A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo

The activity of a high-Km aldehyde dehydrogenase in the liver cytosol was increased by phenobarbital induction. No corresponding increase in the oxidation rate of acetaldehyde in vivo was found, and it is concluded that cytosolic aldehyde dehydrogenase plays only a minor role in the oxidation of acetaldehyde during ethanol metabolism.

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Deep Sequencing Reveals New Roles for MuB in Transposition Immunity and Target-capture, and Redefines the Insular Ter Region of E. coli

10.21203/rs.3.rs-25350/v2 ◽

2020 ◽

Author(s):

David M Walker ◽

Rasika Harshey

Keyword(s):

High Efficiency ◽

Active Regions ◽

Minor Role ◽

Entire Genome ◽

E Coli ◽

Target Capture ◽

Mu Transposition ◽

A Minor

Abstract Background The target capture protein MuB is responsible for the high efficiency of phage Mu transposition within the E. coli genome. However, some targets are off-limits, such as regions immediately outside the Mu ends (cis-immunity) as well as the entire ~37 kb genome of Mu (Mu genome immunity). Paradoxically, MuB is responsible for cis-immunity and is also implicated in Mu genome immunity, but via different mechanisms. This study was undertaken to dissect the role of MuB in target choice in vivo.Results We tracked Mu transposition from six different starting locations on the E. coli genome, in the presence and absence of MuB. The data reveal that Mu’s ability to sample the entire genome during a single hop in a clonal population is independent of MuB, and that MuB is responsible for cis-immunity, plays a minor role in Mu genome immunity, and facilitates insertions into transcriptionally active regions. Unexpectedly, transposition patterns in the absence of MuB have helped extend the boundaries of the insular Ter segment of the E. coli genome.Conclusions The results in this study demonstrate unambiguously the operation of two distinct mechanisms of Mu target immunity, only one of which is wholly dependent on MuB. The study also reveals several interesting and hitherto unknown aspects of Mu target choice in vivo, particularly the role of MuB in facilitating the capture of promoter and translation start site targets, likely by displacing macromolecular complexes engaged in gene expression. So also, MuB facilitates transposition into the restricted Ter region of the genome.

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Chronic treatment with exendin(9–39)amide indicates a minor role for endogenous glucagon-like peptide-1 in metabolic abnormalities of obesity-related diabetes in ob/ob mice

Journal of Endocrinology ◽

10.1677/joe.1.05876 ◽

2005 ◽

Vol 185 (2) ◽

pp. 307-317 ◽

Cited By ~ 15

Author(s):

B D Green ◽

N Irwin ◽

V A Gault ◽

C J Bailey ◽

F P M O’Harte ◽

...

Keyword(s):

Feeding Activity ◽

Minor Role ◽

Metabolic Abnormalities ◽

Similar Treatment ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Glucose Stimulated Insulin Secretion ◽

A Minor

Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic hormone proposed to play a role in both the pathophysiology and treatment of type 2 diabetes. This study has employed the GLP-1 receptor antagonist, exendin-4(9–39)amide (Ex(9–39)) to evaluate the role of endogenous GLP-1 in genetic obesity-related diabetes and related metabolic abnormalities using ob/ob and normal mice. Acute in vivo antagonistic potency of Ex(9–39) was confirmed in ob/ob mice by blockade of the insulin-releasing and anti-hyperglycaemic actions of intraperitoneal GLP-1. In longer term studies, ob/ob mice were given once daily injections of Ex(9–39) or vehicle for 11 days. Feeding activity, body weight, and both basal and glucose-stimulated insulin secretion were not significantly affected by chronic Ex(9–39) treatment. However, significantly elevated basal glucose concentrations and impaired glucose tolerance were evident at 11 days. These disturbances in glucose homeostasis were independent of changes of insulin sensitivity and reversed by discontinuation of the Ex(9–39) for 9 days. Similar treatment of normal mice did not affect any of the parameters measured. These findings illustrate the physiological extrapancreatic glucose-lowering actions of GLP-1 in ob/ob mice and suggest that the endogenous hormone plays a minor role in the metabolic abnormalities associated with obesity-related diabetes.

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Complement Activation Selectively Potentiates the Pathogenicity of the IgG2b and IgG3 Isotypes of a High Affinity Anti-Erythrocyte Autoantibody

Journal of Experimental Medicine ◽

10.1084/jem.20012024 ◽

2002 ◽

Vol 195 (6) ◽

pp. 665-672 ◽

Cited By ~ 109

Author(s):

Samareh Azeredo da Silveira ◽

Shuichi Kikuchi ◽

Liliane Fossati-Jimack ◽

Thomas Moll ◽

Takashi Saito ◽

...

Keyword(s):

Affinity Maturation ◽

Minor Role ◽

Binding Affinities ◽

Effector Cells ◽

High Affinity ◽

Erythrocyte Binding ◽

Igg Isotypes ◽

A Minor

By generating four IgG isotype-switch variants of the high affinity 34–3C anti-erythrocyte autoantibody, and comparing them to the IgG variants of the low affinity 4C8 anti-erythrocyte autoantibody that we have previously studied, we evaluated in this study how high affinity binding to erythrocytes influences the pathogenicity of each IgG isotype in relation to the respective contributions of Fcγ receptor (FcγR) and complement. The 34–3C autoantibody opsonizing extensively circulating erythrocytes efficiently activated complement in vivo (IgG2a = IgG2b > IgG3), except for the IgG1 isotype, while the 4C8 IgG autoantibody failed to activate complement. The pathogenicity of the 34–3C autoantibody of IgG2b and IgG3 isotypes was dramatically higher (>200-fold) than that of the corresponding isotypes of the 4C8 antibody. This enhanced activity was highly (IgG2b) or totally (IgG3) dependent on complement. In contrast, erythrocyte-binding affinities only played a minor role in in vivo hemolytic activities of the IgG1 and IgG2a isotypes of 34–3C and 4C8 antibodies, where complement was not or only partially involved, respectively. The remarkably different capacities of four different IgG isotypes of low and high affinity anti-erythrocyte autoantibodies to activate FcγR-bearing effector cells and complement in vivo demonstrate the role of autoantibody affinity maturation and of IgG isotype switching in autoantibody-mediated pathology.

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Role of Thromboxane A2 as a Mediator of Platelet-Activating-Factor-Induced Aggregation of Human Platelets

Clinical Science ◽

10.1042/cs0770099 ◽

1989 ◽

Vol 77 (1) ◽

pp. 99-103 ◽

Cited By ~ 12

Author(s):

R. K. McCulloch ◽

J. Summers ◽

R. Vandongen ◽

I. L. Rouse

Keyword(s):

Platelet Aggregation ◽

Platelet Activating Factor ◽

Thromboxane A2 ◽

Human Platelets ◽

Minor Role ◽

A Minor ◽

Induced Aggregation

1. At present it is unclear whether platelet-activating-factor (PAF)-induced aggregation is mediated by thromboxane. To obtain further information about this event we have compared the affects of aspirin on platelet aggregation and secretion induced by PAF and collagen. 2. Collagen and PAF induced aggregation and secretion in human platelets in a dose-related manner. 3. Aspirin inhibited the magnitude of both platelet aggregation and secretion induced by PAF and collagen, but the degree of inhibition was much greater for collagen. 4. Aspirin strongly inhibited the aggregation rate of collagen-induced platelet aggregation, but had no measurable effect on the rate of PAF-induced aggregation. 5. Inconsistencies reported in previous studies of the effect of aspirin on PAF-induced platelet aggregation may be explained, in part, by the doses of PAF used and the method of inactivating cyclo-oxygenase (in vitro compared with in vivo). 6. Our results suggest that the initial events of PAF-induced aggregation are independent of thromboxane A2 formation and that thromboxane A2 plays only a minor role in the later phase of PAF-induced aggregation.

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Thrombocytopenia Induced in Mice by Thromboplastin Infusion – Essential Role of the Third Complement Component

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646750 ◽

1978 ◽

Vol 39 (03) ◽

pp. 733-742

Author(s):

Luis A Giraudo ◽

Agustin P Dalmasso

Keyword(s):

Blood Platelet ◽

Total Serum ◽

Minor Role ◽

Slight Reduction ◽

Experimental Conditions ◽

Slow Infusion ◽

A Minor ◽

Deficient Mice

SummaryStudies were performed in mice to investigate the effects of the slow infusion of brain thromboplastin (tissue factor) on blood platelet levels. Thromboplastin caused pronounced thrombocytopenia in all strains of mice tested without histological evidence of intravascular coagulation. The role of the complement system in the thrombocytopenic response to thromboplastin administration was evaluated by using complement-deficient animals. Depending on experimental conditions, the degree of platelet reduction in C5-deficient mice was similar to or significantly lower than in normocomplementemic animals. C5-deficient mice reconstituted with mouse plasma or purified human C5 had a thrombocytopenic reaction identical to that of normocomplementemic controls. The thrombocytopenic response of B10.D2/new and old line mice could be abrogated by inactivating C3 with cobra venom factor prior to the administration of thromboplastin. We conclude that in mice C3 plays a central role in the thrombocytopenia induced by thromboplastin infusion, while C5 (and/or other late acting components) plays only a minor role. In vivo activation of complement by thromboplastin was indicated by the finding that thromboplastin infusion in B10.D2/new mice caused a significant reduction in total serum hemolytic complement and a slight reduction in C3 measured immunochemically. The platelet counts of uninjected B10.D2/new mice were slightly but significantly higher than in B10.D2/old mice.

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The Effect of Path Length and Display Size on Memory for Spatial Information

Experimental Psychology (formerly Zeitschrift für Experimentelle Psychologie) ◽

10.1027/1618-3169/a000137 ◽

2012 ◽

Vol 59 (3) ◽

pp. 147-152 ◽

Cited By ~ 11

Author(s):

Katherine Guérard ◽

Sébastien Tremblay

Keyword(s):

Path Length ◽

Potential Role ◽

Spatial Information ◽

Recall Performance ◽

Minor Role ◽

Length Effect ◽

Serial Memory ◽

Fixed Reference ◽

A Minor

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

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Effects of Myo-inositol Alone and in Combination with Seleno-Lmethionine on Cadmium-Induced Testicular Damage in Mice

Current Molecular Pharmacology ◽

10.2174/1874467212666190620143303 ◽

2019 ◽

Vol 12 (4) ◽

pp. 311-323 ◽

Cited By ~ 3

Author(s):

Salvatore Benvenga ◽

Antonio Micali ◽

Giovanni Pallio ◽

Roberto Vita ◽

Consuelo Malta ◽

...

Keyword(s):

Structural Changes ◽

Natural Antioxidants ◽

Minor Role ◽

Positive Role ◽

Testosterone Levels ◽

Tnf Α ◽

Testicular Lesions ◽

A Minor ◽

Immunohistochemical Analyses

Background: Cadmium (Cd) impairs gametogenesis and damages the blood-testis barrier. Objective: As the primary mechanism of Cd-induced damage is oxidative stress, the effects of two natural antioxidants, myo-inositol (MI) and seleno-L-methionine (Se), were evaluated in mice testes. Methods: Eighty-four male C57 BL/6J mice were divided into twelve groups: 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); Se (0.2 mg/kg/day per os); Se (0.4 mg/kg/day per os); MI (360 mg/kg/day per os); MI plus Se (0.2 mg/kg/day); MI plus Se (0.4 mg/kg/day); CdCl2 (2 mg/kg/day i.p.) plus vehicle; CdCl2 plus MI; CdCl2 plus Se (0.2 mg/kg/day); CdCl2 plus Se (0.4 mg/kg/day); CdCl2 plus MI plus Se (0.2 mg/kg/day); and CdCl2 plus MI plus Se (0.4 mg/kg/day). After 14 days, testes were processed for biochemical, structural and immunohistochemical analyses. Results: CdCl2 increased iNOS and TNF-α expression and Malondialdehyde (MDA) levels, lowered glutathione (GSH) and testosterone, induced testicular lesions, and almost eliminated claudin-11 immunoreactivity. Se administration at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression, maintained GSH, MDA and testosterone levels, structural changes and low claudin-11 immunoreactivity. MI alone or associated with Se at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression and MDA levels, increased GSH and testosterone levels, ameliorated structural organization and increased claudin-11 patches number. Conclusion: We demonstrated a protective effect of MI, a minor role of Se and an evident positive role of the association between MI and Se on Cd-induced damages of the testis. MI alone or associated with Se might protect testes in subjects exposed to toxicants, at least to those with behavior similar to Cd.

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Tcf4 Is Involved in Subset Specification of Mesodiencephalic Dopaminergic Neurons

Biomedicines ◽

10.3390/biomedicines9030317 ◽

2021 ◽

Vol 9 (3) ◽

pp. 317

Author(s):

Simone Mesman ◽

Iris Wever ◽

Marten P. Smidt

Keyword(s):

Neuronal Differentiation ◽

Dopaminergic Neurons ◽

Neuronal Development ◽

Neuronal Population ◽

Minor Role ◽

Initial Increase ◽

E Box ◽

A Minor ◽

Bhlh Factor

During development, mesodiencephalic dopaminergic (mdDA) neurons form into different molecular subsets. Knowledge of which factors contribute to the specification of these subsets is currently insufficient. In this study, we examined the role of Tcf4, a member of the E-box protein family, in mdDA neuronal development and subset specification. We show that Tcf4 is expressed throughout development, but is no longer detected in adult midbrain. Deletion of Tcf4 results in an initial increase in TH-expressing neurons at E11.5, but this normalizes at later embryonic stages. However, the caudal subset marker Nxph3 and rostral subset marker Ahd2 are affected at E14.5, indicating that Tcf4 is involved in correct differentiation of mdDA neuronal subsets. At P0, expression of these markers partially recovers, whereas expression of Th transcript and TH protein appears to be affected in lateral parts of the mdDA neuronal population. The initial increase in TH-expressing cells and delay in subset specification could be due to the increase in expression of the bHLH factor Ascl1, known for its role in mdDA neuronal differentiation, upon loss of Tcf4. Taken together, our data identified a minor role for Tcf4 in mdDA neuronal development and subset specification.

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The role of heredity in cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.4.527 ◽

1989 ◽

Vol 7 (4) ◽

pp. 527-540 ◽

Cited By ~ 19

Author(s):

E G Levine ◽

R A King ◽

C D Bloomfield

Keyword(s):

Molecular Mechanisms ◽

Familial Cancer ◽

Tumor Development ◽

Future Research ◽

Minor Role ◽

Research Activity ◽

Environmental Interactions ◽

Future Research Directions ◽

A Minor

Heredity is generally felt to play a minor role in the development of cancer. This review critically examines this assumption. Topics discussed include evidence for heritable predisposition in animals and humans; the potential importance of genetic-environmental interactions; approaches that are being used to successfully locate genes responsible for heritable predisposition; comparability of genetic findings among heritable and corresponding sporadic malignancies; and future research directions. Breast, colon, and lung cancer are used to exemplify clinical and research activity in familial cancer; clinical phenotypes, segregation and linkage analyses, models for environmental interactions with inherited traits, and molecular mechanisms of tumor development are discussed. We conclude that the contribution of heredity to the cancer burden is greater than generally accepted, and that study of heritable predisposition will continue to reveal carcinogenic mechanisms important to the development of all cancers.

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