Search

Autophagy is a multiple fusion event, initiating with autophagosome formation and culminating with fusion with endo-lysosomes in a Ca

Established genetic risk factors for Alzheimer’s disease (AD) account for only a portion of AD heritability. The aim of this study was to identify novel associations between genetic variants and AD-specific brain atrophy. We conducted genome-wide association studies for brain magnetic resonance imaging measures of hippocampal volume and entorhinal cortical thickness in 2643 Koreans meeting the clinical criteria for AD (n = 209), mild cognitive impairment (n = 1449) or normal cognition (n = 985). A missense variant, rs77359862 (R274W), in the SHANK-associated RH Domain Interactor (SHARPIN) gene was associated with entorhinal cortical thickness (p = 5.0 × 10−9) and hippocampal volume (p = 5.1 × 10−12). It revealed an increased risk of developing AD in the mediation analyses. This variant was also associated with amyloid-β accumulation (p = 0.03) and measures of memory (p = 1.0 × 10−4) and executive function (p = 0.04). We also found significant association of other SHARPIN variants with hippocampal volume in the Alzheimer’s Disease Neuroimaging Initiative (rs3417062, p = 4.1 × 10−6) and AddNeuroMed (rs138412600, p = 5.9 × 10−5) cohorts. Further, molecular dynamics simulations and co-immunoprecipitation indicated that the variant significantly reduced the binding of linear ubiquitination assembly complex proteins, SHPARIN and HOIL-1 Interacting Protein (HOIP), altering the downstream NF-κB signaling pathway. These findings suggest that SHARPIN plays an important role in the pathogenesis of AD.

Autophagy is a multiple fusion event, initiating with autophagosome formation and culminating with fusion with endo-lysosomes in a Ca 2+ -dependent manner. The source of Ca 2+ and the molecular mechanism by which Ca 2+ is provided for this process are not known. The intracellular Ca 2+ permeable channel transient receptor potential mucolipin 3 (TRPML3) localizes in the autophagosome and interacts with the mammalian autophagy-related protein 8 (ATG8) homolog GATE16. Here, we show that lipid-regulated TRPML3 is the Ca 2+ release channel in the phagophore that provides the Ca 2+ necessary for autophagy progress. We generated a TRPML3-GCaMP6 fusion protein as a targeted reporter of TRPML3 compartment localization and channel function. Notably, TRPML3-GCaMP6 localized in the phagophores, the level of which increased in response to nutrient starvation. Importantly, phosphatidylinositol-3-phosphate (PI3P), an essential lipid for autophagosome formation, is a selective regulator of TRPML3. TRPML3 interacted with PI3P, which is a direct activator of TRPML3 current and Ca 2+ release from the phagophore, to promote and increase autophagy. Inhibition of TRPML3 suppressed autophagy even in the presence of excess PI3P, while activation of TRPML3 reversed the autophagy inhibition caused by blocking PI3P. Moreover, disruption of the TRPML3–PI3P interaction abolished both TRPML3 activation by PI3P and the increase in autophagy. Taken together, these results reveal that TRPML3 is a downstream effector of PI3P and a key regulator of autophagy. Activation of TRPML3 by PI3P is the critical step providing Ca 2+ from the phagophore for the fusion process, which is essential for autophagosome biogenesis.

Purpose Spatiotemporal regulation of cell membrane dynamics is a major process that promotes cancer cell invasion by acting as a driving force for cell migration. Beta-Pix (βPix), a guanine nucleotide exchange factor for Rac1, has been reported to be involved in actin-mediated cellular processes, such as cell migration, by interacting with various proteins. As yet, however, the molecular mechanisms underlying βPix-mediated cancer cell invasion remain unclear. Methods The clinical significance of βPix was analyzed in patients with colorectal cancer (CRC) using public clinical databases. Pull-down and immunoprecipitation assays were employed to identify novel binding partners for βPix. Additionally, various cell biological assays including immunocytochemistry and time-lapse video microscopy were performed to assess the effects of βPix on CRC progression. A βPix-SH3 antibody delivery system was used to determine the effects of the βPix-Dyn2 complex in CRC cells. Results We found that the Src homology 3 (SH3) domain of βPix interacts with the proline-rich domain of Dynamin 2 (Dyn2), a large GTPase. The βPix-Dyn2 interaction promoted lamellipodia formation, along with plasma membrane localization of membrane-type 1 matrix metalloproteinase (MT1-MMP). Furthermore, we found that Src kinase-mediated phosphorylation of the tyrosine residue at position 442 of βPix enhanced βPix-Dyn2 complex formation. Disruption of the βPix-Dyn2 complex by βPix-SH3 antibodies targeting intracellular βPix inhibited CRC cell invasion. Conclusions Our data indicate that spatiotemporal regulation of the Src-βPix-Dyn2 axis is crucial for CRC cell invasion by promoting membrane dynamics and MT1-MMP recruitment into the leading edge. The development of inhibitors that disrupt the βPix-Dyn2 complex may be a useful therapeutic strategy for CRC.

The World Health Organization (WHO) recently endorsed the proposal for a Decade of Healthy Ageing (2020-2030). The WHO defines "healthy aging" as "the process of developing and maintaining the functional ability that enables wellbeing in older age." Among the strategies for the Decade of Healthy Ageing, the WHO has suggested enhancing intrinsic capacity, promoting functional ability, and implementing the Integrated Care for Older People (ICOPE) package. The WHO has defined steps for ICOPE evaluation and scale-up and is performing a prospective study in 2-3 countries (low and middle income, high income) to test its feasibility in 2021-2022 and a multinational randomized study to validate its clinical efficacy and effectiveness in 2022-2024. Intrinsic capacity and frailty represent two faces of the same coin, with one indicating the reserves of the individual and the other indicating the deficits that accumulate with age. The Integrated Care of Older Patients with Frailty in Primary Care (ICOOP_Frail) study is the first integrated care program for frailty or functional decline in primary care in Korea. The results suggest that the ICOOP_Frail study can be utilized as a reference for ICOPE studies in Korea or at least to provide important findings for the forthcoming ICOPE implementation study in Korea.

Global disparities in breast cancer care become particularly evident when patients seek definitive care in the United States (USA) after receiving a breast cancer diagnosis and initiating care in low- and middle-income countries (LMICs). We performed a retrospective review of 26 patients with breast cancer who immigrated from LMICs and received care at Bellevue Hospital. Fifteen (58%) presented with advanced disease (stage III or IV), including 7 (27%). All 26 patients required diagnostic work-up in the USA, and all 19 (73.1%) patients with stage 0-III disease underwent surgical excision. Patients from LMICs frequently present with advanced disease and in varying stages of breast cancer treatment. Improving communication with previous providers and fostering a collaborative approach with the international community are essential to developing efficacious treatment plans and improving oncologic outcomes.

Lateral neck lymph node dissection (LND) along with total thyroidectomy is the standard treatment for thyroid cancer patients with metastases to the lateral neck lymph nodes. In general, lateral neck LND removes lymph nodes located at levels II to V ipsilateral to the thyroid cancer and preserves the spinal accessory nerve, internal jugular vein, and sternomastoid muscle during surgery. This video article was written to introduce the robotic bilateral axillo-breast approach for lateral neck LND and to describe the surgical method.

Background Recently, the QPLEX™ human papillomavirus (HPV) genotyping kit (QuantaMatrix, Seoul, Korea), a Microdisk™ technology-based multiplex system, was developed to detect 32 HPV genotypes. We evaluated the analytical performance of this kit by conducting a comparison study, precision evaluation and interference testing. Methods A total of 1594 cervical swab specimens were used to compare the QPLEX™ HPV genotyping kit with other commercially available kits (GeneFinder HPV Liquid Bead MicroArray Genotype polymerase chain reaction [PCR] kit, Infopia, Seoul, Korea; PANArray™ HPV Genotyping Chip, PANAGENE, Daejeon, Korea). For the determination of precision, we evaluated four types of precision profiles: repeatability, lot-to-lot variability, operator-to-operator variability and site-to-site variability. In addition, interference tests were performed with various interferents. Results The results of the QPLEX™ HPV genotyping kit showed almost perfect agreement with the other commercially available HPV genotyping assays. The combined precision was acceptable. In addition, there was no tested interferent that affected the results of the QPLEX™ HPV genotyping kit. Conclusions The QPLEX™ HPV genotyping kit showed acceptable analytical performance in our study. This assay could be a suitable option for HPV genotyping in routine and follow-up tests.

During aggressive cancer progression, cancer cells adapt to unique microenvironments by withstanding various cellular stresses, including endoplasmic reticulum (ER) stress. However, the mechanism whereby cancer cells overcome the ER stress to survive remains to be elucidated. Herein, we demonstrated that microtubule acetylation in cancer cells grown on a stiff matrix promotes cancer progression by preventing excessive ER stress. Downregulation of microtubule acetylation using shRNA or CRSIPR/Cas9 techniques targeting ATAT1, which encodes α-tubulin N-acetyltransferase (αTAT1), resulted in the upregulation of ER stress markers, changes in ER morphology, and enhanced tunicamycin-induced UPR signaling in cancer cells. A set of genes involved in cancer progression, especially focal adhesion genes, were downregulated in both ATAT1-knockout and tunicamycin-treated cells, whereas ATAT1 overexpression restored the gene expression inhibited by tunicamycin. Finally, the expression of ATAT1 and ER stress marker genes were negatively correlated in various breast cancer types. Taken together, our results suggest that disruption of microtubule acetylation is a potent therapeutic tool for preventing breast cancer progression through the upregulation of ER stress. Moreover, ATAT1 and ER stress marker genes may be useful diagnostic markers in various breast cancer types.

Neuroblastomas (NBs) have heterogeneous clinical behavior, from spontaneous regression or differentiation to relentless progression. Evidence from our laboratory and others suggests that neurotrophin receptors contribute to these disparate behaviors. Previously, the role of TRK receptors in NB pathogenesis was investigated. In the present study, the expression of RET and its co‑receptors in a panel of NB cell lines was investigated and responses to cognate ligands GDNF, NRTN, and ARTN with GFRα1‑3 co‑receptor expression, respectively were found to be correlated. RET expression was high in NBLS, moderate in SY5Y, low/absent in NBEBc1 and NLF cells. All cell lines expressed at least one of GFRα co‑receptors. In addition, NBLS, SY5Y, NBEBc1 and NLF cells showed different morphological changes in response to ligands. As expected, activation of RET/GFRα3 by ARTN resulted in RET phosphorylation. Interestingly, activation of TrkA by its cognate ligand NGF resulted in RET phosphorylation at Y905, Y1015, and Y1062, and this was inhibited in a dose‑dependent manner by the TRK inhibitor (CEP‑701). Conversely, RET activation by ARTN in NBLS cells led to phosphorylation of TrkA. This suggests a physical association between RET and TRK proteins, and cross‑talk between these two receptor pathways. Finally, RET, GFR and TRK expression in primary tumors was investigated and a significant association between RET, its co‑receptors and TRK expression was demonstrated. Thus, the present data support a complex model of interacting neurotrophin receptor pathways in the regulation of cell growth and differentiation in NBs.

Dental composites are used as restorative materials to replace tooth structure after the removal of caries, shaping, covering teeth for esthetic purposes and as adhesives. Dentists spend more time replacing existing restorations that fail than they do placing new restorations. Tooth colored restorations are difficult to differentiate from the surrounding tooth structure making them challenging to remove completely without incidental removal of healthy tooth structure. Previous studies have demonstrated that CO(2) lasers in conjunction with spectral feedback can be used to selectively remove composite from tooth surfaces. In addition, we assembled a system feasible for clinical use that incorporates a spectral feedback system, scanning system, articulating arm and a clinical handpiece and subsequently evaluated the performance of that system on extracted teeth. The purpose of this study was to test this system in vivo to demonstrate its efficacy relative to dental clinicians. Eight test subjects with premolar teeth scheduled for extraction for orthodontic reasons had bilateral premolars prepared with small occlusal cavity preparations and filled with dental composite. The laser scanning system was used to remove the composite from one of the preparations and a dental handpiece was used to remove the composite from the other. Cross polarization optical coherence tomography was used to measure the volume of the preparation before and after composite placement and removal. There was no significant difference in the loss of enamel and residual composite between the laser and the handpiece. This study demonstrated that a computer controlled spectral guided CO(2) laser scanning system can be used in vivo to selectively remove composite from tooth surfaces.

Study DesignCross sectional study.PurposeTo characterize the pattern of injury, describe the current clinical management, and determine the outcomes in traumatic spine injury (TSI) patients presenting to a major government hospital in Phnom Penh, Cambodia.Overview of LiteratureThere is a paucity of literature on epidemiology or current clinical practices for TSIs in Cambodia. The findings from this study can thus serve as a valuable resource for future progress in treating TSIs in low-income countries.MethodsThis study was a cross-sectional study of TSI patients admitted to Preah Kossamak Hospital in Phnom Penh, Cambodia. Demographics, cause of spinal injury, spinal level of injury, surgical procedures and techniques, complications, and American Spinal Injury Association (ASIA) grades were recorded and analyzed.ResultsEighty patients were admitted with TSI between October 2013 and June 2014. Falls from heights were the most common cause of TSI, followed by road traffic accidents. 78% of the admitted patients underwent at least one surgical procedure. Without intraoperative imaging, 4 patients (6%) had wrong level surgery, and 1 patient (2%) had misplacement of pedicle screws. Sacral decubitus ulcers were the most common non-surgically related complication. Antibiotics were administered to >90% of patients. There were no in-hospital mortalities. Of the 60 spinal cord injury (SCI) patients, 32% (19/60) showed improvement in their ASIA grade at the time of discharge, and 52% (31/60) showed no change. At follow-up, 32% (19/60) of SCI patients reported improvement, and 8% (5/60) reported no change. However, 36 SCI patients (60%) were lost to follow-up.ConclusionsDespite technological limitations, outcomes of TSI patients in Cambodia appear favorable with evidence of clinical improvement and low mortality.

A 50-year-old woman with a history of systemic lupus erythematosus (SLE) treated with methotrexate and hydroxychloroquine presented to the emergency department for evaluation of numbness and weakness of the left hand that began 12 hours earlier.

This study sought to characterize the epidemiology and outcomes of spinal trauma, with or without a neurologic deficit, at a major government hospital in Phnom Penh, Cambodia. Patient demographics, American Spinal Injury Association (ASIA) score on presentation, location of injury, and cause of injury from 316 patients from September 2013 through December 2016 were compiled. Outcome measures included length of hospitalization and surgical intervention. Falls were the leading cause of spinal injury (50.6%), followed by motor vehicle accidents (29.3%) and other accidents (20.1%). Patients who fell from height had higher surgery rates (P = 0.014), and men had worse ASIA scores (P = 0.0013). Patients with ASIA A-C had a mean age of 38.17 years, whereas the D-E group was on average 42.88 years. Motor vehicle accidents caused the most cervical spine injuries, whereas falls caused more thoracic and lumbar trauma (P = 0.0005). Younger, working men are experiencing more severe spinal injuries, undergoing more surgery, and staying hospitalized longer than other demographics in Phnom Penh. This study characterizes spinal trauma from falls as a public health issue in Cambodia, highlighting the importance of fall injury prevention. Protecting this cohort is an important investment for Cambodia and necessitates workplace reform and safety standard implementation.

Background Procollagen type I N-terminal propeptide (PINP) is one of the most clinically useful bone formation biomarkers. Therefore, the purpose of this study was to independently evaluate the performance of automated total PINP assay and established age- and gender-specific reference intervals for PINP in healthy Korean population. Methods The imprecision, linearity, and detection capability of Elecsys total PINP assay was determined and reference interval was established using 599 serums from Korean population with normal bone mineral densities based on bone densitometry. Age groups were divided into 20s, 30s, 40s, 50s, 60s and over. Results Elecsys total PINP had excellent performance in imprecision, linearity, and detection capability. When partitioning age groups in Korean male and female populations, there was significant difference in total PINP between different age groups. In male populations, PINP level was decreased with increasing age, then it remained steady after middle-age. In female populations, there was a decreasing tendency similar to that in the male population with a sharp increase in the 50 to 59 age group. Conclusions Elecsys total PINP assay showed precise and reliable performance in our study. We established age-related PINP reference intervals for Korean male and female population with normal bone mineral densities.

BACKGROUND The purpose of this study was to calculate the measurement uncertainty of the process of bone mineral density (BMD) analysis using dual energy X-ray absorptiometry with traceability. METHODS Between March 2015 and October 2016, among healthy participants in their 20s and 30s, the study included those who had not taken calcium, vitamin D supplements and steroids and were without a history of osteoporosis, osteopenia and diseases related to osteoporosis. Relational expression of the model was established based on Guide to the Expression of Uncertainty in Measurements and Eurachem and the uncertainty from each factor was evaluated. RESULTS The combined standard uncertainty was 0.015, while the expanded uncertainty was 0.0298. The factor-specific standard uncertainties that occurred in the process of measuring BMD were 0.72% for the calibration curve, 0.9% for the internal quality control (IQC) using Aluminum Spine Phantom, 0.58% for European Spine Phantom (ESP), and 0.9% for the inspector precision (IP). CONCLUSIONS The combined standard uncertainty of the spine BMD corrected with ESP was 0.015 when measured at one time and targeting one participant. The uncertainties of the accuracy of the IQC and the IP were higher than that of the other factors. Therefore, there will be a need for establishment of protocols to lower these uncertainties.

Objectives: The purpose of the study was to investigate the content analysis of daily tooth cleaning service records by caregivers in a long-term care facility. Methods: The data were analyzed by qualitative research based on content analysis of the daily records of the processes and results of daily tooth cleaning service. Twenty caregivers provided tooth, gum and denture cleaning service after breakfast, lunch, and dinner to 48 elderly residents. The study lasted about two weeks(from August 4 to August 20, 2014). The researcher reconstructed the language by repeatedly reviewing the caregivers statements in the records. The content categories were derived from the records through a reiterative manual comparative analysis. Using constant comparison method, reconstructed meanings were incorporated into various meanings and reanalyzed by final categories called as analytic coding. In order to validate the reliability, 6 times of discussion made the common meanings through a master’s degree student and a dental hygiene professor. Results: The caregivers identified lack of understanding and ability to recognize the functional physical and mental changes in the elderly. The elderly had difficulty in recognizing silent communication and daily tooth cleaning. The caregivers were so strenuous in taking care of the daily tooth cleaning service for the elderly. At last, they gave up the daily tooth cleaning service and took on it to the guardians. They found that there was no social supporting network for oral health of the elderly residents. Conclusions: Caregivers had insufficient understanding of the functional physical and mental changes in the elderly residents, and they had difficulty providing daily tooth cleaning service to the elderly due to poor skill and abilities.

Background High-risk type human papilloma virus (HPV) is the most important cause of cervical cancer. Recently, real-time polymerase chain reaction and reverse blot hybridization assay-based HPV DNA genotyping kits are developed. So, we compared the performances of different three HPV genotyping kits using different analytical principles and methods. Methods Two hundred positive and 100 negative cervical swab specimens were used. DNA was extracted and all samples were tested by the MolecuTech REBA HPV-ID, Anyplex II HPV28 Detection, and HPVDNAChip. Direct sequencing was performed as a reference method for confirming high-risk HPV genotypes 16, 18, 45, 52, and 58. Results Although high-level agreement results were observed in negative samples, three kits showed decreased interassay agreement as screening setting in positive samples. Comparing the genotyping results, three assays showed acceptable sensitivity and specificity for the detection of HPV 16 and 18. Otherwise, various sensitivities showed in the detection of HPV 45, 52, and 58. Conclusions The three assays had dissimilar performance of HPV screening capacity and exhibited moderate level of concordance in HPV genotyping. These discrepant results were unavoidable due to difference in type-specific analytical sensitivity and lack of standardization; therefore, we suggested that the efforts to standardization of HPV genotyping kits and adjusting analytical sensitivity would be important for the best clinical performance.

This paper investigated the operating environment for the representative of each agency and the facility workers on the basis of analytical result of recognition changes of the operating environment changes under the operating the long-term care insurance. It was described plans to take positive effect on the operating as follows. The first, on the result of regression analysis, the service administrative range takes the biggest effect on the general recognition of executing the long-term care insurance off and on. The affirmative recognition of the service administrative range had the general recognition on the system be positive effect. But the operator of facility asserts that the care manager`s professionalism related quality of service be strengthened. The second, on the result of regression analysis, in the financial accounting administrative it is revealed the more positive recognition it is, the more positive effects it has. From the difference verification of an operation size from operation subject, the small operation size and personal facility recognize the long term care insurance positively. On the other side the facilities where the operation size is big recognize the system negatively. The long-term care facility should rearrange a support program newly and the government needs to promote the donation activity, because it is needed to reduce the financial burden of facilities.

A common epitope region of enteroviruses was identified by sequence-independent single-primer amplification (SISPA), followed by immunoscreening of 11 cDNA libraries from two Korean enterovirus isolates (echoviruses 7 and 30) and a coxsackievirus B3 (ATCC-VR 30). The putative common epitope region was localized in the N terminus of VP1 when the displayed recombinant proteins from the phages were chased by the convalescent-phase sera. The genomic region encoding the common epitope region was amplified and then expressed by using the vector pGEX-5X-1. The antigenicity of the expressed recombinant protein was identified by Western blotting with guinea pig antisera for six different serotypes of enteroviruses. After successive immunization of mice with the recombinant common epitope protein, splenocytes were extracted and hybridized with P3X63-Ag8-653 cells. A total of 24 hybridomas that produced monoclonal antibodies (MAbs) against the putative common epitope of enteroviruses were selected. Four of these were immunoglobulin G1 isotypes with a kappa light chain. These MAbs recognized 15 Korean endemic serotypes and prototypes of enteroviruses in an indirect immunofluorescence assay. These results suggest that the expressed protein might be a useful antigen for producing group common antibodies and that the use of the MAbs against the putative common epitope of enteroviruses might be a valuable diagnostic tool for rapidly identifying a broad range of enteroviruses.

The present study was performed to identify the susceptible single nucleotide polymorphisms (SNPs) for the prediction of Korean type 2 diabetes mellitus (T2DM) and to clarify the matrilineal origin of Korean T2DM‑specific SNPs. Fourteen SNPs from the adiponectin (ADIPOQ), hepatocyte nuclear factor 4α, phosphoenolpyruvate carboxykinase 1 and glucokinase genes in the Korean population were analyzed. Only one SNP, ‑11,377 C/G on the ADIPOQ gene, was finally determined to be responsible for the incidence of Korean T2DM (P=0.028). The G‑T‑T‑A haplotype at positions ‑11,377, +45, +276 and +349 on the ADIPOQ gene was also associated with a high incidence of Korean T2DM (P=0.023). In addition, the susceptibility of Korean individuals to T2DM appears to be affected by their matrilineal origin. Of note, the group of Southern origin, consisting of mitochondrial DNA macrohaplogroups F and R, was predisposed to T2DM, whereas the group of Northern origin, consisting of haplogroups A and Y, was resistant to T2DM. This implied that the differential genetics between the two groups, which were formed from the initial peopling of the proto‑Korean population via Southern and Northern routes to the present time, may explain their differing susceptibility to T2DM. In conclusion, from Southern Asia Northward, a matrilineal origin of Korean individuals appears to be responsible for the prevalence of Korean T2DM caused by the ‑11,377 G allele.

IL-6 and TNFαwere significantly increased in the bone marrow aspirate samples of patients with active multiple myeloma (MM) compared to those of normal controls. Furthermore, MM patients with advanced aggressive disease had significantly higher levels of IL-6 and TNFαthan those with MM in plateau phase. TNFαincreased interleukin-6 (IL-6) production from MM cells. However, the detailed mechanisms involved in signaling pathways by which TNFαpromotes IL-6 secretion from MM cells are largely unknown. In our study, we found that TNFαtreatments induce MEK and AKT phosphorylation. TNFα-stimulated IL-6 production was abolished by inhibition of JAK2 and IKKβor by small interfering RNA (siRNA) targeting TNF receptors (TNFR) but not by MEK, p38, and PI3K inhibitors. Also, TNFαincreased phosphorylation of STAT3 (ser727) including c-Myc and cyclin D1. Three different types of JAK inhibitors decreased the activation of the previously mentioned pathways. In conclusion, blockage of JAK/STAT-mediated NF-κB activation was highly effective in controlling the growth of MM cells and, consequently, an inhibitor of TNFα-mediated IL-6 secretion would be a potential new therapeutic agent for patients with multiple myeloma.

Members of the Mongol imperial family (designated the Golden family) are buried in a secret necropolis; therefore, none of their burial grounds have been found. In 2004, we first discovered 5 graves belonging to the Golden family in Tavan Tolgoi, Eastern Mongolia. To define the genealogy of the 5 bodies and the kinship among them, SNP and/or STR profiles of mitochondria, autosomes, and Y chromosomes were analyzed. Four of the 5 bodies were determined to carry the mitochondrial DNA haplogroup D4, while the fifth carried haplogroup CZ, indicating that this individual had no kinship with the others. Meanwhile, Y-SNP and Y-STR profiles indicate that the males examined belonged to the R1b-M343 haplogroup. Thus, their East Asian D4 or CZ matrilineal and West Eurasian R1b-M343 patrilineal origins reveal genealogical admixture between Caucasoid and Mongoloid ethnic groups, despite a Mongoloid physical appearance. In addition, Y chromosomal and autosomal STR profiles revealed that the four D4-carrying bodies bore the relationship of either mother and three sons or four full siblings with almost the same probability. Moreover, the geographical distribution of R1b-M343-carrying modern-day individuals demonstrates that descendants of Tavan Tolgoi bodies today live mainly in Western Eurasia, with a high frequency in the territories of the past Mongol khanates. Here, we propose that Genghis Khan and his family carried Y-haplogroup R1b-M343, which is prevalent in West Eurasia, rather than the Y-haplogroup C3c-M48, which is prevalent in Asia and which is widely accepted to be present in the family members of Genghis Khan. Additionally, Tavan Tolgoi bodies may have been the product of marriages between the lineage of Genghis Khan's Borjigin clan and the lineage of either the Ongud or Hongirad clans, indicating that these individuals were members of Genghis Khan's immediate family or his close relatives.

Various cross-reactivities of vitamin D total immunoassays to 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3 are problematic issues to standardizing the assays. We assessed the effects of cross-reactivities to total vitamin D measurements using NIST SRM 972a, the standard reference material for vitamin D that consists of four vials of frozen serum with different concentrations of 25(OH)D. Each concentration of NIST SRM 972a …

BACKGROUND Although dual energy X-ray absorptiometry (DXA) is known to standard equipment for bone mineral density (BMD) measurements. Different results of BMD measurement using a number of different types of devices are difficult to use clinical practice. The purpose of this study was to evaluate discrepancy and standardizations of DXA devices from three manufactures using a European Spine Phantom (ESP). METHODS We calculated the accuracy and precision of 36 DXA devices from three manufacturers (10 Hologic, 16 Lunar, and 10 Osteosys) using a ESP (semi-anthropomorphic). The ESP was measured 5 times on each equipment without repositioning. Accuracy was assessed by comparing BMD (g/cm(2)) values measured on each device with the actual value of the phantom. Precision was assessed by the coefficient of variation (CVsd). RESULTS Lunar devices were, on average, 22%, 8.3%, and 5% overestimation for low (L1) BMD values, medium (L2), and high (L3) BMD values. Hologic devices were, on average, 6% overestimation for L1 BMD, and 5% and 6.2% underestimation for L2 and L3 BMD values. Osteosys devices was, on average, 12.7% (0.063 g/cm(2)), 6.3% (0.062 g/cm(2)), and 5% (0.075 g/cm(2)) underestimation for L1, L2, and L3, respectively. The mean CVsd for L1-L3 BMD were 0.01%, 0.78%, and 2.46% for Lunar, Hologic, and Osteosys devices respectively. CONCLUSIONS The BMD comparison in this study demonstrates that BMD result of three different devices are significant different between three devices. Differences of BMD between three devices are necessary to BMD standardization.

BACKGROUND: The purpose of this study was to find out the cause of discrepancy between various automated immunoassays for 25-hydroxy-vitamin D (25-[OH]D). METHODS: National Institute of Standards & Technology Standard Reference Material (SRM) 972a is SRM for 25-(OH)D and consists of 4 vials of frozen serum with different concentrations of 25-(OH)D. Each concentration was measured 6 times in 3 different immunoassays: ADVIA Vitamin D Total assay (Siemens Healthcare, Erlangen, Germany), ARCHITECT 25-(OH)D (Abbott Laboratories, Abbott Park, IL, USA), and COBAS Vitamin D Total assay (Roche Diagnostics, Basel, Switzerland). RESULTS: When using the certified reference values of SRM 972a as it is, discarding the cross-reactivity of each immunoassay, for ADVIA, the coefficient of determination (R(2)) as a score of regression analysis was 0.8995 and maximal difference between measured value and certified reference value was 3.6 ng/mL in level 3. The R(2) and maximal differences of ARCHITECT were 0.5377 and 6.9 ng/mL, respectively, in level 4. Those of COBAS were 0.3674 and 22.3 ng/mL, respectively, in level 4. When considering cross-reactivities of each immunoassays to various 25-(OH)D metabolites, the ADVIA had R(2) and maximal difference of 0.9254 and 3.3 ng/mL, respectively, in level 3. For ARCHITECT, the R(2) and maximal differences were 0.7602 and 5.1 ng/mL, respectively, in level 1. Those of COBAS were 0.9284 and 4.9 ng/mL, respectively, in level 1. CONCLUSIONS: The cause of discrepancies between vitamin D immunoassays was mainly on the difference in cross-reactivities to various vitamin D metabolites. The discrepancies can be considerably decreased by considering cross-reactivities of each immunoassay.

Split hand/split foot malformation (SHFM; ectrodactyly) is genetically heterogeneous, with mutations identified at five loci (SHFM1 at 7q21.3, SHFM2 at Xq26, SHFM3 at 10q24, SHFM4 at 3q27 and SHFM5 at 2q31). In this study, we attempted to identify and localize the causative allele of a Korean case of SHFM. Pedigree analysis showed that the Korean SHFM was autosomally dominant and its penetrance was high, indicating that it was not caused by SHFM2. Clinical features were variable, but limited to the four limbs unlike SHFM1, SHFM4 and SHFM5. G-banding and FISH failed to identify any chromosomal abnormalities. We also performed mutation screening by SSCP and DNA sequencing, as well as loss of heterozygosity (LOH) analysis, to exclude the possibility that SHFM4 or SHFM5 were involved; these revealed no mutations in gene p63 and no LOH on 2q31, respectively. It therefore appears that the Korean SHFM may be caused by mutation of SHFM3. In fact, linkage analysis using informative microsatellite markers indicated that SHFM3 was linked to D10S577 with a maximum LOD score of 1.15 at recombination fraction zero. Finally, we identified two novel alleles (191 and 211 bp) of D10S577 that have not been found in Western populations.

Background: Although many single nucleotide polymorphisms (SNPs) of mtDNA h ave been found to be associated with type 2 diabetes mellitus, the results of studies using different population samples and different methods are mixed. Therefore, we conducted a genetic association study of mtDNA SNPs and type 2 diabetes mellitus in a Korean sample and compared our results with those of studies co nducted in other human populations. Methods: A total of 298 blood samples from 147 type 2 diabetic patients and 151 normal controls were surveyed for SNPs via PCR directed sequencing. Sequencing analy ses were performed using the SeqMan module of the DNASTAR program. The identified SNPs were compared to previously reported SNP lists on NCBI and V-mitoSNP. Results: A total of 24 SNPs were identified in the MT-RNR2, MR-TL1 and MT-ND1 mtDNA genes in Korean type 2 diabetes mellitus patients and normal controls. The SNPs identified in the Korean sample were not closely associated with the type 2 diabetes mellitus phenotype, a significantly different result from those previously observed in European, Chinese and Japanese samples. Additionally, a haplotype and prevalence analysis could not detect any differences between the type 2 diabetes mellitus patients and normal controls. Conclusion: The 24 mtDNA SNPs were not associ ated with type 2 diabetes mellitus risk in our Korean sample. The results of the present study support the possibilit y that mtDNA SNPs have a differential effect on the risk of type 2 diabetes mellitus according to geographical origin. (Korean Diabetes J 33:382-391, 2009)