Site-Specific Structural Variations Accompanying Tubular Assembly of the HIV-1 Capsid Protein

The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent ¹⁵N and ¹³C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide ¹H nuclei, and quantitative measurements of site-specific ¹⁵N–¹⁵N dipole–dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD–CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 3₁₀-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD–CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD–CTD dimerization interfaces are less significant.     

External control of the Drosophila melanogaster lifespan by combination of 3D oscillating low-frequency electric and magnetic fields

We demonstrate that the lifespan of Drosophila melanogaster population is controllable by a combination of external three-dimensional oscillating low-frequency electric and magnetic fields (3D OLFEMFs). The lifespan was decreased or increased in dependence of the parameters of the external 3D OLFEMFs. We propose that metabolic processes in D. melanogaster’s body are either accelerated (in the case of reduced lifespan) or slowed down (in the case of increased lifespan) in function of 3D OLFEMFs that induce vibrational motions on sub-cellular and larger scales.     

Conformation of the metastasis-inhibiting laminin pentapeptide

The binding of cancer cells to the basement membrane glycoprotein laminin appears to be a critical step in the metastatic process. This binding can be inhibited competitively by a specific pentapeptide sequence (Tyr-Ile-Gly-Ser-Arg) of the laminin B1 chain, and this peptide can prevent metastasis formationin vivo. However, other similar pentapeptide sequences (e.g., Tyr-Ile-Gly-Ser-Glu) have been found to be much less active in metastasis inhibition, raising the possibility that such amino acid substitutions produce structural changes responsible for altering binding to the laminin receptor. In this study, conformational energy analysis has been used to determine the three-dimensional structures of these peptides. The results indicate that the substitution of Glu for the terminal Arg produces a significant conformational change in the peptide backbone at the middle Gly residue. These results have important implications for the design of drugs that may be useful in preventing metastasis formation and tumor spread.     

THE EFFECT OF AEROBIC CONTINUOUS AND INTERVAL TRAINING ON LEFT VENTRICULAR STRUCTURE AND FUNCTION IN MALE NON-ATHLETES

Exercise plays an important role to improve cardiovascular performance. The aim of this study was to compare the effect of aerobic continuous and interval training on the left ventricular structure and function. Twenty untrained healthy male students (aged 18-22 years) were randomly divided into two groups: continuous (C; n = 10) and interval (I; n = 10). The training programme consisted of countryside jogging for 45 min during 8 weeks three times a week at 70% of maximum heart rate (MHR). In each session group C was jogging for 45 min and in group I jogging was performed in 5 nine-minute stages with a four-minute inactive rest between them. M-mode, 2-dimensional, colour and Doppler transthoracic echocardiography were performed, during resting conditions, before and after the training period. After 8-week training the end diastolic diameter, systolic blood pressure and diastolic blood pressure in groups C and I, and the posterior wall thickness and the end systolic diameter in group I showed no significant difference (P > 0.05). On the other hand, the percentage of ejection fraction and shortening fraction in groups C and I, the end systolic diameter and the posterior wall thickness in group C and the interventricular septum thickness in group I demonstrated a significant difference (P ≤ 0.05). Comparing the two groups, only the value of the interventricular septum thickness was significant (P ≤ 0.05). In general, eight-week aerobic continuous and interval training can affect left ventricular structure and function.     

The feasibility of an approximate irregular field dose distribution simulation program applied to a respiratory motion compensation system

PurposeThis study optimized our previously proposed simulation program for the approximate irregular field dose distribution (SPAD) and applied it to a respiratory motion compensation system (RMCS) and respiratory motion simulation system (RMSS). The main purpose was to rapidly analyze the two-dimensional dose distribution and evaluate the compensation effect of the RMCS during radiotherapy.MethodsThis study modified the SPAD to improve the rapid analysis of the dose distribution. In the experimental setup, four different respiratory signal patterns were input to the RMSS for actuation, and an ultrasound image tracking algorithm was used to capture the real-time respiratory displacement, which was input to the RMCS for actuation. A linear accelerator simultaneously irradiated the EBT3 film. The gamma passing rate was used to verify the dose similarity between the EBT3 film and the SPAD, and conformity index (CI) and compensation rate (CR) were used to quantify the compensation effect.ResultsThe Gamma passing rates were 70.48–81.39% (2%/2mm) and 88.23–96.23% (5%/3mm) for various collimator opening patterns. However, the passing rates of the SPAD and EBT3 film ranged from 61.85% to 99.85% at each treatment time point. Under the four different respiratory signal patterns, CR ranged between 21% and 75%. After compensation, the CI for 85%, 90%, and 95% isodose constraints were 0.78, 0.57, and 0.12, respectively.ConclusionsThis study has demonstrated that the dose change during each stage of the treatment process can be analyzed rapidly using the improved SPAD. After compensation, applying the RMCS can reduce the treatment errors caused by respiratory movements.     

Distribution of Karlodinium veneficum in the coastal region of Xiangshan Bay in the East China Sea,as detected by a real-time quantitative PCR assay of ribosomal ITS sequence

Athecate dinoflagellate Karlodinium veneficum is a universal toxic species possessing karlotoxins recognized especially as ichthyotoxic as well as cytotoxic and hemolytic. Blooms of K. veneficum, both single-species or accompanied with other species, occurred more frequently worldwide in recent years, including the coastal region of China. Normally, K. veneficum present in relatively low abundance in phytoplankton communities in estuary regions. Being small and difficult to identify with light microscopy, it has been ignored for a long time till its blooming and toxins being confirmed. How it presents in background level and what is its relationship with critical geological and hydrological environment factors are basically not clear. In this study, the paper reports the application of a real-time quantitative PCR (qPCR) method to investigate the abundance and distribution of K. veneficum in the coastal waters of Xiangshan Bay in the East China Sea (ECS), a typical bay area of harmful algae blooms and heavily affected by anthropogenic activities. The real-time qPCR assay came out being an efficient method at detecting even low cell densities of K. veneficum of different genotypes. A total of 38 field samples of surface (0.5 m) and bottom water (9–100 m in depth) were analyzed and 12 samples were found positive for K. veneficum. At least 3 genotypes of K. veneficum present in this region. Temperatures in sites of K. veneficum positive ranged from 21.7 to 23.4 °C, and salinity levels were between 21.1 and 26.3. The K. veneficum distributed quite extensively in the waters of Xiangshan Bay, cell abundance varied from a low of 4 cells/L to a maximum of 170 cells/L. Most of the samples containing K. veneficum were collected from bottom water in different sites. At three of the 19 sampling sites, K. veneficum was detected in both surface and bottom water samples. Especially at sampling site near Beilun port, where the water is typically muddy with low transparency, relative high cell numbers of K. veneficum were found in both surface and bottom waters. Mixotrophy and vertical migration of K. veneficum could be important eco-physiological factors to consider in terms of understanding these distribution characteristics. The ideal conditions for K. veneficum growth and aggregation in this area still needs further study.     

Genomic analysis and lactose transporter expression in Kluyveromyces marxianus CCT 7735

Kluyveromyces marxianus CCT 7735 has been used to produce ethanol, aromatic compounds, enzymes and heterologous proteins besides assimilates lactose as carbon source. Its genome has 10.7 Mb and encodes 4787 genes distributed in 8 nuclear chromosomes and one mitochondrial. Contrary to Kluyveromyces lactis, which has a unique LAC12 gene (encodes lactose permease), K. marxianus possesses four. The presence of degenerated copies and Solo-LTRs related to retrotransposon TKM close to the LAC12 genes in K. marxianus indicates ectopic recombinations. The Lac12 permeases of K. marxianus and K. lactis are conserved, however the conservation is higher between the copy of the left side of the chromosome three and the unique copy of K. lactis, indicating that this copy is the ancestor. The expression of the four LAC12 genes occurred in aerobiosis and hypoxia. Notably, the high lactose consumption in hypoxia seems to be related to the high expression of the LAC12 genes.     

Incidence and predictors of left atrial thrombus in patients with atrial fibrillation prior to ablation in the real world of China

BackgroundThe present study was to evaluate the value of CHADS2 and CHA2DS2VASC scores on predicting left atrial (LA) or left atrial appendage (LAA) thrombus in atrial fibrillation (AF) patients prior to ablation in the real world of China.Methods and resultsA total of 397 patients with non-valvular AF were analyzed to determine the relationship between CHADS2 and CHA2DS2VASC scores and LA/LAA thrombus identified on transesophageal echocardiography prior to radiofrequency ablation(RFA). LA/LAA thrombus was present in 38 patients (9.6%). There was a strong association between higher CHADS2 score or CHA2DS2VASC score and LA/LAA thrombus. No thrombus was identified in patients with CHA2DS2VASC score of 0 regardless of anticoagulation status. However, LA/LAA thrombus was detected in 2.9% patients with CHADS2 score of 0 without adequate anticoagulation, while no thrombus was present in the patients with CHADS2 score of 0 with adequate anticoagulation. Univariate analysis showed that heart failure (LVEF＜50%), LA≥40 mm, diabetes mellitus, previous stroke or TIA, CAD, hypertension, inadequate anticoagulation therapy, CHADS2 score of ≥2 and CHA2DS2VASC score of ≥2 were significantly associated with LA/LAA thrombus. Multivariable Cox regression analysis demonstrated that CHA2DS2VASC score of ≥2 (p = 0.02) and previous stroke or TIA (p = 0.04) were independently associated with LA/LAA thrombus regardless of anticoagulation status. ROC curve analysis showed that higher CHADS2 score and CHA2DS2VASC score could be similarly used to predict the presence of LA thrombus.ConclusionsBoth higher CHA2DS2VASC and CHADS2 scores were associated with LA/LAA thrombus in non-valvular AF patients prior to ablation. Although CHA2DS2VASC score and CHADS2 score had similar value to predict LA/LAA thrombus, CHA2DS2VASc score was better to identify low-risk patients for LA/LAA thrombus than CHADS2 score without anticoagulation. There will be a possibility of performing AF ablation or cardioversion in patients with a CHA2DS2VASC of 0 without TEE or anticoagulation therapy. The safety need to be verified by more multicentre randomized controlled clinical trails.     

深圳市福田区三维城市景观格局变化特征

城市景观是景观变化最快的类型之一,建成景观与绿地景观格局和功能的相互影响及空间配置是城市景观优化的核心。在紧凑型城市快速发展过程中,城市垂直方向增长成为主要扩展方式。如何定量分析三维城市景观格局变化,为城市景观优化提供科学依据还有待深入。选取深圳市福田区,以高分辨率遥感数据和建筑普查数据为基础,运用景观格局指数和景观连通性等方法定量分析建筑景观和绿地景观变化及空间影响。研究结果表明:(1)2003—2016年,福田区建筑景观主要表现为垂直向的立体扩展模式,新增建筑主要为高层和超高层建筑,建筑平均高度增加6.53 m,立体空间体积增加135.58×10~6 m~3,建筑密度仅增加2.42%,建筑景观高度差异逐渐增大,呈现出明显的三维空间异质性。(2)2003—2016年,建筑景观格局由"阶梯式"转变为"金字塔"形,受益于建筑景观的垂向增长,建成景观与绿地景观比例由1.20∶1调整为0.99∶1,建成景观减少4.03 km~2,绿地景观增加2.80 km~2。(3)建成景观的三维立体化释放了绿地景观用地空间,同时也限制了绿地景观的外部连通性,绿地景观连通性较低,大型绿地斑块间缺乏廊道连通,呈现孤岛化。研究可为城市景观空间优化和国土规划等实践提供科学依据。