Identification and Characterization of Circular Single-Stranded DNA Genomes in Sheep and Goat Milk

In recent years, a variety of circular replicase-encoding single-stranded (CRESS) DNA viruses and unclassified virus-like DNA elements have been discovered in a broad range of animal species and environmental samples. Key questions to be answered concern their presence in the human diet and their potential impact on disease emergence. Especially DNA elements termed bovine meat and milk factors (BMMF) are suspected to act as co-factors in the development of colon and breast cancer. To expand our knowledge on the occurrence of these potential pathogens in human nutrition, a total of 73 sheep and 40 goat milk samples were assayed by combining rolling circle amplification (RCA), PCR and Sanger sequencing. The present study further includes retail milk from the aforementioned species. We recovered 15 single stranded (ss) circular genomes. Of those, nine belong to the family Genomoviridae and six are members of the unclassified group of BMMF. Thus, dairy sheep and goats add to dispersal of CRESS viruses and circular ssDNA elements, which enter the food chain via milk. The presence of these entities is therefore more widespread in Bovidae than initially assumed and seems to be part of the common human nutrition.     

四川省棘球蚴病患者-医生交互系统设计

目的 设计和构建棘球蚴病患者?医生交互系统。方法 采用深度访谈法及头脑风暴法确定系统主要功能模块,基于服务器/客户端模式设计棘球蚴病患者?医生交互系统。结果 四川省棘球蚴病患者?医生交互系统构建成功,并完成初步调试。该系统具备诊疗咨询、服药监督、健康教育和辅助功能4个功能。结论 棘球蚴病患者?医生交互系统有望进一步提高对棘球蚴病患者的管理效能,并为患者提供更为方便快捷的诊疗咨询及健康资讯。 ［关键词］     

Hardening Slurries with Fluidized-Bed Combustion By-Products and Their Potential Significance in Terms of Circular Economy

Hardening slurries (water-bentonite-binder mixtures) constitute a well-established material used broadly, i.a., for cut-off walls in civil and water engineering. Although they usually contain Portland cement, similar to common concrete, their properties differ greatly, mostly due to a much higher water content. This characteristic of hardening slurries creates unique opportunities for the utilization of significant quantities of industrial by-products that are deemed problematic in the concrete industry. This article investigates the effect of the addition of by-products of fluidized-bed combustion of hard, brown coal and municipal sewage sludge, as well as ground granulated blast furnace slag, on the properties of slurries. Unconfined compressive strength tests, as well as mercury porosimetry, scanning electron microscopy, and X-ray diffraction analyses were performed. The results suggest that it is possible to design hardening slurry mixes of desired properties, both in liquid and solid state, containing at least 100–300 kg/m³ of industrial waste. This includes cement-free slurries based entirely on industrial by-products as binders. In addition, the analyzed slurries exhibited good chemical resistance to landfill eluates, at the same time effectively immobilizing heavy metals. It was concluded that hardening slurry technology can ensure the safe deposition of significant amounts of waste that would be otherwise difficult to manage, thus contributing to the circular economy concept.     

酚酞对大鼠结肠动力及肠神经系统的影响研究

目的 探讨长期应用酚酞对结肠肌电及肠神经系统(ENS)的影响。方法 建立大鼠“泻剂结肠”模型，应用电生理、组化及免疫组化技术研究酚酞对大鼠结肠动力、ENS多种神经递质及Cajal间质细胞(ICC)的影响。结果 大鼠饲以酚酞3个月后，结肠慢波频率减慢，结肠肌间丛还原型烟酰胺腺嘌呤二核苷磷酸黄递酶阳性神经细胞数目增多，乙酰胆碱酯酶阳性神经细胞数目减少，一氧化氮合酶免疫反应性增强，生长抑素免疫反应性减弱，肌间丛ICC分布不均匀，突起连接杂乱。结论 长期应用酚酞对结肠动力和ENS有损害作用，在临床治疗顽固性便秘时应避免长期应用酚酞等刺激性泻剂。     

Steady‐state amprenavir and tenofovir pharmacokinetics after coadministration of unboosted or ritonavir‐boosted fosamprenavir with tenofovir disoproxil fumarate in healthy volunteers

Objective

An open‐label, three‐period pharmacokinetic study was conducted to investigate the drug interaction potential between fosamprenavir (FPV) and tenofovir disoproxil fumarate (TDF).

Methods

Thirty‐six healthy subjects received TDF 300 mg once daily (qd) for 7 days (period 1), and then were randomized to 14 days of either FPV 1400 mg twice daily (bid) or FPV/ritonavir (RTV) 700/100 mg bid alone or with TDF (period 2). Subjects continued their randomized dose of FPV for 14 more days, adding or removing TDF based upon its receipt in period 2 (period 3). Twenty‐four‐hour pharmacokinetic sampling was carried out on day 7 of period 1 and on day 14 of periods 2 and 3. Steady‐state plasma amprenavir (APV) and tenofovir (TFV) pharmacokinetics were assessed by noncompartmental analysis and parameter values observed with each regimen were compared using geometric mean ratios with 90% confidence intervals.

Results

After TDF coadministration, APV geometric mean minimum concentration (C_min), maximum concentration (C_max), and area under the plasma concentration–time curve (AUC) increased by 31, 3 and 7% above values observed with unboosted FPV alone; they also increased by 31, 4 and 16% above values observed with FPV/RTV alone. TFV C_min, C_max and AUC decreased by 12, 25 and 15% after FPV coadministration and by 9, 18 and 7% after FPV/RTV coadministration. No significant changes in RTV pharmacokinetics were observed. No differences were noted in adverse events among dosing periods.

Conclusions

In this evaluation of the interaction between FPV and TDF, increases in APV exposures and modest decreases in TFV exposures were observed. These were unlikely to be clinically significant.

     

酵母双杂交系统在痘病毒与宿主相互作用中的研究进展

痘病毒全基因组序列分析为痘病毒的研究提供了丰富的信息。近年来,一些痘病毒编码的蛋白之间,以及病毒蛋白与宿主蛋白之间的相互作用的研究证明其在痘病毒复制、感染、致病及传播过程中起关键作用,因此受到了广泛的关注。酵母双杂交系统是研究蛋白质之间相互作用的重要工具,该技术可以发现新蛋白之间的相互作用,确定蛋白相互作用的区域,从而为研究各蛋白质的生物学功能以及蛋白质之间相互作用的分子机制奠定基础。本文综述了酵母双杂交系统在痘病毒蛋白之间及病毒-宿主相互作用的研究现状及优缺点。     

广场健身活动对冠心病患者病情情绪和自主神经功能的影响

目的:观察“广场健身活动”对冠心病患者病情、情绪和自主神经功能指标的影响,研究其规律性。方法:2003年9月至2005年9月共77例冠心病患者参加了“广场健身活动”(每次60～120min,每周至少坚持5d,6个月为1疗程)。锻炼前后分别测试:①病情指标(病情日记和活动平板心脏检测指标);②心理状态评分指标(SCL-90总分和各因子评分);③心脏自主神经功能指标(时域和频域指标)。对照组为48例同期就诊的同病患者,仅接受药物治疗。结果:广场活动组治疗后的大部分病情指标明显优于治疗前(P<0.05～<0.01),部分病情指标优于对照组(P<0.05)。广场活动组大部分心理情绪评分低于治疗前,部分指标低于对照组(P<0.05～0.01)。两组治疗后大部分自主神经功能指标明显优于治疗前,广场活动组治疗后多数指标明显优于对照组(P<0.05～0.01)。结论:广场健身活动方式可显著改善冠心病患者病情、情绪和心脏自主神经功能指标。     

Incommensurate antiferromagnetism in a pure spin system via cooperative organization of local and itinerant moments

Materials with strong correlations are prone to spin and charge instabilities, driven by Coulomb, magnetic, and lattice interactions. In materials that have significant localized and itinerant spins, it is not obvious which will induce order. We combine electrical transport, X-ray magnetic diffraction, and photoemission studies with band structure calculations to characterize successive antiferromagnetic transitions in GdSi. GdSi has both sizable local moments and a partially nested Fermi surface, without confounding contributions from orbital effects. We identify a route to incommensurate order where neither type of moment dominates, but is rooted in cooperative feedback between them. The nested Fermi surface of the itinerant electrons induces strong interactions between local moments at the nesting vector, whereas the ordered local moments in turn provide the necessary coupling for a spin-density wave to form among the itinerant electrons. This mechanism echoes the cooperative interactions between electrons and ions in charge-density–wave materials, and should be germane across a spectrum of transition-metal and rare-earth intermetallic compounds.     

三维电解剖标测及单根环状标测电极指导下CPVA术治疗心房颤动

目的探讨在三维电解剖标测及单根环状标测电极指导下以环肺静脉口电隔离术（CPVA）为核心治疗心房颤动（房颤）的疗效。方法对32例房颤患者均在CARTO三维电解剖标测及单根环状标测电极指导下行CPVA,其中辅助行碎裂电位消融6例,上腔静脉消融术2例,三尖瓣峡部、二尖瓣峡部及冠状窦内消融各1例。结果26例阵发性房颤不再被诱发,6例慢性房颤中术中房颤终止2例、电复律转为窦性心律4例;手术操作时间（119&#177;37）min,X线透视时间（25&#177;12）min;随访（9&#177;5）个月成功率为90.6%。均无手术并发症。结论三维电解剖标测及单根环状标测电极指导下以CPVA为核心,其他消融方法为辅的房颤消融策略安全有效,可提高消融成功率,缩短手术时间,减少并发症、复发。     

Hypoglycemic therapy and hemostasis in maturity-onset diabetes mellitus: Existence of an early prethrombotic state

Summary We studied 115 patients with uncomplicated maturity-onset diabetes mellitus, 55 males and 60 females; patients were divided into 7 groups according to the hypoglycemic therapy (diet alone, tolbutamide, glibenclamide, phenformin, combination of the last two drugs, insulin, combination of insulin and phenformin). All patients were tested for a prethrombotic state by the simultaneous determination of the following parameters: ADP-induced platelet aggregation, Factor VIII as antigen and procoagulant activity and the plasma levels of fibrinogen and antithrobin III. Our results show that these parameters were markedly altered in diabetic patients when compared to apparently normal subjects of the same age; on the contrary, differences between groups of diabetic patients were very slight and hardly ever statistically significant. These results suggest that the prethrombotic alterations of hemostatic system are very similar in all groups of diabetic patients; this is true also for patients submitted to diet alone, i.e. with slight and usually recent-onset diabetes mellitus. In conclusion, our study suggests the opportunity, at least from the theoretical point of view, of systematic antiaggregant and/or anticoagulant treatment(s) in maturity-onset diabetes mellitus, whose severe and precocious prethrombotic alterations seem to be independent of the hypoglycemic treatment applied.     

Chronic hepatitis C in the state prison system: insights into the problems and possible solutions

The prevalence of chronic hepatitis C virus (HCV) within the correctional system is estimated to be 10–20-times greater than that which is reported in the general population. High-risk behavioral patterns probably account for the greater estimates in this population. Recent observations of more than 780 patient-inmates infected with HCV within the California Department of Corrections suggest a very high prevalence of advanced fibrosis in this population. Observational studies performed in Texas have shown that the rates of chronic liver disease-related deaths have increased significantly between 1989 and 2003, especially among Hispanic patient-inmates. Viral hepatitis accounts for a significant number of these chronic liver disease-related deaths. Identification of high-risk patient-inmates infected with HCV, as well as appropriation of funds for their treatment, should result in a decreased rate of liver-related complications. This should translate into reduced morbidity and cost to correctional institutions, as well as to improved public health and safety.     

Associations between CLCNKA_B tag SNPs with essential hypertension and interactions between genetic and environmental factors in an island population in China

Abstract

Objective: Essential hypertension (EH) is known as the result from the interaction of environmental and genetic factors. We selected tag SNPs of CLCNKA_B genes as gene markers, to elucidate the relationship between CLCNKA_B and EH, and to determine the possible interaction among tag SNPs and dietary factors in island of China. Methods: A case-control study was conducted in Changshan islands of China, blood samples of 806 participants were genotyped, and the general characteristics and dietary habits of them were collected. Unconditional logistic regression (ULR) was used to assess the effects of CLCNKA_B tag SNPs and dietary factors on EH. Generalized multifactor dimensionality reduction (GMDR) was used to test gene–environment interaction for EH risk. Results: Four SNPs were identified as the tag SNPs of CLCNKA_B. Recessive model for rs5253 and rs2275166 were marginal associated with the decrease risk of EH (OR?=?0.36, 95% CI?=?0.12–1.07 for rs5253; OR?=?0.40, 95% CI?=?0.16–1.05 for rs2275166). In GMDR, the five-factor interaction model of rs1010069, salt, marine products, meat and edible oil consumption was the best model, with a maximum CVC of 10/10 and a TBA of 0.638 (p?=?0.001). In ULR, compared with subjects carried wild genotypes and null dietary risk factor, those with three or more dietary risk factors and mutation genotypes had 5.90-fold EH risk (95% CI:2.24–15.53). Conclusion: Though the single loci of tag SNPs of CLCNKA_B are not enough to significantly increase the EH susceptibility, the combination of CLCNKA tag SNP, salt, marine products, meat and edible oil consumption is associated with elevated risk.     

Structural and kinetic modeling of an activating helix switch in the rhodopsin-transducin interface

Extracellular signals prompt G protein-coupled receptors (GPCRs) to adopt an active conformation (R*) and catalyze GDP/GTP exchange in the α-subunit of intracellular G proteins (Gαβγ). Kinetic analysis of transducin (G_tαβγ) activation shows that an intermediary R*·G_tαβγ·GDP complex is formed that precedes GDP release and formation of the nucleotide-free R*·G protein complex. Based on this reaction sequence, we explore the dynamic interface between the proteins during formation of these complexes. We start from the R* conformation stabilized by a G_tα C-terminal peptide (GαCT) obtained from crystal structures of the GPCR opsin. Molecular modeling allows reconstruction of the fully elongated C-terminal α-helix of G_tα (α5) and shows how α5 can be docked to the open binding site of R*. Two modes of interaction are found. One of them – termed stable or S-interaction – matches the position of the GαCT peptide in the crystal structure and reproduces the hydrogen-bonding networks between the C-terminal reverse turn of GαCT and conserved E(D)RY and NPxxY(x)_5,6F regions of the GPCR. The alternative fit – termed intermediary or I-interaction – is distinguished by a tilt (42°) and rotation (90°) of α5 relative to the S-interaction and shows different α5 contacts with the NPxxY(x)_5,6F region and the second cytoplasmic loop of R*. From the 2 α5 interactions, we derive a “helix switch” mechanism for the transition of R*·G_tαβγ·GDP to the nucleotide-free R*·G protein complex that illustrates how α5 might act as a transmission rod to propagate the conformational change from the receptor-G protein interface to the nucleotide binding site.     

Formation and structure of ramified charge transportation networks in an electromechanical system

We present findings in an experiment where we obtain stationary ramified transportation networks in a macroscopic nonbiological system. Our purpose here is to introduce the phenomenology of the experiment. We describe the dynamical formation of the network which consists of three growth stages: (I) strand formation, (II) boundary formation, and (III) geometric expansion. We find that the system forms statistically robust network features, like the number of termini and the number of branch points. We also find that the networks are usually trees, meaning that they lack closed loops; indeed, we find that loops are unstable in the network. Finally, we find that the final topology of the network is sensitive to the initial conditions of the particles, in particular to its geometry.