Two-level inhibition of galK expression by Spot 42: Degradation of mRNA mK2 and enhanced transcription termination before the galK gene

The Escherichia coli gal operon has the structure Pgal-galE-galT-galK-galM. During early log growth, a gradient in gene expression, named type 2 polarity, is established, as follows: galE > galT > galK > galM. However, during late-log growth, type 1 polarity is established in which galK is greater than galT, as follows: galE > galK > galT > galM. We found that type 2 polarity occurs as a result of the down-regulation of galK, which is caused by two different molecular mechanisms: Spot 42-mediated degradation of the galK-specific mRNA, mK2, and Spot 42-mediated Rho-dependent transcription termination at the end of galT. Because the concentration of Spot 42 drops during the transition period of the polarity type switch, these results demonstrate that type 1 polarity is the result of alleviation of Spot 42-mediated galK down-regulation. Because the Spot 42-binding site overlaps with a putative Rho-binding site, a molecular mechanism is proposed to explain how Spot 42, possibly with Hfq, enhances Rho-mediated transcription termination at the end of galT.

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The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

International Journal of Molecular Sciences ◽

10.3390/ijms22020803 ◽

2021 ◽

Vol 22 (2) ◽

pp. 803

Author(s):

Giuseppina Emanuela Grieco ◽

Noemi Brusco ◽

Giada Licata ◽

Daniela Fignani ◽

Caterina Formichi ◽

...

Keyword(s):

Diabetes Mellitus ◽

Metabolic Disorders ◽

Molecular Mechanisms ◽

Β Cell ◽

Physiological Mechanisms ◽

Effective Strategies ◽

Chronic Hyperglycaemia ◽

Shed Light

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.

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Inclusion patterns in zoned garnets from Magerøy, north Norway

Mineralogical Magazine ◽

10.1180/minmag.1984.048.346.03 ◽

1984 ◽

Vol 48 (346) ◽

pp. 21-26 ◽

Cited By ~ 23

Author(s):

T. B. Andersen

Keyword(s):

Rapid Growth ◽

Outer Zone ◽

Prograde Metamorphism ◽

Growth Type ◽

Compositional Zoning ◽

Garnet Porphyroblasts ◽

The Matrix ◽

Quartz Grains

AbstractGarnet porphyroblasts in metasediments from Magerøy crystallized during static metamorphism. They display three optical zones, each having characteristic inclusions and chemistry. The compositional zoning is related to prograde metamorphism (an inner zone, 1, and a graphite-bearing zone) and retrogression (the outer zone, 2). Inclusions of two types are present in zone 1: type 1 are equidimensional remnants of the matrix, preferentially included along planes of rapid growth; type 2 are tubular and represent recrystallized quartz grains concentrated along defects in the garnet lattice. The defects are lineage boundaries between growth segments related to screw dislocations on crystal faces. Crystal growth developed at relatively high degrees of supersaturation, but below the supersaturation required for the development of dendrites. The inclusions suggest rapid growth of zone 1, caused by heat flow from an adjacent interkinematic mafic/ultramafic intrusive complex. The graphite-bearing zone crystallized at the metamorphic peak, while the inclusion-free idioblasfic rim probably developed during retrograde metamorphism.

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Specific down‐regulation of connective tissue growth factor attenuates progression of nephropathy in mouse models of type 1 and type 2 diabetes

The FASEB Journal ◽

10.1096/fj.06-6713com ◽

2007 ◽

Vol 21 (12) ◽

pp. 3355-3368 ◽

Cited By ~ 136

Author(s):

Mausumee Guha ◽

Zhong‐Gao Xu ◽

David Tung ◽

Linda Lanting ◽

Rama Natarajan

Keyword(s):

Type 2 Diabetes ◽

Growth Factor ◽

Connective Tissue ◽

Mouse Models ◽

Connective Tissue Growth Factor ◽

Tissue Growth ◽

Down Regulation

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Altered expression of major renal Na transporters in rats with unilateral ureteral obstruction

AJP Renal Physiology ◽

10.1152/ajprenal.00272.2002 ◽

2003 ◽

Vol 284 (1) ◽

pp. F155-F166 ◽

Cited By ~ 39

Author(s):

Chunling Li ◽

Weidong Wang ◽

Tae-Hwan Kwon ◽

Mark A. Knepper ◽

Søren Nielsen ◽

...

Keyword(s):

Ureteral Obstruction ◽

Molecular Mechanisms ◽

Free Water ◽

Fractional Excretion ◽

Unilateral Ureteral Obstruction ◽

Altered Expression ◽

Compensatory Increase ◽

Type 3

It has been demonstrated previously that ureteral obstruction was associated with downregulation of renal AQP2 expression and an impaired urinary concentrating capacity (Li C, Wang W, Kwon TH, Isikay L, Wen JG, Marples D, Djurhuus JC, Stockwell A, Knepper MA, Nielsen S, and Frøkiær J. Am J Physiol Renal Physiol 281: F163–F171, 2001). In the present study, changes in the expression of major renal Na transporters were examined in a rat model with 24 h of unilateral ureteral obstruction (UUO) to clarify the molecular mechanisms of the marked natriuresis seen after release of UUO. Urine collection for 2 h after release of UUO revealed a significant reduction in urinary osmolality, solute-free water reabsorption, and a marked natriuresis (0.29 ± 0.03 vs. 0.17 ± 0.03 μmol/min, P < 0.05). Consistent with this, immunoblotting revealed significant reductions in the abundance of major renal Na transporters: type 3 Na+/H+exchanger (NHE3; 24 ± 4% of sham-operated control levels), type 2 Na-Pi cotransporter (NaPi-2; 21 ± 4%), Na-K-ATPase (37 ± 4%), type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1; 15 ± 3%), and thiazide-sensitive Na-Cl cotransporter (TSC; 15 ± 4%). Immunocytochemistry confirmed the downregulation of NHE3, BSC-1, and TSC in response to obstruction. In nonobstructed contralateral kidneys, a significant reduction in the abundance of inner medullary Na-K-ATPase and cortical NaPi-2 was found. This may contribute to the compensatory increase in urinary production (23 ± 2 vs. 13 ± 1 μl · min−1 · kg−1) and increased fractional excretion of urinary Na (0.62 ± 0.03 vs. 0.44 ± 0.03%, P < 0.05). In conclusion, downregulation of major renal Na transporters in rats with UUO may contribute to the impairment in urinary concentrating capacity and natriuresis after release of obstruction, and reduced levels of Na-K-ATPase and NaPi-2 in the contralateral nonobstructed kidney may contribute to the compensatory increase in water and Na excretion from that kidney during UUO and after release of obstruction.

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Organ-Based Response to Exercise in Type 1 Diabetes

ISRN Endocrinology ◽

10.5402/2012/318194 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14 ◽

Cited By ~ 5

Author(s):

Lisa Stehno-Bittel

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Type 1 Diabetes ◽

Molecular Mechanisms ◽

Tissue Level ◽

Significant Research ◽

Response To Exercise ◽

Increased Activity

While significant research has clearly identified sedentary behavior as a risk factor for type 2 diabetes and its subsequent complications, the concept that inactivity could be linked to the complications associated with type 1 diabetes (T1D) remains underappreciated. This paper summarizes the known effects of exercise on T1D at the tissue level and focuses on the pancreas, bone, the cardiovascular system, the kidneys, skeletal muscle, and nerves. When possible, the molecular mechanisms underlying the benefits of exercise for T1D are elucidated. The general benefits of increased activity on health and the barriers to increased exercise specific to people with T1D are discussed.

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Epigenetic Control of Pancreatic Regeneration in Diabetes

Genes ◽

10.3390/genes9090448 ◽

2018 ◽

Vol 9 (9) ◽

pp. 448 ◽

Cited By ~ 1

Author(s):

Shruti Balaji ◽

Tiziana Napolitano ◽

Serena Silvano ◽

Marika Friano ◽

Anna Garrido-Utrilla ◽

...

Keyword(s):

Molecular Mechanisms ◽

Β Cells ◽

Β Cell ◽

Pancreatic Cells ◽

Current Review ◽

Cell Sources ◽

Active Research ◽

Insight Into

Both type 1 and type 2 diabetes are conditions that are associated with the loss of insulin-producing β-cells within the pancreas. An active research therefore aims at regenerating these β-cells with the hope that they could restore euglycemia. The approaches classically used consist in mimicking embryonic development, making use of diverse cell sources or converting pre-existing pancreatic cells. Despite impressive progresses and promising successes, it appears that we still need to gain further insight into the molecular mechanisms underlying β-cell development. This becomes even more obvious with the emergence of a relatively new field of research, epigenetics. The current review therefore focuses on the latest advances in this field in the context of β-cell (neo-)genesis research.

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Altered expression of major renal Na transporters in rats with bilateral ureteral obstruction and release of obstruction

AJP Renal Physiology ◽

10.1152/ajprenal.00170.2003 ◽

2003 ◽

Vol 285 (5) ◽

pp. F889-F901 ◽

Cited By ~ 50

Author(s):

Chunling Li ◽

Weidong Wang ◽

Tae-Hwan Kwon ◽

Mark A. Knepper ◽

Søren Nielsen ◽

...

Keyword(s):

Ureteral Obstruction ◽

Molecular Mechanisms ◽

Urinary Tract Obstruction ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Altered Expression ◽

Sodium Transporters ◽

Type 3

Urinary tract obstruction impairs urinary concentrating capacity and reabsorption of sodium. To clarify the molecular mechanisms of these defects, expression levels of renal sodium transporters were examined in rats with 24-h bilateral ureteral obstruction (BUO) or at day 3 or 14 after release of BUO (BUO-R). BUO resulted in downregulation of type 3 Na+/H+ exchanger (NHE3) to 41 ± 14%, type 2 Na-Pi cotransporter (NaPi-2) to 26 ± 6%, Na-K-ATPase to 67 ± 8%, type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) to 20 ± 7%, and thiazide-sensitive cotransporter (TSC) to 37 ± 9%. Immunocytochemistry confirmed downregulation of NHE3, NaPi-2, Na-K-ATPase, BSC-1, and TSC. Consistent with this downregulation, BUO-R was associated with polyuria, reduced urinary osmolality, and increased urinary sodium and phosphate excretion. BUO-R for 3 days caused a persistant downregulation of NHE3 to 53 ± 10%, NaPi-2 to 57 ± 9%, Na-K-ATPase to 62 ± 8%, BSC-1 to 50 ± 12%, and TSC to 56 ± 16%, which was associated with a marked reduction in the net renal reabsorption of sodium (616 ± 54 vs. 944 ± 24 μmol · min-1 · kg-1; P < 0.05) and phosphate (6.3 ± 0.9 vs. 13.1 ± 0.4 μmol · min-1 · kg-1; P < 0.05) demonstrating a defect in renal sodium and phosphate reabsorption capacity. Moreover, downregulation of Na-K-ATPase and TSC persisted in BUO-R for 14 days, whereas NHE3, NaPi-2, and BSC-1 were normalized to control levels. In conclusion, downregulation of renal Na transporters in rats with BUO and release of BUO are likely to contribute to the associated urinary concentrating defect, increased urinary sodium excretion, and postobstructive polyuria.

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Molecular factors involved in the development of diabetic foot syndrome.

Acta Biochimica Polonica ◽

10.18388/abp.2012_2085 ◽

2012 ◽

Vol 59 (4) ◽

Cited By ~ 17

Author(s):

Bożena Bruhn-Olszewska ◽

Anna Korzon-Burakowska ◽

Magdalena Gabig-Cimińska ◽

Paweł Olszewski ◽

Alicja Węgrzyn ◽

...

Keyword(s):

Diabetic Foot ◽

Cellular Response ◽

Molecular Mechanisms ◽

Modern Medicine ◽

Diabetic Foot Syndrome ◽

Charcot Neuroarthropathy ◽

Global Epidemic ◽

General Metabolism

Diabetes is one of the major challenges of modern medicine, as it is considered a global epidemic of the XXI century. The disease often leads to the development of serious, health threatening complications. Diabetic foot syndrome is a characteristic set of anatomical and molecular changes. At the macroscopic level, major symptoms are neuropathy, ischemia and chronic ulceration of the lower limb. In every third patient, the neuropathy develops into Charcot neuroarthropathy characterized by bone and joints deformation. Interestingly, all these complications are a result of impaired healing processes and are characteristic for diabetes. The specificity of these symptoms comes from impaired molecular mechanisms observed in type 1 and type 2 diabetes. Decreased wound and fracture healing reflect gene expression, cellular response, cell functioning and general metabolism. Here we present a comprehensive literature update on the molecular factors contributing to diabetic foot syndrome.

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Regulation of sweetpotato growth and differentiation by glutamate dehydrogenase

Canadian Journal of Botany ◽

10.1139/b97-118 ◽

1997 ◽

Vol 75 (7) ◽

pp. 1070-1078 ◽

Cited By ~ 4

Author(s):

G. O. Osuji ◽

W. C. Madu

Keyword(s):

Glutamate Dehydrogenase ◽

Growth Retardation ◽

Ipomoea Batatas ◽

Normal Growth ◽

Naphthaleneacetic Acid ◽

Growth Type ◽

Combined Supplementation ◽

Type 3

The function of glutamate dehydrogenase was studied in cultured sweetpotato (Ipomoea batatas) nodal explants. The glutamate dehydrogenase was fractionated to charge isomers. Supplementation of the growth medium with either naphthaleneacetic acid or benzyladenine in the presence of 20 mM NH4NO3 induced normal growth (type 1 sweetpotato). The basic and acidic charge isomers of glutamate dehydrogenase were not suppressed. Combined supplementation with 70 mM NH4+ and either 1 mg ∙ L−1 benzyladenine or 0.1 mg ∙ L−1 naphthaleneacetic acid caused growth retardation (type 2 sweetpotato) and the suppression of the basic charge isomers. Combined supplementation with 45 mM NH4+ and either 1 mg ∙ L−1 benzyladenine or 0.1 mg ∙ L−1 naphthaleneacetic acid induced normal growth (type 3 sweetpotato), but the acidic charge isomers were suppressed. Combined supplementation with benzyladenine and naphthaleneacetic acid suppressed all the charge isomers and abolished amination by the enzyme, thereby causing severe growth retardation. The type 1 and type 3 sweetpotato glutamate dehydrogenases were more aminating (Michaelis constant Km = 12.5 and 14.8 mM NH4Cl, respectively) than type 2 sweetpotato glutamate dehydrogenase (Km = 82.6 mM NH4Cl). The differential growth retardations which accompanied the three phases of the suppression of the aminating charge isomers are evidence that the enzyme is aminating in vivo and that it employed that activity in the regulation of sweetpotato growth and differentiation. Key words: glutamate dehydrogenase, amination depression, sweetpotato retardation.

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