Chromosomal bacterial type II toxin–antitoxin systems

2012 ◽  
Vol 58 (5) ◽  
pp. 553-562 ◽  
Author(s):  
Mohammad Adnan Syed ◽  
Céline M. Lévesque

Most prokaryotic chromosomes contain a number of toxin–antitoxin (TA) modules consisting of a pair of genes that encode 2 components, a stable toxin and its cognate labile antitoxin. TA systems are also known as addiction modules, since the cells become “addicted” to the short-lived antitoxin product (the unstable antitoxin is degraded faster than the more stable toxin) because its de novo synthesis is essential for their survival. While toxins are always proteins, antitoxins are either RNAs (type I, type III) or proteins (type II). Type II TA systems are widely distributed throughout the chromosomes of almost all free-living bacteria and archaea. The vast majority of type II toxins are mRNA-specific endonucleases arresting cell growth through the mechanism of RNA cleavage, thus preventing the translation process. The physiological role of chromosomal type II TA systems still remains the subject of debate. This review describes the currently known type II toxins and their characteristics. The different hypotheses that have been proposed to explain their role in bacterial physiology are also discussed.

1985 ◽  
Vol 248 (3) ◽  
pp. R302-R307 ◽  
Author(s):  
W. W. Winder ◽  
M. L. Terry ◽  
V. M. Mitchell

We have investigated the physiological role of the marked increase in plasma epinephrine that occurs in fasted exercising rats. Fasted adrenodemedullated (ADM) rats show a marked reduction in endurance run times compared with sham-operated (SO) controls. After running for 30 min at 21 m/min up a 10% grade, ADM rats' blood glucose was 2.9 +/- 0.1 mM vs. 4.3 +/- 0.2 mM in SO rats. At the same time, blood lactate was 3.0 +/- 0.2 mM in SO rats compared with 1.0 +/- 0.1 mM in ADM rats. Glycogenolysis was impaired in ADM rats in the fast-twitch white region of the quadriceps, lateral gastrocnemius, and soleus muscles but not in the fast-twitch red region of the quadriceps muscle. Hepatic adenosine 3',-5'-cyclic monophosphate was increased to the same extent in ADM and SO rats during exercise. Infusion of epinephrine into ADM rats during exercise corrected the hypoglycemia, restored lactate to normal, and stimulated glycogenolysis in soleus, white quadriceps, and lateral gastrocnemius muscles. Epinephrine-dependent glycogenolysis in contracting type I and noncontracting type II muscle fibers apparently provides essential quantities of lactate for hepatic gluconeogenesis in fasted exercising rats.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1641
Author(s):  
Emily E. S. Brettschneider ◽  
Masaki Terabe

Glioblastoma is an aggressive and deadly cancer, but to date, immunotherapies have failed to make significant strides in improving prognoses for glioblastoma patients. One of the current challenges to developing immunological interventions for glioblastoma is our incomplete understanding of the numerous immunoregulatory mechanisms at play in the glioblastoma tumor microenvironment. We propose that Natural Killer T (NKT) cells, which are unconventional T lymphocytes that recognize lipid antigens presented by CD1d molecules, may play a key immunoregulatory role in glioblastoma. For example, evidence suggests that the activation of type I NKT cells can facilitate anti-glioblastoma immune responses. On the other hand, type II NKT cells are known to play an immunosuppressive role in other cancers, as well as to cross-regulate type I NKT cell activity, although their specific role in glioblastoma remains largely unclear. This review provides a summary of our current understanding of NKT cells in the immunoregulation of glioblastoma as well as highlights the involvement of NKT cells in other cancers and central nervous system diseases.


Minerals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 451
Author(s):  
Galina Palyanova ◽  
Valery Murzin ◽  
Andrey Borovikov ◽  
Nikolay Karmanov ◽  
Sergei Kuznetsov

Composition of native gold and minerals in intergrowth with rhyolites of the Chudnoe Au-Pd-REE deposit (Subpolar Urals, Russia) was studied using optical microscopy, scanning electron microscopy, and electron microprobe analysis. Five varieties of native gold have been identified, based on the set of impurity elements and their quantities, and on intergrown minerals. Native gold in rhyolites from the Ludnaya ore zone is homogeneous and contains only Ag (fineness 720‰, type I). It is in intergrowth with fuchsite or allanite and mertieite-II. In rhyolites from the Slavnaya ore zone, native gold is heterogeneous, has a higher fineness, different sets and contents of elements: Ag, Cu, 840–860‰ (type II); Ag, Cu, Pd, 830–890‰ (III); Ag, Pd, Cu, Hg, 840–870‰ (IV). It occurs in intergrowth with fuchsite, albite, and mertieite-II (type II), or albite, quartz, and atheneite (III), or quartz, albite, K-feldspar, and mertieite-II (IV). High fineness gold (930–1000‰, type V) with low contents of Ag, Cu, and Pd or their absence occurs in the form as microveins, fringes and microinclusions in native gold II–IV. Tetra-auricupride (AuCu) is presented as isometric inclusions in gold II and platelets in the decay structures in gold III and IV. The preliminary data of a fluid inclusions study showed that gold mineralization at the Chudnoe deposit could have been formed by chloride fluids of low and medium salinity at temperatures from 105 to 230 °C and pressures from 5 to 115 MPa. The formation of native gold I is probably related to fuchsitization and allanitization of rhyolites. The formation of native gold II-V is also associated with the same processes, but it is more complicated and occurred later with a significant role of Na-, Si-, and K-metasomatism. The presence of Pd and Cu in the ores and Cr in fuchsite indicates the important role of mafic-ultramafic magmatism.


2021 ◽  
pp. 87-100
Author(s):  
DANILO VUJOVIĆ ◽  
NEDELJKO CVETKOVIĆ

In the last couple of years, with the prolification of the Migrant Crisis and the defeat of the Islamic State, the return of the foreign fighters, who went form Europe to the Caliphate and joined the local conflict, as well as the problem of the homegrown terrorism have become the focal point of almost all national security strategies of European countries. The situation that followed drove the authors to set the possible approaches to solving this challenge to European security as a goal for their research. The subject of this article encompasses the process of deradicalization, as the only humane way to deal with the problem at hand, as well as the process of radicalization, as necessary for understanding the formation of the individuals that pose a threat to the security of Europe. The article also tackles the preventive work directed at those social groups that are deemed susceptible to radicalization, as well as the use of individualized and holistic approach to the radicalized individuals. Special consideration is given to the programs of deradicalization as a form of institutionalized way of dealing with this type of a security risk. In the conclusion the authors give their own view of what is the most adeqaute approach when working with radicalized individuals and the role of certain elements of society in it.


2010 ◽  
Vol 10 ◽  
pp. 2367-2384 ◽  
Author(s):  
Eduardo Pérez-Gómez ◽  
Gaelle del Castillo ◽  
Juan Francisco Santibáñez ◽  
Jose Miguel Lêpez-Novoa ◽  
Carmelo Bernabéu ◽  
...  

Endoglin (CD105) is an auxiliary membrane receptor of transforming growth factor beta (TGF-β) that interacts with type I and type II TGF-β receptors and modulates TGF-β signaling. Endoglin is overexpressed in the tumor-associated vascular endothelium, where it modulates angiogenesis. This feature makes endoglin a promising target for antiangiogenic cancer therapy. In addition, recent studies on human and experimental models of carcinogenesis point to an important tumor cell–autonomous role of endoglin by regulating proliferation, migration, invasion, and metastasis. These studies suggest that endoglin behaves as a suppressor of malignancy in experimental and human epithelial carcinogenesis, although it can also promote metastasis in other types of cancer. In this review, we evaluate the implication of endoglin in tumor development underlying studies developed in our laboratories in recent years.


Reproduction ◽  
2002 ◽  
pp. 799-806 ◽  
Author(s):  
KF Rodriguez ◽  
RM Petters ◽  
AE Crosier ◽  
CE Farin

The aims of this study were to examine the role of transcription and the coincident involvement of type I and type II protein kinase A (PKA) in the resumption of meiosis in murine cumulus-oocyte complexes (COCs) using the transcriptional inhibitors 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) and alpha-amanitin. The first series of experiments was designed to: (i) characterize the role of transcription in gonadotrophin-mediated and spontaneous maturation of murine oocytes; (ii) examine the roles of specific gonadotrophins (FSH versus hCG) and cumulus cells in transcriptionally mediated oocyte maturation; and (iii) determine the reversibility of the transcriptional arrest of meiosis. In the presence of FSH, transcriptional inhibitors arrested germinal vesicle breakdown (GVBD) (DRB: 2 +/- 2% and control: 76 +/- 2%; alpha-amanitin: 4 +/- 4% and control: 70 +/- 4%). Furthermore, cumulus cells were required for transcriptional inhibitors to arrest GVBD (DRB with cumulus cells: 0 +/- 15%; DRB without cumulus cells: 94 +/- 13%; alpha-amanitin with cumulus cells: 15 +/- 2%; alpha-amanitin without cumulus cells: 99 +/- 2%). Thus, in mice, FSH-mediated GVBD uses a transcriptional mechanism, which probably occurs within the cumulus cell compartment. In a second series of experiments, the role of transcription in mediating the resumption of meiosis after activation of either type I or type II PKA was examined. Activation of type I PKA in murine COCs resulted in an arrest of GVBD that was independent of a transcriptional event (with DRB: 7 +/- 9% GVBD; without DRB: 11 +/- 9% GVBD). In contrast, activation of type II PKA resulted in a resumption of meiosis, which required the occurrence of gene transcription (with DRB: 12 +/- 9% GVBD; without DRB: 80 +/- 9% GVBD). As FSH binding to cumulus cells activates the PKA second messenger system, our results indicate that, in cultured murine COCs, FSH binding to cumulus cells results in the activation of type II PKA, which, in turn, mediates a downstream transcriptional event required for the initiation of GVBD.


Development ◽  
1979 ◽  
Vol 53 (1) ◽  
pp. 179-202
Author(s):  
J. T. Hjelle ◽  
K. D. Gibson

Nine-day chick embryos were injected with a β-xyloside and their sternal cartilage was examined 3 days and a week later. Sterna from 16-day embryos showed a reduction in size as compared to controls, with little or no change in the fraction of extracellular space, and a significant decrease in tensile strength. At the ultrastructural level, collagen fibrils in control sterna were dispersed evenly in the interstitial space, with few contacts between adjacent fibrils. In sterna from treated embryos, almost all collagen fibrils were aggregated into clumps and arrays throughout the interstitial space, with fibril-free areas in between. No abnormalities could be detected in the morphology of individual fibrils or in the ultrastructure of the chondrocytes. The changes in spatial distribution of collagen were fully evident 3 days after drug administration. The hydroxyproline/DNA ratio was the same in control and treated sterna, and no changewas observed in the type of collagen. The uronic acid/DNA ratio was reduced by 14% 3 days after drug administration and by 40% after a week. The degree of sulfation of chondroitin sulfate was reduced from 80% in control sterna to 40% in treated sterna; almost allof this chondroitin sulfate was attached to peptide and the sedimentation pattern of the proteoglycan resembled that of normal cartilage proteoglycan. The function of chondroitin sulfate in embryonic cartilage is discussed in terms of our results and others. It is suggested that a major physiological role of the proteoglycan is to control the spatial distribution of collagen fibrils as they assemble to form a cross-linked gel.


1998 ◽  
Vol 274 (2) ◽  
pp. E321-E327 ◽  
Author(s):  
Frederique Diraison ◽  
Michel Beylot

To measure 1) the contribution of hepatic de novo lipogenesis (DNL) and plasma free fatty acid (FFA) reesterification to plasma triglyceride (TG) secretion, and 2) the role of oxidation and hepatic and extrahepatic reesterification in FFA utilization, five normal subjects drank deuterated water and were infused (postabsorptive state) with [1-13C]palmitate and [1,2,3-2H5]glycerol. Total lipid oxidation (Lox) was measured by indirect calorimetry. FFA oxidation (2.76 ± 0.65 μmol ⋅ kg−1 ⋅ min−1) accounted for 45% of FFA turnover rate (Rt) (1.04 μmol ⋅ kg−1 ⋅ min−1) and 91% of Lox; FFA reesterification was 3.27 ± 0.54 μmol ⋅ kg−1 ⋅ min−1. Fractional and absolute TG Rt were 0.21 ± 0.02 h−1 and 0.11 ± 0.05 μmol ⋅ kg−1 ⋅ min−1. DNL accounted for 3.9 ± 0.9% of TG secretion, and hepatic FFA reesterification accounted for 49.4 ± 5.7%; this last process represented a utilization of FFA of 0.16 ± 0.02 μmol ⋅ kg−1 ⋅ min−1. We conclude that, in the postabsorptive state, 1) DNL and FFA reesterification account for only 50–55% of TG secretion, the remaining presumably being provided by stored lipids or lipoproteins taken up by liver, 2) most reesterification occurs in extrahepatic tissues, and 3) oxidation and reesterification each contribute about one-half to FFA utilization; FFA oxidation accounts for almost all Lox.


1984 ◽  
Vol 246 (2) ◽  
pp. F111-F123 ◽  
Author(s):  
D. Marver

The kidney contains three classes of corticosteroid-binding proteins receptors. They include a mineralocorticoid-specific (Type I), a glucocorticoid-specific (Type II), and a corticosterone-specific (Type III) site. The Type I and Type III sites roughly parallel each other along the nephron, with maximal binding occurring in the late distal convoluted or connecting segment and the cortical and medullary collecting ducts. Type II sites occur throughout the nephron, with maximal concentrations appearing in the proximal tubule and the late distal convoluted-cortical collecting duct region. The function of the Type I sites in the connecting segment is unclear since chronic mineralocorticoid therapy does not influence the potential difference in this segment as it does in the cortical collecting tubule. Furthermore, the specific role of Type II versus Type III sites in the distal nephron is unknown. Finally, the possible influence of sodium on both latent and steroid-induced renal cortical and medullary Na-K-ATPase is discussed.


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