Novel Therapeutic Effects in Rat Spinal Cord Injuries: Recovery of the Definitive and Early Spinal Cord Injury by the Administration of Pentadecapeptide BPC 157 Therapy

Recently, marked therapeutic effects pertaining to the recovery of injured rat spinal cords (1 min compression injury of the sacrocaudal spinal cord (S2-Co1) resulting in tail paralysis) appeared after a single intraperitoneal administration of the stable gastric pentadecapeptide BPC 157 at 10 min post-injury. Besides the demonstrated rapid and sustained recovery (1 year), we showed the particular points of the immediate effect of the BPC 157 therapy that began rapidly after its administration, (i) soon after injury (10 min), or (ii) later (4 days), in the rats with a definitive spinal cord injury. Specifically, in counteracting spinal cord hematoma and swelling, (i) in rats that had undergone acute spinal cord injury, followed by intraperitoneal BPC 157 application at 10 min, we focused on the first 10–30 min post-injury period (assessment of gross, microscopic, and gene expression changes). Taking day 4 post-injury as the definitive injury, (ii) we focused on the immediate effects after the BPC 157 intragastric application over 20 min of the post-therapy period. Comparable long-time recovery was noted in treated rats which had definitive tail paralysis: (iii) the therapy was continuously given per orally in drinking water, beginning at day 4 after injury and lasting one month after injury. BPC 157 rats presented only discrete edema and minimal hemorrhage and increased Nos1, Nos2, and Nos3 values (30 min post-injury, (i)) or only mild hemorrhage, and only discrete vacuolation of tissue (day 4, (ii)). In the day 4–30 post-injury study (iii), BPC 157 rats rapidly presented tail function recovery, and no demyelination process (Luxol fast blue staining).     

Variability of the honey bee mite Varroa destructor in Serbia, based on mtDNA analysis

Only two mitochondrial haplotypes (Korea and Japan) of Varroa destructor, the ectoparasitic honey bee mite, are known to be capable of infesting and successfully reproducing in Apis mellifera colonies worldwide. Varroa destructor (then called Varroa jacobsoni) was observed in Serbia for the first time in 1976. In order to obtain insight into the genetic variability of the mites parasitizing A. mellifera we analyzed 45 adult female mites sampled from nine localities dispersed throughout Serbia. Four fragments within cox1, atp6, cox3 and cytb mtDNA genes were sequenced. The Korea haplotype of V. destructor was found to be present at all localities, but also two new haplotypes (Serbia 1 and Peshter 1) were revealed, based on cox1 and cytb sequence variability. The simultaneous occurrence of Korea and Serbia 1 haplotypes was observed at five localities, whereas Peshter 1 haplotype was identifed at only one place.     

Under-exploration of Three-Dimensional Images Leads to Search Errors for Small Salient Targets

1. Download : Download high-res image (162KB)
2. Download : Download full-size image

     

A practical synthesis of N α -Fmoc protected l-threo-β-hydroxyaspartic acid derivatives for coupling via α- or β-carboxylic group

Abstract  

A simple and practical general synthetic protocol towards orthogonally protected tHyAsp derivatives fully compatible with Fmoc solid-phase peptide synthetic methodology is reported. Our approach includes enantioresolution of commercially available d,l-tHyAsp racemic mixture by co-crystallization with l-Lys, followed by ion exchange chromatography yielding enantiomerically pure l-tHyAsp and d-tHyAsp, and their selective orthogonal protection. In this way N ^α -Fmoc protected tHyAsp derivatives were prepared ready for couplings via either α- or β-carboxylic group onto the resins or the growing peptide chain. In addition, coupling of tHyAsp via β-carboxylic group onto amino resins allows preparation of peptides containing tHyAsn sequences, further increasing the synthetic utility of prepared tHyAsp derivatives.     

Evaluation of a composite test of kicking performance

The aim of this study was to evaluate the reliability and sensitivity of variables for the direct assessment of kicking performance in young soccer players. One hundred and six elite young soccer players were divided into 4 age groups (12-15 years). Absolute error (AE), variable error (VE), and constant error (CE) were evaluated as the variables of kicking accuracy, whereas the kicking velocity variables involved the maximum ball velocity (BVmax) and the ball velocity during accurate kicks (BVacc). Results suggested low-to-moderate reliability of the kicking accuracy (intraclass correlation coefficient [ICC] = 0.00-0.67) and high reliability of the kicking velocity variables (ICC = 0.87-0.94). Regarding the sensitivity, most of the variables detected the differences both between the dominant and nondominant legs and among the age groups. Because the evaluated variables should have a property of face validity, the findings obtained generally suggest that AE (and perhaps VE, as the measures of kicking accuracy) and both BVmax and BVacc (as the measures of kicking velocity) could be used within a routine composite test of kicking performance in young elite soccer players. Further development of the evaluated composite test of kicking performance could be based on the involvement of other kicking techniques and on testing the athletes of different ages, levels of skill, or sport specialization.     

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.