Effects of loading on maximum vertical jumps: Selective effects of weight and inertia

A novel loading method was applied to explore selective effects of externally added weight (W), weight and inertia (W+I), and inertia (I) on maximum counter-movement jumps (CMJ) performed with arm swing. Externally applied extended rubber bands and/or loaded vest added W, W+I, and I corresponding to 10-40% of subjects' body mass. As expected, an increase in magnitude of all types of load was associated with an increase in ground reaction forces (GRF), as well as with a decrease in both the jumping performance and power output. However, of more importance could be that discernible differences among the effects of W, W+I, and I were recorded despite a relatively narrow loading range. In particular, an increase in W was associated with the minimal changes in movement kinematic pattern and smallest reduction of jumping performance, while also allowing for the highest power output. Conversely, W+I was associated with the highest ground reaction forces. Finally, the lowest maxima of GRF and power were associated with I. Although further research is apparently needed, the obtained finding could be of potential importance not only for understanding fundamental properties of the neuromuscular system, but also for optimization of loading in standard athletic training and rehabilitation procedures.     

Continuous production of poly([<Emphasis Type="BoldItalic">R</Emphasis>]-3-hydroxybutyrate) by <Emphasis Type="BoldItalic">Cupriavidus necator</Emphasis> in a multistage bioreactor cascade

Poly(hydroxyalkanoates) (PHAs) constitute biodegradable polyesters and are considered among the most promising candidates to replace common petrochemical plastics in various applications. To date, all commercial processes for PHA production employ microbial discontinuous fed-batch fermentations. These processes feature drawbacks such as varying product quality and the inevitable periods of downtime for preparation and post-treatment of the bioreactor equipment. An unprecedented approach to PHA production was chosen in the presented work using a multistage system consisting of five continuous stirred tank reactors in series (5-SCR), which can be considered as a process engineering substitute of a continuous tubular plug flow reactor. The first stage of the reactor cascade is the site of balanced bacterial growth; thereafter, the fermentation broth is continuously fed from the first into the subsequent reactors, where PHA accumulation takes place under nitrogen-limiting conditions. Cupriavidus necator was used as production strain. The focus of the experimental work was devoted to the development of a PHA production process characterized by high productivity and high intracellular polymer content. The results of the experimental work with the reactor cascade demonstrated its potential in terms of volumetric and specific productivity (1.85 g L⁻¹ h⁻¹ and 0.100 g g⁻¹ h⁻¹, respectively), polymer content (77%, w/w) and polymer properties (M _w = 665 kg/mol, PDI = 2.6). Thus, implementing the technology for 5-SCR production of PHB results in an economically viable process. The study compares the outcome of the work with literature data from continuous two-stage PHA production and industrial PHA production in fed-batch mode.     

Discovery of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides active against efflux-mediated resistant Streptococcus pneumoniae

A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides, were discovered, structurally characterized and biologically evaluated. They have shown good antibacterial activity against selected Gram-positive and Gram-negative bacterial strains. These include N″ substituted 9a-(N′-carbamoyl-γ-aminopropyl)- (6a,c), 9a-(N′-thiocarbamoyl-γ-aminopropyl)- (7a,e), 9a-[N′-(β-cyanoethyl)-N′-(carbamoyl-γ-aminopropyl)]- (9a-c, 9g) 9a-[N′-(β-cyanoethyl)-N′-(thiocarbamoyl-γ-aminopropyl)]-derivatives (10d-f) of 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3).Among the synthesized compounds thiourea 7a and urea 9b have shown substantially improved activity comparable to azithromycin (1) and significantly better activity than the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against efflux-mediated resistant S. pneumoniae.     

Testing the ortholog conjecture with comparative functional genomic data from mammals

A common assumption in comparative genomics is that orthologous genes share greater functional similarity than do paralogous genes (the "ortholog conjecture"). Many methods used to computationally predict protein function are based on this assumption, even though it is largely untested. Here we present the first large-scale test of the ortholog conjecture using comparative functional genomic data from human and mouse. We use the experimentally derived functions of more than 8,900 genes, as well as an independent microarray dataset, to directly assess our ability to predict function using both orthologs and paralogs. Both datasets show that paralogs are often a much better predictor of function than are orthologs, even at lower sequence identities. Among paralogs, those found within the same species are consistently more functionally similar than those found in a different species. We also find that paralogous pairs residing on the same chromosome are more functionally similar than those on different chromosomes, perhaps due to higher levels of interlocus gene conversion between these pairs. In addition to offering implications for the computational prediction of protein function, our results shed light on the relationship between sequence divergence and functional divergence. We conclude that the most important factor in the evolution of function is not amino acid sequence, but rather the cellular context in which proteins act.     

MutPred Splice: machine learning-based prediction of exonic variants that disrupt splicing

We have developed a novel machine-learning approach, MutPred Splice, for the identification of coding region substitutions that disrupt pre-mRNA splicing. Applying MutPred Splice to human disease-causing exonic mutations suggests that 16% of mutations causing inherited disease and 10 to 14% of somatic mutations in cancer may disrupt pre-mRNA splicing. For inherited disease, the main mechanism responsible for the splicing defect is splice site loss, whereas for cancer the predominant mechanism of splicing disruption is predicted to be exon skipping via loss of exonic splicing enhancers or gain of exonic splicing silencer elements. MutPred Splice is available at http://mutdb.org/mutpredsplice.     

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.     

The designer leptin antagonist peptide Allo-aca compensates for short serum half-life with very tight binding to the receptor

The leptin receptor antagonist peptide Allo-aca exhibits picomolar activities in various cellular systems and sub-mg/kg subcutaneous efficacies in animal models making it a prime drug candidate and target validation tool. Here we identified the biochemical basis for its remarkable in vivo activity. Allo-aca decomposed within 30 min in pooled human serum and was undetectable beyond the same time period from mouse plasma during pharmacokinetic measurements. The C _max of 8.9 μg/mL at 5 min corresponds to approximately 22 % injected peptide present in the circulation. The half-life was extended to over 2 h in bovine vitreous fluid and 10 h in human tears suggesting potential efficacy in ophthalmic diseases. The peptide retained picomolar anti-proliferation activity against a chronic myeloid leukemia cell line; addition of a C-terminal biotin label increased the IC₅₀ value by approximately 200-fold. In surface plasmon resonance assays with the biotin-labeled peptide immobilized to a NeutrAvidin-coated chip, Allo-aca exhibited exceptionally tight binding to the binding domain of the human leptin receptor with k _a = 5 × 10⁵ M^?1 s^?1 and k _diss = 1.5 × 10^?4 s^?1 values. Peptides excel in terms of high activity and selectivity to their targets, and may activate or inactivate receptor functions considerably longer than molecular turnovers that take place in experimental animals.     

Molecular and ecological features of the soft-muzzled trout Salmo obtusirostris (Heckel, 1852) in the Zeta River, Montenegro

This paper reports about the occurrence of soft-muzzled trout in Montenegro. It was found only in the Zeta River, at three localities, always in low abundance. Results of genetic investigation on twelve microsatellite loci (i.e., high Fst and high heterozygozity values) as well as lack of hybridization with the putative brown trout unequivocally confirm that the soft-muzzled trout from the Zeta River is a species distinct from the putative brown (Salmo cf. farioides) and marble (Salmo marmoratus) trout that live in sympatry with it. This paper also confirms high genetic diversity of Zeta River soft - muzzled trout population. Habitat and feeding analyses revealed that soft-muzzled trout reduce the competition with syntopic putative brown trout by displacing as the bottom-dweller in their common type of habitat, as well as by narrowing its feeding niche and feeding dominantly with the benthic macroinvertebrates, the Gammarus shrimps as their far dominant feeding item. Results also revealed that they did not share the same habitat with marble trout. Due to this population low abundance and their importance on species level, Zeta River soft-muzzled trout conservation needs are urgent in terms of in situ protection and repopulation measures.     

Executive functions predict the success of top-soccer players

While the importance of physical abilities and motor coordination is non-contested in sport, more focus has recently been turned toward cognitive processes important for different sports. However, this line of studies has often investigated sport-specific cognitive traits, while few studies have focused on general cognitive traits. We explored if measures of general executive functions can predict the success of a soccer player. The present study used standardized neuropsychological assessment tools assessing players' general executive functions including on-line multi-processing such as creativity, response inhibition, and cognitive flexibility. In a first cross-sectional part of the study we compared the results between High Division players (HD), Lower Division players (LD) and a standardized norm group. The result shows that both HD and LD players had significantly better measures of executive functions in comparison to the norm group for both men and women. Moreover, the HD players outperformed the LD players in these tests. In the second prospective part of the study, a partial correlation test showed a significant correlation between the result from the executive test and the numbers of goals and assists the players had scored two seasons later. The results from this study strongly suggest that results in cognitive function tests predict the success of ball sport players.