Familial Hyperkalemic Hypertension Genotype With a Negative Phenotype: A CUL3 Mosaicism

ABSTRACT Yersinia pestis has been historically divided into three biovars: antiqua, mediaevalis, and orientalis. On the basis of this study, strains from Microtus-related plague foci are proposed to constitute a new biovar, microtus. Based on the ability to ferment glycerol and arabinose and to reduce nitrate, Y. pestis strains can be assigned to one of four biovars: antiqua (glycerol positive, arabinose positive, and nitrate positive), mediaevalis (glycerol positive, arabinose positive, and nitrate negative), orientalis (glycerol negative, arabinose positive, and nitrate positive), and microtus (glycerol positive, arabinose negative, and nitrate negative). A 93-bp in-frame deletion in glpD gene results in the glycerol-negative characteristic of biovar orientalis strains. Two kinds of point mutations in the napA gene may cause the nitrate reduction-negative characteristic in biovars mediaevalis and microtus, respectively. A 122-bp frameshift deletion in the araC gene may lead to the arabinose-negative phenotype of biovar microtus strains. Biovar microtus strains have a unique genomic profile of gene loss and pseudogene distribution, which most likely accounts for the human attenuation of this new biovar. Focused, hypothesis-based investigations on these specific genes will help delineate the determinants that enable this deadly pathogen to be virulent to humans and give insight into the evolution of Y. pestis and plague pathogenesis. Moreover, there may be the implications for development of biovar microtus strains as a potential vaccine.

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ROMK expression remains unaltered in a mouse model of familial hyperkalemic hypertension caused by the CUL3Δ403-459 mutation

Physiological Reports ◽

10.14814/phy2.12850 ◽

2016 ◽

Vol 4 (13) ◽

pp. e12850 ◽

Cited By ~ 3

Author(s):

Meena Murthy ◽

Thimo Kurz ◽

Kevin M. O'Shaughnessy

Keyword(s):

Mouse Model ◽

Familial Hyperkalemic Hypertension

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WNK4 Kinase: from structure to physiology

AJP Renal Physiology ◽

10.1152/ajprenal.00634.2020 ◽

2021 ◽

Author(s):

Adrian Rafael Murillo-de-Ozores ◽

Alejandro Rodriguez-Gama ◽

Hector Carbajal-Contreras ◽

Gerardo Gamba ◽

Maria Castaneda-Bueno

Keyword(s):

Oxidative Stress ◽

Mouse Models ◽

Serine Threonine Kinase ◽

Gene Encoding ◽

Threonine Kinase ◽

Physiological Conditions ◽

Different Levels ◽

Familial Hyperkalemic Hypertension

With No Lysine (K) kinase 4 (WNK4) belongs to a serine-threonine kinase family characterized by the atypical positioning of its catalytic lysine. Despite the fact that WNK4 has been found in many tissues, the majority of its study has revolved around its function in the kidney, specifically as a positive regulator of the thiazide-sensitive NaCl cotransporter (NCC) in the distal convoluted tubule (DCT) of the nephron. This is explained by the description of gain-of-function mutations in the gene encoding WNK4 that cause Familial Hyperkalemic Hypertension (FHHt). This disease is mainly driven by increased downstream activation of the Ste20-related Proline Alanine Rich Kinase (SPAK)/Oxidative Stress Responsive Kinase 1 (OSR1)-NCC pathway, which increases salt reabsorption in the DCT and indirectly impairs renal K+ secretion. Here, we review the large volume of information that has accumulated about different aspects of WNK4 function. We first review the knowledge on WNK4 structure and enumerate the functional domains and motifs that have been characterized. Then, we discuss WNK4 physiological functions based on the information obtained from in vitro studies and from a diverse set of genetically modified mouse models with altered WNK4 function. We then review in vitro and in vivo evidence on the different levels of regulation of WNK4. Finally, we go through the evidence that has suggested how different physiological conditions act through WNK4 to modulate NCC activity.

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A Rare i (I-negative) Phenotype Blood Found in Japanese Families

Proceedings of the Japan Academy ◽

10.2183/pjab1945.46.889 ◽

1970 ◽

Vol 46 (8) ◽

pp. 889-892 ◽

Cited By ~ 6

Author(s):

Hideo YAMAGUCHI ◽

Yasuto OKUBO ◽

Tadao TOMITA ◽

Hazime YAMANO ◽

Masayoshi TANAKA

Keyword(s):

Negative Phenotype

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Gelatinase-Associated Phenotypes and Genotypes Among Clinical Isolates of Enterococcus faecalis in Poland

Polish Journal of Microbiology ◽

10.33073/pjm-2011-041 ◽

2011 ◽

Vol 60 (4) ◽

pp. 287-292 ◽

Cited By ~ 9

Author(s):

JANUSZ STRZELECKI ◽

WALERIA HRYNIEWICZ ◽

EWA SADOWY

Keyword(s):

Gene Expression ◽

Enterococcus Faecalis ◽

Clonal Complex ◽

Nosocomial Pathogen ◽

Gelatinase Activity ◽

Sensing System ◽

Quorum Sensing System ◽

Invasive Infections ◽

Genetic Events ◽

Negative Phenotype

Enterococcus faecalis is an important nosocomial pathogen causing serious invasive infections. One of the virulence factors of this pathogen, gelatinase GelE, is a protease whose gene expression is regulated by the Fsr quorum sensing system. In this study, we used a well-characterized collection of 153 clinical E. faecalis isolates to investigate the distribution of genes involved in gelatinase expression. Although 140 isolates (91% of the group) harbored the gelE gene, only 81 isolates (53%) produced active gelatinase. The gelatinase-negative phenotype was found in several unrelated clones, and appeared to be caused by various genetic events. Isolates of the hospital-adapted clonal complex 2 (CC2) and of CC40 were uniformly gelatinase-positive, while all the CC87 isolates contained the 23.9 kb deletion encompassing most of the fsr locus and were gelatinase-negative. No significant differences among isolates of different clinical origin and gelatinase activity or presence of the fsr genes were found with the exception of isolates from cerebrospinal fluid, which were more often gelatinase-positive than colonizing isolates.

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Antiangiogenic therapy for breast cancer with triple negative phenotype

Modern Oncology ◽

10.26442/18151434.2021.1.200763 ◽

2021 ◽

Vol 23 (1) ◽

pp. 88-92

Author(s):

Inna P. Ganshina ◽

Kristina A. Ivanova ◽

Olga O. Gordeeva ◽

Aleksandr V. Arkhipov ◽

Liudmila G. Zhukova

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Malignant Tumors ◽

Antiangiogenic Therapy ◽

Treatment Strategies ◽

Her 2 ◽

Triple Negative Phenotype ◽

The Impact ◽

Negative Phenotype

Triple-negative breast cancer is 1024% of all cases of breast cancer and is characterized by the absence of estrogen, progesterone, and HER-2 receptors in the tumor. The therapy of this illness is a difficult clinical case. In contrast to hormone-positive and HER-2-positive phenotypes, in which we successfully use targeted drugs (antiestrogens and anti-HER-2 drugs), for triple-negative breast cancer we have not had such targets for a long time. Thus, despite the impressive results of immunotherapy of triple-negative breast cancer, there remains a fairly large group of patients with negative PD-L1 status, for whom it is necessary to develop other treatment strategies. One of the approaches in the treatment of malignant tumors includes not the impact on tumor cells, but the process of angiogenesis. Antiangiogenic drugs have positively proven themselves in the treatment of a large number of malignant tumors but are underestimated for breast cancer (including triple-negative phenotype). The use of bevacizumab in combinations with cytostatic drugs in breast cancer therapy (including triple-negative breast cancer) has been studied in a large number of clinical trials but was undeservedly forgotten in some countries due to the revoked FDA registration. This review presents the role of bevacizumab in the treatment of patients with triple-negative breast cancer and suggests the conditions when the administration of this drug is justified and leads to better results.

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