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BACKGROUND Gastrointestinal subepithelial tumors (GSTs), incidentally detected during upper gastrointestinal (GI) endoscopy, may be lesions derived from the GI wall or may be caused by compression from external organs. In general, traumatic neuroma is a benign nerve tumor that results from postoperative nerve injury, occurring in the bile duct as one of the complications after cholecystectomy. This is the first case report demonstrating that neuroma of the cystic duct can be incorrectly perceived as a duodenal subepithelial tumor by compressing the duodenal wall. CASE SUMMARY We report the case of a 72-year-old man with traumatic neuroma of the cystic duct after cholecystectomy. This tumor was mistaken for a duodenal subepithelial tumor on preoperative upper GI endoscopy and endoscopic ultrasonography due to external compression of the GI wall. The patient had no symptoms, and his laboratory test results were normal. However, in a series of follow-up endoscopies, the tumor was found to have grown in size, so it was surgically resected. The lesion was completely removed by laparoscopic endoscopic cooperative surgery. The patient was discharged on postoperative day 7 without complications. CONCLUSION Traumatic neuroma of the cystic duct can be mistaken for GSTs in GI endoscopy.

Studies of neuroglial interaction largely depend on cell-specific gene knockout (KO) experiments using Cre recombinase. However, genes known as glial-specific genes have recently been reported to be expressed in neuroglial stem cells, leading to the possibility that a glia-specific Cre driver results in unwanted gene deletion in neurons, which may affect sound interpretation. 2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP) is generally considered to be an oligodendrocyte (OL) marker. Accordingly, Cnp promoter-controlled Cre recombinase has been used to create OL-specific gene targeting mice. However, in this study, using Rosa26-tdTomato-reporter/Cnp-Cre mice, we found that many forebrain neurons and cerebellar Purkinje neurons belong to the lineages of Cnp-expressing neuroglial stem cells. To answer whether gene targeting by Cnp-Cre can induce neuron-autonomous defects, we conditionally deleted an essential autophagy gene, Atg7, in Cnp-Cre mice. The Cnp-Cre-mediated Atg7 KO mice showed extensive p62 inclusion in neurons, including cerebellar Purkinje neurons with extensive neurodegeneration. Furthermore, neuronal areas showing p62 inclusion in Cnp-Cre-mediated Atg7 KO mice overlapped with the neuronal lineage of Cnp-expressing neuroglial stem cells. Moreover, Cnp-Cre-mediated Atg7-KO mice did not develop critical defects in myelination. Our results demonstrate that a large population of central neurons are derived from Cnp-expressing neuroglial stem cells; thus, conditional gene targeting using the Cnp promoter, which is known to be OL-specific, can induce neuron-autonomous phenotypes.

A 16-year-old boy presented with marked weight loss, weakness of the left extremities and dizziness of 2 months duration and vomiting for 2 days. Brain MRI showed an approximately 6.5 × 5.3 cm-sized huge heterogeneous enhancing mass located in the corpus callosum, extending into the lateral ventricle. Open biopsy showed that the lesion consisted of lymphoplasmacytes and plump histiocytes with rhabdoid morphology, which were stained with S-100 protein, CD68 (KP1) and negative for CD1a. Histiocytic tumor was initially diagnosed. Chemotherapy using methotrexate, 6-mercaptopurine, vinblastine, interferon-alpha and dexamethasone was performed. After 5 months, partial removal was done. Microscopically, plump and bizarre tumor cells as well as rhabdoid features were found. Occasional spindle cells and necrosis were also found. These cells were positive for CD163, CD68, lysozyme, CD4, INI-1 and BRG1. BRAF V600E mutation was detected. The lesion was finally diagnosed as histiocytic sarcoma. Radiotherapy (6000 cGy in 30 fractions) was done. Both cerebral and extracerebral histiocytic sarcomas have long been diagnosed by unclarified criteria; its rarity as well as previously unclarified criteria can easily lead to a misinterpretation. Histiocytic sarcoma of the CNS is exceptionally rare in children, associated with an exceptionally poor prognosis. To date, only seven cases of pediatric cerebral histiocytic sarcomas have been reported. The present case is the first pediatric case showing BRAF V600E-mutated intracerebral histiocytic sarcoma.

Objective Myelinated Schwann cells (SCs) in adult peripheral nerves dedifferentiate into immature cells in demyelinating neuropathies and Wallerian degeneration. This plastic SC change is actively involved in the myelin destruction and clearance as demyelinating SCs (DSCs). In inherited demyelinating neuropathy, pathologically differentiated and dysmyelinated SCs constitute the main nerve pathology. Methods We investigated whether this SC plastic status in human neuropathic nerves could be determined by patient sera to develop disease‐relevant serum biomarkers. Based on proteomics analysis of the secreted exosomes from immature SCs, we traced p75 neurotrophin receptor (p75) and neural cell adhesion molecule 1 (NCAM) in the sera of patients with peripheral neuropathy. Results Enzyme‐linked immunosorbent assay (ELISA) revealed that p75 and NCAM were subtype‐specifically expressed in the sera of patients with peripheral neuropathy. In conjunction with these ELISA data, pathological analyses of animal models and human specimens suggested that the presence of DSCs in inflammatory neuropathy and of supernumerary nonmyelinating or dysmyelinating SCs in inherited neuropathy could potentially be distinguished by comparing the expression profiles of p75 and NCAM. Interpretation This study indicates that the identification of disease‐specific pathological SC stages might be a valuable tool for differential diagnosis of peripheral neuropathies.

Objective The development of sarcopenia leads to adverse postoperative outcomes. However, no study has investigated perioperative loss in core muscle and the correlation between core muscle and residual liver volume in living donors for liver transplant. Patients and Methods A total of 457 adult healthy donors who underwent a right lobe hepatectomy without the middle hepatic vein for elective liver transplant were retrospectively analyzed. Abdominal computed tomography was performed within 1 month before surgery and the first week and 3 months after the surgery. The average psoas muscle area between lumbar vertebrae 3 and 4 was measured and normalized by height squared (psoas muscle index [PMI] = psoas muscle area/height2). The initial whole liver volume and remnant left lobe volume were measured on computed tomography images. Results The study cohort included 279 men (61.1%) and 178 women (38.9%). The median preoperative PMIs were 420.9 mm2/m2 (interquartile range, 360.6–487.0 mm2/m2) in men and 280.9 mm2/m2 (interquartile range, 243.5–318.7 mm2/m2) in women. The PMIs in men and women significantly decreased during the first week after surgery, and gradually recovered to preoperative levels during the first 3 months after surgery. Based on the ratio between the remnant left lobe and initial whole liver volume (≥30%), the increase in remnant left lobe volume was not correlated with the decrease in PMI on postoperative day 7. A postoperative U-shaped recovery in the core muscles was present in both male and female donors, independent of the remnant liver ratio. Conclusions Despite the requirements of partial liver regeneration and surgical wound repair, healthy donors did not suffer from sustained core muscle loss after surgery.

The microfluidic 3D cell culture system has been an attractive model because it mimics the tissue and disease model, thereby expanding our ability to control the local cellular microenvironment. However, these systems still have limited value as quantitative assay tools due to the difficulties associated with the manipulation and maintenance of microfluidic cells, and their lack of compatibility with the high-throughput screening (HTS) analysis system. In this study, we suggest a microchannel-free, 3D cell culture system that has a hydrogel-incorporating unit integrated with a multi-well plate (24- to 96-well plate), which can provide better reproducibility in biological experiments. This plate was devised considering the design constraints imposed by various cell biology applications as well as by high-throughput analysis where the physical dimensions of the micro-features in the hydrogel-incorporating units were altered. We also demonstrated that the developed plate is potentially applicable to a variety of quantitative biochemical assays for qRT-PCR, Western blotting, and microplate-reader-based assays, such as ELISA, viability assay, and high content-screening (HCS) as well as the co-culture for biological studies. Human neural progenitor cells (hNPCs) that produce pathogenic Aβ species for modeling Alzheimer's disease (AD) were three-dimensionally cultured, and the efficacy of the inhibitors of Aβ production was assessed by ELISA in order to demonstrate the performance of this plate.

Herein, we present a simple readout of the binding between a chemical drug and its target proteins in the cytoplasm by using a two-step bioorthogonal labeling method combined with spatially-localized expression of proteins. Dasatinib was modified with trans-cyclooctene (TCO), and its cytoplasmic target kinases were expressed in intracellular compartments, such as endosomes and F-actins. After bioorthogonal labeling, the colocalization between Dasatinib and its target proteins was observed in intracellular compartments.

Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The "β-amyloid cascade hypothesis" of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including β-amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery.

A 16-year-old boy presented with marked weight loss, weakness of the left extremities and dizziness of 2 months duration and vomiting for 2 days. Brain MRI showed an approximately 6.5 × 5.3 cm-sized huge heterogeneous enhancing mass located in the corpus callosum, extending into the lateral ventricle. Open biopsy showed that the lesion consisted of lymphoplasmacytes and plump histiocytes with rhabdoid morphology, which were stained with S-100 protein, CD68 (KP1) and negative for CD1a. Histiocytic tumor was initially diagnosed. Chemotherapy using methotrexate, 6-mercaptopurine, vinblastine, interferon-alpha and dexamethasone was performed. After 5 months, partial removal was done. Microscopically, plump and bizarre tumor cells as well as rhabdoid features were found. Occasional spindle cells and necrosis were also found. These cells were positive for CD163, CD68, lysozyme, CD4, INI-1 and BRG1. BRAF V600E mutation was detected. The lesion was finally diagnosed as histiocytic sarcoma. Radiotherapy (6000 cGy in 30 fractions) was done. Both cerebral and extracerebral histiocytic sarcomas have long been diagnosed by unclarified criteria; its rarity as well as previously unclarified criteria can easily lead to a misinterpretation. Histiocytic sarcoma of the CNS is exceptionally rare in children, associated with an exceptionally poor prognosis. To date, only seven cases of pediatric cerebral histiocytic sarcomas have been reported. The present case is the first pediatric case showing BRAF V600E-mutated intracerebral histiocytic sarcoma.

Microglial activation in the central nervous system is a key event in the neuroinflammation that accompanies neurodegenerative diseases such as Alzheimer's disease (AD). Among cytokines involved in microglial activation, amyloid β (Aβ) peptide is known to be a key molecule in the induction of diverse inflammatory products, which may lead to chronic inflammation in AD. However, proteomic studies of microglia in AD are limited due to lack of proper cell or animal model systems. In this study, we performed a proteomic analysis of Aβ-stimulated human microglial cells using SILAC (stable isotope labeling with amino acids in cell culture) combined with LC-MS/MS. Results showed that 60 proteins increased or decreased their abundance by 1.5 fold or greater. Among these, ER-resident proteins such as SERPINH1, PDIA6, PDIA3, and PPIB were revealed to be key molecular biomarkers of human microglial activation by validation of the proteomic results by immunostaining, PCR, ELISA, and Western blot. Taken together, our data suggest that ER proteins play an essential role in human microglial activation by Aβ and may be important molecular therapeutic targets for treatment of AD.

Alzheimer's disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-β plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer's disease posits that the excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer's disease (FAD) mutations exhibit amyloid-β-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer's disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer's disease patients have shown elevated levels of toxic amyloid-β species and phosphorylated tau but did not demonstrate amyloid-β plaques or neurofibrillary tangles. Here we report that FAD mutations in β-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-β, including amyloid-β plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-β generation with β- or γ-secretase inhibitors not only decreased amyloid-β pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-β-mediated tau phosphorylation. We have successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer's disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.

Although there are many types of epilepsy, temporal lobe epilepsy (TLE) is probably in humans the most common and most often studied. TLE represents 40% of the total epilepsy form of the disease and is difficult to treat. Despite a wealth of descriptive data obtained from the disease history of patients, the EEG recording, imaging techniques, and histological studies, the epileptogenic process remains poorly understood. However, it is unlikely that a single factor or a single mechanism can cause many changes associated with this neuropathological phenomenon. MALDI mass spectrometry imaging (MSI) coupled to protein identification, because of its ability to study a wide range of molecules, appears to be suitable for the preparation of molecular profiles in TLE. Seven neuropeptides have been have been identified in Dental gyrus regions of the hippocampus in relation with TLE pathology. Shot-gun studies taking into account gender influence have been performed. Tissue microextraction from control (10) toward 10 TLE patients have been analyzed after trypsin digestion followed by separation on nanoLC coupled to LTQ orbitrap. From the shot-gun analyses, results confirmed the presence of specific neuropeptides precursors and receptors in TLE patients as well as proteins involved in axons regeneration including neurotrophins, ECM proteins, cell surface proteins, membrane proteins, G-proteins, cytoskeleton proteins and tumor suppressors. Among the tumor suppressors identified, the Leucine-rich glioma inactivated 1 (LGI1) protein was found. LGI1 gene recently been demonstrated being implicated in heritability of TLE. We have also demonstrate the presence a complete profile of tumor suppressors in TLE patients, 7 have been identified. Refining this analysis taken into account the gender influence in both control and in TLE reflected the presence of specific proteins between male and female and thus mechanisms in pathology development could be completely different.

BACE1 and presenilin (PS)/γ-secretase play a major role in Alzheimer's disease pathogenesis by regulating amyloid-β peptide generation. We recently showed that these secretases also regulate the processing of voltage-gated sodium channel auxiliary β-subunits and thereby modulate membrane excitability. Here, we report that KCNE1 and KCNE2, auxiliary subunits of voltage-gated potassium channels, undergo sequential cleavage mediated by either α-secretase and PS/γ-secretase or BACE1 and PS/γ-secretase in cells. Elevated α-secretase or BACE1 activities increased C-terminal fragment (CTF) levels of KCNE1 and 2 in human embryonic kidney (HEK293T) and rat neuroblastoma (B104) cells. KCNE-CTFs were then further processed by PS/γ-secretase to KCNE intracellular domains. These KCNE cleavages were specifically blocked by chemical inhibitors of the secretases in the same cell models. We also verified our results in mouse cardiomyocytes and cultured primary neurons. Endogenous KCNE1- and KCNE2-CTF levels increased by 2- to 4-fold on PS/γ-secretase inhibition or BACE1 overexpression in these cells. Furthermore, the elevated BACE1 activity increased KCNE1 processing and shifted KCNE1/KCNQ1 channel activation curve to more positive potentials in HEK cells. KCNE1/KCNQ1 channel is a cardiac potassium channel complex, and the positive shift would lead to a decrease in membrane repolarization during cardiac action potential. Together, these results clearly showed that KCNE1 and KCNE2 cleavages are regulated by BACE1 and PS/γ-secretase activities under physiological conditions. Our results also suggest a functional role of KCNE cleavage in regulating voltage-gated potassium channels.—Sachse, C. C., Kim, Y. H., Agsten, M., Huth, T., Alzheimer, C., Kovacs, D. M., and Kim, D. Y. BACE1 and presenilin/γ-secretase regulate proteolytic processing of KCNE1 and 2, auxiliary subunits of voltage-gated potassium channels.

Alzheimer’s disease (AD) transgenic mice have been used as a standard AD model for basic mechanistic studies and drug discovery. These mouse models showed symbolic AD pathologies including β-amyloid (Aβ) plaques, gliosis and memory deficits but failed to fully recapitulate AD pathogenic cascades including robust phospho tau (p-tau) accumulation, clear neurofibrillary tangles (NFTs) and neurodegeneration, solely driven by familial AD (FAD) mutation(s). Recent advances in human stem cell and three-dimensional (3D) culture technologies made it possible to generate novel 3D neural cell culture models that recapitulate AD pathologies including robust Aβ deposition and Aβ-driven NFT-like tau pathology. These new 3D human cell culture models of AD hold a promise for a novel platform that can be used for mechanism studies in human brain-like environment and high-throughput drug screening (HTS). In this review, we will summarize the current progress in recapitulating AD pathogenic cascades in human neural cell culture models using AD patient-derived induced pluripotent stem cells (iPSCs) or genetically modified human stem cell lines. We will also explain how new 3D culture technologies were applied to accelerate Aβ and p-tau pathologies in human neural cell cultures, as compared the standard two-dimensional (2D) culture conditions. Finally, we will discuss a potential impact of the human 3D human neural cell culture models on the AD drug-development process. These revolutionary 3D culture models of AD will contribute to accelerate the discovery of novel AD drugs.

The “amyloid β hypothesis” of Alzheimer’s disease (AD) has been the reigning hypothesis explaining pathogenic mechanisms of AD over the last two decades. However, this hypothesis has not been fully validated in animal models, and several major unresolved factors remain. We recently developed a human neural cell culture model of AD based on a three-dimensional (3D) cell culture system. This unique, cellular model recapitulates major events of the AD pathogenic cascade, including β-amyloid plaques and neurofibrillary tangles. Our 3D human neural cell culture model system provides a premise for a new generation of cellular AD models that can serve as a novel platform for studying pathogenic mechanisms and for high-throughput drug screening in a human brain-like environment.

Primary hepatoid adenocarcinoma of the endometrium is a rare tumour that is similar to hepatocellular carcinoma histologically. Here, a patient with primary hepatoid carcinoma of the endometrium with a high alphafetoprotein (AFP) level (90,508 ng/mL) is presented in a 75-year-old woman. The pelvic computed tomography and magnetic resonance imaging suggested a submucosal leiomyoma with degeneration or endometrial hyperplasia. However, the endometrial biopsy revealed a primary hepatoid carcinoma of the endometrium. The patient underwent a staging laparotomy including a total abdominal hysterectomy, bilateral salpingo-oophorectomy and lymph node sampling with pelvic cytology. The AFP level can be highly elevated in hepatoid carcinoma of the endometrium.

Various post-translational modifications (PTMs) of pilin in Synechocystis sp. PCC 6803 have been proposed. In this study, we investigated previously unidentified PTMs of pilin by mass spectrometry (MS). MALDI-TOF MS and TOF/TOF MS showed that the molecular mass of the C-terminal lysine of pilin was increased by 42Da, which could represent acetylation (ΔM=42.0470) or trimethylation (ΔM=42.0106). To discriminate between these isobaric modifications, the molecular mass of the C-terminal tryptic peptide was measured using 15T Fourier transform ion cyclotron resonance (FT-ICR) MS. The high magnetic field FT-ICR provided sub-ppm mass accuracy, revealing that the C-terminal lysine was modified by trimethylation. We could also detect the existence of mono- and di-methylation of the C-terminal lysine. Cells expressing a pilin point mutant with glutamine replacing the C-terminal lysine showed dramatically reduced motility and short pili. These findings suggest that trimethylation of pilin at the C-terminal lysine may be essential for the biogenesis of functional pili.

β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the production of β-amyloid (Aβ), one of the major pathogenic molecules of Alzheimer’s disease (AD), and is therefore being actively pursued as a drug target for AD. Adult hippocampal neurogenesis (AHN) is a lifelong process that is known to be important for learning and memory and may have the potential to regenerate damaged neural tissue. In this study, we examined whether BACE1 regulates AHN, which holds important implications for its suitability as a drug target in AD. Cohorts of 2-month-old wild-type (BACE1+/+), heterozygous, and homozygous BACE1 knockout mice (BACE1+/–and BACE1–/–, respectively) were injected with 5-bromo-2′-deoxyuridine (BrdU) and sacrificed 1 day later to examine the impact of loss of BACE1 on neural precursor cell (NPC) proliferation in the adult brain. Parallel cohorts of mice were sacrificed 4 weeks after BrdU injection to determine the effects of BACE1 on survival and differentiation of newborn NPCs. We found that NPC proliferation was increased in BACE1–/–mice compared to BACE1+/+mice, while no difference was observed in NPC survival across genotypes. Differentiation of NPCs to neuronal lineage was impaired in BACE1–/–mice. However, no differences were observed in astrogenesis, the proportion of immature neurons, or the production of oligodendrocytes across genotypes. Importantly, corresponding with a decrease in neuronal differentiation in the absence of a complementary increase in an alternate cell fate, BACE1–/–mice were found to have a pool of undifferentiated NPCs in the hippocampus compared to BACE1+/+and BACE1+/–mice.

An olive-green mutant was generated in Synechocystis sp. strain PCC 6803 by inactivation of the sll0396 gene. Whole-cell absorption spectra of the mutant revealed the missing of phycocyanin peak. An investigation of the low-temperature fluorescence emission spectra revealed that the sll0396Ω mutant has a reduced amount of phycocyanin. Western blot analysis showed that the mutant contained less phycocyanin β- and α-subunits and lacked the 30- and 32-kDa linker polypeptides, and northern blot analysis revealed that the transcription of the 1.4-kb cpcBA gene encoding the phycocyanin β- and α-subunits was lower in the mutant. The Sll0396 protein has a DNA-binding motif and shares homology with known response regulators. Our results indicate that Sll0396 plays a regulatory role in the transcription of the phycocyanin genes during phycobilisome synthesis.

This study aimed to offer groundwork for grasp and evaluation of nutritional status and dietary fiber intake through 24-hr recall method among middle school students in Chungbuk area. In addition, this study attempted to develop food frequency questionnaire (FFQ) for dietary fiber intake. Average calorie intake per person a day was 2035.6 kcal for boys, and 1876.7 kcal for girls which were 75.4% and 93.8% of estimated energy requirement (EER), respectively. Percent estimated average requirements (%EAR) of calcium, iron and folate were the lowest showing 34.3%, 54.2%, 67.5% for boys and 36.6%, 59.2%, 64.4% for girls, respectively. Average dietary fiber intake per day was 17.6±5.3 g for boys and 16.5±4.8 g for girls which indicate 54.8% and 68.8% of adequate intake (AI), respectively. The main food sources of dietary fiber were polished rice and kimchi. The main food source groups were vegetables, cereals and their products were fruits, seaweeds in the order named, indicating 68.44% total dietary fiber intake from vegetables and cereals. From preliminary 39 food items, 19 food items were selected to derive the correlation coefficient of each food item between 24-hr recall and FFQ method. Correlation coefficient was increased from 0.71 to 0.78 with significant level of p

New solutions are proposed to the puzzles of how the Jubilee Year is reckoned and why the Jubilee begins on the Day of Atonement. The Jubilee cycle begins not in the first year of the Sabbath-year cycle, but the seventh, fallow year. The Jubilee begins on the Day of Atonement because of its Sabbath associations.

The HUPO Brain Proteome Project (HUPO BPP) held its 11th workshop in Kolymbari on March 3, 2009. The principal aim of this project is to obtain a better understanding of neurodiseases and ageing, with the ultimate objective of discovering prognostic and diagnostic biomarkers, in addition to the development of novel diagnostic techniques and new medications. The attendees came together to discuss sub-project progress in the clinical neuroproteomics of human or mouse models of Alzheimer's and Parkinson's disease, and to define the needs and guidelines required for more advanced proteomics approaches. With the election of new steering committees, the members of the HUPO BPP elaborated an actual plan promoting activities, outcomes, and future directions of the HUPO BPP to acquire new funding and new participants.

A protein identified in multiple separate bands of a 1-D gel reflects variation in the molecular weight caused by alternative splicing, endoproteolytic cleavage, or PTMs, such as glycosylation or ubiquitination. To characterize such a protein distribution over the bands, we defined an entity called an 'island' as the band region including the bands of the same protein identified sequentially. We quantified the island distribution using a new variable called an Iscore. Previously, as described in Park et al.. (Proteomics 2006, 6, 4978-4986.), we analyzed human brain tissue using a multidimensional MS/MS separation method. Here, the new method of island analysis was applied to the previous proteome data. The soluble and membrane protein fractions of human brain tissue were reanalyzed using the island distribution. The proteome of the soluble fraction exhibited more variation in island positions than that of the membrane fraction. Through the island analysis, we identified protein modifications and protein complexes over the 1-D gel bands.

Alzheimer’s disease (AD) is the most common cause of dementia, and there is currently no cure. The “β-amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including β-amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery.

Stem cell technologies have facilitated the development of human cellular disease models that can be used to study pathogenesis and test therapeutic candidates. These models hold promise for complex neurological diseases such as Alzheimer’s disease (AD) because existing animal models have been unable to fully recapitulate all aspects of pathology. We recently reported the characterization of a novel three-dimensional (3D) culture system that exhibits key events in AD pathogenesis, including extracellular aggregation of β-amyloid and accumulation of hyperphosphorylated tau. Here we provide instructions for the generation and analysis of 3D human neural cell cultures, including the production of genetically modified human neural progenitor cells (hNPCs) with familial AD mutations, the differentiation of the hNPCs in a 3D matrix, and the analysis of AD pathogenesis. The 3D culture generation takes 1–2 days. The aggregation of β-amyloid is observed after 6-weeks of differentiation followed by robust tau pathology after 10–14 weeks.

This paper examines the effect of a computer-assisted career guidance program in South Korean secondary schools. The program used for this study was developed by one of the paper’s co-authors, Young-Hye Kim, based on Harrington & O’Shea’s Career Decision-Making system. MVS (My Vocational Situation) is used for pre-post test. The t-test results indicate that there are some meaningful differences between control and experimental groups on the 9th and the 11th graders in South Korea. There appeared to be gender and age influences on the degree of the effect.

We present a case of a fetal pancreatic cyst, a rare disease in fetal life, detected prenatally at 30 weeks' gestation by ultrasound. Routine ultrasound examination at 30 weeks' gestation by primary obstetrician showed a cyst on the fetal abdomen. Initially, the suspected diagnosis was a mesenteric cyst. Subsequent ultrasound examination at weeks 32, 36 showed a fetal retroperitoneal cyst. A 3.6 kg female neonate was born to 23 yr old woman by spontaneous vaginal delivery at 38 weeks' gestation. The fetus underwent exploratory laparotomy. Histopathologic and immunohistochemical diagnosis revealed the cyst to be a pancreatic cyst. Surgical outcome was excellent. Thus, we report this case of a pancreatic cyst detected via prenatal ultrasonography.

Although there are many types of epilepsy, temporal lobe epilepsy (TLE) is probably in humans the most common and most often studied. TLE represents 40% of the total epilepsy form of the disease and is difficult to treat. Despite a wealth of descriptive data obtained from the disease history of patients, the EEG recording, imaging techniques, and histological studies, the epileptogenic process remains poorly understood. However, it is unlikely that a single factor or a single mechanism can cause many changes associated with this neuropathological phenomenon. MALDI mass spectrometry imaging (MSI) coupled to protein identification, because of its ability to study a wide range of molecules, appears to be suitable for the preparation of molecular profiles in TLE. Seven neuropeptides have been have been identified in Dental gyrus regions of the hippocampus in relation with TLE pathology. Shot-gun studies taking into account gender influence have been performed. Tissue microextraction from control (10) toward 10 TLE patients have been analyzed after trypsin digestion followed by separation on nanoLC coupled to LTQ orbitrap. From the shot-gun analyses, results confirmed the presence of specific neuropeptides precursors and receptors in TLE patients as well as proteins involved in axons regeneration including neurotrophins, ECM proteins, cell surface proteins, membrane proteins, G-proteins, cytoskeleton proteins and tumor suppressors. Among the tumor suppressors identified, the Leucine-rich glioma inactivated 1 (LGI1) protein was found. LGI1 gene recently been demonstrated being implicated in heritability of TLE. We have also demonstrate the presence a complete profile of tumor suppressors in TLE patients, 7 have been identified. Refining this analysis taken into account the gender influence in both control and in TLE reflected the presence of specific proteins between male and female and thus mechanisms in pathology development could be completely different.