kontinuierlichen regenerativen Prozess. Das zweite Projekt fokussiert auf die Rolle von endogenem (wildtypischen) B-RAF in einem durch onkogenes C-RAF induzierten Maus Lungentumormodell. Für unsere Untersuchungen haben wir eine Mauslinie geschaffen, in welcher B-RAF in den C-RAF Lungentumoren konditionell eliminiert werden kann. Eine konditionelle Eliminierung des B-RAF hat die Entstehung von Lungentumoren nicht blockiert, aber zu reduziertem Tumorwachstum geführt. Dieses reduzierte Tumorwachstum konnte auf eine reduzierte Zellproliferation zurückgeführt werden. Außerdem konnten wir durch die B-RAF Elimination eine Reduktion der Intensität der mitogenen Signalkaskade beobachten. Insgesamt deuten die Ergebnisse darauf hin, dass das onkogene Potential von C-RAF in vivo unabhängig von B-RAF ist und eine Kooperation von B-RAF und C-RAF jedoch für die vollständige Aktivierung der mitogenen Signalkaskade wichtig ist
Growth factor induced signaling cascades are key regulatory elements in tissue development, maintenance and regeneration. Deregulation of the cascades has severe consequences, leading to developmental disorders and neoplastic diseases. As a major function in signal transduction, activating mutations in RAF family kinases are the cause of many human cancers. In the first project described in this thesis we focused on B-RAF V600E that has been identified as the most prevalent B-RAF mutant in human cancer. In order to address the oncogenic function of B-RAF V600E, we have generated transgenic mice expressing the activated oncogene specifically in lung alveolar epithelial type II cells. Constitutive expression of B-RAF V600E caused abnormalities in alveolar epithelium formation that led to airspace enlargements. These lung lesions showed signs of tissue remodeling and were often associated with chronic inflammation and low incidence of lung tumors. Inflammatory cell infiltration did not precede the formation of emphysema-like lesions but was rather accompanied with late tumor development. These data support a model where the continuous regenerative process initiated by oncogenic B-RAF-driven alveolar disruption provides a tumor-promoting environment associated with chronic inflammation. In the second project we focused on wild type B-RAF and its role in an oncogenic-C-RAF driven mouse lung tumor model. Toward this aim we have generated compound mice in which we could conditionally deplete B-RAF in oncogenic-C-RAF driven lung tumors. Conditional elimination of B-RAF did not block lung tumor formation however led to reduced tumor growth. The diminished tumor growth was not caused by increased cell death instead was a consequence of reduced cell proliferation. Moreover, B-RAF ablation caused a reduction in the amplitude of the mitogenic signalling cascade. These data indicate that in vivo B-RAF is dispensable for the oncogenic potential of active C-RAF; however it cooperates with oncogenic C-RAF in the activation of the mitogenic cascade
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Books on the topic "RAS wild type"

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Wild ran the rivers: One family's western odyssey. Farmington Hills, Mich: Thorndike Press, a part of Gale, Cengage Learning, 2015.

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Grahame, Kenneth. The wild wood: And, Mole's Christmas. London: Methuen Children's Books, 1991.

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Serebryakov, Andrey. Ecological geology. ru: INFRA-M Academic Publishing LLC., 2021. http://dx.doi.org/10.12737/971374.

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The textbook describes complex natural, geological, geographical, hydrogeological and lithological studies based on modern geological and ecological theories and forming the basis of environmental science. The theoretical views on the ecology of the geological environment are expanded. The tasks of ecological geology and geography, as well as ecological hydrogeology and ecological lithology are substantiated. Attention is paid to the history of geoecological research in the development of new territories. The influence of the tectonic formation of geological structures on the ecological situation of the Earth's lithosphere is studied. The ecological zoning of the lithosphere and hydrosphere is given. The ecological characteristics of sedimentary deposits, which are associated with minerals of important industrial and environmental importance, are given. The ecological properties of various types of mineral raw materials for their application in industry are considered. Meets the requirements of the federal state educational standards of higher education of the latest generation. It is intended for bachelors studying the discipline "Ecological Geology" and Earth sciences, and will also be of interest to environmental specialists in the design and operation of industrial facilities, structures and deposits of natural raw materials.
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Grahame, Kenneth. The wind in thewillows. London: Beehive, 1986.

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Grahame, Kenneth. The wind in the willows. New York: Aladdin Books, 1989.

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Driscoll, Laura. The wind in the willows: The Open Road. New York: Sterling Pub. Co., 2006.

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Grahame, Kenneth. The wind in the willows. London: V. Gollancz, 1988.

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Grahame, Kenneth. The wind in the willows. New York: Wanderer Books, 1987.

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The wind in the willows: Panic at Toad Hall. New York: Nantier, Beall, Minoustchine, 1997.

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Grahame, Kenneth. The wind in the willows. San Diego: Harcourt, 2002.

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Book chapters on the topic "RAS wild type"

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Wittinghofer, Alfred, Sybille M. Franken, Axel J. Scheidig, Hans Rensland, Alfred Lautwein, Emil F. Pai, and Roger S. Goody. "Three-Dimensional Structure and Properties of Wild-Type and Mutant H-ras-Encoded p21." In Ciba Foundation Symposium 176 - The GTPase Superfamily, 6–27. Chichester, UK: John Wiley & Sons, Ltd., 2007. http://dx.doi.org/10.1002/9780470514450.ch2.

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Gärtner, Jan Wilhelm, Daniel D. Loureiro, and Andreas Kronenburg. "Modelling and Simulation of Flash Evaporation of Cryogenic Liquids." In Fluid Mechanics and Its Applications, 233–50. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-09008-0_12.

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AbstractRocket engine manufacturers attempt to replace toxic, hypergolic fuels by less toxic substances such as cryogenic hydrogen and oxygen. Such components will be superheated when injected into the combustion chamber prior to ignition. The liquids will flash evaporate and subsequent mixing will be crucial for a successful ignition of the engine. We now conduct a series of DNS and RANS-type simulations to better understand this mixing process including microscopic processes such as bubble growth, bubble-bubble interactions, spray breakup dynamics and the resulting droplet size distribution. Full scale RANS simulations provide further insight into effects associated with flow dynamic such as shock formation behind the injector outlet. Capturing these gas dynamic effects is important, as they affect the spray morphology and droplet movements.
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Parasuraman, Malathy, and Priyantha Weerasinghe. "Application of mutation breeding techniques in the development of green crop varieties in Sri Lanka: the way forward." In Mutation breeding, genetic diversity and crop adaptation to climate change, 76–82. Wallingford: CABI, 2021. http://dx.doi.org/10.1079/9781789249095.0008.

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Abstract The Department of Agriculture (DOA) in Sri Lanka initiated mutation breeding in the 1960s with the introduction of a cobalt-60 source. The first rice mutant variety, MI 273, was released for general cultivation in 1971. M1 273, derived from irradiation of the H-4 variety, was identified as a drought-tolerant variety. An indirect rice mutant variety, developed by crossing the short mutant line BW267-3 with a highly adaptable variety, was released as BW 372 in 2013. It is moderately tolerant to blast, bacterial leaf blight, brown plant hopper, gall midge and iron toxicity, and thus increases productivity to 3-4 t/ha on lands prone to iron toxicity. The most popular groundnut variety cultivated in the country, 'Tissa', is a mutant developed by irradiation with gamma-rays at 200 Gy. It showed attributes of high yield, medium maturity (90-100 days) and high oil content (42%). 'Tissa' presently covers 80% of the groundnut cultivated area in Sri Lanka. A sesame mutant line, derived from the variety MI-3 irradiated at 200 Gy with 60Co gamma-rays, was released as 'Malee' (ANK-S2) in 1993. It is a high-yielding variety (1.1-1.8 t/ha) resistant to Phytophthora blight. A cherry-type mutant tomato variety, developed by irradiation of seeds with gamma-rays (320 Gy), was released as 'Lanka Cherry' in 2010. Improved attributes are pear-shaped fruits and bacterial wilt resistance. Narrow genetic variability in many crops is a constraint to the development of new varieties adapted to the changing climate. Hence, the DOA is emphasizing integration of induced mutagenesis in conventional breeding programmes to develop resistant/tolerant varieties having high yield, quality and health-promoting functional properties in field and horticultural crops. The newly installed gamma irradiation chamber facilitates the creation of genetic variability in food crops, thus paving the way for the development of greener varieties.
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Sivaradje, G., I. Saravanan, and P. Dananjayan. "Convergence Technology for Enabling Technologies." In Mobile Computing, 961–67. IGI Global, 2009. http://dx.doi.org/10.4018/978-1-60566-054-7.ch078.

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Today, we find a large number of wireless networks based on different radio access technologies (RATs). Every existing RAT has its own merits. Now the focus is turned towards the next-generation communication networks (Akyildiz, Mohanty, & Xie, 2005), which will seamlessly integrate various existing wireless communication networks, such as wireless local area networks (WLANs, e.g., IEEE 802.11 a/b/g and HIPERLAN/2), wireless wide area networks (WWANs, e.g., 1G, 2G, 3G, IEEE 802.20), wireless personal area networks (WPANs, e.g., Bluetooth, IEEE 802.15.1/3/4), and wireless metropolitan area networks (WMANs, e.g., IEEE 802.16) to form a converged heterogeneous architecture (Cavalcanti, Agrawal, Cordeiro, Xie, & Kumar, 2005). Seamless integration does not mean that the RATs are converged into a single network. Instead the services offered by the existing RATs are integrated as shown in Figure 1. Convergence technology is a technology that combines different existing access technologies such as cellular, cordless, WLAN-type systems, short-range wireless connectivity, and wired systems on a common platform to complement each other in an optimum way and to provide a multiplicity of possibilities for current and future services and applications to users in a single terminal. After creating a converged heterogeneous architecture, the next step is to perform a common radio resource management (RRM) (Magnusson, Lundsjo, Sachs, & Wallentin, 2004). RRM helps to maximize the use of available spectrum resources, support mixed traffic types with different QoS requirements, increase trunking capacity and grade of service (GoS), improve spectrum usage by selecting the best RAT based on radio conditions (e.g., path loss), minimize inter-system handover latency, preserve QoS across multiple RATs, and reduce signaling delay.
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Hallinan, Dara. "Genetic Data, Genome Understanding, and Socially Relevant Information." In Protecting Genetic Privacy in Biobanking through Data Protection Law, 7–18. Oxford University Press, 2021. http://dx.doi.org/10.1093/oso/9780192896476.003.0002.

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This chapter discusses the range of types of data which might be subject to genetic analysis to produce socially relevant information. These genetic data include raw genomic data as well as other types of data, such as phenotype data and inheritance data. Genetic analysis of these types of data is currently capable of producing a wide range of socially relevant information, including information concerning identity, genetic relationships, phenotype, health, and social and behavioural traits. It is not the case, however, that each type of genetic data can be subject to only one type of genetic analysis to produce only one type of socially relevant information. Rather, each type of genetic data, particularly genomic data, can be subject to multiple types of genetic analysis. Nor is it necessarily the case that genetic analyses produce socially relevant information which is completely accurate. Rather, the degree of accuracy of information will usually depend on multiple factors. The chapter then looks at the range of parties about whom socially significant information may be produced.
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Sinharay, Ricky. "Radiology." In Oxford Assess and Progress: Clinical Medicine. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780198812968.003.0021.

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You have teased out the history, elicited the signs, and generated a list of differential diagnoses— now to confirm your suspicions, by selecting an appropriate radiological investigation. From the ubiquitous chest X-ray for diagnosing community- acquired pneumonia or congestive cardiac failure to an urgent computed tomography (CT) scan of the brain to confirm a suspected subarachnoid haemorrhage, radiological investiga­tions are an essential (if sometimes overused) resource for diagnosing disease. When working in the acute hospital setting, some knowledge and experience in interpreting X- rays and some types of CT imaging are important in order to ensure your patient is managed correctly and quickly. Going back to basic principles and using your hard- learnt anatomy will set you in good stead when looking at both X- rays and cross- sectional imaging. This chapter has been written to expose you to clinical situations where imaging is required to make a diagnosis or to make a decision on patient management. As well as this, I hope the questions in this chapter will help you think about what the correct modality of imaging to request would be to investigate pathology in the various body systems. For instance, an ultrasound of the liver may be more useful to assess liver cirrhosis than a CT scan (as well as preventing exposures to high- dose radiation). And again, in practice, if there is any doubt about the result of a radiological investigation, or indeed which type of investigation to request, your local radiologist would be more than happy to help.
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Valentini, Silvio. "The forget-restore principle: a paradigmatic Example." In Twenty Five Years of Constructive Type Theory. Oxford University Press, 1998. http://dx.doi.org/10.1093/oso/9780198501275.003.0017.

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The aim of this paper is to give a simple but instructive example of the forget-restore principle, conceived by Giovanni Sambin as a discipline for a constructive development of mathematics and which first appeared in print in the introduction of Sambin and Valentini 1998. The best way to explain such a philosophical position is to quote from that paper: “To build up an abstract concept from a raw flow of data, one must disregard inessential details ... this is obtained by forgetting some information. To forget information is the same as to destroy something, in particular if there is no possibility of restoring that information ... our principle is that an abstraction is constructive ... when information ... is forgotten in such a way that it can be restored at will in any moment.” The example we want to show here refers to Martin-Löf’s intuitionistic type theory (just type theory from now on). We assume knowledge of the main peculiarities of type theory, as formulated in Martin-Löf 1984 or Nordström et al. 1990. Type theory is a logical calculus which adopts those notions and rules which keep total control of the amount of information contained in the different forms of judgement. However, type theory offers a way of “forgetting” information: that is, supposing A set, the form of judgement A true. The meaning of A true is that there exists an element a such that a ∈ A but it does not matter which particular element a is (see also the notion of proof irrelevance in de Bruijn 1980). Thus to pass from the judgement a ∈ A to the judgement A true is а clear example of the forgetting process. We will show that it is a constructive way to forget since, provided that there is a proof of the judgement A true, an element a such that a ∈ A can be reconstructed.
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Lena, Jennifer C. "Three Musics, Four Genres: Rap, Bluegrass, and Bebop Jazz." In Banding Together. Princeton University Press, 2012. http://dx.doi.org/10.23943/princeton/9780691150765.003.0002.

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This chapter examines the progression of three musics through the four genre types, focusing on the hanging mix of the resources they use. These resources include organizational form, scale, and locus; the sources of income and press coverage for artists; the codification of genre ideal, performance, and technological conventions; boundary work; styles of dress, adornment, drugs, politics, and argot; and the invention of a name for the style. In order to focus on the attributes that characterize genre forms, the chapter selectively presents examples from three musical styles: bluegrass, old school rap, and bebop jazz. It hopes that focusing on examples from a sample of musics will highlight the features of genre types and their attributes without producing unnecessary confusion.
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Kataoka, Keiko. "Fermented Brown Rice as a Functional Food." In Rice [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.98840.

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Brown rice, especially in a part of rice bran, contains many kinds of nutrients and biologically active components such as plant polyphenols and phytic acid, but is hard to eat. “Brown rice and rice bran fermented with Aspergillus oryzae (FBRA)” is a processed food that is easier for daily intake, commercially available, and rich in eating experience. During the fermentation process, dietary fibers is partially digested, and free vitamins and phenolic compounds have increased. These fermentation products are utilized for quality control to manage FBRA production. Recently, plant-derived polyphenols have shown anti-oxidative activity and biological function in various disease models. We and other research groups used raw powder FBRA to examine its biological activity through pathological and/or molecular biological analysis. Dietary administration of FBRA showed anti-tumorigenic effects in chemically induced tumors in rodents. Anti-inflammatory effects have been observed in DSS-induced colitis in rat and inflammation-mediated rodent tumor models. I will give an outline of the characteristic of FBRA, and then introduce our recently published work about “Preventive effect of FBRA on spontaneous type 1 diabetes in NOD female mice”, including how to estimate the in vivo effect of dietary FBRA, its possible mechanisms and the limit of this study.
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Muhammad Khan, Waqas, and Wiqar Hussain Shah. "Hybrid Nature Properties of Tl10-xATe6 (A = Pb and Sn) Used as Batteries in Chalcogenide System." In Energy Storage Battery Systems - Fundamentals and Applications. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.95390.

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In future, the most common batteries will be the thallium. As there is many types of batteries but the thallium batteries are better from them. In here, we have made the compound which is more positive work than the other batteries. The different elements are doping in the tellurium telluride to determine the different properties like electrical and thermal properties of nanoparticles. The chalcogenide nanoparticles can be characteristics by the doping of the different metals which are like the holes. We present the effects of Pb and Sn doping on the electrical and thermoelectric properties of Tellurium Telluride Tl10-xPbxTe6 and Tl10-xSnxTe6 (x = 1.00, 1.25, 1.50, 1.75, 2.00) respectively, which were prepared by solid state reactions in an evacuated sealed silica tubes. Structurally, all these compounds were found to be phase pure as confirmed by the x-rays diffractometery (XRD) and energy dispersive X-ray spectroscopy (EDS) analysis. The thermo-power or Seebeck co-efficient (S) was measured for all these compounds which show that S increases with increasing temperature from 295 to 550 K. The Seebeck coefficient is positive for the whole temperature range, showing p-type semiconductor characteristics. Similarly the electrical conductivity (σ) and the power factors have also complex behavior with Pb and Sn concentrations. The power factor (PF = S2σ) observed for Tl10-xPbxTe6 and Tl10-xSnxTe6 compounds are increases with increase in the whole temperature range (290 K–550 K) studied here. Telluride’s are narrow band-gap semiconductors, with all elements in common oxidation states, according to (Tl+)9(Pb3+)(Te2−)6 and (Tl+)9(Sn3+)(Te2−)6. Phases range were investigated and determined with different concentration of Pb and Sn with consequents effects on electrical and thermal properties.
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Conference papers on the topic "RAS wild type"

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Grabocka, Elda, Yuliya Pylayeva-Gupta, Eyoel Yemanaberhan, Veronica Lubkov, Laura Taylor, and Dafna Bar-Sagi. "Abstract PR03: Selective sensitization of mutant K-Ras cancer cells to DNA damage based therapies by targeting wild type H- and N-Ras." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-pr03.

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Tecleab, Awet, and Said M. Sebti. "Abstract 3844: K-Ras is required for maintaining survivin protein stability in human cancer cells harboring mutant but not wild type K-Ras." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-3844.

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Park, Joo Sung, Jung Guk Jeon, Myoung Hee Kang, You Jin Jang, Sun Il Lee, Jae Ho Byun, Jun Suk Kim, and Sang Cheul Oh. "Abstract 1040: The effect of Irinotecan in k-Ras wild and mutant type colon cancer cell lines." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-1040.

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Chang, Yuan-I., Alisa Damnernsawad, Guangyao Kong, Yangang Liu, Qiang Chang, and Jing Zhang. "Abstract A56: Loss of wild-type Kras promotes oncogenic Kras-induced leukemogenesis." In Abstracts: AACR Special Conference on RAS Oncogenes: From Biology to Therapy; February 24-27, 2014; Lake Buena Vista, FL. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1557-3125.rasonc14-a56.

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Ambrogio, Chiara. "Abstract IA05: Dimerization is critical for the functions of wild-type and mutant KRAS." In Abstracts: AACR Special Conference on Targeting RAS-Driven Cancers; December 9-12, 2018; San Diego, CA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1557-3125.ras18-ia05.

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Kang, Myoung Hee, Bo Ram Kim, Sun il Lee, Jun Suk Kim, and Sang Cheul Oh. "Abstract C22: The effect of irinotecan-induced in k-Ras wild and mutant type colon cancer cell lines." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-c22.

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Lindsay, Colin R., Pantelis Nicola, Mariam Jamal-Hanjani, Andrew Wallace, Gareth Wilson, George Burghel, Helene Schlecht, et al. "Abstract B49: “Triple wild-type” co-mutational profile in early-stage KRAS-mutant lung cancer." In Abstracts: AACR Special Conference on Targeting RAS-Driven Cancers; December 9-12, 2018; San Diego, CA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1557-3125.ras18-b49.

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Kang, Myoung Hee, Jung Lim Kim, Bo Ram Kim, Yoo Jin Jang, Sun I. Lee, Jun Suk Kim, and Sang cheul Oh. "Abstract 5128: Different effect of irinotecan induced apoptosis in k-Ras wild and mutant type colon cancer cell lines." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-5128.

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Shankar, Sunita, Jean Ching-Yi Tien, Ronald F. Siebenaler, Seema Chugh, Vijaya L. Dommeti, Sylvia Zelenka-Wang, Jessica Waninger, et al. "Abstract 2577: AGO2 interaction limits wild type RAS activation yet essential for disease progression in oncogenic KRAS driven cancers." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-2577.

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Chattopadhyay, Chandrani, Julie A. Ellerhorst, Suhendan Ekmekcioglu, and Elizabeth A. Grimm. "Abstract 5456: Preferential targeting of N-Ras mutant and other wild type B-Raf human melanoma cells with c-Met inhibitor: a preclinical promise." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-5456.

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Reports on the topic "RAS wild type"

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Miller, Gad, and Jeffrey F. Harper. Pollen fertility and the role of ROS and Ca signaling in heat stress tolerance. United States Department of Agriculture, January 2013. http://dx.doi.org/10.32747/2013.7598150.bard.

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The long-term goal of this research is to understand how pollen cope with stress, and identify genes that can be manipulated in crop plants to improve reproductive success during heat stress. The specific aims were to: 1) Compare heat stress dependent changes in gene expression between wild type pollen, and mutants in which pollen are heat sensitive (cngc16) or heat tolerant (apx2-1). 2) Compare cngc16 and apx2 mutants for differences in heat-stress triggered changes in ROS, cNMP, and Ca²⁺ transients. 3) Expand a mutant screen for pollen with increased or decreased thermo-tolerance. These aims were designed to provide novel and fundamental advances to our understanding of stress tolerance in pollen reproductive development, and enable research aimed at improving crop plants to be more productive under conditions of heat stress. Background: Each year crop yields are severely impacted by a variety of stress conditions, including heat, cold, drought, hypoxia, and salt. Reproductive development in flowering plants is highly sensitive to hot or cold temperatures, with even a single hot day or cold night sometimes being fatal to reproductive success. In many plants, pollen tube development and fertilization is often the weakest link. Current speculation about global climate change is that most agricultural regions will experience more extreme environmental fluctuations. With the human food supply largely dependent on seeds, it is critical that we consider ways to improve stress tolerance during fertilization. The heat stress response (HSR) has been intensively studied in vegetative tissues, but is poorly understood during reproductive development. A general paradigm is that HS is accompanied by increased production of reactive oxygen species (ROS) and induction of ROS-scavenging enzymes to protect cells from excess oxidative damage. The activation of the HSR has been linked to cytosolic Ca²⁺ signals, and transcriptional and translational responses, including the increased expression of heat shock proteins (HSPs) and antioxidative pathways. The focus of the proposed research was on two mutations, which have been discovered in a collaboration between the Harper and Miller labs, that either increase or decrease reproductive stress tolerance in a model plant, Arabidopsis thaliana (i.e., cngc16--cyclic nucleotide gated channel 16, apx2-1--ascorbate peroxidase 2,). Major conclusions, solutions, achievements. Using RNA-seq technology, the expression profiles of cngc16 and apx2 pollen grains were independently compared to wild type under favourable conditions and following HS. In comparison to a wild type HSR, there were 2,776 differences in the transcriptome response in cngc16 pollen, consistent with a model in which this heat-sensitive mutant fails to enact or maintain a normal wild-type HSR. In a comparison with apx2 pollen, there were 900 differences in the HSR. Some portion of these 900 differences might contribute to an improved HSR in apx2 pollen. Twenty-seven and 42 transcription factor changes, in cngc16 and apx2-1, respectively, were identified that could provide unique contributions to a pollen HSR. While we found that the functional HS-dependent reprogramming of the pollen transcriptome requires specific activity of CNGC16, we identified in apx2 specific activation of flavonol-biosynthesis pathway and auxin signalling that support a role in pollen thermotolerance. Results from this study have identified metabolic pathways and candidate genes of potential use in improving HS tolerance in pollen. Additionally, we developed new FACS-based methodology that can quantify the stress response for individual pollen in a high-throughput fashion. This technology is being adapted for biological screening of crop plant’s pollen to identify novel thermotolerance traits. Implications, both scientific and agricultural. This study has provided a reference data on the pollen HSR from a model plant, and supports a model that the HSR in pollen has many differences compared to vegetative cells. This provides an important foundation for understanding and improving the pollen HSR, and therefor contributes to the long-term goal of improving productivity in crop plants subjected to temperature stress conditions. A specific hypothesis that has emerged from this study is that pollen thermotolerance can be improved by increasing flavonol accumulation before or during a stress response. Efforts to test this hypothesis have been initiated, and if successful have the potential for application with major seed crops such as maize and rice.
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Anke, Juliane, Angela Francke, and Tibor Petzoldt. RadVerS - Mit Smartphones generierte Verhaltensdaten im Verkehr – Differenzierung des Nutzerverhaltens unterschiedlicher RadfahrerInnengruppen : Teil 1 des Abschlussberichts. Technische Universität Dresden, September 2021. http://dx.doi.org/10.26128/2021.240.

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Ziel der vorliegenden Studie war es, eine Typologie von RadfahrerInnen in Deutschland zu erarbeiten und diese zu beschreiben. Zu diesem Zweck wurde auf Basis einer umfassenden Literaturrecherche eine groß angelegte Online-Befragung vom 20.11.2017 bis 07.01.2018 durchgeführt. Insgesamt wurden dabei 10.294 auswertbare Datensätze gewonnen. Durch Hauptkomponenten- und Faktorenanalyse wurden neun Faktoren (symbolische Motive, affektive Motive, instrumentelle Motive, subjektive Sicherheit, Identifikation als RadfahrerIn, zeitliche Distanz, Nutzungshäufigkeit, Wetter/Komfort und Regeltreue) extrahiert, die anschließend zur Clusterung der RadfahrerInnen genutzt wurden. Mit Hilfe dieser Faktoren ließen sich vier Typen von RadfahrerInnen identifizieren: passionierter, pragmatischer, funktioneller und ambitionierter Radfahrtyp. Die Typen unterscheiden sich dabei sowohl hinsichtlich der Typologisierungsfaktoren als auch bezüglich infrastruktureller Präferenzen, Unfallhistorie und der Radfahrhäufigkeit für bestimmte Wegezwecke. Die Einbeziehung motivationaler Faktoren erbrachte wichtige Einblicke in die Eigenschaften von RadfahrerInnen. Für den passionierten Radfahrtyp spielen sowohl Faktoren, wie die soziale Anerkennung bzw. Identifikation mit dem Umfeld, die Freude am Fahren als auch Faktoren wie Flexibilität oder Umweltschutz eine wichtige Rolle. Der Pragmatische wird dagegen v.a. instrumentell motiviert, d.h. das Rad wird genutzt, weil es flexibel ist, gut für die eigene Fitness und man damit schnell vorankommt. Insgesamt am wenigsten zum Radfahren motiviert ist der/die funktionelle RadfahrerIn. Für diesen Typ stehen z.B. ökonomische Gründe bei der Radnutzung im Vordergrund und das Fahrrad wird eher als „Mittel zum Zweck“ gesehen. Der Spaß am Fahren sowie die Zugehörigkeit zu oder das Kennenlernen von Personen sind für die ambitionierten RadfahrerInnen Hauptmotive für die Radnutzung. Aus den Kenntnissen der Eigenschaften der vier Radfahrtypen lassen sich u.a. Implikationen für die Radverkehrsförderung ableiten. So könnten z.B. Kampagnen vermitteln, dass das Fahrrad mehr sein kann als nur „Mittel zum Zweck“, um funktionelle und pragmatische Typen zu einer (Mehr-) Nutzung zu ermutigen. Die Arbeit schließt mit einem Ausblick auf Teil 2 des Projektes, bei dem die gewonnenen Erkenntnisse über die Radfahrtypen mit realem Fahrverhalten verknüpft wurden.
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McElwain, Terry F., Eugene Pipano, Guy H. Palmer, Varda Shkap, Stephn A. Hines, and Wendy C. Brown. Protection of Cattle against Babesiosis: Immunization against Babesia bovis with an Optimized RAP-1/Apical Complex Construct. United States Department of Agriculture, September 1999. http://dx.doi.org/10.32747/1999.7573063.bard.

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Previous research and current efforts at control of babesiosis fall short of meeting the needs of countries where the disease is endemic, such as Israel, as well as the needs of exporting countries and countries bordering on endemic areas, such as the U.S. Our long-term goal is to develop improved methods of immunization against bovine babesiosis based on an understanding of the molecular mechanisms of immune protection and parasite targets of a protective immune response. In our previous BARD project, we established the basis for focusing on rhoptry antigens as components of a subunit vaccine against bovine babesiosis, and for additional research to better characterize rhoptry associated protein-1 (RAP-1) as a target of protective immunity. In this continuation BARD project, our objectives were to [1] optimize the immune response against RAP-1, and [2] identify additional rhoptry candidate vaccine antigens. The entire locus encoding B. bovis RAP-1 was sequenced, and the rap-1 open reading frame compared among several strains. Unlike B. bigemina, in which multiple gene copies with variant domains encode RAP-1, the B. bovis RAP-1 locus contains only two identical genes which are conserved among strains. Through testing of multiple truncated constructs of rRAP-1, one or more immunodominant T cell epitopes were mapped to the amino terminal half of RAP-1. At least one linear and one conformational B cell epitope have been demonstrated in the same amino terminal construct, which in B. bigemina RAP-1 also contains an epitope recognized by neutralizing antibody. The amine terminal half of the molecule represents the most highly conserved part of the gene family and contains motifs conserved broadly among the apicomplexa. In contrast, the carboxy terminal half of B. bovis RAP-1 is less well conserved and contains multiple repeats encoding a linear B cell epitope potentially capable of inducing an ineffective, T cell independent, type 2 immune response. Therefore, we are testing an amino terminal fragment of RAP-1 (RAP-1N) in an immunization trial in cattle. Cattle have beer immunized with RAP-1N or control antigen, and IL-12 with Ribi adjuvant. Evaluation of the immune response is ongoing, and challenge with virulent B. bovis will occur in the near future. While no new rhoptry antigens were identified, our studies did identify and characterize a new spherical body antigen (SBP3), and several heat shock proteins (HSP's). The SBP3 and HSP21 antigens stimulate T cells from immune cattle and are considered new vaccine candidates worthy of further testing. Overall, we conclude that a single RAP-1 vaccine construct representing the conserved amino terminal region of the molecule should be sufficient for immunization against all strains of B. bovis. While results of the ongoing immunization trial will direct our next research steps, results at this time are consistent with our long term goal of designing a subunit vaccine which contains only the epitopes relevant to induction of protective immunity. Parallel studies are defining the mechanisms of protective immunity. Apicomplexan protozoa, including babesiosis and malaria, cause persistent diseases for which control is inadequate. The apical organelles are defining features of these complex protozoa, and have been conserved through the evolutionary process, Past and current BARD projects on babesiosis have established the validity and potential of exploiting these conserved organelles in developing improved control methods applicable to all apicomplexan diseases.
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Whitham, Steven A., Amit Gal-On, and Tzahi Arazi. Functional analysis of virus and host components that mediate potyvirus-induced diseases. United States Department of Agriculture, March 2008. http://dx.doi.org/10.32747/2008.7591732.bard.

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The mechanisms underlying the development of symptoms in response to virus infection remain to be discovered in plants. Insight into symptoms induced by potyviruses comes from evidence implicating the potyviral HC-Pro protein in symptom development. In particular, recent studies link the development of symptoms in infected plants to HC-Pro's ability to interfere with small RNA metabolism and function in plant hosts. Moreover, mutation of the highly conserved FRNK amino acid motif to FINK in the HC-Pro of Zucchini yellow mosaic virus (ZYMV) converts a severe strain into an asymptomatic strain, but does not affect virus accumulation in cucurbit hosts. The ability of this FINK mutation to uncouple symptoms from virus accumulation creates a unique opportunity to study symptom etiology, which is usually confounded by simultaneous attenuation of both symptoms and virus accumulation. Our goal was to determine how mutations in the conserved FRNK motif affect host responses to potyvirus infection in cucurbits and Arabidopsis thaliana. Our first objective was to define those amino acids in the FRNK motif that are required for symptoms by mutating the FRNK motif in ZYMV and Turnip mosaic virus (TuMV). Symptom expression and accumulation of resulting mutant viruses in cucurbits and Arabidopsis was determined. Our second objective was to identify plant genes associated with virus disease symptoms by profiling gene expression in cucurbits and Arabidopsis in response to mutant and wild type ZYMV and TuMV, respectively. Genes from the two host species that are differentially expressed led us to focus on a subset of genes that are expected to be involved in symptom expression. Our third objective was to determine the functions of small RNA species in response to mutant and wild type HC-Pro protein expression by monitoring the accumulation of small RNAs and their targets in Arabidopsis and cucurbit plants infected with wild type and mutant TuMV and ZYMV, respectively. We have found that the maintenance of the charge of the amino acids in the FRNK motif of HC-Pro is required for symptom expression. Reduced charge (FRNA, FRNL) lessen virus symptoms, and maintain the suppression of RNA silencing. The FRNK motif is involved in binding of small RNA species including microRNAs (miRNA) and short interfering RNAs (siRNA). This binding activity mediated by the FRNK motif has a role in protecting the viral genome from degradation by the host RNA silencing system. However, it also provides a mechanism by which the FRNK motif participates in inducing the symptoms of viral infection. Small RNA species, such as miRNA and siRNA, can regulate the functions of plant genes that affect plant growth and development. Thus, this binding activity suggests a mechanism by which ZYMVHC-Pro can interfere with plant development resulting in disease symptoms. Because the host genes regulated by small RNAs are known, we have identified candidate host genes that are expected to play a role in symptoms when their regulation is disrupted during viral infections. As a result of this work, we have a better understanding of the FRNK amino acid motif of HC-Pro and its contribution to the functions of HC-Pro, and we have identified plant genes that potentially contribute to symptoms of virus infected plants when their expression becomes misregulated during potyviral infections. The results set the stage to establish the roles of specific host genes in viral pathogenicity. The potential benefits include the development of novel strategies for controlling diseases caused by viruses, methods to ensure stable expression of transgenes in genetically improved crops, and improved potyvirus vectors for expression of proteins or peptides in plants.
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Ali, Ibraheem, Thea Atwood, Renata Curty, Jimmy Ghaphery, Tim McGeary, Jennifer Muilenburg, and Judy Ruttenberg. Research Data Services: Partnerships. Association of Research Libraries and Canadian Association of Research Libraries, January 2022. http://dx.doi.org/10.29242/report.rdspartnerships2022.

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The Association of Research Libraries (ARL)/Canadian Association of Research Libraries (CARL) Joint Task Force on Research Data Services (RDS) formed in 2020 with a two-fold purpose: (1) to demonstrate and commit to the roles research libraries have in stewarding research data and as part of institution-wide research support services and (2) to guide the development of resources for the ARL and CARL memberships in advancing their organizations as collaborative partners with respect to research data services in the context of FAIR (findable, accessible, interoperable, and reusable) data principles and the US National Academies’ Open Science by Design framework. Research libraries will be successful in meeting these objectives if they act collectively and are deeply engaged with disciplinary communities. The task force formed three working groups of data practitioners, representing a wealth of expertise, to research the institutional landscape and policy environment in both the US and Canada. This report of the ARL/CARL RDS task force’s working group on partnerships highlights library RDS programs’ work with partners and stakeholders. The report provides a set of tools for libraries to use when assessing their RDS partnerships, including assessing partnerships using a partnership life cycle, defining the continuum of possible partnerships, and creating a catalog. Not all partnerships will last the entirety of a librarian’s career, and having clear parameters for when to continue or sunset a partnership can reduce ambiguity and free up resources. Recognizing the continuum of possible partnerships can provide the framework by which librarians can understand the nature of each group. From cyclical to seasonal to sporadic, understanding the needs of a type of partnership can help libraries frame their understanding and meet a group where they are. Finally, creating a catalog of partnerships can help libraries see the landscape of the organization, as well as areas for growth. This approach also aligns with OCLC’s 2020 report on Social Interoperability in Research Support: Cross-Campus Partnerships and the University Research Enterprise, which highlights the necessity of building and stewarding partnerships. Developing and providing services in a decentralized organization relies on the ability to build trusted relationships. These tools will help libraries achieve sustainable growth that is in concert with their partners, generating robust, clearly aligned initiatives that benefit all parties, their campuses, and their communities.
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Horwitz, Benjamin, and Barbara Gillian Turgeon. Secondary Metabolites, Stress, and Signaling: Roles and Regulation of Peptides Produced by Non-ribosomal Peptide Synthetases. United States Department of Agriculture, 2005. http://dx.doi.org/10.32747/2005.7696522.bard.

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Fungal pathogens of plants produce a diverse array of small molecules. Often referred to as secondary metabolites because they were thought to be dispensable for basic functions, they may indeed have central roles as signals for the fungal cell, and in interactions with the host. We have identified more than a dozen genes encoding nonribosomal peptide synthetases (NPS) in Cochliobolusheterostrophus, the agent of southern corn leaf blight. The aim of this project was to identify roles of these genes in stress responses and signaling. The first objective was to test a complete collection of C. heterostrophus nonribosomal peptide synthetase (NRPS)-encoding gene deletion mutant and wildtype (WT) strains for sensitivity to various agents of oxidative (ROS) and nitrosative (RNOS) stress, in vitro. The second objective and next step in this part of the project was to study the relevance of sensitivity to ROS and RNOS in the host pathogen interaction, by measuring the production of ROS and RNOS in planta, when plants are inoculated with wild type and mutant strains. A third objective was to study expression of any genes shown to be involved in sensitivity to ROS or RNOS, in vitro and in planta. Another objective was to determine if any of the genes involved in oxidative or nitrosative stress responses are regulated by components of signal transduction pathways (STP) that we have identified and to determine where mechanisms overlap. Study of the collection of nps mutants identified phenotypes relevant for virulence, development and oxidative stress resistance for two of the genes, NPS2 and NPS6. Mutants in genes related to RNOS stress have no virulence phenotypes, while some of those related to ROS stress have reduced virulence as well as developmental phenotypes, so we focused primarily on ROS stress pathways. Furthermore, the identification of NPS2 and NPS6 as encoding for NRPS responsible for siderophore biosynthesis lent a new focus to the project, regulation by Fe. We have not yet developed good methods to image ROS in planta and work in this direction is continuing. We found that NPS6 expression is repressed by Fe, responding over the physiological Fe concentration range. Studying our collection of mutants, we found that conserved MAPK and G protein signal transduction pathways are dispensable for Fe regulation of NPS6, and initiated work to identify other pathways. The transcription factor SreA is one candidate, and is responsible for part, but not all, of the control of NPS6 expression. The results of this project show that the pathogen contends with oxidative stress through several signaling pathways. Loss of the siderophore produced by Nps6 makes the fungus sensitive to oxidative stress, and decreases virulence, suggesting a central role of the ability to sequester and take up extracellular iron in the host-pathogen interaction. Siderophores, and manipulation of Fe levels, could be targets for new strategies to deal with fungal pathogens of maize and other plants.
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Arazi, Tzahi, Vivian Irish, and Asaph Aharoni. Micro RNA Targeted Transcription Factors for Fruit Quality Improvement. United States Department of Agriculture, July 2008. http://dx.doi.org/10.32747/2008.7592651.bard.

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Fruits are unique to flowering plants and represent an important component of human and animal diets. Development and maturation of tomato fruit is a well-programmed process, and yet, only a limited number of factors involved in its regulation have been characterized. Micro-RNAs (miRNAs) are small, endogenous RNAs that regulate gene expression in animals and plants. Plant miRNAs have a vital role in the generation of plant forms through post-transcriptional regulation of the accumulation of developmental regulators, especially transcription factors. Recently, we and others have demonstrated that miRNAs and other type of small RNAs are expressed in tomato fruit, and target putative transcription factors during its development and maturation. The original objectives of the approved proposal were: 1. To identify fruit miRNA transcription factor target genes through a bioinformatic approach. 2. To identify fruit miRNA transcription factor target genes up-regulated in tomato Dicer-like 1 silenced fruit. 3. To establish the biological functions of selected transcription factors and examine their utility for improving fleshy fruit quality trait. This project was approved by BARD as a feasibility study to allow initial experiments to peruse objective 2 as described above in order to provide initial evidence that miRNAs do play a role in fruit development. The approach planned to achieve objective 2, namely to identify miRNA transcription factor targets was to clone and silence the expression of a tomato DCL1 homolog in different stages of fruit development and examine alterations to gene expression in such a fruit in order to identify pathways and target genes that are regulated by miRNA via DCL1. In parallel, we characterized two transcription factors that are regulated by miRNAs in the fruit. We report here on the cloning of tomato DCL1 homolog, characterization of its expression in fruit flesh and peel of wild type and ripening mutants and generation of transgenic plants that silence SlDCL1 specifically in the fruit. Our results suggest that the tomato homolog of DCL1, which is the major plant enzyme involved in miRNA biogenesis, is present in fruit flesh and peel and differentially expressed during various stages of fruit development. In addition, its expression is altered in ripening mutants. We also report on the cloning and expression analysis of Sl_SBP and Sl_ARF transcription factors, which serve as targets of miR157 and miR160, respectively. Our data suggest that Sl_SBP levels are highest during fruit ripening supporting a role for this gene in that process. On the other hand Sl_ARF is strongly expressed in green fruit up to breaker indicating a role for that gene at preripening stage which is consistent with preliminary in_situ analyses that suggest expression in ovules of immature green fruit. The results of this feasibility study together with our previous results that miRNAs are expressed in the fruit indeed provide initial evidence that these regulators and their targets play roles in fruit development and ripening. These genes are expected to provide novel means for genetic improvement of tomato fleshy fruit.
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TERENTIEV, S., O. GRUNINA, and L. PONOMAREVA. FEATURES OF THE PRODUCTION OF DOUGH SEMI-FINISHED PRODUCT PRODUCED USING LENTIL FLOUR. Science and Innovation Center Publishing House, 2022. http://dx.doi.org/10.12731/2070-7568-2022-11-2-4-15-22.

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Bread consumption has a stable increase in the territory of Russia and in particular in the Ulyanovsk and Samara regions. Bread, as a fairly low-priced product, is in high demand among consumers, but this product is not biologically saturated with useful substances, therefore, in modern production, a number of techniques are used to increase the nutritional and biological value of these types of products. In our work, one of these methods will be considered - the introduction of lentil flour into dough preparations. The problem is that the state policy regarding import substitution, aimed at replacing food additives produced abroad, necessitates the use of food additives or raw materials of natural origin produced in the territory of the Russian Federation, and the lack of development of regulatory and technological documentation in this direction is a significant problem for public enterprises. nutrition. Purpose - to carry out the development of a recipe for a test semi-finished product produced with the addition of lentil flour, as a product with a preventive purpose Results: based on the results of the study, a recipe for a test semi-finished product was developed, produced with the addition of lentil flour, as a product with a preventive purpose.
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Choudhary, Ruplal, Victor Rodov, Punit Kohli, Elena Poverenov, John Haddock, and Moshe Shemesh. Antimicrobial functionalized nanoparticles for enhancing food safety and quality. United States Department of Agriculture, January 2013. http://dx.doi.org/10.32747/2013.7598156.bard.

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Original objectives The general goal of the project was to utilize the bactericidal potential of curcumin- functionalizednanostructures (CFN) for reinforcement of food safety by developing active antimicrobial food-contact surfaces. In order to reach the goal, the following secondary tasks were pursued: (a) further enhancement of the CFN activity based on understanding their mode of action; (b) preparing efficient antimicrobial surfaces, investigating and optimizing their performance; (c) testing the efficacy of the antimicrobial surfaces in real food trials. Background to the topic The project dealt with reducing microbial food spoilage and safety hazards. Cross-contamination through food-contact surfaces is one of the major safety concerns, aggravated by bacterial biofilm formation. The project implemented nanotech methods to develop novel antimicrobial food-contact materials based on natural compounds. Food-grade phenylpropanoidcurcumin was chosen as the most promising active principle for this research. Major conclusions, solutions, achievements In agreement with the original plan, the following research tasks were performed. Optimization of particles structure and composition. Three types of curcumin-functionalizednanostructures were developed and tested: liposome-type polydiacetylenenanovesicles, surface- stabilized nanoparticles and methyl-β-cyclodextrin inclusion complexes (MBCD). The three types had similar minimal inhibitory concentration but different mode of action. Nanovesicles and inclusion complexes were bactericidal while the nanoparticlesbacteriostatic. The difference might be due to different paths of curcumin penetration into bacterial cell. Enhancing the antimicrobial efficacy of CFN by photosensitization. Light exposure strengthened the bactericidal efficacy of curcumin-MBCD inclusion complexes approximately three-fold and enhanced the bacterial death on curcumin-coated plastic surfaces. Investigating the mode of action of CFN. Toxicoproteomic study revealed oxidative stress in curcumin-treated cells of E. coli. In the dark, this effect was alleviated by cellular adaptive responses. Under light, the enhanced ROS burst overrode the cellular adaptive mechanisms, disrupted the iron metabolism and synthesis of Fe-S clusters, eventually leading to cell death. Developing industrially-feasible methods of binding CFN to food-contact surfaces. CFN binding methods were developed for various substrates: covalent binding (binding nanovesicles to glass, plastic and metal), sonochemical impregnation (binding nanoparticles to plastics) and electrostatic layer-by-layer coating (binding inclusion complexes to glass and plastics). Investigating the performance of CFN-coated surfaces. Flexible and rigid plastic materials and glass coated with CFN demonstrated bactericidal activity towards Gram-negative (E. coli) and Gram-positive (Bac. cereus) bacteria. In addition, CFN-impregnated plastic material inhibited bacterial attachment and biofilm development. Testing the efficacy of CFN in food preservation trials. Efficient cold pasteurization of tender coconut water inoculated with E. coli and Listeriamonocytogeneswas performed by circulation through a column filled with CFN-coated glass beads. Combination of curcumin coating with blue light prevented bacterial cross contamination of fresh-cut melons through plastic surfaces contaminated with E. coli or Bac. licheniformis. Furthermore, coating of strawberries with CFN reduced fruit spoilage during simulated transportation extending the shelf life by 2-3 days. Implications, both scientific and agricultural BARD Report - Project4680 Page 2 of 17 Antimicrobial food-contact nanomaterials based on natural active principles will preserve food quality and ensure safety. Understanding mode of antimicrobial action of curcumin will allow enhancing its dark efficacy, e.g. by targeting the microbial cellular adaptation mechanisms.
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Tang, Jiqin, Gong Zhang, Jinxiao Xing, Ying Yu, and Tao Han. Network Meta-analysis of Heat-clearing and Detoxifying Oral Liquid of Chinese Medicines in Treatment of Children’s Hand-foot-mouth Disease：a protocol for systematic review. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, January 2022. http://dx.doi.org/10.37766/inplasy2022.1.0032.

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Review question / Objective: The type of study was clinical randomized controlled trial (RCT). The object of study is the patients with HFMD. There is no limit to gender and race. In the case of clear diagnosis standard, curative effect judgment standard and consistent baseline treatment, the experimental group was treated with pure oral liquid of traditional Chinese medicine(A: Fuganlin oral liquid, B: huangzhihua oral liquid, C: Lanqin oral liquid, D: antiviral oral liquid, E: Huangqin oral liquid, F: Pudilan oral liquid, G: Shuanghuanglian oral liquid.)and the control group was treated with ribavirin or any oral liquid of traditional Chinese medicine. The data were extracted by two researchers independently, cross checked and reviewed according to the pre-determined tables. The data extraction content is (1) Basic information (including the first author, published journal and year, research topic). (2) Relevant information (including number of cases, total number of cases, gender, age, intervention measures, course of treatment of the experimental group and the control group in the literature). (3) Design type and quality evaluation information of the included literature. (4) Outcome measures (effective rate, healing time of oral ulcer, regression time of hand and foot rash, regression time of fever, adverse reactions.). The seven traditional Chinese medicine oral liquids are comparable in clinical practice, but their actual clinical efficacy is lack of evidence-based basis. Therefore, the purpose of this study is to use the network meta-analysis method to integrate the clinical relevant evidence of direct and indirect comparative relationship, to make quantitative comprehensive statistical analysis and sequencing of different oral liquid of traditional Chinese medicine with the same evidence body for the treatment of the disease, and then to explore the advantages and disadvantages of the efficacy and safety of different oral liquid of traditional Chinese medicine to get the best treatment plan, so as to provide reference value and evidence-based medicine evidence for clinical optimization of drug selection. Condition being studied: Hand foot mouth disease (HFMD) is a common infectious disease in pediatrics caused by a variety of enteroviruses. Its clinical manifestations are mainly characterized by persistent fever, hand foot rash, oral herpes, ulcers, etc. Because it is often found in preschool children, its immune system development is not perfect, so it is very vulnerable to infection by pathogens and epidemic diseases, resulting in rapid progress of the disease. A few patients will also have neurogenic pulmonary edema Meningitis, myocarditis and other serious complications even lead to death, so effectively improve the cure rate, shorten the course of disease, prevent the deterioration of the disease as the focus of the study. In recent years, traditional Chinese medicine has played an important role in the research of antiviral treatment. Many clinical practices have confirmed that oral liquid of traditional Chinese medicine can effectively play the role of antiviral and improve the body's immunity.
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