SEQ Mapper: A DNA sequence searching tool for massively parallel sequencing data.

The development of massively parallel sequencing (MPS) has increased greatly the scale of DNA sequencing. The analysis of massive data-files from single MPS analysis can be a major challenge if examining the data for potential polymorphic loci. To aid in the analysis of both short tandem repeat (STR) and single nucleotide polymorphisms (SNP), we have designed a new program called SEQ Mapper to search for genetic polymorphisms within a large number of reads generated by MPS. This new program has been designed to perform sequence mapping between reference data and generated reads. As a proof-of-concept, sequences derived from the allelic ladders of five STR loci and data from the amelogenin locus were used as reference data sets. Detecting and recording the polymorphic nature of each STR loci was performed using four levels of search criteria: the entire STR locus spanning the two primers; the STR region plus the two primer sequences; the STR region only; and the two primers only. All the genotypes of 5 STR loci and the amelogenin gene were identified correctly using SEQ Mapper when compared to results obtained from capillary electrophoresis based on 10 test samples in this study. SEQ Mapper is a useful tool to detect STR or SNP alleles generated by MPS in both clinical medicine and forensic genetics.

The importance of steric zipper on the aggregation of the MVGGVV peptide derived from the amyloid beta peptide.

Amyloid-like fibrils are found in many fatal diseases, such as Alzheimer's disease, Parkinson's disease, type II diabetes mellitus, and prion diseases. Recently, the structural characterization of the MVGGVV peptide from the C-terminal hydrophobic segment of the amyloid-B (AB) peptide has revealed a general feature of amyloid-like fibrils, termed as "steric zipper", which is constituted by a tight side-chain complementation of the opposing B-sheet layers. In this study, several all-atom molecular dynamics simulations with explicit water were conducted to investigate the importance of steric zipper on the aggregation of the MVGGVV peptide. Our results show that the structural stability of the MVGGVV oligomers increases with increasing the number of B-strands. We further proposed that the octameric structure (the SH2-ST4 model in this study) is the possible nucleus seed for MVGGVV protofibril formation. Our results also demonstrated that hydrophobic interaction is the principle driving force to stabilize the adjacent B-strands while the steric zipper involved M1, V2, V5 and V6 is responsible for holding the neighboring B-sheet layers together. Finally, a twisted model of the MVGGVV assembly (SH2-ST50), based on the averaged twisted angle of approximately 11.5 degrees between the adjacent B-strands of the SH2-ST4 model, was proposed. Our results gain insights into the aggregation of the MVGGVV peptide in atomic details and may provide a hint for designing new inhibitors able to prevent the fibril formation of the AB peptide.

Molecular dynamics simulations to investigate the structural stability and aggregation behavior of the GGVVIA oligomers derived from amyloid beta peptide.

Several neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases, are associated with amyloid fibrils formed by different polypeptides. Recently, the atomic structure of the amyloid-forming peptide GGVVIA from the C-terminal hydrophobic segment of amyloid-beta (Abeta) peptide has been determined and revealed a dry, tightly self-complementing structure between two beta-sheets, termed as "steric zipper". In this study, several all-atom molecular dynamics simulations with explicit water were conducted to investigate the structural stability and aggregation behavior of the GGVVIA oligomers with various sizes. The results of our single-layer models suggested that the structural stability of the GGVVIA oligomers increases remarkably with increasing the numbers of beta-strands. We further identified that SH2-ST2 may act as a stable seed in prompting amyloid fibril formations. Our results also demonstrated that hydrophobic interaction is the principle driving force to stabilize and associate the GGVVIA oligomers between beta-strands; while the hydrophobic steric zipper formed via the side chains of V3, V4, and I5 plays a critical role in holding the two neighboring beta-sheets together. Single glycine substitution at V3, V4, and I5 directly disrupted the hydrophobic steric zipper between these two beta-sheets, resulting in the destabilization of the oligomers. Our simulation results provided detailed insights into understanding the aggregation behavior of the GGVVIA oligomers in the atomic level. It may also be helpful for designing new inhibitors able to prevent the fibril formation of Abeta peptide.

Streptococcus constellatus causing myocardial abscess complicated by cerebritis.

Streptococcus constellatus infection is a rare cause of myocardial abscess. The complication of cerebritis is also rare. We report a case of S. constellatus bacteremia in a 21-year-old woman who developed fever and watery diarrhea 7 days prior to admission. Computed tomography of the brain showed severe effacement of the cerebral sulci, narrowing of the ventricular system, and severe brain swelling. Echocardiography showed a cystic lesion of about 2 cm(2) over the left atrium. Mannitol and dexamethasone were administered. Hyperventilation was performed. Intravenous penicillin G and ceftazidime were administered but without response. The increased intracranial pressure persisted despite medical treatment. She died 3 days after admission. Culture of cerebrospinal fluid grew S. constellatus and 3 sets of blood cultures grew S. constellatus. This case emphasizes the potential pathogenic role of S. constellatus in myocardial abscess.

Morganella morganii causing solitary liver abscess complicated by pyopericardium and left pleural effusion in a nondiabetic patient.

Morganella morganii is a rare cause of solitary liver abscess in Taiwan. The complication of pyopericardium and pleural effusion in nondiabetic patient with solitary liver abscess are also rare. We present a case of a 48-year-old nondiabetic woman who experienced with epigastric discomfort 1 month prior to admission. Chills and fever developed 2 weeks before admission. Physical examination on admission revealed engorgement of the jugular vein over the right neck, precordial friction rubs, and tenderness over the right upper quadrant of abdomen. Chest film showed mild cardiomegaly and left pleural effusion. Computed tomography of the abdomen showed liver abscess, left hepatic lobe, pyopericardium, and left pleural effusion. M. morganii was isolated from 2 sets of blood cultures, one set of hepatic pus culture, and one set of pericardial pus culture. After pigtail drainage of liver abscess, pyopericardium for 12 days, and ceftriaxone intravenous administration for 19 days, the patient was discharged in stable condition.