Calyculin A from Discodermia Calyx Is a Dual ActionToxin that Blocks Calcium Influx and Inhibits Protein Ser/Thr Phosphatases

Calyculin A (Caly A) is cell permeable toxin widely used in cell biology research as an inhibitor of type 1 and type 2A protein Ser/Thr phosphatases of the PPP family. Here we tested effects of low concentrations of Caly A on proliferation of human cancer and non-cancer cell lines. We found that long-term 0.3 nM Caly A prevented G1 to S phase cell cycle progression in human Hs-68 fibroblasts and ARPE19 epithelial cells, but not human breast cancer MDA-MB-468, MDA-MB-231 and MCF7 cells. These conditions produced no change in cyclin D1 levels or in the phosphorylation of endogenous proteins. However, acute application of 0.3 nM Caly A blocked serum-induced increase in intracellular calcium levels in Hs-68 fibroblasts, but not in MDA-MB-468 breast cancer cells. We propose that subnanomolar Caly A prevents cell cycle progression because it blocks calcium uptake by fibroblasts. This probably involves non-selective cation channels and cancer cell proliferation was not affected because calcium enters these cells by other channels. Our results suggest that calyculin A has dual actions and acts as a channel blocker, in addition to its well-established effects as a phosphatase inhibitor.     

LPS induces apoptosis in macrophages mostly through the autocrine production of TNF-alpha

The deleterious effects of lipopolysaccharide (LPS) during endotoxic shock are associated with the secretion of tumor necrosis factor (TNF) and the production of nitric oxide (NO), both predominantly released by tissue macrophages. We analyzed the mechanism by which LPS induces apoptosis in bone marrow-derived macrophages (BMDM). LPS-induced apoptosis reached a plateau at about 6 hours of stimulation, whereas the production of NO by the inducible NO-synthase (iNOS) required between 12 and 24 hours. Furthermore, LPS-induced early apoptosis was only moderately reduced in the presence of an inhibitor of iNOS or when using macrophages from iNOS -/-mice. In contrast, early apoptosis was paralleled by the rapid secretion of TNF and was almost absent in macrophages from mice deficient for one (p55) or both (p55 and p75) TNF-receptors. During the late phase of apoptosis (12-24 hours) NO significantly contributed to the death of macrophages even in the absence of TNF-receptor signaling. NO-mediated cell death, but not apoptosis induced by TNF, correlated with the induction of p53 and Bax genes. Thus, LPS-induced apoptosis results from 2 independent mechanisms: first and predominantly, through the autocrine secretion of TNF-alpha (early apoptotic events), and second, through the production of NO (late phase of apoptosis). (Blood. 2000;95:3823-3831)     

Brain age estimation reveals older adults’ accelerated senescence after traumatic brain injury

GeroScience - Adults aged 60 and over are most vulnerable to mild traumatic brain injury (mTBI). Nevertheless, the extent to which chronological age (CA) at injury affects TBI-related brain aging...     

External Quality Assessment of Blood Glucose Monitors: Quality Control of Self-Monitoring of Blood Glucose: Why and How?

The control of analytical quality of self-monitoring of blood glucose (SMBG) is recommended as a routine procedure in diabetes management. This control procedure should be easily accessible to patients, convenient, not time-consuming, and provide a reliable assessment of glucose meter performance. Optimally it should be located in the diabetes outpatient clinic. Presently there are two approaches to carrying out SMBG quality control. The first is based on the comparison of results obtained by a controlled glucose meter and use of the laboratory method or point-of-care testing device as a surrogate reference analyzer. The second one is a traditionally organized external quality assessment scheme with use of a dedicated control material, which is distributed to all participants. The recommended allowable meter error in SMBG can be realistically set at 10%.     

Cognitive dysfunction in children with brain tumors at diagnosis

Background

Survivors of brain tumors have a high risk for a wide range of cognitive problems. These dysfunctions are caused by the lesion itself and its surgical removal, as well as subsequent treatments (chemo‐ and/or radiation therapy). Multiple recent studies have indicated that children with brain tumors (BT) might already exhibit cognitive problems at diagnosis, i.e., before the start of any medical treatment. The aim of the present study was to investigate the baseline neuropsychological profile in children with BT compared to children with an oncological diagnosis not involving the central nervous system (CNS).

Methods

Twenty children with BT and 27 children with an oncological disease without involvement of the CNS (age range: 6.1–16.9 years) were evaluated with an extensive battery of neuropsychological tests tailored to the patient's age. Furthermore, the child and his/her parent(s) completed self‐report questionnaires about emotional functioning and quality of life. In both groups, tests were administered before any therapeutic intervention such as surgery, chemotherapy, or irradiation. Groups were comparable with regard to age, gender, and socioeconomic status.

Results

Compared to the control group, patients with BTs performed significantly worse in tests of working memory, verbal memory, and attention (effect sizes between 0.28 and 0.47). In contrast, the areas of perceptual reasoning, processing speed, and verbal comprehension were preserved at the time of measurement.

Conclusion

Our results highlight the need for cognitive interventions early in the treatment process in order to minimize or prevent academic difficulties as patients return to school. Pediatr Blood Cancer 2015;62:1805–1812. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc.     

Diversity and education of the nursing workforce 2006–2016

Background

The Institute of Medicine (IOM) report, The Future of Nursing, included recommendations to increase nurse diversity, the percent of nurses obtaining a bachelor’s degree, and inter-professional education.