Structural characterization of the interaction of α-synuclein nascent chains with the ribosomal surface and trigger factor

The ribosome is increasingly becoming recognized as a key hub for integrating quality control processes associated with protein biosynthesis and cotranslational folding (CTF). The molecular mechanisms by which these processes take place, however, remain largely unknown, in particular in the case of intrinsically disordered proteins (IDPs). To address this question, we studied at a residue-specific level the structure and dynamics of ribosome-nascent chain complexes (RNCs) of α-synuclein (αSyn), an IDP associated with Parkinson’s disease (PD). Using solution-state nuclear magnetic resonance (NMR) spectroscopy and coarse-grained molecular dynamics (MD) simulations, we find that, although the nascent chain (NC) has a highly disordered conformation, its N-terminal region shows resonance broadening consistent with interactions involving specific regions of the ribosome surface. We also investigated the effects of the ribosome-associated molecular chaperone trigger factor (TF) on αSyn structure and dynamics using resonance broadening to define a footprint of the TF–RNC interactions. We have used these data to construct structural models that suggest specific ways by which emerging NCs can interact with the biosynthesis and quality control machinery

Implementing efficient concerted rotations using Mathematica and C code

In this article we demonstrate a general and efficient metaprogramming implementation of concerted rotations using Mathematica. Concerted rotations allow the movement of a fixed portion of a polymer backbone with fixed bending angles, like a protein, while maintaining the correct geometry of the backbone and the initial and final points of the portion fixed. Our implementation uses Mathematica to generate a C code which is then wrapped in a library by a Python script. The user can modify the Mathematica notebook to generate a set of concerted rotations suited for a particular backbone geometry, without having to write the C code himself. The resulting code is highly optimized, performing on the order of thousands of operations per second

pKa Modulation of the Acid/Base Catalyst within GH32 and GH68: A Role in Substrate/Inhibitor Specificity?

Glycoside hydrolases of families 32 (GH32) and 68 (GH68) belong to clan GH-J, containing hydrolytic enzymes (sucrose/fructans as donor substrates) and fructosyltransferases (sucrose/fructans as donor and acceptor substrates). In GH32 members, some of the sugar substrates can also function as inhibitors, this regulatory aspect further adding to the complexity in enzyme functionalities within this family. Although 3D structural information becomes increasingly available within this clan and huge progress has been made on structure-function relationships, it is not clear why some sugars bind as inhibitors without being catalyzed. Conserved aspartate and glutamate residues are well known to act as nucleophile and acid/bases within this clan. Based on the available 3D structures of enzymes and enzyme-ligand complexes as well as docking simulations, we calculated the pKa of the acid-base before and after substrate binding. The obtained results strongly suggest that most GH-J members show an acid-base catalyst that is not sufficiently protonated before ligand entrance, while the acid-base can be fully protonated when a substrate, but not an inhibitor, enters the catalytic pocket. This provides a new mechanistic insight aiming at understanding the complex substrate and inhibitor specificities observed within the GH-J clan. Moreover, besides the effect of substrate entrance on its own, we strongly suggest that a highly conserved arginine residue (in the RDP motif) rather than the previously proposed Tyr motif (not conserved) provides the proton to increase the pKa of the acid-base catalyst

Toward an accurate prediction of inter-residue distances in proteins using 2D recursive neural networks

BACKGROUND: Protein inter-residue contact maps provide a translation and rotation invariant topological representation of a protein. They can be used as an intermediary step in protein structure predictions. However, the prediction of contact maps represents an unbalanced problem as far fewer examples of contacts than non-contacts exist in a protein structure. In this study we explore the possibility of completely eliminating the unbalanced nature of the contact map prediction problem by predicting real-value distances between residues. Predicting full inter-residue distance maps and applying them in protein structure predictions has been relatively unexplored in the past. RESULTS: We initially demonstrate that the use of native-like distance maps is able to reproduce 3D structures almost identical to the targets, giving an average RMSD of 0.5Å. In addition, the corrupted physical maps with an introduced random error of ±6Å are able to reconstruct the targets within an average RMSD of 2Å. After demonstrating the reconstruction potential of distance maps, we develop two classes of predictors using two-dimensional recursive neural networks: an ab initio predictor that relies only on the protein sequence and evolutionary information, and a template-based predictor in which additional structural homology information is provided. We find that the ab initio predictor is able to reproduce distances with an RMSD of 6Å, regardless of the evolutionary content provided. Furthermore, we show that the template-based predictor exploits both sequence and structure information even in cases of dubious homology and outperforms the best template hit with a clear margin of up to 3.7Å. Lastly, we demonstrate the ability of the two predictors to reconstruct the CASP9 targets shorter than 200 residues producing the results similar to the state of the machine learning art approach implemented in the Distill server. CONCLUSIONS: The methodology presented here, if complemented by more complex reconstruction protocols, can represent a possible path to improve machine learning algorithms for 3D protein structure prediction. Moreover, it can be used as an intermediary step in protein structure predictions either on its own or complemented by NMR restraints

Psychometric properties of the serbian version of the operational and organizational police stress questionnaires

The Police Operational Stress Questionnaire (PSQ-Op) and Police Organizational Stress Questionnaire (PSQ-Org) have been used to assess operational and organizational sources of police officers’ occupational stress. Considering that different cultural and socio-economic environments could affect officers’ perception of operational and organizational stress, country specific psychometric properties and cut-off values should be defined. Therefore, this study aimed to investigate the psychometric properties of the Serbian version of the PSQ-Op and PSQ-Org (i.e., translated in Serbian and adjusted to Serbian culture) and to establish cut-off values for low, moderate and high stress. Methods: The PSQ-Op and PSQ-Org were administered to police officers through the Ministry of Interior of the Republic of Serbia. Participants included 1220 police officers (19.0% female) who correctly completed both questionnaires. Cronbach’s α was used to determine the reliability of instruments. Cut-off values for low, moderate and high stress were defined based on the mean and standard deviation of the sample and using percentile analysis. Prevalence of low, moderate and high stress was calculated according to already established cut-off values as well as those calculated based on the study sample. Results: Both instruments showed high reliability (Cronbach’s α = 0.963 [95% Confidence Interval = 0.957–0.964]). Occupational stress levels (low, moderate and high) were distributed differently (p < 0.001) when categorized according to the cut-off values defined in literature and cut-off values based on the study sample. The cut-off values by mean and standard deviation could be used for PSQ-Op, while cut-off values by percentile analysis could be used for PSQ-Org

Specific Physical Ability Prediction in Youth Basketball Players According to Playing Position

This study investigated the hierarchical structure of physical characteristics in elite young (i.e., U17-U19) basketball players according to playing positions. In addition, their predictive value of physical characteristics was determined for the evaluation of players’ physical preparedness. Sixty elite male basketball players performed 13 standardized specific field tests in order to assess the explosive power of lower limbs, speed, and change-of-direction speed. They were divided into three groups according to playing positions (guard [n = 28], forward [n = 22], center [n = 10]). The basic characteristics of the tested sample were: age = 17.36 ± 1.04 years, body height = 192.80 ± 4.49 cm, body mass = 79.83 ± 6.94 kg, and basketball experience = 9.38 ± 2.10 years for guards; age = 18.00 ± 1.00 years, body height = 201.48 ± 3.14 cm, body mass = 90.93 ± 9.85 kg, and basketball experience = 9.93 ± 2.28 years for forwards; and age = 17.60 ± 1.43 years; body height = 207.20 ± 3.29 cm, body mass = 104.00 ± 9.64 kg, and basketball experience = 9.20 ± 1.62 years for centers. For all playing positions factor analysis extracted three factors, which cumulatively explained 76.87, 88.12 and 87.63% of variance, respectively. The assessed performance measures were defined as significant (p < 0.001), with regression models of physical performance index (PPINDEX ). PPINDEX of guards = −6.860 + (0.932 × t-test) − (1.656 × Acceleration 15 m) − (0.020 × Countermovement jump); PPINDEX of forwards = −3.436 − (0.046 × Countermovement jump with arm swing) − (1.295 × Acceleration 15 m) + (0.582 × Control of dribbling); PPINDEX of centers = −4.126 + (0.604 × Control of dribbling) − (1.315 × Acceleration 15 m) − (0.037 × Sargent jump). A model for the evaluation of physical performance of young basketball players has been defined. In addition, this model could be used as a reference model for selection procedures, as well as to monitor the efficacy of applied training programmes within the short, medium and long-term periodization

Влияние шестинедельной контролируемой программы упражнений и частично контролируемой диеты на жировую массу и массу скелетных мышц у взрослых

F. Kukic1, [email protected], ORCID ID: 0000-0002-8625-5375, N. Todorovic2, [email protected], ORCID ID: 0000-0003-4741-0966, N. Cvijanovic2, [email protected], ORCID ID: 0000-0002-7196-6342 1Police Sports Education Center, Abu Dhabi Police, United Arab Emirates, 2Kubo Training Center, Belgrade, Serbia Филип Кукич, кандидат на присуждение степени PhD, руководитель Спортивного образовательного центра полиции, служба подготовки, полиция Абу-Даби. Объединенные Арабские Эмираты, г. Абу-Даби, ул. Карама, Спортивный образовательный центр полиции, аб. ящик 253. E-mail: [email protected], ORCID ID: 0000-0002-8625-5375. Неманя Тородович, магистр наук, операционный руководитель тренировочного центра Кубо. Сербия, Смедеревски пут 3-б, г. Белград, аб. ящик 11050. E-mail: nemanja.tod@ hotmail.com, ORCID ID: 0000-0003-4741-0966. Ненад Цвиянович, магистр наук, руководитель по питанию тренировочного центра Кубо. Сербия, Смедеревски пут 3-б, г. Белград, аб. ящик 11050. E-mail: nenadcvijanovic89@ gmail.com, ORCID ID: 0000-0002-7196-6342.Aim. To investigate the effects of a 6-week of controlled exercise program followed by a semi-controlled dietary regimen on indicators of body fat mass (BF) and skeletal muscle mass (SMM) of adults. Materials and methods. The sample consisted of 28 particpants with the main characteristics of the sample being: age = 29.70 ± 8.35 years, body height (BH) = 177.35 ± 9.36 cm, and body mass (BM) = 105.20 ± 27.06 kg. Body composition parameters, BM, body fat mass (BF), trunk fat (TF), skeletal muscle mass (SMM), percent of body fat (PBF), percent of skeletal muscle mass (PSMM), body mass index (BMI), and index of hypokinesia (IH) were collected before and after six weeks of exercise program and semi-controlled diet regimen. A Paired sample T-test and effect size (ES) were used to determine the effects and their magnitude of the treatment applied. Results. A 6-week treatment significantly affected investigated variables, wherein BF (-6.75 kg,p < 0.001), TF (-3.28 kg,p < 0.001), and SMM (-0.91 kg,p = 0.003) tissue decreased in a different degree, leading to a small but highly significant increase in PSMM (2.60 %, p < 0.001). A decrease in BF and SMM resulted in a significant reduction in BMI, while IH decreased in a smaller degree than BMI because PBF and PSMM changed inversely. Conclusion. Six weeks of a controlled exercise program 3 times/week and semi-controlled diet is an effective approach to the reduction of BM, BF, and TF and to increasing the movement potential by changing the proportions of PBF and PSMM. Цель. Целью данной статьи является установление влияния шестинедельной контролируемой программы упражнений, сопровождаемой частично контролируемой диетой, на показатели жировой массы и массы скелетных мышц у взрослых. Материалы и методы. Выборка состояла из 28 участников со следующими основными характеристиками: возраст = 29,70 ± 8,35 лет, рост = 177,35 ± 9,36 см, вес = 105,20 ± 27,06 кг. Параметры состава тела были зарегистрированы до и после шестинедельной программы упражнений и частично контролируемой диеты: масса тела, жировая масса, жировая масса туловища, масса скелетных мышц, процент жировой массы, процент массы скелетных мышц, индекс массы тела и индекс гипокинезии. Для определения эффекта от используемой программы и его магнитуды применялся двухвыборочный t-тест для связанных выборок и оценка величины эффекта. Результаты. Шестинедельная программа оказала значительное влияние на исследуемые переменные, при этом жировая масса (-6,75 кг, p < 0,001), жировая масса туловища (-3,28 кг, p < 0,001) и масса скелетных мышц (-0,91 кг, p = 0,003) уменьшились в разной степени, что привело к небольшому, но статистически важному увеличению процента массы скелетных мышц (2,60 %, p < 0,001). Снижение жировой массы и массы скелетных мышц привело к значительному понижению индекса массы тела, в то время как индекс гипокинезии снизился в меньшей степени, чем индекс массы тела, потому что процент жировой массы и процент массы скелетных мышц имеют обратную зависимость. Заключение. Шесть недель контролируемой программы упражнений 3 раза в неделю и частично контролируемая диета являются эффективным подходом к снижению массы тела, жировой массы и жировой массы туловища, а также увеличивают двигательный потенциал за счет изменения соотношения процента жировой массы и процента массы скелетных мышц

Accuracy of Body Mass Index and Obesity Status in Police Trainees

The first aim of this study was to compare body mass index (BMI) (indirect method) classification with the body fat percent (PBF) (direct method) and to determine how BMI classifies subjects with different levels of skeletal muscle mass percent (PSMM). The second aim was to determine the prevalence of overweight and obesity status among police trainees (PTs). A total of 103 male PTs participated in this research: age = 21.46 ± 0.64 years, body mass (BM) = 75.97 ± 8.10 kg, body height (BH) = 174.07 ± 6.31 cm, BMI = 25.05 ± 2.12 kg/m2 . The InBody 370 multichannel bioelectrical impedance analysis (BIA) measured body composition. Study results indicated that muscular PTs could be misclassified as overweight and that PBF identified more subjects as obese. Namely, three PTs were obese according to BMI, while 13 were obese according to PBF. The information provided by this research could be used to help professionals understand the importance of measuring body composition, and the inaccuracies in BMI classification. In conclusion, whenever possible PSMM and PBF should replace the utilization of BMI to screen overweight and obesity in PTs. Agencies may think of using BIA as non-invasive, quick and inexpensive measurement tool

Body Composition and Physical Activity of Female Police Officers: Do Occupation and Age Matter?

This study aimed to investigate the differences in the body composition and volume of leisure time physical activity (V-LTPA) of female police officers from two police occupations and to assess the differences when officers are matched by age. Body composition measures including body mass index (BMI), percent body fat (¿), and percent of skeletal muscle mass (%SMM) of female communal police (n = 56) and general police (n = 90) were compared. Officers were allocated into three age groups: 29 years and younger, 30–39 years, and 40 years and older. We used an independent samples t-test, analysis of variance, and multiple analyses of variance to investigate the differences between occupations, between age groups, and between-occupation-within-age differences in body composition. Communal police officers had significantly (p &lt; 0.05) lower BMI and ¿ and higher %SMM compared to general police. Significant differences were found between age groups, with the youngest officers having lower BMI and ¿ and higher %SMM and V-LTPA. Finally, differences in body composition were no longer significant when officers from different occupations were compared within age groups. Police agencies should consider supporting and motivating officers through policies to encourage leisure time physical activities for female officers. Other mechanisms for the management of body composition should also be considered