Performance Development in Adolescent Track and Field Athletes According to Age,Sex and Sport Discipline

Introduction

Sex-specific differences that arise during puberty have a pronounced effect on the training process. However, the consequences this should have for goal-setting, planning and implementation of training for boys and girls of different ages remains poorly understood. The aim of this study was to quantify performance developments in athletic running and jumping disciplines in the age range 11-18 and identify progression differences as a function of age, discipline and sex.

Methods

The 100 all-time best Norwegian male and female 60-m, 800-m, long jump and high jump athletes in each age category from 11 to 18 years were analysed using mixed models with random intercept according to athlete.

Results

Male and female athletes perform almost equally in running and jumping events up to the age of 12. Beyond this age, males outperform females. Relative annual performance development in females gradually decreases throughout the analyzed age period. In males, annual relative performance development accelerates up to the age of 13 (for running events) or 14 (for jumping events) and then gradually declines when approaching 18 years of age. The relative improvement from age 11 to 18 was twice as high in jumping events compared to running events. For all of the analyzed disciplines, overall improvement rates were >50% higher for males than for females. The performance sex difference evolves from < 5% to 10-18% in all the analyzed disciplines from age 11 to 18 yr.

Conclusion

To the authors’ knowledge, this is the first study to present absolute and relative annual performance developments in running and jumping events for competitive athletes from early to late adolescence. These results allow coaches and athletes to set realistic goals and prescribe conditioning programs that take into account sex-specific differences in the rate of performance development at different stages of maturation.     

A pathway for synapsis initiation during zygotene in Drosophila oocytes

Formation of the synaptonemal complex (SC), or synapsis, between homologs in meiosis is essential for crossing over and chromosome segregation [1-4]. How SC assembly initiates is poorly understood but may have a critical role in ensuring synapsis between homologs and regulating double-strand break (DSB) and crossover formation. We investigated the genetic requirements for synapsis in Drosophila and found that there are three temporally and genetically distinct stages of synapsis initiation. In "early zygotene" oocytes, synapsis is only observed at the centromeres. We also found that nonhomologous centromeres are clustered during this process. In "mid-zygotene" oocytes, SC initiates at several euchromatic sites. The centromeric and first euchromatic SC initiation sites depend on the cohesion protein ORD. In "late zygotene" oocytes, SC initiates at many more sites that depend on the Kleisin-like protein C(2)M. Surprisingly, late zygotene synapsis initiation events are independent of the earlier mid-zygotene events, whereas both mid and late synapsis initiation events depend on the cohesin subunits SMC1 and SMC3. We propose that the enrichment of cohesion proteins at specific sites promotes homolog interactions and the initiation of euchromatic SC assembly independent of DSBs. Furthermore, the early euchromatic SC initiation events at mid-zygotene may be required for DSBs to be repaired as crossovers.     

THE DEVELOPMENTAL ROLE OF THE EXTRACELLULAR MATRIX SUGGESTS A MONOPHYLETIC ORIGIN OF THE KINGDOM ANIMALIA

The fundamental events of early development are similar in all animals, including sponges. Recent developments in the molecular biology of the extracellular matrix strongly suggest that the molecular mechanisms behind these events are also similar among all animals. I propose that the complex (collagen, proteoglycan, adhesive glycoprotein, and integrin) system that mediates cell motility and transitions between epithelial and motile cell types is central to multicellularity in animals. I further propose that the extracellular matrix is a deep rooted homology that unites the kingdom Animalia into a monophyletic group of multicellular organisms.     

Perspective: transposable elements, parasitic DNA, and genome evolution

The nature of the role played by mobile elements in host genome evolution is reassessed considering numerous recent developments in many areas of biology. It is argued that easy popular appellations such as "selfish DNA" and "junk DNA" may be either inaccurate or misleading and that a more enlightened view of the transposable element-host relationship encompasses a continuum from extreme parasitism to mutualism. Transposable elements are potent, broad spectrum, endogenous mutators that are subject to the influence of chance as well as selection at several levels of biological organization. Of particular interest are transposable element traits that early evolve neutrally at the host level but at a later stage of evolution are co-opted for new host functions.     

Pre-Dialysis Visits to a Nephrology Department and Major Cardiovascular Events in Patients Undergoing Dialysis

Background and Objectives

Pre-dialysis care by a nephrology out-patient department (OPD) may affect the outcomes of patients who ultimately undergo maintenance dialysis. This study examined the effect of pre-dialysis care by a nephrology OPD on the incidence of one-year major cardiovascular events after initiation of dialysis.

Design, Setting Participants, & Measurements

The study consisted of Taiwanese patients with chronic kidney disease (CKD) who commenced dialysis from 2006 to 2008. The number of nephrology OPD visits during the critical care period (within 6 months of initiation of dialysis) and the early care period (6–36 months before initiation of dialysis) were analyzed. The primary outcome measure was one-year major cardiovascular events.

Results

A total of 1191 CKD patients who initiated dialysis from 2006 to 2008 were included. Binary logistic regression showed that patients with ≧3 visits during the critical care period and those with ≧11 visits during the early care period had fewer composite major cardiovascular events than those with 0 visits. Patients with early referral are less likely to experience composite major cardiovascular events than those with late referral, with aOR 0.574 (95% CI = 0.43–0.77, P<0.001). Patients with both ≧3 visits during critical care period and ≧11 visits during early care period were less likely to experience composite major cardiovascular events (aOR = 0.25, 95% CI = 0.16–0.39, P < 0.001).

Conclusions

Patients with adequate pre-dialysis nephrology OPD visits, not just early referral, may had fewer one-year composite major cardiovascular events after initiation of dialysis. This information may be important to medical care providers and public health policy makers in their efforts to improve the well-being of CKD patients.     

Endocrinization of the early embryo: an emerging role for hormones and hormone-like factors

In the last decade, we witnessed the extension of endocrinologically based concepts and molecules to many other arenas of intercellular communication, e.g. immunology, hematology and cancer biology. At the start of the new decade we are witnessing the beginning of a similar transformation in our understanding of early embryogenesis, i.e. that hormones, growth factors and other hormone-like agents and their receptors, familiar to us in other contexts, may be the long-sought mediators of many key events in early embryogenesis. Why these agents were overlooked before and how they have started to emerge is the theme of this essay. The title 'Endocrinization of the Early Embryo' refers to both the biological and intellectual developments.     

Testing the relationship between foldability and the early folding events of dihydrofolate reductase from Escherichia coli

A "folding element" is a contiguous peptide segment crucial for a protein to be foldable and is a new concept that could assist in our understanding of the protein-folding problem. It is known that the presence of the complete set of folding elements of dihydrofolate reductase (DHFR) from Escherichia coli is essential for the protein to be foldable. Since almost all of the amino acid residues known to be involved in the early folding events of DHFR are located within the folding elements, a close relationship between the folding elements and early folding events is hypothesized. In order to test this hypothesis, we have investigated whether or not the early folding events are preserved in circular permutants and topological mutants of DHFR, in which the order of the folding elements is changed but the complete set of folding elements is present. The stopped-flow circular dichroism (CD) measurements show that the CD spectra at the early stages of folding are similar among the mutants and the wild-type DHFR, indicating that the presence of the complete set of folding elements is sufficient to preserve the early folding events. We have further examined whether or not sequence perturbation on the folding elements by a single amino acid substitution affects the early folding events of DHFR. The results show that the amino acid substitutions inside of the folding elements can affect the burst-phase CD spectra, whereas the substitutions outside do not. Taken together, these results indicate that the above hypothesis is true, suggesting a close relationship between the foldability of a protein and the early folding events. We propose that the folding elements interact with each other and coalesce to form a productive intermediate(s) early in the folding, and these early folding events are important for a protein to be foldable.     

Applications of biomolecular interaction analysis in drug development

Biomolecular interaction analysis (BIA) is now utilised increasingly in drug development to kinetically characterise binding events of relevant components. BIA thereby covers a broad range of applications in early ADME (adsorption, distribution, metabolism and excretion), secondary screens, functional and metabolic assays and in assay development. This versatile technology allows measurements in real time without the need of labelling. A wide range of affinities can be characterised in a near-native state, with high reproducibility, high sensitivity and low sample consumption. However, limitations due to experimental design, and limitations in sample throughput, may occur. Future developments of BIA aim at parallelisation and automatisation and at coupling to platform technologies already established in the drug development process.     

Methylation of cytosolic proteins may be a possible biochemical pathway of early aldosterone action in cultured renal collecting duct cells

The common model of aldosterone-dependent sodium transport is that the hormone increases sodium transport during the "early" and "late" response phases by inducing specific proteins (AIPs). However, in actual biochemical studies, AIPs were mostly detected 6-24 h after aldosterone application. Regarding the physiological early response phase, this implies temporal dissociation of the physiological and biochemical events. The discrepancy raises the question as to whether other biochemical events, such as protein modifications, may be involved in addition to the novo protein synthesis. Labelling of cultured renal collecting duct epithelia for 1-5 h with a radioactive methylgroup donor, S-adenosyl methionine (SAM), following tissue fractionation, resulted in progressive methylations of specific cytosolic proteins. Aldosterone-dependent methylations increased consistently with time, and accounted for a 60% increase in total cytosolic protein content as compared to controls after 5 h labelling. The different methylated proteins showed a molecular weight of 220, 97 and 75 kd and comprised groups of proteins with an isoelectric point of 5.1-5.7 and 6.0-7.5. Methylation of identical proteins was obtained by incubation of the epithelia with unlabelled SAM instead of aldosterone. SAM-induced as well as aldosterone-induced methylation of proteins with an isoelectric point of 6.0-7.5 could be inhibited by the methylation inhibitor S-adenosylhomocysteine. The results indicate that aldosterone may influence the SAM cycle in cultured collecting-duct epithelia during increase of the Na+-transport.     

Energy Sources,Self-organization,and the Origin of Life

The emergence and early developments of life are considered from the point of view that contingent events that inevitably marked evolution were accompanied by deterministic driving forces governing the selection between different alternatives. Accordingly, potential energy sources are considered for their propensity to induce self-organization within the scope of the chemical approach to the origin of life. Requirements in terms of quality of energy locate thermal or photochemical activation in the atmosphere as highly likely processes for the formation of activated low-molecular weight organic compounds prone to induce biomolecular self-organization through their ability to deliver quanta of energy matching the needs of early biochemical pathways or the reproduction of self-replicating entities. These lines of reasoning suggest the existence of a direct connection between the free energy content of intermediates of early pathways and the quanta of energy delivered by available sources of energy.     

Interleukin-1-inducible tumor growth arrest is characterized by activation of cell type-specific "early" gene expression programs.

Human melanoma cells, A375-C6, were "committed" to growth arrest within a few hours of exposure to interleukin-1 (IL-1). Co-treatment with actinomycin D rescued the cells from the "commitment," suggesting that "early" gene activation events may be crucial for growth arrest. To understand the mechanism of IL-1 action, we are studying early genes whose expression is induced by the cytokine. Five early genes associated with IL-1 action in the melanoma cells were isolated by differential screening of a cDNA library, which was enriched for sequences representing IL-1 responsive genes (IRGs). Nucleotide sequencing identified four of the genes as gro-alpha, gro-beta, c-jun and nur77/NGF1-B/NAK1, respectively, while the fifth was judged as novel by GenBank search and designated IRG-9. None of the early genes was uniquely associated with the antiproliferative action of IL-1: other growth-inhibitory as well as growth-stimulatory signals induced these genes in diverse cell types. However, analysis of the induction patterns of the IRGs and other well known early genes revealed that IL-1 action in the melanoma cells is characterized by activation of a unique primary gene expression program. This program was defined by the magnitude and temporal pattern of induction of the five IRGs, feeble induction of c-fos, and lack of induction of Egr-1 and c-myc. We present evidence that this program is growth arrest-specific in the melanoma cells and that distinct cell type-specific programs are associated with IL-1 growth-regulatory actions in other tumor cells. Based on these data, we propose that early genes may play multifunctional roles in tumor growth control, but specificity for the growth arrest action of IL-1 is determined by the composite early gene induction program.     

The early region of SV40 DNA may have more than one gene.

The nucleotide sequence of 70 base pairs (bp) around 0.545 map units (Alu I C and B junction) of the genome from the single Eco RI cleavage site within SV40 DNA is presented. The mRNA transcribed from the early strand template from this stretch contains two copies of the nonsense triplet UAA in each of the three reading frames. Thus at least 25% of the early region of SV40 DNA does not code for the SV40 "A" protein, and the viral contribution to events in the lytic cycle and transformation may be more complex than is generally appreciated.     

Translational regulation in cell stress and apoptosis. Roles of the eIF4E binding proteins

Several mechanisms have been identified by which protein synthesis may be regulated during the response of mammalian cells to physiological stresses and conditions that induce apoptotic cell death (reviewed in Clemens et al., Cell Death and Differentiation 7, 603–615, 2000). Recent developments allow us to up-date this analysis and in this article I concentrate on one particular aspect of this regulation that has not previously been reviewed in depth in relation to apoptosis, viz. the control of the initiation of protein synthesis by eukaryotic initiation factor eIF4E and the eIF4E binding proteins (4E-BPs). Changes in the state of phosphorylation of the 4E-BPs and in the extent of their association with eIF4E occur at an early stage in the response of cells to apoptotic inducers. The review discusses the mechanisms by which these events are regulated and the significance of the changes for the control of protein synthesis, cell proliferation and cell survival.     

Nitric oxide-induced eosinophil apoptosis is dependent on mitochondrial permeability transition (mPT), JNK and oxidative stress: apoptosis is preceded but not mediated by early mPT-dependent JNK activation

Background

Eosinophils are critically involved in the pathogenesis of asthma. Nitric oxide (NO) is produced in high amounts in asthmatic lungs and has an important role as a regulator of lung inflammation. NO was previously shown to induce eosinophil apoptosis mediated via c-jun N-terminal kinase (JNK) and caspases. Our aim was to clarify the cascade of events leading to NO-induced apoptosis in granulocyte macrophage-colony stimulating factor (GM-CSF)-treated human eosinophils concentrating on the role of mitochondria, reactive oxygen species (ROS) and JNK.

Methods

Apoptosis was determined by flow cytometric analysis of relative DNA content, by Annexin-V labelling and/or morphological analysis. Immunoblotting was used to study phospho-JNK (pJNK) expression. Mitochondrial membrane potential was assessed by JC-1-staining and mitochondrial permeability transition (mPT) by loading cells with calcein acetoxymethyl ester (AM) and CoCl₂ after which flow cytometric analysis was conducted. Statistical significance was calculated by repeated measures analysis of variance (ANOVA) or paired t-test.

Results

NO-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) induced late apoptosis in GM-CSF-treated eosinophils. SNAP-induced apoptosis was suppressed by inhibitor of mPT bongkrekic acid (BA), inhibitor of JNK SP600125 and superoxide dismutase-mimetic AEOL 10150. Treatment with SNAP led to late loss of mitochondrial membrane potential. Additionally, we found that SNAP induces early partial mPT (1 h) that was followed by a strong increase in pJNK levels (2 h). Both events were prevented by BA. However, these events were not related to apoptosis because SNAP-induced apoptosis was prevented as efficiently when BA was added 16 h after SNAP. In addition to the early and strong rise, pJNK levels were less prominently increased at 20–30 h.

Conclusions

Here we demonstrated that NO-induced eosinophil apoptosis is mediated via ROS, JNK and late mPT. Additionally, our results suggest that NO induces early transient mPT (flickerings) that leads to JNK activation but is not significant for apoptosis. Thereby, we showed some interesting early events in NO-stimulated eosinophils that may take place even if the threshold for irreversible mPT and apoptosis is not crossed. This study also revealed a previously unknown physiological function for transient mPT by showing that it may function as initiator of non-apoptotic JNK signalling.     

Impact of major life events on breast-cancer-specific mortality: A case fatality study on 8000 breast cancer patients

BackgroundIt has been suggested that long-term activation of the body’s stress–response system and subsequent overexposure to stress hormones may be associated with increased morbidity. However, evidence on the impact of major life events on mortality from breast cancer (BC) remains inconclusive. The main aim of this study is to investigate whether major negatively or positively experienced life events before or after diagnosis have an effect on BC-specific mortality in women who have survived with BC for at least 2 years.MethodsWe conducted a case fatality study with data on life events from a self-administered survey and data on BC from the Finnish Cancer Registry. Cox models were fitted to estimate BC mortality hazard ratios (MRs) between those who have undergone major life events and those who haven’t.ResultsNone of the pre-diagnostic negative life events had any effect on BC-specific mortality. Regarding post-diagnostic events, the effect was greatest in women with moderate scores of events. As for event-specific scores, increased BC mortality was observed with spouse unemployment, relationship problems, and death of a close friend. By contrast, falling in love and positive developments in hobbies were shown to be associated with lower BC mortality (MRs 0.67, 95%CI: 0.49–0.92 and 0.74, 95%CI: 0.57–0.96, respectively). In an analysis restricted to recently diagnosed cases (2007), also death of a child and of a mother was associated with increased BC mortality.ConclusionsSome major life events regarding close personal relationships may play a role in BC-specific mortality, with certain negative life events increasing BC mortality and positive events decreasing it. The observed favorable associations between positive developments in romantic relationships and hobbies and BC mortality are likely to reflect the importance of social interaction and support.     

The molecular biology of platelet-derived growth factor

PDGF is a connective tissue mitogen that has been associated with clotted blood serum for at least 300 million years. It regulates the expression of cell cycle "early genes" in normal fibroblasts. Induction of early genes is preceded by stimulation of a tyrosine-specific kinase. The putative structural gene for PDGF has been acquired by an acutely transforming retrovirus and is expressed in many connective tissue tumors. Further work is needed to determine whether (i) production of PDGF by tumor cells confers a proliferative advantage on these cells, (ii) tyrosine-specific phosphorylations mediate the induction of cell cycle early genes by PDGF, and (iii) products of cell cycle early genes play any functional role in the 10-12 hr chain of events that culminates in replicative DNA synthesis and cell division. In the meantime, these very issues represent candidate functions for other viral oncogenes and their cellular homologs. Some of these genes could act at the onset of the mitogenic cascade by causing the production of automitogenic growth factors. Others may function in the interior of the cascade by promoting tyrosine-specific phosphorylations. Still others may be mutated or rearranged homologs of cell cycle early genes whose expression is normally modulated by extracellular growth factors.     

Tales from the crypt[ic] sites of the extracellular matrix

Proteolytic cleavage of extracellular matrix (ECM) proteins by matrix metalloproteinases and/or conformational changes unmask "cryptic" sites and liberate fragments with biological activities that are not observed in the intact molecule. Cryptic sites and fragments of ECM macromolecules have been implicated in many events governed by cell-ECM interactions, such as migration, invasion, adhesion and differentiation. The unmasking of cryptic sites is a tightly controlled process, reflecting the importance of cryptic ECM functions. This review summarizes and evaluates the current developments regarding cryptic regulatory ECM signals found as ECM-tethered protein epitopes or fragments.     

Epigenetic perturbations in aging stem cells

Stem cells maintain homeostasis in all regenerating tissues during the lifespan of an organism. Thus, age-related functional decline of such tissues is likely to be at least partially explained by molecular events occurring in the stem cell compartment. Some of these events involve epigenetic changes, which may dictate how an aging genome can lead to differential gene expression programs. Recent technological advances have made it now possible to assess the genome-wide distribution of an ever-increasing number of epigenetic marks. As a result, the hypothesis that there may be a causal role for an altered epigenome contributing to the functional decline of cells, tissues, and organs in aging organisms can now be explored. In this paper, we review recent developments in the field of epigenetic regulation of stem cells, and how this may contribute to aging.     

Quinine (Cinchona) and the incurable malaria: India c. 1900-1930s

The early decades of this century witnessed significant developments in the approaches to control of malaria in British India. These included both large-scale preventive measures and curative treatment methods (often referred to as "cinchona" or "quinine" policy). This paper identifies a number of factors that constrained the colonial government's capacity to control malaria through effective cinchona policy. The ideal of achieving "self-sufficiency" and having an efficient form of treatment and distribution within the reach of the masses in India (as originally intended in late 1850s) was far from being achieved. Both government's policy and medical profession seemed to have contributed equally to this failure.