Length-dependent prediction of protein intrinsic disorder

BACKGROUND: Due to the functional importance of intrinsically disordered proteins or protein regions, prediction of intrinsic protein disorder from amino acid sequence has become an area of active research as witnessed in the 6th experiment on Critical Assessment of Techniques for Protein Structure Prediction (CASP6). Since the initial work by Romero et al. (Identifying disordered regions in proteins from amino acid sequences, IEEE Int. Conf. Neural Netw., 1997), our group has developed several predictors optimized for long disordered regions (>30 residues) with prediction accuracy exceeding 85%. However, these predictors are less successful on short disordered regions (≤30 residues). A probable cause is a length-dependent amino acid compositions and sequence properties of disordered regions. RESULTS: We proposed two new predictor models, VSL2-M1 and VSL2-M2, to address this length-dependency problem in prediction of intrinsic protein disorder. These two predictors are similar to the original VSL1 predictor used in the CASP6 experiment. In both models, two specialized predictors were first built and optimized for short (≤30 residues) and long disordered regions (>30 residues), respectively. A meta predictor was then trained to integrate the specialized predictors into the final predictor model. As the 10-fold cross-validation results showed, the VSL2 predictors achieved well-balanced prediction accuracies of 81% on both short and long disordered regions. Comparisons over the VSL2 training dataset via 10-fold cross-validation and a blind-test set of unrelated recent PDB chains indicated that VSL2 predictors were significantly more accurate than several existing predictors of intrinsic protein disorder. CONCLUSION: The VSL2 predictors are applicable to disordered regions of any length and can accurately identify the short disordered regions that are often misclassified by our previous disorder predictors. The success of the VSL2 predictors further confirmed the previously observed differences in amino acid compositions and sequence properties between short and long disordered regions, and justified our approaches for modelling short and long disordered regions separately. The VSL2 predictors are freely accessible for non-commercial use a

Postural stability – a comparison between rowers and field sport athletes

Postural stability (PS) is an important function for maintaining equilibrium during periods of standing still, locomotion, and any motor activities that require high degree of balance. High PS is essential in different sports for the regulation of voluntary movement and for improving athletic physical condition and performance. Purpose: The purpose of this study was to compare the static PS of elite rowing athletes and field sport athletes. Methods: A total of 90 elite athletes (age: 23.9 ± 1.97 years; body height: 174.9 ± 8.9 cm; body weight: 67.7 ± 12.03 kg) were divided into Rowing (N = 47) and Field sport (N = 43) athlete groups. Static PS parameters were assessed with a static double-leg and single-leg standing stability test on a force plate platform. Results: The multivariate analysis of variance showed a general stability difference between the groups (F = 13.255; P ≤ 0.0001), in double leg stability (F = 16.735; P ≤ 0.0001), and left leg (F = 15.097; P ≤ 0.0001) stability parameters. When analyzing variables separately, significant statistical differences were observed in favor of the Rowing group in double leg sway area (p = 0.017; ES = −0.07), double leg center of force (COF) traveled way (p ≤ 0.0001; ES = −27.42), length function of surface (p ≤ 0.0001; ES = −26.86), right leg ML displacement (p = 0.030; ES = −0.46), left leg sway area (p = 0.030; ES = −0.44), left leg COF traveled way (p ≤ 0.0001; ES = −60.63), left leg AP displacement (p = 0.043; ES = −0.44). Conclusion: These results underline the differences in rowing and field sport athletes in terms of static PS. The characteristics of sport and competition may affect PS, and it is important to adjust training modalities for the required level of PS in every sport, especially in rowing

Platelets in Ulcerative Colitis: From Pathophysiology to Therapy

Based on the role of platelets in inflammation and hemostasis it has been assumed that antiplatelet therapy could be beneficial for patients suffering from ulcerative colitis. Platelets present a link between inflammation and coagulation. They have more than 300 active mediators stored in their granules. Upon activation, platelet degranulate and release a lot of microparticles and mediators and interact with other immune and non-immune cells thereby amplifying inflammation. The most important parameters of platelet activation are P-selectin and CD40 ligand expressed on their surface upon activation, and their soluble forms presented in blood. Today, we have potent anti-platelet drugs that can inhibit platelet activation and degranulation, and thereby reduce inflammation. The most important drugs are P2Y12 receptor antagonists such as ticagrelor and clopidogrel and glycoprotein IIbIIIa inhibitors. Ticagrelor is an active drug and besides antiplatelet activity, it has bactericidal activity against Gram-positive strains and Clostridium difficile. Clopidogrel is a prodrug with less anti-inflammatory effect than ticagrelor and no proven bactericidal activity. Glycoprotein IIbIIIa inhibitors are very potent in reducing platelet aggregation but have lower anti-inflammatory potential than ticagrelor and clopidogrel

Zuclopenthixol decanoate in pregnancy: Successful outcomes in two consecutive off springs of the same mother

Introduction. Almost all individual antipsychotics are classified into the intermediate pregnancy risk category as no or limited data exist about human pregnancy outcomes. We presented the case of zuclopenthixol decanoate using in two successive pregnancies of the same woman, which had not been published in the available peer-reviewed literature. Case report. A middle-age female subject who suffered from schizophrenia received zuclopenthixol decanoate injection during her two consecutive pregnancies. About four and a half months before diagnosis of the first pregnancy (~3.5 years after psychosis emergence), zuclopenthixol decanoate (400 mg every other week, im injection) was introduced to the treatment protocol (due to previous non-compliance with halo-peridol and risperidone). A significant clinical improvement was achieved and the dose during pregnancy was reduced to 200 mg once monthly and maintained to date. In both pregnancies the women gave birth to healthy girls who have been developing normally until now, at their ages of 6 months and of 3.5 years. During pregnancy and after giving birth to children the mothers' psychiatric status and her social functioning were significantly improved and are still stable. Close monitoring of the mother's health, a multidisciplinary approach to both her treatment and the monitoring of pregnancies as well as the complete compliance with the prescribed drug protocol were likely to be crucial for the therapeutic success. Conclusion. A favorable outcome of the present case suggests that the zuclopenthixol decanoate is a rational therapeutic option for pregnant women suffering from psychosis when the expected benefit exceed the potential risk, but a definitive evidence for its safety requires large, controlled studies

Neonatal screening of hearing function by otoacustic emissions - a single center experience

Background/Aim. Nowadays development of techniques enables detection of hearing impairment in a very short time, immediately after birth by using otoacoustic emissions. They are low-pitched sounds produced in physiologically clear cochlea and can be recorded in cochlear outer meatus. By this method, complete data are found on a whole presynaptic auditory nervous system functioning that has mostly been affected by pathological changes making it a perfect screening test. Reliability and sensibility of this method is up to 98%. The aim of this study was to present the first results of systematic neonatal screening of hearing function by otoacoustic emissions in the Clinical Center Kragujevac (Kragujevac, Serbia). Methods. This prospective study of neonatal hearing screening function, initiated systematically by the 2008 at the Clinical Center Kragujevac, included full-term newborns and premature born ones, within the first 24 h after birth, using a DPOAEs interacoustics otoread-screener. Retesting was done after a month. Results. From January 1st, 2009 to December 1st, 2010, a total number of examined infants by this method was 1,994 out of which 1,778 were full-term and 216 were premature born. The test passing was higher in the group of full-term babies (92.5%) than in the preterm ones (55.1%). No bilateral answers were recorded in premature born children compared to the full-term ones, of whom a larger number was with missing lateral responses. The results of re-examination test in the group of full-term born and premature newborns were 83.7%, and 61%, respectively. Conclusion. Deliberately provoked transient otoacoustic emission is an efficient method in testing hearing function in newborns, since it is non-invasive, rapid and objective. Its correlation with audibly evoked potentials is very high, which confirms its reliability

Unfoldomics of human diseases: linking protein intrinsic disorder with diseases

<p>Abstract</p> <p>Background</p> <p>Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) lack stable tertiary and/or secondary structure yet fulfills key biological functions. The recent recognition of IDPs and IDRs is leading to an entire field aimed at their systematic structural characterization and at determination of their mechanisms of action. Bioinformatics studies showed that IDPs and IDRs are highly abundant in different proteomes and carry out mostly regulatory functions related to molecular recognition and signal transduction. These activities complement the functions of structured proteins. IDPs and IDRs were shown to participate in both one-to-many and many-to-one signaling. Alternative splicing and posttranslational modifications are frequently used to tune the IDP functionality. Several individual IDPs were shown to be associated with human diseases, such as cancer, cardiovascular disease, amyloidoses, diabetes, neurodegenerative diseases, and others. This raises questions regarding the involvement of IDPs and IDRs in various diseases.</p> <p>Results</p> <p>IDPs and IDRs were shown to be highly abundant in proteins associated with various human maladies. As the number of IDPs related to various diseases was found to be very large, the concepts of the disease-related unfoldome and unfoldomics were introduced. Novel bioinformatics tools were proposed to populate and characterize the disease-associated unfoldome. Structural characterization of the members of the disease-related unfoldome requires specialized experimental approaches. IDPs possess a number of unique structural and functional features that determine their broad involvement into the pathogenesis of various diseases.</p> <p>Conclusion</p> <p>Proteins associated with various human diseases are enriched in intrinsic disorder. These disease-associated IDPs and IDRs are real, abundant, diversified, vital, and dynamic. These proteins and regions comprise the disease-related unfoldome, which covers a significant part of the human proteome. Profound association between intrinsic disorder and various human diseases is determined by a set of unique structural and functional characteristics of IDPs and IDRs. Unfoldomics of human diseases utilizes unrivaled bioinformatics and experimental techniques, paves the road for better understanding of human diseases, their pathogenesis and molecular mechanisms, and helps develop new strategies for the analysis of disease-related proteins.</p

Modified divergence theorem for analysis and optimization of wall reflecting cylindrical UV reactor

In this paper, the modified divergence theorem (MDT), known in earlier literature as the Gauss-Ostrogradsky theorem, was formulated and proposed as a general approach to electromagnetic (EM) radiation, especially ultraviolet (UV) radiation reactor modeling. A formulated mathematical model, based on MDT, for a multilamp UV reactor was applied to all sources in a reactor in order to obtain intensity profiles at chosen surfaces inside the reactor. Applied modification of MDT means that intensity at a real opaque or transparent surface or through a virtual surface, opened or closed, from different sides of the surface are added and not subtracted as in some other areas of physics. The derived model is applied to an example of the multiple UV sources reactor, where sources are arranged inside a cylindrical reactor at the coaxial virtual cylinder, having the radius smaller than the radius of the reactor. In this work, optimization of a reactor means maximum transfer of EM energy sources into the fluid for given fluid absorbance and fluid flow-dose product. The obtained results, for water quality known in advance, give a unique solution for an optimized model of a multilamp reactor geometry. As everyone can easily verify, MDT is a very good starting point for every reactor modeling and analysis