Understanding Three Hydration-Dependent Transitions of Zwitterionic Carboxybetaine Hydrogel by Molecular Dynamics Simulations

In this work, molecular dynamics simulations were performed to study a carboxybetaine methacrylate (CBMA) hydrogel under various swelling states. The water content in this study ranged from 28% to 91% of the total weight of the hydrogel. Three transitions of the CBMA hydrogel were observed as the water content increased. The first transition occurs when the water content increases from 33% to 37%. The observed kink in the self-diffusion coefficient of water indicates that the hydration of the polymer network of the hydrogel is saturated; the further added water is in a less confined state. The second transition was found to be related to the physical cross-links of the polymer network. As the water content rises to above 62%, the lifetime of the physical cross-links decreases significantly. This abrupt change in the lifetime indicates that the transition represents the equilibrium swelling state of the hydrogel. Finally, the third transition was observed when the water content goes above 81%. The significant increases in the bond and angle energies of the polymer network indicate that the hydrogel reaches its upper limit swelling state at this transition. These results are comparable to previously published experimental studies of similar zwitterionic hydrogels

Adaptive evolution of the spike gene of SARS coronavirus: changes in positively selected sites in different epidemic groups

BACKGROUND: It is believed that animal-to-human transmission of severe acute respiratory syndrome (SARS) coronavirus (CoV) is the cause of the SARS outbreak worldwide. The spike (S) protein is one of the best characterized proteins of SARS-CoV, which plays a key role in SARS-CoV overcoming species barrier and accomplishing interspecies transmission from animals to humans, suggesting that it may be the major target of selective pressure. However, the process of adaptive evolution of S protein and the exact positively selected sites associated with this process remain unknown. RESULTS: By investigating the adaptive evolution of S protein, we identified twelve amino acid sites (75, 239, 244, 311, 479, 609, 613, 743, 765, 778, 1148, and 1163) in the S protein under positive selective pressure. Based on phylogenetic tree and epidemiological investigation, SARS outbreak was divided into three epidemic groups: 02–04 interspecies, 03-early-mid, and 03-late epidemic groups in the present study. Positive selection was detected in the first two groups, which represent the course of SARS-CoV interspecies transmission and of viral adaptation to human host, respectively. In contrast, purifying selection was detected in 03-late group. These indicate that S protein experiences variable positive selective pressures before reaching stabilization. A total of 25 sites in 02–04 interspecies epidemic group and 16 sites in 03-early-mid epidemic group were identified under positive selection. The identified sites were different between these two groups except for site 239, which suggests that positively selected sites are changeable between groups. Moreover, it was showed that a larger proportion (24%) of positively selected sites was located in receptor-binding domain (RBD) than in heptad repeat (HR)1-HR2 region in 02–04 interspecies epidemic group (p = 0.0208), and a greater percentage (25%) of these sites occurred in HR1–HR2 region than in RBD in 03-early-mid epidemic group (p = 0.0721). These suggest that functionally different domains of S protein may not experience same positive selection in each epidemic group. In addition, three specific replacements (F360S, T487S and L665S) were only found between 03-human SARS-CoVs and strains from 02–04 interspecies epidemic group, which reveals that selective sweep may also force the evolution of S genes before the jump of SARS-CoVs into human hosts. Since certain residues at these positively selected sites are associated with receptor recognition and/or membrane fusion, they are likely to be the crucial residues for animal-to-human transmission of SARS-CoVs, and subsequent adaptation to human hosts. CONCLUSION: The variation of positive selective pressures and positively selected sites are likely to contribute to the adaptive evolution of S protein from animals to humans

The key role for local base order in the generation of multiple forms of China HIV-1 B'/C intersubtype recombinants

BACKGROUND: HIV-1 is a retrovirus with high rate of recombination. Increasing experimental studies in vitro indicated that local hairpin structure of RNA was associated with recombination by favoring RT pausing and promoting strand transfer. A method to estimate the potential to form stem-loop structure by calculating the folding of randomized sequence difference (FORS-D) has been used to investigate the relationship between secondary structure and evolutionary pressure in some genome. It showed that gene regions under strong positive "Darwinian" selection were associated with positive FORS-D values. In the present study, the sequences of HIV-1 subtypes B' and C, both of which represent the parent strains of CRF07_BC, CRF08_BC and China URFs, were selected to investigate the relationship between natural recombination and secondary structure by calculating the FORS-D values. RESULTS: The apparent higher negative FORS-D value region appeared in the gag-pol gene region (nucleotide 0–3000) of HIV-1 subtypes B' and C. Thirteen (86.7 %) of 15 mosaic fragments and 17 (81 %) of 21 recombination breakpoints occurred in this higher negative FORS-D region. This strongly suggested that natural recombination did not occur randomly throughout the HIV genome, and that there might be preferred (or hot) regions or sites for recombination. The FORS-D analysis of breakpoints showed that most breakpoints of recombinants were located in regions with higher negative FORS-D values (P = 0.0053), and appeared to have a higher negative average FORS-D value than the whole genome (P = 0.0007). The regression analysis also indicated that FORS-D values correlated negatively with breakpoint overlap. CONCLUSION: High negative FORS-D values represent high, base order determined stem-loop potentials and influence mainly the formation of stem-loop structures. Therefore, the present results suggested for the first time that occurrence of natural recombination was associated with high base order-determined stem-loop potential, and that local base order might play a key role in the initiation of natural recombination by favoring the formation of stable stem-loop structures

Induction of mast cell accumulation, histamine release and skin edema by N49 phospholipase A2

<p>Abstract</p> <p>Background</p> <p>It has been recognized that phospholipase A₂(PLA₂) is a crucial component of snake venom, which contributes greatly to snake venom induced inflammation in man. However, the mechanisms through which N49 PLA₂provoke inflammation remain unclear. Recently, a N49 PLA₂, TM-N49 from <it>Protobothrops mucrosquamatus </it>crude venom was characterized in our laboratory. Since the purification procedure developed is able to supply us with relatively large quantity of highly purified TM-N49, we investigated the ability of TM-N49 in induction of inflammation.</p> <p>Results</p> <p>The results showed that TM-N49 provoked a dose dependent increase in microvascular leakage in the skin of rats. The potency of TM-N49 in induction of skin edema appeared similar potency of bradykinin and histamine. Pretreatment of rats with compound 48/80 diminished TM-N49 induced skin reaction and reduced mast cell numbers in rats. Ginkgolide B and cyproheptadine, but not terfenadine and quinacrine, inhibited TM-N49 elicited microvascular leakage when they were co-injected with the stimulus to rat skin. Moreover, TM-N49 was found to induce histamine release from human colon, lung and tonsil mast cells, and both metabolic inhibitors and pertussis toxin were capable of inhibiting TM-N49 elicited histamine release. TM-N49 induced mast cell accumulation in the peritoneum of mice, which was inhibited by co-injection of ginkgolide B, cyproheptadine and terfenadine. Intravenous injection of monoclonal antibodies against CD18, ICAM-1 and CD11a also blocked TM-N49 induced mast cell accumulation.</p> <p>Conclusion</p> <p>TM-N49 is a potent stimulus for skin edema, mast cell activation and accumulation.</p

Carotid and cerebrovascular disease in symptomatic patients with type 2 diabetes: assessment of prevalence and plaque morphology by dual-source computed tomography angiography

<p>Abstract</p> <p>Background</p> <p>Plaque morphology directly correlates with risk of embolism and the recently developed dual-source computed tomography angiography (DSCTA) may help to detect plaques more precisely. The aim of our study was to evaluate the prevalence and morphology of carotid and cerebrovascular atherosclerotic plaques in patients with symptomatic type 2 diabetes mellitus (DM) by DSCTA.</p> <p>Methods</p> <p>From July 2009 to August 2010, DSCTA was prospectively performed in 125 consecutive patients with symptomatic type 2 DM. We retrospectively analyzed plaque type, distribution, and extensive and obstructive natures were determined for each segment for all patients.</p> <p>Results</p> <p>Atherosclerotic plaques were detected in 114 (91.2%) patients. Relatively more noncalcified (45%) and calcified (39%) plaques and less mixed (16%) plaques were observed (p < 0.001). Noncalcified plaques were found mainly in the intracranial arteries (81.8%), mixed plaques in the intracranial arteries (25.2%) and intracranial internal carotid artery (ICA) (56.1%). Calcified plaques were found mainly in the intracranial ICA (65.9%) and extracranial arteries (28.2%) (for all, p < 0.001). Extension of plaques from the 1^stto 5^thsegments was observed in 67 (58.8%) patients and from the 6^thto 10^thsegments in 35 (30.7%) patients. The most common site of all detected plaques was the cavernous segment. Regarding stenosis, there were significantly more nonobstructive than obstructive stenosis (91% vs. 9%, p < 0.001).</p> <p>Conclusion</p> <p>DSCTA detected a high prevalence of plaques in patients with symptomatic type 2 DM. A relatively high proportion of plaques were noncalcified, as well as with nonobstructive stenosis. The distribution of plaques was extensive, with the cavernous portion of ICA being the most common site.</p

Characteristics of coronary artery disease in symptomatic type 2 diabetic patients: evaluation with CT angiography

<p>Abstract</p> <p>Background</p> <p>Coronary artery disease (CAD) is a common and severe complication of type 2 diabetes mellitus (DM). The aim of this study is to identify the features of CAD in diabetic patients using coronary CT angiography (CTA).</p> <p>Methods</p> <p>From 1 July 2009 to 20 March 2010, 113 consecutive patients (70 men, 43 women; mean age, 68 ± 10 years) with type 2 DM were found to have coronary plaques on coronary CTA. Their CTA data were reviewed, and extent, distribution and types of plaques and luminal narrowing were evaluated and compared between different sexes.</p> <p>Results</p> <p>In total, 287 coronary vessels (2.5 ± 1.1 per patient) and 470 segments (4.2 ± 2.8 per patient) were found to have plaques, respectively. Multi-vessel disease was more common than single vessel disease (<it>p </it>< 0.001), and the left anterior descending (LAD) artery (35.8%) and its proximal segment (19.1%) were most frequently involved (all <it>p </it>< 0.001). Calcified plaques (48.8%) were the most common type (<it>p </it>< 0.001) followed by mixed plaques (38.1%). Regarding the different degrees of stenosis, mild narrowing (36.9%) was most common (<it>p </it>< 0.001); however, a significant difference was not observed between non-obstructive and obstructive stenosis (50.4% vs. 49.6%, <it>p </it>= 0.855). Extent of CAD, types of plaques and luminal narrowing were not significantly different between male and female diabetic patients.</p> <p>Conclusions</p> <p>Coronary CTA depicted a high plaque burden in patients with type 2 DM. Plaques, which were mainly calcified, were more frequently detected in the proximal segment of the LAD artery, and increased attention should be paid to the significant prevalence of obstructive stenosis. In addition, DM reduced the sex differential in CT findings of CAD.</p

The LAMOST Complete Spectroscopic Survey of Pointing Area (LaCoSSPAr) in the Southern Galactic Cap I. The Spectroscopic Redshift Catalog

We present a spectroscopic redshift catalog from the LAMOST Complete Spectroscopic Survey of Pointing Area (LaCoSSPAr) in the Southern Galactic Cap (SGC), which is designed to observe all sources (Galactic and extra-galactic) by using repeating observations with a limiting magnitude of $r=18.1~mag$ in two $20~deg^2$ fields. The project is mainly focusing on the completeness of LAMOST ExtraGAlactic Surveys (LEGAS) in the SGC, the deficiencies of source selection methods and the basic performance parameters of LAMOST telescope. In both fields, more than 95% of galaxies have been observed. A post-processing has been applied to LAMOST 1D spectrum to remove the majority of remaining sky background residuals. More than 10,000 spectra have been visually inspected to measure the redshift by using combinations of different emission/absorption features with uncertainty of $\sigma_{z}/(1+z)<0.001$. In total, there are 1528 redshifts (623 absorption and 905 emission line galaxies) in Field A and 1570 redshifts (569 absorption and 1001 emission line galaxies) in Field B have been measured. The results show that it is possible to derive redshift from low SNR galaxies with our post-processing and visual inspection. Our analysis also indicates that up to 1/4 of the input targets for a typical extra-galactic spectroscopic survey might be unreliable. The multi-wavelength data analysis shows that the majority of mid-infrared-detected absorption (91.3%) and emission line galaxies (93.3%) can be well separated by an empirical criterion of $W2-W3=2.4$. Meanwhile, a fainter sequence paralleled to the main population of galaxies has been witnessed both in $M_r$/$W2-W3$ and $M_*$/$W2-W3$ diagrams, which could be the population of luminous dwarf galaxies but contaminated by the edge-on/highly inclined galaxies ($\sim30\%$).Comment: 19 pages, 14 figures, 2 MRT, accepted by ApJ