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Primary drug resistance is an emerging problem in HIV infections. We have investigated the current prevalence of primary resistance in Korea and compared it with previous data. Drug-naive HIV patients attending the outpatient clinic of Seoul National University Hospital between April and August 2006 were enrolled. A medical interview and a genotypic resistance test were performed for each patient. The International AIDS Society-USA Panel consensus statement issued in 2006 was used to define resistance mutations. Eighty-one drug-naive HIV patients were enrolled. Two (2.5) were infected with primary drug-resistant virus M41L and K103N, respectively. In our previous study, conducted between 1998 and 2002, three (6) of 50 subjects harbored resistant viruses. Thus the frequency of primary resistance was lower in the present sample than in the earlier one, though the difference is not statistically significant (p 0.37). In view of our findings, routine antiretroviral resistance tests for drug-naive HIV patients are not obligatory in Korea. [ABSTRACT FROM AUTHOR]

Silicon (Si) has a large theoretical capacity of 4200 mAhg−1 and has great potential as a high-performance anode material for Li ion batteries (LIBs). Meanwhile, nanostructures can exploit the potential of Si and, accordingly, many zero-dimensional (0D) and one-dimensional (1D) Si nanostructures have been studied. Herein, we report on two-dimensional (2D) Si nanostructures, Si nanosheets (SiNSs), as anodes for LIBs. These 2D Si nanostructures, with a thickness as low 5 nm and widths of several micrometers, show reversible crystalline–amorphous phase transformations with the lithi-/delithiation by the dimensionality of morphology and large surface area. The reversible crystalline–amorphous phase transformation provides a structural stability of Li+ insertions and makes SiNSs promising candidates for reliable high-performance LIBs anode materials. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the possibilities of harmful consequences during application of general anesthesia in a patient suffering from vocal process granuloma due to obstructed air-way.

The article illustrates a simple alternative explanation for ø values less than 0 or less than 1 which is the denatured state effects. According to the authors, there is an increasing evidence that the denatured state ensemble can contain energetically important interactions and that mutations can exert energetically significant effects that are comparable to or larger than there effect on the transition state. Details about the three representative ø values are examined.

Influenza A virus (IAV) nonstructural protein 1 (NS1) is a multifunctional virulence factor that interacts with several host factors such as phosphatidylinositol-3-kinase (PI3K). NS1 binds specifically to the p85β regulatory subunit of PI3K and subsequently activates PI3K signaling. Here, Kim et al. show that functionally near-neutral, strain-specific NS1 mutations lead to variations in binding kinetics to p85β exhibit long-range epistatic interactions. Applying NMR they provide evidence that the structural dynamics of the NS1 hydrophobic core have evolved over time and contributed to epistasis.

Objectives Methicillin-resistant Staphylococcus aureus (MRSA), originally restricted to hospitals, has emerged as a significant pathogen in the community. Although MRSA accounts for over 60% of S. aureus in tertiary hospitals in Korea, little is known about the epidemiology of community-associated MRSA (CA-MRSA). Methods From January to July 2005, a hospital laboratory-based survey was conducted in seven community-based or tertiary hospitals. The medical records and Health Insurance Review Agency databases were reviewed and MRSA isolated from patients without apparent risk factors was defined as CA-MRSA. Susceptibilities to 12 antibiotics were tested by the disc diffusion method. SCCmec typing, Panton–Valentine leucocidin (PVL) gene detection and multilocus sequence typing (MLST) were performed according to published protocols. Results Of 3251 S. aureus, 1900 (58.4%) were MRSA. CA-MRSA accounted for 112 (5.9%) of the MRSA. Of the 112 CA-MRSA isolates, 27 and 33 were found to be pathogens and colonizers, respectively. Fifty-two isolates from the patients with chronic otitis media were classified as ‘undetermined’. Most of the 27 CA-MRSA patients had skin and soft tissue infections or acute ear infections. None of the patients died during the study period. Among 72 isolates tested, 64% were multidrug-resistant. SCCmec type IVa was the most common type among the colonizers and pathogens. On MLST analysis, ST72 was predominant, but ST5 and ST239 were prevalent in the ‘undetermined’ group. None possessed the PVL gene. Conclusions Despite MRSA-endemic hospital settings, CA-MRSA infections are not common in Korea. A new clone of CA-MRSA, ST72-SCCmec type IVa without the PVL gene, is the most common form. [ABSTRACT FROM AUTHOR]

Abstract Despite favorable responses to initial chemotherapy, drug resistance is a major cause limiting chemotherapeutic efficacy in many advanced cancers. However, mechanisms that drive drug-specific resistance in chemotherapy for patients with advanced cancers are still unclear. Here, we report a unique role of death-associated protein kinase-related apoptosis-inducing kinase 1 (DRAK1) associated with paclitaxel resistance in cervical cancer cells. Interestingly, DRAK1 protein level was markedly decreased in paclitaxel-resistant cervical cancer cells without affecting its mRNA expression, which resulted in an increase in tumor necrosis factor receptor-associated factor 6 (TRAF6) expression, as well as an activation of TRAF6-mediated nuclear factor-kappa B (NF-κB) signaling cascade, thereby promoting tumor progression. DRAK1 depletion markedly increased the chemotherapeutic IC50 values of paclitaxel in cervical cancer cells. Ectopic expression of DRAK1 inhibited growth of paclitaxel-resistant cervical cancer cells in vitro and in vivo. Furthermore, DRAK1 was markedly underexpressed in chemoresistant cervical cancer patient tissues compared with chemosensitive samples. We found that DRAK1 protein was destabilized through K48-linked polyubiquitination promoted by the Cullin scaffold protein 3 (CUL3) / speckle-type POZ (poxvirus and zinc finger protein) protein (SPOP) E3 ubiquitin ligase in paclitaxel-resistant cells. Collectively, these findings suggest that DRAK1 may serve as a potential predictive biomarker for overcoming paclitaxel resistance in cervical cancer.

Objective: Obesity is a risk factor for endometrial cancer. Recently, visceral fat is strongly associated with obesity-related carcinogenesis, more than subcutaneous fat. In this study, we hypothesized that the visceral fat measured by computed tomography (CT) contributes to the occurrence of endometrial cancer. Methods: A retrospective chart review of patients undergoing primary surgery for endometrial cancer was conducted. The volume of visceral fat was measured by CT scans performed at the fourth lumbar level for all participants. Body fat distributions assessed by a direct method in 52 endometrial cancer cases were compared with those of age- and BMI-matched healthy community controls. Results: Case group showed significantly higher mean visceral fat area (VFA; 76.2 ± 25.0 vs. 62.2 ± 13.9 cm2, P = 0.007). The mean total fat area (TFA; 270.3 ± 99.9 vs. 238.9 ± 53.8 cm2, P = 0.137) and subcutaneous fat area (SFA; 194.2 ± 86.5 vs. 176.7 ± 45.8 cm2, P = 0.315), however, presents no significant differences. VFA showed lower correlation with BMI (r2 = 0.299, P < 0.001) than to SFA (r2 = 0.528, P < 0.001) or TFA (r2 = 0.584, P < 0.001). In receiver operator characteristic (ROC) curve, at a VFA value of 70.8 cm2, sensitivity and specificity of the case group was 55.8% and 75%, respectively. Conclusion: Increased abdominal visceral fat is associated with endometrial cancer risk and can be predicted by measuring CT scans. Furthermore, as the most independent factor of BMI, VFA may provide additional information for representative risks of endometrial cancer.

For the analysis of simultaneous EEG-fMRI recordings, it is vital to use effective artifact removal tools. This applies in particular to the ballistocardiogram (BCG) artifact which is difficult to remove without distorting signals of interest related to brain activity. Here, we documented the use of surrogate source models to separate the artifact-related signals from brain signals with minimal distortion of the brain activity of interest. The artifact topographies used for surrogate separation were created automatically using principal components analysis (PCA-S) or by manual selection of artifact components utilizing independent components analysis (ICA-S). Using real resting-state data from 55 subjects superimposed with simulated auditory evoked potentials (AEP), both approaches were compared with three established BCG artifact removal methods: Blind Source Separation (BSS), Optimal Basis Set (OBS), and a mixture of both (OBS-ICA). Each method was evaluated for its applicability for ERP and source analysis using the following criteria: the number of events surviving artifact threshold scans, signal-to-noise ratio (SNR), error of source localization, and signal variance explained by the dipolar model. Using these criteria, PCA-S and ICA-S fared best overall, with highly significant differences to the established methods, especially in source localization. The PCA-S approach was also applied to a single subject Berger experiment performed in the MRI scanner. Overall, the removal of BCG artifacts by the surrogate methods provides a substantial improvement for the analysis of simultaneous EEG-fMRI data compared to the established methods.

Interest in the unfolded state of proteins has grown with the realization that this state can have considerable structure in the absence of denaturants. Natively unfolded proteins, mutations that unfold proteins under native conditions, and changes in pH that induce unfolding are attractive models for the unfolded state in the absence of denaturant. The unfolded state of the N-terminal domain of ribosomal protein L9 (NTL9) was previously shown to contain significant non-native electrostatic interactions [Cho, J. H., Sato, S., and Raleigh, D. P. (2004) J. Mol. Biol. 338, 827-8371. NTL9 has a mixed α-β structure and folds via a two-state mechanism. We have generated a model of the unfolded state of NTL9 in the absence of denaturant by substitution of an alanine for phenylalanine 5 located in the core of this protein. The CD spectrum of the variant, denoted as F5A, exhibits significantly less structure than the wild type; however, the mean residue ellipticity of F5A at 222 nm (-8200 deg cm² dmol-1) is considerably larger than expected for a fully unfolded protein, indicating that residual secondary structure is populated. F5A also has more residual structure than the urea-unfolded wild type. The stability of F5A is estimated to be at least 1 kcal/mol unfavorable, showing that the unfolded state is populated to 84% or more. NMR pulsed-field gradient measurements yield a hydrodynamic radius of 16.1 Å for wild-type NTL9 and 20.8 Å for the F5A variant in native buffer. The physiologically relevant unfolded state of wild-type NTL9 is likely to be even more compact than F5A since the mutation should reduce the level of hydrophobic clustering in the unfolded state in the absence of denaturant. The hydrodynamic radius of F5A increases to 25.9 Å in 8 M urea, and a value of 23.5 Å is obtained for the wild type under similar conditions. The results show that the unfolded state of F5A in the absence of denaturant is more compact and contains more structure than the urea-unfolded form. [ABSTRACT FROM AUTHOR]

Islet amyloid deposits are a characteristic pathological hallmark of type 2 diabetes mellitus. Islet amyloid polypeptide (IAPP), also referred to as amylin, aggregates in the islet extracellular space to form amyloid deposits in up to 95% of patients with the disease. IAPP is stored with insulin in β-islet cells and is processed in parallel by subtilisin-like prohormone convertases prior to secretion. There is indirect evidence that normal processing of the prohormone precursor, proIAPP, at the N-terminal cleavage site is defective in type 2 diabetes and results in secretion of an N-terminal extended proIAPP intermediate. The N-terminal flanking region of proIAPP is detected in amyloid deposits; however, the C-terminal flanking region is not. Immunohistochemical studies implicate the presence of the heparan sulfate proteoglycan (HSPG) perlecan in islet amyloid deposits, suggesting a role for HSPGs in mediating amyloid deposition in type 2 diabetes and implicating a binding domain in the N-terminus of proIAPP. Initial studies of proIAPP indicated that the HSPG binding region is contained within the first 30 residues. Here, we characterize the potential HSPG binding site of proIAPP in detail by analyzing a set of peptide fragments. Binding is tighter at low pH due to protonation of histidine residues. Deletion studies show that Arg-22 and His-29 play a role in binding. Reduction of the Cys-13 to Cys-18 disulfide leads to a noticeable decrease in binding. We demonstrate the ability of heparan sulfate to induce amyloid formation in N-terminal fragments of proIAPP. The oxidized peptide forms amyloid more rapidly than the reduced variant in the presence of heparan sulfate, but the reduced peptide ultimately forms more extensive amyloid deposits. The potential implications for islet amyloid formation in vivo are discussed. [ABSTRACT FROM AUTHOR]

Biomolecular recognition often involves conformational changes as a prerequisite for binding (i.e., conformational selection) or concurrently with binding (i.e., induced-fit). Recent advances in structural and kinetic approaches have enabled the detailed characterization of protein motions at atomic resolution. However, to fully understand the role of the conformational dynamics in molecular recognition, studies on the binding transition state are needed. Here, we investigate the binding transition state between nonstructural protein 1 (NS1) of the pandemic 1918 influenza A virus and the human p85β subunit of PI3K. 1918 NS1 binds to p85β via conformational selection. We present the free-energy mapping of the transition and bound states of the 1918 NS1:p85β interaction using linear free energy relationship and ϕ-value analyses. We find that the binding transition state of 1918 NS1 and p85β is structurally similar to the bound state with well-defined binding orientation and hydrophobic interactions. Our finding provides a detailed view of how protein motion contributes to the development of intermolecular interactions along the binding reaction coordinate.

The accurate discrimination between bipolar disorder (BD) and schizophrenic patients is crucial because of the considerable overlap between their clinical signs and symptoms (e.g., hallucination and delusion). Recently, electroencephalograms (EEGs) measured in the resting state have been vastly analyzed as a means for classifying the BD and schizophrenic patients, but EEGs evoked by external audio/visual stimuli have been rarely investigated, despite their high signal-to-noise ratio (SNR). In this study, in order to investigate whether EEGs evoked by external stimuli can be used for classifying the BD and schizophrenic patients, we used a visual stimulus modulated at a specific frequency to induce steady-state visual evoked potential (SSVEP). In the experiment, a photic stimulation modulated at 16 Hz was presented to two groups of the schizophrenic and BD patients for 95 s, during which the EEG data were recorded. Statistical measures of SSVEPs (mean, skewness, and kurtosis) described in SNR units were extracted as features to characterize and classify the variations of brain activity patterns in the two groups. Two brain areas, O1 and Fz, showed a statistically significant difference between the two groups for SNR mean and kurtosis, respectively. Among five applied classifiers, k-nearest neighbor provided the highest classification accuracy of 91.30% with the best feature set selected by Fisher score. An acceptable accuracy for binary classification (>70%) was retained until analysis time was reduced up to 10 s using a support vector machine classifier, and 20 s for other classifiers. Our results demonstrate the potential applicability of the proposed SSVEP-based classification approach with relatively short single-trial EEG signals.

The 1918 influenza A virus (IAV) caused the worst flu pandemic in human history. Non-structural protein 1 (NS1) is an important virulence factor of the 1918 IAV and antagonizes host antiviral immune responses. NS1 increases virulence by activating phosphoinositide 3-kinase (PI3K) via binding to the p85β subunit of PI3K. Intriguingly, unlike the NS1 of other human IAV strains, 1918 NS1 hijacks another host protein, CRK, to form a ternary complex with p85β, resulting in hyperactivation of PI3K. However, the molecular basis of the ternary interaction between 1918 NS1, CRK, and PI3K remains elusive. Here, we report the structural and thermodynamic bases of the ternary interaction. We find that the C-terminal tail (CTT) of 1918 NS1 remains highly flexible in the complex with p85β. Thus, the CTT of 1918 NS1 in the complex with PI3K can efficiently hijack CRK. Notably, our study indicates that 1918 NS1 enhances its affinity to p85β in the presence of CRK, which might result in enhanced activation of PI3K. Our results provide structural insight into how 1918 NS1 hijacks two host proteins simultaneously.

An abdominal aortic aneurysm doesn't result in specific symptoms, and so providing a successful diagnosis can be challenging. Patients may require surgery for successful treatment, with the risk of aortic rupture being dependent on diameter. In this study, a CT screen of a patient with an aneurysm of the abdominal aorta was processed. In order to provide a more accurate and comfortable diagnosis, and to more easily determine the diameter of the abdominal aortic aneurysm, the Sobel and Top-hat methods were employed. Using a filtered screen overlap for the CT scan, the aortic diameter of a patient could be compared with the diameter of a healthy individual, thus allowing an immediate and accurate comparison. It was found that with a diameter of more than 40 mm the risk of rupture is higher. [ABSTRACT FROM AUTHOR]

The molecular characterization of symbionts is pivotal for understanding the cross-talk between symbionts and hosts. In addition to valuable knowledge obtained from symbiont genomic studies, the biochemical characterization of symbionts is important to fully understand symbiotic interactions. The bean bug (Riptortus pedestris) has been recognized as a useful experimental insect gut symbiosis model system because of its cultivatable Burkholderia symbionts. This system is greatly advantageous because it allows the acquisition of a large quantity of homogeneous symbionts from the host midgut. Using these naïve gut symbionts, it is possible to directly compare in vivo symbiotic cells with in vitro cultured cells using biochemical approaches. With the goal of understanding molecular changes that occur in Burkholderia cells as they adapt to the Riptortus gut environment, we first elucidated that symbiotic Burkholderia cells are highly susceptible to purified Riptortus antimicrobial peptides. In search of the mechanisms of the increased immunosusceptibility of symbionts, we found striking differences in cell envelope structures between cultured and symbiotic Burkholderia cells. The bacterial lipopolysaccharide O antigen was absent from symbiotic cells examined by gel electrophoretic and mass spectrometric analyses, and their membranes were more sensitive to detergent lysis. These changes in the cell envelope were responsible for the increased susceptibility of the Burkholderia symbionts to host innate immunity. Our results suggest that the symbiotic interactions between the Riptortus host and Burkholderia gut symbionts induce bacterial cell envelope changes to achieve successful gut symbiosis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate magnetic resonance (MR) imaging for the discrimination between low-grade chondrosarcoma and enchondroma. Materials and methods: MR images of 34 patients whowere confirmedwith low-grade chondrosarcoma or enchondromawere retrospectively reviewed. After review of medical records, MR findings in 18 patients with low-grade chondrosarcoma and 16 patients with enchondroma were compared. MR images were retrospectively reviewed for the lesion location (central or eccentric; epiphysis, metaphysic, or diaphysis), margin, contour, mineralized matrix, endosteal scalloping, cortical expansion, cortical destruction, soft tissue mass formation, and periosteal reaction. Signal intensity, the patterns of contrast enhancement (unilocular ormultilobular), soft tissue mass, and adjacent abnormal bonemarrowand soft tissue signal were also reviewed. Statistical analysis was performed with chi-square test. Results: The patients with low-grade chondrosarcoma had a significantly higher incidence of MR findings (P<.05): predominantly intermediate signal on T1-weighted images [72% (13/18) in low-grade chondrosarcoma vs. 25% (4/16) in enchondroma], multilocular appearance on contrast-enhanced T1-weighted images [83% (15/18) vs. 44% (7/16)], cortical destruction [33% (6/18) vs. 0% (0/16)], a soft tissue mass [28% (5/18) vs. 0% (0/16)], adjacent bone marrow and soft tissue abnormal signal [22% (4/18) vs. 0% (0/16)], and an involvement of the epiphysis or flat bone [56% (10/18) vs. 19% (3/16)]. Conclusion: MR imaging shows helpful features for differentiating low-grade chondrosarcoma from enchondroma. [ABSTRACT FROM AUTHOR]