The Potentially Direct Role of Intracellular Calcium Overload in the Electrophysiology of Cardiac Ischemia

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.

Download Full-text

The Costs of Seeking Shelter for Renters With Discrediting Background Records

City and Community ◽

10.1177/15356841211012483 ◽

2021 ◽

pp. 153568412110124

Author(s):

Anna Reosti

Keyword(s):

Financial Burden ◽

Rental Housing ◽

Application Process ◽

Direct Role ◽

Screening Process ◽

Housing Search ◽

Housing Options ◽

Depth Interviews ◽

Rental Housing Market

This study illuminates an understudied pathway through which disadvantage is reproduced in the rental housing market: the housing search, application, and tenant screening process. Using in-depth interviews with 25 housing-seekers with criminal conviction records, past evictions, and damaged credit histories, this article examines the direct role of the rental housing search and application process in reproducing economic precarity and social disadvantage among renters with discrediting background records, beyond delimiting their housing options. Its findings suggest that navigating the housing search from a position of acute market disadvantage comes with significant costs for this population, including the financial burden of repeated application fees and the psychological strains associated with the specter of indefinite housing insecurity. The findings also demonstrate how the housing search process may undermine the willingness of stigmatized renters to contest exploitative or unlawful rental practices by reinforcing awareness of their degraded status in the rental market.

Download Full-text

Regulation of intracellular calcium in N1E-115 neuroblastoma cells: the role of Na+/Ca2+exchange

AJP Cell Physiology ◽

10.1152/ajpcell.00182.2001 ◽

2002 ◽

Vol 282 (5) ◽

pp. C1000-C1008 ◽

Cited By ~ 3

Author(s):

Kara L. Kopper ◽

Joseph S. Adorante

Keyword(s):

Membrane Potential ◽

Intracellular Calcium ◽

Normal Cell ◽

Buffer Capacity ◽

Neuroblastoma Cells ◽

Fold Increase ◽

Scorpion Venom ◽

Reverse Mode ◽

Intracellular Ca

In fura 2-loaded N1E-115 cells, regulation of intracellular Ca2+ concentration ([Ca2+]i) following a Ca2+ load induced by 1 μM thapsigargin and 10 μM carbonylcyanide p-trifluoromethyoxyphenylhydrazone (FCCP) was Na+ dependent and inhibited by 5 mM Ni2+. In cells with normal intracellular Na+ concentration ([Na+]i), removal of bath Na+, which should result in reversal of Na+/Ca2+exchange, did not increase [Ca2+]i unless cell Ca2+ buffer capacity was reduced. When N1E-115 cells were Na+ loaded using 100 μM veratridine and 4 μg/ml scorpion venom, the rate of the reverse mode of the Na+/Ca2+ exchanger was apparently enhanced, since an ∼4- to 6-fold increase in [Ca2+]ioccurred despite normal cell Ca2+ buffering. In SBFI-loaded cells, we were able to demonstrate forward operation of the Na+/Ca2+ exchanger (net efflux of Ca2+) by observing increases (∼ 6 mM) in [Na+]i. These Ni2+ (5 mM)-inhibited increases in [Na+]i could only be observed when a continuous ionomycin-induced influx of Ca2+ occurred. The voltage-sensitive dye bis-(1,3-diethylthiobarbituric acid) trimethine oxonol was used to measure changes in membrane potential. Ionomycin (1 μM) depolarized N1E-115 cells (∼25 mV). This depolarization was Na+dependent and blocked by 5 mM Ni2+ and 250–500 μM benzamil. These data provide evidence for the presence of an electrogenic Na+/Ca2+ exchanger that is capable of regulating [Ca2+]i after release of Ca2+ from cell stores.

Download Full-text

mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells

Journal of Endocrinology ◽

10.1530/joe-12-0351 ◽

2012 ◽

Vol 216 (1) ◽

pp. 21-29 ◽

Cited By ~ 21

Author(s):

Olivier Le Bacquer ◽

Gurvan Queniat ◽

Valery Gmyr ◽

Julie Kerr-Conte ◽

Bruno Lefebvre ◽

...

Keyword(s):

Insulin Secretion ◽

Cell Function ◽

Antagonistic Effect ◽

Dominant Negative ◽

Insulin Content ◽

Insulin Biosynthesis ◽

Direct Role ◽

Β Cell Function ◽

Glucose Stimulated Insulin Secretion

Regulated associated protein of mTOR (Raptor) and rapamycin-insensitive companion of mTOR (rictor) are two proteins that delineate two different mTOR complexes, mTORC1 and mTORC2 respectively. Recent studies demonstrated the role of rictor in the development and function of β-cells. mTORC1 has long been known to impact β-cell function and development. However, most of the studies evaluating its role used either drug treatment (i.e. rapamycin) or modification of expression of proteins known to modulate its activity, and the direct role of raptor in insulin secretion is unclear. In this study, using siRNA, we investigated the role of raptor and rictor in insulin secretion and production in INS-1 cells and the possible cross talk between their respective complexes, mTORC1 and mTORC2. Reduced expression of raptor is associated with increased glucose-stimulated insulin secretion and intracellular insulin content. Downregulation of rictor expression leads to impaired insulin secretion without affecting insulin content and is able to correct the increased insulin secretion mediated by raptor siRNA. Using dominant-negative or constitutively active forms of Akt, we demonstrate that the effect of both raptor and rictor is mediated through alteration of Akt signaling. Our finding shed new light on the mechanism of control of insulin secretion and production by the mTOR, and they provide evidence for antagonistic effect of raptor and rictor on insulin secretion in response to glucose by modulating the activity of Akt, whereas only raptor is able to control insulin biosynthesis.

Download Full-text

Inhibition of hepatic deiodination of thyroxine is caused by selenium deficiency in rats

Biochemical Journal ◽

10.1042/bj2480443 ◽

1987 ◽

Vol 248 (2) ◽

pp. 443-447 ◽

Cited By ~ 99

Author(s):

G J Beckett ◽

S E Beddows ◽

P C Morrice ◽

F Nicol ◽

J R Arthur

Keyword(s):

Thyroid Hormones ◽

Production Rate ◽

Selenium Deficiency ◽

Enzyme Complex ◽

Measurable Effect ◽

Direct Role ◽

Mechanism Of Inhibition ◽

Se Deficiency

Selenium (Se) deficiency produced up to a 14-fold decrease in hepatic tri-iodothyronine (T3) production from thyroxine (T4) in vitro. The T3 production rate could not be restored by the addition of a variety of cofactors, nor by the addition of control homogenate. The impairment in hepatic T3 production observed in Se deficiency was reflected in the concentrations of thyroid hormones circulating in plasma, T4 being increased approx. 40% and T3 being decreased by 30%. However, the fall in plasma T3 concentrations was smaller than might be expected in view of the marked decreased in T3 production. Se deficiency had no measurable effect on plasma reverse-tri-iodothyronine concentrations. The data suggest that Se deficiency produces an inhibition of both 5- and 5′-deiodination, consistent with the widely held view that these reactions are catalysed by the same enzyme complex. The mechanism of inhibition appears not be mediated by changes in thiol levels, but a direct role of Se in the activity of the deiodinase complex cannot be excluded.

Download Full-text