Bone morphogenetic protein (BMP)1-3 enhances bone repair

Small molecules that exhibit biological activity have contributed to the understanding of the molecular mechanisms of various biological phenomena. 5-Bromodeoxyuridine (BrdU) is a thymidine analogue that modulates various biological phenomena such as cellular differentiation and cellular senescence in cultured mammalian cells. Although BrdU is thought to function through changing chromatin structure and gene expression, its precise molecular mechanisms are not understood. To study the molecular mechanism for the action of BrdU, we have employed the yeast Saccharomycescerevisiae as a model system, and screened multi-copy suppressor genes that confer resistance to BrdU. Our genetic screen has revealed that expression of the N-terminal short fragment of TUP1, and also disruption of HDA1 or HOS1, histone deacetylases that interact with TUP1, conferred resistance to BrdU. These results suggest the implication of the chromatin proteins in the function of BrdU, and would provide novel clues to answer the old question of how BrdU modulates various biological phenomena.     

Thermally Targeted Delivery of a c-Myc Inhibitory Polypeptide Inhibits Tumor Progression and Extends Survival in a Rat Glioma Model

Treatment of glioblastoma is complicated by the tumors’ high resistance to chemotherapy, poor penetration of drugs across the blood brain barrier, and damaging effects of chemotherapy and radiation to normal neural tissue. To overcome these limitations, a thermally responsive polypeptide was developed for targeted delivery of therapeutic peptides to brain tumors using focused hyperthermia. The peptide carrier is based on elastin-like polypeptide (ELP), which is a thermally responsive biopolymer that forms aggregates above a characteristic transition temperature. ELP was modified with cell penetrating peptides (CPPs) to enhance delivery to brain tumors and mediate uptake across the tumor cells’ plasma membranes and with a peptide inhibitor of c-Myc (H1). In rats with intracerebral gliomas, brain tumor targeting of ELP following systemic administration was enhanced up to 5-fold by the use of CPPs. When the lead CPP-ELP-fused c-Myc inhibitor was combined with focused hyperthermia of the tumors, an additional 3 fold increase in tumor polypeptide levels was observed, and 80% reduction in tumor volume, delayed onset of tumor-associated neurological deficits, and at least doubled median survival time including complete regression in 80% of animals was achieved. This work demonstrates that a c-Myc inhibitory peptide can be effectively delivered to brain tumors.     

Impact of body composition on performance in fitness tests among personnel of the Croatian navy

The purpose of this study was to determine the impact of body weight on fitness tests among the personnel of the Croatian navy. Forty two naval personnel (age 27 +/- 4.1 years; body mass 86.2 +/- 4.9 kg; height 184.6 +/- 7.4 cm; body fat percentage 17.3 +/- 5.2) participated in this study. In order to evaluate the fitness of the naval servicemen, we applied a testing procedure that included measurements of 7 fitness tests and 15 body anthropometric tests. A negative correlation was found between the body fat percentage and all the analyzed sprint tests and three anaerobic power tests (r), SP5 (r = -0.42), SP10 (r = -0.51), SP20 (r = -0.53), SJ (r = -0.45), CM (r = -0.57), SLJ (r = -0.67). Also a negative correlation was found between the body fat percentage and VO2(max) (r = -0.44). A positive correlation was found between the sprint test and the power performance test and thigh and calf girth. Spiriting ability is influenced by the strength of a person. This is one of the reasons why we found a positive correlation between the sprint test (SP5, SP10 and SP20) and thigh and calf girth. In this study we found a negative correlation between body fat percentages and all the sprint tests and three anaerobic power tests and VO2(max). The ectomorph somatotypes have positive correlations with all variables. The mesomorph somatotypes have the greatest positive correlations with all variables. The endomorph somatotypes have negative correlations with all variables. According to the body composition of Croatian naval servicemen we can conclude that they need a sufficient level of strength and endurance for everyday tasks. The effectiveness of a weight-management program is determined by the success of the participants in losing the necessary amount of weight and being able to maintain that weight loss. This requires long-term tracking of these individuals in a naval environment.     

Multispan mitochondrial outer membrane protein Ugo1 follows a unique Mim1-dependent import pathway

The mitochondrial outer membrane (MOM) harbors several multispan proteins that execute various functions. Despite their importance, the mechanisms by which these proteins are recognized and inserted into the outer membrane remain largely unclear. In this paper, we address this issue using yeast mitochondria and the multispan protein Ugo1. Using a specific insertion assay and analysis by native gel electrophoresis, we show that the import receptor Tom70, but not its partner Tom20, is involved in the initial recognition of the Ugo1 precursor. Surprisingly, the import pore formed by the translocase of the outer membrane complex appears not to be required for the insertion process. Conversely, the multifunctional outer membrane protein mitochondrial import 1 (Mim1) plays a central role in mediating the insertion of Ugo1. Collectively, these results suggest that Ugo1 is inserted into the MOM by a novel pathway in which Tom70 and Mim1 contribute to the efficiency and selectivity of the process.     

The rate of metabolism in marine animals: environmental constraints, ecological demands and energetic opportunities

The rates of metabolism in animals vary tremendously throughout the biosphere. The origins of this variation are a matter of active debate with some scientists highlighting the importance of anatomical or environmental constraints, while others emphasize the diversity of ecological roles that organisms play and the associated energy demands. Here, we analyse metabolic rates in diverse marine taxa, with special emphasis on patterns of metabolic rate across a depth gradient, in an effort to understand the extent and underlying causes of variation. The conclusion from this analysis is that low rates of metabolism, in the deep sea and elsewhere, do not result from resource (e.g. food or oxygen) limitation or from temperature or pressure constraint. While metabolic rates do decline strongly with depth in several important animal groups, for others metabolism in abyssal species proceeds as fast as in ecologically similar shallow-water species at equivalent temperatures. Rather, high metabolic demand follows strong selection for locomotory capacity among visual predators inhabiting well-lit oceanic waters. Relaxation of this selection where visual predation is limited provides an opportunity for reduced energy expenditure. Large-scale metabolic variation in the ocean results from interspecific differences in ecological energy demand.     

Global Trophic Position Comparison of Two Dominant Mesopelagic Fish Families (Myctophidae,Stomiidae) Using Amino Acid Nitrogen Isotopic Analyses

The δ¹⁵N values of organisms are commonly used across diverse ecosystems to estimate trophic position and infer trophic connectivity. We undertook a novel cross-basin comparison of trophic position in two ecologically well-characterized and different groups of dominant mid-water fish consumers using amino acid nitrogen isotope compositions. We found that trophic positions estimated from the δ¹⁵N values of individual amino acids are nearly uniform within both families of these fishes across five global regions despite great variability in bulk tissue δ¹⁵N values. Regional differences in the δ¹⁵N values of phenylalanine confirmed that bulk tissue δ¹⁵N values reflect region-specific water mass biogeochemistry controlling δ¹⁵N values at the base of the food web. Trophic positions calculated from amino acid isotopic analyses (AA-TP) for lanternfishes (family Myctophidae) (AA-TP ∼2.9) largely align with expectations from stomach content studies (TP ∼3.2), while AA-TPs for dragonfishes (family Stomiidae) (AA-TP ∼3.2) were lower than TPs derived from stomach content studies (TP∼4.1). We demonstrate that amino acid nitrogen isotope analysis can overcome shortcomings of bulk tissue isotope analysis across biogeochemically distinct systems to provide globally comparative information regarding marine food web structure.     

The Role of Carrion Supply in the Abundance of Deep-Water Fish off California

Few time series of deep-sea systems exist from which the factors affecting abyssal fish populations can be evaluated. Previous analysis showed an increase in grenadier abundance, in the eastern North Pacific, which lagged epibenthic megafaunal abundance, mostly echinoderms, by 9–20 months. Subsequent diet studies suggested that carrion is the grenadier''s most important food. Our goal was to evaluate if changes in carrion supply might drive the temporal changes in grenadier abundance. We analyzed a unique 17 year time series of abyssal grenadier abundance and size, collected at Station M (4100 m, 220 km offshore of Pt. Conception, California), and reaffirmed the increase in abundance and also showed an increase in mean size resulting in a ∼6 fold change in grenadier biomass. We compared this data with abundance estimates for surface living nekton (pacific hake and jack mackerel) eaten by the grenadiers as carrion. A significant positive correlation between Pacific hake (but not jack mackerel) and grenadiers was found. Hake seasonally migrate to the waters offshore of California to spawn. They are the most abundant nekton species in the region and the target of the largest commercial fishery off the west coast. The correlation to grenadier abundance was strongest when using hake abundance metrics from the area within 100 nmi of Station M. No significant correlation between grenadier abundance and hake biomass for the entire California current region was found. Given the results and grenadier longevity, migration is likely responsible for the results and the location of hake spawning probably is more important than the size of the spawning stock in understanding the dynamics of abyssal grenadier populations. Our results suggest that some abyssal fishes'' population dynamics are controlled by the flux of large particles of carrion. Climate and fishing pressures affecting epipelagic fish stocks could readily modulate deep-sea fish dynamics.     

Dermatoglyphics in patients with hypothyreosis

About 15% of all females and 3% of all males suffers from hypothyreosis. The thyroid disease is the most frequent cause of hypothyreosis, and among people in Croatia who are suffering from that disease 90% have been affected by its autoimmune form. The thyroid diseases are supposed to be caused by the influence of various genetic and external factors and some forms of genetic influences have not yet been studied. Analysis of digito-palmar dermatoglyphics has been used in the research of the role of genetic predisposition in many various diseases. We have analyzed correlation of qualitative and quantitative traits between the group of 50 females suffering from hypothyreosis and a control group of 100 phenotypically healthy females. Quantitative statistical analysis using t-test has indicated only few significantly different variables, while the discriminant analysis has shown 76.9% correctly classified samples. The factor analysis has shown a high percentage of total variance within patients suffering from hypothyreosis, as well as the different structure of individual factors. Qualitative analysis has shown the heterogeneity between the two examined groups. The results of the research have proved that the qualitative characteristics are more unstable than the quantitative ones and they have also shown the instability of genes taking part in hypothyreosis development implying genetic predisposition of the disease.     

Anticancer Activity of Proapoptotic Peptides is Highly Improved by Thermal Targeting using Elastin-like Polypeptides

Inducing apoptosis in cancer cells is an effective strategy for cancer therapy. The cationic ??-helix forming KLAKLAKKLAKLAK peptide (KLAK) has been known to induce apoptosis by disrupting the mitochondria. In the present study, we have designed a thermally targeted KLAK peptide by genetically engineering the KLAK sequence to the carboxy terminus of the heat responsive biopolymer elastin-like polypeptide (ELP). The cellular internalization of ELP-KLAK was made possible by engineering a cell penetrating peptide sequence (SynB1) to the amino terminus of ELP. The SynB1-ELP1-KLAK fusion polypeptide was cytotoxic against both estrogen receptor positive and negative human breast cancer cell lines. The potency of SynB1-ELP1-KLAK was further enhanced when mild hyperthermia was added to the treatment. In response to hyperthermia, SynB1-ELP1-KLAK selectively triggered apoptosis, which was associated with disruption of the mitochondria. The thermally responsive SynB1-ELP-KLAK polypeptide can have improved tumor targeting by the application of mild hyperthermia. Furthermore, the pharmacokinetic properties of ELP can prevent degradation of KLAK in vivo, and the use of SynB1 can mediate tumor cell uptake, thereby augmenting the effect of KLAK.