scholarly journals Involvement of the LlaKR2I Methylase in Expression of the AbiR Bacteriophage Defense System in Lactococcus lactis subsp. lactis biovar diacetylactis KR2

2006 ◽  
Vol 188 (5) ◽  
pp. 1920-1928 ◽  
Author(s):  
Julie M. Yang ◽  
Patricio J. DeUrraza ◽  
Nadya Matvienko ◽  
Daniel J. O'Sullivan
Keyword(s):  
Cell Cycle ◽  
Lactococcus Lactis ◽  
Protective Role ◽  
Gene Organization ◽  
The Novel ◽  
Genetic Determinants ◽  
Abortive Infection ◽  
Methylase Gene

ABSTRACT The native lactococcal plasmid, pKR223, from Lactococcus lactis subsp. lactis biovar diacetylactis KR2 encodes two distinct bacteriophage-resistant mechanisms, the LlaKR2I restriction and modification (R/M) system and the abortive infection (Abi) mechanism, AbiR, that impedes bacteriophage DNA replication. This study completed the characterization of AbiR, revealing that it is the first Abi system to be encoded by three genes, abiRa, abiRb, and abiRc, arranged in an operon and that it requires the methylase gene from the LlaKR2I R/M system. An analysis of deletion and insertion clones demonstrated that the AbiR operon was toxic in L. lactis without the presence of the LlaKR2I methylase, which is required to protect L. lactis from AbiR toxicity. The novelty of the AbiR system resides in its original gene organization and the unusual protective role of the LlaKR2I methylase. Interestingly, the AbiR genetic determinants are flanked by two IS982 elements generating a likely transposable AbiR composite. This observation not only substantiated the novel function of the LlaKR2I methylase in the AbiR system but also illustrated the evolution of the LlaKR2I methylase toward a new and separate cellular function. This unique structure of both the LlaKR2I R/M system and the AbiR system may have contributed to the evolution of the LlaKR2I methylase toward a novel role comparable to that of the cell cycle-regulated methylases that include Dam and CcrM methylases. This new role for the LlaKR2I methylase offers a unique snapshot into the evolution of the cell cycle-regulated methylases from an existing R/M system.

The Protective Role of Selenium in AFB1-Induced Tissue Damage and Cell Cycle Arrest in Chicken’s Bursa of Fabricius

2018 ◽  
Vol 185 (2) ◽  
pp. 486-496 ◽  
Author(s):  
Ping Hu ◽  
Zhicai Zuo ◽  
Fengyuan Wang ◽  
Xi Peng ◽  
Ke Guan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Tissue Damage ◽  
Protective Role ◽  
Bursa Of Fabricius ◽  
Cycle Arrest

scholarly journals Transcription-termination-mediated immunity and its prevention in bacteriophage SfV of Shigella flexneri

2007 ◽  
Vol 88 (11) ◽  
pp. 3187-3197 ◽  
Author(s):  
Fleur Roberts ◽  
Gwen E. Allison ◽  
Naresh K. Verma
Keyword(s):  
Essential Role ◽  
Transcription Termination ◽  
Shigella Flexneri ◽  
Temperate Phage ◽  
The Novel ◽  
Subsequent Infection

The temperate phage SfV encodes the genes responsible for the serotype conversion of Shigella flexneri strains from serotype Y to 5a. Bacteriophages often encode proteins that prevent subsequent infection by homologous phages; the mechanism by which this is accomplished is referred to as superinfection immunity. The serotype conversion mediated following lysogenization of SfV is one such mechanism. Another mechanism is the putative λ-like CI protein within SfV. This study reports the characterization of a third superinfection mechanism, transcription termination, in SfV. The presence of a small immunity-mediating RNA molecule, called CI RNA, and its essential role in the establishment of immunity, is shown. The novel role of the gene orf77, located immediately downstream from the transcription termination region, in inhibiting the establishment of CI RNA-mediated immunity is also presented.

scholarly journals Preparation and Characterization of Water-Based Nano-Perfumes

Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 981 ◽  
Author(s):  
Małgorzata Miastkowska ◽  
Elwira Lasoń ◽  
Elżbieta Sikora ◽  
Katarzyna Wolińska-Kennard
Keyword(s):  
Droplet Size ◽  
Interfacial Area ◽  
High Energy ◽  
Protective Role ◽  
Food Industries ◽  
Low Viscosity ◽  
Oil In Water ◽  
Water Based

The application of nanoemulsions as a novel delivery system for lipophilic materials, such as essential oils, flavors, and fragrances is one of the growing technologies used in cosmetic, pharmaceutical, and food industries. Their characteristic properties, like small droplet size with high interfacial area, transparent or semi-transparent appearance, low viscosity, and high kinetic stability, make them a perfect vehicle for fragrances, in the perfume industry. They could be a great alternative to water-based perfumes, without alcohol, and solve problems related to the oxidation and low bioavailability of fragrances with other non-alcoholic vehicles of perfumes like pomades or gels. The aim of our study was to develop stable Oil-in-Water (O/W) nanoemulsions that are compatible with selected fragrance compositions, without ethanol, polyols, and ionic surfactants, and to study their physicochemical, microbiological, and dermatological properties. The nano-perfume systems were obtained with a low-energy (Phase Inversion Composition; PIC) and with a high-energy (ultrasound, US) method, taking into account the possibility of moving from the laboratory scale to an industrial scale. The optimized nano-perfume formulations, prepared with different methods, yielded the same physicochemical properties (stability, medium droplet size of the inner phase, polydispersity, viscosity, surface tension, pH, density). Stable systems were obtained with a fragrance composition concentration within 6–15% range. These formulations had a low viscosity and a pH suitable for the skin. Moreover, the obtained results confirmed the protective role of nanoemulsions. The peroxide number measurement (POV) showed that the tested fragrance compositions had a high chemical stability. The results of the microbiological tests confirmed that the obtained products were free of microbiological contamination and were appropriately preserved. The dermatological test results confirmed the safety of the developed preparations.

scholarly journals Development and Characterization of Anti-Nitr9 Antibodies

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Radhika N. Shah ◽  
Ivan Rodriguez-Nunez ◽  
Donna D. Eason ◽  
Robert N. Haire ◽  
Julien Y. Bertrand ◽  
...  
Keyword(s):  
Rna Splicing ◽  
Killer Cell ◽  
The Novel ◽  
Natural Killer Cell Receptors ◽  
Hematopoietic Lineage ◽  
Activating Receptors ◽  
Functional Orthologs ◽  
Activating Receptor

The novel immune-type receptors (NITRs), which have been described in numerous bony fish species, are encoded by multigene families of inhibitory and activating receptors and are predicted to be functional orthologs to the mammalian natural killer cell receptors (NKRs). Within the zebrafish NITR family,nitr9is the only gene predicted to encode an activating receptor. However, alternative RNA splicing generates three distinctnitr9transcripts, each of which encodes a different isoform. Althoughnitr9transcripts have been detected in zebrafish lymphocytes, the specific hematopoietic lineage(s) that expresses Nitr9 remains to be determined. In an effort to better understand the role of NITRs in zebrafish immunity, anti-Nitr9 monoclonal antibodies were generated and evaluated for the ability to recognize the three Nitr9 isoforms. The application of these antibodies to flow cytometry should prove to be useful for identifying the specific lymphocyte lineages that express Nitr9 and may permit the isolation of Nitr9-expressing cells that can be directly assessed for cytotoxic (e.g., NK) function.

scholarly journals The novel protective role of P27 in MLN4924-treated gastric cancer cells

2015 ◽  
Vol 6 (8) ◽  
pp. e1867-e1867 ◽  
Author(s):  
Q Zhang ◽  
D Hou ◽  
Z Luo ◽  
P Chen ◽  
B Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Protective Role ◽  
The Novel ◽  
Gastric Cancer Cells

scholarly journals Cell cycle analysis of the activity, subcellular localization, and subunit composition of human CAK (CDK-activating kinase).

1994 ◽  
Vol 127 (2) ◽  
pp. 467-478 ◽  
Author(s):  
J P Tassan ◽  
S J Schultz ◽  
J Bartek ◽  
E A Nigg
Keyword(s):  
Cell Cycle ◽  
Somatic Cell ◽  
Cell Cycle Control ◽  
Gel Filtration ◽  
Multiprotein Complex ◽  
Cyclin Dependent Kinases ◽  
Critical Residue ◽  
Cdk Activating Kinase

The activity of cyclin-dependent kinases (cdks) depends on the phosphorylation of a residue corresponding to threonine 161 in human p34cdc2. One enzyme responsible for phosphorylating this critical residue has recently been purified from Xenopus and starfish. It was termed CAK (for cdk-activating kinase), and it was shown to contain p40MO15 as its catalytic subunit. In view of the cardinal role of cdks in cell cycle control, it is important to learn if and how CAK activity is regulated during the somatic cell cycle. Here, we report a molecular characterization of a human p40MO15 homologue and its associated CAK activity. We have cloned and sequenced a cDNA coding for human p40MO15, and raised specific polyclonal and monoclonal antibodies against the corresponding protein expressed in Escherichia coli. These tools were then used to demonstrate that p40MO15 protein expression and CAK activity are constant throughout the somatic cell cycle. Gel filtration suggests that active CAK is a multiprotein complex, and immunoprecipitation experiments identify two polypeptides of 34 and 32 kD as likely complex partners of p40MO15. The association of the three proteins is near stoichiometric and invariant throughout the cell cycle. Immunocytochemistry and biochemical enucleation experiments both demonstrate that p40MO15 is nuclear at all stages of the cell cycle (except for mitosis, when the protein redistributes throughout the cell), although the p34cdc2/cyclin B complex, one of the major purported substrates of CAK, occurs in the cytoplasm until shortly before mitosis. The absence of obvious changes in CAK activity in exponentially growing cells constitutes a surprise. It suggests that the phosphorylation state of threonine 161 in p34cdc2 (and the corresponding residue in other cdks) may be regulated primarily by the availability of the cdk/cyclin substrates, and by phosphatase(s).

scholarly journals Development of PLGA-Triiodothyronine Nanoparticles for Targeted Delivery in the Cardioprotection Against Ischemic Insult

2021 ◽  
Author(s):  
Ozlem Ozen Karakus ◽  
Noureldien H. E. Darwish ◽  
Taher Salaheldin ◽  
P. C. Taylor Dickinson ◽  
Brian Weil ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Hormone Receptors ◽  
Polymeric Nanoparticles ◽  
Myocardial Damage ◽  
Protective Role ◽  
Ischemic Heart ◽  
H Nmr ◽  
New Strategy

Abstract Background: Ischemic heart disease is the main cause of death globally. Cardioprotection is the process whereby mechanisms that reduce myocardial damage, and activate protective factors, contribute to the preservation of the heart. Targeting these processes could be a new strategy in the treatment of post-ischemic heart failure (HF). Triiodothyronine (T3) and thyroxine (T4), which have multiple effects on the heart, prevent myocardial damage. Results: This study describes the formulation, and characterization, of chemically modified polymeric nanoparticles incorporating T3, to target the thyroid hormone receptors. Modified T3 was conjugated to polylactide-co-glycolide (PLGA) to facilitate the active targeting of PLGA-T3. Modified T3 and PLGA-T3 was characterized with 1H-NMR. Protective role of synthesized Phosphocreatine (PCr) encapsulated PLGA-T3 nanoparticles (PLGA-T3/PCr NPs) and PLGA-T3 nanoparticles (PLGA-T3 NPs) in hypoxia-mediated cardiac cell insults were investigated. Conclusions: Data demonstrated that PLGA-T3/PCr NPs represent a potentially new therapeutic for the control of tissue damage in cardiac ischemia and resuscitation.

scholarly journals The PAF1c Subunit Cdc73 Is Essential for Hematopoiesis and Displays Differential Gene Regulation in MLL-AF9 Driven Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1280-1280
Author(s):  
Nirmalya SAHA ◽  
James Ropa ◽  
Lili Chen ◽  
Hsiang-Yu Hu ◽  
Maria Mysliwski ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Hematopoietic Cells ◽  
Leukemic Cells ◽  
Flow Cytometry Analysis ◽  
Hematopoietic Stem ◽  
Hematopoietic System ◽  
A Cell

Abstract The Polymerase Associated Factor 1 complex (PAF1c) functions at the interface of epigenetics and gene transcription. The PAF1c is a multi-protein complex composed of Paf1, Cdc73, Leo1, Ctr9, Rtf1 and WDR61, which have all been shown to play a role in disease progression and different types of cancer. Previous reports demonstrated that the PAF1c is required for MLL-fusion driven acute myeloid leukemia. This is due, in part, to a direct interaction between the PAF1c and wild type MLL or MLL fusion proteins. Importantly, targeted disruption of the PAF1c-MLL interaction impairs the growth of MLL-fusion leukemic cells but is tolerated by normal hematopoietic stem cells. These data point to differential functions for the PAF1c in normal and malignant hematopoietic cells that may be exploited for therapeutic purposes. However, a detailed exploration of the PAF1c in normal hematopoiesis is currently lacking. Here, we utilize a mouse genetic model to interrogate the role of the PAF1c subunit, Cdc73, in the development and sustenance of normal hematopoiesis. Using hematopoietic-specific constitutive and conditional drivers to express Cre recombinase, we efficiently excise floxed alleles of Cdc73 in hematopoietic cells. VavCre mediated excision of Cdc73 results in embryonic lethality due to hematopoietic failure. Characterization of the hematopoietic system demonstrated that cKit+ hematopoietic stem and progenitor cells (HSPC) are depleted due to Cdc73 knockout. We next investigated the role of Cdc73 in adult hematopoiesis using Mx1Cre mediated excision. Conditional knockout of Cdc73 in the adult hematopoietic system leads to lethality within 15 days of Cdc73 excision while no phenotype was observed in heterozygous Cdc73fl/wt controls. Pathological examination of bones in these mice showed extensive bone marrow failure. Flow cytometry analysis revealed that cKit+ HSPCs in adult mice are ablated following loss of Cdc73. Bone marrow transplantation assays demonstrated a cell autonomous requirement of Cdc73 for HSC function in vivo. To perform cellular characterization of HSPCs upon Cdc73 KO, we optimized excision conditions to capture cKit+ HSPCs with excised Cdc73 but before their exhaustion. Flow cytometry analysis demonstrated that Cdc73 KO leads to a cell cycle defect. Cdc73 excision leads to a 2.5 fold increase in the accumulation of HSPCs in the G0 phase of cell cycle with a reduction in the proliferative phases. This is accompanied with an increase in cellular death as indicated by Annexin V staining. Together, these data indicate that Cdc73 is required for cell cycle progression and HSPC survival. To understand the molecular function of Cdc73, we performed RNAseq analysis to identify genes regulated by Cdc73 in HSPCs. We observed 390 genes are upregulated and 433 genes are downregulated upon loss of Cdc73. Specifically, Cdc73 excision results in upregulation of cell cycle inhibitor genes such as p21 and p57, consistent with the cell cycle defect observed following Cdc73 excision. Further, when comparing our results to leukemic cells, we uncovered key differences in Cdc73 gene program regulation between ckit+ hematopoietic cells and MLL-AF9 AML cells. Loss of Cdc73 in leukemic cells leads to downregulation of genes associated with early hematopoietic progenitors and upregulation of myeloid differentiation genes consistent with previous studies. Interestingly, we observed a more even distribution of expression changes (non-directional) within these gene programs following Cdc73 inactivation in HSPCs. Most importantly, while loss of Cdc73 in MLL-AF9 AML cells leads to a profound downregulation of the Hoxa9/Meis1 gene program, excision of Cdc73 in HSPCs results in a modest non-directional change in expression of the Hoxa9/Meis1 gene program. This was attributed to no change in Hoxa9 and Meis1 expression in HSPCs following excision of Cdc73, in contrast to MLL-AF9 cells where these pro leukemic targets are significantly downregulated. Together, these data indicate an essential role for the PAF1c subunit Cdc73 in normal hematopoiesis but differential roles and context specific functions in normal and malignant hematopoiesis, which may be of therapeutic value for patients with AMLs expressing Hoxa9/Meis1 gene programs. Disclosures No relevant conflicts of interest to declare.

scholarly journals Role of Flavonoids against COVID-19

2021 ◽  
Vol 9 (1) ◽  
pp. 47-55
Author(s):  
Ambreen Fatima ◽  
Yasir H. Siddique
Keyword(s):  
Treatment Strategy ◽  
Protective Role ◽  
The Novel ◽  
Loss Of Life ◽  
The World ◽  
Health Promoting ◽  
Ancient Times ◽  
Novel Coronavirus ◽  
Old Drugs

The novel coronavirus disease (COVID-19) has entered a threatening stage all over the world. Many lives have been lost, and many more are in need of treatment. The mild symptoms may include fever and dry cough, but in severe cases, it could lead to pneumonia and ultimately death in some instances. Though medical scientists all over the globe are working hard to develop a treatment for this disease, yet no definite cure has been found. To date, the treatment strategy is based on adopting strategies to break the transmission of the virus and repurposing of the old drugs to prevent the loss of life. Among the various potent candidates, flavonoids may play a protective role in these times. Studies have already proven various health-promoting properties of flavonoids in earlier viral diseases, like SARS and MERS. Since ancient times, been plants have used to treat a number of human diseases. Different phytoproducts have been previously described to inhibit the replication of numerous viruses. Despite the positive reports for plant-based medications, no successful clinical trials on phytoproducts as anti-COVID agents have been conducted to date. This review highlights the efficacy of flavonoids as a treatment strategy either alone or in combination with other drugs.

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