The non-structural protein 5A (NS5A) of hepatitis c virus interacts with the SH3 domain of human Bin1 using non-canonical binding sites

The hepatitis C virus (HCV) is a major human pathogen that causes severe diseases such as chronic hepatitis, liver cirrhosis and finally hepatocellular carcinoma. Although no enzymatic activity could be attributed yet to the HCV non-structural protein 5A (NS5A), it is indispensable for viral replication and particle assembly. Furthermore, it is associated with a variety of cellular pathways, although their relevance for viral pathogenesis still has to be elucidated. To fulfil its function NS5A interacts with a large number of different proteins including both viral and human ones. NS5A is organized into three domains, which are connected via two low complexity sequences (LCS). The first domain is highly conserved among different HCV genotypes and forms a well-defined globular structure [1]. The domains 2 (D2) and 3 (D3) are less conserved and intrinsically disordered. Nonetheless, three segments in LCS-I and D2 show significant propensities to adopt a-helical structures as could be shown by nuclear magnetic resonance (NMR) chemical shift and 15 N relaxation data [2]. The LCS-II connecting D2 and D3 contains two directly neighbored class II PxxP-motifs, which are important for interactions with Src homology 3 (SH3) domains. SH3 domains mediate protein-protein interactions, often via binding to polyproline II helices. Recent studies also revealed alternative binding mechanisms, mainly involving helical motifs and positively charged amino acid residues. The SH3 domain of the bridging integrator 1 (Bin1) is known to interact with NS5A not only via its PxxP-motifs, but also via two non-canonical binding sites, which will be further described here [3]

The non-structural protein 5A (NS5A) of hepatitis C virus interacts with the SH3 domain of human Bin1 using non-canonical binding sites

The hepatitis C virus (HCV) is a major human pathogen that causes severe diseases such as chronic hepatitis, liver cirrhosis and finally hepatocellular carcinoma. Although no enzymatic activity could be attributed yet to the HCV non-structural protein 5A (NS5A), it is indispensable for viral replication and particle assembly. Furthermore, it is associated with a variety of cellular pathways, although their relevance for viral pathogenesis still has to be elucidated. To fulfil its function NS5A interacts with a large number of different proteins including both viral and human ones. NS5A is organized into three domains, which are connected via two low complexity sequences (LCS). The first domain is highly conserved among different HCV genotypes and forms a well-defined globular structure [1]. The domains 2 (D2) and 3 (D3) are less conserved and intrinsically disordered. Nonetheless, three segments in LCS-I and D2 show significant propensities to adopt a-helical structures as could be shown by nuclear magnetic resonance (NMR) chemical shift and 15 N relaxation data [2]. The LCS-II connecting D2 and D3 contains two directly neighbored class II PxxP-motifs, which are important for interactions with Src homology 3 (SH3) domains. SH3 domains mediate protein-protein interactions, often via binding to polyproline II helices. Recent studies also revealed alternative binding mechanisms, mainly involving helical motifs and positively charged amino acid residues. The SH3 domain of the bridging integrator 1 (Bin1) is known to interact with NS5A not only via its PxxP-motifs, but also via two non-canonical binding sites, which will be further described here [3]

Intuitionistic Fuzzy Time Series Functions Approach for Time Series Forecasting

Fuzzy inference systems have been commonly used for time series forecasting in the literature. Adaptive network fuzzy inference system, fuzzy time series approaches and fuzzy regression functions approaches are popular among fuzzy inference systems. In recent years, intuitionistic fuzzy sets have been preferred in the fuzzy modeling and new fuzzy inference systems have been proposed based on intuitionistic fuzzy sets. In this paper, a new intuitionistic fuzzy regression functions approach is proposed based on intuitionistic fuzzy sets for forecasting purpose. This new inference system is called an intuitionistic fuzzy time series functions approach. The contribution of the paper is proposing a new intuitionistic fuzzy inference system. To evaluate the performance of intuitionistic fuzzy time series functions, twenty-three real-world time series data sets are analyzed. The results obtained from the intuitionistic fuzzy time series functions approach are compared with some other methods according to a root mean square error and mean absolute percentage error criteria. The proposed method has superior forecasting performance among all methods

PROPER: global protein interaction network alignment through percolation matching

Background The alignment of protein-protein interaction (PPI) networks enables us to uncover the relationships between different species, which leads to a deeper understanding of biological systems. Network alignment can be used to transfer biological knowledge between species. Although different PI-network alignment algorithms were introduced during the last decade, developing an accurate and scalable algorithm that can find alignments with high biological and structural similarities among PPI networks is still challenging. Results In this paper, we introduce a new global network alignment algorithm for PPI networks called PROPER. Compared to other global network alignment methods, our algorithm shows higher accuracy and speed over real PPI datasets and synthetic networks. We show that the PROPER algorithm can detect large portions of conserved biological pathways between species. Also, using a simple parsimonious evolutionary model, we explain why PROPER performs well based on several different comparison criteria. Conclusions We highlight that PROPER has high potential in further applications such as detecting biological pathways, finding protein complexes and PPI prediction. The PROPER algorithm is available at http://proper.epfl.ch

Galectin-1 as a potential diagnostic biomarker in polycystic ovary syndrome

OBJECTIVE: This study was aimed at comparing the routine laboratory parameters and Galectin-1 levels of control and polycystic ovarian syndrome patients. PATIENTS AND METHODS: 88 patients diagnosed with polycystic ovary syndrome and 88 healthy controls were considered for the study. Age groups of the patients ranged from 18 to 40. Serum TSH, Beta HCG, glucose, insulin, HOMA-IR, Hb1A1c, triglyceride, total cholesterol, LDL FSH, LH, E2, prolactin, testosterone, SHBG, DHESO4, HDL, Gal-1 levels were analyzed for each subject. RESULTS: FSH, LH, LH/FSH, E2, prolactin, testosterone, SHBG, DHESO4, HDL and Gal-1 values of the subjects included in the study were statistically significantly different between the groups (p<0.05). Gal-1 and DHESO4 showed a strong positive connection (p=0.05). The sensitivity of Gal-1 level in PCOS patients was calculated as 0.997 and specificity as 0.716. CONCLUSIONS: High levels of Gal-1 in PCOS patients suggest that it increases due to overexpression in response to inflammation

Opinions of counselor candidates regarding counseling skills training [Psikolojik dani{dotless}şma becerileri egitimine i·lişkin psikolojik dani{dotless}şman adaylari{dotless}ni{dotless}n görüşleri]

The aim of this study is to contribute to the enhancement of the quality of counseling skills training and counselor education through the medium of understanding the opinions of counselor candidates regarding counseling skills training. The research group consisted of 67 counselor candidates who voluntarily participated in the study. The research data was collected by three different qualitative data collection tools developed by the researchers. Content analysis was carried out and the results indicated five main themes: Counseling Skills, Specific Skills Training Methods, Perceptions of Counseling, Being a Counselor Candidate, the Learning and Teaching Process of Counseling Skills. The results also showed that within the scope of systematic counseling skills training programs, using various skill training methods and instructional technologies which are integrated compatibly was effective. At the same time, the results indicated that counseling skills training provided an increase in professional competency and helped to develop the professional identity of counselor candidates. The results are discussed and interpreted in light of the literature. Besides, some suggestions are provided to counselor educators and researchers. © 2014 Educational Consultancy and Research Center

Cysteine conjugate of paracetamol serves as substrate for kidney cysteine S-conjugates beta-lyase: implications for drug-induced acute kidney injury

56th Congress of the European-Societies-of-Toxicology (EUROTOX) - Toxicology of the Next Generation -- SEP 27-OCT 01, 2021 -- ELECTR NETWORK[No Abstract Available]European Soc Toxico

Origins, evolution and themes of scholarly hospitality sources : 1960–2019

202208 bckwSelf-fundedPublished36 month

Why are faculty unfavorably disposed to MOOCs? – a sharing of views by Chinese hospitality educators

202208 bckwSelf-fundedEarly release18 month

Anatomic variations of the paranasal sinuses detected by computed tomography and the relationship between variations and sex [Paranazal sinüslerin anatomik varyasyonlarinin bilgisayarli tomografi ile degerlendirilmesi ve bunlarin cinsiyetle ilişkisi.]

PubMed ID: 16227725OBJECTIVES: In this study, we evaluated anatomic variations detected by computed tomography (CT) of the paranasal sinuses and their relationship with sex. PATIENTS AND METHODS: Computed tomography scans of the paranasal sinuses of 464 patients (206 males, 258 females; mean age 37.5 years; range 4-87 years) were retrospectively analyzed. In cases requiring further investigation, axial and sagittal views were obtained using multiplanar reformatted images. Bone window images were also obtained particularly to evaluate dehiscence variations. Paranasal sinus variations were classified into eight subgroups according to their origins (nasal septum, ethmoid cells, maxillary sinus, uncinate process, frontal and sphenoid sinuses, orbit, and nasal concha). The frequency of variations was compared between male and females. RESULTS: The most common anatomic variation was agger nasi cells (80.4%) followed by pneumatization of the middle concha (37%). The least encountered variations were pneumatization of the inferior turbinate, bony dehiscence of the ethmoidal roof, and duplication of the middle and superior turbinates. The frequency of variations did not differ significantly with respect to gender (p>0.05) except for frontal hypoplasia, which was more often in females (p<0.05). CONCLUSION: Axial and sagittal views using multiplanar reformatted images can be helpful in eliminating artefacts and in identifying variations of the paranasal sinuses. Utilization of soft tissue and bone windows, when necessary, may facilitate evaluation of dehiscence abnormalities