Risk factors for ANA positivity in healthy persons

Introduction  

The finding of antinuclear antibody (ANA) positivity in a healthy individual is usually of unknown significance and in most cases is benign. However, a subset of such individuals is at risk for development of autoimmune disease. We examined demographic and immunological features that are associated with ANA positivity in clinically healthy persons to develop insights into when this marker carries risk of progression to lupus.     

A yeast model of FUS/TLS-dependent cytotoxicity

FUS/TLS is a nucleic acid binding protein that, when mutated, can cause a subset of familial amyotrophic lateral sclerosis (fALS). Although FUS/TLS is normally located predominantly in the nucleus, the pathogenic mutant forms of FUS/TLS traffic to, and form inclusions in, the cytoplasm of affected spinal motor neurons or glia. Here we report a yeast model of human FUS/TLS expression that recapitulates multiple salient features of the pathology of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, inclusion formation, and cytotoxicity. Protein domain analysis indicates that the carboxyl-terminus of FUS/TLS, where most of the ALS-associated mutations are clustered, is required but not sufficient for the toxicity of the protein. A genome-wide genetic screen using a yeast over-expression library identified five yeast DNA/RNA binding proteins, encoded by the yeast genes ECM32, NAM8, SBP1, SKO1, and VHR1, that rescue the toxicity of human FUS/TLS without changing its expression level, cytoplasmic translocation, or inclusion formation. Furthermore, hUPF1, a human homologue of ECM32, also rescues the toxicity of FUS/TLS in this model, validating the yeast model and implicating a possible insufficiency in RNA processing or the RNA quality control machinery in the mechanism of FUS/TLS mediated toxicity. Examination of the effect of FUS/TLS expression on the decay of selected mRNAs in yeast indicates that the nonsense-mediated decay pathway is probably not the major determinant of either toxicity or suppression.     

Nitrendipine Nanocrystals: Its Preparation,Characterization, and <Emphasis Type="Italic">In Vitro–In Vivo</Emphasis> Evaluation

The present investigation was undertaken with the objective of developing a solid formulation containing nitrendipine nanocrystals for oral delivery. Nitrendipine nanocrystals were prepared using a tandem precipitation–homogenization process. Then, spray drying, a cost-effective method very popular in industrial situations, was employed to convert the nanocrystals into a solid form. The parameters of the preparation process were investigated and optimized. The optimal process was as follows: firstly, nitrendipine/acetone solution (100 mg/ml) was added to a polyvinyl alcohol solution (1 mg/ml) at 10°C, then the pre-suspension was homogenized for 20 cycles at 1,000 bar. Both differential scanning calorimetry and X-ray diffraction analysis indicated that nitrendipine was present in crystalline form. The in vitro dissolution rate of the nanocrystals was significantly increased compared with the physical mixture and commercial tablet. The in vivo testing demonstrated that the C _max of the nanocrystals was approximately 15-fold and 10-fold greater than that of physical mixture and commercial tablet, respectively. In addition, the AUC_0→24 of the nanocrystals was approximately 41-fold and 10-fold greater than that of physical mixture and commercial tablet, respectively.     

Influence of Temperature and Oil Content on the Soil/Air Partition Coefficient for Hexachlorobenzene in Oil-Contaminated Rice Paddy Field Soil

The soil/air partition coefficients (K _SA ) for hexachlorobenzene (HCB) in oil-contaminated (crude oil and diesel) rice paddy field soils were measured in a solid fugacity meter at different oil concentrations over the temperature range of 5 to 30°C at 100% relative humidity. The results showed that values of K _SA increased with a decrease of temperature. As for oil content, there is a critical separate phase concentration (CSPC) above which K _SA increased with increasing of oil content. When oil content is above CSPC, oil plays a role as a separate phase that enhances the sorption capacity of the soil. At a given temperature (20°C) values of CSPC depended on the natural organic matter (NOM) contents of the soil, while for a given oil concentration they depended on the temperature. The normalized oil/air partition coefficients ) for HCB deduced from K _SA for oils and experimentally determined with crude oil/quartz sand system were similar and 0.7–7 times higher than the normalized organic/air partition coefficient ), which implied that oil was a super sorbent. The enthalpies (ΔH_SA) for crude oil and diesel were 64.9 and 55.7 kJ mol^?1, respectively.     

Stucture of the complex between <Emphasis Type="Italic">Mucor pusillus</Emphasis> pepsin and the key domain of κ-casein for site-directed mutagenesis: a combined molecular modeling and docking approach

In the structural-based mutagenesis of Mucor pusillus pepsin (MPP), understanding how κ-casein interacts with MPP is a great challenge for us to explore. Chymosin-sensitive peptide is the key domain of κ-casein that regulates milk clotting through the specific proteolytic cleavage of its peptide bond (Phe¹⁰⁵-Met¹⁰⁶) by MPP to produce insoluble para-κ-casein. Here, we built the model of this large peptide using molecular modeling technique. Docking study showed that MPP can accommodate the designed model with a favorable binding energy and the docked complex has proven to locally resemble the inhibitor-chymosin complex. The catalytic mechanism for the peptide model binding with MPP was explored in terms of substrate-enzyme interaction and property of contacting surface. Some critical amino acid residues in the substrate binding cleft have been identified as an important guide for further site-directed mutagenesis. Glu13 and Leu11 in the S3 region of MPP, predicted as the special mutation sites, were confirmed to retain clotting activity and decrease the proteolytic activity. These novel mutants may provide a promising application for improving cheese flavor.     

RASSF6与肿瘤研究进展

RAS相关结构域家族（Ras Association Domain Family, RASSFs ） 10个成员组成,参与不同的细胞内机制如凋亡、细胞周期控制、微管稳定性等一些家族成员表现出肿瘤抑制功能。目前发现RASSF6在肺癌、宫颈癌等实体瘤中表达下调,可能与肿瘤形成有关,并可作为肿瘤治疗的潜在靶点。本文就RASSF6与肿瘤的研究进展进行综述。     

Notch1 binds and induces degradation of Snail in hepatocellular carcinoma

Background

Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them.

Results

Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes.

Conclusions

Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia - Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key force behind coevolutionary cycles. We discuss how different steps can explain different aspects of the coevolutionary dynamics of the system: the properties of the attachment step, explaining the rapid evolution of infectivity and the properties of later parasite proliferation explaining the evolution of virulence. Our study underlines the importance of resolving the infection process in order to better understand host-parasite interactions.     

The presence of a lipoma in the Eustachian tube: a case report

ABSTRACT: INTRODUCTION: The incidence of lipoma in the Eustachian tube is very rare, and to the best of our knowledge, has not been reported in the literature. Tumors that form in the cartilaginous portion of the Eustachian tube can be successfully removed by an endoscopic approach. CASE PRESENTATION: We report an incidentally-detected lipoma of the Eustachian tube in a 34-year-old Asian woman with a six-year history of persistent otitis media in her right ear. Our patient underwent surgery five years ago for the possibility of a choanal polyp, but her ear symptoms continued to be problematic following the surgery. Our patient was examined at our hospital, and computed tomography revealed a well-defined, hypodense, non-enhancing lesion involving the right Eustachian tube, measuring 1.6x2.4cm. The mass was excised using an endoscopic approach, and was found to originate from the cartilaginous portion of the Eustachian tube. The tumor was sent for histopathologic evaluation. The postoperative course went smoothly, and our patient recovered during follow-up over the next five months. CONCLUSION: Lipoma of the Eustachian tube is very rare compared with other tumors. Improved radiologic modalities aid the diagnosis of this benign tumor. Endoscopic removal of the tumor is possible and has helped in early recovery.     

CCN1 contributes to skin connective tissue aging by inducing age-associated secretory phenotype in human skin dermal fibroblasts

Dermal connective tissue collagen is the major structural protein in skin. Fibroblasts within the dermis are largely responsible for collagen production and turnover. We have previously reported that dermal fibroblasts, in aged human skin in vivo, express elevated levels of CCN1, and that CCN1 negatively regulates collagen homeostasis by suppressing collagen synthesis and increasing collagen degradation (Quan et al. Am J Pathol 169:482–90, 2006, J Invest Dermatol 130:1697–706, 2010). In further investigations of CCN1 actions, we find that CCN1 alters collagen homeostasis by promoting expression of specific secreted proteins, which include matrix metalloproteinases and proinflammatory cytokines. We also find that CCN1-induced secretory proteins are elevated in aged human skin in vivo. We propose that CCN1 induces an “Age-Associated Secretory Phenotype”, in dermal fibroblasts, which mediates collagen reduction and fragmentation in aged human skin.