Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity.

The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β(2)-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles

Behavior Analysis and Recognition of Hidden Populations in Online Social Network Based on Big Data Method

Hidden populations refer to the minority groups that not well-known to the public. Traditional statistical survey methods are difficult to apply in the study of hidden populations because of that the hidden populations individuals are very troublesome to be found and they are not willing to share the inner opinion with the others. On the other hand, with the development of the Web 2.0, the hidden populations gather and share their views in online social networks due to the openness and anonymity of the Internet. So, this paper analyzes the behavioral characteristics of the hidden populations based on their data in online social networks. This paper uses the lesbian population as an example and analyzes the behavioral characteristics of lesbian by analyzing the data of the lesbian population in Douban Group. First, the activity data on lesbian are collected from Douban Group. Second, behavior characteristics of lesbian are analysed, the regional characteristic, temporal characteristic and text characteristic are mined out by big data method. Third, a lesbian recognition model is proposed based on the above analytical characteristics, and the effectiveness of the recognition model is varified by experiment study. The research of this paper is helpful to understand the behavioral characteristics of hidden populations deeply, and provides decision-making basis of management and service for hidden populations

Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta.

Amyloid protein aggregates are associated with dozens of devastating diseases including Alzheimer's, Parkinson's, ALS, and diabetes type 2. While structure-based discovery of compounds has been effective in combating numerous infectious and metabolic diseases, ignorance of amyloid structure has hindered similar approaches to amyloid disease. Here we show that knowledge of the atomic structure of one of the adhesive, steric-zipper segments of the amyloid-beta (Aβ) protein of Alzheimer's disease, when coupled with computational methods, identifies eight diverse but mainly flat compounds and three compound derivatives that reduce Aβ cytotoxicity against mammalian cells by up to 90%. Although these compounds bind to Aβ fibers, they do not reduce fiber formation of Aβ. Structure-activity relationship studies of the fiber-binding compounds and their derivatives suggest that compound binding increases fiber stability and decreases fiber toxicity, perhaps by shifting the equilibrium of Aβ from oligomers to fibers. DOI:http://dx.doi.org/10.7554/eLife.00857.001

Health-related quality of life after mandibular resection for oral cancer: reconstruction with free fibula flap

Objectives: Mandibular resection for oral cancer is often necessary to achieve an adequate margin of tumor clear - ance. Mandibular resection has been associated with a poor health-related quality of life (HRQOL), particularly before free fibula flap to reconstruct the defect. The aim of this study was to evaluate health-related quality of life in patients who have had mandibular resections of oral cancer and reconstruction with free fibula flap. Study D esigns: There were 115 consecutive patients between 2008 and 2011 who were treated by primary surgery for oral squamous cell carcinoma, 34 patients had a mandibular resection. HRQOL was assessed by means of the 14-item Oral Health Impact Profile (OHIP-14) and University of Washington Quality of Life (UW-QOL) question - naires after 12 months postoperatively. Results: In the UW-QOL the best-scoring domain was mood, whereas the lowest scores were for chewing and saliva. In the OHIP-14 the lowest-scoring domain was social disability, followed by handicap, and psychological disability. Conclusions: Mandible reconstruction with free fibula flap would have significantly influenced on patients' quality of life and oral functions. The socio-cultural data show a fairly low level of education for the majority of patients