Long and short sleep duration are both associated with suicidal ideation in Korean employees

Sleep and Biological Rhythms - The aim of this study was to investigate the association between self-reported sleep duration and suicidal ideation in Korean employees. We studied 204,629 employees...     

SUMOylation negatively regulates the stability of CHFR tumor suppressor

CHFR ubiquitin ligase acts as a checkpoint upon DNA damage and its functional inactivation is one of key characteristics of tumor development and metastasis. Despite the crucial role in maintaining genome integrity and cell cycle progression, little is known how CHFR stability is regulated. Here, we showed that CHFR is covalently modified by SUMO-1 at lysine 663 and subsequently destabilized by ubiquitin–proteasome system. While CHFR^K663R substitution mutation does not alter its subcellular localization, SUMOylation-defective CHFR^K663R-stable cells exhibit substantial growth suppression due to the increased stability of CHFR^K663R. Moreover, protein level of CHFR, not CHFR^K663R, is rapidly declined under SUMOylation-promoting conditions, and SENP2 deSUMOylating enzyme reverses its SUMO-modification. Collectively, we demonstrated that CHFR stability is regulated by SUMOylation-dependent proteasomal degradation. Therefore, our study underscores the importance of CHFR SUMOylation as a new regulatory mechanism of CHFR and highlights the emerging role of SUMOylation in modulating protein stability.     

Escherichia coli alpha-ketoglutarate permease is a constitutively expressed proton symporter.

Escherichia coli kgtP which maps at 56.5 min codes for alpha-ketoglutarate permease (KgtP). This protein, expressed from the cloned gene using the T7 polymerase system and [35S]methionine labeling, fractionated with cell membranes. Right-side-out (RSO) membrane vesicles prepared from a kgtP negative mutant strain did not transport alpha-ketoglutarate, but RSO vesicles from the same strain expressing KgtP from a transforming plasmid transported alpha-ketoglutarate effectively as measured by uptake of the 14C-labeled substrate. E. coli JC7623 strain grown in M9 minimal medium with glucose, glycerol, or alpha-ketoglutarate as carbon source contained a 1.3-kilobase RNA which hybridized to nick-translated kgtP probe. In addition, strain MC1061 cultures grown under these same conditions were all capable of transporting alpha-ketoglutarate, demonstrating that KgtP is constitutively expressed. The Km and Vmax of KgtP assayed in strain MC1061 vesicles were 13-46 microM and 8 nmol/min/mg protein, respectively. Uncouplers that permeabilized the membrane to protons inhibited alpha-ketoglutarate transport into energized vesicles, and the addition of alpha-ketoglutarate to vesicle suspensions under non-energized conditions resulted in an increase in pH. These results indicate that KgtP is an alpha-ketoglutarate-proton symporter.     

Hypoglycemia and Medical Expenses in Patients with Type 2 Diabetes Mellitus: An Analysis Based on the Korea National Diabetes Program Cohort

Background and Aims

Hypoglycemia is one of the most important adverse events in individuals with type 2 diabetes mellitus (T2DM). However, hypoglycemia-related events are usually overlooked and have been documented less in clinical practice.

Materials and Methods

We evaluated the incidence, clinical characteristics, and medical expenses of hypoglycemia related events in T2DM patients based on the Korea National Diabetes Program (KNDP), which is the largest multi-center, prospective cohort in Korea (n = 4,350). For accurate outcomes, the KNDP data were merged with claims data from the Health Insurance Review and Assessment Service (HIRA) of Korea.

Results

During a median follow-up period of 3.23 years (95% CI: 3.14, 3.19), 88 subjects (2.02%) were newly diagnosed with hypoglycemia, and the incidence of hypoglycemia was 6.44 cases per 1,000 person-years (PY). Individuals with hypoglycemia were significantly older (59.7±10.7 vs. 53.3±10.4 years, p < 0.001), had more hospital visits (121.94±126.88 days/PY, p < 0.001), had a longer hospital stays (16.13±29.21 days/PY, p < 0.001), and incurred greater medical costs ($2,447.56±4,056.38 vs. $1,336.37±3,403.39 /PY, p < 0.001) than subjects without hypoglycemia.

Conclusion

Hypoglycemia-related events were infrequently identified among the medical records of T2DM subjects. However, they were associated significantly with poor clinical outcomes, and thus, hypoglycemia could have a substantial burden on the Korean national healthcare system.     

Valproic acid inhibits neural progenitor cell death by activation of NF-κB signaling pathway and up-regulation of Bcl-XL

Background  

At the beginning of neurogenesis, massive brain cell death occurs and more than 50% of cells are eliminated by apoptosis along with neuronal differentiation. However, few studies were conducted so far regarding the regulation of neural progenitor cells (NPCs) death during development. Because of the physiological role of cell death during development, aberration of normal apoptotic cell death is detrimental to normal organogenesis.