Glycosylation on Stromal Interaction Molecule-1 Ca2+ sensing region enhances Store Operated Ca2+ Entry

A major intracellular calcium (Ca2+) uptake pathway in excitable and non-excitable eukaryotic cells is store-operated Ca2+ entry (SOCE). Stromal interaction molecule-1 (STIM1) is the key regulator of SOCE and responds to changes in endoplasmic reticulum (ER)-stored Ca2+ through luminal sensing machinery composed of EF-hand and SAM domains (EFSAM). EFSAM can undergo N-glycosylation at Asn131 and Asn171 sites; however, the exact molecular and functional effects of N-glycosylation are unclear. By establishing a site-specific chemical approach to covalently linking glucose to EFSAM and subsequently examining EFSAM biophysical properties, I found that this modification enhances STIM1 activation through localized structural perturbations, decreased Ca2+ binding affinity, reduced stability and enhanced oligomerization. Further, Ca2+ influx via SOCE in HEK293 cells co-expressing Orai1 and STIM1 was diminished when N-glycosylation was blocked. Collectively, my data suggests that N-glycosylation enhances EFSAM response to ER Ca2+ depletion thereby augmenting the role of STIM1 as the ON/OFF regulator of SOCE

A novel de novo mutation in the serine-threonine kinase STK11 gene in a Korean patient with Peutz-Jeghers syndrome

BACKGROUND: Peutz-Jeghers syndrome (PJS) is an unusual autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple gastrointestinal hamartomatous polyps. Patients with PJS are at an increased risk of developing multi-organ cancer, most frequently those involving the gastrointestinal tract. Germline mutation of the STK11 gene, which encodes a serine-threonine kinase, is responsible for PJS. METHODS: Using DNA samples obtained from the patient and his family members, we sequenced nine exons and flanking intron regions of the STK11 gene using polymerase chain reaction (PCR) and direct sequencing. RESULTS: Sequencing of the STK11 gene in the proband of the family revealed a novel 1-base pair deletion of guanine (G) in exon 6 (c.826delG; Gly276AlafsX11). This mutation resulted in a premature termination at codon 286, predicting a partial loss of the kinase domain and complete loss of the C-terminal domain. We did not observe this mutation in both parents of the PJS patient. Therefore, it is considered a novel de novo mutation. CONCLUSION: The results presented herein enlarge the spectrum of mutations of the STK11 gene by identifying a novel de novo mutation in a PJS patient and further support the hypothesis that STK11 mutations are disease-causing mutations for PJS with or without a positive family history

Methods of weight estimation in pediatric resuscitation

Knowing a pediatric patient's weight is crucial in resuscitation since the decision on the dose of resuscitation drug and the size of the instrument is made mostly based on a patient's weight. However, using a scale may not always be practical in resuscitation. Therefore, it is important to know the methods of weight estimation in resuscitation. The weight estimation can be performed based on various factors: visual assessment, age, height, and body habitus. One of the most common problems of these methods is that the weight tends to be underestimated as a patient's age increases. This is due to an inappropriate reflection of body habitus. Further research is needed to overcome this problem

Targeting cysteine thiols for in vitro site-specific glycosylation of recombinant proteins

Stromal interaction molecule-1 (STIM1) is a type-I transmembrane protein located on the endoplasmic reticulum (ER) and plasma membranes (PM). ER-resident STIM1 regulates the activity of PM Orai1 channels in a process known as store operated calcium (Ca2+) entry which is the principal Ca2+ signaling process that drives the immune response. STIM1 undergoes post-translational N-glycosylation at two luminal Asn sites within the Ca2+ sensing domain of the molecule. However, the biochemical, biophysical, and structure biological effects of N-glycosylated STIM1 were poorly understood until recently due to an inability to readily obtain high levels of homogeneous N-glycosylated protein. Here, we describe the implementation of an in vitro chemical approach which attaches glucose moieties to specific protein sites applicable to understanding the underlying effects of N-glycosylation on protein structure and mechanism. Using solution nuclear magnetic resonance spectroscopy we assess both efficiency of the modification as well as the structural consequences of the glucose attachment with a single sample. This approach can readily be adapted to study the myriad glycosylated proteins found in nature

Double Glomus Tumors Originating in the Submandibular and Parotid Regions

Glomus tumors are rare neoplasms that originate from the glomus bodies, an arteriovenous anastomosis with a specialized vascular structure. The most common site for these tumors is the subungal region of the fingers. Occasionally, glomus tumors are found in the middle ear, trachea, nasal cavities, stomach, and lungs. The occurrence in the parotid regions is very rare. While multiple glomus tumors in the whole body are thought to represent only 10% of all cases, instances of multiple tumors in the neck have not yet been reported in the literature. We report a case of double glomus tumors in the submandibular and parotid regions

Moisture dependence of electrical resistivity in under-percolated cement-based composites with multi-walled carbon nanotubes

Cement-based piezoresistive composites have attracted significant attention as smart construction materials for embedding self-sensing capability in concrete infrastructure. Although a number of studies have been conducted using multi-walled carbon nanotubes (MWCNTs) as a functional filler for self-sensing cement-based composites, studies addressing the influence of the internal moisture state on the electrical properties are relatively scant. In this study, we aim to experimentally investigate the effect of internal moisture state on the electrical resistivity of cement-based composites containing MWCNTs as an electrically conductive medium to raise a need for calibration of self-sensing data considering the internal moisture state. To this end, the moisture dependence of electrical resistivity in under-percolated cement-based composites was mainly evaluated, along with other material properties such as strength, shrinkage, and flowability. Results revealed that the electrical resistivity increased almost linearly as the internal relative humidity (IRH) decreased, and the increase was more pronounced below the percolation threshold. In addition, it was found that the strength gained by the microfiller effect of MWCNTs was significantly reduced particularly in under-percolated mixtures, leading to overall strength reductions. Furthermore, this study showed that the more the MWCNT was added, the smaller the flowability was obtained due to the increased viscosity of the mixture. The findings of this study are expected to provide pivotal information for accurate and reliable interpretations of self-sensing data generated by MWCNT-embedded cement-based composites

Good Glycemic Control Is Associated with Better Survival in Diabetic Patients on Peritoneal Dialysis: A Prospective Observational Study

BACKGROUND: The effect of glycemic control after starting peritoneal dialysis (PD) on the survival of diabetic PD patients has largely been unexplored, especially in Asian population. METHODS: We conducted a prospective observational study, in which 140 incident PD patients with diabetes were recruited. Patients were divided into tertiles according to the means of quarterly HbA1C levels measured during the first year after starting PD. We examined the association between HbA1C and all-cause mortality using Cox proportional hazards models. RESULTS: The mean age was 58.7 years, 59.3% were male, and the mean follow-up duration was 3.5 years (range 0.4-9.5 years). The mean HbA1C levels were 6.3%, 7.1%, and 8.5% in the 1(st), 2(nd), and 3(rd) tertiles, respectively. Compared to the 1(st) tertile, the all-cause mortality rates were higher in the 2(nd) [hazard ratio (HR), 4.16; 95% confidence interval (CI), 0.91-18.94; p = 0.065] and significantly higher in the 3(rd) (HR, 13.16; 95% CI, 2.67-64.92; p = 0.002) tertiles (p for trend = 0.005), after adjusting for confounding factors. Cardiovascular mortality, however, did not differ significantly among the tertiles (p for trend = 0.682). In contrast, non-cardiovascular deaths, most of which were caused by infection, were more frequent in the 2(nd) (HR, 7.67; 95% CI, 0.68-86.37; p = 0.099) and the 3(rd) (HR, 51.24; 95% CI, 3.85-681.35; p = 0.003) tertiles than the 1(st) tertile (p for trend = 0.007). CONCLUSIONS: Poor glycemic control is associated with high mortality rates in diabetic PD patients, suggesting that better glycemic control may improve the outcomes of these patients

Risk Factors and Control Strategies for the Rapidly Rising Rate of Breast Cancer in Korea

Due to the aging population and tremendous changes in life style over the past decades, cancer has been the leading cause of death in Korea. The incidence rate of breast cancer is the second highest in Korea, and it has shown an annual increase of 6.8% for the past 6 years. The major risk factors of breast cancer in Korean women are as follows: Early menarche, late menopause, late full-term pregnancy (FTP), and low numbers of FTP. Height and body mass index increased the risk of breast cancer in postmenopausal women only. There are ethnic variations in breast cancer due to the differences in genetic susceptibility or exposure to etiologic agent. With the epidemiological evidences on the possibility of further increase of breast cancer in Korea, the Korean Government began implementing the National Cancer Screening Program against breast cancer in 2002. Five-year survival rates for female breast cancer have improved significantly from 78.0% in early 1993-1995 to 90.0% in 2004-2008. This data indicate that improvement of the survival rate may be partially due to the early diagnosis of breast cancer as well as the increased public awareness about the significance of early detection and organized cancer screening program. The current primary prevention programs are geared towards strengthening national prevention campaigns. In accordance with the improvement in 5-year survival rate, the overall cancer mortality has started to decrease. However, breast cancer death rate and incidence rates are still increasing, which need further organized effort by the Korean Government

Lamellar keratoplasty using position-guided surgical needle and M-mode optical coherence tomography

Deep anterior lamellar keratoplasty (DALK) is an emerging surgical technique for the restoration of corneal clarity and vision acuity. The big-bubble technique in DALK surgery is the most essential procedure that includes the air injection through a thin syringe needle to separate the dysfunctional region of the cornea. Even though DALK is a well-known transplant method, it is still challenged to manipulate the needle inside the cornea under the surgical microscope, which varies its surgical yield. Here, we introduce the DALK protocol based on the position-guided needle and M-mode optical coherence tomography (OCT). Depth-resolved 26-gage needle was specially designed, fabricated by the stepwise transitional core fiber, and integrated with the swept source OCT system. Since our device is feasible to provide both the position information inside the cornea as well as air injection, it enables the accurate management of bubble formation during DALK. Our results show that real-time feedback of needle end position was intuitionally visualized and fast enough to adjust the location of the needle. Through our research, we realized that position-guided needle combined with M-mode OCT is a very efficient and promising surgical tool, which also to enhance the accuracy and stability of DALK