De novo copy number variations in cloned dogs from the same nuclear donor

BACKGROUND: Somatic mosaicism of copy number variants (CNVs) in human body organs and de novo CNV event in monozygotic twins suggest that de novo CNVs can occur during mitotic recombination. These de novo CNV events are important for understanding genetic background of evolution and diverse phenotypes. In this study, we explored de novo CNV event in cloned dogs with identical genetic background. RESULTS: We analyzed CNVs in seven cloned dogs using the nuclear donor genome as reference by array-CGH, and identified five de novo CNVs in two of the seven clones. Genomic qPCR, dye-swap array-CGH analysis and B-allele profile analysis were used for their validation. Two larger de novo CNVs (5.2 Mb and 338 Kb) on chromosomes X and 19 in clone-3 were consistently validated by all three experiments. The other three smaller CNVs (sized from 36.1 to76.4 Kb) on chromosomes 2, 15 and 32 in clone-3 and clone-6 were verified by at least one of the three validations. In addition to the de novo CNVs, we identified a 37 Mb-sized copy neutral de novo loss of heterozygosity event on chromosome 2 in clone-6. CONCLUSIONS: To our knowledge, this is the first report of de novo CNVs in the cloned dogs which were generated by somatic cell nuclear transfer technology. To study de novo genetic events in cloned animals can help understand formation mechanisms of genetic variants and their biological implications

Purification and characterization of angiotensin-1 converting enzyme (ACE)-inhibitory peptide from the jellyfish, Nemopilema nomurai

The Nemopilema nomurai hydrolysate was produced by the reaction of papain, and an angiotensin-Ι converting enzyme (ACE)-inhibitory peptide was purified by using the molecular cut-offs membrane filter, the gel filtration chromatography with Sephadex LH-20 and the reverse phase chromatographic method using C18 and C12 columns. Purification yield of the active peptide was estimated to be 0.2 ± 0.1%, starting from the lyophilized jellyfish. The infrared (IR), proton nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance (13C NMR) and mass spectrometry (MS) spectrometer analyses elucidated that the structure of the purified peptide is tyrosine-isoleucine (Tyr-Ile). The inhibitory concentration at 50% (IC50) and Ki values were calculated to be 2.0 ± 0.3 μg/ml and 3.3 ± 0.3 μM, respectively, which acts as a competitive inhibitor to ACE.Keywords: Angiotensin-Ι converting enzyme, Jellyfish, Nemopilema nomurai, Papain hydrolysate, Tyrosine-IsoleucineAfrican Journal of Biotechnology Vol. 12(15), pp. 1888-189

Extensive Systemic Sarcoidosis with Testicular Involvement Mimicking Metastatic Testicular Cancer

Sarcoidosis is an idiopathic, multisystem disease that rarely involves the genitourinary tract. Here we present an unusual case of testicular sarcoidosis with extensive lymphadenopathy that mimicked a metastatic testicular tumor. A 27-year-old male presented with a palpable right testicular mass accompanied by multiple palpable inguinal lymph nodes. The scrotal ultrasound showed a hypoechoic lesion at the inferior portion of the right testis. Extensive enlarged lymph nodes were noted in multiple areas on the abdominal computed tomography. Preoperative testicular tumor markers were within the normal range. Exploration of the right testis with a frozen section analysis of the right testicular mass and of a palpable right inguinal lymph node showed granulomatous inflammation. The testis was salvaged and the final pathological diagnosis was sarcoidosis. Treatment with high-dose corticosteroids resulted in complete resolution of the intratesticular mass and a significant decrease in the extent of the lymphadenopathy

Unconventional spin-phonon coupling via the Dzyaloshinskii???Moriya interaction

Spin-phonon coupling (SPC) plays a critical role in numerous intriguing phenomena of transition metal oxides (TMOs). In 3d and 4d TMOs, the coupling between spin and lattice degrees of freedom is known to originate from the exchange interaction. On the other hand, the origin of SPC in 5d TMOs remains to be elucidated. To address this issue, we measured the phonon spectra of the 5d pyrochlore iridate Y 2 Ir 2 O 7 using optical spectroscopy. Three infrared-active phonons soften below the N??el temperature of T N ??? 170 K, indicating the existence of strong SPC. Simulations using density functional theory showed that the coupling is closely related to the Ir???O???Ir bond angle. A tight-binding model analysis reveals that this SPC is mainly mediated by the Dzyaloshinskii???Moriya interaction rather than the usual exchange interaction. We suggest that such unconventional SPC may be realized in other 5d TMOs with non-collinear magnetic order

Non-Type I Cystinuria Associated with Mental retardation and Ataxia in a Korean Boy with a New Missence Mutation(G173R) in the SLC7A9 Gene

Cystinuria is an inherited renal and intestinal disease characterized by defective amino acids reabsorption and cystine urolithiasis. It is unusually associated with neurologic symptoms. Mutations in two genes, SLC3A1 and SLC7A9, have been identified in cystinuric patients. This report presents a 13-yr-old boy with cystinuria who manifested difficulty in walking, ataxia, and mental retardation. Somatosensory evoked potential of posterior tibial nerve stimulation showed the central conduction dysfunction through the posterior column of spinal cord. He was diagnosed non-type I cystinuria by urinary amino acid analysis and oral cystine loading test. We screened him and his family for gene mutation by direct sequencing of SLC3A1 and SLC7A9 genes. In this patient, we identified new missence mutation G173R in SLC7A9 gene

Femoral geometry, bone mineral density, and the risk of hip fracture in premenopausal women: a case control study

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background The purpose of this study was to determine the relationships among hip geometry, bone mineral density, and the risk of hip fracture in premenopausal women. Methods The participants in this case–control study were 16 premenopausal women with minimal-trauma hip fractures (fracture group) and 80 age-and BMI-adjusted controls. Subjects underwent dual-energy X-ray absorptiometry (DXA) to assess BMD at the proximal femur and to obtain DXA-derived hip geometry measurements. Results The fracture group had a lower mean femoral neck and total hip BMD than the control group (0.721 ± 0.123 vs. 0.899 ± 0.115, p <0.001 for the femoral neck BMD and 0.724 ± 0.120 vs. 0.923 ± 0.116, p <0.001 for the total hip BMD). In addition, participants in the fracture group had a longer hip axis length (HAL; p = 0.007), narrower neck shaft angle (NSA; p = 0.008), smaller cross sectional area (CSA; p < 0.001) and higher cross sectional moment of inertia (CSMI; p = 0.004) than those in control group. After adjusting for BMD, the fracture group still had a significantly longer mean HAL (p = 0.020) and narrower NSA (p = 0.006) than the control group. Conclusions BMD is an important predictor of hip fracture in premenopausal women. Furthermore, HAL and NSA are BMD-independent predictors of hip fracture in premenopausal women. Hip geometry may be clinically useful for identification of premenopausal women for whom active fracture prevention should be considered

Functional Recapitulation of Smooth Muscle Cells Via Induced Pluripotent Stem Cells From Human Aortic Smooth Muscle Cells

Rationale: Generation of induced pluripotent stem (iPS) cells has been intensively studied by a variety of reprogramming methods, but the molecular and functional properties of the cells differentiated from iPS cells have not been well characterized. Objective: To address this issue, we generated iPS cells from human aortic vascular smooth muscle cells (HASMCs) using lentiviral transduction of defined transcription factors and differentiated these iPS cells back into smooth muscle cells (SMCs). Methods and Results: Established iPS cells were shown to possess properties equivalent to human embryonic stem cells, in terms of the cell surface markers, global mRNA and microRNA expression patterns, epigenetic status of OCT4, REX1, and NANOG promoters, and in vitro/in vivo pluripotency. The cells were differentiated into SMCs to enable a direct, comparative analysis with HASMCs, from which the iPS cells originated. We observed that iPS cell-derived SMCs were very similar to parental HASMCs in gene expression patterns, epigenetic modifications of pluripotency-related genes, and in vitro functional properties. However, the iPS cells still expressed a significant amount of lentiviral transgenes (OCT4 and LIN28) because of partial gene silencing. Conclusions: Our study reports, for the first time, the generation of iPS cells from HASMCs and their differentiation into SMCs. Moreover, a parallel comparative analysis of human iPS cell-derived SMCs and parental HASMCs revealed that iPS-derived cells possessed representative molecular and in vitro functional characteristics of parental HASMCs, suggesting that iPS cells hold great promise as an autologous cell source for patient-specific cell therapy. (Circ Res. 2010;106:120-128.)Yu JY, 2007, SCIENCE, V318, P1917, DOI 10.1126/science.1151526Hanna J, 2007, SCIENCE, V318, P1920, DOI 10.1126/science.1152092Takahashi K, 2007, CELL, V131, P861, DOI 10.1016/j.cell.2007.11.019Byrne JA, 2007, NATURE, V450, P497, DOI 10.1038/nature06357Lee TH, 2007, PLOS MED, V4, P1101, DOI 10.1371/journal.pmed.0040186Matsumura H, 2007, NAT METHODS, V4, P23, DOI 10.1038/NMETH973Aoi T, 2008, SCIENCE, V321, P699, DOI 10.1126/science.1154884Dimos JT, 2008, SCIENCE, V321, P1218, DOI 10.1126/science.1158799Barroso-delJesus A, 2008, MOL CELL BIOL, V28, P6609, DOI 10.1128/MCB.00398-08Aasen T, 2008, NAT BIOTECHNOL, V26, P1276, DOI 10.1038/nbt.1503Stadtfeld M, 2008, SCIENCE, V322, P945, DOI 10.1126/science.1162494Okita K, 2008, SCIENCE, V322, P949, DOI 10.1126/science.1164270Tateishi K, 2008, J BIOL CHEM, V283, P31601, DOI 10.1074/jbc.M806597200Zhang JH, 2009, CIRC RES, V104, pE30, DOI 10.1161/CIRCRESAHA.108.192237Soldner F, 2009, CELL, V136, P964, DOI 10.1016/j.cell.2009.02.013Chang SA, 2008, STEM CELLS, V26, P1901, DOI 10.1634/stemcells.2007-0708Park IH, 2008, NATURE, V451, P141, DOI 10.1038/nature06534Lowry WE, 2008, P NATL ACAD SCI USA, V105, P2883, DOI 10.1073/pnas.0711983105Laurent LC, 2008, STEM CELLS, V26, P1506, DOI 10.1634/stemcells.2007-1081Kim JB, 2008, NATURE, V454, P646, DOI 10.1038/nature07061Ross JJ, 2006, J CLIN INVEST, V116, P3139, DOI 10.1172/JCI28184Takahashi K, 2006, CELL, V126, P663Yu JY, 2006, STEM CELLS, V24, P168, DOI 10.1634/stemcells.2005-0292Cowan CA, 2005, SCIENCE, V309, P1369, DOI 10.1126/science.1116447Adhikary S, 2005, NAT REV MOL CELL BIO, V6, P635, DOI 10.1038/nrm1703DALLAFAVERA R, 1982, P NATL ACAD SCI-BIOL, V79, P78241

Primary Squamous Cell Carcinoma of the Liver Initially Presenting with Pseudoachalasia

Pseudoachalasia secondary to primary squamous cell carcinoma (SCC) of the liver is extremely rare and has not been reported until now. Here, we report a unique case of primary SCC of the liver initially presenting with progressive dysphagia along with short periods of significant weight loss. A 58-year-old man initially presented with progressive dysphagia along with significant weight loss over brief periods of time. The radiographic and manometric findings were consistent with achalasia. Subsequent esophagogastroduodenoscopy revealed a moderately dilated esophagus without evidence of neoplasm or organic obstruction. However, firm resistance was encountered while traversing the esophagogastric junction (EGJ), although no mucosal lesion was identified. Due to the clinical suspicion of the presence of a malignant tumor, endoscopic ultrasonography (EUS) and computed tomography scans of the chest and abdomen were obtained. A huge hepatic mass with irregular margins extending to the EGJ was found. EUS-guided fine-needle aspiration was performed, and the mass was diagnosed as a primary SCC of the liver by immunohistochemical staining

Self-esteem as a Moderator of the Effects of Happiness, Depression, and Hostility on Suicidality Among Early Adolescents in Korea

Objectives The purpose of this study was to investigate the role of self-esteem as a moderator of the factors influencing suicidality among middle-schoolers. Methods Moderated multiple regression analysis was applied to assess the influence of happiness, depression, and hostility on suicidality and to determine the degree to which self-esteem served as a moderator of those relationships. Data were collected from 268 students at a middle school in Busan, Korea, using a self-administered structured questionnaire. Results Happiness, depression, and hostility had significant direct effects on suicidality. Self-esteem showed no direct effect, but had a significant moderating effect on the relationship between hostility and suicidal behavior. Conclusions These results suggest that various interventions, such as counseling programs, should be designed to alleviate hostility and depression and to enhance happiness and self-esteem among early adolescents