Glucose repression of the Escherichia coli sdhCDAB operon, revisited: regulation by the CRP·cAMP complex

Expression of the Escherichia coli sdhCDAB operon encoding the succinate dehydrogenase complex is regulated in response to growth conditions, such as anaerobiosis and carbon sources. An anaerobic repression of sdhCDAB is known to be mediated by the ArcB/A two-component system and the global Fnr anaerobic regulator. While the cAMP receptor protein (CRP) and Cra (formerly FruR) are known as key mediators of catabolite repression, they have been excluded from the glucose repression of the sdhCDAB operon. Although the glucose repression of sdhCDAB was reported to involve a mechanism dependent on the ptsG expression, the molecular mechanism underlying the glucose repression has never been clarified. In this study, we re-examined the mechanism of the sdhCDAB repression by glucose and found that CRP directly regulates expression of the sdhCDAB operon and that the glucose repression of this operon occurs in a cAMP-dependent manner. The levels of phosphorylated enzyme IIA(Glc) and intracellular cAMP on various carbon sources were proportional to the expression levels of sdhC-lacZ. Disruption of crp or cya completely abolished the glucose repression of sdhC-lacZ expression. Together with data showing correlation between the intracellular cAMP concentrations and the sdhC-lacZ expression levels in several mutants and wild type, in vitro transcription assays suggest that the decrease in the CRP·cAMP level in the presence of glucose is the major determinant of the glucose repression of the sdhCDAB operon

Retroperitoneal hematoma after coil embolization of cerebral aneurysm -A case report-

We present the case of a 57-year-old man who developed retroperitoneal hemorrhage due to unintentional arterial puncture during femoral artery cannulation for Guglielmi detachable coil embolization. On emergence from anesthesia, he developed severe hypotension. Computed tomographic angiogram of the abdomen showed retroperitoneal hematomas around the urinary bladder, liver, and spleen. Because femoral artery cannulation is a common procedure for intravascular embolization in neuroradiologic procedures, Clinicians should be aware of the development of severe hematomas as a consequence of femoral artery puncture

Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation

Vaccinia-related kinases (VRKs) are multifaceted serine/threonine kinases that play essential roles in various aspects of cell signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3-deficient mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social interaction, and impaired context-dependent spatial memory. A significant decrease in dendritic spine number and arborization were identified in the hippocampus CA1 of VRK3-deficient mice. These mice also exhibited a reduced rectification of AMPA receptor-mediated current and changes in expression of synaptic and signaling proteins, including tyrosine receptor kinase B (TrkB), Arc, and CaMKII alpha. Notably, TrkB stimulation with 7,8-dihydroxyflavone reversed the altered synaptic structure and function and successfully restored autism-like behavior in VRK3-deficient mice. These results reveal that VRK3 plays a critical role in neurodevelopmental disorders and suggest a potential therapeutic strategy for ASD.112Ysciescopu

Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Recent efforts have been made to link complex human traits and disease susceptibility to DNA copy numbers. The leptin receptor (LEPR) has been implicated in obesity and diabetes. Mutations and genetic variations of <it>LEPR </it>gene have been discovered in rodents and humans. However, the association of DNA copy number variations at the <it>LEPR </it>gene locus with human complex diseases has not been reported. In an attempt to study DNA copy number variations associated with metabolic traits and type 2 diabetes mellitus (T2DM), we targeted the <it>LEPR </it>gene locus in DNA copy number analyses.</p> <p>Results</p> <p>We identified DNA copy number variations at the <it>LEPR </it>gene locus among a Korean population using genome-wide SNP chip data, and then quantified copy numbers of the E2 DNA sequence in the first two exons overlapped between <it>LEPR </it>and <it>LEPROT </it>genes by the quantitative multiplex PCR of short fluorescent fragment (QMPSF) method. Among the non-diabetic subjects (n = 1,067), lower E2 DNA copy numbers were associated with higher fasting glucose levels in men (<it>p </it>= 1.24 × 10^-7) and women (<it>p </it>= 9.45 × 10^-5), as well as higher total cholesterol levels in men (<it>p </it>= 9.96 × 10^-7). In addition, the significant association between lower E2 DNA copy numbers and lower level of postprandial 2hr insulin was evident only in non-diabetic women, whereas some obesity-related phenotypes and total cholesterol level exhibited significant associations only in non-diabetic men. Logistic regression analysis indicated that lower E2 DNA copy numbers were associated with T2DM (odds ratio, 1.92; 95% CI, 1.26~2.96; p < 0.003) in our nested case-control study. Interestingly, the E2 DNA copy number exhibited a negative correlation with LEPR gene expression, but a positive correlation with LEPROT gene expression.</p> <p>Conclusions</p> <p>This work suggests that a structural variation at the <it>LEPR </it>gene locus is functionally associated with complex metabolic traits and the risk of T2DM.</p

Heterogeneous nuclear ribonucleoprotein (hnRNP) L promotes DNA damage-induced cell apoptosis by enhancing the translation of p53

The tumor suppressor p53 is an essential gene in the induction of cell cycle arrest, DNA repair, and apoptosis. p53 protein is induced under cellular stress, blocking cell cycle progression and inducing DNA repair. Under DNA damage conditions, it has been reported that post-transcriptional regulation of p53 mRNA contributes to the increase in p53 protein level. Here we demonstrate that heterogeneous nuclear ribonucleoprotein (hnRNP) L enhances p53 mRNA translation. We found that hnRNP L is increased and binds to the 5&apos; UTR of p53 mRNA in response to DNA damage. Increased hnRNP L caused enhancement of p53 mRNA translation. Conversely, p53 protein levels were decreased following hnRNP L knock-down, rendering them resistant to apoptosis and arrest in the G2/M phase after DNA damage. Thus, our findings suggest that hnRNP L functions as a positive regulator of p53 translation and promotes cell cycle arrest and apoptosis.11Ysciescopu

Electroacupuncture Delays Hypertension Development through Enhancing NO/NOS Activity in Spontaneously Hypertensive Rats

Using spontaneously hypertensive rats (SHR), this study investigated whether electroacupuncture (EA) could reduce early stage hypertension by examining nitric oxide (NO) levels in plasma and nitric oxide synthase (NOS) levels in the mesenteric resistance artery. EA was applied to the acupuncture point Governor Vessel 20 (GV20) or to a non-acupuncture point in the tail twice weekly for 3 weeks under anesthesia. In conscious SHR and normotensive Wistar Kyoto (WKY) rats, blood pressure was determined the day after EA treatment by the tail-cuff method. We measured plasma NO concentration, and evaluated endothelial NO syntheses (eNOS) and neuronal NOS (nNOS) protein expression in the mesenteric artery. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower after 3 weeks of GV20 treatment than EA at non-acupuncture point and no treatment control in SHR. nNOS expression by EA was significantly different between both WKY and no treatment SHR control, and EA at GV20 in SHR. eNOS expression was significantly high in EA at GV 20 compared with no treatment control. In conclusion, EA could attenuate the blood pressure elevation of SHR, along with enhancing NO/NOS activity in the mesenteric artery in SHR

Regulation of autophagic cell death by glycogen synthase kinase-3 beta in adult hippocampal neural stem cells following insulin withdrawal

Background: Neural stem cells (NSCs) hold great potential for the treatment of neurodegenerative diseases. However, programmed cell death (PCD) provoked by the harsh conditions evident in the diseased brain greatly undermines the potential of NSCs. Currently, the mechanisms of PCD that effect NSCs remain largely unknown. Results: We have previously reported that hippocampal neural stem (HCN) cells derived from the adult rat brain undergo autopahgic cell death (ACD) following insulin withdrawal without hallmarks of apoptosis despite their normal apoptotic capabilities. In this study, we demonstrate that glycogen synthase kinase 3β (GSK-3β) induces ACD in insulin-deprived HCN cells. Both pharmacological and genetic inactivation of GSK-3β significantly decreased ACD, while activation of GSK-3β increased autophagic flux and caused more cell death without inducing apoptosis following insulin withdrawal. In contrast, knockdown of GSK-3α barely affected ACD, lending further support to the critical role of GSK-3β. Conclusion: Collectively, these data demonstrate that GSK-3β is a key regulator of ACD in HCN cells following insulin withdrawal. The absence of apoptotic indices in GSK-3β-induced cell death in insulin-deprived HCN cells corroborates the notion that HCN cell death following insulin withdrawal represents the genuine model of ACD in apoptosis-intact mammalian cells and identifies GSK-3β as a key negative effector of NSC survival downstream of insulin signaling. © 2015 Ha et al.; licensee BioMed Central.1

Pediatricians and Emergency Physicians’ Recognition and Training Regarding Child Abuse

Purpose To explore the recognition levels and educational experiences of child abuse among physicians. Methods We conducted an electronic questionnaire survey of pediatricians and emergency physicians. Results Of the 245 total respondents, 63% remarked that child abuse occurred “frequently” in Korea. One hundred twenty-seven (51.8%) respondents experienced an abused child during their practice, and only 55.9% reported the event. Regarding the knowledge for obligation of report as a medical specialist, 45.7% knew where they should report the case, and 39.2% of the respondents knew the phone number of the “Child Protection Agency”. Most respondents (70.2%) answered that they had never received an education about child abuse. Some respondents answered that they had not reported a suspected abused case because they were not certain that the case was abuse and thereby felt discomfort in making the report. To enhance child abuse reports, respondents thought that an immediate intervention is necessary for the reported case. Also, they answered that their confidentialities have to be assured and that the education about child abuse is needed. Conclusion The survey results show that pediatricians and emergency physicians often do not report suspected abuse despite their suspicion of the seriousness and frequent occurrence of child abuse. Such behaviors are affected by the recognition and knowledge levels about child abuse, the experience of training for child abuse, and discomfort of the reporting process. For medical specialists’ attention and reporting of abuse, repetitive education, appropriate public relations and improvement of the reporting process are needed