scholarly journals NHE2X3 DKO mice exhibit gender-specific NHE8 compensation

2011 ◽  
Vol 300 (4) ◽  
pp. G647-G653 ◽  
Author(s):  
Hua Xu ◽  
Jing Li ◽  
Rongji Chen ◽  
Bo Zhang ◽  
Chunhui Wang ◽  
...  
Keyword(s):  
Sodium Absorption ◽  
Mrna Synthesis ◽  
Wild Type ◽  
Double Knockout ◽  
Sodium Hydrogen Exchanger ◽  
Wild Type Male ◽  
Wild Type Female ◽  
Important Player ◽  
First Time ◽  
Gender Specific

NHE8, the newest member of the sodium/hydrogen exchanger family, is expressed in the epithelial cells of the intestine and the kidney. Intestinal expression of NHE8 is significantly higher than that of NHE2 and NHE3 at a young age, suggesting that NHE8 is an important player for intestinal sodium absorption during early development. The current study was designed to explore if NHE8 plays a compensatory role for the loss of NHE2 and NHE3 function in NHE2X3 double-knockout (NHE2X3 DKO) mice. We further explored the regulatory mechanism(s) responsible for the change in NHE8 expression in NHE2X3 DKO mice. We found that >95% of NHE2X3 DKO mice survived through weanling. However, only 60% of male NHE2X3 DKO mice and 88% of female NHE2X3 DKO mice survived to 6 wk of life. We also found that the expression of NHE8 in wild-type female mice was higher compared with wild-type male mice after puberty. In NHE2X3 KDO mice, NHE8 expression was increased in females but not in males. Using Caco-2 cells as a model of the small intestine, we showed that testosterone inhibited endogenous NHE8 expression by reducing NHE8 mRNA synthesis, whereas estrogen had no effect on NHE8 expression. Thus our data show for the first time that intestinal NHE8 has a compensatory role in NHE2X3 DKO mice and this regulation is gender-dependent.

scholarly journals Impaired mucin synthesis and bicarbonate secretion in the colon of NHE8 knockout mice

2012 ◽  
Vol 303 (3) ◽  
pp. G335-G343 ◽  
Author(s):  
Hua Xu ◽  
Bo Zhang ◽  
Jing Li ◽  
Chunhui Wang ◽  
Huacong Chen ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
Physiological Role ◽  
Normal Serum ◽  
Sodium Absorption ◽  
Bicarbonate Secretion ◽  
Embryonic And Fetal Development ◽  
Sodium Hydrogen Exchanger ◽  
Important Player ◽  
Normal Serum Sodium

Sodium/hydrogen exchanger 8 (NHE8), the newest member of the SLC9 family, is expressed at the apical membrane of the epithelial cells in the intestine and the kidney. Although NHE8 has been shown to be an important player for intestinal sodium absorption early in development, its physiological role in the intestine remains unclear. Here, we successfully created a NHE8 knockout (NHE8−/−) mouse model to study the function of this transporter in the intestinal tract. Embryonic stem cells containing interrupted NHE8 gene were injected into mouse blastocyst to produce NHE8+/− chimeras. NHE8−/− mice showed no lethality during embryonic and fetal development. These mice had normal serum sodium levels and no signs of diarrhea. Apically expressed NHE2 and NHE3 were increased in the small intestine of the NHE8−/− mice in compensation. The number of goblet cells and mucin (MUC)-positive cells in the colon was reduced in NHE8−/− mice along with mucosal pH, MUC2 expression as well as downregulated in adenoma (DRA) expression. Therefore, the role of NHE8 in the intestine involves both sodium absorption and bicarbonate secretion.

Genetic and demographic effects of single wild-type immigrants on a mutant population of Tribolium castaneum

1986 ◽  
Vol 28 (6) ◽  
pp. 1003-1008 ◽  
Author(s):  
Michael A. Delgado ◽  
DuWayne C. Englert
Keyword(s):  
Tribolium Castaneum ◽  
Wild Type ◽  
Gene Frequencies ◽  
Treatment Groups ◽  
Female Immigrant ◽  
Rate Of Increase ◽  
Wild Type Male ◽  
Wild Type Female ◽  
In The Wild ◽  
Type Gene

The effects of single wild-type immigrants on populations of Tribolium castaneum initially homozygous for the antennapedia (ap) allele were examined in reference to gene frequencies and age structures. One population received a wild-type male, another received a wild-type female, and the control population received no wild-type immigrant. The rate of increase in the wild-type gene frequency was significantly higher in the female immigrant population. Rapid increase in heterozygosity for this population resulted in a higher average number of adults than for the other two treatment groups. No significant differences in the numbers of larvae and pupae were observed. Results indicated increased larval survivability to be the major factor in establishment of the wild-type gene and the sex of the immigrant in the rate of increase.Key words: Tribolium, population, selection, immigration, antennapedia.

scholarly journals Somatostatin regulates NHE8 protein expression via the ERK1/2 MAPK pathway in DSS-induced colitis mice

2016 ◽  
Vol 311 (5) ◽  
pp. G954-G963 ◽  
Author(s):  
Xiao Li ◽  
Lin Cai ◽  
Hua Xu ◽  
Chong Geng ◽  
Jing Lu ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Somatostatin Receptor ◽  
Mucosal Injury ◽  
Sodium Absorption ◽  
Colonic Tissue ◽  
Pathological Conditions ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger ◽  
First Time ◽  
Stimulation Of

Previous studies reported that administration of somatostatin (SST) to human patients mitigated their diarrheal symptoms. Octreotide (an analog of SST) treatment in animals resulted in upregulation of sodium/hydrogen exchanger 8 (NHE8). NHE8 is important for water/sodium absorption in the intestine, and loss of NHE8 function results in mucosal injury. Thus we hypothesized that NHE8 expression is inhibited during colitis and that SST treatment during pathological conditions can restore NHE8 expression. Our data showed for the first time that NHE8 is expressed in the human colonic tissue and that NHE8 expression is decreased in ulcerative colitis (UC) patients. We also found that octreotide could stimulate colonic NHE8 expression in colitic mice. Furthermore, the somatostatin receptor 2 (SSTR2) agonist seglitide and the somatostatin receptor 5 (SSTR5) agonist L-817,818 could restore NHE8 expression via its role in suppressing ERK1/2 phosphorylation. Our study uncovered a novel mechanism of SST stimulation of NHE8 expression in colitis.

scholarly journals Sex differences in the development of prolactinoma in mice overexpressing hCGβ: role of TGFβ1

2017 ◽  
Vol 232 (3) ◽  
pp. 535-546 ◽  
Author(s):  
Erika Y Faraoni ◽  
María Andrea Camilletti ◽  
Alejandra Abeledo-Machado ◽  
Laura D Ratner ◽  
Fernanda De Fino ◽  
...  
Keyword(s):  
Sex Differences ◽  
Target Genes ◽  
Tumor Development ◽  
Wild Type ◽  
Physiological Level ◽  
Wild Type Male ◽  
Males And Females ◽  
Gender Specific

Female transgenic mice that overexpress the human chorionic gonadotrophin β subunit (hCGβ+) develop prolactinomas, whereas hCGβ+ males do not. The high levels of circulating hCG induce massive luteinization in the ovary of hCGβ+ females, and progesterone becomes the primary steroid hormone produced, but estradiol remains at physiological level. The involvement of high levels of progesterone in lactotroph proliferation is not clearly understood; hence, the pathogenesis of prolactinomas in hCGβ+ females remains unclear. TGFβ1 is an inhibitor of lactotroph function, and the reduced TGFβ1 activity found in prolactinomas has been proposed to be involved in tumor development. The aim of the present work was to study the role of TGFβ1 in the gender-specific development of prolactinomas in hCGβ+ mice. We compared the expression of different components of the pituitary TGFβ1 system in males and females in this model. We found reduced TGFβ1 levels, reduced expression of TGFβ1 target genes, TGFβ1 receptors, Ltbp1, Smad4 and Smad7 in hCGβ+ female pituitaries. However, no differences were found between the transgenic and wild-type male pituitaries. We postulate that decreased pituitary TGFβ1 activity in hCGβ+ females is involved in the development of prolactinomas. In fact, we demonstrated that an in vivo treatment carried out for increasing pituitary TGFβ1 activity, was successful in reducing the prolactinoma development, and the hyperprolactinemia in hCGβ+ females. Moreover, the stronger TGFβ1 system found in males could protect them from excessive lactotroph proliferation. Sex differences in the regulation of the pituitary TGFβ1 system could explain gender differences in the incidence of prolactinoma.

scholarly journals Polyadenylation of Influenza Virus mRNA Transcribed In Vitro from Model Virion RNA Templates: Requirement for 5′ Conserved Sequences

1998 ◽  
Vol 72 (2) ◽  
pp. 1280-1286 ◽  
Author(s):  
David C. Pritlove ◽  
Leo L. M. Poon ◽  
Ervin Fodor ◽  
Jane Sharps ◽  
George G. Brownlee
Keyword(s):  
Influenza Virus ◽  
Mrna Synthesis ◽  
Wild Type ◽  
Binding Properties ◽  
Vitro Assay ◽  
Point Mutant ◽  
Polymerase Binding ◽  
First Time ◽  
Polyadenylated Mrna

ABSTRACT Here we report the development of two independent assays which demonstrate for the first time that exogenous model RNA templates based on influenza virus virion RNA (vRNA) are transcribed in vitro to produce polyadenylated mRNA. We investigated the activities of mutated templates with known polymerase binding properties to test our model that polyadenylation occurs when a polymerase complex, which is bound to conserved 5′ sequences of vRNA, prevents read-through of the U track at which polyadenylation subsequently occurs by reiterative copying. Mutated templates with perturbed polymerase binding sites (i.e., a deletion mutant lacking the first 4 5′ residues and a U→A point mutant at the third residue) initiated transcription in the in vitro assay but failed to produce polyadenylated transcripts, whereas an A→U point mutant at the fourth residue, which retained polymerase binding properties similar to those of the wild type, produced polyadenylated transcripts. Our results show that nucleotides within the conserved 5′ sequence are required for polyadenylation and support the hypothesis that polymerase binding to 5′ sequences of the template is required for mRNA synthesis.

scholarly journals Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo

Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 54
Author(s):  
Christine Landlinger ◽  
Lenka Tisakova ◽  
Vera Oberbauer ◽  
Timo Schwebs ◽  
Abbas Muhammad ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Bactericidal Activity ◽  
High Selectivity ◽  
Ex Vivo ◽  
Vaginal Microbiome ◽  
Wild Type ◽  
Wild Type Enzyme ◽  
Promising Alternative ◽  
First Time

Bacterial vaginosis is characterized by an imbalance of the vaginal microbiome and a characteristic biofilm formed on the vaginal epithelium, which is initiated and dominated by Gardnerella bacteria, and is frequently refractory to antibiotic treatment. We investigated endolysins of the type 1,4-beta-N-acetylmuramidase encoded on Gardnerella prophages as an alternative treatment. When recombinantly expressed, these proteins demonstrated strong bactericidal activity against four different Gardnerella species. By domain shuffling, we generated several engineered endolysins with 10-fold higher bactericidal activity than any wild-type enzyme. When tested against a panel of 20 Gardnerella strains, the most active endolysin, called PM-477, showed minimum inhibitory concentrations of 0.13–8 µg/mL. PM-477 had no effect on beneficial lactobacilli or other species of vaginal bacteria. Furthermore, the efficacy of PM-477 was tested by fluorescence in situ hybridization on vaginal samples of fifteen patients with either first time or recurring bacterial vaginosis. In thirteen cases, PM-477 killed the Gardnerella bacteria and physically dissolved the biofilms without affecting the remaining vaginal microbiome. The high selectivity and effectiveness in eliminating Gardnerella, both in cultures of isolated strains as well as in clinically derived samples of natural polymicrobial biofilms, makes PM-477 a promising alternative to antibiotics for the treatment of bacterial vaginosis, especially in patients with frequent recurrence.

scholarly journals Seed morphology uncovers 1500 years of vine agrobiodiversity before the advent of the Champagne wine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vincent Bonhomme ◽  
Jean-Frédéric Terral ◽  
Véronique Zech-Matterne ◽  
Sarah Ivorra ◽  
Thierry Lacombe ◽  
...  
Keyword(s):  
Middle Ages ◽  
Climatic Changes ◽  
Seed Morphology ◽  
Crucial Aspect ◽  
Wild Type ◽  
Grape Seeds ◽  
The Social ◽  
Reference Collection ◽  
Grape Varieties ◽  
First Time

AbstractA crucial aspect of viticulture is finally unveiled as the historical dynamics of its agrobiodiversity are described in the Champagne region for the first time. Outline analyses were carried out to compare the morphology of archaeological grape seeds from Troyes and Reims (first c. AD to fifteenth c. AD) with that of a reference collection of modern seeds, including wild vines and traditional grape varieties, believed to be ancient and characteristic of the French vine heritage. This allows us to document the chronological dynamics of the use of the wild Vitis type and of the diversity of the varieties used, based on morphological disparity. After showing the existence of morphological types corresponding to geographical groups, we highlight a geochronological dynamic. Our results show that the wild type is used throughout the series, up to the Middle Ages. In addition, domestic forms, morphologically related to southern varietal groups, are very early involved in the Champagne grape agrodiversity. The groups corresponding to the typical grape varieties of today do not appear until the second millennium. These previously unsuspected dynamics are discussed in light of the social, societal and climatic changes documented for the period.

scholarly journals A Novel and Efficient High-Yield Method for Preparing Bacterial Ghosts

Toxins ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 420
Author(s):  
Yi Ma ◽  
Liu Cui ◽  
Meng Wang ◽  
Qiuli Sun ◽  
Kaisheng Liu ◽  
...  
Keyword(s):  
Large Scale ◽  
Expression System ◽  
High Yield ◽  
Wild Type ◽  
High Quality ◽  
Efficient Protection ◽  
Bacterial Ghosts ◽  
Cell Envelopes ◽  
Extracellular Structures ◽  
First Time

Bacterial ghosts (BGs) are empty cell envelopes possessing native extracellular structures without a cytoplasm and genetic materials. BGs are proposed to have significant prospects in biomedical research as vaccines or delivery carriers. The applications of BGs are often limited by inefficient bacterial lysis and a low yield. To solve these problems, we compared the lysis efficiency of the wild-type protein E (EW) from phage ΦX174 and the screened mutant protein E (EM) in the Escherichia coli BL21(DE3) strain. The results show that the lysis efficiency mediated by protein EM was improved. The implementation of the pLysS plasmid allowed nearly 100% lysis efficiency, with a high initial cell density as high as OD600 = 2.0, which was higher compared to the commonly used BG preparation method. The results of Western blot analysis and immunofluorescence indicate that the expression level of protein EM was significantly higher than that of the non-pLysS plasmid. High-quality BGs were observed by SEM and TEM. To verify the applicability of this method in other bacteria, the T7 RNA polymerase expression system was successfully constructed in Salmonella enterica (S. Enterica, SE). A pET vector containing EM and pLysS were introduced to obtain high-quality SE ghosts which could provide efficient protection for humans and animals. This paper describes a novel and commonly used method to produce high-quality BGs on a large scale for the first time.

Increased susceptibility of purinergic receptor-deficient mice to lung infection withPseudomonasaeruginosa

2005 ◽  
Vol 289 (5) ◽  
pp. L890-L895 ◽  
Author(s):  
Cara Geary ◽  
Henry Akinbi ◽  
Tom Korfhagen ◽  
Jean-Etienne Fabre ◽  
Richard Boucher ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Purinergic Receptors ◽  
Tissue Injury ◽  
Purinergic Receptor ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Sublethal Dose ◽  
Wild Type ◽  
Double Knockout

Purinergic receptors are expressed throughout the respiratory system in diverse cell types. The efficiency of mucus clearance in the airways, the cascade leading to tissue injury, and inflammation are modulated by autocrine/paracrine release of nucleotides and signaling by purinergic receptors. We assessed the role of purinergic receptors in innate host defense of the lung in vivo by infecting mice deficient in P2Y1, P2Y2, or both receptors with intratracheal instillation of Pseudomonas aeruginosa. After P. aeruginosa challenge, all double knockout (P2Y1/P2Y2−/−) mice succumbed within 30 h of challenge, whereas 85% of the wild-type mice survived. Thirty-three percent of wild-type mice survived beyond 96 h. Single knockout mice, P2Y1−/−, or P2Y2−/−, exhibited intermediate survivals. Twenty-four hours following intratracheal instillation of a sublethal dose of P. aeruginosa, the level of total protein in bronchoalveolar lavage fluid was 1.8-fold higher in double knockout than in wild-type mice ( P < 0.04). Total cell count in bronchoalveolar lavage fluids at 4 h and levels of IL-6 and macrophage inflammatory protein-2 in lung homogenates at 24 h postchallenge were significantly reduced in P2Y1/P2Y2−/− mice relative to wild-type mice. These findings suggest that purinergic receptors exert a protective role against infection of the lungs by P. aeruginosa by decreasing protein leak and enhancing proinflammatory cytokine response.

scholarly journals Tumor formation in p53 mutant ovaries transplanted into wild-type female hosts

Oncogene ◽  
2004 ◽  
Vol 23 (46) ◽  
pp. 7722-7725 ◽  
Author(s):  
Chun-Ming Chen ◽  
Junn-Liang Chang ◽  
Richard R Behringer
Keyword(s):  
Tumor Formation ◽  
Wild Type ◽  
Wild Type Female
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