Insight into mechanism of in vitro insulin secretion increase induced by antipsychotic clozapine: Role of FOXA1 and mitochondrial citrate carrier

2013 ◽  
Vol 23 (8) ◽  
pp. 978-987 ◽  
Author(s):  
A. Menga ◽  
V. Infantino ◽  
F. Iacobazzi ◽  
P. Convertini ◽  
F. Palmieri ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Citrate Carrier ◽  
In Vitro Insulin Secretion ◽  
Insight Into

scholarly journals Dissemination of Rat Cytomegalovirus through Infected Granulocytes and Monocytes In Vitro and In Vivo

2003 ◽  
Vol 77 (20) ◽  
pp. 11274-11278 ◽  
Author(s):  
B. W. A. van der Strate ◽  
J. L. Hillebrands ◽  
S. S. Lycklama à Nijeholt ◽  
L. Beljaars ◽  
C. A. Bruggeman ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Systemic Infection ◽  
Insight Into

ABSTRACT The role of leukocytes in the in vivo dissemination of cytomegalovirus was studied in this experiment. Rat cytomegalovirus (RCMV) could be transferred to rat granulocytes and monocytes by cocultivation with RCMV-infected fibroblasts in vitro. Intravenous injection of purified infected granulocytes or monocytes resulted in a systemic infection in rats, indicating that our model is a powerful tool to gain further insight into CMV dissemination and the development of new antivirals.

A Novel Insight into the Role of Entry Tears in Type B Aortic Dissection: Pressure Measurements in an in Vitro Model

2017 ◽  
Vol 40 (10) ◽  
pp. 563-574 ◽  
Author(s):  
Stefania Marconi ◽  
Ettore Lanzarone ◽  
Hector De Beaufort ◽  
Michele Conti ◽  
Santi Trimarchi ◽  
...  
Keyword(s):  
False Lumen ◽  
Patient Characteristics ◽  
Acute Type ◽  
Type B ◽  
Type B Dissection ◽  
Vitro Model ◽  
Insight Into

Introduction Predicting aortic growth in acute type B dissection is fundamental in planning interventions. Several factors are considered to be growth predictors in the literature and, among them, size and location of entry tears have been recognized to particularly influence the false lumen pressure. In this study, we develop an in vitro setting to analyze the actual impact of size and location of the entry tears on false lumen pressure, in the absence of other confounding factors such as the deformability of the aortic wall. Methods We formalize some indexes that synthetically describe the false lumen pressure with respect to the true lumen pressure. Then, we experimentally derive their values in several configurations of the in vitro setting, and we look for trends in the indexes with respect to the size and location of entry tears. Results: Results show that the tears have a relevant impact on the false lumen pressure, but that their size and location alone are not enough to explain the phenomena observed in vivo. Conclusions To predict the behavior of acute type B dissection, we therefore recommend not limiting to size and location, as many effects may derive from the interactions between these parameters and other patient characteristics.

scholarly journals Systematic characterization and genetic interaction analysis of adhesins in Candida albicans virulence

2020 ◽  
Author(s):  
Sierra Rosiana ◽  
Liyang Zhang ◽  
Grace H. Kim ◽  
Alexey V. Revtovich ◽  
Arjun Sukumaran ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Genetic Interaction ◽  
Interaction Analysis ◽  
Genetic Interactions ◽  
Fungal Virulence ◽  
C Elegans ◽  
Adhesin Proteins ◽  
Insight Into

AbstractCandida albicans is a microbial fungus that exists as a commensal member of the human microbiome and an opportunistic pathogen. Cell surface-associated adhesin proteins play a crucial role in C. albicans’ ability to undergo cellular morphogenesis, develop robust biofilms, colonize, and cause infection in a host. However, a comprehensive analysis of the role and relationships between these adhesins has not been explored. We previously established a CRISPR-based platform for efficient generation of single- and double-gene deletions in C. albicans, which was used to construct a library of 144 mutants, comprising 12 unique adhesin genes deleted singly, or in every possible combination of double deletions. Here, we exploit this adhesin mutant library to explore the role of adhesin proteins in C. albicans virulence. We perform a comprehensive, high-throughput screen of this library, using Caenorhabditis elegans as a simplified model host system, which identified mutants critical for virulence and significant genetic interactions. We perform follow-up analysis to assess the ability of high- and low-virulence strains to undergo cellular morphogenesis and form biofilms in vitro, as well as to colonize the C. elegans host. We further perform genetic interaction analysis to identify novel significant negative genetic interactions between adhesin mutants, whereby combinatorial perturbation of these genes significantly impairs virulence, more than expected based on virulence of the single mutant constituent strains. Together, this yields important new insight into the role of adhesins, singly and in combinations, in mediating diverse facets of virulence of this critical fungal pathogen.SummaryCandida albicans is a human fungal pathogen and cause of life-threatening systemic infections. Cell surface-associated adhesins play a central role in this pathogen’s ability to establish infection. Here, we provide a comprehensive analysis of adhesin factors, and their role in fungal virulence. Exploiting a high-throughput workflow, we screened an adhesin mutant library using C. elegans as a simple model host, and identified mutants and genetic interactions involved in virulence. We found that adhesin mutants are impaired in in vitro pathogenicity, irrespective of their virulence. Together, this work provides new insight into the role of adhesin factors in mediating fungal virulence.

scholarly journals Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Brianna J. Klein ◽  
Suk Min Jang ◽  
Catherine Lachance ◽  
Wenyi Mi ◽  
Jie Lyu ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Memory Impairment ◽  
Target Genes ◽  
Epigenetic Mark ◽  
Mechanistic Insight ◽  
Genomic Analyses ◽  
Insight Into

Abstract Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORFDPF). The crystal structure of MORFDPF in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORFDPF in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORFDPF with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription.

scholarly journals Wingless-Type MMTV Integration Site Family Member 5a Is a Key Secreted Islet Stellate Cell-Derived Product that Regulates Islet Function

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Xu ◽  
Jun Liang ◽  
H. F. Geng ◽  
Jun Lu ◽  
Rui Li ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Family Member ◽  
Stellate Cell ◽  
Integration Site ◽  
Islet Function ◽  
Insulin Production ◽  
The Status ◽  
Secretory Products

Background. Emerging evidence suggests that T2DM is attributable to the dysfunction of β-cells and the activation of islet stellate cells (ISCs). The wingless-type MMTV integration site family member 5a (Wnt5a)/frizzled 5 (Fzd5) signalling pathway might take part in this process. Our study is aimed at defining the status of ISCs during β-cell insulin secretion homeostasis by determining the role of the Wnt5a protein in the regulation of insulin production. We examined the effects of the status of ISCs on β-cell insulin secretion in normoglycemic db/m and hyperglycaemic db/db mice. Methods. iTRAQ protein screening and RNA interference were used to determine novel ISC-derived secretory products that may use other mechanisms to influence the function of islets. Results. We showed a significant reduction in insulin secretion by β-cells in vitro when they were cocultured with db/db ISCs compared to when they were cocultured with ISCs isolated from normoglycemic db/m mice; in addition, both Wnt5a and its receptor Fzd5 were more highly expressed by quiescent ISCs than by activated db/db ISCs. Treatment with exogenous Wnt5a increased the secretion of insulin in association with the deactivation of ISCs. Conclusion. Our observations revealed that the Wnt5a protein is a key effector of ISC-mediated improvement in islet function.

scholarly journals A possible role of plasma glutathione in glucose-mediated insulin secretion: in vitro and in vivo studies in rats

Diabetologia ◽  
1989 ◽  
Vol 32 (11) ◽  
Author(s):  
H.P.T. Ammon ◽  
S. Klumpp ◽  
A. Fu� ◽  
E.J. Verspohl ◽  
H. Jaeschke ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
In Vivo Studies ◽  
Plasma Glutathione ◽  
Insulin Secretion In Vitro

scholarly journals Chronic Microcystin-LR Exposure Induces Hepatocarcinogenesis via Increased Gankyrin in Vitro and in Vivo

2018 ◽  
Vol 49 (4) ◽  
pp. 1420-1430 ◽  
Author(s):  
Lixiong He ◽  
Yujing Huang ◽  
Qiaonan Guo ◽  
Hui Zeng ◽  
Chuanfen Zheng ◽  
...  
Keyword(s):  
Low Dose ◽  
Soft Agar ◽  
Tumor Formation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
L02 Cells ◽  
Insight Into

Background/Aims: Our recent study indicated that the serum microcystin-LR (MC-LR) level is positively linked to the risk of human hepatocellular carcinoma (HCC). Gankyrin is over-expressed in cancers and mediates oncogenesis; however, whether MC-LR induces tumor formation and the role of gankyrin in this process is unclear. Methods: We induced malignant transformation of L02 liver cells via 35 passages with exposure to 1, 10, or 100 nM MC-LR. Wound healing, plate and soft agar colony counts, and nude mice tumor formation were used to evaluate the tumorigenic phenotype of MC-LR-treated cells. Silencing gankyrin was used to confirm its function. We established a 35-week MC-LR exposure rat model by twice weekly intraperitoneal injection with 10 μg/kg body weight. In addition, 96 HCC patients were tested for tumor tissue gankyrin expression and serum MC-LR levels. Results: Chronic low-dose MC-LR exposure increased proliferation, mobility, clone and tumor formation abilities of L02 cells as a result of gankyrin activation, while silencing gankyrin inhibited the carcinogenic phenotype of MC-LR-treated cells. MC-LR also induced neoplastic liver lesions in Sprague-Dawley rats due to up-regulated gankyrin. Furthermore, a trend of increased gankyrin was observed in humans exposed to MC-LR. Conclusion: These results suggest that MC-LR induces hepatocarcinogenesis in vitro and in vivo by increasing gankyrin levels, providing new insight into MC-LR carcinogenicity studies.

Hyperglycemic athymic nude mice: factors affecting in vitro insulin secretion

1992 ◽  
Vol 263 (6) ◽  
pp. E1131-E1133
Author(s):  
A. Zeidler ◽  
P. Edwards ◽  
J. Goldman ◽  
S. Kort ◽  
W. P. Meehan ◽  
...  
Keyword(s):  
Animal Model ◽  
Insulin Secretion ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Factors Affecting ◽  
In Vitro Insulin Secretion ◽  
Insulin Secretion In Vitro ◽  
And Control

The strain of athymic nude male mice (ANM) developed at the University of Southern California (USC) exhibits spontaneous hyperglycemia and relative hypoinsulinemia in vivo. To investigate factors that influence insulin secretion in this animal model of non-insulin-dependent diabetes mellitus, we utilized the isolated perfused mouse pancreas of the ANM-USC and control BALB/c mice. We compared in vitro glucose-induced insulin secretion in ANM-USC and control mice, inhibition of secretion by somatostatin, and variability of insulin secretion over the two-year period it took to complete these experiments. Glucose-induced insulin secretion from the isolated pancreas was biphasic in both ANM-USC and controls. Insulin secretion was quantitatively equal to or greater than control mice, depending on the phase of secretion analyzed and the source of the control mice. In contrast to pancreases of control mice, insulin secretion from ANM-USC pancreases was relatively resistant to inhibition of insulin secretion by somatostatin. Variability in insulin secretion over the two years in which these experiments were performed was greater from pancreases of control than that observed from pancreases of the ANM-USC. The hyperglycemic ANM-USC mouse does not demonstrate diminished insulin secretion in vitro yet is relatively hypoinsulinemic in vivo. Thus circulating factors other than somatostatin might contribute to the insulinopenic stage in this animal model.

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